Sixty patients were studied with measurable histologically confirmed lung cancer which was too widespread to allow treatment by surgery or radical radiotherapy. Fifteen patients with small cell carcinoma were treated with etoposide, cyclophosphamide and adriamycin. Twenty-four patients with adenocarcinoma and 4 patients with large cell carcinoma were treated with vincristine, methotrexate, bleomycin, cis-platinum and hydrocortisone. Seventeen patients with epidermoid carcinoma were treated with cis-platinum, bleomycin and prednisolone. Of the 60 patients, 6 (10%) showed complete remission, 30 (50%) showed partial remission, 10 (16.7%) showed minor response, 11 (18.3%) were unchanged and 3 (5%) were progressive. Thus the percentage response to these chemotherapy regimens was 60% in total. Median survival time of cases during of small cell, epidermoid and adenocarcinoma were 56.6±0.8, 30.7±22.3 and 18.3±10.7 weeks, respectively. These regimens were useful for the treatment of lung cancer.

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Since Balior et al. reported that superoxide is generated by phagocytizing neutrophils, widespread interest in bactericidal systems and tissue injury by this free radical and its derivatives has resulted in a rapidly growing literature. In this study, superoxide production (SOP) by neutrophils in untreated patients with primary lung cancer was measured in order to evaluate host defence immunity to infections, and this evaluation was followed through courses of chemotherapy and radiotherapy. The effects of cytotoxic agents on SOP by neutrophils were examined.
1) The mean SOP value in 71 untreated patients was 4.93±2.14 nmol/5×10⁵ cell/min., which was not significantly depressed compared with that of normal cases (5.22±1.22), though 21 patients (30%) showed abnormal SOP (9 elevated, 12 depressed).
2) There was no correlation between SOP and age or histological type.
3) A statistically non-significant tendency toward decreasing SOP according to the progress of clinical stage was seen.
4) In 6 of 9 patients who had received COMP (Cyclophosphamide, Oncovin, Methotrexate and Procarbazine) therapy, SOP was markedly depressed close to 0 in 2 weeks after treatment and came back to within the normal range three or four weeks later. This suppression was not observed in other combination of cytotoxic drugs.
These results may suggest that high susceptibility to infection among patients with lung cancer would be found in a few patients with clinical progressive stage or in patients receiving special chemotherapy such as COMP therapy.
5) In the evaluation of the in vitro effects of cytotoxic drugs on SOP by neutrophils, ACNU, Procarbazine, Mitomycin C, Vincristine, Cyclophosphamide and Bleomycin showed more than 20% enhancement at low concentrations (1-10 ug/ml), while ACNU, 5-FU, Methotrexate and Adriamycin showed more than 20% suppression only at high concentrations (100-1000 ug/ml). From these results, it is considered that marked depression of SOP observed in COMP therapy would be explained as a consequence of damage of immature neutrophils by cytotoxic drug-generated oxygen radicals in bone marrow.
6) The SOP was measured periodically in 15 irradiated patients. Marked increase of SOP was seen in all cases after the start of radiotherapy and significantly higher SOP was observed in patients developing radiation pneumonitis on chest X-ray film.
These results suggest not only that measurement of neutrophil SOP is a useful method to predict the occurrence of radiation pneumonitis, but also that superoxide generated by neutrophils of these patients may participate in the pathogenesis of radiation injuries of the lung.

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Clinical evaluation of surgical therapy for lung cancer with pleural carcinomatosis was discussed. In nine clinically evaluated patients, (5 adenocarcinoma, 2 squamous cell carcinoma and 2 large cell carcinoma) pneumonectomy with pleurectomy, i.e. so-called pleuropneumonectomy, was performed. To date, two patients, climinally disease-free are surviving. One patient whose staging factor was E₀, n₀ and anotherpatient with E₂, n₁, have survived for 51 months and 15 months respectively. Both cases were adenocarcinoma. Seven other cases died at the period of 1.5M, 4M, 6M, 7M (2cases), 9M and 25M postoperatively. Though the overall median survival time was 7 months, some cases showed the possibility of longer survival time.
Retrospectively cases of E₂ or n₂, might not have been an indication for surgical treatment because of the poor prognosis. Consequently, the N factor was thought to be the most important prognostic factor.

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Clinical features and post-operative results of 97 resected large cell carcinomas of the lung were studied. X-ray findings showed a tumor type in 91 out of 97, 93.8%, and the diameter or the tumor was larger than 4 cm in 53.8%. However, the tumor was visible by bronchofiberscopy in only 24.7%. These clinical features suggest that most of the large cell carcinomas arise from the periphery of the lung and grow rapidly.
By p-TNM stage classification, 40 out of 97 (41.2%) were stage 1, and 46 (47.4%) were stage 3. The stage of the disease in patients with large cell carcinoma was slightly more advanced than adenocarcinoma and squamous cell carcinoma. However, the post-operative longterm survival rates after curative and relatively curative resection in large cell carcinoma, were situated between those of squamous cell carcinoma and adenocarcinoma, showing no significant differences. The five-year survival rate of large cell carcinomas after curative resections was 53.1%, while it was 28.5% after relatively curative resections. Post-operative results of non-curative resection were significantly poorer in large cell carcinoma comparing with adenocarcinoma and squamous cell carcinoma. Therefore, it is concluded that the post-operative results of large cell carcinoma can be expected to be fairly good, if they are detected and resected at an early stage.

