✓ This study includes 182 patients with intracranial gliomas who received bromodeoxyuridine (BUdR), 200 mg/sq m intravenously, at the time of craniotomy but before tumor biopsy. The tumor specimens were stained for BUdR using the immunoperoxidase method; the BUdR labeling index (LI), or S-phase fraction, was calculated as the percentage of BUdR-positive cells. The median BUdR LI's for 127 primary moderately anaplastic astrocytomas, highly anaplastic astrocytomas, and glioblastomas (< 1%, 2.7%, and 7.3%, respectively; range 0% to 38.1%) were not significantly different from those of 55 similar recurrent tumors (< 1%, 4.3%, and 7.4%, respectively; range 0% to 30.5%). The mean LI was significantly higher in tumors from patients over 50 years of age than in tumors from younger patients (p < 0.001). This age-related difference in LI's was found in both groups of patients with astrocytomas but not in those with glioblastomas. Kaplan-Meier survival curves showed a significantly greater probability of survival among patients whose tumors had LI's of less than 1% than among those with LI's greater than 5%; survival probability of patients with tumor LI's of 1% to 5% was intermediate between the two extremes. Thus, the BUdR LI appears to reflect the proliferative potential more accurately than the histopathological diagnosis and should therefore be considered an important factor in determining the prognosis of individual patients with intracranial gliomas and in selecting their treatment.
Takao Hoshino, Michael Prados, Charles B. Wilson, Kyung Gi Cho, Kyu-Sung Lee and Richard L. Davis
Isabelle M. Germano, Masami Ito, Kyung G. Cho, Takao Hoshino, Richard L. Davis and Charles B. Wilson
✓ One hundred fifty-two intracranial gliomas of various types were reviewed in order to correlate the histopathological features with the proliferative potential of each tumor as reflected by the bromodeoxyuridine (BUdR) labeling index (LI). Patients undergoing surgical removal of gliomas were given a 30-minute intravenous infusion of BUdR (150 to 200 mg/sq m) to label S-phase tumor cells. The tumor specimens were stained immunohistochemically for BUdR and processed for routine histopathological diagnosis. The BUdR LI was calculated as the percentage of labeled cells among cells analyzed. Twenty-seven histological features in three categories (degenerative, vascular, and cellular changes) were considered. A significantly higher BUdR LI (p < 0.05) was found in tumors with necrosis than in those without this feature; tumors with both coagulative and liquefactive necrosis had the highest BUdR LI (p < 0.05). Increased vascularity was also associated with a higher BUdR LI (p < 0.05). Although tumors with abnormal mitotic figures had a significantly higher BUdR LI than those without, the number of mitoses did not correlate with a higher BUdR LI. These results suggest that the number of mitoses is not a good indicator of tumor growth rate. Necrosis and increased vascularity should be heavily weighted in predicting the proliferative potential of individual gliomas.
Michael S. B. Edwards, William M. Wara, Raul C. Urtasun, Michael Prados, Victor A. Levin, Dorcas Fulton, Charles B. Wilson, John Hannigan and Pamela Silver
✓ Fifty-three patients (19 adults and 34 children) harboring brain-stem glioma were treated with hyperfractionated radiation therapy (100 cGy twice a day, 5 days/wk, to a total dose of 7200 cGy). For the entire group, the median time to tumor progression (TTP) was 59 weeks (adults 66 weeks, children 44 weeks) and the median survival time was 74 weeks (adults 92 weeks, children 64 weeks). Statistically significant prognostic factors associated with a decrease in TTP and median survival times (adults < children) were: patient's age, a clinical history of less than 2 months, widespread brain-stem dysfunction, and a diffuse tumor as seen on magnetic resonance imaging. A finding of glioblastoma multiforme at histological analysis was associated with a statistical trend toward poorer survival, but in general tumor histology was not predictive of outcome. No evidence of an increase in acute or delayed radiation toxicity was seen with this fractionation schedule and total dose. This study suggests that hyperfractionation prolongs the TTP and survival time for many patients with brain-stem glioma. However, there remains a group of patients who are only moderately helped by this technique and for whom more aggressive treatment is warranted.
