Cytopathologic features of pituitary carcinoma with
cervical vertebral bone metastasis: a case report.
Ceyhan
K, Yagmurlu
B, Dogan
BE, Erdogan
N, Bulut
S, Erekul
S.
Division of Clinical Cytology, Department of Pathology, School of Medicine,
University of Ankara, Turkey. korayceyhan@yahoo.com
BACKGROUND: Pituitary carcinomas are extremely rare tumors of the
adenohypophysis. The presence of craniospinal and/or systemic extracranial
metastases is the only reliable criterion for the diagnosis of pituitary
carcinoma. To date, only 2 cases have been reported correctly by fine needle
aspiration biopsy (FNAB). We present an additional case of pituitary
carcinoma with FNAB features. CASE: A 60-year-old woman presented with
clinical features of Cushing's disease and a pituitary tumor. She underwent
transsphenoidal resection of the tumor. The initial diagnosis was an
adrenocorticotrophic hormone (ACTH)-producing invasive pituitary adenoma.
The patient presented again with neck pain 6 years after the operation.
Magnetic resonance imaging revealed metastatic tumor masses at the level of
C5-C6 of the cervical vertebrae. Intraoperative fine needle aspiration and
incomplete excision of metastatic tumors were performed. Cytologically,
tumor cells were composed of a combination of loose groups and single cells.
Neoplastic cells had a relatively monotonous appearance and displayed
characteristic neuroendocrine tumor features. Immunocytochemistry from cell
block sections revealed AE1/ AE3, synaptophysin chromogranin A and ACTH
positivity in the tumor cells. CONCLUSION: Pituitary carcinoma with
extracranial systemic metastases demonstrates typical neuroendocrine
features on fine needle aspiration. In the differential diagnosis,
metastatic neuroendocrine carcinomas should be kept in mind. In the absence
of sufficient clinical data, these 2 entities cannot be distinguished
correctly through the cytologic features.
Publication Types:
PMID: 16610696 [PubMed - indexed for MEDLINE]
| 2: Cancer.
2006 Mar 15;106(6):1372-81. |
|
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Interstitial 125I radiosurgery of supratentorial de novo
WHO Grade 2 astrocytoma and oligoastrocytoma in adults: long-term results
and prognostic factors.
Kreth
FW, Faist
M, Grau
S, Ostertag
CB.
Department of Neurosurgery, Grosshadern Clinic, Ludwig-Maximilians-University,
Marchioninistrasse 15, 81377 Munich, Germany. fkreth@med.uni-muenchen.de
BACKGROUND: Detailed long-term outcome data are not available for adult
patients with World Health Organization (WHO) Grade 2 astrocytoma or
oligoastrocytoma. METHODS: A previously published short-term data set of 239
adult patients with circumscribed de novo supratentorial astrocytoma (187
patients) and oligoastrocytoma (52 patients) treated with interstitial
iodine-125 ((125)I) radiosurgery as primary treatment (1979-1992) was
revisited. Survival, progression-free survival, functionally independent
survival, postrecurrence survival, and time to malignant transformation were
estimated with the Kaplan-Meier method. Prognostic factors were obtained
from the Cox multivariate proportional hazards model. RESULTS: Five-, 10-,
and 15-year survival was 56%, 37%, and 26%, respectively (median follow-up,
10.3 yrs). Progression-free survival was 45%, 21%, and 14%, respectively.
The corresponding malignant transformation rates were 33%, 54%, and 67%. No
leveling off of the Kaplan-Meier curves could be observed for any of the
chosen endpoints. Age > 50 years, a tumor volume > 20 mL, and/or a
Karnofsky score < or = 80 were associated with decreased survival or
progression-free survival. Age > 35 years and/or a tumor volume > 20
mL increased risk of malignant transformation. Prognostic factors determined
subsets of patients with 10-year survival ranging from as low as 6% to as
high as 55% and progression-free survival ranging 1-31%. CONCLUSIONS:
Long-term tumor stabilization is rare. As outcome is mainly determined by
treatment-independent factors, minimization of any treatment-related risk
must be considered essential. (c) 2006 American Cancer Society.
PMID: 16470609 [PubMed - indexed for MEDLINE]
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Congenital glioblastoma multiforme with abnormal
vascularity presenting as intracranial hemorrhage in prenatal ultrasound.
Sell
M, Huber-Schumacher
S, van
Landeghem FK.
Institute of Pathology, Vivantes Klinikum Neukolln, Rudower Strasse 48,
12351, Berlin, Germany, manfredsell@web.de.
BACKGROUND: A rare case of a congenital brain neoplasm with intratumoral
massive hemorrhage suggested by prenatal ultrasound examination in a 32-week
gestational age male fetus is reported. The child died shortly after birth
due to cardiorespiratory insufficiency. METHODS: Autopsy disclosed a large
well-delimited tumor with a sponge-like appearance due to high
vascularization, which involved nearly the whole left cerebral hemisphere
and led to marked hydrocephalus by secondary aqueductal stenosis.
Histological and immunohistochemical examination confirmed the diagnosis of
a malignant glioma with features of a glioblastoma multiforme (GBM) matching
well with previous findings in primary pediatric GBMs. FINDINGS: The present
case demonstrates that malignant congenital neoplasms should be considered
in the differential diagnosis of fetal intracranial hemorrhage.
PMID: 16673148 [PubMed - as supplied by publisher]
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Genomic alterations in human malignant glioma cells
associate with the cell resistance to the combination treatment with tumor
necrosis factor-related apoptosis-inducing ligand and chemotherapy.
