Lung cancer is one of the most important cancers in Japan, because it has been the highest cause of cancer deaths in Japan since 1998. Recently, treatment strategies of radiation therapy are improving strivingly owing to improvement of medical physics and development anti-cancer drugs concomitantly available to radiation therapy. The Clinical Guidelines for Lung Cancer were established by experts in 2003. In 2005, first revision was performed. We were engaged in the revision of the Clinical Cancer Guidelines for Lung Cancer and then, we reviewed these guidelines in terms of radiation oncology.

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Pulmonary cytology is mostly employed as the final diagnosis for lung lesions when there are technical limitations of pulmonary biopsy. Cytology makes it possible to predict the histologic type necessary for the treatment decision. Pulmonary cytology is classified into sputum cytology, brushing cytology and needle aspiration cytology of lesions by bronchoscopy or fluoroscopy. Therefore, it is important to choose the most appropriate technique according to the location of lesions. Although the accuracy of diagnosis by cytology depends on biopsy, histology, location or progression of lesions, the positive rate by cytology exceeds 90% and closely corresponds with histology. In particular, sputum cytology is effectively applied to radiologically occult early central-type cancers. The correlation of the morphology of lung cancer cells with post-operative outcome or the effects of chemotherapy has been extensively studied, and progress has been made with examinations of lung cancer cells at the molecular level. Practical feedback on the clinical applications of cytological studies is anticipated.

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The plain chest radiograph still plays an important role as the first examination to determine thoracic diseases, especially lung cancer. Because plain chest radiography is simple and cheap, and it can demonstrate the entire thorax, much information concerning chest diseases, including lung cancer can be obtained. Furthermore, diagnostic capability of plain chest radiographs is raised by correlations with CT and MRI. However it has limitations in the detection of early lung cancer. Information such as mediastinal reflexion, which appear on plain chest radiographs are also important for depicting lung cancer, but they are not always signs of early lung cancer. Consequently, the important role of plain chest radiograph in the diagnosis of early lung cancer consisted not only depicting solid and irregular small nodules in the peripheral lung fields and secondary changes due to lung cancer such as lobar and segmental atelectasis or pneumonia, but also excluding benign nodules such as bone islands, nipples, granulomas with calcification and arterio-venous fistulas etc.

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Current surgical therapy for solid malignant tumors has changed remarkably. There are three common subjects, regardless of the kind of tumor. The changes regarding lung tumor operation were reviewed. I) Reduction in amount of resected tissue: The Lung Cancer Study Group first reported a randomized study showing that limited resection was inferior to lobectomy, producing a large impact on the subject, although one can find several questionable points in the report. However, many studies on segmentectomy for small peripheral tumors continued to be published from Japan and finally, some positive data began to appear from America. II) Shortening of the incision length: Development of video assisted thoracic surgery (VATS) and the increasing number of early cancer cases dramatically changed common knowledge of surgery, that is "The golden rule in surgery is a large incision and a wide view". Moreover surgeons must remember that VATS is only a means to enter the thoracic cavity, i.e., just an approach. What comes first is the quality of the operation. VATS with direct vision, known as hybrid VATS, or without direct vision, referred to as complete VATS, is not a point to be discussed. What patients are concerned about is the quality of the operation, not the kind of vision. Thus, minimal invasiveness comes second. When sufficient reduction of burden on the patient is obtained using a new technique without losing quality, which is correctly judged by the surgeon, one can define it as VATS. If a second learning curve is required by a trained surgeon, the curve should be reasonably short and sharp. III) Reduction in mediastinal lymph node dissection (MLND): The purpose of MLND is changing. Enormous amount of clinical data concerning the behavior of lymph node metastasis have disclosed the following: 1) a tumor with complete ground glass opacity (GGO) and high tumor disappearance rate (TDR) on CT does not require MLND, not even N1 node sampling, 2) the significance of both subcarinal lymph node dissection in cases of an upper lobe tumor and upper MLND in middle or lower lobe tumors is limited. A marked change of stage ratio in operative cases must have resulted from three factors: a) the increasing number of early cancers detected by new diagnostic equipment, b) development of operative tools and video technique, and c) advances in chemo-radiotherapy. One more hidden reason seems to be the lack of satisfaction on the part of both surgeons and patients regarding extended resection. This trend has probably accelerated due to avoidance of more risky operations which may lead to lawsuits. The general thoracic surgeon of the 21 century must be prepared with new techniques using video apparatus and tools, and conservative procedures to face both the increased number of patients in whom early lung cancer is detected and the unchanged number of those with advanced lung cancer.

