| 1: Clin
Neuropathol. 2005 Jan-Feb;24(1):13-8. |
|
Ganglioside (GD2) expression and intermediary filaments
in astrocytic tumors.
Mennel HD, Lell B.
Department of Neuropathology, Medical Center of Pathology, Philipps
University, Marburg, Germany. mennelh@med.uni-marburg.de
The search of proliferation markers in astrocytic tumors that may serve as
targets for therapeutic interventions, is in full progress. Membrane-bound
signal transducers for growth factors are amongst the substances of
interest. Gangliosides are lipid-sugar compounds localized on the cell
membrane that are thought to modify pertinent signals and, therefore, may
influence a variety of functions in normal and pathologic conditions
including those that act upon tumor growth. Intracranial supratentorial
astrocytic gliomas of the adult represent a tumor group, that may be divided
into three grades of malignancy, the most anaplastic member being the
glioblastoma. A stepwise anaplasia is assumed and accompanied by genetic
events that are partly specific for these grades. In earlier investigations,
it had been shown that there is a tendency towards formation of more simple
members of the ganglioside family with ongoing malignancy of those tumors.
Yet, the results were only partly congruent and the correlation to tumor
grades rather loose. We, therefore, investigated the occurrence of triaose
gangliosides within these tumors in situ by immunohistochemistry. In this
paper, we corroborate our earlier observation that triaose gangliosides
preferentially occur within the cytoplasm of large protoplasmic and
gemistocytic astrocytes. The potency of the expression of GD2 is calculated
and plotted against the expression of two markers of intermediate glial
filaments, namely GFAP (glial fibrillary acid protein) and vimentine. A high
interdependence of the three compounds could be demonstrated by correlation
analysis. Thus, the conclusion must be drawn that the correlation of
ganglioside patterns to the proliferation of astrocytic tumors is as poor as
that of GFAP or vimentin expression, respectively.
PMID: 15696779 [PubMed - indexed for MEDLINE]
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| 2: Int
J Cancer. 2005 Feb 18; [Epub ahead of print] |
|
-
Recombinant adeno-associated virus (rAAV) expressing
TFPI-2 inhibits invasion, angiogenesis and tumor growth in a human
glioblastoma cell line.
Yanamandra N, Kondraganti S, Gondi CS, Gujrati M, Olivero WC, Dinh DH,
Rao JS.
Program of Cancer Biology, Department of Biomedical and Therapeutic
Sciences, University of Illinois College of Medicine, Peoria, IL, USA.
Recombinant adeno-associated viruses (rAAV) have become the vector of choice
for many gene therapy protocols. rAAVs have a number of attractive features
including long-term transgene expression and the ability to transduce both
dividing and non-dividing cells. We have shown previously the anti-cancer
role of tissue factor pathway inhibitor-2 (TFPI-2), a matrix-associated
serine protease inhibitor, in human glioblastomas. As a result of our
present study, in which 0.8-kb fragment of human TFPI-2 was cloned into the
adeno-associated viral vectors (rAAA-TFPI-2), rAAV-TFPI-2 infection of SNB19
cells significantly increased TFPI-2 as determined by Western blotting. As
assessed by spheroid and Matrigel assays, infection of SNB19 cells with
rAAV-TFPI-2 significantly reduced migration and invasion in a dose-dependent
manner. Tumor spheroids infected with rAAV-TFPI-2 and co-cultured with fetal
rat brain aggregates did not invade rat brain aggregates, whereas 90-95% of
the mock and AAV-CMV infected cells invaded rat brain aggregates. In vitro
angiogenesis studies (tumor cells co-cultured with endothelial cells or
endothelial cells seeded on matrigel) showed reduction of capillary-like
structure formation in rAAV-TFPI-2-treated cells as compared to parental and
mock-transfected cells. In in vivo angiogenesis results demonstrated the
formation of microvessels in SNB19 parental cells and this formation was
inhibited when the SNB19 cells were infected with rAAV-TFPI-2. Further, we
observed a large reduction of tumor growth in SNB19 cells treated with
rAAV-TFPI-2 virus injected intracerebrally when compared to controls. Our
study demonstrates that rAAV-TFPI-2-mediated gene therapy offers a novel
tool for the treatment of brain tumors. (c) 2005 Wiley-Liss, Inc.
