Effect of High-Dose Tamoxifen on Malignant Gliomas

Oh, Yeon Chul,Kim, Jung Hoon,Lee, Jung Kyo,Kim, Chang Jin,Kwon, Yang,Rhim, Seung Chul,Kwun, Byung Duck,Whang, C. Jin 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.9

배양된 신경교종에서 tomoxifen은 핵산의 합성 및 세포의 증식을 억제할 수 있음을 in vitro study상 알 수 있다. 이러한 성장 억제는 tamoxifen의 항에스트로겐 특성에 의존하지 않고, protein kinase C라는 효소의 억제를 통해서 이루어지는 듯 하다. 저자들은 1991년 2월부터 1993년 1월까지 본원 신경외과에 입원하여 수술 후 부가적 치료로써 고용량 tamoxifen을 병행한 28명의 악성 신경교종환자들에서 고용량 tamoxifen의 부가적 치료 효과 및 그 부작용을 알아보기 위하여 본 임상실험을 시행하였다. 고용량 tamoxifen의 부가적 치료효과는 통계학적으로 유의하게 증가된 생존기간 및 생존율로 정의하였다. Tamoxifen 치료군의 경우 처음에는 약제의 부작용을 알아보기 위하여 표준 항에 스트로겐 용량인 20㎎을 하루에 2회 경구 투여하였으며, 특별한 문제가 없으면 1달 이상에 걸쳐 매주 용량을 증가하여 100㎎을 하루 2회 경구 투여하였다. Tamoxifen 사용 후 역형성 성상세포종과 다형성 교아세포종간의 생존기간 및 생존율을 비교하여 보았을 때 역형성 성상세포종에서 다형성 교아세포종보다 중간 생존율이 약간 높았으나 통계학적 유의한 차이는 없었다. 또한 치료 방법(방사선 단독 치료군, 방사선 치료와 ACNU 화학요법을 병행한 치료군, 그리고 방사선 치료와 tamoxifen을 병행은 치료군)에 따른 생존기간 및 생존율을 비교하여 보았을 때, tamoxifen 치료군에서 다른 치료군들보다 생존기간 및 생존율이 약간 높았으나 역시 통계학적 의미는 없었다. 고용량 tamoxifen으로 치료하였던 대부분의 환자들에서 심한 부작용은 관찰할 수 없었다. Tamoxifen 용량을 증가시키는 동안 5명의 환자에서 식욕부진 증상이 발생하였으며, 다른 합병증들로서 무월경, 오심/구토, 그리고 변비 등을 관찰할 수 있었으나 혈액학적 변화는 관찰할 수 없었다 저자들은 고용량 tamoxifen을 악성 신경교종 환자에서 비교적 안전하게 사용할 수 있다고 생각한다. 본 임상실험 결과는 만족스럽지 못했으나 저자들은 제한된 본 연구결과로 악성 신경교종 환자들에서 고용량 tamoxifen의 치료 효과를 단정할 수 없다고 생각하며, 따라서 이 약제에 대한 보다 광범위한 연구가 이루어져야만 한다고 생각한다. In vitro studies have shown that the nonsteroidal antiestrogen tamoxifen can suppress deoxyribonucleic acid(DNA) synthesis and cell proliferation in cultured human gliomas. This frowth 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 Febrary 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(20㎎ orally bid/day) to observe for any side effect and if tolerated, the dose was increased weekly to achieve target doses(100㎎ orally bid/day) over a 1 month period. We compared the survival times/rates between anaplastic astrocytomas and glioblastoma multiformes. Although the median survival time was slightly longer in anaplastic astrocytomas and glioblastoma multiformes, there was no statistical difference of survival curves between two groups at the p=0.05 level. We also exmamined the survival times/rates of malignant gliomas according to treatment modalities(radiotherapy along, 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 can be administered safely to malignant glioma 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.

말단비대증의 신경외과적인 고찰

여인욱,김창진,권양,임승철,이정교,권병덕,황충진 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.11

From May, 1989 to December, 1991, 25 patients were diagnosed as acromegaly and treated by surgical and/or radiosurgical procedure. The most common presenting symptom is acromegalic feature(60%), followed by, in order, headache, cranial nerve palsy, dyspnea, general weakness and anemia. Preoperative endocrineological evaluation included plasma level of growth hormone, somatomedin-C. High resolution computed tomography(CT) and/or magnetic resonance imaging(MRI) was done as imaging studies. Preoperative tumor size was above 10㎜ in all cases. The level of hormone was not correlated with extension, site and size of tumors. Of the 25 patients, 14 underwent TSA(2 cases followed by radiation therapy), 4 underwent cranotomy(3 cases followed by radiation therapy), 3 underwent craniotomy and TSA(all 3 cases followed by radiation therapy), 2 underwent craniotomy and Gamma Knife Radiosurgery and 2 underwent Gamma Knife Radiosurgery only. There was no operative mortality. Postoperatively, 11 patients of 23 patients(48%) were normalized in growth hormon level (GH<5ng/㎖) and tumor was disappeared in 8 patients of 21 patients(38%) in follow up MRI or high resolution CT studies. Correlation between GH and somatomedin-C was present. However, GH may be a better indicator in predicting postoperative result than somatomedin-C.

