cDNA microarray analysis may provide the whole features of an organism. After sequencing the whole human genome and understanding the functions of each gene, we may use expression patterns of genes to discuss biological phenomena. Also, to classify tumors, expression profiling is a very attractive method because pathological diagnosis per se is based on observations of entire features, not of particular aspects, of a tumor. In this review, several recent studies on expression profiling of lung cancers are mentioned. Four major histologies were recapitulated by expression profiling. In adenocarcinomas, which include various components, several subtypes were discovered, some of which correlated significantly with prognosis, formerly not detected by conventional histological analysis. It is expected in the future that growing interests may be taken in relations between gene and protein expression with regard to feedback mechanism, which is particularly important for transcription factors.

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Objective. According to the “Clinical Practice Guidelines for Lung Cancer in Japan” published in 2003, postoperative adjuvant chemotherapy may not be performed as a standard therapy (Grade of recommendation C) because the efficacy has not been established. However, recently reported large-scale clinical trials have demonstrated the efficacy of postoperative adjuvant chemotherapy. Thus, the objective of the present study is to asses the validity of the “Clinical Practice Guidelines” based on recent evidence revealed in clinical trials. Methods. Randomized controlled trials (RCTs) on the efficacy of postoperative adjuvant therapy that had not been identified at the time of determining the “Clinical Practice Guidelines” were identified by searches Medline and the Annual Meeting Proceedings of the American Society of Clinical Oncology. Results. Five new RCTs were identified. Three of 4 RCTs in which platinum-based chemotherapy was employed and the other one RCT where UFT was employed showed that postoperative chemotherapy was effective. Conclusions. In addition to the RCTs, a multivariate analysis showed the efficacy of postoperative administration of UFT. Based on recently reported evidence, the “Guidelines” should be corrected as follows: postoperative adjuvant chemotherapy should be performed as a standard therapy (Grade of recommendation B).

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Objective. Although we can detect small lesions by CT screening, it is unknown whether this leads to improvements in survival rates and lung cancer mortality. The purpose of this study was to determine the relationship between tumor size and survival in patients with stage IA non-small cell lung cancer (NSCLC). Methods. We retrospectively analyzed 219 patients with p-stage IA NSCLC resected from 1987 to 2002. The following patients were excluded: 1) patients who underwent partial resection or segmentectomy, 2) patients with multiple lung carcinomas, 3) patients who did not undergo mediastinal lymph node dissection. Kaplan-Meier survival analysis was performed to estimate the 5-year survival stratified by tumor size. The influence of age, gender, histology, differentiation, lymphatic or vascular invasion and tumor size on survival was analyzed using a Cox proportional hazards regression model. Results. The median age was 67 years, males consisted of 63%, adenocarcinoma 70%, and median tumor size 20 mm. The 5-year survival rate for all patients was 76.3%. The 5-year survival rates stratified by tumor size were 95.8% for 24 patients with tumor size<10 mm, 72.6% for 96 patients with tumor size 11-20 mm, 75.0% for 99 patients with tumor size 21-30 mm. There was a statistically significant difference in survival between the<10 mm group and the 21-30 mm group. Multivariate analyses revealed 3 significant prognostic factors: age (p=0.0004), differentiation (p=0.0405), and tumor size (p=0.0495). Conclusions. These data suggest that tumor size within stage IA is a prognostic factor. Improved small nodule detection with screening CT may improve lung cancer survival.

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Objictive. When chemotherapy is conducted for the treatment of non-small cell lung cancer. (NSCLC), we must pay attention to the degree of impairment of pulmonary function. So far, it is not clear whether the smoking affects pulmonary function in a different manner according to the histological types of lung cancer; squamous cell carcinoma and adenocarcinoma of the lung. In order to clarify these issues, we investigated the relation of smoking index (SI), location of cancerous lesions, and pulmonary function in patients with NSCLC. Study design. A total of 307 cases (squamous cell carcinoma; 117, adenocarcinoma; 190), with bronchial lesions located at sites proximal to the orifice of segmental bronchi (central lesions), or beyond (peripheral lesions) using fiberoptic bronchoscopy, was divided into two groups according to SI. There were 159 cases with an SI of more than 800 (high SI), and 148 less than 400 (low SI). Results. Age and SI were higher in squamous cell carcinoma than in adenocarcinoma, and restrictive and obstructive disturbances and a decrease in DLco and widened alveolar-arterial oxygen difference (AaDO₂) were more prominent in squamous cell carcinoma than in adenocarcinoma. Similar results were obtained from analyses in the patients with peripheral lesions. In particular, disturbance of diffusion capacity was more prominent in squamous cell carcinoma than in adenocarcinoma. Moreover, when the subjects were limited to the patients with peripheral lesions, pulmonary functions in the high SI group tended to be more markedly disturbed than in the low SI group. In squamous cell carcinoma, however, V₂₅/Ht and DLco did not show a significant difference between high SI and low SI groups with deteriorations of these parameters being observed even in patients with low SI. Conclusion. It is concluded that the disturbance of respiratory function is more prominent in squamous cell carcinoma than in adenocarcinoma. Smoking affects the disturbance of respiratory functions in NSCLC with peripheral lesions. Squamous cell carcinoma shows greater impairment of the peripheral airways and diffusion capacity than adenocarcinoma, even in patients with an SI of less than 400.