PMID: 15723303 [PubMed - as supplied by publisher]
| 3: J
Neurosurg. 2005 Jan;102 Suppl:180-4. |
|
Does gamma knife surgery stimulate cellular immune
response to metastatic brain tumors? A histopathological and
immunohistochemical study.
Szeifert GT, Salmon I, Rorive S, Massager N, Devriendt D, Simon S,
Brotchi J, Levivier M.
Department of Neurosurgery, Centre Gamma Knife, Hopital Academique Erasme,
Brussels, Belgium.
OBJECT: The aim of this study was to analyze the cellular immune response
and histopathological changes in secondary brain tumors after gamma knife
surgery (GKS). METHODS: Two hundred ten patients with cerebral metastases
underwent GKS. Seven patients underwent subsequent craniotomy for tumor
removal between 1 and 33 months after GKS. Four of these patients had one
tumor, two patients had two tumors, and one patient had three. Histological
and immunohistochemical investigations were performed. In addition to
routine H & E and Mallory trichrome staining, immunohistochemical
reactions were conducted to characterize the phenotypic nature of the cell
population contributing to the tissue immune response to neoplastic deposits
after radiosurgery. Light microscopy revealed an intensive lymphocytic
infiltration in the parenchyma and stroma of tumor samples obtained in
patients in whom surgery was performed over 6 months after GKS. Contrary to
this, extensive areas of tissue necrosis with either an absent or scanty
lymphoid population were observed in the poorly controlled neoplastic
specimens obtained in cases in which surgery was undertaken in patients less
than 6 months after GKS. Immunohistochemical characterization demonstrated
the predominance of CD3-positive T cells in the lymphoid infiltration.
CONCLUSIONS: Histopathological findings of the present study are consistent
with a cellular immune response of natural killer cells against metastatic
brain tumors, presumably stimulated by the ionizing energy of focused
radiation.
PMID: 15662806 [PubMed - indexed for MEDLINE]
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| 4: J
Neurosurg. 2005 Jan;102 Suppl:147-50. |
|
Gamma knife surgery for brain metastases in patients
harboring four or more lesions: survival and prognostic factors.
Nam TK, Lee JI, Jung YJ, Im YS, An HY, Nam DH, Park K, Kim JH.
Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, South Korea.
OBJECT: This study was performed to evaluate the role of gamma knife surgery
(GKS) in patients with a large number (four or more) of metastatic brain
lesions. METHODS: The authors retrospectively reviewed the outcome in 130
patients who underwent GKS for metastatic lesions. Eighty-four patients
presented with one to three lesions (Group A) and 46 presented with four or
more lesions (Group B). The overall median survival time after GKS was 35
weeks. The median survival time in Group A (48 weeks) was significantly
longer (p = 0.005) than the survival time in Group B (26 weeks). The
recursive partitioning analysis (RPA) class was the only significant
prognostic factor identified in multivariate analysis. The median survival
for patients in RPA Classes I, II, and III was 72, 48, and 19 weeks,
respectively, in Group A and 36 and 13 weeks for Classes II and III in Group
B. The number of lesions, tumor volume, whole brain radiotherapy, primary
tumor site, age, and sex did not affect survival significantly. CONCLUSIONS:
It is suggested that GKS provides an increase in survival time even in
patients with a large number (four or more) of metastatic lesions.
Concerning the selection of patients for GKS, RPA class should be considered
as the most important factor and multiplicity of the lesions alone should
not be a reason for withholding GKS.
PMID: 15662799 [PubMed - indexed for MEDLINE]
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| 5: J
Neurosurg. 2005 Jan;102 Suppl:134-9. |
|
Cyst formation following gamma knife surgery for
intracranial meningioma.
Shuto T, Inomori S, Fujino H, Nagano H, Hasegawa N, Kakuta Y.
