Ch. B. Ostertag

The monoclonal antibody Ki-67 as a marker for proliferating cells in stereotactic biopsies of brain tumours

SummaryThe monoclonal antibody Ki-67 has been tested as a marker of proliferating cells in 52 stereotactic brain tumour biopsies. The antibody reacts with a nuclear protein expressed in G1,S, G2n and Mphases of the cell cycle. Using the immunoperoxidase technique on squash preparations the percentage of Ki-67 positive cells was determined as a fraction of the total number of tumour cells present. This Ki-67 index was in close correlation with the histological grade. Highest values were found in a pineal germinoma (46.3%) and in 3 primary cerebral non-Hodgkin lymphomas (mean 39.5%). Among the gliomas, the highest fraction of proliferating cells was seen in 2 anaplastic paediatric brain stem gliomas (mean 17.4%) and in an anaplastic ependymoma (12.5%). Anaplastic astrocytomas and glioblastomas varied considerably with mean values of 9.5% and 8%, respectively. To some extent this variability may reflect tumour heterogeneity which is more likely to manifest in small stereotactic samples than in large tissue specimens obtained during open surgery. Pilocytic astrocytomas, mixed gliomas and fibrillary astrocytomas had moderate to low percentages.Ki-67 staining of squash preparations can easily be performed on a rountine basis and is, in our experience, superior to frozen sections. This method allows the determination of the growth fraction of an individual tumour and could become an important additional criterion for the decision among alternative and potentially harmful therapeutic regimens.

Iodine-125 interstitial irradiation for cerebral gliomas

SummaryIn this retrospective review the outcome of 539 patients is evaluated, who from 1979 through 1991 underwent stereotactic biopsy and interstitial irradiation using iodine-125 implants. Permanent (lost) 125-I implants were used in 345 cases (64%) (1979–1985), temporary (removable) implants in 194 cases (36%) (1985–1991).The patients were selected for interstitial irradiation on the basis of histological classification, location and circumscription of their tumours (106 pilocytic astrocytomas, 251 astrocytomas WHO grade II, 29 oligodendrogliomas, 44 oligo-astrocytomas, 75 anaplastic astrocytomas and 34 glioblastomas). Diffusely infiltrative non-delineated gliomas and gliomas crossing the midline were excluded.Five-year survival rates were 77% for pilocytic astrocytomas, 65% for astrocytomas WHO II, 80% for oligo-astrocytomas, and 58% for oligodendrogliomas. The 2-year survival rates were 36% for anaplastic gliomas and 16% for glioblastomas. Operative morbidity due to stereotactic biopsy, implantation, and explantation of seeds was 3.9%. In the subgroups of patients with astrocytomas (WHO-II), pilocytic astrocytomas and malignant gliomas age was a significant factor predicting survival.Patients with astrocytomas WHO II who received temporary implants had a significantly better outcome than those with permanent implants. Radiation toxicity (3.1%) was seen mostly among the permanent (lost) implants. No patients required re-operation due to radionecrosis. The findings among this subgroup of gliomas indicate that interstitial implant irradiation using 125-I is effective in controlling tumour growth and is well tolerated. Patients with differentiated and circumscribed gliomas particularly benefit from the treatment.

Interstitial 125-iodine radiosurgery of low-grade gliomas of the insula of Reil

SummaryBetween 1979 and 1991 67 patients with low-grade gliomas of the insula (of Reil) were treated with 125-iodine interstitial radiosurgery. Retrospective analysis with a median follow-up of 55 months demonstrated a 5- and 10-year survival rate of 54% and 47%, respectively, for all low-grade gliomas treated and a 5- and 10-year survival rate of 57% for 49 patients with astrocytomas WHO grade II analysed separately. The median Karnofsky performance status of survivors was 90%. Malignant change was the cause of death in 85%, failure to control tumour growth in the remaining cases. Multivariate analysis with a Cox proportional hazard model identified solely the pre-operative Karnofsky performance score of 70–80 vs. 90% as a prognostic factor for outcome (p=0.001, risk ratio 3. 62), but not age, gender, tumour volume, length of disease before treatment, mode of implantation, or major vs. moderate or no shrinkage of tumour volume after interstitial radiosurgery.Thus, 125-iodine radiosurgery yielded survival rates in these deep-seated insular gliomas comparable to those reported after surgery and radiation therapy of lobar tumours. This was achieved with a low peri-operative mortality and morbidity and at low costs.

