Concerning the question of the effectiveness of lung cancer screening by previous randomized controlled trials, the resultsof four case-control studies, conducted recently by the Ministry of Health and Welfare, Japan, were reported at the IASLC 2000 congress, and revealed that lung cancer screening could decrease the risk for lung cancer deaths by 30-60%.However, the influence of lung cancer screening lasted for only 1 year, while that of some cancer screening programs forother organs lasted for more than 1 year, which indicates that, for lung cancer patients, the opportunity of cure would belost by a miss in one screening. Since lung cancer screening with insufficient quality control does not lead to a decrease inlung cancer death, every effort for the improvement of quality control in screening systems must be made. Informationdisclosure on the quality control of each screening system, offered by many companies, should be strongly promotedthrough activating the Prefectural Council for Quality Assurance of Mass Screening.

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Objective: This study was designed to understand the pathogenetic mechanism of pleural carcinomatosis.
Patients and Methods: We collected 207 surgical cases of primary lung cancer and identified 43 cases with positiveintraoperative pleural lavage cytology (PLC). We then histologically examined the pulmonary ligament (PL), visceralpleura (VP) and parietal pleura (PP) in these cases and found that 24 cases belonged to either the p0 or p1 categoriesof the Classification of Lung Cancer of the Japan Lung Cancer Society. Unfortunately the surgical cases were unsuitablefor investigation of PL, because of severe operative manipulation involving the ligament. However, 15 autopsy cases of primarylung cancer and 63 of extrapulmonary primary origin were similarly investigated.
Results: Surgical cases: Positive PLC cases showed a statistically significantly higher involvement in lymphatics andblood vessels of the lung parenchyma and hilar lymph nodes, than cases with negative PLC (p<0.001). Autopsy cases: Varying degrees of pleural carcinomatosis were found in 8 cases (53.3%) of primary lung tumors, which were all adenocarcinomain 2 out of the 8 cases, however, tumor cells were found, only in the PL. In addition, varying degrees of pleuralcarcinomatosis were observed in 21 cases (33.3%) of extrapulmonary origin, in which combined PL involvement was onlyobserved in 5 cases. Furthermore, cancer cell clusters were found in the lymphatic cisterns of the PL in 29 autopsy cases (37.2%).
Conclusion: There was also evidence of permeation of tumor cells in the cisterns into the pleural cavity via adjacentstomas in the PL. The PL was found to be a site with numerous lymphatic cisterns with stomas in the thoracic cavity. As aresult, we consider that tumor invasion into the subpleural lymphatics might be a prerequisite for the development ofpleural carcinomatosis.

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Objective: We quantitatively measured thymidine phosphorylase (TP) activity of normal (non-tumor-bearing) lungtissues in non-small lung cancer, and investigated the relationships with various clinical backgrounds.
Methods: Both normal lung tissues and tumor tissues were obtained from 39 patients with primary lung cancer undergoinga pulmonary lobectomy. The tissue TP activity was quantitatively measured with a sandwich enzyme immunoassay.
Results: The mean value of TP activity in tumor tissues was significantly higher than that in normal lung tissues (226U/mg protein vs. 46U/mg protein, p<;0.0001). TP activity of normal lung tissues varied from 10U/mg protein to 136U/mg protein, and was high in male patients (male; 56.1U/mg protein vs. female; 29.3U/mg protein, p=0.001), heavysmokers (Brinkmann Index (BI) =600 or >600; 57.9U/mg protein vs. BI<600; 31.7U/mg protein, p=0.001) or presenceof interstitial changes on chest CT (positive; 63.0U/mg protein vs. negative; 36.2, p=0.002). In 8 of 9 patients, in whominterstitial inflammation (infiltration of chronic inflammatory cells) was histologically identified, the TP level of normallung tissues was higher than 50U/mg protein. The high level of TP activity might be attributed to some active inflammatorycells in the interstitium and reflect the presence of interstitial inflammation. We are now investigating the usefulnessof TP activity of lung tissues as a marker of activity of interstitial pneumonia.

