Potent cytotoxic activity against L cells as well as a number of cultured human lung cancer cell lines was found in the carcinomatous pleural effusion and ascites afterintrapleural or intraperitoneal injections of OK-432. Such effusions also showed to inhibit the transplanted tumor growth in nude mice and induce significant prolongation of survival time of these mice, whereas they showed no effect on normal cells at all.
The activity was detected at around 14-18 Kd MW by partial purification of DEAE-A50 and Sephadex G-200 and was resistant to heat treatment at 56°Cfor 30 min., suggesting strongly that the activity was mediated by TNF.
It was considered that TNF as well as TNF-inducing agents such as OK-432 could be an effective agent for managing human lung cancers.

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We performed bronchial arterial infusion (BAI) of 50 mg cisplatin in eight lung cancer patients. Postoperatively the platinum concentration in the tumor (average: 11.5 microgram/g·tissue) was more than twice the concentration in the normal lung tissue in five resected cases. We also detected high serum concentrations of active cisplatin (over 3 microgram/ml) during arterial infusion. It was considered that the concentration of active cisplatin in bronchial artery blood sufficiently reached the tumor inhibition dose level for adenocarcinoma of the lung.
In conclusion, because of the improvement of cisplatin transport to the tumor, BAI of cisplatin for lung cancer should be an effective local therapy.

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Seventeen resected cases of early squamous cell carcinoma of the lung were studied by electron microscopy and the following results were obtained. 1) The 17 cases had no acinar differentiation and were classified on the basis of the electron microscopic appearance of tumor cells in the basal layer as follows. Type I is a tumor in which the cells have prominent cytoplasmic processes, wide intercellular spaces, dark cytoplasm, many desmosomes (Ds) and tonofilaments (Tf) (5 cases). Type III is a tumor in which the cells have relatively clear cytoplasm with some cytoplasmic processes and some intercellular spaces (7 cases). Type II is an intermediate type between type I and type III (5 cases). 2) These cell types had good correlation with the pattern of invasion, depth of invasion, dissolution of basement membrane, mitotic count and cellular atypia. 3) Three cases had many small dense core granules.

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The cell characteristics according to degree of histological differentiation and subtypes were examined immunohistochemically using the avidin-biotin-peroxidase complex method, in 100 cases (50 well differentiated (WD) and 50 poorly differentiated (PD) types) of adenocarcinoma of the lung.
WD and PD adenocarcinomas were extensively positively stained with antibodies against keratin (98%), epithelial membrane antigen (98%), secretory component (71%) and carcinoembryonic antigen (75%). The high percentage positivity of these antibodies demonstrated them to be good markers for epithelial cell differentiation in lung adenocarcinoma. Lactoferrin (LF) was a relatively good marker of WD adenocarcinoma of bronchial gland cell type (43%) and PD adenocarcinoma (36%). LF might be a good marker for bronchial gland cell differentiation. All WD adenocarcinomas of the goblet cell type were positively stained with anti-lysozyme (Lys) antibody and Lys was a specific marker for differentiation of adenocarcinoma of the goblet cell type. WD adenocarcinoma of type II alveolar epithelial cell type, although only one case was examined, more than half of Clara cell type (56%) and some cases of PD adenocarcinoma (10%) were positively stained with anti-surfactant apoprotein (Apo) antibody. Ultrastructurally, Apo-positive cases showed the presence of osmiophilic lamellar inclusion bodies in some tumor cells. A few cases of WD (4%) and PD (8%) adenocarcinoma were positively stained with anti-calcitonin (CT) antibody. In CT-positive cases, neurosecretory type granules were present in tumor cells ultrastructurally. There were no cases with immunoreactive gastrin-releasing peptide. These findings suggested that staining patterns of neuroendocrine markers in adenocarcinoma were different from those in small cell carcinoma. WD adenocarcinomas were more positively stained with anti-neuron-specific enolase (NSE) antibodies (46%) and Leu 7 (48%) than PD adenocarcinomas (18% and 32%). NSE and Leu 7 were not necessarily specific markers for neuroendocrine cell differentiation.
These results indicated that adenocarcinoma of the lung showed immunohistochemical heterogeneity within a histological type, subtypes and individual tumors.

