| 1: Cancer. 2005 Nov 1; [Epub
ahead of print] |
|
-
Topotecan as a radiosensitizer in the treatment of
children with malignant diffuse brainstem gliomas.
Bernier-Chastagner
V, Grill
J, Doz
F, Bracard
S, Gentet
JC, Marie-Cardine
A, Luporsi
E, Margueritte
G, Lejars
O, Laithier
V, Mechinaud
F, Millot
F, Kalifa
C, Chastagner
P.
Radiotherapy Service, Centre Alexis Vautrin, Vandoeuvre-les-Nancy, France.
BACKGROUND: The current Phase II study was conducted to evaluate the
survival and toxicity observed in children with newly diagnosed brainstem
gliomas who were treated with the daily radiotherapy with topotecan used as
a radiosensitizer. METHODS: Eligible patients were those ages 3-18 years
with previously untreated tumors arising in the pons diagnosed within the
previous 6 months. Histologic confirmation was not mandatory provided that
the clinical and magnetic resonance imaging findings were typical for a
diffusely infiltrating brainstem lesion. Treatment was comprised of a 6-week
course of topotecan administered intravenously at a dose of 0.4 mg/m(2)/day
over 30 minutes within 1 hour before irradiation. Radiotherapy was comprised
of a once-daily treatment of 1.8 grays (Gy) per fraction to a total dose of
54 Gy. RESULTS: Thirty-two patients were included in the current study
between August 2000 and October 2002. All patients completed the combined
treatment in accordance with the treatment design. Only partial responses
were observed, occurring in 40% of the patients. The 9-month and 12-month
survival rates were 34.4% +/- 8% and 25.5% +/- 8%, respectively. The median
duration of survival for these 32 patients was 8.3 months. An intratumoral
cystic/necrotic change was observed in five patients, with clinical
impairment noted in two patients. One intratumoral hemorrhage occurred
during radiotherapy, and was associated with transitory neurologic
impairment. CONCLUSIONS: The findings of the current study regarding newly
diagnosed brainstem glioma patients treated with topotecan given as a
radiosensitizing agent did not reproduce the encouraging results obtained in
preclinical studies. Therefore, the concomitant combination of topotecan and
radiotherapy at this schedule and these doses cannot be recommended for the
treatment of patients with brainstem gliomas. Cancer 2005. (c) 2005 American
Cancer Society.
PMID: 16265674 [PubMed - as supplied by publisher]
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| 2: Cancer Res. 2005 Nov
1;65(21):9982-90. |
|
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Myxoma virus is a novel oncolytic virus with significant
antitumor activity against experimental human gliomas.
Lun
X, Yang
W, Alain
T, Shi
ZQ, Muzik
H, Barrett
JW, McFadden
G, Bell
J, Hamilton
MG, Senger
DL, Forsyth
PA.
Department of Oncology, University of Calgary, and Tom Baker Cancer Centre,
Calgary, Alberta, Canada.
Myxoma virus, a poxvirus previously considered rabbit specific, can
replicate productively in a variety of human tumor cells in culture. The
purpose of this study was to determine if there was efficacy or toxicities
of this oncolytic virus against experimental models of human malignant
gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In
vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully
permissive for myxoma virus replication and killed by infection. In vivo,
intracerebral (i.c.) myxoma virus inoculation was well tolerated and
produced only minimal focal inflammatory changes at the site of viral
inoculation. U87 and U251 orthotopic xenograft models were used to assess
myxoma virus efficacy in vivo. A single intratumoral injection of myxoma
virus dramatically prolonged median survival compared with treatment with
UV-inactivated myxoma virus. Median survival was not reached in myxoma
virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251;
P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma
virus-treated animals (12 of 13, 92%) were alive and apparently
"cured" when the experiment was finished (>130 days).
Interestingly, we found a selective and long-lived myxoma virus infection in
gliomas in vivo. This is the first demonstration of the oncolytic activity
of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of
the rabbit host, its capacity to be genetically modified, its ability to
produce a long-lived infection in human tumor cells, and the lack of
preexisting antibodies in the human population suggest that myxoma virus may
be an attractive oncolytic agent against human malignant glioma.
PMID: 16267023 [PubMed - in process]
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| 3: Cancer Res. 2005 Nov
1;65(21):9843-50. |
|
-
Cerebrospinal fluid proteomic analysis reveals
dysregulation of methionine aminopeptidase-2 expression in human and mouse
neurofibromatosis 1-associated glioma.
Dasgupta
B, Yi
Y, Hegedus
B, Weber
JD, Gutmann
DH.
Department of Neurology, Washington University School of Medicine, St.
Louis, Missouri 63110, USA.