Diagnostic value of CT in patients with huntington's chorea and their offspring

SummaryStriatal and cortical atrophy are significant features in the pathology of Huntingtons chorea (HCh). A correlative study revealed that the CT findings of atrophy in HCh (8 patients) parallel the clinical and neurophysiological findings. In offspring (8 subjects) of HCh patients, however, the CT changes were insignificant although neurophysiological data were already suspicious in four of them. One patient with hereditary non-progressive chorea showed no CT changes at all. Perhaps with a more sensitive CT scanning technique minor morphological alterations may also be detected and used for a pre-clinical diagnosis.ZusammenfassungAtrophien des Corpus striatum und der Hirnrinde sind typische pathologische Veränderungen bei Chorea Huntington (H.Ch.). Eine vergleichende Untersuchung konnte Parallelen zwischen computertomographischen Atrophiezeichen bei 8 Choreapatienten und neurophysiologischen Befunden zeigen. Bei 8 Nachkommen waren die Veränderungen im Computertomogramm (CT) unspezifisch und geringfügig, obwohl 4 von ihnen in den neurophysiologischen Untersuchungen auffällig waren. Ein Patient mit hereditärer nicht-progressiver Chorea zeigte keinerlei CT-Veränderungen. Es bleibt empfindlicheren CT-Scannern vorbehalten, feinere morphologische Veränderungen zu erfassen, die für die präklinische Diagnose der Chorea Huntington nützlich wären.

Stereotactic management of congenital midline cysts

SummaryThe treatment of congenital midline cysts remains a controversial issue. The Stereotactic management of 27 patients (6 symptomatic cavum septi pellucidi/cavum Vergae, 6 suprasellar cysts, 5 intraventricular cysts, 4 parasagittal cysts, and 6 supracollicular cysts) is reviewed. In 23 patients Stereotactic ventriculo-cystostomy by catheter implantation (internal drainage) led to clinical recovery or improvement accompanied by decreased cyst size. In four patients the internal drainage was not sufficient and was therefore completed as a ventriculo-atrial shunt system. Three minor complications (bleeding, aseptic meningitis, catheter infection) led to no sequelae. The results suggest that Stereotactic internal drainage of these benign lesions is a safe, minimally invasive and efficient procedure.

Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease.

SummaryThe concentrations of somatostatin-like immunoreactivity (SLI) in lateral ventricular fluid of patients with extrapyramidal motor disease were determined by specific radio-immunoassay. Mean SLI levels were significantly lower in patients with Parkinsons disease (mean ± SEM); 42.9±2.9 fmol/ml) and in patients with dystonic syndromes (39.4±3.2) than in patients with benign essential tremor (65.3±9.7). The lowest levels were found in patients with athetosis (34.7±5.4). In parkinsonian patients somatostatin levels correlated with the degree of akinesia, rigidity and autonomic disturbances.

Experimental Data on Early and Late Morphologic Effects of Permanently Implanted Gamma and Beta Sources (Iridium-192, Iodine-125 and Yttrium-90) in the Brain

To study the radiation response of normal brain tissue to interstitial irradiation Iodine-125 seeds and Iridium-192 wire pieces were permanently implanted into the subcortical white matter in beagle dogs. Sequential observations on physiologic and morphologic changes were carried out up to one year after implantation. To study the radiation effects of Iodine-125 implants on neoplastic tissue, Avian-sarcoma-virus induced gliomas and sarcomas in beagle brains were permanently implanted with Iodine-125 seeds under CT stereotactic conditions. The intratumoral placement produced sharply defined necroses with central mineralization.