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To clarify the histogenesis of lung adenocarcinoma, multiple specimens including lung tumor and non-neoplastic lung tissues were examined histologically and immunohistochemically in 131 surgically resected lung cancer cases. Six new small or minute adenocarcinomas were incidentally found in adenocarcinoma cases. Adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH) existed in 29 cases (22.1%) and 16 cases (12.2%), respectively. In 65 cases of adenocarcinoma, AH and AAH were present in 22 cases (34.4%) and 12 cases (18.8%), respectively. In adenocarcinoma cases, AH and AAH were more frequent and occured more multiply than in squamous cell carcinoma cases. In 11 cases of multiple primary lung cancer, both AH and AAH occured more frequently (72.2%) than in solitary lung cancer cases. There were 6 cases in which foci of adenocarcinoma and AAH coexisted. Immunohistochemically, surfactant apoprotein-positive cells were present focally or diffusely in cases of adenocarcinoma, AAH and AH. Therefore, it is suggested that some adenocarcinomas might originate from AAH.

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Nervous system involvement occurred in 79 of 374 primary lung cancer patients. We divided the neurological lesions, into five compartments; intracranial, spinal cord, nerve root, peripheral nerve, and meninx. Involvements in these compartments were analyzed in tests of whether they were solitary or multiple.
Involvement had a tendency to be multiple, rather than solitary. Multiple involvements in one compartment were seen in 34 patients (43%), and multiple involvements in more than two compartments were seen in 12 patients (15%). In addition they could occur simultaneously or metachronously. Many kinds of neurological symptoms were seen and they frequently corresponded to the anatomical localization of the lesion.

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The effectiveness of annual chest radiographical screening for detection of lung cancer in the Miyagi program was studied. It employed chest miniature (70mm or 100mm) radiographs in screening. Most non-specific shadows were effectively excluded from further examination by reviewing previous chest miniature radiographs in a file. A total of 56 primary lung cancers were detected out of a total of 223, 796 participants in 1985. The mean size of the nodular tumor shadows in 44 cases was 29 mm, and 30 cases (68%) were of 30 mm or smaller in size. Resection was performed in 37 cases, of which 26 cases were postsurgical Stage Ia lung cancer cases. In 28 of 40 incidence cases there was evidence of tumor on previous chest radiographs. Furthermore, 6 cases of 8 early lung cancer cases detected had evidence of tumor on previous chest radiographs. The size of the tumor shadow seemed to be smaller and the stage to be earlier in cases with evidence of cancer on previous radiographs than in cases without evidence of cancer. This may indicate that the rate of growth of the latter is greater than that of the former.

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In order to assess the clinical effectiveness of adjuvant immunotherapy with Nocardia rubra cell wall skeleton (N-CWS), a randomized prospective controlled study was performed with operable non-small cell lung cancer patients at our institution between November 1, 1978 and October 31, 1982.A total of 146 patients were entered into this trial.Of the 146 patients, 51 patients in the N-CWS group (immunotherapy group) and 55 patients in the control group (non-immunotherapy group) were eligible for statistical analysis.The patients were surveyed as of October 31, 1984 and the effectiveness of N-CWS was appraised by comparing the survival rate curves between the N-CWS and control groups.
As a result, in patients with curative and relatively curative resection, p-T_1-2N₀M₀ (surgico-pathological stage I) or p-T₃N_0-1M₀, the survival rate curves of the N-CWS group were better than those of the control group, but there was no statistical significance.In addition, the remission duration of the N-CWS group in p-T_1-2N₀M₀ was longer than that of the control group.This result suggested that treatment by N-CWS alone was useful to control microscopic distant metastasis in patients with p-T_1-2N₀M₀ of non-small cell lung cancer.
The main adverse reactions to N-CWS were skin lesions at the injected sites and fever, but these were not serious.

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A case of lung cancer in a 73 year-old man producing alfa-fetoprotein (AFP) and human chorionic gonadotropin (hCG) is reported.
The peak level of serum AFP was 1827 ng/ml, and serum hCG 130 mIU/ml (hCG beta 4.4 ng/ml). Irradiation and chemotherapy were initially effective, but the tumor soon become uncontrollable. He expired some 5 months after admission. Autopsy disclosed primary lung cancer in the right lower lobe with multiple metastases in both lungs, liver, heart, pancreas, and lymph nodes. No sign of germ cell tumor was present.
Histologically the tumor was adenosquamous carcinoma with a choriocarcinoma-like component. With the PAP method, AFP was positively stained in adenocarcinoma cells and hCG in choriocarcinoma-like cells. The non-binding proportion of AFP to lectin was measured. It was 82% to concanavalin-A, and 0% to LCA.
This non-binding proportion was different from that of hepatocellular carcinoma, similar to AFP-producing gastrointestinal malignancies or yolk sac tumor. This fact may provide a clue to the origin of this lung cancer.

