[Clinical features and prognosis of thymoma and thymic carcinoma].
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Biomedical subjects
Publications and source records attributed to N Miyazawa.
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An infant with multiple cerebral infarctions and chronic subdural hematoma is reported. The infarctions were found after repeated tappings of the hematoma. Angiography did not demonstrate any occlusion of the main arteries. The infarctions were thought to be caused by thrombosis of the hanging cerebral veins. The pathogenesis and significance of the venous infarctions in an infantile subdural hematoma are discussed.
The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors.
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Lung resection for metastatic lung tumors from cancers of other organs has shown a significant curative success rate among affected patients. Hepatectomy also shows promise as a good curative approach for patients with liver metastasis from cancers of various abdominal organs. Descriptive data and their analysis of metastases by Bross and Viadana indicate a cascade spreading process. The fact that key-sites such as the lung and/or liver which, for some time, have proved a stumbling block to the generalization of cancers by metastases, has led to the success of therapy for metastasis in the clinical field. Chemotherapy as an adjuvant therapy to surgery for key-site metastatic foci is anticipated to raise future cure rates.
Twenty-four cases of thymic epithelial tumors, including 18 cases of thymoma, five cases of squamous cell carcinoma, and one case of undifferentiated carcinoma, were studied immunohistochemically using monoclonal antibody Leu-7 (HNK-1) and antikeratin antibody. Seven cases of non-neoplastic thymic tissues were also studied. Leu-7 antibody stained epithelial cells in the outer cortex of the normal thymus, and antikeratin antibody stained thymic epithelial cells in both cortex and medulla of the normal thymus. Seventeen thymomas and one undifferentiated carcinoma were focally or diffusely stained with Leu-7, some showing cortical and medullary differentiation as seen in the normal thymus. On the other hand, none of the five squamous cell carcinomas were stained with Leu-7. All thymomas stained for keratin in varying degrees, and all squamous cell carcinomas were diffusely and strongly stained with antikeratin antibody. It is concluded that normal thymic epithelial cells showed zonal differentiation, and neoplastic cells were considered to retain these characteristics to some extent; i.e., thymomas had the same phenotype of epithelial cells of the cortex, especially the outer cortex of the thymus in some instances (Leu-7-positive, keratin-positive) and of both cortex and medulla (mixture of Leu-7-positive and -negative cells) with organoid arrangement in other instances, and thymic squamous cell carcinoma had the same phenotype as epithelial cells in the thymic medulla (Leu-7-negative, keratin-positive).
The expression of vimentin in pulmonary carcinomas was studied in 285 cases of surgically resected lung cancer from our hospital files. Formalin fixed, paraffin-embedded sections were studied by immunoreactive staining techniques using two monoclonal antibodies against vimentin. Cases demonstrating vimentin positivity by the avidin-biotin-peroxidase method included 11 of 129 adenocarcinomas studied (8.5%), and 15 of 61 large cell carcinomas studied (24.6%). Vimentin expression was not seen in any of the 51 squamous cell carcinomas or 35 small cell carcinomas in our series. The positive cases of adenocarcinoma were in moderately and poorly differentiated cancers. Four of the eight giant cell carcinomas (50%) demonstrated vimentin expression. All cases that exhibited vimentin positivity were studied for cytokeratin expression. Coexpression of vimentin and cytokeratin was demonstrated not only within the same tumor but also within the same cells in some cases stained by double antibody technique, including both adenocarcinomas and large cell carcinomas. Similar immunoreactive methods were also applied to sections from human lung cancer transplants grown in the nude mouse. Of 28 tumors studied, four of 11 adenocarcinomas (36%) and all 4 large cell carcinomas demonstrated coexpression of vimentin and cytokeratin, while none of the five squamous cell carcinomas or eight small cell carcinomas expressed vimentin.