Individuals affected with the neurofibromatosis 1 (NF1) tumor predisposition
syndrome are prone to the development of multiple nervous system tumors,
including optic pathway gliomas (OPG). The NF1 tumor suppressor gene
product, neurofibromin, functions as a Ras GTPase-activating protein, and
has been proposed to regulate cell growth by inhibiting Ras activity. Recent
studies from our laboratory have shown that neurofibromin also regulates the
mammalian target of rapamycin activity in a Ras-dependent fashion, and that
the rapamycin-mediated mammalian target of rapamycin inhibition ameliorates
the Nf1-/- astrocyte growth advantage. Moreover, Nf1-deficient astrocytes
exhibit increased protein translation. As part of a larger effort to
identify protein markers for NF1-associated astrocytomas that could be
exploited for therapeutic drug design, we did an objective proteomic
analysis of the cerebrospinal fluid from genetically engineered Nf1 mice
with optic glioma. One of the proteins found to be increased in the
cerebrospinal fluid of OPG-bearing mice was the eukaryotic initiation
factor-2alpha binding protein, methionine aminopeptidase 2 (MetAP2). In this
study, we show that Nf1 mouse OPGs and NF1-associated human astrocytic
tumors, but not sporadic pilocytic or other low-grade astrocytomas,
specifically expressed high levels of MetAP2. In addition, we show that
Nf1-deficient astrocytes overexpress MetAP2 in vitro and in vivo, and that
treatment with the MetAP2 inhibitor fumagillin significantly reduces Nf1-/-
astrocyte proliferation in vitro. These observations suggest that MetAP2 is
regulated by neurofibromin, and that MetAP2 inhibitors could be potentially
employed to treat NF1-associated tumor proliferation.
PMID: 16267007 [PubMed - in process]
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| 4: J
Clin Oncol. 2005 Nov 1;23(31):7951-7. |
|
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{beta}-Catenin Status Predicts a Favorable Outcome in
Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group
Brain Tumour Committee.
Ellison
DW, Onilude
OE, Lindsey
JC, Lusher
ME, Weston
CL, Taylor
RE, Pearson
AD, Clifford
SC.
Northern Institute for Cancer Research, Paul O'Gorman Building, University
of Newcastle, Newcastle-upon-Tyne, NE2 4HH, United Kingdom; e-mail:
D.W.Ellison@ncl.ac.uk.
PURPOSE Identifying pathobiological correlates of clinical behavior or
therapeutic response currently represents a key challenge for
medulloblastoma research. Nuclear accumulation of the beta-catenin protein
is associated with activation of the Wnt/Wg signaling pathway, and mutations
affecting components of this pathway have been reported in approximately 15%
of sporadic medulloblastomas. We tested the hypothesis that nuclear
immunoreactivity for beta-catenin is a prognostic marker in medulloblastoma,
and assessed the relationship between nuclear beta-catenin immunoreactivity
and mutations of CTNNB1 and APC. PATIENTS AND METHODS Medulloblastomas from
children entered onto the International Society for Pediatric Oncology
(SIOP)/United Kingdom Children's Cancer Study Group (UKCCSG) PNET3 trial (n
= 109) were examined for beta-catenin immunoreactivity, and where tissue was
available, evidence of CTNNB1 and APC mutations. The results were correlated
with clinicopathologic variables, principally outcome. Results Children with
medulloblastomas that showed a nucleopositive beta-catenin immunophenotype
(27 of 109; 25%) had significantly better overall (OS) and event-free (EFS)
survivals than children with tumors that showed either
membranous/cytoplasmic beta-catenin immunoreactivity or no immunoreactivity
(P = .0015 and P = .0026, respectively). For beta-catenin nucleopositive and
nucleonegative medulloblastomas, 5-year OS was 92.3% (95% CI, 82% to 100%)
versus 65.3% (95% CI, 54.8 to 75.7%), and 5-year EFS was 88.9% (95% CI, 77%
to 100%) versus 59.5% (95% CI, 48.8 to 70.2%), respectively. Mutations in
CTNNB1 were found exclusively among medulloblastomas that demonstrated
nuclear beta-catenin immunoreactivity, but no evidence of APC mutation was
found in these cases. All children with beta-catenin nucleopositive large
cell/anaplastic medulloblastomas and beta-catenin nucleopositive
medulloblastomas presenting with metastatic disease are alive at least 5
years postdiagnosis. CONCLUSION Nuclear accumulation of beta-catenin appears
to be a marker of favorable outcome in medulloblastoma, and should be
investigated further in large group-wide trials.
PMID: 16258095 [PubMed - in process]
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| 5: J
Clin Oncol. 2005 Oct 1;23(28):7152-60. |
|
-
Intellectual and functional outcome of children 3 years
old or younger who have CNS malignancies.
Fouladi
M, Gilger
E, Kocak
M, Wallace
D, Buchanan
G, Reeves
C, Robbins
N, Merchant
T, Kun
LE, Khan
R, Gajjar
A, Mulhern
R.
Department of Hematology-Oncology, St Jude Children's Research Hospital, 332
N Lauderdale, Memphis, TN 38105-2794, USA. maryam.fouladi@stjude.org
PURPOSE: To evaluate the impact of tumor location, clinical parameters, and
therapy on neurocognitive, neuroendocrine, and functional outcomes in
children < or = 3 years old with intracranial CNS malignancies who
survived at least 2 years after diagnosis. PATIENTS AND METHODS: Records
were retrospectively reviewed for 194 children diagnosed from 1985 to 1999
at St Jude Children's Research Hospital (Memphis, TN). RESULTS: The median
age at diagnosis was 1.8 years (range, 0.1 to 3.5 years). Median follow-up
was 7.64 years (2.0 to 19.4 years). Tumors were infratentorial (102),
diencephalic (53), and hemispheric (39); 47% required ventriculoperitoneal
shunts, 36% developed seizure disorders, and 20% developed severe
ototoxicity. Therapy included no radiation therapy (RT) in 57 (30%), local
RT in 87 (45%), and craniospinal irradiation (CSI) in 49 (25%). Overall
survival at 10 years was 78 +/- 4%. In a longitudinal analysis of 126
patients with at least one neurocognitive evaluation (NE), the mean rate of
intelligence quotient (IQ) change for patients who received CSI (-1.34
points per year) and local RT (-0.51 points per year) was significantly
different from the no RT group (0.91 points per year; P = .005 and P = .036,
respectively). Patients with hemispheric tumors had a significantly greater
IQ decline (-1.52 points per year) than those with midline tumors (0.59
points per year; P = .038). Among those with NE > or = 5 years after
diagnosis, 71.4% of CSI recipients compared with 23% of local RT recipients
had IQ less than 70 (P = .021). Patients undergoing CSI were more likely to
develop endocrinopathies (P < .0001) and to require special education (P
= .0007). CONCLUSION: In young children with CNS tumors, CSI and hemispheric
location are associated with significant declines in IQ scores.