Department of Neurosurgery, Yokohama Rosai Hospital, Yokohama, Kanagawa,
Japan. shuto@yokohamah.rofuku.go.jp
OBJECT: The authors conducted a study to evaluate the clinical significance
of cyst formation or enlargement after gamma knife surgery (GKS) for
intracranial benign meningiomas. METHODS: The medical records of 160
patients with 184 tumors were examined for those with follow-up data of more
than 2 years among 270 patients who underwent GKS for intracranial
meningiomas between February 1992 and November 2001. Cyst formation or
enlargement following GKS was observed in five patients, one man and four
women (mean age 61.2 years). The tumor location was the sphenoid ridge in
one case, petroclival in two, tentorium in one, and parasagittal region in
one. All patients underwent surgery before GKS. The mean tumor volume was
10.5 cm3, the mean margin dose was 13.4 Gy (median 14 Gy), and the mean
maximum dose was 27.5 Gy (median 24.1 Gy). At the time of GKS three tumors
were associated with cyst, of which two enlarged after radiosurgery. Three
cysts developed de novo after GKS. Three of the five patients needed surgery
to treat the cyst formation or enlargement. Histological examination
demonstrated various findings such as tumor necrosis, proliferation of small
vessels, vascular obliteration, and hemosiderin deposits. CONCLUSIONS: New
cyst formation following GKS for benign intracranial meningioma is
relatively rare; however, both preexisting and newly developed cysts tend to
enlarge after GKS and often require surgery.
Publication Types:
PMID: 15662796 [PubMed - indexed for MEDLINE]
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| 6: J
Neurosurg. 2005 Jan;102 Suppl:128-33. |
|
Gamma knife surgery for brain metastases from lung
cancer.
Pan HC, Sheehan J, Stroila M, Steiner M, Steiner L.
Lars Leksell Center of Gamma Surgery, Department of Neurological Surgery,
University of Virginia, Charlottesville, Virginia 22908, USA.
OBJECT: The authors conducted a study to evaluate the safety and efficacy of
gamma knife surgery (GKS) for the treatment of brain metastases from lung
cancer. METHODS: Between February 1993 and May 2003 191 patients underwent
treatment for 424 brain metastases from non-small (171 cases) and small cell
lung carcinoma (20 cases). Imaging and clinical status were monitored every
3 months following the treatment. Kaplan-Meier survival curves, Cox
proportional hazards regression for risk factor analysis, and nonparametric
methods for evaluating tumor response were used. There was no difference in
median survival following combined whole-brain radiation therapy (WBRT) and
gamma knife surgery (14 months) and GKS alone (15 months). There was also no
difference between the median survival rates for either tumor type. In the
multivariate analysis, age less than 65 years, Karnofsky Performance Scale
score greater than 70, normal neurological status, multiple GKS treatments,
and pre-GKS craniotomy were related to longer survival. Tumor control rates
varied according to the volume of the metastases and were as follows: 84.4%
(< 0.5 cm3), 94% (0.5-2 cm3), 89.1% (2-4 cm3), 93.4% (4-8 cm3), 85.7%
(8-14 cm3), and 87.5% (> 14 cm3). Four lesions required post-GKS
craniotomy due to swelling or rapid tumor progression. The rate of tumor
shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower
in tumors with previous WBRT, and lower for margin doses less than 14 Gy.
CONCLUSIONS: The risk-benefit ratio of GKS in this series was satisfactory.
There was no difference in response rates of the two tumor types, and WBRT
did not improve the duration of survival.
PMID: 15662795 [PubMed - indexed for MEDLINE]
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| 7: J
Neurosurg. 2005 Jan;102 Suppl:75-80. |
|
Analysis of long-term outcomes and prognostic factors in
patients with non-small cell lung cancer brain metastases treated by gamma
knife radiosurgery.
Gerosa M, Nicolato A, Foroni R, Tomazzoli L, Bricolo A.
Department of Neurological and Vision Sciences, University Hospital, Verona,
Italy. massimo.gerosa@univr.it
OBJECT: The authors conducted a study to evaluate the long-term outcomes and
prognostic factors for survival in a large series of patients treated by
gamma knife surgery (GKS) for non-small cell lung cancer (NSCLC) brain
metastases. METHODS: The study is based on the retrospective analysis of
clinical and radiological records obtained during a 10-year period
(1993-2003), concerning 836 lesions in 504 patients. The lesions were
primary in 86% and recurrent 14% of the cases; they were solitary in 31%,
single in 29%, and multiple in 40%. The mean follow-up period was 16 months
(range 4-113 months). The most common histological types were adenocarcinoma
(51%) and squamous cell carcinoma (27%). Dose planning parameters were as
follows: mean target volume 6.2 cm3 (range 0.06-22.5 cm3); mean prescription
dose 21.4 Gy (range 15.5-28 Gy); and mean number of isocenters 6.7 (range
one-18). Progression-free and actuarial survival curves were calculated
using the Kaplan-Meier method. The main factors affecting survival were
determined by unimultivariate analysis (log-rank test and Cox proportional
hazard models). Analysis of long-term outcomes seemed to confirm that GKS is
a primary therapeutic option in these patients. The 1-year local tumor
control rate was 94%. The overall median survival was 14.5 months, with
extremely rewarding quality of life indices. The recursive partitioning
analysis classification was the dominant prognostic factor. CONCLUSIONS:
Gamma knife surgery is a useful treatment for brain metastases from NSCLC.