경막외 및 경막내 접근법을 이용한 상상돌기주위의 크거나 거대 동맥류의 외과적 치료

황충진,김창진,권병덕 대한신경외과학회 1994 Journal of Korean neurosurgical society Vol.23 No.6

Between May, 1992 and April, 1993, four patients with paraclinoid aneurysms were treated by a direct operative approach. Two patients had large aneurysms, all of which had ruptured, presented with subarachnoid hemorrhage(SAH). The other two patients had giant aneurysms, causing visual symptoms by optic nerve compression. All patients were treated by a combined extradural and intradural approach. All the aneurysms were successfully clipped and collapsed or resected, eliminating the risk of rebleeding and decompressing the visual system immediately and effectively, while preserving the blood flow of the carotid artery and its branches. Removal of the individual bony structure including anterior clinoid process(ACP) and orbital roof at the skull base extradurally provides a better and safer exposure of the aneurysm, and of the ophthalmic segment of the carotid artery than does excessive retraction of the brain. This technique also affords exposure of the internal carotid artery proximal to the lesion and ophthalmic artery, which is important in securing safe and complete occlusion of the aneurysm. Authors present operative technique, summary of cases, and literature review.

뇌하수체 선종의 치료에서 감마나이프의 역할

권양,황충진 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.9

The treatment of choice for symptomatic pituitary adenomas varies according to the hormone secreting types of the adenoma and can include pharmacology surgery, or radiotherapy. The recent development of radiological imaging and microsurgery has made surgery the treatment of choice for most pituitary tumors. However, the long-term tumor control rate after microsurgery varies from 50% to as high as 80%. During the last 38 months (1990.5-1990.9, 1991.5-1994.2), 34 cases of pituitary adenomas were treated by gamma knife at Asan Medical Center. There were 11 cases of prolactinomas, 9 cases of acromegaly, 8 cases of ACTH-secreting tumors and 6 cases of non-functioning tumors. Seventeen patients underwent gamma knife radiosurgery for recurrent or remaining tumors after resective surgery. Another 17 patients were treated primarily with gamma knife. In microadenomas, the mean tumor volume was 221 cumm and the mean marginal dose was 33.1 Gy. In microadenomas, the mean tumor volume was 2690 cumm and the mean marginal dose was 22.6 Gy. Twenty-seven patients have had an average follow-up period of 26 months with a range from 3 to 48 months. As a result, five out of eight prolactinoma patients had normalization of prolactin hypersecretion and seven patients showed clinical cure. On follow-up imaging studies, five out of seven tumors showed no changes in their size, while two showed marked reduction. Two out of for ACTH-producing tumor patients showed normalization of 24 hour urine cortisol levels. On follow-up imaging studies of the two cases, the tumor of one patient disappeared and the other one showed no change. Three out of six acromegalic patients showed clinical responses. Two out of five non-functioning tumors showed reduction in size and three showed no changes. In conclusion, gamma knife radiosurgery seems to be effective as adjuvant therapy for the treatment of remaining or recurrent pituitary adenomas after surgery and primary treatment modality in selective patients.

뇌간 신경교종의 증식형태, 병리 및 예후 : Growth Patterns, Pathology, and Prognosis

나영신,황충진 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.12

A retrospective study of 29 cases of brain-stem gliomas(BSG's) from 1989 to 1993, was performed to determine prognostic factors. Our study also analyzed clinical features, growth patterns, pathologic findings and modalities of treatment in patients with brain-stem gliomas. The patients ranged in age from 6 to 65 years, most commonly in the first decade. The symptom duration prior to diagnosis was ½ to 36 months (mean 1½ months). The most common symptom and sign were cranial nerve palsies, especially 6th or 7th cranial nerve. The growth patterns of BSG's were classified into diffuse tumors(17 patients), exophytic(9 patients), focal(2 patients) and cervicomedullary (1 patient). Twenty three of 29 patients were diagnosed pathologically by means of stereotactic biopsy (13 patients) and open surgery(10 patients). The Pathologic findings were low grade astrocytoma in 9 patients, oligodendroglioma (3 patients), malignant astrocytoma (7 patients), and glioblastoma multiforme (4 patients). A significant correlation between diffuse growth pattern and malignant pathologic finding could be obtained (P=0.05). The methods of radiation therapy for BSG's were conventional (10 patients), hyperfractionated (13 patients), and Gamma knife radiosurgery (6 patients). The median survival time was 12 months. The Poor prognostic factors determined in our study were 1) short symptom duration prior to diagnosis(≤2 months), 2) diffuse growth pattern, 3) malignant pathologic finding, 4) tumor without cystic portion, and 5) tumor without hydrocephalus.

