| 1: J Neurooncol. 2004 Oct;70(1):87-90. |
|
Carcinomatous meningitis in cancer of the uterine cervix.
Rentinck ME, Schrijver HM, Kneppers E, Zijlmans JC, van Groeningen CJ.
Department of Medical Oncology, VU Medical Center, Amsterdam, The
Netherlands.
Carcinomatous meningitis is extremely rare in cervical cancer. The diagnosis
of carcinomatous meningitis is a difficult one when clinical symptoms are
limited and radiographic imaging is normal. Demonstration of malignant cells
in the cerebrospinal fluid remains the gold standard to establish the
diagnosis. For patients without bulky disease who can be treated with
radiotherapy, standard treatment for carcinomatous meningitis is
chemotherapy, which may be administered intrathecally. Despite the poor
prognosis, treatment may result in effective palliation. We describe a
54-year-old patient who was diagnosed with carcinomatous meningitis in the
course of metastatic cervical cancer and who responded to administration of
intrathecal methotrexate.
Publication Types:
- Case Reports
- Review
- Review of Reported Cases
PMID: 15527113 [PubMed - indexed for MEDLINE]
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| 2: J Neurooncol. 2004 Oct;70(1):83-5. |
|
Testicular seminoma 16 years after treatment for CNS
germinoma.
Maity A, Shu HK, Judkins AR, Fisher MJ, Dwyer-Joyce LE, Vaughn DJ.
Department of Radiation Oncology, Hospital of the University of
Pennsylvania, Philadelphia 19104, USA. maity@xrt.upenn.edu
Most patients with intracranial germinomas will be cured and become
long-term survivors. Physicians caring for these patients should recognize
that these patients may be at risk for disease-related and/or
treatment-related late sequelae. We report the case of a 27-year-old man who
developed testicular seminoma 16 years after treatment for intracranial
germinoma. Like their testicular cancer counterparts, long-term survivors of
intracranial germinomas may have a susceptibility to develop a subsequent
germ cell tumor. These patients require lifelong medical follow-up and
should be encouraged to perform testicular self-examination at the
appropriate age.
Publication Types:
PMID: 15527112 [PubMed - indexed for MEDLINE]
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| 3: J Neurooncol. 2004 Oct;70(1):77-82. |
|
Reducing the overall treatment time for radiotherapy of
metastatic spinal cord compression (MSCC): 3-year results of a prospective
observational multi-center study.
Rades D, Fehlauer F, Hartmann A, Wildfang I, Karstens JH, Alberti W.
Department of Radiation Oncology, University Hospital Hamburg, Hamburg,
Germany. Rades.dir@gmx.net
BACKGROUND: This prospective multi-center study investigates a reduction of
the overall treatment time for radiotherapy of MSCC, which is important for
these mostly disabled patients. PATIENTS AND METHODS: Two standard
fractionation schedules, 30 Gy/10 fractions/2 weeks (n = 71) and 40 Gy/20
fractions/4 weeks (n = 65) were compared for functional outcome and
ambulatory status. Motor function was graded using an 8-point-scale before
RT, at the end and at 6, 12 and 24 weeks after RT. A multi-variate analysis
was performed for functional outcome. Included variables were the
fractionation schedule and the three relevant prognostic factors. These
factors are the type of primary tumor, the time of developing motor deficits
before RT and the pre-treatment ambulatory status. RESULTS: The ambulatory
rates were 49% in the 30 Gy group and 52% in the 40 Gy group before RT (P =
0.888), and 56% and 60% after RT (P = 0.888). Improvement of motor function
occurred in 45% of the 30 Gy group and 40% of the 40 Gy group (P = 0.752).
The relevant prognostic factors were comparably distributed in both groups.
According to the multivariate analysis, a slower development of motor
deficits (P < 0.001), a favorable histology (P = 0.040) and being
ambulatory (P = 0.045) were associated with better functional outcome,
whereas the fractionation schedule had no significant impact (P = 0.311).
CONCLUSIONS: The data suggest both schedules to be comparably effective for
functional outcome. Thus, 30 Gy/10 fractions/2 weeks should be applied
instead of 40 Gy/20 fractions/4 weeks. The reduction of the overall
treatment time from 4 to 2 weeks means less discomfort for the paraparetic
or paraplegic patient.
