| 1: Br J Cancer.
2006 Oct 23;95(8):1062-9. |
|
-
Prognostic value of increase in transcript levels of Tp73
DeltaEx2-3 isoforms in low-grade glioma patients.
Wager
M, Guilhot
J, Blanc
JL, Ferrand
S, Milin
S, Bataille
B, Lapierre
F, Denis
S, Chantereau
T, Larsen
CJ, Karayan-Tapon
L.
1Neurosurgery Department, University Hospital, Poitiers, France.
Glial tumours are a devastating, poorly understood condition carrying a
gloomy prognosis for which clinicians sorely lack reliable predictive
parameters facilitating a sound treatment strategy. Tp73, a p53 family
member, expresses two main classes of isoforms - transactivatory activity
(TA)p73 and DeltaTAp73 - exhibiting tumour suppressor gene and oncogene
properties, respectively. The authors examined their expression status in
high- and low-grade adult gliomas. Isoform-specific real-time reverse
transcription-polymerase chain reaction was used for the analysis of Tp73
isoform transcript expression in a series of 51 adult patients harbouring
glial tumours, in order to compare tumour grades with each other, and with
non-tumoural samples obtained from epileptic patients as well. Our data
demonstrate increase of TAp73 and DeltaTAp73 transcript levels at onset and
early stage of the disease. We also show that DeltaEx2-3 isoform expression
in low-grade tumours anticipates clinical and imaging progression to higher
grades, and correlates to the patients' survival. Expression levels of P1
promoter generated Tp73 isoforms - and particularly DeltaEx2-3 - indeed
allow for prediction of the clinical progression of low-grade gliomas in
adults. Our data are the first such molecular biology report regarding
low-grade tumours and as such should be of help for sound decision-making.British
Journal of Cancer (2006) 95, 1062-1069. doi:10.1038/sj.bjc.6603410
www.bjcancer.com.
PMID: 17047653 [PubMed - in process]
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| 2: Br J Cancer.
2006 Oct 23;95(8):991-7. Epub 2006 Oct 3. |
|
-
Secondary dissemination in children with high-grade
malignant gliomas and diffuse intrinsic pontine gliomas.
Wagner
S, Benesch
M, Berthold
F, Gnekow
AK, Rutkowski
S, Strater
R, Warmuth-Metz
M, Kortmann
RD, Pietsch
T, Wolff
JE.
1Department of Pediatric Hematology and Oncology, Klinik St Hedwig,
University of Regensburg, Regensburg, Germany.
In children, treatment regimen for high-grade gliomas (HGG) and diffuse
intrinsic pontine gliomas (DIPG) are generally not stratified according to
disease stage. The hypothesis was that secondary disseminating disease (SDD)
in children with HGG is related to an even worse outcome. Description of SDD
pattern was performed. In total, 270 children with newly diagnosed HGG or
DIPG were eligible for retrospective analysis of SDD. Medical and computer
records of these patients were reviewed for demographic characteristics,
sites of dissemination, prognostic variables. Forty-six (17%) of the 270
patients had developed SDD. The median time to SDD was 8.2 months. The
median overall survival (OS) after dissemination was 3.2 months. The SDD was
located parenchymal in the supratentorial (34.8%), infratentorial (6.5%),
supratentorial and infratentorial (19.6%), spinal (10.9%), spinal and
cerebral (6.5%) regions of the CNS, or leptomeningeal (21.7%). For HGG
patients, the median OS was shorter among patients with SDD than among
patients without SDD (1.02 vs 1.41 years, P=0.0495). In the group of
patients with SDD, patients with cerebrospinal fluid dissemination had a
worse outcome compared with patients with parenchymal metastases.
Summarising, SDD is a negative prognostic factor for patients with HGG
outside the pons. Treatment stratification should be considered.British
Journal of Cancer (2006) 95, 991-997. doi:10.1038/sj.bjc.6603402
www.bjcancer.com.
PMID: 17047647 [PubMed - in process]
-
| 3: Cancer. 2006 Oct 13; [Epub
ahead of print] |
|
-
Cotreatment with a novel phosphoinositide analogue
inhibitor and carmustine enhances chemotherapeutic efficacy by attenuating
AKT activity in gliomas.
Van
Meter TE, Broaddus
WC, Cash
D, Fillmore
H.
Department of Neurosurgery, Virginia Commonwealth University, Medical
College of Virginia Campus, Richmond, Virginia.
BACKGROUND.: Heightened activity of the AKT signaling pathway is prominent
in malignant gliomas and has been suggested to play a role in treatment
resistance. Selective targeting of AKT, therefore, may increase
chemosensitivity. Recently, a novel class of AKT-selective inhibitors has
been described, including SH-6, a phosphatidylinositol analogue. METHODS.:
The effects of SH-6 on AKT signaling were tested in glioma cells, and the
putative role of AKT signaling in chemoresistance was tested by attenuating
AKT signaling pharmacologically and genetically. The initial
characterization of SH-6 included treatment of glioma cells with increasing
doses of SH-6 (0.30-30 muM) and examining the effects on AKT signaling
proteins by Western blot analyses and in kinase assays with
immunoprecipitated AKT1. Dose-response studies with SH-6 administered to
glioma cell lines were performed using a luminescent cell-viability assay
(0.1-30 muM). Studies examining the effect of carmustine, either alone or in
combination with either the phosphatidylinositol 3-kinase inhibitor LY294002
or SH-6, were performed by cell viability assays and clonogenic survival
assays. The effect of carmustine on AKT activity as a response to treatment
also was examined. Caspase assays were used to examine the potential role of
apoptosis in SH-6/ carmustine -elicited cell death. Finally, the induction
of a dominant-negative AKT1 transgene was used in combination with
carmustine to demonstrate the role of AKT1 in carmustine chemoresistance.
RESULTS.: Serum-stimulated phosphorylation of AKT1 was inhibited by SH-6 at
doses >/=10 muM (>70% decrease in Threonine 308 and Serine 473
phosphorylation of AKT1). In adenosine triphosphate assays, 72 hours of
treatment with SH-6 led to 50% lethal doses near 10 muM for 2 cell lines
tested. SH-6 enhancement of carmustine-mediated cell death led to
synergistic increases in Caspase 3/Capsase 7 activity, implicating apoptosis
as the cell death mechanism. In clonogenic assays, SH-6 cotreatment with
carmustine significantly decreased the number of colonies at 10 muM (P <
.05) compared with carmustine alone. No decrease was observed in cells that
were treated with SH-6 alone (10 muM). LY294002 (10 muM) was also able to
enhance the effects of carmustine significantly in both cell lines.
CONCLUSIONS.: In the current study, the authors characterized the efficacy
of a new class of adjuvant chemotherapeutics that show promise in enhancing
the efficacy of standard chemotherapy regimens in gliomas. Cancer 2006. (c)
2006 American Cancer Society.
PMID: 17041888 [PubMed - as supplied by publisher]
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| 4: Cancer. 2006 Sep
15;107(6):1355-64. |
|
-
Linear accelerator radiosurgery for pituitary
macroadenomas: a 7-year follow-up study.
Voges
J, Kocher
M, Runge
M, Poggenborg
J, Lehrke
R, Lenartz
D, Maarouf
M, Gouni-Berthold
I, Krone
W, Muller
RP, Sturm
V.
Department of Stereotaxy and Functional Neurosurgery, University of Cologne,
Cologne, Germany. j.voges@uni-koeln.de
BACKGROUND: A prospective study was conducted to assess the efficacy and
side effects of linear accelerator (LINAC)-based radiosurgery (RS) performed
with a reduced dose of therapeutic radiation for patients with surgically
inaccessible pituitary macroadenomas. METHODS: From August 1990 through
January 2004, 175 patients with pituitary macroadenomas were treated with
LINAC-RS according to a prospective protocol. To minimize the risk for
radiation-induced damage of the pituitary function, the therapeutic dose to
be applied was limited to 20 grays. RESULTS: Among 175 patients, 142
patients who had a minimum follow-up of 12 months (mean +/- standard
deviation, 81.9 +/- 37.2 months) were included in the current study. The
local tumor control rate was 96.5%, and the tumor response rate was 32.4%.
The mean time (+/- standard deviation) from LINAC-RS to normalization of
pathologic hormone secretion was 36.2 +/- 24.0 months. The probability for
normalization was 34.3% at 3 years and 51.1% at 5 years. The frequency of
endocrine cure (defined as the normalization of hormone secretion without
specific medication intake) was 35.2% (mean +/- standard deviation time to
cure, 42.1 +/- 25.0 months). Patients with Cushing disease had a
statistically significant greater chance of achieving a cure (P = .001).
