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Friedman, Allan Howard

Overview:

At the present time, I am participating in collaborative research in the areas of primary malignant brain tumors, epilepsy and subarachnoid hemorrhage.

Primary malignant brain tumors are increasing in frequency. Patients harboring glioblastoma, the most malignant primary brain tumor, have a life expectancy of less than one year. In colloboration with the Division of Neurology and the Department of Pathology, clinical and laboratory trials have been initiated to identify better treatment for this condition. At present, trials of monoclonal antibodies and novel chemotherapeutic agents are being carried out.

Although physicians have been interested in seizures since the time of Hippocrates, the origin of seizures remains obscure. At Duke University we have treated approximately thirty seizure patients a year by removing abnormal portions of brain. Tissue from these resections is being analyzed for genetics and receptor abnormalities. Positron emission tomography and magnetic resonance imaging are being used to ferret out the origin of the patient's seizures.

Approximately 28,000 patients each year suffer a ruptured intracranial aneurysm. Approximately ten percent of these patients have a genetic predisposition to forming intracranial aneurysms. In conjunction with the Division of Neurology, we are screening candidate genes searching for the cause of intracranial aneurysms.

Positions:

Guy L. Odom Professor of Neurosurgery, in the School of Medicine

Neurosurgery
School of Medicine

Professor of Neurosurgery

Neurosurgery
School of Medicine

Chief, Division of Neurosurgery in the Department of Surgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1974

M.D. — University of Illinois

News:

Grants:

Gene Targeted Therapy of Brain Tumors

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
September 30, 2009
End Date
February 29, 2012

Novel Targeted Therapeutics for CNS Malignancies

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Collaborating Investigator
Start Date
February 10, 2006
End Date
December 31, 2011

IPA - Bharathi Hattiangady

Administered By
Neurosurgery
AwardedBy
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
October 01, 2010
End Date
September 30, 2011

IPA - Bing Shuai

Administered By
Neurosurgery
AwardedBy
Durham Veterans Affairs Medical Center
Role
Principal Investigator
Start Date
July 01, 2010
End Date
June 30, 2011

Changes in Functional Status Across Therapy for Primary Gilioma

Administered By
Radiation Oncology
AwardedBy
National Cancer Institute
Role
Consultant
Start Date
September 21, 2006
End Date
August 31, 2009

Phase II Study of 44Gy from 131I-81C6 for CNS Tumors

Administered By
Neurosurgery, Neuro-Oncology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
September 29, 2003
End Date
August 31, 2006

GCRC CAP

Administered By
Neurosurgery
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
September 01, 2000
End Date
August 31, 2005

Therapy of Temodar plus O6-BG in Malignant Glioma

Administered By
Neurology, General & Community Neurology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
April 01, 2003
End Date
March 31, 2005

ZD1839 Therapy of Glioblastoma Multiforme

Administered By
Pediatrics
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
April 01, 2001
End Date
March 31, 2003

Temozolomide Resistance in CNS Tumors

Administered By
Pediatrics
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1999
End Date
March 31, 2001

Src On Malignant Human Gliomas And Medulloblastomas

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
April 01, 1993
End Date
March 31, 1994
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Publications:

Masson's tumor of the pineal region: case report.

Intracranial intravascular papillary endothelial hyperplasia (IPEH), also referred to as Masson's tumor, is a condition that rarely occurs in the nervous system. IPEH most frequently occurs extracranially in the skin of the face, skull, neck, and trunk and can easily be mistaken clinically, radiologically, and histologically for angiosarcoma, organizing hematoma, or other vascular malformations. IPEH accounts for roughly 2% of all vascular tumors and is extremely rare intracranially, with only 23 reported cases compared with more than 300 cases of IPEH occurring in the skin and subcutaneous tissue. To date, it has never been reported to occur in the pineal region. The authors report the case of a patient with an IPEH in the pineal region who underwent complex resection and experienced reversal of neurological symptoms.

Authors
Charalambous, LT; Penumaka, A; Komisarow, JM; Hemmerich, AC; Cummings, TJ; Codd, PJ; Friedman, AH
MLA Citation
Charalambous, LT, Penumaka, A, Komisarow, JM, Hemmerich, AC, Cummings, TJ, Codd, PJ, and Friedman, AH. "Masson's tumor of the pineal region: case report." Journal of neurosurgery (August 4, 2017): 1-6.
PMID
28777021
Source
epmc
Published In
Journal of neurosurgery
Publish Date
2017
Start Page
1
End Page
6
DOI
10.3171/2017.2.jns162350

Isolated Deep Ear Canal Pain: Possible Role of Auricular Branch of Vagus Nerve-Case Illustrations with Cadaveric Correlation.

Glossopharyngeal, nervus intermedius, and vagus neuralgias can all present with ear pain. However, to our knowledge, there have been no reports of otalgia as the only symptom of vagus neuralgia. The seventh, ninth, and tenth cranial nerves have many interneural connections, and the exact anatomy and pathophysiology of these neuralgias are often not clear. Moreover, symptoms due to involvement of any of these nerves can be difficult to attribute solely to 1 of them. The overlapping sensory innervation of the external auditory canal can lead to misdiagnosis in patients suffering from otalgia. This report presents a case of pure otalgia due to vascular compression of the vagus nerve (VN) and considers the microanatomic differences between glossopharyngeal and nervus intermedius neuralgia via cadaveric dissections. We report 2 cases of external auditory canal pain that continued following microvascular treatment of trigeminal neuralgia. Intraoperatively and at secondary operation, the posterior inferior cerebellar artery was found to be adherent and to penetrate between the fibers of the VN. Following microvascular treatment of the VN, the pain resolved.This is the first report of vagus neuralgia presenting solely with ear pain. Surgeons should be aware that primary external auditory canal pain can be due to vagus neuralgia via its auricular branch and that such patients can be misdiagnosed with glossopharyngeal or nervus intermedius neuralgias.

Authors
Watanabe, K; Tubbs, RS; Satoh, S; Zomorodi, AR; Liedtke, W; Labidi, M; Friedman, AH; Fukushima, T
MLA Citation
Watanabe, K, Tubbs, RS, Satoh, S, Zomorodi, AR, Liedtke, W, Labidi, M, Friedman, AH, and Fukushima, T. "Isolated Deep Ear Canal Pain: Possible Role of Auricular Branch of Vagus Nerve-Case Illustrations with Cadaveric Correlation." World neurosurgery 96 (December 2016): 293-301.
PMID
27593717
Source
epmc
Published In
World Neurosurgery
Volume
96
Publish Date
2016
Start Page
293
End Page
301
DOI
10.1016/j.wneu.2016.08.102

Microsurgical resection of vestibular schwannomas: complication avoidance.

Vestibular schwannoma (VS) surgery requires appropriate patient selection, meticulous microsurgical technique and optimal post-operative care. Focused radiation is an effective alternative for the treatment of smaller VSs. For VS surgery to remain a reasonable option, surgery must be performed with a limited number of complications. Complication rates for VS surgery have increased over the last decade. This is likely due to (1) decreased surgical volume and as a result decreased microsurgical experience, (2) larger tumors undergoing surgery while smaller tumors are reserved for radiation, and (3) surgery for previously radiated tumors resulting in more difficult anatomic dissection. Appropriate management of complications is paramount. Herein, we discuss complications related to VS microsurgery and methods of avoidance. Specifically, we discuss the most frequently encountered complications, intraoperative monitoring and finally, methods of addressing these complications. With meticulous microsurgical technique, careful intraoperative monitoring and vigilant perioperative care one will ensure optimal patient outcomes.

Authors
Rahimpour, S; Friedman, AH; Fukushima, T; Zomorodi, AR
MLA Citation
Rahimpour, S, Friedman, AH, Fukushima, T, and Zomorodi, AR. "Microsurgical resection of vestibular schwannomas: complication avoidance." Journal of neuro-oncology 130.2 (November 2016): 367-375. (Review)
PMID
27650193
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
130
Issue
2
Publish Date
2016
Start Page
367
End Page
375
DOI
10.1007/s11060-016-2260-4

The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.

Preclinical studies have found differential effects of isoflurane and propofol on the Alzheimer's disease (AD)-associated markers tau, phosphorylated tau (p-tau) and amyloid-β (Aβ).We asked whether isoflurane and propofol have differential effects on the tau/Aβ ratio (the primary outcome), and individual AD biomarkers. We also examined whether genetic/intraoperative factors influenced perioperative changes in AD biomarkers.Patients undergoing neurosurgical/otolaryngology procedures requiring lumbar cerebrospinal fluid (CSF) drain placement were prospectively randomized to receive isoflurane (n = 21) or propofol (n = 18) for anesthetic maintenance. We measured perioperative CSF sample AD markers, performed genotyping assays, and examined intraoperative data from the electronic anesthesia record. A repeated measures ANOVA was used to examine changes in AD markers by anesthetic type over time.The CSF tau/Aβ ratio did not differ between isoflurane- versus propofol-treated patients (p = 1.000). CSF tau/Aβ ratio and tau levels increased 10 and 24 h after drain placement (p = 2.002×10-6 and p = 1.985×10-6, respectively), mean CSF p-tau levels decreased (p = 0.005), and Aβ levels did not change (p = 0.152). There was no interaction between anesthetic treatment and time for any of these biomarkers. None of the examined genetic polymorphisms, including ApoE4, were associated with tau increase (n = 9 polymorphisms, p > 0.05 for all associations).Neurosurgery/otolaryngology procedures are associated with an increase in the CSF tau/Aβ ratio, and this increase was not influenced by anesthetic type. The increased CSF tau/Aβ ratio was largely driven by increases in tau levels. Future work should determine the functional/prognostic significance of these perioperative CSF tau elevations.

Authors
Berger, M; Nadler, JW; Friedman, A; McDonagh, DL; Bennett, ER; Cooter, M; Qi, W; Laskowitz, DT; Ponnusamy, V; Newman, MF; Shaw, LM; Warner, DS; Mathew, JP; James, ML; MAD-PIA trial team,
MLA Citation
Berger, M, Nadler, JW, Friedman, A, McDonagh, DL, Bennett, ER, Cooter, M, Qi, W, Laskowitz, DT, Ponnusamy, V, Newman, MF, Shaw, LM, Warner, DS, Mathew, JP, James, ML, and MAD-PIA trial team, . "The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial." Journal of Alzheimer's disease : JAD 52.4 (April 15, 2016): 1299-1310.
Website
http://hdl.handle.net/10161/12508
PMID
27079717
Source
epmc
Published In
Journal of Alzheimer's disease : JAD
Volume
52
Issue
4
Publish Date
2016
Start Page
1299
End Page
1310
DOI
10.3233/jad-151190

Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival.

The prognosis of elderly patients with glioblastoma (GBM) is universally poor. Currently, few studies have examined postoperative outcomes and the effects of various modern therapies such as bevacizumab on survival in this patient population. In this study, the authors evaluated the effects of various factors on overall survival in a cohort of elderly patients with newly diagnosed GBM.A retrospective review was performed of elderly patients (≥ 65 years old) with newly diagnosed GBM treated between 2004 and 2010. Various characteristics were evaluated in univariate and multivariate stepwise models to examine their effects on complication risk and overall survival.A total of 120 patients were included in the study. The median age was 71 years, and sex was distributed evenly. Patients had a median Karnofsky Performance Scale (KPS) score of 80 and a median of 2 neurological symptoms on presentation. The majority (53.3%) of the patients did not have any comorbidities. Tumors most frequently (43.3%) involved the temporal lobe, followed by the parietal (35.8%), frontal (32.5%), and occipital (15.8%) regions. The majority (57.5%) of the tumors involved eloquent structures. The median tumor size was 4.3 cm. Every patient underwent resection, and 63.3% underwent gross-total resection (GTR). The vast majority (97.3%) of the patients received the postoperative standard of care consisting of radiotherapy with concurrent temozolomide. The majority (59.3%) of patients received additional agents, most commonly consisting of bevacizumab (38.9%). The median survival for all patients was 12.0 months; 26.7% of patients experienced long-term (≥ 2-year) survival. The extent of resection was seen to significantly affect overall survival; patients who underwent GTR had a median survival of 14.1 months, whereas those who underwent subtotal resection had a survival of 9.6 months (p = 0.038). Examination of chemotherapeutic effects revealed that the use of bevacizumab compared with no bevacizumab (20.1 vs 7.9 months, respectively; p < 0.0001) and irinotecan compared with no irinotecan (18.0 vs 9.7 months, respectively; p = 0.027) significantly improved survival. Multivariate stepwise analysis revealed that older age (hazard ratio [HR] 1.06 [95% CI1.02-1.10]; p = 0.0077), a higher KPS score (HR 0.97 [95% CI 0.95-0.99]; p = 0.0082), and the use of bevacizumab (HR 0.51 [95% CI 0.31-0.83]; p = 0.0067) to be significantly associated with survival.This study has demonstrated that GTR confers a modest survival benefit on elderly patients with GBM, suggesting that safe maximal resection is warranted. In addition, bevacizumab significantly increased the overall survival of these elderly patients with GBM; older age and preoperative KPS score also were significant prognostic factors. Although elderly patients with GBM have a poor prognosis, they may experience enhanced survival after the administration of the standard of care and the use of additional chemotherapeutics such as bevacizumab.

Authors
Babu, R; Komisarow, JM; Agarwal, VJ; Rahimpour, S; Iyer, A; Britt, D; Karikari, IO; Grossi, PM; Thomas, S; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Komisarow, JM, Agarwal, VJ, Rahimpour, S, Iyer, A, Britt, D, Karikari, IO, Grossi, PM, Thomas, S, Friedman, AH, and Adamson, C. "Glioblastoma in the elderly: the effect of aggressive and modern therapies on survival." Journal of neurosurgery 124.4 (April 2016): 998-1007.
PMID
26452121
Source
epmc
Published In
Journal of neurosurgery
Volume
124
Issue
4
Publish Date
2016
Start Page
998
End Page
1007
DOI
10.3171/2015.4.jns142200

Surgical management of vestibular schwannomas after failed radiation treatment.

Increasing numbers of patients with vestibular schwannoma (VS) have been treated with focused-beam stereotactic radiation treatment (SRT) including Gamma knife, CyberKnife, X-knife, Novalis, or proton beam therapy. The purpose of this study was to document the incidence of tumor regrowth or symptoms that worsened or first developed following SRT and to discuss surgical strategies for patients who have failed SRT for VS. A consecutive series of 39 patients with SRT failed VS were surgically treated. Clinical symptoms, tumor regrowth at follow-up, intraoperative findings, and surgical outcome were evaluated. There were 15 males and 24 females with a mean age of 51.8 years. Thirty-six patients (92.3%) demonstrated steady tumor growth after SRT. Two (5.1%) patients with slight increase of the mass underwent surgical resection because of development of unbearable facial pain. Symptoms that worsened or newly developed following SRT in this series were deafness (41%), dizziness (35.9%), facial numbness (25.6%), tinnitus (20.5%), facial nerve palsy (7.7%), and facial pain (7.7%). Intraoperative findings demonstrated fibrous changes of the tumor mass, cyst formation, and brownish-yellow or purple discoloration of the tumor capsule. Severe adhesions between the tumor capsule and cranial nerves, vessels, and the brainstem were observed in 69.2%. Additionally, the facial nerve was more fragile and irritable in all cases. Gross total resection (GTR) was achieved in 33.3% of patients, near-total resection (NTR) in 35.9%, and subtotal resection (STR) in 30.8% of patients. New facial nerve palsy was seen in seven patients (19.4%) postoperatively. Our findings suggest that patients with VS who fail SRT with either tumor progression or worsening of clinical symptoms will have an increased rate of adhesions to the neurovascular structures and may have radiation-influenced neuromalacia. Salvage surgery of radiation-failed tumors is more difficult and will have a higher risk of postoperative complications. Radical total resection may not be feasible, and conservative modality of subtotal resection needs to be considered to avoid new neurologic deficits.

Authors
Nonaka, Y; Fukushima, T; Watanabe, K; Friedman, AH; Cunningham, CD; Zomorodi, AR
MLA Citation
Nonaka, Y, Fukushima, T, Watanabe, K, Friedman, AH, Cunningham, CD, and Zomorodi, AR. "Surgical management of vestibular schwannomas after failed radiation treatment." Neurosurgical review 39.2 (April 2016): 303-312.
PMID
26782633
Source
epmc
Published In
Neurosurgical Review
Volume
39
Issue
2
Publish Date
2016
Start Page
303
End Page
312
DOI
10.1007/s10143-015-0690-7

MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.

The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while correlating positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.

Authors
Hu, J; Sun, T; Wang, H; Chen, Z; Wang, S; Yuan, L; Liu, T; Li, H-R; Wang, P; Feng, Y; Wang, Q; McLendon, RE; Friedman, AH; Keir, ST; Bigner, DD; Rathmell, J; Fu, X-D; Li, Q-J; Wang, H; Wang, X-F
MLA Citation
Hu, J, Sun, T, Wang, H, Chen, Z, Wang, S, Yuan, L, Liu, T, Li, H-R, Wang, P, Feng, Y, Wang, Q, McLendon, RE, Friedman, AH, Keir, ST, Bigner, DD, Rathmell, J, Fu, X-D, Li, Q-J, Wang, H, and Wang, X-F. "MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B." Cancer cell 29.1 (January 2016): 49-60.
Website
http://hdl.handle.net/10161/11667
PMID
26766590
Source
epmc
Published In
Cancer Cell
Volume
29
Issue
1
Publish Date
2016
Start Page
49
End Page
60
DOI
10.1016/j.ccell.2015.12.005

Central Nervous System Cancers, Version 1.2015.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Central Nervous System (CNS) Cancers provide interdisciplinary recommendations for managing adult CNS cancers. Primary and metastatic brain tumors are a heterogeneous group of neoplasms with varied outcomes and management strategies. These NCCN Guidelines Insights summarize the NCCN CNS Cancers Panel's discussion and highlight notable changes in the 2015 update. This article outlines the data and provides insight into panel decisions regarding adjuvant radiation and chemotherapy treatment options for high-risk newly diagnosed low-grade gliomas and glioblastomas. Additionally, it describes the panel's assessment of new data and the ongoing debate regarding the use of alternating electric field therapy for high-grade gliomas.

Authors
Nabors, LB; Portnow, J; Ammirati, M; Baehring, J; Brem, H; Brown, P; Butowski, N; Chamberlain, MC; Fenstermaker, RA; Friedman, A; Gilbert, MR; Hattangadi-Gluth, J; Holdhoff, M; Junck, L; Kaley, T; Lawson, R; Loeffler, JS; Lovely, MP; Moots, PL; Mrugala, MM; Newton, HB; Parney, I; Raizer, JJ; Recht, L; Shonka, N; Shrieve, DC; Sills, AK; Swinnen, LJ; Tran, D; Tran, N; Vrionis, FD; Weiss, S; Wen, PY; McMillian, N; Engh, AM
MLA Citation
Nabors, LB, Portnow, J, Ammirati, M, Baehring, J, Brem, H, Brown, P, Butowski, N, Chamberlain, MC, Fenstermaker, RA, Friedman, A, Gilbert, MR, Hattangadi-Gluth, J, Holdhoff, M, Junck, L, Kaley, T, Lawson, R, Loeffler, JS, Lovely, MP, Moots, PL, Mrugala, MM, Newton, HB, Parney, I, Raizer, JJ, Recht, L, Shonka, N, Shrieve, DC, Sills, AK, Swinnen, LJ, Tran, D, Tran, N, Vrionis, FD, Weiss, S, Wen, PY, McMillian, N, and Engh, AM. "Central Nervous System Cancers, Version 1.2015." Journal of the National Comprehensive Cancer Network : JNCCN 13.10 (October 2015): 1191-1202.
PMID
26483059
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
13
Issue
10
Publish Date
2015
Start Page
1191
End Page
1202
DOI
10.6004/jnccn.2015.0148

Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide.

Therapeutic vaccination of patients with cancer-targeting tumor-associated antigens is a promising strategy for the specific eradication of invasive malignancies with minimal toxicity to normal tissues. However, as increasingly potent modalities for stimulating immunologic responses are developed for clinical evaluation, the risk of inflammatory and autoimmune toxicities also may be exacerbated. In this report, we describe the induction of a severe (grade 3) immunologic reaction in a patient with newly diagnosed glioblastoma (GBM) receiving autologous RNA-pulsed dendritic cell (DC) vaccines admixed with GM-CSF and administered coordinately with cycles of dose-intensified temozolomide. Shortly after the eighth administration of the admixed intradermal vaccine, the patient experienced dizziness, flushing, conjunctivitis, headache, and the outbreak of a disseminated macular/papular rash and bilateral indurated injection sites. Immunologic workup of patient reactivity revealed sensitization to the GM-CSF component of the vaccine and the production of high levels of anti-GM-CSF autoantibodies during vaccination. Removal of GM-CSF from the DC vaccine allowed continued vaccination without incident. Despite the known lymphodepletive and immunosuppressive effects of temozolomide, these observations demonstrate the capacity for the generation of severe immunologic reactivity in patients with GBM receiving DC-based therapy during adjuvant dose-intensified temozolomide.

Authors
Mitchell, DA; Sayour, EJ; Reap, E; Schmittling, R; DeLeon, G; Norberg, P; Desjardins, A; Friedman, AH; Friedman, HS; Archer, G; Sampson, JH
MLA Citation
Mitchell, DA, Sayour, EJ, Reap, E, Schmittling, R, DeLeon, G, Norberg, P, Desjardins, A, Friedman, AH, Friedman, HS, Archer, G, and Sampson, JH. "Severe adverse immunologic reaction in a patient with glioblastoma receiving autologous dendritic cell vaccines combined with GM-CSF and dose-intensified temozolomide." Cancer immunology research 3.4 (April 2015): 320-325.
PMID
25387895
Source
epmc
Published In
Cancer Immunology Research
Volume
3
Issue
4
Publish Date
2015
Start Page
320
End Page
325
DOI
10.1158/2326-6066.cir-14-0100

Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: A single-center experience with 102 patients

© 2012 by the Congress of Neurological Surgeons. BACKGROUND: Surgical outcomes for intramedullary spinal cord tumors are affected by many variables including tumor histology and preoperative neurological function. OBJECTIVE: To analyze the impact of tumor histology on neurological outcome in primary intramedullary spinal cord tumors. METHODS: A retrospective review of 102 consecutive patients with intramedullary spinal cord tumors treated at a single institution between January 1998 and March 2009. RESULTS: Ependymomas were the most common tumors with 55 (53.9%), followed by 21 astrocytomas (20.6%), 12 hemangioblastomas (11.8%), and 14 miscellaneous tumors (13.7%). Gross tota l resection was achieved in 50 ependymomas (90.9%), 3 astrocytomas (14.3%), 11 hemangioblastomas (91.7%), and 12 miscellaneous tumors (85.7%). At a mean follow-up of 41.8 months (range, 1-132 months), we observed recurrences in 4 ependymoma cases (7.3%), 10 astrocytoma cases (47.6%), 1 miscellaneous tumor case (7.1%), and no recurrence in hemangioblastoma cases. When analyzed by tumor location, there was no difference in neurological outcomes (P = .66). At the time of their last follow-up visit, 11 patients (20%) with an ependymoma improved, 38 (69%) remained the same, and 6 (10.9%) worsened. In patients with an astrocytoma, 1 (4.8%) improved, 10 (47.6%) remained the same, and 10 (47.6%) worsened. One patient (8.3%) with a hemangioblastoma improved and 11 (91.7%) remained the same. No patient with a hemangioblastoma worsened. In the miscellaneous tumor group, 2 (14.3%) improved, 10 (71.4%) remained the same, and 2 (14.3%) worsened. Preoperative neurological status (P = .02), tumor histology (P = .005), and extent of resection (P , .0001) were all predictive of functional neurological outcomes. CONCLUSION: Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence.

Authors
Karikari, IO; Nimjee, SM; Hodges, TR; Cutrell, E; Hughes, BD; Powers, CJ; Mehta, AI; Hardin, C; Bagley, CA; Isaacs, RE; Haglund, MM; Friedman, AH
MLA Citation
Karikari, IO, Nimjee, SM, Hodges, TR, Cutrell, E, Hughes, BD, Powers, CJ, Mehta, AI, Hardin, C, Bagley, CA, Isaacs, RE, Haglund, MM, and Friedman, AH. "Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: A single-center experience with 102 patients." Neurosurgery 76 (March 26, 2015): 188-197.
Source
scopus
Published In
Neurosurgery
Volume
76
Publish Date
2015
Start Page
188
End Page
197
DOI
10.1227/NEU.0b013e3181fe3794

Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients.

After stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses. As such, autologous DCs generated ex vivo have been pulsed with tumour antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers including glioblastoma, the factors dictating DC vaccine efficacy remain poorly understood. Here we show that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumour-antigen-specific DCs. To assess the effect of vaccine site pre-conditioning in humans, we randomized patients with glioblastoma to pre-conditioning with either mature DCs or Td unilaterally before bilateral vaccination with DCs pulsed with Cytomegalovirus phosphoprotein 65 (pp65) RNA. We and other laboratories have shown that pp65 is expressed in more than 90% of glioblastoma specimens but not in surrounding normal brain, providing an unparalleled opportunity to subvert this viral protein as a tumour-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumour growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve anti-tumour immunotherapy.

Authors
Mitchell, DA; Batich, KA; Gunn, MD; Huang, M-N; Sanchez-Perez, L; Nair, SK; Congdon, KL; Reap, EA; Archer, GE; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; Coan, A; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Sampson, JH
MLA Citation
Mitchell, DA, Batich, KA, Gunn, MD, Huang, M-N, Sanchez-Perez, L, Nair, SK, Congdon, KL, Reap, EA, Archer, GE, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, Coan, A, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Sampson, JH. "Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients." Nature 519.7543 (March 11, 2015): 366-369.
PMID
25762141
Source
epmc
Published In
Nature
Volume
519
Issue
7543
Publish Date
2015
Start Page
366
End Page
369
DOI
10.1038/nature14320

Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: a single-center experience with 102 patients.

BACKGROUND: Surgical outcomes for intramedullary spinal cord tumors are affected by many variables including tumor histology and preoperative neurological function. OBJECTIVE: To analyze the impact of tumor histology on neurological outcome in primary intramedullary spinal cord tumors. METHODS: A retrospective review of 102 consecutive patients with intramedullary spinal cord tumors treated at a single institution between January 1998 and March 2009. RESULTS: Ependymomas were the most common tumors with 55 (53.9%), followed by 21 astrocytomas (20.6%), 12 hemangioblastomas (11.8%), and 14 miscellaneous tumors (13.7%). Gross total resection was achieved in 50 ependymomas (90.9%), 3 astrocytomas (14.3%), 11 hemangioblastomas (91.7%), and 12 miscellaneous tumors (85.7%). At a mean follow-up of 41.8 months (range, 1-132 months), we observed recurrences in 4 ependymoma cases (7.3%), 10 astrocytoma cases (47.6%), 1 miscellaneous tumor case (7.1%), and no recurrence in hemangioblastoma cases. When analyzed by tumor location, there was no difference in neurological outcomes (P = .66). At the time of their last follow-up visit, 11 patients (20%) with an ependymoma improved, 38 (69%) remained the same, and 6 (10.9%) worsened. In patients with an astrocytoma, 1 (4.8%) improved, 10 (47.6%) remained the same, and 10 (47.6%) worsened. One patient (8.3%) with a hemangioblastoma improved and 11 (91.7%) remained the same. No patient with a hemangioblastoma worsened. In the miscellaneous tumor group, 2 (14.3%) improved, 10 (71.4%) remained the same, and 2 (14.3%) worsened. Preoperative neurological status (P = .02), tumor histology (P = .005), and extent of resection (P < .0001) were all predictive of functional neurological outcomes. CONCLUSION: Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence.

Authors
Karikari, IO; Nimjee, SM; Hodges, TR; Cutrell, E; Hughes, BD; Powers, CJ; Mehta, AI; Hardin, C; Bagley, CA; Isaacs, RE; Haglund, MM; Friedman, AH
MLA Citation
Karikari, IO, Nimjee, SM, Hodges, TR, Cutrell, E, Hughes, BD, Powers, CJ, Mehta, AI, Hardin, C, Bagley, CA, Isaacs, RE, Haglund, MM, and Friedman, AH. "Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: a single-center experience with 102 patients." Neurosurgery 76 Suppl 1 (March 2015): S4-S13.
PMID
25692367
Source
epmc
Published In
Neurosurgery
Volume
76 Suppl 1
Publish Date
2015
Start Page
S4
End Page
S13
DOI
10.1227/01.neu.0000462073.71915.12

Oncolytic polio virotherapy of cancer.

Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the proinflammatory and immunogenic effects of viral tumor infection (oncolytic immunotherapy) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic.

Authors
Brown, MC; Dobrikova, EY; Dobrikov, MI; Walton, RW; Gemberling, SL; Nair, SK; Desjardins, A; Sampson, JH; Friedman, HS; Friedman, AH; Tyler, DS; Bigner, DD; Gromeier, M
MLA Citation
Brown, MC, Dobrikova, EY, Dobrikov, MI, Walton, RW, Gemberling, SL, Nair, SK, Desjardins, A, Sampson, JH, Friedman, HS, Friedman, AH, Tyler, DS, Bigner, DD, and Gromeier, M. "Oncolytic polio virotherapy of cancer." Cancer 120.21 (November 2014): 3277-3286. (Review)
PMID
24939611
Source
epmc
Published In
Cancer
Volume
120
Issue
21
Publish Date
2014
Start Page
3277
End Page
3286
DOI
10.1002/cncr.28862

Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Central Nervous System Cancers provide multidisciplinary recommendations for the clinical management of patients with cancers of the central nervous system. These NCCN Guidelines Insights highlight recent updates regarding the management of metastatic brain tumors using radiation therapy. Use of stereotactic radiosurgery (SRS) is no longer limited to patients with 3 or fewer lesions, because data suggest that total disease burden, rather than number of lesions, is predictive of survival benefits associated with the technique. SRS is increasingly becoming an integral part of management of patients with controlled, low-volume brain metastases.

Authors
Nabors, LB; Portnow, J; Ammirati, M; Brem, H; Brown, P; Butowski, N; Chamberlain, MC; DeAngelis, LM; Fenstermaker, RA; Friedman, A; Gilbert, MR; Hattangadi-Gluth, J; Hesser, D; Holdhoff, M; Junck, L; Lawson, R; Loeffler, JS; Moots, PL; Mrugala, MM; Newton, HB; Raizer, JJ; Recht, L; Shonka, N; Shrieve, DC; Sills, AK; Swinnen, LJ; Tran, D; Tran, N; Vrionis, FD; Wen, PY; McMillian, NR; Ho, M
MLA Citation
Nabors, LB, Portnow, J, Ammirati, M, Brem, H, Brown, P, Butowski, N, Chamberlain, MC, DeAngelis, LM, Fenstermaker, RA, Friedman, A, Gilbert, MR, Hattangadi-Gluth, J, Hesser, D, Holdhoff, M, Junck, L, Lawson, R, Loeffler, JS, Moots, PL, Mrugala, MM, Newton, HB, Raizer, JJ, Recht, L, Shonka, N, Shrieve, DC, Sills, AK, Swinnen, LJ, Tran, D, Tran, N, Vrionis, FD, Wen, PY, McMillian, NR, and Ho, M. "Central nervous system cancers, version 2.2014. Featured updates to the NCCN Guidelines." Journal of the National Comprehensive Cancer Network : JNCCN 12.11 (November 2014): 1517-1523.
PMID
25361798
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
12
Issue
11
Publish Date
2014
Start Page
1517
End Page
1523
DOI
10.6004/jnccn.2014.0151

Morbidity, mortality, and health care costs for patients undergoing spine surgery following the ACGME resident duty-hour reform: Clinical article.

OBJECT: The Accreditation Council for Graduate Medical Education (ACGME) implemented resident duty-hour restrictions on July 1, 2003, in concern for patient and resident safety. Whereas studies have shown that duty-hour restrictions have increased resident quality of life, there have been mixed results with respect to patient outcomes. In this study, the authors have evaluated the effect of duty-hour restrictions on morbidity, mortality, length of stay (LOS), and charges in patients who underwent spine surgery. METHODS: The Nationwide Inpatient Sample was used to evaluate the effect of duty-hour restrictions on complications, mortality, LOS, and charges by comparing the prereform (2000-2002) and postreform (2005-2008) periods. Outcomes were compared between nonteaching and teaching hospitals using a difference-in-differences (DID) method. Results A total of 693,058 patients were included in the study. The overall complication rate was 8.6%, with patients in the postreform era having a significantly higher rate than those in the pre-duty-hour restriction era (8.7% vs. 8.4%, p < 0.0001). Examination of hospital teaching status revealed complication rates to decrease in nonteaching hospitals (8.2% vs. 7.6%, p < 0.0001) while increasing in teaching institutions (8.6% vs. 9.6%, p < 0.0001) in the duty-hour reform era. The DID analysis to compare the magnitude in change between teaching and nonteaching institutions revealed that teaching institutions to had a significantly greater increase in complications during the postreform era (p = 0.0002). The overall mortality rate was 0.37%, with no significant difference between the pre- and post-duty-hour eras (0.39% vs. 0.36%, p = 0.12). However, the mortality rate significantly decreased in nonteaching hospitals in the postreform era (0.30% vs. 0.23%, p = 0.0008), while remaining the same in teaching institutions (0.46% vs. 0.46%, p = 0.75). The DID analysis to compare the changes in mortality between groups revealed that the difference between the effects approached significance (p = 0.069). The mean LOS for all patients was 4.2 days, with hospital stay decreasing in nonteaching hospitals (3.7 vs. 3.5 days, p < 0.0001) while significantly increasing in teaching institutions (4.7 vs. 4.8 days, p < 0.0001). The DID analysis did not demonstrate the magnitude of change for each group to differ significantly (p = 0.26). Total patient charges were seen to rise significantly in the post-duty-hour reform era, increasing from $40,000 in the prereform era to $69,000 in the postreform era. The DID analysis did not reveal a significant difference between the changes in charges between teaching and nonteaching hospitals (p = 0.55). CONCLUSIONS: The implementation of duty-hour restrictions was associated with an increased risk of postoperative complications for patients undergoing spine surgery. Therefore, contrary to its intended purpose, duty-hour reform may have resulted in worse patient outcomes. Additional studies are needed to evaluate strategies to mitigate these effects and assist in the development of future health care policy.

Authors
Babu, R; Thomas, S; Hazzard, MA; Lokhnygina, YV; Friedman, AH; Gottfried, ON; Isaacs, RE; Boakye, M; Patil, CG; Bagley, CA; Haglund, MM; Lad, SP
MLA Citation
Babu, R, Thomas, S, Hazzard, MA, Lokhnygina, YV, Friedman, AH, Gottfried, ON, Isaacs, RE, Boakye, M, Patil, CG, Bagley, CA, Haglund, MM, and Lad, SP. "Morbidity, mortality, and health care costs for patients undergoing spine surgery following the ACGME resident duty-hour reform: Clinical article." Journal of neurosurgery. Spine 21.4 (October 2014): 502-515.
PMID
24995600
Source
epmc
Published In
Journal of neurosurgery. Spine
Volume
21
Issue
4
Publish Date
2014
Start Page
502
End Page
515
DOI
10.3171/2014.5.spine13283

miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways.

Glioblastoma (GBM) is the most common and lethal brain tumor in adults. Glioma-initiating cells (GICs) are stem-like cells that have been implicated in glioblastoma progression and recurrence; however, the distinct properties of GICs and non-GICs within GBM tumors are largely uncharacterized. Here, we evaluated stem cell-associated microRNA (miR) expression in GICs from GBM patients and GICs derived from xenografted human glioma cell lines and determined that miR-33a promotes GIC growth and self-renewal. Moreover, evaluation of a GBM tissue array revealed that higher miR-33a expression was associated with poor prognosis of GBM patients. Antagonizing miR-33a function in GICs reduced self-renewal and tumor progression in immune-compromised mice, whereas overexpression of miR-33a in non-GICs promoted the display of features associated with GICs. We identified the mRNAs encoding phosphodiesterase 8A (PDE8A) and UV radiation resistance-associated gene (UVRAG) as direct miR-33a targets. PDE8A and UVRAG negatively regulated the cAMP/PKA and NOTCH pathways, respectively; therefore, miR-33a-dependent reduction of these proteins promoted growth and self-renewal of GICs by enhancing PKA and NOTCH activity. Furthermore, in GBM specimens, there was an inverse correlation between the expression levels of miR-33a and PDE8A and UVRAG expression. These findings reveal a miR-33a-centered signaling network that promotes GIC maintenance and has potential as a therapeutic target for GBM treatment.

Authors
Wang, H; Sun, T; Hu, J; Zhang, R; Rao, Y; Wang, S; Chen, R; McLendon, RE; Friedman, AH; Keir, ST; Bigner, DD; Li, Q-J; Wang, H; Wang, X-F
MLA Citation
Wang, H, Sun, T, Hu, J, Zhang, R, Rao, Y, Wang, S, Chen, R, McLendon, RE, Friedman, AH, Keir, ST, Bigner, DD, Li, Q-J, Wang, H, and Wang, X-F. "miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways." The Journal of clinical investigation 124.10 (October 2014): 4489-4502.
PMID
25202981
Source
epmc
Published In
Journal of Clinical Investigation
Volume
124
Issue
10
Publish Date
2014
Start Page
4489
End Page
4502
DOI
10.1172/jci75284

A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma.

Robust methodology that allows objective, automated, and observer-independent measurements of brain tumor volume, especially after resection, is lacking. Thus, determination of tumor response and progression in neurooncology is unreliable. The objective of this study was to determine if a semi-automated volumetric method for quantifying enhancing tissue would perform with high reproducibility and low interobserver variability.Fifty-seven MR images from 13 patients with glioblastoma were assessed using our method, by 2 neuroradiologists, 1 neurosurgeon, 1 neurosurgical resident, 1 nurse practitioner, and 1 medical student. The 2 neuroradiologists also performed traditional 1-dimensional (1D) and 2-dimensional (2D) measurements. Intraclass correlation coefficients (ICCs) assessed interobserver variability between measurements. Radiological response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) guidelines and Macdonald criteria. Kappa statistics described interobserver variability of volumetric radiological response determinations.There was strong agreement for 1D (RECIST) and 2D (Macdonald) measurements between neuroradiologists (ICC = 0.42 and 0.61, respectively), but the agreement using the authors' novel automated approach was significantly stronger (ICC = 0.97). The volumetric method had the strongest agreement with regard to radiological response (κ = 0.96) when compared with 2D (κ = 0.54) or 1D (κ = 0.46) methods. Despite diverse levels of experience of the users of the volumetric method, measurements using the volumetric program remained remarkably consistent in all users (0.94).Interobserver variability using this new semi-automated method is less than the variability with traditional methods of tumor measurement. This new method is objective, quick, and highly reproducible among operators with varying levels of expertise. This approach should be further evaluated as a potential standard for response assessment based on contrast enhancement in brain tumors.

Authors
Kanaly, CW; Mehta, AI; Ding, D; Hoang, JK; Kranz, PG; Herndon, JE; Coan, A; Crocker, I; Waller, AF; Friedman, AH; Reardon, DA; Sampson, JH
MLA Citation
Kanaly, CW, Mehta, AI, Ding, D, Hoang, JK, Kranz, PG, Herndon, JE, Coan, A, Crocker, I, Waller, AF, Friedman, AH, Reardon, DA, and Sampson, JH. "A novel, reproducible, and objective method for volumetric magnetic resonance imaging assessment of enhancing glioblastoma." Journal of neurosurgery 121.3 (September 2014): 536-542.
PMID
25036205
Source
epmc
Published In
Journal of neurosurgery
Volume
121
Issue
3
Publish Date
2014
Start Page
536
End Page
542
DOI
10.3171/2014.4.jns121952

Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors.

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular characteristics which may aid in the treatment of these aggressive tumors.

Authors
Babu, R; Kranz, PG; Agarwal, V; McLendon, RE; Thomas, S; Friedman, AH; Bigner, DD; Adamson, C
MLA Citation
Babu, R, Kranz, PG, Agarwal, V, McLendon, RE, Thomas, S, Friedman, AH, Bigner, DD, and Adamson, C. "Malignant brainstem gliomas in adults: clinicopathological characteristics and prognostic factors." Journal of neuro-oncology 119.1 (August 2014): 177-185.
PMID
24838419
Source
epmc
Published In
Journal of Neuro-Oncology
Volume
119
Issue
1
Publish Date
2014
Start Page
177
End Page
185
DOI
10.1007/s11060-014-1471-9

Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures following the ACGME resident duty-hour restrictions.

On July 1, 2003, the Accreditation Council for Graduate Medical Education (ACGME) implemented duty-hour restrictions for resident physicians due to concerns for patient and resident safety. Though duty-hour restrictions have increased resident quality of life, studies have shown mixed results with respect to patient outcomes. In this study, the authors have evaluated the effect of duty-hour restrictions on morbidity, mortality, length of stay, and charges in patients who underwent brain tumor and cerebrovascular procedures.The Nationwide Inpatient Sample was used to evaluate the effect of duty-hour restrictions on complications, mortality, length of stay, and charges by comparing the pre-reform (2000-2002) and post-reform (2005-2008) periods. Outcomes were compared between nonteaching and teaching hospitals using a difference-in-differences (DID) method.A total of 90,648 patients were included in the analysis. The overall complication rate was 11.7%, with the rates not significantly differing between the pre- and post-duty hour eras (p = 0.26). Examination of hospital teaching status revealed that complication rates decreased in nonteaching hospitals (12.1% vs 10.4%, p = 0.0004) and remained stable in teaching institutions (11.8% vs 11.9%, p = 0.73) in the post-reform era. Multivariate analysis demonstrated a significantly higher complication risk in teaching institutions (OR 1.33 [95% CI 1.11-1.59], p = 0.0022), with no significant change in nonteaching hospitals (OR 1.11 [95% CI 0.91-1.37], p = 0.31). A DID analysis to compare the magnitude in change between teaching and nonteaching institutions revealed that teaching hospitals had a significantly greater increase in complications during the post-reform era than nonteaching hospitals (p = 0.040). The overall mortality rate was 3.0%, with a significant decrease occurring in the post-reform era in both nonteaching (5.0% vs 3.2%, p < 0.0001) and teaching (3.2% vs 2.3%, p < 0.0001) hospitals. DID analysis to compare the changes in mortality between groups did not reveal a significant difference (p = 0.40). The mean length of stay for all patients was 8.7 days, with hospital stay decreasing from 9.2 days to 8.3 days in the post-reform era (p < 0.0001). The DID analysis revealed a greater length of stay decrease in nonteaching hospitals than teaching institutions, which approached significance (p = 0.055). Patient charges significantly increased in the post-reform era for all patients, increasing from $70,900 to $96,100 (p < 0.0001). The DID analysis did not reveal a significant difference between the changes in charges between teaching and nonteaching hospitals (p = 0.17).The implementation of duty-hour restrictions correlated with an increased risk of postoperative complications for patients undergoing brain tumor and cerebrovascular neurosurgical procedures. Duty-hour reform may therefore be associated with worse patient outcomes, contrary to its intended purpose. Due to the critical condition of many neurosurgical patients, this patient population is most sensitive and likely to be negatively affected by proposed future increased restrictions.

Authors
Babu, R; Thomas, S; Hazzard, MA; Friedman, AH; Sampson, JH; Adamson, C; Zomorodi, AR; Haglund, MM; Patil, CG; Boakye, M; Lad, SP
MLA Citation
Babu, R, Thomas, S, Hazzard, MA, Friedman, AH, Sampson, JH, Adamson, C, Zomorodi, AR, Haglund, MM, Patil, CG, Boakye, M, and Lad, SP. "Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures following the ACGME resident duty-hour restrictions." Journal of neurosurgery 121.2 (August 2014): 262-276.
PMID
24926647
Source
epmc
Published In
Journal of neurosurgery
Volume
121
Issue
2
Publish Date
2014
Start Page
262
End Page
276
DOI
10.3171/2014.5.jns1314

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.

Authors
Zhang, L; Chen, LH; Wan, H; Yang, R; Wang, Z; Feng, J; Yang, S; Jones, S; Wang, S; Zhou, W; Zhu, H; Killela, PJ; Zhang, J; Wu, Z; Li, G; Hao, S; Wang, Y; Webb, JB; Friedman, HS; Friedman, AH; McLendon, RE; He, Y; Reitman, ZJ; Bigner, DD; Yan, H
MLA Citation
Zhang, L, Chen, LH, Wan, H, Yang, R, Wang, Z, Feng, J, Yang, S, Jones, S, Wang, S, Zhou, W, Zhu, H, Killela, PJ, Zhang, J, Wu, Z, Li, G, Hao, S, Wang, Y, Webb, JB, Friedman, HS, Friedman, AH, McLendon, RE, He, Y, Reitman, ZJ, Bigner, DD, and Yan, H. "Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas." Nature genetics 46.7 (July 2014): 726-730.
PMID
24880341
Source
epmc
Published In
Nature Genetics
Volume
46
Issue
7
Publish Date
2014
Start Page
726
End Page
730
DOI
10.1038/ng.2995

Hearing preservation surgery for vestibular schwannomas via the retrosigmoid transmeatal approach: surgical tips.

Maximum tumor extirpation with preservation of the facial and cochlear nerve function is the goal of surgery for vestibular schwannoma. To preserve cochlear nerve function, the surgeon must employ a detailed knowledge of microanatomy, precise microsurgical techniques, and persistence. This paper describes the "pearls" of surgical techniques based on the anatomical study inside the mastoid from the view of the retrosigmoid transmeatal approach. A total of 592 consecutive patients underwent surgical removal of unilateral vestibular schwannoma (VS) between January 1994 and December 2009. The hearing preservation rate was 53.7 % for large vestibular schwannomas (>20 mm in diameter) and 74.1 % for tumors of all sizes. The key procedures for hearing preservation surgery are as follows: bloodless microdissection, sufficient coring-debulking, capsular elevation to locate the facial and cochlear nerves both electrophysiologically and by visual observation, sharp dissection of the facial and cochlear nerves, and avoidance of heat and mechanical injury to the nerves, the internal auditory artery, and the brain stem. Besides these techniques, appropriate instruments are essential to preserve hearing. The function of the facial and cochlear nerves should be the foremost concern. Meticulous techniques and the knowledge of microsurgical anatomy lead to hearing preservation with maximum tumor removal.

Authors
Wanibuchi, M; Fukushima, T; Friedman, AH; Watanabe, K; Akiyama, Y; Mikami, T; Iihoshi, S; Murakami, T; Sugino, T; Mikuni, N
MLA Citation
Wanibuchi, M, Fukushima, T, Friedman, AH, Watanabe, K, Akiyama, Y, Mikami, T, Iihoshi, S, Murakami, T, Sugino, T, and Mikuni, N. "Hearing preservation surgery for vestibular schwannomas via the retrosigmoid transmeatal approach: surgical tips." Neurosurgical review 37.3 (July 2014): 431-444.
PMID
24752423
Source
epmc
Published In
Neurosurgical Review
Volume
37
Issue
3
Publish Date
2014
Start Page
431
End Page
444
DOI
10.1007/s10143-014-0543-9

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas

Authors
Zhang, L; Chen, LH; Wan, H; Yang, R; Wang, Z; Feng, J; Yang, S; Jones, S; Wang, S; Zhou, W; Zhu, H; Killela, PJ; Zhang, J; Wu, Z; Li, G; Hao, S; Wang, Y; Webb, JB; Friedman, HS; Friedman, AH; McLendon, RE; He, Y; Reitman, ZJ; Bigner, DD; Yan, H
MLA Citation
Zhang, L, Chen, LH, Wan, H, Yang, R, Wang, Z, Feng, J, Yang, S, Jones, S, Wang, S, Zhou, W, Zhu, H, Killela, PJ, Zhang, J, Wu, Z, Li, G, Hao, S, Wang, Y, Webb, JB, Friedman, HS, Friedman, AH, McLendon, RE, He, Y, Reitman, ZJ, Bigner, DD, and Yan, H. "Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas." Nature Genetics 46.7 (June 1, 2014): 726-730.
Source
crossref
Published In
Nature Genetics
Volume
46
Issue
7
Publish Date
2014
Start Page
726
End Page
730
DOI
10.1038/ng.2995

Surgical management of nonvascular lesions around the oculomotor nerve.

OBJECTIVE: Schwannomas originating from the oculomotor nerve are extremely rare. We report our experience in the management of oculomotor schwannomas and other lesions mimicking them, and discuss operative strategy for these rare tumors emphasizing oculomotor nerve preservation. METHODS: The clinical records of our patients and all those reported in the literature focusing on oculomotor schwannomas were reviewed and analyzed. The clinical presentations, operative approaches, complications, and results were studied. RESULTS: Between 1983 and 2010, six patients with primary oculomotor nerve lesions were treated. Three of them had schwannomas. Two others had pathologies that mimicked an oculomotor schwannoma and one was suspected as schwannoma. In the literature there were 55 previous cases of oculomotor schwannomas reported (surgical treated, 41 cases; observed, 9; gamma knife surgery treated, 2; autopsy, 3). Patients presented most commonly with diplopia, followed by headache and ptosis as initial symptoms. Out of 55 patients including the present 3 cases (3 autopsy cases were excluded), 30 patients (54.5%) finally developed oculomotor nerve palsy. Fifteen of 44 patients (34.1%) who underwent surgery developed persistent postoperative oculomotor palsy. Among them, 6 patients developed total palsy after surgery. Five of 12 patients (41.7%) who did not undergo surgery also developed oculomotor palsy. Oculomotor schwannomas most often grow its cisternal segment (48.3%) followed by intracavernous (39.6%) and cisternocavernous segments (12.1%). CONCLUSION: The microsurgical resection of oculomotor schwannomas carries a risk of worsening preoperative oculomotor nerve function; however, this is often transient. Considerable technical training and microanatomical knowledge of the region is required to optimize outcome.

Authors
Nonaka, Y; Fukushima, T; Friedman, AH; Kolb, LE; Bulsara, KR
MLA Citation
Nonaka, Y, Fukushima, T, Friedman, AH, Kolb, LE, and Bulsara, KR. "Surgical management of nonvascular lesions around the oculomotor nerve." World Neurosurg 81.5-6 (May 2014): 798-809.
PMID
23182737
Source
pubmed
Published In
World Neurosurgery
Volume
81
Issue
5-6
Publish Date
2014
Start Page
798
End Page
809
DOI
10.1016/j.wneu.2012.11.067

The genetic landscape of anaplastic astrocytoma.

Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type, we sequenced the exome of a cohort of A3s (n=16). For comparison and to illuminate the genomic landscape of other glioma subtypes, we also included in our study diffuse astrocytoma WHO grade II (A2, n=7), oligoastrocytoma WHO grade II (OA2, n=2), anaplastic oligoastrocytoma WHO grade III (OA3, n=4), and GBM (n=28). Exome sequencing of A3s identified frequent mutations in IDH1 (75%, 12/16), ATRX (63%, 10/16), and TP53 (82%, 13/16). In contrast, the majority of GBMs (75%, 21/28) did not contain IDH1 or ATRX mutations, and displayed a distinct spectrum of mutations. Finally, our study also identified novel genes that were not previously linked to this tumor type. In particular, we found mutations in Notch pathway genes (NOTCH1, NOTCH2, NOTCH4, NOTCH2NL), including a recurrent NOTCH1-A465Tmutation, in 31% (5/16) of A3s. This study suggests genetic signatures will be useful for the classification of gliomas.

Authors
Killela, PJ; Pirozzi, CJ; Reitman, ZJ; Jones, S; Rasheed, BA; Lipp, E; Friedman, H; Friedman, AH; He, Y; McLendon, RE; Bigner, DD; Yan, H
MLA Citation
Killela, PJ, Pirozzi, CJ, Reitman, ZJ, Jones, S, Rasheed, BA, Lipp, E, Friedman, H, Friedman, AH, He, Y, McLendon, RE, Bigner, DD, and Yan, H. "The genetic landscape of anaplastic astrocytoma." Oncotarget 5.6 (March 30, 2014): 1452-1457.
PMID
24140581
Source
pubmed
Published In
Oncotarget
Volume
5
Issue
6
Publish Date
2014
Start Page
1452
End Page
1457
DOI
10.18632/oncotarget.1505

Impact of PhD training on scholarship in a neurosurgical career.

OBJECT: The purpose of this study was to report the prevalence of neurosurgeons with both medical degrees (MDs) and doctorates (PhDs) at top-ranked US academic institutions and to assess whether the additional doctorate education is associated with substantive career involvement in academia as well as greater success in procuring National Institutes of Health (NIH) research funding compared with an MD-only degree. METHODS: The authors reviewed the training of neurosurgeons across the top 10 neurosurgery departments chosen according to academic impact (h index) to examine whether MD-PhD training correlated significantly with career outcomes in academia. RESULTS: Six hundred thirteen neurosurgery graduates and residents between the years 1990 and 2012 were identified for inclusion in this analysis. Both MD and PhD degrees were held by 121 neurosurgeons (19.7%), and an MD alone was held by 492. Over the past 2 decades, MD-PhD trainees represented a gradually increasing percentage of neurosurgeons, from 10.2% to 25.7% (p < 0.01). Of the neurosurgeons with MD-PhD training, a greater proportion had appointments in academic medicine compared with their MD-only peers (73.7% vs 52.3%, p < 0.001). Academic neurosurgeons with both degrees were also more likely to have received NIH funding (51.9% vs 31.8%, p < 0.05) than their single-degree counterparts in academia. In a national analysis of all active NIH R01 grants awarded in neurosurgery, MD-PhD investigators held a disproportionate number, more than 4-fold greater than their representation in the field. CONCLUSIONS: Dual MD-PhD training is a significant factor that may predict active participation in and funding for research careers among neurological surgeons at top-ranked academic institutions. These findings and their implications are of increasing relevance as the population of neurosurgeons with dual-degree training continues to rise.

Authors
Choi, BD; DeLong, MR; DeLong, DM; Friedman, AH; Sampson, JH
MLA Citation
Choi, BD, DeLong, MR, DeLong, DM, Friedman, AH, and Sampson, JH. "Impact of PhD training on scholarship in a neurosurgical career." J Neurosurg 120.3 (March 2014): 730-735.
PMID
24359004
Source
pubmed
Published In
Journal of neurosurgery
Volume
120
Issue
3
Publish Date
2014
Start Page
730
End Page
735
DOI
10.3171/2013.11.JNS122370

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.

Authors
Killela, PJ; Pirozzi, CJ; Healy, P; Reitman, ZJ; Lipp, E; Rasheed, BA; Yang, R; Diplas, BH; Wang, Z; Greer, PK; Zhu, H; Wang, CY; Carpenter, AB; Friedman, H; Friedman, AH; Keir, ST; He, J; He, Y; McLendon, RE; Herndon, JE; Yan, H; Bigner, DD
MLA Citation
Killela, PJ, Pirozzi, CJ, Healy, P, Reitman, ZJ, Lipp, E, Rasheed, BA, Yang, R, Diplas, BH, Wang, Z, Greer, PK, Zhu, H, Wang, CY, Carpenter, AB, Friedman, H, Friedman, AH, Keir, ST, He, J, He, Y, McLendon, RE, Herndon, JE, Yan, H, and Bigner, DD. "Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas." Oncotarget 5.6 (March 2014): 1515-1525.
PMID
24722048
Source
epmc
Published In
Oncotarget
Volume
5
Issue
6
Publish Date
2014
Start Page
1515
End Page
1525

Surgical management of nonvascular lesions around the oculomotor nerve

Objective: Schwannomas originating from the oculomotor nerve are extremely rare. We report our experience in the management of oculomotor schwannomas and other lesions mimicking them, and discuss operative strategy for these rare tumors emphasizing oculomotor nerve preservation. Methods: The clinical records of our patients and all those reported in the literature focusing on oculomotor schwannomas were reviewed and analyzed. The clinical presentations, operative approaches, complications, and results were studied. Results: Between 1983 and 2010, six patients with primary oculomotor nerve lesions were treated. Three of them had schwannomas. Two others had pathologies that mimicked an oculomotor schwannoma and one was suspected as schwannoma. In the literature there were 55 previou s cases of oculomotor schwannomas reported (surgical treated, 41 cases; observed, 9; gamma knife surgery treated, 2; autopsy, 3). Patients presented most commonly with diplopia, followed by headache and ptosis as initial symptoms. Out of 55 patients including the present 3 cases (3 autopsy cases were excluded), 30 patients (54.5%) finally developed oculomotor nerve palsy. Fifteen of 44 patients (34.1%) who underwent surgery developed persistent postoperative oculomotor palsy. Among them, 6 patients developed total palsy after surgery. Five of 12 patients (41.7%) who did not undergo surgery also developed oculomotor palsy. Oculomotor schwannomas most often grow its cisternal segment (48.3%) followed by intracavernous (39.6%) and cisternocavernous segments (12.1%). Conclusion: The microsurgical resection of oculomotor schwannomas carries a risk of worsening preoperative oculomotor nerve function; however, this is often transient. Considerable technical training and microanatomical knowledge of the region is required to optimize outcome. © 2014 Elsevier Inc. All rights reserved.

Authors
Nonaka, Y; Fukushima, T; Friedman, AH; Kolb, LE; Bulsara, KR
MLA Citation
Nonaka, Y, Fukushima, T, Friedman, AH, Kolb, LE, and Bulsara, KR. "Surgical management of nonvascular lesions around the oculomotor nerve." World Neurosurgery 81.5-6 (January 1, 2014): 798-809. (Review)
Source
scopus
Published In
World Neurosurgery
Volume
81
Issue
5-6
Publish Date
2014
Start Page
798
End Page
809
DOI
10.1016/j.wneu.2012.11.067

Impact of PhD training on scholarship in a neurosurgical career: Clinical article

Object. The purpose of this study was to report the prevalence of neurosurgeons with both medical degrees (MDs) and doctorates (PhDs) at top-ranked US academic institutions and to assess whether the additional doctorate education is associated with substantive career involvement in academia as well as greater success in procuring National Institutes of Health (NIH) research funding compared with an MD-only degree. Methods. The authors reviewed the training of neurosurgeons across the top 10 neurosurgery departments chosen according to academic impact (h index) to examine whether MD-PhD training correlated significantly with career outcomes in academia. Results. Six hundred thirteen neurosurgery graduates and residents between the years 1990 and 2012 were identified for inclusion in this analysis. Both MD and PhD degrees were held by 121 neurosurgeons (19.7%), and an MD alone was held by 492. Over the past 2 decades, MD-PhD trainees represented a gradually increasing percentage of neurosurgeons, from 10.2% to 25.7% (p < 0.01). Of the neurosurgeons with MD-PhD training, a greater proportion had appointments in academic medicine compared with their MD-only peers (73.7% vs 52.3%, p < 0.001). Academic neurosurgeons with both degrees were also more likely to have received NIH funding (51.9% vs 31.8%, p < 0.05) than their single-degree counterparts in academia. In a national analysis of all active NIH R01 grants awarded in neurosurgery, MD-PhD investigators held a disproportionate number, more than 4-fold greater than their representation in the field. Conclusions. Dual MD-PhD training is a significant factor that may predict active participation in and funding for research careers among neurological surgeons at top-ranked academic institutions. These findings and their implications are of increasing relevance as the population of neurosurgeons with dual-degree training continues to rise. ©AANS, 2014.

Authors
Choi, BD; DeLong, MR; DeLong, DM; Friedman, AH; Sampson, JH
MLA Citation
Choi, BD, DeLong, MR, DeLong, DM, Friedman, AH, and Sampson, JH. "Impact of PhD training on scholarship in a neurosurgical career: Clinical article." Journal of Neurosurgery 120.3 (January 1, 2014): 730-735.
Source
scopus
Published In
Journal of neurosurgery
Volume
120
Issue
3
Publish Date
2014
Start Page
730
End Page
735
DOI
10.3171/2013.11.JNS122370

Hearing preservation surgery for vestibular schwannomas via the retrosigmoid transmeatal approach: Surgical tips

Maximum tumor extirpation with preservation of the facial and cochlear nerve function is the goal of surgery for vestibular schwannoma. To preserve cochlear nerve function, the surgeon must employ a detailed knowledge of microanatomy, precise microsurgical techniques, and persistence. This paper describes the "pearls" of surgical techniques based on the anatomical study inside the mastoid from the view of the retrosigmoid transmeatal approach. A total of 592 consecutive patients underwent surgical removal of unilateral vestibular schwannoma (VS) between January 1994 and December 2009. The hearing preservation rate was 53.7 % for large vestibular schwannomas ( > 20 mm in diameter) and 74.1 % for tumors of all sizes. The key procedures for hearing preservation surgery are as follows: bloodless microdissection, sufficient coring-debulking, capsular elevation to locate the facial and cochlear nerves both electrophysiologically and by visual observation, sharp dissection of the facial and cochlear nerves, and avoidance of heat and mechanical injury to the nerves, the internal auditory artery, and the brain stem. Besides these techniques, appropriate instruments are essential to preserve hearing. The function of the facial and cochlear nerves should be the foremost concern. Meticulous techniques and the knowledge of microsurgical anatomy lead to hearing preservation with maximum tumor removal. © 2014 Springer-Verlag.

Authors
Wanibuchi, M; Fukushima, T; Friedman, AH; Watanabe, K; Akiyama, Y; Mikami, T; Iihoshi, S; Murakami, T; Sugino, T; Mikuni, N
MLA Citation
Wanibuchi, M, Fukushima, T, Friedman, AH, Watanabe, K, Akiyama, Y, Mikami, T, Iihoshi, S, Murakami, T, Sugino, T, and Mikuni, N. "Hearing preservation surgery for vestibular schwannomas via the retrosigmoid transmeatal approach: Surgical tips." Neurosurgical Review 37.3 (January 1, 2014): 431-444.
Source
scopus
Published In
Neurosurgical Review
Volume
37
Issue
3
Publish Date
2014
Start Page
431
End Page
444
DOI
10.1007/s10143-014-0543-9

Malignant brainstem gliomas in adults: Clinicopathological characteristics and prognostic factors

Adult malignant brainstem gliomas (BSGs) are poorly characterized due to their relative rarity. We have examined histopathologically confirmed cases of adult malignant BSGs to better characterize the patient and tumor features and outcomes, including the natural history, presentation, imaging, molecular characteristics, prognostic factors, and appropriate treatments. A total of 34 patients were identified, consisting of 22 anaplastic astrocytomas (AAs) and 12 glioblastomas (GBMs). The overall median survival for all patients was 25.8 months, with patients having GBMs experiencing significantly worse survival (12.1 vs. 77.0 months, p = 0.0011). The majority of tumors revealed immunoreactivity for EGFR (93.3 %) and MGMT (64.7 %). Most tumors also exhibited chromosomal abnormalities affecting the loci of epidermal growth factor receptor (92.9 %), MET (100 %), PTEN (61.5 %), and 9p21 (80 %). AAs more commonly appeared diffusely enhancing (50.0 vs. 27.3 %) or diffusely nonenhancing (25.0 vs. 0.0 %), while GBMs were more likely to exhibit focal enhancement (54.6 vs. 10.0 %). Multivariate analysis revealed confirmed histopathology for GBM to significantly affect survival (HR 4.80; 95 % CI 1.86-12.4; p = 0.0012). In conclusion, adult malignant BSGs have an overall poor prognosis, with GBM tumors faring significantly worse than AAs. As AAs and GBMs have differing imaging characteristics, tissue diagnosis may be necessary to accurately determine patient prognosis and identify molecular ch aracteristics which may aid in the treatment of these aggressive tumors. © 2014 Springer Science+Business Media.

Authors
Babu, R; Kranz, PG; Agarwal, V; McLendon, RE; Thomas, S; Friedman, AH; Bigner, DD; Adamson, C
MLA Citation
Babu, R, Kranz, PG, Agarwal, V, McLendon, RE, Thomas, S, Friedman, AH, Bigner, DD, and Adamson, C. "Malignant brainstem gliomas in adults: Clinicopathological characteristics and prognostic factors." Journal of Neuro-Oncology 119.1 (January 1, 2014): 177-185.
Source
scopus
Published In
Journal of Neuro-Oncology
Volume
119
Issue
1
Publish Date
2014
Start Page
177
End Page
185
DOI
10.1007/s11060-014-1471-9

Oncolytic polio virotherapy of cancer

© 2014 American Cancer Society. Recently, the century-old idea of targeting cancer with viruses (oncolytic viruses) has come of age, and promise has been documented in early stage and several late-stage clinical trials in a variety of cancers. Although originally prized for their direct tumor cytotoxicity (oncolytic virotherapy), recently, the proinflammatory and immunogenic effects of viral tumor infection (oncolytic immunotherapy) have come into focus. Indeed, a capacity for eliciting broad, sustained antineoplastic effects stemming from combined direct viral cytotoxicity, innate antiviral activation, stromal proinflammatory stimulation, and recruitment of adaptive immune effector responses is the greatest asset of oncolytic viruses. However, it also is the source for enormous mechanistic complexity that must be considered for successful clinical translation. Because of fundamentally different relationships with their hosts (malignant or not), diverse replication strategies, and distinct modes of tumor cytotoxicity/killing, oncolytic viruses should not be referred to collectively. These agents must be evaluated based on their individual merits. In this review, the authors highlight key mechanistic principles of cancer treatment with the polio:rhinovirus chimera PVSRIPO and their implications for oncolytic immunotherapy in the clinic.

Authors
Brown, MC; Dobrikova, EY; Dobrikov, MI; Walton, RW; Gemberling, SL; Nair, SK; Desjardins, A; Sampson, JH; Friedman, HS; Friedman, AH; Tyler, DS; Bigner, DD; Gromeier, M
MLA Citation
Brown, MC, Dobrikova, EY, Dobrikov, MI, Walton, RW, Gemberling, SL, Nair, SK, Desjardins, A, Sampson, JH, Friedman, HS, Friedman, AH, Tyler, DS, Bigner, DD, and Gromeier, M. "Oncolytic polio virotherapy of cancer." Cancer 120.21 (January 1, 2014): 3277-3286. (Review)
Source
scopus
Published In
Cancer
Volume
120
Issue
21
Publish Date
2014
Start Page
3277
End Page
3286
DOI
10.1002/cncr.28862

Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort.

OBJECT: Tumors of the cerebellopontine angle (CPA) have always proven difficult for neurosurgeons to optimally manage. Studies investigating the natural history and treatment of vestibular schwannomas have dominated the literature in this regard. Distinguishing meningiomas from schwannomas in this location carries particular importance as each tumor type has certain prognostic and surgical considerations. In this study, the authors have characterized the outcomes of 34 patients surgically treated for CPA meningiomas and have investigated various factors that may affect postoperative neurological function. METHODS: The medical records of patients with CPA meningiomas who underwent surgery from 2005 to 2013 at the Duke University Health System were reviewed. Various patient, clinical, and tumor data were gathered from the medical records including patient demographics, pre- and postoperative neurological examinations, duration of symptoms, procedural details, tumor pathology and size, and treatment characteristics. Differences in continuous variables were then analyzed using the Student t-test while categorical variables were evaluated using the chi-square test. RESULTS: A total of 34 patients underwent surgical treatment for CPA meningiomas during the 8-year period. Jugular foramen invasion was seen in 17.6% of tumors, with nearly half (41.2%) extending into the internal acoustic canal. The most common presenting symptom was hearing loss (58.8%), followed by headache (52.9%) and facial numbness/pain (50.0%). The most common cranial nerve (CN) affected was CN X (11.8%), followed by CNs VI and VII (5.9%). Postoperatively, no patients experienced a decrease in hearing, with only 5.9% of patients experiencing facial nerve palsies. Patients with tumors larger than 3 cm had a significantly higher incidence of permanent CN deficits than those with smaller tumors (45.5% vs 5.9%, respectively; p = 0.011). Also, tumor extension into the jugular foramen was associated with the occurrence of lower CN deficits, none of which occurred in tumors without jugular foramen invasion. Internal acoustic canal tumor extension was not seen to be associated with postoperative complications or CN deficits. CONCLUSIONS: Meningiomas of the CPA are challenging lesions to treat surgically. However, the risk of facial palsy and hearing loss is significantly lower when compared with vestibular schwannomas. Novel methods for preoperative differentiation are needed to appropriately counsel patients on surgical risks. Also, due to the significant potential for neurological deficits, further studies are needed to investigate the utility of radiotherapy for these lesions.

Authors
Agarwal, V; Babu, R; Grier, J; Adogwa, O; Back, A; Friedman, AH; Fukushima, T; Adamson, C
MLA Citation
Agarwal, V, Babu, R, Grier, J, Adogwa, O, Back, A, Friedman, AH, Fukushima, T, and Adamson, C. "Cerebellopontine angle meningiomas: postoperative outcomes in a modern cohort." Neurosurgical focus 35.6 (December 2013): E10-.
PMID
24289118
Source
epmc
Published In
Neurosurgical focus
Volume
35
Issue
6
Publish Date
2013
Start Page
E10
DOI
10.3171/2013.10.focus13367

Anatomical location dictating major surgical complications for intradural extramedullary spinal tumors: a 10-year single-institutional experience.

OBJECT: Intradural extramedullary (IDEM) neoplasms are uncommon lesions that can pose a challenge for resection. Numerous factors affect the resectability and ultimately the outcome of these lesions. The authors report their 10-year institutional experience with the resection of IDEM neoplasms, focusing on the effect of location on surgical outcomes. METHODS: The authors performed a retrospective review of 96 consecutive patients who presented with a cervical and/or thoracic IDEM tumor that was resected between February 2000 and July 2009. All patients underwent MRI, and the axial location of the tumor was categorized as anterior, posterior, or lateral. Postoperative complications were assessed, as was neurological status at the patient's last follow-up clinic visit. Major complications assessed included CSF leakage requiring lumbar drainage, reexploration for epidural hematoma, and major postoperative neurological deficits. RESULTS: The mean ± SD age at presentation was 51.16 ± 17.87 years. Major surgical approach-related complications occurred in 15% of patients. Major non-approach related surgical complications occurred in 7.1% of patients, while minor complications occurred in 14.2% of patients. Postoperative neurological deficits occurred most commonly in the thoracic spine between T-1 and T-8. Based on axial spinal cord location, the surgery-related complications rates for all anterior tumors (n = 12) was 41.6%, whereas that for all lateral tumors (n = 69) was 4.4% and that for all posteriorly located tumors (n = 17) was 0%. CONCLUSIONS: Spinal IDEM tumors that are anteriorly located in the upper thoracic spine were found to have the highest rate of surgery-related complications and postoperative neurological deficits. This finding may be associated with the unforgiving anatomy of the upper thoracic spine in which there is a higher cord-to-canal ratio and a tenuous vascular supply.

Authors
Mehta, AI; Adogwa, O; Karikari, IO; Thompson, P; Verla, T; Null, UT; Friedman, AH; Cheng, JS; Bagley, CA; Isaacs, RE
MLA Citation
Mehta, AI, Adogwa, O, Karikari, IO, Thompson, P, Verla, T, Null, UT, Friedman, AH, Cheng, JS, Bagley, CA, and Isaacs, RE. "Anatomical location dictating major surgical complications for intradural extramedullary spinal tumors: a 10-year single-institutional experience." Journal of neurosurgery. Spine 19.6 (December 2013): 701-707.
PMID
24116680
Source
epmc
Published In
Journal of neurosurgery. Spine
Volume
19
Issue
6
Publish Date
2013
Start Page
701
End Page
707
DOI
10.3171/2013.9.spine12913

Less invasive transjugular approach with Fallopian bridge technique for facial nerve protection and hearing preservation in surgery of glomus jugulare tumors.

For the past three decades, surgery of glomus jugulare tumors (GJTs) has been characterized by extensive combined head and neck, neuro-otologic, and neurosurgical approaches. In recent years, the authors have modified the operative technique to a less invasive approach for preservation of cranial nerves while achieving satisfactory tumor resection. We evaluated and compared the clinical outcomes of our current less invasive approach with our previous more extensive procedures. The clinical records of 39 cases of GJT surgically treated between 1992 and 2011 were retrospectively reviewed. The less invasive transjugular approach with Fallopian bridge technique (LI-TJ) was used for the most recent five cases. The combined transmastoid-transjugular and high cervical (TM-HC) approach was performed in 30 cases, while four cases were treated with a transmastoid-transsigmoid approach with facial nerve translocation. Operative technique, extent of tumor resection, operating time, hospital stay, and morbidity were examined through the operative records, and a comparison was made between the LI-TJ cases and the more invasive cases. No facial nerve palsy was seen in the LI-TJ group while the TM-HC group demonstrated six cases (17.6%) of facial palsy (House-Brackmann facial nerve function grading scale grade II and III). The complication rate was 0 % in the LI-TJ group and 16.7% in the more invasive group. The mean operative time and hospital stay were shorter in the LI-TJ group (6.4 h and 4.3 days, respectively) compared with the more invasive group (10.7 h and 8.0 days, respectively). The LI-TJ approach with Fallopian bridge technique provided adequate tumor resection with cranial preservation and definitive advantage over the more extensive approach.

Authors
Nonaka, Y; Fukushima, T; Watanabe, K; Friedman, AH; McElveen, JT; Cunningham, CD; Zomorodi, AR
MLA Citation
Nonaka, Y, Fukushima, T, Watanabe, K, Friedman, AH, McElveen, JT, Cunningham, CD, and Zomorodi, AR. "Less invasive transjugular approach with Fallopian bridge technique for facial nerve protection and hearing preservation in surgery of glomus jugulare tumors." Neurosurg Rev 36.4 (October 2013): 579-586.
PMID
23739840
Source
pubmed
Published In
Neurosurgical Review
Volume
36
Issue
4
Publish Date
2013
Start Page
579
End Page
586
DOI
10.1007/s10143-013-0482-x

Clinical characteristics and treatment of malignant brainstem gliomas in elderly patients.

Adult brainstem gliomas (BSG) are uncommon tumors that constitute only 2% of all brain tumors. Due to its rare occurrence in the elderly (60 years and older), there is no literature discussing the natural history, prognosis, and best treatment strategy for malignant BSG in this population to our knowledge. We report seven elderly patients with malignant BSG and propose treatment strategies to manage these aggressive tumors. The median age at onset in this cohort was 65 years, with the majority of patients being male (71.4%) and Caucasian (85.7%). The median duration of symptoms prior to presentation was 0.5 months, with the most common symptoms being facial weakness, blurry vision, headache, and extremity weakness. Tumors were most commonly located in the pons (85.7%), with one tumor being located in the tectal plate. Five of seven (71.4%) patients underwent biopsies, with two patients undergoing partial resections. Following tissue diagnosis, patients received radiation therapy and concurrent temozolomide, followed by additional chemotherapeutics upon progression. Side effects as a result of treatment were seen in three patients and all involved reversible hematological complications such as neutropenia and thrombopenia. The median time to progression was 6.7 months and the median overall survival was 13.5 months. While malignant BSG in elderly patients are aggressive gliomas with an overall poor prognosis, these patients are able to safely undergo aggressive chemoradiotherapy, resulting in improved survival. Resection may be considered for select patients in which the tumor is mostly exophytic, near the brainstem surface, and easily accessible.

Authors
Babu, R; Kranz, PG; Karikari, IO; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Kranz, PG, Karikari, IO, Friedman, AH, and Adamson, C. "Clinical characteristics and treatment of malignant brainstem gliomas in elderly patients." J Clin Neurosci 20.10 (October 2013): 1382-1386.
PMID
23850399
Source
pubmed
Published In
Journal of Clinical Neuroscience
Volume
20
Issue
10
Publish Date
2013
Start Page
1382
End Page
1386
DOI
10.1016/j.jocn.2012.12.011

Central nervous system cancers.

Primary and metastatic tumors of the central nervous system are a heterogeneous group of neoplasms with varied outcomes and management strategies. Recently, improved survival observed in 2 randomized clinical trials established combined chemotherapy and radiation as the new standard for treating patients with pure or mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For metastatic disease, increasing evidence supports the efficacy of stereotactic radiosurgery in treating patients with multiple metastatic lesions but low overall tumor volume. These guidelines provide recommendations on the diagnosis and management of this group of diseases based on clinical evidence and panel consensus. This version includes expert advice on the management of low-grade infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas, medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain metastases. The full online version, available at NCCN. org, contains recommendations on additional subtypes.

Authors
Nabors, LB; Ammirati, M; Bierman, PJ; Brem, H; Butowski, N; Chamberlain, MC; DeAngelis, LM; Fenstermaker, RA; Friedman, A; Gilbert, MR; Hesser, D; Holdhoff, M; Junck, L; Lawson, R; Loeffler, JS; Maor, MH; Moots, PL; Morrison, T; Mrugala, MM; Newton, HB; Portnow, J; Raizer, JJ; Recht, L; Shrieve, DC; Sills, AK; Tran, D; Tran, N; Vrionis, FD; Wen, PY; McMillian, N; Ho, M; National Comprehensive Cancer Network,
MLA Citation
Nabors, LB, Ammirati, M, Bierman, PJ, Brem, H, Butowski, N, Chamberlain, MC, DeAngelis, LM, Fenstermaker, RA, Friedman, A, Gilbert, MR, Hesser, D, Holdhoff, M, Junck, L, Lawson, R, Loeffler, JS, Maor, MH, Moots, PL, Morrison, T, Mrugala, MM, Newton, HB, Portnow, J, Raizer, JJ, Recht, L, Shrieve, DC, Sills, AK, Tran, D, Tran, N, Vrionis, FD, Wen, PY, McMillian, N, Ho, M, and National Comprehensive Cancer Network, . "Central nervous system cancers." Journal of the National Comprehensive Cancer Network : JNCCN 11.9 (September 2013): 1114-1151.
PMID
24029126
Source
epmc
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
11
Issue
9
Publish Date
2013
Start Page
1114
End Page
1151
DOI
10.6004/jnccn.2013.0132

Comparison of postoperative nausea between benign and malignant brain tumor patients undergoing awake craniotomy: a retrospective analysis.