Publication Types:
PMID: 15527111 [PubMed - indexed for MEDLINE]
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| 4: J Neurooncol. 2004 Oct;70(1):73-5. |
|
Intracranial metastatic esthesioneuroblastoma responsive
to temozolomide.
Wick W, Wick A, Kuker W, Dichgans J, Weller M.
Department of Neurology, University of Tubingen Medical School, Tubingen,
Germany. wolfgang.wick@uni-tuebingen.de
Successful management of a heavily pretreated 58-year-old woman with
metastatic esthesioneuoblastoma using temozolomide is reported. There is no
standard treatment of this tumors with extra- and intracranial
manifestations. The response, long term stability and high quality of life
using temozolomide for this tumor entity should be recognized.
Publication Types:
PMID: 15527110 [PubMed - indexed for MEDLINE]
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| 5: J Neurooncol. 2004 Oct;70(1):67-71. |
|
Carcinomatous meningitis as the presenting manifestation
of gallbladder carcinoma: case report and review of the literature.
Shen Y, Blumenthal DT, Digre K, Cessna MH, Gopez EV.
Department of Neurology, University of Utah Hospital, Salt Lake City, UT
84132, USA. jason.shen@usa.net
The primary tumors that typically cause carcinomatous meningitis include
lung cancer, breast cancer, leukemia, lymphoma and melanoma. A variety of
neurological signs and symptoms can be seen depending on the extent and
location of the meningeal metastasis. Once the diagnosis of carcinomatous
meningitis is confirmed, the search for the primary tumor can be a challenge
and at times may require extensive radiographic or even surgical evaluation
to obtain specimen for pathological confirmation. Here we report a patient
who presented with bilateral cranial nerve VIII and cerebellar symptoms, and
was diagnosed with carcinomatous meningitis. Only after an exploratory
laporatomy did it become clear that the initial symptoms were related to a
metastatic gallbladder carcinoma.
Publication Types:
PMID: 15527109 [PubMed - indexed for MEDLINE]
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| 6: J Neurooncol. 2004 Oct;70(1):35. |
|
Melanocytoma.
Bannykh S, Piepmeier J, Baehring J.
Departments of Pathology, Neurosurgery and Neurology, Yale University School
of Medicine, USA.
Publication Types:
PMID: 15527105 [PubMed - indexed for MEDLINE]
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| 7: J Neurooncol. 2004 Oct;70(1):1-2. |
|
Neuro-oncology in a nutshell.
Baehring JM.
Department of Neurosurgery, Yale University School of Medicine, New Haven,
CT, USA.
Publication Types:
PMID: 15527100 [PubMed - indexed for MEDLINE]
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| 8: J Neurooncol. 2004 Aug-Sep;69(1-3):291-318. |
|
Spinal cord and intradural-extraparenchymal spinal
tumors: current best care practices and strategies.
Parsa AT, Lee J, Parney IF, Weinstein P, McCormick PC, Ames C.
Department of Neurological Surgery, University of California, San Francisco,
CA 94143, USA. parsaa@neurosurg.ucsf.edu
The management of patients with intradural spinal tumors differs in many
respects from approaches taken for patients with intracranial tumors.
Intramedullary lesions are often completely surrounded by normal spinal
cord, displacing vital functional tracts eccentrically. Extramedullary
lesions can drastically compress the spinal cord and nerve roots, reducing
normal tissue to a ribbon-like consistency. The small amount of normal
tissue relative to tumor has implications for surgery and postoperative
adjuvant therapy. In addition, operative intervention must take spinal
stability into consideration. In this report, we describe the current best
care practices and strategies for patients with a diagnosis of spinal
astrocytoma, ependymoma, hemangioblastoma, schwannoma, and meningioma.
Treatment of patients with intradural tumors of the spinal cord and
adjoining structures has changed over the past 20 years. Advances in many
disciplines including neuroradiology, neurosurgery, neurooncology, and
neuropathology have contributed to expediting diagnosis and improving
outcomes.
Publication Types:
PMID: 15527097 [PubMed - indexed for MEDLINE]
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| 9: J Neurooncol. 2004 Aug-Sep;69(1-3):257-72. |
|
Stereotactic radiosurgery for pituitary adenomas: a
review of the literature.
Laws ER, Sheehan JP, Sheehan JM, Jagnathan J, Jane JA Jr, Oskouian R.
University of Virginia, Charlottesville, VA 22908, USA.