PMID: 15662785 [PubMed - indexed for MEDLINE]
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| 8: J
Neurosurg. 2005 Jan;102 Suppl:59-70. |
|
Relative roles of microsurgery and stereotactic
radiosurgery for the treatment of patients with cranial meningiomas: a
single-surgeon 4-year integrated experience with both modalities.
Linskey ME, Davis SA, Ratanatharathorn V.
Department of Neurological Surgery and Radiation Oncology, University of
Arkansas for Medical Sciences, Little Rock, Arkansas, USA. mlinskey@uci.edu
OBJECT: The authors sought to assess the respective roles of microsurgery
and gamma knife surgery (GKS) in the treatment of patients with meningiomas.
METHODS: The authors culled from a 4-year prospective database data on 74
cases of meningiomas. Thirty-eight were treated with GKS and 35 with
microsurgery. Simpson Grade 1 or 2 resection was achieved in 86.1 % of
patients who underwent microsurgery. Patients who underwent GKS received a
mean margin dose of 16.4 Gy (range 14-20 Gy). The mean tumor coverage was
94.7%, and the mean conformity index was 1.76. Significant differences
between the two treatment groups (GKS compared with microsurgery) included
age (mean 60 compared with 50.7 years), volume (mean 7.85 cm3 compared with
44.4 cm3), treatment history (55.3% compared with 14.3%), and tumor location
(cavernous sinus/petroclival, 14 compared with three). The median follow up
was 21.5 months (range 1.5-50 months). In patients with benign meningiomas
GKS tumor control was 96.8% with one recurrence at the margin. The
recurrence rate was zero of 27 for Simpson Grade 1 or 2 resection and three
of four for higher grades in those patients who underwent microsurgery.
There was no procedure-related mortality or permanent major neurological
morbidity. The mean Karnofsky Performance Scale score was maintained for
both forms of treatment. Symptoms improved in 48.4% of patients undergoing
microsurgery and 16.7% of those who underwent GKS. Transient and permanent
cranial nerve morbidity was 7.9 compared with 2.9%, and 5.3 compared with
8.5% for GKS and microsurgery, respectively. In a patient satisfaction
survey 93.1% of microsurgery patients and 91.2% of GKS patients were highly
satisfied. CONCLUSIONS: Both GKS and microsurgery serve important roles in
the overall management of patients with meningiomas. Both are safe and
effective and provide high degrees of satisfaction when used for
differentially selected patients.
PMID: 15662783 [PubMed - indexed for MEDLINE]
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| 9: J
Neurosurg. 2005 Jan;102 Suppl:19-24. |
|
Low-grade gliomas treated by fractionated gamma knife
surgery.
Simonova G, Novotny J Jr, Liscak R.
Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital,
Prague, Czech Republic. gabriela.simonova@homolka.cz
OBJECT: The authors sought to evaluate local tumor control, complications,
and progression-free survival in patients harboring low-grade gliomas who
were treated with Leksell gamma knife surgery (GKS). METHODS: During a
6-year period 70 patients were treated for verified low-grade gliomas (Grade
I or II) by GKS. Statistical analysis was based on 68 patients; two patients
were lost to follow up. The median patient age was 17 years. The median
target volume was 4200 mm.3 The median prescription dose was 25 Gy. The
median number of fractions was five. Ninety-five percent of patients were
treated in five daily fractions. Partial or complete tumor regression was
achieved in 83% of patients with a median time to response of 18 months.
There was moderate acute or late toxicity in not more than 5% of patients.
In this series the progression-free survival was 92% at 3 years and 88% at 5
years. CONCLUSIONS: Relatively high local tumor control with minimal
complications was achieved.