PMID: 16192599 [PubMed - indexed for MEDLINE]
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| 6: J
Natl Cancer Inst. 2005 Nov 2;97(21):1589-600. |
|
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Expression of transcription factor E2F1 and telomerase in
glioblastomas: mechanistic linkage and prognostic significance.
Alonso
MM, Fueyo
J, Shay
JW, Aldape
KD, Jiang
H, Lee
OH, Johnson
DG, Xu
J, Kondo
Y, Kanzawa
T, Kyo
S, Bekele
BN, Zhou
X, Nigro
J, McDonald
JM, Yung
WK, Gomez-Manzano
C.
Department of Neuro-Oncology, University of Texas M.D. Anderson Cancer
Center, Houston, TX 77030, USA.
BACKGROUND: Several tumor suppressor pathways have been identified as
modulators of telomerase function. We examined the functional role of the
retinoblastoma-E2F1 pathway in regulating telomerase activity in malignant
gliomas. METHODS: Adenovirus vectors were used to transfer cDNAs into human
glioblastoma and sarcoma cells. Telomerase activity was assessed with a
telomere repeat amplification protocol. Promoter activity in cancer cells
was assessed with promoter-luciferase reporter constructs. Promoter binding
was assessed with the chromatin immunoprecipitation (ChIP) assay. We
isolated astrocytes from E2F1 transgenic mice and normal mice for in vivo
studies. We evaluated the expression of E2F1 and hTERT (the catalytic
subunit of human telomerase) mRNAs by reverse transcriptase-polymerase chain
reaction and proteins in human glioblastoma samples by immunoblot analysis.
Associations between survival among 61 glioblastoma multiforme patients and
expression of E2F1 and hTERT mRNA and protein were examined with
Kaplan-Meier analysis, the log-rank test, and Cox proportional hazards
regression models. All statistical tests were two-sided. RESULTS: Ectopic
E2F1 expression increased hTERT promoter activity in cancer cells. We
detected an interaction between E2F1 protein and the hTERT promoter.
Transgenic E2F1 astrocytes contained functional telomerase protein. E2F1
mRNA expression and hTERT mRNA expression were statistically significantly
correlated in human glioblastoma specimens (R = .8; P < .001). Longer
median survival was statistically significantly associated with lower E2F1
mRNA expression in tumors (103.6 weeks) rather than with higher expression
(46.1 weeks) (difference = 57.5 weeks; 95% confidence interval [CI] = 14.7
to 159.7; log-rank P = .002). E2F1 mRNA was the only factor that was
statistically significantly associated with overall survival in a
multivariable model (P = .04). Among 27 patients with glioblastoma
multiforme samples, the expression of E2F1 protein was statistically
significantly associated with survival (log-rank P < .001). CONCLUSIONS:
E2F1 may participate in telomerase activity regulation in malignant glioma
cells. Its expression appears to be strongly associated with the survival of
patients with malignant brain tumors.
PMID: 16264179 [PubMed - in process]
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| 7: J
Neuropathol Exp Neurol. 2005 Oct;64(10):891-901. |
|
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Altered expression of immune defense genes in pilocytic
astrocytomas.
Huang
H, Hara
A, Homma
T, Yonekawa
Y, Ohgaki
H.
International Agency for Research on Cancer, Lyon, France, and Department of
Neurosurgery, University of Zurich, Zurich, Switzerland.
Pilocytic astrocytoma (WHO grade I) is a circumscribed, slowly growing,
benign astrocytoma that most frequently develops in the cerebellar
hemispheres and in midline structures and occurs predominantly in childhood
and adolescence. In contrast to diffusely infiltrating gliomas in adults
(e.g. grade II astrocytomas, oligodendrogliomas), survival of patients with
pilocytic astrocytoma is excellent after surgical intervention. To search
for potential molecular mechanisms underlying its benign biologic behavior,
we compared gene expression profiles of pilocytic astrocytomas (8 cases)
with those of normal cerebellum (4 cases), low-grade astrocytomas (WHO grade
II; 15 cases), and oligodendrogliomas (WHO grade II; 17 cases) by cDNA array
analysis. A number of immune system-related genes such as HLA-DRalpha,
HLA-DPB1, HLA-DQB1, IgG3, IgGK, FCER1G, A2M, FCRN, IFI-56K, and DAP12 were
upregulated in pilocytic astrocytomas relative to normal cerebellum, grade
II astrocytomas, and oligodendrogliomas. Genes expressed at higher levels in
pilocytic astrocytomas than in grade II astrocytomas and oligodendrogliomas
include HLA-DRalpha, HLA-DPA1, HLA-DPB1, HLA-DQB1, A2M, TIMP1, TIMP2,
CDKN1A, and SOCS3 and those expressed at lower levels include EGFR and
PDGFRA. Hierarchical clustering analysis using the entire set of 1176 genes
distinguished pilocytic astrocytomas from grade II astrocytomas and
oligodendrogliomas. Clustering analysis using selected subgroups of genes
based on their molecular functions revealed that immune system-related genes
(75 genes) or cell adhesion, migration, and angiogenesis-related genes (69
genes) showed similar power to the entire gene set for separation of
pilocytic astrocytomas from diffusely infiltrating low-grade gliomas.