OBJECTIVE: Pituitary adenomas are very common neoplasms and represent
between 10 and 20% of all primary brain tumors. Historically, the treatment
armamentarium for pituitary adenomas included medical management,
microsurgery, and fractionated radiotherapy. More recently, radiosurgery has
emerged as a viable treatment option. The goal of this research is to define
accurately the efficacy, safety, and role of radiosurgery for treatment of
pituitary adenomas. METHODS: Medical literature databases from 1965 to 2003
were searched for articles pertaining to pituitary adenomas and stereotactic
radiosurgery. Each study was evaluated for the number of patients,
radiosurgical parameters (e.g. tumor margin dose), length of follow-up,
tumor growth control rate, complications, and rate of hormonal normalization
in the case of functioning adenomas. RESULTS: A total of 34 published
studies including 1567 patients were reviewed. Radiosurgery offers a tumor
growth control rate of approximately 90%. The reported rates of hormonal
normalization for functioning adenomas vary substantially. This range is in
part due to widespread differences in endocrinological criteria utilized for
post-radiosurgical assessment. Thus far, the risks of radiation induced
neoplasia and cerebral vasculopathy associated with radiosurgery appear to
be lower than for fractionated radiation therapy. The incidence of other
serious complications following radiosurgery is quite low. CONCLUSIONS:
Although surgical resection typically is the primary treatment modality,
stereotactic radiosurgery offers safe and effective treatment for recurrent
or residual pituitary adenomas. In rare instances, radiosurgery may be the
best initial treatment for patients with pituitary adenomas. Refinements in
the radiosurgical technique will likely lead to improved outcomes.
Publication Types:
PMID: 15527095 [PubMed - indexed for MEDLINE]
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| 10: J Neurooncol. 2004 Aug-Sep;69(1-3):237-56. |
|
Transsphenoidal and transcranial surgery for pituitary
adenomas.
Couldwell WT.
Department of Neurosurgery, University of Utah School of Medicine, Salt Lake
City, UT 84132-2303, USA. william.couldwell@hsc.utah.edu
This paper reviews the progress made over the first century of pituitary
surgery. The goals of surgery for pituitary tumors are to eliminate tumor
mass effect and perform as complete a removal as possible, retain pituitary
function, and normalize any hormonal hypersecretion. Since the initial
transsphenoidal approach performed in Austria by Schloffer, the
transsphenoidal approach has become the preferred surgical approach to most
pituitary tumors. The history and development of the transsphenoidal
approach to the sella is discussed, as are the contemporary techniques of
microscopic and endoscopic pituitary surgery. The continued evolution of the
variations and extension of the transsphenoidal approach to other lesions
are reviewed. The indications and use of a transcranial approach to remove
pituitary tumors are discussed. More recently, stereotactic radiosurgery
(SRS) has become an important adjuvant management technique in the
management of difficult pituitary adenomas, especially with cavernous sinus
invasion.
Publication Types:
PMID: 15527094 [PubMed - indexed for MEDLINE]
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| 11: J Neurooncol. 2004 Aug-Sep;69(1-3):221-36. |
|
Surgical strategies for treating patients with pineal
region tumors.
Bruce JN, Ogden AT.
Department of Neurological Surgery, The Neurological Institute, Columbia
University, New York, NY 10032, USA. jnb2@columbia.edu
Optimal management of pineal region tumors depends on securing an accurate
histologic diagnosis to facilitate management customized to the nuances of
specific pathologies. As an initial step, surgical intervention by either
stereotactic biopsy or open surgery is necessary to obtain tissue for
pathologic examination. Stereotactic biopsy has the benefit of relative ease
and minimal morbidity but is associated with greater likelihood of
diagnostic inaccuracy compared to open surgery where more extensive tissue
sampling is possible. The role of surgical debulking in the management of
pineal tumors is clearly defined for some tumors but is less evident for
others. Among the one third of pineal tumors that are benign or low grade,
complete surgical resection is achievable and constitutes optimal management
with excellent long-term recurrence-free survival. The benefits of
aggressive surgical resection among malignant tumors are less clear but
several studies have correlated degree of tumor removal with improved
outcome. Advances in technology, surgical technique, and post-operative care
have minimized surgical complications, however all surgical procedures in
the pineal region, including both stereotactic biopsy and open surgery, are
potentially hazardous. Advanced judgment, experience, and expertise are
necessary to achieve rates of success sufficient to justify aggressive
management. Management strategies using stereotactic biopsy, endoscopy, and
radiosurgery can also provide favorable outcomes in some cases. Selective
incorporation of these innovations can be expected to improve the already
highly favorable outcome for all pineal region tumors.