PMID: 15662774 [PubMed - indexed for MEDLINE]
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| 10: J
Neurosurg. 2005 Jan;102 Suppl:1-3. |
|
Mechanisms of edema after gamma knife surgery for
meningiomas. Report of two cases.
El Shehaby A, Ganz JC, Reda WA, Hafez A.
Gamma Knife Center, Cairo, Egypt.
The authors describe two patients in whom tumor swelling and brain swelling
(and possible tumor swelling), respectively, developed after undergoing
gamma knife surgery. One had a skull defect with a palpable parasagittal
tumor. One had neurofibromatosis Type 2 with multiple tumors, one of which
was parasagittal.
Publication Types:
PMID: 15662770 [PubMed - indexed for MEDLINE]
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| 11: J
Neurosurg. 2005 Jan;102(1):167-8. |
|
Multiple meningiomas in a patient with Rubinstein-Taybi
syndrome. Case report.
Verstegen MJ, van den Munckhof P, Troost D, Bouma GJ.
Departments of Neurosurgery and Neuropathology, Academic Medical Center,
University of Amsterdam, The Netherlands. M.J.Verstegen@amc.uva.nl
The authors report a case of multiple meningiomas in a 37-year-old woman
with Rubinstein-Taybi syndrome. The patient harbored a bifrontal ossifying
meningioma and multiple intracranial meningiomas. She underwent surgery for
the frontal ossifying meningioma and a right frontoparietal meningioma.
Publication Types:
PMID: 15658110 [PubMed - indexed for MEDLINE]
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| 12: J
Neurosurg. 2005 Jan;102(1):148-51. |
|
Incontinence after brain glioma surgery: new insights
into the cortical control of micturition and continence. Case report.
Duffau H, Capelle L.
Department of Neurosurgery, Hopital Salpetriere, Paris, France.
hugues.duffau@psl.ap-hop-paris.fr
Cortical control of micturition and continence remains poorly understood.
The authors report two cases of patients who presented with prolonged
urinary disturbances after resection of a brain glioma. Accurate
anatomofunctional correlations determined using postoperative magnetic
resonance imaging support the following: 1) the implication of the posterior
portion of the right anterior cingulate gyms in the perception of bladder
sensation and maintenance of continence; 2) the involvement of the right
anterior insula in bladder relaxation; and 3) the role of the right inferior
frontal cortex in the decision concerning whether to initiate a micturition.
On the basis of these results, a preliminary model of a cortical network
associated with micturition and continence is proposed.
Publication Types:
PMID: 15658106 [PubMed - indexed for MEDLINE]
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| 13: J
Neurosurg. 2005 Jan;102(1):17-23. |
|
Meningiomas of the cerebellopontine angle with extension
into the internal auditory canal.
Roser F, Nakamura M, Dormiani M, Matthies C, Vorkapic P, Samii M.
Department of Neurosurgery, Klinikum Hannover Nordstadt, Hannover, Germany.
f.roser@gmx.de
OBJECT: Only some meningiomas of the cerebellopontine angle (CPA) extend
into the internal auditory canal (IAC) or arise from its dural lining. The
authors investigated cases of CPA tumors in which the meningioma was
inserted in the dura mater in or at the ICA or infiltrated a cranial nerve.
METHODS: The authors reviewed patient charts including surgical and clinical
records, intraoperative recordings of auditory evoked potentials, records of
postoperative auditory examinations, and imaging studies. In a series of 421
patients harboring CPA meningiomas, 72 patients in whom there was dural
involvement of the IAC were investigated. Total tumor resection was achieved
in 86.1%. In 34 patients, opening of the IAC was required for total tumor
removal; this procedure did not influence the patient functional outcome.
Among patients with secondary involvement of the IAC, anatomical
preservation of the facial and cochlear nerves was obtained in 94%, whereas
among patients in whom the lesion arose from the dura in or at the IAC these
values were 80 and 75%, respectively. Functional preservation of the seventh
and eighth cranial nerves in cases of tumor extension within the IAC was 86
and 77%, respectively, whereas in cases in which the IAC was involved it was
only 60%. In four of five patients in whom the tumor had its origin in the
dura mater within the IAC, the seventh or eighth cranial nerve had to be
sacrificed to achieve tumor removal because of the lesion's infiltrative
behavior. Facial nerve reconstruction by sural grafting was performed in the
same operative procedure. CONCLUSIONS: Meningiomas of the CPA involving the
IAC require special surgical management. Dural involvement of the IAC
requires opening by using a diamond drill, a procedure that does not
influence cranial nerve outcome. The increased rate of cranial nerve
morbidity is attributed to the infiltrative behavior of these meningiomas.