BACKGROUND: Benign and malignant brain tumors have different histopathological characteristics, including different degrees of tissue infiltration and inflammatory response. The aim of this retrospective study was to compare the incidence of postoperative nausea between the two categories of brain tumors in patients undergoing awake craniotomy. METHODS: After IRB approval, we retrospectively extracted data from perioperative records between January 2005 and December 2010. Patients were divided based on the postoperative histopathological diagnosis into two groups, benign and malignant. The incidence of nausea, rescue anti-emetics, pain scores and postoperative analgesic requirements were compared between the two groups up to 12 hours postoperatively. Intraoperative anti-emetic, anesthetic, and analgesic regimens were also assessed. Limitations of this study include the retrospective design, the arbitrary dichotomization of tumors as benign or malignant, and the inability to gather accurate data regarding vomiting from the medical record. RESULTS: Data from 415 patients were available for analysis, with 115 patients in the benign group and 300 patients in the malignant tumor group. A higher postoperative mean pain score was found in the benign brain tumor group compared to the malignant brain tumor group (P < 0.05). However, there was no difference in the incidence of nausea between the two groups. CONCLUSION: The different histopathological characteristics of brain tumors have no association with postoperative nausea in patients undergoing awake craniotomy. Patients with benign brain tumors experience more pain than patients with malignant brain tumors. This difference in postoperative pain may be due to the younger age of the patients in the benign group.

Authors
Ouyang, MW; McDonagh, DL; Phillips-Bute, B; James, ML; Friedman, AH; Gan, TJ
MLA Citation
Ouyang, MW, McDonagh, DL, Phillips-Bute, B, James, ML, Friedman, AH, and Gan, TJ. "Comparison of postoperative nausea between benign and malignant brain tumor patients undergoing awake craniotomy: a retrospective analysis." Curr Med Res Opin 29.9 (September 2013): 1039-1044.
PMID
23731201
Source
pubmed
Published In
Current Medical Research and Opinion
Volume
29
Issue
9
Publish Date
2013
Start Page
1039
End Page
1044
DOI
10.1185/03007995.2013.811070

Does midline shift predict postoperative nausea in brain tumor patients undergoing awake craniotomy? A retrospective analysis.

BACKGROUND: The presence of midline shift on neuroradiologic studies in brain tumor patients represents mass effect from the tumor and surrounding edema. We hypothesized that baseline cerebral edema as measured by midline shift would increase postoperative nausea (PON). We studied the incidence of PON in brain tumor patients, with and without midline shift on preoperative magnetic resonance (MRI) or computed tomographic (CT) imaging, undergoing awake craniotomy. METHODS: After IRB approval, we retrospectively extracted data from perioperative records between January 2005 and December 2010. Post-craniotomy nausea and pain scores were collected. Intraoperative anti-emetic, anesthetic, and analgesic regimens were assessed. Both the rescue anti-emetic and cumulative postoperative analgesic requirements were collected up to 12 hours postoperatively. The amount of midline shift on preoperative neuroimaging was gathered from radiology reports. Univariate comparisons between groups (no midline shift vs. midline shift) were made with t-tests for continuous variables, and chi-square tests for categorical variables. A multivariable analysis was performed to identify predictors of postoperative nausea. Limitations of this study include the retrospective design and the inability to gather accurate data regarding vomiting from the medical record. RESULTS: Data from 386 patients were available for analysis. Patients were divided into two groups: no midline shift (n = 283) and midline shift (n = 103). The mean midline shift distance was 5.96 mm (95% CI [5.32, 6.59]). There was no difference in the incidence of nausea or pain scores between the two groups. More malignant brain tumor patients were in the midline shift group, as determined by the postoperative histopathological diagnosis (P < 0.05). Patients in the midline shift group also had longer anesthesia and surgical times (P < 0.05). CONCLUSION: In patients undergoing a standardized anesthetic for awake craniotomy for tumor resection, the presence of preoperative midline shift did not correlate with postoperative nausea.

Authors
Ouyang, MW; McDonagh, DL; Phillips-Bute, B; James, ML; Friedman, AH; Gan, TJ
MLA Citation
Ouyang, MW, McDonagh, DL, Phillips-Bute, B, James, ML, Friedman, AH, and Gan, TJ. "Does midline shift predict postoperative nausea in brain tumor patients undergoing awake craniotomy? A retrospective analysis." Curr Med Res Opin 29.9 (September 2013): 1033-1038.
PMID
23731200
Source
pubmed
Published In
Current Medical Research and Opinion
Volume
29
Issue
9
Publish Date
2013
Start Page
1033
End Page
1038
DOI
10.1185/03007995.2013.811071

Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology.

OBJECT: Low-grade astrocytomas are slow-growing, infiltrative gliomas that over time may progress into more malignant tumors. Various factors have been shown to affect the time to progression and overall survival including age, performance status, tumor size, and the extent of resection. However, more recently it has been suggested that histological subtypes (fibrillary, protoplasmic, and gemistocytic) may impact patient outcome. In this study the authors have performed a large comparative population-based analysis to examine the characteristics and survival of patients with the various subtypes of WHO Grade II astrocytomas. METHODS: Patients diagnosed with fibrillary, protoplasmic, and gemistocytic astrocytomas were identified through the Surveillance, Epidemiology, and End Results (SEER) database. The chi-square test and Student t-test were used to evaluate differences in patient and treatment characteristics between astrocytoma subtypes. Kaplan-Meier analysis was used to assess overall survival, and the log-rank test was used to evaluate the differences between survival curves. Univariate and multivariate analyses were also performed to determine the effect of various patient, tumor, and treatment variables on overall survival. RESULTS: A total of 500 cases were included in the analysis, consisting of 326 fibrillary (65.2%), 29 protoplasmic (5.8%), and 145 gemistocytic (29%) variants. Gemistocytic astrocytomas presented at a significantly older age than the fibrillary variant (46.8 vs 37.7 years, p < 0.0001), with protoplasmic and fibrillary subtypes having a similar age. Although protoplasmic and fibrillary variants underwent radiotherapy at similar rates, gemistocytic tumors more frequently received radiotherapy (p = 0.0001). Univariate analysis revealed older age, larger tumor size, and the use of radiotherapy to be poor prognostic factors, with resection being associated with improved survival. The gemistocytic subtype (hazard ratio [HR] 1.62 [95% CI 1.27-2.07], p = 0.0001) also resulted in significantly worse survival than fibrillary tumors. Bivariate analyses demonstrated that older age, the use of radiotherapy, and resection significantly influenced median survival. Tumor subtype also affected median survival; patients who harbored gemistocytic tumors experienced less than half the median survival of fibrillary and protoplasmic tumors (38 vs 82 months, p = 0.0003). Multivariate analysis revealed increasing age (HR 1.05 [95% CI 1.04-1.05], p < 0.0001), larger tumor size (HR 1.02 [95% CI 1.01-1.03], p = 0.0002), and the use of resection (HR 0.70 [95% CI 0.52-0.94], p = 0.018) to be independent predictors of survival. Examination of tumor subtype revealed that the gemistocytic variant (HR 1.30 [95% CI 0.98-1.74], p = 0.074) was associated with worse patient survival than fibrillary tumors, although this only approached significance. The protoplasmic subtype did not affect overall survival (p = 0.33). CONCLUSIONS: Gemistocytic tumor histology was associated with worse survival than fibrillary and protoplasmic astrocytomas. As protoplasmic astrocytomas have a survival similar to fibrillary tumors, there may be limited utility to the identification of this rare variant. However, increased attention should be paid to the presence of gemistocytes in low-grade gliomas as this is associated with shorter time to progression, increased malignant transformation, and reduced overall survival.

Authors
Babu, R; Bagley, JH; Park, JG; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Bagley, JH, Park, JG, Friedman, AH, and Adamson, C. "Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology." J Neurosurg 119.2 (August 2013): 434-441.
PMID
23662821
Source
pubmed
Published In
Journal of neurosurgery
Volume
119
Issue
2
Publish Date
2013
Start Page
434
End Page
441
DOI
10.3171/2013.4.JNS122329

Outcome and prognostic factors in adult cerebellar glioblastoma.

Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4-3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8 years, p < 0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p < 0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8 months, p = 0.24), with similar rates of long-term (greater than 2 years) survival (13.4% versus 10.6%, p = 0.21). Multivariate analysis revealed age greater than 40 years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47-3.28; p = 0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24-0.47; p < 0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45-0.96; p = 0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar.

Authors
Babu, R; Sharma, R; Karikari, IO; Owens, TR; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Sharma, R, Karikari, IO, Owens, TR, Friedman, AH, and Adamson, C. "Outcome and prognostic factors in adult cerebellar glioblastoma." Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 20.8 (August 2013): 1117-1121.
PMID
23706183
Source
epmc
Published In
Journal of Clinical Neuroscience
Volume
20
Issue
8
Publish Date
2013
Start Page
1117
End Page
1121
DOI
10.1016/j.jocn.2012.12.006

Clinicopathological characteristics and treatment of rhabdoid glioblastoma Clinical article

Authors
Babu, R; Hatef, J; McLendon, RE; Cummings, TJ; Sampson, JH; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Hatef, J, McLendon, RE, Cummings, TJ, Sampson, JH, Friedman, AH, and Adamson, C. "Clinicopathological characteristics and treatment of rhabdoid glioblastoma Clinical article." JOURNAL OF NEUROSURGERY 119.2 (August 2013): 412-419.
PMID
23641829
Source
wos-lite
Published In
Journal of neurosurgery
Volume
119
Issue
2
Publish Date
2013
Start Page
412
End Page
419
DOI
10.3171/2013.3.JNS121773

Vestibular schwannomas in the modern era: epidemiology, treatment trends, and disparities in management.

OBJECT: There are a variety of treatment options for the management of vestibular schwannomas (VSs), including microsurgical resection, radiotherapy, and observation. Although the choice of treatment is dependent on various patient factors, physician bias has been shown to significantly affect treatment choice for VS. In this study the authors describe the current epidemiology of VS and treatment trends in the US in the modern era. They also illustrate patient and tumor characteristics and elucidate their effect on tumor management. METHODS: Patients diagnosed with VS were identified through the Surveillance, Epidemiology, and End Results database, spanning the years 2004-2009. Age-adjusted incidence rates were calculated and adjusted using the 2000 US standard population. The chi-square and Student t-tests were used to evaluate differences between patient and tumor characteristics. Multivariate logistic regression was performed to determine the effects of various patient and tumor characteristics on the choice of tumor treatment. RESULTS: A total of 6225 patients with VSs treated between 2004 and 2009 were identified. The overall incidence rate was 1.2 per 100,000 population per year. The median age of patients with VS was 55 years, with the majority of patients being Caucasian (83.16%). Of all patients, 3053 (49.04%) received surgery only, with 1466 (23.55%) receiving radiotherapy alone. Both surgery and radiation were only used in 123 patients (1.98%), with 1504 patients not undergoing any treatment (24.16%). Increasing age correlated with decreased use of surgery (OR 0.95, 95% CI 0.95-0.96; p<0.0001), whereas increasing tumor size was associated with the increased use of surgery (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Older age was associated with an increased likelihood of conservative management (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Racial disparities were also seen, with African American patients being significantly less likely to receive surgical treatment compared with Caucasians (OR 0.50, 95% CI 0.35-0.70; p<0.0001), despite having larger tumors at diagnosis. CONCLUSIONS: The incidence of vestibular schwannomas in the US is 1.2 per 100,000 population per year. Although many studies have demonstrated improved outcomes with the use of radiotherapy for small- to medium-sized VSs, surgery is still the most commonly used treatment modality for these tumors. Racial disparities also exist in the treatment of VSs, with African American patients being half as likely to receive surgery and nearly twice as likely to have their VSs managed conservatively despite presenting with larger tumors. Further studies are needed to elucidate the reasons for treatment disparities and investigate the nationwide trend of resection for the treatment of small VSs.

Authors
Babu, R; Sharma, R; Bagley, JH; Hatef, J; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Sharma, R, Bagley, JH, Hatef, J, Friedman, AH, and Adamson, C. "Vestibular schwannomas in the modern era: epidemiology, treatment trends, and disparities in management." J Neurosurg 119.1 (July 2013): 121-130.
PMID
23432451
Source
pubmed
Published In
Journal of neurosurgery
Volume
119
Issue
1
Publish Date
2013
Start Page
121
End Page
130
DOI
10.3171/2013.1.JNS121370

Contemporary surgical management of vestibular schwannomas: analysis of complications and lessons learned over the past decade.

BACKGROUND: Despite advanced microsurgical techniques, more refined instrumentation, and expert team management, there is still a significant incidence of complications in vestibular schwannoma surgery. OBJECTIVE: To analyze complications from the microsurgical treatment of vestibular schwannoma by an expert surgical team and to propose strategies for minimizing such complications. METHODS: Surgical outcomes and complications were evaluated in a consecutive series of 410 unilateral vestibular schwannomas treated from 2000 to 2009. Clinical status and complications were assessed postoperatively (within 7 days) and at the time of follow-up (range, 1-116 months; mean, 32.7 months). RESULTS: Follow-up data were available for 357 of the 410 patients (87.1%). Microsurgical tumor resection was performed through a retrosigmoid approach in 70.7% of cases. Thirty-three patients (8%) had intrameatal tumors and 204 (49.8%) had tumors that were <20 mm. Gross total resection was performed in 306 patients (74.6%). Hearing preservation surgery was attempted in 170 patients with tumors <20 mm, and good hearing was preserved in 74.1%. The main neurological complication was facial palsy (House-Brackmann grade III-VI), observed in 14% of patients (56 cases) postoperatively; however, 59% of them improved during the follow-up period. Other neurological complications were disequilibrium in 6.3%, facial numbness in 2.2%, and lower cranial nerve deficit in 0.5%. Nonneurological complications included cerebrospinal fluid leaks in 7.6%, wound infection in 2.2%, and meningitis in 1.7%. CONCLUSION: Many of these complications are avoidable through further refinement of operative technique, and strategies for avoiding complications are proposed.

Authors
Nonaka, Y; Fukushima, T; Watanabe, K; Friedman, AH; Sampson, JH; Mcelveen, JT; Cunningham, CD; Zomorodi, AR
MLA Citation
Nonaka, Y, Fukushima, T, Watanabe, K, Friedman, AH, Sampson, JH, Mcelveen, JT, Cunningham, CD, and Zomorodi, AR. "Contemporary surgical management of vestibular schwannomas: analysis of complications and lessons learned over the past decade." Neurosurgery 72.2 Suppl Operative (June 2013): ons103-ons115.
PMID
23037828
Source
pubmed
Published In
Neurosurgery
Volume
72
Issue
2 Suppl Operative
Publish Date
2013
Start Page
ons103
End Page
ons115
DOI
10.1227/NEU.0b013e3182752b05

Long-term economic impact of coiling vs clipping for unruptured intracranial aneurysms.

BACKGROUND: : Treatment of unruptured intracranial aneurysms (UIAs) involves endovascular coiling or aneurysm clipping. While many studies have compared these treatment modalities with respect to various clinical outcomes, few studies have investigated the economic costs associated with each procedure. OBJECTIVE: : To determine the reoperation rate, postoperative complications, and inpatient and outpatient costs associated with surgical or endovascular treatment of patients with UIAs in the United States. METHODS: : We utilized the MarketScan database to examine patients who underwent surgical clipping or endovascular coiling procedures for UIAs from 2000 to 2009, comparing reoperation rates, complications, and angiogram and healthcare resource use. Propensity score matching techniques were used to match patients. RESULTS: : We identified 4,504 patients with surgically treated UIAs, with propensity score matching of 3,436 patients. Reoperation rates were significantly lower in the clipping group compared to the coiling group at 1- (P < .001), 2- (P < .001), and 5 years (P < .001) following the procedure. However, postoperative complications (immediate, 30 and 90 days) were significantly higher in those undergoing surgical clipping. Although hospital length of stay and costs were higher in the clipping group for the index procedure, the number of postoperative angiograms and outpatient services used at 1, 2, and 5 years were significantly higher in the coiling group. CONCLUSION: : Though surgical clipping resulted in lower reoperation rates, it was associated with higher complication rates and initial costs. However, overall costs at 2 and 5 years were similar to endovascular coiling due to the significantly higher number of follow-up angiograms and outpatient costs in these patients. ABBREVIATIONS: : SAH, subarachnoid hemorrhageUIAs, unruptured intracranial aneurysms.

Authors
Lad, SP; Babu, R; Rhee, MS; Franklin, RL; Ugiliweneza, B; Hodes, J; Nimjee, SM; Zomorodi, AR; Smith, TP; Friedman, AH; Patil, CG; Boakye, M
MLA Citation
Lad, SP, Babu, R, Rhee, MS, Franklin, RL, Ugiliweneza, B, Hodes, J, Nimjee, SM, Zomorodi, AR, Smith, TP, Friedman, AH, Patil, CG, and Boakye, M. "Long-term economic impact of coiling vs clipping for unruptured intracranial aneurysms." Neurosurgery 72.6 (June 2013): 1000-1011.
PMID
23612602
Source
pubmed
Published In
Neurosurgery
Volume
72
Issue
6
Publish Date
2013
Start Page
1000
End Page
1011
DOI
10.1227/01.neu.0000429284.91142.56

TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome X-linked (ATRX) or death-domain associated protein (DAXX) have been shown to underlie a telomere maintenance mechanism not involving telomerase (alternative lengthening of telomeres), and point mutations in the promoter of the telomerase reverse transcriptase (TERT) gene increase telomerase expression and have been shown to occur in melanomas and a small number of other tumors. To further define the tumor types in which this latter mechanism plays a role, we surveyed 1,230 tumors of 60 different types. We found that tumors could be divided into types with low (<15%) and high (≥15%) frequencies of TERT promoter mutations. The nine TERT-high tumor types almost always originated in tissues with relatively low rates of self renewal, including melanomas, liposarcomas, hepatocellular carcinomas, urothelial carcinomas, squamous cell carcinomas of the tongue, medulloblastomas, and subtypes of gliomas (including 83% of primary glioblastoma, the most common brain tumor type). TERT and ATRX mutations were mutually exclusive, suggesting that these two genetic mechanisms confer equivalent selective growth advantages. In addition to their implications for understanding the relationship between telomeres and tumorigenesis, TERT mutations provide a biomarker that may be useful for the early detection of urinary tract and liver tumors and aid in the classification and prognostication of brain tumors.

Authors
Killela, PJ; Reitman, ZJ; Jiao, Y; Bettegowda, C; Agrawal, N; Diaz, LA; Friedman, AH; Friedman, H; Gallia, GL; Giovanella, BC; Grollman, AP; He, T-C; He, Y; Hruban, RH; Jallo, GI; Mandahl, N; Meeker, AK; Mertens, F; Netto, GJ; Rasheed, BA; Riggins, GJ; Rosenquist, TA; Schiffman, M; Shih, I-M; Theodorescu, D; Torbenson, MS; Velculescu, VE; Wang, T-L; Wentzensen, N; Wood, LD; Zhang, M; McLendon, RE; Bigner, DD; Kinzler, KW; Vogelstein, B; Papadopoulos, N; Yan, H
MLA Citation
Killela, PJ, Reitman, ZJ, Jiao, Y, Bettegowda, C, Agrawal, N, Diaz, LA, Friedman, AH, Friedman, H, Gallia, GL, Giovanella, BC, Grollman, AP, He, T-C, He, Y, Hruban, RH, Jallo, GI, Mandahl, N, Meeker, AK, Mertens, F, Netto, GJ, Rasheed, BA, Riggins, GJ, Rosenquist, TA, Schiffman, M, Shih, I-M, Theodorescu, D, Torbenson, MS, Velculescu, VE, Wang, T-L, Wentzensen, N, Wood, LD, Zhang, M, McLendon, RE, Bigner, DD, Kinzler, KW, Vogelstein, B, Papadopoulos, N, and Yan, H. "TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal." Proc Natl Acad Sci U S A 110.15 (April 9, 2013): 6021-6026.
PMID
23530248
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
110
Issue
15
Publish Date
2013
Start Page
6021
End Page
6026
DOI
10.1073/pnas.1303607110

Middle fossa approach for total resection of petrous apex cholesterol granulomas: use of vascularized galeofascial flap preventing recurrence.

BACKGROUND: Cholesterol granulomas (CGs) of the petrous apex (PA) are rare, benign, expanding lesions. Surgical treatment is recommended for patients with symptomatic disease; however, the optimal surgical procedure is still controversial due to high recurrence rates. The main treatment strategy is divided into drainage and complete resection. OBJECTIVE: We advocate radical resection of the lesion by the middle fossa approach and reconstruction with a vascularized galeofascial flap. METHODS: A 10-year retrospective case review of 17 patients undergoing surgical treatment of PA CGs between 2000 and 2010 was undertaken. Operative outcomes and surgical complications were analyzed. In addition, our operative method and the related anatomy are described from cadaveric dissections. RESULTS: All but 1 patient was operated on via a middle fossa approach. Using the middle fossa approach, radical resection of all PA CGs was achieved with obliteration of the cyst cavity using a vascularized flap. Important surrounding structures included the internal auditory canal, cochlea, petrous carotid artery, and abducens nerve. There was 1 death caused by internal carotid artery occlusion. No other major complications or cranial nerve deficits occurred postoperatively. Clinical recurrence occurred in 1 patient (5.9%). CONCLUSION: Our technique of radical resection and reconstruction with a vascularized flap has the advantage of being less invasive with less cosmetic deformity and allows preservation of cranial nerve function with a low recurrence rate. Knowledge of the surgical anatomy and the characteristics of CG is prudent because important neurovascular structures may be exposed behind the CG wall due to bony erosion.

Authors
Kusumi, M; Fukushima, T; Mehta, AI; Cunningham, CD; Friedman, AH; Fujii, K
MLA Citation
Kusumi, M, Fukushima, T, Mehta, AI, Cunningham, CD, Friedman, AH, and Fujii, K. "Middle fossa approach for total resection of petrous apex cholesterol granulomas: use of vascularized galeofascial flap preventing recurrence." Neurosurgery 72.1 Suppl Operative (March 2013): 77-86.
PMID
22986599
Source
pubmed
Published In
Neurosurgery
Volume
72
Issue
1 Suppl Operative
Publish Date
2013
Start Page
77
End Page
86
DOI
10.1227/NEU.0b013e3182724354

A comprehensive analysis of 41 patients with rosette-forming glioneuronal tumors of the fourth ventricle.

The rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a recently described, rare, and distinct tumor of the glioneuronal family. The presentation, natural history, and treatment response of these tumors has been unclear as there are no significant series of a sizeable population with long-term follow-up. We report a comprehensive analysis of 41 patients with RGNT to provide the most current understanding of this rare tumor. Treatment of these patients has consisted of resection via the transvermian and telovelar approaches, with one patient requiring radiotherapy due to tumor recurrence. Various unique imaging characteristics may allow for the preoperative identification of these tumors. Resection via the telovelar approach should be considered for symptomatic tumors and those that pose a risk of obstructive hydrocephalus. Due to their benign nature and low propensity for recurrence, subtotal resection may be appropriate for those that are adherent to the brainstem. Radiotherapy may be considered for patients with tumor recurrence.

Authors
Zhang, J; Babu, R; McLendon, RE; Friedman, AH; Adamson, C
MLA Citation
Zhang, J, Babu, R, McLendon, RE, Friedman, AH, and Adamson, C. "A comprehensive analysis of 41 patients with rosette-forming glioneuronal tumors of the fourth ventricle." J Clin Neurosci 20.3 (March 2013): 335-341. (Review)
PMID
23375398
Source
pubmed
Published In
Journal of Clinical Neuroscience
Volume
20
Issue
3
Publish Date
2013
Start Page
335
End Page
341
DOI
10.1016/j.jocn.2012.09.003

Thickness of subcutaneous fat as a risk factor for infection in cervical spine fusion surgery.

BACKGROUND: Surgical site infections increase the incidence of morbidity and mortality as well as health-care expenses. The cost of care increases threefold to fourfold as a consequence of surgical site infection after spinal surgery. The aim of the present study was to determine the role of subcutaneous fat thickness in the development of surgical site infection following cervical spine fusion surgery. METHODS: We performed a retrospective review of a consecutive cohort of 213 adult patients who underwent posterior cervical spine fusion between 2006 and 2008 at Duke University Medical Center. The horizontal distance from the lamina to the skin surface at the C5 level and the thickness of subcutaneous fat were measured, and the ratio of the fat thickness to the total distance at the surgical site was determined. Previously identified risk factors for the development of surgical site infection were also recorded. RESULTS: Twenty-two of the 213 patients developed a postoperative infection. Obesity (body mass index ≥ 30 kg/m2) was not a significant risk factor for surgical site infection; the body mass index (and 95% confidence interval) was 29.4 ± 1.2 kg/m2 in the patients who developed a surgical site infection compared with 28.9 ± 0.94 kg/m2 in the patients without an infection. However, the thickness of subcutaneous fat and the ratio of the fat thickness to the lamina-to-skin distance were both significant risk factors for infection. The thickness of subcutaneous fat was 27.0 ± 2.5 mm in the patients who developed a surgical site infection group compared with 21.4 ± 0.88 mm in the patients without an infection (p = 0.042). The ratio of fat thickness to total thickness was 0.42 ± 0.019 in the patients who developed a surgical site infection compared with 0.35 ± 0.01 in the patients without an infection (p = 0.020). Multivariate analysis revealed this ratio to be an independent risk factor for developing a postoperative infection (odds ratio, 3.18; 95% confidence interval, 1.02 to 9.97). CONCLUSIONS: The study demonstrated that the thickness of subcutaneous fat at the surgical site is a factor in the development of surgical site infection following cervical spine fusion and deserves assessment in the preoperative evaluation.

Authors
Mehta, AI; Babu, R; Sharma, R; Karikari, IO; Grunch, BH; Owens, TR; Agarwal, VJ; Sampson, JH; Lad, SP; Friedman, AH; Kuchibhatla, M; Bagley, CA; Gottfried, ON
MLA Citation
Mehta, AI, Babu, R, Sharma, R, Karikari, IO, Grunch, BH, Owens, TR, Agarwal, VJ, Sampson, JH, Lad, SP, Friedman, AH, Kuchibhatla, M, Bagley, CA, and Gottfried, ON. "Thickness of subcutaneous fat as a risk factor for infection in cervical spine fusion surgery." J Bone Joint Surg Am 95.4 (February 20, 2013): 323-328.
PMID
23426766
Source
pubmed
Published In
The Journal of Bone and Joint Surgery
Volume
95
Issue
4
Publish Date
2013
Start Page
323
End Page
328
DOI
10.2106/JBJS.L.00225

Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas

Authors
Bagley, JH; Babu, R; Friedman, AH; Adamson, C
MLA Citation
Bagley, JH, Babu, R, Friedman, AH, and Adamson, C. "Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas." NEUROSURGICAL FOCUS 34.2 (February 2013).
PMID
23373452
Source
wos-lite
Published In
Neurosurgical focus
Volume
34
Issue
2
Publish Date
2013
DOI
10.3171/2012.12.FOCUS12343

Evaluation of Variation in the Course of the Facial Nerve, Nerve Adhesion to Tumors, and Postoperative Facial Palsy in Acoustic Neuroma

Authors
Sameshima, T; Morita, A; Tanikawa, R; Fukushima, T; Friedman, AH; Zenga, F; Ducati, A; Mastronardi, L
MLA Citation
Sameshima, T, Morita, A, Tanikawa, R, Fukushima, T, Friedman, AH, Zenga, F, Ducati, A, and Mastronardi, L. "Evaluation of Variation in the Course of the Facial Nerve, Nerve Adhesion to Tumors, and Postoperative Facial Palsy in Acoustic Neuroma." JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE 74.1 (February 2013): 39-43.
PMID
24436886
Source
wos-lite
Published In
Journal of Neurological Surgery, Part B: Skull Base
Volume
74
Issue
1
Publish Date
2013
Start Page
39
End Page
43
DOI
10.1055/s-0032-1329625

Clinical characteristics and treatment of malignant brainstem gliomas in elderly patients

Adult brainstem gliomas (BSG) are uncommon tumors that constitute only 2% of all brain tumors. Due to its rare occurrence in the elderly (60 years and older), there is no literature discussing the natural history, prognosis, and best treatment strategy for malignant BSG in this population to our knowledge. We report seven elderly patients with malignant BSG and propose treatment strategies to manage these aggressive tumors. The median age at onset in this cohort was 65 years, with the majority of patients being male (71.4%) and Caucasian (85.7%). The median duration of symptoms prior to presentation was 0.5 months, with the most common symptoms being facial weakness, blurry vision, headache, and extremity weakness. Tumors were most commonly located in the pons (85.7%), with one tumor being located in the tectal plate. Five of seven (71.4%) patients underwent biopsies, with two patients undergoing partial resections. Following tissue diagnosis, patients received radiation therapy and concurrent temozolomide, followed by additional chemotherapeutics upon progression. Side effects as a result of treatment were seen in three patients and all involved reversible hematological complications such as neutropenia and thrombopenia. The median time to progression was 6.7 months and the median overall survival was 13.5 months. While malignant BSG in elderly patients are aggressive gliomas with an overall poor prognosis, these patients are able to safely undergo aggressive chemoradiotherapy, resulting in improved survival. Resection may be considered for select patients in which the tumor is mostly exophytic, near the brainstem surface, and easily accessible. © 2013 Elsevier Ltd. All rights reserved.

Authors
Babu, R; Kranz, PG; Karikari, IO; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Kranz, PG, Karikari, IO, Friedman, AH, and Adamson, C. "Clinical characteristics and treatment of malignant brainstem gliomas in elderly patients." Journal of Clinical Neuroscience 20.10 (2013): 1382-1386.
Source
scival
Published In
Journal of Clinical Neuroscience
Volume
20
Issue
10
Publish Date
2013
Start Page
1382
End Page
1386
DOI
10.1016/j.jocn.2012.12.011

Middle fossa approach for total resection of petrous apex cholesterol granulomas: Use of vascularized galeofascial flap preventing recurrence

Background: Cholesterol granulomas (CGs) of the petrous apex (PA) are rare, benign, expanding lesions. Surgical treatment is recommended for patients with symptomatic disease; however, the optimal surgical procedure is still controversial due to high recurrence rates. The main treatment strategy is divided into drainage and complete resection. Objective: We advocate radical resection of the lesion by the middle fossa approach and reconstruction with a vascularized galeofascial flap. Methods: A 10-year retrospective case review of 17 patients undergoing surgical treatment of PA CGs between 2000 and 2010 was undertaken. Operative outcomes and surgical complications were analyzed. In addition, our operative method and the related anatomy are described from cadaveric dissections. Results: All but 1 patient was operated on via a middle fossa approach. Using the middle fossa approach, radical resection of all PA CGs was achieved with obliteration of the cyst cavity using a vascularized flap. Important surrounding structures included the internal auditory canal, cochlea, petrous carotid artery, and abducens nerve. There was 1 death caused by internal carotid artery occlusion. No other major complications or cranial nerve deficits occurred postoperatively. Clinical recurrence occurred in 1 patient (5.9%). Conclusion: Our technique of radical resection and reconstruction with a vascularized flap has the advantage of being less invasive with less cosmetic deformity and allows preservation of cranial nerve function with a low recurrence rate. Knowledge of the surgical anatomy and the characteristics of CG is prudent because important neurovascular structures may be exposed behind the CG wall due to bony erosion. © 2012 by the Congress of Neurological Surgeons.

Authors
Kusumi, M; Fukushima, T; Mehta, AI; Cunningham, CD; Friedman, AH; Fujii, K
MLA Citation
Kusumi, M, Fukushima, T, Mehta, AI, Cunningham, CD, Friedman, AH, and Fujii, K. "Middle fossa approach for total resection of petrous apex cholesterol granulomas: Use of vascularized galeofascial flap preventing recurrence." Neurosurgery 72 (2013): ons77-ons86.
Source
scival
Published In
Neurosurgery
Volume
72
Publish Date
2013
Start Page
ons77
End Page
ons86
DOI
10.1227/NEU.0b013e3182724354

Long-term economic impact of coiling vs clipping for unruptured intracranial aneurysms

Background: Treatment of unruptured intracranial aneurysms (UIAs) involves endovascular coiling or aneurysm clipping. While many studies have compared these treatment modalities with respect to various clinical outcomes, few studies have investigated the economic costs associated with each procedure. Objective: To determine the reoperation rate, postoperative complications, and inpatient and outpatient costs associated with surgical or endovascular treatment of patients with UIAs in the United States. Methods: We utilized the MarketScan database to examine patients who underwent surgical clipping or endovascular coiling procedures for UIAs from 2000 to 2009, comparing reoperation rates, complications, and angiogram and healthcare resource use. Propensity score matching techniques were used to match patients. Results: We identified 4,504 patients with surgically treated UIAs, with propensity score matching of 3,436 patients. Reoperation rates were significantly lower in the clipping group compared to the coiling group at 1- (P < 001), 2- (P < 001), and 5 years (P < 001) following the procedure. However, postoperative complications (immediate, 30 and 90 days) were significantly higher in those undergoing surgical clipping. Although hospital length of stay and costs were higher in the clipping group for the index procedure, the number of postoperative angiograms and outpatient services used at 1, 2, and 5 years were significantly higher in the coiling group. Conclusion: Though surgical clipping resulted in lower reoperation rates, it was associated with higher complication rates and initial costs. However, overall costs at 2 and 5 years were similar to endovascular coiling due to the significantly higher number of follow-up angiograms and outpatient costs in these patients. Copyright © 2013 Congress of Neurological Surgeons.

Authors
Lad, SP; Babu, R; Rhee, MS; Franklin, RL; Ugiliweneza, B; Hodes, J; Nimjee, SM; Zomorodi, AR; Smith, TP; Friedman, AH; Patil, CG; Boakye, M
MLA Citation
Lad, SP, Babu, R, Rhee, MS, Franklin, RL, Ugiliweneza, B, Hodes, J, Nimjee, SM, Zomorodi, AR, Smith, TP, Friedman, AH, Patil, CG, and Boakye, M. "Long-term economic impact of coiling vs clipping for unruptured intracranial aneurysms." Neurosurgery 72.6 (2013): 1000-1011.
Source
scival
Published In
Neurosurgery
Volume
72
Issue
6
Publish Date
2013
Start Page
1000
End Page
1011
DOI
10.1227/01.neu.0000429284.91142.56

Contemporary surgical management of vestibular schwannomas: Analysis of complications and lessons learned over the past decade

BACKGROUND:: Despite advanced microsurgical techniques, more refined instrumentation, and expert team management, there is still a significant incidence of complications in vestibular schwannoma surgery. OBJECTIVE:: To analyze complications from the microsurgical treatment of vestibular schwannoma by an expert surgical team and to propose strategies for minimizing such complications. METHODS:: Surgical outcomes and complications were evaluated in a consecutive series of 410 unilateral vestibular schwannomas treated from 2000 to 2009. Clinical status and complications were assessed postoperatively (within 7 days) and at the time of follow-up (range, 1-116 months; mean, 32.7 months). RESULTS:: Follow-up data were available for 357 of the 410 patients (87.1%). Microsurgical tumor resection was performed through a retrosigmoid approach in 70.7% of cases. Thirty-three patients (8%) had intrameatal tumors and 204 (49.8%) had tumors that were <20 mm. Gross total resection was performed in 306 patients (74.6%). Hearing preservation surgery was attempted in 170 patients with tumors <20 mm, and good hearing was preserved in 74.1%. The main neurological complication was facial palsy (House-Brackmann grade III-VI), observed in 14% of patients (56 cases) postoperatively; however, 59% of them improved during the follow-up period. Other neurological complications were disequilibrium in 6.3%, facial numbness in 2.2%, and lower cranial nerve deficit in 0.5%. Nonneurological complications included cerebrospinal fluid leaks in 7.6%, wound infection in 2.2%, and meningitis in 1.7%. CONCLUSION:: Many of these complications are avoidable through further refinement of operative technique, and strategies for avoiding complications are proposed. ABBREVIATIONS:: ABR, auditory brainstem responseAICA, anterior inferior cerebellar arteryCN, cranial nerveCPA, cerebellopontine angleFN, facial nerveGTR, gloss total resectionH-B, House-BrackmannHPS, hearing preservation surgeryNTR, near-total resectionSRT, stereotactic radiation therapySTR, subtotal resectionVAFE, vascular, adherent, fibrous, and engulfingVS, vestibular schwannoma. Copyright © 2012 by theCongress of Neurological Surgeons.

Authors
Nonaka, Y; Fukushima, T; Watanabe, K; Friedman, AH; Sampson, JH; McElveen, JT; Cunningham, CD; Zomorodi, AR
MLA Citation
Nonaka, Y, Fukushima, T, Watanabe, K, Friedman, AH, Sampson, JH, McElveen, JT, Cunningham, CD, and Zomorodi, AR. "Contemporary surgical management of vestibular schwannomas: Analysis of complications and lessons learned over the past decade." Neurosurgery 72 (2013): ons103-ons115.
Source
scival
Published In
Neurosurgery
Volume
72
Publish Date
2013
Start Page
ons103
End Page
ons115
DOI
10.1227/NEU.0b013e3182752b05

Outcome and prognostic factors in adult cerebellar glioblastoma

Cerebellar glioblastoma multiforme (GBM) occurs rarely in adults, accounting for 0.4-3.4% of all GBM. Current studies have all involved small patient numbers, limiting the clear identification of prognostic factors. Additionally, while few studies have compared cerebellar GBM to their supratentorial counterparts, there is conflicting data regarding their relative prognosis. To better characterize outcome and identify patient and treatment factors which affect survival, the authors analyzed cases of adult cerebellar GBM from the Surveillance, Epidemiology, and End Results database. A total of 247 adult patients with cerebellar GBM were identified, accounting for 0.67% of all adult GBM. Patients with cerebellar GBM were significantly younger than those with supratentorial tumors (56.6 versus 61.8 years, p < 0.0001), but a larger percentage of patients with supratentorial GBM were Caucasian (91.7% versus 85.0%, p < 0.0001). Overall median survival did not differ between those with cerebellar and supratentorial GBM (7 versus 8 months, p = 0.24), with similar rates of long-term (greater than 2 years) survival (13.4% versus 10.6%, p = 0.21). Multivariate analysis revealed age greater than 40 years (hazard ratio [HR]: 2.20; 95% confidence interval [CI]: 1.47-3.28; p = 0.0001) to be associated with worse patient survival, while the use of radiotherapy (HR: 0.33; 95% CI: 0.24-0.47; p < 0.0001) and surgical resection (HR: 0.66; 95% CI: 0.45-0.96; p = 0.028) were seen to be independent favorable prognostic factors. In conclusion, patients with cerebellar GBM have an overall poor prognosis, with radiotherapy and surgical resection significantly improving survival. As with supratentorial GBM, older age is a poor prognostic factor. The lack of differences between supratentorial and cerebellar GBM with respect to overall survival and prognostic factors suggests these tumors to be biologically similar. © 2013 Elsevier Ltd. All rights reserved.

Authors
Babu, R; Sharma, R; Karikari, IO; Owens, TR; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Sharma, R, Karikari, IO, Owens, TR, Friedman, AH, and Adamson, C. "Outcome and prognostic factors in adult cerebellar glioblastoma." Journal of Clinical Neuroscience 20.8 (2013): 1117-1121.
Source
scival
Published In
Journal of Clinical Neuroscience
Volume
20
Issue
8
Publish Date
2013
Start Page
1117
End Page
1121
DOI
10.1016/j.jocn.2012.12.006

Less invasive transjugular approach with Fallopian bridge technique for facial nerve protection and hearing preservation in surgery of glomus jugulare tumors

For the past three decades, surgery of glomus jugulare tumors (GJTs) has been characterized by extensive combined head and neck, neuro-otologic, and neurosurgical approaches. In recent years, the authors have modified the operative technique to a less invasive approach for preservation of cranial nerves while achieving satisfactory tumor resection. We evaluated and compared the clinical outcomes of our current less invasive approach with our previous more extensive procedures. The clinical records of 39 cases of GJT surgically treated between 1992 and 2011 were retrospectively reviewed. The less invasive transjugular approach with Fallopian bridge technique (LI-TJ) was used for the most recent five cases. The combined transmastoid-transjugular and high cervical (TM-HC) approach was performed in 30 cases, while four cases were treated with a transmastoid-transsigmoid approach with facial nerve translocation. Operative technique, extent of tumor resection, operating time, hospital stay, and morbidity were examined through the operative records, and a comparison was made between the LI-TJ cases and the more invasive cases. No facial nerve palsy was seen in the LI-TJ group while the TM-HC group demonstrated six cases (17.6 %) of facial palsy (House-Brackmann facial nerve function grading scale grade II and III). The complication rate was 0 % in the LI-TJ group and 16.7 % in the more invasive group. The mean operative time and hospital stay were shorter in the LI-TJ group (6.4 h and 4.3 days, respectively) compared with the more invasive group (10.7 h and 8.0 days, respectively). The LI-TJ approach with Fallopian bridge technique provided adequate tumor resection with cranial preservation and definitive advantage over the more extensive approach. © 2013 Springer-Verlag Berlin Heidelberg.

Authors
Nonaka, Y; Fukushima, T; Watanabe, K; Friedman, AH; Jr, JTM; III, CDC; Zomorodi, AR
MLA Citation
Nonaka, Y, Fukushima, T, Watanabe, K, Friedman, AH, Jr, JTM, III, CDC, and Zomorodi, AR. "Less invasive transjugular approach with Fallopian bridge technique for facial nerve protection and hearing preservation in surgery of glomus jugulare tumors." Neurosurgical Review 36.4 (2013): 579-586.
Source
scival
Published In
Neurosurgical Review
Volume
36
Issue
4
Publish Date
2013
Start Page
579
End Page
586
DOI
10.1007/s10143-013-0482-x

Convection enhanced delivery of macromolecules for brain tumors.

The blood brain barrier (BBB) poses a significant challenge for drug delivery of macromolecules into the brain. Convection-enhanced delivery (CED) circumvents the BBB through direct intracerebral infusion using a hydrostatic pressure gradient to transfer therapeutic compounds. The efficacy of CED is dependent on the distribution of the therapeutic agent to the targeted region. Here we present a review of convection enhanced delivery of macromolecules, emphasizing the role of tracers in enabling effective delivery anddiscuss current challenges in the field.

Authors
Mehta, AI; Choi, BD; Ajay, D; Raghavan, R; Brady, M; Friedman, AH; Pastan, I; Bigner, DD; Sampson, JH
MLA Citation
Mehta, AI, Choi, BD, Ajay, D, Raghavan, R, Brady, M, Friedman, AH, Pastan, I, Bigner, DD, and Sampson, JH. "Convection enhanced delivery of macromolecules for brain tumors." Current drug discovery technologies 9.4 (December 2012): 305-310.
PMID
22339074
Source
epmc
Published In
Current drug discovery technologies
Volume
9
Issue
4
Publish Date
2012
Start Page
305
End Page
310
DOI
10.2174/157016312803305951

Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients.

BACKGROUND: Bevacizumab improves outcome for most recurrent glioblastoma patients, but the duration of benefit is limited and survival after initial bevacizumab progression is poor. We evaluated bevacizumab continuation beyond initial progression among recurrent glioblastoma patients as it is a common, yet unsupported practice in some countries. METHODS: We analysed outcome among all patients (n=99) who received subsequent therapy after progression on one of five consecutive, single-arm, phase II clinical trials evaluating bevacizumab regimens for recurrent glioblastoma. Of note, the five trials contained similar eligibility, treatment and assessment criteria, and achieved comparable outcome. RESULTS: The median overall survival (OS) and OS at 6 months for patients who continued bevacizumab therapy (n=55) were 5.9 months (95% confidence interval (CI): 4.4, 7.6) and 49.2% (95% CI: 35.2, 61.8), compared with 4.0 months (95% CI: 2.1, 5.4) and 29.5% (95% CI: 17.0, 43.2) for patients treated with a non-bevacizumab regimen (n=44; P=0.014). Bevacizumab continuation was an independent predictor of improved OS (hazard ratio=0.64; P=0.04). CONCLUSION: The results of our retrospective pooled analysis suggest that bevacizumab continuation beyond initial progression modestly improves survival compared with available non-bevacizumab therapy for recurrent glioblastoma patients require evaluation in an appropriately randomised, prospective trial.

Authors
Reardon, DA; Herndon, JE; Peters, KB; Desjardins, A; Coan, A; Lou, E; Sumrall, AL; Turner, S; Lipp, ES; Sathornsumetee, S; Rich, JN; Sampson, JH; Friedman, AH; Boulton, ST; Bigner, DD; Friedman, HS; Vredenburgh, JJ
MLA Citation
Reardon, DA, Herndon, JE, Peters, KB, Desjardins, A, Coan, A, Lou, E, Sumrall, AL, Turner, S, Lipp, ES, Sathornsumetee, S, Rich, JN, Sampson, JH, Friedman, AH, Boulton, ST, Bigner, DD, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab continuation beyond initial bevacizumab progression among recurrent glioblastoma patients." Br J Cancer 107.9 (October 23, 2012): 1481-1487.
PMID
23037712
Source
pubmed
Published In
British Journal of Cancer
Volume
107
Issue
9
Publish Date
2012
Start Page
1481
End Page
1487
DOI
10.1038/bjc.2012.415

Preauricular transzygomatic anterior infratemporal fossa approach for tumors in or around infratemporal fossa lesions.

Various surgical approaches to the infratemporal fossa (ITF) have been reported. Among them, the preauricular transzygomatic anterior ITF approach (anterior ITF approach) has been used for exposure of the antero-superior part of the ITF. The purpose of this article is to show anatomical dissections using the anterior ITF approach and to evaluate our surgical experience using this approach. An anatomical study of the anterior ITF approach was performed using six sides of three cadaveric heads. Clinical course was retrospectively reviewed for 34 patients who underwent microsurgical resection of tumor in or around the ITF using this approach. Medical, surgical, and neuroimaging records of these patients were evaluated. The key point of this approach was mobilization of the second and third divisions of the trigeminal nerve after drilling of the lateral loop between the foramina rotundum and ovale. After mobilization of the trigeminal nerve, the auditory tube, tensor veli palatini muscle, and pharyngobasilar membrane could be seen. Removal of the pterygoid muscles and plates allowed surgical access to the ITF, orbit, maxillary sinus, pterygopalatine fossa, and parapharyngeal space. We used this approach in 31 patients with skull base tumors between 1994 and 2007. Gross total removal was achieved in 27 of the 31 patients. No mortality or severe morbidity was encountered. Therefore, the anterior ITF approach provides easy access to the ITF and adjacent regions without destruction of important organs.

Authors
Ohue, S; Fukushima, T; Kumon, Y; Ohnishi, T; Friedman, AH
MLA Citation
Ohue, S, Fukushima, T, Kumon, Y, Ohnishi, T, and Friedman, AH. "Preauricular transzygomatic anterior infratemporal fossa approach for tumors in or around infratemporal fossa lesions." Neurosurg Rev 35.4 (October 2012): 583-592.
PMID
22527629
Source
pubmed
Published In
Neurosurgical Review
Volume
35
Issue
4
Publish Date
2012
Start Page
583
End Page
592
DOI
10.1007/s10143-012-0389-y

2012 Young Investigator Award winner: The distribution of body mass as a significant risk factor for lumbar spinal fusion postoperative infections.

STUDY DESIGN: A retrospective review. OBJECTIVE: The purpose of this study was to determine the role in body habitus and weight distribution on developing a surgical site infection (SSI). SUMMARY OF BACKGROUND DATA: SSI after lumbar spine surgery remains a significant cause of morbidity. The literature demonstrates an increased risk of postoperative infections associated with obesity, diabetes, and multilevel surgeries. METHODS: A retrospective review was performed on a consecutive cohort of 298 adult patients who underwent lumbar spine fusion surgeries between 2006 and 2008 at the Duke University Medical Center. Previously identified risk factors (i.e., number of levels, diabetes, body mass index [BMI]) were collected, as well as the horizontal distance from the lamina to the skin surface (measured at L4) and thickness of subcutaneous fat at the surgical site. RESULTS: Among the 298 patients, 24 (8%) had postoperative infections. Of the previously identified risk factors, number of levels (P = 0.0078) was found to be significantly associated with infections, whereas BMI (P = 0.16) and diabetes (P = 0.13) were found not to be statistically significant. Obesity (BMI ≥30) (P = 0.025), skin to lamina distance (P = 0.046), and thickness of the subcutaneous fat (P = 0.035) were found to be significant risk factors for SSI. CONCLUSION: Our findings suggest that in obese patients, the distribution of body mass is more predictive of SSI than the absolute BMI and deserves attention in preoperative evaluation.

Authors
Mehta, AI; Babu, R; Karikari, IO; Grunch, B; Agarwal, VJ; Owens, TR; Friedman, AH; Bagley, CA; Gottfried, ON
MLA Citation
Mehta, AI, Babu, R, Karikari, IO, Grunch, B, Agarwal, VJ, Owens, TR, Friedman, AH, Bagley, CA, and Gottfried, ON. "2012 Young Investigator Award winner: The distribution of body mass as a significant risk factor for lumbar spinal fusion postoperative infections." Spine 37.19 (September 2012): 1652-1656.
PMID
22146285
Source
epmc
Published In
Spine
Volume
37
Issue
19
Publish Date
2012
Start Page
1652
End Page
1656
DOI
10.1097/brs.0b013e318241b186

Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.

Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas ( more than 10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.

Authors
Jiao, Y; Killela, PJ; Reitman, ZJ; Rasheed, AB; Heaphy, CM; de Wilde, RF; Rodriguez, FJ; Rosemberg, S; Oba-Shinjo, SM; Nagahashi Marie, SK; Bettegowda, C; Agrawal, N; Lipp, E; Pirozzi, C; Lopez, G; He, Y; Friedman, H; Friedman, AH; Riggins, GJ; Holdhoff, M; Burger, P; McLendon, R; Bigner, DD; Vogelstein, B; Meeker, AK; Kinzler, KW; Papadopoulos, N; Diaz, LA; Yan, H
MLA Citation
Jiao, Y, Killela, PJ, Reitman, ZJ, Rasheed, AB, Heaphy, CM, de Wilde, RF, Rodriguez, FJ, Rosemberg, S, Oba-Shinjo, SM, Nagahashi Marie, SK, Bettegowda, C, Agrawal, N, Lipp, E, Pirozzi, C, Lopez, G, He, Y, Friedman, H, Friedman, AH, Riggins, GJ, Holdhoff, M, Burger, P, McLendon, R, Bigner, DD, Vogelstein, B, Meeker, AK, Kinzler, KW, Papadopoulos, N, Diaz, LA, and Yan, H. "Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas." Oncotarget 3.7 (July 2012): 709-722.
PMID
22869205
Source
pubmed
Published In
Oncotarget
Volume
3
Issue
7
Publish Date
2012
Start Page
709
End Page
722
DOI
10.18632/oncotarget.588

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention.

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

Authors
Babu, R; Bagley, JH; Di, C; Friedman, AH; Adamson, C
MLA Citation
Babu, R, Bagley, JH, Di, C, Friedman, AH, and Adamson, C. "Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention." Neurosurg Focus 32.4 (April 2012): E8-. (Review)
PMID
22463118
Source
pubmed
Published In
Neurosurgical focus
Volume
32
Issue
4
Publish Date
2012
Start Page
E8
DOI
10.3171/2012.1.FOCUS11366

The use of motor mapping to aid resection of eloquent gliomas.

Surgery remains one of the oldest and still most important forms of treatment for patients with glioma. The advantages of surgical resection for glioma must be balanced with the potential of operative morbidity to surrounding eloquent brain. To that end, advances in functional brain mapping allow for safer operations with more aggressive surgical resections. A brief history of motor mapping as well as its present day use in aiding resection of eloquent gliomas is discussed.

Authors
Choi, BD; Mehta, AI; Batich, KA; Friedman, AH; Sampson, JH
MLA Citation
Choi, BD, Mehta, AI, Batich, KA, Friedman, AH, and Sampson, JH. "The use of motor mapping to aid resection of eloquent gliomas." Neurosurg Clin N Am 23.2 (April 2012): 215-vii. (Review)
PMID
22440865
Source
pubmed
Published In
Neurosurgery Clinics of North America
Volume
23
Issue
2
Publish Date
2012
Start Page
215
End Page
vii
DOI
10.1016/j.nec.2012.01.013

Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma.

We evaluated the efficacy of carboplatin, irinotecan, and bevacizumab among bevacizumab-naïve, recurrent glioblastoma (GBM) patients in a phase 2, open-label, single arm trial. Forty eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day one, while bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3A-enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first two cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, non-compliance, or voluntary withdrawal. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints included safety and median overall survival (OS). All patients had progression after standard therapy. The median age was 51 years. Sixteen patients (40%) had a KPS of 90-100, while 27 (68%) were at first progression. The median time from original diagnosis was 11.4 months. The PFS-6 rate was 46.5% (95% CI: 30.4, 61.0%) and the median OS was 8.3 months [95% confidence interval (CI): 5.9, and 10.7 months]. Grade 4 events were primarily hematologic and included neutropenia and thrombocytopenia in 20 and 10%, respectively. The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. Eleven patients (28%) discontinued study therapy due to toxicity and 17 patients (43%) required dose modification. One patient died due to treatment-related intestinal perforation. The addition of carboplatin and irinotecan to bevacizumab significantly increases toxicity but does not improve anti-tumor activity to that achieved historically with single-agent bevacizumab among bevacizumab-naïve, recurrent GBM patients. (ClinicalTrials.gov number NCT00953121).

Authors
Reardon, DA; Desjardins, A; Peters, KB; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Bulusu, A; Threatt, S; Friedman, AH; Vredenburgh, JJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, KB, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Bulusu, A, Threatt, S, Friedman, AH, Vredenburgh, JJ, and Friedman, HS. "Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naïve, recurrent glioblastoma." J Neurooncol 107.1 (March 2012): 155-164.
PMID
21986722
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
107
Issue
1
Publish Date
2012
Start Page
155
End Page
164
DOI
10.1007/s11060-011-0722-2

Tentorial detachment technique in the combined petrosal approach for petroclival meningiomas.

OBJECT: The combined petrosal approach is a suitable technique for the resection of medium-to-large petroclival meningiomas (PCMs). Multiple technical modifications have been reported to increase the surgical corridor, including the method of dural and tentorial opening. The authors describe their method of dural opening and tentorial resection, and detail the microanatomy related to their technique to clarify pitfalls and effects. METHODS: The relationship of temporal bridging veins and cranial nerves (CNs) around the tentorial resection area was examined during the combined petrosal approach in 20 cadaveric specimens. The authors also reviewed their 23 consecutive clinical cases treated using this technique between 2002 and 2010, focusing on the effects and risks of the procedure. RESULTS: In the authors' method, the tentorial resection extends from 5 to 10 mm anterior to the junction of the sigmoid sinus and the superior petrosal sinus ("sinodural point") to the trigeminal fibrous ring and the dural sleeve of CN IV. Temporal bridging veins enter the transverse sinus no more than 5 mm anterior to the sinodural point. The CN IV should be freed from its tentorial dural sleeve while avoiding disruption of the posterior cavernous sinus. The clinical data demonstrate a total resection rate of 78.3%, intraoperative estimated blood loss < 400 ml at a rate of 80.9%, and a venous congestion rate of 0%. CONCLUSIONS: Understanding the anatomical relationship between the tentorium and temporal bridging veins and CNs IV-VI allows neurosurgeons the ability to develop a combined petrosal approach to PCMs that will effectively supply a wide operative corridor after resecting the tentorium, while significantly devascularizing tumors.

Authors
Kusumi, M; Fukushima, T; Mehta, AI; Aliabadi, H; Nonaka, Y; Friedman, AH; Fujii, K
MLA Citation
Kusumi, M, Fukushima, T, Mehta, AI, Aliabadi, H, Nonaka, Y, Friedman, AH, and Fujii, K. "Tentorial detachment technique in the combined petrosal approach for petroclival meningiomas." J Neurosurg 116.3 (March 2012): 566-573.
PMID
22196100
Source
pubmed
Published In
Journal of neurosurgery
Volume
116
Issue
3
Publish Date
2012
Start Page
566
End Page
573
DOI
10.3171/2011.11.JNS11985

Trigeminal schwannomas: skull base approaches and operative results in 105 patients.

BACKGROUND: Trigeminal schwannomas make up 0.8% to 8% of all intracranial schwannomas. OBJECTIVE: To analyze our surgical experience with trigeminal schwannomas. METHODS: We performed 107 operations on 105 patients harboring trigeminal schwannomas over the past 30 years. We classified the tumors as peripheral, ganglion cavernous, posterior fossa root, and dumbbell types according to the portion of the nerve that gave rise to the tumor. RESULTS: Fourteen were peripheral-type tumors (13.1%), 39 (36.4%) were ganglion cavernous type, 22 (20.6%) were posterior fossa root type, and 32 (30.0%) were dumbbell type. Sixty-five tumors were solid, 35 were mixed, and only 7 were cystic. Among solid tumors, 14 were vascular, fibrous, and adherent to adjacent structures. Total or near-total removal was performed in 86 cases (81.9%), and subtotal removal was achieved in 18 (17.1%). The most common symptom was facial hypesthesia, occurring in 69 patients. This symptom improved in 11 patients, persisted in 50 patients, and worsened in 8 patients after surgery. New postoperative hypesthesia was observed in 8 patients. The second most common symptom was facial pain, observed in 24 patients. Facial pain subsided in 22 and persisted in 2 patients after surgery. Diplopia was observed in 21 patients. This symptom improved postoperatively in 14 patients, persisted in 6 patients, and worsened in 1 patient. CONCLUSION: The present series demonstrates acceptable results using microsurgical treatment to remove trigeminal schwannomas. Pain and diplopia may be relieved after surgery; however, hypesthesia frequently remains or may be worsened by surgery.

Authors
Wanibuchi, M; Fukushima, T; Zomordi, AR; Nonaka, Y; Friedman, AH
MLA Citation
Wanibuchi, M, Fukushima, T, Zomordi, AR, Nonaka, Y, and Friedman, AH. "Trigeminal schwannomas: skull base approaches and operative results in 105 patients." Neurosurgery 70.1 Suppl Operative (March 2012): 132-143. (Review)
PMID
21796003
Source
pubmed
Published In
Neurosurgery
Volume
70
Issue
1 Suppl Operative
Publish Date
2012
Start Page
132
End Page
143
DOI
10.1227/NEU.0b013e31822efb21

Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme.

PURPOSE: To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). METHODS AND MATERIALS: A total of 125 patients with newly diagnosed GBM were enrolled in the study, and received standard radiation therapy and daily temozolomide. All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8-Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m(2) daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. RESULTS: Of the 125 patients, 120 (96%) completed the protocol-specified radiation therapy. Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. After radiation therapy, 3 patients had progressive disease, 2 had severe fatigue and decreased performance status, 1 patient had a colonic perforation, and 1 had a rectal fissure; these 7 patients therefore did not proceed with the protocol-specified adjuvant temozolomide, bevacizumab, and irinotecan. However, 113 patients (90%) were able to continue on study. CONCLUSIONS: The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM.

Authors
Vredenburgh, JJ; Desjardins, A; Kirkpatrick, JP; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Bailey, L; Threatt, S; Sampson, J; Friedman, A; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Kirkpatrick, JP, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Bailey, L, Threatt, S, Sampson, J, Friedman, A, and Friedman, HS. "Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme." Int J Radiat Oncol Biol Phys 82.1 (January 1, 2012): 58-66.
PMID
21036490
Source
pubmed
Published In
International Journal of Radiation: Oncology - Biology - Physics
Volume
82
Issue
1
Publish Date
2012
Start Page
58
End Page
66
DOI
10.1016/j.ijrobp.2010.08.058

A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma.

BACKGROUND: Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells. OBJECTIVE: To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete T(Regs) while permitting vaccine-stimulated immune responses. METHODOLOGY: A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ). RESULTS AND CONCLUSIONS: Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study. TRIAL REGISTRATION: ClinicalTrials.gov NCT00626015.

Authors
Sampson, JH; Schmittling, RJ; Archer, GE; Congdon, KL; Nair, SK; Reap, EA; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; Coan, A; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Mitchell, DA
MLA Citation
Sampson, JH, Schmittling, RJ, Archer, GE, Congdon, KL, Nair, SK, Reap, EA, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, Coan, A, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Mitchell, DA. "A pilot study of IL-2Rα blockade during lymphopenia depletes regulatory T-cells and correlates with enhanced immunity in patients with glioblastoma." PLoS One 7.2 (2012): e31046-.
PMID
22383993
Source
pubmed
Published In
PloS one
Volume
7
Issue
2
Publish Date
2012
Start Page
e31046
DOI
10.1371/journal.pone.0031046

Comments

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Comments." Neurosurgery 70.4 (2012): 801--.
Source
scival
Published In
Neurosurgery
Volume
70
Issue
4
Publish Date
2012
Start Page
801-
DOI
10.1227/NEU.0b013e3181f74139

Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

BACKGROUND: The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open-label, single-arm trial was evaluated. METHODS: Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m(2) for patients on CYP3A enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m(2) for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first 2 cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, noncompliance, or voluntary withdrawal. The primary end point was progression-free survival at 6 months (PFS-6), and secondary end points included safety and median overall survival (OS). RESULTS: All patients had progression on at least 1 prior bevacizumab regimen and 56% enrolled after either second or third overall progression. The median OS was 5.8 months (95% confidence interval [CI], 4.0-7.0 months) and PFS-6 rate was 16% (95% CI, 5.0%-32.5%). The most common grade 3 or 4 events were hematologic and occurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatment-related deaths. CONCLUSIONS: Carboplatin, irinotecan, and bevacizumab was associated with modest activity and adequate safety among recurrent GBM patients who progressed on bevacizumab previously.

Authors
Reardon, DA; Desjardins, A; Peters, KB; Vredenburgh, JJ; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Coan, A; Threatt, S; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, KB, Vredenburgh, JJ, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Coan, A, Threatt, S, Friedman, AH, and Friedman, HS. "Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy." Cancer 117.23 (December 1, 2011): 5351-5358.
PMID
21590689
Source
pubmed
Published In
Cancer
Volume
117
Issue
23
Publish Date
2011
Start Page
5351
End Page
5358
DOI
10.1002/cncr.26188

Microsurgical management of hypoglossal schwannomas over 3 decades: a modified grading scale to guide surgical approach.

BACKGROUND: Schwannomas originating from the hypoglossal nerve are extremely rare. Microsurgical resection with the goal for cure has traditionally been associated with a high risk of postoperative deficits. OBJECTIVE: To summarize our clinical experience using tailored cranial base approaches for these formidable lesions. METHODS: The clinical records of 13 patients were retrospectively reviewed. In addition, all reported patients in the literature were reviewed. The extreme lateral infrajugular transcondylar-transtubercular exposure approach was used in all of our patients. Based on our experience and literature analysis, we propose the following modified grading scale to facilitate surgical planning: type A, intradural tumors; type B, dumbbell-shaped tumors; type C, extracranial tumors; and type D, peripheral tumors. RESULTS: All 13 patients underwent total, near-total, or subtotal tumor resection. Eight patients were men, 5 were women (mean age, 41.7 years). Sural nerve graft reconstruction for the hypoglossal nerve was performed in 4 patients. Three of the 4 patients in whom nerve reconstruction was performed regained satisfactory movement of their tongue. In the review of the literature, the mean patient age was 45.8 years. Patients presented with tongue atrophy (91.6%), headache (60.9%), and dysphagia (31.8%). The tumors were categorized as type A in 31.7% of these patients, type B in 38.6%, type C in 6.2%, and type D in 23.4%. CONCLUSION: The extreme lateral infrajugular transcondylar-transtubercular exposure approach, which is a modification of the extreme lateral suboccipital approach, provides sufficient exposure for most intracranial dumbbell-shaped hypoglossal schwannomas. Hypoglossal nerve reconstruction using a sural nerve graft improves tongue atrophy and movement for patients with resected nerves.

Authors
Nonaka, Y; Grossi, PM; Bulsara, KR; Taniguchi, RM; Friedman, AH; Fukushima, T
MLA Citation
Nonaka, Y, Grossi, PM, Bulsara, KR, Taniguchi, RM, Friedman, AH, and Fukushima, T. "Microsurgical management of hypoglossal schwannomas over 3 decades: a modified grading scale to guide surgical approach." Neurosurgery 69.2 Suppl Operative (December 2011): ons121-ons140. (Review)
PMID
21709593
Source
pubmed
Published In
Neurosurgery
Volume
69
Issue
2 Suppl Operative
Publish Date
2011
Start Page
ons121
End Page
ons140
DOI
10.1227/NEU.0b013e31822a547b

A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with temozolomide for patients with malignant glioma.

We conducted a phase I clinical trial of the combination of SCH 66336 with temozolomide administered on the standard 5-day dosing schedule. The primary objective was to determine the maximum tolerated dose and dose limiting toxicity (DLT) of twice daily SCH 66336 when administered with temozolomide to adults with malignant glioma previously treated with radiation therapy. Patients were enrolled to two strata: stratum A, patients not on enzyme-inducing antiepileptic drugs (EIAEDs); stratum B, patients receiving EIAEDs. Temozolomide was administered at a dose of 150 mg/m(2) daily for five days for the first 28-day cycle and escalated to 200 mg/m(2), during subsequent cycles. SCH 66336 was administered twice daily on a continuous daily dosing schedule. The starting dose of SCH 66336 was 75 mg twice daily for stratum A and 125 mg twice daily for stratum B. Cohorts of 3-6 patients were treated per dose level until DLT was observed. Thirty six patients were enrolled on study, including 21 patients on stratum A and 15 on stratum B. All DLTs were grade 3 events and included hepatic, gastrointestinal, renal, thrombotic and constitutional events. No grade 4 or 5 toxicities were observed. The phase II dose of SCH 66336 when combined with temozolomide is 150 mg twice daily for patients not on EIAEDs and 175 mg twice daily for patients on EIAEDs.

Authors
Desjardins, A; Reardon, DA; Peters, KB; Threatt, S; Coan, AD; Herndon, JE; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Peters, KB, Threatt, S, Coan, AD, Herndon, JE, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "A phase I trial of the farnesyl transferase inhibitor, SCH 66336, with temozolomide for patients with malignant glioma." J Neurooncol 105.3 (December 2011): 601-606.
PMID
21735117
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
105
Issue
3
Publish Date
2011
Start Page
601
End Page
606
DOI
10.1007/s11060-011-0627-0

Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans.

Lymphodepletion augments adoptive cell transfer during antitumor immunotherapy, producing dramatic clinical responses in patients with malignant melanoma. We report that the lymphopenia induced by the chemotherapeutic agent temozolomide (TMZ) enhances vaccine-driven immune responses and significantly reduces malignant growth in an established model of murine tumorigenesis. Unexpectedly, despite the improved antitumor efficacy engendered by TMZ-induced lymphopenia, there was a treatment related increase in the frequency of immunosuppressive regulatory T cells (T(Regs); P = .0006). Monoclonal antibody (mAb)-mediated inhibition of the high-affinity IL-2 receptor α (IL-2Rα/CD25) during immunotherapy in normal mice depleted T(Regs) (73% reduction; P = .0154) but also abolished vaccine-induced immune responses. However, during lymphodepletion, IL-2Rα blockade decreased T(Regs) (93% reduction; P = .0001) without impairing effector T-cell responses, to augment therapeutic antitumor efficacy (66% reduction in tumor growth; P = .0024). Of clinical relevance, we also demonstrate that anti-IL-2Rα mAb administration during recovery from lymphodepletive TMZ in patients with glioblastoma reduced T(Reg) frequency (48% reduction; P = .0061) while permitting vaccine-stimulated antitumor effector cell expansion. To our knowledge, this is the first report of systemic antibody-mediated T(Reg) depletion during lymphopenia and the consequent synergistic enhancement of vaccine-driven cellular responses, as well as the first demonstration that anti-IL-2Rα mAbs function differentially in nonlymphopenic versus lymphopenic contexts.

Authors
Mitchell, DA; Cui, X; Schmittling, RJ; Sanchez-Perez, L; Snyder, DJ; Congdon, KL; Archer, GE; Desjardins, A; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Reardon, DA; Vredenburgh, JJ; Bigner, DD; Sampson, JH
MLA Citation
Mitchell, DA, Cui, X, Schmittling, RJ, Sanchez-Perez, L, Snyder, DJ, Congdon, KL, Archer, GE, Desjardins, A, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Reardon, DA, Vredenburgh, JJ, Bigner, DD, and Sampson, JH. "Monoclonal antibody blockade of IL-2 receptor α during lymphopenia selectively depletes regulatory T cells in mice and humans." Blood 118.11 (September 15, 2011): 3003-3012.
PMID
21768296
Source
pubmed
Published In
Blood
Volume
118
Issue
11
Publish Date
2011
Start Page
3003
End Page
3012
DOI
10.1182/blood-2011-02-334565

Midsubtemporal ridge as a predictor of the lateral loop formed by the maxillary nerve and mandibular nerve: a cadaveric morphological study.

BACKGROUND: The lateral loop formed by the maxillary nerve (V2) and the mandibular nerve (V3) consists of a part of the far lateral triangle of the cavernous sinus. Because this triangle becomes a surgical corridor of the preauricular infratemporal fossa approach and a landmark of the extradural approach for the ganglion-type trigeminal schwannomas, identification of the lateral loop has important implications at the early stage of middle cranial base surgery. We realized that a bony ridge usually existed just lateral to the lateral loop. OBJECTIVE: To nominate midsubtemporal ridge (MSR) as the name for this anatomically unnamed bony ridge and to clarify its features. METHODS: Using 35 cadaver heads, we measured the shape of the MSR on both sides and the distance between the MSR and the adjacent structures. RESULTS: The MSR was recognized in 60 of 70 specimens (85.7%). The bony protrusion was 2.9 ± 1.1 mm in height, 6.0 ± 2.1 mm in width, and 9.1 ± 3.2 mm in length. A single peak with anteroposterior length was common in 47 of 60 specimens (78.3%). The MSR was located at the midpoint of the V2 and V3 in 28 specimens (46.7%) and existed 10.7 ± 3.6 mm lateral from the line that bound the foramen rotundum and the foramen ovale. CONCLUSION: We demonstrate morphological characteristics of the MSR. These data on the MSR will assist the surgeon in identifying the lateral loop as a surgical landmark during middle cranial base surgery.

Authors
Wanibuchi, M; Murakami, G; Yamashita, T; Minamida, Y; Fukushima, T; Friedman, AH; Fujimiya, M; Houkin, K
MLA Citation
Wanibuchi, M, Murakami, G, Yamashita, T, Minamida, Y, Fukushima, T, Friedman, AH, Fujimiya, M, and Houkin, K. "Midsubtemporal ridge as a predictor of the lateral loop formed by the maxillary nerve and mandibular nerve: a cadaveric morphological study." Neurosurgery 69.1 Suppl Operative (September 2011): ons95-ons98.
PMID
21346652
Source
pubmed
Published In
Neurosurgery
Volume
69
Issue
1 Suppl Operative
Publish Date
2011
Start Page
ons95
End Page
ons98
DOI
10.1227/NEU.0b013e31821247f5

Convection-enhanced delivery.

Authors
Sampson, JH; Raghavan, R; Brady, M; Friedman, AH; Bigner, D
MLA Citation
Sampson, JH, Raghavan, R, Brady, M, Friedman, AH, and Bigner, D. "Convection-enhanced delivery." J Neurosurg 115.3 (September 2011): 463-464.
PMID
21619413
Source
pubmed
Published In
Journal of neurosurgery
Volume
115
Issue
3
Publish Date
2011
Start Page
463
End Page
464
DOI
10.3171/2010.11.JNS101801

Colocalization of gadolinium-diethylene triamine pentaacetic acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans.

BACKGROUND: Convection-enhanced delivery (CED) permits site-specific therapeutic drug delivery within interstitial spaces at increased dosages through circumvention of the blood-brain barrier. CED is currently limited by suboptimal methodologies for monitoring the delivery of therapeutic agents that would permit technical optimization and enhanced therapeutic efficacy. OBJECTIVE: To determine whether a readily available small-molecule MRI contrast agent, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), could effectively track the distribution of larger therapeutic agents. METHODS: Gd-DTPA was coinfused with the larger molecular tracer, I-labeled human serum albumin (I-HSA), during CED of an EGFRvIII-specific immunotoxin as part of treatment for a patient with glioblastoma. RESULTS: Infusion of both tracers was safe in this patient. Analysis of both Gd-DTPA and I-HSA during and after infusion revealed a high degree of anatomical and volumetric overlap. CONCLUSION: Gd-DTPA may be able to accurately demonstrate the anatomic and volumetric distribution of large molecules used for antitumor therapy with high resolution and in combination with fluid-attenuated inversion recovery (FLAIR) imaging, and provide additional information about leaks into cerebrospinal fluid spaces and resection cavities. Similar studies should be performed in additional patients to validate our findings and help refine the methodologies we used.

Authors
Sampson, JH; Brady, M; Raghavan, R; Mehta, AI; Friedman, AH; Reardon, DA; Petry, NA; Barboriak, DP; Wong, TZ; Zalutsky, MR; Lally-Goss, D; Bigner, DD
MLA Citation
Sampson, JH, Brady, M, Raghavan, R, Mehta, AI, Friedman, AH, Reardon, DA, Petry, NA, Barboriak, DP, Wong, TZ, Zalutsky, MR, Lally-Goss, D, and Bigner, DD. "Colocalization of gadolinium-diethylene triamine pentaacetic acid with high-molecular-weight molecules after intracerebral convection-enhanced delivery in humans." Neurosurgery 69.3 (September 2011): 668-676.
PMID
21430586
Source
pubmed
Published In
Neurosurgery
Volume
69
Issue
3
Publish Date
2011
Start Page
668
End Page
676
DOI
10.1227/NEU.0b013e3182181ba8

Calcifying pseudoneoplasm of the cerebellopontine angle: case report.

BACKGROUND AND IMPORTANCE: Calcifying pseudoneoplasms are rare tumors of the neuraxis. To our knowledge, this is only the second reported case in the literature of calcifying pseudoneoplasm of the cerebellopontine angle. The etiology and natural history of these neoplasms are not well understood. This case report provides a thorough review of the histology and potential origins of calcifying pseudoneoplasm. CLINICAL PRESENTATION: A 34-year-old previously healthy man presented with a 6-month history of progressive worsening headaches, fatigue, tinnitus, dizziness, and blurry vision. Neurological examination was notable for tongue deviation, tongue atrophy, and left uvula deviation. Computed tomography (CT) scanning showed a 3.3 × 3.5 cm densely calcified posterior fossa mass appearing to arise from the occipital bone. Magnetic resonance imaging (MRI) revealed a 4.3 × 2.9 × 2.9 cm left posterior fossa enhancing mass with the margin tip from the left occipital condyle. A transcondylar approach was used to resect the lesion. The mass was found to have eroded through the bone into the foramen magnum. Histopathological examination confirmed the diagnosis of calcifying pseudoneoplasm of the cerebellopontine angle. CONCLUSION: Calcifying pseudoneoplasms should be considered in the differential diagnosis of calcified cerebellopontine angle tumors. Histopathologic diagnosis is extremely important in the characterization of these lesions in order to direct the course of appropriate management. An inaccurate diagnosis of a malignant tumor can result in potentially harmful and unnecessary therapies, as prognosis for these lesions is generally favorable.

Authors
Hodges, TR; Karikari, IO; Nimjee, SM; Tibaleka, J; Friedman, AH; Cummings, TJ; Fukushima, T; Friedman, AH
MLA Citation
Hodges, TR, Karikari, IO, Nimjee, SM, Tibaleka, J, Friedman, AH, Cummings, TJ, Fukushima, T, and Friedman, AH. "Calcifying pseudoneoplasm of the cerebellopontine angle: case report." Neurosurgery 69.1 Suppl Operative (September 2011): onsE117-onsE120.
PMID
21415795
Source
epmc
Published In
Neurosurgery
Volume
69
Issue
1 Suppl Operative
Publish Date
2011
Start Page
onsE117
End Page
onsE120
DOI
10.1227/neu.0b013e3182155511

Epidemiology.

Authors
Sampson, JH; Herndon, JE; Friedman, AH; Abernethy, AP
MLA Citation
Sampson, JH, Herndon, JE, Friedman, AH, and Abernethy, AP. "Epidemiology." J Neurosurg 115.2 (August 2011): 256-257.
PMID
21529133
Source
pubmed
Published In
Journal of neurosurgery
Volume
115
Issue
2
Publish Date
2011
Start Page
256
End Page
257
DOI
10.3171/2011.1.JNS102066

Exercise behavior, functional capacity, and survival in adults with malignant recurrent glioma.

PURPOSE: Identifying strong markers of prognosis are critical to optimize treatment and survival outcomes in patients with malignant recurrent glioma. We investigated the prognostic significance of exercise behavior and functional capacity in this population. PATIENTS AND METHODS: Using a prospective design, 243 patients with WHO grades 3 to 4 recurrent malignant glioma and Karnofsky performance status (KPS) ≥ 70 completed a self-administered questionnaire that assessed exercise behavior and performed a 6-minute walk test (6MWT) to assess functional capacity. Cox proportional models were used to estimate the risk of all-cause mortality according to 6MWT distance (6MWD; < 390 meters, 390-489 meters, > 489 meters) and exercise behavior (metabolic equivalent [MET] -h/wk) adjusted for KPS and other important clinical factors. RESULTS: Median follow-up was 27.43 months. During this period, 149 deaths were recorded (61% of the total sample). Exercise behavior was an independent predictor of survival (P = .0081). Median survival was 13.03 months for patients reporting < 9 MET-h/wk relative to 21.84 months for those reporting ≥ 9 MET-h/wk. Exercise behavior added incremental prognostic value beyond that provided by KPS, age, sex, grade, and number of prior progressions (P < .001). Compared with patients reporting < 9 MET-h/wk, the adjusted hazard ratio for mortality was 0.64 (95% CI, 0.46 to 0.91) for patients reporting ≥ 9 MET-h/wk. Functional capacity was not an independent predictor of prognosis. CONCLUSION: Exercise behavior is a strong independent predictor of survival that provides incremental prognostic value to KPS as well as traditional markers of prognosis in malignant recurrent glioma.

Authors
Ruden, E; Reardon, DA; Coan, AD; Herndon, JE; Hornsby, WE; West, M; Fels, DR; Desjardins, A; Vredenburgh, JJ; Waner, E; Friedman, AH; Friedman, HS; Peters, KB; Jones, LW
MLA Citation
Ruden, E, Reardon, DA, Coan, AD, Herndon, JE, Hornsby, WE, West, M, Fels, DR, Desjardins, A, Vredenburgh, JJ, Waner, E, Friedman, AH, Friedman, HS, Peters, KB, and Jones, LW. "Exercise behavior, functional capacity, and survival in adults with malignant recurrent glioma." J Clin Oncol 29.21 (July 20, 2011): 2918-2923.
PMID
21690470
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
29
Issue
21
Publish Date
2011
Start Page
2918
End Page
2923
DOI
10.1200/JCO.2011.34.9852

The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma.