Publication Types:
PMID: 15527093 [PubMed - indexed for MEDLINE]
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| 12: J Neurooncol. 2004 Aug-Sep;69(1-3):191-8. |
|
Evolving role of skullbase surgery for patients with low
and high grade malignancies.
DeMonte F.
Department of Neurosurgery and Head and Neck Surgery, The University of
Texas M.D. Anderson Cancer Center Houston, TX 77030, USA.
fdemonte@mdanderson.org
Malignancy involving the skull base remains a formidable management
challenge. Advances and refinements in diagnostic imaging, instrumentation,
microvascular reconstruction, and an improved overall appreciation of the
anatomy of the skullbase have extended the boundaries of tumor resectability
and in some cases, obviated the need for adjuvant therapies. Successful
management of high-grade malignancy however, requires a carefully
constructed multi-modal treatment plan to maximize patient outcome. Over the
course of an 11-year period, 259 patients with skullbase malignancies were
treated by the author in the setting of a tertiary care comprehensive cancer
center. All patients were evaluated by a multidisciplinary team experienced
in the assessment and treatment of skullbase malignancy. Management
paradigms were constructed and treatment based on categorization into low or
high-grade malignancy was recommended and undertaken. This manuscript
discusses this patient population and the outcome of the management
paradigms that were constructed. Differences in outcome based on the
characterization of malignancies as either low or high grade is discussed.
Complications of treatment and patient reported quality of life outcomes are
reviewed.
Publication Types:
PMID: 15527090 [PubMed - indexed for MEDLINE]
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| 13: J Neurooncol. 2004 Aug-Sep;69(1-3):139-50. |
|
Pediatric surgical neuro-oncology: current best care
practices and strategies.
Rutka JT, Kuo JS.
The Arthur and Sonia Labatt Brain Tumour Research Centre and Division of
Neurosurgery, The Hospital for Sick Children, University of Toronto,
Toronto, Ontario, Canada. james.rutka@sickkids.ca
Significant advances have been made in the diagnosis and treatment of
childhood brain tumors. Gross total surgical resection combined with
appropriate adjuvant therapies can achieve a high rate of disease control
for low grade gliomas, ependymomas and medulloblastomas. High grade gliomas,
tumors involving the optic apparatus or diencepahalic structures, diffuse
brainstem lesions, and recurrent or metastatic disease still pose
considerable therapeutic challenges. We review the current treatment
strategies of the three most common types of pediatric brain tumors:
gliomas, medulloblastomas and ependymomas, and discuss current and future
diagnostic and therapeutic modalities.
Publication Types:
PMID: 15527086 [PubMed - indexed for MEDLINE]
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| 14: J Neurooncol. 2004 Aug-Sep;69(1-3):101-17. |
|
Neurosurgical delivery of chemotherapeutics, targeted
toxins, genetic and viral therapies in neuro-oncology.
Chiocca EA, Broaddus WC, Gillies GT, Visted T, Lamfers ML.
Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts
General Hospital, Harvard Medical School, Charlestown, MA, USA.
Local delivery of biologic agents, such as gene and viruses, has been tested
preclinically with encouraging success, and in some instances clinical
trials have also been performed. In addition, the positive pressure infusion
of various therapeutic agents is undergoing human testing and approval has
already been granted for routine clinical use of biodegradable implants that
diffuse a chemotherapeutic agent into peritumoral regions. Safety in glioma
patients has been shown, but anticancer efficacy needs additional
refinements in the technologies employed. In this review, we will describe
these modalities and provide a perspective on needed improvements that
should render them more successful.
Publication Types:
PMID: 15527083 [PubMed - indexed for MEDLINE]
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| 15: J Neurooncol. 2004 Aug-Sep;69(1-3):83-100. |
|
Stereotactic radiosurgery and interstitial brachytherapy
for glial neoplasms.
McDermott MW, Berger MS, Kunwar S, Parsa AT, Sneed PK, Larson DA.
