Objectives. The Japanese Clinical Practice Guidelines for Lung Cancer have been developed and updated several times according to the current evidence of clinical trials and meta-analyses. The Osaka Lung Cancer Study Group (OLCSG) conducted a questionnaire survey on the postoperative adjuvant chemotherapy for stage I-IIIA non-small cell lung cancer (NSCLC) since 2003. Methods. A questionnaire was sent to doctors at OLCSG member hospitals, and clinical data, such as the number of surgical resections for NSCLC and regimens of postoperative adjuvant chemotherapy for stage I-IIIA NSCLC, in 2003 (Group A), 2006 (Group B) and 2009 (Group C), and 2012 (Group D) were obtained. Results. The data of 5807 cases (2798 stage IA, 1282 stage IB, 718 stage II and 638 stage IIIA) in 4 groups were collected from 30 institutions (Group A-C) and 17 institutions (Group D). Adjuvant chemotherapy was performed in 10.0% of stage IA patients, 36.4% of stage IB patients, 45.6% of stage II patients, and 60.7% of stage IIIA patients. The rate of adjuvant chemotherapy in each stage of Groups B-D increased as compared with Group A. The postoperative chemotherapy regimens used included uracil-tegafur (UFT) in approximately 80% of stage IA and IB patients. While both platinum-based regimens and UFT were used at a similar rate (approximately 40%) in stage II and IIIA patients of Group A, the former was commonly used in more than 60% of stage II patients and in more than 70% of stage IIIA patients in Groups B-D. In particular, carboplatin (CBDCA) +paclitaxel (PTX) was mainly used in stage II-IIIA patients in Group B, whereas cisplatin (CDDP) +vinorelbine (VNR) was increasingly used in patients in Groups C-D. In addition, new platinum-based regimens and molecular target agents were interestingly applied through clinical trials in patients in Group D. Conclusions. The situation and regimen of postoperative adjuvant chemotherapy for stage I-IIIA NSCLC has significantly changed according to the developed and updated edition of the Japanese Clinical Practice Guidelines for Lung Cancer. Therefore, under the current developments of new anti-tumor agents or regimens, carefully selecting chemotherapy regimens according to a significant amount of evidence in clinical practice is necessary.

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Objective. The aim of this study was to prove the antiemetic efficacy of aprepitant in patients treated with a combined regimen of pemetrexed and carboplatin. Methods. A phase II trial of a combined regimen of carboplatin (AUC 6) and pemetrexed (500 mg/m²) was conducted. The two drugs were administered on day 1 and every 3 weeks thereafter. Aprepitant was not administered during the first course but was given as an additional treatment from the second course to 14 patients who experienced grade ≥2 nausea in the first course, in order to investigate its antiemetic efficacy. Results. There were 11 male and 3 female patients, with a median age of 62 years. Four patients had a performance status (PS) of 0, and 10 had a PS of 1. All of the cases were of adenocarcinoma. During the first course, grade 2 and 3 nausea occurred in 12 and 2 patients; grade 0, 1, and 2 vomiting, in 7, 6, and 1 patients; and grade 1, 2, and 3 anorexia, in 6, 6, and 2 patients, respectively. All of the cases corresponded to the delayed phase. During the second course, grade 0, 1, and 2 nausea occurred in 8, 2, and 4 patients; grade 0 and 1 vomiting, in 13 and 1 patients; and grade 0, 1, and 2 anorexia, in 7, 3, and 4 patients, respectively; which indicated a significant improvement. The severity of nausea, vomiting and anorexia decreased in 11 (78.5%), 13 (92.8%); and 8 (57.1%) patients, respectively. Conclusion. Aprepitant was an effective antiemetic in patients who were treated with pemetrexed/carboplatin and could be useful in the delayed phase.

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Objective. The University Hospital Medical Information Network (UMIN)-Clinical Trials Registry (CTR) is a unique web-based registry of clinical trials in Japan. Clinical trials must be registered to a public database when submitting to medical journals. We evaluated the current status of the publication of Japanese lung cancer clinical trials using the UMIN-CTR. Methods. We searched for trials that had been registered to the UMIN-CTR before October 2005 to identify publications associated with the trial results in the UMIN-CTR database. Forty-eight trials concerning lung cancer treatment were found. A final search for publications was performed using the PubMed and UMIN-CTR databases on December 2014. Results. Thirty-one (64.6%) trials were published. Among them, 16 showed positive results concerning primary endpoints and 15 had negative ones. There was no significant difference in publication rates according to the number of participants (≥100 and <100). The studies in which a planned final analysis date in the UMIN-CTR was described by an investigator were significantly more frequently published than those without this description (84.2% vs 51.4%, p=0.021). Conclusion. Approximately two-thirds of trials including negative trials have been published. The UMIN-CTR serves a function as the Japanese clinical trial registry.

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Background. In pulmonary cryptococcosis, solitary nodular shadows are sometimes noted in the lung, making it difficult to distinguish from lung cancer. We herein report our recent experience with two cases of pulmonary cryptococcosis in patients in whom a solitary nodular shadow in the lung was observed on a chest X-ray film. Cases. In Case 1, an abnormal shadow was detected during a health checkup. In Case 2, a shadow was detected on a chest X-ray film that was taken during an outpatient visit for hypertension. In both cases, chest computed tomography showed no daughter shadows, and the shadows with spiculation and pleural indentation tended to increase in size. Although lung cancer was suspected, the diagnosis was not confirmed by bronchoscopy. Surgical resection was thus performed, and a diagnosis of pulmonary cryptococcosis was established. The patients were treated with azole antifungal drugs for three months after surgery, and no recurrence has been observed to date. Conclusion. We experienced two cases of pulmonary cryptococcosis in which lung cancer was suspected. Surgical resection is considered to be useful for the diagnosis and treatment of cryptococcosis when lung cancer cannot be ruled out based on imaging and bronchoscopic findings.