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Objective: In order to evaluate the influence of normal chest structures on radiologic detection of lung cancers, we examinedthe location of lesions detected by screening.
Methods: The study comprised 132 cases (135 lesions) of lung cancer. They were detected by miniature chest X-rayfilms taken at annual screenings between April 1991 and March 1999, and consisted of 98 adenocarcinomas and 37 peripheralsquamous cell carcinomas. They were separated into groups by stage, tumor size and histological type. The locationof the lesions was plotted on a schematic representation of the posteroanterior (PA) view, and their distribution patternswere compared among groups. The areas where early detection of lung cancer was difficult, and the areas where it waseasy, as well as the areas of intermediate difficulty were represented on the schematic PA view. The borders around difficultareas were drawn with reference to the distribution pattern of lesions more than 3cm in diameter, while thosearound easy areas were based on the distribution pattern of stage I lesions 2cm or less in diameter. The remaining areaswere designated as intermediate areas. The proportion of stage I lung cancers and other indices for three areas were estimatedin order to determine differences among them. The distribution pattern of adenocarcinomas was compared withthat of squamous cell carcinomas. Previously missed lung cancers among the 135 lesions were identified retrospectivelyfrom serial X-ray films. Potentially detectable nodules on previous chest X-ray films were classified as missed lung cancers.The distribution pattern of missed lung cancers is also shown.
Results: Most of the stage IA lung cancers were detected in the area where no large normal structures were superimposedon the nodules. Stage III and stage IV lung cancers showed a wider distribution, and the superimposition of normalstructures such as the heart, great vessels, pulmonary peripheral vessels, diaphragm, ribs surrounding the apex, clavicleand the tip of the first rib on a considerable number of nodules. There were statistically significant differences among thethree areas in the proportion of lesions 2cm or less in diameter. The proportions of stage I lung cancers within the difficult, intermediate, and easy areas were 34%, 57% and 75% respectively. The ratio of squamous cell carcinomas to adenocarcinomaswithin difficult areas was higher than that outside them. There was no statistically significant difference in theproportion of missed lung cancers among the three areas. “Areas where lung cancer lesions were often missed” and “areaswhere early lung cancers could hardly be detected” showed different appearances.
Conclusion: The superimposition of normal chest structures markedly influenced the stage and size of adenocarcinomaand peripheral squamous cell carcinoma as detected by chest X-ray. Gross classification of lung fields was made inrelation to the efficiency of radiologic detection of early lung cancer.

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Background: This report describes a very rare case of localized malignant pleural mesothelioma with remarkable osseousand cartilaginous differentiation.
Case: A 72-year-old man was admitted to hospital with dry cough and severe dyspnea. A chest X-ray and CT on admissionshowed a huge mass (20×16cm in diameter) occupying the right thoracic cavity and anterior mediastinum. Therewere many calcifications in the tumor, and pleural effusion in the right pleural cavity. Chest CT revealed that the huge tumorcompressed the heart and the right lung, and the right main bronchus and the main pulmonary artery had been occluded.Microscopic examination of the needle biopsy specimen did not yield a definitive diagnosis. No malignant cell wasrecognized in pleural effusion, but serum NSE level was high (19.4ng/ml).
The tumor, together with the right lung, was resected. The mass was too huge to be removed by a median sternotomyincision or usual postero-lateral incision, so we performed a transverse thoracosternotomy. The weight of the resectedmass with the right lung was 2370g, and the volume of the evacuated bloody right pleural effusion was 2300ml. The sternumwas replaced with hard marlex mesh like a sandwich, and it was fixed with stainless wire. Hard marlex mesh wasused to fix the sternum after transverse sternotomy, to prevent respiratory failure. His postoperative course was uneventful.
Conclusion: The pathological diagnosis was malignant sarcomatoid mesothelioma with extensive ossification. This appearsto be the 17th reported case in the world and the 5th case in Japan.

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Background: There are a few reports of pulmonary toxicity concerning combined chemotherapy with gemcitabin (GEM) and docetaxel (TXT). In this report, we describe five cases with non-small cell lung cancer which developed interstitialpnemonitis as drug adverse reaction under the treatment of combined chemotherapy with GEM (800-1000mg/m², day 1 & 8) and TXT (50-60mg/m², day 8) every 3 weeks.
Cases: Out of 25 patients treated with combined chemotherapy from August 1999 to April 2001, five patients showedinterstitial pneumonitis, and all showed the same toxicity pattern on days 15-18 in the 2nd course with the same events, such as fever, hypoxia, LDH elevation and interstitial shadow on X-ray film. These patients responded to steroid therapyand recovered quickly. Three of these 5 patients showed cutaneous toxicity (eruption or itch) before pulmonary toxicity.We observed this pulmonary toxicity only in this combination, and not in other combinations such as TXT and other (none out of 46 cases) or GEM and other (none out of 30 cases) in this period.
Conclusion: Careful attention should be paid in these rare cases. It is necessary to investigate incidences and mechanismsof this toxicity in the future.