PURPOSE: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective. EXPERIMENTAL DESIGN: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent. RESULTS: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2-25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4-74.9). The median progression-free survival was 14.2 months (95% CI: 12-16). CONCLUSION: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established.

Authors
Vredenburgh, JJ; Desjardins, A; Reardon, DA; Peters, KB; Herndon, JE; Marcello, J; Kirkpatrick, JP; Sampson, JH; Bailey, L; Threatt, S; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Reardon, DA, Peters, KB, Herndon, JE, Marcello, J, Kirkpatrick, JP, Sampson, JH, Bailey, L, Threatt, S, Friedman, AH, Bigner, DD, and Friedman, HS. "The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma." Clin Cancer Res 17.12 (June 15, 2011): 4119-4124.
PMID
21531816
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
12
Publish Date
2011
Start Page
4119
End Page
4124
DOI
10.1158/1078-0432.CCR-11-0120

Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy.

We evaluated the efficacy of metronomic etoposide or temozolomide administered with bevacizumab among recurrent glioblastoma (GBM) patients who progressed on prior bevacizumab therapy in a phase 2, open-label, two-arm trial. Twenty-three patients received bevacizumab (10 mg/kg) every 2 weeks with either oral etoposide (50 mg/m2) daily for 21 consecutive days each month or daily temozolomide (50 mg/m2). The primary endpoint was 6-month progression-free survival (PFS-6) and secondary endpoints included safety and overall survival. Both the etoposide and temozolomide arms of the study closed at the interim analysis due to lack of adequate anti-tumor activity. No radiographic responses were observed. Although 12 patients (52%) achieved stable disease, PFS-6 was 4.4% and the median PFS was 7.3 weeks. The only grade 4 adverse event was reversible neutropenia. Grade 3 toxicities included fatigue (n = 2) and infection (n = 1). Metronomic etoposide or temozolomide is ineffective when administered with bevacizumab among recurrent GBM patients who have progressed on prior bevacizumab therapy. Alternative treatment strategies remain critically needed for this indication.

Authors
Reardon, DA; Desjardins, A; Peters, K; Gururangan, S; Sampson, J; Rich, JN; McLendon, R; Herndon, JE; Marcello, J; Threatt, S; Friedman, AH; Vredenburgh, JJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Peters, K, Gururangan, S, Sampson, J, Rich, JN, McLendon, R, Herndon, JE, Marcello, J, Threatt, S, Friedman, AH, Vredenburgh, JJ, and Friedman, HS. "Phase II study of metronomic chemotherapy with bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy." J Neurooncol 103.2 (June 2011): 371-379.
PMID
20853132
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
103
Issue
2
Publish Date
2011
Start Page
371
End Page
379
DOI
10.1007/s11060-010-0403-6

A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.

Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features. The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies. However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009. These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma. Given the potent antipermeability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma. Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm. Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.

Authors
Reardon, DA; Turner, S; Peters, KB; Desjardins, A; Gururangan, S; Sampson, JH; McLendon, RE; Herndon, JE; Jones, LW; Kirkpatrick, JP; Friedman, AH; Vredenburgh, JJ; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Turner, S, Peters, KB, Desjardins, A, Gururangan, S, Sampson, JH, McLendon, RE, Herndon, JE, Jones, LW, Kirkpatrick, JP, Friedman, AH, Vredenburgh, JJ, Bigner, DD, and Friedman, HS. "A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma." J Natl Compr Canc Netw 9.4 (April 2011): 414-427. (Review)
PMID
21464146
Source
pubmed
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
4
Publish Date
2011
Start Page
414
End Page
427

Monitoring radiographic brain tumor progression.

Determining radiographic progression in primary malignant brain tumors has posed a significant challenge to the neuroncology community. Glioblastoma multiforme (GBM, WHO Grade IV) through its inherent heterogeneous enhancement, growth patterns, and irregular nature has been difficult to assess for progression. Our ability to detect tumor progression radiographically remains inadequate. Despite the advanced imaging techniques, detecting tumor progression continues to be a clinical challenge. Here we review the different criteria used to detect tumor progression, and highlight the inherent challenges with detection of progression.

Authors
Mehta, AI; Kanaly, CW; Friedman, AH; Bigner, DD; Sampson, JH
MLA Citation
Mehta, AI, Kanaly, CW, Friedman, AH, Bigner, DD, and Sampson, JH. "Monitoring radiographic brain tumor progression." Toxins 3.3 (March 15, 2011): 191-200. (Review)
PMID
22069705
Source
epmc
Published In
Toxins
Volume
3
Issue
3
Publish Date
2011
Start Page
191
End Page
200
DOI
10.3390/toxins3030191

Imaging of convection enhanced delivery of toxins in humans.

Drug delivery of immunotoxins to brain tumors circumventing the blood brain barrier is a significant challenge. Convection-enhanced delivery (CED) circumvents the blood brain barrier through direct intracerebral application using a hydrostatic pressure gradient to percolate therapeutic compounds throughout the interstitial spaces of infiltrated brain and tumors. The efficacy of CED is determined through the distribution of the therapeutic agent to the targeted region. The vast majority of patients fail to receive a significant amount of coverage of the area at risk for tumor recurrence. Understanding this challenge, it is surprising that so little work has been done to monitor the delivery of therapeutic agents using this novel approach. Here we present a review of imaging in convection enhanced delivery monitoring of toxins in humans, and discuss future challenges in the field.

Authors
Mehta, AI; Choi, BD; Raghavan, R; Brady, M; Friedman, AH; Bigner, DD; Pastan, I; Sampson, JH
MLA Citation
Mehta, AI, Choi, BD, Raghavan, R, Brady, M, Friedman, AH, Bigner, DD, Pastan, I, and Sampson, JH. "Imaging of convection enhanced delivery of toxins in humans." Toxins 3.3 (March 15, 2011): 201-206. (Review)
PMID
22069706
Source
epmc
Published In
Toxins
Volume
3
Issue
3
Publish Date
2011
Start Page
201
End Page
206
DOI
10.3390/toxins3030201

Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma.

Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely but may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces a survival benefit in GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity of an experimental EGFRvIII-targeted peptide vaccine in patients with GBM undergoing treatment with serial cycles of standard-dose (STD) (200 mg/m(2) per 5 days) or dose-intensified (DI) TMZ (100 mg/m(2) per 21 days). All patients receiving STD TMZ exhibited at least a transient grade 2 lymphopenia, whereas those receiving DI TMZ exhibited a sustained grade 3 lymphopenia (<500 cells/μL). CD3(+) T-cell (P = .005) and B-cell (P = .004) counts were reduced significantly only in the DI cohort. Patients in the DI cohort had an increase in the proportion of immunosuppressive regulatory T cells (T(Reg); P = .008). EGFRvIII-specific immune responses developed in all patients treated with either regimen, but the DI TMZ regimen produced humoral (P = .037) and delayed-type hypersensitivity responses (P = .036) of greater magnitude. EGFRvIII-expressing tumor cells were also eradicated in nearly all patients (91.6%; CI(95): 64.0%-99.8%; P < .0001). The median progression-free survival (15.2 months; CI(95): 11.0-18.5 months; hazard ratio [HR] = 0.35; P = .024) and overall survival (23.6 months; CI(95): 18.5-33.1 months; HR = 0.23; P = .019) exceeded those of historical controls matched for entry criteria and adjusted for known prognostic factors. EGFRvIII-targeted vaccination induces patient immune responses despite therapeutic TMZ-induced lymphopenia and eliminates EGFRvIII-expressing tumor cells without autoimmunity.

Authors
Sampson, JH; Aldape, KD; Archer, GE; Coan, A; Desjardins, A; Friedman, AH; Friedman, HS; Gilbert, MR; Herndon, JE; McLendon, RE; Mitchell, DA; Reardon, DA; Sawaya, R; Schmittling, R; Shi, W; Vredenburgh, JJ; Bigner, DD; Heimberger, AB
MLA Citation
Sampson, JH, Aldape, KD, Archer, GE, Coan, A, Desjardins, A, Friedman, AH, Friedman, HS, Gilbert, MR, Herndon, JE, McLendon, RE, Mitchell, DA, Reardon, DA, Sawaya, R, Schmittling, R, Shi, W, Vredenburgh, JJ, Bigner, DD, and Heimberger, AB. "Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma." Neuro Oncol 13.3 (March 2011): 324-333.
PMID
21149254
Source
pubmed
Published In
Neuro-Oncology
Volume
13
Issue
3
Publish Date
2011
Start Page
324
End Page
333
DOI
10.1093/neuonc/noq157

A novel method for volumetric MRI response assessment of enhancing brain tumors.

Current radiographic response criteria for brain tumors have difficulty describing changes surrounding postoperative resection cavities. Volumetric techniques may offer improved assessment, however usually are time-consuming, subjective and require expert opinion and specialized magnetic resonance imaging (MRI) sequences. We describe the application of a novel volumetric software algorithm that is nearly fully automated and uses standard T1 pre- and post-contrast MRI sequences. T1-weighted pre- and post-contrast images are automatically fused and normalized. The tumor region of interest is grossly outlined by the user. An atlas of the nasal mucosa is automatically detected and used to normalize levels of enhancement. The volume of enhancing tumor is then automatically calculated. We tested the ability of our method to calculate enhancing tumor volume with resection cavity collapse and when the enhancing tumor is obscured by subacute blood in a resection cavity. To determine variability in results, we compared narrowly-defined tumor regions with tumor regions that include adjacent meningeal enhancement and also compared different contrast enhancement threshold levels used for the automatic calculation of enhancing tumor volume. Our method quantified enhancing tumor volume despite resection cavity collapse. It detected tumor volume increase in the midst of blood products that incorrectly caused decreased measurements by other techniques. Similar trends in volume changes across scans were seen with inclusion or exclusion of meningeal enhancement and despite different automated thresholds for tissue enhancement. Our approach appears to overcome many of the challenges with response assessment of enhancing brain tumors and warrants further examination and validation.

Authors
Kanaly, CW; Ding, D; Mehta, AI; Waller, AF; Crocker, I; Desjardins, A; Reardon, DA; Friedman, AH; Bigner, DD; Sampson, JH
MLA Citation
Kanaly, CW, Ding, D, Mehta, AI, Waller, AF, Crocker, I, Desjardins, A, Reardon, DA, Friedman, AH, Bigner, DD, and Sampson, JH. "A novel method for volumetric MRI response assessment of enhancing brain tumors. (Published online)" PLoS One 6.1 (January 26, 2011): e16031-.
PMID
21298088
Source
pubmed
Published In
PloS one
Volume
6
Issue
1
Publish Date
2011
Start Page
e16031
DOI
10.1371/journal.pone.0016031

Fourth ventricular schwannoma: identical clinicopathologic features as schwann cell-derived schwannoma with unique etiopathologic origins.

Background. To our knowledge, this is the sixth reported case in the literature of fourth ventricular schwannoma. The etiology and natural history of intraventricular schwannomas is not well understood. A thorough review of potential etiopathogenic mechanisms is provided in this case report. Case Description. A 69-year-old man presented with an incidentally found fourth ventricular tumor during an evaluation for generalized weakness, gait instability, and memory disturbance. Magnetic resonance imaging (MRI) revealed a heterogeneously enhancing lesion in the fourth ventricle. A suboccipital craniotomy was performed to resect the lesion. Histopathological examination confirmed the diagnosis of schwannoma (WHO grade I). Conclusions. Schwannomas should be considered in the differential diagnosis of intraventricular tumors. Although the embryologic origins may be different from nerve sheath-derived schwannomas, the histologic, clinical, and natural history appear identical and thus should be managed similarly.

Authors
Hodges, TR; Karikari, IO; Nimjee, SM; Tibaleka, J; Cummings, TJ; Radhakrishnan, S; Friedman, AH
MLA Citation
Hodges, TR, Karikari, IO, Nimjee, SM, Tibaleka, J, Cummings, TJ, Radhakrishnan, S, and Friedman, AH. "Fourth ventricular schwannoma: identical clinicopathologic features as schwann cell-derived schwannoma with unique etiopathologic origins." Case reports in medicine 2011 (January 2011): 165954-.
PMID
22194753
Source
epmc
Published In
Case Reports in Medicine
Volume
2011
Publish Date
2011
Start Page
165954
DOI
10.1155/2011/165954

Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: a single-center experience with 102 patients.

BACKGROUND: Surgical outcomes for intramedullary spinal cord tumors are affected by many variables including tumor histology and preoperative neurological function. OBJECTIVE: To analyze the impact of tumor histology on neurological outcome in primary intramedullary spinal cord tumors. METHODS: A retrospective review of 102 consecutive patients with intramedullary spinal cord tumors treated at a single institution between January 1998 and March 2009. RESULTS: Ependymomas were the most common tumors with 55 (53.9%), followed by 21 astrocytomas (20.6%), 12 hemangioblastomas (11.8%), and 14 miscellaneous tumors (13.7%). Gross total resection was achieved in 50 ependymomas (90.9%), 3 astrocytomas (14.3%), 11 hemangioblastomas (91.7%), and 12 miscellaneous tumors (85.7%). At a mean follow-up of 41.8 months (range, 1-132 months), we observed recurrences in 4 ependymoma cases (7.3%), 10 astrocytoma cases (47.6%), 1 miscellaneous tumor case (7.1%), and no recurrence in hemangioblastoma cases. When analyzed by tumor location, there was no difference in neurological outcomes (P = .66). At the time of their last follow-up visit, 11 patients (20%) with an ependymoma improved, 38 (69%) remained the same, and 6 (10.9%) worsened. In patients with an astrocytoma, 1 (4.8%) improved, 10 (47.6%) remained the same, and 10 (47.6%) worsened. One patient (8.3%) with a hemangioblastoma improved and 11 (91.7%) remained the same. No patient with a hemangioblastoma worsened. In the miscellaneous tumor group, 2 (14.3%) improved, 10 (71.4%) remained the same, and 2 (14.3%) worsened. Preoperative neurological status (P = .02), tumor histology (P = .005), and extent of resection (P < .0001) were all predictive of functional neurological outcomes. CONCLUSION: Tumor histology is the most important predictor of neurological outcome after surgical resection because it predicts resectability and recurrence.

Authors
Karikari, IO; Nimjee, SM; Hodges, TR; Cutrell, E; Hughes, BD; Powers, CJ; Mehta, AI; Hardin, C; Bagley, CA; Isaacs, RE; Haglund, MM; Friedman, AH
MLA Citation
Karikari, IO, Nimjee, SM, Hodges, TR, Cutrell, E, Hughes, BD, Powers, CJ, Mehta, AI, Hardin, C, Bagley, CA, Isaacs, RE, Haglund, MM, and Friedman, AH. "Impact of tumor histology on resectability and neurological outcome in primary intramedullary spinal cord tumors: a single-center experience with 102 patients." Neurosurgery 68.1 (January 2011): 188-197.
PMID
21099707
Source
epmc
Published In
Neurosurgery
Volume
68
Issue
1
Publish Date
2011
Start Page
188
End Page
197
DOI
10.1227/neu.0b013e3181fe3794

Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma.

Sorafenib, an oral VEGFR-2, Raf, PDGFR, c-KIT and Flt-3 inhibitor, is active against renal cell and hepatocellular carcinomas, and has recently demonstrated promising activity for lung and breast cancers. In addition, various protracted temozolomide dosing schedules have been evaluated as a strategy to further enhance its anti-tumor activity. We reasoned that sorafenib and protracted, daily temozolomide may provide complementary therapeutic benefit, and therefore performed a phase 2 trial among recurrent glioblastoma patients. Adult glioblastoma patients at any recurrence after standard temozolomide chemoradiotherapy received sorafenib (400 mg twice daily) and continuous daily temozolomide (50 mg/m²/day). Assessments were performed every eight weeks. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary end points were radiographic response, overall survival (OS), safety and sorafenib pharmacokinetics. Of 32 enrolled patients, 12 (38%) were on CYP3-A inducing anti-epileptics (EIAEDs), 17 (53%) had 2 or more prior progressions, 15 had progressed while receiving 5-day temozolomide, and 12 (38%) had failed either prior bevacizumab or VEGFR inhibitor therapy. The most common grade ≥ 3 toxicities were palmer-planter erythrodysesthesia (19%) and elevated amylase/lipase (13%). Sorafenib pharmacokinetic exposures were comparable on day 1 regardless of EIAED status, but significantly lower on day 28 for patients on EIAEDs (P = 0.0431). With a median follow-up of 93 weeks, PFS-6 was 9.4%. Only one patient (3%) achieved a partial response. In conclusion, sorafenib can be safely administered with daily temozolomide, but this regimen has limited activity for recurrent GBM. Co-administration of EIAEDs can lower sorafenib exposures in this population.

Authors
Reardon, DA; Vredenburgh, JJ; Desjardins, A; Peters, K; Gururangan, S; Sampson, JH; Marcello, J; Herndon, JE; McLendon, RE; Janney, D; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Vredenburgh, JJ, Desjardins, A, Peters, K, Gururangan, S, Sampson, JH, Marcello, J, Herndon, JE, McLendon, RE, Janney, D, Friedman, AH, Bigner, DD, and Friedman, HS. "Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma." J Neurooncol 101.1 (January 2011): 57-66.
PMID
20443129
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
101
Issue
1
Publish Date
2011
Start Page
57
End Page
66
DOI
10.1007/s11060-010-0217-6

Comments

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Comments." Neurosurgery 69.SUPPL. 2 (2011): 240--.
Source
scival
Published In
Neurosurgery
Volume
69
Issue
SUPPL. 2
Publish Date
2011
Start Page
240-
DOI
10.1227/NEU.0b013e31822a19a3

Trigeminal schwannomas - skull base approaches and operative results in 105 patients -

BACKGROUND: Trigeminal schwannomas comprise 0.8 to 8% of all intracranial schwannomas. OBJECTIVE: To analyze our surgical experience with trigeminal schwannomas. METHODS: We performed 107 operations on 105 patients harboring trigeminal schwannomas over the past 30 years. We classified the tumors as peripheral, ganglion cavernous, posterior fossa root and dumbbell types according to the portion of the nerve that gave rise to the tumor. RESULTS: 14 (13.1%) were peripheral type tumors, 39 (36.4%) were ganglion cavernous type, 22 (20.6%) were posterior fossa root type and 32 (30.0%) were dumbbell type. 65 tumors were solid, 35 were mixed and only 7 tumors were cystic. Among solid tumors, 14 were vascular, fibrous and adherent to adjacent structures. Total or near-total removal was performed in 86 cases (81.9%) and subtotal removal was achieved in 18 (17.1%). The most common symptom was facial hypesthesia, occurring in 69 patients. This symptom improved in 11 patients, persisted in 50 and worsened in 8 patients following surgery. New postoperative hypesthesia was observed in 8 patients. The second most common symptom was facial pain, observed in 24 patients. Facial pain subsided in 22 and persisted in 2 patients after surgery. Diplopia was observed in 21 patients. This symptom postoperatively improved in 14 patients, persisted in 6 and worsened in one patient. CONCLUSION: The present series demonstrates acceptable results using microsurgical treatment for the removal of trigeminal schwannomas. Pain and diplopia may be relieved after surgery; however, hyhpesthesia frequently remains or may be worsened by surgery.

Authors
Wanibuchi, M; Fukushima, T; Zomordi, AR; Nonaka, Y; Friedman, AH
MLA Citation
Wanibuchi, M, Fukushima, T, Zomordi, AR, Nonaka, Y, and Friedman, AH. "Trigeminal schwannomas - skull base approaches and operative results in 105 patients -." Neurosurgery (2011).
Source
scival
Published In
Neurosurgery
Publish Date
2011
DOI
10.1227/NEU.0b013e31822efb21

Central nervous system cancers: Clinical practice guidelines in oncology

Authors
Brem, SS; Bierman, PJ; Brem, H; Butowski, N; Chamberlain, MC; Chiocca, EA; DeAngelis, LM; Fenstermaker, RA; Friedman, A; Gilbert, MR; Hesser, D; Junck, L; Linette, GP; Loeffler, JS; Maor, MH; Michael, M; Moots, PL; Morrison, T; Mrugala, M; Nabors, LB; Newton, HB; Portnow, J; Raizer, JJ; Recht, L; Shrieve, DC; Jr, AKS; Vrionis, FD; Wen, PY
MLA Citation
Brem, SS, Bierman, PJ, Brem, H, Butowski, N, Chamberlain, MC, Chiocca, EA, DeAngelis, LM, Fenstermaker, RA, Friedman, A, Gilbert, MR, Hesser, D, Junck, L, Linette, GP, Loeffler, JS, Maor, MH, Michael, M, Moots, PL, Morrison, T, Mrugala, M, Nabors, LB, Newton, HB, Portnow, J, Raizer, JJ, Recht, L, Shrieve, DC, Jr, AKS, Vrionis, FD, and Wen, PY. "Central nervous system cancers: Clinical practice guidelines in oncology." JNCCN Journal of the National Comprehensive Cancer Network 9.4 (2011): 352-400.
PMID
21464144
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
9
Issue
4
Publish Date
2011
Start Page
352
End Page
400

Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma.

PURPOSE: Immunologic targeting of tumor-specific gene mutations may allow precise eradication of neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely expressed in glioblastoma multiforme (GBM) and other neoplasms. PATIENTS AND METHODS: A phase II, multicenter trial was undertaken to assess the immunogenicity of an EGFRvIII-targeted peptide vaccine and to estimate the progression-free survival (PFS) and overall survival (OS) of vaccinated patients with newly diagnosed EGFRvIII-expressing GBM with minimal residual disease. Intradermal vaccinations were given until toxicity or tumor progression was observed. Sample size was calculated to differentiate between PFS rates of 20% and 40% 6 months after vaccination. RESULTS: There were no symptomatic autoimmune reactions. The 6-month PFS rate after vaccination was 67% (95% CI, 40% to 83%) and after diagnosis was 94% (95% CI, 67% to 99%; n = 18). The median OS was 26.0 months (95% CI, 21.0 to 47.7 months). After adjustment for age and Karnofsky performance status, the OS of vaccinated patients was greater than that observed in a control group matched for eligibility criteria, prognostic factors, and temozolomide treatment (hazard ratio, 5.3; P = .0013; n = 17). The development of specific antibody (P = .025) or delayed-type hypersensitivity (P = .03) responses to EGFRvIII had a significant effect on OS. At recurrence, 82% (95% CI, 48% to 97%) of patients had lost EGFRvIII expression (P < .001). CONCLUSION: EGFRvIII-targeted vaccination in patients with GBM warrants investigation in a phase III, randomized trial.

Authors
Sampson, JH; Heimberger, AB; Archer, GE; Aldape, KD; Friedman, AH; Friedman, HS; Gilbert, MR; Herndon, JE; McLendon, RE; Mitchell, DA; Reardon, DA; Sawaya, R; Schmittling, RJ; Shi, W; Vredenburgh, JJ; Bigner, DD
MLA Citation
Sampson, JH, Heimberger, AB, Archer, GE, Aldape, KD, Friedman, AH, Friedman, HS, Gilbert, MR, Herndon, JE, McLendon, RE, Mitchell, DA, Reardon, DA, Sawaya, R, Schmittling, RJ, Shi, W, Vredenburgh, JJ, and Bigner, DD. "Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma." J Clin Oncol 28.31 (November 1, 2010): 4722-4729.
PMID
20921459
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
28
Issue
31
Publish Date
2010
Start Page
4722
End Page
4729
DOI
10.1200/JCO.2010.28.6963

Intraoperative floppy iris syndrome: report of a case and histopathologic analysis.

OBJECTIVE: To understand the role of the α(1A)-adrenoreceptors (ARs) in the pathophysiologic mechanism of intraoperative floppy iris syndrome (IFIS). METHODS: Iris specimens from a patient with tamsulosin hydrochloride-induced IFIS were obtained during trabeculectomy. Specimens underwent histological analysis and immunohistochemical analysis with antibodies specific for actin, myoglobin, α(1A)-ARs, and myosin. Iris specimens from a patient without IFIS were used for comparison. Samples were processed for transmission electron microscopy. RESULTS: Histological examination showed normal dilator muscle, arterioles, stroma, and pigment epithelium. Actin, myosin, and myoglobin distribution and intensities were similar between IFIS and non-IFIS tissue. The staining pattern and colocalization with myosin suggested that α(1A)-ARs are present in iris arteriolar muscularis in addition to the dilator muscle in both IFIS and control irides. Significantly less staining of IFIS tissue was found compared with the non-IFIS iris. Ultrastructures of melanocytes and stroma appeared to be normal. Iris arterioles possessed thick endothelial basement membranes, semilongitudinally oriented muscularis, and abundant perivascular collagen coats. CONCLUSIONS: We confirm the presence of α(1A)-ARs in human iris by results of immunohistochemical analysis. The α(1A)-ARs localize to iris arteriolar muscularis in addition to the iris dilator muscle. This localization suggests that IFIS may develop because of iris vascular dysfunction and that iris vasculature may have structural in addition to nutritive functions.

Authors
Panagis, L; Basile, M; Friedman, AH; Danias, J
MLA Citation
Panagis, L, Basile, M, Friedman, AH, and Danias, J. "Intraoperative floppy iris syndrome: report of a case and histopathologic analysis." Archives of ophthalmology 128.11 (November 2010): 1437-1441. (Academic Article)
Source
manual
Published In
Archives of Ophthalmology
Volume
128
Issue
11
Publish Date
2010
Start Page
1437
End Page
1441
DOI
10.1001/archophthalmol.2010.243

Critical assessment of operative approaches for hearing preservation in small acoustic neuroma surgery: retrosigmoid vs middle fossa approach.

BACKGROUND: For hearing preservation in acoustic neuroma (AN) surgery, the middle fossa (MF) or retrosigmoid (RS) approach can be used. Recent literature advocates the use of the MF approach, especially for small ANs. OBJECTIVE: To present our critical analysis of operative results comparing these 2 approaches. METHODS: We reviewed 504 consecutive AN resections performed between November 1998 and September 2007 and identified 43 MF and 82 RS approaches for tumors smaller than 1.5 cm during hearing preservation surgery. Individual cases were examined postoperatively with respect to hearing ability, facial nerve activity, operative time, blood loss, and symptoms resulting from retraction of the cerebellar or temporal lobes. RESULTS: Good hearing function (American Academy of Otolaryngology-Head and Neck Surgery class B or better) was preserved in 76.7% of patients undergoing surgery via the MF approach and in 73.2% of the RS group (P = .9024). Temporary facial nerve weakness was more frequent in the MF group (P = .0249). However, late (8-12 months) follow-up examinations showed good recovery in both groups. The mean operative time was 7.45 hours for the MF group and 5.2 hours for the RS group (P = .0318). The mean blood loss was 280.5 mL for the MF group and 80.8 mL for the RS group (P < .0001). Temporary symptoms of temporal lobe edema (drowsiness or speech disturbance) were noted in 6 MF cases. No cerebellar dysfunction was noted in the RS group. CONCLUSIONS: Although hearing and facial nerve function assessed at approximately 1 year was similar with these 2 approaches, the RS approach provided several advantages over the MF approach for ANs smaller than 1.5 cm.

Authors
Sameshima, T; Fukushima, T; McElveen, JT; Friedman, AH
MLA Citation
Sameshima, T, Fukushima, T, McElveen, JT, and Friedman, AH. "Critical assessment of operative approaches for hearing preservation in small acoustic neuroma surgery: retrosigmoid vs middle fossa approach." Neurosurgery 67.3 (September 2010): 640-644.
PMID
20647969
Source
pubmed
Published In
Neurosurgery
Volume
67
Issue
3
Publish Date
2010
Start Page
640
End Page
644
DOI
10.1227/01.NEU.0000374853.97891.FB

Ophthalmic findings in a patient with CD8-positive T cell lymphoma and a hydroa vacciniforme-like eruption.

Authors
Zamecki, KJ; Friedman, AH; Raab, EL
MLA Citation
Zamecki, KJ, Friedman, AH, and Raab, EL. "Ophthalmic findings in a patient with CD8-positive T cell lymphoma and a hydroa vacciniforme-like eruption." The British journal of ophthalmology 94.9 (September 2010): 1266-1267. (Academic Article)
Source
manual
Published In
British Journal of Ophthalmology
Volume
94
Issue
9
Publish Date
2010
Start Page
1266
End Page
1267
DOI
10.1136/bjo.2008.149583

Combined microsurgical and endovascular treatment of a giant left middle cerebral artery aneurysm.

Giant fusiform aneurysms of the middle cerebral artery (MCA) bifurcation pose significant treatment challenges. A giant fusiform aneurysm of the left MCA in a pediatric patient, which persisted despite Hunterian ligation of the M1 and double barrel superficial temporal artery (STA) to M2 bypasses, is reported. The aneurysm was trapped by endovascular coiling of the feeding M2 trunk through the STA anastamosis. Hunterian ligation combined with extracranial-intracranial bypass is an effective technique for treating giant fusiform aneurysms of the MCA bifurcation for patients who fail balloon test occlusions. However, in certain cases, flow reversal may not eliminate the aneurysm and continued aneurysm filling may occur through retrograde filling from the bypass recipient vessels. In these cases, endovascular trapping of the aneurysm may be undertaken through the bypass graft. The feasibility of this management scheme is demonstrated.

Authors
Zomorodi, A; Bulsara, KR; Friedman, AH; Alexander, MJ
MLA Citation
Zomorodi, A, Bulsara, KR, Friedman, AH, and Alexander, MJ. "Combined microsurgical and endovascular treatment of a giant left middle cerebral artery aneurysm." J Neurointerv Surg 2.3 (September 2010): 213-216.
PMID
21990628
Source
pubmed
Published In
Journal of NeuroInterventional Surgery
Volume
2
Issue
3
Publish Date
2010
Start Page
213
End Page
216
DOI
10.1136/jnis.2009.001883

Chemopotentiation by ultrafractionated radiotherapy in glioblastoma resistant to conventional therapy.

INTRODUCTION: Induced radiation resistance (IRR) and hyper-radiosensitivity (HRS) are well-described phenomena in basic literature, yet few reports have been published in which such phenomena are exploited clinically for the benefit of patients. Glioblastoma is a prime example. CASE AND METHODS: The case of an 82-year-old woman is described whose resected frontoparietal glioblastoma progressed through treatment administered according to standard methods. With review board and patient approval, we continued her treatment using radiotherapy and temozolomide, but drastically modified the radiotherapy fractionation, administering 50 cGy twice daily on each of the first 5 days of a 14-day cycle. Temozolomide was administered on the first 4 days of each cycle. We use the term "ultrafractionated radiotherapy" to refer to the extremely low doses of radiation used in this case. RESULTS: This modified regimen resulted in regression of the contrast-enhancing areas of disease recurrence identified on MRI, and the patient survived approximately 6 months following recurrence of her disease, having received 5 cycles of additional therapy after prior full-dose treatment. CONCLUSIONS: Ultrafractionated radiotherapy and concurrent temozolomide were efficacious and tolerable in this patient whose glioblastoma previously progressed through conventional treatment. Additional studies of this approach are warranted.

Authors
Jahraus, CD; Friedman, AH
MLA Citation
Jahraus, CD, and Friedman, AH. "Chemopotentiation by ultrafractionated radiotherapy in glioblastoma resistant to conventional therapy." Tumori 96.5 (September 2010): 771-775.
PMID
21302627
Source
pubmed
Published In
Tumori
Volume
96
Issue
5
Publish Date
2010
Start Page
771
End Page
775

Unilateral hypoglossal nerve palsy caused by an intraneural ganglion cyst.

The authors describe a rare case of unilateral hypoglossal nerve palsy caused by an intraneural ganglion cyst. Three similar cases have been reported with pathological classification still under consideration. One case was classified as an intraneural ganglion cyst and 2 cases were classified as atlantooccipital joint synovial cysts.

Authors
Nonaka, Y; Grossi, PM; Filomena, CA; Friedman, AH; Fukushima, T
MLA Citation
Nonaka, Y, Grossi, PM, Filomena, CA, Friedman, AH, and Fukushima, T. "Unilateral hypoglossal nerve palsy caused by an intraneural ganglion cyst." J Neurosurg 113.2 (August 2010): 380-383.
PMID
20113159
Source
pubmed
Published In
Journal of neurosurgery
Volume
113
Issue
2
Publish Date
2010
Start Page
380
End Page
383
DOI
10.3171/2010.1.JNS091526

Poor drug distribution as a possible explanation for the results of the PRECISE trial.

OBJECT: Convection-enhanced delivery (CED) is a novel intracerebral drug delivery technique with considerable promise for delivering therapeutic agents throughout the CNS. Despite this promise, Phase III clinical trials employing CED have failed to meet clinical end points. Although this may be due to inactive agents or a failure to rigorously validate drug targets, the authors have previously demonstrated that catheter positioning plays a major role in drug distribution using this technique. The purpose of the present work was to retrospectively analyze the expected drug distribution based on catheter positioning data available from the CED arm of the PRECISE trial. METHODS: Data on catheter positioning from all patients randomized to the CED arm of the PRECISE trial were available for analyses. BrainLAB iPlan Flow software was used to estimate the expected drug distribution. RESULTS: Only 49.8% of catheters met all positioning criteria. Still, catheter positioning score (hazard ratio 0.93, p = 0.043) and the number of optimally positioned catheters (hazard ratio 0.72, p = 0.038) had a significant effect on progression-free survival. Estimated coverage of relevant target volumes was low, however, with only 20.1% of the 2-cm penumbra surrounding the resection cavity covered on average. Although tumor location and resection cavity volume had no effect on coverage volume, estimations of drug delivery to relevant target volumes did correlate well with catheter score (p < 0.003), and optimally positioned catheters had larger coverage volumes (p < 0.002). Only overall survival (p = 0.006) was higher for investigators considered experienced after adjusting for patient age and Karnofsky Performance Scale score. CONCLUSIONS: The potential efficacy of drugs delivered by CED may be severely constrained by ineffective delivery in many patients. Routine use of software algorithms and alternative catheter designs and infusion parameters may improve the efficacy of drugs delivered by CED.

Authors
Sampson, JH; Archer, G; Pedain, C; Wembacher-Schröder, E; Westphal, M; Kunwar, S; Vogelbaum, MA; Coan, A; Herndon, JE; Raghavan, R; Brady, ML; Reardon, DA; Friedman, AH; Friedman, HS; Rodríguez-Ponce, MI; Chang, SM; Mittermeyer, S; Croteau, D; Puri, RK; PRECISE Trial Investigators,
MLA Citation
Sampson, JH, Archer, G, Pedain, C, Wembacher-Schröder, E, Westphal, M, Kunwar, S, Vogelbaum, MA, Coan, A, Herndon, JE, Raghavan, R, Brady, ML, Reardon, DA, Friedman, AH, Friedman, HS, Rodríguez-Ponce, MI, Chang, SM, Mittermeyer, S, Croteau, D, Puri, RK, and PRECISE Trial Investigators, . "Poor drug distribution as a possible explanation for the results of the PRECISE trial." J Neurosurg 113.2 (August 2010): 301-309.
PMID
20020841
Source
pubmed
Published In
Journal of neurosurgery
Volume
113
Issue
2
Publish Date
2010
Start Page
301
End Page
309
DOI
10.3171/2009.11.JNS091052

Surgical management of brainstem cavernomas: selection of approaches and microsurgical techniques.

This study reviewed surgical experience with brainstem cavernomas in an attempt to define optimal surgical approaches and risks associated with surgical management. Clinical courses were retrospectively reviewed for 36 consecutive patients (12 men, 24 women; mean age, 42 years) who underwent microsurgical resection of brainstem cavernomas between 1996 and 2006. Medical records, surgical records, and neuroimaging examinations were evaluated. All 36 patients presented with > or =1 hemorrhage from the cavernomas and preoperatively displayed some neurological symptoms. Surgical approach was midline suboccipital for 16 pontine and/or medullary cavernomas under the floor of the fourth ventricle, retrosigmoid for 10 lateral mesencephalic, pontine, and/or medullary cavernomas, occipital transtentorial for 2 thalamomesencephalic and 3 mesencephalic cavernomas, combined petrosal for 2 pontine cavernomas, and other for 3 cavernomas. Complete resection according to postoperative magnetic resonance imaging was achieved in 33 of 36 patients. No mortality was encountered in this study. New neurological deficit occurred in the early postoperative period for 18 patients, but was transient in 15 of these. Neurological state as of final follow-up was improved in 16 patients (44%), unchanged in 17 (47%), and worsened in 3 (8%) compared with preoperatively. In conclusion, symptomatic brainstem cavernomas should be considered for surgical treatment. Careful selection of the optimal operative approach and a meticulous microsurgical technique are mandatory.

Authors
Ohue, S; Fukushima, T; Kumon, Y; Ohnishi, T; Friedman, AH
MLA Citation
Ohue, S, Fukushima, T, Kumon, Y, Ohnishi, T, and Friedman, AH. "Surgical management of brainstem cavernomas: selection of approaches and microsurgical techniques." Neurosurg Rev 33.3 (July 2010): 315-322.
PMID
20358241
Source
pubmed
Published In
Neurosurgical Review
Volume
33
Issue
3
Publish Date
2010
Start Page
315
End Page
322
DOI
10.1007/s10143-010-0256-7

Retrosigmoid suprafloccular transhorizontal fissure approach for resection of brainstem cavernous malformation.

OBJECTIVE: This study examined the usefulness of a surgical approach (retrosigmoid suprafloccular transhorizontal fissure approach) for resection of brainstem cavernous malformations (CMs). METHODS: An anatomic study concerning the retrosigmoid suprafloccular transhorizontal fissure approach was performed with 3 cadaveric heads. Clinical course was retrospectively reviewed for 10 patients who underwent microsurgical resection of brainstem CMs with this approach. Medical, surgical, and neuroimaging records of these patients were evaluated. RESULTS: In the anatomic study, after standard suboccipital retrosigmoid craniotomy, the horizontal fissure on the petrosal surface of the cerebellum was dissected between the superior semilunar lobule and flocculus. With this approach, the root entry zone of the trigeminal nerve and the middle cerebellar peduncle could be exposed by superior retraction of the superior semilunar lobule. The lateral surface of the pons was then easily visible around the root entry zone. When this approach was used for 10 brainstem CMs, complete resection was achieved in 9 patients (90%). No mortality was encountered in this study. New neurological deficits occurred in the early postoperative period for 4 patients but were transient in 3 patients. Neurological status at final follow-up was improved in 4 patients (40%), unchanged in 5 patients (50%), and worse in 1 patient (10%) compared with preoperative conditions. CONCLUSION: The retrosigmoid suprafloccular transhorizontal fissure approach is useful for the resection of lateral pontine CMs.

Authors
Ohue, S; Fukushima, T; Friedman, AH; Kumon, Y; Ohnishi, T
MLA Citation
Ohue, S, Fukushima, T, Friedman, AH, Kumon, Y, and Ohnishi, T. "Retrosigmoid suprafloccular transhorizontal fissure approach for resection of brainstem cavernous malformation." Neurosurgery 66.6 Suppl Operative (June 2010): 306-312.
PMID
20489521
Source
pubmed
Published In
Neurosurgery
Volume
66
Issue
6 Suppl Operative
Publish Date
2010
Start Page
306
End Page
312
DOI
10.1227/01.NEU.0000369703.67562.BB

Skull base training and education using an artificial skull model created by selective laser sintering.

INTRODUCTION: Practicing skull base approaches on cadavers affords the surgeon a chance to learn complex anatomical relationships and to practice surgical skills. However, there are ethical or legal problems in obtaining cadaver material in some countries. In addition, there is always risk of transmitting infections with cadaveric material. In order to get around these problems, we created a whole skull model which reproduces the detailed anatomy within the skull base using a selective laser sintering (SLS) technique. MATERIALS AND METHODS: The first author's head was scanned using multidetector-row computed tomography. The data were reconstructed and converted into the standard triangulation language file system. Powdered material comprised of polyamide nylon and glass beads was laser-sintered in accord with the data derived from the head CT. The model was dissected under a surgical microscope using a high-speed drill, suction, and other surgical instruments. RESULTS AND DISCUSSION: The appearance of both inner and outer cranial surfaces, including sutures, foramens, fissures, and protrusions, were clearly demonstrated. The artificial mastoid did not melt from the heat of the drill when a mastoidectomy was performed. The anatomical structures inside the mastoid and of paranasal sinuses were accurately reproduced in the model. CONCLUSION: The model created using SLS should be very useful for the teaching skull base approaches avoiding the ethical, legal, and infection problems inherent in cadavers.

Authors
Wanibuchi, M; Ohtaki, M; Fukushima, T; Friedman, AH; Houkin, K
MLA Citation
Wanibuchi, M, Ohtaki, M, Fukushima, T, Friedman, AH, and Houkin, K. "Skull base training and education using an artificial skull model created by selective laser sintering." Acta Neurochir (Wien) 152.6 (June 2010): 1055-1059.
PMID
20401499
Source
pubmed
Published In
Acta Neurochirurgica
Volume
152
Issue
6
Publish Date
2010
Start Page
1055
End Page
1059
DOI
10.1007/s00701-010-0624-7

Is the rate of congenital heart defects detected by fetal echocardiography among pregnancies conceived by in vitro fertilization really increased?: a case-historical control study.

OBJECTIVE: We investigated the prenatal prevalence of congenital heart defects (CHDs) among in vitro fertilization (IVF) pregnancies at a referral program in the United States. METHODS: Study patients were referred for fetal echocardiography between April 1, 2006, and May 1, 2009, due to IVF. An IVF pregnancy was defined as a patient who conceived with IVF with or without intracytoplasmic sperm injection. Congenital heart defect odds relative to historical data were calculated by standard methods. P < .05 was considered statistically significant. RESULTS: During the study period, we performed fetal echocardiography on 749 consecutive IVF pregnancies. Overall, the frequency of CHDs was 1.1% (95% confidence interval, 0.3%-1.8%) per pregnancy. Compared to earlier historical population data, IVF pregnancies had a significantly higher risk of CHDs (odds ratios, 7.3 [3.6-14.7] and 2.9 [1.4-5.9], respectively). However, compared to more contemporary population data, there was no difference in the CHD risk between IVF gestations and naturally conceived pregnancies. Further analysis indicated that IVF twin pregnancies were as much as 12.5 (4.6-33.5) times as likely to have CHDs compared to a general population. CONCLUSIONS: In this study population, the frequency of CHDs in IVF pregnancies was higher than early historical population data; however, it was similar to that of a more contemporary general population. Further analysis showed that this increase was mainly driven by IVF twin gestations. Previous reports of increased CHD risk in pregnancies conceived via IVF may have been due, in part, to an increased frequency of higher-order pregnancies seen among these patients.

Authors
Bahtiyar, MO; Campbell, K; Dulay, AT; Kontic-Vucinic, O; Weeks, BP; Friedman, AH; Copel, JA
MLA Citation
Bahtiyar, MO, Campbell, K, Dulay, AT, Kontic-Vucinic, O, Weeks, BP, Friedman, AH, and Copel, JA. "Is the rate of congenital heart defects detected by fetal echocardiography among pregnancies conceived by in vitro fertilization really increased?: a case-historical control study." J Ultrasound Med 29.6 (June 2010): 917-922.
PMID
20498466
Source
pubmed
Published In
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
Volume
29
Issue
6
Publish Date
2010
Start Page
917
End Page
922

Timing of symptomatic vasospasm in aneurysmal subarachnoid hemorrhage: the effect of treatment modality and clinical implications.

A better prediction of the time course of symptomatic vasospasm (SVSP) might have a significant impact on the management and prevention of delayed neurologic ischemic deficit (DIND). We studied the influence of the treatment for ruptured aneurysm on SVSP timing. We retrospectively analyzed data of consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted in our center between 1999 and 2005, treated within 72 hours of the rupture by surgical clipping or endovascular coiling and in accordance with our neuroscience unit protocol. We analyzed the presence of SVSP and recorded the timing of occurrence after the aneurysmal repair intervention. Data on demographics, premorbid conditions, time elapsed from the subarachnoid hemorrhage onset and intervention, and clinical and radiologic characteristics at admission were collected. The first occurrence of postintervention SVSP was recorded and compared between the 2 treatment groups using a proportional hazards regression model, including significant covariates. Of the 67 patients analyzed, 21 (31%) underwent endovascular coiling and 46 (69%) underwent surgical clipping. The baseline variables were similar in the 2 groups. The median time from the procedure to clinical vasospasm was 4 days in the coiled patients and 7 days in the clipped patients. In a proportional hazards model regression analysis including age, sex, Fisher and Hunt-Hess grades, time between onset to procedure, and intervention type, only intervention type emerged as a significant predictor of time to SVSP after intervention (likelihood ratio chi2 = 16.8; P < .00). Treatment modality of ruptured intracranial aneurysm may influence the timing of SVSP occurrence.

Authors
Ionita, CC; Baker, J; Graffagnino, C; Alexander, MJ; Friedman, AH; Zaidat, OO
MLA Citation
Ionita, CC, Baker, J, Graffagnino, C, Alexander, MJ, Friedman, AH, and Zaidat, OO. "Timing of symptomatic vasospasm in aneurysmal subarachnoid hemorrhage: the effect of treatment modality and clinical implications." J Stroke Cerebrovasc Dis 19.2 (March 2010): 110-115.
PMID
20189086
Source
pubmed
Published In
Journal of Stroke & Cerebrovascular Diseases
Volume
19
Issue
2
Publish Date
2010
Start Page
110
End Page
115
DOI
10.1016/j.jstrokecerebrovasdis.2009.11.009

Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma.

BACKGROUND: The study was undertaken to evaluate cardiorespiratory fitness, skeletal muscle function, and body composition of patients with newly diagnosed and untreated, postsurgical primary malignant glioma. METHODS: By using a cross-sectional design, patients with clinically stable (10 +/- 7 days postsurgery) high-grade glioma (HGG; n = 25) or low-grade glioma (LGG; n = 10) were studied. Participants performed a cardiopulmonary exercise test (CPET) with expired gas analysis to assess cardiorespiratory fitness (peak oxygen consumption, VO2peak). Other physiological outcomes included skeletal muscle cross-sectional area (CSA; magnetic resonance imaging), isokinetic muscle strength (isokinetic dynamometer), and body composition (air displacement plethysmography). Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain scale. RESULTS: CPET was a feasible and safe procedure to assess VO2peak, with no serious adverse events. VO2peak indexed to total body weight and lean body mass (LBM) for both groups was 13.0 mL x weight x min(-1) and 19 mL x LBM x min(-1), the equivalent to 59% and 38% below age- and sex-predicted normative values, respectively. Skeletal muscle strength and mid-thigh CSA were lower in HGG relative to LGG patients (83 vs 125 Nm, P = .025; 94 vs 119 cm2, P = .171, respectively). Skeletal muscle isokinetic strength, CSA, and body composition outcomes predicted VO2peak (r = -0.59 to 0.68, P < .05). CONCLUSIONS: Postsurgical glioma patients have markedly reduced cardiorespiratory fitness, isokinetic strength, and CSA. Prospective studies are now required to determine whether such abnormalities influence treatment toxicity and clinical outcome as well as to test the effect of appropriately selected interventions to prevent and/or mitigate dysfunction.

Authors
Jones, LW; Friedman, AH; West, MJ; Mabe, SK; Fraser, J; Kraus, WE; Friedman, HS; Tresch, MI; Major, N; Reardon, DA
MLA Citation
Jones, LW, Friedman, AH, West, MJ, Mabe, SK, Fraser, J, Kraus, WE, Friedman, HS, Tresch, MI, Major, N, and Reardon, DA. "Quantitative assessment of cardiorespiratory fitness, skeletal muscle function, and body composition in adults with primary malignant glioma." Cancer 116.3 (February 1, 2010): 695-704.
PMID
20029975
Source
pubmed
Published In
Cancer
Volume
116
Issue
3
Publish Date
2010
Start Page
695
End Page
704
DOI
10.1002/cncr.24808

Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma.

We evaluated the anti-tumor activity and safety of erlotinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent glioblastoma (GBM) in a phase 2, open-label, single-arm trial. Thirty-two patients received daily erlotinib and sirolimus. The doses of erlotinib and sirolimus were 150 mg and 5 mg for patients not on concurrent CYP3A-inducing anti-epileptics (EIAEDS), and 450 mg and 10 mg for patients on EIAEDS. Evaluations were performed every two months. The primary endpoint was 6-month progression-free survival and secondary endpoints included safety and overall survival. Archival tumor samples were assessed for EGFR, EGFRvIII, PTEN, pAKT and pS6. Enrolled patients were heavily pre-treated including 53% who had received three or more prior chemotherapy agents and 28% who had received prior bevacizumab therapy. The most common grade > or = 2 adverse events were rash (59%), mucositis (34%) and diarrhea (31%). Grade 3 or higher events were rare. Best radiographic response included stable disease in 15 patients (47%); no patients achieved either a CR or PR. The estimated 6-month progression-free survival was 3.1% for all patients. Progression-free survival was better for patients not on EIAEDs (P = 0.03). Tumor markers failed to show an association with PFS except for increased pAKT expression which achieved borderline significance (P = 0.045). Although neither rash nor diarrhea had an association with outcome, hyperlipidemia was associated with longer PFS (P = 0.029). Erlotinib plus sirolimus was well tolerated but had negligible activity among unselected recurrent GBM patients. (ClinicalTrials.gov number: NCT0062243).

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Friedman, AH; Herndon, JE; Marcello, J; Norfleet, JA; McLendon, RE; Sampson, JH; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Gururangan, S, Friedman, AH, Herndon, JE, Marcello, J, Norfleet, JA, McLendon, RE, Sampson, JH, and Friedman, HS. "Phase 2 trial of erlotinib plus sirolimus in adults with recurrent glioblastoma." J Neurooncol 96.2 (January 2010): 219-230.
PMID
19562254
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
96
Issue
2
Publish Date
2010
Start Page
219
End Page
230
DOI
10.1007/s11060-009-9950-0

Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study.

PURPOSE: To investigate the feasibility of longitudinal assessment of functional performance measures in newly diagnosed postsurgical malignant glioma patients. METHODS: Patients with histologically confirmed, clinically stable, postsurgical, and previously untreated high-grade glioma (HGG) or low-grade glioma (LGG) were studied. Using a prospective design, all participants performed a cardiopulmonary exercise test with expired gas analysis to assess cardiorespiratory function (VO(2peak)) immediately following surgical resection (mean, 10 days). Additional functional outcomes were skeletal muscle cross-sectional area (CSA) via magnetic resonance imaging, isokinetic muscle strength (isokinetic dynamometry), and body composition (air displacement plethysmography). Quality of life (QOL) was assessed by the Functional Assessment of Cancer Therapy-Brain scale. All study assessments were repeated at 6 and 24 weeks following surgery. RESULTS: Thirty-five patients (HGG, n = 25; LGG, n = 10) completed baseline assessments. Of these, 20 HGG (80%) and nine LGG (90%) and 15 HGG (60%) and nine LGG (90%) patients completed study assessments at 6 weeks and 24 weeks, respectively. Intention-to-treat analyses indicated several significant time-by-group interactions, with favorable improvements in functional and QOL endpoints from baseline to 24 weeks in the LGG cohort and unfavorable changes in the HGG cohort. Per-protocol analyses including participants assessed at all three study timepoints indicated significant improvements in VO(2peak) and fatigue from baseline to 24 weeks in the HGG cohort; peak workload, body composition, and muscle strength improved from baseline to 6 weeks (all p-values < .05). CONCLUSIONS: Longitudinal quantitative functional assessments are safe and feasible among select patients undergoing chemoradiation for primary malignant glioma. Large prospective studies investigating the clinical importance of these measures appear warranted.

Authors
Jones, LW; Mourtzakis, M; Peters, KB; Friedman, AH; West, MJ; Mabe, SK; Kraus, WE; Friedman, HS; Reardon, DA
MLA Citation
Jones, LW, Mourtzakis, M, Peters, KB, Friedman, AH, West, MJ, Mabe, SK, Kraus, WE, Friedman, HS, and Reardon, DA. "Changes in functional performance measures in adults undergoing chemoradiation for primary malignant glioma: a feasibility study." Oncologist 15.6 (2010): 636-647.
PMID
20484122
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
636
End Page
647
DOI
10.1634/theoncologist.2009-0265

Response

Authors
Nonaka, Y; Grossi, PM; Filomena, CA; Friedman, AH; Fukushima, T
MLA Citation
Nonaka, Y, Grossi, PM, Filomena, CA, Friedman, AH, and Fukushima, T. "Response." Journal of Neurosurgery 113.6 (2010): 1332-1333.
Source
scival
Published In
Journal of neurosurgery
Volume
113
Issue
6
Publish Date
2010
Start Page
1332
End Page
1333
DOI
10.3171/2010.7.JNS101025

Comments

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Comments." Neurosurgical Review 33.4 (2010): 393-394.
Source
scival
Published In
Neurosurgical Review
Volume
33
Issue
4
Publish Date
2010
Start Page
393
End Page
394
DOI
10.1007/s10143-010-0275-4

Comments

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Comments." Neurosurgery 66.5 (2010): 968--.
Source
scival
Published In
Neurosurgery
Volume
66
Issue
5
Publish Date
2010
Start Page
968-
DOI
10.1227/01.NEU.0000367726.49003.F1

Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Gururangan, S; Sampson, JH; Sathornsumetee, S; McLendon, RE; Herndon, JE; Marcello, JE; Norfleet, J; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Gururangan, S, Sampson, JH, Sathornsumetee, S, McLendon, RE, Herndon, JE, Marcello, JE, Norfleet, J, Friedman, AH, Bigner, DD, and Friedman, HS. "Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study." Br J Cancer 101.12 (December 15, 2009): 1986-1994.
PMID
19920819
Source
pubmed
Published In
British Journal of Cancer
Volume
101
Issue
12
Publish Date
2009
Start Page
1986
End Page
1994
DOI
10.1038/sj.bjc.6605412

Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy.

This phase II trial evaluated efficacy and safety of temozolomide (TMZ) in combination with irinotecan (CPT-11) before radiotherapy in patients with newly diagnosed glioblastoma multiforme (GBM). Prior to radiotherapy, patients were treated with a maximum of three 6-week cycles of TMZ and CPT-11. Patients received TMZ at a dose of 200 mg/m(2)/day on days 1-5 and CPT-11 on days 1, 8, 22, and 29, with a dose adjustment for enzyme-inducing antiepileptic drug use. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), safety, and tumor O(6)-methylguanine-DNA methyltransferase (MGMT) expression. Of the 42 patients treated, 8 (19%) patients achieved a partial response. Median PFS and median OS were 3.1 and 13.8 months, respectively. Grade 3 or 4 AEs were documented in 36% of patients, most of which were hematologic (29%). Twenty-four percent of patients had grade 3 or 4 non-hematologic AEs, with gastrointestinal AEs being the most common (12%) Two patients died, one of intracranial hemorrhage and one of treatment-related renal failure. Low MGMT expression, compared with high MGMT expression, showed no significant difference in ORR (25 vs. 8%), median PFS (14 vs. 5 months) or OS (21 vs. 15 months). Although TMZ plus CPT-11 is at least comparable in efficacy to TMZ alone, this combination appears more toxic and poorly tolerated. The lack of correlation of activity with MGMT expression is intriguing, but needs further evaluation in subsequent trials.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Friedman, AH; Sampson, JH; McLendon, RE; Herndon, JE; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Friedman, AH, Sampson, JH, McLendon, RE, Herndon, JE, and Friedman, HS. "Phase II trial of temozolomide (TMZ) plus irinotecan (CPT-11) in adults with newly diagnosed glioblastoma multiforme before radiotherapy." J Neurooncol 95.3 (December 2009): 393-400.
PMID
19533023
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
95
Issue
3
Publish Date
2009
Start Page
393
End Page
400
DOI
10.1007/s11060-009-9937-x

Simple identification of the third segment of the extracranial vertebral artery by extreme lateral inferior transcondylar-transtubercular exposure (ELITE).

PURPOSE: The exposure of the third segment of the extracranial vertebral artery (V3) is an important step in the extreme lateral inferior transcondylar-transtubercular exposure (ELITE) approach. The muscular suboccipital triangle provides one of the landmarks to identify the V3 segment; however, identification of this triangle and dissection of the V3 segment is not always straightforward in the actual surgery. Blind dissection below the level of the foramen magnum can lead to vertebral artery injury. While the surgeon may be able to readily define the V3 segment of the vertebral artery by feeling its pulse, it is important to have a safe systematic approach to finding the V3 segment when the vessel is illusive. We propose a simple method to identify the V3 segment avoiding accidental injury of the vertebral artery. METHODS: Sixteen cadaver heads (using both sides) were prepared by injecting red- or blue-coloured silicone into their arteries and veins, respectively. We performed an ELITE bilaterally on each cadaver head following four key bony landmarks. A postauricular lazy S-shaped skin incision was made centered just behind the mastoid tip. The posterior neck muscles were cut along the line of the skin incision behind the attachment of the sternocleidomastoid muscle to expose the occipital bone. All the incised muscles were reflected anteriorly as the ELITE is a dorsolateral approach. A suboccipital craniotomy was made exposing the posterior half of the sigmoid sinus up to the inferior retrosigmoid point (point A). The foramen magnum was opened after the craniotomy was completed. The dura on the foramen magnum was followed posteriorly in order to identify the occipital midline dural point (point B) that is identified by the bony ridge at the junction of the posterior fossa dura on the foramen magnum and the posterior most aspect of the spinal dura. The posterior tubercle of C1 (point C) was identified directly inferior to Point B. The posterior arch of C1 was followed anteriorly from the tubercle to find the "J-groove", which cradles the vertebral artery (point D). The V3 segment lies above this groove, covering the paravertebral venous plexus. We measured the distances between the landmarks introduced above after completion of the exposure. RESULTS: The distance between points A and B was 30.5 +/- 5.6 mm, points B-C was 10.4 +/- 2.3 mm, points C-D was 19.1 +/- 3.8 mm. The V3 segment was identified using the anatomical relationships described above in all heads. In no cadaver specimen was the artery injured. CONCLUSIONS: Identification of the V3 segment of the vertebral artery by systematically detecting the four anatomical points defined above is simple and much safer than a direct dissection below the foramen magnum.

Authors
Wanibuchi, M; Fukushima, T; Zenga, F; Friedman, AH
MLA Citation
Wanibuchi, M, Fukushima, T, Zenga, F, and Friedman, AH. "Simple identification of the third segment of the extracranial vertebral artery by extreme lateral inferior transcondylar-transtubercular exposure (ELITE)." Acta Neurochir (Wien) 151.11 (November 2009): 1499-1503.
PMID
19657583
Source
pubmed
Published In
Acta Neurochirurgica
Volume
151
Issue
11
Publish Date
2009
Start Page
1499
End Page
1503
DOI
10.1007/s00701-009-0360-z

Alpha1-adrenergic blockers and intraoperative floppy-iris syndrome.

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Alpha1-adrenergic blockers and intraoperative floppy-iris syndrome." Arch Ophthalmol 127.11 (November 2009): 1538-1539.
PMID
19901226
Source
pubmed
Published In
Archives of Ophthalmology
Volume
127
Issue
11
Publish Date
2009
Start Page
1538
End Page
1539
DOI
10.1001/archophthalmol.2009.280

Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients.

The purpose of this study was to determine the safety of tinzaparin for deep vein thrombosis prophylaxis in newly diagnosed grade III-IV malignant glioma patients. Patients were initiated on daily tinzaparin at a fixed dose of 4,500 IU subcutaneously between 48 h and 4 weeks post-operative for planned duration of 12 months. During chemotherapy cycles, blood counts were monitored weekly and tinzaparin was held if the platelet count decreased to <50,000 and was re-initiated at a platelet count >100,000. Forty patients were enrolled into the study, 35 with glioblastoma multiforme and 5 with anaplastic astrocytoma. Possible attributable toxicity was limited to two patients who developed CNS hemorrhages (one grade 1 and one grade 2) and one patient with an increase in liver enzymes (grade 3). There were no patients with a grade 4 or 5 CNS hemorrhages or systemic hemorrhages >or=grade 2. The median time on prophylactic tinzaparin was 161 days (range of 5 to 601 days). One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin. Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients.

Authors
Perry, SL; Bohlin, C; Reardon, DA; Desjardins, A; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Perry, SL, Bohlin, C, Reardon, DA, Desjardins, A, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients." J Neurooncol 95.1 (October 2009): 129-134.
PMID
19415455
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
95
Issue
1
Publish Date
2009
Start Page
129
End Page
134
DOI
10.1007/s11060-009-9911-7

Hearing preservation in surgery for large vestibular schwannomas.

OBJECT: Hearing preservation remains a challenging problem in vestibular schwannoma (VS) surgery. The ability to preserve hearing in patients with large tumors is subject to particular difficulty. In this study, the authors focus on hearing preservation in patients harboring large VSs. METHODS: A total of 344 consecutive patients underwent surgical removal of VSs over the past 9 years. Of these 344 cases, 195 VSs were > 20 mm in maximum cisternal diameter. Of the 195 cases, hearing preservation surgery was attempted for 54 patients who had a Class A, B, C, or D preoperative hearing level; that is, a pure tone average or= 50% according to the Sanna/Fukushima classification. The tumors were classified as moderately large (21-30 mm based on the largest extrameatal diameter), large (31-40 mm), and giant (>or= 41 mm) according to the international criteria. The authors categorized patients with Class A, B, C, D, or E hearing (pure tone average or= 40%) as having preserved hearing postoperatively. RESULTS: Forty-one tumors (75.9%) were totally removed and 13 (24.1%) had near-total removal. Of the 54 patients, 29 maintained their hearing postoperatively; the overall hearing preservation rate was 53.7%. Analysis based on the preoperative hearing level showed that hearing was preserved in 14 (77.8%) of 18 cases for Class A; in 8 (47.1%) of 17 cases for Class B; in 4 (57.1%) of 7 cases for Class C; and in 3 (25.0%) of 12 cases for Class D. In addition, according to the analysis based on the tumor size, 20 (52.6%) of 38 patients with moderately large tumors retained their hearing, as did 5 (50.0%) of 10 patients with large tumors and 4 (66.7%) of 6 patients with giant tumors. Complications included 2 cases of bacterial meningitis that were cured by intravenous injection of antibiotics, 3 cases of subcutaneous CSF leakage that resolved without any surgical repair, and 1 case of temporary abducent nerve palsy. There were no deaths in this series. CONCLUSIONS: The results indicate that successful hearing preservation surgery in large VSs is possible with meticulous technique and attention to adhesions between the tumor and the cochlear nerves.

Authors
Wanibuchi, M; Fukushima, T; McElveen, JT; Friedman, AH
MLA Citation
Wanibuchi, M, Fukushima, T, McElveen, JT, and Friedman, AH. "Hearing preservation in surgery for large vestibular schwannomas." J Neurosurg 111.4 (October 2009): 845-854.
PMID
19344218
Source
pubmed
Published In
Journal of neurosurgery
Volume
111
Issue
4
Publish Date
2009
Start Page
845
End Page
854
DOI
10.3171/2008.12.JNS08620

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.

Authors
Sampson, JH; Archer, GE; Mitchell, DA; Heimberger, AB; Herndon, JE; Lally-Goss, D; McGehee-Norman, S; Paolino, A; Reardon, DA; Friedman, AH; Friedman, HS; Bigner, DD
MLA Citation
Sampson, JH, Archer, GE, Mitchell, DA, Heimberger, AB, Herndon, JE, Lally-Goss, D, McGehee-Norman, S, Paolino, A, Reardon, DA, Friedman, AH, Friedman, HS, and Bigner, DD. "An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme." Mol Cancer Ther 8.10 (October 2009): 2773-2779.
PMID
19825799
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
8
Issue
10
Publish Date
2009
Start Page
2773
End Page
2779
DOI
10.1158/1535-7163.MCT-09-0124

An eclectic review of the history of peripheral nerve surgery.

We take our present concepts of nerve repair for granted. In fact, the pioneers who established these principles traveled a road filled with erroneous dogma, bad advice, and misleading data. The lessons learned from a review of the history of peripheral nerve surgery are applicable to all neurosurgical disciplines. In honor of Dr. David Kline's distinguished career, we will review 3 aspects of the history of peripheral nerve surgery: Can an injured nerve regain function? How do peripheral nerves regenerate? When should a neuroma in continuity be resected?

Authors
Friedman, AH
MLA Citation
Friedman, AH. "An eclectic review of the history of peripheral nerve surgery." Neurosurgery 65.4 Suppl (October 2009): A3-A8.
PMID
19927076
Source
pubmed
Published In
Neurosurgery
Volume
65
Issue
4 Suppl
Publish Date
2009
Start Page
A3
End Page
A8
DOI
10.1227/01.NEU.0000346252.53722.D3

Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma.

This phase I clinical trial conducted with patients who had recurrent or progressive malignant glioma (MG) was designed to determine the maximum tolerated dose (MTD) and toxicity of three different 5-day dosing regimens of temozolomide (TMZ) in combination with O(6)-benzylguanine (O(6)-BG). Both TMZ and O(6)-BG were administered on days 1-5 of a 28-day treatment cycle. A bolus infusion of O(6)-BG was administered at 120 mg/m(2) over 1 h on days 1, 3, and 5, along with a continuous infusion of O(6)-BG at 30 mg/m(2)/day. TMZ was administered at the end of the first bolus infusion of O(6)-BG and then every 24 h for 5 days during the continuous infusion of O(6)-BG. Patients were accrued to one of three 5-day dosing regimens of TMZ. Twenty-nine patients were enrolled into this study. The dose-limiting toxicities (DLTs) were grade 4 neutropenia, leukopenia, and thrombocytopenia. The MTD for TMZ for the three different 5-day dosing schedules was determined as follows: schedule 1, 200 mg/m(2) on day 1 and 50 mg/m(2)/day on days 2-5; schedule 2, 50 mg/m(2)/day on days 1-5; and schedule 3, 50 mg/m(2)/day on days 1-5 while receiving pegfilgrastim. Thus, the 5-day TMZ dosing schedule that maximized the total dose of TMZ when combined with O(6)-BG was schedule 1. This study provides the foundation for a phase II trial of O(6)-BG in combination with a 5-day dosing schedule of TMZ in TMZ-resistant MG.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Walker, A; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Walker, A, and Friedman, HS. "Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma." Neuro Oncol 11.5 (October 2009): 556-561.
PMID
19289491
Source
pubmed
Published In
Neuro-Oncology
Volume
11
Issue
5
Publish Date
2009
Start Page
556
End Page
561
DOI
10.1215/15228517-2009-007

Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy.

BACKGROUND: Glioblastoma multiforme (GBM), the most lethal type of brain tumor, has a 1-year median survival. The effect of carmustine wafers on the survival of newly diagnosed GBM patients treated with radiotherapy (RT) and concurrent temozolomide (TMZ) plus RT plus rotational chemotherapy was investigated. METHODS: An institutional review board-approved retrospective study was conducted in 85 newly diagnosed GBM patients who received surgical resection with and without carmustine wafers followed by RT and concurrent TMZ plus rotational chemotherapy. Treatment group comparisons were conducted using the log-rank test. Survival experience of the Duke cohort was examined within specific patient subgroups defined by the original Radiation Therapy Oncology Group (RTOG) recursive partition analysis (RPA) class and compared with the European Organization for Research and Treatment of Cancer (Stupp) and RTOG trial. RESULTS: Overall 1- and 2-year survival for the noncarmustine wafer cohort were 69% and 29%, respectively, with a median survival of 72.7 weeks. One- and 2-year survival for the carmustine wafer cohort were 81% and 47%, with median survival of 89.5 weeks. Carmustine wafer was not an independent predictor (P=.110) of survival after adjustment for RPA class. The proportion of patients in the carmustine wafer cohort who lived longer than predicted based upon Stupp regimen results was significantly greater than 0.5 (P<.006); similar results based upon the RTOG trial data were observed (P<.001). CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone. Prospective randomized trials are needed to rigorously compare the carmustine wafer regimen to the Stupp and postradiation multimodality regimens.

Authors
Affronti, ML; Heery, CR; Herndon, JE; Rich, JN; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Affronti, ML, Heery, CR, Herndon, JE, Rich, JN, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Friedman, AH, Bigner, DD, and Friedman, HS. "Overall survival of newly diagnosed glioblastoma patients receiving carmustine wafers followed by radiation and concurrent temozolomide plus rotational multiagent chemotherapy." Cancer 115.15 (August 1, 2009): 3501-3511.
PMID
19514083
Source
pubmed
Published In
Cancer
Volume
115
Issue
15
Publish Date
2009
Start Page
3501
End Page
3511
DOI
10.1002/cncr.24398

Assessment of physical functioning in recurrent glioma: preliminary comparison of performance status to functional capacity testing.

BACKGROUND: Performance status (PS) scoring systems are tools of immense clinical importance in the management of patients with malignant disease but these tools are subjective and do not provide an objective evaluation of physical functioning. We conducted a pilot study to explore the feasibility and clinical utility of functional capacity testing to assess physical functioning in recurrent primary malignant glioma patients. PATIENTS AND METHODS: Using a cross-sectional design, consecutive patients with recurrent glioma performed a six minute walk (6MW) test to assess functional capacity. Performance status was assessed using Karnofsky Performance Status (KPS) scoring system. QOL was assessed by the Functional Assessment of Cancer Therapy-Brain scale. Self-reported exercise behavior was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ). RESULTS: A total of 171 patients were recruited and tested. Seventy percent were diagnosed with glioblastoma multiforme (WHO grade IV) and 85% were undergoing therapy. Median KPS was 90% (range, 70-100%). Median 6MW distance was 400 m (range, 102-630 m), equivalent to 56 +/- 13% (range, 14-87%) of that predicted for age and sex. KPS, self-reported exercise, and QOL increased across 6MW distance quartiles (P < 0.05) although there was considerable variation within each category. 6MW distance and KPS were significantly correlated with each other (r = 0.34, P < 0.01) and several QOL domains (range, r = -0.43 to 0.46, P < 0.05). CONCLUSIONS: 6MW distance is a clinically feasible tool that provides an objective measure of physical functioning in select patients with recurrent glioma. Further research is required to investigate the prognostic value of these tests in patients with advanced malignancy.

Authors
Jones, LW; Cohen, R-R; Mabe, SK; West, MJ; Desjardins, A; Vredenburgh, JJ; Friedman, AH; Reardon, DA; Waner, E; Friedman, HS
MLA Citation
Jones, LW, Cohen, R-R, Mabe, SK, West, MJ, Desjardins, A, Vredenburgh, JJ, Friedman, AH, Reardon, DA, Waner, E, and Friedman, HS. "Assessment of physical functioning in recurrent glioma: preliminary comparison of performance status to functional capacity testing." J Neurooncol 94.1 (August 2009): 79-85.
PMID
19212703
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
94
Issue
1
Publish Date
2009
Start Page
79
End Page
85
DOI
10.1007/s11060-009-9803-x

Tamsulosin and the intraoperative floppy iris syndrome.

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Tamsulosin and the intraoperative floppy iris syndrome." JAMA 301.19 (May 20, 2009): 2044-2045.
PMID
19454645
Source
pubmed
Published In
JAMA : the journal of the American Medical Association
Volume
301
Issue
19
Publish Date
2009
Start Page
2044
End Page
2045
DOI
10.1001/jama.2009.704

Gait abnormalities and inflammatory cytokines in an autologous nucleus pulposus model of radiculopathy.

STUDY DESIGN: The authors investigated gait abnormalities and mechanical hypersensitivity associated with invertebral disc herniation in a rat model of radiculopathy. Further evaluation involved assessing how nucleus pulposus (NP) injury affected systemic cytokine expression and molecular changes at the dorsal root ganglion (DRG). OBJECTIVE: The objective of this work was to describe the gait and behavioral changes in an animal model of disc-herniation induced radiculopathy. A second objective included examining how these functional changes correlated with neuroinflammation and autoreactive lymphocyte immune activation. SUMMARY OF BACKGROUND DATA: Animal models of radiculopathy describe demyelination, slowed nerve conduction, and heightened pain sensitivity after application of autologous NP to the DRG. The quantitative impact of disc herniation on animal locomotion has not been investigated. Further, while local inflammation occurs at the injury site, the role of autoimmune cytokines reactive against previously immune-sequestered NP requires investigation. METHODS: NP-treated animals (n = 16) received autologous tail NP placed onto the L5 DRG exposed by unilateral facetectomy, and control animals (n = 16) underwent exposure only. At weekly time points, animals were evaluated for mechanical allodynia, thermal hyperalgesia, and gait characteristics through digitized video analysis. Serum cytokine content was measured after animal sacrifice, and immunohistochemistry tested DRG tissue for mediators of inflammation and immune activation. RESULTS: Sensory testing revealed mechanical allodynia in the affected limb of NP-treated rats compared with sham animals (P < 0.01) at all time points. Gait analysis reflected functional locomotive consequences of marked asymmetry (P = 0.048) and preference to bear weight on the contralateral limb (duty factor imbalance, P < 0.01) at early time points. Equivalent serum cytokine expression occurred in both groups, confirming the local inflammatory nature of this disease model. Immunohistochemistry of the sectioned DRGs revealed equivalent postsurgical inflammatory activation (interleukin 23, P = 0.47) but substantial early immune activation in the NP-treated group (interleukin 17, P = 0.01). CONCLUSION: This model of radiculopathy provides evidence of altered gait in a model of noncompressive disc herniation. Systemic inflammation was absent, but mechanical allodynia, local inflammation, and autoreactive immune activation were observed. Future work will involve therapeutic interventions to rescue animals from the phenotype of inflammatory radiculopathy.

Authors
Shamji, MF; Allen, KD; So, S; Jing, L; Adams, SB; Schuh, R; Huebner, J; Kraus, VB; Friedman, AH; Setton, LA; Richardson, WJ
MLA Citation
Shamji, MF, Allen, KD, So, S, Jing, L, Adams, SB, Schuh, R, Huebner, J, Kraus, VB, Friedman, AH, Setton, LA, and Richardson, WJ. "Gait abnormalities and inflammatory cytokines in an autologous nucleus pulposus model of radiculopathy." Spine (Phila Pa 1976) 34.7 (April 1, 2009): 648-654.
PMID
19333095
Source
pubmed
Published In
Spine
Volume
34
Issue
7
Publish Date
2009
Start Page
648
End Page
654
DOI
10.1097/BRS.0b013e318197f013

Impact of ruptured cerebral aneurysm coiling and clipping on the incidence of cerebral vasospasm and clinical outcome.

BACKGROUND: This study assessed the impact of treatment modality of aneurysmal subarachnoid hemorrhage (aSAH) on the rate of vasospasm (VSP), mortality, and hospital length of stay (LOS) of patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We analyzed patients with aSAH admitted between 1999 and 2005 undergoing either endovascular coiling (EC) or surgical clipping (SC) within 72 hours of onset. Clinical VSP was defined as neurological deficits unexplained by another etiology. Radiological VSP was defined based on transcranial Doppler (TCD) ultrasound, digital subtraction angiography (DSA), and CT criteria. Bivariate and logistic regression analysis was used to determine VSP predictors. RESULTS: Of 216 patients included, 98 (45%) underwent EC and 118 (55%) underwent SC. Clinical VSP was found in 26% of EC and 40% of SC patients (P < .03). TCD VSP, angiographic VSP, and CT infarctions were all significantly higher in the SC group. Mortality was similar in both groups however the LOS was longer in the SC patients (P= .03). Multivariate analysis showed that SC doubled the risk of clinical VSP (P < .03) and tripled the risk of composite VSP (P < .0006). CONCLUSIONS: Our study reveals that EC has a lower rate of VSP, shorter LOS, and comparable mortality to SC in aSAH.

Authors
Zaidat, OO; Ionita, CC; Hussain, SI; Alexander, MJ; Friedman, AH; Graffagnino, C
MLA Citation
Zaidat, OO, Ionita, CC, Hussain, SI, Alexander, MJ, Friedman, AH, and Graffagnino, C. "Impact of ruptured cerebral aneurysm coiling and clipping on the incidence of cerebral vasospasm and clinical outcome." J Neuroimaging 19.2 (April 2009): 144-149.
PMID
18681928
Source
pubmed
Published In
Journal of Neuroimaging
Volume
19
Issue
2
Publish Date
2009
Start Page
144
End Page
149
DOI
10.1111/j.1552-6569.2008.00285.x

Primary intramedullary melanocytoma of the spinal cord: case report.

OBJECTIVE: The authors report 2 cases of primary intramedullary spinal melanocytomas in 2 patients who presented with lower extremity numbness and/or weakness. CLINICAL PRESENTATION: Magnetic resonance imaging of the spine, thoracic laminectomy, and histological examination revealed the diagnosis. TECHNIQUE: Microscopic and immunohistochemical analysis revealed the diagnosis of primary melanocytoma. CONCLUSION: Melanocytomas of the spine are rare lesions without distinctive imaging characteristics and pose a preoperative diagnostic challenge. A review of the relevant literature and clinical behavior of this uncommon tumor entity is provided.

Authors
Karikari, IO; Powers, CJ; Bagley, CA; Cummings, TJ; Radhakrishnan, S; Friedman, AH
MLA Citation
Karikari, IO, Powers, CJ, Bagley, CA, Cummings, TJ, Radhakrishnan, S, and Friedman, AH. "Primary intramedullary melanocytoma of the spinal cord: case report." Neurosurgery 64.4 (April 2009): E777-E778.
PMID
19349809
Source
epmc
Published In
Neurosurgery
Volume
64
Issue
4
Publish Date
2009
Start Page
E777
End Page
E778
DOI
10.1227/01.neu.0000341516.22126.aa

fMRI activation mapping as a percentage of local excitation: consistent presurgical motor maps without threshold adjustment.

