Hiroshi Otsu

Intraoperative radiotherapy for advanced carcinoma of the pancreas.

A detailed retrospective analysis of the efficacy of intraoperative radiotherapy (IOR) in advanced carcinoma of the pancreas is presented. During a 10‐year period from 1973 through 1982, 70 patients with advanced carcinoma of the pancreas were treated by multimodal methods, separate or combined therapy of surgery, IOR, and chemotherapy in two different institutions. Among these, 33 patients underwent IOR, mostly combined with additive surgery. A single dose of 20.1 to 40.0 Gy with 8 to 25 meV electrons was delivered through radiation cones ranging from 6 to 10 cm in diameter. Excellent relief was noticed in 50% of the patients who had complained of pain. Among Stage IV patients, a significant difference of survival rate was observed between IOR and control groups (P < 0.05); the mean survival time of the IOR group was 4.6 ± 2.6 (SD) and that of the control group 2.5 ± 1.4 (SD) months. Intraoperative radiotherapy proved to be effective in prolonging the survival of patients with advanced stage of the lesion.

Comparison of dose-dependent enhancing effects of γ-ray irradiation on urethan-induced lung tumorigenesis in athymic nude (nu/nu) mice and euthymic (nu/+) littermates

The role of immunological surveillance in carcinogenesis is still controversial. In our previous experiments, urethan-induced lung tumorigenesis in athymic (nu/nu) mice and euthymic (nu/+) littermates was examined, and it was concluded that immunosurveillance mediated by T cells could not be demonstrated. However, the reported enhancement of development of various tumors following ionizing radiation might be achieved through modulating the host immunological conditions. In the present experiment,nu/nu and littermatenu/+ mice were treated with 1–4 Gy γ-rays alone at 6 weeks of age or treated with urethan at 0.5 mg/g body weight when aged 14 days followed by 1–4 Gy γ-rays 4 weeks later. Lung tumors were assessed at 6.5 months of age. Ionizing radiation itself caused a very low incidence of these lesions. On the other hand, multiplicities and incidences of lung tumors after urethan treatment at 0.5 mg/g body weight were similar between the two phenotypically different groups of mice (1.66 and 1.84 tumors/mouse, 73% and 80% incidences, fornu/nu andnu/+ cases respectively). This urethan-induced lung tumorigenesis was significantly enhanced by γ-rays in bothnu/nu andnu/+ mice, and the magnitude of tumor enhancement was somewhat higher innu/+ mice than innu/nu mice, especially with a 2-Gy dose. In conclusion, it may be said that lung tumorigenicity of γ-ray irradiation itself and the enhancing effect of radiation on urethan-induced tumorigenesis are scarcely influenced by immunosurveillance mechanisms mediated by T cells

Induction of myeloid leukemias in C3H/He mice with low-dose rate irradiation

Abstract C3H/He male mice were exposed to whole body gamma-ray irradiation at 8 weeks of age. Radiation at a high-dose rate of 88.2 cGyears/min with doses of 0.125–5.0 Gyears, a medium dose rate of 9.56 cGyears/min with doses of 1.0–5.0 Gyears, and low-dose rates of 0.0298 cGyear/min with doses of 1.0–10 Gyears, 0.0067 cGyear/min with doses of 1.0–10.0 Gyears or 0.0016 cGyear/min with doses of 1.0–4.0 Gyears were delivered from 137 Cs sources. The mice in the low-dose rate groups were irradiated continuously for 22 h daily during a period of 3 to 200 days. All the mice were maintained for their entire life span and were pathologically examined after their death. Myeloid leukemia developed significantly more frequently in the irradiated groups with doses over 1 Gyear than in the unirradiated groups. The maximum values were 23.5% in the high-dose rate group, 11% in the medium dose rate group, 7.3%, 7.2%, 6.3% in the low-dose rate groups, and 0.99% in the unirradiated control group. These dose–effect curves had their highest values on each curve at about 3 Gyears. We obtained the dose and dose rate effectiveness factor (DDREF) values of 2.96 by linear fittings for their dose–response curves of the dose ranges in which leukemia incidences were increasing.