Li
YC, Tzeng
CC, Song
JH, Tsia
FJ, Hsieh
LJ, Liao
SJ, Tsai
CH, Van
Meir EG, Hao
C, Lin
CC.
Authors' Affiliations: Department of Biomedical Sciences, Chung Shan Medical
University.
PURPOSE: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is
currently under clinical development as a cancer therapeutic agent. Many
human malignant glioma cells, however, are resistant to TRAIL treatment. We,
therefore, investigated the genomic alterations in TRAIL-resistant malignant
glioma cells. EXPERIMENTAL DESIGN: Seven glioma cell lines and two primary
cultures were first analyzed for their sensitivity to TRAIL and chemotherapy
and then examined for the genomic alterations in key TRAIL apoptotic genes
by comparative genomic hybridization (CGH), G-banding/spectral karyotyping,
and fluorescence in situ hybridization (FISH). RESULTS: CGH detected loss of
the chromosomal regions that contain the following genes: 8p12-p23 (DR4 and
DR5), 2q33-34 (caspase-8), 11q13.3 (FADD), 22q11.2 (Bid), and 12q24.1-q24.3
(Smac/DIABLO) in TRAIL-resistant cell lines. Spectral karyotyping showed
numerical and structural aberrations involving the chromosomal regions
harboring these genes. A combination of G-banding/spectral karyotyping and
FISH further defined the loss or gain of gene copy of these genes and
further showed the simultaneous loss of one copy of DR4/DR5, caspase-8, Bid,
and Smac in two near-triploid cell lines that were resistant to the
combination treatment with TRAIL and chemotherapy. Loss of the caspase-8
locus was also detected in a primary culture in correlation with the culture
resistance to the combined TRAIL and chemotherapy treatment. CONCLUSIONS:
The study identifies chromosomal alterations in TRAIL apoptotic genes in the
glioma cells that are resistant to the treatment with TRAIL and
chemotherapy. These genetic alterations could be used to predict the
responsiveness of malignant gliomas to TRAIL-based therapies in clinical
treatment of the tumors.
PMID: 16675563 [PubMed - in process]
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Inhibition of vascular endothelial growth factor (VEGF)-A
causes a paradoxical increase in tumor blood flow and up-regulation of VEGF-D.
Moffat
BA, Chen
M, Kariaapper
MS, Hamstra
DA, Hall
DE, Stojanovska
J, Johnson
TD, Blaivas
M, Kumar
M, Chenevert
TL, Rehemtulla
A, Ross
BD.
Department of Radiology, Center for Molecular Imaging, University of
Michigan Medical School, Ann Arbor, Michigan 48109-0503, USA.
PURPOSE: Vascular endothelial growth factor (VEGF)-A is an important
mediator of angiogenesis in almost all solid tumors. The aim of this study
was to evaluate the effect of VEGF-A expression on tumor growth, perfusion,
and chemotherapeutic efficacy in orthotopic 9L gliosarcomas. EXPERIMENTAL
DESIGN: Stable 9L cell lines underexpressing and overexpressing VEGF-A were
generated. Anatomic, susceptibility contrast, and continuous arterial
spin-labeling magnetic resonance imaging were used to quantify the volume,
blood volume, and blood flow of tumors orthotopically grown from these and
wild-type 9L cells. Histologic, immunohistochemical, and quantitative
reverse transcription-PCR analyses were also done on excised tumors.
Finally, the effects of carmustine chemotherapy were also evaluated.
RESULTS: Orthotopic tumors underexpressing VEGF-A had slower growth rates
(increased median survival), greater blood flow, vessel density, and VEGF-D
expression, but no statistical difference in blood volume and
chemotherapeutic sensitivity, compared with tumors with wild-type levels of
VEGF-A. Tumors overexpressing VEGF-A had faster growth rates, greater blood
volume, vessel density, and blood flow but no statistical difference in VEGF-D
expression and chemotherapeutic sensitivity compared with wild-type VEGF-A-expressing
tumors. CONCLUSION: Blood volume and blood flow are independent and
different biomarkers of tumor perfusion. Therefore, both should be measured
when characterizing the efficacy of antiangiogenic therapies.
Underexpression of VEGF-A does not result in complete inhibition of
angiogenesis. Moreover, these tumors have a different perfusion phenotype,
suggesting that angiogenesis is mediated by an alternative pathway. The
results indicate that VEGF-D is a plausible alternative mediator of this
angiogenesis.
PMID: 16533777 [PubMed - indexed for MEDLINE]
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Hypofractionated high-dose irradiation for the treatment
of malignant astrocytomas using simultaneous integrated boost technique by
IMRT.
Iuchi
T, Hatano
K, Narita
Y, Kodama
T, Yamaki
T, Osato
K.
Division of Neurological Surgery, Chiba Cancer Center, Chiba, Japan.
PURPOSE: We evaluated the clinical significance of hypofractionated
high-dose irradiation using simultaneous integrated boost technique with
intensity-modulated radiation therapy (IMRT) for the treatment of malignant
astrocytomas (MAs). METHODS AND MATERIALS: Twenty-five patients with MAs
were treated by IMRT. Three layered planning target volumes (PTVs) were
contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was
the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of
perifocal edema. Irradiation was performed in 8 fractions, and only the dose
for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for
PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared
with 60 MA patients treated by conventional external beam irradiation (EBI).
RESULTS: The progression-free survival of patients in the IMRT group was
significantly longer than that in the EBI group (p < 0.0001). No distant
failure was observed in both groups. In the IMRT group, dissemination was
the most frequent cause of death (70%). The overall survival of patients in
the IMRT group was better than that in the EBI group (p = 0.043).