Side effects of LINAC-RS were deterioration of anterior pituitary function
(12.3%), radiation-induced tissue damage (2.8%), and radiation-induced
neuropathy (1.4%). CONCLUSIONS: LINAC-RS using a lower therapeutic radiation
dose achieved local tumor control and normalization or cure of hormone
secretion comparable to the results achieved with gamma-knife RS. Compared
with the latter, the time to normalization or endocrine cure was delayed,
most probably as a result of dose reduction. However, the lower therapeutic
radiation dose did not prevent radiation-induced damage of pituitary
function completely. (c) 2006 American Cancer Society.
PMID: 16894526 [PubMed - indexed for MEDLINE]
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| 5: Cancer Res. 2006 Oct
15;66(20):10199-204. |
|
-
Comparative proteomic profiles of meningioma subtypes.
Okamoto
H, Li
J, Vortmeyer
AO, Jaffe
H, Lee
YS, Glasker
S, Sohn
TS, Zeng
W, Ikejiri
B, Proescholdt
MA, Mayer
C, Weil
RJ, Oldfield
EH, Zhuang
Z.
Surgical Neurology Branch and Protein/Peptide Sequencing Facility, National
Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland.
Meningiomas are classified into three groups (benign, atypical, and
anaplastic) based on morphologic characteristics. Atypical meningiomas,
which are WHO grade 2 tumors, and anaplastic meningiomas, which are WHO
grade 3 tumors, exhibit an increased risk of recurrence and premature death
compared with benign WHO grade 1 tumors. Although atypical and anaplastic
meningiomas account for <10% of all of meningiomas, it can be difficult
to distinguish them from benign meningiomas by morphologic criteria alone.
We used selective tissue microdissection to examine 24 human meningiomas and
did two-dimensional gel electrophoresis to determine protein expression
patterns. Proteins expressed differentially by meningiomas of each WHO grade
were identified and sequenced. Proteomic analysis revealed protein
expression patterns unique to WHO grade 1, 2, and 3 meningiomas and
identified 24 proteins that distinguish each subtype. Fifteen proteins
showed significant changes in expression level between benign and atypical
meningiomas, whereas nine distinguished atypical from anaplastic meningiomas.
Differential protein expression was confirmed by Western blotting and
immunohistochemistry. We established differential proteomic profiles that
characterize and distinguish meningiomas of increasing grades. The proteins
and proteomic profiles enhance understanding of the pathogenesis of
meningiomas and have implications for diagnosis, prognosis, and treatment.
(Cancer Res 2006; 66(20): 10199-204).
PMID: 17047085 [PubMed - in process]
-
| 6: Cancer Res. 2006 Oct
15;66(20):10024-31. |
|
-
c-Jun NH2-Terminal Kinase 2{alpha}2 Promotes the
Tumorigenicity of Human Glioblastoma Cells.
Cui
J, Han
SY, Wang
C, Su
W, Harshyne
L, Holgado-Madruga
M, Wong
AJ.
Department of Neurosurgery and Cancer Biology Program, Stanford University
Medical Center, Stanford, California.
c-Jun NH(2)-terminal kinases (JNK) are members of the mitogen-activated
protein kinase family and have been implicated in the formation of several
human tumors, especially gliomas. We have previously shown that a 55 kDa JNK
isoform is constitutively active in 86% of human brain tumors and then
showed that it is specifically a JNK2 isoform and likely to be either
JNK2alpha2 or JNK2beta2. Notably, we found that only JNK2 isoforms possess
intrinsic autophosphorylation activity and that JNK2alpha2 has the strongest
activity. In the present study, we have further explored the contribution of
JNK2 isoforms to brain tumor formation. Analysis of mRNA expression by
reverse transcription-PCR revealed that JNK2alpha2 is expressed in 91% (10
of 11) of glioblastoma tumors, whereas JNK2beta2 is found in only 27% (3 of
11) of tumors. Both JNK2alpha2 and JNK2beta2 mRNAs are expressed in normal
brain (3 of 3). Using an antibody specific for JNK2alpha isoforms, we
verified that JNK2alpha2 protein is expressed in 88.2% (15 of 17) of
glioblastomas, but, interestingly, no JNK2alpha2 protein was found in six
normal brain samples. To evaluate biological function, we transfected U87MG
cells with green fluorescent protein-tagged versions of JNK1alpha1,
JNK2alpha2, and JNK2alpha2APF (a dominant-negative mutant), and derived cell
lines with stable expression. Each cell line was evaluated for various
tumorigenic variables including cellular growth, soft agar colony formation,
and tumor formation in athymic nude mice. In each assay, JNK2alpha2 was
found to be the most effective in promoting that phenotype. To identify
effectors specifically affected by JNK2alpha2, we analyzed gene expression.
Gene profiling showed several genes whose expression was specifically
up-regulated by JNK2alpha2 but down-regulated by JNK2alpha2APF, among which
eukaryotic translation initiation factor 4E (eIF4E) shows the greatest
change. Because AKT acts on eIF4E, we also examined AKT activation.
Unexpectedly, we found that JNK2alpha2 could specifically activate AKT. Our
data provides evidence that JNK2alpha2 is the major active JNK isoform and
is involved in the promotion of proliferation and growth of human
glioblastoma tumors through specific activation of AKT and overexpression of
eIF4E. (Cancer Res 2006; 66(20): 10024-31).
PMID: 17047065 [PubMed - in process]
-
| 7: Cancer Res. 2006 Oct
15;66(20):9895-902. |
|
-
Protein disulfide isomerase expression is related to the
invasive properties of malignant glioma.
Goplen
D, Wang
J, Enger
PO, Tysnes
BB, Terzis
AJ, Laerum
OD, Bjerkvig
R.
Department of Biomedicine, University of Bergen.
By serial transplantation of human glioblastoma biopsies into the brain of
immunodeficient nude rats, two different tumor phenotypes were obtained.
Initially, the transplanted xenografts displayed a highly invasive phenotype
that showed no signs of angiogenesis. By serial transplantation in animals,
the tumors changed to a less invasive, predominantly angiogenic phenotype.
To identify novel proteins related to the invasive phenotype, the xenografts
were analyzed using a global proteomics approach. One of the identified
proteins was protein disulfide isomerase (PDI) A6 precursor. PDI is a
chaperone protein that mediates integrin-dependent cell adhesion. It is both
present in the cytosol and at the cell surface. We show that PDI is strongly
expressed on invasive glioma cells, in both xenografts and at the invasive
front of human glioblastomas. Using an in vitro migration assay, we also
show that PDI is expressed on migrating glioma cells. To determine the
functional significance of PDI in cell migration, we tested the effect of a
PDI inhibitor, bacitracin, and a PDI monoclonal antibody on glioma cell
migration and invasion in vitro. Both tumor spheroids derived from human
glioblastoma xenografts in nude rat brain and cell line spheroids were used.
The PDI antibody, as well as bacitracin, inhibited tumor cell migration and
invasion. The anti-invasive effect of bacitracin was reversible after
withdrawal of the inhibitor, indicating a specific, nontoxic effect. In
conclusion, using a global proteomics approach, PDI was identified to play
an important role in glioma cell invasion, and its action was effectively
inhibited by bacitracin. (Cancer Res 2006; 66(20): 9895-902).
PMID: 17047051 [PubMed - in process]
-
| 8: Cancer Res. 2006 Oct
15;66(20):9809-9817. |
|
-
PAX6 Suppresses the Invasiveness of Glioblastoma Cells
and the Expression of the Matrix Metalloproteinase-2 Gene.
Mayes
DA, Hu
Y, Teng
Y, Siegel
E, Wu
X, Panda
K, Tan
F, Yung
WK, Zhou
YH.
Departments of Neurobiology and Developmental Sciences and Biostatistics,
and Arkansas Cancer Research Center, University of Arkansas for Medical
Sciences, Little Rock, Arkansas and Departments of Neuro-Oncology, The
University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Glioblastoma multiforme (GBM) is the most invasive brain tumor. We have
previously reported that the transcription factor PAX6 suppresses the
tumorigenecity of GBM cells. By an in vitro Matrigel invasion assay on two
GBM cell lines stably transfected with wild-type and/or two mutant forms of
PAX6, this study displays the first evidence that PAX6 inhibits the
invasiveness of GBM cells and that the DNA-binding domain of PAX6 is
required for this function. Using real-time quantitative reverse
transcription-PCR (RT-PCR), gelatin zymography, and immunohistochemistry
assays, the expression of the gene encoding matrix metalloproteinase-2
(MMP2) in GBM cell lines grown in vitro or in intracranial xenografts in
nude mice was shown to be repressed by either stable or adenoviral-mediated
overexpression of PAX6. Luciferase promoter assays revealed PAX6-mediated
suppression of MMP2 promoter activity. Electrophoretic mobility shift assays
showed direct binding of PAX6 to the MMP2 promoter. A significant reverse
correlation (P < 0.05) occurred between PAX6 and MMP2 expression
quantified by real-time quantitative RT-PCR in 41 GBMs, 43 anaplastic
astrocytomas, and 7 adjacent normal tissues. Interestingly, the degree and
significance of the reverse correlation increased after excluding
astrocytomas, whereas it became insignificant after excluding GBMs. In GBM
cells stably transfected with a dominant negative mutant PAX6 showing
increased MMP2 expression and invasiveness, knock-down of MMP2 revealed that
MMP2 is one of the PAX6 target genes mediating its suppression of invasion.
