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Twenty-seven patients with Graves' disease and progressive ophthalmopathy in an advanced stage underwent a transtemporal orbital decompression. The short-term results, i.e. within 2 months, of 48 operations are reported. Prior to the decompression, oral prednisolone, 20–60 mg daily, was given for 2 to 9 months to 15 patients. A minority of patients experienced temporary improvement during steroid administration. Cushing's syndrome was initiated in all patients. Prednisolone little altered the course of the progressive ophthalmopathy. Orbital decompression was followed by increasing visual acuity in 8/22 eyes with disturbed vision, a temporary decrease in 6 eyes, and unaltered visual acuity in the remaining 8 eyes. The decompression removed oedema of the optic disc in all eyes, cured glaucoma in 3 out of 5 patients, caused retraction of the eye bulbs by 5–6 mm in almost all operated cases, and increased compressibility of the orbital content from low (2–5 mm) to normal (6–10 mm) values. Surgery also relieved photophobia and lacrimation, but the effect on diplopia was uncertain. Generally, the decompression was followed by a rapid improvement of the orbital congestion and the patients recovered satisfactorily from the surgery.

Fifteen patients were treated in the Gamma Knife Unit and followed for 18 months or longer. Four patients had Cushing's disease, 4 had acromegaly, 3 had Nelson's syndrome and 3 had prolactinomas. One patient had no endocrinopathy. One of the patients with acromegaly and 2 of those with prolactinomas had been operated prior to Gamma Knife treatment. Radiological tumor localization was not an insuperable problem in this series. The effect of Gamma Knife treatment on the anterior pituitary neoplasia, as such, was consistently successful. All the tumors which received 10 Gy or more to the edge showed either a reduction in volume or at least cessation of growth. On the other hand, the effect of the treatment was less consistent in respect to the endocrinopathies. These results are discussed in respect of dose and tumor size. It is suggested that the role of the Gamma Knife in the treatment of pituitary adenomas requires further clarification, based on prospective studies.

The invasiveness of human intracranial tumours was studied in an organ culture system. Biopsies from six glioblastomas, four astrocytomas, two mixed gliomas, one ependymoma, four meningiomas and two carcinoma metastases were cut into fragments of 0.5 mm diameter, and placed in agar overlay tissue culture. The tumour specimens formed spheroids which were co-cultured with cell aggregates or fragments from fetal rat brain for up to 10 days in vitro. The invasiveness of the glioblastoma spheroids was characterised by a gradual destruction of normal brain tissue by tumour cells, followed by replacement of normal tissue by these cells. Co-cultures from two glioblastomas showed lesions in the normal brain tissue in areas removed from the tumour cells. Tumour spheroids from four glioblastomas totally destroyed the normal brain tissue without any change in the original tumour spheroid configuration. The low-grade gliomas were less invasive than the glioblastomas. The meningiomas and the metastases were non-invasive. This organ culture assay appeared to reflect the in situ invasive behaviour of the brain tumours examined. It is suggested that it may be used for evaluating the aggressiveness of individual brain tumours with the specific aim of correlating clinical data with the biological character of the tumour.

In Bergen, 20 patients with meningiomas have been treated with a follow-up period in excess of 1 year. While this is too short a period to allow more than tentative conclusions to be drawn, some trends can be determined nonetheless. There has been some variation in the reporting of the results of treatment of meningiomas, with one group producing a reduction in size in 7% of patients and another in 34%. In the current material, 10 patients received 10 Gy or less to the edge of the tumor. In 4 of these 12 patients there was increase in the volume of the tumor within 1 year of treatment. Ten of the patients received 12 Gy or more to the edge of the tumor. Of these 10 patients, 4 had tumors which showed a reduction in volume. It is suggested that the difference in the reported rate of tumor volume reduction is related to differences in dose, which is discussed in relation to other treatment parameters.

The effects of radiation on direction on directional migration in monolayer cultures and brain tissue invasion by two glioblastoma cell lines (D-54 MG, D-247 MG) were investigated. The Leksell Gamma Unit was the radiation source and invasion was registered in an in vitro invasion assay developed in our laboratory. As tumor spheroids and brain tissue aggregates were treated simultaneously in cocultures; the effects of radiation on the interaction between the two tissues could be investigated. Tumor spheroids from both cell lines retained their ability to invade and destroy normal brain tissue, even after irradiation with 47.6 Gy. However, while the D-54 MG tumor spheroids showed a dose-dependent reduction of invasion, tumor spheroids from the D-247 MG cell line did not. In addition, radiation produced a dose dependent inhibition of directional migration of cells from D-54 MG spheroids. A similar significant inhibition of directional migration was found in D-247 MG, but it was not dose-dependent. Transmission electron microscopy revealed a loosening of the neuropil in the brain tissue of irradiated cocultures. However, this structural change did not seem to affect the invasiveness of the tumor. In this preliminary study, irradiation could not prevent invasion of two different glioblastoma cell lines into fetal rat brain tissue. Further studies using the same technique may help to understand the influence of ionizing radiation upon the invasion process in gliomas.

