Clinicopathological study of diffuse type brainstem gliomas: analysis of 40 autopsy cases

Diffuse type brainstem glioma is one of the most malignant types of brain tumors and the prognosis is extremely poor. The proliferative potential of these tumors is presumed to be very high, but there is little information about the cell kinetics of brainstem glioma because surgical resection is rarely performed. The histological grade, tumor spread, growth potential, and prognosis were evaluated in 40 autopsy cases of diffuse type brainstem glioma. To quantify the growth potentials of individual tumors, the proliferating cell indices of Ki-67 (MIB-1) and proliferating cell nuclear antigen (PCNA) monoclonal antibodies were measured. Mean MIB-1 and PCNA proliferating cell indices were 20.4% (24 cases) and 37.0% (28 cases), respectively, in 34 glioblastomas. The median survival time was 40 weeks in 22 treated patients. The mean PCNA proliferating cell index was 10.8% in four of five anaplastic astrocytomas and the median survival time in four treated patients was 91 weeks. The MIB-1 and PCNA proliferating cell indices of one astrocytoma were 2.9% and 20.3%, respectively, and the survival time was 56 weeks. The overall median survival time was 32 weeks. There was a significant difference in PCNA proliferating cell indices between glioblastomas and anaplastic astrocytomas (p < 0.05) and there was a significant difference in survival time between glioblastomas (40 weeks) and anaplastic astrocytomas plus astrocytoma (74 weeks) among the treated patients (p < 0.05). Supratentorial extension was more frequent in glioblastomas than in anaplastic astrocytomas (p < 0.05). Our results suggest that the majority of diffuse type brainstem gliomas are glioblastoma and the proliferative potential is probably as high as that of adult supratentorial glioblastoma. Supratentorial extension and dissemination are relatively frequent in the advanced stage. Anaplastic astrocytoma or astrocytoma is rarer and less infiltrative and proliferative, and carries a slightly better prognosis than glioblastoma.     

Intrinsic brain-stem tumors of childhood: surgical indications

This report summarizes the first author's experience with radical excision of intrinsic non-exophytic brain-stem gliomas in 34 pediatric patients. On retrospective analysis, these tumors may be classified into three subgroups: focal, diffuse, and cervicomedullary. A focal neoplasm is a circumscribed mass less than 2 cm in diameter and without associated edema. Tumors of a larger size or in which the "focal" neoplasm is associated with a large area of apparent edema are classified as diffuse. Cervicomedullary neoplasms occur at the junction of the medulla and spinal cord and involve both of the structures but do not extend rostrally into the pons. A radical tumor excision was carried out in all patients, and the only mortality and morbidity occurred in children harboring diffuse gliomas. All of the diffuse gliomas were malignant (grade III or IV astrocytomas), whereas three of the four focal astrocytomas and all of the cervicomedullary tumors were grade II astrocytomas. No patient with a diffuse astrocytoma was benefitted by surgery, while two of the focal astrocytomas and all of the cervicomedullary neoplasms either became stable or improved postoperatively. It is concluded that, although surgery may be accomplished within the substance of the brain stem with low morbidity and mortality rates, it is not indicated for malignant astrocytomas as it has no impact on the biology of the neoplasm. Therefore, while primary radical excision is recommended for cervicomedullary neoplasms, which are often benign, the more traditional radiation therapy and/or chemotherapy remain appropriate for tumors above the medulla.     

Treatment and survival of low-grade astrocytoma in adults--1977-1988.

A retrospective review of the records of the Division of Neuropathology at the New York University Medical Center between 1977 and 1988 revealed 53 cases of adult supratentorial astrocytomas. Fifty were fibrillary, and three were gemistocytic. Two additional patients had pilocytic tumors and were not included in the study. The majority of patients had either a subtotal (64%) or gross total resection (19%). Biopsy (17%) was performed for deep-seated lesions and for those lesions confined to eloquent cortex. Forty-eight patients (91%) received postoperative radiation therapy. The median survival was 7 1/4 years with a 5-year survival of 64%. Multivariate regression analysis demonstrated that the most important prognosticators for improved survival were young age, absence of contrast enhancement of the original tumor on computed tomography (CT) and the performance status of the patient. Patients with hemispheric tumors died from dedifferentiation into an anaplastic astrocytoma or a glioblastoma multiforme, with a median time to recurrence of 4.5 years from the original surgery. Survival from the time of recurrence was 12 months. Subsequent operations confirmed progression towards malignancy in six of seven (86%) recurrent tumors. CT contrast enhancement of the original tumor was associated with a 6.8-fold increase in risk for later recurrence. Patients with thalamic tumors (six patients) had a poor prognosis with a median survival of less than 2 years. A review of their CT scans suggest that four died of progressive low-grade disease; however, confirmatory autopsy data were available for only one patient. This study supports others that have shown improved survival for adult patients with astrocytomas treated in the CT era.     