Overall data delineated a mechanism for the suppressive function of PAX6 in
GBM: suppression of cell invasion by repressing the expression of
proinvasive genes such as MMP2. (Cancer Res 2006; 66(20): 9809-17).
PMID: 17047041 [PubMed - as supplied by publisher]
-
| 9: Int
J Cancer. 2006 Oct 16; [Epub ahead of print] |
|
-
Synergism between GM-CSF and IFNgamma: Enhanced
immunotherapy in mice with glioma.
Smith
KE, Janelidze
S, Visse
E, Badn
W, Salford
L, Siesjo
P, Darabi
A.
Glioma Immunotherapy Group, Rausing Laboratory, Division of Neurosurgery,
Department of Clinical Sciences, University of Lund, Sweden.
Glioblastoma multiforme is the most common malignant primary brain tumor and
also one of the most therapy-resistant tumors. Because of the dismal
prognosis, various therapies modulating the immune system have been
developed in experimental models. Previously, we have shown a 37-70% cure in
a rat glioma model where rats were peripherally immunized with tumor cells
producing IFNgamma. On the basis of these results, we wanted to investigate
whether a combination of GM-CSF and IFNgamma could improve the therapeutic
effect in a mouse glioma model, GL261 (GL-wt). Three biweekly
intraperitoneal (i.p.) immunizations with irradiated GM-CSF-transduced GL261
cells (GL-GM) induced a 44% survival in mice with intracranial glioma. While
treatment of GL-wt and GL-GM with IFNgamma in vitro induced upregulation of
MHC I and MHC II on the tumor cells, it could not enhance survival after
immunization. However, immunizations with GL-GM combined with recombinant
IFNgamma at the immunization site synergistically enhanced survival with a
cure rate of 88%. Tumors from mice receiving only 1 immunization on Day 10
after tumor inoculation were sectioned on Day 20 for analysis of leukocyte
infiltration. Tumor volume was reduced and the infiltration of macrophages
was denser in mice immunized with GL-GM combined with IFNgamma compared with
that of both wildtype and nonimmunized mice. To our knowledge, this is the
first study to demonstrate a synergy between GM-CSF and IFNgamma in
experimental immunotherapy of tumors, by substantially increasing survival
as well as inducing a potent anti-tumor response after only 1 postponed
immunization. (c) 2006 Wiley-Liss, Inc.
PMID: 17044023 [PubMed - as supplied by publisher]
-
| 10: J Neurooncol.
2006 Oct 19; [Epub ahead of print] |
|
Clinical trial of CPT-11 and VM-26/VP-16 for patients
with recurrent malignant brain tumors.
Feun
LG, Marini
A, Landy
H, Markoe
A, Heros
D, Robles
C, Herrera
C, Savaraj
N.
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL,
33136, USA, lfeun@med.miami.edu.
CPT-11 is a potent inhibitor of topoisomerase I and has shown antitumor
activity in brain xenografts and in clinical trials in recurrent/progressive
malignant glioma. VM-26 and VP-16 are topoisomerase II inhibitors and have
also shown activity in phase II trials. We performed a phase II trial of
intravenous CPT-11 (125 mg/m(2)) followed 24 h later by VM-26 (125 mg/m(2)).
VP-16 (125 mg/m(2)) was later substituted for VM-26 due to drug shortage.
For patients on anticonvulsants, the starting dose for all drugs was 150
mg/m(2). Drugs were given weekly for 3 weeks followed by 1-week rest.
Twenty-five patients were entered into the study. Three patients (12%) had
improvement in CAT/MRI brain scans (95% confidence interval 3-31%). Fatigue
and myelosuppression, mainly leukopenia, were the main toxicities. This
combination of the topoisomerase I inhibitor CPT-11 followed by the
topoisomerase II inhibitor, VM-26 or VP-16, has shown modest antitumor
activity comparable to that reported for each drug singly. Myelosuppression
is the main toxicity when topoisomerase I and II inhibitors are combined
together.
PMID: 17051317 [PubMed - as supplied by publisher]
-
| 11: J Neurooncol.
2006 Oct 18; [Epub ahead of print] |
|
-
Hypermethylation of the proapoptotic gene TMS1/ASC:
prognostic importance in glioblastoma multiforme.
Martinez
R, Schackert
G, Esteller
M.
Department of Neurosurgery, University of Dresden, Fetscherstr. 74, D-01307,
Dresden, Germany.
The identification of clinical subsets of glioblastomas (GBM) associated
with different molecular genetic profiles had opened the possibility to
design tailored therapies to individual patients. One of the most intrigued
subtypes is the long-term survival (LTS) GBM, which responds better to
current therapies. The present investigation on GBM from 50 consecutive GBM
displaying classic survival and seven LTS GBM is based on molecular
epigenetic, clinical and histopathological analyses. Our aim was to
recognize biomarkers useful to distinguish LTS from classic GBM. We analyzed
the promoter methylation status of key regulator genes implicated in tumor
invasion (TIMP2, TIMP3), apoptosis and inflammation (TMS1/ASC, DAPK) as well
as overall survival, therapy status and tumor pathological features. For the
first purpose a methylation-specific PCR approach was performed to analyze
the CpG island promoter methylation status of each gene. The overall TMS1/ASC
methylation rate in the 57 analyzed tumors was 21.05%. Hypermethylation of
TMS1/ASC was significantly more frequent in LTS GBM (57.1% vs. 16%, P =
0.029, Fisher's exact test). DAPK promoter hypermethylation was only
observed in the LTS subset (14.3%) whereas TIMP2 and TIMP3 were unmethylated
in both GBM collectives. Our results strongly suggest that, compared to
classic GBM, LTS GBM display distinct epigenetic characteristics which might
provide additional prognostic biomarkers for the assessment of this
malignancy.
PMID: 17048097 [PubMed - as supplied by publisher]
-
| 12: J Neurooncol.
2006 Aug;79(1):19-30. Epub 2006 Jun 29. |
|
-
Angiogenic patterns and their quantitation in high grade
astrocytic tumors.
Sharma
S, Sharma
MC, Gupta
DK, Sarkar
C.
Department of Pathology, All India Institute of Medical Sciences, 110029,
New Delhi, India.
BACKGROUND: The objectives of this study on high grade astrocytic tumors
were (i) to establish differences, if any, between grades III & IV
tumors among angiogenic parameters, both qualitative and quantitative, and
(ii) to correlate angiogenic parameters with proliferation indices, namely
T2a and MIB1 labeling indices. DESIGN: Twenty nine consecutive cases of WHO
grades III (11) and IV (18) astrocytic tumors diagnosed in the year-2004
were studied, using H&E and CD34, MIB1 and T2a immunostaining by
streptavidin biotin technique. Angiogenic patterns were studied and
parameters quantitated using Image Pro Plus software (four hotspots) on CD34
immunostained sections to determine intratumoral microvessel density (iMVD),
microvascular area (MVA), aspect, mean diameter (MD) and fractal dimension
(FD). RESULTS: Main angiogenic patterns of capillary (18) and glomeruloid
(9) types were best developed in glioblastomas. Statistically significant
differences (P<0.05) were seen between grades III and IV in iMVD, aspect,
MD and FD, but not in angiogenic patterns or MVA (P = 0.27). Statistically
significant differences (P<0.05) were seen between glioblastomas with
glomeruloid vs. capillary types in iMVD and FD, but not in MVA, aspect and
mean vessel diameter. T2a values correlated with MIB1 labeling indices (R =
0.965, P<0.001). Intratumoral endothelial MIB1 LI was significantly
higher in grade IV as compared to grade III, but did not correlate with
angiogenic parameters. No correlation of angiogenic patterns and
proliferation indices was noted (R = -0.221, P = 0.26). Limited follow up
data showed all recurrent grade IV tumors to be of glomeruloid type.
CONCLUSION: Increased angiogenesis in grade IV, as compared to grade III,
astrocytic tumors is characterized by an increased number/density of
vessels: an increase in vessels characterized by disproportionate
lengthening and likely associated with the infiltrative properties of the
tumors; and an increase in pliable, irregularly shaped or structured
vessels. In addition, there is a greater frequency of glomeruloid structures
indicating inadequate directional migration of the newly formed vessels. The
lack of correlation of these angiogenesis parameters with the MIB1 and T2a
proliferation indices reflects the complexity of angiogenesis parameters in
high grade gliomas. Further studies are needed to determine the usefulness
of the angiogenic parameters in the improved diagnosis (grading) and
prognosis of astrocytic tumors.
