Background. Gefitinib is an epidermal growth factor receptor inhibitor and has been reported to be effective in non-small cell lung cancer. Dramatic responses to gefitinib were observed in some patients with clinical factors, such as adenocarcinoma-histology, female-gender, and non-smokers. However, the efficacy of re-treatment with gefitinib after acquisition of resistance for patients who showed a favorable response to initial therapy of gefitinib remains unknown. Purpose and methods. We retrospectively analyzed patients with regard to the following criteria: 1) cases of good response to initial therapy of gefitinib, 2) cases treated with chemotherapy after acquisition of resistance to the initial gefitinib therapy, and 3) cases attempted to re-treatment with gefitinib after the chemotherapy. Results. Nine cases enrolled in the present study were all adenocarcinoma and female. The patients were initially treated with gefitinib in the 1st-4th line setting, and were re-treated with gefitinib in the 3rd-6th line setting. Three cases achieved a partial response (PR) in re-treatment with gefitinib. The objective response rate was 33.3% (95%CI, 7.5-70.1%). They also achieved a PR in initial treatment with gefitinib and the interval from the cessation to re-treatment of gefitinib ranged from 6.5 to 11 months. Overall survival time of all cases ranged from 13.5 to 50 months, with a median survival time of 24.6 months. The median survival time after re-treatment with gefitinib was 7.4 months. Conclusion. Re-treatment with gefitinib is an alternative therapy for the patients who showed a favorable response to initial gefitinib therapy.

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Objective. In the radiation therapy of lung cancer, radiation pneumonitis (RP) is a clinically important adverse event. The usefulness of V20 (the percentage of lung volume receiving more than 20 Gy) and NTCP (normal tissue complication probability) obtained from the dose-volume histogram (DVH) are reported. In this study, we examined the usefulness of mean lung dose (MLD). It is of great benefit that MLD can follow the additivity rule; i.e. summation of more than 2 courses of radiation therapy. Materials and Methods. We enrolled 104 non-small cell lung cancer patients treated with more than 40 Gy thoracic radiotherapy, between October 2001 and December 2005. We analyzed the relationship either MLD, V20, or NTCP obtained from DVH and the incidence of RP. Results. RP developed as follows: Grade 0-1 in 70, Grade 2 or greater (moderate to severe RP) in 34. The averages of MLD, V20 and NTCP were greater in patients with Grade 2-3 RP than in patients with Grade 0-1 RP. Univariate and multivariate analysis also showed a significant relation between each parameter and the incidence of moderate to severe RP. Moderate to severe RP was not observed with a MLD of 13 Gy. Conclusion. MLD is a practical and valuable predicting factor for RP in Japan where more than 2 courses of radiation therapy are used.

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Objective. Pleuritis carcinomatosa, a terminal stage of lung cancer, requires the effective control of malignant effusion to maintain performance status. Methods. Nine patients with pleuritis carcinomatosa were treated by thoracoscopic talc pleurodesis. Practical procedure was as follows. #1. Complete removal of malignant effusion and safe needle puncture were secured by thoracoscopy. #2. Five to 10 grams of talc was sprayed manually. #3. Excellent placement of thoracic tubes at apex and costophrenic angle was possible by thoracoscopy. #4. The extubation of thoracic tubes were performed 7 days after the procedure. Perfect control of the effusion was obtained in all patients, although 1 of 9 patients died 50 days after the talc pleurodesis without discharge. Conclusion. Video assisted thoracoscopic surgery (VATS) pleurodesis by using talc effectively eliminated the malignant pleural effusion, although the procedure required general anesthesia with one lung ventilation. This procedure should be performed at the early stage of the lesion to maintain good performance status.

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Objective. In Niigata city, all processes of mass screening by photofluorography have been managed with high quality. We analyzed the results of mass screening and evaluate the efficacy of quality control. Methods. The results of lung cancer mass screening by photofluorography in Niigata city during the 15 years from 1989 to 2003 were analyzed. Results. The total screenings by photofluorography during 15 years was 237,741 (male/female: 0.30/0.70). In overall 25,713 (10.8%) abnormalities were detected, and 12,765 (5.4%) individuals were judged to need further examination, after comparative interpretation. In total, 12,378 (97.0%) individuals out of 12,765 underwent further examination, and 288 cases with lung cancer were detected (detection rate 121 per 100,000), excluding detected cases by only sputum cytology. Standardized detection ratio during 11 years, from 1989 to 1999, was 0.91 (male: 0.72, female: 1.39). Among 288 detected cases, clinical stage I cases were 224 (78%), resected cases were 220 (76%) and completely resected cases were 199 (69%). The 5-year and 10-year survival rates of all cases by Kaplan-Meier method were 65.1% and 58.0%. Conclusion. Indices of mass screening for lung cancer, detection rate, standardized detection ratio, proportion of early stage lung cancer, resection rate, survival rate, and others, were excellent compared with previous reports of the past. Even with mass screening for lung cancer by photofluorography, it was thought to be possible improve the results by high quality control.