If affected nerve segments have to be sacrificed, immediate reconstruction
enables satisfactory long-term results.
PMID: 15658091 [PubMed - indexed for MEDLINE]
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| 14: Neurology.
2005 Jan 25;64(2):350-2. |
|
-
Intracranial meningioma and ionizing radiation in medical
and occupational settings.
Phillips LE, Frankenfeld CL, Drangsholt M, Koepsell TD, van Belle G,
Longstreth WT Jr.
Neuroepidemiology Group, Department of Epidemiology,School of Public Health
and Community Medicine, University of Washington, Seattle, USA.
In a population-based case-control study of 200 cases and 400 controls in
western Washington State, the authors assessed associations between
meningioma and ionizing radiation in medical and occupational settings. No
significant associations were observed for diagnostic studies or
occupational settings, but associations were observed for radiation therapy
to head or neck (odds ratio 3.7, 95% CI 1.5 to 9.5), especially for
neoplastic conditions. Only four patients (2%) had meningiomas that followed
high-dose cranial radiation.
PMID: 15668439 [PubMed - in process]
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| 15: Neurology.
2004 Feb 24;62(4):619. |
|
Comment in:
Bright red nuclei.
Pittock SJ, Weinshenker BG, Lucchinetti CF.
Department of Neurology, Mayo Clinic, 200 First Street, SW, Rochester, MN
55905, USA. lucchinetti.claudia@mayo.edu
Publication Types:
PMID: 14981180 [PubMed - indexed for MEDLINE]
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| 16: Neurology.
2004 Feb 24;62(4):548-55. |
|
Comment in:
Cognitive functions in survivors of primary central
nervous system lymphoma.
Correa DD, DeAngelis LM, Shi W, Thaler H, Glass A, Abrey LE.
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York
10021, USA. corread@mskcc.org
BACKGROUND: The standard treatment for primary CNS lymphoma (PCNSL) involves
high-dose methotrexate-based (MTX) chemotherapy and whole brain radiotherapy
(WBRT). This combined regimen prolongs patient survival, but also carries a
substantial risk for delayed neurotoxicity particularly in the elderly.
However, cognitive outcome evaluations have not been included in most
clinical trials. OBJECTIVE: To assess cognitive functioning and quality of
life in PCNSL survivors treated either with WBRT +/- MTX-based chemotherapy
or chemotherapy alone. METHODS: Twenty-eight PCNSL patients in disease
remission received a post-treatment baseline neuropsychological evaluation,
and a subset of patients were available for an 8-month follow-up evaluation.
Assessment of quality of life and extent of white matter disease on MRI were
also performed. RESULTS: Patients displayed mild to moderate impairments
across several cognitive domains. These were of sufficient severity to
reduce quality of life in half of the patient sample. Comparisons according
to treatment type revealed more pronounced cognitive impairment,
particularly in the memory and attention/executive domains, among patients
treated with WBRT +/- chemotherapy. Extent of white matter disease
correlated with attention/executive, memory, and language impairment.
CONCLUSIONS: PCNSL survivors treated with WBRT +/- chemotherapy displayed
more pronounced cognitive dysfunction than patients treated with MTX-based
chemotherapy alone.
PMID: 14981169 [PubMed - indexed for MEDLINE]
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| 17: Neurology.
2004 Feb 24;62(4):544-7. |
|
Comment in:
Cognitive status and quality of life after treatment for
primary CNS lymphoma.
Harder H, Holtel H, Bromberg JE, Poortmans P, Haaxma-Reiche H,
Kluin-Nelemans HC, Menten J, van den Bent MJ.