CONCLUSIONS: Our regimen of IMRT contributed to the control of both the
regional and infiltrating tumors, resulting in better survival of patients.
PMID: 16580493 [PubMed - indexed for MEDLINE]
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Response of asymptomatic brain metastases from small-cell
lung cancer to systemic first-line chemotherapy.
Seute
T, Leffers
P, Wilmink
JT, ten
Velde GP, Twijnstra
A.
Department of Neurology, University Hospital Maastricht, Maastricht, The
Netherlands. tatseute@yahoo.co.uk
PURPOSE: The purpose of this study was to investigate the radiologic
response of asymptomatic brain metastases (BM) from small-cell lung cancer
(SCLC) to first-line systemic chemotherapy. PATIENTS AND METHODS: From 1990
to 2003, 181 consecutive patients with SCLC were enrolled onto this study.
Patients were examined by a neurologist on a regular basis. Magnetic
resonance imaging (MRI) of the brain was performed routinely before (at
diagnosis of SCLC) and after first-line systemic chemotherapy. Patients were
treated with combination chemotherapy consisting of cyclophosphamide,
doxorubicin, and etoposide. Clinically manifest BM were treated with
whole-brain radiotherapy (WBRT). The response rate (RR) of BM was assessed
by changes in the size or the number of enhanced lesions on MRI using
standard criteria. RESULTS: Synchronous asymptomatic BM were found in 24
SCLC patients (13%). In six (27%) of the 22 assessable patients, the
asymptomatic BM responded to systemic chemotherapy. A systemic response was
found in 16 patients (73%). All patients became symptomatic during
follow-up. The symptom-free survival did not differ between cranial
responders and cranial nonresponders. CONCLUSION: The RR of asymptomatic BM
from SCLC to systemic chemotherapy is 27% and evidently lower than the
systemic RR. Future studies should focus on the possible beneficial effect
of WBRT for patients with asymptomatic synchronous BM.
PMID: 16648509 [PubMed - in process]
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Autophagic cell death of malignant glioma cells induced
by a conditionally replicating adenovirus.
Ito
H, Aoki
H, Kuhnel
F, Kondo
Y, Kubicka
S, Wirth
T, Iwado
E, Iwamaru
A, Fujiwara
K, Hess
KR, Lang
FF, Sawaya
R, Kondo
S.
Department of Neurosurgery, University of Texas M. D. Anderson Cancer
Center, Houston, TX 77030, USA.
BACKGROUND: Conditionally replicating adenoviruses (CRAds) can be engineered
to replicate selectively in cancer cells and cause cancer-specific cell
lysis; thus they are considered a promising cancer therapy. METHODS: To
elucidate the mechanisms by which CRAds induce cancer-specific cell death,
we infected normal human fibroblasts (MRC5, telomerase negative), human
malignant glioma (U373-MG and U87-MG), human cervical cancer (HeLa), and
human prostate cancer (PC3) cells (all telomerase positive) with CRAds
regulated by the human telomerase reverse transcriptase promoter (hTERT-Ad)
or control nonreplicating adenoviruses (Ad-GFP). Nonapoptotic autophagy was
assessed in Ad-GFP- and hTERT-Ad-infected cells by examining cell
morphology, the development of acidic vesicular organelles, and the
conversion of microtubule-associated protein 1 light chain 3 from the
cytoplasmic form to the autophagosome membrane form; signaling via mammalian
target of rapamycin (mTOR), an autophagy-associated molecule, was monitored
by western blot analysis. We also compared the growth of subcutaneous
gliomas in nude mice that were treated by intratumoral injection with Ad-GFP
or hTERT-Ad. Survival of athymic mice carrying intracranial gliomas treated
by intratumoral injection with Ad-GFP or hTERT-Ad was compared by using the
Kaplan-Meier method and the Cox-Mantel log-rank analysis. All statistical
tests were two-sided. RESULTS: hTERT-Ad induced tumor-specific autophagic
cell death in tumor cells and in subcutaneous gliomas. hTERT-Ad-induced
autophagy was associated with hTERT-Ad infection kinetics. The mTOR
signaling pathway was suppressed in tumor cells and in subcutaneous gliomas
treated with hTERT-Ad compared with GFP-Ad or no treatment as shown by
reduced phosphorylation of mTOR's downstream target p70S6 kinase (p70S6K).
hTERT-Ad treatment of mice (n = 7) slowed growth of subcutaneous gliomas
(mean tumor volume = 39 mm3, 95% confidence interval [CI] = 23 to 54 mm3)
compared with GFP-Ad treatment (n = 7) (mean tumor volume = 200 mm3, 95% CI
= 149 to 251 mm3) at day 7 (volume difference = 161 mm3, 95% CI = 126 to 197
mm3; P < .001). Mice carrying intracranial tumors that were treated with
three intratumoral injections of hTERT-Ad survived longer (53 days) than
after treatment with GFP-Ad (29 days) (seven mice per group, difference = 24
days, 95% CI = 20 to 28 days; P < .001). CONCLUSIONS: hTERT-Ad may kill
telomerase-positive cancer cells by inducing autophagic cell death.
PMID: 16670388 [PubMed - in process]
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A Case of Relapsing Glioblastoma Multiforme Responding to
Vinorelbine.
Biassoni
V, Casanova
M, Spreafico
F, Gandola
L, Massimino
M.
Department of Pediatric, Istituto Nazionale per lo Studio e la Cura dei
Tumori, 20133, Milan, Italy, acinorev26@virgilio.it.