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Objective. The therapeutic usefulness of the WHO classification of thymoma was evaluated. Methods. Fifty-one patients with thymomas (male: 30, female: 21) underwent a resection between 1990 to 2005 at this institution. These patients were categorized according to both the WHO classification and the Masaoka staging system. The patients with Type C thymomas were excluded from this study. Results. According to the WHO classification the 51 patients were categorized as Type A-1 patient (2.0%), AB-18 (35.3), B1-16 (31.4), B2-11 (21.6), B3-5 (9.8), while according to the Masaoka staging the classification was stage I-30 (58.8), II-7 (13.7), III-10 (19.6), IVa-3 (5.9), IVb-1 (2.0). The total number of patients with Type A, AB, and B1 accounted for 81.1% of patients with Masaoka stage I and II, Type B2 and B3 patients accounted for 64.3% of patients with Masaoka stage III and IV. The 5- and 10- year survival rates of the patients based on the WHO classification were as follows; Type A-100%, 100%, AB-100%, 90.0%, B1-88.9%, 88.9%, B2-83.3%, 41.7%, respectively, while in Type B3 the 4-year survival rate was 66.7%. The 5- and 10- year survival rates of the patients with groups of Type A/AB/B1 and Type B2/B3 were 95.7%, 89.7% and 77.4%, 38.7%, respectively. Although no significant difference in the survival rate was observed between the 2 groups, Type B2/B3 group tended to have a poor prognosis in comparison to the Type A/AB/B1 group. Tumor recurrence was identified in 6 (12.8%) out of 47 patients with a complete resection. Whereas 1 (2.9%) of 34 patients of Type A/AB/B1 showed a recurrence and the number of recurrent Type B2/B3 lesions was 5 (38.5%) of 13 patients. There was no prognositc difference between the groups of Type A/AB/B1 and Type B2/B3 according to Masaoka stages I and II. However, in Masaoka stage III and IV thymomas, the survival rate of the patients with Type B2/B3 was significantly poorer than that of Type A/AB/B1 (p=0.03). Conclusions. A distinction between the groups with Type A/AB/B1 and Type B2/B3 thymomas based on the WHO classification may be useful for predicting both recurrence as well as the prognosis in a resected thymoma. In addition, this grouping is considered to play a more important prognostic role in the patients with Masaoka stage III and IV thymomas than in those with stage I and II thymomas.

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Background. We report a rare case of small lung cancer incidentally detected during treatment of a spontaneous pneumothorax. Case. A 53-year-old man consulted a doctor for dyspnea in May 2006. He was referred our hospital for treatment of a left spontaneous pneumothorax, which was effectively treated by chest drainage. On chest computed tomography (CT), there was a subpleural nodule in the left S¹⁺² with visceral pleural indentation, which consisted of peripheral ground glass opacity and a central high-attenuation zone. We found slight enlargement of the central high-attenuation zone and definite pleural indentation 2 months later, although the size of nodule had not changed. In July 2006, a thoracoscopic biopsy yielded a diagnosis of adenocarcinoma, and a left S¹⁺²+S³ segmentectomy and lymphadenectomy were performed. Examination of the resected specimens revealed a well differentiated papillary adenocarcioma (pT1N0M0 stage IA). Conclusion. We often encounter cases of small lung cancer on advance CT finding, and it is necessary to examine CT carefully in order to find other lesions in patients with spontaneous pneumothorax. As peripheral ground glass opacity and a central high-attenuation zone suggest malignancy, detailed examinations should be performed when a small nodule has not decreased after observation.