Immunohistochemistry revealed that HLA-DRalpha is expressed diffusely in
neoplastic cells in pilocytic astrocytomas, whereas in oligodendrogliomas,
expression was limited to scattered reactive astrocytes. These results
suggest that gene expression profiles of pilocytic astrocytomas differ
significantly from those of diffusely infiltrating low-grade gliomas and
that their benign biologic behavior may be related to upregulation of immune
defense-associated genes.
PMID: 16215461 [PubMed - indexed for MEDLINE]
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| 8: J Neurosurg.
2005 Oct;103(4):702-6. |
|
Gliomatosis cerebri: quantitative proof of vessel
recruitment by cooptation instead of angiogenesis.
Bernsen
H, Van
der Laak J, Kusters
B, Van
der Ven A, Wesseling
P.
Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, The
Netherlands. h.bersen@cwz.nl
OBJECT: Gliomas are the most common primary brain tumors, many of which
(especially astrocytic and oligodendroglial neoplasms) are characterized by
diffuse infiltrative growth in the preexisting brain tissue. Gliomatosis
cerebri is a rare glial tumor and represents an extreme example of such
diffuse infiltrative growth. This growth pattern not only hampers curative
treatment but also allows for vessel cooptation rather than tumor
angiogenesis as a way of vessel recruitment by the tumor tissue. The goal of
this study was to establish the extent to which tumor angiogenesis occurs in
gliomatosis cerebri. METHODS: Computerized image analysis was performed to
assess quantitatively two microvascular parameters (vessel density and
diameter) in different areas of a brain harboring a gliomatosis cerebri.
These regions were the cerebral white and gray matter in which there was a
diffuse infiltrative tumor, cerebral white and gray matter in which there
was a more compact growth pattern of tumor cells, and normal cerebral white
and gray matter. In addition, the authors performed immunohistochemical
stainings for blood-brain barrier (BBB) characteristics (Glut-1 and PgP) on
samples obtained in these different areas. The results of the quantitative
analysis strongly indicated that in gliomatosis cerebri tumor, angiogenesis
was completely absent, a finding that is corroborated by the fact that the
microvasculature in gliomatosis cerebri persists in exhibiting
immunohistochemical characteristics of the BBB. CONCLUSIONS: The results of
this study may help resolve the difficulties in radiological detection and
delineation of the diffuse infiltrative part of glial brain tumors and put
the expectations for antiangiogenic treatment of such tumors into
perspective.
PMID: 16266053 [PubMed - in process]
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| 9: J Neurosurg.
2005 Sep;103(3 Suppl):277-81. |
|
Neonatal hypothalamic hamartoma: a differentiating
nonlethal hamartoblastoma.
Saxonhouse
MA, Yachnis
AT, Burchfield
DJ, Quisling
R, Sullivan
MP, Pincus
DW.
Division of Neonatology, Department of Pediatrics, Shands Children's
Hospital, University of Florida College of Medicine, Gainesville, Florida
32610-0296, USA. saxonma@peds.ufl.edu
The authors report on a patient with a large hypothalamic hamartoma with a
cleft lip and palate and seizures. Neuroimaging revealed a large extraaxial,
intradural mass in the prepontine and interpeduncular cisterns with
significant distortion of the brainstem. A stereotactic transfontanel needle
biopsy revealed a cellular lesion that contained immature-appearing
neuroepithelial cells consistent with prior descriptions of hypothalamic
hamartoblastoma. While having a low level of proliferation by Ki67 (MIB-1)
labeling, the lesion also contained evidence of neuronal maturation, with
many cells expressing neuronal nuclear antigen as observed during
immunohistochemical analysis. Further clinical evaluation revealed no other
significant congenital abnormalities, and the patient was discharged home.
Outpatient follow up has continued for 2 years and the patient has been
doing well, requiring no further treatment. This case illustrates that,
despite its immature and proliferative histological appearance, this rare
neonatal mass can be regarded as a "differentiating" hypothalamic
hamartoma and can have a favorable prognosis.
Publication Types:
PMID: 16238084 [PubMed - indexed for MEDLINE]
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| 10: J Neurosurg.
2005 Sep;103(3 Suppl):272-6. |
|
Intramedullary capillary hemangioma associated with
hydrocephalus in an infant.
Iannelli
A, Lupi
G, Castagna
M, Valleriani
A, Bacherini
F.
Department of Neurosurgery, University of Pisa, Italy.
a.iannelli@ao-pisa.toscana.it
This 3-month-old child presented with an enlarging head circumference
arising from communicating hydrocephalus with large subarachnoid spaces in
the posterior fossa. Neuroimaging performed to clarify the origin and
pathogenesis of the hydrocephalus revealed a vascular lesion within the
dorsal spinal cord. Insertion of a cerebrospinal fluid shunt and total
removal of the spinal tumor were performed successfully. Histological
examination of the medullar lesion demonstrated a capillary hemangioma.