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Background. Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a malignant epithelial tumor that is defined by the rearrangement of the NUT gene on chromosome 15q14. Tumors with NUT gene rearrangement have recently been recognized as NMC. The name is based on their location: they occur on the physical midline organs. The therapeutic approaches for NMC have not yet been established due to the rarity of the disease, and the tumor is known to be associated with a poor prognosis. Case. A 32-year-old man was admitted to our hospital with dyspnea and in a state of shock due to the presence of a huge mass and pleural effusion in the left lung. A thoracoscopic biopsy of the pleura led to a diagnosis of NMC with translocation of the t(15;19) gene and the BRD4-NUT fusion gene. The tumor rapidly increased in size, despite the provision of a combination chemotherapy regimen that consisted of carboplatin and paclitaxel. The patient died due to NMC, two months after the diagnosis. Conclusion. We experienced a case of NMC of the lung that was resistant to combination chemotherapy. NMC should be considered in cases that show anaplastic carcinoma when an immunohistochemical analysis reveals poorly defined characteristics.

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Background. Neuroendocrine carcinomas of the middle mediastinum are rare. Case. A 51-year-old woman with numbness of the extremities sought evaluation by a physician who referred her to our hospital for investigation of an abnormal shadow on a chest X-ray. Chest CT showed a mass of 72×52 mm in size, in the anterior and middle mediastinum. The mass was diagnosed as an undifferentiated carcinoma based on the results of an endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) biopsy. The primary tumor could not be found in a whole-body evaluation. After preoperative chemoradiotherapy, a middle mediastinal tumorectomy was performed. An immunohistochemical investigation revealed that the tumor was positive for synaptophysin, CAM5.2 and EMA and that it was negative for TTF-1. Thymic tissue could not be found around the tumor. The tumor was histopathologically diagnosed as large cell neuroendocrine carcinoma (pTxN2M0). No tumor recurrence has been observed in the 15 months since surgery. Conclusion. We reported a case of neuroendocrine carcinoma of the middle mediastinum that was differentially diagnosed from a thymic neuroendocrine tumor. It is difficult to preoperatively diagnose neuroendocrine carcinomas in the middle mediastinum. EBUS-TBNA may assist in the diagnosis of masses that occur in the middle mediastinum.

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Background. Large cell neuroendocrine carcinoma is rare disease that can be classified as a poorly differentiated neuroendocrine carcinoma of the thymic epithelium. Patient. A 68-year-old woman presented with an abnormal shadow on a chest radiograph. A chest computed tomography (CT) scan showed a well-defined mass shadow measuring 50×40 mm in the superior mediastinum. The tumor was completely resected through median sternotomy. The macroscopic findings of the resected specimen revealed that the tumor was 62×45×33 mm and that it had not infiltrated into other organs. The pathological findings revealed large tumor cells with neuroendocrine architectural features such as nesting, palisading, and rosette-like features. Immunohistochemical staining showed that the tumor was thyroid transcription factor-1-negative, chromogranin A-positive, and synaptophysin-positive. Based on the findings, the patient was diagnosed with large cell neuroendocrine carcinoma of the thymus. Partial extracapsular invasion was observed. Accordingly, the tumor was classified as stage II based on Masaoka's classification and stage II (T2N0M0) based on the WHO classification. After surgery, she received adjuvant chemotherapy (cisplatin+etoposide 4 courses), and she has been survived with no relapse for 17 months. Conclusion. There are few reports on thymic large cell neuroendocrine carcinoma. We should therefore continue to accumulate more cases to establish the optimal method of treatment.

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Background. Leukoencephalopathy is a pathological status associated with multifocal demyelination of cerebral white matter. The successful advancement of anticancer therapies has resulted in survivors who suffer from leukoencephalopathy caused by anticancer drugs and cranial irradiation. Case. A 74-year-old man, who was diagnosed with limited disease small cell lung cancer of the right upper lobe, underwent cisplatin and irinotecan chemotherapy. The therapy was discontinued due to severe anemia. Complete response to chemotherapy allowed the patient to be observed with treatment only for anemia. After 15 months of observation, relapse was detected in the cranium. Whole-brain irradiation of 30 Gy in 3 Gy fractions was performed. Three months after irradiation therapy, the patient suffered from leukoencephalopathy. He has remained alive for seven months after discharge with no recurrence of lung cancer, while his activity of daily living (ADL) has deteriorated gradually. Conclusion. When patients with a previous history of chemotherapy exhibit severe adverse events or worsened performance status, the dose fractionation method should be selected in consideration of neurotoxicity, which can develop early after irradiation.

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Background. During the administration of EGFR-TKI, the appearance of interstitial pneumonitis should be noted. Case. An 81-year-old woman with adenocarcinoma of the lung, which expressed an EGFR point mutation, was administered gefitinib. However, she developed resistance to gefitinib, and therefore, the drug was switched to afatinib. Before the switch, a faint ground-glass opacity was observed in the right middle and lower lobe, which worsened after the treatment change. Subsequently, according to the findings obtained with Grocott's staining of lung biopsy tissue and positivity for serum Cryptococcus antigen, the patient was diagnosed with pulmonary cryptococcosis. Conclusion. If abnormal shadows on lung radiographs cannot be conclusively identified at the time of the differential diagnosis, then a lung biopsy should be actively performed, and further treatment should be decided only after making a definitive diagnosis.

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