Yasunosuke Suzuki

Pulmonary fibrosis in asbestos insulation workers with lung cancer: a radiological and histopathological evaluation.

This study was undertaken to determine the relation between radiographic and histological manifestations of pulmonary asbestosis (interstitial fibrosis) in insulation workers who had died of lung cancer. Of 450 confirmed deaths from lung cancer a chest radiograph suitable for determining evidence of pneumoconiosis was obtained in 219. Of these cases, 138 also had a tissue specimen submitted that was suitable for histological study to determine the extent of histological fibrosis. There was a significant albeit limited correlation between the radiographic and histological findings (r = 0.27, p less than 0.0013). All 138 cases had histological evidence of parenchymal fibrosis; in 25 (18%), however, there was no radiographic evidence of parenchymal fibrosis. In 10 cases (7%) both parenchymal and pleural disease were undetectable on the radiograph. Thus a negative chest radiograph does not exclude the presence of interstitial fibrosis (asbestosis) in a substantial proportion of insulation workers previously exposed to asbestos who develop lung cancer.

Malignant mesothelioma induced by asbestos and zeolite in the mouse peritoneal cavity

The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. As controls, 182 mice treated with and without saline solution were used. Both asbestos types and fibrous erionite frequently produced malignant peritoneal tumors after long latency; tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 (73 fibrous, 9 biphasic, and 1 epithelial) of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinoma of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In these cases, asbestos or erionite-tissue burden followed by fibrosis was frequently observed. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis. Long-term persistence of asbestos or fibrous erionite around progenitor cells of the induced tumors and the consequent fibrosis seemed to be an important precondition of the malignant transformation of the progenitor cells.

Analysis of Asbestos Fibers in Lung Parenchyma, Pleural Plaques, and Mesothelioma Tissues of North American Insulation Workers

Asbestos fibers and ferruginous bodies (FBs) in lung parenchyma, lung cancer tissues, pleural plaques, and pleural and peritoneal mesothelioma tissues from 13 North American insulation workers were analyzed and quantified using an analytical transmission electron microscope and a polarized microscope. Diseases from which these workers suffered included asbestosis, lung cancer, and mesothelioma. They had been occupationally exposed to materials containing chrysotile and amosite; their pathological diagnoses, occupational and cigarette smoking histories, and clinical summaries have been reported. Large numbers of FBs were found in the lungs and small numbers found in extrapulmonary sites. Most of the FBs had cores of amosite fibers. In all instances, lung parenchyma and lung cancer tissues showed chrysotile and amosite fibers in high concentrations (63.1 x 10(6) and 150.2 x 10(6) fibers/g dry tissue as mean values, respectively). Crocidolite fibers were seen in seven of the 13 cases, but in much smaller numbers. Other amphiboles were rarely found. In pleural plaques and in pleural and peritoneal mesothelioma tissues, amosite fibers were markedly fewer in number, whereas chrysotile fibers were seen in similar numbers as in the lungs. No significant differences in the size distribution of asbestos fibers were seen in the different sites. However, the mean widths of chrysotile fibers were thinner than those of amosite fibers. These results strongly suggest that translocation of inhaled asbestos fibers from the lung to other tissues, such as the pleura and the peritoneum, occurs frequently, and that chrysotile may be more actively translocated from the lung, compared to amosite or amphibole asbestos. The likelihood of translocation seems to be strongly related to the thinness of the fibers. Translocated chrysotile fibers may play an important role in the induction of either malignant mesothelioma and/or hyaline plaques, since the asbestos fibers detected in both these sites were mainly chrysotile.

Mineral phases and some reexamined characteristics of the international union against cancer standard asbestos samples

Standard asbestos samples to be used for biomedical research were first prepared by the International Union Against Cancer (UICC) in 1966 in the United Kingdom and South Africa. Using modern techniques, X-ray diffractometry, analytical transmission electron microscopy, and thermal analysis, we have now analyzed these UICC samples to determine the mineral compositions (mineral phases) and their respective quantities. UICC chrysotile A (from Zimbabwe) contains 2% fibrous anthophyllite as impurity; chrysotile B (from Canada) does not contain any fibrous impurities, only non-fibrous minerals. UICC amosite and crocidolite are almost pure. UICC anthophyllite has 20-30% talc as impurity. The chemical compositions and fiber size distributions of the UICC asbestos samples have also been determined. The mean widths of the fibers of chrysotile A and B are smaller than those of the amphibole fibers. This agrees well with the earlier results which showed the two chrysotile samples to have a larger respirable fraction than the amphiboles.

Malignant mesothelioma in a cohort of asbestos insulation workers: clinical presentation, diagnosis, and causes of death

Malignant mesothelioma has been rare in the general population. In recent decades its incidence has risen dramatically, parallel to the increasing use of asbestos in industry since 1930. Altogether 17,800 asbestos insulation workers, members of the International Association of Heat and Frost Insulators and Asbestos Workers (AFL-CIO-CLC) in the United States and Canada, were enrolled for prospective study on 1 January 1967 and followed up to the present. Every death that occurs is investigated by our laboratory. One hundred and seventy five deaths from mesothelioma occurred among the 2221 men who died in 1967-76 and 181 more such deaths in the next eight years. Altogether, 356 workers had died of malignant mesothelioma (pleural or peritoneal) by 1984. Diagnosis of mesothelioma was accepted only after all available clinical, radiological, and pathological material was reviewed by our laboratory and histopathological confirmation by the pathology unit made in each case. One hundred and thirty four workers died of pleural and 222 of peritoneal mesothelioma. Age at onset of exposure, age at onset of the disease, and age at death were similar in both groups of patients. Significant difference was noted only in the time elapsed from onset of exposure to the development of first symptoms, which was longer in the group with peritoneal mesothelioma. Shortness of breath, either new or recently increased, and chest pain were the most frequent presenting symptoms in the group with pleural mesothelioma; abdominal pain and distension were frequent in the patients with peritoneal mesothelioma. Pleural effusion or ascites were found in most patients. The most effective approach to the diagnosis of malignant pleural mesothelioma in these cases was by open lung biopsy; exploratory laparotomy was best for diagnosing peritoneal mesothelioma. Patients with pleural mesothelioma died principally from pulmonary insufficiency whereas those with peritoneal mesothelioma succumbed after a period of pronounced wasting.