Department of Neurosurgery, University of California, San Francisco, CA,
USA. mcdermottm@neuro.ucsf.edu
The application of focal radiation therapies in the management of malignant
gliomas has gone through a number of stages. Earlier efforts to improve
local control of malignant gliomas involved the use of brachytherapy.
Despite some early encouraging results, Phase 3 studies did not prove a
significant survival benefit for the addition of brachytherapy for newly
diagnosed glioblastoma. Most recently radiosurgery has been employed using
the same rationale in that improved local control may improve survival.
Results of the RTOG Phase 3 study are pending final publication, but early
abstracted reports are negative. While radiosurgery and brachytherapy
continue to be used as a form of therapy for selected patients with
recurrent gliomas, new information from metabolic imaging studies suggests
our problem with these techniques in part may be related to targeting. This
paper reviews the recent literature and results of the use of brachytherapy
and radiosurgery in the management of newly diagnosed and recurrent
malignant gliomas.
Publication Types:
PMID: 15527082 [PubMed - indexed for MEDLINE]
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| 16: J Neurooncol. 2004 Aug-Sep;69(1-3):35-54. |
|
The changing role of stereotaxis in surgical
neuro-oncology.
Linskey ME.
Department of Neurological Surgery, University of California, Irvine, UCI
Medical Centre, Orange, CA 92868-3298, USA. mlinskey@uci.edu
PURPOSE: Evaluate evolution and time course of stereotactic neurosurgery
within surgical neuro-oncology. METHODS: MEDLINE search 1966-2003
sub-stratified and analyzed for annual trends. AANS/CNS membership databases
for Joint Sections. ACRC neuro-oncology program database 1998-2003. RESULTS:
Tumor stereotaxis emerged in 1980 and became the dominant stereotactic
publication topic by 1984. Frame-based tumor stereotaxis led publications
through 1994, when supplanted by stereotactic radiosurgery (SR).
Brachytherapy led SR 1982-1987, but then fell behind, reducing to pre-1983
levels by 1996. SR publications currently comprise 65% of stereotactic tumor
articles and publication rate continues to rise at a steady rate. Frameless
stereotaxis (FS) publications began to increase in 1993 and growth is larger
than the corresponding fall in frame-based volumetric resection
publications. Data suggest increased utilization for cases that would have
otherwise utilized ultrasound or gone without image guidance. Intraoperative
MR developed predominantly as complimentary technology to FS. Tumor
diagnostic needle biopsy publications continue to be mostly frame-based,
while FS techniques are largely resection focused. This may change as
>80% of our tumors biopsied with frame-based techniques would be
candidates for FS biopsy based solely on lesion size, location, and
technique accuracy considerations. CNS parenchymal delivery of experimental
therapies continues to be predominantly frame-based. CONCLUSION: The role of
tumor stereotaxis in surgical neuro-oncology is important, but changing. SR
is increasingly dominating the subspecialty. Stereotactic tumor resection
has become a mainstream neurosurgical procedure due to FS, and this will
likely occur with needle biopsy as well. Delivery of experimental therapies
remains predominantly frame-based, but may need to transition to FS in order
to gain wider mainstream acceptance and applicability once efficacy is
demonstrated.
Publication Types:
PMID: 15527079 [PubMed - indexed for MEDLINE]
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| 17: J Neurooncol. 2004 Aug-Sep;69(1-3):19-23. |
|
Chairman's reflection on the past, present and future of
neurosurgical oncology.
Sawaya R.
AANS/CNS Section on Tumors, The University of Texas M. D. Anderson Cancer
Center, Houston, TX 77030, USA. rsawaya@mdanderson.org
The development of neurosurgical oncology as a subspecialty is closely tied
to the development of neurosurgery as a whole. Therefore, the progress that
has taken place in the diagnosis and the surgical management of
neurosurgical disorders has been widely applied to oncologic disorders
affecting the nervous system. The challenges and opportunities that
characterize the specialty are grouped into five general categories. These
are issues that are related to (1) the management of a large and diverse
patient population, (2) the proper training of neurosurgeons to develop the
set of required technical skills, (3) the lack of disease curability and its
associated opportunity for research endeavors, (4) the importance of the
multidisciplinary coordination of care in a horizontal matrix model, and (5)
the psychosocial dimensions that are a part of the complexity of human
nature. Based on a current assessment of the subspecialty, a perspective on
the unfolding future is obtained. This future can be characterized by a
stronger workforce, a broader connectivity and representations, and an
improved scientific inquiry.