Stephen M. Rupp and Charles B. Wilson
✓ A case of spontaneous cerebrospinal fluid (CSF) leak from a sacral nerve root sleeve is reported. The leak resulted in CSF hypotension, which failed to resolve with prolonged bed rest. An epidural blood patch using autologous blood placed percutaneously via the caudal canal was successful in treating the problem.
Takao Hoshino, Luis A. Rodriguez, Kyung G. Cho, Kyu S. Lee, Charles B. Wilson, Michael S. B. Edwards, Victor A. Levin and Richard L. Davis
✓ The proliferative potential of low-grade astrocytomas was estimated in 47 patients. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR), 150 to 200 mg/sq m, at the time of craniotomy to label cells in deoxyribonucleic acid (DNA) synthesis; the percentage of S-phase cells, or BUdR labeling index (LI), of each tumor was determined immunohistochemically. In 29 patients (60%), the tumors had BUdR LI's of less than 1%, indicating a slow growth rate; only three (10%) of these patients died of recurrent tumor during a follow-up period of up to 3½ years. In contrast, of the 18 patients (40%) whose tumors had BUdR LI's of 1% or more, 12 (67%) had a recurrence and nine died during the same follow-up period. These results show that the proliferative potential, as reflected by the BUdR LI, is an important prognostic factor that separates low-grade astrocytomas into two groups and provides a more scientific rationale for selecting treatment for individual patients.
Brian T. Andrews and Charles B. Wilson
✓ The authors reviewed 38 cases of suprasellar meningioma to determine the correlation between tumor site and postoperative visual outcome. Progressive visual loss, the most frequent initial complaint (94.7%), occurred over a mean of 24½ months, was most often unilateral (18 patients) or bilateral but asymmetrical (14 patients), and was severe (20/200 vision or worse) in 23 patients; 24 patients had visual field abnormalities. Computerized tomography or magnetic resonance studies clearly delineated the lesions but did not appear to permit earlier diagnosis. Eleven patients had tumors limited to the tuberculum sellae; the tumor extended from the tuberculum sellae onto the planum sphenoidale in nine patients, into one optic canal in eight, onto the diaphragma sellae in seven, and onto the medial sphenoid wing in three. Patients with tumors affecting the optic canal had severe unilateral visual loss more often than those with tumors at other sites. Tumors limited to the tuberculum sellae were most often completely resected; postoperative recovery of vision was also most frequent in patients with tumors at this site. Tumors involving the diaphragma sellae or the medial sphenoid wing were least often completely removed and most likely to be associated with postoperative visual deterioration. Overall, 42% of patients had improved vision postoperatively, 30% remained unchanged, and 28% were worse. After a mean follow-up period of 38 months, 24 patients are doing well, four have significant visual disability, and three are blind or doing poorly. Two patients died of causes unrelated to their tumor. Three patients have had tumor recurrence.
Donald A. Ross and Charles B. Wilson
✓ Of 214 patients with acromegaly who underwent transsphenoidal microsurgical resection of a pituitary adenoma, 54% had growth hormone (GH) levels below 5 ng/ml and 74% had levels less than 10 ng/ml immediately after surgery. Among the 174 patients who could be contacted for long-term follow-up review (average duration 76 months), most recent GH determinations were available for 165. Of these 165 patients, 131 (79.4%) have a GH level less than 5 ng/ml and 153 (92.7%) have a level below 10 ng/ml; these represent 75.3% and 87.9%, respectively, of the total 174 patients reviewed. Fifty-two patients received postoperative radiation therapy. Nine patients underwent reoperation. There were five cases of tumor recurrence following an apparent surgical cure (4.3%), nine new instances of anterior pituitary hypofunction (5%), and five failures of multimodality therapy (2.3%). There were no perioperative deaths, five cases of cerebrospinal fluid leak requiring surgical repair (2.2%), and four cases of postoperative meningitis (1.8%). Permanent diabetes insipidus did not occur. Two of 52 patients who were irradiated postoperatively had severe complications; 23 (54.8%) of 42 patients who were available for follow-up evaluation had developed panhypopituitarism; and eight (19%) of 42 had normal pituitary function an average of 44 months postirradiation.