Chiasmal gliomas: appearance and long-term changes demonstrated by computerized tomography

A survey of 22 cases showed the broad spectrum of lesions collectively termed "chiasmal gliomas." Three computerized tomography (CT) patterns were diagnostic: a tubular thickening of the optic nerve and chiasm, a suprasellar tumor with contiguous optic nerve expansion, and a suprasellar tumor with optic tract involvement. Globular suprasellar tumors lacking these features required a histological examination for diagnosis. Tumor growth was documented by CT in only three chiasmal gliomas; all were the globular type. Failing visual function did not reflect chiasmal tumor growth, and stable vision did not exclude it. Both patients with tubular optic nerve thickening and two of three patients with unilateral optic nerve expansion had neurofibromatosis. Five tumors became smaller after irradiation. Complications of radiation therapy included calcification of lenticular nuclei and remote infarcts. In patients who underwent biopsy, the CT appearance did not differentiate juvenile pilocytic astrocytoma from anaplastic astrocytoma. Thus, CT guides the diagnosis and neurosurgical treatment of chiasmal gliomas, establishing the need for biopsy or ventricular shunting.     

Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.     

Intraoperative radiation therapy for malignant glioma

Intraoperative radiation therapy (IOR) is an ideal means of exterminating residual tumor after surgical resection. In this study, the clinical results of IOR using a Scanditronix Microtron MM-22 were evaluated in 14 patients with malignant glioma, five of whom had recurrent tumors. Between July, 1985 and October, 1986, 11 patients with glioblastoma multiforme (GB) were irradiated 18 times (mean, 1.6 times/case), and three with astrocytoma (Kernohan grade III) underwent IOR once each. The target-absorbed dose at 1 to 2 cm deeper than the tumor resection surface was 15 to 50 Gy. During irradiation, a cotton bolus was placed in the dead space after over 91% of the tumor had been resected. As a rule, external irradiation therapy was also given postoperatively at a dose of 30 to 52 Gy. One patient died of pneumonia and disseminated intravascular coagulation syndrome 1 month postoperatively. The 1- and 2-year survival rates of the remaining 13 patients were 84.6% and 61.5%, respectively; among the 10 with GB, they were 80% and 50%. Generally, the smaller the tumor size, the better the results. There were no adverse effects, despite the dose 15 to 50 Gy applied temporally to the tumor bed. IOR was especially effective against small, localized tumors, but was not always beneficial in cases of large tumors, particularly those with a contralateral focus. The improved survival rate in this series demonstrates that IOR is significantly effective in the "induction of remission" following surgical excision of malignant gliomas.     

Results of nuclear magnetic resonance with cerebral glioma. Comparison with computed tomography

Our experience using nuclear magnetic resonance (NMR) in eight patients with abnormalities on computed tomography (CT) scans suggesting glioma is reported. Three patients underwent biopsies. Two patients had grade II astrocytomas. Difficulty was encountered confirming the diagnosis of astrocytoma on frozen sections in one patient, and permanent sections were required for diagnosis in the other. The third patient to undergo biopsy had a grade III anaplastic mixed glioma. Biopsy of subsequent patients with probable gliomas was not done because of the risk of producing neurological deficit. The NMR images suggest that lower-grade astrocytomas are well circumscribed, whereas higher-grade gliomas affect adjacent association bundles by direct extension of tumor cells or vasogenic edema.     

