Pituitary adenomas treated by microsurgery with or without Gamma Knife surgery: experience in 122 cases.

The clinical outcome of 122 patients with pituitary adenomas treated by microsurgery and/or Gamma Knife radiosurgery (GKRS) was analyzed to evaluate patient selection criteria and the role of GKRS. Sixty-six resections were performed in 59 patients. All tumors were macroadenomas, except for 5 ACTH-producing adenomas. Twenty-four of the 31 hypersecreting adenomas showed normal serum hormone values after treatment. Postoperative complications were rhinorrhea, cranial nerve palsies, and a small thalamic infarct. GKRS was performed on 18 of the operated patients because of residual tumors, mostly in the cavernous sinus. Thirty-five of the 63 patients treated by GKRS were followed for more than 2 years. All adenomas except 2 were stable or had decreased in size. Eleven of 17 functioning adenomas showed normal serum hormone values after treatment. It is concluded that tumors that compress the optic pathway should be removed and that residual tumors in the cavernous sinus are good indications for radiosurgery.

The role of intravascular embolization prior to radiosurgery of cerebral arteriovenous malformations. from the standpoint of hemorrhage and early obliteration after gamma knife radiosurgery.

The role of intravascular embolization prior to radiosurgery of cerebral arteriovenous malformations was evaluated based on the basis of the results of gamma knife radiosurgery in relation to hemorrhage and early obliteration after treatment. Nine of 213 patients experienced hemorrhage 4 to 42 months after radiosurgery. All AVMs in these patients had dilated feeding arteries, and the flow of the AVM was rapid and/or high. An intranidal aneurysm was seen in one patient. Drainage of all AVMs consisted of a single and/or deep draining veins, and venous obstruction was found in six. Sixty-three of 87 patients followed for more than four years after radiosurgery were examined angiographically, and total obliteration of AVM was observed in 52 of them (82.5%). Early obliteration was found in 19 of the 34 patients examined within 12 months. The obliteration rate was significantly higher in slow- and low-flow AVMs (73.9%) than in rapid- and/or high-flow AVMs (18.2%). It is concluded that the role of intravascular embolization prior to radiosurgery is not only decreasing the size of the AVM but decreasing the risk of hemorrhage and shortening the latency period by decreasing their flow rate and flow volume.

Radiobiological effects of gamma knife radiosurgery on brain tumors studied in autopsy and surgical specimens.

To elucidate the radiobiological effect of Gamma Knife radiosurgery on brain tumors, we performed a histological study on nine cases. In two, the material was obtained at autopsy and in seven following surgery. In the central region of the radiation field, destructive changes occurred both in tumor cells and in vessels. In the peripheral area, destructive and proliferative vascular changes were intermingled with residual tumor tissue. Immunohistochemical staining of surgical specimens showed that the vascular proliferative changes consisted of pericytic proliferation with or without endothelial proliferation. These characteristic changes might suppress tumor growth, at least in the short-term.

Gamma Knife radiosurgery for acoustic schwannoma: effects of low radiation dose and functional prognosis.

The effects of relatively low dose Gamma Knife irradiation on acoustic schwannoma were evaluated in 29 patients followed over 2 years after treatment. The mean dose delivered to the tumor periphery was 12.1 Gy. Lowering of the magnetic resonance signal intensity in the tumor center appeared in 69% and signs of tumor shrinkage appeared in 59% of cases. The cyst in the tumor enlarged in 3 cases, and 2 cases developed hydrocephalus. The percentage of pure-tone hearing preservation was 82% at 3 months, 73% at 6 months, 68% at 12 months. 64% at 18 months and 59% at 24 months in 22 out of 29 cases. Relatively low dose Gamma Knife radiosurgery was effective in suppressing tumor growth, with preservation of hearing.

Pathobiology of cerebral gliomas in children and the role of radiosurgery.