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A 56 year-old male was admitted because of an abnormal chest roentogenogram showing a solitary thin-walled cavity in the left upper lung field. Laboratory data revealed increased CEA levels (4.0 ng/ml). Although examination with the flexible fiberoptic bronchoscope and sputum cytology showed no abnormal findings, a left upper lobectomy was performed. On macroscopic examination, a thin walled cavity in the S¹⁺² region was 20 × 18 mm in diameter and 2-4 mm in wall thickness. Microscopic examination of cavity wall demonstrated squamous cell carcinoma. A chronic eczema like lesion on the left scrotal region was disclosed as Bowen's disease by histological examination.

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Two cases of lung cancer in which the patients were treated with preoperative chemotherapy followed by surgery are reported. This strategy for cancer treatment is known as downstaging or neoadjuvant chemotherapy.
The first case was a 32 year-old male diagnosed as having poorly differentiated squamous cell carcinoma of the lung. The tumor was considered to be unresectable due to extensive local growth. However after palliative chemotherapy, it became possible to perform surgery. Histological examination of the resected lung or regional lymph nodes disclosed no resilual tumor cells.
The second case was a 71 year-old male who underwent left upper lobectomy for modorately differentiated squamous cell carcinoma of the lung. Left pneumonectomy seemed necessary at the initial bronchoscopic evaluation. However surgery was rejected because of impairment of pulmonary function and the higher operative risk in persons over 70 years of age. After two courses of chemotherapy, the tumor became markedly reduced in size and left upper lobectomy was performed. In this case only isolated foci of malignant cells were found in otherwise necrotic tissue. There was no tumor in the regional lymph nodes.
In regard to the chemotherapy regimen, both cases received CDDP and the down-staging chemotherapy was effective. The duration between chemotherapy and operation was 2-3 weeks. Both patients are free of disease at present, 7 and 30 months after surgery, respectively.
In this study the efficacies of down-staging chemotherapy in two cases of lung cancer are reported. However it seems too early to conclude that this strategy would improve the indications of surgery even in cases initially scheduled for surgery. A randomized study would be necessary to answer this question.

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A case with quadruple cancer, which consisted of gastric cancer, colon cancer, rectal cancer and lung cancer, was reported. An 80-year-old male, who had undergone resection for gastric cancer and transverse colon cancer 11 years ago, was admitted to our hospital for surgical treatment of rectal cancer. His chest x-ray on admission showed a tumor-like shadow in the right middle lobe. Cytological examination by bronchoscopy showed primary adenocarcinoma of the lung.
Low anterior resection of the rectum was performed, and two months later, right middle lobectomy of the lung was done. Each tumor had a different histological appearance. He died of thrombosis of the superior mesenteric artery and pneumonia four years after the surgery of the lung. However, no sign of recurrence was observed clinically.

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We reported two cases of bronchial mucoepidermoid carcinoma in a 20-year-old male and 50-year-old female. In the first patient the tumor originated in left basal bronchus and invaded into surrounding lung parenchima with lymph node metastasis. Leftpneumonectomy and mediastinal lymph node dissection was performed. The female patient had polypoid carcinoma in the left upper lobe branch. Left upper sleeve lobectomy was performed with mediastinal lymph node dissection. In both cases no recurrence is apparent at over two and half years after operation.
There are reports that low grade mucoepidermoid tumor metastasized to other organs, even though the patients received a “curative operation”. From these reports we think the most suitable operation method should be decided according the results of frozen section and other findings.

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A 59 year-old man was admitted to our department complaining of ataxia, astasia and nystagmus. Chest X-ray revealed a small mass shadow in the left lower lung field.Transbronchial brushing specimens showed small cell carcinoma. Cerebral CT scan showed no findings suggestive of metastasis.
Under a diagnosis of lung cancer with subacute cerebellar degeneration, left lower lobectomy with partial resection of S₅ was performed.
Preoperative plasmapheresis and steroid therapy were not effective, but improvement of cerebellar symptoms was seen for 1 week postoperatively. The histological diagnosis was intermediate type small cell carcinoma.

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