PMID: 16807783 [PubMed - indexed for MEDLINE]
-
| 13: J Neurooncol.
2006 Aug;79(1):31-2. Epub 2006 Jun 23. |
|
-
Images in neuro-oncology: choroid plexus carcinoma.
Baehring
JM, Duncan
C, Ogle
E, Kim
J.
Department of Neurosurgery,Yale University School of Medicine, New Haven,
CT, USA. joachim.baehring@yale.edu
Publication Types:
PMID: 16794748 [PubMed - indexed for MEDLINE]
-
| 14: J Neurooncol.
2006 Aug;79(1):73-5. Epub 2006 May 23. |
|
-
Concurrent craniospinal radiotherapy and intrathecal
chemotherapy in patient with acute promyelocytic leukemia second relapsed in
central nervous system (CNS) following allogeneic stem cell transplantation.
Lee
HY, Kim
KM, Kang
MH, Kang
JH, Kang
KM, Lee
GW.
Publication Types:
PMID: 16718520 [PubMed - indexed for MEDLINE]
-
| 15: J Neurooncol.
2006 Aug;79(1):57-9. Epub 2006 Apr 14. |
|
-
Spinal extramedullary anaplastic ependymoma with spinal
and intracranial metastases.
Schuurmans
M, Vanneste
JA, Verstegen
MJ, van
Furth WR.
Department of Neurology, Sint Lucas Andreas Ziekenhuis, Amsterdam, The
Netherlands. m.schuurmans@slaz.nl
We describe a 29-year-old woman who presented with progressive neck pain,
sensory deficit and weakness in both arms. Magnetic resonance imaging (MRI)
of the cervical spine revealed an extramedullary tumor with severe spinal
cord compression. During surgery an intradural extramedullary tumor was
found. Further imaging showed a second lumbar spinal tumor. Microscopy of
both tumors showed that both tumors were anaplastic ependymomas, which
almost never present as extramedullary tumors. Two years after surgery, an
intracranial extracerebral metastasis was found, without evidence of spinal
recurrence.
Publication Types:
PMID: 16614942 [PubMed - indexed for MEDLINE]
-
| 16: J Neurooncol.
2006 Aug;79(1):41-3. Epub 2006 Apr 6. |
|
-
Giant invasive pituitary prolactinoma with falsely low
serum prolactin: the significance of 'hook effect'.
Fleseriu
M, Lee
M, Pineyro
MM, Skugor
M, Reddy
SK, Siraj
ES, Hamrahian
AH.
Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic
Foundation, Cleveland, Ohio 44195, USA.
The authors report a case of a patient with giant, invasive skull base tumor
extending to the parasellar area discovered incidentally during the work-up
for decreased memory. The patient's neurological exam was otherwise
unremarkable. Endocrine evaluation performed at a local hospital showed a
moderate hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the
large size of the tumor, the elevated prolactin (PRL) was interpreted to be
secondary to stalk effect and patient underwent debulking surgery through a
transcranial approach. Immunostaining of the excised tumor tissue was
strongly positive for prolactin. His prolactin was found to be 13,144 ng/ml
in our lab after surgery confirming the diagnosis of invasive giant
prolactinoma. The patient developed a complete right third, fourth and sixth
nerve palsy postoperatively. He was started on Cabergoline with
normalization of his prolactin level and more than 50% decrease in residual
tumor size over 9 months periods. There has been no clinically significant
improvement in his right eye ophthalmoplegia since surgery. This case
highlights the importance of 'Hook Effect' resulting in falsely low
prolactin level, which may have significant therapeutic implication.
Publication Types:
PMID: 16598425 [PubMed - indexed for MEDLINE]
-
| 17: J Neurooncol.
2006 Aug;79(1):45-50. Epub 2006 Apr 6. |
|
-
Correlation of endoscopic biopsy with tumor marker status
in primary intracranial germ cell tumors.
Luther
N, Edgar
MA, Dunkel
IJ, Souweidane
MM.
Department of Neurological Surgery, Weill Medical College of Cornell
University, New York, NY, USA.
We retrospectively analyzed the results of eight patients who underwent
endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor
(GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF)
tumor markers and treatment outcome in order to determine the reliability of
GCT sampling by this method. A biopsy diagnosis was made in each patient,
and the tumor histology correlated with tumor marker measurements for all
six patients diagnosed with germinoma and for one with a yolk sac tumor. One
biopsy revealed only mature teratoma, an inconclusive result since the
patient's serum and CSF tumor markers were elevated. No morbidity was
experienced as a result of the operative procedure. Five of six patients
diagnosed with germinoma responded completely to radiation therapy and are
without evidence of disease, while one suffered a likely germinoma
recurrence and was subsequently successfully retreated. We conclude that
endoscopic biopsy of marker-negative germ cell tumors is a safe, reliable
method of establishing a diagnosis of germinoma. However, endoscopic biopsy
may fail to yield an accurate diagnosis in cases of malignant non-germinomatous
tumor. We would thus conclude that when primary germ cell tumor is
considered, endoscopic tumor biopsy is recommended in patients with a
negative biochemical analysis, but not suggested for patients presenting
with elevated tumor markers.
Publication Types:
PMID: 16598424 [PubMed - indexed for MEDLINE]
-
| 18: J Neurooncol.
2006 Aug;79(1):67-72. Epub 2006 Apr 1. |
|
-
Malignant transformation eight years after removal of a
benign epidermoid cyst: a case report.
Tamura
K, Aoyagi
M, Wakimoto
H, Tamaki
M, Yamamoto
K, Yamamoto
M, Ohno
K.
Department of Neurosurgery, Graduate School, Tokyo Medical and Dental
University, Bunkyo-ku, Tokyo, Japan.
Malignant transformation of benign epidermoid cysts is rare and their
prognosis remains poor. A 56-year-old woman presented with left facial
hypoesthesia and photophobia in the left eye. She had undergone removal of a
benign epidermoid cyst in the cerebellopontine angle 8 years previously.
Magnetic resonance imaging of the brain revealed a cystic lesion in the left
cerebellopontine angle. The cyst wall was enhanced by gadolinium-DTPA. She
underwent removal again and the histopathologic diagnosis was squamous cell
carcinoma. Gamma knife radiosurgery was performed on the remnant lesion with
a marginal dose of 15 Gy. The tumor shrank rapidly for 2 months after
radiosurgery, but recurred 9 months later. She underwent radiosurgery again
with a marginal dose of 12 Gy. A gradual increase in the size of the
enhanced lesion was seen during the 4-month follow-up period subsequent to
the second radiosurgery. Careful observation, employing serial magnetic
resonance images, is necessary for incompletely resected epidermoid cysts
because intervals before malignant transformation reportedly range from 3
months to 33 years. Newly identified contrast enhancement strongly indicates
malignant change in epidermoid cysts. Gamma knife radiosurgery may be useful
for short-term control of intracranial squamous cell carcinomas, but
long-term effects are presently unknown.
Publication Types:
PMID: 16583265 [PubMed - indexed for MEDLINE]
-
| 19: J Neurooncol.
2006 Aug;79(1):51-6. Epub 2006 Mar 24. |
|
-
The role of Gamma Knife Radiosurgery in the management of
unresectable gross disease or gross residual disease after surgery in
ependymoma.
Lo
SS, Abdulrahman
R, Desrosiers
PM, Fakiris
AJ, Witt
TC, Worth
RM, Dittmer
PH, Desrosiers
CM, Frost
S, Timmerman
RD.
Department of Radiation Oncology, Indiana University Medical Center, 535
Barnhill Drive, RT 041, Indianapolis, IN 46202, USA.
PURPOSE/OBJECTIVE: To evaluate the efficacy and the toxicity of Gamma Knife
(GK)-based stereotactic radiosurgery (SRS) in the management of gross
disease in ependymoma. MATERIALS AND METHODS: Eight patients with 13
ependymomas were treated with GK-based SRS in our institution for gross
disease. Five patients were treated for recurrent disease that developed
after surgery and external beam radiotherapy (EBRT), two received SRS to the
gross disease after surgery and EBRT, and one received SRS alone (in a 1.3
year old child). Median EBRT dose was 54.4 Gy (range 50-55.8 Gy). Median SRS
dose was 14 Gy (range 12-20 Gy). Seven of eight (87.5%) patients had SRS to
a single lesion and one of eight (12.5%) patients had treatment to six
tumors in three different sessions. RESULTS: The median follow up was 30.2
months (range 8-65.4 months). Out of the eight patients treated with SRS,
six (75%) were alive, four (50%) were alive with no recurrence, two (25%)
were alive with recurrence, and two (25%) died of recurrent disease. Both
patients treated with SRS as a boost were alive and without recurrence. Out
of the five patients who received SRS as salvage treatment, three (60%) were
alive, two (40%) were alive without recurrence, two (40%) developed distant
failure, and three (60%) had in-field control. Two patients who received SRS
to their brainstem lesions developed symptoms related to radionecrosis and
were successfully treated with steroid with good control of symptoms.