Twenty-five gliomas of the cerebral hemisphere in children were examined. Most hemispheric gliomas in children have relatively clear margins and less infiltrative potential. Radiosurgery has a role in the treatment of these tumors in addition to reducing the risk of radiation injuries developing later. Fifteen patients were alive 1-27 years (mean 8.4) following treatment and 10 patients died. Histologic examination demonstrated 10 differentiated gliomas, 10 poorly differentiated gliomas and 5 other gliomas. Most tumors had relatively clear margins on computed tomography and/or magnetic resonance images, and peritumoral edema was slight. In 9 autopsy cases, tumor dissemination and/or metastasis were seen in 7. However, tumor infiltration was not extensive, and clear tumor margins were found in some cases. Thus, cerebral gliomas in children have relatively clear margins and low infiltrative potential. Radiosurgery has a role in the treatment of these tumors.

Gamma thalamotomy for parkinsonian and other kinds of tremor.

On the basis of our experiences with selective ventralis intermedius thalamotomy with microrecording, certain cases of tremor with Parkinson's disease (PD, six cases), intentional tremor (one case) and essential tremor (one case) were treated by Gamma Knife. In all cases, 140-150 Gy were irradiated using 4-mm collimators. Three different strategies were used. (1) Gamma thalamotomy as the primary surgical treatment. (2) As a secondary treatment, irradiation of the symmetric point of the contralateral selective thalamotomy. (3) Extension of the previous thalamotomy. For the first three cases (all PD), a special plug pattern (100 plugs) was used, but was not employed for the later cases. No acute untoward effects were noted, and overall there appeared to be a reduction in tremor. The time course of tremor reduction varied from case to case, from about 5-6 months to 1 year.

Gamma knife radiosurgery for acoustic schwannoma: early effects and preservation of hearing.

The effects of relatively low dose gamma knife irradiation on acoustic schwannoma were evaluated. The signal intensity change and tumor shrinkage on magnetic resonance (MR) images, change in hearing, and complications in 28 patients (mean age 47.0 +/- 13.6 yrs) were studied. Three patients had bilateral tumors. Six were already deaf when treated. The maximum tumor diameter was 35 mm. The mean dose delivered to the tumor was 12.1 +/- 1.6 Gy at the periphery, and 25.2 +/- 4.3 Gy at the center. The mean follow-up time was 16 months and the longest 24 months. Lowering of the MR signal intensity in the tumor center appeared after 3 months at earliest but generally after 6 months. Signs of tumor shrinkage appeared within 12 months on average. Cyst in the tumor enlarged rapidly after treatment in two patients. The percentage of hearing preservation was 85% (17/20) at 3 months, 80% (16/20) at 6 months, 72% (13/18) at 9 months, 75% (12/16) at 12 months, 67% (8/12) at 15 months, 60% (6/10) at 18 months, and 50% (2/4) at 24 months. Subtle changes in hearing were detected by speech tone audiometry. Temporary facial numbness and weakness was seen in one patient each. No patient had lower cranial nerve paresis. Relatively low dose gamma knife radiosurgery is effective in suppressing growth of acoustic schwannoma with preservation of hearing.

[Evaluation of nuclear morphometric risk grade as a prognostic factor of early breast cancer].

The prognostic significance of nuclear areas was studied in 241 patients with primary stage I or II breast cancer. The mean follow-up period was 56.4 months. The nuclear areas of 100 breast cancer cells in HE stained specimen in each patient were measured by means of an image analyzing system, and the mean nuclear area (MNA) and standard deviation of nuclear area (SDNA) were calculated. MNA and SDNA were significantly larger in patients with recurrence than without it. Patients were divided into 2 groups according to the Nuclear Morphometric Risk Grade (NMRG), which was defined as follows: high risk: MNA > or = 80 microns 2 and SDNA > or = 28 microns 2; low risk: MNA < 80 microns 2 or SDNA < 28 microns 2. High risk patients revealed significantly poor disease free and overall survival than low risk patients (p < 0.0001, p < 0.0001). Furthermore, NMRG was a significant prognostic factor in node-negative patients. Cox multivariate analysis showed that nodal status and NMRG were independent predictors of tumor recurrence (n:p = 0.001; NMRG:p = 0.27) and survival (n:p < 0.001; in the NMRG:p = 0.0007). NMRG was a strong prognostic factor in patients in the early stage and it might support the decision for or against adjuvant therapy.

A case of infantile febrile psoriasiform dermatitis.