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Objectives. The aim of this study was to evaluate changes in serum carcinoembryonic antigen (CEA) level as a surrogate marker for tumor response. Patients and Methods. During an 11-year period from 1995 through 2005, 24 non-small cell lung cancer (NSCLC) patients with high serum CEA level (>5 ng/ml) at presentation, who received chemotherapy followed by surgery were retrospectively analyzed. We compared changes in serum CEA level with response evaluation criteria in solid tumors (RECIST), WHO criteria or histologic response for evaluating tumor response to chemotherapy in NSCLC. Result. When we compared serum CEA level before chemotherapy with that obtained after chemotherapy, it significantly decreased in partial response (PR) group defined by RECIST or WHO criteria [P=0.004, P=0.008, respectively]. On the contrary, in patients whose responses were either stable disease (SD) or no change (NC), there was no significant difference. CEA level decreased significantly in patients in whom less than one-third of tumor cells were viable [P=0.008] but not in whom more than two-thirds of tumor cells were viable. From the receiver-operating characteristic curve analysis, 60% reduction of CEA level was an appropriate cut-off value in predicting good response to the chemotherapy. When set at that level, the sensitivity of CEA for RECIST was 82% and the specificity was 69%. Conclusion. Determination of changes in serum CEA level appeared to be useful as a surrogate index for evaluation of tumor response to chemotherapy that would result in comparable judgment with RECIST in patients with NSCLC who had elevated CEA level before treatment.

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Objective. We examined the influence of multiple primary cancers and their clinical features on outcome in cases of excised lung cancer. Methods. We targeted 101 out of 731 cases (13.8%) which presented multiple primary cancers in lung cancer operations performed in our hospital between January 1996 and December 2005. We then conducted comparative analysis with the clinical features and outcome of the 619 cases which did not present multiple primary cancers. Results. Many of the multiple primary cancers were present in the stomach, large intestine, breast, uterus, head and neck. The cases of lung cancer with multiple primary cancers did not show a significant difference compared to the cases of lung cancer alone in terms of age, sex, histological type, degree of differentiation, or pathological stage. There were many cases of lung squamous cell carcinoma in the patients with existing esophagus, head and neck cancer. Furthermore, there was a high percentage of lung adenocarcinoma in patients with existing breast, uterus, thyroid, or prostate cancer. The 5-year-survival rate after resection of lung cancer in patients with multiple primary cancers was 59.4%, which was significantly lower than the 71.3% 5-year-survival rate of patients with only lung cancer. The 5-year-survival rates after resection of lung cancer in cases of synchronous and metachronous multiple primary cancers were 57.5% and 65.6%, respectively. The cause of death of patients with lung cancer and multiple primary cancers was lung cancer in 12 cases (42.9%) and cancers of other organs in 6 cases (21.4%). Conclusion. The presence of multiple primary cancers, particularly synchronous cancers, is an adverse prognostic factor in cases of resected lung cancer. Whole body screening including examination of the digestive tract should be performed before and after lung resection.

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Background. Malignant pleural mesothelioma (MPM) is a refractory disease with poor prognosis. Most MPM advances intrathoracically with pleural effusion and tumor growth that induces respiratory failure. Cases. We provided topical interferon (IFN) treatment for 4 patients with MPM, mainly to control pleural effusion and chest wall tumor. Three cases (cases no. 1-3) received IFN-α and one case (case no. 4) received IFN-β. Intrathoracic IFN-α injections temporarily reduced pleural effusion in cases no. 1-3, who had 28-, 40-, 43-month survival, respectively. In case no. 4, intrathoracic and intratumoral IFN-β injections along with chemotherapy (gemcitabine plus cisplatin) induced marked reduction of pleural effusion and tumor size. As adverse effects, all cases, except for case 4, who also received chemotherapy, had only grade 1 fever. Conclusion. Topical IFN treatment for MPM was tolerable and useful for local control.