Childhood malignant gliomas are rare and their clinical behavior is almost
as aggressive as in adults: they resist treatment, progress rapidly and
often spread. Therapeutic strategies at relapse deserve an experimental
approach, since none of the conventional-dose treatments have demonstrated a
clear superiority over the others and no randomized trials have proved that
high-dose chemotherapy is better than conventional treatment.Vinorelbine is
a semi-synthetic vinca alkaloid with an in vitro and in vivo experimentally
proven broad spectrum of activity, including against malignant brain
glioma.We report our experience with a 19-year-old girl with glioblastoma
multiforme (GBM) of the deep temporal region recurring 6 months after
completing an intensive treatment that included preradiation chemotherapy
(chemotherapy as a preradiation "sandwich" phase) with a
myeloablative course of thiotepa, tumor bed radiotherapy and postradiation
maintenance chemotherapy. The GBM proved fully responsive to intravenous
vinorelbine, with a subsequent progression-free interval lasting more than
24 months. This case report suggests that vinorelbine is effective against
high-grade pediatric glioma and, since this evidence has only one precedent
in the literature (and given the generally poor prognosis for this tumor),
even this single success seems worth reporting.
PMID: 16670944 [PubMed - as supplied by publisher]
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In vitro and in vivo potentiating the cytotoxic effect of
radiation on human U251 gliomas by the c-Met antisense oligodeoxynucleotides.
Sheng-Hua
C, Zhi-An
Z, Xian-Hou
Y, Zhi-Qiang
L, Pu-Cha
J.
Department of Neurosurgery, Affiliated Third People's Hospital, Medical
College of Shanghai Jiaotong University, Shanghai, 201900, China,
shenghuachu@126.com.
C-Met, a receptor tyrosine kinase, and its ligand, hepatocyte growth factor
(HGF), are critical in cellular proliferation, motility, and invasion, and
are known to be overexpressed in gliomas, which are related to the repair of
damaged DNA. In this study, we investigated both in vitro and in vivo
whether inhibition of the c-Met gene by antisense oligonucleotides (ODNs)
enhances the cytotoxic effect of radiation on human U251 gliomas. A volume
of 100 nM of c-Met antisense ODNs inhibited the level of mRNA by more than
95% and reduced the protein expression by about 70%. Treatment of human U251
glioma cells with 100 nM of c-Met antisense ODNs significantly enhanced the
radiation-induced cell kill compared to control cells, and cells treated
with nonsense ODNs. When the glioma cells were implanted in the cisterna
magna of nude mice followed by treatment with c-Met antisense ODNs, the
survival time of the nude mice was markedly prolonged compared to that of
the untreated group (P < 0.001, logrank test). In addition, the
combination of antisense ODNs and irradiation extended the survival time of
the glioma-bearing nude mice much longer than could be achieved with
radiation alone (P < 0.0001, logrank test). These results suggest that
inhibition of c-Met can be expected to serve as a novel potentiator for
radiation therapy in human U251 gliomas.
PMID: 16648987 [PubMed - as supplied by publisher]
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Suberoylanilide hydroxamic acid is effective in
preclinical studies of medulloblastoma.
Spiller
SE, Ravanpay
AC, Hahn
AW, Olson
JM.
Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA,
98109, USA.
PURPOSE: Suberoylanilide hydroxamic acid (SAHA) has been studied in adult
solid and hematologic malignancies. However, little information has been
reported on the effects of SAHA on central nervous system (CNS) tumors
including medulloblastoma, the most common malignant brain tumor in
children. We investigated SAHA in preclinical medulloblastoma models to
determine its anti-cancer efficacy as well as its ability to affect
intracranial lesions when administered systemically. EXPERIMENTAL DESIGN AND
RESULTS: Tissue culture studies were performed treating primary human
fibroblasts, established medulloblastoma cell lines, and primary human
medulloblastoma tumors with SAHA. At 10 microM concentration, SAHA had
little effect on normal fibroblasts but caused >90% apoptosis in cultured
medulloblastoma cells. Primary medulloblastomas from patients were sensitive
to SAHA compared to vehicle alone in ex vivo studies. In athymic mice with
medulloblastoma xenograft tumors, oral SAHA resulted in apoptosis of tumor
tissue and significantly slowed tumor growth. In the ND2:Smo transgenic
mouse medulloblastoma model, SAHA treatment caused significant apoptosis in
these cerebellar tumors. CONCLUSIONS: SAHA effectively induces cell death in
established medulloblastoma cell lines, human patient primary tumor
cultures, medulloblastoma xenografts and intracranial spontaneous
medulloblastomas. Fibroblasts in culture and mice treated with SAHA did not
reveal prohibitive toxicity profiles. These findings support the advancement
of SAHA to pediatric clinical trials.
PMID: 16645722 [PubMed - as supplied by publisher]
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Gene expression profiles of
1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant
C6 rat glioma cells.
Nakagawa
T, Kubota
T, Ido
K, Sakuma
T, Matsuda
K.
Faculty of Medical Sciences, Department of Neurosurgery, Univeristy of
Fukui, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, 910-1193, Fukui, Japan,
tnkgw@fmsrsa.fukui-med.ac.jp.