Publication Types:
PMID: 15527077 [PubMed - indexed for MEDLINE]
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| 18: J Neurooncol. 2004 Aug-Sep;69(1-3):1-18. |
|
History of the AANS/CNS joint section on tumors and
preface to the 20th anniversary Journal of Neuro-Oncology Special Issue.
Barker FG 2nd, Linskey ME.
Neurosurgical Service, Massachusetts General Hospital and Harvard Medical
School, Boston, MA, USA. barker@helix.mgh.harvard.edu
The Joint Section on Tumors of the American Association of Neurological
Surgeons (AANS) and the Congress of Neurological Surgeons (CNS) was formed
in 1984, at the suggestion of Dr. Edward R. Laws, Jr. and with Dr. Mark
Rosenblum as the first Section Chair. The Joint Section on Tumors is the
first professional organization devoted to the study and treatment of brain
tumors. Its initial goals were to 'assist in the education of neurosurgeons
in neuro-oncology and to serve as a resource [to the AANS and CNS] and other
national groups on the clinical treatment of and research into nervous
system tumors'. During its 20-year history, the Section has facilitated both
open and invited talks at the neurosurgical national meetings, conducted its
own Satellite Symposia, and instituted multiple awards and grants. Members
have conducted research surveys and national practice pattern studies, and
have collected and disseminated information on clinical protocols, research
funding opportunities, and fellowships in neurosurgical oncology. Guidelines
for brain tumor treatment and for neuro-oncology fellowships for surgeons
have been written by Section committees. Studies presented orally at Section
meetings, 1999-2002, had a remarkably high rate of full publication compared
to other meetings - 73% actuarial at 4 years after presentation. Finally,
nationwide in-hospital mortality rates for craniotomy for malignant glioma
have fallen from 8 to 2% during the Section's existence. These data suggest
that the Section's goals of educating all surgeons in neurosurgical oncology
are being successfully met. A bibliography of secondary sources on the
history of brain tumor surgery is appended.
Publication Types:
PMID: 15527076 [PubMed - indexed for MEDLINE]
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| 19: J Neuropathol Exp Neurol. 2004 Oct;63(10):1072-9. |
|
Loss of heterozygosity at 6q is frequent and concurrent
with 3p loss in sporadic and familial capillary hemangioblastomas.
Lemeta S, Pylkkanen L, Sainio M, Niemela M, Saarikoski S,
Husgafvel-Pursiainen K, Bohling T.
Department of Pathology, University of Helsinki, Finland.
Capillary hemangioblastoma is a benign tumor, occurring sporadically or as a
manifestation of von Hippel-Lindau (VHL) disease. Inactivation of the VHL
gene at 3p25-26 has been demonstrated in all VHL-associated
hemangioblastomas. However, the VHL gene has been found to be inactivated in
only 20% to 50% of sporadic tumors. So far, no other gene has been reported
to be involved in the development of hemangioblastomas. DNA losses at 6q are
frequent alterations in hemangioblastomas, as shown by comparative genomic
hybridization. We therefore analyzed 15 hemangioblastomas for loss of
heterozygosity (LOH) on chromosome 3p and 6q to reveal the frequency of
allelic losses and to determine minimal deleted areas. We detected LOH at 6q
for one or more markers in 11 (73%) out of 15 cases (in 9 of 11 sporadic and
in 2 of 4 VHL-associated tumors). The analyses revealed a minimal 3-megabase
(Mb) deleted region at 6q23-24, where 9 of 11 (82%) informative cases showed
LOH. LOH at 3p was seen in 14 out of 15 tumors. LOH occurred concurrently at
6q and 3p in 67% of cases. Our data strongly suggests that a tumor
suppressor gene located at 6q23-24 is involved in tumorigenesis of
hemangioblastomas, in addition to the VHL gene.
PMID: 15535134 [PubMed - indexed for MEDLINE]
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| 20: J Neurosurg. 2004 Dec;101(6):960-9. |
|
Intraoperative infrared imaging of brain tumors.
Gorbach AM, Heiss JD, Kopylev L, Oldfield EH.