Proposed mechanisms for increased intracranial pressure and spinal cord
lesions are presented. A spinal hemangioma in this age range associated with
hydrocephalus has not been reported previously, but spinal lesions must be
considered in the presence of hydrocephalus with no clear origin.
Publication Types:
PMID: 16238083 [PubMed - indexed for MEDLINE]
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| 11: J Neurosurg.
2005 Sep;103(3 Suppl):266-9. |
|
Noncommunicating spinal extradural arachnoid cyst causing
spinal cord compression in a child.
Liu
JK, Cole
CD, Sherr
GT, Kestle
JR, Walker
ML.
Department of Neurosurgery, Primary Children's Medical Center, University of
Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Extradural arachnoid cysts in the spine are relatively uncommon causes of
spinal cord compression in the pediatric population that are thought to
arise from congenital defects in the dura mater. Most reports describe such
cysts communicating with the intrathecal subarachnoid space through a small
defect in the dura. The authors describe the case of a child who presented
with spinal cord compression caused by a large spinal extradural arachnoid
cyst that did not communicate with the intradural subarachnoid space. An
11-year-old girl presented with urinary urgency, progressive lower-extremity
weakness, myelopathy, and severe gait ataxia. Magnetic resonance imaging of
the spine demonstrated a large extradural arachnoid cyst extending from T-8
to T-12. The patient underwent a thoracic laminoplasty for en bloc resection
of the spinal extradural arachnoid cyst. Intraoperatively, the dura was
intact and there was no evidence of communication into the intradural
subarachnoid space. Postoperatively, the patient's motor strength and
ambulation improved immediately, and no subsequent cerebrospinal fluid leak
occurred. Noncommunicating spinal extradural arachnoid cysts are extremely
rare lesions that can cause spinal cord compression in children. Because the
dura remains intact, they can be removed entirely without subsequent dural
repair. The authors review the literature and discuss the proposed
underlying mechanisms of formation of these arachnoid cysts.
Publication Types:
PMID: 16238081 [PubMed - indexed for MEDLINE]
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| 12: J Neurosurg.
2005 Sep;103(3 Suppl):253-9. |
|
Bobble-head doll syndrome successfully treated with an
endoscopic ventriculocystocisternostomy.
Hagebeuk
EE, Kloet
A, Grotenhuis
JA, Peeters
EA.
Department of Child Neurology, Medisch Centrum Haaglanden, Westeinde, The
Hague. e.e.hagebeuk@amc.uva.nl
The bobble-head doll syndrome (BHDS) is characterized by a back-and-forth
movement of the head with a frequency of 2 to 3 Hz, which increases during
walking and excitement and decreases during concentration. The head
movements are accompanied by macrocephaly, ocular disturbances, psychomotor
retardation, and sometimes endocrine dysfunction. The BHDS is frequently
associated with a suprasellar arachnoid cyst. The authors present the case
of a 4-year-old patient with BHDS; an endoscopic cystoventriculostomy was
performed by fenestrating a cyst in the suprasellar region. After wide
fenestration of the cyst wall that was protruding and obstructing the
foramen of Monro, the cyst was entered with the endoscope and a small,
natural, valvelike communication of the cyst with the basal prepontine
cistern was seen close to the basilar artery. This communication was widened
by balloon dilation. After completion of the ventriculocystocisternostomy,
the cyst collapsed and the obstruction of the aqueduct was resolved. In view
of the source mechanism and cerebrospinal fluid dynamics of the suprasellar
arachnoid cyst, a ventriculocystocisternostomy is an important treatment
option for BHDS arising from a suprasellar cyst. Three years after
treatment, the head bobbing had resolved completely and psychomotor
development was improving. Delay of diagnosis and treatment of this
condition can cause permanent neurological dysfunction and psychomotor
retardation. The authors recommend early ventriculocystocisternostomy as a
physiologically based treatment for BHDS originating from a suprasellar
cyst.
Publication Types:
PMID: 16238079 [PubMed - indexed for MEDLINE]
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| 13: J Neurosurg.
2005 Sep;103(3 Suppl):247-52. |
|
Persistent hydrocephalus after early surgical management
of posterior fossa tumors in children: is routine preoperative endoscopic
third ventriculostomy justified?
Morelli
D, Pirotte
B, Lubansu
A, Detemmerman
D, Aeby
A, Fricx
C, Berre
J, David
P, Brotchi
J.
Department of Neurosurgery, Erasme Hospital, Universite, Libre de Bruxelles,
Brussels, Belgium.
OBJECT: The authors evaluate the incidence of persistent hydrocephalus after
early surgical management of pediatric posterior fossa tumors and the
indicators for routine preoperative endoscopic third ventriculostomy (ETV).