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Tissue polypeptide antigen (TPA), immunosuppressive acidic protein (IAP), ferritin and carcinoembryonic antigen (CEA) were measured in 86 patients with primary lungcancer.
Positive rate of TPA, IAP, Ferritin and CEA were as follows, TPA: 81.8%, IAP: 91.1%, CEA: 68.8%, Ferritin: 38.1%. Different correlations between all tumor markers appeared in squamous cell carcinoma and adenocarcinoma. Therefore, it is necessary to consider histological differences when lung cancer is diagnosed by means of combination assay.
IAP and TPA correlated with survival time in cases of primary lung cancer. furthermore, there was even better correlation between survival time and the value obtained by multiplying TPA by IAP. It was concluded that the TPA×IAP value was a useful parameter to estimate prognosis in cases of primary lung cancer.

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The applicability of nuclear morphometry in differential diagnosis and prognisis of adenocarcinoma of the lung was examined using image analysers (Olympus VIP-21CH and Kontron MOP-03) on tissue sections. First, mean nuclear area (MNA) was measured in 12 cases of well differentiated adenocarcinoma, 8 cases of atypical adenomatous hyperplasia (AAH) and 5 cases of adenomatous hyperplasia (AH). In adenocarcinoma cases, NINA was significantly larger than that of AAH and AH and the standard deviation (SD) of nuclear area was greater in adenocarcinoma than that in AAH and AH. MNA and SD of nuclear area in AH were the smallest in these three groups. Many cases of AAH were morphometrically distinguishable from adenocarcinoma cases, and there were two cases in which adenocarcinoma and AAH coexisted. Secondly, the mean nuclear diameter and MNA were measured in 85 cases of adenocarcinoma less than 3 cm in diameter, and the correlation between these morphometrical factors and 5-year survival rate was examined. The survival rate in adenocarcinoma cases with small-sized nuclei was apparently higher than that of larger ones, even in 40 cases of Stage Ia (T₁N₀M₀) adenocarcinomas. Therefore, these factors are considered to be important for prediction of prognosis.

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Although it is well known that the prognosis of early hilar type lung cancer is relatively good, there are also some non-early stage hilar type lung cancer cases that have good prognoses. We therefore, examined histologically 19 such cases to determine what factors were most important for determining prognosis.
The results showed that the most important prognostic factor was the N-factor rather than location or depth of invasion. Non-early stage I hilar type lung cancer with only intrapulmonary lymph node metastasis had good prognosis. Therefore, we designated the criteria of curatively treatable hilar type lung cancer as follows; 1. primary site localized as far as the 4th order bronchi, 2. invasion of tumor confined to within peribronchial tissue or lung parenchyma 10mm from the bronchial adventitia, 3. metastasis limited to the intrapulmonary region, 4. no cancer invasion at the resected margine of bronchi.
The prognosis of hilar type lung cancer which satisfied all the above, was as good as that of early stage hilar type lung cancer.

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We examined superoxide anion (O₂^-)-generating activity and cytostatic activity against two lung cancer cell lines of polymorphonuclear leukocytes (PMN) from a patient with pulmonary giant cell carcinoma in whom there was marked granulocytosis. There was a high level of colonystimulating factor (CSF) in both serum and the supernatant of culture of the primary tumor.The PMN from the patient produced almost three times more O₂^- than did the PMN from healthy donors and other patients with lung cancers but no granulocytosis. Cytostatic activity of cells from the patient against lung cancer cell lines was also augmented, as compared to that of controls.However, following total extripation of the tumor, the level of CSF in the serum decreased, as did activity of PMN for O₂^- generation and cytostasis against lung cancer cell lines reverted to normal levels.
These results imply the possibility that CSF is able to activate the function of the PMN in vivo.

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In a 70 year-old woman, radical surgery for triple cancer, including a lung cancer, a laryngeal cancer and a thyroid cancer, was performed. Twenty one months before lobectomy for lung cancer, she underwent resection of a laryngeal cancer and a thyroid cancer.
One hundred eighty one cases of triple cancer in the Japanese literature from 1923 to 1983 were reviewed. In 181 cases, the digestive system was the most common site of carcinoma. In 48 of 181 cases, total resection of the triple cancer was performed. However, resection of triple cancer inclusive of a lung cancer constituted only 5 of the 48 cases.

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Reoperation for bronchogenic carcinoma after a successful primary operation is increasing recently with the progress in surgical therapy. We have performed three successive operations for an initial right lower lobe squamous cell carcinoma in a patient who is still alive 58 months after the initial operation. The first surgery was bilobectomy (middle and lower lobes), and the second operation was carried out 20 months after the first, while the third operation was performed 48 months after the initial one. A review of the literature showed that reoperation for recurrent or metachronous multiple bronchogenic carcinoma has generally resulted in relatively good prognosis. Therefore, reoperation should be considered for patients who have adequate cardiopulmonary reserve but without metastasis or other diseases.

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Yolk sac tumor of the mediastinum is relatively rare. Thirty four cases were collected from the Japanese literature by the author. A 30 year-old male patient with an enlarged abnormal shadow of the anterior mediastinum extending to the left lung field was admitted. On admission, the serum alpha fetoprotein (AFP) level increased to 19, 000 ng/ml and the LDH level increased to 1078 IU/1. The clinical diagnosis was malignant germ cell tumor, and through a median sternotomy, the tumor which infiltrated the pericardium, left upper lobeand left pulmonary artery was removed completely with combined left pneumonectomy and partialresection of the pericardium on October 25, 1984. Serum AFP and LDH levels decreased rapidly after the surgery. Histologic examination showed a pure type of yolk sac tumor. The result of an immunopathological study using the PAP method showed a positive localization of AFP granules in tumor cells forming endodermal sinus structures. Postoperative irradiation with 3300 rads in total and chemotherapy with Vincristine, Cyclophosphamide, 5FU and MMC have been carried out. The re-elevation of serum AFP and LDH levels was associated with metastasis to the right lung and the cervical lymph nodes. The patient was treated conservatively until April 18, 1985 when he expired.

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