A commentary on the biology and growth kinetics of low-grade and high-grade gliomas

Cell kinetics studies of patients with various gliomas published in the past decade have shown that the average labeling index (LI) obtained from a pulse of 3H-thymidine is very high in medulloblastomas (12.0% +/- 1.3%, standard error of the mean) and glioblastoma multiforme (9.3% +/- 1.0%), low in well differentiated gliomas (less than 1%), and intermediate in anaplastic astrocytomas (4.0% +/- 0.8%). The higher the LI, the faster the tumor grows, probably reflecting a larger growth fraction. In tumor tissues obtained at autopsy, two glioblastomas diluted out the labeling compound in the 2- to 4-month interval after labeling, whereas three glioblastomas and two anaplastic astrocytomas retained labeled neoplastic cells for 3 weeks to 5 months. Most patients whose tumors contained foci of labeled cells at autopsy survived longer. Well differentiated gliomas harbored labeled cells for 2 1/2 to 7 years. These findings indicate that the kinetics of proliferation in well differentiated gliomas are different from those in glioblastomas or anaplastic astrocytomas.     

Efficacy of Post Operative Adjuvant Therapy with Human Interferon Beta, MCNU and Radiation (IMR) for Malignant Glioma: Comparison Among Three Protocols

Summary  In order to develop ultimate adjuvant therapy for malignant gliomas, we analysed 77 patients with malignant gliomas (29 anaplastic astrocytomas (AAs) and 48 glioblastoma multiformes (GMs)) treated by three protocols of IMR therapy (human interferon-beta (HuIFN-β), MCNU and radiation).  In protocol 1 (n=45: AA=13, GM=32), 1 ×10⁶ IU of HuIFN-β was administrated intravenously once a day for 7 days. On day 2, MCNU was administrated at a dose of 2 mg/kg b.w. intravenously and from day 3, radiation was started in five weekly fractions of 2 Gy for 6 weeks. Total dose was 60 Gy. Protocol 2 (n=19: AA=11, GM=8) was comparable with protocol 1 except HuIFN-β was administrated twice a day at a dose of 1×10⁶ IU each. Protocol 3 (n=13: AA=5, GM=8) differed from protocol 2 only in a high dose-hyperfractionated radiation which was given twice a day at a dose of 1.5 Gy each and for a total dose of 66 Gy. Antitumor effects were evaluated by survival and response rate determined by decrease of tumor size. Significant improvement was obtained in patients with AAs by protocol 2 and 3. Response rates of patients with AAs and GMs were 46.2% and 50% in protocol 1, 63.6% and 50% in protocol 2, and 80% and 50% in protocol 3, respectively. One and two year survival rates in AAs were 46.4% and 34.8% in protocol 1, both 75% in protocol 2, and both 100% in protocol 3. Survival rates in GMs were not different among them. Except of radiation necrosis, which was observed in 38.5% of the patients under protocol 3, there was no significant difference in the adverse effects among the three protocols.  In the present study, the efficacy of IMR therapy for patients with malignant gliomas, especially for AAs, was cofirmed. We conclude that twice a day administrations of HuIFN-β in combination with a high dose-hyperfractionated radiation provide increased efficacy in IMR therapy.     

Treatment of recurrent brain stem gliomas and other central nervous system tumors with 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine

Twenty-one patients with recurrent malignant central nervous system gliomas were treated with a combination of 5-fluorouracil, CCNU, hydroxyurea, and 6-mercaptopurine. Thirteen patients had brain stem gliomas, 3 patients had spinal cord gliomas, 3 patients had thalamic gliomas, and 2 patients had cerebellar astrocytomas. All patients had received radiation therapy, and 4 brain stem patients had also been treated with chemotherapy. Sixteen patients (76%) responded to treatment with either stabilization of disease or improvement. Nine of the 13 patients with brain stem gliomas (71%) had response or stabilization of disease. The median time to tumor progression (TTP) for the brain stem patients who responded or had stabilization of disease was 25 weeks. The median survival from recurrence for the brain stem glioma patients was 27 weeks. Patients with cerebellar, thalamic, and spinal cord tumors did very well, with an 87% response or stabilization of disease and a median TTP of 122 weeks.     