National Institute of Neurological Disorders and Stroke, Bioengineering and
Physical Science, Warren Grant Magnuson Clinical Center, National Institutes
of Health, Bethesda, Maryland 20892-5766, USA. gorbach@helix.nih.gov
OBJECT: Although clinical imaging defines the anatomical relationship
between a brain tumor and the surrounding brain and neurological deficits
indicate the neurophysiological consequences of the tumor, the effect of a
brain tumor on vascular physiology is less clear. METHODS: An infrared
camera was used to measure the temperature of the cortical surface before,
during, and after removal of a mass in 34 patients (primary brain tumor in
21 patients, brain metastases in 10 and falx meningioma, cavernous angioma,
and radiation necrosis-astrocytosis in one patient each). To establish the
magnitude of the effect on blood flow induced by the tumor, the images were
compared with those from a group of six patients who underwent temporal
lobectomy for epilepsy. In four cases a cerebral artery was temporarily
occluded during the course of the surgery and infrared emissions from the
cortex before and after occlusion were compared to establish the
relationship of local temperature to regional blood flow. Discrete
temperature gradients were associated with surgically verified lesions in
all cases. Depending on the type of tumor, the cortex overlying the tumor
was either colder or warmer than the surrounding cortex. Spatial
reorganization of thermal gradients was observed after tumor resection.
Temperature gradients of the cortex in patients with tumors exceeded those
measured in the cortex of patients who underwent epilepsy surgery.
CONCLUSIONS: Brain tumors induce changes in cerebral blood flow (CBF) in the
cortex, which can be made visible by performing infrared imaging during
cranial surgery. A reduction in CBF beyond the tumor margin improves after
removal of the lesion.
PMID: 15599965 [PubMed - in process]
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| 21: J Neurosurg. 2004 Dec;101(6):1012-7. |
|
Aurora-B dysfunction of multinucleated giant cells in
glioma detected by site-specific phosphorylated antibodies.
Fujita M, Mizuno M, Nagasaka T, Wakabayashi T, Maeda K, Ishii D, Arima T,
Kawajiri A, Inagaki M, Yoshida J.
Department of Neurosurgery, Nagoya University Graduate School of Medicine,
Japan.
OBJECT: The origin of multinucleated giant cells in glioma has not been made
clear. In a previous paper the authors studied multinucleated giant tumor
cells by using mitosis-specific phosphorylated antibodies to determine the
phosphorylation of intermediate filaments and demonstrated that these cells
stay in the early mitotic stage, undergoing neither fusion nor degeneration.
In the current study the authors investigated the possible genetic causes of
multinucleated giant tumor cells. METHODS: Cultured mono- or multinucleated
human glioma cells were immunostained with monoclonal antibodies (mAbs) 4A4,
YT33, TM71, HTA28, YG72, and alphaAIM-1. The three former antibodies
revealed a particular mitotic cell cycle through site-specific
phosphorylation of vimentin; that is, the early phase, mid phase, and late
phase, respectively. The three later antibodies demonstrated phosphorylation
of H3 at Ser28, phosphorylation of vimentin at Ser72, and aurora-B,
respectively, making it possible to identify aurora-B distribution and
function during mitosis. In addition, paraffin-embedded tissue sections
obtained in three patients with giant cell glioblastoma were also examined.
Multinucleated giant tumor cells immunoreacted with the mAb 4A4 and
alphaAIM-1 but not with YT33, TM71, HTA28, and YG72 in vitro and in vivo.
CONCLUSIONS: Findings in this study indicated that multinucleated giant
tumor cells remain in the early mitotic phase because of aurora-B
dysfunction, effecting aberrations in cytoplasmic cleavage without affecting
nuclear division.
PMID: 15597762 [PubMed - in process]
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| 22: J Neurosurg. 2004 Dec;101(6):1004-11. |
|
Distribution kinetics of targeted cytotoxin in glioma by
bolus or convection-enhanced delivery in a murine model.
Kawakami K, Kawakami M, Kioi M, Husain SR, Puri RK.
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene
Therapies, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, Maryland 20892, USA.
OBJECT: Interleukin-13 receptor (IL-13R)-targeted cytotoxin (IL-13-PE38)
displays a potent antitumor activity against a variety of human tumors
including glioblastoma multiforme (GBM) and, thus, this agent is being
tested in the clinical trial for the treatment of recurrent GBM. In this
study, the authors determined the safety and distribution kinetics of IL-13
cytotoxin when infused intracranially by a bolus injection and by
convection-enhanced delivery (CED) in an athymic nude mouse model of GBM.
