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がん進展制御研究所, EML4-ALK lung cancer accounts for approximately 3-7% of non-small-cell lung cancer cases. To investigate the molecular mechanism underlying tumor progression and targeted drug sensitivity/resistance in EML4-ALK lung cancer, clinically relevant animal models are indispensable. In this study, we found that the lung adenocarcinoma cell line A925L expresses an EML4-ALK gene fusion (variant 5a, E2:A20) and is sensitive to the ALK inhibitors crizotinib and alectinib. We further established highly tumorigenic A925LPE3 cells, which also have the EML4-ALK gene fusion (variant 5a) and are sensitive to ALK inhibitors. By using A925LPE3 cells with luciferase gene transfection, we established in vivo imaging models for pleural carcinomatosis, bone metastasis, and brain metastasis, all of which are significant clinical concerns of advanced EML4-ALK lung cancer. Interestingly, crizotinib caused tumors to shrink in the pleural carcinomatosis model, but not in bone and brain metastasis models, whereas alectinib showed remarkable efficacy in all three models, indicative of the clinical efficacy of these ALK inhibitors. Our in vivo imaging models of multiple organ sites may provide useful resources to analyze further the pathogenesis of EML4-ALK lung cancer and its response and resistance to ALK inhibitors in various organ microenvironments. © 2015 The Authors.

The efficacy of postoperative radiotherapy (PORT) for thymic epithelial tumors is still controversial. Using the Japanese Association for Research on the Thymus (JART) database, this study was aimed at clarifying the efficacy of PORT for Masaoka stage II and III thymic carcinoma and thymoma.

Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

Background. Treatment of tracheostenosis after tracheostomy in pediatric patients is often difficult. Mucopolysaccharidosis is a lysosomal storage disease that may induce obstruction of the airways. Case Presentation. A 16-year-old male patient underwent long-term follow-up after postnatal diagnosis of type II mucopolysaccharidosis. At 11 years of age, tracheostomy was performed for mucopolysaccharidosis-induced laryngeal stenosis. One week prior to presentation, he was admitted to another hospital on an emergency basis for major dyspnea. He was diagnosed with tracheostenosis caused by granulation. The patient was then referred to our institution. The peripheral view of his airway was difficult because of mucopolysaccharidosis-induced tracheomalacia. For airway management, a mediastinal tracheostoma was created with extracorporeal membrane oxygenation. To maintain the blood flow, the skin incision for the mediastinal tracheal hole was sharply cut without an electrotome. The postoperative course was uneventful, and the patient was weaned from the ventilator on postoperative day 19. He was discharged 1.5 months postoperatively. Although he was referred to another institution because of respiratory failure caused by his primary disease 6 months postoperatively, his airway management remained successful for 1.5 years postoperatively. Conclusion. Mediastinal tracheostomy was useful for treatment of tracheostenosis caused by granulation tissue formation after a tracheostomy.

目的.切除可能悪性胸膜中皮腫の手術成績向上のためには集学的治療が必要であるが,その至適治療法は確立していない.術前化学療法,手術および術後放射線治療からなる集学的治療のコンプライアンスと安全性を検証するために前向き臨床試験立案を計画した.研究計画.文部科学省科学技術振興調整費"アスベスト関連疾患への総括的取り組み"の一環として,臨床試験が計画された.結果.多施設共同のfeasibility試験が承認され,現在開始された.適格症例は,シスプラチンとペメトレキセドによる化学療法を3コース行った後に胸膜肺全摘除術と術後の放射線治療により治療される.主要評価項目は完全切除率と治療関連死亡率であり,向こう3年間で40例の適格症例の本臨床試験への参加が期待されている.結論.本臨床試験の完遂により切除可能胸膜中皮腫に対する集学的治療のfeasibilityが確認されれば,引き続いて臨床的有効性を検証する第II相試験へ進む予定である., Objective. Multimodality therapy is essential to improve surgical outcomes of potentially resectable malignant pleural mesothelioma (MPM), but optimal treatment has not yet been established. To assess compliance and safety of a multimodality therapy consisting of preoperative chemotherapy, surgery and postoperative radiation, a prospective clinical study is planned. Method. We conducted this prospective study as a project of the "Comprehensive approach of asbestos-related diseases" supported by the "Special Coordination Fund for Promoting Science and Technology of the MEXT of Japan". Results. A multi-institutional feasibility study was approved and is now ongoing. Eligible patients will be treated with 3 cycles of chemotherapy using cisplatin and pemetrexed, followed by extrapleural pneumonectomy and postoperative hemithoracic radiation. Primary endpoints are the rate of complete resection and the mortality rate. The expected number of eligible patients participating in the study is 40 during the next 3 years. Conclusion. When this study is completed and the feasibility of multimodality treatment for resectable MPM is confirmed, a phase II study to assess the efficacy may be planned.