Morphology of Intracranial Tumours and Adjacent Brain Structures Following Interstitial Iodine-125 Radiotherapy

Analysis of 8 autopsied cases with permanent 125I implantation demonstrates that interstitial irradiation of CNS neoplasms causes extensive focal tumour necroses. In some cases, complete tumour regression resulted, with no viable neoplastic cells detectable at autopsy. In large gliomas of the cerebral hemispheres and basal ganglia, central radiation-induced necroses were present, but peripheral tumour masses progressed and ultimately determined the clinical outcome. In patients with tumours located in basal midline structures, interstitial 125I produced areas of delayed radionecrosis extending into the adjacent normal brain tissue. All of these patients were treated with external radiation in addition to interstitial implantation, indicating cumulative radiation toxicity.

Interstitial Implant Radiosurgery for Cerebral Metastases

The effectiveness of interstitial implant radiosurgery (IRS) as an alternative or adjuvant treatment to radiotherapy (WBRT) or surgery of cerebral metastases remains unclear. In a retrospective study (1982-1991) we analysed four therapeutic regimes after stereotactic biopsy: IRS with a tumour dose of 60 Gy in combination with WBRT (40 Gy/5 x 2 Gy/week--38 patients), IRS only (tumour dose 60 Gy--22 patients), WBRT only (40 Gy/5 x 2 Gy/week--49 patients), and IRS only for recurrent cerebral metastases (tumour dose 60 Gy--21 patients). Low-activity iodine-125 seeds were used exclusively. IRS was performed in the case of circumscribed, mostly solitary metastases < or = 4 cm in diameter. Patients undergoing combined treatment had the best survival, with a median survival time of 17 months in comparison with 12 months after IRS alone and 7.7 months after WBRT. The median survival of patients with recurrent metastases after IRS was 6 months. A comparison of treatments in the multivariate analysis showed that IRS + WBRT was not superior to IRS alone. The metastases could be locally controlled in every case. There were no radionecroses requiring treatment. Most favourable determinants after IRS or IRS + WBRT were a solitary metastasis and a long time interval between diagnosis of the primary and diagnosis of the cerebral metastases. Our results demonstrate the effectiveness of IRS. For a single cerebral metastasis, IRS as a minimally invasive method offers major advantages.

Retrospective analysis of treatment outcome in 315 patients with oligodendroglial brain tumors

Although chemotherapy with procarbazine, lomustine and vincristine (PCV) is considered to be well tolerated, side effects frequently lead to dose reduction or even discontinuation of treatment of oligodendroglial brain tumors. The primary objective of the analysis was to retrospectively compare progression-free survival (PFS) after PCV vs. PC chemotherapy (without vincristine to avoid side effects). Patients were retrospectively identified from a database containing our patients between 1990 and 2003. For the selected cases, all histopathology reports were re-evaluated by a local neuropathologist. Based on the updated histology data, patients were included in the study if they had at least one histological diagnosis of an oligodendroglial tumor. PFS after start of PCV (n = 61) and PC (n = 84) chemotherapy identical (median 30 months). Multivariate analysis adjusting for prognostic imbalances favouring the PC group showed a minor, statistically non-significant benefit for PCV (hazard ratio 0.81, 95% confidence interval 0.53–1.25; p = 0.346). Younger age (< 50 y) was a statistically significant predictor of longer PFS. Significant advantages in terms of overall survival after first diagnosis of oligodendroglial tumor (OS, n = 315) were found for patients < 50 y (p < 0.001), oligodendrogliomas versus oligoastrocytomas (p = 0.002), and WHO°II vs. °III (p < 0.001). Three risk groups regarding OS were identified. Findings support the hypothesis that PC may be as effective as PCV chemotherapy, while avoiding the additonal risks of vincristine. Younger age, lower tumor grade and histology of an oligodendroglioma were identified to be favorable prognostic factors.