Department of Neuro-oncology, Erasmus MC, Daniel den Hoed Cancer Center,
Rotterdam, The Netherlands. h.harder@erasmusmc.nl
OBJECTIVE: To evaluate the cognitive status and quality of life (QOL) in a
cohort of 19 consecutive patients treated in a prospective European
Organization for Research and Treatment of Cancer study (20962) for primary
CNS lymphoma (PCNSL). All patients were in complete remission after combined
modality treatment with IV and intrathecal high-dose methotrexate
(MTX)-based chemotherapy followed by whole brain radiotherapy (WBRT).
METHODS: An extensive neuropsychological assessment, including QOL measures,
was conducted in 19 patients with PCNSL. The results were compared with
matched control subjects with systemic hematologic malignancies treated with
systemic chemotherapy or non-CNS radiotherapy. In addition, a
neuroradiologic evaluation was carried out in 18 patients with PCNSL.
RESULTS: Cognitive impairment was found in 12 patients with PCNSL (63%)
despite a complete tumor response. Four patients (21%) showed severe
cognitive deficits, and the percentage of impaired test indices correlated
with age. In comparison, only two control subjects (11%) showed cognitive
dysfunction (p = 0.002). Forty-two percent of the patients with PCNSL, in
contrast to 81% of the control subjects, resumed work. White matter
abnormalities were observed in 14 patients with PCNSL, and 14 had cortical
atrophy. Cortical atrophy correlated with cognitive functioning, age, and
Karnofsky performance score. Group differences in cognitive status and QOL
could not be explained by anxiety, depression, or fatigue. CONCLUSIONS:
Combined modality treatment for primary CNS lymphoma is associated with
cognitive impairment even in patients aged <60 years.
PMID: 14981168 [PubMed - indexed for MEDLINE]
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| 18: Neurology.
2004 Feb 24;62(4):532-3. |
|
Comment on:
Neurocognitive outcomes in primary CNS lymphoma (PCNSL).
O'Neill BP.
Publication Types:
PMID: 14981164 [PubMed - indexed for MEDLINE]
-
| 19: Neurosurgery.
2005 Feb;56(2):242-8; discussion 242-8. |
|
-
Local and sustained delivery of 5-fluorouracil from
biodegradable microspheres for the radiosensitization of malignant glioma: a
randomized phase II trial.
Menei P, Capelle L, Guyotat J, Fuentes S, Assaker R, Bataille B, Francois
P, Dorwling-Carter D, Paquis P, Bauchet L, Parker F, Sabatier J, Faisant N,
Benoit JP.
Department of Neurosurgery, Institut National de la Sante et de la Recherche
Medicale, Unite 646, University Hospital, Angers, France.
phmenei@chu-angers.fr
OBJECTIVE: This study was a randomized, multicenter Phase II trial comparing
the effect of perioperative implantation of 5-fluorouracil-releasing
microspheres followed by early radiotherapy (Arm A) and early radiotherapy
alone (Arm B) in patients with gross total resection of high-grade glioma.
METHODS: Patients were randomized on clinical and radiological assumption of
supratentorial high-grade glioma. All patients underwent surgery, and after
resection and histological confirmation, patients randomized to Arm A
received multiple injections of microsphere suspension (130 mg of
5-fluorouracil). Conventional fractionated radiotherapy (59.4 Gy) was
initiated between the second and the seventh day after surgery for both
arms. RESULTS: A total of 95 patients were randomized. Seventy-seven
patients were treated and analyzed in intention to treat for efficacy and
safety. Overall survival was 15.2 months in Arm A and 13.5 months in Arm B.
In the subpopulation of patients with complete resection, overall survival
was 15.2 months in Arm A versus 12.3 months in Arm B. However, these
differences were not significant. Safety was acceptable with prophylactic
high doses of corticosteroids. CONCLUSION: It may be hypothesized that the
implantation of 5-fluorouracil-loaded microspheres in the wall of the cavity
resection did increase the overall survival, but the present study was not
designed and sufficiently powered to demonstrate this.
PMID: 15670372 [PubMed - in process]
-
| 20: Oncogene.
2005 Jan 24; [Epub ahead of print] |
|
-
GPR56 is a GPCR that is overexpressed in gliomas and
functions in tumor cell adhesion.
Shashidhar S, Lorente G, Nagavarapu U, Nelson A, Kuo J, Cummins J,
Nikolich K, Urfer R, Foehr ED.
1AGY Therapeutics Inc., 270 East Grand Avenue, South San Francisco, CA
94080, USA.