METHODS: Between 1989 and 2004, 160 children with a posterior fossa tumor
were treated at Erasme Hospital in Brussels, Belgium. Hydrocephalus was
present at admission in 114 of the patients. Thirty-one patients had severe
hydrocephalus (Evans index [EI] > 0.4). Twenty-four of these and the 83
patients with mild hydrocephalus (EI between 0.3 and 0.4) were treated with
early posterior fossa surgery (Group 1; 107 patients). In this group, 93
patients underwent a total or subtotal tumor resection associated with
external ventricular drainage (Group 1A), and 14 underwent a stereotactic
biopsy associated with an ETV (Group 1B). The 53 remaining patients
underwent elective posterior fossa surgery (Group 2). Early tumor resection
(Group 1A) resolved hydrocephalus in 85 (91%) of 93 patients, whereas an ETV
resolved intracranial hypertension in 11 patients (Group 1B). In Group 1,
persistent hydrocephalus affected 11 (10%) of 107 patients, seven of whom
had symptoms and were treated (three with shunts and four with ETVs).
Persistent hydrocephalus was more frequent in children with severe
preoperative hydrocephalus (p = 0.002) and with medulloblastomas (p =
0.0154). A total of 22 technically successful ETV procedures were performed.
The ETV success rate for controlling hydrocephalus was 81% (18 of 22) and
the rate of severe complications was 9% (two of 22). CONCLUSIONS: An ETV is
an efficient procedure for controlling hydrocephalus associated with
posterior fossa tumor. The authors confirm that a routine postoperative ETV
is indicated for treating persistent hydrocephalus. For preventing it,
however, they recommend early posterior fossa surgery whenever possible. The
low rate of persistent hydrocephalus does not justify adopting routine
preoperative ETVs.
PMID: 16238078 [PubMed - indexed for MEDLINE]
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| 14: J Neurosurg.
2005 Sep;103(3):448-54. |
|
Predictors of diabetes insipidus after transsphenoidal
surgery: a review of 881 patients.
Nemergut
EC, Zuo
Z, Jane
JA Jr, Laws
ER Jr.
Department of Anesthesiology, University of Virginia Health System,
Charlottesville, Virginia 22908, USA. en3x@virginia.edu
OBJECT: Diabetes insipidus (DI) is a common complication of transsphenoidal
surgery. The purpose of this study was to elucidate patient- and
surgery-specific risk factors for DI. METHODS: The perioperative records of
881 patients who had undergone transsphenoidal microsurgery at the authors'
institution between January 1995 and June 2001 were reviewed. Among 857
patients without preoperative DI, the overall incidence of immediate
postoperative DI was 18.3%, with 12.4% of patients requiring treatment with
desmopressin at some point during their hospitalization. Persistent DI
requiring long-term treatment with desmopressin was noted in 2% of all
patients. An observable intraoperative cerebrospinal fluid (CSF) leak was
strongly associated with an increased incidence of both transient (33.3%)
and persistent (4.4%) DI. Craniopharyngioma and Rathke cleft cyst (RCC) were
also associated with an increased incidence of transient and persistent DI,
whereas repeated operation was not. Among patients with pituitary adenomas,
those with Cushing's disease had an increased risk of transient (22.2%), but
not persistent, DI. Patients with a microadenoma were more likely to suffer
transient DI than those harboring a macroadenoma (21.6 compared with 14.3%)
but were not more likely to experience persistent DI. CONCLUSIONS: Diabetes
insipidus remains a common complication of transsphenoidal surgery; however,
it is most frequently transient in nature. Patients with an intraoperative
CSF leak, a microadenoma, a craniopharyngioma, or an RCC appear to have an
increased risk of transient DI. Risk factors for persistent DI include an
intraoperative CSF leak, a craniopharyngioma, or an RCC.
PMID: 16235676 [PubMed - indexed for MEDLINE]
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| 15: J
Nucl Med. 2005 Nov;46(11):1923-30. |
|
-
Evaluation of 76Br-FBAU as a PET Reporter Probe for
HSV1-tk Gene Expression Imaging Using Mouse Models of Human Glioma.
Cho
SY, Ravasi
L, Szajek
LP, Seidel
J, Green
MV, Fine
HA, Eckelman
WC.
NeuroOncology Branch, National Cancer Institute and National Institute of
Neurological Disorders and Stroke, National Institutes of Health, Bethesda,
Maryland.
The utility of 5-(76)Br-bromo-2'-fluoro-2'-deoxyuridine ((76)Br-FBAU), a
uracil analog, as a PET reporter probe for use with the herpes simplex virus
type 1 thymidine kinase (HSV1-tk) reporter gene system for gene expression
imaging was evaluated in vivo and in vitro using human and rat glioma cells.
METHODS: Human glioma cell lines U87 and U251 were transduced with
replication-defective adenovirus constitutively expressing HSV1-tk (Ad.TK)
or a control expressing green fluorescent protein (Ad.GFP). These cells were
incubated with (76)Br-FBAU for 20-120 min to determine the percentage of
total dose uptake. In vitro uptake of equimolar concentrations (1.8 x 10(-8)
mol/L) of (76)Br-FBAU and
2'-fluoro-2'-deoxy-5-iodouracil-beta-d-arabinofuranoside ((14)C-FIAU) was
also determined in RG2-TK rat glioma cells stably expressing HSV1-tk and in
control RG2 cells at 30-120 min. In vivo uptake of (76)Br-FBAU was
determined in subcutaneous U87 tumor intratumorally transduced with Ad.TK by
ex vivo biodistribution. Uptake in intracranial U87 tumors transduced with
Ad.TK expressing HSV1-tk was measured by brain autoradiography. In vivo PET
was performed on subcutaneous and intracranial U87 tumors transduced with
Ad.TK and on subcutaneous and intracranial stably expressing RG2-TK tumors.