PURPOSE: To evaluate the performance of a relative activation amplitude algorithm, versus standard t-value thresholding, for reliably establishing the location, amplitude, and spatial extent of functional magnetic resonance imaging (fMRI) brain activation for presurgical planning. MATERIALS AND METHODS: Diagnostic fMRI maps from 42 neurosurgical patients performing a simple hand movement task were analyzed. Relative activation maps were made by normalizing statistical t-value maps to the local peak activation amplitude within each functional brain region. The spatial distribution of activation was quantified and compared across mapping algorithms, subjects, and scan duration. RESULTS: Whereas the spatial distribution of blood oxygenation level-dependent (BOLD) t-value statistical activation maps was highly variable across subjects and scan duration, the spatial distribution of relative activation maps was highly reproducible both within individual subjects and across different subjects. In every case the 40% most active voxels in the cortical hand region were consistently localized to the pre- and postcentral gyri of the sensorimotor cortex. CONCLUSION: The reproducibility and anatomical specificity of the spatiotemporal pattern of BOLD activation makes relative amplitude fMRI mapping a useful tool for clinical imaging, where accuracy, reproducibility, and quality control are critical concerns.

Authors
Voyvodic, JT; Petrella, JR; Friedman, AH
MLA Citation
Voyvodic, JT, Petrella, JR, and Friedman, AH. "fMRI activation mapping as a percentage of local excitation: consistent presurgical motor maps without threshold adjustment." J Magn Reson Imaging 29.4 (April 2009): 751-759.
PMID
19306363
Source
pubmed
Published In
Journal of Magnetic Resonance Imaging
Volume
29
Issue
4
Publish Date
2009
Start Page
751
End Page
759
DOI
10.1002/jmri.21716

Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma.

PURPOSE: This phase II trial was designed to define the role of O(6)-benzylguanine (O(6)-BG) in restoring temozolomide sensitivity in patients with recurrent or progressive, temozolomide-resistant malignant glioma and to evaluate the safety of administering O(6)-BG in combination with temozolomide. PATIENTS AND METHODS: Patients were accrued into two independent strata on the basis of histology: glioblastoma multiforme (GBM) and anaplastic glioma. Both temozolomide and O(6)-BG were administered on day 1 of a 28-day treatment cycle. Patients were administered a 1-hour O(6)-BG infusion at a dose of 120 mg/m(2) followed immediately by a 48-hour infusion at a dose of 30 mg/m(2)/d. Temozolomide was administered orally within 60 minutes of the end of the 1-hour O(6)-BG infusion at a dose of 472 mg/m(2). The primary end point was objective response rate. Secondary end points included progression-free survival, overall survival, and safety. RESULTS: Sixty-six of 67 patients who enrolled were treated with temozolomide and O(6)-BG. One of 34 patients (3%) with GBM (95% CI, 0.1% to 15%) and five of 32 assessable patients (16%) with anaplastic glioma (95% CI, 5% to 33%) were responders. The most commonly reported adverse events were grade 4 hematologic events experienced in 48% of the patients. CONCLUSION: O(6)-BG when added to a 1-day dosing regimen of temozolomide was able to restore temozolomide sensitivity in patients with temozolomide-resistant anaplastic glioma, but there seemed to be no significant restoration of temozolomide sensitivity in patients with temozolomide-resistant GBM.

Authors
Quinn, JA; Jiang, SX; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Walker, A; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Walker, A, and Friedman, HS. "Phase II trial of temozolomide plus o6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma." J Clin Oncol 27.8 (March 10, 2009): 1262-1267.
PMID
19204199
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
8
Publish Date
2009
Start Page
1262
End Page
1267
DOI
10.1200/JCO.2008.18.8417

IDH1 and IDH2 mutations in gliomas.

BACKGROUND: A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower-grade gliomas (secondary glioblastomas). METHODS: We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system (CNS) tumors and 494 non-CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes. RESULTS: We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower-grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein. CONCLUSIONS: Mutations of NADP(+)-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.

Authors
Yan, H; Parsons, DW; Jin, G; McLendon, R; Rasheed, BA; Yuan, W; Kos, I; Batinic-Haberle, I; Jones, S; Riggins, GJ; Friedman, H; Friedman, A; Reardon, D; Herndon, J; Kinzler, KW; Velculescu, VE; Vogelstein, B; Bigner, DD
MLA Citation
Yan, H, Parsons, DW, Jin, G, McLendon, R, Rasheed, BA, Yuan, W, Kos, I, Batinic-Haberle, I, Jones, S, Riggins, GJ, Friedman, H, Friedman, A, Reardon, D, Herndon, J, Kinzler, KW, Velculescu, VE, Vogelstein, B, and Bigner, DD. "IDH1 and IDH2 mutations in gliomas." N Engl J Med 360.8 (February 19, 2009): 765-773.
PMID
19228619
Source
pubmed
Published In
The New England journal of medicine
Volume
360
Issue
8
Publish Date
2009
Start Page
765
End Page
773
DOI
10.1056/NEJMoa0808710

Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme.

PURPOSE: This phase II trial was designed to define the efficacy of Gliadel wafers in combination with an infusion of O6-benzylguanine (O6-BG) that suppresses tumor O6-alkylguanine-DNA alkyltransferase (AGT) levels in patients with recurrent glioblastoma multiforme for 5 days and to evaluate the safety of this combination therapy. EXPERIMENTAL DESIGN: This was a phase II, open-label, single center trial. On gross total resection of the tumor, up to eight Gliadel wafers were implanted. Bolus infusion of O6-BG was administered at 120 mg/m2 over 1 hour on days 1, 3, and 5, along with a continuous infusion at 30 mg/m2/d. The primary end points were 6-month overall survival (OS) and safety, and the secondary end points were 1-year, 2-year, and median OS. RESULTS: Fifty-two patients were accrued. The 6-month OS was 82% [95% confidence interval (95% CI), 72-93%]. The 1- and 2-year OS rates were 47% (95% CI, 35-63%) and 10% (95% CI, 3-32%), respectively. The median OS was 50.3 weeks (95% CI, 36.1-69.4 weeks). Treatment-related toxicity with this drug combination included grade 3 hydrocephalus (9.6%), grade 3 cerebrospinal fluid (CSF) leak (19.2%), and grade 3 CSF/brain infection (13.4%). CONCLUSION: The efficacy of implanted Gliadel wafers may be improved with the addition of O6-BG. Although systemically administered O6-BG can be coadministered with Gliadel wafers safely, it may increase the risk of hydrocephalus, CSF leak, and CSF/brain infection. Future trials are required to verify that inhibition of tumor AGT levels by O6-BG results in increased efficacy of Gliadel wafers without added toxicity.

Authors
Quinn, JA; Jiang, SX; Carter, J; Reardon, DA; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Bigner, DD; Sampson, JH; McLendon, RE; Herndon, JE; Threatt, S; Friedman, HS
MLA Citation
Quinn, JA, Jiang, SX, Carter, J, Reardon, DA, Desjardins, A, Vredenburgh, JJ, Rich, JN, Gururangan, S, Friedman, AH, Bigner, DD, Sampson, JH, McLendon, RE, Herndon, JE, Threatt, S, and Friedman, HS. "Phase II trial of Gliadel plus O6-benzylguanine in adults with recurrent glioblastoma multiforme." Clin Cancer Res 15.3 (February 1, 2009): 1064-1068.
PMID
19188181
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
15
Issue
3
Publish Date
2009
Start Page
1064
End Page
1068
DOI
10.1158/1078-0432.CCR-08-2130

Introduction: peripheral nerve surgery--biology, entrapment, and injuries.

Surgery aimed at repairing damaged peripheral nerves has a long history. Refuting the time-honored nihilism of Hippocrates and Galen that an injured nerve cannot regain function, a few adventurous medieval surgeons attempted to repair severed nerves. However, the ability of a peripheral nerve repair to restore function was not generally accepted until 1800. Neurosurgeons, beginning with Harvey Cushing, have had an interest in repairing damaged peripheral nerves. Significant progress in the treatment of peripheral nerve injuries resulted from experience with the numerous injuries that occurred during World Wars I and II. Surgeons steadily defined the anatomy of peripheral nerves and developed techniques for decompressing and repairing peripheral nerves. Kline and Dejonge developed an intraoperative electrophysiological technique for detecting axons regenerating across a damaged segment of nerve. In the second 2 decades of the 20th century, distal nerve transfers were rediscovered whereby the proximal end of a less essential nerve is used to reinnervate the distal end of a nerve, providing a more vital function.

Authors
Friedman, AH; Elias, WJ; Midha, R
MLA Citation
Friedman, AH, Elias, WJ, and Midha, R. "Introduction: peripheral nerve surgery--biology, entrapment, and injuries." Neurosurg Focus 26.2 (February 2009): E1-.
PMID
19435439
Source
pubmed
Published In
Neurosurgical focus
Volume
26
Issue
2
Publish Date
2009
Start Page
E1
DOI
10.3171/FOC.2009.26.2.E1

The association of breast cancer and meningioma in men and women: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "The association of breast cancer and meningioma in men and women: Commentary." Neurosurgery 65.3 (2009): 489--.
Source
scival
Published In
Neurosurgery
Volume
65
Issue
3
Publish Date
2009
Start Page
489-
DOI
10.1227/01.NEU.0000350876.91495.E0

Computerized assessment of vessel morphological changes during treatment of glioblastoma multiforme: Report of a case imaged serially by MRA over four years

A patient with glioblastoma multiforme underwent serial computerized analysis of tumor-associated vasculature defined from magnetic resonance angiographic (MRA) scans obtained over almost a four year period. The clinical course included tumor resection with subsequent radiation therapy, a long symptom-free interval, emergence of a new malignant focus, resection of that focus, a stroke, and treatment with chemotherapy and anti-angiogenic therapy. Image analysis methods included segmentation of vessels from each MRA and statistical comparison of vessel morphology over 4 regions of interest (the initial tumor site, the second tumor site, a distant control region, and the entire brain) to the same 4 regions of interest in 50 healthy volunteers (26 females and 24 males; mean age 39 years). Results suggested that following completion of focal radiation therapy (RT) vessel shape abnormalities, if elevated at the time of RT completion, may progressively normalize for months in focal regions, that progressively severe vessel shape abnormalities can precede the emergence of a gadolinium enhancing lesion by months, that lesion resection can produce a dramatic but highly transient drop in abnormal vessel tortuosity both focally and globally, and that treatment with anti-angiogenic agents does not necessarily normalize vessel shape. Quantitative measurements of vessel morphology as defined from MRA may provide useful insights into tumor development and response to therapy. © 2008 Elsevier Inc. All rights reserved.

Authors
Bullitt, E; Ewend, M; Vredenburgh, J; Friedman, A; Lin, W; Wilber, K; Zeng, D; Aylward, SR; Reardon, D
MLA Citation
Bullitt, E, Ewend, M, Vredenburgh, J, Friedman, A, Lin, W, Wilber, K, Zeng, D, Aylward, SR, and Reardon, D. "Computerized assessment of vessel morphological changes during treatment of glioblastoma multiforme: Report of a case imaged serially by MRA over four years." NeuroImage 47.SUPPL. 2 (2009): T143-T151.
PMID
19103295
Source
scival
Published In
NeuroImage
Volume
47
Issue
SUPPL. 2
Publish Date
2009
Start Page
T143
End Page
T151
DOI
10.1016/j.neuroimage.2008.10.067

Management of postneurosurgical bone flap loss caused by infection.

LEARNING OBJECTIVES: After studying this article, the participant should: 1. Be able to define indications and timing for secondary cranioplasty. 2. Understand the surgical options for reconstructing the cranium and overlying soft-tissue defect including their advantages and disadvantages. 3. Be able to apply this knowledge to the clinical setting of an infectious bone flap loss. BACKGROUND: Infection after craniotomy occurs in approximately 1.1 to 8.1 percent of cases and often necessitates bone flap removal. For a secondary cranioplasty, there is an increased risk of recurrent infection, which influences the reconstructive plan. The soft tissue/scalp is frequently compromised by infection, sequelae of prior surgery, and/or adjuvant radiation therapy. METHODS: A literature review was conducted to compile and summarize the indications for secondary cranioplasty after infectious bone flap loss, the timing of the procedure, and the surgical options for bone and soft-tissue reconstruction. In coordination with soft-tissue coverage, cranioplasty options include alloplastic reconstruction, allogeneic or autogenous bone grafts, and free tissue transfer. RESULTS: The literature review identified the following factors that must be considered in the treatment plan for secondary cranioplasty after postneurosurgical bone flap loss: indications, timing of reconstruction, soft-tissue status and the need for soft-tissue reconstruction, and method of cranioplasty. CONCLUSIONS: Treatment recommendations for cranioplasty in the clinical setting of infectious postneurosurgical bone flap loss are presented. These guidelines consider the risk factors for a recurrent infection, the condition of the soft-tissue coverage, and the concavity of the preoperative cranial deformity.

Authors
Baumeister, S; Peek, A; Friedman, A; Levin, LS; Marcus, JR
MLA Citation
Baumeister, S, Peek, A, Friedman, A, Levin, LS, and Marcus, JR. "Management of postneurosurgical bone flap loss caused by infection." Plast Reconstr Surg 122.6 (December 2008): 195e-208e. (Review)
PMID
19050490
Source
pubmed
Published In
Plastic and Reconstructive Surgery
Volume
122
Issue
6
Publish Date
2008
Start Page
195e
End Page
208e
DOI
10.1097/PRS.0b013e3181858eee

Anatomy, morphogenesis, diagnosis, management, and outcomes for neonates with common arterial trunk.

Authors
Colon, M; Anderson, RH; Weinberg, P; Mussatto, K; Bove, E; Friedman, AH
MLA Citation
Colon, M, Anderson, RH, Weinberg, P, Mussatto, K, Bove, E, and Friedman, AH. "Anatomy, morphogenesis, diagnosis, management, and outcomes for neonates with common arterial trunk." Cardiology in the young 18 Suppl 3 (December 2008): 52-62. (Academic Article)
Source
manual
Published In
Cardiology in the Young
Volume
18 Suppl 3
Publish Date
2008
Start Page
52
End Page
62
DOI
10.1017/S1047951108003296

Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas.

PURPOSE: Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma, salvage therapies following recurrence offer essentially palliative benefit. We did a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan for patients with recurrent grade 3 malignant glioma. EXPERIMENTAL DESIGN: Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab (10 mg/kg) and irinotecan every 14 days, a second cohort (n=24) was treated with bevacizumab (15 mg/kg) every 3 weeks with irinotecan on days 1, 8, 22, and 29 of each 42-day cycle. For both cohorts, the dose of irinotecan was 340 mg/m(2) for patients on enzyme-inducing antiepileptic drugs (EIAED) and 125 mg/m(2) for patients not on EIAEDs. After each 6-week cycle, patients were evaluated with a physical examination and magnetic resonance imaging. RESULTS: The 6-month progression-free survival was 55% (95% confidence interval, 36-70%). The 6-month overall survival was 79% (95% confidence interval, 61-89%). Twenty patients (61%) had at least a partial response. Outcome did not differ between the two treatment cohorts. Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient, and one patient who developed thrombotic thrombocytopenic purpura. CONCLUSION: Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma.

Authors
Desjardins, A; Reardon, DA; Herndon, JE; Marcello, J; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Sampson, J; Bailey, L; Bigner, DD; Friedman, AH; Friedman, HS; Vredenburgh, JJ
MLA Citation
Desjardins, A, Reardon, DA, Herndon, JE, Marcello, J, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Sampson, J, Bailey, L, Bigner, DD, Friedman, AH, Friedman, HS, and Vredenburgh, JJ. "Bevacizumab plus irinotecan in recurrent WHO grade 3 malignant gliomas." Clin Cancer Res 14.21 (November 1, 2008): 7068-7073.
PMID
18981004
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
21
Publish Date
2008
Start Page
7068
End Page
7073
DOI
10.1158/1078-0432.CCR-08-0260

Microsurgical management of 53 jugular foramen schwannomas: lessons learned incorporated into a modified grading system.

OBJECT: Due to the proximity and involvement of critical neurovascular structures, the resection of jugular foramen schwannomas can pose a formidable challenge. The authors review their experience in the microsurgical management of jugular foramen schwannomas and propose a modified grading scale to guide surgical management. METHODS: All jugular foramen schwannoma cases treated by the senior author (T.F.) between 1980 and 2004 were retrospectively reviewed. The average age at presentation, surgical approach, tumor characteristics, cranial nerve (CN) deficits, and tumor recurrence rates were assessed. The authors present the following modified grading scale: Type A, intradural tumors; Type B, dumbbell-shaped tumors; and Type C, triple dumbbell tumors with a high cervical extension. RESULTS: The authors treated jugular foramen tumors in 129 patients during the study period. Of these, 53 patients (41%) had jugular foramen schwannomas. The mean patient age was 52 years (range 14-74 years); there were 12 male and 41 female patients. The mean follow-up period was 8.4 years. Patients presented most commonly with deficits of the vagus nerve, followed by vestibular/cochlear nerve and glossopharyngeal nerve deficits. Gross-total resection of the tumor was achieved in 48 patients (90.5%). New postoperative paresis in a previously normal CN was not seen; however, worsening of preoperative CN deficits was frequently noted. The highest incidence occurred with the glossopharyngeal and vagus nerves (30%), with 26% of the deficits being permanent. There were no deaths related to surgery in this series. Three patients (5.7%) experienced tumor recurrence. CONCLUSIONS: The microsurgical resection of jugular foramen schwannomas carries a risk of worsening preoperative CN deficits; however, these are often transient. Based on their experience, the authors have formulated a grading scale that predicts the optimal surgical approach to these lesions. Considerable technical training and microneuroanatomical knowledge of the region is required. The modified grading scale presented facilitates preoperative planning.

Authors
Bulsara, KR; Sameshima, T; Friedman, AH; Fukushima, T
MLA Citation
Bulsara, KR, Sameshima, T, Friedman, AH, and Fukushima, T. "Microsurgical management of 53 jugular foramen schwannomas: lessons learned incorporated into a modified grading system." J Neurosurg 109.5 (November 2008): 794-803.
PMID
18976067
Source
pubmed
Published In
Journal of neurosurgery
Volume
109
Issue
5
Publish Date
2008
Start Page
794
End Page
803
DOI
10.3171/JNS/2008/109/11/0794

Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: technical case report.

OBJECTIVE: Neurophysiological intraoperative monitoring of the glossopharyngeal nerve has been performed only with needle electrodes inserted into the pharyngeal muscles or soft palate. We describe a noninvasive method of monitoring this cranial nerve. METHODS: A 30-year-old man who presented with headache, as well as speech and swallowing difficulty, underwent surgical resection of a right vagus nerve schwannoma. Neurophysiological intraoperative monitoring of multiple lower cranial nerves, including the glossopharyngeal and vagus nerves, was performed. RESULTS: The glossopharyngeal nerve was monitored with an adhesive surface electrode mounted on the cuff of a laryngeal mask airway, and the vagus nerve was monitored with a similar electrode mounted on the endotracheal tube. Successful monitoring allowed separation of the glossopharyngeal nerve from the tumor, and there was no postoperative swallowing deficit. CONCLUSION: Monitoring of the glossopharyngeal nerve with surface electrodes is possible and reliable, but it must be combined with vagus nerve monitoring.

Authors
Husain, AM; Wright, DR; Stolp, BW; Friedman, AH; Keifer, JC
MLA Citation
Husain, AM, Wright, DR, Stolp, BW, Friedman, AH, and Keifer, JC. "Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: technical case report." Neurosurgery 63.4 Suppl 2 (October 2008): 277-278.
PMID
18981820
Source
pubmed
Published In
Neurosurgery
Volume
63
Issue
4 Suppl 2
Publish Date
2008
Start Page
277
End Page
278
DOI
10.1227/01.NEU.0000316425.21752.E2

Synthesis and characterization of a thermally-responsive tumor necrosis factor antagonist.

Numerous antagonists of tumor necrosis factor alpha (TNFalpha) have been developed to attenuate inflammation and accompanying pain in many disease processes. Soluble TNF receptor type II (sTNFRII) is one such antagonist that sequesters TNFalpha away from target receptors and attenuates its activity. Systemic delivery of soluble TNF receptors or other antagonists may have deleterious side effects associated with immune suppression, so that strategies for locally targeted drug delivery are of interest. Elastin-like polypeptides (ELPs) are biopolymers capable of in situ drug depot formation through thermally-driven supramolecular complexes at physiological temperatures. A recombinant fusion protein between ELP and sTNFRII was designed and evaluated for retention of bivalent functionality. Thermal sensitivity was observed by formation of supramolecular submicron-sized particles at 32 degrees C, with gradual resolubilization from the depot observed at physiological temperatures. In vitro refolding of the sTNFRII domain was required and the purified product exhibited an equilibrium dissociation constant for interacting with TNFalpha that was seven-fold higher than free sTNFRII. Furthermore, anti-TNF activity was observed in inhibiting TNFalpha-mediated cytotoxicity in the murine L929 fibrosarcoma assay. Potential advantages of this ELP-sTNFRII fusion protein as an anti-TNFa drug depot include facility of injection, in situ depot formation, low endotoxin content, and functionality against TNFalpha.

Authors
Shamji, MF; Chen, J; Friedman, AH; Richardson, WJ; Chilkoti, A; Setton, LA
MLA Citation
Shamji, MF, Chen, J, Friedman, AH, Richardson, WJ, Chilkoti, A, and Setton, LA. "Synthesis and characterization of a thermally-responsive tumor necrosis factor antagonist." J Control Release 129.3 (August 7, 2008): 179-186.
PMID
18547669
Source
pubmed
Published In
Journal of Controlled Release
Volume
129
Issue
3
Publish Date
2008
Start Page
179
End Page
186
DOI
10.1016/j.jconrel.2008.04.021

Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma.

PURPOSE: A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temozolomide regardless of AGT activity. The purpose of this study was to determine the role of MMR deficiency in mediating resistance in samples from patients with both newly diagnosed malignant gliomas and those who have failed temozolomide therapy. EXPERIMENTAL DESIGN: The roles of AGT and MMR deficiency in mediating resistance in glioblastoma multiforme were assessed by immunohistochemistry and microsatellite instability (MSI), respectively. The mutation status of the MSH6 gene, a proposed correlate of temozolomide resistance, was determined by direct sequencing and compared with data from immunofluorescent detection of MSH6 protein and reverse transcription-PCR amplification of MSH6 RNA. RESULTS: Seventy percent of newly diagnosed and 78% of failed-therapy glioblastoma multiforme samples expressed nuclear AGT protein in > or = 20% of cells analyzed, suggesting alternate means of resistance in 20% to 30% of cases. Single loci MSI was observed in 3% of patient samples; no sample showed the presence of high MSI. MSI was not shown to correlate with MSH6 mutation or loss of MSH6 protein expression. CONCLUSIONS: Although high AGT levels may mediate resistance in a portion of these samples, MMR deficiency does not seem to be responsible for mediating temozolomide resistance in adult malignant glioma. Accordingly, the presence of a fraction of samples exhibiting both low AGT expression and MMR proficiency suggests that additional mechanisms of temozolomide resistance are operational in the clinic.

Authors
Maxwell, JA; Johnson, SP; McLendon, RE; Lister, DW; Horne, KS; Rasheed, A; Quinn, JA; Ali-Osman, F; Friedman, AH; Modrich, PL; Bigner, DD; Friedman, HS
MLA Citation
Maxwell, JA, Johnson, SP, McLendon, RE, Lister, DW, Horne, KS, Rasheed, A, Quinn, JA, Ali-Osman, F, Friedman, AH, Modrich, PL, Bigner, DD, and Friedman, HS. "Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma." Clin Cancer Res 14.15 (August 1, 2008): 4859-4868.
PMID
18676759
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
15
Publish Date
2008
Start Page
4859
End Page
4868
DOI
10.1158/1078-0432.CCR-07-4807

Cryptococcal meningitis in patients with glioma: a report of two cases.

OBJECTIVE AND IMPORTANCE: We describe two patients with high-grade glioma undergoing treatment with corticosteroids and chemotherapy who presented with cryptococcal meningitis and sepsis. This report of two cases highlights the importance of examining the efficacy of prophylactic antibiotic and/or antifungal regimens in this patient population due to their increased risk of opportunistic infections. CLINICAL PRESENTATION: A 73-year-old man with a history of glioblastoma multiforme (GBM), on dexamethasone and status post radiation therapy and two cycles of temozolamide, presented with decreased level of consciousness for 24 h and was found to have cerebrospinal fluid (CSF) and blood cultures positive for Cryptococcus neoformans. A 33-year-old man with a history of anaplastic astrocytoma, on dexamethasone and status post radiation therapy, four cycles of temozolomide and two cycles of Lomustine (CCNU), presented with headache, dizziness and photophobia and was found to have CSF and blood cultures positive for Cryptococcus neoformans. INTERVENTION: Both patients were treated with an initial regimen of amphotericin B and flucytosine for a minimum of two weeks and switched to fluconazole for 6 months to 1 year of treatment. CONCLUSION: Patients with high-grade glioma treated with long-term corticosteroid therapy and chemotherapy are at increased risk of developing opportunistic infections. The two patients reported here developed cryptococcal meningitis and sepsis. Prophylactic regimens with either fluconazole or itraconazole currently exist that effectively decrease the incidence of both cryptococcal infections. Further investigations into the risk:benefit ratio of primary prophylactic therapy in this patient population may prove beneficial.

Authors
Choi, JD; Powers, CJ; Vredenburgh, JJ; Friedman, AH; Sampson, JH
MLA Citation
Choi, JD, Powers, CJ, Vredenburgh, JJ, Friedman, AH, and Sampson, JH. "Cryptococcal meningitis in patients with glioma: a report of two cases." J Neurooncol 89.1 (August 2008): 51-53.
PMID
18398572
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
89
Issue
1
Publish Date
2008
Start Page
51
End Page
53
DOI
10.1007/s11060-008-9581-x

Treatment of neuroinflammation by soluble tumor necrosis factor receptor Type II fused to a thermally responsive carrier.

OBJECT: Biochemical irritation of the dorsal root ganglion (DRG) after intervertebral disc herniation contributes to radiculopathy through tumor necrosis factor-alpha (TNFalpha)-mediated inflammation. Soluble TNF receptor Type II (sTNFRII) sequesters this cytokine, providing clinical benefit. Previous work involving conjugation of sTNFRII with thermally responsive elastin-like polypeptide (ELP) yielded a chimeric protein (ELP-sTNFRII) with in vitro anti-TNFalpha bioactivity. Furthermore, temperature-triggered ELP aggregation into a "depot" prolongs protein residence time following perineural injection. In this study the authors evaluated the inflammatory phenotype of DRG explants after TNFalpha stimulation, and assessed the abilities of sTNFRII or ELP-sTNFRII to attenuate these neuro-inflammatory changes. METHODS: Rat lumbar DRGs (35 animals) were treated in 6 groups, as follows: control; TNFalpha (25 ng/ml); TNFalpha with low-(0.2 microg/ml) or high-dose (1 microg/ml) sTNFRII; and TNFalpha with low-(52.5 microg/ml) or high-dose (262.5 microg/ml) ELP-sTNFRII. After 24 hours, supernatant was evaluated for inflammatory cytokines (interleukin [IL]-1, IL-6, and IL-10); prostaglandin E2; and metabolites (glutamate, lactate, and pyruvate). Single-factor analysis of variance with post hoc Dunn analysis (alpha = 0.05) was used to assess treatment differences. RESULTS: Incubation of explants with TNFalpha caused metabolic stress reflected by an increased lactate/pyruvate ratio (1.8 +/- 0.5-fold) and extracellular glutamate (79 +/- 8% increase). Inflammatory activation was observed with heightened IL-6 release (5.2 +/- 1.4-fold) and prostaglandin E2 production (14 +/- 3-fold). An autoregulatory response occurred with an 11.8 +/- 0.6-fold increase in sTNFRI shedding. Treatment with high doses of sTNFRII or ELP-sTNFRII reversed all changes. Values are expressed as the mean +/- standard deviation. CONCLUSIONS: These results demonstrate that TNFalpha stimulation of DRG explants yields a phenotype of neurotoxic metabolite release and inflammatory mediator expression. Coincubation with either sTNFRII or ELP-sTNFRII antagonizes TNFalpha activity to abrogate these changes, suggesting potential for therapeutic intervention to treat peripheral nerve inflammatory disease.

Authors
Shamji, MF; Jing, L; Chen, J; Hwang, P; Ghodsizadeh, O; Friedman, AH; Richardson, WJ; Setton, LA
MLA Citation
Shamji, MF, Jing, L, Chen, J, Hwang, P, Ghodsizadeh, O, Friedman, AH, Richardson, WJ, and Setton, LA. "Treatment of neuroinflammation by soluble tumor necrosis factor receptor Type II fused to a thermally responsive carrier." J Neurosurg Spine 9.2 (August 2008): 221-228.
PMID
18764758
Source
pubmed
Published In
Journal of neurosurgery. Spine
Volume
9
Issue
2
Publish Date
2008
Start Page
221
End Page
228
DOI
10.3171/SPI/2008/9/8/221

Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors.

The purpose of this study is to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and intracerebral distribution of a recombinant toxin (TP-38) targeting the epidermal growth factor receptor in patients with recurrent malignant brain tumors using the intracerebral infusion technique of convection-enhanced delivery (CED). Twenty patients were enrolled and stratified for dose escalation by the presence of residual tumor from 25 to 100 ng/ml in a 40-ml infusion volume. In the last eight patients, coinfusion of (123)I-albumin was performed to monitor distribution within the brain. The MTD was not reached in this study. Dose escalation was stopped at 100 ng/ml due to inconsistent drug delivery as evidenced by imaging the coinfused (123)I-albumin. Two DLTs were seen, and both were neurologic. Median survival after TP-38 was 28 weeks (95% confidence interval, 26.5-102.8). Of 15 patients treated with residual disease, two (13.3%) demonstrated radiographic responses, including one patient with glioblastoma multiforme who had a nearly complete response and remains alive >260 weeks after therapy. Coinfusion of (123)I-albumin demonstrated that high concentrations of the infusate could be delivered >4 cm from the catheter tip. However, only 3 of 16 (19%) catheters produced intraparenchymal infusate distribution, while the majority leaked infusate into the cerebrospinal fluid spaces. Intracerebral CED of TP-38 was well tolerated and produced some durable radiographic responses at doses

Authors
Sampson, JH; Akabani, G; Archer, GE; Berger, MS; Coleman, RE; Friedman, AH; Friedman, HS; Greer, K; Herndon, JE; Kunwar, S; McLendon, RE; Paolino, A; Petry, NA; Provenzale, JM; Reardon, DA; Wong, TZ; Zalutsky, MR; Pastan, I; Bigner, DD
MLA Citation
Sampson, JH, Akabani, G, Archer, GE, Berger, MS, Coleman, RE, Friedman, AH, Friedman, HS, Greer, K, Herndon, JE, Kunwar, S, McLendon, RE, Paolino, A, Petry, NA, Provenzale, JM, Reardon, DA, Wong, TZ, Zalutsky, MR, Pastan, I, and Bigner, DD. "Intracerebral infusion of an EGFR-targeted toxin in recurrent malignant brain tumors." Neuro Oncol 10.3 (June 2008): 320-329.
PMID
18403491
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
3
Publish Date
2008
Start Page
320
End Page
329
DOI
10.1215/15228517-2008-012

Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma.

We determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate, an inhibitor of the receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR), the proto-oncogene product c-kit, and the fusion protein Bcr-Abl, when administered for 8 days in combination with temozolomide (TMZ) to malignant glioma (MG) patients. MG patients who had not failed prior TMZ were eligible to receive TMZ at a dose of 150-200 mg/m(2) per day on days 4-8 plus imatinib mesylate administered orally on days 1-8 of each 4-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing antiepileptic drugs (EIAEDs). The imatinib dose was escalated in successive cohorts of patients independently for each stratum. Imatinib, at doses ranging from 400 mg to 1,200 mg, was administered with TMZ to 65 patients: 52 (80%) with glioblastoma multiforme (GBM) and 13 (20%) with grade III MG. At enrollment, 34 patients (52%) had stable disease, and 33 (48%) had progressive disease; 30 patients (46%) were on EIAEDs. The MTD of imatinib for patients concurrently receiving or not receiving EIAEDs was 1,000 mg. DLTs were hematologic, gastrointestinal, renal, and hepatic. Pharmacokinetic analyses revealed lowered exposures and enhanced clearance among patients on EIAEDs. Among GBM patients with stable disease at enrollment (n=28), the median progression-free and overall survival times were 41.7 and 56.1 weeks, respectively. Imatinib doses up to 1,000 mg/day for 8 consecutive days are well tolerated when combined with standard TMZ dosing for MG patients. A subsequent phase 2 study is required to further evaluate the efficacy of this regimen for this patient population.

Authors
Reardon, DA; Desjardins, A; Vredenburgh, JJ; Sathornsumetee, S; Rich, JN; Quinn, JA; Lagattuta, TF; Egorin, MJ; Gururangan, S; McLendon, R; Herndon, JE; Friedman, AH; Salvado, AJ; Friedman, HS
MLA Citation
Reardon, DA, Desjardins, A, Vredenburgh, JJ, Sathornsumetee, S, Rich, JN, Quinn, JA, Lagattuta, TF, Egorin, MJ, Gururangan, S, McLendon, R, Herndon, JE, Friedman, AH, Salvado, AJ, and Friedman, HS. "Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma." Neuro Oncol 10.3 (June 2008): 330-340.
PMID
18359865
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
3
Publish Date
2008
Start Page
330
End Page
340
DOI
10.1215/15228517-2008-003

Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma.

Angiogenesis, the growth of new blood vessels from previously existing vasculature, is a requirement for tumor growth and metastasis. The first US FDA-approved drugs targeting angiogenesis have shown potential in the treatment of malignant gliomas. Immunotherapy as a treatment modality lends itself well to specifically targeting angiogenesis in tumors and may represent a powerful tool in the treatment of malignant gliomas. This review focuses on developments in immunotherapy targeting angiogenesis and tumor-vascular-specific endothelial cells using a variety of immunotherapeutic strategies including monoclonal antibodies and conjugated immunotoxins, as well as cellular, peptide, DNA and dendritic cell vaccines.

Authors
Everson, RG; Graner, MW; Gromeier, M; Vredenburgh, JJ; Desjardins, A; Reardon, DA; Friedman, HS; Friedman, AH; Bigner, DD; Sampson, JH
MLA Citation
Everson, RG, Graner, MW, Gromeier, M, Vredenburgh, JJ, Desjardins, A, Reardon, DA, Friedman, HS, Friedman, AH, Bigner, DD, and Sampson, JH. "Immunotherapy against angiogenesis-associated targets: evidence and implications for the treatment of malignant glioma." Expert Rev Anticancer Ther 8.5 (May 2008): 717-732. (Review)
PMID
18471045
Source
pubmed
Published In
Expert Review of Anticancer Therapy
Volume
8
Issue
5
Publish Date
2008
Start Page
717
End Page
732
DOI
10.1586/14737140.8.5.717

Prenatal course of isolated muscular ventricular septal defects diagnosed only by color Doppler sonography: single-institution experience.

OBJECTIVE: Counseling patients with an isolated ventricular septal defect (i-VSD) is clinically important because with high-resolution ultrasound equipment, more small muscular VSDs are now being diagnosed. The prevalence of these lesions is not yet completely described, and the frequency with which muscular VSDs resolve in utero has also not been extensively reported. METHODS: We investigated the perinatal course of isolated muscular VSDs diagnosed only on color Doppler examinations and followed between January 1, 2005, and December 31, 2006. A complete evaluation of the fetal heart was performed by gray scale, spectral Doppler, and color Doppler examinations. RESULTS: We performed a total of 2583 fetal echocardiographic examinations on 2410 fetuses during 2318 pregnancies. The study group included 78 twin gestations (3.4%) and 7 triplet gestations (0.3%). There were 16 fetuses with an i-VSD (6.6/1000 fetuses) within the study group. The mean gestational age +/- SD at diagnosis was 23.5 +/- 4.3 weeks. Two of the i-VSDs (12.5%) spontaneously resolved prenatally. One fetus with an i-VSD had trisomy 21 and also had increased nuchal translucency in the first trimester. One i-VSD was diagnosed among 22 fetuses with trisomy 21 examined during the study period. CONCLUSIONS: An i-VSD is a common congenital heart defect. Prenatal resolution of i-VSDs is less frequent than reported in the literature. A larger cohort is needed to provide a better risk estimate for aneuploidy in the presence of an i-VSD.

Authors
Bahtiyar, MO; Dulay, AT; Weeks, BP; Friedman, AH; Copel, JA
MLA Citation
Bahtiyar, MO, Dulay, AT, Weeks, BP, Friedman, AH, and Copel, JA. "Prenatal course of isolated muscular ventricular septal defects diagnosed only by color Doppler sonography: single-institution experience." Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 27.5 (May 2008): 715-720. (Academic Article)
Source
manual
Published In
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
Volume
27
Issue
5
Publish Date
2008
Start Page
715
End Page
720

An injectable and in situ-gelling biopolymer for sustained drug release following perineural administration.

STUDY DESIGN: This study evaluated whether the aggregation behavior of a thermally responsive elastin-like polypeptide (ELP) prolongs protein residence time at the dorsal root ganglion (DRG). This work involves development of a sustained-release drug delivery vehicle to provide high and sustained levels of biologic therapeutics to the dorsal root ganglion while minimizing systemic exposure. OBJECTIVE: To study the potential of the ELP biopolymer to sustain release and lower systemic exposure of bioactive peptides following perineural administration. SUMMARY OF BACKGROUND DATA: Anticytokine treatment for lumbar radiculopathy may offer clinical improvement, but exposes patients to systemic toxicities of immunosuppression. ELPs are environmentally responsive polypeptides that undergo a phase transition on heating to form an insoluble aggregate. Drug conjugates with ELP exhibit both temperature-sensitivity and in vitro bioactivity. Monomer resolubilization yields solution-phase molecules, and this reversible aggregation behavior may create a perineural drug depot to sustain drug delivery to an inflamed nerve. METHODS: This experiment involved 48 rats in which radiolabeled ELPs (aggregating or soluble) were injected overlying the L5 dorsal root ganglion. Animals were killed at 6 different time points, and radioactivity associated with the injected segment, serum, and other tissues was evaluated. RESULTS: The aggregating ELP demonstrated a 7-fold longer perineural half-life compared with the soluble ELP. This supports the hypothesis that the aggregating ELP forms a depot from which slow resolubilization and clearance provides sustained, local protein release. Furthermore, serum radioactivity reached a lower peak for the aggregating group, demonstrating slower absorption of the aggregating protein into the systemic circulation. CONCLUSION: These results suggest that ELP aggregation confer the benefit of perineural compartment longevity for bioactive therapeutics delivered fused with this carrier. This may sustain release of potent immunomodulator therapeutics to treat local neuroinflammation. Desirable features include delivery of high local doses and protection against systemic exposure and associated toxicity.

Authors
Shamji, MF; Whitlatch, L; Friedman, AH; Richardson, WJ; Chilkoti, A; Setton, LA
MLA Citation
Shamji, MF, Whitlatch, L, Friedman, AH, Richardson, WJ, Chilkoti, A, and Setton, LA. "An injectable and in situ-gelling biopolymer for sustained drug release following perineural administration." Spine (Phila Pa 1976) 33.7 (April 1, 2008): 748-754.
PMID
18379401
Source
pubmed
Published In
Spine
Volume
33
Issue
7
Publish Date
2008
Start Page
748
End Page
754
DOI
10.1097/BRS.0b013e3181695773

Molecular strategies for the treatment of malignant glioma--genes, viruses, and vaccines.

The standard treatment paradigm of surgery, radiation, and chemotherapy for malignant gliomas has only a modest effect on survival. It is well emphasized in the literature that despite aggressive multimodal therapy, most patients survive approximately 1 year after diagnosis, and less than 10% survive beyond 2 years. This dismal prognosis provides the impetus for ongoing investigations in search of improved therapeutics. Standard multimodal therapy has largely reached a plateau in terms of effectiveness, and there is now a growing body of literature on novel molecular approaches for the treatment of malignant gliomas. Gene therapy, oncolytic virotherapy, and immunotherapy are the major investigational approaches that have demonstrated promise in preclinical and early clinical studies. These new molecular technologies each have distinct advantages and limitations, and none has yet demonstrated a significant survival benefit in a phase II or III clinical trial. Molecular approaches may not lead to the discovery of a "magic bullet" for these aggressive tumors, but they may ultimately prove synergistic with more conventional approaches and lead to a broadening of the multimodal approach that is the current standard of care. This review will discuss the scientific background, therapeutic potential, and clinical limitations of these novel strategies with a focus on those that have made it to clinical trials.

Authors
Selznick, LA; Shamji, MF; Fecci, P; Gromeier, M; Friedman, AH; Sampson, J
MLA Citation
Selznick, LA, Shamji, MF, Fecci, P, Gromeier, M, Friedman, AH, and Sampson, J. "Molecular strategies for the treatment of malignant glioma--genes, viruses, and vaccines." Neurosurg Rev 31.2 (April 2008): 141-155. (Review)
PMID
18259789
Source
pubmed
Published In
Neurosurgical Review
Volume
31
Issue
2
Publish Date
2008
Start Page
141
End Page
155
DOI
10.1007/s10143-008-0121-0

A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost.

The purpose of this study was to determine the feasibility and assess the efficacy and toxicity, among newly diagnosed malignant glioma patients, of administering (131)I-labeled murine antitenascin monoclonal antibody 81C6 ((131)I-81C6) into a surgically created resection cavity (SCRC) to achieve a patient-specific, 44-Gy boost to the 2-cm SCRC margin. A radioactivity dose of (131)I-81C6 calculated to achieve a 44-Gy boost to the SCRC was administered, followed by conventional external beam radiotherapy (XRT) and chemotherapy. Twenty-one patients were enrolled in the study: 16 with glioblastoma multiforme (GBM) and 5 with anaplastic astrocytoma. Twenty patients received the targeted 44-Gy boost (+/-10%) to the SCRC. Attributable toxicity was mild and limited to reversible grade 3 neutropenia or thrombocytopenia (n = 3; 14%), CNS wound infections (n = 3; 14%), and headache (n = 2; 10%). With a median follow-up of 151 weeks, median overall survival times for all patients and those with GBM are 96.6 and 90.6 weeks, respectively; 87% of GBM patients are alive at 1 year. It is feasible to consistently achieve a 44-Gy boost dose to the SCRC margin with patient-specific dosing of (131)I-81C6. Our study regimen ((131)I-81C6 + XRT + temozolomide) was well tolerated and had encouraging survival. To determine if selection of good-prognosis patients affects outcome associated with this approach, the U.S. Food and Drug Administration has approved a trial randomizing newly diagnosed GBM patients to either our study regimen or standard XRT plus temozolomide.

Authors
Reardon, DA; Zalutsky, MR; Akabani, G; Coleman, RE; Friedman, AH; Herndon, JE; McLendon, RE; Pegram, CN; Quinn, JA; Rich, JN; Vredenburgh, JJ; Desjardins, A; Guruangan, S; Boulton, S; Raynor, RH; Dowell, JM; Wong, TZ; Zhao, X-G; Friedman, HS; Bigner, DD
MLA Citation
Reardon, DA, Zalutsky, MR, Akabani, G, Coleman, RE, Friedman, AH, Herndon, JE, McLendon, RE, Pegram, CN, Quinn, JA, Rich, JN, Vredenburgh, JJ, Desjardins, A, Guruangan, S, Boulton, S, Raynor, RH, Dowell, JM, Wong, TZ, Zhao, X-G, Friedman, HS, and Bigner, DD. "A pilot study: 131I-antitenascin monoclonal antibody 81c6 to deliver a 44-Gy resection cavity boost." Neuro Oncol 10.2 (April 2008): 182-189.
PMID
18287339
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
2
Publish Date
2008
Start Page
182
End Page
189
DOI
10.1215/15228517-2007-053

Identification of distinct and overlapping cortical areas for bilingual naming and reading using cortical stimulation. Case report.

A bilingual pediatric patient who underwent tumor resection was mapped extraoperatively using cortical stimulation to preserve English and Hebrew languages. The authors mapped both languages by using 4 tasks: 1) English visual naming, 2) Hebrew visual naming, 3) read English/respond Hebrew, and 4) Hebrew reading. Essential cortical sites for primary and secondary languages were compared, photographically recorded, and plotted onto a schematic brain of the patient. Three types of sites were found in this patient: 1) multiuse sites (multiple tasks, both languages) in frontal, temporal, and parietal areas; 2) single-task sites (1 task, both languages) in postcentral and parietal areas; and 3) single-use sites (1 task, 1 language) in frontal, temporal, and parietal areas. These results lend support to the concept that bilingual patients can have distinct cortical representations of each language and of different language tasks, in addition to overlapping or shared sites that support both languages and multiple tasks.

Authors
Serafini, S; Gururangan, S; Friedman, A; Haglund, M
MLA Citation
Serafini, S, Gururangan, S, Friedman, A, and Haglund, M. "Identification of distinct and overlapping cortical areas for bilingual naming and reading using cortical stimulation. Case report." J Neurosurg Pediatr 1.3 (March 2008): 247-254.
PMID
18352772
Source
pubmed
Published In
Journal of neurosurgery. Pediatrics
Volume
1
Issue
3
Publish Date
2008
Start Page
247
End Page
254
DOI
10.3171/PED/2008/1/3/247

Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma.

Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression. In this study, we report on the investigation of detecting HCMV in the tumors and peripheral blood of patients with newly diagnosed glioblastoma multiforme (GBM). Using immunohistochemistry, in situ hybridization, and polymerase chain reaction amplification of viral DNA, the detection of HCMV was investigated in tumor and blood specimens from patients with GBM as well as in the peripheral blood of normal volunteers and patients undergoing craniotomy for diagnoses other than GBM. We found that a high percentage (>90%) of GBM tumors, not surrounding normal brain, are associated with HCMV nucleic acids and proteins. Furthermore, a significant proportion of patients (80%) with newly diagnosed GBM have detectable HCMV DNA in their peripheral blood, while sero-positive normal donors and other surgical patients did not exhibit detectable virus, suggesting either a systemic reactivation of HCMV within patients with GBM or shedding of viral DNA from infected tumor cells into the periphery. These results confirm the association of HCMV with malignant gliomas and demonstrate that subclinical HCMV viremia (presence of viral DNA in blood without clinical symptoms of infection) is a previously unrecognized disease spectrum in patients with GBM.

Authors
Mitchell, DA; Xie, W; Schmittling, R; Learn, C; Friedman, A; McLendon, RE; Sampson, JH
MLA Citation
Mitchell, DA, Xie, W, Schmittling, R, Learn, C, Friedman, A, McLendon, RE, and Sampson, JH. "Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma." Neuro Oncol 10.1 (February 2008): 10-18.
PMID
17951512
Source
pubmed
Published In
Neuro-Oncology
Volume
10
Issue
1
Publish Date
2008
Start Page
10
End Page
18
DOI
10.1215/15228517-2007-035

Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6.

UNLABELLED: alpha-Particle-emitting radionuclides, such as (211)At, with a 7.2-h half-life, may be optimally suited for the molecularly targeted radiotherapy of strategically sensitive tumor sites, such as those in the central nervous system. Because of the much shorter range and more potent cytotoxicity of alpha-particles than of beta-particles, (211)At-labeled agents may be ideal for the eradication of tumor cells remaining after surgical debulking of malignant brain tumors. The main goal of this study was to investigate the feasibility and safety of this approach in patients with recurrent malignant brain tumors. METHODS: Chimeric antitenascin monoclonal antibody 81C6 (ch81C6) (10 mg) was labeled with 71-347 MBq of (211)At by use of N-succinimidyl 3-[(211)At]astatobenzoate. Eighteen patients were treated with (211)At-labeled ch81C6 ((211)At-ch81C6) administered into a surgically created resection cavity (SCRC) and then with salvage chemotherapy. Serial gamma-camera imaging and blood sampling over 24 h were performed. RESULTS: A total of 96.7% +/- 3.6% (mean +/- SD) of (211)At decays occurred in the SCRC, and the mean blood-pool percentage injected dose was < or = 0.3. No patient experienced dose-limiting toxicity, and the maximum tolerated dose was not identified. Six patients experienced grade 2 neurotoxicity within 6 wk of (211)At-ch81C6 administration; this neurotoxicity resolved fully in all but 1 patient. No toxicities of grade 3 or higher were attributable to the treatment. No patient required repeat surgery for radionecrosis. The median survival times for all patients, those with glioblastoma multiforme, and those with anaplastic astrocytoma or oligodendroglioma were 54, 52, and 116 wk, respectively. CONCLUSION: This study provides proof of concept for regional targeted radiotherapy with (211)At-labeled molecules in oncology. Specifically, the regional administration of (211)At-ch81C6 is feasible, safe, and associated with a promising antitumor benefit in patients with malignant central nervous system tumors.

Authors
Zalutsky, MR; Reardon, DA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; McLendon, RE; Wong, TZ; Bigner, DD
MLA Citation
Zalutsky, MR, Reardon, DA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, McLendon, RE, Wong, TZ, and Bigner, DD. "Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6." J Nucl Med 49.1 (January 2008): 30-38.
PMID
18077533
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
49
Issue
1
Publish Date
2008
Start Page
30
End Page
38
DOI
10.2967/jnumed.107.046938

Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multi-dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer. ©2008 Macmillan Publishers Limited. All rights reserved.

Authors
McLendon, R; Friedman, A; Bigner, D; Meir, EGV; Brat, DJ; Mastrogianakis, GM; Olson, JJ; Mikkelsen, T; Lehman, N; Aldape, K; Yung, WKA; Bogler, O; Weinstein, JN; VandenBerg, S; Berger, M; Prados, M; Muzny, D; Morgan, M; Scherer, S; Sabo, A; Nazareth, L; Lewis, L; Hall, O; Zhu, Y; Ren, Y; Alvi, O; Yao, J; Hawes, A; Jhangiani, S; Fowler, G; Lucas, AS; Kovar, C; Cree, A; Dinh, H; Santibanez, J; Joshi, V; Gonzalez-Garay, ML; Miller, CA; Milosavljevic, A; Donehower, L; Wheeler, DA; Gibbs, RA et al.
MLA Citation
McLendon, R, Friedman, A, Bigner, D, Meir, EGV, Brat, DJ, Mastrogianakis, GM, Olson, JJ, Mikkelsen, T, Lehman, N, Aldape, K, Yung, WKA, Bogler, O, Weinstein, JN, VandenBerg, S, Berger, M, Prados, M, Muzny, D, Morgan, M, Scherer, S, Sabo, A, Nazareth, L, Lewis, L, Hall, O, Zhu, Y, Ren, Y, Alvi, O, Yao, J, Hawes, A, Jhangiani, S, Fowler, G, Lucas, AS, Kovar, C, Cree, A, Dinh, H, Santibanez, J, Joshi, V, Gonzalez-Garay, ML, Miller, CA, Milosavljevic, A, Donehower, L, Wheeler, DA, and Gibbs, RA et al. "Comprehensive genomic characterization defines human glioblastoma genes and core pathways." Nature 455.7216 (2008): 1061-1068.
PMID
18772890
Source
scival
Published In
Nature
Volume
455
Issue
7216
Publish Date
2008
Start Page
1061
End Page
1068
DOI
10.1038/nature07385

Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: Technical case report

OBJECTIVE: Neurophysiological intraoperative monitoring of the glossopharyngeal nerve has been performed only with needle electrodes inserted into the pharyngeal muscles or soft palate. We describe a noninvasive method of monitoring this cranial nerve. METHODS: A 30-year-old man who presented with headache, as well as speech and swallowing difficulty, underwent surgical resection of a right vagus nerve schwannoma. Neurophysiological intraoperative monitoring of multiple lower cranial nerves, including the glossopharyngeal and vagus nerves, was performed. RESULTS: The glossopharyngeal nerve was monitored with an adhesive surface electrode mounted on the cuff of a laryngeal mask airway, and the vagus nerve was monitored with a similar electrode mounted on the endotracheal tube. Successful monitoring allowed separation of the glossopharyngeal nerve from the tumor, and there was no postoperative swallowing deficit. CONCLUSION: Monitoring of the glossopharyngeal nerve with surface electrodes is possible and reliable, but it must be combined with vagus nerve monitoring.

Authors
Husain, AM; Wright, DR; Stolp, BW; Friedman, AH; Keifer, JC
MLA Citation
Husain, AM, Wright, DR, Stolp, BW, Friedman, AH, and Keifer, JC. "Neurophysiological intraoperative monitoring of the glossopharyngeal nerve: Technical case report." Neurosurgery 63.4 SUPPL. (2008): ONS277-ONS278.
Source
scival
Published In
Neurosurgery
Volume
63
Issue
4 SUPPL.
Publish Date
2008
Start Page
ONS277
End Page
ONS278
DOI
10.1227/01.NEU.0000316425.21752.E2

Polyethylene glycol hydrogel dural sealant may reduce incisional cerebrospinal fluid leak after posterior fossa surgery: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Polyethylene glycol hydrogel dural sealant may reduce incisional cerebrospinal fluid leak after posterior fossa surgery: Commentary." Neurosurgery 63.1 SUPPL. (2008): ONS186-.
Source
scival
Published In
Neurosurgery
Volume
63
Issue
1 SUPPL.
Publish Date
2008
Start Page
ONS186
DOI
10.1227/01.NEU.0000313116.28200.67

Safety and accuracy of bedside external ventricular drain placement: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Safety and accuracy of bedside external ventricular drain placement: Commentary." Neurosurgery 63.1 SUPPL. (2008): ONS167-.
Source
scival
Published In
Neurosurgery
Volume
63
Issue
1 SUPPL.
Publish Date
2008
Start Page
ONS167
DOI
10.1227/01.NEU.0000312390.83127.7F

Morphometric three-dimensional computed tomography anatomy of the hypoglossal canal

Optimal surgical exposure during the transcondylar approach may result in injury to the hypoglossal nerve. This study evaluated the utility of three-dimensional computed tomography (3-D CT) as a means of obtaining detailed anatomic information in an individual patient prior to surgery involving the hypoglossal canal. We studied 20 hypoglossal canals in ten patients using 3-D CT reconstructed from 1-mm CT slices. Detailed anatomic measurements were performed to define the relationship of the hypoglossal canal to the occipital condyles and clivus. The relationship of the hypoglossal canal to the occipital condyles and clivus were extremely variable. From the outer table of the clivus in the midline, the extracranial opening of the hypoglossal canal was 20.3+2.7 mm (range 15.7-24.7 mm). The intracranial opening was 7.4+2.3 mm (range 6.2-11.5 mm) from the inner table of the clivus. From the superior aspect of the condyle, the inner opening was 11.0+1.4 mm (range 8.7-12.7 mm) and the outer opening was 19.1+2.4 mm (range 14.3-22.8 mm). From the lowest point of the condyle, the outer opening was 12.4+2.1 mm (range 9.1-15.6 mm). The posterior condylar emissary vein was 12.2+3.0 mm from the intracranial opening of the hypoglossal canal. Three-dimensional CT is a useful tool for assessing critical anatomic relationships and tailoring surgical approaches for individual patients. The amount of bone that can be safely removed without violating the hypoglossal canal can be determined preoperatively for each patient. © 2008 Springer-Verlag.

Authors
Bulsara, KR; Asaoka, K; Aliabadi, H; Kanaly, C; Friedman, A; Fukushima, T
MLA Citation
Bulsara, KR, Asaoka, K, Aliabadi, H, Kanaly, C, Friedman, A, and Fukushima, T. "Morphometric three-dimensional computed tomography anatomy of the hypoglossal canal." Neurosurgical Review 31.3 (2008): 299-302.
PMID
18481127
Source
scival
Published In
Neurosurgical Review
Volume
31
Issue
3
Publish Date
2008
Start Page
299
End Page
302
DOI
10.1007/s10143-008-0143-7

The history of neurosurgery at emory University in Atlanta, Georgia: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "The history of neurosurgery at emory University in Atlanta, Georgia: Commentary." Neurosurgery 62.6 (2008): 1369--.
Source
scival
Published In
Neurosurgery
Volume
62
Issue
6
Publish Date
2008
Start Page
1369-
DOI
10.1227/01.NEU.0000316849.10866.F6

Central nervous system cancers: Clinical Practice Guidelines in Oncology™

Authors
Brem, SS; Bierman, PJ; Black, P; Brem, H; Chamberlain, MC; Chiocca, EA; DeAngelis, LM; Fenstermaker, RA; Friedman, A; Gilbert, MR; Glass, J; Grossman, SA; Heimberger, AB; Junck, L; Linette, GP; Loeffler, JJ; Maor, MH; Moots, P; Mrugala, M; Nabors, LB; Newton, HB; Olivi, A; Portnow, J; Prados, M; Raizer, JJ; Shrieve, DC; Jr, AKS
MLA Citation
Brem, SS, Bierman, PJ, Black, P, Brem, H, Chamberlain, MC, Chiocca, EA, DeAngelis, LM, Fenstermaker, RA, Friedman, A, Gilbert, MR, Glass, J, Grossman, SA, Heimberger, AB, Junck, L, Linette, GP, Loeffler, JJ, Maor, MH, Moots, P, Mrugala, M, Nabors, LB, Newton, HB, Olivi, A, Portnow, J, Prados, M, Raizer, JJ, Shrieve, DC, and Jr, AKS. "Central nervous system cancers: Clinical Practice Guidelines in Oncology™." JNCCN Journal of the National Comprehensive Cancer Network 6.5 (2008): 456-504.
PMID
18492461
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
6
Issue
5
Publish Date
2008
Start Page
456
End Page
504

Comments

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Comments." Neurosurgery 62.5 (2008): E1163-.
Source
scival
Published In
Neurosurgery
Volume
62
Issue
5
Publish Date
2008
Start Page
E1163
DOI
10.1227/01.NEU.0000315283.97499.A3

Extent of resection and survival in glioblastoma multiforme: Identification of and adjustment for bias - Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Extent of resection and survival in glioblastoma multiforme: Identification of and adjustment for bias - Commentary." Neurosurgery 62.3 (2008): 574-575.
Source
scival
Published In
Neurosurgery
Volume
62
Issue
3
Publish Date
2008
Start Page
574
End Page
575
DOI
10.1227/01.neu.0000317304.31579.17

Infectious complications of temporary spinal catheter insertion for diagnosis of adult hydrocephalus and idiopathic intracranial hypertension: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Infectious complications of temporary spinal catheter insertion for diagnosis of adult hydrocephalus and idiopathic intracranial hypertension: Commentary." Neurosurgery 62.2 (2008): 436--.
Source
scival
Published In
Neurosurgery
Volume
62
Issue
2
Publish Date
2008
Start Page
436-
DOI
10.1227/01.neu.0000316010.19012.35

Challenges and opportunities for recruiting a new generation of neurosurgeons.

Several factors have converged to raise concern among program directors about attracting and training the next generation of neurosurgeons. These include the relatively new duty-hour regulations, the projected physician shortage, and the preference of many current medical students for controllable lifestyles. Attracting top talent into training programs may require innovations geared to Generation X such as policies supporting work-life balance, flexible work options, lots of feedback, mentoring programs, talented leadership, and standardized communication strategies during patient handoffs. Larger programmatic changes may also be needed such as "competency-based" training and additional years of training for mastery of highly specialized procedures.

Authors
Brown, AJ; Friedman, AH
MLA Citation
Brown, AJ, and Friedman, AH. "Challenges and opportunities for recruiting a new generation of neurosurgeons." Neurosurgery 61.6 (December 2007): 1314-1319.
PMID
18162912
Source
pubmed
Published In
Neurosurgery
Volume
61
Issue
6
Publish Date
2007
Start Page
1314
End Page
1319
DOI
10.1227/01.neu.0000306111.62797.08

Prevalence of congenital heart defects in monochorionic/diamniotic twin gestations: a systematic literature review.

OBJECTIVE: Congenital heart defects (CHDs) affect approximately 0.5% of all neonates. Recent literature points to a possible increase in the CHD prevalence among monochorionic/diamniotic (MC/DA) twin gestations. We hypothesized that MC/DA twin pregnancy is a risk factor for CHD. METHODS: A systematic review of all published English literature was conducted on MEDLINE (Ovid and PubMed) from January 2000 through April 2007 using the medical subject heading terms "congenital heart defect" and "monozygotic twins." Four observational studies were included in the final analysis. Published historical data were used for the population background risk of CHD. Relative risk (RR) estimates with 95% confidence intervals (CIs) were calculated by fixed and random effect models. RESULTS: We included a total of 40 fetuses with CHDs among 830 fetuses from MC/DA twin gestations. Compared with the population, CHDs were significantly more prevalent in MC/DA twins regardless of the presence of twin-twin transfusion syndrome (TTTS) (RR, 9.18; 95% CI, 5.51-15.29; P < .001). Monochorionic/diamniotic twin gestations affected by TTTS were more likely to be complicated by CHDs than those that did not have TTTS (RR, 2.78; 95% CI, 1.03-7.52; P = .04). Ventricular septal defects were the most frequent heart defects. Pulmonary stenosis and atrial septal defects were significantly more prevalent in pregnancies complicated with TTTS. CONCLUSIONS: Monochorionic/diamniotic twin gestation appears to be a risk factor for CHDs. Conditions that lead to abnormal placentation may also contribute to abnormal heart development, especially in MC/DA twin pregnancies complicated with TTTS. Fetal echocardiography may be considered for all MC/DA twin gestations because ventricular septal defects and pulmonary stenosis are the most common defects.

Authors
Bahtiyar, MO; Dulay, AT; Weeks, BP; Friedman, AH; Copel, JA
MLA Citation
Bahtiyar, MO, Dulay, AT, Weeks, BP, Friedman, AH, and Copel, JA. "Prevalence of congenital heart defects in monochorionic/diamniotic twin gestations: a systematic literature review." J Ultrasound Med 26.11 (November 2007): 1491-1498. (Review)
PMID
17957043
Source
pubmed
Published In
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
Volume
26
Issue
11
Publish Date
2007
Start Page
1491
End Page
1498

Bevacizumab plus irinotecan in recurrent glioblastoma multiforme.

PURPOSE: The prognosis for patients with recurrent glioblastoma multiforme is poor, with a median survival of 3 to 6 months. We performed a phase II trial of bevacizumab, a monoclonal antibody to vascular endothelial growth factor, in combination with irinotecan. PATIENTS AND METHODS: This phase II trial included two cohorts of patients. The initial cohort, comprising 23 patients, received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks. The dose of irinotecan was based on the patient's anticonvulsant: Patients taking enzyme-inducing antiepileptic drugs (EIAEDs) received 340 mg/m2, and patients not taking EIAEDs received 125 mg/m2. After this regimen was deemed safe and effective, the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks, in anticipation of a phase III randomized trial of irinotecan versus irinotecan and bevacizumab. The second cohort, comprising 12 patients, received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1, 8, 22, and 29. Each cycle was 6 weeks long and concluded with patient evaluations, including magnetic resonance imaging. RESULTS: The 6-month progression-free survival among all 35 patients was 46% (95% CI, 32% to 66%). The 6-month overall survival was 77% (95% CI, 64% to 92%). Twenty of the 35 patients (57%; 95% CI, 39% to 74%) had at least a partial response. One patient developed a CNS hemorrhage, which occurred in his 10th cycle. Four patients developed thromboembolic complications (deep venous thrombosis and/or pulmonary emboli). CONCLUSION: Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity.

Authors
Vredenburgh, JJ; Desjardins, A; Herndon, JE; Marcello, J; Reardon, DA; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Sampson, J; Wagner, M; Bailey, L; Bigner, DD; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Herndon, JE, Marcello, J, Reardon, DA, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Sampson, J, Wagner, M, Bailey, L, Bigner, DD, Friedman, AH, and Friedman, HS. "Bevacizumab plus irinotecan in recurrent glioblastoma multiforme." J Clin Oncol 25.30 (October 20, 2007): 4722-4729.
PMID
17947719
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
25
Issue
30
Publish Date
2007
Start Page
4722
End Page
4729
DOI
10.1200/JCO.2007.12.2440

Identification, imaging, functional assessment and management of congenital coronary arterial abnormalities in children.

The coronary arteries, the vessels through which both substrate and oxygen are provided to the cardiac muscle, normally arise from paired stems, right and left, each arising from a separate and distinct sinus of the aortic valve. The right coronary artery runs through the right atrioventricular groove, terminating in the majority of instances in the inferior interventricular groove. The main stem of the left coronary artery bifurcates into the anterior descending, or interventricular, and the circumflex branches. Origin of the anterior descending and circumflex arteries from separate orifices from the left sinus of Valsalva occurs in about 1% of the population, while it is also frequent to find the infundibular artery arising as a separate branch from the right sinus of Valsalva. Anomalies of the coronary arteries can result from rudimentary persistence of an embryologic coronary arterial structure, failure of normal development or normal atrophy as part of development, or misplacement of connection of a an otherwise normal coronary artery. Anomalies, therefore, can be summarized in terms of abnormal origin or course, abnormal number of coronary arteries, lack of patency of the orifice of coronary artery, or abnormal connections of the arteries. Anomalous origin of the left coronary artery from the pulmonary trunk occurs with an incidence of approximately 1 in 300,000 children. The degree of left ventricular dysfunction produced likely relates to the development of collateral vessels that arise from the right coronary artery, and provide flow into the left system. Anomalous origin of either the right or the left coronary artery from the opposite sinus of Valsalva can be relatively innocuous, but if the anomalous artery takes an interarterial course between the pulmonary trunk and the aorta, this can underlie sudden death, almost invariably during or immediately following strenuous exercise or competitive sporting events. Distal anomalies of the coronary arteries most commonly involve abnormal connections, or fistulas, between the right or left coronary arterial systems and a chamber or vessel. We discuss the current techniques available for imaging these various lesions, along with their functional assessment, concluding with a summary of current strategies for management.

Authors
Friedman, AH; Fogel, MA; Stephens, P; Hellinger, JC; Nykanen, DG; Tweddell, J; Feltes, TF; Rome, JJ
MLA Citation
Friedman, AH, Fogel, MA, Stephens, P, Hellinger, JC, Nykanen, DG, Tweddell, J, Feltes, TF, and Rome, JJ. "Identification, imaging, functional assessment and management of congenital coronary arterial abnormalities in children." Cardiol Young 17 Suppl 2 (September 2007): 56-67. (Review)
PMID
18039399
Source
pubmed
Published In
Cardiology in the Young
Volume
17 Suppl 2
Publish Date
2007
Start Page
56
End Page
67
DOI
10.1017/S1047951107001163

Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions.

Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (123I-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique.

Authors
Sampson, JH; Raghavan, R; Brady, ML; Provenzale, JM; Herndon, JE; Croteau, D; Friedman, AH; Reardon, DA; Coleman, RE; Wong, T; Bigner, DD; Pastan, I; Rodríguez-Ponce, MI; Tanner, P; Puri, R; Pedain, C
MLA Citation
Sampson, JH, Raghavan, R, Brady, ML, Provenzale, JM, Herndon, JE, Croteau, D, Friedman, AH, Reardon, DA, Coleman, RE, Wong, T, Bigner, DD, Pastan, I, Rodríguez-Ponce, MI, Tanner, P, Puri, R, and Pedain, C. "Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions." Neuro Oncol 9.3 (July 2007): 343-353.
PMID
17435179
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
3
Publish Date
2007
Start Page
343
End Page
353
DOI
10.1215/15228517-2007-007

A brief history of surgery for peripheral nerve sheath tumors.

The authors present a brief and selective history of surgery for peripheral nerve tumors to illustrate how the current understanding of the nature of disease influences the choice of surgical intervention. There was very little understanding of the anatomy and function of peripheral nerves in ancient times; consequently, surgical treatments for peripheral nerve tumors were based on the writings of authorities. The confusion between traumatic neuromas and genuine nerve sheath tumors coupled with the belief that manipulation of a peripheral nerve might be lethal to the patient stifled the development of surgical techniques for the management of nerve tumors in the 18th and 19th centuries. It was not until the 20th century, with an increased understanding of the microscopic anatomy of nerve sheath tumors, that efficacious surgical treatments for these diseases were developed. Continued advances in the understanding of the biology of these tumors will continue to impact their surgical management.

Authors
Powers, CJ; Friedman, AH
MLA Citation
Powers, CJ, and Friedman, AH. "A brief history of surgery for peripheral nerve sheath tumors. (Published online)" Neurosurg Focus 22.6 (June 15, 2007): E1-.
PMID
17613200
Source
pubmed
Published In
Neurosurgical focus
Volume
22
Issue
6
Publish Date
2007
Start Page
E1

Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects.

INTRODUCTION: The neurohistological findings in patients treated with targeted beta emitters such as (131)I are poorly described. We report a histopathologic analysis from patients treated with combined external beam therapy and a brachytherapy consisting of a (131)I-labeled monoclonal antibody (mAb) injected into surgically created resection cavities during brain tumor resections. METHODS: Directed tissue samples of the cavity walls were obtained because of suspected tumor recurrence from 28 patients. Samples and clinical follow-up were evaluated on all patients (Group A) based on total radiation dose received and a subset of these (n=18; Group B, proximal therapy subset) who had received external beam therapy within

Authors
McLendon, RE; Akabani, G; Friedman, HS; Reardon, DA; Cleveland, L; Cokgor, I; Herndon, JE; Wikstrand, C; Boulton, ST; Friedman, AH; Bigner, DD; Zalutsky, MR
MLA Citation
McLendon, RE, Akabani, G, Friedman, HS, Reardon, DA, Cleveland, L, Cokgor, I, Herndon, JE, Wikstrand, C, Boulton, ST, Friedman, AH, Bigner, DD, and Zalutsky, MR. "Tumor resection cavity administered iodine-131-labeled antitenascin 81C6 radioimmunotherapy in patients with malignant glioma: neuropathology aspects." Nucl Med Biol 34.4 (May 2007): 405-413.
PMID
17499730
Source
pubmed
Published In
Nuclear Medicine and Biology
Volume
34
Issue
4
Publish Date
2007
Start Page
405
End Page
413
DOI
10.1016/j.nucmedbio.2007.01.009

Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas.

PURPOSE: Recent reports demonstrate the activity of imatinib mesylate, an ATP-mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme. We performed the current phase 2 study to evaluate this regimen among patients with recurrent WHO grade III malignant glioma (MG). PATIENTS AND METHOD: Patients with grade III MG at any recurrence, received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme inducing anti-epileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Clinical assessments were performed monthly and radiographic assessments were obtained at least every 2 months. The primary endpoint was 6-month progression-free survival (PFS) rate. RESULTS: Thirty-nine patients were enrolled. All patients had progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. The median number of episodes of prior progression was 2 (range, 1-7) and the median number of prior treatment regimens was 3 (range, 1-8). With a median follow-up of 82.9 weeks, 24% of patients were progression-free at 6 months. The radiographic response rate was 10%, while 33% achieved stable disease. Among patients who achieved at least stable disease at first evaluation, the 6-month and 12-month PFS rates were 53% and 29%, respectively. The most common grade 3 or greater toxicities were hematologic and complicated less than 4% of administered courses. CONCLUSION: Imatinib mesylate plus hydroxyurea, is well tolerated and associated with anti-tumor activity in some patients with recurrent grade 3 MG.

Authors
Desjardins, A; Quinn, JA; Vredenburgh, JJ; Sathornsumetee, S; Friedman, AH; Herndon, JE; McLendon, RE; Provenzale, JM; Rich, JN; Sampson, JH; Gururangan, S; Dowell, JM; Salvado, A; Friedman, HS; Reardon, DA
MLA Citation
Desjardins, A, Quinn, JA, Vredenburgh, JJ, Sathornsumetee, S, Friedman, AH, Herndon, JE, McLendon, RE, Provenzale, JM, Rich, JN, Sampson, JH, Gururangan, S, Dowell, JM, Salvado, A, Friedman, HS, and Reardon, DA. "Phase II study of imatinib mesylate and hydroxyurea for recurrent grade III malignant gliomas." J Neurooncol 83.1 (May 2007): 53-60.
PMID
17245623
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
83
Issue
1
Publish Date
2007
Start Page
53
End Page
60
DOI
10.1007/s11060-006-9302-2

Temozolomide in children with progressive low-grade glioma.

We conducted a phase II study to assess the efficacy of oral temozolomide (TMZ) in children with progressive low-grade glioma. Thirty eligible patients were enrolled on this study. Median age at enrollment was 10 years (range, 4-18 years). Eligible patients received TMZ (200 mg/m(2) per day) by mouth for five days every four weeks. Patients received a median of nine cycles (range, 2-12 cycles) of treatment. Best responses in the 26 patients (86%) with optic pathway glioma (OPG)/pilocytic astrocytoma (PA) included partial response in 3 patients (11%), minor response in 1 (4%), stable disease in 10 (38%), and progressive disease in 12 (46%). Only one of four patients with fibrillary astrocytoma had stable disease for 29 months after TMZ. The overall disease stabilization rate in patients with OPG/PA was 54%, and disease control was maintained for a median interval of 34 months. Seventeen of 26 patients had progressive disease either on or off therapy, and three have died of disease. The two-year progression-free and overall survivals in patients with OPG/PA were 49% (95% CI, 30%-67%) and 96% (95% CI, 89%-100%), respectively. Worst toxicity related to TMZ in all 30 patients included grade 2-4 thrombocytopenia in seven patients, grade 2-4 neutropenia in seven, grade 2 skin rash in one, and intratumor hemorrhage in one. TMZ given in this schedule was successful in stabilizing disease in a significant proportion of the patients with OPG/PA, with manageable toxicity.

Authors
Gururangan, S; Fisher, MJ; Allen, JC; Herndon, JE; Quinn, JA; Reardon, DA; Vredenburgh, JJ; Desjardins, A; Phillips, PC; Watral, MA; Krauser, JM; Friedman, AH; Friedman, HS
MLA Citation
Gururangan, S, Fisher, MJ, Allen, JC, Herndon, JE, Quinn, JA, Reardon, DA, Vredenburgh, JJ, Desjardins, A, Phillips, PC, Watral, MA, Krauser, JM, Friedman, AH, and Friedman, HS. "Temozolomide in children with progressive low-grade glioma." Neuro Oncol 9.2 (April 2007): 161-168.
PMID
17347491
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
2
Publish Date
2007
Start Page
161
End Page
168
DOI
10.1215/15228517-2006-030

Free flap reconstruction of the scalp and calvaria of major neurosurgical resections in cancer patients: lessons learned closing large, difficult wounds of the dura and skull.

BACKGROUND: Reconstruction of major neurosurgical resections can present a significant challenge because of the morbidity of radiation therapy, cerebrospinal fluid leaks, bacterial contamination from sinus exposure, and functional and cosmetic deformity from the size and location of the defect. The authors present their experience with free tissue reconstruction of scalp and calvarial defects. In particular, the authors examine their results in relation to major comorbidities, such as preoperative cerebrospinal fluid leak, history of smoking, and perioperative radiation therapy. METHODS: From 1997 to 2004, 22 patients requiring neurosurgical or head and neck resection for cancer from a single institution who underwent reconstruction with 24 flaps were examined retrospectively. Factors examined included patient demographics, indication for surgery, type of flap used, exposed critical structures, comorbidity, complications, and outcomes. RESULTS: Of the 22 patients, seven had a cerebrospinal fluid leak present at the time of their reconstructive surgery. Of the seven, one patient died as a result of a stroke postoperatively. Of the remaining six patients, two had partial flap necrosis (33 percent). However, all six flaps survived, with resolution of cerebrospinal fluid leak. In comparison, of the 15 patients (17 flaps) without a cerebrospinal fluid leak, three had partial flap necrosis (18 percent; not significant). With regard to smoking status, the partial flap necrosis rate was 30 percent in smokers versus a rate of 14 percent in nonsmokers, although this was not statistically significant. Only one patient who received perioperative radiation (11 of 22 patients) developed partial flap necrosis. CONCLUSIONS: The authors' data support the concept that free tissue transfer is a viable option in reconstruction of cranial defects. Although complications can occur in this high-risk population, successful reconstruction with free flaps was possible. Difficult problems, such as recurrent cerebrospinal fluid leaks and large irradiated wounds, can be managed and resolved successfully using this technique.

Authors
Wang, HT; Erdmann, D; Olbrich, KC; Friedman, AH; Levin, LS; Zenn, MR
MLA Citation
Wang, HT, Erdmann, D, Olbrich, KC, Friedman, AH, Levin, LS, and Zenn, MR. "Free flap reconstruction of the scalp and calvaria of major neurosurgical resections in cancer patients: lessons learned closing large, difficult wounds of the dura and skull." Plast Reconstr Surg 119.3 (March 2007): 865-872.
PMID
17312489
Source
pubmed
Published In
Plastic and Reconstructive Surgery
Volume
119
Issue
3
Publish Date
2007
Start Page
865
End Page
872
DOI
10.1097/01.prs.0000240830.19716.c2

Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma.

PURPOSE: Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy. This study was conducted to determine if the combination of a novel antiangiogenic therapy, bevacizumab, and a cytotoxic agent, irinotecan, is safe and effective for patients with recurrent grade III-IV glioma. EXPERIMENTAL DESIGN: We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma. Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded. Patients were scheduled to receive bevacizumab and irinotecan i.v. every 2 weeks of a 6-week cycle. Bevacizumab was administered at 10 mg/kg. The dose of irinotecan was determined based on antiepileptic use: patients taking enzyme-inducing antiepileptic drugs received 340 mg/m(2), whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m(2). Toxicity and response were assessed. RESULTS: Thirty-two patients were assessed (23 with grade IV glioma and 9 with grade III glioma). Radiographic responses were noted in 63% (20 of 32) of patients (14 of 23 grade IV patients and 6 of 9 grade III patients). The median progression-free survival was 23 weeks for all patients (95% confidence interval, 15-30 weeks; 20 weeks for grade IV patients and 30 weeks for grade III patients). The 6-month progression-free survival probability was 38% and the 6-month overall survival probability was 72%. No central nervous system hemorrhages occurred, but three patients developed deep venous thromboses or pulmonary emboli, and one patient had an arterial ischemic stroke. CONCLUSIONS: The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.