One hundred and sixty-eight different specimens of human carcinoma of the lung were tested for in vitro drug sensitivity using the human tumor clonogenic assay (HTCA) originally described by Hamburger and Salmon. One hundred and twenty-two (73%) specimens grew adequately for chemosensitivity testing. Most tumors were resistant to chemotherapeutic drugs, but in vitro sensitivity, regardless of the type of drugs, varied markedly from specimen to specimen. Although response rates to individual drugs ranged between 9% and 23%, half the specimens tested were sensitive in vitro to at least one drug. A higher in vitro sensitivity rate was observed in small cell lung carcinoma (31%) than in non-small cell lung carcinoma (17%). The frequency of in vitro sensitivity was greater for patients who had received no prior chemotherapy than those who were in relapse. These in vitro results are similar to current clinical experience. There was a significant association between in vitro sensitivity of cells from a primary tumor as compared to its metastases. Overall HTCA appears to be useful in selecting appropriate chemotherapy for individual patients with carcinoma of the lung.
Thirty-seven patients with histologically confirmed small cell carcinoma (SCLC), who underwent surgical resection at the National Cancer Center Hospital between 1963 and 1983, were reviewed. They were divided into two groups, 25 patients who were operated on between 1963 to 1979 and 12 who were operated on between 1980 and 1983. When these two groups were compared, a significant difference in 5-year survival was found (8% vs 50%). An accumulation of various factors including adjuvant chemotherapy was considered to contribute to the improvement in survival. After carefully analyzing these factors, we have come to the conclusion that adjuvant chemotherapy was the most important factor among them. An additional six patients with SCLC, who were operated on in 1984 and 1985, were also studied. They were either those who were given an adequate dose of combination chemotherapy before surgical resection or those whose local carcinoma which recurred after complete response was achieved by chemotherapy and/or chest radiation was surgically removed. In two cases, a tumor-like mass which was clearly visible on X-ray film and in the surgeon's hand at the time of thoracotomy revealed a histopathological "cure." In another two cases, tissue diagnosis of SCLC which was obtained without thoracotomy before chemotherapy and/or radiation was started was reported as NSCLC after the resected specimen was histo-pathologically examined. In both of them, the cancer tissue was made up of NSCLC of small cell type. A discrepancy between clinical TNM after treatment and pathological TNM was noted in two cases. Microinvasion and micrometastases, which were the reasons for the discrepancy, are considered to be a core of eventual recurrence following induction of complete response.
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The reliability of the preoperative CT diagnosis was studied in patients with pulmonary metastases from osteosarcoma and colorectal cancer as compared with surgical and pathological findings. Seventy-six lesions among 111 surgically proven metastatic nodules were detected preoperatively by CT. But the predictive rate varied greatly depending upon the site and size of the lesions. CT is not so useful in subpleural and apical sites or with nodules of less than 0.2 cm in diameter.
KW 2083, which is a new mitomycin C derivative currently under clinical investigation, was tested for its antitumor effect on the growth of human carcinoma of the lung by using an in vitro clonogenic assay system. The in vitro results in this study were as follows: We succeeded in producing clonal growth at a high rate in all histologic types of carcinoma of the lung in the assay system. That is, 61 of 81 specimens (75%) of either primary or metastatic tumors gave adequate growth for chemosensitivity testing. The in vitro responses to vindesine, adriamycin, mitomycin C and melphalan (substituted for cyclophosphamide in vitro), as standard anticancer drugs for chemotherapy of carcinoma of the lung were 18, 23, 18 and 19%, respectively, which are in good general agreement with the clinical responses to these drugs reported previously. Therefore, the clonogenic assay system might prove to be a very effective tool for an in vitro phase II study of new drugs. The rate of response to KW 2083 tested simultaneously in 51 cancer specimens was 22%, which was superior to that of mitomycin C. These results indicate that KW 2083 might be more useful than mitomycin C in clinical practice.
By using a human tumor clonogenic assay, cisplatin plus vindesine regimen was evaluated in 17 carcinoma of the lung. The cisplatin (0.2 microgram/ml) plus vindesine (0.005 microgram/ml) combination was synergistic and additive cell killing in 10 and 4, respectively, of 17 specimens. On the other hand, only three specimens showed antagonistic cell killing from this drug combination. Our results indicated that this in vitro assay provides a new method which can predict the effects of the combination of drugs on individual patients.