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Objective. We evaluted long-term follow-up results of concurrent chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC), and patients underwent surgery after CRT.Patients and Methods. Between January 1992 and April 2001, 82 patients with histologically proven NSCLC, stage II-III, were entered into this study. Chemotherapy consisted of cisplatin (20 mg/m² on days 1-5, 22-26) and VP-16 (30 mg/m² on days 1-5, 22-26) or cisplatin (10 mg/body) daily. Conventional thoracic radiotherapy was delivered at 2 Gy daily reaching a total dose of 60 Gy or 66 Gy. Thirty-two patients underwent surgery 4-5 weeks after CRT. Results. The median survival time, 2 and 5-year survival rates of 82 patients who underwent CRT and 32 patients who underwent surgery after CRT were 17 months, 41.8%, 19.4% and 14 months, 40.2%, 22.1%. The most common grade 3 and 4 toxicities included leukopenia (34.1%), thrombocytopenia (14.6%), esophagitis (2.4%), and radiation pnuemonitis (11.0%). There were no treatment related deaths. Conclusions. Our study of concurrent chemoradiotherapy for NSCLC demonstrated the potential to provide long-term survival and the safety.

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Background. Pleuritis carcinomatosa is difficult to diagnose only by pleural fluid analysis and radiographic findings. We describe a case of adenocarcinoma of the lung associated with massive mucinous pleural effusion, which was diagnosed by video-assisted thoracoscopy (VATS). Case. In January 1999, a 64-year-old man was admitted to our hospital with a chief complaint of right back pain. Radiographic examination disclosed abundant effusion in the right chest. Neither cytological examination of the pleural effusion nor histological examination of the pleura obtained by percutaneous pleural biopsy revealed malignant cells. Tuberculous pleuritis was diagnosed and antituberculous therapy was initiated. Antituberculous chemotherapy had no effect on exudate production, since thoracentesis yielded large amounts of mucinous fluid. CA19-9 levels in serum and pleural effusion were high. Biopsy specimens obtained from the right pleura under VATS revealed papillary adenocarcinoma with mucin production. No obvious primary lesion was found in the lung field, but a diagnosis of pleuritis carcinomatosa originating from lung adenocarcinoma was established after further examination. Despite conservative treatment, he died on January 30, 2003 because of respiratory insufficiency due to metastasis to the contralateral lung and abundant bilateral pleural effusion. Postmortem examination revealed 2.5l of mucinous effusion in the right thoracic cavity and massive involvement of the right lung by the tumor. The right lung was atelectatic and with pleural thickening. There were metastases in the contralateral lung, and hilar and mediastinal lymphnodes but no distant metastases were detected. Conclusion. This was an extremely rare case of papillary adenocarcinoma of the lung characterized by massive production of mucinous fluid in the pleural cavity.

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Background. Primary mediastinal paraganglioma is rare, accounting for only 2% of a large series of neural tumors of the thorax. Case. A 73-year-old Japanese man was hospitalized because of dyspnea, fever, general fatigue and cough. Chest X-ray and, CT and MRI of the chest revealed a tumor 14 cm in diameter which had invaded the pericardium, the inferior vena cava, the diaphragm, and the left atrium. The patient died of heart failure. At autopsy, the tumor was found to have originated from the outside of the posterior atrium and to have invaded the mid-mediastinum without distant metastasis. Histologically, tumor cells were large-polymorphous and showed nuclear pleomorphism. Immunohistochemical staining showed that tumor cells were positive for synaptophysin and NSE, and electron microscopic examination revealed neurosecretory granules of the epinephrine type in the cytoplasm. Therefore, this tumor was diagnosed as cardiac malignant paraganglioma. Conclusion. An autopsy case of cardiac malignant paraganglioma is reported. Immunohistochemical staining and electron microscopy can be helpful particularly when light microscopic findings are atypical.

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Background. Sixty-six cases of cancer of unknown origins affecting only the hilar and/or mediastinal lymph nodes have been reported in the Japanese literature. Although it is a relatively rare clinical entity, there is a possibility that a pulmonologist could encounter such a case in clinical medicine. We present two cases of cancer of unknown origin involving the hilar and mediastinal lymph nodes. Case 1. A 68-year-old woman had enlarged right hilar and mediastinal lymph nodes, suggesting malignancy without a pulmonary lesion. We performed systematic right hilar and mediastinal lymph node dissection following right lower lobectomy and found adenocarcinoma in the enlarged lymph nodes but no carcinoma in the resected lung. The patient showed no sign of cancer recurrence until she died of Parkinsonism 4 years after surgery. Case 2. A 54-year-old man had an enlarged right hilar lymph node without pulmonary nodule. He underwent systematic right hilar and mediastinal lymph node dissection and right upper lobectomy. The resected hilar lymph node contained large cell carcinoma, but we could not find any carcinoma in the resected lung. He suffered recurrence in the mediastinal lymph nodes and pleura, and died of respiratory failure 17 months postoperatively. Conclusion. We performed systematic hilar and mediastinal lymph node dissection following lung resection for 2 cases with hilar and/or mediastinal lymph node cancer of unknown origin. Although many reports have suggested that lymph node resection or dissection without lung resection is an appropriate surgical procedure, this approach is still controversial. The surgical procedure should be decided mainly on the basis of the location of the affected lymph node, with adequate informed consent. Because the prognosis of resected cases is relatively good, surgery is considered the first treatment choice.

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