Authors
Vredenburgh, JJ; Desjardins, A; Herndon, JE; Dowell, JM; Reardon, DA; Quinn, JA; Rich, JN; Sathornsumetee, S; Gururangan, S; Wagner, M; Bigner, DD; Friedman, AH; Friedman, HS
MLA Citation
Vredenburgh, JJ, Desjardins, A, Herndon, JE, Dowell, JM, Reardon, DA, Quinn, JA, Rich, JN, Sathornsumetee, S, Gururangan, S, Wagner, M, Bigner, DD, Friedman, AH, and Friedman, HS. "Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma." Clin Cancer Res 13.4 (February 15, 2007): 1253-1259.
PMID
17317837
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
4
Publish Date
2007
Start Page
1253
End Page
1259
DOI
10.1158/1078-0432.CCR-06-2309

Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: Descriptive effects of target anatomy and catheter positioning

OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence drug distribution. The primary objective of this study was to quantitatively describe the distribution of a high molecular weight agent by CED relative to target anatomy and catheter position in patients with malignant gliomas. METHODS: Seven adult patients with recurrent malignant gliomas underwent intracerebral infusion of the tumor-targeted cytotoxin, cintredekin besudotox, concurrently with I-labeled human serum albumin. High-resolution single-photon emission computed tomographic images were obtained at 24 and 48 hours and were coregistered with magnetic resonance imaging scans. The distribution of I-labeled human serum albumin relative to target anatomy and catheter position was analyzed. RESULTS: Intracerebral CED infusions were well-tolerated and some resulted in a broad distribution of I-labeled human serum albumin, but target anatomy and catheter positioning had a significant influence on infusate distribution even within non-contrast-enhancing areas of brain. Intratumoral infusions were anisotropic and resulted in limited coverage of the enhancing tumor area and adjacent peritumoral regions. CONCLUSIONS: CED has the potential to deliver high molecular weight agents into tumor-infiltrated brain parenchyma with volumes of distribution that are clinically relevant. Target tissue anatomy and catheter position are critical parameters in optimizing drug delivery. Copyright © by the Congress of Neurological Surgeons.

Authors
Sampson, JH; Brady, ML; Petry, NA; Croteau, D; Friedman, AH; Friedman, HS; Wong, T; Bigner, DD; Pastan, I; Puri, RK; Pedain, C
MLA Citation
Sampson, JH, Brady, ML, Petry, NA, Croteau, D, Friedman, AH, Friedman, HS, Wong, T, Bigner, DD, Pastan, I, Puri, RK, and Pedain, C. "Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: Descriptive effects of target anatomy and catheter positioning." Neurosurgery 60.2 SUPPL.1 (February 1, 2007).
Source
scopus
Published In
Neurosurgery
Volume
60
Issue
2 SUPPL.1
Publish Date
2007
DOI
10.1227/01.NEU.0000249256.09289.5F

Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning.

OBJECTIVE: Convection-enhanced delivery (CED) holds tremendous potential for drug delivery to the brain. However, little is known about the volume of distribution achieved within human brain tissue or how target anatomy and catheter positioning influence drug distribution. The primary objective of this study was to quantitatively describe the distribution of a high molecular weight agent by CED relative to target anatomy and catheter position in patients with malignant gliomas. METHODS: Seven adult patients with recurrent malignant gliomas underwent intracerebral infusion of the tumor-targeted cytotoxin, cintredekin besudotox, concurrently with 123I-labeled human serum albumin. High-resolution single-photon emission computed tomographic images were obtained at 24 and 48 hours and were coregistered with magnetic resonance imaging scans. The distribution of 123I-labeled human serum albumin relative to target anatomy and catheter position was analyzed. RESULTS: Intracerebral CED infusions were well-tolerated and some resulted in a broad distribution of 123I-labeled human serum albumin, but target anatomy and catheter positioning had a significant influence on infusate distribution even within non-contrast-enhancing areas of brain. Intratumoral infusions were anisotropic and resulted in limited coverage of the enhancing tumor area and adjacent peritumoral regions. CONCLUSIONS: CED has the potential to deliver high molecular weight agents into tumor-infiltrated brain parenchyma with volumes of distribution that are clinically relevant. Target tissue anatomy and catheter position are critical parameters in optimizing drug delivery.

Authors
Sampson, JH; Brady, ML; Petry, NA; Croteau, D; Friedman, AH; Friedman, HS; Wong, T; Bigner, DD; Pastan, I; Puri, RK; Pedain, C
MLA Citation
Sampson, JH, Brady, ML, Petry, NA, Croteau, D, Friedman, AH, Friedman, HS, Wong, T, Bigner, DD, Pastan, I, Puri, RK, and Pedain, C. "Intracerebral infusate distribution by convection-enhanced delivery in humans with malignant gliomas: descriptive effects of target anatomy and catheter positioning." Neurosurgery 60.2 Suppl 1 (February 2007): ONS89-ONS98.
PMID
17297371
Source
pubmed
Published In
Neurosurgery
Volume
60
Issue
2 Suppl 1
Publish Date
2007
Start Page
ONS89
End Page
ONS98
DOI
10.1227/01.NEU.0000249256.09289.5F

Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group.

BACKGROUND: Since the initial utilization of heart transplantation as therapy for end-stage pediatric heart disease, improvements have occurred in outcomes with heart transplantation and surgical therapies for congenital heart disease along with the application of medical therapies to pediatric heart failure that have improved outcomes in adults. These events justify a reevaluation of the indications for heart transplantation in congenital heart disease and other causes of pediatric heart failure. RESULTS: A working group was commissioned to review accumulated experience with pediatric heart transplantation and its use in patients with unrepaired and/or previously repaired or palliated congenital heart disease (children and adults), in patients with pediatric cardiomyopathies, and in pediatric patients with prior heart transplantation. Evidence-based guidelines for the indications for heart transplantation or retransplantation for these conditions were developed. CONCLUSIONS: This evaluation has led to the development and refinement of indications for heart transplantation for patients with congenital heart disease and pediatric cardiomyopathies in addition to indications for pediatric heart retransplantation.

Authors
Surgery, CECRESDBDTHMRCJKKKRKRSHEDBDNRMMBKCUAHFAHFJKYAHACOCDITYAHACOCCAHACOCNAHACOC; Anesthesia, QOC; Group, ORIW
MLA Citation
Surgery, CECRESDBDTHMRCJKKKRKRSHEDBDNRMMBKCUAHFAHFJKYAHACOCDITYAHACOCCAHACOCNAHACOC, Anesthesia, QOC, and Group, ORIW. "Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Surgery and Anesthesia; and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 115.5 (February 2007): 658-676. (Academic Article)
Source
manual
Published In
Circulation
Volume
115
Issue
5
Publish Date
2007
Start Page
658
End Page
676
DOI
10.1161/CIRCULATIONAHA.106.180449

Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme.

Cloretazine (VNP40101M) is a newly synthesized alkylating agent belonging to a novel class of alkylating agents called 1,2-bis(sulfonyl)hydrazines. Agents that belong to this class do not produce vinylating and chloroethylating species, and hence this class of alkylating agents is thought to have minimal systemic toxicity. Cloretazine produces two short-lived active species: 1,2-bis(methylsulfonyl)-1-(2-chloroethyl) hydrazine (a chloroethylating species) and a thiophilic carbamoylating methylisocyanate species. The chloroethylating species preferentially produces lesions at the O(6) position of guanine. The methylisocyanate species may inhibit O(6)-alkylguanine-DNA alkyltransferase, an important mechanism of resistance against alkylating agents. The purpose of this study was to determine the efficacy and tolerability of Cloretazine in patients with recurrent glioblastoma multiforme. The basis for the determination of efficacy was the proportion of patients alive without evidence of disease progression six months after initiation of treatment. Patients with recurrent glioblastoma multiforme received Cloretazine (300 mg/m(2)) intravenously every six weeks. Radiographic response, survival data, and toxicity were assessed. Thirty-two patients were enrolled. Median age was 56 years; 24 patients (75%) were men. At six months, two patients were alive and progression free, so the six-month progression-free survival (PFS) was 6%. The median PFS was 6.3 weeks. There were no objective radiographic responses. Twelve patients had stable disease for at least one cycle, but only two patients received more than three cycles. Nine patients experienced grade 4 thrombocytopenia and three patients experienced grade 4 neutropenia. Cloretazine administered every six weeks was relatively well tolerated, although this schedule has insignificant activity for patients with recurrent glioblastoma multiforme.

Authors
Badruddoja, MA; Penne, K; Desjardins, A; Reardon, DA; Rich, JN; Quinn, JA; Sathornsumetee, S; Friedman, AH; Bigner, DD; Herndon, JE; Cahill, A; Friedman, HS; Vredenburgh, JJ
MLA Citation
Badruddoja, MA, Penne, K, Desjardins, A, Reardon, DA, Rich, JN, Quinn, JA, Sathornsumetee, S, Friedman, AH, Bigner, DD, Herndon, JE, Cahill, A, Friedman, HS, and Vredenburgh, JJ. "Phase II study of Cloretazine for the treatment of adults with recurrent glioblastoma multiforme." Neuro Oncol 9.1 (January 2007): 70-74.
PMID
17108065
Source
pubmed
Published In
Neuro-Oncology
Volume
9
Issue
1
Publish Date
2007
Start Page
70
End Page
74
DOI
10.1215/15228517-2006-022

Cerebellopontine angle craniopharyngioma: case report and literature review.

The authors report an unusual case of adamantinomatous craniopharyngioma occurring in isolation in the cerebellopontine angle of a 12-year-old female. The patient presented with a 1-year history of nausea, vomiting, and headache. MRI revealed a left cerebellopontine angle tumor without connection to the suprasellar space. Following near-total resection, histological review confirmed the lesion as an adamantinomatous craniopharyngioma. This is only the third published report of craniopharyngioma occurring in isolation in the cerebellopontine angle. The case report and a brief review of the literature are presented.

Authors
Powers, CJ; New, KC; McLendon, RE; Friedman, AH; Fuchs, HE
MLA Citation
Powers, CJ, New, KC, McLendon, RE, Friedman, AH, and Fuchs, HE. "Cerebellopontine angle craniopharyngioma: case report and literature review." Pediatr Neurosurg 43.2 (2007): 158-163. (Review)
PMID
17337933
Source
pubmed
Published In
Pediatric neurosurgery
Volume
43
Issue
2
Publish Date
2007
Start Page
158
End Page
163
DOI
10.1159/000098394

Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Angiotensin converting enzyme inhibition for arterial hypertension reduces the risk of recurrence in patients with chronic subdural hematoma possibly by an antiangiogenic mechanism: Commentary." Neurosurgery 61.4 (2007): 793--.
Source
scival
Published In
Neurosurgery
Volume
61
Issue
4
Publish Date
2007
Start Page
793-
DOI
10.1227/01.NEU.0000298907.56012.E8

Wound complications associated with the use of bovine serum albumin-glutaraldehyde surgical adhesive in pediatric patients: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Wound complications associated with the use of bovine serum albumin-glutaraldehyde surgical adhesive in pediatric patients: Commentary." Neurosurgery 60.4 SUPPL. 2 (2007): ONS-309.
Source
scival
Published In
Neurosurgery
Volume
60
Issue
4 SUPPL. 2
Publish Date
2007
Start Page
ONS
End Page
309
DOI
10.1227/01.NEU.0000255416.55560.D2

Free flap transfer for the treatment of intractable postcraniotomy subdural empyemas and epidural abscesses: Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Free flap transfer for the treatment of intractable postcraniotomy subdural empyemas and epidural abscesses: Commentary." Neurosurgery 60.2 SUPPL.1 (2007): ONS-87.
Source
scival
Published In
Neurosurgery
Volume
60
Issue
2 SUPPL.1
Publish Date
2007
Start Page
ONS
End Page
87
DOI
10.1227/01.NEU.0000249253.63546.19

In vivo imaging in a murine model of glioblastoma - Commentary

Authors
Bullitt, E; Friedman, A
MLA Citation
Bullitt, E, and Friedman, A. "In vivo imaging in a murine model of glioblastoma - Commentary." Neurosurgery 60.2 (2007): 370-371.
Source
scival
Published In
Neurosurgery
Volume
60
Issue
2
Publish Date
2007
Start Page
370
End Page
371
DOI
10.1227/01.NEU.0000249264.80579.37

Primary spinal intramedullary adrenal cortical adenoma associated with spinal dysraphism: Case report

OBJECTIVE: The authors report a primary spinal intramedullary adrenal cortical adenoma in a patient with spinal dysraphism presenting with bilateral leg pain and urinary frequency. METHODS: Magnetic resonance imaging, L2 laminectomy with resection of mass, and pathological and immunohistochemical analysis of resected mass revealed the diagnosis. RESULTS: Microscopic and immunohistochemical findings confirmed the diagnosis as a primary intramedullary tumor of adrenal cortical origin. CONCLUSION: The occurrence of a primary adrenal tumor in the spinal cord is rare and difficult to explain based on our understanding of embryology. A review of the relevant literature and discussion of the pathophysiology and clinical implications is provided. Copyright © by the Congress of Neurological Surgeons.

Authors
Karikari, IO; Uschold, TD; Selznick, LA; Carter, JH; Cummings, TJ; Friedman, AH
MLA Citation
Karikari, IO, Uschold, TD, Selznick, LA, Carter, JH, Cummings, TJ, and Friedman, AH. "Primary spinal intramedullary adrenal cortical adenoma associated with spinal dysraphism: Case report." Neurosurgery 59.5 (November 1, 2006): 1155-1159.
Source
scopus
Published In
Neurosurgery
Volume
59
Issue
5
Publish Date
2006
Start Page
1155
End Page
1159
DOI
10.1227/01.NEU.0000245588.31334.83

Jugular tubercle: Morphometric analysis and surgical significance.

OBJECT: Maximizing intradural exposure via the extreme lateral infrajugular transcondylar-transtubercular exposure (ELITE) approach depends on understanding the fundamental anatomy of the jugular tubercle (JT). Drilling the JT can maximize the extent of exposure achieved with the ELITE approach. Removing the JT is critical for optimizing access to the inferior and midclival areas, vertebrobasilar artery junction, and ventral pons and medulla. METHODS: In this cadaveric study, the individual structural variations in the JT were evaluated in 100 split occipital bones. The mean length of the JT was 1.65 +/- 0.36 cm (range 1.2-3 cm); its mean width was 1.15 +/- 0.16 cm (range 0.7-1.7 cm); and its mean thickness was 0.61 +/- 0.15 cm (range 0.2-1 cm). The authors analyzed the difference in morphometric data with regard to right and left sides and found no statistically significant difference between the two sides. Furthermore, data from the morphometric study were compared with the results of 20 measurements obtained from three-dimensional computed tomography (3D CT) scans. Accordingly, the mean length of the JT was 1.35 +/- 0.15 cm (range 1-2.8 cm); the mean width, 1.10 +/- 0.12 cm (range 0.8-1.3 cm); and the mean thickness, 0.51 +/- 0.18 cm (range 0.2-1 cm). CONCLUSIONS: Morphometric data on the JT contribute significantly to the neurosurgeon's task of skull base drilling. The 3D CT scans were useful in the preoperative planning.

Authors
Mintelis, A; Sameshima, T; Bulsara, KR; Gray, L; Friedman, AH; Fukushima, T
MLA Citation
Mintelis, A, Sameshima, T, Bulsara, KR, Gray, L, Friedman, AH, and Fukushima, T. "Jugular tubercle: Morphometric analysis and surgical significance." J Neurosurg 105.5 (November 2006): 753-757.
PMID
17121139
Source
pubmed
Published In
Journal of neurosurgery
Volume
105
Issue
5
Publish Date
2006
Start Page
753
End Page
757
DOI
10.3171/jns.2006.105.5.753

Primary spinal intramedullary adrenal cortical adenoma associated with spinal dysraphism: case report.

OBJECTIVE: The authors report a primary spinal intramedullary adrenal cortical adenoma in a patient with spinal dysraphism presenting with bilateral leg pain and urinary frequency. METHODS: Magnetic resonance imaging, L2 laminectomy with resection of mass, and pathological and immunohistochemical analysis of resected mass revealed the diagnosis. RESULTS: Microscopic and immunohistochemical findings confirmed the diagnosis as a primary intramedullary tumor of adrenal cortical origin. CONCLUSION: The occurrence of a primary adrenal tumor in the spinal cord is rare and difficult to explain based on our understanding of embryology. A review of the relevant literature and discussion of the pathophysiology and clinical implications is provided.

Authors
Karikari, IO; Uschold, TD; Selznick, LA; Carter, JH; Cummings, TJ; Friedman, AH
MLA Citation
Karikari, IO, Uschold, TD, Selznick, LA, Carter, JH, Cummings, TJ, and Friedman, AH. "Primary spinal intramedullary adrenal cortical adenoma associated with spinal dysraphism: case report." Neurosurgery 59.5 (November 2006): E1144-E1144.
PMID
17143207
Source
epmc
Published In
Neurosurgery
Volume
59
Issue
5
Publish Date
2006
Start Page
E1144
End Page
E1144
DOI
10.1227/01.neu.0000245588.31334.83

Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience.

OBJECT: Impairment of endothelial nitric oxide synthase (eNOS), endothelium-dependent relaxation, and cerebrovascular autoregulation all occur in vasospastic cerebral arteries following subarachnoid hemorrhage (SAH). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, both improve endothelial function and increase eNOS messenger RNA, protein, and enzymatic activity threefold. Increasing experimental evidence in animal models of SAH suggests that statins may ameliorate cerebral vasospasm. The authors hypothesized that patients chronically treated with statins would have a decreased risk of symptomatic vasospasm after SAH. METHODS: The authors retrospectively reviewed the charts of 115 patients with SAH who were consecutively admitted to the Neuroscience Intensive Care Unit of Duke University between 1998 and 2001. The independent association of statin therapy to symptomatic vasospasm was assessed using multivariate logistic regression analysis. Fifteen patients (13%) admitted with SAH were receiving statin therapy for at least 1 month before admission. Forty-nine patients (43%) experienced symptomatic vasospasm a mean of 5.8 +/- 3 days after onset of SAH. Current statin therapy on admission (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.01-0.77) was independently associated with an 11-fold reduction in the risk of symptomatic vasospasm. Fisher Grade 3 SAH (OR 2.82, 95% CI 1.50-5.71) and rupture of anterior cerebral or internal carotid artery aneurysm (OR 3.77, 95% CI 1.29-10.91) were independently associated with an increased risk of symptomatic vasospasm. CONCLUSIONS: In this retrospective case series, patients who received statin therapy for at least 1 month demonstrated an 11-fold decrease in the risk of developing symptomatic vasospasm after SAH.

Authors
McGirt, MJ; Blessing, R; Alexander, MJ; Nimjee, SM; Woodworth, GF; Friedman, AH; Graffagnino, C; Laskowitz, DT; Lynch, JR
MLA Citation
McGirt, MJ, Blessing, R, Alexander, MJ, Nimjee, SM, Woodworth, GF, Friedman, AH, Graffagnino, C, Laskowitz, DT, and Lynch, JR. "Risk of cerebral vasopasm after subarachnoid hemorrhage reduced by statin therapy: A multivariate analysis of an institutional experience." J Neurosurg 105.5 (November 2006): 671-674.
PMID
17121126
Source
pubmed
Published In
Journal of neurosurgery
Volume
105
Issue
5
Publish Date
2006
Start Page
671
End Page
674
DOI
10.3171/jns.2006.105.5.671

Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma.

Promoter hypermethylation of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT) has been associated with an enhanced response to chloroethylating and methylating agents in patients with malignant glioma. The purpose of this study was to compare three distinct yet related indices for measuring AGT to determine if these assays could be used interchangeably when AGT status is to be used to guide chemotherapeutic decisions. Real-time methylation-specific PCR (MSP), assessed as the ratio of methylated AGT copies to internal beta-actin control, was used to quantitate AGT hypermethylation in 32 glioma samples. Data were compared with AGT enzyme activity as well as immunohistochemical detection of AGT protein from the same samples. Hypermethylation of the AGT promoter was detected in 19 of 31 (61%) samples evaluable by MSP. Low-level AGT, defined as <20% nuclear AGT staining by immunohistochemistry, was found in 10 of 32 samples (31%), whereas 12 of 32 (38%) had low levels of AGT activity. Correlation of immunohistochemistry to AGT activity was statistically significant (P = 0.014) as was the correlation of immunohistochemistry to MSP (P = 0.043), whereas MSP compared with AGT activity (P = 0.246) was not significant. Cross-tabulation of immunohistochemistry and MSP data based on prognostic groups, where good prognosis was represented by an immunohistochemistry of <20% and an MSP ratio >12, showed no significant relationship (P = 0.214), suggesting that one assay cannot be used interchangeably for another. The observed discordance between respective measures of AGT based on prognosis supports further standardization of AGT assays designed to guide therapeutic practice. The data also suggest that consideration be given to the large population of AGT-expressing cells within samples when therapeutic strategies based on tumor methylation are used.

Authors
Maxwell, JA; Johnson, SP; Quinn, JA; McLendon, RE; Ali-Osman, F; Friedman, AH; Herndon, JE; Bierau, K; Bigley, J; Bigner, DD; Friedman, HS
MLA Citation
Maxwell, JA, Johnson, SP, Quinn, JA, McLendon, RE, Ali-Osman, F, Friedman, AH, Herndon, JE, Bierau, K, Bigley, J, Bigner, DD, and Friedman, HS. "Quantitative analysis of O6-alkylguanine-DNA alkyltransferase in malignant glioma." Mol Cancer Ther 5.10 (October 2006): 2531-2539.
PMID
17041097
Source
pubmed
Published In
Molecular cancer therapeutics
Volume
5
Issue
10
Publish Date
2006
Start Page
2531
End Page
2539
DOI
10.1158/1535-7163.MCT-06-0106

Preoperative functional MR imaging localization of language and motor areas: effect on therapeutic decision making in patients with potentially resectable brain tumors.

PURPOSE: To prospectively evaluate the effect of preoperative functional magnetic resonance (MR) imaging localization of language and motor areas on therapeutic decision making in patients with potentially resectable brain tumors. MATERIALS AND METHODS: The Institutional Review Board approved this HIPAA-compliant study, and each patient gave written informed consent. Thirty-nine consecutive patients (19 male, 20 female; mean age, 42.2 years) referred for functional MR imaging for possible tumor resection were prospectively evaluated. A preoperative diagnosis of brain tumor was made in all patients. Sentence completion and bilateral hand squeeze tasks were used to map language and sensory motor areas. Neurosurgeons completed questionnaires regarding the proposed treatment plan before and after functional MR imaging and after surgery. They also gave confidence ratings for functional MR imaging results and estimated the effect on surgical time, extent of resection, and surgical approach. The effect of functional MR imaging on changes in treatment plan was assessed with the Wilcoxon signed rank test. Differences in confidence ratings between altered and unaltered treatment plans were assessed with the Mann-Whitney U test. The estimated influence of functional MR imaging on surgical time, extent of resection, and surgical approach was denoted with summary statistics. RESULTS: Treatment plans before and after functional MR imaging differed in 19 patients (P < .05), with a more aggressive approach recommended after imaging in 18 patients. There were no significant differences in confidence ratings for functional MR imaging between altered and unaltered plans. Functional MR imaging resulted in reduced surgical time (estimated reduction, 15-60 minutes) in 22 patients who underwent surgery, a more aggressive resection in six, and a smaller craniotomy in two. CONCLUSION: Functional MR imaging enables the selection of a more aggressive therapeutic approach than might otherwise be considered because of functional risk. In certain patients, surgical time may be shortened, the extent of resection increased, and craniotomy size decreased.

Authors
Petrella, JR; Shah, LM; Harris, KM; Friedman, AH; George, TM; Sampson, JH; Pekala, JS; Voyvodic, JT
MLA Citation
Petrella, JR, Shah, LM, Harris, KM, Friedman, AH, George, TM, Sampson, JH, Pekala, JS, and Voyvodic, JT. "Preoperative functional MR imaging localization of language and motor areas: effect on therapeutic decision making in patients with potentially resectable brain tumors." Radiology 240.3 (September 2006): 793-802.
PMID
16857981
Source
pubmed
Published In
Radiology
Volume
240
Issue
3
Publish Date
2006
Start Page
793
End Page
802
DOI
10.1148/radiol.2403051153

Potential additional indicators for pacemaker requirement in isolated congenital atrioventricular block.

Low heart rate is the predominantly used indication for pacemaker intervention in patients with isolated congenital atrioventricular block (CAVB). The aim of this study was to compare the difference in heart rates recorded with ECG and Holter monitoring between paced (PM) and nonpaced (NPM) patients with isolated CAVB before pacemaker implantation to identify additional predictors for future PM need. Retrospective evaluation of atrial and ventricular rates (electrocardiography) and minimal and maximal (Holter) heart rates in 129 CAVB patients prior to PM implantation (n = 93) was performed, and results are expressed in V adjusted for age and sex. The average V score for the atrial rate was 0.51 (n = 50) in the PM group and 0.60 (n = 22) in the NPM group (not-significant). The average z score for the ventricular (average) rate was -0.91 (n = 83) in the PM group and -0.93 (n = 33) in the NPM group (not-significant). Minimal heart rate was -0.94 (n = 61) in the PM group and -0.86 (n = 25) in the NPM group (not significant). Maximal heart rate was -0.96 (n = 61) in the PM group and -0.95 (n = 26) in the NPM group (not significant). Initial recordings of the average heart rate and the minimal and maximal heart rate recorded during Holter monitoring do not seem to predict future pacemaker need in patients with CAVB. Studies with exercise stress tests are needed to confirm these findings.

Authors
Breur, JM; Udink ten Cate, FE; Kapusta, L; Boramanand, N; Cohen, MI; Crosson, JE; Lubbers, LJ; Friedman, AH; Brenner, JI; Vetter, VL; Meijboom, EJ
MLA Citation
Breur, JM, Udink ten Cate, FE, Kapusta, L, Boramanand, N, Cohen, MI, Crosson, JE, Lubbers, LJ, Friedman, AH, Brenner, JI, Vetter, VL, and Meijboom, EJ. "Potential additional indicators for pacemaker requirement in isolated congenital atrioventricular block." Pediatric cardiology 27.5 (August 2006): 564-568. (Academic Article)
Source
manual
Published In
Pediatric Cardiology
Volume
27
Issue
5
Publish Date
2006
Start Page
564
End Page
568
DOI
10.1007/s00246-004-0629-1

Three-dimensional computed tomographic analysis of the relationship between the arcuate eminence and the superior semicircular canal

OBJECTIVE: The location of the superior semicircular canal (SSC) is often determined intraoperatively based on its topographic association with the arcuate eminence (AE). This determination is not always possible because of the potential variability in the relationship between these two structures. The goal of this study was to describe the three-dimensional (3-D) relationship between the AE and SSC using 3-D computed tomography (CT) and to evaluate the utility of 3-D CT for preoperative planning for surgical approaches to the middle cranial fossa. METHODS: We studied 11 patients (22 sides) radiographically using 0.8- to 1-mm thick reconstructed CT images. A standard set of structural relationships was measured between the AE, SSC, and other regional landmarks. RESULTS: 3-D CT clearly demonstrated the relationships between traditional landmarks along the petrous ridge and middle cranial fossa. The relationship between the arcuate eminence and SSC was found to be highly variable. The average distance between the tips of the two structures was found to be 5.7 mm (range, 2.7-10.4 mm). CONCLUSIONS: There is significant variability in the relationship between the AE and the SSC. The AE is not a consistent or reliable landmark for identifying the precise position of the SSC. Detailed preoperative information regarding the relationship between the AE, SSC, and other bony landmarks can be easily and quickly assessed using 3-D CT. Copyright © Congress of Neurological Surgeons.

Authors
Bulsara, KR; Leveque, JC; Gray, L; Fukushima, T; Friedman, AH; Villavicencio, AT
MLA Citation
Bulsara, KR, Leveque, JC, Gray, L, Fukushima, T, Friedman, AH, and Villavicencio, AT. "Three-dimensional computed tomographic analysis of the relationship between the arcuate eminence and the superior semicircular canal." Neurosurgery 59.1 SUPPL. 1 (July 1, 2006).
Source
scopus
Published In
Neurosurgery
Volume
59
Issue
1 SUPPL. 1
Publish Date
2006
DOI
10.1227/01.NEU.0000219929.13839.B8

Three-dimensional computed tomographic analysis of the relationship between the arcuate eminence and the superior semicircular canal.

OBJECTIVE: The location of the superior semicircular canal (SSC) is often determined intraoperatively based on its topographic association with the arcuate eminence (AE). This determination is not always possible because of the potential variability in the relationship between these two structures. The goal of this study was to describe the three-dimensional (3-D) relationship between the AE and SSC using 3-D computed tomography (CT) and to evaluate the utility of 3-D CT for preoperative planning for surgical approaches to the middle cranial fossa. METHODS: We studied 11 patients (22 sides) radiographically using 0.8- to 1-mm thick reconstructed CT images. A standard set of structural relationships was measured between the AE, SSC, and other regional landmarks. RESULTS: 3-D CT clearly demonstrated the relationships between traditional landmarks along the petrous ridge and middle cranial fossa. The relationship between the arcuate eminence and SSC was found to be highly variable. The average distance between the tips of the two structures was found to be 5.7 mm (range, 2.7-10.4 mm). CONCLUSIONS: There is significant variability in the relationship between the AE and the SSC. The AE is not a consistent or reliable landmark for identifying the precise position of the SSC. Detailed preoperative information regarding the relationship between the AE, SSC, and other bony landmarks can be easily and quickly assessed using 3-D CT.

Authors
Bulsara, KR; Leveque, J-C; Gray, L; Fukushima, T; Friedman, AH; Villavicencio, AT
MLA Citation
Bulsara, KR, Leveque, J-C, Gray, L, Fukushima, T, Friedman, AH, and Villavicencio, AT. "Three-dimensional computed tomographic analysis of the relationship between the arcuate eminence and the superior semicircular canal." Neurosurgery 59.1 Suppl 1 (July 2006): ONS7-ON12.
PMID
16888555
Source
pubmed
Published In
Neurosurgery
Volume
59
Issue
1 Suppl 1
Publish Date
2006
Start Page
ONS7
End Page
ON12
DOI
10.1227/01.NEU.0000219929.13839.B8

Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results.

UNLABELLED: Results from animal experiments have shown that human IgG2/mouse chimeric antitenascin 81C6 (ch81C6) monoclonal antibody exhibited higher tumor accumulation and enhanced stability compared with its murine parent. Our objective was to determine the effect of these differences on the maximum tolerated dose (MTD), pharmacokinetics, dosimetry, and antitumor activity of (131)I-ch81C6 administered into the surgically created resection cavity (SCRC) of malignant glioma patients. METHODS: In this phase I trial, eligible patients received a single injection of (131)I-ch81C6 administered through a Rickham catheter into the SCRC. Patients were stratified as newly diagnosed and untreated (stratum A), newly diagnosed after external beam radiotherapy (XRT) (stratum B), and recurrent (stratum C). (131)I-ch81C6 was administered either before (stratum A) or after (stratum B) conventional XRT for newly diagnosed patients. In addition, chemotherapy was prescribed for all patients after (131)I-ch81C6 administration. Dose escalation was performed independently for each stratum. Patients were observed for toxicity and response until death or progressive disease. RESULTS: We treated 47 patients with (131)I-ch81C6 doses up to 4.44 GBq (120 mCi), including 35 with newly diagnosed tumors (strata A and B) and 12 with recurrent disease (stratum C). Dose-limiting hematologic toxicity defined the MTD to be 2.96 GBq (80 mCi) for all patients, regardless of treatment strata. Neurologic dose-limiting toxicity developed in 3 patients; however, none required further surgery to debulk radiation necrosis. Median survival was 88.6 wk and 65.0 wk for newly diagnosed and recurrent patients, respectively. CONCLUSION: The MTD of (131)I-ch81C6 is 2.96 GBq (80 mCi) because of dose-limiting hematologic toxicity. Although encouraging survival was observed, (131)I-ch81C6 was associated with greater hematologic toxicity, probably due to the enhanced stability of the IgG2 construct, than previously observed with (131)I-murine 81C6.

Authors
Reardon, DA; Quinn, JA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Pegram, CN; Provenzale, JM; Dowell, JM; Rich, JN; Vredenburgh, JJ; Desjardins, A; Sampson, JH; Gururangan, S; Wong, TZ; Badruddoja, MA; Zhao, X-G; Bigner, DD; Zalutsky, MR
MLA Citation
Reardon, DA, Quinn, JA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Pegram, CN, Provenzale, JM, Dowell, JM, Rich, JN, Vredenburgh, JJ, Desjardins, A, Sampson, JH, Gururangan, S, Wong, TZ, Badruddoja, MA, Zhao, X-G, Bigner, DD, and Zalutsky, MR. "Novel human IgG2b/murine chimeric antitenascin monoclonal antibody construct radiolabeled with 131I and administered into the surgically created resection cavity of patients with malignant glioma: phase I trial results." J Nucl Med 47.6 (June 2006): 912-918.
PMID
16741299
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
47
Issue
6
Publish Date
2006
Start Page
912
End Page
918

Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies.

OBJECTIVES: Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a larger volume of distribution (Vd) of a radiolabeled monoclonal antibody (mAb) than a bolus injection. METHODS: Patients harboring a recurrent glioblastoma multiforme that reacted with the antitenascin mAb 81C6 during immunohistochemical analysis were randomized to receive an intratumoral injection of the human-murine chimeric mAb Ch81C6, which had been labeled with the 123I tracer. The mAb was administered by either a bolus injection or CED via a stereotactically placed catheter; between 48 and 72 hours later the mAb was again administered using the other technique. Injections of escalating doses of a 131I-labeled therapeutic mAb were then delivered using the technique shown to produce the largest Vd by single-photon emission computerized tomography. CONCLUSIONS: Convection-enhanced delivery has enormous potential for administering drugs to sites within the central nervous system. For the relatively small volumes injected in this study, however, CED did not provide a significant increase in the Vd when compared with the bolus injection. Nevertheless, a clear cross-over effect was seen, which was probably related to the temporal proximity of the two infusions.

Authors
Sampson, JH; Akabani, G; Friedman, AH; Bigner, D; Kunwar, S; Berger, MS; Bankiewicz, KS
MLA Citation
Sampson, JH, Akabani, G, Friedman, AH, Bigner, D, Kunwar, S, Berger, MS, and Bankiewicz, KS. "Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies. (Published online)" Neurosurg Focus 20.4 (April 15, 2006): E14-.
PMID
16709019
Source
pubmed
Published In
Neurosurgical focus
Volume
20
Issue
4
Publish Date
2006
Start Page
E14
DOI
10.3171/foc.2006.20.4.9

Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma.

PURPOSE: We performed a retrospective study of patients with diffuse pontine glioma (DPG) who suffered neuraxis metastasis (NM) and characterized the incidence, clinical features, radiologic findings, and patterns of disease dissemination. METHODS: Magnetic resonance imaging (MRI) of brain and spine was used to assess NM. Some patients also underwent magnetic resonance spectroscopy (MRS) (6 patients) and fluorodeoxyglucose positron emission tomography (FDG-PET) scans (13 patients) to further evaluate areas of metastatic disease. Three patients had histologic confirmation of disease at the site of NM. RESULTS: Between 1986 and 2003, 18 of 96 patients (17.3%) with DPG developed NM. The median age at diagnosis was 8 years (range, 4-17). All patients had adjuvant chemotherapy and/or focal radiotherapy at diagnosis. The NM occurred at a median of 15 months from diagnosis of DPG (range, 3-96). Three patterns of NM were seen on MRI of brain and spine in these patients; 8 (39%) had parenchymal (PM), 4 (22%) leptomeningeal (PM), 2 (11%) subependymal, and in 5 a combination of two or more patterns. The MRS and FDG-PET scan of suspected areas of metastatic disease was consistent with tumor in 6 of 6 and 12 of 13 patients who underwent these procedures respectively. Three patients also had histologic confirmation of malignant glioma at the site of NM. Despite salvage therapy, all 18 patients have died of disease at a median of 5 months (range, 0.5-20) from diagnosis of neuraxis spread. CONCLUSION: Our study emphasizes the need for screening patients with DPG for NM at the time of recurrence.

Authors
Gururangan, S; McLaughlin, CA; Brashears, J; Watral, MA; Provenzale, J; Coleman, RE; Halperin, EC; Quinn, J; Reardon, D; Vredenburgh, J; Friedman, A; Friedman, HS
MLA Citation
Gururangan, S, McLaughlin, CA, Brashears, J, Watral, MA, Provenzale, J, Coleman, RE, Halperin, EC, Quinn, J, Reardon, D, Vredenburgh, J, Friedman, A, and Friedman, HS. "Incidence and patterns of neuraxis metastases in children with diffuse pontine glioma." J Neurooncol 77.2 (April 2006): 207-212.
PMID
16568209
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
77
Issue
2
Publish Date
2006
Start Page
207
End Page
212
DOI
10.1007/s11060-005-9029-5

Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma.

Immunosuppression is frequently associated with malignancy and is particularly severe in patients with malignant glioma. Anergy and counterproductive shifts toward T(H)2 cytokine production are long-recognized T-cell defects in these patients whose etiology has remained elusive for >30 years. We show here that absolute counts of both CD4(+) T cells and CD4(+)CD25(+)FOXP3(+)CD45RO(+) T cells (T(regs)) are greatly diminished in patients with malignant glioma, but T(regs) frequently represent an increased fraction of the remaining CD4 compartment. This increased T(reg) fraction, despite reduced counts, correlates with and is sufficient to elicit the characteristic manifestations of impaired patient T-cell responsiveness in vitro. Furthermore, T(reg) removal eradicates T-cell proliferative defects and reverses T(H)2 cytokine shifts, allowing T cells from patients with malignant glioma to function in vitro at levels equivalent to those of normal, healthy controls. Such restored immune function may give license to physiologic antiglioma activity, as in vivo, T(reg) depletion proves permissive for spontaneous tumor rejection in a murine model of established intracranial glioma. These findings dramatically alter our understanding of depressed cellular immune function in patients with malignant glioma and advance a role for T(regs) in facilitating tumor immune evasion in the central nervous system.

Authors
Fecci, PE; Mitchell, DA; Whitesides, JF; Xie, W; Friedman, AH; Archer, GE; Herndon, JE; Bigner, DD; Dranoff, G; Sampson, JH
MLA Citation
Fecci, PE, Mitchell, DA, Whitesides, JF, Xie, W, Friedman, AH, Archer, GE, Herndon, JE, Bigner, DD, Dranoff, G, and Sampson, JH. "Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma." Cancer Res 66.6 (March 15, 2006): 3294-3302.
PMID
16540683
Source
pubmed
Published In
Cancer Research
Volume
66
Issue
6
Publish Date
2006
Start Page
3294
End Page
3302
DOI
10.1158/0008-5472.CAN-05-3773

Primary myxoma of the parafalcine meninges. Case report.

The authors report on an unusual case of a primary intracranial myxoma in a 39-year-old woman. The patient presented with headache and generalized seizure. Magnetic resonance imaging revealed a large right frontal tumor resembling a parasagittal meningioma. A gross-total resection was performed, and histological review confirmed the lesion as a myxoma. Results of additional workup revealed the absence of a primary myxoma elsewhere. This case represents the third published report of a primary intracranial myxoma and the second report of a supratentorial myxoma.

Authors
Powers, CJ; Pizzi, CC; Cummings, TJ; Friedman, AH
MLA Citation
Powers, CJ, Pizzi, CC, Cummings, TJ, and Friedman, AH. "Primary myxoma of the parafalcine meninges. Case report." J Neurosurg 104.3 (March 2006): 440-443.
PMID
16572660
Source
pubmed
Published In
Journal of neurosurgery
Volume
104
Issue
3
Publish Date
2006
Start Page
440
End Page
443
DOI
10.3171/jns.2006.104.3.440

Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma.

PURPOSE: To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gefitinib, a receptor tyrosine kinase inhibitor of the epidermal growth factor receptor, plus sirolimus, an inhibitor of the mammalian target of rapamycin, among patients with recurrent malignant glioma. PATIENTS AND METHODS: Gefitinib and sirolimus were administered on a continuous daily dosing schedule at dose levels that were escalated in successive cohorts of malignant glioma patients at any recurrence who were stratified based on concurrent use of CYP3A-inducing anticonvulsants [enzyme-inducing antiepileptic drugs, (EIAED)]. Pharmacokinetic and archival tumor biomarker data were also assessed. RESULTS: Thirty-four patients with progressive disease after prior radiation therapy and chemotherapy were enrolled, including 29 (85%) with glioblastoma multiforme and 5 (15%) with anaplastic glioma. The MTD was 500 mg of gefitinib plus 5 mg of sirolimus for patients not on EIAEDs and 1,000 mg of gefitinib plus 10 mg of sirolimus for patients on EIAEDs. DLTs included mucositis, diarrhea, rash, thrombocytopenia, and hypertriglyceridemia. Gefitinib exposure was not affected by sirolimus administration but was significantly lowered by concurrent EIAED use. Two patients (6%) achieved a partial radiographic response, and 13 patients (38%) achieved stable disease. CONCLUSION: We show that gefitinib plus sirolimus can be safely coadministered on a continuous, daily dosing schedule, and established the recommended dose level of these agents in combination for future phase 2 clinical trials.

Authors
Reardon, DA; Quinn, JA; Vredenburgh, JJ; Gururangan, S; Friedman, AH; Desjardins, A; Sathornsumetee, S; Herndon, JE; Dowell, JM; McLendon, RE; Provenzale, JM; Sampson, JH; Smith, RP; Swaisland, AJ; Ochs, JS; Lyons, P; Tourt-Uhlig, S; Bigner, DD; Friedman, HS; Rich, JN
MLA Citation
Reardon, DA, Quinn, JA, Vredenburgh, JJ, Gururangan, S, Friedman, AH, Desjardins, A, Sathornsumetee, S, Herndon, JE, Dowell, JM, McLendon, RE, Provenzale, JM, Sampson, JH, Smith, RP, Swaisland, AJ, Ochs, JS, Lyons, P, Tourt-Uhlig, S, Bigner, DD, Friedman, HS, and Rich, JN. "Phase 1 trial of gefitinib plus sirolimus in adults with recurrent malignant glioma." Clin Cancer Res 12.3 Pt 1 (February 1, 2006): 860-868.
PMID
16467100
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
12
Issue
3 Pt 1
Publish Date
2006
Start Page
860
End Page
868
DOI
10.1158/1078-0432.CCR-05-2215

Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients. PATIENTS AND METHODS: In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy. RESULTS: With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis. CONCLUSION: In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.

Authors
Reardon, DA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; McLendon, RE; Pegram, CN; Provenzale, JM; Quinn, JA; Rich, JN; Vredenburgh, JJ; Desjardins, A; Gururangan, S; Badruddoja, M; Dowell, JM; Wong, TZ; Zhao, X-G; Zalutsky, MR; Bigner, DD
MLA Citation
Reardon, DA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, McLendon, RE, Pegram, CN, Provenzale, JM, Quinn, JA, Rich, JN, Vredenburgh, JJ, Desjardins, A, Gururangan, S, Badruddoja, M, Dowell, JM, Wong, TZ, Zhao, X-G, Zalutsky, MR, and Bigner, DD. "Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results." J Clin Oncol 24.1 (January 1, 2006): 115-122.
PMID
16382120
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
24
Issue
1
Publish Date
2006
Start Page
115
End Page
122
DOI
10.1200/JCO.2005.03.4082

Cranioplasty after trephination using a novel biodegradable burr hole cover: Technical case report - Commentary

Authors
Friedman, AH; Chandler, WF; Sekhar, LN
MLA Citation
Friedman, AH, Chandler, WF, and Sekhar, LN. "Cranioplasty after trephination using a novel biodegradable burr hole cover: Technical case report - Commentary." Neurosurgery 58.SUPPL. 1 (2006): ONS-176.
Source
scival
Published In
Neurosurgery
Volume
58
Issue
SUPPL. 1
Publish Date
2006
Start Page
ONS
End Page
176

FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery: Commentary

Authors
Gonzalez-Martinez, J; Bingaman, WE; Friedman, AH; Doyle, WK
MLA Citation
Gonzalez-Martinez, J, Bingaman, WE, Friedman, AH, and Doyle, WK. "FLAIR-/T1-/T2-co-registration for image-guided diagnostic and resective epilepsy surgery: Commentary." Neurosurgery 58.SUPPL. 1 (2006): ONS-74-ONS-75-.
Source
scival
Published In
Neurosurgery
Volume
58
Issue
SUPPL. 1
Publish Date
2006
Start Page
ONS-74-ONS-75

Primary malignant melanoma of the cerebellopontine angle: A diagnostic dilemma: Case report - Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Primary malignant melanoma of the cerebellopontine angle: A diagnostic dilemma: Case report - Commentary." Neurosurgery 59.6 (2006): E1336-.
Source
scival
Published In
Neurosurgery
Volume
59
Issue
6
Publish Date
2006
Start Page
E1336
DOI
10.1227/01.NEU.0000245613.86484.36

Patient outcomes after vestibular schwannoma management: A prospective comparison of microsurgical resection and stereotactic radiosurgery - Commentary

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Patient outcomes after vestibular schwannoma management: A prospective comparison of microsurgical resection and stereotactic radiosurgery - Commentary." Neurosurgery 59.1 (2006): 84--.
Source
scival
Published In
Neurosurgery
Volume
59
Issue
1
Publish Date
2006
Start Page
84-
DOI
10.1227/01.NEU.0000219217.14930.14

Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations: Commentary

Authors
Kirkpatrick, JP; Friedman, AH
MLA Citation
Kirkpatrick, JP, and Friedman, AH. "Multisession CyberKnife radiosurgery for intramedullary spinal cord arteriovenous malformations: Commentary." Neurosurgery 58.6 (2006): 1089--.
Source
scival
Published In
Neurosurgery
Volume
58
Issue
6
Publish Date
2006
Start Page
1089-
DOI
10.1227/01.NEU.0000215891.25153.BA

Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation: Commentary

Authors
Friedman, AH; Komotar, RJ; Jr, ESC; Mathiesen, T; Marshall, LF; Grossman, RG
MLA Citation
Friedman, AH, Komotar, RJ, Jr, ESC, Mathiesen, T, Marshall, LF, and Grossman, RG. "Delayed posttraumatic acute subdural hematoma in elderly patients on anticoagulation: Commentary." Neurosurgery 58.5 (2006): 856--.
Source
scival
Published In
Neurosurgery
Volume
58
Issue
5
Publish Date
2006
Start Page
856-
DOI
10.1227/01.NEU.0000209653.82936.96

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PURPOSE: We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). RESULTS: Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. CONCLUSION: Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Authors
Reardon, DA; Egorin, MJ; Quinn, JA; Rich, JN; Gururangan, S; Vredenburgh, JJ; Desjardins, A; Sathornsumetee, S; Provenzale, JM; Herndon, JE; Dowell, JM; Badruddoja, MA; McLendon, RE; Lagattuta, TF; Kicielinski, KP; Dresemann, G; Sampson, JH; Friedman, AH; Salvado, AJ; Friedman, HS
MLA Citation
Reardon, DA, Egorin, MJ, Quinn, JA, Rich, JN, Gururangan, S, Vredenburgh, JJ, Desjardins, A, Sathornsumetee, S, Provenzale, JM, Herndon, JE, Dowell, JM, Badruddoja, MA, McLendon, RE, Lagattuta, TF, Kicielinski, KP, Dresemann, G, Sampson, JH, Friedman, AH, Salvado, AJ, and Friedman, HS. "Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme." J Clin Oncol 23.36 (December 20, 2005): 9359-9368.
PMID
16361636
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
36
Publish Date
2005
Start Page
9359
End Page
9368
DOI
10.1200/JCO.2005.03.2185

Survival analysis of presumptive prognostic markers among oligodendrogliomas.

BACKGROUND: Allelic losses of 1p and 19q arms correlate with the oligodendroglial phenotype as well as with sensitivity to radiotherapy and chemotherapy. Furthermore, the DNA repair gene, methylguanine methyltransferase (MGMT), is diminished in 80% of oligodendroglial tumors and represents a possible mechanism for this therapeutic sensitivity. However, the authors questioned the relevance of genetic testing and measuring MGMT levels in tumors that were diagnostic of oligodendroglioma. METHODS: The authors performed a retrospective analysis of 1p, 19q, 9p21, TP53, and MGMT status in 46 patients with oligodendrogliomas to address any relations that may exist among these markers with regard to progression-free survival (PFS) and total survival. Methodologies included comparative genomic hybridization; loss of heterozygosity (LOH) on 1p, 19q, and 9p21; TP53 mutational analysis; and immunohistochemistry for MGMT. RESULTS: The authors found that survival among patients with light microscopically diagnosed oligodendroglial tumors demonstrating LOH of 1p and 19q trended toward statistical significance (P = 0.102 and P = 0.058, respectively). 9p21 LOH was significant as a predictor of PFS only among anaplastic oligodendrogliomas in this cohort (P = 0.033). TP53 mutation was found to be significantly predictive of a shorter survival (P = 0.027) among all patients and exhibited a strong trend toward a shorter PFS (P = 0.060). Low-level MGMT labeling index (LI) (< 20%) was noted in 86% of all oligodendroglial tumors. MGMT LI was not found to correlate with an improved PFS or total survival in this cohort, recognizing that median survival was not reached after a median follow-up of 104 months. CONCLUSIONS: 9p21 and TP53 mutational status assisted in developing a stricter subclassification of these tumors with prognostic significance. MGMT levels were decreased in a majority of oligodendrogliomas.

Authors
McLendon, RE; Herndon, JE; West, B; Reardon, D; Wiltshire, R; Rasheed, BKA; Quinn, J; Friedman, HS; Friedman, AH; Bigner, DD
MLA Citation
McLendon, RE, Herndon, JE, West, B, Reardon, D, Wiltshire, R, Rasheed, BKA, Quinn, J, Friedman, HS, Friedman, AH, and Bigner, DD. "Survival analysis of presumptive prognostic markers among oligodendrogliomas." Cancer 104.8 (October 15, 2005): 1693-1699.
PMID
16116609
Source
pubmed
Published In
Cancer
Volume
104
Issue
8
Publish Date
2005
Start Page
1693
End Page
1699
DOI
10.1002/cncr.21362

Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma.

BACKGROUND: The authors determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of irinotecan (CPT-11), a topoisomerase I inhibitor, when administered with temozolomide among patients with recurrent malignant glioma (MG). METHODS: Patients with MG at any recurrence received temozolomide (TMZ) at a dose of 200 mg/m(2)/day on Days 1-5 plus CPT-11 administered as a 90-minute intravenous infusion during Weeks 1, 2, 4, and 5 of each 6-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing anticonvulsants (enzyme-inducing antiepileptic drugs [EIAEDs]). The CPT-11 dose was escalated in successive cohorts of patients independently for each stratum. RESULTS: CPT-11, at doses ranging from 40 mg/m(2) to 375 mg/m(2), was administered with TMZ to 107 patients. Ninety-one patients (85%) had recurrent glioblastoma multiforme (GBM) and 16 (15%) had recurrent anaplastic glioma. Sixty-eight patients (64%) were given EIAEDs. The MTD of CPT-11 for patients concurrently receiving and not receiving EIAEDs was 325 mg/m(2) and 125 mg/m(2), respectively. The DLTs were hematologic, gastrointestinal, and hepatic. Fifteen patients (14%) achieved either a radiographic complete (n = 5) or partial (n = 10) response across a wide range of CPT-11 dose levels. Patients with recurrent GBM who achieved radiographic response had a median time to disease progression of 54.9 weeks. CONCLUSIONS: The current study built on preclinical observations designed to increase the clinical activity of topoisomerase I inhibitors. CPT-11, administered at full dose levels, was well tolerated in combination with TMZ. Furthermore, durable responses were observed in this recurrent population. Ongoing Phase II studies will evaluate the efficacy of this regimen and its application to other malignancies.

Authors
Reardon, DA; Quinn, JA; Rich, JN; Desjardins, A; Vredenburgh, J; Gururangan, S; Sathornsumetee, S; Badruddoja, M; McLendon, R; Provenzale, J; Herndon, JE; Dowell, JM; Burkart, JL; Newton, HB; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Rich, JN, Desjardins, A, Vredenburgh, J, Gururangan, S, Sathornsumetee, S, Badruddoja, M, McLendon, R, Provenzale, J, Herndon, JE, Dowell, JM, Burkart, JL, Newton, HB, Friedman, AH, and Friedman, HS. "Phase I trial of irinotecan plus temozolomide in adults with recurrent malignant glioma." Cancer 104.7 (October 1, 2005): 1478-1486.
PMID
16088964
Source
pubmed
Published In
Cancer
Volume
104
Issue
7
Publish Date
2005
Start Page
1478
End Page
1486
DOI
10.1002/cncr.21316

Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. PATIENTS AND METHODS: For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. RESULTS: The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. CONCLUSION: This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.

Authors
Quinn, JA; Desjardins, A; Weingart, J; Brem, H; Dolan, ME; Delaney, SM; Vredenburgh, J; Rich, J; Friedman, AH; Reardon, DA; Sampson, JH; Pegg, AE; Moschel, RC; Birch, R; McLendon, RE; Provenzale, JM; Gururangan, S; Dancey, JE; Maxwell, J; Tourt-Uhlig, S; Herndon, JE; Bigner, DD; Friedman, HS
MLA Citation
Quinn, JA, Desjardins, A, Weingart, J, Brem, H, Dolan, ME, Delaney, SM, Vredenburgh, J, Rich, J, Friedman, AH, Reardon, DA, Sampson, JH, Pegg, AE, Moschel, RC, Birch, R, McLendon, RE, Provenzale, JM, Gururangan, S, Dancey, JE, Maxwell, J, Tourt-Uhlig, S, Herndon, JE, Bigner, DD, and Friedman, HS. "Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma." J Clin Oncol 23.28 (October 1, 2005): 7178-7187.
PMID
16192602
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
23
Issue
28
Publish Date
2005
Start Page
7178
End Page
7187
DOI
10.1200/JCO.2005.06.502

Movement-attention coupling in infancy and attention problems in childhood.

Adaptive behavior requires the integration of body movement and attention. Therefore, individual differences in integration of movement and attention during infancy may have significance for development. We contacted families whose 8-year-old children (n=26; 16 females, 10 males; mean age 8 y 2 mo, SD 8 mo) participated in a previous study of movement-attention coupling at 1 or 3 months of age, to assess parent-reported attention or hyperactivity problems using the Child Behavior Checklist and Diagnostic and Statistical Manual of Mental Disorders (4th edn) criteria. Parent-reported attention problems at 8 years of age were associated with less suppression of body movement at onset of looking, and greater rebound of body movement following its initial suppression at 3 months, but not at 1 month. Parent-reported hyperactivity was not related to any of the infant movement-attention measures. Results suggests that the dynamic integration of movement and attention early in life may have functional significance for the development of attention problems in childhood.

Authors
Friedman, AH; Watamura, SE; Robertson, SS
MLA Citation
Friedman, AH, Watamura, SE, and Robertson, SS. "Movement-attention coupling in infancy and attention problems in childhood." Dev Med Child Neurol 47.10 (October 2005): 660-665.
PMID
16174308
Source
pubmed
Published In
Developmental Medicine & Child Neurology
Volume
47
Issue
10
Publish Date
2005
Start Page
660
End Page
665
DOI
10.1017/S0012162205001350

Chemotherapy and novel therapeutic approaches in malignant glioma.

Glial neoplasms represent 0.5-1% of all cancers in most Western countries. Malignant gliomas are among the most devastating cancers, leading to death in most cases. They present unique challenges due to their location, aggressive biological behavior and diffuse infiltrative growth. Notwithstanding the development of new surgical and radiation techniques in the last thirty years, a cure for malignant gliomas remains elusive. In this article, we will review the standard and new therapies used for malignant gliomas. As standard therapies, surgery, radiation therapy and systemic chemotherapy, are in a continuous process of evolution. Multiple chemotherapies have been used in malignant gliomas, as single agents, in combination, or with different modes of administration, including high-dose chemotherapy with stem cell rescue and intra-arterial chemotherapy. The last decade has been noticeable for the advent of a better understanding of the biology of malignant gliomas. This has stimulated active research in multiples areas and the advent of new treatment strategies. Techniques to circumvent the resistance mechanisms to chemotherapy have been evaluated, tyrosine kinase inhibitors have shown activity in malignant primary brain tumors and radioimmunotherapy remains an area of active research. In this article, we review the past, present and future treatments of malignant gliomas with a special interest on chemotherapy, resistance mechanisms and tyrosine kinase inhibitors.

Authors
Desjardins, A; Rich, JN; Quinn, JA; Vredenburgh, J; Gururangan, S; Sathornsumetee, S; Reardon, DA; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Desjardins, A, Rich, JN, Quinn, JA, Vredenburgh, J, Gururangan, S, Sathornsumetee, S, Reardon, DA, Friedman, AH, Bigner, DD, and Friedman, HS. "Chemotherapy and novel therapeutic approaches in malignant glioma. (Published online)" Front Biosci 10 (September 1, 2005): 2645-2668. (Review)
PMID
15970525
Source
pubmed
Published In
Frontiers in bioscience : a journal and virtual library
Volume
10
Publish Date
2005
Start Page
2645
End Page
2668

Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial.

BACKGROUND AND PURPOSE: Cerebral vasospasm remains a major source of morbidity after aneurysmal subarachnoid hemorrhage (SAH). We demonstrate that simvastatin reduces serum markers of brain injury and attenuates vasospasm after SAH. METHODS: Patients with angiographically documented aneurysmal SAH were randomized within 48 hours of symptom onset to receive either simvastatin (80 mg daily; n=19) or placebo (n=20) for 14 days. Plasma alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase were recorded weekly to evaluate laboratory evidence of hepatitis or myositis. Serum markers of brain injury were recorded daily. The primary end point of vasospasm was defined as clinical impression (delayed ischemic deficit not associated with rebleed, infection, or hydrocephalus) in the presence of > or =1 confirmatory radiographic test (angiography or transcranial Doppler demonstrating mean V(MCA) >160 m/sec). RESULTS: There were no significant differences in laboratory-defined transaminitis or myositis between groups. No patients developed clinical symptoms of myopathy or hepatitis. Plasma von Willebrand factor and S100beta were decreased 3 to 10 days after SAH (P<0.05) in patients receiving simvastatin versus placebo. Highest mean middle cerebral artery transcranial Doppler velocities were significantly lower in the simvastatin-treated group (103+/-41 versus 149+/-47; P<0.01). In addition, vasospasm was significantly reduced (P<0.05) in the simvastatin-treated group (5 of 19) compared with those who received placebo (12 of 20). CONCLUSIONS: The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.

Authors
Lynch, JR; Wang, H; McGirt, MJ; Floyd, J; Friedman, AH; Coon, AL; Blessing, R; Alexander, MJ; Graffagnino, C; Warner, DS; Laskowitz, DT
MLA Citation
Lynch, JR, Wang, H, McGirt, MJ, Floyd, J, Friedman, AH, Coon, AL, Blessing, R, Alexander, MJ, Graffagnino, C, Warner, DS, and Laskowitz, DT. "Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial." Stroke 36.9 (September 2005): 2024-2026.
PMID
16051891
Source
pubmed
Published In
Stroke
Volume
36
Issue
9
Publish Date
2005
Start Page
2024
End Page
2026
DOI
10.1161/01.STR.0000177879.11607.10

Predictors of outcome of myocarditis.

Heart failure from myocarditis may be transient or may progress to unremitting severe cardiac failure. This study was performed to determine the outcomes and prognostic features of pediatric patients with myocarditis. Patients with the diagnosis of myocarditis between 1990 and 2001 were identified through the coding system of Yale-New Haven Hospital. A total of 28 patients were included, with ages ranging from 1 day to 20 years. Before discharge, 11 patients developed unremitting severe cardiac failure. Of the remaining 17 patients, at the time of discharge 10 had normal systolic function and 7 had decreased systolic function. Unremitting cardiac failure developed in 9 of 14 patients (64%) with an ejection fraction or = 30% on admission (p

Authors
Kühn, B; Shapiro, ED; Walls, TA; Friedman, AH
MLA Citation
Kühn, B, Shapiro, ED, Walls, TA, and Friedman, AH. "Predictors of outcome of myocarditis." Pediatric cardiology 25.4 (September 2005): 379-384. (Academic Article)
Source
manual
Published In
Pediatric Cardiology
Volume
25
Issue
4
Publish Date
2005
Start Page
379
End Page
384
DOI
10.1007/s00246-003-0568-2

A retrospective analysis of a remifentanil/propofol general anesthetic for craniotomy before awake functional brain mapping.

UNLABELLED: We performed this study to summarize drug dosing, physiologic responses, and anesthetic complications from an IV general anesthetic technique for patients undergoing craniotomy for awake functional brain mapping. Review of 98 procedures revealed "most rapid" IV infusion rates for remifentanil 0.05, 0.05-0.09 microg x kg(-1) x min(-1) and propofol 115, 100-150 microg x kg(-1) x min(-1). The infusions lasted for 78, 58-98 min. Intraoperative emergence from general anesthesia was 9 (6-13) min after discontinuing IV infusions to allow for brain mapping and was independent of infusion duration and duration of craniotomy before mapping. Spontaneous ventilation was generally satisfactory during drug infusion, as evidenced by Sao(2) = 95% (92%-98%) and Paco(2) = 50 (47-55) mm Hg. However, we recorded at least one 30-s epoch of apnea in 69 of 96 patients. Maximum systolic arterial blood pressure was 150 (139-175) mm Hg and minimal systolic arterial blood pressure was 100 (70-150) mm Hg during drug infusion. Three patients experienced intraoperative seizures. Two patients did not tolerate the awake state and required reinduction of general anesthesia. No patients required endotracheal intubation or discontinuation of surgery. This general anesthetic technique is effective for craniotomy with awake functional brain mapping and offers an alternative to continuous wakefulness or other IV sedation techniques. IMPLICATIONS: An IV general anesthetic technique using remifentanil and propofol is an effective method allowing for reliable emergence for intraoperative awake functional brain mapping during craniotomy.

Authors
Keifer, JC; Dentchev, D; Little, K; Warner, DS; Friedman, AH; Borel, CO
MLA Citation
Keifer, JC, Dentchev, D, Little, K, Warner, DS, Friedman, AH, and Borel, CO. "A retrospective analysis of a remifentanil/propofol general anesthetic for craniotomy before awake functional brain mapping." Anesth Analg 101.2 (August 2005): 502-508.
PMID
16037168
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
101
Issue
2
Publish Date
2005
Start Page
502
End Page
508
DOI
10.1213/01.ANE.0000160533.51420.44

Myxopapillary ependymoma and fatty filum in an adult with tethered cord syndrome: a shared embryological lesion? Case report.

OBJECTIVE AND IMPORTANCE: Myxopapillary ependymoma and fatty fila are traditionally thought to arise via completely different pathophysiologies. Recognition of these distinct pathologies in the same patient is important for appropriate treatment and prognosis. CLINICAL PRESENTATION: A 28-year-old woman presented with low back pain, bilateral leg radiculopathies, and mild leg weakness suggestive of tethered cord syndrome. Magnetic resonance imaging revealed lesions in the area of the conus medullaris consistent with a myxopapillary ependymoma and fatty filum. INTERVENTION: Under the surveillance of intraoperative electromyographic monitoring, the patient underwent an L4-S2 laminectomy for transection of the fatty filum and gross total resection of the mass. Histopathological examination confirmed the presence of these two distinct pathologies. CONCLUSION: We report an unusual case of a myxopapillary ependymoma coexisting with a fatty filum in an adult patient. To the best of our knowledge, this association has not yet been reported. This raises the interesting question of a possible associative or causative relationship between these distinct pathologies, which have traditionally been thought to arise from different mechanisms.

Authors
Adamson, DC; Cummings, TJ; Friedman, AH
MLA Citation
Adamson, DC, Cummings, TJ, and Friedman, AH. "Myxopapillary ependymoma and fatty filum in an adult with tethered cord syndrome: a shared embryological lesion? Case report." Neurosurgery 57.2 (August 2005): E373-.
PMID
16094143
Source
pubmed
Published In
Neurosurgery
Volume
57
Issue
2
Publish Date
2005
Start Page
E373

Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.

UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy. METHODS: Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients. RESULTS: This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival. CONCLUSION: This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

Authors
Akabani, G; Reardon, DA; Coleman, RE; Wong, TZ; Metzler, SD; Bowsher, JE; Barboriak, DP; Provenzale, JM; Greer, KL; DeLong, D; Friedman, HS; Friedman, AH; Zhao, X-G; Pegram, CN; McLendon, RE; Bigner, DD; Zalutsky, MR
MLA Citation
Akabani, G, Reardon, DA, Coleman, RE, Wong, TZ, Metzler, SD, Bowsher, JE, Barboriak, DP, Provenzale, JM, Greer, KL, DeLong, D, Friedman, HS, Friedman, AH, Zhao, X-G, Pegram, CN, McLendon, RE, Bigner, DD, and Zalutsky, MR. "Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study." J Nucl Med 46.6 (June 2005): 1042-1051.
PMID
15937318
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
46
Issue
6
Publish Date
2005
Start Page
1042
End Page
1051

Surgical management of petroclival meningiomas: defining resection goals based on risk of neurological morbidity and tumor recurrence rates in 137 patients.

OBJECTIVE: Meningiomas arising from the petroclival region remain a challenging surgical problem. Because of the substantial risk of neurological morbidity, uniformly pursuing a gross total resection (GTR) to minimize tumor recurrence rates may not be justified. We sought to define optimal resection goals based on risk factors for postoperative neurological morbidity and tumor recurrence rates. METHODS: This series represents our experience with 137 meningiomas arising from the petroclival region resected between June 1993 and October 2002. There were 38 male and 99 female patients with a mean age of 53 years. RESULTS: GTR was achieved in 40% of patients, and near total resection (NTR) was achieved in 40% of patients. One operative death occurred. Twenty-six percent of patients experienced new postoperative cranial nerve deficits, paresis, or ataxia when assessed at a mean follow-up of 8.3 months. The risk of cranial nerve deficits increased with prior resection (P < 0.001), preoperative cranial nerve deficit (P = 0.005), tumor adherence to neurovascular structures (P = 0.046), and fibrous tumor consistency (P = 0.005). The risk of paresis or ataxia increased with prior resection (P = 0.001) and tumor adherence (P = 0.045). Selective NTR rather than GTR in patients with adherent or fibrous tumors significantly reduced the rate of neurological deficits. Radiographic recurrence or progression occurred in 17.6% of patients at a mean follow-up of 29.8 months. Tumor recurrence rates after GTR and NTR did not differ significantly (P = 0.111). CONCLUSION: Intraoperatively defined tumor characteristics played a critical role in identifying the subset of patients with an increased risk of postoperative deficits. By selectively pursuing an NTR rather than a GTR, neurological morbidity was reduced significantly without significantly increasing the rate of tumor recurrence.

Authors
Little, KM; Friedman, AH; Sampson, JH; Wanibuchi, M; Fukushima, T
MLA Citation
Little, KM, Friedman, AH, Sampson, JH, Wanibuchi, M, and Fukushima, T. "Surgical management of petroclival meningiomas: defining resection goals based on risk of neurological morbidity and tumor recurrence rates in 137 patients." Neurosurgery 56.3 (March 2005): 546-559. (Review)
PMID
15730581
Source
pubmed
Published In
Neurosurgery
Volume
56
Issue
3
Publish Date
2005
Start Page
546
End Page
559

Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma.

BACKGROUND: In the current study, the authors report a Phase II trial of irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant glioma (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients with recurrent disease. METHODS: Patients with MG at any type of recurrence received CPT-11, administered as a 90-minute intravenous infusion on Weeks 1, 2, 4, and 5 of each 6-week cycle plus celecoxib, which was administered continuously at a dose of 400 mg twice a day. CPT-11 was given at a dose of 350 mg/m(2) for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and at a dose of 125 mg/m(2) for those patients not receiving EIAEDs. Assessments were performed after every cycle. The primary endpoint was radiographic response and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and therapeutic safety. RESULTS: Thirty-four of the 37 patients enrolled in the current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with recurrent anaplastic astrocytoma (AA). Twenty-one patients were receiving EIAEDs and 16 patients were not. The median follow-up time was 76.9 weeks. Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe. Hematologic toxicities of >/= Grade 3 (according the second version of the Common Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic toxicity, occurred with equal frequency (8%), regardless of whether the patient was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent GBM, achieved an objective radiographic response whereas an additional 13 patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6-month PFS was reported to be 25.1%. The median OS was 31.5 weeks. CONCLUSIONS: The results of the current study confirm that CPT-11 plus celecoxib can be safely administered concurrently at full dose levels, and that this regimen has encouraging activity among heavily pretreated patients with recurrent MG.

Authors
Reardon, DA; Quinn, JA; Vredenburgh, J; Rich, JN; Gururangan, S; Badruddoja, M; Herndon, JE; Dowell, JM; Friedman, AH; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Vredenburgh, J, Rich, JN, Gururangan, S, Badruddoja, M, Herndon, JE, Dowell, JM, Friedman, AH, and Friedman, HS. "Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma." Cancer 103.2 (January 15, 2005): 329-338.
PMID
15558802
Source
pubmed
Published In
Cancer
Volume
103
Issue
2
Publish Date
2005
Start Page
329
End Page
338
DOI
10.1002/cncr.20776

Surgical exposure of the sciatic nerve in the gluteal region: Anatomic and historical comparison of two approaches

OBJECTIVE: To increase awareness among neurosurgeons of alternative surgical approaches to lesions of the sciatic nerve in the gluteal region. METHODS: The dominant surgical approach to lesions of the proximal sciatic nerve involves detachment and medial reflection of the gluteus maximus through a questionmark incision. An alternative to this infragluteal exposure is a transgluteal approach, which provides access to the sciatic nerve by splitting the gluteus maximus through a curvilinear incision. We explored the anatomy and surgical history of these approaches through cadaveric study, our own case series, and a literature review. RESULTS: The infragluteal approach uses a larger incision, extensive dissection, and postoperative bracing while allowing wide exposure of the nerve inferiorly into the thigh. By contrast, the transgluteal approach minimizes dissection and spares muscle attachments but requires meticulous attention to hemostasis and provides a more focal exposure of the sciatic nerve. During the past century, the infragluteal approach has been described more frequently and has become increasingly popular among peripheral-nerve surgeons. For comparison, we present three patients in whom the transgluteal approach was used to treat substantial lesions of the proximal sciatic nerve. CONCLUSION: At the present time, the majority of peripheral nerve surgeons use an infragluteal approach to the proximal sciatic nerve. However, for select patients with well-defined and localized lesions, the transgluteal approach may provide sufficient nerve exposure with lowered operative complexity and postoperative morbidity.

Authors
Patil, PG; Friedman, AH
MLA Citation
Patil, PG, and Friedman, AH. "Surgical exposure of the sciatic nerve in the gluteal region: Anatomic and historical comparison of two approaches." Neurosurgery 56.1 SUPPL. (January 1, 2005). (Review)
Source
scopus
Published In
Neurosurgery
Volume
56
Issue
1 SUPPL.
Publish Date
2005
DOI
10.1227/01.NEU.0000144169.84261.9D

Surgical exposure of the sciatic nerve in the gluteal region: anatomic and historical comparison of two approaches.

OBJECTIVE: To increase awareness among neurosurgeons of alternative surgical approaches to lesions of the sciatic nerve in the gluteal region. METHODS: The dominant surgical approach to lesions of the proximal sciatic nerve involves detachment and medial reflection of the gluteus maximus through a question-mark incision. An alternative to this infragluteal exposure is a transgluteal approach, which provides access to the sciatic nerve by splitting the gluteus maximus through a curvilinear incision. We explored the anatomy and surgical history of these approaches through cadaveric study, our own case series, and a literature review. RESULTS: The infragluteal approach uses a larger incision, extensive dissection, and postoperative bracing while allowing wide exposure of the nerve inferiorly into the thigh. By contrast, the transgluteal approach minimizes dissection and spares muscle attachments but requires meticulous attention to hemostasis and provides a more focal exposure of the sciatic nerve. During the past century, the infragluteal approach has been described more frequently and has become increasingly popular among peripheral-nerve surgeons. For comparison, we present three patients in whom the transgluteal approach was used to treat substantial lesions of the proximal sciatic nerve. CONCLUSION: At the present time, the majority of peripheral nerve surgeons use an infragluteal approach to the proximal sciatic nerve. However, for select patients with well-defined and localized lesions, the transgluteal approach may provide sufficient nerve exposure with lowered operative complexity and postoperative morbidity.

Authors
Patil, PG; Friedman, AH
MLA Citation
Patil, PG, and Friedman, AH. "Surgical exposure of the sciatic nerve in the gluteal region: anatomic and historical comparison of two approaches." Neurosurgery 56.1 Suppl (January 2005): 165-171.
PMID
15799806
Source
pubmed
Published In
Neurosurgery
Volume
56
Issue
1 Suppl
Publish Date
2005
Start Page
165
End Page
171

Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study.

Glioblastoma multiforme remains refractory to conventional therapy, and novel therapeutic modalities are desperately needed. TP-38 is a recombinant chimeric protein containing a genetically engineered form of the cytotoxic Pseudomonas exotoxin fused to transforming growth factor (TGF)-alpha. TGF-alpha binds with high affinity to the epidermal growth factor receptor, which is uniformly overexpressed in malignant gliomas, often because of gene amplification. Prior to therapy with TP-38, the patient described here was completely refractory to multiple other therapies, with radiographic and pathologic evidence of tumor progression. After therapy, she improved clinically, was weaned off steroids and anti-convulsants, and experienced a progressive decrease in enhancing tumor volume. Despite multiple prior recurrences, she has not progressed for >43 months after TP-38 therapy. Small remaining areas of enhancement demonstrate no evidence of tumor histologically and are hypometabolic on positron emission tomography. This report describes a dramatic and sustained clinical and radiographic response in a patient with a bifrontal glioblastoma multiforme treated with intratumoral infusion of a novel targeted toxin, TP-38.

Authors
Sampson, JH; Reardon, DA; Friedman, AH; Friedman, HS; Coleman, RE; McLendon, RE; Pastan, I; Bigner, DD
MLA Citation
Sampson, JH, Reardon, DA, Friedman, AH, Friedman, HS, Coleman, RE, McLendon, RE, Pastan, I, and Bigner, DD. "Sustained radiographic and clinical response in patient with bifrontal recurrent glioblastoma multiforme with intracerebral infusion of the recombinant targeted toxin TP-38: case study." Neuro Oncol 7.1 (January 2005): 90-96.
PMID
15701286
Source
pubmed
Published In
Neuro-Oncology
Volume
7
Issue
1
Publish Date
2005
Start Page
90
End Page
96
DOI
10.1215/S1152851703000589

Central nervous system cancers Clinical Practice Guidelines in Oncology

In the year 2005, an estimated 18,500 new cases of primary brain and nervous system neoplasms will be diagnosed in the United States. These tumors will be responsible for approximately 12,760 deaths. The incidence of primary malignant brain tumors has been increasing over the past 25 years, especially in elderly persons (rates are increasing at about 1.2% each year). Metastatic disease to the central nervous system (CNS) occurs much more frequently, with an incidence about 10 times that of primary brain tumors. It is estimated between 20% and 40% of patients with systemic cancer will develop brain metastases. © Journal of the National Comprehensive Cancer Network.

Authors
Brem, SS; Bierman, PJ; Black, P; Blumenthal, DT; Brem, H; Chamberlain, MC; Chiocca, EA; DeAngelis, LM; Fenstermaker, RA; Fine, HA; Friedman, A; Glass, J; Grossman, SA; Heimberger, AB; Junck, L; Levin, V; Loeffler, JJ; Maor, MH; Narayana, A; Newton, HB; Olivi, A; Portnow, J; Prados, M; Raizer, JJ; Rosenfeld, SS; Shrieve, DC; Jr, AKS; Spence, AM; Vrionis, FD
MLA Citation
Brem, SS, Bierman, PJ, Black, P, Blumenthal, DT, Brem, H, Chamberlain, MC, Chiocca, EA, DeAngelis, LM, Fenstermaker, RA, Fine, HA, Friedman, A, Glass, J, Grossman, SA, Heimberger, AB, Junck, L, Levin, V, Loeffler, JJ, Maor, MH, Narayana, A, Newton, HB, Olivi, A, Portnow, J, Prados, M, Raizer, JJ, Rosenfeld, SS, Shrieve, DC, Jr, AKS, Spence, AM, and Vrionis, FD. "Central nervous system cancers Clinical Practice Guidelines in Oncology." JNCCN Journal of the National Comprehensive Cancer Network 3.5 (2005): 644-690.
PMID
16194456
Source
scival
Published In
Journal of the National Comprehensive Cancer Network : JNCCN
Volume
3
Issue
5
Publish Date
2005
Start Page
644
End Page
690

External rotation as a result of suprascapular nerve neurotization in obstetric brachial plexus lesions: Comments

Authors
Laurent, JP; Friedman, AH; Adelson, PD; Sutton, LN
MLA Citation
Laurent, JP, Friedman, AH, Adelson, PD, and Sutton, LN. "External rotation as a result of suprascapular nerve neurotization in obstetric brachial plexus lesions: Comments." Neurosurgery 57.3 (2005): 536-537.
Source
scival
Published In
Neurosurgery
Volume
57
Issue
3
Publish Date
2005
Start Page
536
End Page
537

Management and outcomes of 42 surgical suprascapular nerve injuries and entrapments: Comments

Authors
Huang, JH; Zager, EL; Friedman, AH; Boulis, NM; Kliot, MM
MLA Citation
Huang, JH, Zager, EL, Friedman, AH, Boulis, NM, and Kliot, MM. "Management and outcomes of 42 surgical suprascapular nerve injuries and entrapments: Comments." Neurosurgery 57.1 (2005): 126-127.
Source
scival
Published In
Neurosurgery
Volume
57
Issue
1
Publish Date
2005
Start Page
126
End Page
127

Surgical management of 10 genitofemoral neuralgias at the Louisiana State University Health Sciences Center - Comments

Authors
Huang, JH; Zager, EL; McGillicuddy, JE; Friedman, AH; Boulis, NM
MLA Citation
Huang, JH, Zager, EL, McGillicuddy, JE, Friedman, AH, and Boulis, NM. "Surgical management of 10 genitofemoral neuralgias at the Louisiana State University Health Sciences Center - Comments." Neurosurgery 56.2 (2005): 302-303.
Source
scival
Published In
Neurosurgery
Volume
56
Issue
2
Publish Date
2005
Start Page
302
End Page
303

Surgical exposure of the sciatic nerve in the gluteal region: Anatomic and historical comparison of two approaches

OBJECTIVE: To increase awareness among neurosurgeons of alternative surgical approaches to lesions of the sciatic nerve in the gluteal region. METHODS: The dominant surgical approach to lesions of the proximal sciatic nerve involves detachment and medial reflection of the gluteus maximus through a questionmark incision. An alternative to this infragluteal exposure is a transgluteal approach, which provides access to the sciatic nerve by splitting the gluteus maximus through a curvilinear incision. We explored the anatomy and surgical history of these approaches through cadaveric study, our own case series, and a literature review. RESULTS: The infragluteal approach uses a larger incision, extensive dissection, and postoperative bracing while allowing wide exposure of the nerve inferiorly into the thigh. By contrast, the transgluteal approach minimizes dissection and spares muscle attachments but requires meticulous attention to hemostasis and provides a more focal exposure of the sciatic nerve. During the past century, the infragluteal approach has been described more frequently and has become increasingly popular among peripheral-nerve surgeons. For comparison, we present three patients in whom the transgluteal approach was used to treat substantial lesions of the proximal sciatic nerve. CONCLUSION: At the present time, the majority of peripheral nerve surgeons use an infragluteal approach to the proximal sciatic nerve. However, for select patients with well-defined and localized lesions, the transgluteal approach may provide sufficient nerve exposure with lowered operative complexity and postoperative morbidity.