GPR56 (also known as TM7XN1) is a newly discovered orphan G-protein-coupled
receptor (GPCR) of the secretin family that has a role in the development of
neural progenitor cells and has been linked to developmental malformations
of the human brain. GPR56 diverges from other secretin-like family members
in that it has an extremely large N-terminal extracellular region (381 amino
acids) and contains a novel feature among this new subclass, consisting of
four cysteine residues that define a GPCR proteolytic site (GPS motif)
located just before the first transmembrane spanning domain. The rest of the
amino-terminal domain contains a large number of possible N- and O-linked
glycosylation sites similar to mucin-like proteins. These features suggest a
role in cell-cell, or cell-matrix interactions. Here, we demonstrate
upregulation of GPR56 in glioblastoma multiforme tumors using functional
genomics. Immunohistochemistry studies confirmed the expression of GPR56
protein in a majority of glioblastoma/astrocytoma tumor samples with
undetectable levels of expression in normal adult brain tissue.
Immunofluorescence analysis of human glioma cells using anti-GPR56
antibodies demonstrate that GPR56 is expressed on the leading edge of
membrane filopodia and colocalizes with alpha-actinin. Purified recombinant
GPR56 extracellular domain protein inhibits glioma cell adhesion and causes
abnormal cytoskeletal morphology and cell rounding. These results indicate
that the extracellular domain may compete for unidentified ligand(s), and
block the normal function of GPR56 in cell attachment. In reporter assays,
overexpression of GPR56 activates the NF-kappaB, PAI-1 and TCF
transcriptional response elements. These pathways have been implicated in
cytoskeletal signaling, adhesion and tumor biology. The above results
indicate that GPR56 serves as an adhesion GPCR and is involved in adhesion
signaling.Oncogene advance online publication, 24 January 2005;
doi:10.1038/sj.onc.1208395.
PMID: 15674329 [PubMed - as supplied by publisher]
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| 21: Pediatr
Neurosurg. 2004 Mar-Apr;40(2):70-4. |
|
-
Spinal cord compression caused by extradural arachnoid
cysts. Clinical examples and review.
Chang IC, Chou MC, Bell WR, Lin ZI.
Institute of Medicine, Chung-Shan Medical University, Department of Spinal
Surgery,Chung-Shan Medical University Hospital, Taichung, Taiwan.
Most spinal arachnoid cysts are asymptomatic and detected incidentally
during magnetic resonance imaging or myelography. The etiology of
intraspinal arachnoid cyst is not yet clear. We present two children with
three spinal extradural arachnoid cysts and each cyst protruded from a
separate dura defect. In both patients, plain radiographs demonstrated
widening of the interpedicular distance, which suggested progressive
widening of the spinal bony canal. Limited laminectomy was performed to
remove the intraspinal cysts. Separate dura defects, the apparent
predisposing factors, were also found and repaired. The patients completely
recovered neurologically. Radical cyst removal and dura defect closure are
the surgical intervention of choice in patients with symptomatic extradural
arachnoid cyst.
Publication Types:
PMID: 15292636 [PubMed - indexed for MEDLINE]
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| 22: Pediatr
Neurosurg. 2004 Mar-Apr;40(2):59-63. |
|
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Endoscopic cyst fenestration outcomes in children one
year of age or less.
Sikorski CW, Yamini B, Frim DM.
Section of Pediatric Neurosurgery, University of Chicago Children's
Hospital, Chicago, Ill., USA.
The use of endoscopic fenestration (EF) is becoming an increasingly common
treatment for symptomatic intracranial cysts. Very little data exist
regarding outcomes for this procedure in children 1 year of age or younger.
We retrospectively reviewed the clinical outcomes of 8 children 1 year of
age or less treated at our institution with endoscopic cyst fenestration.
The mean follow-up was roughly 2.5 years. These data were combined with 17
other cases obtained from the published literature. EF was successful in
rendering patients shunt-free or minimizing the number of ventricular
catheters in 18 of 26 operations. There were 8 outright failures -- two in 1
patient. Given the risks and complications of cerebrospinal fluid shunting
in children less than 1 year of age, we advocate the consideration of EF as
initial treatment of symptomatic intracranial cysts.
PMID: 15292634 [PubMed - indexed for MEDLINE]
|
Volume 4, Number 11 - 28 February 2005