An infant suffered from psoriasiform dermatitis complicated by severe constitutional symptoms. During his 12 months of hospitalization, the symptoms exacerbated periodically despite numerous therapeutic trials. Histologic findings revealed lichenoid psoriasiform dermatitis with striking eosinophilic necrosis of epidermal cells and satellite cell necrosis. Immunohistochemically, CD1+ Langerhans cells had almost disappeared, and CD8+ cytotoxic-suppressor T cells were predominant over CD4+ helper-inducer T cells in the epidermis. These findings in the skin biopsy specimens suggested some similarity to graft-versus-host disease but no known cause of that disorder was proved. Finally, methotrexate was effective. The patient became afebrile, and his skin lesions improved, leaving almost no scarring. This patient seems to have had specific clinical features that do not correspond with any of the known dermatitis. Clinical, histologic, and laboratory findings did not uncover any etiologic factors.

Classification of arteriovenous malformations for radiosurgery. Neuroimaging, histopathology and radiobiologic effects.

Arteriovenous malformations (AVMs) were classified based on morphologic and hemodynamic factors. They were categorized as Moya type, shunt type or mixed type on the basis of hemodynamic factors, and as homogeneous or heterogeneous types on the basis of morphology. Histopathologic and radiobiologic characteristics were evaluated with respect to these AVM types. Classification depending on the type as well as the size of an AVM is important for modern treatment modalities, especially radiosurgery.

Gamma Knife thalamotomy for the treatment of functional disorders.

Gamma Knife thalamotomy was performed with a 4-mm collimator in 2 cases with thalamic pain following a stroke and in 1 case of Parkinson's disease with tremor. In both cases with pain the maximum dose of 130 Gy was focused at the mediocaudal region of the previous thalamic lesion. In the case with tremor in Parkinson's disease, the maximum dose was 150 Gy. Longer follow-up is now proceeding, but the short-term results are encouraging. Based on data obtained from selective thalamotomy with depth microrecording, Gamma Knife thalamotomy could be a safe and effective technique for the treatment of these functional disorders.

Fractionated Gamma Knife radiosurgery for malignant gliomas: neurobiological effects and FDG-PET studies.

Experimental single-dose neural irradiation was performed in rats and monkeys. Acute and 'early' late damage was observed following single high-dose treatments. By contrast, following a single low-dose treatment, neither 'early' nor 'delayed' late damage was noted. Based on these experiments, a clinical trial of fractionated Gamma Knife surgery for malignant gliomas was begun, and patients were followed by FDG-PET studies. An acute response of the tumor was obtained without damage to the surrounding brain. Fractionated Gamma Knife surgery is a potential alternative treatment for malignant gliomas.

Gamma Knife radiosurgery for the treatment of brainstem tumors.

Ten patients with brainstem tumors (BST) underwent Gamma Knife radiosurgery. In 5 cases, there were definitive histological diagnoses; ependymoma (n = 3) and CNS lymphoma (n = 2). The others were diagnosed as ependymoma (n = 1), CNS lymphoma (n = 2) and glioma (n = 2) on clinical grounds. Of 4 cases with ependymoma, the tumor showed a marked response in 3 cases. Of 4 cases with CNS lymphoma, all responded rapidly and the clinical symptoms improved markedly. However, in the 2 cases with glioma, the tumor remained unchanged or continued to grow. Gamma Knife radiosurgery was effective in local growth control of BST without adverse effects. An alternative treatment design will be required in glioma cases.

Origin of ischemia-induced glutamate efflux in the CA1 field of the gerbil hippocampus: an in vivo brain microdialysis study.