Pediatric high grade gliomas: Clinico-pathological profile,therapeutic approaches and factors affecting overall survival

IntroductionPediatric high grade gliomas are rare tumors of the central nervous system. Treatment is multidisciplinary, comprising surgical excision followed by radiotherapy and/or chemotherapy.Objectivesdescribe these tumors’ characteristics as seen in our institution, and identify factors associated with better overall survival.Patients and methodsWe conducted a retrospective study of 30 cases of pediatric high grade glioma treated consecutively in our institution over a 20-year period. Brainstem tumors and patients aged more than 22 years were excluded. Univariate analysis was conducted to determine factors associated with better overall survival.ResultsThe series comprised 30 pediatric high grade gliomas: 27 glioblastomas and 3 anaplastic astrocytomas. The sex ratio was 1.7. Mean age was 13 years. Tumors were mainly located in the cerebral hemispheres (63.3%). Median tumor size was 5 cm. Glioblastomas were subdivided into 26 cases of classical subtype (96.3%) and 1 case of epithelioid subtype (3.7%). Surgical strategy consisted in tumor resection in 24 cases (80%). Twenty-one patients (70%) received postoperative radiotherapy. Therapeutic response at end of treatment was complete in 7 cases (23.3%). Postoperative radiation therapy and complete treatment response were significantly associated with improved overall survival in all high grade gliomas and also specifically in glioblastomas (P < 0.001 and P = 0.005, respectively).ConclusionOur results suggest that postoperative radiotherapy and complete treatment response are predictive factors for better overall survival in pediatric high grade glioma.     

Trends and Outcomes in the Treatment of Gliomas Based on Data during 2001–2004 from the Brain Tumor Registry of Japan

The committee of Brain Tumor Registry of Japan (BTRJ) was founded in 1973 and conducts surveys and analyses of incidence, therapeutic methods, and treatment outcomes of primary and metastatic brain tumors with the cooperation of the Japan Neurosurgical Society members. Newly diagnosed 3,000–4,000 primary brain tumors and 600–1,000 brain metastases patients were enrolled in each year. This report describes the trends and treatment outcomes of gliomas from BTRJ volume 13, including 13,431 patients with primary brain tumors who newly started treatment from 2001 to 2004. Data from 382 diffuse astrocytomas (DAs), 121 oligodendrogliomas (OLs), 90 oligoastrocytomas (OAs), 513 anaplastic astrocytomas (AAs), 126 anaplastic oligodendrogliomas (AOs), 106 anaplastic oligoastrocytomas (AOAs), and 1,489 glioblastomas (GBMs) were analyzed for overall survival (OS) and progression free survival (PFS) depending on age, symptoms, Karnofsky performance status, location of the tumor, extent of resection (EOR), initial radiotherapy and chemotherapy. The 5-year PFS rates of the patients with DA, OL + OA, AA, AO + AOA, and GBM were 57.0%, 74.6%, 28.7%, 54.0%, and 9.2%, and the 5-year OS rates were 75.0%, 90.0%, 41.1%, 68.2%, and 10.1%, respectively. Higher EOR ≥ 75% in DA and OL + OA and that ≥ 50% in AA, AO + AOA, and GBM significantly prolonged OS. Complications and cause of death were also reported. BTRJ had been edited for all the patients, researchers, and especially for clinicians at bedside to give useful information about brain tumors and to contribute to the advances in brain tumor treatment. This report revealed various clinical problematic issues pertaining to the diagnosis and treatment of gliomas.     

In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling

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 fraction 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.     

Prognostic implications of the bromodeoxyuridine labeling index of human gliomas

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 (less than 1%, 2.7%, and 7.3%, respectively; range 0% to 38.1%) were not significantly different from those of 55 similar recurrent tumors (less than 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 less than 0.001). The 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.     

Histologic and clinical factors of prognostic significance in astrocytic gliomas

The three-tiered system of classification of astrocytic gliomas that distinguishes the well differentiated astrocytoma, the anaplastic astrocytoma and the glioblastoma seems to better correlate with outcome. The knowledge of factors (histologic, clinical, radiologic and therapeutic) affecting survival in both well differentiated and anaplastic astrocytomas is limited. In both types young age and high performance status are associated with a better prognosis. The prognostic value of many factors in well differentiated tumors is still debated: this is the case for the number of mitoses, the enhancement on CT, the extent of surgery and the usefulness of postoperative radiotherapy. In anaplastic astrocytomas there is agreement about the prognostic value of endothelial proliferations: their presence is correlated with a poor prognosis. Post operative radiotherapy (5.500-6.000 cGy) significantly improves the survival time, whereas is still not known the true value of the extent of resection.     

