Toshihiro Kobuke

Skin tumor risk among atomic-bomb survivors in Japan

Objectives: Elevated risks of skin cancer following high doses of ionizing radiation have long been known. Recent reports on atomic-bomb survivors indicate that nonmelanoma skin cancer can be induced at low to medium doses. We studied atomic-bomb survivors to determine the effects of radiation on specific histologic types of skin cancer and to describe the dose-response relationship.Methods: Cases of melanoma, nonmelanoma skin cancers, and Bowens disease were ascertained between 1958 and 1987 for the 80,000 cohort members through the population-based Hiroshima and Nagasaki (Japan) tumor registries augmented by searches of other records.Results: An excess of basal cell carcinoma (n=80), with some suggestion of a non-linear dose-response, was observed. The excess risk decreased markedly as age at exposure increased, and there was no evidence for an interaction between ionizing and ultraviolet radiation. No dose-response was found for squamous cell carcinoma (n=69). The excess relative risk point-estimates were large, but statistically nonsignificant for both melanoma (n=10) and Bowens disease (n=26).Conclusions: The basal layer of the epidermis appears to be quite sensitive to radiation carcinogenesis, particularly at a young age. The suprabasal layer seems to be more resistant, as shown by the lack of an association for squamous cell carcinomas.

Duodenal gangliocytic paraganglioma with lymph node metastasis in a 17-year-old boy

A case of duodenal gangliocytic paraganglioma (DGP) in a 17‐year‐old boy is presented. In this case a lymph node in the peripancreatic region was involved by a metastatic tumor. A review of the literature on DGP indicates that this case represents the youngest patient and is the second case of DGP with metastasis. Immunohistochemical staining for neuron‐specific enolase (NSE), neurofilament (NF), pancreatic polypeptide, and somatostatin showed positive results for epithelioid and ganglion‐like cells, whereas spindle cells showed immunoreactivities for S‐100 protein, NSE, and NF. The histogenesis of DGP is discussed.

Hepatocellular Tumorigenicity of Butylated Hydroxytoluene Administered Orally to B6C3F1 Mice

Butylated hydroxytoluene (BHT), a preservative widely found in food as a food additive, was orally administered at concentrations of 1% and 2% of the diet to B6C3F1 mice for 104 consecutive weeks. Treated animals underwent a 16‐week recovery period prior to pathological examination. In male mice administered BHT, the incidence of mice with either a hepatocellular adenoma or a focus of cellular alteration in the liver was increased in a clear dose‐response relationship. The incidences of male mice with other tumors and the incidences of female mice with any tumor were not significantly increased as a consequence of BHT administration. The results of this study indicate BHT to be tumorigenic to the liver of the B6C3F1 male mouse.

Histologic characteristics of skin cancer in Hiroshima and Nagasaki: Background incidence and radiation effects

Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic‐bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population‐based study of spontaneous as well as radiation‐related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic‐bomb radiation exposure did not differ between UV‐exposed and shielded parts of the body, suggesting the additivity of the radiation‐related and background BCC risks.

EARLY CANCER AND RELATED LESIONS IN THE BRONCHIAL EPITHELIUM IN FORMER WORKERS OF MUSTARD GAS FACTORY

The bronchial epithelium in stepwise transverse sections was examined histologically in 66 male autopsy cases, composed of the groups of 19 mustard gas (MG) ex‐workers with lung cancer, 17 MG ex‐workers with non‐lung cancer, 10 non‐MG lung cancer cases, and 20 non‐MG non‐lung cancer cases. Foci of moderate or severe atypical cellular lesion or dysplasia, or of carcinoma in situ (CIS) in total slides of each group, were counted as 146 in 3,485, 72 in 2, 226, 70 in 3,797, and 18 in 4,611, respectively. The relative frequency of moderate or severe dysplasia and CIS in MG exposed non‐lung cancer cases resembled that found in lung cancer cases of both MG and non‐MG exposed. Seven CIS lesions were detected from among all MG‐exposed cases and one CIS was found in a non‐MG lung cancer case. Six out of eight CIS examples were adjoined by dysplasia. A multi‐variate analysis revealed a significant correlation between the incidence of atypical lesions and MG exposure, though the incidence of atypical lesions was also influenced significantly by age, smoking, and chronic bronchitis. The incidence of atypical lesions was significantly higher in cases of squamous cell lung cancer than those of other histological types, particularly small cell cancer.

Tumorigenicity study of disodium glycyrrhizinate administered orally to mice

Disodium glycyrrhizinate (DG) was administered at concentrations of 0.15 (maximum tolerated dose), 0.08, 0.04 or 0% in the drinking-water to groups of 50, 70, 60 and 60 male B6C3F1 mice, respectively. Female groups, each consisting of 50 mice, were given DG in the drinking-water at concentrations of 0.3 (maximum tolerated dose), 0.15, 0.08 or 0%. Treatment was continued for 96 wk and the experiment was terminated at wk 110. There was no difference between treated and control groups in tumour incidence, in the latent period before tumours appeared or in the distribution of different types of tumour. Thus the long-term oral administration of DG to mice did not yield any evidence of chronic toxicity or tumorigenicity.

Lack of Tumorigenicity of Aminopyrine Orally Administered to B6C3F1 Mice

To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1, mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study.

Tumorigenicity study of ferric citrate administered orally to mice

Ferric citrate (FC) was orally administered at concentrations of 0.12 (maximum tolerated dose) or 0.06% in the drinking water to male and female B6C3F1 mice. Treatment was continued for 96 wk and the experiment was terminated at wk 100. There was no significant difference between treated and control groups in the tumour incidence or in the distribution of different types of tumour. Thus the long-term oral administration of FC to mice did not yield any evidence of chronic toxicity or tumorigenicity.

Central pontine myelinolysis accompanied by multifocal pseudocalcifications.

A 44‐year‐old diabetic female became unconscious one month prior to death due to acute suppurative meningitis. Although cerebrospinal fluid findings normalized with the administration of antibiotics, the status of unconsciousness did not improve and she expired. Examination of the brain revealed a small, relatively ill‐defined, demyelinated lesion in the central part of the anterior pons, with which hypertrophied astrocytes, lymphocytes, macrophages phagocytizing disintegrated myelin were present. Neuronal perikarya and axons were well preserved. The findings are pathognomonic of central pontine myelinolysis. Moreover, multifocal, granular and rosary‐shaped or nodular pseudocalcifications were noted within the lesion as an unusual additional finding. Only a few comparable cases of central pontine myelinolysis accompanied by pseudocalciflcation have been reported.