Authors
Patil, PG; Friedman, AH
MLA Citation
Patil, PG, and Friedman, AH. "Surgical exposure of the sciatic nerve in the gluteal region: Anatomic and historical comparison of two approaches." Neurosurgery 56.1 SUPPL. (2005): ONS-165-ONS-170-.
Source
scival
Published In
Neurosurgery
Volume
56
Issue
1 SUPPL.
Publish Date
2005
Start Page
ONS-165-ONS-170
DOI
10.1227/01.NEU.0000144169.84261.9D

Brain metastases from malignant melanoma

Authors
Sampson, JH; Shafman, TD; Carter, JH; Friedman, AH; Seigler, HF
MLA Citation
Sampson, JH, Shafman, TD, Carter, JH, Friedman, AH, and Seigler, HF. "Brain metastases from malignant melanoma." Textbook of Neuro-Oncology (2005): 430-438.
Source
scival
Published In
Textbook of Neuro-Oncology
Publish Date
2005
Start Page
430
End Page
438
DOI
10.1016/B978-0-7216-8148-1.50059-0

Ependymoma

Authors
Friedman, AH; McLendon, RE; Provenzale, JN; Friedman, HS
MLA Citation
Friedman, AH, McLendon, RE, Provenzale, JN, and Friedman, HS. "Ependymoma." Textbook of Neuro-Oncology (2005): 190-198.
Source
scival
Published In
Textbook of Neuro-Oncology
Publish Date
2005
Start Page
190
End Page
198
DOI
10.1016/B978-0-7216-8148-1.50028-0

Xanthogranuloma of the sciatic nerve: case report.

OBJECTIVE AND IMPORTANCE: Xanthogranulomas involving the central or peripheral nervous system are extraordinarily rare. None have been reported in the lower extremity. Here, we report and characterize the first case of xanthogranuloma of the sciatic nerve. CLINICAL PRESENTATION: A 58-year-old woman presented with poorly localized right back and groin pain. Magnetic resonance imaging studies revealed an enhancing lesion of the sciatic nerve in the right gluteal region. INTERVENTION: The sciatic nerve xanthogranuloma was resected without complication. CONCLUSION: Our report indicates that xanthogranuloma, although extremely rare, may occur throughout the nervous system. Our evaluation demonstrates that such lesions involving the peripheral nervous system have similar pathological characteristics to xanthogranulomas that more commonly occur in the skin.

Authors
Patil, PG; Cummings, TJ; Nunley, JA; Friedman, AH
MLA Citation
Patil, PG, Cummings, TJ, Nunley, JA, and Friedman, AH. "Xanthogranuloma of the sciatic nerve: case report." Neurosurgery 55.6 (December 2004): 1435-.
PMID
15574230
Source
pubmed
Published In
Neurosurgery
Volume
55
Issue
6
Publish Date
2004
Start Page
1435

Training pediatric residents to evaluate congenital heart disease in the current era.

Working with young pediatricians to create an exciting educational environment in which to learn cardiology remains a challenge for all of us. Numerous forces impact our efforts, making the process of training residents to evaluate and treat congenital heart disease in the current era a dynamic and, at times, difficult endeavor. This article considers the changes that have occurred in the medical school graduate who chooses pediatrics and subsequently pediatric cardiology as a career; explores the changes in the graduate medical training guidelines, requirements, and restrictions that have been put into place within the last several years; and discusses the seemingly constant advances in scientific understanding and technology that shape our field and move us forward as a discipline.

Authors
Weeks, B; Friedman, AH
MLA Citation
Weeks, B, and Friedman, AH. "Training pediatric residents to evaluate congenital heart disease in the current era." Pediatric clinics of North America 51.6 (December 2004): 1641-51, ix. (Academic Article)
Source
manual
Published In
Pediatric Clinics of North America
Volume
51
Issue
6
Publish Date
2004
Start Page
1641
End Page
51, ix
DOI
10.1016/j.pcl.2004.07.003

Acquired subretinal flecks secondary to hypovitaminosis A in a patient with hepatitis C.

Authors
Elison, JR; Friedman, AH; Brodie, SE
MLA Citation
Elison, JR, Friedman, AH, and Brodie, SE. "Acquired subretinal flecks secondary to hypovitaminosis A in a patient with hepatitis C." Documenta ophthalmologica. Advances in ophthalmology 109.3 (November 2004): 279-281. (Academic Article)
Source
manual
Published In
Documenta Ophthalmologica
Volume
109
Issue
3
Publish Date
2004
Start Page
279
End Page
281

Malignant peripheral nerve sheath tumor of the spine after radiation therapy for Hodgkin's lymphoma.

We report the development of a malignant peripheral nerve sheath tumor (MPNST) in 2 patients after irradiation for Hodgkin's lymphoma. Clinicians should be aware of this uncommon, but important fatal complication of radiation therapy. The first case is a 37-year-old man who was diagnosed with nodular sclerosing (NS) Hodgkin's lymphoma and underwent successful mantle radiation. He presented to our neurosurgery service with a left C6 radiculopathy 6 years later. The second case is a 30-year-old female diagnosed with NS Hodgkin's lymphoma. She did well with extensive radiotherapy until 5 years later when she developed severe right arm and chest pain secondary to recurrent lymphoma. After aggressive radio- and chemotherapy, she presented to the neurosurgery service with a right Horner's syndrome, right C6 radiculopathy, and weakness of her right triceps and wrist extensors. Both patients obtained magnetic resonance imaging revealing intradural extramedullary cervical nerve root associated mass lesions. Two years after radiation therapy for his Hodgkin's lymphoma, the first patient underwent a C6 laminectomy at an outside institution for resection of a benign neurofibroma. Four years later, he underwent a posterior C5-7 laminectomy with lateral mass plate fusion and partial excision of a recurrent mass diagnosed as a MPNST. The second patient underwent a C5-6 hemilaminectomy and partial resection of a tumor also pathologically consistent with MPNST. We present 2 case reports of patients who developed neurofibrosarcomatous tumors with malignant transformation after undergoing radiation therapy for Hodgkin's lymphoma. Despite prompt surgical resection, these tumors exhibited aggressive behavior. Numerous cases of soft tissue tumors have been described to arise in areas of prior radiation therapy; however, there have been rare reports of de novo MPNST after radiation therapy, especially in the setting of Hodgkin's lymphoma. Postirradiation MPNST should be considered in the differential diagnosis of a painful, enlarging mass in a previously irradiated area.

Authors
Adamson, DC; Cummings, TJ; Friedman, AH
MLA Citation
Adamson, DC, Cummings, TJ, and Friedman, AH. "Malignant peripheral nerve sheath tumor of the spine after radiation therapy for Hodgkin's lymphoma." Clin Neuropathol 23.5 (September 2004): 245-255.
PMID
15581029
Source
pubmed
Published In
Clinical neuropathology
Volume
23
Issue
5
Publish Date
2004
Start Page
245
End Page
255

Electrical Stimulation of the Conus Medullaris to Control Bladder Emptying in Paraplegia: A Ten-Year Review

Authors
Nashold, BS; Friedman, H; Grimes, J
MLA Citation
Nashold, BS, Friedman, H, and Grimes, J. "Electrical Stimulation of the Conus Medullaris to Control Bladder Emptying in Paraplegia: A Ten-Year Review." Stereotactic and Functional Neurosurgery 45.1-2 (July 1, 2004): 40-43.
Source
crossref
Published In
Stereotactic and functional neurosurgery
Volume
45
Issue
1-2
Publish Date
2004
Start Page
40
End Page
43
DOI
10.1159/000101576

Experience Using Two CT-Guided Stereotactic Biopsy Methods

Authors
Bullard, DE; Nashold, BS; Osborne, D; Burger, PC; Byrd, R; Schold, C; Oakes, WJ; Friedman, A; Triolo, P; Dubois, P
MLA Citation
Bullard, DE, Nashold, BS, Osborne, D, Burger, PC, Byrd, R, Schold, C, Oakes, WJ, Friedman, A, Triolo, P, and Dubois, P. "Experience Using Two CT-Guided Stereotactic Biopsy Methods." Stereotactic and Functional Neurosurgery 46.1-4 (July 1, 2004): 188-192.
Source
crossref
Published In
Stereotactic and functional neurosurgery
Volume
46
Issue
1-4
Publish Date
2004
Start Page
188
End Page
192
DOI
10.1159/000101260

Correlation of serum brain natriuretic peptide with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage.

OBJECTIVE: Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and may exacerbate delayed ischemic neurological deficits. We examined the temporal relationship between serum BNP elevation, hyponatremia, and the onset of delayed ischemic neurological deficits and determined whether serum BNP levels correlated with the 2-week outcome after SAH. METHODS: Serum BNP and sodium were measured prospectively every 12 hours for 14 days in 40 consecutive patients admitted with SAH. All patients remained euvolemic, underwent transcranial Doppler assessment every 48 hours, and underwent angiography at the onset of delayed neurological deficits. New-onset neurological deficits were attributed to vasospasm only in the absence of other causes and when supported by transcranial Doppler or cerebral angiography. RESULTS: Sixteen patients (40%) experienced symptomatic cerebral vasospasm after SAH. A more than threefold increase in admission serum BNP was associated with the onset of hyponatremia (P < 0.05). Mean BNP levels were similar between vasospasm and nonvasospasm patients fewer than 3 days after SAH (126 +/- 39 pg/ml versus 154 +/- 40 pg/ml; P = 0.61) but were elevated in the vasospasm cohort 4 to 6 days after SAH (285 +/- 67 pg/ml versus 116 +/- 30 pg/ml; P < 0.01), 7 to 9 days after SAH (278 +/- 72 pg/ml versus 166 +/- 45 pg/ml; P < 0.01), and 9 to 12 days after SAH (297 +/- 83 pg/ml versus 106 +/- 30 pg/ml; P < 0.01). BNP level remained independently associated with vasospasm adjusting for Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval, 1.1-1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4-fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after vasospasm onset. Patients with increasing BNP levels from admission demonstrated no change (0 +/- 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 +/- 2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without increasing serum BNP levels. CONCLUSION: Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.

Authors
McGirt, MJ; Blessing, R; Nimjee, SM; Friedman, AH; Alexander, MJ; Laskowitz, DT; Lynch, JR
MLA Citation
McGirt, MJ, Blessing, R, Nimjee, SM, Friedman, AH, Alexander, MJ, Laskowitz, DT, and Lynch, JR. "Correlation of serum brain natriuretic peptide with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage." Neurosurgery 54.6 (June 2004): 1369-1373.
PMID
15157293
Source
pubmed
Published In
Neurosurgery
Volume
54
Issue
6
Publish Date
2004
Start Page
1369
End Page
1373

Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme.

PURPOSE: We have reported previously that tumors expressing wild-type epidermal growth factor receptor (EGFR) in a murine model are sensitive to the EGFR tyrosine kinase inhibitor gefitinib, whereas tumors expressing mutant EGFR variant III (EGFRvIII) are resistant. Determination of how this differential inhibition occurs may be important to patient selection and treatment criteria, as well as the design of future therapeutics for glioblastoma multiforme. EXPERIMENTAL DESIGN: We have determined and quantified how treatment with gefitinib at commonly used, noncytotoxic doses affects neoplastic functions ascribed to EGFRvIII, including downstream signaling by Akt, DNA synthesis, and cellular invasion. In doing so, we have tested and compared a series of wild-type and mutant EGFRvIII-expressing fibroblast and glioblastoma cell lines in vitro after treatment with gefitinib. RESULTS: The results of these experiments demonstrate that short-term treatment with gefitinib (approximately 24 h) does not reduce phosphorylation of EGFRvIII, whereas EGFR phosphorylation is inhibited in a dose-dependent manner. However, after daily treatment with gefitinib, phosphorylation declines for EGFRvIII by day 3 and later. Nevertheless, after 7 days of daily treatment, cells that express and are dependent on EGFRvIII for tumorigenic growth are not effectively growth inhibited. This may be due in part to phosphorylation of Akt, which is inhibited in EGFR-expressing cells after treatment with gefitinib, but is unaffected in cells expressing EGFRvIII. Cell cycle analysis shows that nascent DNA synthesis in EGFR-expressing cells is inhibited in a dose-dependent manner by gefitinib, yet is unaffected in EGFRvIII-expressing cells with increasing dosage. Furthermore, cells expressing EGFRvIII demonstrate greater invasive capability with increasing gefitinib concentration when compared with cells expressing EGFR after treatment. CONCLUSIONS: We conclude that the neoplastic phenotype of EGFRvIII is relatively resistant to gefitinib and requires higher doses, repeated dosing, and longer exposure to decrease receptor phosphorylation. However, this decrease does not effectively inhibit the biologically relevant processes of DNA synthesis, cellular growth, and invasion in cells expressing EGFRvIII.

Authors
Learn, CA; Hartzell, TL; Wikstrand, CJ; Archer, GE; Rich, JN; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Learn, CA, Hartzell, TL, Wikstrand, CJ, Archer, GE, Rich, JN, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Resistance to tyrosine kinase inhibition by mutant epidermal growth factor receptor variant III contributes to the neoplastic phenotype of glioblastoma multiforme." Clin Cancer Res 10.9 (May 1, 2004): 3216-3224.
PMID
15131063
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
10
Issue
9
Publish Date
2004
Start Page
3216
End Page
3224

An eclectic history of peripheral nerve surgery.

It is hard to decide where history stops and contemporary development of peripheral nerve surgery begins. This article provides an eclectic view of the history of peripheral nerve surgery. In trying to keep the story moving, the publications of many authors have been omitted. For this, we are sorry. We have also stopped short of reporting the contemporary history of molecular biology as applied to peripheral nerve regeneration. The future of peripheral nerve repairs lies in our understanding of the molecular cascades that stimulate axon growth and guide the axon to its proper destination. We hope that this review shows the reader that researchers who got us where we are traveled a road filled with erroneous dogma, bad advice,and misleading data. We believe that the lessons learned from those who brought us back to the right path are applicable to many disciplines.

Authors
Little, KM; Zomorodi, AR; Selznick, LA; Friedman, AH
MLA Citation
Little, KM, Zomorodi, AR, Selznick, LA, and Friedman, AH. "An eclectic history of peripheral nerve surgery." Neurosurg Clin N Am 15.2 (April 2004): 109-123.
PMID
15177311
Source
pubmed
Published In
Neurosurgery Clinics of North America
Volume
15
Issue
2
Publish Date
2004
Start Page
109
End Page
123
DOI
10.1016/j.nec.2003.12.002

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma.

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs.

Authors
Quinn, JA; Reardon, DA; Friedman, AH; Rich, JN; Sampson, JH; Vredenburgh, J; Gururangan, S; Provenzale, JM; Walker, A; Schweitzer, H; Bigner, DD; Tourt-Uhlig, S; Herndon, JE; Affronti, ML; Jackson, S; Allen, D; Ziegler, K; Bohlin, C; Lentz, C; Friedman, HS
MLA Citation
Quinn, JA, Reardon, DA, Friedman, AH, Rich, JN, Sampson, JH, Vredenburgh, J, Gururangan, S, Provenzale, JM, Walker, A, Schweitzer, H, Bigner, DD, Tourt-Uhlig, S, Herndon, JE, Affronti, ML, Jackson, S, Allen, D, Ziegler, K, Bohlin, C, Lentz, C, and Friedman, HS. "Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma." Neuro Oncol 6.2 (April 2004): 145-153.
PMID
15134629
Source
pubmed
Published In
Neuro-Oncology
Volume
6
Issue
2
Publish Date
2004
Start Page
145
End Page
153
DOI
10.1215/S1152851703000498

Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma.

In preclinical studies, BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, plus CPT-11 (irinotecan) exhibits schedule-dependent, synergistic activity against malignant glioma (MG). We previously established the maximum tolerated dose of CPT-11 when administered for 4 consecutive weeks in combination with BCNU administered on the first day of each 6-week cycle. We now report a phase 2 trial of BCNU plus CPT-11 for patients with MG. In the current study, BCNU (100 mg/m2) was administered on day 1 of each 6-week cycle. CPT-11 was administered on days 1, 8, 15, and 22 at 225 mg/m2 for patients receiving CYP3A1- or CYP3A4-inducing anticonvulsants and at 125 mg/m2 for those not on these medications. Newly diagnosed patients received up to 3 cycles before radiotherapy, while recurrent patients received up to 8 cycles. The primary end point of this study was radiographic response, while time to progression and overall survival were also assessed. Seventy-six patients were treated, including 37 with newly diagnosed tumors and 39 with recurrent disease. Fifty-six had glioblastoma multiforme, 18 had anaplastic astrocytoma, and 2 had anaplastic oligodendroglioma. Toxicities (grade > or =3) included infections (13%), thromboses (12%), diarrhea (10%), and neutropenia (7%). Interstitial pneumonitis developed in 4 patients. Five newly diagnosed patients (14%; 95% CI, 5%-29%) achieved a radiographic response (1 complete response and 4 partial responses). Five patients with recurrent MG also achieved a response (1 complete response and 4 partial responses; 13%; 95% CI, 4%-27%). More than 40% of both newly diagnosed and recurrent patients achieved stable disease. Median time to progression was 11.3 weeks for recurrent glioblastoma multiforme patients and 16.9 weeks for recurrent anaplastic astrocytoma/ anaplastic oligodendroglioma patients. We conclude that the activity of BCNU plus CPT-11 for patients with MG appears comparable to that of CPT-11 alone and may be more toxic.

Authors
Reardon, DA; Quinn, JA; Rich, JN; Gururangan, S; Vredenburgh, J; Sampson, JH; Provenzale, JM; Walker, A; Badruddoja, M; Tourt-Uhlig, S; Herndon, JE; Dowell, JM; Affronti, ML; Jackson, S; Allen, D; Ziegler, K; Silverman, S; Bohlin, C; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Reardon, DA, Quinn, JA, Rich, JN, Gururangan, S, Vredenburgh, J, Sampson, JH, Provenzale, JM, Walker, A, Badruddoja, M, Tourt-Uhlig, S, Herndon, JE, Dowell, JM, Affronti, ML, Jackson, S, Allen, D, Ziegler, K, Silverman, S, Bohlin, C, Friedman, AH, Bigner, DD, and Friedman, HS. "Phase 2 trial of BCNU plus irinotecan in adults with malignant glioma." Neuro Oncol 6.2 (April 2004): 134-144.
PMID
15134628
Source
pubmed
Published In
Neuro-Oncology
Volume
6
Issue
2
Publish Date
2004
Start Page
134
End Page
144

Awake craniotomy for malignant glioma resection

Authors
Little, KM; Friedman, AH
MLA Citation
Little, KM, and Friedman, AH. "Awake craniotomy for malignant glioma resection." International Congress Series 1259 (February 2004): 409-414.
Source
crossref
Published In
International Congress Series
Volume
1259
Publish Date
2004
Start Page
409
End Page
414
DOI
10.1016/S0531-5131(03)01727-8

Phase II trial of gefitinib in recurrent glioblastoma.

PURPOSE: To evaluate the efficacy and tolerability of gefitinib (ZD1839, Iressa; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. PATIENTS AND METHODS: This was an open-label, single-center phase II trial. Fifty-seven patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient initially received 500 mg of gefitinib orally once daily; dose escalation to 750 mg then 1,000 mg, if a patient received enzyme-inducing antiepileptic drugs or dexamethasone, was allowed within each patient. RESULTS: Although no objective tumor responses were seen among the 53 assessable patients, only 21% of patients (11 of 53 patients) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53 patients) underwent at least six 4-week cycles, and the 6-month event-free survival (EFS) was 13% (seven of 53 patients). The median EFS time was 8.1 weeks, and the median overall survival (OS) time from treatment initiation was 39.4 weeks. Adverse events were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent at higher doses. Withdrawal caused by drug-related adverse events occurred in 6% of patients (three of 53 patients). Although the presence of diarrhea positively predicted favorable OS from treatment initiation, epidermal growth factor receptor expression did not correlate with either EFS or OS. CONCLUSION: Gefitinib is well tolerated and has activity in patients with recurrent glioblastoma. Further study of this agent at higher doses is warranted.

Authors
Rich, JN; Reardon, DA; Peery, T; Dowell, JM; Quinn, JA; Penne, KL; Wikstrand, CJ; Van Duyn, LB; Dancey, JE; McLendon, RE; Kao, JC; Stenzel, TT; Ahmed Rasheed, BK; Tourt-Uhlig, SE; Herndon, JE; Vredenburgh, JJ; Sampson, JH; Friedman, AH; Bigner, DD; Friedman, HS
MLA Citation
Rich, JN, Reardon, DA, Peery, T, Dowell, JM, Quinn, JA, Penne, KL, Wikstrand, CJ, Van Duyn, LB, Dancey, JE, McLendon, RE, Kao, JC, Stenzel, TT, Ahmed Rasheed, BK, Tourt-Uhlig, SE, Herndon, JE, Vredenburgh, JJ, Sampson, JH, Friedman, AH, Bigner, DD, and Friedman, HS. "Phase II trial of gefitinib in recurrent glioblastoma." J Clin Oncol 22.1 (January 1, 2004): 133-142.
PMID
14638850
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
22
Issue
1
Publish Date
2004
Start Page
133
End Page
142
DOI
10.1200/JCO.2004.08.110

Median Nerve Excursion during Endoscopic Carpal Tunnel Release

OBJECTIVE: Restriction of the excursion of the nerve has been accepted as a pathogenetic element in carpal tunnel syndrome. The goal of this article was to evaluate the median nerve excursion in the carpal tunnel measured as a function of wrist position before and after endoscopic carpal tunnel release (ECTR) on 28 hands of 22 patients. METHODS: The position of cylindrical stainless steel markers embedded within the median nerve was measured by a direct radiographic technique. Each upper extremity was examined in three wrist positions. Then, endoscopic release with Menon's technique was performed, and the measurements were repeated. RESULTS: In this prospective clinical study, most (93%) of the patients experienced resolution of their symptoms. Before and after ECTR, median nerve excursion was linear and was affected by wrist position. Before ECTR, when the wrist was moved from the end of dorsiflexion to the end of palmar flexion, the median nerve underwent a mean total excursion of 28.8 mm at the wrist. A comparison of the before and after ECTR excursion showed no statistical differences in the amount of motion. CONCLUSION: The single-portal ECTR does not seem to influence the median nerve excursion for the wrist positions studied in patients with carpal tunnel syndrome. The results from this in vivo study showed longitudinal gliding of the median nerve twice as great as in in vitro studies.

Authors
Tuzuner, S; Özkaynak, S; Acikbas, C; Yildirim, A; Huang, JH; Zager, EL; Friedman, AH; Kline, DG; Gruen, JP
MLA Citation
Tuzuner, S, Özkaynak, S, Acikbas, C, Yildirim, A, Huang, JH, Zager, EL, Friedman, AH, Kline, DG, and Gruen, JP. "Median Nerve Excursion during Endoscopic Carpal Tunnel Release." Neurosurgery 54.5 (2004): 1155-1161.
PMID
15113471
Source
scival
Published In
Neurosurgery
Volume
54
Issue
5
Publish Date
2004
Start Page
1155
End Page
1161

Postherpetic neuralgia

Postherpetic neuralgia (PHN) is a chronic neuropathic pain syndrome defined as pain persisting more than 3 months after the resolution of herpes zoster-associated rash. It is often characterized as spontaneous aching or burning with paroxysmal shooting pains in the affected dermatome and may be accompanied by allodynia or hyperalgesia. There is an increased incidence of PHN in elderly patients, patients with ophthalmic herpes zoster, and immunocompromised patients. PHN may result from dorsal horn destruction, although pathophysiologic changes in more proximal central structures and distal peripheral structures have been described. Based on randomized, controlled studies, the most effective medical therapies include gabapentin, topical lidocaine, tricyclic antidepressants, and oral opioid analgesics. Surgical interventions for refractory cases including intrathecal drug administration, central ablative procedures, and central electrical stimulation continue to meet with limited success.

Authors
Little, KM; Friedman, AH
MLA Citation
Little, KM, and Friedman, AH. "Postherpetic neuralgia." Seminars in Neurosurgery 15.1 (2004): 93-98.
Source
scival
Published In
Seminars in Neurosurgery
Volume
15
Issue
1
Publish Date
2004
Start Page
93
End Page
98
DOI
10.1055/s-2004-830017

Cerebellar Malignant Fibrous Histiocytoma: Case Report and Literature Review

OBJECTIVE AND IMPORTANCE: Malignant fibrous histiocytoma in the central nervous system is uncommon. Fewer than 70 cases have been documented and, to the best of our knowledge, this is the first case arising from the cerebellum. CLINICAL PRESENTATION: A 44-year-old woman presented with headaches, vomiting, and dizziness. A neurological examination revealed right cerebellar syndrome. Brain computed tomographic scans revealed an isodense tumor in the right cerebellar hemisphere. The breast ultrasonographic, bone scintigraphic, and thoracoabdominal computed tomographic findings were normal. INTERVENTION: The patient was surgically treated. The tumor recurred 1.5 months later, demonstrating hemorrhagic characteristics on brain computed tomographic scans. The patient underwent a second operation, followed by radiotherapy. CONCLUSION: Malignant fibrous histiocytoma is still a controversial entity, and the lack of specific criteria means that it must be diagnosed via the process of elimination. With currently available therapy, our review can provide only a very poor prognosis. The median survival time was 27 months. In attempts to develop better therapeutic strategies, total excision and radiotherapy seem to represent the best treatment approach.

Authors
Hamlat, A; Adn, M; Caulet-Maugendre, S; Guegan, Y; Friedman, AH; Rock, JP; Commins, DL; Haddix, T; IV, GRH
MLA Citation
Hamlat, A, Adn, M, Caulet-Maugendre, S, Guegan, Y, Friedman, AH, Rock, JP, Commins, DL, Haddix, T, and IV, GRH. "Cerebellar Malignant Fibrous Histiocytoma: Case Report and Literature Review." Neurosurgery 54.3 (2004): 745-752.
PMID
15028153
Source
scival
Published In
Neurosurgery
Volume
54
Issue
3
Publish Date
2004
Start Page
745
End Page
752

Intraventricular Solitary Fibrous Tumor: An Unusual Tumor with Radiological, Ultrastructural and Immunohistochemical Evaluation: Case Report

OBJECTIVE AND IMPORTANCE: Intracranial solitary fibrous tumors have been described previously, but intraventricular solitary fibrous tumors are extremely rare. We present what is, to our knowledge, the first reported case of solitary fibrous tumor in the third ventricle. CLINICAL PRESENTATION: A 63-year-old man presented with weakness of his lower extremities and headaches. Computed tomography and magnetic resonance imaging of the brain revealed an enhancing mass in the posterior part of the third ventricle. INTERVENTION: The tumor originated from the wall of the left internal cerebral vein and extended to the posterior part of the third ventricle. Nearly total excision was performed via an infratentorial-supracerebellar approach. CONCLUSION: The differential diagnosis of intracranial solitary fibrous tumors includes fibroblastic meningioma, meningeal hemangiopericytoma, neurofibroma, and schwannoma. The differential diagnosis in the present case was greatly helped by the immunohistochemical and ultrastructural findings, along with a disease-free 3.5-year follow-up. These findings are presented with reference to previous reports.

Authors
Koçak, A; Çayli, SR; Saraç, K; Aydin, NE; Kanpolat, Y; Ugur, HC; Friedman, AH; Oyesiku, NM; Rock, JP
MLA Citation
Koçak, A, Çayli, SR, Saraç, K, Aydin, NE, Kanpolat, Y, Ugur, HC, Friedman, AH, Oyesiku, NM, and Rock, JP. "Intraventricular Solitary Fibrous Tumor: An Unusual Tumor with Radiological, Ultrastructural and Immunohistochemical Evaluation: Case Report." Neurosurgery 54.1 (2004): 213-217.
PMID
14683560
Source
scival
Published In
Neurosurgery
Volume
54
Issue
1
Publish Date
2004
Start Page
213
End Page
217

Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer.

PURPOSE: The monoclonal antibody (MAb) trastuzumab (Herceptin) effectively treats HER2-overexpressing extracerebral breast neoplasms. Delivery of such macromolecule therapeutic agents to intracerebral metastases, however, is limited by the tight junctions characteristic of the cerebral vasculature. Direct intracerebral microinfusion (ICM) is a technique that bypasses this blood-brain barrier and allows for a greater delivery of drugs directly into intracerebral tumors. EXPERIMENTAL DESIGN: A human breast cancer cell line transfected to overexpress HER2, MCF-7/HER2-18, was transplanted into the cerebrum of athymic rats. Saline, trastuzumab, or an isotype-matched control MAb was delivered systemically or by ICM to assess toxicity and efficacy. RESULTS: No clinical or histological toxicity related to trastuzumab was evident under any of the conditions studied. Delivery of trastuzumab (2 mg/kg) i.p. led to a median survival of 26.5 days, whereas treatment with trastuzumab (2 mg/kg) by ICM increased the median survival by 96% to 52 days, with two of nine rats surviving >120 days (P = 0.009). Treatment with an isotype-matched control MAb (16 mg/kg) resulted in a median survival of 21 days, which did not differ significantly from the survival of rats treated by ICM with saline (16 days; P = 0.42). Treatment by ICM with trastuzumab (16 mg/kg) led to a median survival of 45 days, with 2 of 10 rats surviving >120 days. These results represent 181% and 114% increases in median survival over the saline and MAb controls, respectively (P < 0.001). CONCLUSION: ICM of trastuzumab is safe and superior to systemic delivery as therapy for HER2-overexpressing intracerebral neoplasms in an athymic rat model.

Authors
Grossi, PM; Ochiai, H; Archer, GE; McLendon, RE; Zalutsky, MR; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Grossi, PM, Ochiai, H, Archer, GE, McLendon, RE, Zalutsky, MR, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer." Clin Cancer Res 9.15 (November 15, 2003): 5514-5520.
PMID
14654531
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
15
Publish Date
2003
Start Page
5514
End Page
5520

Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors.

TP-38 is a recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin, PE-38. After in vitro and in vivo animal studies that showed specific activity and defined the maximum tolerated dose (MTD), we investigated this agent in a Phase I trial. The primary objective of this study was to define the MTD and dose limiting toxicity of TP-38 delivered by convection-enhanced delivery in patients with recurrent malignant brain tumors. Twenty patients were enrolled in the study and doses were escalated from 25 ng/mL to 100 with a 40 mL infusion volume delivered by two catheters. One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. The overall median survival after TP-38 for all patients was 23 weeks whereas for those without radiographic evidence of residual disease at the time of therapy, the median survival was 31.9 weeks. Overall, 3 of 15 patients, with residual disease at the time of therapy, have demonstrated radiographic responses and one patient with a complete response and has survived greater than 83 weeks.

Authors
Sampson, JH; Akabani, G; Archer, GE; Bigner, DD; Berger, MS; Friedman, AH; Friedman, HS; Herndon, JE; Kunwar, S; Marcus, S; McLendon, RE; Paolino, A; Penne, K; Provenzale, J; Quinn, J; Reardon, DA; Rich, J; Stenzel, T; Tourt-Uhlig, S; Wikstrand, C; Wong, T; Williams, R; Yuan, F; Zalutsky, MR; Pastan, I
MLA Citation
Sampson, JH, Akabani, G, Archer, GE, Bigner, DD, Berger, MS, Friedman, AH, Friedman, HS, Herndon, JE, Kunwar, S, Marcus, S, McLendon, RE, Paolino, A, Penne, K, Provenzale, J, Quinn, J, Reardon, DA, Rich, J, Stenzel, T, Tourt-Uhlig, S, Wikstrand, C, Wong, T, Williams, R, Yuan, F, Zalutsky, MR, and Pastan, I. "Progress report of a Phase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-alpha and a mutated form of the Pseudomonas exotoxin termed PE-38 (TP-38) for the treatment of malignant brain tumors." J Neurooncol 65.1 (October 2003): 27-35.
PMID
14649883
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
65
Issue
1
Publish Date
2003
Start Page
27
End Page
35

Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors.

PURPOSE: The epidermal growth factor receptor (EGFR) is often amplified and structurally rearranged in malignant gliomas and other tumors such as breast and lung, with the most common mutation being EGFRvIII. In the study described here, we tested in mouse models a vaccine consisting of a peptide encompassing the tumor-specific mutated segment of EGFRvIII (PEP-3) conjugated to keyhole limpet hemocyanin [KLH (PEP-3-KLH)]. EXPERIMENTAL DESIGN: C57BL/6J or C3H mice were vaccinated with PEP-3-KLH and subsequently challenged either s.c. or intracerebrally with a syngeneic melanoma cell line stably transfected with a murine homologue of EGFRvIII. Control mice were vaccinated with KLH. To test its effect on established tumors, C3H mice were also challenged intracerebrally and subsequently vaccinated with PEP-3-KLH. RESULTS: S.c. tumors developed in all of the C57BL/6J mice vaccinated with KLH in Freund's adjuvant, and there were no long-term survivors. Palpable tumors never developed in 70% of the PEP-3-KLH-vaccinated mice. In the C57BL/6J mice receiving the PEP-3-KLH vaccine, the tumors that did develop were significantly smaller than those in the control group (P < 0.05). PEP-3-KLH vaccination did not result in significant cytotoxic responses in standard cytotoxicity assays; however, antibody titers against PEP-3 were enhanced. The passive transfer of sera from the immunized mice to nonimmunized mice protected 31% of the mice from tumor development (P < 0.05). In vivo depletion studies showed that the effector cell population was natural killer and CD8+ T cells, and in vitro assays showed that macrophages could lyse target tumor cells with serum from the PEP-3-KLH-vaccinated mice. Peptide vaccination was also sufficiently potent to have marked efficacy against intracerebral tumors, resulting in a >173% increase in median survival time, with 80% of the C3H mice achieving long-term survival (P = 0.014). In addition, C3H mice with established intracerebral tumor that received a single treatment of PEP-3-KLH showed a 26% increase in median survival time, with 40% long-term survival (P = 0.007). CONCLUSIONS: Vaccination with an EGFRvIII-specific peptide is efficacious against both s.c. and established intracerebral tumors. The therapeutic effect of peptide vaccination may be mediated, in part, by antibody-dependent cellular cytotoxicity.

Authors
Heimberger, AB; Crotty, LE; Archer, GE; Hess, KR; Wikstrand, CJ; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Heimberger, AB, Crotty, LE, Archer, GE, Hess, KR, Wikstrand, CJ, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Epidermal growth factor receptor VIII peptide vaccination is efficacious against established intracerebral tumors." Clin Cancer Res 9.11 (September 15, 2003): 4247-4254.
PMID
14519652
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
11
Publish Date
2003
Start Page
4247
End Page
4254

Congenitally absent C-7 pedicle presenting as a jumped locked facet. Case illustration.

Authors
Dimitrov, DF; Bronec, PR; Friedman, AH
MLA Citation
Dimitrov, DF, Bronec, PR, and Friedman, AH. "Congenitally absent C-7 pedicle presenting as a jumped locked facet. Case illustration." J Neurosurg 99.2 Suppl (September 2003): 239-.
PMID
12956469
Source
pubmed
Published In
Journal of neurosurgery
Volume
99
Issue
2 Suppl
Publish Date
2003
Start Page
239

High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.

PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.

Authors
Gururangan, S; McLaughlin, C; Quinn, J; Rich, J; Reardon, D; Halperin, EC; Herndon, J; Fuchs, H; George, T; Provenzale, J; Watral, M; McLendon, RE; Friedman, A; Friedman, HS; Kurtzberg, J; Vredenbergh, J; Martin, PL
MLA Citation
Gururangan, S, McLaughlin, C, Quinn, J, Rich, J, Reardon, D, Halperin, EC, Herndon, J, Fuchs, H, George, T, Provenzale, J, Watral, M, McLendon, RE, Friedman, A, Friedman, HS, Kurtzberg, J, Vredenbergh, J, and Martin, PL. "High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas." J Clin Oncol 21.11 (June 1, 2003): 2187-2191.
PMID
12775745
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
11
Publish Date
2003
Start Page
2187
End Page
2191
DOI
10.1200/JCO.2003.10.096

Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

OBJECT: The identification of patients at an increased risk for cerebral vasospasm after subarachnoid hemorrhage (SAH) may allow for more aggressive treatment and improved patient outcomes. Note, however, that blood clot size on admission remains the only factor consistently demonstrated to increase the risk of cerebral vasospasm after SAH. The goal of this study was to assess whether clinical, radiographic, or serological variables could be used to identify patients at an increased risk for cerebral vasospasm. METHODS: A retrospective review was conducted in all patients with aneurysmal or spontaneous nonaneurysmal SAH who were admitted to the authors' institution between 1995 and 2001. Underlying vascular diseases (hypertension or chronic diabetes mellitus), Hunt and Hess and Fisher grades, patient age, aneurysm location, craniotomy compared with endovascular aneurysm stabilization, medications on admission, postoperative steroid agent use, and the occurrence of fever, hydrocephalus, or leukocytosis were assessed as predictors of vasospasm. Two hundred twenty-four patients were treated for SAH during the review period. One hundred one patients (45%) developed symptomatic vasospasm. Peak vasospasm occurred 5.8 +/- 3 days after SAH. There were four independent predictors of vasospasm: Fisher Grade 3 SAH (odds ratio [OR] 7.5, 95% confidence interval [CI] 3.5-15.8), peak serum leukocyte count (OR 1.09, 95% CI 1.02-1.16), rupture of a posterior cerebral artery (PCA) aneurysm (OR 0.05, 95% CI 0.01-0.41), and spontaneous nonaneurysmal SAH (OR 0.14, 95% CI 0.04-0.45). A serum leukocyte count greater than 15 x 10(9)/L was independently associated with a 3.3-fold increase in the likelihood of developing vasospasm (OR 3.33, 95% CI 1.74-6.38). CONCLUSIONS: During this 7-year period, spontaneous nonaneurysmal SAH and ruptured PCA aneurysms decreased the odds of developing vasospasm sevenfold and 20-fold, respectively. The presence of Fisher Grade 3 SAH on admission or a peak leukocyte count greater than 15 x 10(9)/L increased the odds of vasospasm sevenfold and threefold, respectively. Monitoring of the serum leukocyte count may allow for early diagnosis and treatment of vasospasm.

Authors
McGirt, MJ; Mavropoulos, JC; McGirt, LY; Alexander, MJ; Friedman, AH; Laskowitz, DT; Lynch, JR
MLA Citation
McGirt, MJ, Mavropoulos, JC, McGirt, LY, Alexander, MJ, Friedman, AH, Laskowitz, DT, and Lynch, JR. "Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage." J Neurosurg 98.6 (June 2003): 1222-1226.
PMID
12816268
Source
pubmed
Published In
Journal of neurosurgery
Volume
98
Issue
6
Publish Date
2003
Start Page
1222
End Page
1226
DOI
10.3171/jns.2003.98.6.1222

MRI-guided stereotactic biopsy in the diagnosis of glioma: comparison of biopsy and surgical resection specimen.

BACKGROUND: Although there has been a dramatic increase in the accessibility and utilization of high-resolution MRI techniques for the evaluation of brain tumors, there is currently only a single report comparing stereotactic brain biopsy specimen to subsequent resection specimen exclusively in the management of gliomas. METHODS: The diagnoses in 43 cases of astrocytic brain tumors were derived using MRI-guided stereotactic biopsy followed by open resection of the lesion. The histologic diagnoses yielded by biopsy were compared with subsequent histologic diagnosis after open tumor resection. All biopsies and histologic diagnoses were made by the same surgeon and pathologist, respectively. RESULTS: In 23 patients undergoing resection <60 days after biopsy, the biopsy diagnosis was consistent with resection diagnosis in 18 cases (79%) and led to the correct treatment in 22 cases (96%). Recurrent glioblastoma multiforme (GBM) was undergraded as anaplastic astrocytoma in 4 patients. GBM was misdiagnosed as radiation necrosis in 1 patient. MR-nonenhancing lesions [10/10 (100%)] yielded histology that correlated with subsequent craniotomy, while only 8/13 (61%) MR-enhancing lesions yielded histology that was consistent with that at craniotomy (p < 0.05). In 20 patients undergoing resection because of radiologic tumor progression (mean 7 months after biopsy), 6/6 (100%) biopsy diagnoses of a specific glioma grade correlated with resection diagnosis, while only 6/14 (43%) biopsy diagnoses of radiation effect correlated with resection diagnosis (p < 0.01). CONCLUSION: MRI-guided stereotactic brain biopsy specimen accurately represents the grade of the larger glioma mass sufficiently to guide subsequent therapy. Enhancement on MR may be a negative prognostic indicator of biopsy accuracy.

Authors
McGirt, MJ; Villavicencio, AT; Bulsara, KR; Friedman, AH
MLA Citation
McGirt, MJ, Villavicencio, AT, Bulsara, KR, and Friedman, AH. "MRI-guided stereotactic biopsy in the diagnosis of glioma: comparison of biopsy and surgical resection specimen." Surg Neurol 59.4 (April 2003): 277-281.
PMID
12748009
Source
pubmed
Published In
World Neurosurgery
Volume
59
Issue
4
Publish Date
2003
Start Page
277
End Page
281

Use of the peak troponin value to differentiate myocardial infarction from reversible neurogenic left ventricular dysfunction associated with aneurysmal subarachnoid hemorrhage.

OBJECT: Differentiating myocardial infarction (MI) from reversible neurogenic left ventricular dysfunction (stunned myocardium [SM]) associated with aneurysmal subarachnoid hemorrhage (SAH) is critical for early surgical intervention. The authors hypothesized that the cardiac troponin (cTn) trend and/or echocardiogram could be used to differentiate between the two entities. METHODS: A retrospective study was conducted for the period between 1995 and 2000. All patients included in the study met the following criteria: 1) no history of cardiac problems; 2) new onset of abnormal cardiac function (ejection fraction [EF] < 40% on echocardiograms); 3) serial cardiac markers (cTn and creatine kinase MB isoform [CK-MB]); 4) surgical intervention for their aneurysm; and 5) cardiac output monitoring either by repeated echocardiograms or invasive hemodynamic monitoring during the first 4 days post-SAH when the patients were euvolemic. Of the 350 patients with SAH, 10 (2.9%) had severe cardiac dysfunction. Of those 10, six were women and four were men. The patients' mean age was 53.5 years (range 29-75 years) and their SAH was classified as Hunt and Hess Grade III or IV. Aneurysm distribution was as follows: basilar artery tip (four); anterior communicating artery (two); middle cerebral artery (one); posterior communicating artery (two); and posterior inferior cerebellar artery (one). The mean EFonset was 33%. The changes on echocardiograms in these patients did not match the findings on electrocardiograms (EKGs). Within 4.5 days, dramatic improvement was seen in cardiac output (from 4.93 +/- 1.16 L/minute to 7.74 +/- 0.88 L/minute). Compared with historical controls in whom there were similar levels of left ventricular dysfunction after MI, there was no difference in peak CK-MB. A 10-fold difference, however, was noted in cTn values (0.22 +/- 0.25 ng/ml; control 2.8 ng/ml; p < 0.001). CONCLUSIONS: The authors determined the following: 1) that the CK-MB trend does not allow differentiation between SM and MI; 2) that echocardiograms revealing significant inconsistencies with EKGs are indicative of SM; and 3) that cTn values less than 2.8 ng/ml in patients with EFs less than 40% are consistent with SM.

Authors
Bulsara, KR; McGirt, MJ; Liao, L; Villavicencio, AT; Borel, C; Alexander, MJ; Friedman, AH
MLA Citation
Bulsara, KR, McGirt, MJ, Liao, L, Villavicencio, AT, Borel, C, Alexander, MJ, and Friedman, AH. "Use of the peak troponin value to differentiate myocardial infarction from reversible neurogenic left ventricular dysfunction associated with aneurysmal subarachnoid hemorrhage." J Neurosurg 98.3 (March 2003): 524-528.
PMID
12650423
Source
pubmed
Published In
Journal of neurosurgery
Volume
98
Issue
3
Publish Date
2003
Start Page
524
End Page
528
DOI
10.3171/jns.2003.98.3.0524

Phase II trial of temozolomide in patients with progressive low-grade glioma.

PURPOSE: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. PATIENTS AND METHODS: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m(2)/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. RESULTS: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to infinity months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced > or = grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. CONCLUSION: Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.

Authors
Quinn, JA; Reardon, DA; Friedman, AH; Rich, JN; Sampson, JH; Provenzale, JM; McLendon, RE; Gururangan, S; Bigner, DD; Herndon, JE; Avgeropoulos, N; Finlay, J; Tourt-Uhlig, S; Affronti, ML; Evans, B; Stafford-Fox, V; Zaknoen, S; Friedman, HS
MLA Citation
Quinn, JA, Reardon, DA, Friedman, AH, Rich, JN, Sampson, JH, Provenzale, JM, McLendon, RE, Gururangan, S, Bigner, DD, Herndon, JE, Avgeropoulos, N, Finlay, J, Tourt-Uhlig, S, Affronti, ML, Evans, B, Stafford-Fox, V, Zaknoen, S, and Friedman, HS. "Phase II trial of temozolomide in patients with progressive low-grade glioma." J Clin Oncol 21.4 (February 15, 2003): 646-651.
PMID
12586801
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
21
Issue
4
Publish Date
2003
Start Page
646
End Page
651
DOI
10.1200/JCO.2003.01.009

Primary orbital angiomatous meningioma.

Authors
Elahi, E; Meltzer, MA; Friedman, AH; Som, PM
MLA Citation
Elahi, E, Meltzer, MA, Friedman, AH, and Som, PM. "Primary orbital angiomatous meningioma." Arch Ophthalmol 121.1 (January 2003): 124-127.
PMID
12523900
Source
pubmed
Published In
Archives of Ophthalmology
Volume
121
Issue
1
Publish Date
2003
Start Page
124
End Page
127

Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evaluation of recurrent malignant astrocytoma compared with a lesion due to radiation effect.

OBJECT: The prognostic value of differentiating between recurrent malignant glioma and a lesion due to radiation effect by performing stereotactic biopsy has not been assessed. Thus, this study was undertaken to determine such value. METHODS: Between 1995 and 2001, 114 patients underwent magnetic resonance (MR) imaging-guided stereotactic biopsy to differentiate lesions caused by a recurrence of malignant astrocytoma and by radiation effect. All patients had previously undergone tumor resection (World Health Organization Grade III or IV) followed by radiotherapy. Disease diagnosis based on biopsy and patient characteristics were assessed as predictors of survival according to results of a multivariate Cox regression analysis. The diagnosis determined with the aid of biopsy was compared with that established during a subsequent resection in 26 patients. Survival following stereotactic biopsy was markedly increased in patients suffering from radiation effect compared with those harboring recurrent malignant glioma (p < 0.0001). In patients with radiation effect on biopsy, an increasing patient age (p < 0.05), having had two compared with one prior resection (p < 0.05), and a decreasing time from radiotherapy to biopsy (p < 0.001) were factors associated with decreased survival. Nevertheless, in patients with biopsy-defined radiation effect at second progression or with an age younger than 50 years the survival rate remained higher than that in patients with recurrent tumor on biopsy (p < 0.01). A biopsy-based diagnosis of radiation effect obtained less than 5 months after radiotherapy was not associated with an increased rate of patient survival compared with a diagnosis of recurrent malignant glioma on biopsy (p = 0.286). Eighty-six percent of lesions initially determined to be due to radiation effect on biopsy fewer than 5 months after radiotherapy were characterized as recurrent glioma by a mean of 11 months later. In contrast, only 25% of lesions initially diagnosed as attributable to radiation effect on biopsy more than 5 months after radiotherapy were classified as recurrent glioma a mean of 12 months later (p < 0.05). CONCLUSIONS: With the aid of stereotactic biopsy the authors demonstrated prognostic significance in differentiating recurrent malignant astrocytoma from a lesion due to radiation effect in patients presenting more than 5 months after having undergone radiotherapy. In patients who presented earlier than 5 months after radiotherapy, radiation effect on biopsy was not associated with an improved rate of survival compared with that in patients harboring recurrent malignant astrocytoma.

Authors
McGirt, MJ; Bulsara, KR; Cummings, TJ; New, KC; Little, KM; Friedman, HS; Friedman, AH
MLA Citation
McGirt, MJ, Bulsara, KR, Cummings, TJ, New, KC, Little, KM, Friedman, HS, and Friedman, AH. "Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evaluation of recurrent malignant astrocytoma compared with a lesion due to radiation effect." J Neurosurg 98.1 (January 2003): 14-20.
PMID
12546347
Source
pubmed
Published In
Journal of neurosurgery
Volume
98
Issue
1
Publish Date
2003
Start Page
14
End Page
20
DOI
10.3171/jns.2003.98.1.0014

Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evaluation of recurrent malignant astrocytoma compared with a lesion due to radiation effect

Object. The prognostic value of differentiating between recurrent malignant glioma and a lesion due to radiation effect by performing stereotactic biopsy has not been assessed. Thus, this study was undertaken to determine such value. Methods. Between 1995 and 2001, 114 patients underwent magnetic resonance (MR) imaging-guided stereotactic biopsy to differentiate lesions caused by a recurrence of malignant astrocytoma and by radiation effect. All patients had previously undergone tumor resection (World Health Organization Grade III or IV) followed by radiotherapy. Disease diagnosis based on biopsy and patient characteristics were assessed as predictors of survival according to results of a multivariate Cox regression analysis. The diagnosis determined with the aid of biopsy was compared with that established during a subsequent resection in 26 patients. Survival following stereotactic biopsy was markedly increased in patients suffering from radiation effect compared with those harboring recurrent malignant glioma (p < 0.0001). In patients with radiation effect on biopsy, an increasing patient age (p < 0.05), having had two compared with one prior resection (p < 0.05), and a decreasing time from radiotherapy to biopsy (p < 0.001) were factors associated with decreased survival. Nevertheless, in patients with biopsy-defined radiation effect at second progression or with an age younger than 50 years the survival rate remained higher than that in patients with recurrent tumor on biopsy (p < 0.01). A biopsy-based diagnosis of radiation effect obtained less than 5 months after radiotherapy was not associated with an increased rate of patient survival compared with a diagnosis of recurrent malignant glioma on biopsy (p = 0.286). Eighty-six percent of lesions initially determined to be due to radiation effect on biopsy fewer than 5 months after radiotherapy were characterized as recurrent glioma by a mean of 11 months later. In contrast, only 25% of lesions initially diagnosed as attributable to radiation effect on biopsy more than 5 months after radiotherapy were classified as recurrent glioma a mean of 12 months later (p < 0.05). Conclusions. With the aid of stereotactic biopsy the authors demonstrated prognostic significance in differentiating recurrent malignant astrocytoma from a lesion due to radiation effect in patients presenting more than 5 months after having undergone radiotherapy. In patients who presented earlier than 5 months after radiotherapy, radiation effect on biopsy was not associated with an improved rate of survival compared with that in patients harboring recurrent malignant astrocytoma.

Authors
McGirt, MJ; Bulsara, KR; Cummings, TJ; New, KC; Little, KM; Friedman, HS; Friedman, AH
MLA Citation
McGirt, MJ, Bulsara, KR, Cummings, TJ, New, KC, Little, KM, Friedman, HS, and Friedman, AH. "Prognostic value of magnetic resonance imaging-guided stereotactic biopsy in the evaluation of recurrent malignant astrocytoma compared with a lesion due to radiation effect." Journal of Neurosurgery 98.1 SUPPL. (2003): 14-20.
Source
scival
Published In
Journal of Neurosurgery
Volume
98
Issue
1 SUPPL.
Publish Date
2003
Start Page
14
End Page
20

Rate of resolution of histologically verified intracranial tuberculomas

OBJECTIVE: The goal of this study was to determine the rate of radiological resolution of histopathologically proven tuberculomas treated with antituberculous therapy (ATT). The effects of the size of the tuberculomas, the number of tuberculomas, and the addition of corticosteroid therapy on the rate of resolution of the tuberculomas were also studied. METHODS: Twenty-eight patients (age range, 5-48 yr; 14 male and 14 female patients) with histologically proven intracranial tuberculomas were prospectively monitored with contrast-enhanced computed tomographic scans. The patients received ATT consisting of rifampicin and isoniazid for a period of 18 months, with ethambutol and/or pyrazinamide for a minimum of 3 months. Fifteen patients also received corticosteroid therapy for 1 to 6 weeks. Of the 28 patients, 17 patients underwent partial excision, 6 underwent open biopsy, and 5 underwent stereotactic biopsy of their tuberculomas. RESULTS: Kaplan-Meier analysis revealed that, after 9 months of ATT, only 18.2% of the patients demonstrated complete resolution of their tuberculomas; even after 18 months of ATT, 69.2% of the patients had residual lesions. By 24 months, 54% of the patients demonstrated complete resolution of their tuberculomas. Although the number of tuberculomas, corticosteroid administration, prior treatment with ATT, and the duration of symptoms before presentation (<6 mo versus >6 mo) did not influence the rate of resolution, larger tuberculomas (maximal size, >4 cm) were observed to resolve more slowly than smaller tuberculomas (<4 cm) (P = 0.02). CONCLUSION: More than two-thirds of patients with partially excised or biopsied intracranial tuberculomas exhibited persistent lesions on computed tomographic scans, even after 18 months of ATT. Therefore, the duration of ATT for patients with intracranial tuberculomas should be based on the radiological responses of the tuberculomas. Our data suggest that some patients with intracranial tuberculomas might require prolonged periods of ATT.

Authors
Poonnoose, SI; Rajshekhar, V; Hall, WA; Friedman, AH; Grossman, RG; Khamlichi, AE
MLA Citation
Poonnoose, SI, Rajshekhar, V, Hall, WA, Friedman, AH, Grossman, RG, and Khamlichi, AE. "Rate of resolution of histologically verified intracranial tuberculomas." Neurosurgery 53.4 (2003): 873-879.
PMID
14519219
Source
scival
Published In
Neurosurgery
Volume
53
Issue
4
Publish Date
2003
Start Page
873
End Page
879

Preoperative evaluation of neural tracts by use of three-dimensional anisotropy contrast imaging in a patient with brainstem cavernous angioma: Technical case report

OBJECTIVE AND IMPORTANCE: We describe a case of brainstem cavernous angioma in which the neural tracts were evaluated before surgery by three-dimensional anisotropy contrast (3-DAC) magnetic resonance imaging. CLINICAL PRESENTATION: A 64-year-old man presented with a cavernous angioma located intrinsically in the brainstem and manifesting as gait ataxia. 3-DAC imaging demonstrated that the lesion was located outside the left inferior cerebellar peduncle and inside the middle cerebellar peduncle. INTERVENTION: The intact brain surface was incised, and the lesion was removed successfully on the basis of the preoperative 3-DAC images. The patient exhibited temporary exacerbation of his gait ataxia, but the symptom improved 3 months after surgery. Postoperative 3-DAC imaging demonstrated resection of the lesion and preservation of the left inferior and middle cerebellar peduncles. CONCLUSION: 3-DAC imaging may provide essential information about the neural tracts for the planning of brainstem surgery.

Authors
Kashimura, H; Inoue, T; Ogasawara, K; Ogawa, A; Zee, C-S; Provenzale, JM; Friedman, AH; Yoshida, J; DiLuna, M; Gunel, M
MLA Citation
Kashimura, H, Inoue, T, Ogasawara, K, Ogawa, A, Zee, C-S, Provenzale, JM, Friedman, AH, Yoshida, J, DiLuna, M, and Gunel, M. "Preoperative evaluation of neural tracts by use of three-dimensional anisotropy contrast imaging in a patient with brainstem cavernous angioma: Technical case report." Neurosurgery 52.5 (2003): 1226-1230.
PMID
12699571
Source
scival
Published In
Neurosurgery
Volume
52
Issue
5
Publish Date
2003
Start Page
1226
End Page
1230

Transient choroid plexus cysts and benign asymmetrical ventricles: A case suggesting a possible link: Case report

OBJECTIVE AND IMPORTANCE: Brain magnetic resonance imaging scans occasionally reveal asymmetrical ventricles with no identifiable cause. A case is presented that highlights a possible connection between transient choroid plexus cysts and benign asymmetrical ventricles. CLINICAL PRESENTATION: The patient was a 2.5-week-old asymptomatic boy. Transcranial ultrasound and magnetic resonance imaging revealed the infant to have a left frontal horn choroid plexus cyst and a mildly dilated left lateral ventricle. Head circumference was at 90% of the norm for age. The neurological examination revealed nothing abnormal. Four months later, follow-up magnetic resonance imaging revealed complete resolution of the cyst with persistent ventricular asymmetry. INTERVENTION: No surgical intervention was undertaken. The lesion was assessed via x-ray. CONCLUSION: Spontaneously resolving choroid plexus cysts of infancy causing outflow obstruction of the lateral ventricle may be one of the underlying causes of benign asymmetrical ventricles.

Authors
Heilman, CB; Zerris, VA; Grossman, RG; Milhorat, TH; Friedman, AH
MLA Citation
Heilman, CB, Zerris, VA, Grossman, RG, Milhorat, TH, and Friedman, AH. "Transient choroid plexus cysts and benign asymmetrical ventricles: A case suggesting a possible link: Case report." Neurosurgery 52.1 (2003): 213-215.
PMID
12493120
Source
scival
Published In
Neurosurgery
Volume
52
Issue
1
Publish Date
2003
Start Page
213
End Page
215
DOI
10.1097/00006123-200301000-00027

Pacemaker therapy in isolated congenital complete atrioventricular block.

The aim of this study was to evaluate the effect of pacemaker (PM) therapy in patients with isolated congenital complete atrioventricular block (CCAVB). Patients with CCAVB eventually quality for PM implantation, however, timing remains controversial. Retrospective evaluation of left ventricular end-diastolic diameter (LVEDD), shortening fraction (SF), and cardiothoracic ratio (CTR) in 149 CCAVB patients, before, at, and after PM implantation was carried out. LVEDD shows an average increase of 0.48%/month in non-PM patients, and an average decrease of 0.88%/month in PM patients. SF shows an average increase of 0.10%/month in non-PM, and an average decrease of 0.32%/month in PM patients. CTR shows an average increase of 0.02%/month in non-PM, and an average decrease of 0.19%/month in PM patients. The difference between the non-PM and PM groups is significant (P = 0.05) for all variables. Symptomatic patients show no significant change in LVEDD after PM therapy (from 66.5% before to 68.5% after PM therapy). Asymptomatic patients do show a significant (P

Authors
Breur, JM; Udink Ten Cate, FE; Kapusta, L; Cohen, MI; Crosson, JE; Boramanand, N; Lubbers, LJ; Friedman, AH; Brenner, JI; Vetter, VL; Sreeram, N; Meijboom, EJ
MLA Citation
Breur, JM, Udink Ten Cate, FE, Kapusta, L, Cohen, MI, Crosson, JE, Boramanand, N, Lubbers, LJ, Friedman, AH, Brenner, JI, Vetter, VL, Sreeram, N, and Meijboom, EJ. "Pacemaker therapy in isolated congenital complete atrioventricular block." Pacing and clinical electrophysiology : PACE 25.12 (December 2002): 1685-1691. (Academic Article)
Source
manual
Published In
Pacing and Clinical Electrophysiology
Volume
25
Issue
12
Publish Date
2002
Start Page
1685
End Page
1691

Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa).

Iressa (ZD1839) is a p.o.-active, selective, epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways implicated in cancer cell proliferation, survival, and host-dependent processes promoting cancer growth. EGFR is up-regulated in primary malignant tumors of the central nervous system (CNS) and in many systemic tumors that metastasize to the CNS. The purpose of our study was to evaluate the efficacy and toxicity of p.o.-administered ZD1839 for the treatment of established intracerebral (i.c.) tumors expressing EGFR or the tumorigenic mutated variant EGFRvIII, which is constitutively phosphorylated. Oral administration of ZD1839 at 50 or 100 mg/kg/day for 3 weeks in athymic mice with established i.c. A431 human epidermoid carcinoma expressing EGFR increased median survival by 88% (P = 0.009) and 105% (P < 0.001), respectively. Additionally, there was no evidence of systemic or CNS toxicity. However, ZD1839 failed to inhibit either s.c. or i.c. in vivo tumor growth when tumorigenicity was conferred by EGFRvIII. Western blotting revealed that treatment with ZD1839 virtually ablated phosphorylation of EGFR Tyr-1173 in A431 tumors. However, treatment of NR6M tumors with ZD1839 only partially decreased phosphorylation of EGFRvIII Tyr-1173 while up-regulating overall expression, suggesting that EGFRvIII may not be susceptible to the same molecular mechanisms of tyrosine kinase inhibition as EGFR. In conclusion, ZD1839 is active in a brain tumor model expressing EGFR, but not EGFRvIII, as EGFR mutations may lead to relative therapeutic resistance. On the basis of these observations, we believe that clinical trials of ZD1839 against brain tumors expressing EGFR are warranted, but that special consideration should be given to tumors that coexpress EGFRvIII.

Authors
Heimberger, AB; Learn, CA; Archer, GE; McLendon, RE; Chewning, TA; Tuck, FL; Pracyk, JB; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Heimberger, AB, Learn, CA, Archer, GE, McLendon, RE, Chewning, TA, Tuck, FL, Pracyk, JB, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (iressa)." Clin Cancer Res 8.11 (November 2002): 3496-3502.
PMID
12429640
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
8
Issue
11
Publish Date
2002
Start Page
3496
End Page
3502

Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Endothelial damage and intimal proliferation occur in vasospastic cerebral arteries after subarachnoid hemorrhage (SAH). In the peripheral vasculature, endothelial damage increases intimal matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) levels, causing neointimal proliferation. We hypothesized that serum von Willebrand factor (vWF) (a marker of endothelial cell death), MMP-9, and VEGF levels could serve as prognostic markers in predicting the occurrence of cerebral vasospasm. METHODS: Venous serum vWF, MMP-9, and VEGF levels were prospectively measured daily, for 12 days or until the onset of vasospasm, for 45 consecutive patients admitted with SAH (n = 38) or admitted for elective aneurysm clipping (control subjects, n = 7). The development of transcranial Doppler flow velocities of more than 180 cm/s and/or new focal neurological deficits with angiographically confirmed vasospasm was considered the onset of vasospasm. To establish whether these markers were specific for vasospasm versus ischemia, blood samples were obtained from a concurrent group of 42 patients within 24 hours after stroke onset unrelated to SAH. RESULTS: Fifty-seven percent of patients (22 of 38 patients) developed vasospasm, 4 to 11 days after SAH (median, 7 d). Mean peak serum vWF, MMP-9, and VEGF levels were increased in the SAH prevasospasm cohort, compared with the SAH nonvasospasm cohort (vWF, 5526 +/- 929 versus 4934 +/- 599 ng/ml, P = 0.01; MMP-9, 705 +/- 338 versus 438 +/- 154 ng/ml, P = 0.006; VEGF, 0.12 +/- 0.06 versus 0.06 +/- 0.06 ng/ml, P = 0.023). Mean peak vWF, MMP-9, and VEGF levels for the focal ischemia cohort (vWF, 4645 +/- 875 ng/ml, P = 0.01; MMP-9, 250 +/- 308 ng/ml, P = 0.001; VEGF, 0.03 +/- 0.04 ng/ml, P = 0.001) were markedly lower in comparison with the SAH prevasospasm cohort and were unchanged in comparison with the control cohort. vWF levels of more than 5500 ng/ml, VEGF levels of more than 0.12 ng/ml, and MMP levels of more than 700 ng/ml each independently increased the odds of subsequent vasospasm (18-, 20-, and 25-fold, respectively). CONCLUSION: The development of cerebral vasospasm after SAH was preceded by increases in serum vWF, MMP-9, and VEGF levels. Increased serum vWF, MMP-9, and VEGF levels could accurately predict the onset of cerebral vasospasm after SAH. These factors were not elevated by SAH alone or in a separate cohort of patients with ischemic stroke, suggesting that these factors might play a role in the pathogenesis of human cerebral vasospasm.

Authors
McGirt, MJ; Lynch, JR; Blessing, R; Warner, DS; Friedman, AH; Laskowitz, DT
MLA Citation
McGirt, MJ, Lynch, JR, Blessing, R, Warner, DS, Friedman, AH, and Laskowitz, DT. "Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage." Neurosurgery 51.5 (November 2002): 1128-1134.
PMID
12383357
Source
pubmed
Published In
Neurosurgery
Volume
51
Issue
5
Publish Date
2002
Start Page
1128
End Page
1134

Management of malignant tumors of the anterior skull base: experience with 76 patients.

As the management of anterior cranial fossa malignancies has undergone significant evolution, decreases in morbidity and mortality rates have occurred. In this article, the authors discuss the clinical presentation, neuroimaging findings, and management options for common anterior skull base malignancies. Also discussed are surgery-related indications and principles.

Authors
Bulsara, KR; Fukushima, T; Friedman, AH
MLA Citation
Bulsara, KR, Fukushima, T, and Friedman, AH. "Management of malignant tumors of the anterior skull base: experience with 76 patients. (Published online)" Neurosurg Focus 13.4 (October 15, 2002): e5-.
PMID
15771404
Source
pubmed
Published In
Neurosurgical focus
Volume
13
Issue
4
Publish Date
2002
Start Page
e5

Current options for the treatment of neoplastic meningitis.

Neoplastic meningitis, which is the diffuse involvement of the leptomeninges by infiltrating cancer cells, may be caused by many systemic tumors. The treatment options for neoplastic meningitis disease remain unsatisfactory. In this review article, we discuss the pathogenesis and cytology of neoplastic meningitis and the options for treatment, including intrathecal chemotherapy, systemic chemotherapy, and newer agents such as cytokines and monoclonal antibodies.

Authors
Cokgor, I; Friedman, AH; Friedman, HS
MLA Citation
Cokgor, I, Friedman, AH, and Friedman, HS. "Current options for the treatment of neoplastic meningitis." J Neurooncol 60.1 (October 2002): 79-88. (Review)
PMID
12416549
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
60
Issue
1
Publish Date
2002
Start Page
79
End Page
88

Pediatric grand rounds: a tribute to Norman J. Siegel, M.D.

At ceremonies held in Baltimore Maryland on May, 4, 2002, Dr. Howard A Pearson, Professor of Pediatrics, was awarded the John A. Howland award of the American Pediatric Society, probably the most prestigious award of American Pediatrics. Dr. Pearson had been nominated for the award by Dr. Norman Siegel. The Department of Pediatrics Grand Rounds on Wednesday noon, October 26, 2002 was originally scheduled as a repetition of the presentation by Dr. Siegel and the acceptance by Dr. Pearson for those who could not be in Baltimore. However; in a number of meetings, unknown to Dr. Siegel, it was unanimously decided that it would be very appropriate to instead honor him as he stepped down from his position as Vice- and Interim Chairman of Pediatrics, and to formally thank him for his long and faithful service to the Department of Pediatrics, the Yale University School of Medicine, and the Yale New Haven Hospital.

Authors
Pearson, HA; Hostetter, MK; Friedman, AH
MLA Citation
Pearson, HA, Hostetter, MK, and Friedman, AH. "Pediatric grand rounds: a tribute to Norman J. Siegel, M.D." Yale J Biol Med 75.5-6 (September 2002): 307-312.
PMID
14580112
Source
pubmed
Published In
The Yale journal of biology and medicine
Volume
75
Issue
5-6
Publish Date
2002
Start Page
307
End Page
312

Molecular markers of prognosis in astrocytic tumors.

BACKGROUND: Astrocytoma is a primary brain tumor that affects 20,000 Americans each year. To date, only age and histologic grade stand out as independent predictors of survival. There is now increased interest in the use of molecular markers as objective standards against which to establish diagnosis and grade. METHODS: The study evaluated human glioma tumor suppressor genes and associated loci in fresh snap-frozen gliomas from 63 males and 37 females, with a median age of 42 years, including 19 low-grade astrocytomas. The tumor samples were selected so that about equal numbers of glioblastomas from younger and older patients were represented in the series. Methods for suppressor gene and genetic loci evaluation included loss of heterozygosity (LOH) analysis, multiplex polymerase chain reaction analysis, and gene sequencing. RESULTS: Low-grade astrocytomas had the least number of molecular abnormalities. LOH on 9p and/or CDKN2A deletion occurred more often in glioblastomas (P < 0.001), LOH on 17p/TP53 mutations occurred more frequently in anaplastic astrocytomas (AAs; P = 0.112), and LOH on 10q/PTEN mutation frequency was similar in glioblastomas and AAs (P < 0.001). Poorer survival was associated significantly with the occurrence of either deletion of p16 (P = 0.031), LOH on 9p (P = 0.016), or LOH on 10q (P = 0.0007). The absence of LOH on 17p and the presence of PTEN mutation were associated marginally with survival. Even though TP53 mutations were more frequent among younger patients with glioblastoma, they had no statistically significant effect on survival after adjustment for age (P = 0.62). In all multivariate models, age and grade were the only significant predictors of survival or were nearly significant predictors of survival. CONCLUSIONS: The results suggest that LOH on 9p and p16 deletions may prove to be objective standards for the diagnosis of patients with high-grade gliomas, although the absence of these abnormalities is nonprognostic.

Authors
Rasheed, A; Herndon, JE; Stenzel, TT; Raetz, JGM; Kendelhardt, J; Friedman, HS; Friedman, AH; Bigner, DD; Bigner, SH; McLendon, RE
MLA Citation
Rasheed, A, Herndon, JE, Stenzel, TT, Raetz, JGM, Kendelhardt, J, Friedman, HS, Friedman, AH, Bigner, DD, Bigner, SH, and McLendon, RE. "Molecular markers of prognosis in astrocytic tumors." Cancer 94.10 (May 15, 2002): 2688-2697.
PMID
12173338
Source
pubmed
Published In
Cancer
Volume
94
Issue
10
Publish Date
2002
Start Page
2688
End Page
2697

Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma.

PURPOSE: We conducted a phase II trial of carmustine (BCNU) plus the O(6)-alkylguanine-DNA alkyltransferase inhibitor O(6)-benzylguanine (O(6)-BG) to define the activity and toxicity of this regimen in the treatment of adults with progressive or recurrent malignant glioma resistant to nitrosoureas. PATIENTS AND METHODS: Patients were treated with O(6)-BG at an intravenous dose of 120 mg/m(2) followed 1 hour later by 40 mg/m(2) of BCNU, with cycles repeated at 6-week intervals. RESULTS: Eighteen patients were treated (15 with glioblastoma multiforme, two with anaplastic astrocytoma, and one with malignant glioma). None of the 18 patients demonstrated a partial or complete response. Two patients exhibited stable disease for 12 weeks before their tumors progressed. Three patients demonstrated stable disease for 6, 12, and 18 weeks before discontinuing therapy because of hematopoietic toxicity. Twelve patients experienced reversible > or = grade 3 hematopoietic toxicity. There was no difference in half-lives (0.56 +/- 0.21 hour v 0.54 +/- 0.20 hour) or area under the curve values (4.8 +/- 1.7 microg/mL/h v 5.0 +/- 1.3 microg/mL/h) of O(6)-BG for patients receiving phenytoin and those not treated with this drug. CONCLUSION: These results indicate that O(6)-BG plus BCNU at the dose schedule used in this trial is unsuccessful in producing tumor regression in patients with nitrosourea-resistant malignant glioma, although stable disease was seen in five patients for 6, 12, 12, 12, and 18 weeks. Future use of this approach will require strategies to minimize dose-limiting toxicity of BCNU such as regional delivery or hematopoietic stem-cell protection.

Authors
Quinn, JA; Pluda, J; Dolan, ME; Delaney, S; Kaplan, R; Rich, JN; Friedman, AH; Reardon, DA; Sampson, JH; Colvin, OM; Haglund, MM; Pegg, AE; Moschel, RC; McLendon, RE; Provenzale, JM; Gururangan, S; Tourt-Uhlig, S; Herndon, JE; Bigner, DD; Friedman, HS
MLA Citation
Quinn, JA, Pluda, J, Dolan, ME, Delaney, S, Kaplan, R, Rich, JN, Friedman, AH, Reardon, DA, Sampson, JH, Colvin, OM, Haglund, MM, Pegg, AE, Moschel, RC, McLendon, RE, Provenzale, JM, Gururangan, S, Tourt-Uhlig, S, Herndon, JE, Bigner, DD, and Friedman, HS. "Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma." J Clin Oncol 20.9 (May 1, 2002): 2277-2283.
PMID
11980998
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
9
Publish Date
2002
Start Page
2277
End Page
2283
DOI
10.1200/JCO.2002.09.084

Management of tumor bed cysts after chemotherapeutic wafer implantation. Report of four cases.

Adjuvant use of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) wafers with surgical resection is becoming common for the treatment of malignant gliomas. Cyst formation in the tumor resection cavity is a recently described complication associated with the use of BCNU wafers. There is currently no report in which successful management of this complication without additional surgical intervention is described. The authors describe four patients in whom postoperative cysts developed in the tumor resection cavity after placement of BCNU wafers. These include a 38-year-old man with a left frontoparietal tumor, a 48-year-old man with a right frontal lobe tumor, a 78-year-old man with a left parietooccipital tumor, and a 61-year-old woman with a left frontotemporal tumor. Histopathological studies of biopsy samples revealed malignant glioma in each patient. All four patients had unremarkable perioperative courses, were discharged within 3 to 8 days of surgery, and subsequently returned with acute neurological deterioration. Follow-up magnetic resonance (MR) imaging demonstrated cyst formation with significant mass effect at the previous resection site. Three patients were treated with high-dose dexamethasone and returned to their neurological baseline over an 8-day period. The fourth patient improved after surgical drainage and biopsy sampling of the cyst, which revealed no evidence of infection or recurrent tumor, but again sought medical care 2 weeks later with cyst recurrence necessitating high-dose steroid therapy. On MR images at least a 30% reduction in cyst size was demonstrated in all four patients, each of whom remained clinically stable at 2, 6, 6, and 4 months of follow-up review. Neurosurgeons should be aware of the potential for postoperative cyst formation accompanied by clinically significant mass effect after BCNU wafer implantation, as well as the potential for successful nonsurgical management leading to clinical and radiological improvement.

Authors
McGirt, MJ; Villavicencio, AT; Bulsara, KR; Friedman, HS; Friedman, AH
MLA Citation
McGirt, MJ, Villavicencio, AT, Bulsara, KR, Friedman, HS, and Friedman, AH. "Management of tumor bed cysts after chemotherapeutic wafer implantation. Report of four cases." J Neurosurg 96.5 (May 2002): 941-945.
PMID
12005403
Source
pubmed
Published In
Journal of neurosurgery
Volume
96
Issue
5
Publish Date
2002
Start Page
941
End Page
945
DOI
10.3171/jns.2002.96.5.0941

Diagnosis of cardiac defects: where we've been, where we are and where we're going.

There has been tremendous development in the field of prenatal diagnosis of cardiac disease in the last 30 years. Early work centered on the technical aspects of providing an accurate assessment of cardiac structure and function. Techniques of fetal cardiac screening have been developed and utilized throughout the world. More recently, investigators have begun to explore the ramifications of fetal cardiac diagnosis by assessing measures of outcome. In this article, the field of fetal echocardiography, as a screening tool for identifying congenital heart disease, and its impact on disease outcome is reviewed.

Authors
Friedman, AH; Kleinman, CS; Copel, JA
MLA Citation
Friedman, AH, Kleinman, CS, and Copel, JA. "Diagnosis of cardiac defects: where we've been, where we are and where we're going." Prenat Diagn 22.4 (April 2002): 280-284. (Review)
PMID
11981908
Source
pubmed
Published In
Prenatal Diagnosis
Volume
22
Issue
4
Publish Date
2002
Start Page
280
End Page
284
DOI
10.1002/pd.305

Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience.

A phase II study of irinotecan (CPT-11) was conducted at Duke University Medical Center, Durham, NC, to evaluate the activity of this agent in children with high-risk malignant brain tumors. A total of 22 children were enrolled in this study, including 13 with histologically verified recurrent malignant brain tumors (glioblastoma multiforme [GBM] 4, anaplastic astrocytoma 1, ependymoma 5, and medulloblastoma/primitive neuroectodermal tumor 3), 5 with recurrent diffuse pontine glioma, and 4 with newly diagnosed GBM. All patients with recurrent tumor had prior chemotherapy and/or irradiation. Each course of CPT-11 consisted of 125 mg/m ( 2 ) per week given i.v. for 4 weeks followed by a 2-week rest period. Patients with recurrent tumors received therapy until disease progression or unacceptable toxicity. Patients with newly diagnosed tumors initially received 3 cycles of treatment to assess tumor response and then were allowed radiotherapy at physician's choice; patients who demonstrated a response to CPT-11 prior to radiotherapy were allowed to continue the drug after radiation until disease progression or unacceptable toxicity. A 25% to 50% dose reduction was made for grade III-IV toxicity. Responses were assessed after every course by gadolinium-enhanced MRI of the brain and spine. Twenty-two patients received a median of 2 courses of CPT-11 (range, 1-16). Responses were seen in 4 of 9 patients with GBM or anaplastic astrocytoma (44%; 95% confidence interval, 11%-82%) (complete response in 2 patients with recurrent GBM lasting 9 months and 48+ months; partial response in one patient with a newly diagnosed midbrain GBM lasting 18 months prior to radiotherapy; and partial response lasting 11 months in 1 patient with recurrent anaplastic astrocytoma), 1 of 5 patients with recurrent ependymoma (partial response initially followed by stable disease lasting 11 months), and none of 5 patients with recurrent diffuse pontine glioma. Two of 3 patients with medulloblastoma/primitive neuroectodermal tumor had stable disease for 9 and 13 months. Toxicity was mainly myelosuppression, with 12 of 22 patients (50%) suffering grade II-IV neutropenia. Seven patients required dose reduction secondary to neutropenia. CPT-11, given in this schedule, appears to be active in children with malignant glioma, medulloblastoma, and ependymoma with acceptable toxicity. Ongoing studies will demonstrate if activity of CPT-11 can be enhanced when combined with alkylating agents, including carmustine and temozolomide.

