Objective. To clarify the usefulness of assessing T790M status in non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) gene mutations at the time of acquiring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) resistance. Methods. Of 93 primary non-small cell lung cancer patients with EGFR mutations at the primary site treated in our institution over the last 6 years, 16 were assessed for the T790M mutation. The location and method of detecting T790M, frequency of this mutation, and response to a second EGFR-TKI were retrospectively analyzed. Results. The localization of EGFR mutations in the primary site was G719C in 1, G719C+L858R in 1, exon 19 deletion in 6, and L858R in 8, respectively. Locations of T790M were neck lymph nodes in 4 patients, mediastinal lymph node in 1, pleural effusion in 6, cerebrospinal fluid in 1, and lung tumor in 4. T790M was detected in 6 out of 16 cases (38%). The same EGFR mutations as in the primary site were detected in the other 10 cases. Eleven patients were treated with readministration of EGFR-TKI. Cases without T790M (n=8) showed significantly longer progression-free survival (PFS) than those with T790M (n=3) (median PFS: 15.0 months vs. 1.0 month, p=0.009). Conclusions. Screening for T790M in non-small cell lung cancer at the time of acquiring EGFR-TKI resistance is useful for selecting patients who will respond to EGFR-TKI readministration.

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Background. With the advent of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients, causes of death from a wide variety of cancers have recently been increasing among this population in the United States and Europe. However, few reports have described patients with HIV who have been suffered from non-AIDS-defining cancer and undergone surgery for lung cancer in Japan. Cases. Case 1: A man in his 50s who was suffering from HIV infection from a month before his admission was given a diagnosis of lung cancer of the right upper lobe. His clinical stage was T2aN0M0. We performed video-assisted thoracoscopic surgery (VATS) lobectomy of right upper lobe and mediastinal lymph node dissection. Pathological diagnosis was adenocarcinoma (pT2aN2M0). The patient then received 4 cycles of adjuvant chemotherapy with cisplatin/vinorelbine. He has been well with no evidence of cancer recurrence for 10 months. Case 2: A man in his 70s was found to have lung cancer of the left upper lobe. His lung cancer clinical stage was T2bN0M0. He had a 20 year history of HIV infection, and underwent VATS lingular segmentectomy and mediastinal lymph node dissection because surgery was restricted by his low respiratory function. The pathological diagnosis was adenocarcinoma (pT3N2M0). Following surgery, the patient received 4 cycles of adjuvant chemotherapy with cisplatin/gemcitabine. However, intrapulmonary metastases appeared 10 months later. He has since been treated using docetaxel. Conclusion. We think that surgical treatment can be recommended for resectable lung cancer patients with HIV infection like non-HIV infectious cases. Adjuvant chemotherapy following surgery for non-small cell lung cancer was safe in these cases. However several points have not yet been established like drug interactions between antiretroviral agents and antitumor agents or adaptation for chemotherapy. The results of surgery in patients with HIV infection are satisfactory with these treatments as long as performance status, organ functions and immunological status remain good.

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Background. In mesothelioma, there are no clinically specific tumor markers, and it is difficult to evaluate an effective therapy from serum markers. Case. A 64-year old man presenting with general malaise and abdominal distension was admitted for observation showed elevated serum CRP, and ascites recognized by abdominal ultrasonography. The patient showed continuing high fever, and high levels of WBC and CRP, and was scheduled for diagnostic laparoscopy. A laparoscopic examination revealed a peritoneal tumor, and epithelial mesothelioma was observed histopathologically from the biopsy finding. This case was diagnosed as malignant thoracoabdominal mesothelioma, because thoracoabdominal enhanced CT showed abdominal mass, ascites, diffuse peritoneal thickening of 30-50 mm, and abnormal pleural thickening along the diaphragm. The antitumor drugs, pemetrexed and cisplatin were prescribed and while effective in reducing the volume of ascites, showed no effect on the thoracoabdominal thickening. Serum IL-6 level was high, and IL-6 antibody staining was positive. An IL-6-producing tumor was diagnosed and IL-6 production was thought to be accompanied by the onset of leukocytosis, thrombocytosis, elevated CRP levels, and fever. STAT3 antibody staining was positive, indicating the JAK-STAT pathway. Conclusion. The serum IL-6 level in this case was considered reflective of therapeutic efficacy.