RESULTS: U87 and U251 cells transduced with Ad.TK had significantly
increased uptake of (76)Br-FBAU compared with cells transduced with Ad.GFP
over 20-120 min. In stably expressing cells at 120 min, (14)C-FIAU uptake in
RG2-TK tumor cells was 11.3 %ID (percentage injected dose) and in RG2
control cells was 1.7 %ID, and (76)Br-FBAU uptake in RG2-TK tumor cells was
14.2 %ID and in RG2 control cells was 1.5 %ID. Ex vivo biodistribution of
subcutaneous U87 tumors transduced with Ad.TK accumulated (76)Br-FBAU
significantly more than in the control Ad.GFP transduced tumor and normal
tissue, with the lowest uptake in brain. Autoradiography showed localized
uptake in intracranial U87 and U251 cells transduced with Ad.TK. PET image
analyses of mice with RG2-TK tumors resulted in an increased
tumor-to-background ratio of 13 and 26 from 2 to 6 h after injection,
respectively, in intracranial tumors. CONCLUSION: (76)Br-FBAU accumulates in
glioma cells constitutively expressing HSV1-tk by either adenoviral
transduction or in stably expressing cell lines both in vitro and in vivo.
(76)Br-FBAU shows promise as a PET reporter probe for use with the HSV1-tk
in vivo gene expression imaging system.
PMID: 16269608 [PubMed - in process]
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| 16: J
Nucl Med. 2005 Nov;46(11):1858-65. |
|
-
Evaluation of Pharmacokinetics of
4-Borono-2-18F-Fluoro-L-Phenylalanine for Boron Neutron Capture Therapy in a
Glioma-Bearing Rat Model with Hyperosmolar Blood-Brain Barrier Disruption.
Hsieh
CH, Chen
YF, Chen
FD, Hwang
JJ, Chen
JC, Liu
RS, Kai
JJ, Chang
CW, Wang
HE.
Institute of Radiological Sciences, National Yang-Ming University, Taipei,
Taiwan.
This study evaluated the pharmacokinetics and biodistribution of
4-borono-2-(18)F-fluoro-l-phenylalanine ((18)F-FBPA) after intracarotid
injection and with blood-brain barrier disruption (BBB-D) in F98
glioma-bearing F344 rats. The pharmacokinetics of l-p-boronophenylalanine
(BPA) and (18)F-FBPA following different administration routes were compared
to demonstrate the optimal delivery route and the time period for thermal
neutron irradiation. METHODS: F98 glioma-bearing rats were injected
intravenously or intracarotidly with (18)F-FBPA and BPA and with or without
mannitol-induced hyperosmotic BBB-D. The boron concentration and (18)F
radioactivity in tissues were determined by invasive (inductively coupled
plasma mass spectroscopy, gamma-counting) and noninvasive PET methods.
RESULTS: The biodistributions of (18)F-FBPA and BPA in F98 glioma-bearing
rats were similar after intracarotid administration with BBB-D. The
accumulation of BPA and (18)F-FBPA in brain tumor and the
tumor-to-ipsilateral brain ratios were the highest after intracarotid
injection with BBB-D, whereas the retention of boron drugs in contralateral
brains exhibited only nonsignificant differences compared with those after
intracarotid injection without BBB-D and intravenous injection. The high
boron concentration in brain tumor (76.6 mug/g) and the high
tumor-to-ipsilateral brain ratio (6.3) may afford enough radiation doses to
destroy the tumor cells while sparing the normal tissues in boron neutron
capture therapy. The pharmacokinetic parameters of k(el), k(12), k(21), and
V(1) for intracarotid injection of (18)F-FBPA with BBB-D derived from the
open 2-compartment model are 0.0206 +/- 0.0018 min(-1), 0.0260 +/- 0.0016
min(-1), 0.0039 +/- 0.0003 min(-1), and 3.1 +/- 0.1 mL, respectively. The
effect of BBB-D varied depending on the anesthetic agents used and the
anesthetic conditions. A smaller degree of BBB-D and, thus, lower boron
concentrations in tumor and ipsilateral brain were observed under isoflurane
anesthesia than under ketamine anesthesia. The k(12)/k(21) ratio may serve
as a good indication for evaluating the extent of BBB-D, tumor uptake, and
tumor-to-brain ratio after intracarotid injection of boron compounds.
CONCLUSION: Our findings provide important information for establishing an
optimal treatment protocol when intracarotid injection with BPA after BBB-D
is applied in clinical boron neutron capture therapy.
PMID: 16269600 [PubMed - in process]
-
| 17: Surg Neurol.
2005 Nov;64 Suppl 2:S82-8. |
|
-
An analysis of stereotactic biopsy of brain tumors and
nonneoplastic lesions: a prospective clinicopathologic study.
Heper
AO, Erden
E, Savas
A, Ceyhan
K, Erden
I, Akyar
S, Kanpolat
Y.
Department of Pathology, School of Medicine, Ankara University, Shhiye,
Ankara 06100, Turkey.