Carcinogenic and fibrogenic effects of zeolites: preliminary observations.

Abstract Two natural zeolite minerals, erionite, a fibrous form, and mordenite, a mixture of fibrous and granular types, were injected intraperitoneally into 45 Swiss albino male mice with a single administration of 10 or 30 mg of zeolite suspended in 1 cc of saline solution. The erionite was 0.4–24 μm in length (1 μm average, 95% shorter than 8 μm) and 0.01–2.5 μm in width (0.1 μm average, 94.4% smaller than 1 μm). The granular mordenite was 0.33–5.7 μm in the long axis and 0.27–1.67 μm in the short axis. The fibrous mordenite was 0.4–6 μm in length and 0.05–0.67 μm in width. Thirteen untreated mice and five mice treated with 10 mg chrysotile (Calidria, 90% shorter than 1 μm) were used as controls. Six of ten mice treated with 10 mg of erionite developed malignant peritoneal tumors between 8 and 22 months after the single administration. The neoplasms in four of the six animals were consistent with malignant mesothelioma. Two of four chrysotile-treated controls also developed malignant peritoneal mesotheliomas between 9 and 16 months. A fibrogenic effect was noted in both the erionite-and mordenite-treated mice, the effect being more pronounced in the former. Fibrotic lesions induced by these mineral fibers commonly presented in the primary site of these induced peritoneal tumors. Findings suggest that the carcinogenic and fibrogenic effects of the fibrous erionite are similar to those of asbestos.

Diagnostic Criteria for Human Diffuse M a lignant Mesothelioma

Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long‐term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocyto‐chemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma. Acta Pathol Jpn 42: 767–786, 1992.

Pulmonary tumors induced in mice by vinyl chloride monomer

Abstract Neoplastic effects of vinyl chloride were studied in lungs of 27 mice exposed to vinyl chloride monomer at 2500 and 6000 ppm for 5 and 6 months. Pulmonary tumors were observed in 26 of 27 experimental animals. By light microscopy, the tumors were multiple and arranged in either tubulo-papillary or adenomatous formations. Although occasional mitotic divisions and invaginations into the bronchiolar lumen were observed, no metastases were found. By electron microscopy, short microvilli, tight junctions between two adjacent cells, appearance of osmiophilic lamellar bodies, large mitochondria of irregular shape, well-developed Golgi complexes, continuous or discontinuous basement membranes, occasional appearance of “sequestration” and of crystalloids, and lack of both cilia and mucous secretory granules were observed as characteristic features of the neoplastic cells. Some of the cells were poorly differentiated and were equipped with poorly developed organoids, without formation of osmiophilic lamellar bodies. The pulmonary tumors corresponded to “alveologenic tumors or alveologenic cancer.” It is suggested that the neoplastic cells were transformed from type II alveolar epithelium via its hyperplastic form. It is concluded that mouse lung is an extremely sensitive indicator of the oncogenicity of vinyl chloride.

Neoplastic effect of vinyl chloride in mouse lung—Lower doses and short-term exposure

Neoplastic pulmonary effects of lower doses of vinyl chloride (0 = control, 1, 10, 100, 300, and 600 ppm) and short-term exposure (4 weeks) by inhalation have been studied by light and electron microscopy in 220 mice. Except for dead or seriously sick animals, a large majority of the animals were sacrificed at three different stages: immediately after exposure, 12 weeks later, and 40 or 41 weeks after exposure. Six mice (4: 600 ppm, 2: 0 ppm) were kept longer than 41 weeks to examine the effects of the chemical after a long-term recovery period. Alveologenic tumors were first observed 10 weeks after exposure to 600 ppm. In the subgroups exposed to higher concentrations (600 and 300 ppm) the incidence of tumors was higher and their appearance was earlier than in the subgroups exposed to lower concentrations (100, 10, and 1 ppm). These findings indicated a dose-response relationship for incidence of alveologenic tumors, and the latency period was inversely related to dose. By light and electron microscopy, there was no obvious evidence that tumor cells were derived from Clara cells of the terminal bronchioles. Rather, neoplastic cells in both the tubulopapillary and adenomatous forms of the pulmonary tumors possessed all or some of the ultrastructural characteristics of type II alveolar cells, based on observations of mitochondria, microvilli, osmiophilic lamellar bodies, and other criteria. Type II alveolar cells are therefore considered to be the most sensitive in mice to the neoplastic effect of vinyl chloride.

Histopathologic classification of bronchogenic carcinomas among a cohort of workers occupationally exposed to beryllium

Pathology specimens were examined and classified according to WHO criteria for 27 of 47 individuals identified by death certificate diagnosis as having died from lung cancer, among a cohort of 3055 white males occupationally exposed to beryllium. Twenty-five of the 27 lung tumor specimens were verified as bronchogenic carcinoma: 5 epidermoid; 9 small cell anaplastic; 6 adenocarcinoma, bronchogenic type; 2 adenocarcinoma, bronchiolar-alveolar type; and 3 large cell undifferentiated. Pathology and/or autopsy reports, available for an additional 10 of the 47 individuals, substantiated the death certificate diagnosis.