In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can suppress deoxyribonucleic acid(DNA) synthesis and cell proliferation in cultured human gliomas. This growth suppression is independent on its antiestrogenic properties. Tamoxifen may act through the inhibition of the enzyme protein kinase C(PKC), which transduces mitogenic signals from the cell surface to the nucleus. In order to evaluate the therapeutic response and side effect of high-dose tamoxifen, we performed a clinical study of 28 patients with malignant gliomas who were treated with high-dose tamoxifen in our hospital between February 1991 and January 1993. An effect was defined as a statistically improved survival times/rates. In patients who were assigned to receive high-dose tamoxifen, it was first administered at standard antiestrogen doses(20mg orally bid/day) to observe for any side effect and if tolerated, the dose was increased weekly to achieve target doses(100mg orally bid/day) over a 1 month period. We compared the survival times/rates between anaplastic astrocytomas and glioblastoma mutiformes. Although the median survival time was slightly longer in anaplastic astrocytomas than that of glioblastoma multiformes, there was no statistical difference of survival curves between two groups at the p=0.05 level. We also examined the survival times/rates of malignant gliomas according to treatment modalities(radiotherapy alone, radiotherapy plus ACNU, and radiotherapy plus tamoxifen). Although the survival rate and time were slightly higher in radiotherapy plus tamoxifen group than those of another treatment groups, we could not find the statistical significance of survival curves between three treatment groups(p>0.05). High-dose oral tamoxifen appeared to be well tolerated in most patients. Five patients developed anorexia following dose escalation of tamoxifen. Another complications were amenorrhea, nausea/vomiting, and constipation. There were no changes in hematological studies that could be attributed to tamoxifen. We think that high-dose tamoxifen cah be administered safely to malignant gliomas patients. Our results were not impressive. We conclude that the definition of the true efficacy of high-dose tamoxifen in patients harboring malignant gliomas is not possible from this limited study, and a further large scale, randomized trial of this agent is necessary.
Amenorrhea ; Anorexia ; Astrocytoma ; Cell Proliferation ; Constipation ; Estrogen Receptor Modulators ; Female ; Glioblastoma ; Glioma* ; Humans ; Nimustine ; Protein Kinase C ; Protein Kinases ; Radiotherapy ; Survival Rate ; Tamoxifen*

With the ever- increasing number of intact aneurysms revealed by modern imaging, the options for their management are assuming greater importance. The surgical management of patients with unruptured intracranial aneurysms continues to be contoversial, and the criteria for withholding treatment or choosing between endovscular embolization and conventional microsurgery are not well delineated. In order to define the surgical result for unruptured intracranial aneurysms, 41 patients(from June 1989 to May 1995) with surgically treated unruptured aneurysms were analyzed. They were categorized as incidental, multiple or aneurysm with mass effect. Subarachnoid hemorrhage from another aneurysm(multiple) was the most common presentation(19 patients). Eleven patients were presented with incidental findings unrelated to aneurysmal subarachnoid hemorrhage or direct aneurysmal mass effect, and 11 patients were presented with mass effect such as cranial nerve palsy or brain stem compression. We could perform direct neck clipping presented with mass effect such as cranial nerve palsy or brain stem compression. We could perform direct neck clipping with without wrapping in 37 patients, trapping in 2, and wrapping in 1. One patient with giant vertebrobasilar artery aneurysm(greater than 25mm in diameter) which was presented with mass effect could not be treated adequately. Instances of morbidity included cranial nerve injury in 4 patients, hemiparesis in 3, hematoma in 2, and major hemispheric infarction in 1. One patient presented with mass effect, died from major hemispheric infarction after surgery of proximal internal carotid artery aneurysm with a size greater than 25mm in diameter. Two patients, who underwent surgery for giant vertebrobasilar artery aneurysms presented with mass effect, were in poor state due to persistent cranial nerve palsy and homiparesis. In general overall outcome was very good. Excellent or good outcome was achieved in 38 patients(92.7%) while 3 patients(7.3%) either died or was/were in poor condition. The aneurysm size was correlated well with the surgical outcome. We have achieved excellent or good out comes in 100% of patients with aneurysms 25mm or less in diameter. However, with aneurysms greater than 25mm in diameter, the outcomes were very poor with 75% of these patients in poor state or dead. "Surgery in unruptured aneurysms?" The answer was "Yes". We believe the size and location of the aneurysm are the key predictons of risk for sugical morbidity.
Aneurysm ; Arteries ; Brain Stem ; Carotid Artery, Internal ; Cranial Nerve Diseases ; Cranial Nerve Injuries ; Hematoma ; Humans ; Incidental Findings ; Infarction ; Intracranial Aneurysm* ; Microsurgery ; Neck ; Paresis ; Subarachnoid Hemorrhage ; Withholding Treatment