Chemotherapy in itself is suspected to cause the development or selection of
drug-resistant tumor cells, which have more aggressive phenotypes. The
authors investigated the differential changes of gene expression in the
1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU)-resistant
subline of the C6 rat glioma (C6AR2), which was established from C6 rat
glioma cells by exposure to ACNU in vitro. The resistance to ACNU of C6AR2
was confirmed by MTS assay. The increased expression of O
(6)-methylguanine-DNA methyltransferase in C6AR2 cells was shown using
RT-PCR. C6AR2 cells displayed a higher proliferative activity relative to C6
cells. Analysis with cDNA array showed that 19 genes were transcriptionally
up-regulated and 16 genes down-regulated in C6AR2 cells compared to C6
cells. They belonged to various functional classes of genes beside the
drug-resistant system. Among them, the down-regulation of several genes in
C6AR2 cells, including c-kit, pleiotrophin, platelet-derived growth factor
receptor-alpha, peripheral myelin protein-22 and NG2 chondroitin sulfate
proteoglycan, which are expressed originally in developmental glial linages,
were verified using semi-quantitative RT-PCR. In addition, the gene
expression of astroglial intermediate filament proteins, including GFAP,
vimentin and nestin, were decreased in C6AR2 cells relative to C6 cells in
semi-quantitative RT-PCR and immunocytochemistry. These findings may
represent an undifferentiated state of ACNU-resistant glioma cells and a
more aggressive phenotype in recurrent tumors following chemotherapy.
PMID: 16645721 [PubMed - as supplied by publisher]
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Glioblastoma multiforme of the pineal region.
Amini
A, Schmidt
RH, Salzman
KL, Chin
SS, Couldwell
WT.
Department of Neurosurgery, University of Utah School of Medicine, Suite
3B409, 30 North 1900 East, Salt Lake City, UT, 84132-2303, USA,
william.couldwell@hsc.utah.edu.
Glioblastoma multiforme (GBMs) tumors are exceedingly rare tumors in the
pineal region. We present three cases in which patients presented with a
pineal/posterior third ventricular region mass and review all the previously
reported cases in the literature. Pineal region GBM seems to be a very
aggressive tumor with a high rate of leptomeningeal and ependymal metastatic
disease. Patients usually present with signs and symptoms of hydrocephalus
and Parinaud's syndrome. The clinical and radiological characteristics of
pineal GBM do not differentiate it from other malignancies of this region,
thus surgical biopsy is generally required for definitive diagnosis.
Glioblastoma should be considered in the differential diagnosis of the
pineal region tumors, especially when evidence of leptomeningeal or
ependymal metastatic disease is present.
PMID: 16645719 [PubMed - as supplied by publisher]
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Maintenance treatment with interferon-gamma and low-dose
cyclophosphamide for pediatric high-grade glioma.
Wolff
JE, Wagner
S, Reinert
C, Gnekow
A, Kortmann
RD, Kuhl
J, Van
Gool SW.
Department of Pediatrics, MD Anderson Cancer Center, Unit 87, University of
Texas, 1515 Holcombe Blvd, Houston, TX , 77030, USA.
BACKGROUND: The prognosis of high-grade glioma in children is poor. PURPOSE:
Interferon-gamma may increase the immune surveillance of glioma cells.
Earlier clinical evidence had shown that low dose cyclophosphamide (CPM)
increased immune response. METHODS: After induction treatment with
simultaneous radiation and chemotherapy, patients were treated with
individually increasing interferon-gamma (IFN-gamma) doses starting from 25
microg/m(2)/d s.c. increasing up to a maximum of 175 microg/m(2)/d within 7
weeks. Cyclophosphamide was given at 300 mg/m(2) i.v. every 21 days. Forty
pediatric glioma patients were enrolled (median age: 8.5 year, male: n =
22). Tumor locations included cerebral cortex (n = 8), basal ganglia (n =
4), brainstem (n = 24), cerebellum (n = 3), spinal cord (n = 1). Histologies
were GBM (n = 14), AA (n = 14), LGG (n = 2, diffuse intrinsic pontine glioma).
There was grade IV toxicity for thrombocytopenia (10%) and leucopenia
(2.5%), grade III toxicity for central nervous (2.5%) and hepatic (5%) side
effects, no toxic death. The observation time of the six surviving patients
was: 1.2, 1.9, 4.2, 4.4, 4.6 and 4.7 years respectively. The median overall
survival (1 year) was not significantly different from a historical control
group (0.8 years). The survival of pontine gliomas appeared even inferior
when compared to the previous protocol (n.s.). CONCLUSION: Maintenance
treatment with IFN-gamma and low dose CPM has no sufficient beneficial
effect for the treatment of high-grade glioma.
PMID: 16645718 [PubMed - as supplied by publisher]
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Radical surgery after chemotherapy: a new therapeutic
strategy to envision in grade II glioma.
Duffau
H, Taillandier
L, Capelle
L.
Department of Neurosurgery, UMR-S678, Inserm/UPMC, Hopital Salpetriere,
47-83 Bd de l'hopital, 75651, Paris, Cedex 13, France, hugues.duffau@psl.ap-hop-paris.fr.
While surgery is proned in low-grade glioma (LGG), the invasion of
functional areas frequently prevents a complete resection. We report the
first case of a patient operated on for a left frontal LGG, diagnosed
because of seizures, with partial resection due to an invasion of the
controlateral hemisphere. Chemotherapy enabled a regression of this
controlateral extension. Postchemotherapy surgery performed with
intraoperative functional mapping then allowed a complete resection, without
sequelae. The patient has a normal socio-professional life, with no seizure.
No other treatment was given. There was no recurrence, with a follow-up of 2
years since the second surgery (3.5 years since the first symptom). We
propose a new therapeutic strategy in unresectable LGG, with preoperative
chemotherapy, to make a radical surgery possible in a second step, while
preserving the quality of life.
