Objective. Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a key drug in the treatment of EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). Gefitinib treatment is often associated with skin and mucosal toxicities, and liver dysfunction. There have been few reports on the efficacy and safety of gefitinib in elderly patients with EGFR mutation-positive advanced NSCLC. Methods. We retrospectively assessed the efficacy and safety of gefitinib in 52 patients with EGFR mutation-positive advanced NSCLC who were 70 years of age or older and who were treated with gefitinib (250 mg, once daily). In addition, we compared the efficacy and safety in patients who were 70 to 79 years of age with that in patients who were 80 years of age or older. Results. The study population included 52 patients (35 [67%] were females and 13 [25%] were performance status of ≥2). All of the patients had adenocarcinoma. The median age was 75 years (range, 70-89 years) and 15 patients (29%) were 80 years of age or older. The response rate was 73.1% (95% confidence interval, 59.0 to 84.4%) and the disease control rate was 90.4% (95% confidence interval, 79.0 to 96.8%). The median progression-free survival time was 10.7 months (range, 0 to 36 months) and the median survival time was 23.1 months (range, 0 to 66 months). The common adverse events were skin toxicities (51%), liver dysfunction (33%), and diarrhea (25%). Two patients (4%) died of gefitinib-related interstitial lung disease. The dose of gefitinib was reduced in 16 patients (31%) and gefitinib treatment was discontinued in 11 patients (21%) due to toxicities, mainly skin rashes and liver dysfunction. The response rates, survival rates, the incidence of adverse events, and the rates of dose reduction or gefitinib discontinuation did not differ between the two age groups. Conclusion. Gefitinib treatment is effective for elderly patients with EGFR mutation-positive advanced NSCLC; however, approximately half of the patients required a dose reduction or the discontinuation of gefitinib treatment due to toxicities. It is important for elderly patients to be treated with a suitable dose of gefitinib.

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Objective. According to the Clinical Cancer Guidelines for lung cancer, which were established by the Japan Lung Cancer Society, lobectomy is recommended for patients with clinical stage IA non-small cell lung cancer (NSCLC). Although patients who are poor candidates for lobectomy may be offered limited resection or stereotactic body radiotherapy (SBRT), there are few reports comparing the prognosis of patients undergoing these therapeutic modalities. We herein performed a retrospective analysis to compare the therapeutic efficacy of limited resection with that of SBRT in patients with clinical stage IA NSCLC who were ineligible for lobectomy. Methods. Patients who underwent limited resection or SBRT for clinical stage IA NSCLC from January 2009 to March 2015 were included in the present study. Results. Twenty patients underwent limited resection (all patients received wedge resection), and 20 patients underwent SBRT. The mean follow-up period was significantly longer in the limited resection group (limited resection, 1385 days; SBRT, 851 days; P<0.01). The mean age of the patients in the SBRT group was significantly older (73.9 years versus 78.9 years; P=0.05), and the Eastern Cooperative Oncology Group performance status (0/1/2) of the SBRT group was significantly poorer (5/14/1 versus 0/15/5; P=0.02). There were no significant differences between limited resection and SBRT regarding the 5-year local control rate (84.4% versus 77.8%; P=0.82), the 5-year disease free survival rate (73.2% versus 45.7%; P=0.14), or the 5-year overall survival rate (82.5% versus 50.6%; P=0.14). Conclusions. Our results suggest that limited resection and SBRT have a degree of therapeutic efficacy for patients with clinical stage IA NSCLC who are ineligible for lobectomy. However, a randomized trial is still needed to determine the standard therapy for these patients.

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Background. Thymic carcinoma is a cause of a cancer-associated dermatomyositis. Case. A 73-year-old female was referred to our hospital with sudden-onset dermatitis and was diagnosed with dermatomyositis. Since steroid therapy was accompanied by the waxing and waning of the patient's skin symptoms, cancer-associated dermatomyositis was suspected. Chest computed tomography revealed a lobular anterior mediastinal tumor of 42 mm in diameter with mediastinal and supraclavicular lymphadenopathy. Thymectomy with resection of the invaded pericardium and left brachiocephalic vein and lymphadenectomy were performed via median sternotomy. A pathological examination revealed a poorly differentiated squamous cell carcinoma of the thymus with metastatic lymph nodes (pT1aN2M0, stage IVb). Although the clinical symptoms of dermatomyositis were ameliorated soon after resection, the patient's skin rashes worsened after the recurrence of thymic carcinoma. Conclusion. The abrupt development of symptoms and the remission of skin symptoms in response to the therapeutic process were helpful as evidence of thymic cancer-associated dermatomyositis.