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Background. Small cell lung cancer is highly sensitive to chemotherapy and radiation therapy. Standard therapies have been established for first line treatment. However, most cases develop relapse. To improve the prognosis, not only first line standard therapy but also second line standard therapy is very important. Case. A 74-year-old man was treated with 4 cycles of CDDP and CPT-11 therapy. Thereafter, he showed complete response (CR) and remained in remission till December 2005. During the middle of December 2005, he developed severe pain in the left femoral neck. Multiple bone metastases were detected by bone scintigram. He was considered to be in a sensitive relapse state because 12 months had passed since the last chemotherapy. However his Eastern Cooperative Oncology Group performance status (PS) at that time was 3 due to renal insufficiency as well as difficulty in eating and walking by himself. Considering these factors, we selected amrubicin monotherapy as second line therapy. After administration of amrubicin, the severity of pain quickly regressed. Bone scintigram after 4 cycles of amrubicin therapy demonstrated remarkable improvement of the multiple bone metastases. Furthermore maintaining CR for about 15 months following amrubicin therapy was observed. Conclusion. There have been some reports of a phase II trial showing the potential of amrubicin to be a standard second line therapy for small cell lung cancer. In these reports, there has not been any citation about improvement of multiple bone metastases or long term maintenance of CR. This case might be significant from the perspective of improving multiple bone metastases and maintaining CR for about 15 months following amrubicin therapy.

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In order to reduce cancer mortality by screening, it is first necessary, to evaluate the efficacy of cancer screening in terms of mortality reduction based on scientific evidence (cancer screening assessment), then to properly implement the screening for which efficacy has been already established (cancer screening management). The Japanese Research Group for Development of Cancer Screening Guidelines supported by Grand-in-Aid for Cancer Research from the Japanese Ministry of Health, Labour and Welfare fixed a standard procedure to develop cancer screening guidelines and updated the guideline for lung cancer according to this procedure. The group evaluated that "Chest X-ray for the non-high-risk group and chest X-ray combined with sputum cytology for high-risk group" was 2+ (moderate-quality case-control or cohort studies evaluating mortality reduction) as a level of evidence and B (fair evidence to recommend the service) for a level of recommendation. For "Low-dose CT", it is evaluated to be 2- (poor-quality case-control or cohort studies evaluating mortality reduction) and I (insufficient evidence to recommend for or against), respectively.

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Recently, the number of participants in lung cancer screening has been decreasing in Okayama Prefecture, which may lower the screening effects to improve lung cancer mortality and as a result many municipalities may stop lung cancer screening in the near future. In Japan, lung cancer screening has already been abandoned in 109 (5%) municipalities, since they considered that the effectiveness of lung cancer screening was inferior to that of screening programs for other cancers. In this report, we discussed the following issues in lung cancer screening today by analyzing questionnaires for bureaucrat responsible for lung cancer screening. Due to their insufficient knowledge about lung cancer, up-to-date information or cumulative knowledge was not efficiently used in screening. Though the bureaucrat understood the importance of quality control of screening, quality control was not included in the specification form for public bidding for selecting the screening agency. It was surprising that some officers understood neither the difference between tuberculosis screening and lung cancer screening nor the purpose of screening. These results indicate that these officers failed to explain the necessity of lung cancer screening for the community and emphasize the usefulness of selecting the appropriate agency with high accuracy for the financial manager. In conclusion, the bureaucrat responsible for lung cancer screening have to understand "cancer screening with high quality" in the nation's statement, and give equal opportunities for lung cancer screening to the community. The screening agency has the responsibility to increase the number of participation of individuals in lung cancer screening.

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Objective and Methods. The chairs of the official quality control committee for lung cancer mass screening program in every prefecture were sent questionnaires in September 2006, in order to evaluate how the quality control program worked. The interview focused on the quality of screening techniques and devices. Results. A total of 41 chairs (87%) answered the questionnaires. Many of them did not know precisely about techniques and devices of screening centers. This situation reflects the official report of the Ministry of Health and Welfare in 1997. On the other hand, a few prefectures began to manage the quality assurance program. Conclusion. Most of the official quality control meetings for prefectural lung cancer mass screening programs did not have substantial arguments about quality assurance, and did not control it. This situation should be improved.

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Objective. The problems of quality control of present lung cancer screening programs were clarified, and the direction for quality control in the future was examined. Method and Result. In comparison to breast cancer screening, it is more difficult for lung cancer screening to decrease variability in the quality of taking and interpreting chest radiograms taken for tuberculosis screening. The following method is devised as measures. I) Report of screening accuracy, II) Activity enhancement of the life-style related disease management conferences in the prefectures, III) Introduction of screening accuracy into contract requirements by municipalities and screening offices. Conclusion. It is necessary to inform the community of large about screening accuracy, and for bureaucrat in change to recognize that quality control is important.