METHODS: For the safety studies, athymic nude mice were given intracranial
infusions of IL-13 cytotoxin into normal parenchyma by either a bolus
injection or a 7-day-long CED. Toxicity was assessed by performing a
histological examination of the mouse brains. For the drug distribution
studies, nude mice with intracranially implanted U251 GBM tumors were given
an intratumor bolus or a CED infusion of IL-13 cytotoxin. Brain tumor
samples obtained between 0.25 and 72 hours after the infusion were assessed
for drug distribution kinetics by performing immunohistochemical and Western
blot analyses. Based on the histological changes in the tumor and brain, the
maximum tolerated dose of intracranial IL-13 cytotoxin infusion in nude mice
was determined to be 4 microg when delivered by a bolus injection and 10
microg when CED was used. Drug distribution reached the maximum level 1 hour
after the bolus injection and the volume of distribution was determined to
be 19.3 +/- 5.8 mm3. Interleukin-13 cytotoxin was barely detectable 6 hours
after the injection. Interestingly, when delivered by bolus injections IL-13
cytotoxin exhibited superior distribution in larger rather than smaller
tumors. Convection-enhanced delivery was superior for drug distribution in
the U251 tumors because when CED was used the drug remained in the tumors 6
hours after the infusion. CONCLUSIONS: These studies provide confirmation of
a previous hypothesis that CED of IL-13 cytotoxin is superior to bolus
injections not only for the safety of the normal brain but also for
maintaining drug levels for a prolonged period in infused brain tumors.
These findings are highly relevant and important for the optimal clinical
development of IL-13 cytotoxin or any other targeted antitumor agent for GBM
therapy, in which multiple routes of delivery of an agent are being
contemplated.
PMID: 15597761 [PubMed - in process]
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| 23: J Neurosurg. 2004 Dec;101(6):970-6. |
|
Stereotactic biopsy guidance in adults with
supratentorial nonenhancing gliomas: role of perfusion-weighted magnetic
resonance imaging.
Maia AC, Malheiros SM, da Rocha AJ, Stavale JN, Guimaraes IF, Borges LR,
Santos AJ, da Silva CJ, de Melo JG, Lanzoni OP, Gabbai AA, Ferraz FA.
Centro de Medicina Diagnostica Fleury, Sao Paulo/SP, Brazil.
antonio.maia@fleury.com.br
OBJECT: The. diagnosis of low-grade glioma (LGG) cannot be based exclusively
on conventional magnetic resonance (MR) imaging studies, and target
selection for stereotactic biopsy is a crucial issue given the high risk of
sampling errors. The authors hypothesized that perfusion-weighted imaging
could provide information on the microcirculation in presumed supratentorial
LGGs. METHODS: All adult patients with suspected (nonenhancing)
supratentorial LGGs on conventional MR imaging between February 2001 and
February 2004 were included in this study. Preoperative MR imaging was
performed using a dynamic first-pass gadopentate dimeglumine-enhanced spin
echo-echo planar perfusion-weighted sequence, and the tumors' relative
cerebral blood volume (rCBV) measurements were expressed in relation to the
values observed in contralateral white matter. In patients with
heterogeneous tumors a stereotactic biopsy was performed in the higher
perfusion areas before resection. Among 21 patients (16 men and five women
with a mean age of 36 years, range 23-60 years), 10 had diffuse astrocytomas
(World Health Organization Grade II) and 11 had other LGGs and anaplastic
gliomas. On perfusion-weighted images demonstrating heterogeneous tumors,
areas of higher rCBV focus were found to be oligodendrogliomas or anaplastic
astrocytomas on stereotactic biopsy; during tumor resection, however,
specimens were characterized predominantly as astrocytomas. Diffuse
astrocytomas were associated with significantly lower mean rCBV values
compared with those in the other two lesion groups (p < 0.01). The rCBV
ratio cutoff value that permitted better discrimination between diffuse
astrocytomas and the other lesion groups was 1.2 (80% sensitivity and 100%
specificity). CONCLUSIONS: Perfusion-weighted imaging is a feasible method
of reducing the sampling error in the histopathological diagnosis of a
presumed LGG, particularly by improving the selection of targets for
stereotactic biopsy.
PMID: 15597757 [PubMed - in process]
|
Volume 3, Supplement 23 - 30 December 2004