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Background. Although the incidence of lung cancer in patients with human immunodeficiency virus (HIV) infection is increasing, the clinical course of lung cancer in HIV-infected patients is poorer than that seen in HIV-negative patients. Case. A 63-year-old man was referred to our hospital for further examination of a mass shadow detected on chest radiography. He was given a diagnosis of HIV infection during preoperative examinations. Highly active antiretroviral therapy was started at that time. By a percutaneous CT-guided fine-needle biopsy, the tumor was determined to be adenocarcinoma. The patient was clinically diagnosed with cT1bN0M0 stage IA disease and underwent right upper lobectomy with systematic lymph node dissection. The postoperative pathological diagnosis was solid adenocarcinoma (pT1bN1M0 stage IIA). His postoperative course was uneventful. Following surgery, the patient received 6 cycles of carboplatin (CBDCA) and vinorelbine (VNR) combination therapy. He is currently being followed up for 53 months after surgery. Conclusion. The result of surgical treatment and adjuvant chemotherapy following surgery in lung cancer patients with HIV infection are satisfactory as long as the performance status, organ functions and immunological status remain good.

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Background. Paraneoplastic neurological syndrome is a neurological disorder associated with various malignancies and is considered to be caused by autoimmune mechanisms, but not by symptoms due to tumor progression itself. Small cell lung cancer is the most common type of malignancy accompanied with paraneoplastic neurological syndrome. Case. A 77-year-old male was referred to our hospital for further examination of general fatigue, gait disturbance and dysuria. On admission, diverse neurological symptoms, such as dysarthria, dysphagia, motor and sensory disturbance in lower extremities and autonomic dysregulation, were observed. Further examination yielded the diagnosis of Lambert-Eaton myasthenic syndrome with positive results for anti-amphiphysin and anti-ganglioside antibodies. Swelling of the mediastinal lymph nodes and elevated ProGRP were detected, and a definitive diagnosis of small cell lung cancer (cTXN2M1b: Stage IV) was made. As the administration of intravenous immunoglobulin failed to ameliorate his neurological symptoms and general condition (PS 4), we determined that there were no indications for chemotherapy. He was subsequently transferred to a palliative care hospital and died nearly one year after the development of his initial symptoms. Conclusion. We experienced a case of small cell lung cancer with diverse neurological symptoms due to the presence of paraneoplastic neurological syndrome.

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Background. The standard therapy for limited stage small cell lung cancer (SCLC) is chemoradiation. Although it is considered to be highly responsive to initial therapy, SCLC usually becomes drug resistant and recurs. The pathological changes that occur at the time of the acquisition of drug resistance have not been reported. On the other hand, it is reported that surgical excision may improve the survival rate of patients with stage IA SCLC. Case. A 75-year-old man was referred to our department for a nodular shadow of the right middle lobe that was pointed out in an examination prior to surgery to repair an abdominal aortic aneurysm. He was diagnosed with stage IA SCLC on the basis of bronchoscopy and radiological examinations. The tumor went into almost complete remission after 4 courses of chemotherapy with carboplatin and etoposide. However, the tumor recurred eight months later. He was again diagnosed with stage IA SCLC by bronchoscopy and radiological examinations. The same chemotherapy was repeated but was stopped after 2 courses due to poor tolerability. He underwent right middle lobectomy, followed by prophylactic cranial irradiation. He has now been under observation without recurrence for 3 years. Pathological examinations were performed three times in the clinical course of the present case. The bronchoscopic biopsy specimen taken just before the second chemotherapy was almost the same as that taken before the first chemotherapy. However, the surgically removed tumor showed highly atypical features with multiple mitotic figures and rosette formation. Conclusion. Curative surgery can be performed in some patients in which yc-stage IA SCLC recurs after chemotherapy and acquires drug resistance.

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Background. In cases of lung cancer accompanied by multiple pulmonary nodules, it is important to determine whether or not the nodules are intrapulmonary metastasis from the primary tumor. Pulmonary angiomyolipoma (AML) is a rare disease that is occasionally accompanied by lymphangiomyomatosis (LAM), which sometimes exhibits pulmonary nodules. Case. The patient was a 65-year-old woman who had undergone right nephrectomy due to a renal AML rupture at the age of 33. A pulmonary nodule was observed in the mid-lung field on a chest X-ray at the age of 65. Chest computed tomography (CT) revealed an irregularly-shaped nodule with a maximum diameter of 1.9 cm in the lingula of the left lung as well as bilateral multiple small nodules with a homogeneous fat density and cysts. Fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated FDG accumulation in the nodule in the lingula but not in the other nodules. The CT attenuation values of the multiple small nodules were consistent with the value of fat. These results, as well as patient's history of renal AML, suggested primary lung cancer accompanied by pulmonary AML. Surgery was performed. After partial resection, the multiple small nodules were diagnosed, based on the intraoperative examination of frozen sections, as lipomas and the single nodule in the lingula was diagnosed as an adenocarcinoma. A left upper lobectomy with lymph node dissection (ND2a-1) was performed. A pathological examination revealed stage IA pulmonary adenocarcinoma (T1aN0M0). In addition, an immunohistochemical analysis revealed estrogen receptor (ER), α-smooth muscle actin and Melan-A positivity. The multiple small nodules were therefore diagnosed as AML, while the cystic lesions were diagnosed as LAM. Conclusion. We report a very rare case of lung cancer coexisting with pulmonary AML and LAM. A precise diagnosis is important in cases where lung cancer is accompanied by multiple pulmonary nodules, in order to distinguish the primary lung tumor from pulmonary metastasis. In our case, the CT attenuation values and FDG-PET were useful for the differential diagnosis.

