フランスにおける社会立法と内縁

論

W. M. エヴァン編 「法と社会学」

書

成年養子の実態 (I) : 北海道石狩・後志支庁管内の実態調査

資

成年養子の実態 (II) : 北海道石狩・後志支庁管内の実態調査

研究ノー

Brain tumor associated with hypomelanosis of Ito

The authors report a case of choroid plexus papilloma in a girl with hypomelanosis of Ito, and they review the literature in brief. Hypomelanosis of Ito is a rare neurocutaneous syndrome characterized by cutaneous hypopigmented whorls, streaks, and patches along lines of Blaschko. Most patients exhibit CNS manifestations, including psychomotor retardation, seizures, hypotonia, and ataxia. A 6-year-old girl with hypomelanosis of Ito was referred to the authors’ hospital with bilateral tumors in the lateral ventricles. The right lateral ventricle tumor was surgically removed. Immunohistochemical investigations revealed the tumor to be a choroid plexus papilloma (WHO Grade I). A chromosomal investigation revealed that the tumor tissue demonstrated a large loss of heterozygosity at chromosome 10. The case reported here serves as a reminder that de novo brain tumors may arise in patients with chromosomal mosaicism

アクセイ シンケイ コウシュ ニ タイスル チュウセイシ ホソク リョウホウ : コンゴウ ビーム ネツチュウセイシ ト ネツガイチュウセイシ ビーム オ モチイタ アタラシイ チリョウ センリャク

The purpose of this study was to clarify the clinical interim results of boron neutron capture therapy (BNCT) using mixed epithermal-and thermal neutron beams in patients with malignant glioma. The mixed neutron beam for BNCT has been used clinically since 1998. Its great advantage consists of its greater ability than the pure thermal neutron beam to reach sites deep from the brain surface. Sixteen patients with malignant glioma (glioblastoma n=14, anaplastic ependymoma n=1, PNET n=1) underwent mixed epithermal-and thermal neutron beam treatment between 1998 and 2003. They included 2 children younger than 3 years. Sodium borocaptate (Na2B12H11SH, BSH ; 80-100 mg/kg) was administered intravenously at 12-15 hr before neutron irradiation. The radiation dose (i.e. physical dose of boron n-alpha reaction) in the he protocol used between 1997 and 2000 (Protocol A) prescribed a maximum tumor volume dose of 15 Gy. In 2001, a new dose-escalated protocol was introduced (Protocol B) ; it prescribes a minimum tumor volume dose of 18 Gy or, alternatively, a minimum target volume dose of 15 Gy. In both protocols, the maximum vascular radiation dose to the brain surface is not to exceed 15 Gy. Of the 12 patients, 8 were treated according to Protocols A and 4 according to Protocol B. Since 2002, the radiation dose was reduced to 80-90% dose of Protocol B because of acute radiation injury. A new Protocol was applied to four glioblastoma patients (Protocol C). Of the 8 patients treated under Protocol A, 7 died (dissemination n=4, local recurrence, infection, unknown causes, n=1 each). Of the 4 patients treated under Protocol B, 2 died. Concerning the adverse effects of BNCT, Protocol B resulted in higher complication rates with respect to both acute and delayed radiation injury. The estimated median survival time after diagnosis and after BNCT in all patients were 16.7 and 14.6 months, respectively. In 8 patients of Protocol A, the estimated median survival time after diagnosis was 16.0 months ; 1-year and 2-year survival rate were 75.0% and 12.5%, respectively. On the other hand, in 8 patients in Protocol B and C, the estimated median survival time after diagnosis was 15.5 months ; 1-year and 2-year survival rate were 80.0% and 53.3%, respectively. Our limited clinical evaluation suggests that BNCT could achieve local control of glioblastomas at the primary site and that possible dose escalation is limited. While the dose escalation can contribute to the improvement of survival rate, it results in the radiation injury. We conclude that not only the radiation dose at the target point, but also the distribution of neutron flux in the radiation field may contribute to the cure of glioblastoma by BNCT. Computation-assisted dose planning can contribute to improved clinical results following BNCT and to the prevention of cerebrospinal fluid dissemination. We will introduce pure epithermal neutron beam instead of mixed neutron beam in the near future. It has greater advantage than mixed neutron beam to deep-seated glioma because it has a peak in neutron flux at 2-3 cm depth from the brain surface. The dose-planning system and pure epithermal neutron beam can lead to further improvements in the clinical outcomes and the avoidance of adverse effects in brain tumor patients subjected to BNCT

中性子捕捉療法における硼素化合物の薬物動態と腫瘍内移行

BNCT (boron neutron capture therapy) is based on the intracellular nuclear reaction that occurs between the boron-10 nucleus and a thermal neutron. Upon capture, the boron nucleus disintegrates into highly energetic alpha (4He) and lithium (7Li) particles. Because of the short pathways of these heavy particles and 10B accumulation in target tissues, the great potential advantage of BNCT is a selective tumor destruction without significant damage to normal brain tissue. Since 1968, we have treated 146 patients with malignant brain tumors by BNCT. The 5-year survival rate of malignant glioma was 29%. Important factors which improve the results of BNCT are boron concentration in the tumor and neutron sauces. We have used BSH (mercaptoundecahydrododecaborate, Na2B12H11SH) as a boron compound in all patients. BSH is characterized by the absence of toxic side effects and represents the only promising boron carrier applied for the therapy of malignant glioma. However, data on the biodistribution and pharmacokinetics of BSH are few and lack in stadardization. We retrospectively analyzed the biodistribution and pharmacokinetics of BSH in 146 patients treated by BNCT from 1968 to 1994. 1) Pharmacokinetic parameters and standard expression of blood boron content of BSH were calculated by the two-compartment model theory in intra-arterial and intra-venous infusion groups. The parameters revealed that BSH could move easily from blood to the peripheral organs with sustained retention and that elimination was very slow. (CL=3.43L/hr, Vss=181.8 L, MRT=53.0 hrs) 2) Pharmacokinetic parameters were calculated in each case. The patients were divided into two groups : the intra-arterial (56 patients) and the intra-venous (31 patients) groups. BSH was administered into cervical brain arteries in the intra-arterial group, and peripheral veins in the intra-venous group. BSH in the intra-arterial infusion group was found to move from blood into the peripheral organs more easily than that of the intravenous infusion group. 3) In patients with malignant glioma, the average values of boron concentration in the tumor and the tumor to blood ratio (T /B ratio) after intra-arterial infusion (44 patients with 53 samples) were 26.8 μg/g and 1. 77 respectively. On the other hand, after intravenous infusion (13 patients with 13 samples) the values were 20. 9 μg/ g and 1. 33 respectively. There were no statistical significant differences in the average values of boron concentration in the tumor and the T /B ratio between the intra-arterial and the intravenous groups. 4) Both the average values of boron concentration in the tumor and the T /B ratio in patients with malignant glioma showed about 2. 7 and 3. 0 times higher that those of low grade glioma. However, there were no statistical significant differences in the tumoral boron concentration and the T /B ratio between cases of anaplastic astrocytoma and glioblastoma