CONCLUSIONS: GK-based SRS appears to be a feasible and safe treatment
modality for patients with ependymoma with unresectable gross disease or
gross residual disease after surgery. SRS provides reasonable local control
but out-of-field tumor progression remains an issue. For patients who
receive SRS as a boost, the local control appears to be excellent.
PMID: 16557349 [PubMed - indexed for MEDLINE]
-
| 20: J
Neuropathol Exp Neurol. 2006 Sep;65(9):905-13. |
|
-
Apoptosis and proliferation markers in diffusely
infiltrating astrocytomas: profiling of 17 molecules.
Liu
X, Chen
N, Wang
X, He
Y, Chen
X, Huang
Y, Yin
W, Zhou
Q.
Pathology Department, West China Hospital, West China Medical School,
Sichuan University, Chengdu, China.
Caspases and inhibitor of apoptosis proteins (IAPs) are antagonizing key
apoptosis regulators. Limited studies of a few IAPs indicated their roles in
astrocytomas. However, the overall expression status and significance of
apoptosis regulators in astrocytomas is not clear. We examined the
expression profile of the caspases (CASP3, 6, 7, 8, 9, 10, and 14), APAF1,
SMAC, BCL2, the IAPs (BIRC5/survivin, CIAP1, CIAP2, XIAP, and LIVIN), and
the proliferation markers Ki67 and PHH3 in 78 diffusely infiltrating
astrocytomas and 24 normal brain samples by immunohistochemistry. Western
blotting for major caspases and IAPs and reverse transcription-polymerase
chain reaction analyses for IAPs were performed on a subset of 27 fresh
samples. Our data showed BIRC5 nuclear labeling index (BIRC5-N) was the
apoptosis marker most significantly different in World Health Organization
grade II to IV astrocytomas and most strongly associated with proliferative
activity. Expression level of other apoptosis-related proteins was modest or
low in astrocytomas and did not correlate significantly with tumor grade or
proliferation. Apoptosis regulators and proliferation markers were not
detected in astrocytes of normal brain by immunostaining. This expression
profile suggested involvement of apoptosis regulators in astrocytoma
tumorigenesis, but tumor progression was more closely associated with
proliferative advantages of which BIRC5 nuclear expression appeared to be a
manifestation.
PMID: 16957584 [PubMed - indexed for MEDLINE]
-
| 21: J Neurosurg.
2006 Oct;105(4):555-60. |
|
Gamma knife surgery for metastatic brain tumors from
renal cell carcinoma.
Shuto
T, Inomori
S, Fujino
H, Nagano
H.
Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama, Kanagawa,
Japan. shuto@yokohamah.rofuku.go.jp
OBJECT: The authors evaluated the results of Gamma Knife surgery (GKS) for
the treatment of metastatic brain tumors from renal cell carcinoma (RCC).
METHODS: The authors conducted a retrospective review of the clinical
characteristics and treatment outcomes in 69 patients with metastatic brain
tumors from RCC who underwent GKS at the authors' institution. Fifty-one
patients were men, and 18 were women. The mean patient age was 64.2 years
(range 45-85 years). The 69 patients underwent a total of 104 GKS procedures
for treatment of 314 tumors. Eighteen patients received repeated GKS.
Follow-up magnetic resonance (MR) imaging was used at a mean of 7.1 months
after GKS to evaluate the change in 132 tumors after treatment. The mean
prescription dose at the tumor margin was 21.8 Gy. The tumor growth control
rate was 82.6%. Tumor volume and the delivered peripheral dose were
significantly correlated with tumor growth control on univariate and
multivariate analyses. Sixty (45.5%) of the 132 tumors assessed with MR
imaging were associated with apparent peritumoral edema at the time of GKS.
After treatment, peritumoral edema disappeared in 27 tumors, decreased in
13, was unchanged in 16, and progressed in four. Newly developed peritumoral
edema after GKS was rare. The delivered peripheral dose was significantly
correlated with control of peritumoral edema. The overall median survival
time after GKS was 9.5 months. In this study, 34 patients died of systemic
disease and 10 died of progressive brain metastases. Multivariate analysis
showed that the number of lesions at the first GKS, the Karnofsky
Performance Scale score at the first GKS, the recursive partitioning
analysis classification, and the interval from diagnosis of RCC to brain
metastasis were significantly correlated with survival time. CONCLUSIONS:
Gamma Knife surgery is effective for metastatic brain tumors from RCC. The
disappearance rate of tumors is relatively low, but growth control is high.
The delivered dose to the tumor margin is significantly correlated with the
control of peritumoral edema. Gamma Knife surgery should be used as the
initial treatment modality, if possible, even in patients with multiple
metastases. Repeated GKS is recommended for newly developed brain metastases
because of the low sensitivity of RCC to conventional radiation therapy.
PMID: 17044558 [PubMed - in process]
-
| 22: J Neurosurg.
2006 Oct;105(4):538-43. |
|
Indications for surgery in patients with asymptomatic
meningiomas based on an extensive experience.
Yano
S, Kuratsu
J; Kumamoto
Brain Tumor Research Group.
Department of Neurosurgery, Faculty of Medical and Pharmaceutical Sciences,
Kumamoto University Graduate School, Kumamoto, Japan. yanos@kaiju.medic.kumamoto-u.ac.jp
OBJECT: To determine the indications for surgery in patients harboring
asymptomatic meningiomas, the authors retrospectively analyzed the natural
course and surgical outcome of asymptomatic meningiomas and then compared
these to the natural course and surgical outcome of symptomatic meningiomas.
METHODS: Between 1989 and 2003, 1434 patients harboring meningiomas, who
were treated in Kumamoto Prefecture, Japan, were enrolled in this study. Six
hundred three patients had asymptomatic lesions and 831 had symptomatic
ones. The authors analyzed the sizes of the lesions at detection, their
growth over time, and any appearances of symptoms associated with previously
asymptomatic meningiomas. The authors then compared the surgery-related
morbidity rates associated with asymptomatic and symptomatic meningiomas
arising at different locations. Of the 603 asymptomatic meningiomas, 351
(58.2%) were treated conservatively. Tumor growth was observed in 25 (37.3%)
of 67 patients who participated in follow up for longer than 5 years, and
symptoms developed in 11 (16.4%) of the 67 patients over a mean follow-up
period of 3.9 years. Among the 213 patients with surgically treated
asymptomatic meningiomas, the morbidity rate was 4.4% in patients younger
than 70 years of age and 9.4% in those 70 years of age or older. Although
the total morbidity rate was lower in patients with asymptomatic lesions
than in those with symptomatic ones, it exceeded 6% in patients whose
asymptomatic tumors were located at the convexity or falx. CONCLUSIONS:
Approximately 63% of asymptomatic meningiomas did not exhibit tumor growth,
and only 6% of all patients with these lesions experienced symptoms during
the observation period. To avoid surgery-related incidences of morbidity in
patients with asymptomatic meningiomas, conservative treatment with close
follow-up review may be the best therapeutic strategy.
PMID: 17044555 [PubMed - in process]
-
| 23: J Neurosurg.
2006 Oct;105(4):536-7; discussion 537. |
|
Asymptomatic meningiomas.
Couldwell
WT.
Publication Types:
PMID: 17044554 [PubMed - in process]
-
| 24: J Neurosurg.
2006 Oct;105(4):514-25. |
|
Results of attempted radical tumor removal and venous
repair in 100 consecutive meningiomas involving the major dural sinuses.
Sindou
MP, Alvernia
JE.
Department of Neurosurgery, Hopital Neurologique Pierre Wertheimer,
Universite Claude-Bernard de Lyon, France. marc.sindou@chu-lyon.fr
OBJECT: Radical removal of meningiomas involving the major dural sinuses
remains controversial. In particular, whether the fragment invading the
sinus must be resected and whether the venous system must be reconstructed
continue to be issues of debate. In this paper the authors studied the
effects, in terms of tumor recurrence rate as well as morbidity and
mortality rates, of complete lesion removal including the invaded portion of
the sinus and the consequences of restoring or not restoring the venous
circulation. METHODS: The study consisted of 100 consecutive patients who
had undergone surgery for meningiomas originating at the superior sagittal
sinus in 92, the transverse sinus in five, and the confluence of sinuses in
three. A simplified classification scheme based on the degree of sinus
involvement was applied: Type I, lesion attachment to the outer surface of
the sinus wall; Type II, tumor fragment inside the lateral recess; Type III,
invasion of the ipsilateral wall; Type IV, invasion of the lateral wall and
roof; and Types V and VI, complete sinus occlusion with or without one wall
free, respectively. Lesions with Type I invasion were treated by peeling the
outer layer of the sinus wall. In cases of sinus invasion Types II to VI,
two strategies were used: a nonreconstructive (coagulation of the residual
fragment or global resection) and a reconstructive one (suture, patch, or
bypass). Gross-total tumor removal was achieved in 93% of cases, and sinus
reconstruction was attempted in 45 (65%) of the 69 cases with wall and lumen
invasion. The recurrence rate in the study overall was 4%, with a follow-up
period from 3 to 23 years (mean 8 years). The mortality rate was 3%, all
cases due to brain swelling after en bloc resection of a Type VI meningioma
without venous restoration. Eight patients--seven of whom harbored a lesion
in the middle third portion of the superior sagittal sinus--had permanent
neurological aggravation, likely due to local venous infarction. Six of
these patients had not undergone a venous repair procedure. CONCLUSIONS: The
relatively low recurrence rate in the present study (4%) favors attempts at
complete tumor removal, including the portion invading the sinus. The
subgroup of patients without venous reconstruction displayed statistically
significant clinical deterioration after surgery compared with the other
subgroups (p = 0.02). According to this result, venous flow restoration
seems justified when not too risky.