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Background. Therapeutic options for lung cancer with anaplastic lymphoma kinase (ALK) fusion gene are limited, however, crizotinib is a promising molecular-targeted drug. We herein experienced a case in which desensitization therapy for crizotinib-induced drug allergy enabled us to continue cancer treatment. Case. A 63-year-old woman experienced disease recurrence after thoracic operation for lung cancer. Lung adenocarcinoma involved the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Therefore, we administered treatment with crizotinib 250 mg twice a day. During treatment with crizotinib, a high fever, rash, and liver dysfunction developed. Therefore, we discontinued crizotinib treatment. After recovery from the side effects due to crizotinib, we challenged the patient with desensitization therapy with crizotinib. Desensitization enabled us to continue treatment without apparent complications. In addition, a treatment response to crizotinib was observed during desensitization therapy. Conclusion. When patients experience serious complications due to treatment with crizotinib, desensitization therapy might be an effective treatment option.

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Background. The clinical use of 3rd generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has become more important in the treatment of patients in whom T790M mutations are detected. At present, however, bronchoscopic re-biopsy is not widely conducted. We report three cases of bronchoscopic re-biopsy in patients with EGFR-mutant adenocarcinoma. Case Reports. Cases 1 and 2 were classified as stage IV (EGFR mutation: exon19 deletion), while case 3 was classified as stage I (EGFR mutation: exon21 L858R point mutation) with poor lung function and multiple ground-glass nodules (GGNs) at other lobes. All patients received EGFR-TKI as a 1st line therapy. The treatments were discontinued due to disease progression, and subsequent bronchoscopic re-biopsies of the primary lesions were performed. Case 1: EBUS showed curved echoes around the access bronchus, making it difficult to collect a tissue sample with a forceps. The cytological diagnosis confirmed class V with an exon19 deletion, without a T790M mutation; the histopathological diagnosis was negative. Case 2: EBUS revealed the guide-sheath adjacent to the target lesion. However, both the cytological and histopathological results were negative. Case 3: EBUS showed the target lesion, but the number of procedures was reduced due to bleeding. Although exon21 L858R and T790M mutations were detected from the cytological sample, the histopathological results were negative. Conclusion. Bronchoscopic re-biopsy appears to be difficult due to pathological tissue changes and tumor shrinkage after treatment. The targeted lesion and diagnostic procedures should be carefully selected in response to each case.

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Background. Granulocyte-colony-stimulating factor (G-CSF)-producing lung cancer is associated with a poor prognosis. Case. Case 1: A 68-year-old man was admitted to our hospital due to bloody sputum and arthralgia in his right shoulder. A large mass was identified in his right upper lobe. It was diagnosed as lung cancer (poorly-differentiated non-small cell, stage IV) by CT-guided needle lung biopsy. Although he received systemic chemotherapy, the disease progression was not controllable. He died 3 months after the diagnosis. Case 2: A 64-year-old man presented with an invasive lesion in the right lower lobe. It was diagnosed as lung cancer (adenocarcinoma, stage IIB). Although partial pneumonectomy and lymph-adenectomy were performed, the postoperative pathology showed vessel invasion of the chest wall. Despite the administration of systemic chemotherapy, the patient's the disease progression was not controllable. He died 7 months after the diagnosis. Serum examinations revealed that both cases had leukocytosis and a high concentration of G-CSF. In addition, the tumor cells were positively stained with anti-recombinant human G-CSF monoclonal antibody. Conclusion. Further investigation is therefore necessary to elucidate the prognosis of G-CSF producing lung cancer.

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Objective. The aim of this paper is to learn about the pitfalls in lung nodule detection on a posteroanterior chest radiographs, to understand the imaging findings of mimicking lung nodules, and to reveal various types of pseudolesion. Methods. Many cases that I have experienced are shown and outlined. Results. Various pitfalls in the diagnosis of chest radiographs are included, such as a lung nodule overlapped by a lung apex, an underdiaphragm, and a mediastinum. We should be aware of the findings that mimic lung nodules, such as the ossification of the first rib cartilage, nipple shadows, apical opacity, azygos lobes, bone islands, and osteophytes. Pseudolesions include normal variants such as pericardial fat pads, aortic nipples, rib anomalies, deformation of the normal anatomical structures, the shadow of an object on the skin, and characteristic chest X-ray shadows. Conclusion. It is important to be aware of the many pitfalls on chest radiographs, the findings that mimic lung nodules, and pseudolesions. This will enable the precise diagnosis of lung nodules on chest radiographs.

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Lung cancer, which has a poor prognosis, is the leading cause of cancer death in Japan. Because the symptoms are minimal in the early stages of this cancer, most patients are diagnosed after they have reached an advanced stage and mainly receive chemotherapy. EGFR gene mutation and the ALK fusion gene are representative driver mutations in lung cancer and are the target of molecular target drugs. Genetic testing is essential for anti-cancer drug selection in patients with lung cancer because molecular target drugs are very effective for patients with genetic abnormalities. Lung cancer treatment has entered a new era of personalized medicine in which drugs are tailored to individual genetic abnormalities.

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