Authors
Turner, CD; Gururangan, S; Eastwood, J; Bottom, K; Watral, M; Beason, R; McLendon, RE; Friedman, AH; Tourt-Uhlig, S; Miller, LL; Friedman, HS
MLA Citation
Turner, CD, Gururangan, S, Eastwood, J, Bottom, K, Watral, M, Beason, R, McLendon, RE, Friedman, AH, Tourt-Uhlig, S, Miller, LL, and Friedman, HS. "Phase II study of irinotecan (CPT-11) in children with high-risk malignant brain tumors: the Duke experience." Neuro Oncol 4.2 (April 2002): 102-108.
PMID
11916501
Source
pubmed
Published In
Neuro-Oncology
Volume
4
Issue
2
Publish Date
2002
Start Page
102
End Page
108

Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas.

PURPOSE: To assess the efficacy and toxicity of intraresection cavity (131)I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma. PATIENTS AND METHODS: In this phase II trial, 120 mCi of (131)I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy. RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis. CONCLUSION: Median survival achieved with (131)I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with (131)I-labeled 81C6 compares favorably with either (125)I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of (131)I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.

Authors
Reardon, DA; Akabani, G; Coleman, RE; Friedman, AH; Friedman, HS; Herndon, JE; Cokgor, I; McLendon, RE; Pegram, CN; Provenzale, JM; Quinn, JA; Rich, JN; Regalado, LV; Sampson, JH; Shafman, TD; Wikstrand, CJ; Wong, TZ; Zhao, X-G; Zalutsky, MR; Bigner, DD
MLA Citation
Reardon, DA, Akabani, G, Coleman, RE, Friedman, AH, Friedman, HS, Herndon, JE, Cokgor, I, McLendon, RE, Pegram, CN, Provenzale, JM, Quinn, JA, Rich, JN, Regalado, LV, Sampson, JH, Shafman, TD, Wikstrand, CJ, Wong, TZ, Zhao, X-G, Zalutsky, MR, and Bigner, DD. "Phase II trial of murine (131)I-labeled antitenascin monoclonal antibody 81C6 administered into surgically created resection cavities of patients with newly diagnosed malignant gliomas." J Clin Oncol 20.5 (March 1, 2002): 1389-1397.
PMID
11870184
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
20
Issue
5
Publish Date
2002
Start Page
1389
End Page
1397
DOI
10.1200/JCO.2002.20.5.1389

Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes.

Ceramide is an important cellular lipid involved in signal transduction and the biosynthesis of complex sphingolipids. It can be hydrolyzed into sphingosine, another important signaling lipid, by the activity of ceramidases. Point mutations in the gene (Asah1) encoding one ceramidase, acid ceramidase (AC), lead to the lysosomal storage disorder Farber disease (FD). To investigate the role of AC in mammalian development, we disrupted the mouse gene Asah1 in embryonic stem cells by homologous recombination mediated insertion of an AC targeting vector into the wild-type sequence. Genotype analysis of over 150 offspring or embryos from heterozygous intercrosses revealed an absence of Asah1(-/-) individuals at embryonic day (E) 8.5 or later, although the ratio of wild-type to Asah1(+/-) individuals from these intercrosses was 1:2. Northern blot analysis showed that AC expression was turned on early in development, by E7.0, and continued through at least E17. In contrast, expression of the related lipid hydrolase, acid sphingomyelinase, was shut down by E11. Asah1(+/-) mice survived and lived a normal lifespan, but developed a progressive lipid storage disease in several of their organs, particularly the liver. These histopathological findings in Asah1(+/-) animals correlated with an up to twofold increase in the ceramide content of these tissues and a reduction n AC activity, confirming that the gene insertion event disrupted AC activity and ceramide metabolism. These results provide direct in vivo evidence that normal ceramide metabolism, and AC activity in particular, is essential for mammalian development. The animals and embryos described here should be a valuable resource for investigators studying the role of ceramide in cell growth and development, as well as those interested in the pathogenesis of FD and other sphingolipid storage disorders.

Authors
Li, CM; Park, JH; Simonaro, CM; He, X; Gordon, RE; Friedman, AH; Ehleiter, D; Paris, F; Manova, K; Hepbildikler, S; Fuks, Z; Sandhoff, K; Kolesnick, R; Schuchman, EH; Hepbiloikler, S
MLA Citation
Li, CM, Park, JH, Simonaro, CM, He, X, Gordon, RE, Friedman, AH, Ehleiter, D, Paris, F, Manova, K, Hepbildikler, S, Fuks, Z, Sandhoff, K, Kolesnick, R, Schuchman, EH, and Hepbiloikler, S. "Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes." Genomics 79.2 (February 2002): 218-224. (Academic Article)
Source
manual
Published In
Genomics
Volume
79
Issue
2
Publish Date
2002
Start Page
218
End Page
224
DOI
10.1006/geno.2002.6686

Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma.

OBJECTIVE: Dendritic cells (DCs) are specialized cells of the immune system that are capable of generating potent immune responses that are active even within the "immunologically privileged" central nervous system. However, immune responses generated by DCs have also been demonstrated to produce clinically significant autoimmunity. Targeting the epidermal growth factor receptor variant III (EGFRvIII), which is a mutation specific to tumor tissue, could eliminate this risk. The purpose of this study was to demonstrate that DC-based immunizations directed solely against this tumor-specific antigen, which is commonly found on tumors that originate within or metastasize to the brain, could be efficacious. METHODS: C3H mice were vaccinated with DCs mixed with a keyhole limpet hemocyanin conjugate of the tumor-specific peptide, PEP-3, which spans the EGFRvIII mutation, or the random-sequence peptide, PEP-1, and were intracerebrally challenged with a syngeneic melanoma expressing a murine homologue of EGFRvIII. RESULTS: Systemic immunization with DCs mixed with PEP-3-keyhole limpet hemocyanin generated antigen-specific immunity. Among mice challenged with intracerebral tumors, this resulted in an approximately 600% increase in the median survival time (>300 d, P < 0.0016), relative to control values. Sixty-three percent of mice treated with DCs mixed with the tumor-specific peptide survived in the long term and 100% survived rechallenge with tumor, indicating that antitumor immunological memory was also induced. CONCLUSION: In a murine melanoma model, immunization with DCs mixed with tumor-specific peptide results in an antigen-specific immunological response that recognizes the EGFRvIII mutation, has potent antitumor efficacy against intracerebral tumors that express EGFRvIII, and results in long-lasting antitumor immunity.

Authors
Heimberger, AB; Archer, GE; Crotty, LE; McLendon, RE; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Heimberger, AB, Archer, GE, Crotty, LE, McLendon, RE, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Dendritic cells pulsed with a tumor-specific peptide induce long-lasting immunity and are effective against murine intracerebral melanoma." Neurosurgery 50.1 (January 2002): 158-164.
PMID
11844246
Source
pubmed
Published In
Neurosurgery
Volume
50
Issue
1
Publish Date
2002
Start Page
158
End Page
164

Endoscopic cranioplasty with calcium phosphate cement for pterional bone defect after frontotemporal craniotomy: Technical note

OBJECTIVE: Postoperative pterional depression is a minor but unpleasant sequela of frontotemporal craniotomy. We developed a simple method for repair of this condition with the use of an endoscope and calcium phosphate cement. METHODS: The cranial defect was approached by means of endoscopic visualization through a small incision within the hairline. The defect was repaired with an injectable calcium phosphate cement. RESULTS: The bone defect was easily accessed and readily repaired in all five patients. No adverse reactions to the implant were observed. Satisfactory cosmetic results were obtained in all patients treated with the use of this method. CONCLUSION: This minimally invasive cranioplasty technique proved to be effective for the repair of the postoperative pterional defect.

Authors
Kubo, S; Takimoto, H; Kato, A; Yoshimine, T; Chandler, WF; Friedman, AH; Brotchi, J; Sekhar, LN; Khalid, H
MLA Citation
Kubo, S, Takimoto, H, Kato, A, Yoshimine, T, Chandler, WF, Friedman, AH, Brotchi, J, Sekhar, LN, and Khalid, H. "Endoscopic cranioplasty with calcium phosphate cement for pterional bone defect after frontotemporal craniotomy: Technical note." Neurosurgery 51.4 (2002): 1094-1096.
PMID
12234424
Source
scival
Published In
Neurosurgery
Volume
51
Issue
4
Publish Date
2002
Start Page
1094
End Page
1096
DOI
10.1097/00006123-200210000-00046

Surgical treatment of nocardial brain abscesses

OBJECTIVE: Nocardial brain abscesses are associated with significant morbidity and mortality rates. The optimal management remains unclear. We reviewed the surgical outcomes of patients treated with a relatively uniform policy at a single institution. METHODS: Eleven patients were treated at the Royal Adelaide Hospital between 1970 and 2001. Their clinical presentations, surgical treatment, and outcomes were reviewed. RESULTS: Clinical presentations most frequently involved focal neurological deficits (91%). Predisposing factors were identified for 63% of the patients. Nine patients were treated only with aspiration and long-term chemotherapy. Two patients underwent craniotomy and lesion excision. The majority of patients required either one or two procedures. There were no deaths in this series. Management complications were observed for three patients. Abscess aspiration was complicated by parenchymal hemorrhage and ventriculitis for one patient and temporary worsening of hemiparesis for two patients. CONCLUSION: Our results suggest that aspiration alone (repeated as clinically indicated) is a safe, efficacious treatment for the majority of patients with nocardial brain abscesses.

Authors
Lee, GYF; Daniel, RT; Brophy, BP; Reilly, PL; Friedman, AH; Grossman, RB; Hall, WA; Chandler, WF
MLA Citation
Lee, GYF, Daniel, RT, Brophy, BP, Reilly, PL, Friedman, AH, Grossman, RB, Hall, WA, and Chandler, WF. "Surgical treatment of nocardial brain abscesses." Neurosurgery 51.3 (2002): 668-672.
PMID
12188944
Source
scival
Published In
Neurosurgery
Volume
51
Issue
3
Publish Date
2002
Start Page
668
End Page
672
DOI
10.1097/00006123-200209000-00010

Isolated, giant cerebellopontine angle craniopharyngioma in a patient with Gardner syndrome: Case report

OBJECTIVE AND IMPORTANCE: We report the case of a 29-year-old man with Gardner syndrome and an isolated, giant cerebellopontine angle craniopharyngioma. Our description of this patient is only the second case report of a craniopharyngioma arising primarily in the cerebellopontine angle. CLINICAL PRESENTATION: The patient presented with a 1-year history of progressive neurological impairment and headache. On the basis of the patient's history of multiple dermal fibromas, a cranial osteoma, familial adenomatous polyposis (FAP), a total abdominal colectomy, and an adenoma of the ampulla of Vater, we diagnosed the patient's condition as Gardner syndrome. INTERVENTION: Magnetic resonance imaging showed a large cerebellopontine angle tumor, which was removed through a suboccipital retromastoid craniotomy. The pathological features were those of an adamantinomatous craniopharyngioma. The patient has done well postoperatively and has no new neurological deficits. A careful retrospective review of the preoperative imaging shows that this tumor was located exclusively in the posterior fossa and was not an extension of a sellar, suprasellar, or clival craniopharyngioma. CONCLUSION: We present the second reported case of FAP and craniopharyngioma. There is no known genetic link between FAP and craniopharyngioma. Now that the patient has manifested a primary tumor of the central nervous system with FAP, it is unclear whether he should be classified as having Turcot syndrome. For this patient, we recommended vigilant follow-up imaging and forgoing external beam radiotherapy unless there is a documented recurrence of his craniopharyngioma.

Authors
Link, MJ; Driscoll, CLW; Giannini, C; Friedman, AH; Jr, ESC; Gilles, FH; IV, GRH
MLA Citation
Link, MJ, Driscoll, CLW, Giannini, C, Friedman, AH, Jr, ESC, Gilles, FH, and IV, GRH. "Isolated, giant cerebellopontine angle craniopharyngioma in a patient with Gardner syndrome: Case report." Neurosurgery 51.1 (2002): 221-226.
PMID
12182421
Source
scival
Published In
Neurosurgery
Volume
51
Issue
1
Publish Date
2002
Start Page
221
End Page
226
DOI
10.1097/00006123-200207000-00033

Cerebellar hemorrhage after spinal surgery: Report of two cases and literature review

OBJECTIVE AND IMPORTANCE: Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedures. We describe our experience with two cases of cerebellar hemorrhage after spinal surgery and review the three cases previously reported in the literature to determine whether these cases provide insight regarding the pathogenesis of remote cerebellar hemorrhage. CLINICAL PRESENTATION: One of our patients developed cerebellar hemorrhage in the vermis and right hemisphere after transpedicular removal of a partially intradural T9-T10 herniated disc with the patient in the prone position. The other patient developed cerebellar hemorrhage in the vermis and bilateral hemispheres after L3-S1 decompression and instrumentation with the patient in the prone position, during which the dura was inadvertently opened. INTERVENTION: The first patient was treated conservatively and had mild residual dysarthria and gait ataxia 2 months after surgery. The second patient underwent exploration and revision of the lumbar wound with primary dural repair. The cerebellar hemorrhage was treated conservatively, and the patient had mild dysarthria and ataxia 1 month after surgery. CONCLUSION: Cerebellar hemorrhage must be considered in patients with unexplained neurological deterioration after spinal surgery. Dural opening with loss of cerebrospinal fluid has occurred in every reported case of cerebellar hemorrhage complicating a spinal procedure, supporting the hypothesis that loss of cerebrospinal fluid is central to the pathogenesis of this condition. Because remote cerebellar hemorrhage can occur after procedures with the patient in the supine, sitting, and prone positions, patient positioning seems unlikely to play a causative role in its occurrence.

Authors
Friedman, JA; Ecker, RD; Piepgras, DG; Duke, DA; Friedman, AH; Breeze, RE; McCormick, PC
MLA Citation
Friedman, JA, Ecker, RD, Piepgras, DG, Duke, DA, Friedman, AH, Breeze, RE, and McCormick, PC. "Cerebellar hemorrhage after spinal surgery: Report of two cases and literature review." Neurosurgery 50.6 (2002): 1361-1364.
PMID
12015857
Source
scival
Published In
Neurosurgery
Volume
50
Issue
6
Publish Date
2002
Start Page
1361
End Page
1364
DOI
10.1097/00006123-200206000-00030

Prognostic significance of amino acid transport imaging in patients with brain tumors

OBJECTIVE: To evaluate the prognostic significance of presence, intensity, and extent of amino acid uptake in patients with suspected primary or recurrent brain tumors. METHODS: We retrospectively analyzed 181 consecutive studies of amino acid uptake using single-photon emission computed tomography and the amino acid L-[3-123I]iodo-α-methyltyrosine (IMT). In a blinded analysis, all studies were evaluated for presence, maximal uptake (IMTmax), and extent (IMText) of focal tracer uptake. RESULTS: The most frequent tumors were 53 astrocytomas (World Health Organization Grade I-III), 41 glioblastomas, 16 metastases, 13 oligodendrogliomas (Grade II-III), and 10 medulloblastomas. The other patients exhibited various parenchymal tumors or nonneoplastic lesions. IMT uptake was present in 69% of the patients with IMTmax ranging from 1.4 to 6.2. IMTmax and IMText were significant predictors of survival in the whole group. When the group was divided according to primary versus recurrent tumor, only the primary tumors achieved a high level of significance (P < 0.01). When patients without any IMT uptake were excluded from the analysis, statistical significance for both IMTmax and IMText was lost. Multiple regression analysis, including IMTmax, IMText, age, and tumor grade, revealed only extent of IMT uptake as an independent predictor of prognosis. CONCLUSION: Absence of IMT uptake is a significant predictor of long-term survival in patients with suspected primary or recurrent brain tumors. Only the extent of a given lesion provided minor supplementary prognostic information as compared with histopathology and age. These findings suggest caution in relating high amino acid uptake values to poor prognosis, despite the capability of amino acid imaging to help determine the presence and extent of gliomas.

Authors
Weckesser, M; Matheja, P; Schwarzrock, A; Rickert, CH; Sträter, R; Palkovic, S; Riemann, B; Kopka, K; Lüdemann, P; Paulus, W; Wassmann, H; Schober, O; Friedman, AH; Glick, RP; Piepmeier, JM; Berger, MS; Warnke, PC
MLA Citation
Weckesser, M, Matheja, P, Schwarzrock, A, Rickert, CH, Sträter, R, Palkovic, S, Riemann, B, Kopka, K, Lüdemann, P, Paulus, W, Wassmann, H, Schober, O, Friedman, AH, Glick, RP, Piepmeier, JM, Berger, MS, and Warnke, PC. "Prognostic significance of amino acid transport imaging in patients with brain tumors." Neurosurgery 50.5 (2002): 958-965.
PMID
11950398
Source
scival
Published In
Neurosurgery
Volume
50
Issue
5
Publish Date
2002
Start Page
958
End Page
965
DOI
10.1097/00006123-200205000-00007

Stability of fibrin sealant in cerebrospinal fluid: An in vitro study

OBJECTIVE: The in vitro stability of fibrin sealant in cerebrospinal fluid (CSF) was investigated to verify the efficacy of intracranial application of fibrin sealant. METHODS: Human CSF was collected from 11 patients. Fibrin glue spheres (diameter, 5 mm) were incubated in CSF specimens at 37°C. At 2, 4, 8, 24, and 48 hours, the diameter of the spheres was measured and the ultrastructure was evaluated by transmission electron microscopy. A control group consisted of sealant spheres in physiological saline (n = 2). RESULTS: In all CSF samples, the fibrin sealant did not degrade with time. The size, consistency, color, and shape of the sealant remained unchanged, even 48 hours after placement in the CSF. Transmission electron microscopic analysis of the fibrin sealant revealed an amorphous, fibrinous meshwork. No morphological differences existed between fibrin sealant complex placed in the CSF for different time periods and sealant placed in physiological saline. CONCLUSION: Within the limitations of this in vitro study, human CSF has no adverse effects on fibrin sealant in terms of alteration of structure and morphology. Fibrin sealant is stable in a CSF environment and can be effectively used in the cisternal or subarachnoidal space.

Authors
Menovsky, T; Vries, JD; Weerman, MVDB; Grotenhuis, JA; Grossman, RG; Friedman, AH; Stieg, PE; Riina, HA; Chandler, WF
MLA Citation
Menovsky, T, Vries, JD, Weerman, MVDB, Grotenhuis, JA, Grossman, RG, Friedman, AH, Stieg, PE, Riina, HA, and Chandler, WF. "Stability of fibrin sealant in cerebrospinal fluid: An in vitro study." Neurosurgery 51.6 (2002): 1453-1456.
PMID
12445351
Source
scival
Published In
Neurosurgery
Volume
51
Issue
6
Publish Date
2002
Start Page
1453
End Page
1456
DOI
10.1097/00006123-200212000-00016

Necrotizing neurosarcoidosis of the cranial base resembling an en plaque sphenoid wing meningioma: Case report

OBJECTIVE AND IMPORTANCE: Necrotizing sarcoid granuloma (NSG) has been recognized as a histological variant of sarcoidosis. Two cases of neurosarcoidosis (NS) with NSG with concomitant systemic disease have been described previously. We present an unusual case of primary NS-NSG that resembled an en plaque cranial base meningioma. CLINICAL PRESENTATION: A 51-year-old man presented with a 3-month history of progressive left visual deterioration and proptosis. Brain magnetic resonance imaging demonstrated a large cranial base lesion occupying the left anterior clinoid process and sphenoid wing, extending to the left frontotemporal convexity. A second dura-based lesion was observed in the right parietal convexity. Both lesions enhanced homogeneously after administration of intravenous contrast medium. Magnetic resonance imaging characteristics were consistent with a typical clinoidal meningioma with an en plaque extension laterally. INTERVENTION: A left frontotemporal craniotomy with extradural removal of the anterior clinoid process was performed. When the dura was opened, a red fibrous mass was identified. Intraoperative histological analysis revealed the presence of necrotizing and noncaseating granulomas. Postoperatively, cerebrospinal fluid, erythrocyte sedimentation rate, C-reactive protein, and serum and cerebrospinal fluid angiotensin-converting enzyme values were normal. The search for acid-fast bacilli or fungi was negative. A diagnosis of primary NS-NSG was made. The patient began long-term high-dose corticosteroid therapy. One and a half years after surgery, his vision had improved significantly and the lesions were stable as revealed by magnetic resonance imaging. CONCLUSION: The first case of primary NS-NSG in the absence of systemic sarcoidosis is reported. NS should be included in the differential diagnosis of dura-based lesions resembling meningioma.

Authors
Tobias, S; Prayson, RA; Lee, JH; Friedman, AH; Samdani, A; Brem, H; Rock, JP; Pollock, BE
MLA Citation
Tobias, S, Prayson, RA, Lee, JH, Friedman, AH, Samdani, A, Brem, H, Rock, JP, and Pollock, BE. "Necrotizing neurosarcoidosis of the cranial base resembling an en plaque sphenoid wing meningioma: Case report." Neurosurgery 51.5 (2002): 1290-1294.
PMID
12383376
Source
scival
Published In
Neurosurgery
Volume
51
Issue
5
Publish Date
2002
Start Page
1290
End Page
1294
DOI
10.1097/00006123-200211000-00030

Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy.

Determination of side of seizure onset is critical for a successful outcome following epilepsy surgery. Little is known about the significance of lateralized seizure termination. Sustained seizure activity contralateral to side of seizure onset, following termination of ictal activity ipsilateral to side of onset, may suggest the presence of an independent focus. Such activity, if present, should predict a poor outcome. We studied side of seizure termination in 13 patients undergoing monitoring with bitemporal depth electrodes and correlated this to outcome following anterior temporal lobectomy (ATL). Side of seizure onset was determined for all seizures during that evaluation. Based on side of final cessation of ictal activity, patients were classified as having ipsilateral final termination or simultaneous termination (Group 1; N=6) or contra-lateral or mixed final termination (Group 2; N=7). The Duke outcome classification system was used. At the end of 2 years follow-up, 6/6 patients in Group 1 and 3/7 patients in Group 2 were seizure free. We conclude that lateralized seizure termination during evaluation with depth electrodes may be useful in predicting outcome following ATL. Continued seizure activity contralateral to side of seizure onset (following termination of ictal activity ipsilateral to side of onset) predicts a poor outcome. This may indicate the presence of an independent seizure focus opposite to the side of surgery.

Authors
Verma, A; Lewis, D; VanLandingham, KE; Husain, AM; Friedman, AH; Thompson, E; Radtke, RA
MLA Citation
Verma, A, Lewis, D, VanLandingham, KE, Husain, AM, Friedman, AH, Thompson, E, and Radtke, RA. "Lateralized seizure termination: relationship to outcome following anterior temporal lobectomy." Epilepsy Res 47.1-2 (November 2001): 9-15.
PMID
11673016
Source
pubmed
Published In
Epilepsy Research
Volume
47
Issue
1-2
Publish Date
2001
Start Page
9
End Page
15

Intractable epilepsy following radiosurgery for arteriovenous malformation.

Radiosurgery is often used to treat arteriovenous malformations (AVMs) located in deep brain locations. Most of these procedures are successful not only in obliterating the AVM but also in decreasing the frequency and severity of associated seizures. Although radiosurgery is occasionally associated with the development of easy-to-control seizures immediately postoperatively, there have been no reports of intractable epilepsy developing after radiosurgery. In this report, however, a case is presented in which a patient underwent gamma knife surgery (GKS) for an AVM, after which intractable epilepsy and mesial temporal sclerosis (MTS) gradually developed. A 37-year-old right-handed woman underwent GKS for a right mesial parietotemporooccipital AVM. One year later, the AVM had reduced in size, but the patient began to experience complex partial seizures (CPSs). These CPSs initially occurred at a frequency of one per month, but 6 months later they were occurring every other week. She also started having secondarily generalized tonic-clonic seizures (GTCSs) once per month. Over the next year the frequency of her seizures gradually increased to several CPSs per day and two to three GTCSs per week, despite treatment with various combinations of antiepileptic drugs. By this time her AVM had decreased to one half of its original size. Video-electroencephalography monitoring demonstrated that both the CPSs and GTCSs were arising from the right posterior quadrant. Magnetic resonance imaging revealed not only the presence of the right-sided AVM, but also right-sided MTS. The patient underwent surgical resection of the AVM and right temporal lobectomy. She has been free from seizure for longer than 1 year. Radiosurgery may be associated with intractable epilepsy and MTS.

Authors
Husain, AM; Mendez, M; Friedman, AH
MLA Citation
Husain, AM, Mendez, M, and Friedman, AH. "Intractable epilepsy following radiosurgery for arteriovenous malformation." J Neurosurg 95.5 (November 2001): 888-892.
PMID
11702882
Source
pubmed
Published In
Journal of neurosurgery
Volume
95
Issue
5
Publish Date
2001
Start Page
888
End Page
892
DOI
10.3171/jns.2001.95.5.0888

Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas.

Both Gliadel wafers [1,3-bis(2-chloroethyl)-1-nitrosourea] and temozolomide (TEMO) have been shown in independent studies to prolong survival of patients with recurrent malignant glioma following surgery and radiotherapy. On the basis of preclinical evidence of synergism between Gliadel wafers and TEMO, a phase I study was designed to evaluate the toxicity of combining these 2 agents in the treatment of patients with recurrent supratentorial malignant glioma. All patients had surgical resection of the tumor at relapse, and up to 8 Gliadel (3.85%) wafers were placed in the surgical cavity following resection. Two weeks after surgery, TEMO was given orally daily for 5 days. Cohorts of 3 patients received TEMO at daily doses of 100 mg/m2, 150 mg/m2, and 200 mg/m2, respectively. Patients were assessed for toxicity 4 weeks after start of the first course of TEMO. Contrast-enhanced MRI of the brain was used to assesstumor response after the first cycle of TEMO. Patients with stable disease or response after the first cycle of TEMO were allowed to continue treatment at the same dose every 4 weeks for 12 cycles or until disease progression or unacceptable toxicity. Ten patients with a median age of 47 years (range, 22-66 years) were enrolled in this study. There were 7 patients with glioblastoma multiforme and 3 patients with anaplastic astrocytoma. Three patients were treated with TEMO at the first dose level of 100 mg/m2, 4 at the second dose level of 150 mg/m2, and 3 at the third dose level of 200 mg/m2. The 10 patients received a median of 3 cycles (range, 1-12 cycles) of TEMO following placement of Gliadel wafers. The treatment was well tolerated, with only 1 patient suffering grade III thrombocytopenia at the highest dose level. Two patients at each dose level had no evidence of disease progression after treatment. Four patients suffered progressive disease on therapy. Our study demonstrates that TEMO can be given safely after placement of Gliadel (3.85%) wafers. The recommended dosage for TEMO for a phase II study of this combination is 200 mg/m2 per day for 5 days.

Authors
Gururangan, S; Cokgor, L; Rich, JN; Edwards, S; Affronti, ML; Quinn, JA; Herndon, JE; Provenzale, JM; McLendon, RE; Tourt-Uhlig, S; Sampson, JH; Stafford-Fox, V; Zaknoen, S; Early, M; Friedman, AH; Friedman, HS
MLA Citation
Gururangan, S, Cokgor, L, Rich, JN, Edwards, S, Affronti, ML, Quinn, JA, Herndon, JE, Provenzale, JM, McLendon, RE, Tourt-Uhlig, S, Sampson, JH, Stafford-Fox, V, Zaknoen, S, Early, M, Friedman, AH, and Friedman, HS. "Phase I study of Gliadel wafers plus temozolomide in adults with recurrent supratentorial high-grade gliomas." Neuro Oncol 3.4 (October 2001): 246-250.
PMID
11584894
Source
pubmed
Published In
Neuro-Oncology
Volume
3
Issue
4
Publish Date
2001
Start Page
246
End Page
250

Surgical approaches to pineal region tumors.

Direct surgical resection of pineal region tumors has become safer, more effective, and now plays an essential role in their management. Tissue diagnosis allows for the initiation of appropriate therapies and resection can be curative or improve the efficacy of adjuvant therapies. Several approaches have been reported. Based on our operative experience with 57 patients over a 20-year period, we conclude that the Infratentorial Supracerebellar and Parieto-Occipital Paramedian Transtentorial approaches provide excellent exposure while allowing minimally invasive, relatively low risk access to the majority of pineal region tumors. Indications, positioning, techniques, advantages, and disadvantages are discussed. A review of other approaches, pertinent historical remarks, and a discussion of the role of surgery in the contemporary management of pineal region tumors are presented.

Authors
Little, KM; Friedman, AH; Fukushima, T
MLA Citation
Little, KM, Friedman, AH, and Fukushima, T. "Surgical approaches to pineal region tumors." J Neurooncol 54.3 (September 2001): 287-299. (Review)
PMID
11767294
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
54
Issue
3
Publish Date
2001
Start Page
287
End Page
299

Clinical Studies in Non-chromosome 4-Linked Facioscapulohumeral Muscular Dystrophy.

OBJECTIVES: To characterize clinically and molecularly a large, non-chromosome 4-linked facioscapulohumeral muscular dystrophy (FSHMD) family. METHODS: Neurological evaluations of affected (N = 55) and at-risk (N = 48) individuals were performed along with selected laboratory analyses, including creatine kinase testing, muscle biopsy, p13E-11 fragment analysis, and cytogenetic studies. Genetic analyses of the scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy regions on chromosome 12 were performed using genetic markers flanking the intervals of interest and parametric LOD score analyses. RESULTS: Clinically, the FSHMD in individuals in this family is indistinguishable from that observed in chromosome 4-linked FSHMD. Fragment analysis with p13E-11 showed no small fragment segregating with the family and no evidence for 4:10 translocation or deletion of the p13E-11 binding site. Linkage analysis excluded the loci for autosomal-dominant scapuloperoneal muscular dystrophy and scapuloperoneal muscular atrophy. CONCLUSIONS: This family is clinically similar to patients with the chromosome 4-linked FSHMD. These data support our previous hypothesis of genetic heterogeneity within FSHMD.

Authors
Tim, RW; Gilbert, JR; Stajich, JM; Rampersaud, E; Viles, KD; Tawil, R; Padberg, GW; Frants, R; van der Maarel, S; Bossen, EH; Friedman, AH; Pericak-Vance, MA; Speer, MC
MLA Citation
Tim, RW, Gilbert, JR, Stajich, JM, Rampersaud, E, Viles, KD, Tawil, R, Padberg, GW, Frants, R, van der Maarel, S, Bossen, EH, Friedman, AH, Pericak-Vance, MA, and Speer, MC. "Clinical Studies in Non-chromosome 4-Linked Facioscapulohumeral Muscular Dystrophy." J Clin Neuromuscul Dis 3.1 (September 2001): 1-7.
PMID
19078645
Source
pubmed
Published In
Journal of Clinical Neuromuscular Disease
Volume
3
Issue
1
Publish Date
2001
Start Page
1
End Page
7

Three-dimensional computed tomographic cranial base measurements for improvement of surgical approaches to the petrous carotid artery and apex regions.

OBJECTIVE: The bony and vascular anatomic features in the region of the petrous apex can vary significantly. These variations affect the operative view obtained via extended subtemporal or anterior transpetrosal approaches to cranial base lesions for individual patients. The goal of this study was to evaluate three-dimensional computed tomography as a means of obtaining detailed preoperative anatomic information regarding bony and vascular landmarks and spatial relationships in the region of the petrous carotid artery and petrous apex. METHODS: We radiographically studied 15 patients (30 sides), using 0.8- to 1-mm-thick, reconstructed, computed tomographic images. Special attention was given to the course of the petrous carotid artery. RESULTS: The petrous carotid artery was located lateral to the trigeminal impression. The size of the petrous apex medial to the horizontal petrous carotid artery was observed to be variable. The width of bone from the trigeminal impression to the wall of the internal auditory canal averaged 9.6 mm (range, 5.2-16.1 mm). A variable amount of bone overlying the internal auditory canal (4.5 mm) was also present. Multiple other relationships among key landmarks were quantified. CONCLUSION: There is significant variability in the anatomic features of the petrous apex among patients. For each patient, detailed preoperative information regarding the amount of bone to be removed during a cranial base procedure can be obtained using three-dimensional computed tomography. This information may be critical for determination of the amount of extra exposure that can be achieved via an anterior petrosectomy for each patient.

Authors
Villavicencio, AT; Leveque, JC; Bulsara, KR; Friedman, AH; Gray, L
MLA Citation
Villavicencio, AT, Leveque, JC, Bulsara, KR, Friedman, AH, and Gray, L. "Three-dimensional computed tomographic cranial base measurements for improvement of surgical approaches to the petrous carotid artery and apex regions." Neurosurgery 49.2 (August 2001): 342-352.
PMID
11504110
Source
pubmed
Published In
Neurosurgery
Volume
49
Issue
2
Publish Date
2001
Start Page
342
End Page
352

Ectopic cardiac calcification associated with hyperparathyroidism in a boy with hypophosphatemic rickets.

An adolescent with hypophosphatemic rickets developed cardiac calcifications in the absence of hypercalcemia or elevation of the phosphocalcic product (the product of the total serum calcium and phosphorus concentrations). Cardiac calcifications led to aortic and mitral valve dysfunction, myocardial calcification, and arrhythmia. Hyperparathyroidism probably played a significant role in the development of this complication, which emphasizes the necessity for intermittent assessment of parathyroid status in individuals receiving medical therapy for hypophosphatemic rickets.

Authors
Moltz, KC; Friedman, AH; Nehgme, RA; Kleinman, CS; Carpenter, TO
MLA Citation
Moltz, KC, Friedman, AH, Nehgme, RA, Kleinman, CS, and Carpenter, TO. "Ectopic cardiac calcification associated with hyperparathyroidism in a boy with hypophosphatemic rickets." Curr Opin Pediatr 13.4 (August 2001): 373-375.
PMID
11717565
Source
pubmed
Published In
Current Opinion in Pediatrics
Volume
13
Issue
4
Publish Date
2001
Start Page
373
End Page
375

Long term response in a patient with neoplastic meningitis secondary to melanoma treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14 F(ab')(2): a case study.

Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressive hearing loss, severe headaches, nausea, vomiting, and a rapid decline in neurologic status. She was referred to Duke University Medical Center after conventional chemotherapy for malignant melanoma failed. She was enrolled in a Phase I trial of (131)I-labeled monoclonal antibody Mel-14 F(ab')(2) fragment administered intrathecally. Within a year after her treatment, she recovered, having a normal neurologic exam except for residual bilateral hearing loss. The authors discuss dosimetry, preclinical, and clinical studies conducted with Mel-14 F(ab')(2) and introduce a potentially promising therapy option in the treatment of neoplastic meningitis in patients with malignant melanoma. Currently, the patient remains neurologically normal except for a mild bilateral hearing loss more than 4 years after treatment and has no radiographic evidence of neoplastic meningitis.

Authors
Cokgor, I; Akabani, G; Friedman, HS; Friedman, AH; Zalutsky, MR; Zehngebot, LM; Provenzale, JM; Guy, CD; Wikstrand, CJ; Bigner, DD
MLA Citation
Cokgor, I, Akabani, G, Friedman, HS, Friedman, AH, Zalutsky, MR, Zehngebot, LM, Provenzale, JM, Guy, CD, Wikstrand, CJ, and Bigner, DD. "Long term response in a patient with neoplastic meningitis secondary to melanoma treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14 F(ab')(2): a case study." Cancer 91.9 (May 1, 2001): 1809-1813.
PMID
11335907
Source
pubmed
Published In
Cancer
Volume
91
Issue
9
Publish Date
2001
Start Page
1809
End Page
1813

Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children.

OBJECTIVE: We sought to identify the risk factors predicting the development of dilated cardiomyopathy (DCM) in patients with isolated congenital complete atrioventricular block (CCAVB). BACKGROUND: Recently evidence has emerged that a subset of patients with CCAVB develop DCM. METHODS: This was a retrospective study of 149 patients with CCAVB who had heart size and left ventricular (LV) function assessed by echocardiography and chest radiography over a follow-up period of 10 +/- 7 years. RESULTS: Nine patients developed DCM at the age of 6.5 +/- 5 years. No definite cause could be identified. In these nine patients, CCAVB was diagnosed in eight at 23 +/- 2.3 weeks gestation and in one at birth. Maternal SSA/SSB antibodies were confirmed in seven of the nine patients. Pacemakers were implanted in eight patients in the first month and in one patient at five years of age. The initial left ventricular end-diastolic dimension (LVEDD) was in the 96th +/- 2.6 percentile and the cardiothoracic (CT) ratio was 64 +/- 3.8% in the nine patients who developed DCM, and differed significantly in patients with CCAVB (p

Authors
Udink ten Cate, FE; Breur, JM; Cohen, MI; Boramanand, N; Kapusta, L; Crosson, JE; Brenner, JI; Lubbers, LJ; Friedman, AH; Vetter, VL; Meijboom, EJ
MLA Citation
Udink ten Cate, FE, Breur, JM, Cohen, MI, Boramanand, N, Kapusta, L, Crosson, JE, Brenner, JI, Lubbers, LJ, Friedman, AH, Vetter, VL, and Meijboom, EJ. "Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children." Journal of the American College of Cardiology 37.4 (March 2001): 1129-1134. (Academic Article)
Source
manual
Published In
JACC - Journal of the American College of Cardiology
Volume
37
Issue
4
Publish Date
2001
Start Page
1129
End Page
1134

Utility of three-dimensional computed tomographic angiography for assessment of relationships between the vertebrobasilar system and the cranial base.

OBJECTIVE: The optimal surgical exposure for basilar tip aneurysms is dictated by the relationship of the basilar bifurcation to the cranial base. This study was designed to evaluate three-dimensional computed tomographic angiography as a means of obtaining detailed anatomic information on the basilar artery and the surrounding cranial base in individual patients before surgery. METHODS: We studied 30 patients using three-dimensional computed tomographic angiographic reconstructions from 1-mm computed tomographic slices. Detailed anatomic measurements were performed to define the relationship between the basilar artery and the cranial base. Particular attention was paid to the height of the dorsum sellae and its relationship to the basilar bifurcation. RESULTS: The heights of the basilar apex and the vertebrobasilar junction, relative to the cranial base, were extremely variable. Considerable asymmetries in the heights of the left and right posterior clinoid processes were identified; in one case, this difference was more than 1 cm (mean difference in height, 0.9 mm; range, 0-10.3 mm). The heights of the posterior clinoid processes above the sellar floor ranged from 5.8 to 14.1 mm (mean height, 9.5 mm). We were able to determine the feasibility of the pterional/orbitozygomatic, middle fossa/ anterior petrosal, and presigmoid retrolabyrinthine approaches to an individual basilar bifurcation. We also estimated the amount of bone removal required and determined the operative distances via those approaches. CONCLUSION: Three-dimensional computed tomographic angiography is a useful tool for assessing critical anatomic relationships and represents an adjunct to conventional angiography in the planning of individualized, precisely tailored, cranial base approaches to the vertebrobasilar system.

Authors
Villavicencio, AT; Gray, L; Leveque, JC; Fukushima, T; Kureshi, S; Friedman, AH
MLA Citation
Villavicencio, AT, Gray, L, Leveque, JC, Fukushima, T, Kureshi, S, and Friedman, AH. "Utility of three-dimensional computed tomographic angiography for assessment of relationships between the vertebrobasilar system and the cranial base." Neurosurgery 48.2 (February 2001): 318-326.
PMID
11220374
Source
pubmed
Published In
Neurosurgery
Volume
48
Issue
2
Publish Date
2001
Start Page
318
End Page
326

Evaluation and surgical repair of brachial plexus injuries

Traumatic injuries of the brachial plexus may result in severe and permanent loss of motor and sensory function of the involved extremity. The neurosurgeon's ability to improve the functional outcome following a plexus injury requires an understanding of the functional anatomy of the brachial plexus, the pathophysiology of nerve injury, and the natural history of these lesions. Primary reanastomosis, neurolysis, and nerve grafting techniques are commonly used to restore normal axonal continuity. When these options are unavailable, muscle and tendon transfers or neurotization techniques have been successful in achieving functional restoration of limb movements.

Authors
Gabriel, EM; Villavicencio, AT; Friedman, AH
MLA Citation
Gabriel, EM, Villavicencio, AT, and Friedman, AH. "Evaluation and surgical repair of brachial plexus injuries." Seminars in Neurosurgery 12.1 (2001): 29-48.
Source
scival
Published In
Seminars in Neurosurgery
Volume
12
Issue
1
Publish Date
2001
Start Page
29
End Page
48

Surgical approaches to pineal region tumors

Direct surgical resection of pineal tumors has become safer, more effective, and now plays an essential role in their management. Tissue diagnosis allows for the initiation of appropriate therapies and resection can be curative or improve the efficacy of adjuvant therapies. Several approaches have been reported. Based on our operative experience with 57 patients over a 20-year period, we conclude that the Infratentorial Supracerebellar and Parieto-Occipital Paramedian Transtentorial approaches provide excellent exposure while allowing minimally invasive, relatively low risk access to the majority of pineal tumors. Indications, positioning, techniques, advantages, and disadvantages are discussed. A review of other approaches, pertinent historical remarks, and a discussion of the role of surgery in the contemporary management of pineal region tumors are presented.

Authors
Little, KM; Friedman, AH; Fukushima, T
MLA Citation
Little, KM, Friedman, AH, and Fukushima, T. "Surgical approaches to pineal region tumors." Journal of Neuro-Oncology 54.SPEC. ISS. (2001): 287-299.
Source
scival
Published In
Journal of Neuro-Oncology
Volume
54
Issue
SPEC. ISS.
Publish Date
2001
Start Page
287
End Page
299
DOI
10.1023/A:1012766902431

Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment. PATIENTS AND METHODS: In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of (131)I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment. RESULTS: We treated 42 patients with (131)I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively. CONCLUSION: The MTD for administration of (131)I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.

Authors
Cokgor, I; Akabani, G; Kuan, CT; Friedman, HS; Friedman, AH; Coleman, RE; McLendon, RE; Bigner, SH; Zhao, XG; Garcia-Turner, AM; Pegram, CN; Wikstrand, CJ; Shafman, TD; Herndon, JE; Provenzale, JM; Zalutsky, MR; Bigner, DD
MLA Citation
Cokgor, I, Akabani, G, Kuan, CT, Friedman, HS, Friedman, AH, Coleman, RE, McLendon, RE, Bigner, SH, Zhao, XG, Garcia-Turner, AM, Pegram, CN, Wikstrand, CJ, Shafman, TD, Herndon, JE, Provenzale, JM, Zalutsky, MR, and Bigner, DD. "Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas." J Clin Oncol 18.22 (November 15, 2000): 3862-3872.
PMID
11078500
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
18
Issue
22
Publish Date
2000
Start Page
3862
End Page
3872
DOI
10.1200/JCO.2000.18.22.3862

Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine (O(6)-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O(6)-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O(6)-BG with recurrent or progressive malignant glioma. PATIENTS AND METHODS: Patients were treated with O(6)-BG at a dose of 100 mg/m(2) followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O(6)-BG, 8-oxo-O(6)-BG, and 8-oxoguanine concentration. RESULTS: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m(2)) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O(6)-BG rapidly disappeared from plasma (elimination half-life = 0. 54 +/- 0.14 hours) and was converted to a longer-lived metabolite, 8-oxo-O(6)-BG (elimination half-life = 5.6 +/- 2.7 hours) and further to 8-oxoguanine. There was no detectable O(6)-BG 5 hours after the start of the O(6)-BG infusion; however, 8-oxo-O(6)-BG and 8-oxoguanine concentrations were detected 25 hours after O(6)-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O(6)-BG was 17.5 times greater than the mean AUC for O(6)-BG. CONCLUSION: These results indicate that the MTD of BCNU when given in combination with O(6)-BG at a dose of 100 mg/m(2) is 40 mg/m(2) administered at 6-week intervals. This study provides the foundation for a phase II trial of O(6)-BG plus BCNU in nitrosourea-resistant malignant glioma.

Authors
Friedman, HS; Pluda, J; Quinn, JA; Ewesuedo, RB; Long, L; Friedman, AH; Cokgor, I; Colvin, OM; Haglund, MM; Ashley, DM; Rich, JN; Sampson, J; Pegg, AE; Moschel, RC; McLendon, RE; Provenzale, JM; Stewart, ES; Tourt-Uhlig, S; Garcia-Turner, AM; Herndon, JE; Bigner, DD; Dolan, ME
MLA Citation
Friedman, HS, Pluda, J, Quinn, JA, Ewesuedo, RB, Long, L, Friedman, AH, Cokgor, I, Colvin, OM, Haglund, MM, Ashley, DM, Rich, JN, Sampson, J, Pegg, AE, Moschel, RC, McLendon, RE, Provenzale, JM, Stewart, ES, Tourt-Uhlig, S, Garcia-Turner, AM, Herndon, JE, Bigner, DD, and Dolan, ME. "Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma." J Clin Oncol 18.20 (October 15, 2000): 3522-3528.
PMID
11032594
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
18
Issue
20
Publish Date
2000
Start Page
3522
End Page
3528
DOI
10.1200/JCO.2000.18.20.3522

Temozolomide delivered by intracerebral microinfusion is safe and efficacious against malignant gliomas in rats.

Intracerebral microinfusion (ICM) is an innovative technique of delivering therapeutic agents throughout large portions of the brain that circumvents the blood-brain barrier, minimizes systemic toxicity, and provides a homogeneous distribution of the infused agent. Temozolomide is a novel methylating agent with proven efficacy against malignant gliomas (MGs) after systemic administration but with dose-limiting myelotoxicity. Because MGs rarely metastasize, systemic drug delivery is unnecessary. Therefore, we evaluated the efficacy and toxicity of ICM with temozolomide in an athymic rat model of human MGs. Treatment of rats by ICM with temozolomide 3 days after intracerebral challenge with D54 human MG xenograft increased median survival by 128% compared with rats treated by ICM with saline, by 113% compared with rats treated with i.p. saline, and by 100% compared with rats treated with i.p. temozolomide (P < 0.001). Delay of treatment until 9 days after tumor challenge still resulted in a 23% increase in median survival in rats treated by ICM of temozolomide compared with rats treated with i.p. temozolomide. In addition, overall, 21.7% of rats treated by ICM with temozolomide survived for > 100 days without clinical or histological evidence of tumor. The dose of temozolomide delivered by ICM in this study was limited only by drug solubility, and no neurological or systemic toxicity could be attributed to ICM with temozolomide. Therefore, ICM of temozolomide may offer significant advantages in the treatment of MGs.

Authors
Heimberger, AB; Archer, GE; McLendon, RE; Hulette, C; Friedman, AH; Friedman, HS; Bigner, DD; Sampson, JH
MLA Citation
Heimberger, AB, Archer, GE, McLendon, RE, Hulette, C, Friedman, AH, Friedman, HS, Bigner, DD, and Sampson, JH. "Temozolomide delivered by intracerebral microinfusion is safe and efficacious against malignant gliomas in rats." Clin Cancer Res 6.10 (October 2000): 4148-4153.
PMID
11051269
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
6
Issue
10
Publish Date
2000
Start Page
4148
End Page
4153

Fiber dissection technique: lateral aspect of the brain.

OBJECTIVE: The fiber dissection technique involves peeling away the white matter tracts of the brain to display its three-dimensional anatomic organization. Early anatomists demonstrated many tracts and fasciculi of the brain using this technique. The complexities of the preparation of the brain and the execution of fiber dissection have led to the neglect of this method, particularly since the development of the microtome and histological techniques. Nevertheless, the fiber dissection technique is a very relevant and reliable method for neurosurgeons to study the details of brain anatomic features. METHODS: Twenty previously frozen, formalin-fixed human brains were dissected from the lateral surface to the medial surface, using the operating microscope. Each stage of the process is described. The primary dissection tools were handmade, thin, wooden spatulas with tips of various sizes. RESULTS: We exposed and studied the myelinated fiber bundles of the brain and acquired a comprehensive understanding of their configurations and locations. CONCLUSION: The complex structures of the brain can be more clearly defined and understood when the fiber dissection technique is used. This knowledge can be incorporated into the preoperative planning process and applied to surgical strategies. Fiber dissection is time-consuming and complex, but it greatly adds to our knowledge of brain anatomic features and thus helps improve the quality of microneurosurgery. Because other anatomic techniques fail to provide a true understanding of the complex internal structures of the brain, the reestablishment of fiber dissection of white matter as a standard study method is recommended.

Authors
Türe, U; Yaşargil, MG; Friedman, AH; Al-Mefty, O
MLA Citation
Türe, U, Yaşargil, MG, Friedman, AH, and Al-Mefty, O. "Fiber dissection technique: lateral aspect of the brain." Neurosurgery 47.2 (August 2000): 417-426.
PMID
10942015
Source
pubmed
Published In
Neurosurgery
Volume
47
Issue
2
Publish Date
2000
Start Page
417
End Page
426

Inhibitory simple partial (non-convulsive) status epilepticus after intracranial surgery.

OBJECTIVES: To report on five patients who developed, 2 to 4 days after an intracranial neurosurgical procedure, new, persistent, focal neurological deficits which were due to inhibitory simple partial (non-convulsive) status epilepticus, and resolved with anticonvulsant treatment. METHODS: The age range of the five patients was 15-74 years. The operations were: aneurysm clipping (three patients) and resections of an oligodendroglioma and a cavernous haemangioma (one patient each). The new focal deficits were: right hemiparesis and aphasia (two patients), aphasia alone (two patients), and left hemiparesis (one patient). The deficits were not explained by CT (obtained in all patients) or cerebral angiography (performed in two). RESULTS: Electroencephalography showed, in all patients, continuous or intermittent focal seizures arising from cortex regionally relevant to the clinical dysfunction. Subtle positive epileptic phenomena (jerking) occurred intermittently in three patients as a late concommitant. Administration of anticonvulsant drugs resulted in significant improvement within 24 hours in four patients, with parallel resolution of ictal EEG activity. The fifth patient improved more slowly. Two patients relapsed when anticonvulsant concentrations fell, and improved again when they were raised. CONCLUSIONS: It is suggested that inhibitory simple partial (non-convulsive) status epilepticus be considered in the differential diagnosis when a new unexplained neurological deficit develops after an intracranial neurosurgical procedure. An EEG may help to diagnose this condition, leading to definitive treatment.

Authors
Armon, C; Radtke, RA; Friedman, AH
MLA Citation
Armon, C, Radtke, RA, and Friedman, AH. "Inhibitory simple partial (non-convulsive) status epilepticus after intracranial surgery." J Neurol Neurosurg Psychiatry 69.1 (July 2000): 18-24.
PMID
10864598
Source
pubmed
Published In
Journal of neurology, neurosurgery, and psychiatry
Volume
69
Issue
1
Publish Date
2000
Start Page
18
End Page
24

Comparative genetic patterns of glioblastoma multiforme: potential diagnostic tool for tumor classification.

Cytogenetic and molecular genetic studies of glioblastoma multiforme (GBM) have shown that the most frequent alterations are gains of chromosome 7, losses of 9p loci and chromosome 10, and gene amplification, primarily of the epidermal growth factor receptor (EGFR) gene. Although this profile is potentially useful in distinguishing GBM from other tumor types, the techniques used tend to be labor intensive, and some can detect only gains or losses of genetic loci. Comparative genomic hybridization (CGH) is a powerful technique capable of identifying both gains and losses of DNA sequences. The present study compares the CGH evaluation of 22 GBM with classic cytogenetics, loss of heterozygosity by allelotyping, and gene amplification by Southern blot analysis to determine the reliability of CGH in the genetic characterization of GBM. The CGH and karyotypic data were consistent in showing gain of chromosome 7 accompanied by a loss of chromosome 10 as the most frequent abnormality, followed by a loss of 9p in 17 of 22 GBM cases. Loss of heterozygosity of chromosomes 10 (19/22) and 9p (9/22) loci confirmed the underrepresentation by CGH. Genomic amplifications were observed by CGH in 5 of the 10 cases where gene amplification was detected by Southern blot analysis. The data show that CGH is equally reliable, compared with the more established genetic methods, for recognizing the prominent genetic alterations associated with GBM and support its use as a plausible adjunct to glioma classification.

Authors
Wiltshire, RN; Rasheed, BK; Friedman, HS; Friedman, AH; Bigner, SH
MLA Citation
Wiltshire, RN, Rasheed, BK, Friedman, HS, Friedman, AH, and Bigner, SH. "Comparative genetic patterns of glioblastoma multiforme: potential diagnostic tool for tumor classification." Neuro Oncol 2.3 (July 2000): 164-173.
PMID
11302337
Source
pubmed
Published In
Neuro-Oncology
Volume
2
Issue
3
Publish Date
2000
Start Page
164
End Page
173

Castleman's disease confined to the leptomeninges.

We report a rare case of the plasma cell variant of Castleman's disease confined to the leptomeninges in a 42-year-old female. Flow cytometry demonstrated a minor monoclonal kappa light chain population, and conventional Southern blotting confirmed clonal rearrangement of the J(H) immunoglobulin heavy-chain gene. Polymerase chain reaction for Epstein-Barr virus and Kaposi's sarcoma-associated herpes virus was negative. The patient is disease-free five years after surgical resection. To our knowledge, clonal gene rearrangement has not been previously reported in the plasma cell variant of localized intracranial Castleman's disease.

Authors
Cummings, TJ; Gong, JZ; Friedman, AH; McLendon, RE
MLA Citation
Cummings, TJ, Gong, JZ, Friedman, AH, and McLendon, RE. "Castleman's disease confined to the leptomeninges." Ann Clin Lab Sci 30.3 (July 2000): 278-282. (Review)
PMID
10945568
Source
pubmed
Published In
Annals of Clinical and Laboratory Science
Volume
30
Issue
3
Publish Date
2000
Start Page
278
End Page
282

Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors.

The epidermal growth factor receptor (EGFR) is often amplified and rearranged structurally in tumors of the brain, breast, lung, and ovary. The most common mutation, EGFRvIII, is characterized by an in-frame deletion of 801 base pairs, resulting in the generation of a novel tumor-specific epitope at the fusion junction. A murine homologue of the human EGFRvIII mutation was created, and an IgG2a murine mAb, Y10, was generated that recognizes the human and murine equivalents of this tumor-specific antigen. In vitro, Y10 was found to inhibit DNA synthesis and cellular proliferation and to induce autonomous, complement-mediated, and antibody-dependent cell-mediated cytotoxicity. Systemic treatment with i.p. Y10 of s.c. B16 melanomas transfected to express stably the murine EGFRvIII led to long-term survival in all mice treated (n = 20; P < 0.001). Similar therapy with i.p. Y10 failed to increase median survival of mice with EGFRvIII-expressing B16 melanomas in the brain; however, treatment with a single intratumoral injection of Y10 increased median survival by an average 286%, with 26% long-term survivors (n = 117; P < 0.001). The mechanism of action of Y10 in vivo was shown to be independent of complement, granulocytes, natural killer cells, and T lymphocytes through in vivo complement and cell subset depletions. Treatment with Y10 in Fc receptor knockout mice demonstrated the mechanism of Y10 to be Fc receptor-dependent. These data indicate that an unarmed, tumor-specific mAb may be an effective immunotherapy against human tumors and potentially other pathologic processes in the "immunologically privileged" central nervous system.

Authors
Sampson, JH; Crotty, LE; Lee, S; Archer, GE; Ashley, DM; Wikstrand, CJ; Hale, LP; Small, C; Dranoff, G; Friedman, AH; Friedman, HS; Bigner, DD
MLA Citation
Sampson, JH, Crotty, LE, Lee, S, Archer, GE, Ashley, DM, Wikstrand, CJ, Hale, LP, Small, C, Dranoff, G, Friedman, AH, Friedman, HS, and Bigner, DD. "Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors." Proc Natl Acad Sci U S A 97.13 (June 20, 2000): 7503-7508.
PMID
10852962
Source
pubmed
Published In
Proceedings of the National Academy of Sciences of USA
Volume
97
Issue
13
Publish Date
2000
Start Page
7503
End Page
7508
DOI
10.1073/pnas.130166597

Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis.

Gliomas of the optic nerve, although typically of pilocytic (WHO grade I) histology, can present within the spectrum of astrocytic neoplasia including glioblastoma (WHO grade IV). In certain cases, histologic features alone make the distinction between pilocytic and diffuse astrocytomas difficult. We reviewed 22 cases of optic nerve gliomas, 19 of which were pilocytic astrocytomas (PA), and 3 of which were diffuse, non-pilocytic astrocytomas. The cases were evaluated for their clinical course, radiographic appearance, histologic grade, and proliferation indices as detected by MIB-1 (Ki-67) and p53 antibodies. Of the 19 PA, 14 showed no tumor growth by magnetic resonance imaging, and had Ki-67 and p53 labeling indices (LI) of < 1%. The other 5 PA exhibited aggressive behavior manifest by marked diffuse infiltrative tumor growth causing death in 2 patients, 1 of whom was diagnosed with neurofibromatosis type 1 (immunoperoxidase and radiographs not available), and marked local growth with an average time to growth of 39.3 months, a Ki-67 LI of 2-3%, and a p53 LI of < 1% in three others. Three of the five aggressive PA histologically demonstrated a finely reticulated pattern, a pattern that appears as an exaggeration or expansion of the normal neuroglia of the optic nerve, and may simulate a diffuse low-grade astrocytoma. Two demonstrated the coarsely reticulated pattern, with the biphasic and microcystic pattern typical of PA. Three diffuse astrocytomas (2 anaplastic astrocytomas and 1 glioblastoma) originated clinically and radiographically from the optic nerve, and revealed a Ki-67 LI of 2-12%, a p53 LI of 2-8%, and an average time to growth of 8 months. We conclude that the majority of PA of the optic nerve are non-aggressive, stabilize radiographically, and have Ki-67 and p53 LI < 1%. However, a subpopulation of PA has a propensity for aggressive behavior, and are identified by a Ki-67 LI of 2-3% and a p53 LI of < 1%. Diffuse astrocytomas have both Ki-67 and p53 LI > 2%. Thus, in cases of aggressive optic nerve tumors in which the histologic review of biopsy material cannot confidently confirm the diagnosis of pilocytic or diffuse fibrillary glioma, a p53 LI of > 1% appears to favor the diagnosis of diffuse astrocytoma.

Authors
Cummings, TJ; Provenzale, JM; Hunter, SB; Friedman, AH; Klintworth, GK; Bigner, SH; McLendon, RE
MLA Citation
Cummings, TJ, Provenzale, JM, Hunter, SB, Friedman, AH, Klintworth, GK, Bigner, SH, and McLendon, RE. "Gliomas of the optic nerve: histological, immunohistochemical (MIB-1 and p53), and MRI analysis." Acta Neuropathol 99.5 (May 2000): 563-570.
PMID
10805102
Source
pubmed
Published In
Acta Neuropathologica
Volume
99
Issue
5
Publish Date
2000
Start Page
563
End Page
570

A lost contact lens and Actinomyces colonization in an asymptomatic patient.

Authors
Kruger, SJ; Mindel, JS; Friedman, AH
MLA Citation
Kruger, SJ, Mindel, JS, and Friedman, AH. "A lost contact lens and Actinomyces colonization in an asymptomatic patient." Arch Ophthalmol 118.4 (April 2000): 586-587.
PMID
10766153
Source
pubmed
Published In
Archives of Ophthalmology
Volume
118
Issue
4
Publish Date
2000
Start Page
586
End Page
587

Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy.

PURPOSE: The objective of this study was to perform the dosimetry and evaluate the dose-response relationships in newly diagnosed patients with malignant brain tumors treated by direct injections of (131)I-labeled 81C6 monoclonal antibody (MAb) into surgically created resection cavities (SCRCs). METHODS AND MATERIALS: Absorbed doses to the 2-cm-thick shell as measured from the margins of the resection cavity interface were estimated for 42 patients with primary brain tumors. MR images were used to assess the enhanced-rim volume as a function of time after radiolabeled MAb therapy. Biopsy samples were obtained from 15 patients and 1 autopsy. RESULTS: The average absorbed dose [range] to the 2-cm shell region was 32 [3-59] Gy. For the endpoint of minimal time to MR contrast enhancement, the optimal absorbed dose and initial dose-rate were 43 +/- 16 Gy and 0. 41 +/- 0.10 Gy/h, respectively. There was a correlation between the absorbed dose and dose rate to the shell region and biopsy outcome (tumor recurrence, radionecrosis, and tumor recurrence and/or radionecrosis). In this Phase I study, the maximum tolerated dose (MTD) was 120 mCi. At this MTD, the estimated average absorbed dose and initial dose rate to the 2-cm shell were 41 [9-89] Gy and 0.51 [0.24-1.13] Gy/h, respectively. These values are in agreement with the optimal values based on the time to MR lesion rim enhancement. CONCLUSIONS: The average absorbed dose to the 2-cm shell region varied considerably and mainly depended on cavity volume. In future clinical trials, the administered activity of (131)I-labeled 81C6 MAb may be adjusted based on cavity volume in order to deliver the optimal absorbed dose of 43 Gy rather than giving a fixed administered activity.

Authors
Akabani, G; Cokgor, I; Coleman, RE; González Trotter, D; Wong, TZ; Friedman, HS; Friedman, AH; Garcia-Turner, A; Herndon, JE; DeLong, D; McLendon, RE; Zhao, XG; Pegram, CN; Provenzale, JM; Bigner, DD; Zalutsky, MR
MLA Citation
Akabani, G, Cokgor, I, Coleman, RE, González Trotter, D, Wong, TZ, Friedman, HS, Friedman, AH, Garcia-Turner, A, Herndon, JE, DeLong, D, McLendon, RE, Zhao, XG, Pegram, CN, Provenzale, JM, Bigner, DD, and Zalutsky, MR. "Dosimetry and dose-response relationships in newly diagnosed patients with malignant gliomas treated with iodine-131-labeled anti-tenascin monoclonal antibody 81C6 therapy." Int J Radiat Oncol Biol Phys 46.4 (March 1, 2000): 947-958.
PMID
10705017
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
46
Issue
4
Publish Date
2000
Start Page
947
End Page
958

Parasitic lesion of the insula suggesting cerebral sparganosis: case report.

Cerebral sparganosis, a parasitic disease, rarely produces a chronic active inflammatory response in the brain. Clinically and radiographically the process may mimic a neoplasm. We report a 30-year-old man who underwent surgical exploration for a mass in the insular cortex. Histology revealed a densely fibrotic mass heavily infiltrated with plasma cells and lymphocytes, in which were embedded parasitic forms consistent with sparganosis. We describe the MRI appearances and pathologic features. Intracranial mass lesions secondary to sparganosis must be considered in patients with a history of travel to endemic areas, especially Asia.

Authors
Cummings, TJ; Madden, JF; Gray, L; Friedman, AH; McLendon, RE
MLA Citation
Cummings, TJ, Madden, JF, Gray, L, Friedman, AH, and McLendon, RE. "Parasitic lesion of the insula suggesting cerebral sparganosis: case report." Neuroradiology 42.3 (March 2000): 206-208.
PMID
10772144
Source
pubmed
Published In
Neuroradiology
Volume
42
Issue
3
Publish Date
2000
Start Page
206
End Page
208

Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis.

OBJECTIVE: To determine seizure outcome and its predictors in patients with medically refractory temporal lobe epilepsy (TLE) after temporal lobectomy (TL). BACKGROUND: TL is the most common surgical procedure performed in adolescents and adults for the treatment of medically refractory TLE. Seizure outcome has been reported extensively during the first few postoperative years, but little is known beyond that time. METHODS: The authors analyzed seizure outcome in 79 patients who underwent TL for epilepsy at the Duke University Medical Center from 1962 through 1984. Patients with less than 2 years of follow-up and degenerative disorders were excluded. Predictors of seizure outcome were analyzed using Kaplan-Meier survival analyses. RESULTS: The mean follow-up was 14 years (range, 2.1 to 33.6 years). Using Engel's classification, 65% of patients were class I, 15% were class II, 11% were class III, and 9% were class IV. At least one postoperative seizure occurred in 55% of subjects. The majority of recurrences (86%) took place within 2 years of surgery. Later recurrences tended not to lead to medical intractability. Higher monthly preoperative seizure frequency was associated with poor seizure outcome. A seizure-free state at 2 years was found to be a better predictor of long-term outcome than the 6-, 12-, and 18-month landmarks. CONCLUSIONS: TL provides sustained, long-term benefit in patients with medically refractory TLE. Seizure-free status at 2 years from the time of surgery is predictive of long-term remission.

Authors
Foldvary, N; Nashold, B; Mascha, E; Thompson, EA; Lee, N; McNamara, JO; Lewis, DV; Luther, JS; Friedman, AH; Radtke, RA
MLA Citation
Foldvary, N, Nashold, B, Mascha, E, Thompson, EA, Lee, N, McNamara, JO, Lewis, DV, Luther, JS, Friedman, AH, and Radtke, RA. "Seizure outcome after temporal lobectomy for temporal lobe epilepsy: a Kaplan-Meier survival analysis." Neurology 54.3 (February 8, 2000): 630-634.
PMID
10680795
Source
pubmed
Published In
Neurology
Volume
54
Issue
3
Publish Date
2000
Start Page
630
End Page
634

Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma.

To evaluate the efficacy and toxicity of dendritic cell (DC) based therapy for intracerebral gliomas, we utilized a cell line derived from an astrocytoma that arose spontaneously in a VM/Dk mouse. This astrocytoma mirrors human gliomas phenotypically, morphologically and secretes transforming growth factor (TGF)-betas, immunosuppressive cytokines secreted by human gliomas. Systemic vaccination of mice with DCs pulsed with tumor homogenate followed by intracranial tumor challenge produced a > 160% increase in median survival (p = 0.016) compared with mice vaccinated with PBS or unpulsed DCs (p = 0.083). Fifty percent of mice treated with pulsed DCs survived long-term. Immunologic memory was demonstrated by survival of mice rechallenged with tumor. Both cell-mediated and humoral immunity was induced. On histological examination only focal areas of demyelination at the tumor implantation site were present. There was no evidence that autoimmune encephalomyelitis was induced by DC vaccination. Therefore, in a murine model, vaccination with DCs pulsed with glioma tumor homogenate is a safe and effective therapy against a syngeneic glioma located in the immunologically privileged central nervous system (CNS).

Authors
Heimberger, AB; Crotty, LE; Archer, GE; McLendon, RE; Friedman, A; Dranoff, G; Bigner, DD; Sampson, JH
MLA Citation
Heimberger, AB, Crotty, LE, Archer, GE, McLendon, RE, Friedman, A, Dranoff, G, Bigner, DD, and Sampson, JH. "Bone marrow-derived dendritic cells pulsed with tumor homogenate induce immunity against syngeneic intracerebral glioma." J Neuroimmunol 103.1 (February 1, 2000): 16-25.
PMID
10674985
Source
pubmed
Published In
Journal of Neuroimmunology
Volume
103
Issue
1
Publish Date
2000
Start Page
16
End Page
25

Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure.

OBJECT: It is taken for granted that patients with hypertension are at greater risk for intracerebral hemorrhage during neurosurgical procedures than patients with normal blood pressure. The anesthesiologist, therefore, maintains mean arterial blood pressure (MABP) near the lower end of the autoregulation curve, which in patients with preexisting hypertension can be as high as 110 to 130 mm Hg. Whether patients with long-standing hypertension experience more hemorrhage than normotensive patients after brain surgery if their blood pressure is maintained at the presurgical hypertensive level is currently unknown. The authors tested this hypothesis experimentally in a rodent model. METHODS: Hemorrhage and edema in the brain after needle biopsy was measured in vivo by using three-dimensional magnetic resonance (MR) microscopy in the following groups: WKY rats, acutely hypertensive WKY rats, spontaneously hypertensive rats (SHR strain), and SHR rats treated with either sodium nitroprusside or nicardipine. Group differences were compared using Tukey's studentized range test followed by individual pairwise comparisons of groups and adjusted for multiple comparisons. There were no differences in PaCO2, pH, and body temperature among the groups. The findings in this study indicated that only acutely hypertensive WKY rats had larger volumes of hemorrhage. Chronically hypertensive SHR rats with MABPs of 130 mm Hg did not have larger hemorrhages than normotensive rats. There were no differences in edema volumes among groups. CONCLUSIONS: The brains of SHR rats with elevated systemic MABPs are probably protected against excessive hemorrhage during surgery because of greater resistance in the larger cerebral arteries and, thus, reduced cerebral intravascular pressures.

Authors
Benveniste, H; Kim, KR; Hedlund, LW; Kim, JW; Friedman, AH
MLA Citation
Benveniste, H, Kim, KR, Hedlund, LW, Kim, JW, and Friedman, AH. "Cerebral hemorrhage and edema following brain biopsy in rats: significance of mean arterial blood pressure." J Neurosurg 92.1 (January 2000): 100-107.
PMID
10616088
Source
pubmed
Published In
Journal of neurosurgery
Volume
92
Issue
1
Publish Date
2000
Start Page
100
End Page
107
DOI
10.3171/jns.2000.92.1.0100

Resident curriculum guidelines for neurosurgery. Congress of Neurological Surgeons Education Committee.

Authors
Traynelis, VC; Andrews, BT; Awad, IA; Batjer, HH; Belzberg, A; Leibrock, L; Couldwell, W; Follett, K; Friedman, A; Loftus, CM; Maniker, A; Mapstone, T; Pollock, BE; Jr, SSS; Valadka, A; Wolfla, C
MLA Citation
Traynelis, VC, Andrews, BT, Awad, IA, Batjer, HH, Belzberg, A, Leibrock, L, Couldwell, W, Follett, K, Friedman, A, Loftus, CM, Maniker, A, Mapstone, T, Pollock, BE, Jr, SSS, Valadka, A, and Wolfla, C. "Resident curriculum guidelines for neurosurgery. Congress of Neurological Surgeons Education Committee." Clinical neurosurgery 47 (2000): 589-681.
PMID
11197727
Source
scival
Published In
Clinical neurosurgery
Volume
47
Publish Date
2000
Start Page
589
End Page
681

Rubral tremor of Holmes, rare case of pathological tremor: case report

The authors present a very rare case of Holmes tremor (previously known as rubral or midbrain tremor). In all described till now cases the tremor was due to a known and revealed in laboratory or neuroimaging cause. We present an unusual case of a 42-year old woman with unilateral tremor of right extremities (mostly proximal part of upper extremity) which started abruptly 3 years ago. She had no suffer any serious disease before the onset of symptoms and her family history was also negative. The tremor was present at rest but accelerated during specific postures and active movements. The laboratory tests including: copper and ceruloplasmin concentrations, blood analysis for acanthocytes, evoked potentials, EEG, CT, MRI, MRA and SPECT did not reveal any significant changes. Treatment attempts with neuroleptics, clonazepam, L-dopa, valproic acid, biperiden were almost completely ineffective except local injections of botulinum toxin (Botox, Allergan, 150 U) into the muscles of right arm girdle which moderately alleviated tremor. We did not find any underlying pathology as a cause of tremor, clinically the same as symptomatic cases described in literature. We suggest the possibility of idiopathic origin of tremor in our case, although a very small size of lesion (f.i. ischaemic) could be undetectable in the described tests.

Authors
Sławek, J; Szymkiewicz-Rogowska, A; Friedman, A
MLA Citation
Sławek, J, Szymkiewicz-Rogowska, A, and Friedman, A. "Rubral tremor of Holmes, rare case of pathological tremor: case report." Neurologia i Neurochirurgia Polska 34.4 (2000): 775-782.
PMID
11105309
Source
scival
Published In
Neurologia i Neurochirurgia Polska
Volume
34
Issue
4
Publish Date
2000
Start Page
775
End Page
782

Carpal tunnel release: Surgical considerations

Entrapment of the median nerve at the carpal tunnel is the most common entrapment neuropathy. Although nocturnal paresthesias are the most common initial manifestation of carpal tunnel syndrome, the patient may also note hand numbness, clumsiness, pain radiating up the arm, and weakness or atrophy of thenar eminence muscles. The most important step in treating carpal tunnel syndrome is the diagnosis. A thorough knowledge of the normal and aberrant anatomy of the structures surrounding the carpal canal and uncompromised visualization of the transverse ligament are crucial to avoiding complications during the surgical release. Since Sir James Learmonth first described the surgical release of the transverse carpal ligament in 1933, several variations of the technique have been described. Most recently, several innovative procedures involving the endoscope have been introduced in the literature. Endoscopic methods include the two-portal techniques of Chow, Resnick, and Brown; the proximal uniportal techniques of Okutsu, Agee, and Menon; and the distal uniportal approach of Mirza. Proponents of endoscopic carpal tunnel release claim a decrease in postoperative palmar tenderness, a more rapid restoration of grip strength, and an earlier return to work as the major advantages of those techniques. These benefits of endoscopic carpal tunnel release must be weighed against the limited surgical exposure with concomitant risks of incomplete ligament release and inadvertent neurovascular or tendon injury. This review discusses the details of the various surgical procedures, both open and endoscopic, as well as discuss the potential benefits and complications associated with each.

Authors
Kureshi, SA; Friedman, AH
MLA Citation
Kureshi, SA, and Friedman, AH. "Carpal tunnel release: Surgical considerations." Techniques in Neurosurgery 6.1 (2000): 5-13.
Source
scival
Published In
Techniques in Neurosurgery
Volume
6
Issue
1
Publish Date
2000
Start Page
5
End Page
13

Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group.

PURPOSE: To determine the antitumor efficacy and safety profile of temozolomide in patients with malignant astrocytoma at first relapse. PATIENTS AND METHODS: This open-label, multicenter, phase II trial enrolled 162 patients (intent-to-treat [ITT] population). After central histologic review, 111 patients were confirmed to have had an anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma. Chemotherapy-naive patients were treated with temozolomide 200 mg/m(2)/d. Patients previously treated with chemotherapy received temozolomide 150 mg/m(2)/d; the dose could be increased to 200 mg/m(2)/d in the absence of grade 3/4 toxicity. Therapy was administered orally on the first 5 days of a 28-day cycle. RESULTS: Progression-free survival (PFS) at 6 months, the primary protocol end point, was 46% (95% confidence interval, 38% to 54%). The median PFS was 5.4 months, and PFS at 12 months was 24%. The median overall survival was 13.6 months, and the 6- and 12-month survival rates were 75% and 56%, respectively. The objective response rate determined by independent central review of gadolinium-enhanced magnetic resonance imaging scans of the ITT population was 35% (8% complete response [CR], 27% partial response [PR]), with an additional 26% of patients with stable disease (SD). The median PFS for patients with SD was 4.4 months, with 33% progression-free at 6 months. Maintenance of progression-free status and objectively assessed response (CR/PR/SD) were both associated with health-related quality-of-life (HQL) benefits. Adverse events were mild to moderate, with hematologic side effects occurring in less than 10% of patients. CONCLUSION: Temozolomide demonstrated good single-agent activity, an acceptable safety profile, and documented HQL benefits in patients with recurrent AA.

Authors
Yung, WK; Prados, MD; Yaya-Tur, R; Rosenfeld, SS; Brada, M; Friedman, HS; Albright, R; Olson, J; Chang, SM; O'Neill, AM; Friedman, AH; Bruner, J; Yue, N; Dugan, M; Zaknoen, S; Levin, VA
MLA Citation
Yung, WK, Prados, MD, Yaya-Tur, R, Rosenfeld, SS, Brada, M, Friedman, HS, Albright, R, Olson, J, Chang, SM, O'Neill, AM, Friedman, AH, Bruner, J, Yue, N, Dugan, M, Zaknoen, S, and Levin, VA. "Multicenter phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. Temodal Brain Tumor Group." J Clin Oncol 17.9 (September 1999): 2762-2771.
PMID
10561351
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
17
Issue
9
Publish Date
1999
Start Page
2762
End Page
2771
DOI
10.1200/JCO.1999.17.9.2762

Regional treatment of epidermal growth factor receptor vIII-expressing neoplastic meningitis with a single-chain immunotoxin, MR-1.

The incidence of neoplastic meningitis is on the rise. Neoplastic meningitis can result from a direct seeding of the neuraxis by primary brain tumors or by hematogeneous spread of systemic solid tumors. A frequent genetic alteration in primary brain tumors such as gliomas is an in-frame deletion in the epidermal growth factor receptor (EGFR) gene EGFRvIII, which brings together what were normally distant polypeptide sequences in the intact receptor. A novel glycine is formed at the fusion junction, resulting in a unique and tumor-specific target. By using phage display, we have isolated a single-chain antibody specific for the EGFRvIII mutation and expressed it with a modified form of the Pseudomonas exotoxin to form the immunotoxin MR1scFvPE38KDEL (MR-1). The multiple dose toxicity and therapeutic efficacy of MR-1 immunotoxin were tested in an athymic rat model of neoplastic meningitis. The maximally tolerated doses in non-tumor-bearing rats were three doses of 3 microg each. For therapeutic studies, the target was a neoplastic meningitis induced by intrathecal inoculation of the EGFRvIII-expressing human glioma U87MG.deltaEGFR. A dose escalation study compared the survival of three equal doses of 1, 2, and 3 microg of MR-1 immunotoxin with saline or 3 microg of the control immunotoxin specific for the interleukin 2 receptor, anti-Tac. All animals treated with three doses of saline or 3 microg of anti-Tac died, with median survival of 7 and 10 days, respectively. There were 75% (six of eight) long-term survivors in the group treated with three doses of 1 microg and 57% (four of seven) long-term survivors in the groups treated with three doses of either 2 or 3 microg of MR-1 immunotoxin. None of the MR-1 immunotoxin-treated groups reached median survival by the termination of the study at 53 days. Therefore, median survival was estimated to be >53 days, resulting in an estimated increase in median survival of >657% compared with saline and 430% versus anti-Tac. Compartmental therapy with three doses of 2 microg of MR-1 immunotoxin is effective in the treatment of EGFRvIII-expressing neoplastic meningitis. This dose was found to have no clinical or histopathological effects on non-tumor-bearing animals. MR-1 immunotoxin is, therefore, considered specific and safe within its therapeutic window. Phase I clinical trials for tumors invading the intrathecal space that express the EGFRvIII target should be initiated.