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Background. Localized malignant mesothelioma of the pleura (LMM) is an extremely rare tumor, and the preoperative diagnosis is known to be difficult. Moreover, the biologic association between LMM and diffuse malignant mesothelioma of the pleura (DMM) remains unclear. Therefore, the standard treatment of LMM has not been established. Case. A 58-year-old male chartered accountant with a smoking index 540 was referred to our hospital for investigation of an abnormal chest shadow detected on a regular health checkup. A chest radiograph and computed tomography scan revealed a mass with a smooth margin and heterogeneous inner structure in the right chest wall, and an extra-pleural sign. Exudative pleural effusion was found and the hyaluronic acid level was 26100 ng/ml. Cytologic examination revealed no malignant cells in the effusion. For diagnostic and therapeutic purposes, surgery was performed for total removal of the tumor together with resection of the chest wall (removal of the 6th and 7th ribs) and partial resection of right middle and lower lobes. Histopathologic examination revealed a 60-mm tumor located within the parietal pleura, and the final diagnosis was a biphasic type of LMM based on immunohistochemical studies. The tumor relapsed at the right chest wall 10 months after the operation, and extra-pleural pneumonectomy was successfully performed. Conclusion. We reported a case of LMM treated primarily by radical resection, which subsequently relapsed and was again treated by extra-pleural pneumonectomy. The relapsed disease was considered to be an isolated dissemination, and different from DMM. According to previous reports, the prognosis of LMM is better than that of DMM. Further studies of the pathologic behavior and establishment of standard treatment are clearly warranted.

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Background. Solitary fibrous tumor (SFT) is a neoplasm that usually involves the pleura; less frequently, it affects a host of other sites. We report an operated case of intrapulmonary malignant solitary fibrous tumor (intrapulmonary MSFT) in which FDG positron emission tomography (FDG-PET) showed abnormal uptake. Case. The patient was a 77-year-old man with a chief complaint of a growing mass lesion on chest computed tomography (CT). The CT showed a circumscribed mass in the right middle lobe (S⁴). FDG-PET showed abnormal uptake in the tumor with a maximal standardized uptake value (SUV (max)) of 7.35. CT-guided percutaneous needle biopsy revealed a mesenchymal tumor and didn't yield a conclusion. Based on the high SUV (max) on FDG-PET, we suspected malignant tumor and performed right middle lobectomy under video-assisted thoracoscopy. Histopathological examination showed massive proliferation of atypical spindle cells with high cellularity and more than 4 mitotic figures per 10 high-power fields. The tumor cells were immunoreactive for vimentin and CD34 but not for cytokeratin. Based on the histopathological and immunohistochemical findings, the tumor was diagnosed as MSFT. Conclusion. We reported a case of intrapulmonary MSFT with abnormal uptake on FDG-PET. Immunohistochemistry results were essential in establishing the correct diagnosis of SFT.

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Background. Pulmonary mucosa-associated lymphoid tissue (MALT) type lymphoma is a relatively rare entity. Only a limited numbers of articles have been published on FDG-PET results of pulmonary MALT type lymphoma. Case. A 60-year-old woman with cough and malaise had a 1.5-cm pulmonary nodule in the right lower lobe which was detected on a chest CT examination. The nodule showed low-grade FDG accumulation on PET. Then inflammatory lesion or lung cancer was suspected. Core needle biopsy by video-assisted thoracoscopic surgery was performed and plasmacytoma or lymphoma was suspected. Then wedge resection of the right lower lobe was performed. The histopathological diagnosis was pulmonary marginal zone B-cell lymphoma of the MALT type, exhibiting marked plasma cell differentiation. Conclusion. To the best of our knowledge, only 10 cases of pulmonary MALT type lymphomas with FDG-PET results, including our case have been reported. Eight cases showed FDG-PET positive uptake but 2 cases were negative. Pulmonary MALT type lymphoma should be considered in the differential diagnosis of pulmonary lesions with positive FDG-PET uptake. We report a case of pulmonary MALT type lymphoma with low-grade FDG accumulation on PET.

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Background. Mucinous ("colloid") adenocarcinoma of the lung is a rare malignancy. Case. A 71-year-old woman was admitted to our hospital because of an abnormal shadow in the right lung field on a routine health check chest X-ray. Chest CT showed a consolidation 80 mm in diameter in right lower lobe. FDG-PET (fluorodeoxyglucose-positron emission tomography) showed no accumulation in the lesion. Through the follow up, the size of the lesion was not changed. The diagnosis was not defined by percutaneous CT-guided needle biopsy. We performed an operation for definite diagnosis and treatment. Sure core needle biopsy intra-operative frozen section histology showed carcinoma with abundant mucin, a right lower lobectomy with lymph node dissection was performed. The pathologic classification was determined with mucinous ("colloid") adenocarcinoma, T2N0M0, Stage IB. Conclusion. We here report a case of mucinous ("colloid") adenocarcinoma for which diagnosis was difficult.

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[in Japanese]

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