BACKGROUND: Appropriate management of progressive, unverified brain lesions
should be guided by conclusive pathological diagnosis. Stereotactic biopsy
(SB) is established as a less invasive surgical procedure that provides
diagnosis. In this prospective study, we analyzed the diagnostic
difficulties and risk of SB in the various brain mass lesions, the rate of
conclusive pathological diagnosis, and the rate of and the reasons for
discrepancy between the intraoperative smear results and conclusive paraffin
diagnosis. METHODS: Using computed tomography (CT) and/or magnetic resonance
imaging (MRI), 130 cases underwent SB procedure to assess intra-axial brain
mass lesions. A CT-MRI fusion and a multiplanar image processing
stereotactic program were used in cases who had lesions adjacent to the
neurovascular and critical areas. The intraoperative evaluations were made
with the smear preparations (SPs) of 1 or 2 biopsy specimens. The conclusive
diagnosis was achieved by paraffin preparations of the remainder of the
biopsies. The discrepancy between the smear results and the conclusive
diagnosis was analyzed. RESULTS: Conclusive histopathologic diagnosis was
achieved in 99.23% of the cases. A discrepancy between smear results and
conclusive diagnosis was detected in 6.98% of the conclusively diagnosed
cases. The major reasons for the discrepancy were necrosis and improper
quality of the preparations. There was no mortality, and hemorrhage-related
morbidity was observed in 1 case (0.7%). CONCLUSIONS: Necrosis and the
improper quality of the smear preparations (SPs) can cause difficulties in
establishing a histopathologic diagnosis in SB. Small tissue samples do not
decrease the diagnostic yield with the new stereotactic technologies used by
an experienced team consisting of a neurosurgeon, pathologist, and
radiologist.
PMID: 16256850 [PubMed - in process]
-
| 18: Surg Neurol.
2005 Nov;64 Suppl 2:S67-71. |
|
-
Evaluation of petrosal sinus patency with 3-dimensional
contrast-enhanced magnetic resonance venography in petroclival meningiomas
for surgical strategy.
Deda
H, Erden
I, Yagmurlu
B.
Department of Neurosurgery, Ankara University School of Medicine, Ankara
06100, Turkey.
BACKGROUND: The aim of this study was to perform a detailed anatomical
analysis of petroclival venous structures as well as their patencies with 3D
contrast-enhanced (CE) magnetic resonance venography (MRV) and to identify
the potential contribution of these data to the therapeutic approach.
METHODS: Ten patients (8 women and 2 men) with unilateral petroclival
meningioma were examined using 3D CE MRV in addition to conventional brain
protocol. Both coronal source and multiplanar reconstructed images were
evaluated for the anatomical orientation. Patency of the cavernous sinus,
superior petrosal sinus (SPS), and inferior petrosal sinus (IPS) was
assessed. RESULTS: All the patients had a unilateral meningioma (7 on the
right and 3 on the left) at the petroclival region. Both SPS and IPS were
visualized with adequate intraluminal contrast enhancement in 6 patients,
but IPS was absent in 3 on the lesion side, with a patent superior petrosal
sinus as the drainage route. One patient had a partially occluded SPS, with
IPS being the main course of cavernous sinus drainage. CONCLUSIONS: Cerebral
venous anatomy is a challenge to display with noninvasive methods because of
flow dynamics, and CE 3D imaging seems to be the modality of choice to
evaluate the variational anatomy and patency, which is essential in
petroclival meningiomas. Because the cavernous sinus drains into either IPS
or SPS, the patent sinus should be protected in surgery if there is tumoral
occlusion of the others.
PMID: 16256846 [PubMed - in process]
-
| 19: Surg Neurol.
2005 Nov;64S2:S58-S66. |
|
-
Changing treatment strategy of cavernous sinus
meningiomas: experience of a single institution.
Pamir
MN, Kilic
T, Bayrakli
F, Peker
S.
Institute of Neurological Sciences, Marmara University, PK 53 Maltepe,
Istanbul 81532, Turkey.
BACKGROUND: Oncological treatment of a neoplasm is more than surgical
removal of the tumor. Probably, this truth is the reason for the ongoing
discussion on cavernous sinus meningiomas in the last decade. Debate on
optimal management of cavernous sinus meningiomas aims to compare the
different treatment strategies: (a) radical surgical resection and (b)
conservative surgical resection complemented with radiosurgical treatment.
MATERIALS AND METHODS: Natural history of the change in the management
strategy of cavernous sinus meningiomas in our department before and after
GK facility became available in 1997 allowed us to compare the 2
aforementioned strategies. Before installation of a Leksell GK unit at the
hospital in 1997, the neurosurgical team at Marmara University Institute of
Neurological Sciences and Faculty of Medicine (Istanbul, Turkey) treated
patients with cavernous sinus meningioma using radical resection (radical
strategy, group A, 10 patients). After 1997, the same neurosurgical team
used understanding of surgical removal of the extracavernous sinus tumor
component with GK irradiation of the intracavernous part (conservative
strategy, group B, 12 patients). Another group of patients, who were treated
with GK as a first-step treatment, was analyzed (GK group, group C, 26
patients). RESULTS: At the end of the third year, more stable tumor volume
control was achieved in groups B and C; after the second year, an incline in
the tumor volume-time graph was detected. Group B resulted in less cranial
nerve-related complications; a certain degree of improvement in cranial
nerve deficits was observed. CONCLUSION: Comparing 2 different management
strategies for cavernous sinus meningiomas in the same hospital setting
using the same neurosurgical group, we conclude that extracavernous
resection followed by GK is as effective as radical surgery. Considering
cranial nerve complications and third-year tumor volume control achievement,
conservative approach yielded better results. Longer follow-up with larger
series is necessary.
PMID: 16256845 [PubMed - as supplied by publisher]
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Volume 4, Number 46 - 8 November 2005