A Leksell Gamma Knife has been used at Haukeland Hospital, Bergen, since October 1988. This is a powerful instrument in the treatment of some intracranial lesions. The article briefly describes the principles of treatment and the uses and limitations of the Gamma Knife.

Four patients with pituitary dependent Cushing's syndrome were treated with external irradiation to the pituitary using 60Co gamma irradiation given with a stereotactic technique. The size of the sella turcica was normal or slightly enlarged in all patients. The doses given varied between 7000 and 10 000 rad, and the observation time ranged between 14 and 20 months. Three of the patients showed complete clinical remission and one marked improvement. One patient developed ACTH insufficiency, while none developed insufficient secretion of other pituitary hormones. No complications of the irradiation were observed.

Fourty-two consecutive patients with craniopharyngioma were treated by "stereotactic approach", i.e. preferentially stereotactic puncture and installation of colloid isotope into cystic tumours and external stereotactic single dose irradiation to solid tumour parts. In a minority of cases, such treatment was less suitable, and surgical removal and/or radiotherapy was used. There was no peroperative mortality. A long-term follow up (observation time 10-23 years) of the 31 patients alive indicated that they were socially well adapted with a high rate of fulltime work and a low rate of intercurrent disease. In spite of substitution therapy for pituitary insufficiency in most cases, the patients were subjectively seldom disturbed by their disease. Our results support a change in the choice of therapy for craniopharyngioma patients, from open neurosurgery to the less invasive stereotactic techniques.

A pituitary tumor secreting TSH only was diagnosed in a 19-year-old male. The patient was clinically euthyroid, but showed elevated TSH, T3 and T4 levels in blood. After selective excision of the tumor it was analyzed with regard to morphology, type of hormone secretion and DNA content. A considerable pleomorphism of pituitary tumor cells occurred. During in vitro culture only TSH was secreted. The tumor had an aneuploid DNA content.

A multi-modality treatment programme, where stereotactic methods were used preferentially, gave results in a consecutive series of craniopharyngiomas, not inferior to those reported after microsurgical removal. Fourty-two patients with a follow-up range of 10-23 years are reported.

On the basis of remarkable results from transplantation experiments in animals, the author in 1979 suggested autologous transplantation of catecholamine tissue to the brain as tentative treatment for parkinsonism. Experiences from four patients thus treated are reported comprehensively. Transitory rewarding effects were seen when the transplant was deposited in the putamen. The potential prospects for this principally new therapeutic paradigm are discussed, as well as possible improvements in the method.

Stereotactic radiosurgery was used for selective destruction of adrenocorticotropic hormone (ACTH)-producing adenomas in 18 patients with Cushing's syndrome. A radiation-induced lesion in the most anterior part of the sella turcica caused remission of the disease. The acute increase in ACTH and cortisol secretion that occurred in the majority of patients had no predictable relationship to the final outcome. Decreased cortisol excretion during the first three weeks after treatment was positively correlated to favourable long-term results. The treatment is a therapeutic alternative to open selective excision of the adenoma.

In 1951 Leksell first coined the term "radiosurgery" indicating a new tool for the neurosurgeon by means of ionizing radiations. The technique consists of cross-firing a stereotactic target with several well-collimated "shots" of radiation. This produces well-defined lesions in the brain without opening the skull. After several significant improvements of this technique, now assisted by a computer, today it is possible to "tailormake" composite radiation fields for any single lesion. Some interesting clinical applications are Cushing's disease, acoustic tumors, pineal region tumors and arteriovenous malformations.

In order to study tumor invasiveness, the authors used a model system which allows the direct interaction between glioma cells and normal brain tissue to be studied. The spiral needle biopsy technique provides a tissue core with a completely preserved architecture from brain tumors. These biopsies, once cultured, produce three-dimensional multicellular tumor spheroids; they display morphological features similar to those of the original tumor in vivo. As a target fetal rat brain cell aggregates were used, in order to study the invasive process in the microscope. Not surprisingly, different tumors show different patterns of invasion; this variability is not yet clearly correlated with the clinical course of the patient.

Four patients are described with a colloid cyst in the anterior part of the third ventricle, causing obstruction of the foramina of Monro. Stereotactic aspiration of the cyst was performed after exact neuroradiological localization, including CT scan. The great advantages of the technique presented are discussed.

The therapy of craniopharyngiomas has always been a challenge for the neurosurgeon. These tumors often display a cystic or polycystic portion usually bigger than the solid portion. This paper reports therapeutic results in a series of 42 cases; the follow-up range is 10 to 23 yrs. The results are particularly rewarding in the group treated by stereotactic methods exclusively. In any case the optimal management of a craniopharyngioma should include a careful study of the anatomy of the tumor and the intracystic treatment as the first choice if more than 50% of the total tumor bulk is cystic and the number of cysts reasonable.

A new instrument for stereotactic evacuation of intracerebral haematomas is presented, as well as preliminary clinical experiences. A combined screw-and-suction technique makes possible the evacuation of even densely coagulated clots. The principle for a limited removal of a hemorrhagic mass in the brain is discussed.

(1972). Closed Stereotaxic Hypophysectomy by Means of 60Co Gamma Radiation. Acta Radiologica: Therapy, Physics, Biology: Vol. 11, No. 6, pp. 545-555.