Authors
Archer, GE; Sampson, JH; Lorimer, IA; McLendon, RE; Kuan, CT; Friedman, AH; Friedman, HS; Pastan, IH; Bigner, DD
MLA Citation
Archer, GE, Sampson, JH, Lorimer, IA, McLendon, RE, Kuan, CT, Friedman, AH, Friedman, HS, Pastan, IH, and Bigner, DD. "Regional treatment of epidermal growth factor receptor vIII-expressing neoplastic meningitis with a single-chain immunotoxin, MR-1." Clin Cancer Res 5.9 (September 1999): 2646-2652.
PMID
10499644
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
5
Issue
9
Publish Date
1999
Start Page
2646
End Page
2652

Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization.

Oligodendroglial neoplasms are a subgroup of gliomas with distinctive morphological characteristics. In the present study we have evaluated a series of these tumors to define their molecular profiles and to determine whether there is a relationship between molecular genetic parameters and histological pattern in this tumor type. Loss of heterozygosity (LOH) for 1p and 19q was seen in 17/23 (74%) well-differentiated oligodendrogliomas, in 18/23 (83%) anaplastic oligodendrogliomas, and in 3/8 (38%) oligoastrocytomas grades II and III. LOH for 17p and/or mutations of the TP53 gene occurred in 14 of these 55 tumors. Only one of the 14 cases with 17p LOH/TP53 gene mutation also had LOH for 1p and 19q, and significant astrocytic elements were seen histologically in the majority of these 14 tumors. LOH for 9p and/or deletion of the CDKN2A gene occurred in 15 of these 55 tumors, and 11 of these cases were among the 24 (42%) anaplastic oligodendrogliomas. Comparative genomic hybridization (CGH) identified the majority of cases with 1p and 19q loss and, in addition, showed frequent loss of chromosomes 4, 14, 15, and 18. These findings demonstrate that oligodendroglial neoplasms usually have loss of 1p and 19q whereas astrocytomas of the progressive type frequently contain mutations of the TP53 gene, and that 9p loss and CDKN2A deletions are associated with progression from well-differentiated to anaplastic oligodendrogliomas.

Authors
Bigner, SH; Matthews, MR; Rasheed, BK; Wiltshire, RN; Friedman, HS; Friedman, AH; Stenzel, TT; Dawes, DM; McLendon, RE; Bigner, DD
MLA Citation
Bigner, SH, Matthews, MR, Rasheed, BK, Wiltshire, RN, Friedman, HS, Friedman, AH, Stenzel, TT, Dawes, DM, McLendon, RE, and Bigner, DD. "Molecular genetic aspects of oligodendrogliomas including analysis by comparative genomic hybridization." Am J Pathol 155.2 (August 1999): 375-386.
PMID
10433931
Source
pubmed
Published In
The American journal of pathology
Volume
155
Issue
2
Publish Date
1999
Start Page
375
End Page
386
DOI
10.1016/S0002-9440(10)65134-6

Eyelid healing after carbon dioxide laser skin resurfacing: histological analysis.

OBJECTIVE: To clarify in vivo healing of eyelid skin after carbon dioxide (CO2) laser resurfacing. DESIGN: Patients requesting upper eyelid blepharoplasty consented to undergo previous CO2 laser skin resurfacing of the upper eyelid skin segments to be excised at various time intervals. After blepharoplasty, the skin specimens were analyzed histopathologically by 2 masked pathologists. PATIENTS: Eight patients with Fitzpatrick skin types I and II. INTERVENTION: Upper eyelid CO2 laser resurfacing 1,2, 4, or 12 weeks before planned upper eyelid blepharoplasty. MAIN OUTCOME MEASURES: Epidermis: thickness, polarity, contour, and constituents. Dermis: repair zone thickness, vascular and inflammatory pattern, collagen deposition, and elastic fiber changes. RESULTS: The epidermis regenerated within 7 to 10 days. By 3 months, the epidermis revealed flattening of the rete peg pattern with restoration of polarity, keratinocytes, and melanocytes. The 3-month dermis demonstrated a fibrotic repair zone (500-700 microm), new elastic fibers, and telangiectatic capillaries. CONCLUSIONS: Eyelids heal similarly to other skin regions treated by CO2 laser resurfacing. This cutaneous healing is analogous to that previously reported with use of chemical peels. Histological changes may explain the skin smoothing and wrinkle reduction seen clinically.

Authors
Mannor, GE; Phelps, RG; Friedman, AH; Meltzer, M
MLA Citation
Mannor, GE, Phelps, RG, Friedman, AH, and Meltzer, M. "Eyelid healing after carbon dioxide laser skin resurfacing: histological analysis." Arch Ophthalmol 117.7 (July 1999): 913-916.
PMID
10408456
Source
pubmed
Published In
Archives of Ophthalmology
Volume
117
Issue
7
Publish Date
1999
Start Page
913
End Page
916

Treatment of neoplastic meningitis with intrathecal temozolomide.

Neoplastic meningitis (NM) results from leptomeningeal dissemination of cancers arising within the central nervous system or metastasizing to the leptomeninges from systemic neoplasms. The inability to produce therapeutic drug levels intrathecally (i.t.) with systemic administration and the minimal efficacy of chemotherapeutic agents currently available for direct i.t. use limit therapy. Temozolomide [8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4([3H])-one] is a novel methylating agent with proven activity against intraparenchymal malignant gliomas (MGs). Insolubility of the standard formulation prevents its efficacious use as an i.t. agent, however. To overcome this obstacle, we have developed a unique microcrystalline formulation of temozolomide with greatly enhanced solubility. Treatment of athymic rats bearing subarachnoid MER- human MG xenografts with four doses of i.t. microcrystalline temozolomide over a 2-week period produced a 142% increase in median survival at individual doses of 2.2 micromol (P = 0.0073) and a >367% increase in median survival at individual doses of 6.8 micromol (P = 0.0015). At the higher dose tested, three of eight rats treated developed no neurological symptoms and had no evidence of residual tumor on histological examination after treatment. Use of this microcrystalline formulation in athymic rats bearing subarachnoid MER+ human MG xenografts increased median survival >132% (P < 0.0058) at both dose levels tested. Toxicity directly attributable to the i.t. administration of microcrystalline temozolomide was exhibited in the highest dose groups only and was limited to small patchy areas of focal demyelination involving <5% of spinal cord long tracks.

Authors
Sampson, JH; Archer, GE; Villavicencio, AT; McLendon, RE; Friedman, AH; Bishop, WR; Bigner, DD; Friedman, HS
MLA Citation
Sampson, JH, Archer, GE, Villavicencio, AT, McLendon, RE, Friedman, AH, Bishop, WR, Bigner, DD, and Friedman, HS. "Treatment of neoplastic meningitis with intrathecal temozolomide." Clin Cancer Res 5.5 (May 1999): 1183-1188.
PMID
10353755
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
5
Issue
5
Publish Date
1999
Start Page
1183
End Page
1188

Irinotecan therapy in adults with recurrent or progressive malignant glioma.

PURPOSE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. PATIENTS AND METHODS: Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (i.v.) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients. RESULTS: All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment. CONCLUSION: Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance.

Authors
Friedman, HS; Petros, WP; Friedman, AH; Schaaf, LJ; Kerby, T; Lawyer, J; Parry, M; Houghton, PJ; Lovell, S; Rasheed, K; Cloughsey, T; Stewart, ES; Colvin, OM; Provenzale, JM; McLendon, RE; Bigner, DD; Cokgor, I; Haglund, M; Rich, J; Ashley, D; Malczyn, J; Elfring, GL; Miller, LL
MLA Citation
Friedman, HS, Petros, WP, Friedman, AH, Schaaf, LJ, Kerby, T, Lawyer, J, Parry, M, Houghton, PJ, Lovell, S, Rasheed, K, Cloughsey, T, Stewart, ES, Colvin, OM, Provenzale, JM, McLendon, RE, Bigner, DD, Cokgor, I, Haglund, M, Rich, J, Ashley, D, Malczyn, J, Elfring, GL, and Miller, LL. "Irinotecan therapy in adults with recurrent or progressive malignant glioma." J Clin Oncol 17.5 (May 1999): 1516-1525.
PMID
10334539
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
17
Issue
5
Publish Date
1999
Start Page
1516
End Page
1525
DOI
10.1200/JCO.1999.17.5.1516

Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus.

PURPOSE: Despite advances in microsurgical technique, many cavernous sinus meningiomas remain unresectable or only partially resectable, prompting referral of patients for radiation therapy. Stereotactic radiosurgery is recommended as therapy at some institutions. We evaluated our experience with fractionated radiotherapy to permit comparison with single-fraction radiosurgery. MATERIALS AND METHODS: Between July 1985 and January 1998, 21 women and 7 men were treated for primary (21) or recurrent (7) cavernous sinus meningiomas. Of these, 22 tumors were subtotally resected and 6 were unresectable. Of the 28 lesions, 26 were categorized histologically as benign (16), aggressive-benign (7), or malignant (3); 2 were not biopsied. All patients were treated with fractionated photon irradiation to a median dose of 53.1 Gy. We assessed prognostic factors for overall (OS) and progression-free survival (PFS), including age, gender, presentation (primary vs. recurrent), extent of surgical resection, radiotherapy dose, and technique. Influence of radiotherapy dose and technique on acute and late treatment toxicities was analyzed. RESULTS: One patient died of disease and 2 others were alive with progressive disease at last follow-up, yielding 8-year actuarial OS and PFS of 96% and 81%, respectively. Univariate analysis showed that none of the prognostic factors tested was significantly associated with OS or PFS. There were two late side effects of treatment: an orbital sac fibrosis and a 6-month decline of cognitive function documented by formal neuropsychiatric testing. Neither radiotherapy dose nor technique significantly influenced late toxicity. CONCLUSION: For unresectable or subtotally resected cavernous sinus meningiomas, fractionated radiotherapy provides patients with excellent progression-free survival and minimal treatment-related toxicity.

Authors
Maguire, PD; Clough, R; Friedman, AH; Halperin, EC
MLA Citation
Maguire, PD, Clough, R, Friedman, AH, and Halperin, EC. "Fractionated external-beam radiation therapy for meningiomas of the cavernous sinus." Int J Radiat Oncol Biol Phys 44.1 (April 1, 1999): 75-79.
PMID
10219797
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
44
Issue
1
Publish Date
1999
Start Page
75
End Page
79

Dosimetry of 131I-labeled 81C6 monoclonal antibody administered into surgically created resection cavities in patients with malignant brain tumors.

UNLABELLED: The objective of this study was to perform the dosimetry of 131I-labeled 81C6 monoclonal antibody (MAb) in patients with recurrent malignant brain tumors, treated by direct injections of MAb into surgically created resection cavities (SCRCs). METHODS: Absorbed dose estimates were performed for nine patients. Dosimetry was performed retrospectively using probe counts (during patient isolation) and whole-body and SPECT images thereafter. Absorbed doses were calculated for the SCRC interface and for regions of interest (ROIs) 1 and 2 cm thick, measured from the margins of cavity interface. Also, mean absorbed doses were calculated for normal brain, liver, spleen, thyroid gland, stomach, bone marrow and whole body. The average residence time for the SCRC was 111 h (65-200h). RESULTS: The average absorbed dose per unit injected activity (range) to the SCRC interface and ROIs 1 and 2 cm thick from the cavity interface were 31.9 (7.8-84.2), 1.9 (0.7-3.6) and 1.0 (0.4-1.8) cGy/MBq, respectively. Average absorbed doses per unit administered activity to brain, liver, spleen, thyroid, stomach, bone marrow and whole body were 0.18, 0.03, 0.08, 0.05, 0.02, 0.02 and 0.01 cGy/MBq, respectively. The high absorbed dose delivered to the SCRC interface may have produced an increase in cavity volume independent of tumor progression. CONCLUSION: At the maximum tolerated dose of 3700 MBq 131I-labeled 81C6 MAb, the absorbed doses to the SCRC interface and ROIs of 1 and 2 cm thickness were estimated to be 1180, 71 and 39 Gy, respectively. The estimated average absorbed dose to the brain was 6.5 Gy. There was no neurological toxicity and minimal hematologic toxicity at this maximum tolerated administration level.

Authors
Akabani, G; Reist, CJ; Cokgor, I; Friedman, AH; Friedman, HS; Coleman, RE; Zhao, XG; Bigner, DD; Zalutsky, MR
MLA Citation
Akabani, G, Reist, CJ, Cokgor, I, Friedman, AH, Friedman, HS, Coleman, RE, Zhao, XG, Bigner, DD, and Zalutsky, MR. "Dosimetry of 131I-labeled 81C6 monoclonal antibody administered into surgically created resection cavities in patients with malignant brain tumors." J Nucl Med 40.4 (April 1999): 631-638.
PMID
10210222
Source
pubmed
Published In
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Volume
40
Issue
4
Publish Date
1999
Start Page
631
End Page
638

Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke.

BACKGROUND: Topotecan activity was evaluated for the treatment of malignant glioma. METHODS: Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throughout text.]at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). RESULTS: Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. CONCLUSIONS: These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.

Authors
Friedman, HS; Kerby, T; Fields, S; Zilisch, JE; Graden, D; McLendon, RE; Houghton, PJ; Arbuck, S; Cokgor, I; Friedman, AH
MLA Citation
Friedman, HS, Kerby, T, Fields, S, Zilisch, JE, Graden, D, McLendon, RE, Houghton, PJ, Arbuck, S, Cokgor, I, and Friedman, AH. "Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke." Cancer 85.5 (March 1, 1999): 1160-1165.
PMID
10091802
Source
pubmed
Published In
Cancer
Volume
85
Issue
5
Publish Date
1999
Start Page
1160
End Page
1165

Diagnosis of phacoanaphylactic endophthalmitis by fine needle aspiration biopsy.

Diagnosis of phacoanaphylactic endophthalmitis (or lens induced uveitis), a rare autoimmune disease, is difficult due to variable clinical presentation. We sought to diagnose a case based on the cytopathology of the anterior chamber aspirate. This is a case report of spontaneous phacoanaphylactic endophthalmitis in a 79-year-old woman with no history of eye trauma or surgery. After clinical examination, diagnostic anterior chamber paracentesis was performed. Cytologic examination of the aspirate revealed polymorphonuclear leukocytes, histiocytes, and plasma cells surrounding amorphous lens material. A mature cataract was removed subsequently, and the eye has remained free of inflammation postoperatively. As the clinical diagnosis of phacoanaphylactic endophthalmitis is often difficult, cytopathology of an anterior chamber aspiration specimen may be useful in diagnosing this rare, treatable condition. As far as we know, this is the first case report of the diagnosis of phacoanaphylactic endophthalmitis solely by anterior chamber fine needle aspiration biopsy.

Authors
Hochman, M; Sugino, IK; Lesko, C; Friedman, AH; Zarbin, MA
MLA Citation
Hochman, M, Sugino, IK, Lesko, C, Friedman, AH, and Zarbin, MA. "Diagnosis of phacoanaphylactic endophthalmitis by fine needle aspiration biopsy." Ophthalmic Surg Lasers 30.2 (February 1999): 152-154.
PMID
10037211
Source
pubmed
Published In
Ophthalmic surgery and lasers
Volume
30
Issue
2
Publish Date
1999
Start Page
152
End Page
154

Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy.

PURPOSE: Interictal [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) reveals regional hypometabolism in 60-80% of patients with mesial temporal lobe epilepsy (MTLE). The extent of hypometabolism generally extends beyond the epileptogenic zone. The pathophysiology underlying this widespread change is unknown. This study evaluated the relation between hippocampal neuronal loss and hypometabolism in patients with MTLE. METHODS: Forty-three patients with MTLE after anterior temporal lobectomy were included. Pathology demonstrated mesial temporal sclerosis (n = 41) or endfolium sclerosis (n = 2). Interictal FDG-PET scans were graded by visual analysis on a scale ranging from normal (grade 1) to severe (grade 5) hypometabolism. Neuronal counting was performed in the subiculum, hippocampal subfields, and dentate granular cell layer (DG). Neuronal density of patients was compared with that of seven autopsy controls. Data were compared by using Student's t tests and Kruskal-Wallis one-way analysis of variance (ANOVA). RESULTS: Significant neuronal loss in CA1 through CA4 and DG was found in patients compared with controls. Neuronal density in the subiculum, CA1, CA4, and DG did not correlate with severity of hypometabolism. However, patients with abnormal FDG-PET had higher neuronal density in CA2 and CA3 versus patients with normal studies. CONCLUSIONS: This study supports a previous observation that degree of FDG-PET hypometabolism does not parallel severity of hippocampal neuronal loss in MTLE.

Authors
Foldvary, N; Lee, N; Hanson, MW; Coleman, RE; Hulette, CM; Friedman, AH; Bej, MD; Radtke, RA
MLA Citation
Foldvary, N, Lee, N, Hanson, MW, Coleman, RE, Hulette, CM, Friedman, AH, Bej, MD, and Radtke, RA. "Correlation of hippocampal neuronal density and FDG-PET in mesial temporal lobe epilepsy." Epilepsia 40.1 (January 1999): 26-29.
PMID
9924898
Source
pubmed
Published In
Epilepsia
Volume
40
Issue
1
Publish Date
1999
Start Page
26
End Page
29

Chemotherapy for adults with malignant glioma.

Authors
Cokgor, I; Friedman, HS; Friedman, AH
MLA Citation
Cokgor, I, Friedman, HS, and Friedman, AH. "Chemotherapy for adults with malignant glioma." Cancer Invest 17.4 (1999): 264-272. (Review)
PMID
10225006
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
17
Issue
4
Publish Date
1999
Start Page
264
End Page
272

Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats.

The current study was designed to evaluate the toxicity and activity of Spartaject Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 micromol of intrathecal Spartaject Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 micromol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 micromol x 1, 6.2 micromol x 4 and 4.1 micromol x 4, respectively, against D-456 MG. A single dose of 8.1 micromol of intrathecal Spartaject Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 micromol x 1), 52.3% (2.0 micromol x 4), and 23% (8.1 micromol x 4) (p < 0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose-response relationships of alkylating agents, provide rationale for further evaluation of this agent.

Authors
Archer, GE; Sampson, JH; McLendon, RE; Friedman, AH; Colvin, OM; Rose, M; Sands, H; McCullough, W; Fuchs, HE; Bigner, DD; Friedman, HS
MLA Citation
Archer, GE, Sampson, JH, McLendon, RE, Friedman, AH, Colvin, OM, Rose, M, Sands, H, McCullough, W, Fuchs, HE, Bigner, DD, and Friedman, HS. "Intrathecal busulfan treatment of human neoplastic meningitis in athymic nude rats." J Neurooncol 44.3 (1999): 233-241.
PMID
10720203
Source
pubmed
Published In
Journal of Neuro-Oncology
Volume
44
Issue
3
Publish Date
1999
Start Page
233
End Page
241

Three-dimensional ct angiography for planning skull base approaches to vertebrobasilar aneurysms: a radiographic and cadaveric study

Three-dimensional CTA was evaluated as a means of acquiring detailed anatomic measurements of the relationships between bony landmarks at the base of the skull and the vertebrobasilar system. Thirty normal patients underwent CT angiography with 1-mm slices reconstructed into dynamic 3D images. Particular attention was paid to the heights and distances between the clivus. the petrous apex, and the vertebrobasilar system. Usefulness of these measurements was then evaluated in 10 cadaveric dissections. Considerable assymetries in the heights of the left versus the right posterior clinoid processes were identifed. in some cases more than a centimeter (mean difference in height, 2.7 mm; range. 0.2-11 mm). Location of the vertebrobasilar system was also extremely variable, as were the angles required for clip placement. 3-D CTA is a safe and reliable tool for appreciating critical anatomic relationships and represents an indispensable adjunct to conventional angiography when planning individualized skull base approaches to the vertebrobasilar system.

Authors
Villavicencio, AT; Cray, L; Kureshi, S; Friedman, AH
MLA Citation
Villavicencio, AT, Cray, L, Kureshi, S, and Friedman, AH. "Three-dimensional ct angiography for planning skull base approaches to vertebrobasilar aneurysms: a radiographic and cadaveric study." Skull Base Surgery 9.SUPPL. 1 (1999): 33--.
Source
scival
Published In
Skull base surgery
Volume
9
Issue
SUPPL. 1
Publish Date
1999
Start Page
33-

Three-dimensional ct angiography for evaluating anatomic variations of the skull base in the region of the intrapetrous carotid

Introduction: We evaluated 3-D CTA as a means of obtaining detailed anatomic information regarding differences in bony landmarks and spatial relationships in the region of the petrous carotid. Methods: Thirty patients underwent CT angiography with 1-mm slices reconstructed into dynamic 3-D images. Special attention was given to the course and landmarks surrounding the petrous carotid. Results: Highly variable amounts of bone were present between the carotid and the petrous apex. The width of bone from the trigeminal impression to the posterior wall of the IAC averaged 12.1 mm (range, 8.5 to 14.2 mm). Considerable variations were also present in the bony portion of the EAC and the tympanic bone which would require different amounts of drilling in order to expose the ascending portion of the intrapetrous carotid medial to the eustacian tube. Conclusions: This technique may have important therapeutic implications with regards to planning skull base approaches and minimizing potential complications.

Authors
Villavicencio, AT; Gray, L; Kureshi, S; Friedman, AH
MLA Citation
Villavicencio, AT, Gray, L, Kureshi, S, and Friedman, AH. "Three-dimensional ct angiography for evaluating anatomic variations of the skull base in the region of the intrapetrous carotid." Skull Base Surgery 9.SUPPL. 1 (1999): 33--.
Source
scival
Published In
Skull base surgery
Volume
9
Issue
SUPPL. 1
Publish Date
1999
Start Page
33-

Topotecan treatment of adults with primary malignant glioma

BACKGROUND. Topotecan activity was evaluated for the treatment of malignant glioma. METHODS. Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan {AU: Please verify all dosages here and throughout text.}at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). RESULTS. Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. CONCLUSIONS. These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.

Authors
Friedman, HS; Kerby, T; Fields, S; Zilisch, JE; Graden, D; McLendon, RE; Houghton, PJ; Arbuck, S; Cokgor, I; Friedman, AH
MLA Citation
Friedman, HS, Kerby, T, Fields, S, Zilisch, JE, Graden, D, McLendon, RE, Houghton, PJ, Arbuck, S, Cokgor, I, and Friedman, AH. "Topotecan treatment of adults with primary malignant glioma." Cancer 85.5 (1999): 1160-1165.
Source
scival
Published In
Cancer
Volume
85
Issue
5
Publish Date
1999
Start Page
1160
End Page
1165
DOI
10.1002/(SICI)1097-0142(19990301)85:5<1160::AID-CNCR21>3.0.CO;2-F

DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma.

PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS: Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS: Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION: These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.

Authors
Friedman, HS; McLendon, RE; Kerby, T; Dugan, M; Bigner, SH; Henry, AJ; Ashley, DM; Krischer, J; Lovell, S; Rasheed, K; Marchev, F; Seman, AJ; Cokgor, I; Rich, J; Stewart, E; Colvin, OM; Provenzale, JM; Bigner, DD; Haglund, MM; Friedman, AH; Modrich, PL
MLA Citation
Friedman, HS, McLendon, RE, Kerby, T, Dugan, M, Bigner, SH, Henry, AJ, Ashley, DM, Krischer, J, Lovell, S, Rasheed, K, Marchev, F, Seman, AJ, Cokgor, I, Rich, J, Stewart, E, Colvin, OM, Provenzale, JM, Bigner, DD, Haglund, MM, Friedman, AH, and Modrich, PL. "DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma." J Clin Oncol 16.12 (December 1998): 3851-3857.
PMID
9850030
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
16
Issue
12
Publish Date
1998
Start Page
3851
End Page
3857
DOI
10.1200/JCO.1998.16.12.3851

Seizure onset from periventricular nodular heterotopias: depth-electrode study.

The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80% arose from the hippocampi and 20% from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.

Authors
Kothare, SV; VanLandingham, K; Armon, C; Luther, JS; Friedman, A; Radtke, RA
MLA Citation
Kothare, SV, VanLandingham, K, Armon, C, Luther, JS, Friedman, A, and Radtke, RA. "Seizure onset from periventricular nodular heterotopias: depth-electrode study." Neurology 51.6 (December 1998): 1723-1727.
PMID
9855532
Source
pubmed
Published In
Neurology
Volume
51
Issue
6
Publish Date
1998
Start Page
1723
End Page
1727

Gliomas.

Authors
Cokgor, I; Friedman, AH; Friedman, HS
MLA Citation
Cokgor, I, Friedman, AH, and Friedman, HS. "Gliomas." Eur J Cancer 34.12 (November 1998): 1910-1915. (Review)
PMID
10023314
Source
pubmed
Published In
European Journal of Cancer
Volume
34
Issue
12
Publish Date
1998
Start Page
1910
End Page
1915

Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma.

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy is the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT), which removes chlorethylation or methylation damage from the O6-position of guanine. O6-benzylguanine (O6-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial to define the presurgical dose required for depletion of tumor AGT activity in patients with malignant glioma. MATERIALS AND METHODS: Patients were to be treated 18 hours before craniotomy with intravenous doses that ranged between 40 and 100 mg/m2 given over 1 hour. Resected tumor was snap-frozen in liquid nitrogen and AGT activity analyzed by high-pressure liquid chromatography (HPLC). Up to 13 patients were treated at a specific dose of O6-BG, with a target end point of > or = 11 of 13 patients with undetectable tumor AGT levels (< 10 fmol/mg protein). RESULTS: Thirty patients with malignant gliomas were enrolled, with 11 of 11 patients treated at 100 mg/m2 O6-BG demonstrating tumor AGT levels less than 10 fmol/mg protein. No toxicity was noted in any patient treated. CONCLUSION: These results indicate that 100 mg/m2 of O6-BG can maintain tumor AGT levels less than 10 fmol/mg protein for at least 18 hours after treatment, a time interval in which bis(2-chloroethyl)nitrosourea (BCNU)-induced chloroethyl adducts are fully converted into interstrand cross-links. A 100-mg/m2 dose of O6-BG will be used in combination with BCNU in another phase I trial designed to determine the maximal-tolerated dose of BCNU.

Authors
Friedman, HS; Kokkinakis, DM; Pluda, J; Friedman, AH; Cokgor, I; Haglund, MM; Ashley, DM; Rich, J; Dolan, ME; Pegg, AE; Moschel, RC; McLendon, RE; Kerby, T; Herndon, JE; Bigner, DD; Schold, SC
MLA Citation
Friedman, HS, Kokkinakis, DM, Pluda, J, Friedman, AH, Cokgor, I, Haglund, MM, Ashley, DM, Rich, J, Dolan, ME, Pegg, AE, Moschel, RC, McLendon, RE, Kerby, T, Herndon, JE, Bigner, DD, and Schold, SC. "Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma." J Clin Oncol 16.11 (November 1998): 3570-3575.
PMID
9817277
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
16
Issue
11
Publish Date
1998
Start Page
3570
End Page
3575
DOI
10.1200/JCO.1998.16.11.3570

Case 4--1998. Cardiopulmonary bypass and hypothermic circulatory arrest for basilar artery aneurysm clipping.

Authors
Weiss, L; Grocott, HP; Rosania, RA; Friedman, A; Newman, MF; Warner, DS
MLA Citation
Weiss, L, Grocott, HP, Rosania, RA, Friedman, A, Newman, MF, and Warner, DS. "Case 4--1998. Cardiopulmonary bypass and hypothermic circulatory arrest for basilar artery aneurysm clipping." J Cardiothorac Vasc Anesth 12.4 (August 1998): 473-479.
PMID
9713741
Source
pubmed
Published In
Journal of Cardiothoracic and Vascular Anesthesia
Volume
12
Issue
4
Publish Date
1998
Start Page
473
End Page
479

Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): preliminary results. Writing Committee for The Brain Tumor Center at Duke.

BACKGROUND: Exploration of the role of chemotherapy in the treatment of low grade glioma, including oligodendroglioma, has been limited to the pediatric population, reflecting the sensitivity of young patients to radiation-induced toxicity and a desire to avoid this intervention (7-12). PROCEDURE: Nine adults with progressive oligodendroglioma were treated with carboplatin at a dose of 560 mg/m2 administered at 4 week intervals. RESULTS: Eight patients have demonstrated stable disease as determined by serial MRI imaging at 2-3 month intervals with neither tumor regression nor growth noted. The ongoing duration of tumor control ranges between 6-22 months. Three patients have completed therapy with carboplatin and continue with stable dis-ease off chemotherapy. One patient progressed after 1 year of therapy with histologic confirmation of growth of well differentiated oligodendroglioma. Toxicity was limited to grade 3 thrombocytopenia in 3 patients and grade 3 neutropenia in 2 patients. CONCLUSIONS: Carboplatin appears to be active in the treatment of adults with progressive oligodendroglioma. Further trials are warranted to more precisely define the role of carboplatin in the treatment of these tumors.

Authors
Friedman, HS; Lovell, S; Rasheed, K; Friedman, AH
MLA Citation
Friedman, HS, Lovell, S, Rasheed, K, and Friedman, AH. "Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): preliminary results. Writing Committee for The Brain Tumor Center at Duke." Med Pediatr Oncol 31.1 (July 1998): 16-18.
PMID
9607424
Source
pubmed
Published In
Pediatric Blood and Cancer
Volume
31
Issue
1
Publish Date
1998
Start Page
16
End Page
18

Retinopathy associated with pancreatitis in a child with maple syrup urine disease.

Authors
Danias, J; Raab, EI; Friedman, AH
MLA Citation
Danias, J, Raab, EI, and Friedman, AH. "Retinopathy associated with pancreatitis in a child with maple syrup urine disease." Br J Ophthalmol 82.7 (July 1998): 841-842. (Letter)
PMID
9924384
Source
pubmed
Published In
British Journal of Ophthalmology
Volume
82
Issue
7
Publish Date
1998
Start Page
841
End Page
842

Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy.

PURPOSE: This retrospective study reports the long-term surgical outcome of patients with medically refractory epilepsy and vascular malformations who were treated with lesionectomy. A detailed analysis of surgical failures had been performed in an attempt to define predictors of surgical success and failure. METHODS: Fifteen patients with medically intractable epilepsy and angiographically occult vascular malformations (AOVMs) were treated surgically with lesionectomy at Duke University Medical Center. Lesionectomy consisted of removal of the AOVM and surrounding hemosiderin-stained brain only, without the use of electrocorticography (ECoG) to guide resection. RESULTS: Eleven (73%) patients are seizure free after lesionectomy. Three showed no significant improvement, and one patient died, presumably after a seizure. Age of onset, duration of seizures, age at resection, and gender did not affect outcome. All patients with neocortical AOVMs in whom EEG findings correlated with the site of the lesion were seizure free after lesional resection. Treatment failures were associated with the presence of multiple intracranial lesions, poorly localized or diffuse EEG findings, discordant positron emission tomography (PET) imaging, or with a lesion in close proximity to the limbic system. CONCLUSIONS: Lesionectomy, with removal of surrounding hemosiderin-stained brain, can be considered the procedure of choice in carefully selected patients with epilepsy with occult vascular malformations.

Authors
Kraemer, DL; Griebel, ML; Lee, N; Friedman, AH; Radtke, RA
MLA Citation
Kraemer, DL, Griebel, ML, Lee, N, Friedman, AH, and Radtke, RA. "Surgical outcome in patients with epilepsy with occult vascular malformations treated with lesionectomy." Epilepsia 39.6 (June 1998): 600-607.
PMID
9637602
Source
pubmed
Published In
Epilepsia
Volume
39
Issue
6
Publish Date
1998
Start Page
600
End Page
607

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results.

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.

Authors
Bigner, DD; Brown, MT; Friedman, AH; Coleman, RE; Akabani, G; Friedman, HS; Thorstad, WL; McLendon, RE; Bigner, SH; Zhao, XG; Pegram, CN; Wikstrand, CJ; Herndon, JE; Vick, NA; Paleologos, N; Cokgor, I; Provenzale, JM; Zalutsky, MR
MLA Citation
Bigner, DD, Brown, MT, Friedman, AH, Coleman, RE, Akabani, G, Friedman, HS, Thorstad, WL, McLendon, RE, Bigner, SH, Zhao, XG, Pegram, CN, Wikstrand, CJ, Herndon, JE, Vick, NA, Paleologos, N, Cokgor, I, Provenzale, JM, and Zalutsky, MR. "Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results." J Clin Oncol 16.6 (June 1998): 2202-2212.
PMID
9626222
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
16
Issue
6
Publish Date
1998
Start Page
2202
End Page
2212
DOI
10.1200/JCO.1998.16.6.2202

Analysis of DNA mismatch repair proteins in human medulloblastoma.

During replication, the primary function of the eukaryotic DNA mismatch repair (MMR) system is to recognize and correct mismatched base pairs within the DNA helix. Deficiencies in MMR have been reported previously in cases of hereditary nonpolyposis colorectal cancer and sporadic tumors occurring in a variety of tissues including gliomas. Furthermore, recent evidence indicates that the MMR system may be involved in mediating therapeutic sensitivity to alkylating agents. In this study, 22 neoplastic tissue samples from 22 patients who underwent surgical resection for medulloblastoma, a common cerebellar tumor of childhood, were assayed for the presence or absence of MMR polypeptides using Western blot and immunohistochemical techniques. Results from these experiments indicate that the MMR system is not commonly deficient in medulloblastoma.

Authors
Lee, SE; Johnson, SP; Hale, LP; Li, J; Bullock, N; Fuchs, H; Friedman, A; McLendon, R; Bigner, DD; Modrich, P; Friedman, HS
MLA Citation
Lee, SE, Johnson, SP, Hale, LP, Li, J, Bullock, N, Fuchs, H, Friedman, A, McLendon, R, Bigner, DD, Modrich, P, and Friedman, HS. "Analysis of DNA mismatch repair proteins in human medulloblastoma." Clin Cancer Res 4.6 (June 1998): 1415-1419.
PMID
9626457
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
4
Issue
6
Publish Date
1998
Start Page
1415
End Page
1419

Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas.

In this study, the authors sought to investigate the response rate and toxicity of carboplatin in patients with progressive low-grade glioma (LGG). Thirty-two patients with progressive LGG were treated with carboplatin at a dosage of 560 mg/m(2). Treatment was given at 4-week intervals and continued until the disease progressed, unacceptable toxicity supervened, or for 12 additional courses after achieving maximal response. Patients with stable disease were treated with a total of 12 cycles. All patients were treated as outpatients. Patients were evaluated for response to treatment and toxicity. All patients received a minimum of two cycles of carboplatin, and were examined for response. A partial response was achieved in nine patients (28%) and a minimal response in two (6%), for an overall response rate of 34% (11 of 32 patients). Eighteen patients (56%) had stable disease. A partial response was achieved in the nine patients after a median of six cycles (range 4-11 cycles), a minimal response was achieved in the two patients after five cycles. Glioma progression was noted in three patients after three, five, and five cycles, respectively. The 11 patients in whom some response was achieved had either an optic pathway tumor or a juvenile pilocytic astrocytoma. Twenty-six of the 32 patients had those characteristics, making the response rate in that group 42% (11 of 26 patients). Thirty-two patients received a total of 387 cycles of chemotherapy. Hematological toxicity was moderate. Twenty-one patients developed thrombocytopenia (platelet count < 50,000/microl); three patients required one platelet transfusion each. Nine patients developed neutropenia (absolute neutrophil count < 500/microl); one developed fever and required administration of antibiotic agents. One dose adjustment in each of the patients prevented further thrombocytopenia and neutropenia. Two patients with stable disease died of respiratory complications. One patient developed Grade III ototoxicity after receiving five cycles, one patient developed hypersensitivity to carboplatin, and none developed nephrotoxicity. Carboplatin given at a dosage of 560 mg/m(2) every 4 weeks has activity in patients with progressive LGG. This drug regimen is relatively simple and well tolerated. Further investigation and longer follow-up study are warranted.

Authors
Moghrabi, A; Friedman, HS; Ashley, DM; Bottom, KS; Kerby, T; Stewart, E; Bruggers, C; Provenzale, JM; Champagne, M; Hershon, L; Watral, M; Ryan, J; Rasheed, K; Lovell, S; Korones, D; Fuchs, H; George, T; McLendon, RE; Friedman, AH; Buckley, E; Longee, DC
MLA Citation
Moghrabi, A, Friedman, HS, Ashley, DM, Bottom, KS, Kerby, T, Stewart, E, Bruggers, C, Provenzale, JM, Champagne, M, Hershon, L, Watral, M, Ryan, J, Rasheed, K, Lovell, S, Korones, D, Fuchs, H, George, T, McLendon, RE, Friedman, AH, Buckley, E, and Longee, DC. "Phase II study of carboplatin (CBDCA) in progressive low-grade gliomas." Neurosurg Focus 4.4 (April 15, 1998): e3-.
PMID
17168503
Source
pubmed
Published In
Neurosurgical focus
Volume
4
Issue
4
Publish Date
1998
Start Page
e3

Images in cardiovascular medicine. Kawasaki disease: coronary aneurysms in mother and son.

Authors
Bruckheimer, E; Bulbul, Z; McCarthy, P; Madri, JA; Friedman, AH; Hellenbrand, WE
MLA Citation
Bruckheimer, E, Bulbul, Z, McCarthy, P, Madri, JA, Friedman, AH, and Hellenbrand, WE. "Images in cardiovascular medicine. Kawasaki disease: coronary aneurysms in mother and son." Circulation 97.4 (February 3, 1998): 410-411.
PMID
9468215
Source
pubmed
Published In
Circulation
Volume
97
Issue
4
Publish Date
1998
Start Page
410
End Page
411

Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma.

UNLABELLED: Brain metastases are a common and devastating complication in patients with malignant melanoma. Therapeutic options for these patients are limited, and the prognosis is usually poor. OBJECT: A retrospective review of 6953 patients with melanoma treated at a single institution was undertaken to identify demographic factors associated with the development of clinically significant brain metastases in 702 of these patients and to determine the factors influencing the prognosis of this population to permit more informed recommendations regarding surgical therapy. METHODS: Factors found to be associated with the development of brain metastases included male gender, primary lesions located on mucosal surfaces or on the skin of the trunk or head and neck, thick or ulcerated primary lesions, and histological findings of acral lentiginous or nodular lesions. The overall median survival time of all patients with brain metastases was 113.2 days, and these metastases contributed to the death of 94.5% of the patients in this group. Patients with primary lesions located in the head or neck region had a significantly shorter survival time relative to other patients with brain metastases, whereas patients with a single brain metastasis, patients without lung or multiple other visceral metastases, and patients whose initial presentation with melanoma included a brain metastasis had a significantly better prognosis. The small group of patients who survived for more than 3 years was characterized by the presence of a surgically treated, single brain metastasis in the absence of other visceral metastatic disease. CONCLUSIONS: Although most patients with brain metastases resulting from melanoma have a dismal prognosis, some who are likely to survive for longer periods can be identified. In these patients surgical resection can significantly prolong meaningful survival. The decision to recommend surgery should be based primarily on the resectability of the brain metastases and on the status and number of other organs with metastatic lesions.

Authors
Sampson, JH; Carter, JH; Friedman, AH; Seigler, HF
MLA Citation
Sampson, JH, Carter, JH, Friedman, AH, and Seigler, HF. "Demographics, prognosis, and therapy in 702 patients with brain metastases from malignant melanoma." J Neurosurg 88.1 (January 1998): 11-20.
PMID
9420067
Source
pubmed
Published In
Journal of neurosurgery
Volume
88
Issue
1
Publish Date
1998
Start Page
11
End Page
20
DOI
10.3171/jns.1998.88.1.0011

Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): Preliminary results

Background. Exploration of the role of chemotherapy in the treatment of low grade glioma, including oligodendroglioma, has been limited to the pediatric population, reflecting the sensitivity of young patients to radiation-induced toxicity and a desire to avoid this intervention (7-12). Procedure. Nine adults with progressive oligodendroglioma were treated with carboplatin at a dose of 560 mg/m2 administered at 4 week intervals. Results. Eight patients have demonstrated stable disease as determined by serial MRI imaging at 2-3 month intervals with neither tumor regression nor growth noted. The ongoing duration of tumor control ranges between 6-22 months. Three patients have completed therapy with carboplatin and continue with stable dis-ease off chemotherapy. One patient progressed after 1 year of therapy with histologic confirmation of growth of well differentiated oligodendroglioma. Toxicity was limited to grade 3 thrombocytopenia in 3 patients and grade 3 neutropenia in 2 patients. Conclusions. Carboplatin appears to be active in the treatment of adults with progressive oligodendroglioma. Further trials are warranted to more precisely define the role of carboplatin in the treatment of these tumors.

Authors
Friedman, HS; Lovell, S; Rasheed, K; Friedman, AH
MLA Citation
Friedman, HS, Lovell, S, Rasheed, K, and Friedman, AH. "Treatment of adults with progressive oligodendroglioma with carboplatin (CBDCA): Preliminary results." Medical and Pediatric Oncology 31.1 (1998): 16-18.
Source
scival
Published In
Pediatric Blood and Cancer
Volume
31
Issue
1
Publish Date
1998
Start Page
16
End Page
18
DOI
10.1002/(SICI)1096-911X(199807)31:1<16::AID-MPO3>3.0.CO;2-2

PTEN gene mutations are seen in high-grade but not in low-grade gliomas.

The PTEN gene, located on 10q23, has recently been implicated as a candidate tumor suppressor gene in brain, breast and prostate tumors. In the present study, 123 brain tumors, including various grades and histological types of gliomas occurring in children and adults, were analyzed for PTEN mutations by SSCP assay and sequencing. Mutations in the PTEN gene were found in 13 of 42 adult glioblastomas and 3 of 13 adult anaplastic astrocytomas, whereas none of the 21 low-grade adult gliomas or the 22 childhood gliomas of all grades showed mutations. The single medulloblastoma with a mutation was a recurrent tumor that also possessed a p53 mutation. High-grade adult gliomas with PTEN mutations included cases that also contained gene amplification or p53 gene mutations, as well as cases that did not contain either of these abnormalities. There was no obvious relationship between presence of PTEN mutation and survival; however, there was a tendency for PTEN mutations to occur in older age group patients. This analysis suggest that PTEN gene mutations are restricted to high-grade adult gliomas and that this abnormality is independent of the presence or absence of gene amplification or p53 gene mutation in these tumors.

Authors
Rasheed, BK; Stenzel, TT; McLendon, RE; Parsons, R; Friedman, AH; Friedman, HS; Bigner, DD; Bigner, SH
MLA Citation
Rasheed, BK, Stenzel, TT, McLendon, RE, Parsons, R, Friedman, AH, Friedman, HS, Bigner, DD, and Bigner, SH. "PTEN gene mutations are seen in high-grade but not in low-grade gliomas." Cancer Res 57.19 (October 1, 1997): 4187-4190.
PMID
9331072
Source
pubmed
Published In
Cancer Research
Volume
57
Issue
19
Publish Date
1997
Start Page
4187
End Page
4190

Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII.

The potential of therapeutic targeting of tumor cell surface epidermal growth factor receptors (EGFRs) by modified ligands or specific antibodies has been limited by the normal tissue distribution of the receptor. The identification and characterization of a variant of this receptor, EGFRvIII, which is not expressed in normal tissues but has been described in gliomas, non-small cell lung carcinomas, and breast carcinomas, has provided a highly specific, internalizing target for antibody-mediated approaches. To determine the feasibility of immunotargeting EGFRvIII, we have assessed the qualitative distribution and quantitative expression at both the population and cellular levels of EGFRvIII in 21 biopsy samples of human gliomas by indirect analytical and quantitative flow cytometry and by immunohistochemical assay of frozen and formalin-fixed tissue. Consistent with previous reports, 50% of gliomas tested (1 of 2 anaplastic astrocytomas, 7 of 12 glioblastoma multiforme, and 2 of 6 oligodendrogliomas) expressed EGFRvIII, as determined by a minimum of 2 separate assays. Minimum estimates of the proportion of positive tumor cells in these populations ranged from 37-86%; in four of five cases in which quantitation of the EGFRvIII density/cell was performed, values of 2.7-6.8 x 10(5) were obtained with monoclonal antibody (mAb) L8A4 (EGFRvIII specific), levels consistent with successful in vivo immunotargeting. Confocal microscopic analysis confirmed that the subcellular localization of EGFRvIII was identical to that described for EGFR: predominant cell membrane expression, with some perinuclear distribution suggestive of localization to the Golgi region. Neither EGFR nor EGFRvIII was found within the nucleus. This study establishes for the first time that approximately 50% of human glioma biopsies contain cell populations expressing a sufficient number of membrane-expressed EGFRvIIIs to mediate specific anti-EGFRvIII mAb localization. Coupled with previous demonstrations of the rapid internalization of specific mAb-EGFRvIII complexes and the susceptibility of the targeted cells to isotope or toxin-mediated cytotoxicity, this study establishes the validity of targeting EGFRvIII for therapy of mutant receptor-positive gliomas, breast carcinomas, and non-small cell lung carcinomas.

Authors
Wikstrand, CJ; McLendon, RE; Friedman, AH; Bigner, DD
MLA Citation
Wikstrand, CJ, McLendon, RE, Friedman, AH, and Bigner, DD. "Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII." Cancer Res 57.18 (September 15, 1997): 4130-4140.
PMID
9307304
Source
pubmed
Published In
Cancer Research
Volume
57
Issue
18
Publish Date
1997
Start Page
4130
End Page
4140

Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy.

To determine whether lesional neocortical temporal lobe epilepsy (NTLE) can be differentiated from mesial temporal lobe epilepsy (MTLE) during the noninvasive presurgical evaluation, we compared the historical features, seizure symptomatology, and surface EEG of 8 patients seizure free after neocortical temporal resection with preservation of mesial structures and 20 patients after anterior temporal lobectomy for MTLE. Seizure symptomatology of 107 seizures (28 NTLE, 79 MTLE) was analyzed. One hundred one ictal EEGs (19 NTLE, 82 MTLE) were reviewed for activity at seizure onset; presence, distribution, and frequency of lateralized rhythmic activity (LRA); and distribution of postictal slowing. Seizure symptomatology and EEG data were compared between groups, and sensitivity, specificity, and positive and negative predictive values were determined for variables that differed significantly. Multiple logistic regression was used to determine whether patients could be correctly classified as having MTLE or NTLE. MTLE patients were younger at onset of habitual seizures and more likely to have a prior history of febrile seizures, CNS infection, perinatal complications, or head injury. NTLE seizures lacked features commonly exhibited in MTLE, including automatisms, contralateral dystonia, searching head movements, body shifting, hyperventilation, and postictal cough or sigh. NTLE ictal EEG recordings demonstrated lower mean frequency of LRA that frequently had a hemispheric distribution, whereas LRA in MTLE seizures was maximal over the ipsilateral temporal region. We conclude that it may be possible to differentiate lesional NTLE from MTLE on the basis of historical features, seizure symptomatology, and ictal surface EEG recordings. This may assist in the identification of patients with medically refractory nonlesional NTLE who frequently require intracranial monitoring and more extensive or tailored resections.

Authors
Foldvary, N; Lee, N; Thwaites, G; Mascha, E; Hammel, J; Kim, H; Friedman, AH; Radtke, RA
MLA Citation
Foldvary, N, Lee, N, Thwaites, G, Mascha, E, Hammel, J, Kim, H, Friedman, AH, and Radtke, RA. "Clinical and electrographic manifestations of lesional neocortical temporal lobe epilepsy." Neurology 49.3 (September 1997): 757-763.
PMID
9305337
Source
pubmed
Published In
Neurology
Volume
49
Issue
3
Publish Date
1997
Start Page
757
End Page
763

Complications in the treatment of carpal tunnel syndrome.

Complications may result from every facet of the management of carpal tunnel syndrome. The authors review the common errors in diagnosis, nonoperative management, and operative treatment, with emphasis on prevention and resolution of complications. In general, surgeons can minimize complications by taking a thorough patient history, performing a comprehensive physical examination, and possessing a precise knowledge of the appropriate anatomy. Endoscopic techniques appear to offer some advantage over conventional open techniques with regard to the patient's postoperative incision pain, preservation of grip strength, and time to return to work; however, these advantages may be potentially negated by the risk of injury to neurovascular structures and tendons.

Authors
Henkin, P; Friedman, AH
MLA Citation
Henkin, P, and Friedman, AH. "Complications in the treatment of carpal tunnel syndrome." Neurosurg Focus 3.1 (July 15, 1997): e10-.
PMID
15099047
Source
pubmed
Published In
Neurosurgical focus
Volume
3
Issue
1
Publish Date
1997
Start Page
e10
DOI
10.3171/foc.1997.3.4.11

Surgical anatomy of the carpal tunnel.

The author describes and details the anatomy of the carpal tunnel and surrounding structures pertinent to the surgical treatment of carpal tunnel syndrome. Potential complications of both open and endoscopic carpal tunnel release are discussed as well as techniques to avoid or minimize poor patient outcomes.

Authors
Friedman, AH
MLA Citation
Friedman, AH. "Surgical anatomy of the carpal tunnel." Neurosurg Focus 3.1 (July 15, 1997): e1-.
PMID
15099039
Source
pubmed
Published In
Neurosurgical focus
Volume
3
Issue
1
Publish Date
1997
Start Page
e1

Management of fetal cardiac arrhythmias.

While most fetal cardiac arrhythmias are benign in nature, some may be dangerous and require prenatal treatment. This article reviews the differential diagnoses of fetal tachycardias and bradycardias, as well as treatment and management approaches.

Authors
Copel, JA; Friedman, AH; Kleinman, CS
MLA Citation
Copel, JA, Friedman, AH, and Kleinman, CS. "Management of fetal cardiac arrhythmias." Obstet Gynecol Clin North Am 24.1 (March 1997): 201-211. (Review)
PMID
9086526
Source
pubmed
Published In
Obstetrics and Gynecology Clinics of North America
Volume
24
Issue
1
Publish Date
1997
Start Page
201
End Page
211

Brachial plexus compression by venous aneurysms. Case illustration.

Authors
Gabriel, EM; Friedman, AH
MLA Citation
Gabriel, EM, and Friedman, AH. "Brachial plexus compression by venous aneurysms. Case illustration." J Neurosurg 86.2 (February 1997): 311-.
PMID
9010437
Source
pubmed
Published In
Journal of neurosurgery
Volume
86
Issue
2
Publish Date
1997
Start Page
311
DOI
10.3171/jns.1997.86.2.0311

Craniocerebral plasmacytoma: MR features.

We report the MR imaging findings in two patients with solitary craniocerebral plasmacytoma, a benign plasma cell tumor that can arise from the skull, the dura, or, rarely, the brain. In both patients, the lesion was extraaxial and nearly isointense with gray matter on T2-weighted MR images, and diffusely enhanced after administration of contrast material, bearing some similarities to meningioma. A diagnosis of solitary craniocerebral plasmacytoma should be considered when a mass with these imaging features is seen, because total excision may not be necessary for this radiosensitive tumor.

Authors
Provenzale, JM; Schaefer, P; Traweek, ST; Ferry, J; Moore, JO; Friedman, AH; McLendon, RE
MLA Citation
Provenzale, JM, Schaefer, P, Traweek, ST, Ferry, J, Moore, JO, Friedman, AH, and McLendon, RE. "Craniocerebral plasmacytoma: MR features." AJNR Am J Neuroradiol 18.2 (February 1997): 389-392.
PMID
9111682
Source
pubmed
Published In
American Journal of Neuroradiology
Volume
18
Issue
2
Publish Date
1997
Start Page
389
End Page
392

Predictors of outcome of epilepsy surgery: multivariate analysis with validation.

PURPOSE: To identify predictors of outcome of epilepsy surgery, using the Duke experience, applying multivariate analysis and validation techniques. To compare the results of different modeling algorithms. Few previous studies have reported multivariate analysis, or validated their results. METHODS: Records of 116 patients with focal resections for intractable epilepsy from January 1, 1980 through June 30, 1989 were analyzed. Primary outcome variable was patient's condition in second postoperative year: seizure free (except auras), or not. Three predictors of biologic interest were specified a priori for confirmatory analysis. Additional predictors were considered within exploratory analysis. Logistic regression techniques were applied to assess relations with pre- and postoperative predictors. Internal validity was assessed by repeated random selection of training and validation samples, used in conjunction with bootstrap techniques. RESULTS: By using multivariate analysis, percentage of epileptic EEG activity arising from the site of resection and either imaging localization or lack of use of invasive monitoring were the only statistically significant preoperative predictors for good outcome at 2 years. Presence of seizures within 2 months of surgery was a significant postoperative predictor for a poor outcome. Adding more variables did not result in significantly improved models. Use of validation techniques reduced the degree of optimism in the predictive value of the models. CONCLUSIONS: Pooling of data from multiple institutions is needed to attain the large sample sizes needed for multivariate analysis with validation.

Authors
Armon, C; Radtke, RA; Friedman, AH; Dawson, DV
MLA Citation
Armon, C, Radtke, RA, Friedman, AH, and Dawson, DV. "Predictors of outcome of epilepsy surgery: multivariate analysis with validation." Epilepsia 37.9 (September 1996): 814-821.
PMID
8814093
Source
pubmed
Published In
Epilepsia
Volume
37
Issue
9
Publish Date
1996
Start Page
814
End Page
821

Reply from the Authors: Neuro-Behcet's disease in Japan

Authors
Devlin, T; Gray, L; Allen, NB; Friedman, AH; Tien, R; Morgenlander, JC
MLA Citation
Devlin, T, Gray, L, Allen, NB, Friedman, AH, Tien, R, and Morgenlander, JC. "Reply from the Authors: Neuro-Behcet's disease in Japan." Neurology 47.2 (August 1, 1996): 614-615.
Source
crossref
Published In
Neurology
Volume
47
Issue
2
Publish Date
1996
Start Page
614
End Page
615
DOI
10.1212/WNL.47.2.614-a

Autosomal dominant cataracts of the fetus: early detection by transvaginal ultrasound.

Cataracts are lens opacities that account for approximately 10% of blindness in children. We report on four consecutive pregnancies in a woman at risk for recurrent autosomal dominant cataracts in which extensive ultrasound studies were helpful in establishing the correct diagnosis. The normal appearance of the fetal lens is that of a ring with a central sonolucency, but in cases of cataracts the lens appears hyperechogenic to various degrees. In the first pregnancy, normal lenses were seen at 15 postmenstrual weeks and, at birth, the baby girl had normal lenses. In the second pregnancy, the male fetus was affected by a left-sided cataract and a right-sided anophthalmia which were diagnosed at 16 postmenstrual weeks. The histological examination of the specimen from the aborted fetus correlated with the sonographic diagnosis. The third pregnancy, also a male fetus, had bilateral cataracts suspected at 14 weeks, but the final diagnosis was made at 19 weeks and confirmed at 21 weeks. The couple opted to terminate the pregnancy and the histology confirmed the presence of congenital cataracts. In the fourth pregnancy, we diagnosed asymmetry of the orbital sizes and bilateral cataracts at 15 weeks. In conclusion, the diagnosis of fetal cataract from the second trimester of pregnancy is possible and imaging of the fetal lenses should be part of the routine anatomical survey. Since the exact onset of fetal cataracts is uncertain at present, in cases at risk, serial sonograms may be indicated.

Authors
Monteagudo, A; Timor-Tritsch, IE; Friedman, AH; Santos, R
MLA Citation
Monteagudo, A, Timor-Tritsch, IE, Friedman, AH, and Santos, R. "Autosomal dominant cataracts of the fetus: early detection by transvaginal ultrasound." Ultrasound Obstet Gynecol 8.2 (August 1996): 104-108.
PMID
8883312
Source
pubmed
Published In
Ultrasound in Obstetrics and Gynecology
Volume
8
Issue
2
Publish Date
1996
Start Page
104
End Page
108
DOI
10.1046/j.1469-0705.1996.08020104.x

Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results.

We aimed to determine the maximum tolerated dose (MTD) of 131I-labeled 81C6 in patients with leptomeningeal neoplasms or brain tumor resection cavities with subarachnoid communication and to identify any objective responses. 81C6 is a murine IgG monoclonal antibody that reacts with tenascin in gliomas/carcinomas but does not react with normal adult brain. 131I-labeled 81C6 delivers intrathecal (IT) radiation to these neoplasms. This study was a Phase I trial in which patients were treated with a single IT dose of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating doses of 131I (starting dose, 40 mCi; 20 mCi escalations) on 10 mg 81C6. MTD is defined as the highest dose resulting in serious toxicity in no more than two of six patients. Serious toxicity is defined as grade III/IV nonhematological toxicity or major hematological toxicity. We treated 31 patients (8 pediatric and 23 adult). Eighteen had glioblastoma multiforme. Patients were treated with 131I doses from 40 to 100 mCi. Hematological toxicity was dose limiting and correlated with the administered 131I dose. No grade III/IV nonhematological toxicities were encountered. A partial response occurred in 1 patient and disease stabilization occurred in 13 (42%) of 31 patients. Twelve patients are alive (median follow-up, > 320 days); five are progression free >409 days median posttreatment. The MTD of a single IT administration of 131I-labeled 81C6 in adults is 80 mCi 131I-labeled 81C6. The MTD in pediatric patients was not reached at 131I doses up to 40 mCi normalized for body surface area.

Authors
Brown, MT; Coleman, RE; Friedman, AH; Friedman, HS; McLendon, RE; Reiman, R; Felsberg, GJ; Tien, RD; Bigner, SH; Zalutsky, MR; Zhao, XG; Wikstrand, CJ; Pegram, CN; Herndon, JE; Vick, NA; Paleologos, N; Fredericks, RK; Schold, SC; Bigner, DD
MLA Citation
Brown, MT, Coleman, RE, Friedman, AH, Friedman, HS, McLendon, RE, Reiman, R, Felsberg, GJ, Tien, RD, Bigner, SH, Zalutsky, MR, Zhao, XG, Wikstrand, CJ, Pegram, CN, Herndon, JE, Vick, NA, Paleologos, N, Fredericks, RK, Schold, SC, and Bigner, DD. "Intrathecal 131I-labeled antitenascin monoclonal antibody 81C6 treatment of patients with leptomeningeal neoplasms or primary brain tumor resection cavities with subarachnoid communication: phase I trial results." Clin Cancer Res 2.6 (June 1996): 963-972.
PMID
9816257
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
2
Issue
6
Publish Date
1996
Start Page
963
End Page
972

A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium.

PURPOSE: This study was designed to evaluate strategies to overcome the resistance of anaplastic gliomas of the brain to external beam radiotherapy (ERT) plus carmustine (BCNU). Patients were > or = 15 years of age, had a histologic diagnosis of malignant glioma, and a Karnofsky performance status (KPS) > or = 60%. METHODS AND MATERIALS: In Randomization 1, patients were assigned to receive either ERT alone (61.2 Gy) or ERT plus mitomycin C (Mito, IV 12.5 mg/m(2)) during the first and fourth week of ERT. After this treatment, patients went on to Randomization 2, where they were assigned to receive either BCNU (i.v. 200 mg/m(2)) given at 6-week intervals or 6-mercaptopurine (6- MP, 750 mg/m(2) IV daily for 3 days every six weeks), with BCNU given on the third day of the 6-MP treatment. Three hundred twenty-seven patients underwent Randomization 1. One hundred sixty-four received ERT alone, and 163 received ERT + Mito [average 52.7 years; 63% male; 69% glioblastoma multiforme (GBM); 66% had a resection; 56% KPS > or = 90%]. Step-wise analysis of survival from Randomization 1 or 2 indicates that survival was significantly diminished by: (a) age > or = 45 years (b) KPS < 90%; (c) GBM/gliosarcoma histology; (d) stereotactic biopsy as opposed to open biopsy or resection. Median survival from Randomization 1 in both arms (ERT + Mito) was 10.8 months. Median survival from Randomization 2 was 9.3 months for BCNU/6MP vs. 11.4 months for the BCNU group (p = 0.35). Carmustine/6-MP showed a possible survival benefit for histologies other than GBM/GS. Two hundred and thirty-three patients underwent Randomization 2. The proportion of patients in the ERT group who terminated study prior to Randomization 2 was significantly less in the ERT group than in the ERT + Mito group (20 vs. 37%, p < 0.001). CONCLUSIONS: (a) The addition of Mito to ERT had no impact on survival; (b) patients treated with ERT + Mito were at greater risk of terminating therapy prior to Randomization 2; (c) there was not a significant survival benefit to the addition of 6-MP to BCNU.

Authors
Halperin, EC; Herndon, J; Schold, SC; Brown, M; Vick, N; Cairncross, JG; Macdonald, DR; Gaspar, L; Fischer, B; Dropcho, E; Rosenfeld, S; Morowitz, R; Piepmeier, J; Hait, W; Byrne, T; Salter, M; Imperato, J; Khandekar, J; Paleologos, N; Burger, P; Bentel, GC; Friedman, A
MLA Citation
Halperin, EC, Herndon, J, Schold, SC, Brown, M, Vick, N, Cairncross, JG, Macdonald, DR, Gaspar, L, Fischer, B, Dropcho, E, Rosenfeld, S, Morowitz, R, Piepmeier, J, Hait, W, Byrne, T, Salter, M, Imperato, J, Khandekar, J, Paleologos, N, Burger, P, Bentel, GC, and Friedman, A. "A phase III randomized prospective trial of external beam radiotherapy, mitomycin C, carmustine, and 6-mercaptopurine for the treatment of adults with anaplastic glioma of the brain. CNS Cancer Consortium." Int J Radiat Oncol Biol Phys 34.4 (March 1, 1996): 793-802.
PMID
8598355
Source
pubmed
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
34
Issue
4
Publish Date
1996
Start Page
793
End Page
802

Outcome of temporal lobectomy in adolescents

We performed temporal lobectomy in 23 young patients with intractable complex partial seizures (CPS) at an average age of 14.5 years. At a mean follow-up interval of 4.8 years, we reevaluated the patients to assess the surgical outcome; 74% were seizure-free. Cognitive testing showed slight improvement in Full-scale I.Q. scores and in some subtest scores. Wechsler Memory Scales had not changed significantly from the preoperative scores. Both pre- and postoperative Minnesota Multiphasic Personality Inventories 168 (MMPIs) were obtained in nine patients; and only postoperative MMPIs were obtained in 18. Pre- and postoperative social function, reported by the patients in a structured interview with a clinical psychologist (H.S.S.), was scored by a rating scale. All patients reported postoperative improvement in social function, although of variable degree. Patients were divided into a well-adjusted and a poorly adjusted group based on their postoperative social function. As compared with the well-adjusted group, the poorly adjusted group reported more preoperative social problems, had lower preoperative and postoperative I.Q. scores, had poorer postoperative seizure control, and had higher postoperative MMPI scores.

Authors
Lewis, DV; Jr, RJT; Santos, CC; Oakes, WJ; Radtke, RA; Friedman, AH; Lee, N; Swartzwelder, HS
MLA Citation
Lewis, DV, Jr, RJT, Santos, CC, Oakes, WJ, Radtke, RA, Friedman, AH, Lee, N, and Swartzwelder, HS. "Outcome of temporal lobectomy in adolescents." Journal of Epilepsy 9.3 (1996): 198-205.
Source
scival
Published In
Journal of Epilepsy
Volume
9
Issue
3
Publish Date
1996
Start Page
198
End Page
205
DOI
10.1016/0896-6974(96)00013-8

Perioperative management of aneurysmal subarachnoid hemorrhage: Part 2. Postoperative management.

Authors
McGrath, BJ; Guy, J; Borel, CO; Friedman, AH; Warner, DS
MLA Citation
McGrath, BJ, Guy, J, Borel, CO, Friedman, AH, and Warner, DS. "Perioperative management of aneurysmal subarachnoid hemorrhage: Part 2. Postoperative management." Anesth Analg 81.6 (December 1995): 1295-1302. (Review)
PMID
7486121
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
81
Issue
6
Publish Date
1995
Start Page
1295
End Page
1302

Thromboembolic complications after Fontan operations.

BACKGROUND: Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed. METHODS AND RESULTS: We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (+/- SD) follow-up of 5.2 +/- 4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1 +/- 5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery. CONCLUSIONS: Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.

Authors
Rosenthal, DN; Friedman, AH; Kleinman, CS; Kopf, GS; Rosenfeld, LE; Hellenbrand, WE
MLA Citation
Rosenthal, DN, Friedman, AH, Kleinman, CS, Kopf, GS, Rosenfeld, LE, and Hellenbrand, WE. "Thromboembolic complications after Fontan operations." Circulation 92.9 Suppl (November 1, 1995): II287-II293.
PMID
7586425
Source
pubmed
Published In
Circulation
Volume
92
Issue
9 Suppl
Publish Date
1995
Start Page
II287
End Page
II293

Reply from the author:

Authors
Alberts, MJ; Friedman, AH
MLA Citation
Alberts, MJ, and Friedman, AH. "Reply from the author:." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 22.04 (November 1995): 333-333.
Source
crossref
Published In
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Volume
22
Issue
04
Publish Date
1995
Start Page
333
End Page
333
DOI
10.1017/S0317167100039603

Perioperative management of aneurysmal subarachnoid hemorrhage: Part 1. Operative management.

Authors
Guy, J; McGrath, BJ; Borel, CO; Friedman, AH; Warner, DS
MLA Citation
Guy, J, McGrath, BJ, Borel, CO, Friedman, AH, and Warner, DS. "Perioperative management of aneurysmal subarachnoid hemorrhage: Part 1. Operative management." Anesth Analg 81.5 (November 1995): 1060-1072. (Review)
PMID
7486047
Source
pubmed
Published In
Anesthesia and Analgesia
Volume
81
Issue
5
Publish Date
1995
Start Page
1060
End Page
1072

Thrombosis of the pulmonary artery stump after distal ligation.

Authors
Rosenthal, DN; Bulbul, ZR; Friedman, AH; Hellenbrand, WE; Kleinman, CS
MLA Citation
Rosenthal, DN, Bulbul, ZR, Friedman, AH, Hellenbrand, WE, and Kleinman, CS. "Thrombosis of the pulmonary artery stump after distal ligation." J Thorac Cardiovasc Surg 110.5 (November 1995): 1563-1565.
PMID
7475209
Source
pubmed
Published In
Journal of Thoracic and Cardiovascular Surgery
Volume
110
Issue
5
Publish Date
1995
Start Page
1563
End Page
1565
DOI
10.1016/S0022-5223(95)70080-3

Metastatic melanoma to the spine. Demographics, risk factors, and prognosis in 114 patients.

STUDY DESIGN: One-hundred-fourteen patients with metastatic melanoma of the spine were retrospectively reviewed. OBJECTIVE: The goal was to define the demographics, risk factors, and prognosis for this population. SUMMARY OF BACKGROUND DATA: The incidence of melanoma is increasing faster than any other cancer. Therefore, orthopedic and neurologic surgeons will be increasingly confronted by patients with spinal metastases from melanoma. However, the demographics, risk factors, and prognosis remain unclear. METHODS: From 7010 consecutive patients with melanoma, 114 were identified with clinically or radiographically evident spinal metastases. A comparison was made between these patients and the remainder of the population with melanoma seen at our institution using contingency table analysis with statistical significance determined by a chi-squared test. Survival data were represented by Kaplan-Meier curves, and log-rank testing was used for statistical comparisons. RESULTS: Risk factors associated with the development of these metastases included primary lesions that were ulcerated, deeper than 0.76 mm, or of Clark level II, or located on the trunk or mucosal surfaces. The median survival time for all patients was 86 days, but this was reduced in patients with more than one metastatic site in addition to the spine. CONCLUSION: The prognosis for most patients with spinal metastases from melanoma is dismal. However, patients with metastatic disease limited to the spine and one other organ may survive for a relatively prolonged time and may be candidates for surgical intervention directed toward symptomatic relief.

Authors
Spiegel, DA; Sampson, JH; Richardson, WJ; Friedman, AH; Rossitch, E; Hardaker, WT; Seigler, HF
MLA Citation
Spiegel, DA, Sampson, JH, Richardson, WJ, Friedman, AH, Rossitch, E, Hardaker, WT, and Seigler, HF. "Metastatic melanoma to the spine. Demographics, risk factors, and prognosis in 114 patients." Spine (Phila Pa 1976) 20.19 (October 1, 1995): 2141-2146.
PMID
8588172
Source
pubmed
Published In
Spine
Volume
20
Issue
19
Publish Date
1995
Start Page
2141
End Page
2146

Fast spin-echo, magnetic resonance imaging-measured hippocampal volume: correlation with neuronal density in anterior temporal lobectomy patients.

To assess the value of magnetic resonance imaging (MRI)-measured hippocampal volume in the detection of hippocampal sclerosis, we studied 28 patients undergoing anterior temporal lobectomy for medically intractable mesial temporal lobe epilepsy. Hippocampal volumetry and visual analysis of T2 signal change were performed using fast spin-echo T2-weighed MRI. Quantitative neuronal density measurements were performed in the resected hippocampal specimens. There was a significant correlation between MRI-measured absolute hippocampal volume (AHV) and neuronal density in CA1, CA2, and CA3 subfields (p < 0.0001, p < 0.01, and p < 0.05, respectively). Differential hippocampal volume (side-to-side volume difference) failed to detect bilateral atrophy in three patients, but the bilateral hippocampal atrophy was recognized by considering AHV in these patients. This study suggests that MRI-measured AHV can be of value in elevating patients with mesial temporal lobe epilepsy, especially when there is no side-to-side difference in hippocampal volumetry.

Authors
Lee, N; Tien, RD; Lewis, DV; Friedman, AH; Felsberg, GJ; Crain, B; Hulette, C; Osumi, AK; Smith, JS; VanLandingham, KE
MLA Citation
Lee, N, Tien, RD, Lewis, DV, Friedman, AH, Felsberg, GJ, Crain, B, Hulette, C, Osumi, AK, Smith, JS, and VanLandingham, KE. "Fast spin-echo, magnetic resonance imaging-measured hippocampal volume: correlation with neuronal density in anterior temporal lobectomy patients." Epilepsia 36.9 (September 1995): 899-904.
PMID
7649129
Source
pubmed
Published In
Epilepsia
Volume
36
Issue
9
Publish Date
1995
Start Page
899
End Page
904

Neuro-Behçet's disease: factors hampering proper diagnosis.

We reviewed the clinical course of nine patients with neuro-Behçet's disease to assess difficulties in making this diagnosis. Factors delaying proper diagnosis included lack of accurate history and physical examination, lack of recognition of an underlying systemic syndrome and its relationship to the neurologic symptoms, presence of intermittently normal CSF studies, and use of noncontrasted neuroimaging techniques.

Authors
Devlin, T; Gray, L; Allen, NB; Friedman, AH; Tien, R; Morgenlander, JC
MLA Citation
Devlin, T, Gray, L, Allen, NB, Friedman, AH, Tien, R, and Morgenlander, JC. "Neuro-Behçet's disease: factors hampering proper diagnosis." Neurology 45.9 (September 1995): 1754-1757.
PMID
7675240
Source
pubmed
Published In
Neurology
Volume
45
Issue
9
Publish Date
1995
Start Page
1754
End Page
1757

Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25.

The high incidence of loss of chromosome 10 alleles in glioblastoma multiforme suggests the presence on this chromosome of a tumor suppressor gene that is important in glioma tumorigenesis and progression. Our initial deletion mapping studies using restriction fragment length polymorphism markers indicated a common deletion region in 10q24-qter. In an attempt to localize the deleted region further, we screened a panel of 117 gliomas for loss of heterozygosity for chromosome 10 loci using 10 microsatellite markers. Seventeen tumors showed partial loss of a copy of chromosome 10 and were further analysed using 28 additional microsatellite markers. Of these, 10 had terminal deletion in the q arm, three had deletions in both p and q arms, two contained interstitial deletion in 10q and two carried deletions in 10p. In the 15 tumors with deletions in 10q, the minimal overlapping deletion region was in distal 10q between markers D10S587 and D10S216. Loci D10S587 and D10S216 are approximately mapped to a 5 cM region in 10q25.1.

Authors
Rasheed, BK; McLendon, RE; Friedman, HS; Friedman, AH; Fuchs, HE; Bigner, DD; Bigner, SH
MLA Citation
Rasheed, BK, McLendon, RE, Friedman, HS, Friedman, AH, Fuchs, HE, Bigner, DD, and Bigner, SH. "Chromosome 10 deletion mapping in human gliomas: a common deletion region in 10q25." Oncogene 10.11 (June 1, 1995): 2243-2246.
PMID
7784070
Source
pubmed
Published In
Oncogene: Including Oncogene Reviews
Volume
10
Issue
11
Publish Date
1995
Start Page
2243
End Page
2246

The restoration of elbow flexion with intercostal nerve transfers.

Seventeen patients with absent elbow flexion secondary to brachial plexus avulsion injury underwent intercostal neurotization of the biceps muscle. Followup was performed at an average of 5 years. The average age in this series was 21.8 years; the mean time interval from injury to the surgical procedure was 6 months. Eight of the 17 patients (47%) obtained good or excellent results as defined by Nagano et al. Five patients had muscle function ratings of M2 but were unable to power the elbow against gravity. The overall success rate theoretically may be increased by (1) decreasing the time interval from injury to neurotization to < 5 months; (2) selecting patients < 50 years of age; and (3) using adjuvant surgical procedures after neurotization, including tendon transfers and shoulder arthrodesis, which may improve results from good to excellent.

Authors
Ruch, DS; Friedman, A; Nunley, JA
MLA Citation
Ruch, DS, Friedman, A, and Nunley, JA. "The restoration of elbow flexion with intercostal nerve transfers." Clin Orthop Relat Res 314 (May 1995): 95-103.
PMID
7634657
Source
pubmed
Published In
Clinical Orthopaedics and Related Research ®
Issue
314
Publish Date
1995
Start Page
95
End Page
103

Risk of intracranial aneurysms in families with subarachnoid hemorrhage.

BACKGROUND: Genetic factors may be important in the etiology of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have reported the familial occurrence of SAH and IA, although in most cases asymptomatic family members were not studied with elective angiography. The examination of data from large sibships could provide important information about the frequency of IA occurrence in at-risk individuals and the mode of inheritance for familial SAH/IA. METHODS: We reviewed published case series of sibships with SAH and at least four siblings, in which at least one sibling underwent elective angiography. Data were collected on age-of-onset, clinical events, presence of hypertension, angiographic findings, and outcome. Patients were classified as "affected" if they had a SAH or if an IA was detected by elective angiography, and "unaffected" if they were asymptomatic and had a negative angiogram. RESULTS: Seven case series with 52 individuals (26 men and 26 women) met our inclusion criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of 52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%. CONCLUSIONS: Based on data from these sibships, angiography of asymptomatic at-risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA segregated with a pattern that was consistent with an autosomal dominant trait in this selected series of sibships, although other factors could produce these findings.

Authors
Alberts, MJ; Quinones, A; Graffagnino, C; Friedman, A; Roses, AD
MLA Citation
Alberts, MJ, Quinones, A, Graffagnino, C, Friedman, A, and Roses, AD. "Risk of intracranial aneurysms in families with subarachnoid hemorrhage." Can J Neurol Sci 22.2 (May 1995): 121-125.
PMID
7627913
Source
pubmed
Published In
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques
Volume
22
Issue
2
Publish Date
1995
Start Page
121
End Page
125

Fast spin-echo MR in hippocampal sclerosis: correlation with pathology and surgery.

PURPOSE: To identify the extent of hippocampal sclerosis in temporal lobe epilepsy with fast spin-echo MR and correlate it with histopathologic findings and surgical outcome. METHODS: MR images of 30 patients with temporal lobe epilepsy and pathologically proved hippocampal sclerosis and 30 control subjects were obtained using a fast spin-echo technique with 4000/100/4 (repetition time/echo time/excitations), 16 echo train, 2- to 3-mm section thickness with interleave, 256 x 256 matrix, and 18-cm field of view. Criteria for MR diagnosis of hippocampal sclerosis included hippocampal atrophy diagnosed with MR volumetry and/or T2-weighted signal change. Hippocampal sectional areas were plotted, and T2 signal changes were topographically evaluated to identify the extent of hippocampal sclerosis, which was subsequently correlated with histopathologic findings and surgical outcome. RESULTS: Hippocampal sclerosis was diffuse, involving both hippocampal head and body, in 96.7% of patients (29 of 30 patients). One patient had normal MR findings. Focal hippocampal sclerosis was not seen. Histopathologic findings of hippocampal sclerosis were present in all 29 patients who had abnormal MR findings. Eighty-six percent of patients (18 of 21 patients), who were followed for at least 1 year after temporal lobectomy, were seizure free (81%, 17 of 21 patients) or significantly improved (5%, 1 of 21 patients). CONCLUSION: Fast spin-echo MR enables accurate definition of the extent of hippocampal sclerosis in patients with temporal lobe epilepsy. All cases of hippocampal sclerosis identified in this study involved the hippocampus diffusely. However, leaving the posterior portion of the hippocampus during surgery does not seem to be a major factor influencing surgical outcome.

Authors
Kim, JH; Tien, RD; Felsberg, GJ; Osumi, AK; Lee, N; Friedman, AH
MLA Citation
Kim, JH, Tien, RD, Felsberg, GJ, Osumi, AK, Lee, N, and Friedman, AH. "Fast spin-echo MR in hippocampal sclerosis: correlation with pathology and surgery." AJNR Am J Neuroradiol 16.4 (April 1995): 627-636.
PMID
7611014
Source
pubmed
Published In
American Journal of Neuroradiology
Volume
16
Issue
4
Publish Date
1995
Start Page
627
End Page
636

Shadow cells in an intracranial dermoid cyst.

A case of an intracranial dermoid cyst containing shadow cells is presented. This case expands the group of lesions in which shadow cells, indicative of hair matrical differentiation, have been described.

Authors
Hitchcock, MG; Ellington, KS; Friedman, AH; Provenzaie, JM; McLendon, RE
MLA Citation
Hitchcock, MG, Ellington, KS, Friedman, AH, Provenzaie, JM, and McLendon, RE. "Shadow cells in an intracranial dermoid cyst." Arch Pathol Lab Med 119.4 (April 1995): 371-373.
PMID
7726731
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
119
Issue
4
Publish Date
1995
Start Page
371
End Page
373