✓ The cases of seven patients with intramedullary, cryptic vascular malformations of the spinal cord are reported. In all patients, the clinical course was progressive; a Brown-Séquard syndrome was the most common presenting symptom complex. Magnetic resonance (MR) imaging was performed in all patients. The pattern seen most often was a focus of high signal (on both T1- and T2-weighted MR images) surrounded by a larger zone of low signal (best seen on T2-weighted images), and was remarkably similar for all patients. Six patients underwent surgical exploration; removal of the lesions halted the progression of symptoms in five patients, and one patient had worsened sensory function after surgery. Motor function did not decrease postoperatively in any patient. The one patient who refused surgery has continued to decline neurologically. Histopathological examination of surgical specimens showed a cavernous malformation in one patient, a venous malformation in one, venous varices in two, and organizing hematomas in two; these findings are markedly different from those in previously reported cases of cryptic vascular malformations.
Stanley L. Barnwell, Christopher F. Dowd, Richard L. Davis, Michael S. B. Edwards, Philip H. Gutin and Charles B. Wilson
Ali K. Choucair, Victor A. Levin, Philip H. Gutin, Richard L. Davis, Pamela Silver, Michael S. B. Edwards and Charles B. Wilson
✓ To determine the percentage of patients who developed multiple central nervous system (CNS) gliomas during postoperative radiation therapy and chemotherapy, the authors reviewed the records of 1047 patients treated between December 2, 1976, and August 16, 1985, who had an original diagnosis of supratentorial glioblastoma multiforme or other anaplastic glioma. The occurrence of multiple lesions was verified by neurodiagnostic studies (computerized tomography or myelography) or by findings at operation or autopsy. Twelve patients (1.1%) who presented with multiple lesions were excluded from this analysis. There were 405 patients with glioblastoma multiforme; their median age was 46.5 years (range 22 to 70 years). Eighteen (5%) of these patients had multiple CNS lesions, five of which were in the spinal cord. The median time from diagnosis to detection of the second lesion in this group was 59.5 weeks (range 10 to 182 weeks). There were 630 patients with anaplastic glioma (which included mixed malignant glioma and highly anaplastic, gemistocytic, moderately anaplastic, and anaplastic astrocytomas); their median age was 30 years (range 2 to 62 years). Fifty-four (8.6%) of these patients had multiple lesions, 10 of which were in the spinal cord; only one case of extraneural metastasis was found. The median time from diagnosis to detection of the second lesion in this group was 101 weeks (range 14 to 459 weeks). These results show that more than 90% of CNS gliomas recur at the site of the original tumor. Considering the high frequency of intellectual dysfunction after whole-brain radiation therapy, the use of focal radiation fields appears to be the most judicious approach to the treatment of patients with gliomas.
Takao Hoshino, Tadashi Nagashima, Judith A. Murovic, Charles B. Wilson, Michael S. B. Edwards, Philip H. Gutin, Richard L. Davis and Stephen J. DeArmond
✓ Thirty-eight patients undergoing surgical removal of neuroectodermal tumors of the central nervous system were given a 1-hour intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, to label tumor cells in the deoxyribonucleic acid (DNA) synthesis phase (S-phase). The excised tumor specimens were divided into two portions: one was fixed with 70% ethanol and embedded in paraffin and the other was digested with an enzyme cocktail to make a single-cell suspension. The paraffin-embedded tissues were stained by an indirect peroxidase method using anti-BUdR monoclonal antibody (MA) as the first antibody. Single-cell suspensions were reacted with fluorescein isothiocyanate (FITC)-conjugated anti-BUdR MA's for flow cytometric analysis. S-phase cells that had incorporated BUdR into their DNA were well stained by both methods. The percentage of BUdR-labeled cells, or S-phase fraction, was calculated in tissue sections by microscopic examination and in single-cell suspensions by flow cytometric analysis. The biological malignancy of the tumors was reflected in the S-phase fractions, which were 5% to 20% for glioblastoma multiforme, medulloblastoma, and highly anaplastic astrocytoma, but less than 1% in most moderately anaplastic astrocytomas, ependymomas, and mixed gliomas. Two juvenile pilocytic astrocytomas and two low-grade astrocytomas from children had high S-phase fractions despite the fairly benign and slow-growing nature of these tumors. These results indicate that the S-phase fraction obtained immunocytochemically with anti-BUdR MA's may provide useful information in estimating the biological malignancy of human central nervous system tumors in situ.
Victor A. Levin, William M. Wara, Richard L. Davis, Pamela Vestnys, Kenneth J. Resser, Kathleen Yatsko, Stephen Nutik, Philip H. Gutin and Charles B. Wilson
✓ The authors report the results of a randomized study conducted to evaluate the relative benefit of treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or the combination of procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, and vincristine (PCV) administered after radiation therapy with hydroxyurea to 76 evaluable patients with glioblastoma multiforme and 72 patients with other anaplastic gliomas. The primary end-point of the study was time to tumor progression. For better-risk patients with Karnofsky performance scores of 70 to 100, results suggest that PCV was of greater benefit than BCNU (p = 0.15 for glioblastoma multiforme; p = 0.13 for other anaplastic gliomas). Median times to tumor progression were 31 and 32 weeks for patients with glioblastoma multiforme; 25th percentile times to progression were 70 and 40 weeks for patients treated with PCV and BCNU, respectively. For patients with other anaplastic gliomas treated with PCV and BCNU, median times to progression were 123 and 77 weeks, respectively. Multivariate analysis showed that the prognostic variables of age and Karnofsky scores were important for patients with glioblastoma multiforme and other anaplastic gliomas, and that the extent of surgical resection was important for those with other anaplastic gliomas.
Philip H. Gutin, Steven A. Leibel, William M. Wara, Ali Choucair, Victor A. Levin, Theodore L. Philips, Pamela Silver, Vasco Da Silva, Michael S. B. Edwards, Richard L. Davis, Keith A. Weaver and Sharon Lamb
✓ The authors report survival data for the first 41 patients treated for recurrent malignant gliomas with interstitial brachytherapy at the University of California, San Francisco (1980–1984). Iodine-125 (125I) sources were temporarily implanted using stereotaxic techniques. The median survival period for 18 patients with recurrent glioblastomas was 52 weeks after brachytherapy; two patients are alive more than 5 years after brachytherapy. The median survival period for 23 patients with recurrent anaplastic astrocytomas is 153 weeks after brachytherapy, with 10 patients alive more than 3 years and four patients alive more than 4 years after brachytherapy. Both groups did significantly better (p < 0.01) than groups of patients with the same diagnoses and similar general characteristics who were treated at recurrence with chemotherapy alone. Because of deterioration of their clinical condition and evidence of recurrence from computerized tomographic scans, 17 (41%) of 41 patients required reoperation 20 to 72 weeks after brachytherapy. Despite the invariable presence of apparently viable tumor cells mixed with necrotic tissue in the resected specimen, nine patients have survived more than 2 years after reoperation and two of the nine are still alive 4 years after reoperation. The authors conclude that brachytherapy with temporarily implanted 125I sources for well-circumscribed, hemispheric, recurrent malignant gliomas is effective and offers a chance for long-term survival even though focal radiation necrosis can seriously degrade the quality of survival in a minority of patients.