뇌농양의 치료에 있어서 정위적 흡인술의 사용

이호연,김창진,권양,임승철,이정교,권병덕,황충진 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.4

Twelve cases of brain abscess treated in Asan medical center during the recent 3 years from June, 1989 to December, 1992 were reviewed. The paients consisted of 6 males and 6 females. The metastatic abscess(hematogenous spread) constituted the largest group(58%), and most of them had been suffering from systemic medical disease. Headache was by far the most common symptom and the parietal lobe was the most common site. Fourteen operations in 12 patients consisted of 9 stereotactic aspirations(including 2 reoperation cases), 2 exisions, 2 ultrasono-guided aspirations, and one free-hand aspiration. Among these procedures, 12 aspirations yielded complete resolution in 9 cases(including second aspiration for another lesion in 1 patient), 1 persistent abscess requiring reoperation, and 1 mortality. The stereotactic aspiration of the brain abscess provided a surgical solution with relatively low risk in the poor candidate for receiving general anesthesia, in multiple lesions, and in lesions of deep or eloquent area.

순환정지와 저체온 및 Barbiturate를 이용한 후혈행 뇌동맥류 수술 3례 : 3 Cases

권양,김창진,임승철,권병덕,황충진,김삼현,황연미,한성민 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.2

Direct approach of technically difficult or inoperable intracranial aneurysms may become possible using complete circulatory arrest with extracorporeal circulation and profound hypotherima and barbiturate cerebral protecion. To avoid difficulties associated with closed chest method, open chest method was used by direct cannulation of the right artium and aorta through the chest. 3 patiens with posterior cirulation aneurysms operated on with these techniques ; 1 large basilar bifurcation aneurysm and 1 irregular shaped vertebro-basilar junction aneurysm and 1 posterior cerebral artery aneurysm were operated on and all had excellent results. Careful attention was needed to the depth of hypothermia, duration of total circulatory arrest, and hemostasis which important factors in the success of these methods.

낭성수막종에 대한 임상적 분석

이철,김창진,권양,임승철,이정교,권병덕,황충진 대한신경외과학회 1993 Journal of Korean neurosurgical society Vol.22 No.10

Intracranial meningioma associated with cyst cyst formation in unusual finding, which sometimes makes confusion in preoperative diagnosis. We experienced eleven cases of the cystic meningioma among 188 intracranial meningiomas who underwent operation from June 1989 to May 1993 at the Asan Medical Center. Clinical manifestations, findings of magnetic resonance imaging, preoperative diagnosis, and histopathology were analyzed. Among the 11 patients, the cyst of four were intratumoral type and seven were peritumoral type. There was no relationship between cyst formation and histological type of meningioma.

방사선 치료로 발생한 소아의 신경교종 : 증례 보고

이철,김창진,권양,임승철,이정교,권병덕,황충진 대한신경외과학회 1993 Journal of Korean neurosurgical society Vol.22 No.11

A case of cerebral glioma which was developed 5 years after brain irradiation for medulloblastoma is reported. The etiology and pathogenesis of human glioma are still unknown. The possible causal role of radiation therapy in inducing cerebral glioma is discussed on the basis of these observations.

자발성 뇌출혈환자의 치료와 뇌정위수술 및 보존적 치료의 비교분석

이채혁,김창진,권양,임승철,이정교,권병덕,황충진 대한신경외과학회 1992 Journal of Korean neurosurgical society Vol.21 No.3

The treatment of patients with spontaneous intracerebral hemorrhage remains a matter of debate in neurosurgery and neurology. We analyzed 203 patients with spontaneous intracerebral hematoma and compared the result of treatment between two groups : 100 patients with stereotactic hematoma evacuation and 103 patients with conservative treatment. Evaluation of outcome was performed at discharge with Glasgow come scale, motor deficit, Glasgow outcome scle. Stereotactic surgical patients with medium sized(20-50㏄) hematoma, which located in basal gaglia and thalamic area made a significantly better functional recovery than did patients with conservative treated group. Patients with relatively mild neurologic deficit preoperatively had better functional outcomes in the stereotactic surgical group. Stuporous of comatose patients had no better outcome after surgery, but showed a significantly lower mortality rate than conservative treated group. There was no significant difference in the outcome in relation to the timing of surgery, but rebleeding risk was high on early operated patients. Stereotactic surgery can minimized the brain damage and be performed under local anesthesia, so there was a trend toward better quality of survival and chance of survival in the operated group.