PMID: 16645710 [PubMed - as supplied by publisher]
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Ultrasonic bone curettage for optic canal unroofing and
anterior clinoidectomy. Technical note.
Chang
HS, Joko
M, Song
JS, Ito
K, Inoue
T, Nakagawa
H.
Department of Neurological Surgery, Aichi Medical University, Aichi, Japan.
chang@aichi-med-u.ac.jp
Extradural unroofing of the optic canal and subsequent mobilization of the
optic nerve is a useful technique in the surgical treatment of parasellar
tumors; however, the drilling procedure itself is associated with the risk
of optic nerve damage. A safer technique would certainly be beneficial. The
ultrasonic bone curette is a device developed in Japan for safer bone
removal. Its use in intradural anterior clinoidectomy and opening of the
internal auditory meatus has been reported before. In this article the
authors describe their experience in using this device for extradural
unroofing of the optic canal in patients with parasellar tumors. Between
March 2002 and November 2004, the aforementioned technique was used in the
treatment of eight patients with parasellar tumors. After undertaking a
frontotemporal craniotomy and orbital osteotomy, an ultrasonic bone curette
was used to unroof the optic canal via an epidural approach; in five cases
anterior clinoidectomy was added subsequently. Using an ultrasonic bone
curette, unroofing of the optic canal was completed safely and required much
less expertise than that required for standard drilling. The mortality and
major morbidity rates were 0%. The visual function outcome was satisfactory,
with the overall visual status improving in all seven patients in whom this
symptom was present preoperatively. The ultrasonic bone curette makes the
unroofing of the optic canal safer and easier, possibly improving the visual
outcome of patients undergoing surgery for parasellar tumors.
PMID: 16619669 [PubMed - indexed for MEDLINE]
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Cranial surgery with an expanded compact intraoperative
magnetic resonance imager. Technical note.
Schulder
M, Salas
S, Brimacombe
M, Fine
P, Catrambone
J, Maniker
AH, Carmel
PW.
Department of Neurological Surgery, New Jersey Medical School, Newark, New
Jersey 07103-2499, USA. schulder@umdnj.edu
In this article the authors report the implementation of an expanded compact
intraoperative magnetic resonance (iMR) imager that is designed to overcome
significant limitations of an earlier unit. The PoleStar N20 iMR imager has
a stronger magnetic field than its predecessor (0.15 tesla compared with
0.12 tesla), a wider gap between magnet poles, and an ergonomically improved
gantry design. The additional time needed in the operating room (OR) for use
of iMR imaging and the number of sessions per patient were recorded.
Stereotactic accuracy of the integrated navigational tool was assessed using
a water-covered phantom. Of the 55 patients who have undergone surgery in
the PoleStar N20 device, diagnoses included glioma in 13, meningioma in 12,
pituitary adenoma in nine, other skull base lesions in seven, and
miscellaneous other diagnoses. The extra time required for use of the system
averaged 1.1 hours (range 0.5-2 hours). Imaging sessions averaged 2.3 per
surgery (range one-six sessions). Measurement of stereotactic accuracy
revealed that T1-weighted images were the most accurate. Thinner slices
yielded measurably greater accuracy, although this was of questionable
clinical significance (all sequences < or =4 mm had a mean error of <
or = 1.8 mm). The position of the phantom in the center compared with the
periphery of the magnetic field did not affect accuracy (mean error 0.9 mm
for each). The PoleStar N20 appears to make intraoperative neuroimaging with
a low-field-strength magnet much more practical than it was with the
first-generation device. Greater ease of positioning resulted in a decrease
in added time in the OR and encouraged a larger number of imaging sessions.
Publication Types:
PMID: 16619667 [PubMed - indexed for MEDLINE]
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Dural plasmacytoma revealing multiple myeloma. Case
report.
Haegelen
C, Riffaud
L, Bernard
M, Carsin-Nicol
B, Morandi
X.
Department of Neurosurgery, Pontchaillou Hospital, Rennes, France.
The authors describe the case of a 72-year-old woman with dural plasmacytoma
revealing an immunoglobulin (Ig) G-kappa multiple myeloma (MM). She
presented with headaches and left hemiparesis. Magnetic resonance imaging
demonstrated a right frontal extraaxial lesion arising from the dura mater,
and biological studies revealed hypercalcemia, hyperproteinemia, and a serum
gamma globulin peak. A diagnosis of IgG-kappa MM was based on microscopic
examination and immunohistochemical analysis of the dural plasmacytoma as
well as on signs of systemic myeloma after surgery. The patient died 3 years
after the first symptoms of MM despite systemic chemotherapy and no
recurrence of the dural plasmacytoma. Myelomatous involvement of the dura
mater is a rare occurrence given that only three cases have been reported to
date. Nevertheless, this pathological entity should be differentiated from
solitary dural plasmacytoma (SDP) because the prognosis is radically
different. Progression seems to be correlated with systemic disease in
contrast to the long-term survival associated with SDP. Careful systemic
evaluation should be made in such a presentation to rule out MM, which would
require different management and has a different prognosis.
Publication Types:
PMID: 16619666 [PubMed - indexed for MEDLINE]
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Dissociated expressive and receptive language functions
on magnetoencephalography, functional magnetic resonance imaging, and
amobarbital studies. Case report and review of the literature.
Kamada
K, Takeuchi
F, Kuriki
S, Todo
T, Morita
A, Sawamura
Y.