PMID: 17044551 [PubMed - in process]
-
| 25: J Neurosurg.
2006 Oct;105(4):511-3; discussion 513. |
|
Meningiomas involving the sinus.
Heros
RC.
Publication Types:
PMID: 17044550 [PubMed - in process]
-
| 26: J Neurosurg.
2006 Sep;105(3 Suppl):219-26. |
|
Outcomes in patients undergoing single-trajectory
endoscopic third ventriculostomy and endoscopic biopsy for midline tumors
presenting with obstructive hydrocephalus.
O'Brien
DF, Hayhurst
C, Pizer
B, Mallucci
CL.
Department of Neurosurgery and Oncology, Royal Liverpool Children's Hospital
NHS Trust, Liverpool, United Kingdom. dfobstl@hotmail.com
OBJECT: The primary aim of this study was to evaluate the success of
endoscopic third ventriculostomy (ETV) as a treatment for obstructive
hydrocephalus secondary to midline tumors (midbrain, pontine, pineal, tectal
plate, thalamic, and third ventricular regions). In addition, the study
examined the role and value of endoscopic tumor biopsy (ETB) in the
management of such cases. All surgical procedures were performed through a
single-trajectory approach. METHODS: A retrospective analysis of clinical
notes, operation records, and pre- and postventriculostomy neuroimaging data
was performed to determine the success or failure and complications of ETV
and ETB in 42 patients presenting with tumor-induced obstructive
hydrocephalus. Patient data were derived from an endoscopy database
initiated in 1998. The study population included 21 female and 21 male
patients (mean age 37 years, range 5-77 years). All 42 patients underwent an
ETV; 33 of the 42 underwent an ETV and an ETB (single-trajectory). One
patient was excluded from the follow-up analysis due to rapid deterioration
of his condition from tumor progression. The duration of follow up ranged
from 3 to 84 months (mean 32 months). At the last follow up, 11 patients
with ETVs had undergone shunt placement and two patients had undergone
repeated ETVs, giving a long-term success rate of 68% (28 of 41 cases) for
single ETV as a treatment for hydrocephalus at presentation. Statistical
analysis revealed no significant relationship (p > 0.92) between tumor
location and ETV success or failure. The mean time to ETV failure was 32
weeks. Histological examination of biopsy specimens was non-diagnostic in
eight (24%) of the 33 cases in which ETB was performed. Seven of these cases
involved pineal region tumors and one involved a tectal plate tumor. There
was no death or major morbidity associated with ETV and ETB in this series.
CONCLUSIONS: Endoscopic third ventriculostomy is a safe and durable means of
controlling hydrocephalus in tumor cases. Its success rate is
high--comparable to that reported in aqueduct stenosis cases. Although ETB
is probably not as accurate for diagnosis as biopsy with frame-based
stereotactic guidance, it is associated with a lower mortality rate and, in
the correct clinical setting, may be justifiably attempted as an initial
biopsy procedure at the same time as ETV via a single-trajectory approach.
Publication Types:
PMID: 16970236 [PubMed - indexed for MEDLINE]
-
| 27: J Neurosurg.
2006 Sep;105(3 Suppl):194-202. |
|
Neuroendoscopic management of interhemispheric cysts in
children.
Cinalli
G, Peretta
P, Spennato
P, Savarese
L, Varone
A, Vedova
P, Grimaldi
G, Ragazzi
P, Ruggiero
C, Cianciulli
E, Maggi
G.
Department of Pediatric Neurosurgery, Santobono-Pausilipon Children's
Hospital, Naples, Italy. giuseppe.cinalli@fastwebnet.it
OBJECT: Interhemispheric arachnoid cysts are very rare, and they are often
associated with complex brain malformations such as corpus callosum agenesis
and hydrocephalus. Debate remains concerning the proper management of these
lesions. Placement of shunts and microsurgical marsupialization of the cyst
are the traditional options. Using endoscopic methods to create areas of
communication between the cyst, the ventricular system, and/or the
subarachnoid space is an attractive alternative to the use of shunts and
microsurgery. METHODS: Between 2000 and 2005, seven consecutive pediatric
patients with interhemispheric arachnoid cysts underwent neuroendoscopic
treatment involving cystoventriculostomy in two patients, cystocisternostomy
in two, and cystoventriculocisternostomy in three. There were three cases of
associated hydrocephalus, six cases of corpus callosum agenesis, and one
case of corpus callosum hypogenesis. The follow-up period ranged from 12 to
49 months (mean 31.6 months). Endoscopic procedures were completely
successful in all but two patients. In one of the remaining two patients, a
repeated endoscopic cystocisternostomy was performed with success because of
closure of the previous stoma. In the other, a subcutaneous collection of
cerebrospinal fluid (CSF) was managed by insertion of an lumboperitoneal
shunt. A subdural collection of CSF developed in three patients; it was
treated with insertion of a subduroperitoneal shunt in one patient and
managed conservatively in the other two patients, resolving spontaneously
without further treatment. Neurodevelopmental evaluation performed in six
patients showed normal intelligence (total intelligence quotient [IQ] >
80) in three patients, mild developmental delay (total IQ 50-80) in two, and
severe developmental delay (total IQ < 50) in one. CONCLUSIONS:
Endoscopic treatment of interhemispheric cysts can be considered a useful
alternative to traditional treatments, even if some complications are to be
expected, such as subdural or subcutaneous CSF collections and CSF leaks due
to thinness of cerebral mantle and to the often-associated multifactorial
hydrocephalus.
Publication Types:
PMID: 16970232 [PubMed - indexed for MEDLINE]
-
| 28: J Neurosurg.
2006 Sep;105(3 Suppl):169-76. |
|
Comment in:
Is there a "July phenomenon" in pediatric
neurosurgery at teaching hospitals?
Smith
ER, Butler
WE, Barker
FG 2nd.
Neurosurgical Service, Massachusetts General Hospital, Boston 02114, USA.
OBJECT: Concern for patient safety, among other reasons, recently prompted
sweeping changes in resident work policies in the US. Some have speculated
that the arrival of new interns and residents at teaching hospitals each
July might cause an annual transient increase in poor patient outcomes and
inefficient care. METHODS: Data were analyzed for 4323 craniotomies for
tumor resection and 22,072 shunt operations performed in pediatric patients
between 1988 and 2000 in US nonfederal hospitals (Nationwide Inpatient
Sample, Healthcare Cost and Utilization Project, Agency for Healthcare
Research and Quality, Rockville, MD). In-hospital mortality rates, discharge
outcome, complications, and efficiency measures (length of stay [LOS] and
hospital charges) for patients treated in July and August were compared with
similar data for patients in other months. There were no significant
increases in any adverse end point for either tumor or shunt operations in
July and August. Odds ratios (95% confidence interval [CI]) for outcome of
tumor craniotomies performed in July and August compared with outcome for
tumor craniotomies performed in other months were as follows: for mortality
rate, 0.43 (0.14-1.32); for adverse discharge disposition, 1.03 (0.71-1.51);
for neurological complications, 1.00 (0.63-1.59); for transfusion, 0.70
(0.41-1.19). Hospital charges were 0.5% lower (range -6 to 5%) in July and
August, and LOS was 3% shorter (range -8 to 3%). Odds ratios (95% CI) for
July or August shunt surgery compared with shunt surgery performed in other
months were as follows: for mortality rate, 0.96 (0.58-1.60); for adverse
discharge disposition, 0.85 (0.66-1.11); for neurological complications,
1.27 (0.75-2.16); for transfusion, 0.81 (0.48-1.37). Hospital charges were
0.2% higher in July and August (range -3 to 3%), and LOS was 3% shorter
(range -5 to 0.5%). CONCLUSIONS: Although moderate increases in some adverse
end points could not be excluded, there was no evidence that brain tumor or
shunt surgery performed in pediatric patients at US teaching hospitals
during July and August is associated with more frequent adverse patient
outcome or inefficient care than similar surgery performed during other
months.