Supratentorial gliomas: surgical considerations and immediate postoperative results. Gross total resection versus partial resection

Forty-two patients with supratentorial gliomas not involving the basal ganglia (extraganglionic) were studied pre- and postoperatively with computed tomographic (CT) scans to evaluate the effect of the extent of surgical resection on the immediate postoperative results. Thirty-three patients (79%) had malignant astrocytic gliomas (glioblastoma or anaplastic astrocytoma), 4 patients (10%) had well-differentiated astrocytomas, and 5 (12%) had oligodendrogliomas. The median age was 58 years, and the median Karnofsky rating was 70. There was no operative mortality. Six patients (14%) had surgical complications. A gross total resection was defined as the absence of any abnormal enhancement on the postoperative CT scan. A nearly gross total resection had been accomplished when less than 10% of the preoperatively enhancing mass was still seen. A partial resection was indicated by the presence of more than 10% of the enhancing lesion on the postoperative CT scan. A gross total or nearly gross total resection was accomplished in 36 patients (86%), and an improved or stable postoperative neurological status was present in 35 of these patients (97%). In contrast, the rate of neurological morbidity after a partial resection was 40%. Supratentorial extraganglionic gliomas, regardless of their histological type, generally were well-circumscribed lesions except at the level of the ventricular wall, where glioblastomas and anaplastic astrocytomas blended with the subependymal white matter from which they seemed to arise.     

Brachytherapy of recurrent malignant brain tumors with removable high-activity iodine-125 sources

Thirty-seven patients harboring recurrent malignant primary or metastatic brain tumors were treated by 40 implantations of high-activity iodine-125 (125I) sources. All patients had been treated with irradiation and most had been treated with chemotherapeutic agents, primarily nitrosoureas. Implantations were performed using computerized tomography (CT)-directed stereotaxy; 125I sources were held in one or more afterloaded catheters that were removed after the desired dose (minimum tumor dose of 3000 to 12,000 rads) had been delivered. Patients were followed with sequential neurological examinations and CT scans. Results of 34 implantation procedures were evaluable: 18 produced documented tumor regression (response) for 4 to 13+ months; five, performed in deteriorating patients, resulted in disease stability for 4 to 12 months. The overall response rate was 68%. In 11 patients, implantation did not halt clinical deterioration. At exploratory craniotomy 5 to 12 months after implantation, focal radiation necrosis was documented in two patients whose tumor had responded initially and then progressed, and in three patients whose disease had progressed initially (four glioblastomas, one anaplastic astrocytoma); histologically identifiable tumor was documented in two of these patients. All improved after resection of the focal necrotic mass and are still alive 10, 15, 19, 24, and 25 months after the initial implantation procedure; only one patient has evidence of tumor regrowth. The median follow-up period after implantation for the malignant glioma (anaplastic astrocytoma and glioblastoma multiforme) group is 9 months, with 48% of patients still surviving. While direct comparison with the results of chemotherapy is difficult, results obtained in this patient group with interstitial brachytherapy are probably superior to results obtained with chemotherapy.     

Changes in 1H-MRS in glioma patients before and after irradiation: the significance of quantitative analysis of choline-containing compounds

The evaluation of the response to radiation therapy in brain tumor patients is a major and an important issue. Although CT and MRI can measure changes in tumor size, it is difficult to use these imaging methods to evaluate the viability or the proliferation activity of a tumor. In this study, we investigated the metabolite changes in glioma patients using 1H-MRS from before to after radiation therapy, to see whether or not early metabolic changes occur during therapy. Seven patients with histologically proven glioma (1 astrocytoma, 1 anaplastic astrocytoma, 2 oligoastrocytoma, 1 oligodendroglioma, 2 glioblastoma) were examined by means of 1H-MRS using a point-resolved spectroscopy (PRESS) sequence with a repetition time of 2,000 ms and echo times of 68 ms, 136 ms and 272 ms. The 1H-MRS was evaluated by both the spectrum pattern and the quantification of the metabolites. As to radiation therapy, each patient received a total dose of 64.8 Gy (1.8 Gy/fraction) with a 10-MeV linear accelerator. The results revealed that the concentration of choline-containing compounds (Cho) was 4.55 +/- 1.08 mmol/kg wet weight before radiation therapy and was reduced to 2.69 +/- 0.56 mmol/kg wet weight (p < 0.01) after radiation therapy. Moreover, both the N-acetylaspartate (NAA) peak and creatine/phosphocreatine (t-Cr) peak were lower after radiation therapy than before. The peaks of both the lipids (Lip) and lactate (Lac) were higher after radiation therapy than before. In conclusion, Cho concentration is thought to be a useful marker for the evaluation of early post-radiation response. The effect of radiation therapy can be evaluated according to the value of Cho. Further long-term MRS study is needed to prove whether or not the decrease of the Cho value in the present study will change before recurrence at later stages.     