Michael S. B. Edwards, Roger J. Hudgins, Charles B. Wilson, Victor A. Levin and William M. Wara
✓ The authors believe that the preferred treatment for pineal region tumors in children requires definitive surgery with a histological diagnosis and that a conservative approach consisting of shunting and radiation therapy no longer seems to be appropriate. The results are reported of a retrospective review of the presentation, treatment, and outcome of 36 children under the age of 18 years treated between 1974 and 1986. Eleven children had germinomas (two-cell type), seven had astrocytomas, and the remaining 18 had 15 histologically different tumor types. Surgery was performed on 30 patients; there were no deaths, but a 10% rate of persistent morbidity was found. The median follow-up period was 4 years. Nine (82%) of 11 patients with germinomas are alive without evidence of recurrence; one child died from recurrent tumor in the pineal region and another is presently being treated for recurrent tumor of the spinal cord. Six (86%) of the seven patients with astrocytoma are well after biopsy and radiation therapy. Of the remaining 18 children, five (28%) died from tumor progression.
The cerebrospinal fluid (CSF) tumor markers α-fetoprotein and β-human chorionic gonadotropin were helpful in determining the presence of malignant germ-cell tumors, particularly those with a poor prognosis. Magnetic resonance imaging was useful for diagnosis and for planning the operative approach. Magnetic resonance images showed the presence of pineal region tumors in four children with hydrocephalus who had no evidence of tumor on computerized tomography scans.
Because the great variety of tumor types found in the pineal region must be treated in different ways and because improved microsurgical and stereotaxic surgical techniques have made mortality and morbidity rates acceptably low, a biopsy diagnosis should be obtained in all patients. Preoperative assessment of CSF tumor markers and cytology is useful for the identification of patients who have a poor prognosis.
Howard P. Charman, Daniel H. Lowenstein, Kyung G. Cho, Stephen J. DeArmond and Charles B. Wilson
✓ A 65-year-old man with a history of exposure to industrial solvents developed a primary cerebral angiosarcoma in the left posterior parieto-occipital lobe. The tumor had features typical of angiosarcoma on light and electron microscopy, immunohistochemical evidence of factor VIII-related antigen produced in tumor cells, and a high labeling index with bromodeoxyuridine. The relationship of angiosarcoma to toxins and viruses is discussed.
Victor A. Levin, Luis A. Rodriguez, Michael S. B. Edwards, William Wara, Hsiu-Chih Liu, Dorcas Fulton, Richard L. Davis, Charles B. Wilson and Pamela Silver
✓ Forty-seven patients with medulloblastoma were treated postoperatively with procarbazine, followed by craniospinal radiation therapy in combination with hydroxyurea. The radiation dose to the posterior fossa was 55 Gy; the spinal cord received 25 Gy and the whole brain 25 to 35 Gy (mean 33 Gy).
Seventeen tumors recurred. Only one initial recurrence was in the spinal subarachnoid space; 10 (59%) were in the posterior fossa, and four (24%) were supratentorial. The estimated 5-year disease-free survival probability was 55%; the 5-year overall survival rate was 66%. Myelotoxicity occurred in 38% of patients, but in only one case was it severe enough to warrant reducing the total dose of radiation. It was concluded that good-risk medulloblastoma patients may be treated with radiation dosages as low as 25 Gy to the spinal axis and to the whole brain without increasing the risk of recurrence outside the posterior fossa. Chemotherapy with procarbazine followed by radiation therapy and hydroxyurea during radiation therapy was well tolerated and may play a role in reducing radiation dosages outside the posterior fossa.