In vivo brain microdialysis experiments were performed in the gerbil to evaluate the origin of accumulation of extracellular glutamate under transient ischemia. Microdialysis probes were positioned in the CA1 field of the hippocampus in which proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals had been induced by 5-min ischemia 10-14 days before the microdialysis experiment; in the white matter of the cerebral cortex, which contained few neurons, few presynaptic terminals, and many astrocytes; or in the histologically normal CA1 field of the hippocampus, and then 5- or 20-min ischemia was induced. When 5-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter of the cerebral cortex, whereas a significant increase in glutamate (15-fold) was observed in the histologically normal CA1 field. When 20-min ischemia was induced, no significant increase in glutamate content was observed in the CA1 field that showed proliferation of astrocytes, death of CA1 pyramidal neurons, and damage of presynaptic terminals and in the white matter during the first 10 min after the onset of 20-min ischemia, but remarkable ischemia-induced increases in glutamate were observed during the last 10 min of 20-min ischemia in both areas. An excessive increase in glutamate (100-fold) was observed during 20-min ischemia in the normal CA1 field of the hippocampus. When a probe was positioned in the CA1 field of the hippocampus in which presynaptic terminals of Schaffer collaterals and commissural fibers had been eliminated by bilateral kainate injections into the lateral ventricles 4-7 days before the microdialysis experiment and then 5-min ischemia was induced, a significant increase in glutamate was observed during the last half of 5-min ischemia. These results suggest that the efflux of glutamate from astrocytes does not contribute to the large ischemia-induced glutamate accumulation in the CA1 field of the hippocampus during 5-min ischemia but contributes to the ischemia-induced increase in glutamate level during ischemia with a longer duration and that ischemia-induced efflux of glutamate in the CA1 field during 5-min ischemia originates mainly from neuronal elements: presynaptic terminals and post-synaptic neurons.

[Blood concentrations of thrombomodulin in patients with various diseases].

Concentrations of thrombomodulin in blood plasma were measured by a one-step sandwich enzyme immunoassay (EIA). The concentrations in normal healthy subjects were 9.9 +/- 2.9 ng/ml. The concentrations were found to be significantly higher in patients with SLE, RA and other collagen diseases in their active stages than at their non-active stages. The concentrations increased in patients with DIC, and significantly higher levels were observed when DIC was complicated by multiple organ failure. These findings indicate that plasma concentrations of thrombomodulin may be a useful parameter for vascular injuries caused by inflammatory processes or coagulation/fibrinolysis reactions.

Delayed and severe toxicities of a herbicide containing glufosinate and a surfactant.

We report a case of a 59-y-old woman who ingested a herbicide containing glufosinate. Though suffering from severe toxicity of this herbicide, she did not develop convulsions, which experimentally occurs in rats treated with glufosinate. The mechanisms of convulsions are not clear. Several clinical findings in poisoning by this herbicide are suspected to be caused by the surfactant components.

Radiosensitive craniopharyngiomas: the role of radiosurgery.

Clinical characteristics of radiosensitive craniopharyngiomas and histologically identical tumours were re-evaluated from among 53 patients. There were 9 squamous cell type and 3 mixed type tumours. Early effects of radiosurgery for two recent cases are reported. Radiosurgery may have an important role to play in the treatment of craniopharyngiomas, especially of the squamous cell type.

Long-term follow-up study of conventional irradiation for brain tumours in children: a role for radiosurgery.

21 younger patients (less than 10 years of age) with brain tumours, treated by conventional irradiation, were followed 5 to 20 years (mean 12), using CT scan and/or MR imaging, in order to evaluate adverse effects on the developing brain. Pathological changes such as brain atrophy, lesions in the white matter, calcifications in the brain, and angiopathy were observed in 13 (62%) out of 21 cases. The incidence of abnormalities was related to the age at treatment and the follow-up period. All six cases treated at or under 5 years old and followed more than 10 years showed pathological changes in the brain. In order to minimize the radiation damage, 5 patients with brain tumours less than 5 years old were treated by gamma knife surgery. The early results encourage further trials. Radiosurgery may play a role as an alternative treatment or as a component of future multidisciplinary treatment for brain tumours is children.

Dantrolene protects against ischemic, delayed neuronal death in gerbil brain.

The effect was examined of dantrolene, a drug for malignant hyperthermia acting through preventing release of Ca from the ryanodine-type intracellular stores in muscle cells, on ischemic delayed neuronal death in field CA1 of gerbil hippocampus. Dantrolene (1.6 mM in concentration, 3 microliters each in volume), when administered bilaterally in the lateral ventricles 30 min after reperfusion after transient forebrain ischemia for 3 min at 37 degrees C, significantly protected against the neuronal death. It is proposed that the dantrolene-sensitive (most likely, the ryanodine-type) intracellular Ca stores in CA1 pyramidal cells play a pivotal role in the development of ischemic neuronal damage.