Gemistocytic astrocytomas: a reappraisal

Although gemistocytic astrocytomas are considered slow-growing astrocytomas, they often behave aggressively. To clarify the biological and clinical behavior of these rare tumors, the authors retrospectively identified 59 patients with gemistocytic astrocytoma whose tumors were diagnosed and treated between June, 1976, and July, 1989. Three patients who were lost to follow-up review were excluded, as were two whose original slides could not be obtained and three whose tumors were diagnosed at recurrence or at autopsy. The pathological material of the remaining 51 patients was reviewed using two sets of histological criteria. Thirteen patients (Group A) had "pure" gemistocytic astrocytoma, defined as a glial tumor with more than 60% gemistocytes/high-power field and a background of fibrillary astrocytes. Fifteen patients (Group B) had "mixed" gemistocytic astrocytoma, defined as a glial tumor with 20% to 60% gemistocytes/high-power field and a background of anaplastic astrocytes. Twenty-three tumors did not meet these criteria and were excluded from analysis. The median age of the patients was 48.5 years in Group A and 38.3 years in Group B (p less than 0.05). In both groups, the median Karnofsky Performance Scale score was greater than 90%. All patients underwent surgical procedures (four total and 19 partial resections, and five biopsies) and postoperative radiation therapy. The majority also had interstitial brachytherapy, chemotherapy, or both. Ten patients had one reoperation for tumor recurrence and one had two reoperations; other treatments for recurrence included brachytherapy, chemotherapy, and repeat irradiation. All four patients who originally underwent gross total resection are still alive; all five who had a biopsy have died. There was no significant difference in median survival times between groups: 136.5 weeks in Group A (range 10 to 310+ weeks) and 135.6 weeks in Group B (range 31 to 460+ weeks). Analysis of all 28 patients showed a better prognosis for patients less than 50 years of age (185 vs. 36 weeks survival time; p less than 0.001), patients with preoperative symptoms lasting for more than 6 months (228.1 vs. 110.2 weeks survival time; p less than 0.05), and patients with seizures as the first symptom (185.7 vs. 80 weeks survival time; p less than 0.01). Survival time did not correlate with the presence of perivascular lymphocytic infiltration. The authors conclude that the presence of at least 20% gemistocytes in a glial neoplasm is a poor prognostic sign, irrespective of the pathological background. It is proposed that gemistocytic astrocytomas be classified with anaplastic astrocytomas and treated accordingly.     

Reoperation in the treatment of recurrent intracranial malignant gliomas

Fifty-five consecutive patients with recurrent intracranial malignant gliomas were reoperated at Memorial Sloan-Kettering Cancer Center from 1972 to 1983. The patients were 10 to 70 years old (median, 48 years). Thirty-five patients (64%) had glioblastoma multiforme, and 20 (36%) had anaplastic astrocytoma. The median interval between the first operation and reoperation was 43 weeks. The Karnofsky rating before reoperation ranged from 40 to 90 (median, 70). Eleven patients (20%) had more than one reoperation. The mortality rate was 1.4% per procedure, and the morbidity rate was 16% per procedure. After reoperation, 41 patients (75%) had chemotherapy and/or radiation therapy. The median survival for all patients was 92 weeks. The median survival after reoperation was 36 weeks. Patients with Karnofsky ratings of greater than or equal to 70, with anaplastic astrocytomas, or in whom gross total removal of the tumor was undertaken lived longer than their respective counterparts (P less than 0.05). Prereoperation Karnofsky rating and extent of surgical resection were the most important independent factors related to survival after reoperation according to multivariate analysis (P less than 0.01 and P less than 0.05, respectively). Twenty-five patients (45%) had improved Karnofsky ratings after reoperation, and the 32 patients (58%) who were independent after reoperation were able to stay so for more than 6 months of their survival time (median value). Reoperation is feasible and can be accomplished with acceptable mortality and morbidity. When intracranial malignant gliomas recur, the combined use of reoperation and adjuvant therapy prolongs good quality life.(ABSTRACT TRUNCATED AT 250 WORDS)