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Background: Thoracic empyema due to perforation by lung cancer is rare.
Case: A 73-year-old man with thoracic empyema was admitted to our hospital. Chest X-ray film, CT and thoracoscopy revealed fibropurulent phase empyema and the patient received thoracic drainage, pleural irrigation and drip infusion of antibiotics. Chest CT after thoracic drainage showed a lesion of the right middle lobe, which was supposed to be the cause of thoracic empyema, i.e. pulmonary abscess, lung cancer and so on. Eight days after admission, operation was performed. Thoracotomy revealed empyema due to perforation by lung cancer, and lobectomy of the right middle lobe with decortication was performed. The postoperative course was uneventful and the patient was discharged on the 28th postoperative day.
Conclusion: We conclude that cleaning of the thoracic space by pleural drainage and irrigation enables one-stage radi-cal operation of fibropurulent phase thoracic empyema deriving from lung cancer itself.

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Background: Recently, some cases of lung tumors producing granulocyte colony-stimulating factors (G-CSFs) have been reported. Most of the tumors were carcinomas such as large cell carcinomas. We report a rare case of pulmonary sarcoma producing G-CSF.
Case: A 65-year-old man complaining of fever was transferred to our hospital for further examination of an abnormal shadow on chest X-ray film. His laboratory data on admission showed marked leukocytosis (31900/μl), 95% of which consisted of neutrophils. Percutaneous biopsy yielded a diagnosis of an undifferentiated malignant tumor in his chest. After confirming that there was no distant metastasis, he underwent upper right lobectomy with chest wall resection. The surface of the excised tumor showed marked yellowish area of necrosis and hemorrhage with scattered abscess. Pathological examination of the resected specimen revealed that the tumor consisted of two different components, namely, large cell carcinoma with giant cells and spindle cell sarcomatous lesions infiltrated with multiple neutrophils. More than 90% of the tumor consisted of sarcomatous lesions although there was some variation in both components. Immunohistochemically, the spindle cell component was stained with Vimentin, muscle-specific actin (MSA), and both components were stained by the anti-rhG-CSF monoclonal antibody. On admission, the serum G-CSF level was 37.8pg/ml, which increased to 38.9pg/ml immediately before surgery and decreased to 77.9pg/ml after surgery. The post operative chemotherapy had no effect and he died 4 months after surgery.
Conclusion: This appears to be a rare case of pulmonary sarcoma producing G-CSF. We measured the serum G-CSF levels at several points during his clinical course. The serum G-CSF levels may have been related to the development of the tumor.

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Background: Most lung adenocarcinomas show poor prognosis. However, some cases of slowly progressive adenocarcinoma have been reported.
Case: A case of a 43-year old man with lung adenocarcinoma was reported. An abnormal shadow was pointed out in the left middle lung field on the chest X-ray film in 1994, but he did not undergo further examination. When he was admitted to a hospital complaining of cough and bloody sputum in 1999, the chest X-ray film revealed a mass in the left middle lung field and multiple nodular densities in bilateral lung fields. The diagnosis of adenoid cystic carcinoma of the lung was made by a transbronchial lung biopsy of the left S⁶. He visited our hospital for further examination. We performed transbronchial lung biopsy of the right S²b, S³a, S⁴a and S⁸a. The histological findings showed that tumor cells proliferated with a cribriform pattern and some tumor cells were surrounded with much mucinous material. Immunohistochemically, the findings suggested that myoepithelial cells were not present, and the basal membrane did not exist in the duct like structure. Thus, we diagnosed this case as a mucous-producing lung adenocarcinoma, not as adenoid cystic carcinoma. Although chemothrapy was not effective, his performance status is still good in July, 2001.
Concusion: Some cases of mucus-producing lung adenocarcinomas grow very slowly.

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Background: Pulmonary sarcoma arising in the pulmonary artery is extremely rare, and its diagnosis is seldom made preoperatively. However, an early diagnosis and surgical resection remain the mainstay of treatment.
Case: A surgically treated case of left pulmonary artery sarcoma is herein reported. A 60-year-old with left pulmonary artery sarcoma preoperatively diagnosed by a CT-guided needle biopsy was operated two months after his initial presentation in order to relieve his chief complaint of hemoptysis. The tumor was completely and successfully resected by a left pneumonectomy with a bilateral mediastinal nodal dissection. The histological diagnosis of the resected specimen was intimal sarcoma of the anterior superior segmental branch of the left pulmonary artery, and no lymph node metastasis was observed. Two years after the operation, the patient is alive without any evidence of local recurrence or distant metastasis.
Conclusion: The finding of this case suggested that an improved survival can be achieved for this disease with an early diagnosis and an appropriate surgical resection.

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