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Asbestos is a generic term for 6 fibrous silicate minerals, whose extreme toxicities are closely related to its fibrous nature. With decreases in heavy occupational exposure to asbestos, pulmonary fibrosis, i.e. asbestosis, is waning in incidence, but asbestos-related pleural diseases including mesothelioma have been increasing in most industrialized countries. Mesothelioma, which has a strong etiological relationship with asbestos exposure, is increasing in incidence and is predicted to continue to increase into the next decade. Most asbestos exposure occurs via occupational exposure, therefore, mesothelioma rates are higher in those areas around industries utilizing blue asbestos, such as shipbuilding and asbestos factories. In June 2005, an asbestos factory in Amagasaki, Hyogo, documented a significant number of asbestos-related deaths among their employees as well as the residents who lived around the factory, which triggered social and medico-legal problems of asbestos-related diseases in Japan. A major concern is the cases without any proven occupational asbestos exposure, which represent 17% of the total cases. Are these mesotheliomas due to environmental exposure in the vicinity of asbestos factories or due to indoor exposure? In response, the Ministry of the Environment has initiated retrospective research on mesothelioma in Amagasaki, Hyogo, Sennan, Osaka, and Tosu, Saga to evaluate the potential effects of environmental exposure. Malignant mesothelioma is a highly lethal and particularly refractory tumor for which treatments have been far from satisfactory in achieving clinical responses. The diffuse nature of the disease makes it difficult for the surgeon to perform a radical resection, and combined modality treatments have been attempted in order to establish standard treatment for mesothelioma. Newer chemotherapeutic regimens, including pemetrexed and cisplatin combination, have shown encouraging response rates and survival benefits for mesothelioma. Multicenter clinical trials are planned in Japan for malignant pleural mesothelioma just now, which will lead to implementation of scientific mesothelioma register.

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Low-dose CT screening for lung cancer has become widespread, and while it is evident that it is sensitive for lung cancer detection, the very high false-positive rate has been problematic. In reported studies, 30-70% of subjects have at least one lung nodule on initial CT scans. However, only 2-3% of the detected nodules are malignant. Moreover, since CT screening has not yet been proved to help reduce mortality from lung cancer, guidelines for the diagnosis and follow-up of lung nodules detected on screening CT are very important. The cost-benefit effect must be considered in making these guidelines. In our country, the guidelines for the diagnosis and follow-up on single helical screening CT was developed by the Japanese Society of CT Screening in 2005. In this paper, we discuss about the problem of diagnosis and follow-up for lung nodules detected on low-dose CT screening based on these guidelines.

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For periodic medical screening of lung cancer by low dose computed tomography (CT), it is essential, for efficient and accurate CT examination of a large number of patients, to establish a new medical examination system. To attain this, we assessed the inclusion of a certified radiological technician in CT screening for lung cancer (CT screener) as a factor for "construction of a new medical examination model" in "a new medical examination model and of improvement in the efficacy of medical examination" (The Tsuchiya Group for construction of a new screening model and improvement in the screening efficiency). The results of the assessment are reported herein, with a discussion of future prospects. A person is qualified as a CT screener by qualification test after he/she receives professional training. Only a qualified physician for CT screening of lung cancer, which will be assessed in the future, can work as a CT screener. The work of a CT screener would include 3 aspects: first, imaging under optimum scanning conditions according to the needs of the individual patients, with the aim of reducing the exposure to radiation; second, supply CT images with the maximum image information to physicians; third, identification of pulmonary nodules on CT images during the primary image-reading. We aim for the establishment of a system which will allow wide-ranging CT screening with high accuracy by arranging 3 systems, including a qualified physician for CT screening of lung cancer, a qualified technical expert for CT screening of lung cancer, and a high-class facility for the treatment of lung cancer.

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Many problems hinder CT screening from being accepted throughout the world. These are efficacy and how much resource can be involved in CT screening. We proposed about the education and recognition in this symposium. We would like to examine it in detail at the committee of the combination about specialist's qualifications. We think that we should use e-learning for training to educate in remote places. We can easily evaluate the education results.

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Many studies have investigated the efficacy of repeated screening with low-dose helical CT for lung cancer, which would theoretically allow earlier detection. However, none of the published trials are controlled, and they have not yet proven a decrease in mortality. There are presently 4 ongoing randomized controlled trials. It is anticipated that some results of these trials will be published after 2009. Until then, we are compelled to estimate the efficacy of repeated CT screening on the basis of the results of case studies with no control groups. In such circumstances, the case study by the Anti-Lung Cancer Association has demonstrated the presence of a stage shift, for the first time, which is an indirectly suggested a decrease in lung cancer mortality. Moreover, the results of this case study has also suggested the possibility that the design of present randomized controlled trials did not possess enough detection power to prove a decrease in lung cancer mortality. Therefore, from now on, we have to recognize the necessity that, even if the results of randomized controlled trials are not positive, we should not simply conclude that the repeated CT screening is invalid. The validity of the trial design itself needs to be reexamined.

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[in Japanese]

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[in Japanese]

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