Pulmonary ground-glass opacity (GGO) nodules, which do not grow remarkably, are often observed without treatment. Lung tumors coexisting with inflammation and infection are difficult to diagnose. In this paper, we describe a very rare case of a pulmonary mixed GGO nodule with pleural dissemination. In 67-year-old female, chest computed tomography (CT) showed a mixed GGO nodule that had not grown remarkably in the right lung. For 6 years, the mixed GGO had been treated as nontuberculous mycobacterial infection. She was referred to our department for further investigation of the mixed GGO. We suspected lung cancer and performed lung segmentectomy. The tissue showed pleural dissemination. Coexisting nontuberculous mycobacteria (NTM) delayed the clinical diagnosis. Peripheral lung nodules should be resected or diagnosed as soon as possible, despite manifesting as a slow growth.

背景.平成18年度文部科学省科学技術振興調整費「アスベスト関連疾患への総括的取り組み」の一環として,我が国における悪性胸膜中皮腫に対する集学的治療の現状を調査した.対象と方法.2002年1月?2006年12月の5年間に悪性胸膜中皮腫に対して胸膜肺全摘術(EPP)を完遂した症例のみを対象とした.アンケートは本プロトコールへの参加表明施設とJCOG参加施設の計69施設に送付し,うち61施設から返答を得た.結果.対象5年間にEPPを完遂した症例は計171例,男性/女性154例/17例,右/左91例/80例,年齢14?78歳,平均59歳.手術後30日以内の死亡は1例(間質性肺炎),在院死は6例(腫瘍再発4例.MRSA膿胸1例,肺梗塞1例).シスプラチンを含む術前化学療法を行った症例は38例,うち12例ではシスプラチンを含む術前化学療法と術後片側全胸郭照射を完遂した.術後生存期間の中央値は23ヶ月であった.結論.我が国の悪性胸腹中皮腫に対するEPPは症例数の増加と安全性の改善が確認された.しかし,集学的治療のfeasibilityに関しては現時点でなお十分なデータが存在しない., Background. We investigated the current status of multi-modality treatment for malignant pleural mesothelioma in Japan as part of the campaign entitled "Comprehensive Strategy Against Asbestos-related Diseases" , which was funded by the 2006 Special Coordination Fund for Promoting Science and Technology from the Japan Science and Technology Agency. Methods. We evaluated cases of extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma between January 2002 and December 2006. A questionnaire was sent to a total of 69 institutions, and was returned by 61 of them. Results. A total of 171 patients underwent EPP for malignant pleural mesothelioma during the study period. They consisted of 154 males and 17 females, and the age ranged between 14 and 78 with the average of 59. The side of EPP was on the right in 91 and on the left in 80 cases. One postoperative death due to interstitial pneumonia and 6 in-hospital deaths due to tumor recurrence (n=4), MRSA empyema (n=1), and pulmonary infarction (n=1) were noted. Preoperative chemotherapy with cisplatin was given in 38 patients, and 12 out of 38 underwent postoperative hemithorax radiation therapy. The median survival was 23 months. Conclusions. The present study showed an increase of cases and also improvement of surgical mortality of EPP for malignant pleural mesothelioma in comparison with former studies. However, we still do not have clinical evidence regarding the feasibility of multi-modality treatment for malignant pleural mesothelioma.