PMID: 16970228 [PubMed - indexed for MEDLINE]
-
| 29: Neurosurgery. 2006
Oct;59(4 Suppl 2):ONS470-3. |
|
-
Intratumoral Hydrogen Peroxide Injection during
Meningioma Resection.
Lichtenbaum
R, de
Souza AA, Jafar
JJ.
Department of Neurosurgery, New York University School of Medicine, New
York, New York (Lichtenbaum, Jafar) Department of Neurosurgery, Faculdade de
Ciencias Medicas de Minas Gerais, Belo Horizonte, Brazil (de Souza).
OBJECTIVE:: Meningiomas, although histologically benign, pose a particular
challenge to the neurosurgeon because of their extensive and exuberant
vascularity. They often bleed extensively during resection until separated
from their blood supply. There are a wide variety of hemostatic agents
available to the neurosurgeon. Most of these means of hemostasis involve
some sort of chemical, electrical, or compressive action. Although
anecdotally known to be useful, the use of hydrogen peroxide as an
intracranial hemostatic agent in meningioma surgery has not been formally
reported. We report a technique of meningioma resection that uses
intratumoral hydrogen peroxide injection, reducing the potential for blood
loss and shortening resection times. METHODS:: Seventy-five patients
underwent resection of a meningioma using the direct intratumoral H2O2
injection technique. The locations of these meningiomas included convexity
and cranial-based lesions. None of the patients underwent preoperative
endovascular embolization. RESULTS:: The use of this technique greatly
facilitated the removal of these tumors. No evidence of air embolism
occurred during Doppler surveillance and no other significant side effects
attributable to H2O2 application were observed. CONCLUSION:: We demonstrate
a previously unreported technique of meningioma resection that uses direct
intratumoral hydrogen peroxide injection, potentially reducing blood loss,
shortening resection times, and obviating the need for preoperative
embolization.
PMID: 17041519 [PubMed - in process]
-
| 30: Neurosurgery. 2006
Oct;59(4 Suppl 2):ONS426-34. |
|
-
Extended Bifrontal Craniotomy for Midline Anterior Fossa
Meningiomas: Minimization of Retraction-related Edema and Surgical Outcomes.
Chi
JH, Parsa
AT, Berger
MS, Kunwar
S, McDermott
MW.
Department of Neurological Surgery, University of California, San Francisco,
San Francisco, California.
OBJECTIVE:: Meningiomas of the anterior cranial base can be approached with
a variety of techniques. The extended bifrontal approach is often thought to
be associated with increased morbidity because of the need for extensive
removal of the bone and longer surgical times. The authors have attempted to
quantitate retraction-related edema occurring after surgery to determine
whether the extra bone removal limits retraction and reduces the chance of
brain injury. METHODS:: Charts were reviewed for patients who underwent
extended bifrontal craniotomies performed for meningiomas at the University
of California, San Francisco, between 1997 and 2005. Magnetic resonance
imaging scans obtained before and after surgery were reviewed for brain
edema as indicated by fluid-attenuated inversion recovery/T2 abnormality and
grouped into four categories: A, no edema; B, edema restricted to the gyrus
rectus; C, edema beyond the gyrus rectus; and D, extensive bifrontal edema.
RESULTS:: Forty-five patients were identified. Fifty-four percent of
patients had tumors with a diameter of more than 4 cm. Simpson Grade 2 or 3
resection was achieved in 82% of patients, and the average operative time
was 12.3 hours. Vision outcome was favorable in 74% of patients. Extent of
fluid-attenuated inversion recovery abnormality remained unchanged in 87.5%,
with 91% of patients in categories A or B edema remaining in those
categories after surgery. There were no infections and there were two
cerebrospinal fluid leaks. CONCLUSION:: The extended bifrontal approach is a
safe surgical procedure with limited morbidity that the authors think: 1)
prevents secondary brain injury from excessive retraction; 2) offers great
flexibility of view for the surgeon; and 3) should be considered the
preferred approach compared with the standard bifrontal craniotomy for large
tumors of the anterior cranial base.
PMID: 17041513 [PubMed - in process]
-
| 31: Oncogene. 2006 Oct 16; [Epub
ahead of print] |
|
-
A novel inhibitor of the STAT3 pathway induces apoptosis
in malignant glioma cells both in vitro and in vivo.
Iwamaru
A, Szymanski
S, Iwado
E, Aoki
H, Yokoyama
T, Fokt
I, Hess
K, Conrad
C, Madden
T, Sawaya
R, Kondo
S, Priebe
W, Kondo
Y.
1Department of Neurosurgery, The University of Texas MD Anderson Cancer
Center, Houston, TX, USA.
Signal transducer and activator of transcription-3 (STAT3) is constitutively
activated in a variety of cancer types, including malignant gliomas. STAT3
is activated by phosphorylation of a tyrosine residue, after which it
dimerizes and translocates into the nucleus. There it regulates the
expression of several genes responsible for proliferation and survival at
the transcriptional level. A selective inhibitor of STAT3 phosphorylation,
AG490, has been shown to inhibit growth and induce apoptosis in some cancer
cell types. However, although AG490 routinely shows in vitro anticancer
activity, it has not consistently demonstrated an in vivo anticancer effect
in animal models. Here, we have tested WP1066, a novel inhibitor
structurally related to AG490 but significantly more potent and active,
against human malignant glioma U87-MG and U373-MG cells in vitro and in
vivo. IC(50) values for WP1066 were 5.6 muM in U87-MG cells and 3.7 muM in
U373-MG cells, which represents 18-fold and eightfold increases in potency,
respectively, over that of AG490. WP1066 activated Bax, suppressed the
expression of c-myc, Bcl-X(L) and Mcl-1, and induced apoptosis. Systemic
intraperitoneal administration of WP1066 in mice significantly (P<0.001)
inhibited the growth of subcutaneous malignant glioma xenografts during the
30-day follow-up period. Immunohistochemical analysis of the excised tumors
revealed that phosphorylated STAT3 levels in the WP1066 treatment group
remained inhibited at 3 weeks after the final WP1066 injection, whereas
tumors from the control group expressed high levels of phosphorylated STAT3.
We conclude that WP1066 holds promise as a therapeutic agent against
malignant gliomas.Oncogene advance online publication, 16 October 2006;
doi:10.1038/sj.onc.1210031.
PMID: 17043651 [PubMed - as supplied by publisher]
-
| 32: Pediatr Neurol.
2006 Aug;35(2):122-5. |
|
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Transverse myelitis after therapy for primitive
neuroectodermal tumors.
Ullrich
NJ, Marcus
K, Pomeroy
SL, Turner
CD, Zimmerman
M, Lehmann
LE, Scott
RM, Goumnerova
L, Gillan
E, Kieran
MW, Chi
SN.
Department of Neurology, Children's Hospital Boston and Dana-Farber Cancer
Institute, Boston, Massachusetts 02115, USA. nicole.ullrich@childrens.harvard.edu
Traditional therapy for malignant primitive neuroectodermal tumors in
children includes surgery, multi-agent chemotherapy, and radiation. Given
the poor prognosis with conventional therapy alone, newer treatment
approaches have incorporated high-dose chemotherapy followed by autologous
stem cell rescue. Treatment with chemotherapy and radiation is not without
unanticipated and unwanted side effects. Specifically, radiation-induced
damage to the central nervous system can occur, though the frequency is
thought to be acceptably low. This report describes two cases of
treatment-related transverse myelitis in patients who received induction
chemotherapy and craniospinal irradiation followed by high-dose chemotherapy
with autologous stem cell rescue. Other patients treated with a similar
strategy but different sequence and timing of treatment did not experience
symptoms of myelitis, suggesting that the specific timing of radiation in
relationship to the chemotherapy may be of critical importance.
Publication Types:
PMID: 16876009 [PubMed - indexed for MEDLINE]
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| 33: Rev Neurol.
2006 Jul 16-31;43(2):88-94. |
|
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[Pediatric neuro-oncology]
[Article in Spanish]
Navajas-Gutierrez
A.
Departmento de Pediatria, Universidad del Pais Vasco, Unidad de Oncologia
Pediatrica, Hospital de Cruces, Barakaldo, Vizcaya, Espana.