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo,
Japan. kamady-k@umin.ac.jp
Dissociated language functions are largely invalidated by standard
techniques such as the amobarbital test and cortical stimulation. Language
studies in which magnetoencephalography (MEG) and functional magnetic
resonance (fMR) imaging are used to record data while the patient performs
lexicosemantic tasks have enabled researchers to perform independent brain
mapping for temporal and frontal language functions (MEG is used for
temporal and fMR imaging for frontal functions). In this case report, the
authors describe a right-handed patient in whom a right-sided insular glioma
was diagnosed. The patient had a right-lateralized receptive language area,
but expressive language function was identified in the left hemisphere on
fMR imaging- and MEG-based mapping. Examinations were performed in 20
right-handed patients with low-grade gliomas (control group) for careful
comparison with and interpretation of this patient's results. In these
tests, all patients were asked to generate verbs related to acoustically
presented nouns (verb generation) for fMR imaging, and to categorize as
abstract or concrete a set of visually presented words consisting of three
Japanese letters for fMR imaging and MEG. The most prominent display of fMR
imaging activation by the verb-generation task was observed in the left
inferior and middle frontal gyri in all participants, including the patient
presented here. Estimated dipoles identified with the abstract/concrete
categorization task were concentrated in the superior temporal and
supramarginal gyri in the left hemisphere in all control patients. In this
patient, however, the right superior temporal region demonstrated
significantly stronger activations on MEG and fMR imaging with the
abstract/concrete categorization task. Suspected dissociation of the
language functions was successfully mapped with these two imaging modalities
and was validated by the modified amobarbital test and the postoperative
neurological status. The authors describe detailed functional profiles
obtained in this patient and review the cases of four previously described
patients in whom dissociated language functions were found.
Publication Types:
PMID: 16619665 [PubMed - indexed for MEDLINE]
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Preoperative endovascular brain mapping for
intraoperative volumetric image guidance: preliminary concept and
feasibility in animal models.
Mericle
RA, Richter
EO, Eskioglu
E, Watkins
C, Prokai
L, Batich
C, Santra
S.
Department of Neurological Surgery, University of Florida McKnight Brain
Institute, Gainesville, Florida, USA. Robert.mericle@Vanderbilt.edu
OBJECT: The authors describe a novel concept for brain mapping in which an
endovascular approach is used, and they demonstrate its feasibility in
animal models. The purpose of endovascular brain mapping is to delineate
clearly the nonfunctional brain parenchyma when a craniotomy is performed
for resection. The nonfunctional brain will be stained with sharp visual
margins, differentiating it from the functional, nonstained brain. The
authors list four essential criteria for developing an ideal endovascular
mapping agent, and they describe seven potential approaches for
accomplishing a successful endovascular brain map. METHODS: Four Sprague-Dawley
rats and one New Zealand white rabbit were used to determine initial
feasibility of the procedure. The animals were anesthetized, and the
internal carotid artery was catheterized. Four potential brain mapping
agents were infused into the right hemisphere of the five animals.
Afterward, the brains were removed and each was analyzed both grossly and
histologically. Fluorescein and FD&C Green No. 3 provided good visual
clarity and margins, but required blood-brain barrier (BBB) manipulation.
Tantalum particles enabled avoidance of BBB manipulation, but provided
inadequate visual clarity, probably because of their size. A Sudan black
"cocktail" provided excellent clarity and margins despite
remaining in the brain capillaries. CONCLUSIONS: This is a novel application
of the endovascular approach, and has broad potential for clinical
neurosurgical brain mapping. The animal models in this study establish the
feasibility of the procedure. However, further study is required to
demonstrate safety, minimize toxicity, investigate stain durability, and
improve the characteristics of potential mapping agents. The authors are
planning to conduct future studies for identification of mapping agents that
do not require BBB manipulation or vascular occlusion.
PMID: 16619661 [PubMed - indexed for MEDLINE]
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The impact of genotype on outcome in oligodendroglioma:
validation of the loss of chromosome arm 1p as an important factor in
clinical decision making.
Kanner
AA, Staugaitis
SM, Castilla
EA, Chernova
O, Prayson
RA, Vogelbaum
MA, Stevens
G, Peereboom
D, Suh
J, Lee
SY, Tubbs
RR, Barnett
GH.
The Brain Tumor Institute, The Cleveland Clinic Taussig Cancer Center, The
Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
OBJECT: Oligodendrogliomas are rare primary brain tumors. They comprise
approximately 5 to 33% of all glial tumors but differ from astrocytomas by
being associated with a more favorable prognosis, making their correct
identification important. Allelic loss of chromosome arms 1p and 19q is
found in a substantial subpopulation of tumors with an oligodendroglioma
phenotype. Anaplastic oligodendrogliomas with allelic loss of 1p have been
associated with chemosensitivity and a longer patient survival period.
METHODS: Oligodendroglial neoplasms were studied using fluorescence in situ
hybridization of formalin-fixed, paraffin-embedded tissue specimens;
reference and target probe sets were used to map the telomeric regions of 1p
and 19q. The results were correlated with the clinical characteristics of
patients treated at our institution between 1993 and 2003. Data obtained in
96 patients were analyzed. This included 63 patients (65.6%) with World
Health Organization (WHO) Grade II oligodendroglioma, 22 (23%) with Grade
III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma. Analysis
of 1p in patients with pure oligodendroglioma revealed a loss of 1p in 42
patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%)
there was concordance for combined loss or retention of both 1p and 19q (p
< 0.0001). Patients with oligodendroglioma in whom a loss of 1p was
present fared significantly better, and this outcome was unrelated to the
treatment modality or WHO grade, compared with patients in whom 1p was
intact (p < 0.05). CONCLUSIONS: To the authors' knowledge, this study
includes the largest published series of WHO Grade II oligodendroglioma and
1p analysis. The results suggest that the association between long-term
survival and 1p loss in oligodendroglioma is unrelated to treatment. The
authors of further prospective studies may better determine the true value
of the allelic loss of 1p and its implication for clinical decision making.