INTRODUCTION: Pediatric neuro-oncology is getting more important for various
reasons, brain tumours are the most frequent solid tumours in children below
fifteen year of age, besides due to the recent advances in neuro-image
techniques that make possible an early diagnosis and the fact that the
children are usually treated in pediatric oncology units, with protocols
that are internationally based allow a better survival with a better degree
of evidence. DEVELOPMENT: Actually the brain tumours should be classified
according to their biological, genetic and molecular risk factors and their
treatment should consider also the familial predisposition for developing a
brain tumour, and the molecular markers expressed by the tumour. The
objective of this work is to review the special characteristics of the brain
tumours in the pediatric population and the differences with the brain
tumours in adults, also to give the incidence and survival data of brain
tumours in pediatric population from Spain based in the data from the
National Registry of Pediatric Tumours. Also the clinical signs and symptoms
of presentation that should alert for diagnosis in children, and how to make
a diagnostic strategy based on the clinical manifestations, the image
modalities for diagnosis, and the treatment strategy to be used based in
multinational protocols, and stratified by histological, biological and
genetic markers of risk are emphasized. Finally we describe the
characteristics of the three more common histological subtypes because their
prevalence in pediatric population; gliomas, medulloblastomas/primitive
neuroectodermal tumours and ependymomas. CONCLUSION: Improving prognosis of
brain tumors in childhood has to be achieved by early despistage throughout
image and biological techniques, following multicentric protocols in
specialized units and stratified treatments regarding the biological risk in
order to diminish morbility and sequels.
Publication Types:
PMID: 16838256 [PubMed - indexed for MEDLINE]
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| 34: Rev Neurol.
2006 Apr 16-30;42(8):510-1. |
|
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[Cerebellar seizures: can we speak of such a thing?]
[Article in Spanish]
Iglesias-Escalera
G, Guardia-Nieto
L, Usano-Carrasco
AI, Martinez-Badas
I, Cueto-Calvo
E, Sarrion-Cano
M.
Publication Types:
PMID: 16625516 [PubMed - indexed for MEDLINE]
-
| 35: Rev Neurol.
2006 Apr 16-30;42(8):508-10. |
|
-
[Hemicerebellitis versus cerebellar tumour]
[Article in Spanish]
Madrid-Madrid
A, Ariza-Aranda
S, Martinez-Anton
J, Mora-Ramirez
MD, Delgado-Marques
MP.
Publication Types:
PMID: 16625515 [PubMed - indexed for MEDLINE]
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| 36: Surg Neurol.
2006 Sep;66(3):332; author reply 332. |
|
-
Comment on:
The second case of de novo intracranial germinoma
association with Klinefelter's syndrome.
Phowthongkum
P.
Publication Types:
- Case Reports
- Comment
- Letter
PMID: 16935655 [PubMed - indexed for MEDLINE]
-
| 37: Surg Neurol.
2006 Sep;66(3):246-50; discussion 250-1. |
|
-
The role of diffusion-weighted imaging in the
differential diagnosis of intracranial cystic mass lesions: a report of 147
lesions.
Reddy
JS, Mishra
AM, Behari
S, Husain
M, Gupta
V, Rastogi
M, Gupta
RK.
Department of Neurosurgery, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Lucknow-226014, India.
BACKGROUND: The objective of this study is to evaluate the sensitivity and
specificity of DWI in differentiating brain abscesses from other
intracranial cystic lesions. METHODS: One hundred fifteen patients with 147
cystic lesions (mean age, 26.4 year) were prospectively studied with DWI on
a 1.5-T magnetic resonance imaging. Lesions appearing hyperintense on DWI
with the ADC values of lower than 0.9 +/- 0.13 x 10(-3) mm(2)/s (mean +/-
SD) were considered as brain abscess, whereas hypointense lesions on DWI
with the ADC values 2.2 +/- 0.9 x 10(-3) mm(2)/s were categorized as
nonabscess cystic lesions. RESULTS: Ninety-three of 97 brain abscess lesions
were hyperintense on DWI, with significantly low (P = .0001) ADC value (0.87
+/- 0.05 x 10(-3) mm(2)/s) (mean +/- SEM), compared with 48 nonabscess
lesions (2.89 +/- 0.05 x 10(-3) mm(2)/s). Four of 97 brain abscess lesions
in 65 patients were false negative, and 2 of 50 nonabscess lesions in 50
patients were false positive for the diagnosis of brain abscess. The ADC
value of the tumor cysts (2.9 +/- 0.05 x 10(-3) mm(2)/s) was significantly
lower (P = .02) compared with benign cysts and neurocysticercosis (3.2 +/-
0.05 x 10(-3) mm(2)/s) among nonabscess group. The sensitivity of DWI for
the differentiation of brain abscesses from nonabscesses was 96%;
specificity, 96%; positive predictive value, 98%; negative predictive value,
92%; and accuracy of the test, 96%. CONCLUSIONS: Diffusion-weighted imaging
has high sensitivity and specificity for the differentiation of brain
abscess from other nonabscess intracranial cystic lesions.
PMID: 16935625 [PubMed - indexed for MEDLINE]
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| 38: Pediatr Neurosurg.
2006;42(6):347-53. |
|
-
Survival analysis of 81 children with primary spinal
gliomas: a population-based study.
Tseng
JH, Tseng
MY.
Division of Neurosurgery, Department of Surgery, National Taiwan University
Hospital, Taipei, Taiwan.
Primary spinal gliomas are rare. Most clinical studies are based on single
centers with small numbers of patients and limited length of follow-up.
Because data from the Cancer Registry cover larger numbers of patients and
longer durations of follow-up, our objective was to define prognostic
factors that might predict the survival at a national population level. From
1971 to 1995, data of 81 children (age <15 years) with primary spinal
gliomas from the Cancer Registry of England and Wales were analyzed. Median
survival and crude survival rates in respect of 7 variables (age, sex,
morphology, WHO grade, socioeconomic status, geographical region, and period
of diagnosis) were calculated using the Kaplan-Meier method. The Cox
regression was performed for estimating hazard ratios (HR) for death.
Results showed that the 1-, 5-, and 10-year crude survival rates for this
population were 72.84, 60.49, and 58.0%, respectively. Both univariate and
multivariate analyses revealed that only morphology (HR 2.79 for
nonependymoma, p = 0.05) and WHO grade (HR 6.74 for high grade, p = 0.01)
were significant prognostic factors. Results from this population-based
study are very helpful for comparison with other population-based studies
and for public health purposes. Copyright (c) 2006 S. Karger AG, Basel.
PMID: 17047414 [PubMed - in process]
-
| 39: Pediatr Neurosurg.
2006;42(5):311-5. |
|
-
Excision of juvenile pilocytic astrocytoma of the
midbrain after radiotherapy.
Tsuboi
K, Matsuda
W, Nakamura
K, Takano
S, Matsumura
A.
Department of Neurosurgery, Doctoral Program in Functional and Regulatory
Medical Sciences, Graduate School of Comprehensive Human Sciences,
University of Tsukuba, Tsukuba, Japan. tsuboi-k@md.tsukuba.ac.jp
A 13-year-old girl presented with consciousness disturbance, right
hemiparesis, and impairment of hearing, swallowing, and ocular movements. A
magnetic resonance image demonstrated marked hydrocephalus due to a large
cystic tumor (40 x 40 x 30 mm) in the midbrain. Emergency ventricular
drainage and stereotactic cyst puncture dramatically improved her condition.
Since her family did not agree to surgery on the brain stem, radiotherapy
was performed after ventriculoperitoneal shunting. Conventional radiotherapy
of 50.4 Gy was temporarily effective, and the growth of the tumor was
stabilized until approximately 8 months later when regrowth was noticed. At
this stage, with the consent of her family, the tumor was removed via an
infratentorial supracerebellar approach. The pathological diagnosis was
juvenile pilocytic astrocytoma. The postoperative course was uneventful. No
recurrence has been observed during the follow-up period of more than 6
years. This case study shows that initial excision may be appropriate for
some low-grade focal lesions in the midbrain when the histological diagnosis
and consent have been obtained. Copyright 2006 S. Karger AG, Basel.
Publication Types:
PMID: 16902345 [PubMed - indexed for MEDLINE]
-
| 40: Pediatr Neurosurg.
2006;42(5):304-7. |
|
-
Osteochondroma of the cervical spine extending multiple
segments with cord compression.
Moon
KS, Lee
JK, Kim
YS, Kwak
HJ, Joo
SP, Kim
IY, Kim
JH, Kim
SH.
Department of Neurosurgery, Chonnam National University Hospital and Medical
School, Gwangju, Korea.
Involvement of the cervical spinal cord by a solitary osteochondroma is
rare. We describe a case of cervical osteochondroma extending from C5 to C7
in a 16-year-old male. The tumor, arising from the inner aspect of the C6
spinous process, projected longitudinally into the spinal canal and
compressed the spinal cord; this caused clinical symptoms associated with
myelopathy and radiculopathy. Total excision of the tumor by C5-C7
hemilaminectomy resulted in a good functional recovery. Copyright 2006 S.
Karger AG, Basel.
Publication Types:
PMID: 16902343 [PubMed - indexed for MEDLINE]
-
| 41: Pediatr Neurosurg.
2006;42(5):299-303. |
|
-
Unusual clinical and MRI features of a cerebellopontine
angle medulloepithelioma. Case report and review of literature.
Syal
R, |
Volume 5, Number 43 - 25 October 2006