PMID: 16619658 [PubMed - indexed for MEDLINE]
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Intrinsic brainstem epidermoid cyst. Case report and
review of the literature.
Recinos
PF, Roonprapunt
C, Jallo
GI.
Department of Neurosurgery, The Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA.
Brainstem epidermoid cysts are rare lesions, with only 18 reported cases in
the literature and only five purely intrinsic epidermoid cysts within this
group. The authors present the case of a 3-year-old girl with a history of
chronic headaches, progressive diplopia, and relapsing and remitting mild
right hemiparesis who was found to harbor an intrinsic brainstem epidermoid
cyst at the pontomedullary junction. Initial working diagnoses included
intrinsic brainstem astrocytoma and cavernoma. After tumor enlargement and
progressive symptoms, a diffusion-weighted (DW) magnetic resonance (MR)
imaging sequence was performed and a definitive diagnosis of an intrinsic
brainstem epidermoid cyst was made in the patient. The patient underwent a
suboccipital craniotomy and complete resection of the cyst with the aid of
intraoperative neurophysiological monitoring. Three years after the
operation, the patient is neurologically intact and no evidence of tumor
recurrence has been found. The rarity of brainstem epidermoid cysts can make
their diagnosis difficult; thus a DW MR imaging sequence of the brain is a
useful diagnostic modality. Intrinsic brainstem epidermoid cysts can be
removed safely, in a manner similar to that used for the surgical treatment
of focal tumors.
Publication Types:
PMID: 16619643 [PubMed - indexed for MEDLINE]
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Spontaneous involution of a large pineal region
hemorrhagic cyst in an infant. Case report.
Nimmagadda
A, Sandberg
DI, Ragheb
J.
Department of Neurological Surgery, University of Miami Miller School of
Medicine, Florida, USA.
The authors report the case of a newborn presenting at birth with
macrocephaly and a large pineal region hemorrhagic cyst without neurological
deficit. No neurosurgical intervention was performed, and subsequent imaging
studies demonstrated complete involution of the cyst.
Publication Types:
PMID: 16619640 [PubMed - indexed for MEDLINE]
-
-
Prolonged but reversible migraine-like episodes long
after cranial irradiation.
Partap
S, Walker
M, Longstreth
WT Jr, Spence
AM.
Division of Pediatric Neurology, Children's Hospital and Regional Medical
Center, University of Washington, Seattle, WA, USA.
The authors describe three patients with prolonged but reversible episodes
of severe headaches and focal neurologic deficits developing years after
irradiation for cranial neoplasms. Despite extensive evaluations, etiology
of episodes in these three and eight other previously reported patients
remains undetermined. Whether they all have the same condition is uncertain.
Although some had cortical gadolinium enhancement on MRI, all 11 patients
returned to baseline over hours to weeks.
Publication Types:
PMID: 16606929 [PubMed - indexed for MEDLINE]
-
-
Mature teratoma of the lateral ventricle in adulthood:
preoperative CT and MRI diagnosis.
Lai
PH, Hsu
SS, Lo
YS, Ho
JT.
Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung,
Taiwan. phlai@isca.vghks.gov.tw
Publication Types:
PMID: 16606903 [PubMed - indexed for MEDLINE]
| 26: Oncogene.
2006 May 1; [Epub ahead of print] |
|
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Identification of expressed genes characterizing
long-term survival in malignant glioma patients.
Yamanaka
R, Arao
T, Yajima
N, Tsuchiya
N, Homma
J, Tanaka
R, Sano
M, Oide
A, Sekijima
M, Nishio
K.
1Department of Neurosurgery, Brain Research Institute, Niigata University,
Niigata City, Japan.
Better understanding of the underlying biology of malignant gliomas is
critical for the development of early detection strategies and new
therapeutics. This study aimed to define genes associated with survival. We
investigated whether genes coupled with a class prediction model could be
used to define subgroups of high-grade gliomas in a more objective manner
than standard pathology. RNAs from 29 malignant gliomas were analysed using
Agilent microarrays. We identified 21 genes whose expression was most
strongly and consistently related to patient survival based on univariate
proportional hazards models. In six out of 10 genes, changes in gene
expression were validated by quantitative real-time PCR. After adjusting for
clinical covariates based on a multivariate analysis, we finally obtained a
statistical significance level for DDR1 (discoidin domain receptor family,
member 1), DYRK3 (dual-specificity tyrosine-(Y)-phosphorylation-regulated
kinase 3) and KSP37 (Ksp37 protein). In independent samples, it was
confirmed that DDR1 protein expression was also correlated to the prognosis
of glioma patients detected by immunohistochemical staining. Furthermore, we
analysed the efficacy of the short interfering RNA (siRNA)-mediated
inhibition of DDR1 mRNA synthesis in glioma cell lines. Cell proliferation
and invasion were significantly suppressed by siRNA against DDR1. Thus, DDR1
can be a novel molecular target of therapy as well as an important
predictive marker for survival in patients with glioma. Our method was
effective at classifying high-grade gliomas objectively, and provided a more
accurate predictor of prognosis than histological grading.Oncogene advance
online publication, 1 May 2006; doi:10.1038/sj.onc.1209585.
PMID: 16652150 [PubMed - as supplied by publisher]
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Volume 5, Number 19 - 8 May 2006