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Background. Pulmonary malignant lymphoma is a rare disease. Diagnosis is difficult since it has various manifestations. Case. A 56-year-old man was referred to our hospital because a nodule on chest X-ray. Chest CT showed a nodule with a cavity in the left upper lobe. Lung cancer was suspected and he was operated on diagnosis and treatment. The resected specimen was diagnosed as pulmonary malignant lymphoma. After surgery he received chemotherapy. He is alive without any evidence of recurrence. Conclusion. We report a surgical case of pulmonary malignant lymphoma with cavity, and review some case reports. Pulmonary malignant lymphoma presents various manifestations; therefore, it should be included in the differential diagnosis of nodules. For a nodule with a suspicious of malignancy, surgical resection can be one of choices for histopathological diagnosis and treatment.

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Background. The safety and efficacy of salvage surgery of locally advanced non-small cell lung cancer (LA-NSCLC) with local recurrence after chemoradiotherapy is not established. However, a small number of patients were treated with salvage surgery according to our experience. Case. A 58-year-old man visited his local hospital complaining of cough. A chest X-ray revealed a right upper mediastinal mass and a left hilar mass. He was referred to our hospital and primary squamous cell carcinoma of the left upper lobe was diagnosed. The staging was T2aN3M0 (IIIB). He received concurrent chemoradiotherapy consisting of 6 cycles of carboplatin and paclitaxel with conventional radiation therapy of 60 Gy. Two and half years later, progression of primary lung tumor was observed. During the second line treatment with gemcitabine and vinorelbine, massive hemoptysis required emergency admission. CT showed a tumor with a cavity adjoining the left pulmonary artery. To prevent recurrence of hemoptysis, he received complete left pneumonectomy with a patch plasty of the pulmonary artery, salvage surgery under cardiopulmonary bypass. He is disease-free after more than 5 years. Conclusion. Although the role of salvage surgery for locoregional recurrence of LA-NSCLC after effective chemoradiotherapy needs further investigations, salvage surgery can offer a potential for long-term survival in some cases.

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Background. Good syndrome is a disease entity of thymoma complicated with hypogammaglobulinemia. It is therefore important to prevent and control infections. Case. A 75-year-old Japanese man was admitted to our hospital to evaluate a mediastinal enlargement on chest radiograph. His computed tomography and magnetic resonance imaging findings raised suspicions of thymoma, and a thymectomy was performed. Pathological findings revealed World Health Organization (WHO) classification type A thymoma. Four years after thymectomy, he started to complain of symptoms of productive cough and purulent sputum. In spite of several antimicrobial treatments by a family doctor, his respiratory symptoms and chest X-ray findings deteriorated. He was then introduced to our hospital. At the second visit, his chest and sinus computed tomography showed diffuse pulmonary centrilobular nodules and bilateral maxillary sinusitis, and the initial diagnosis was sinobronchial syndrome. He also showed hypogammaglobulinemia, was negative for HLA-B54 and B-lymphocytes were absent in peripheral blood, therefore, Good syndrome was finally diagnosed. Long-term administration of clarithromycin improved his clinical respiratory symptoms and chest radiological findings. Conclusion. We present a case of Good syndrome diagnosed long after thymectomy and also successfully treated with long-term macrolide treatment. Physicians and surgeons should keep in mind that Good syndrome can occur long after thymectomy, and early evaluation of humoral immunity and radiological examination of upper and lower respiratory tracts is important to diagnose this disease.

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Background. A diagnosis of metastatic small intestine tumor in patients with lung cancer is difficult. There are several reports of diagnosis by double-balloon enteroscopy (DBE). Case. A 62-year-old man was admitted because of melena and severe anemia. Chest X-ray also revealed an abnormal pulmonary mass, suggesting lung cancer. Upper and lower gastrointestinal tract endoscopic findings failed to identify the bleeding source. As a result of capsule endoscopy and DBE showed the protruding lesion with an ulcer in the upper jejunum. The histological findings revealed atypical cell, it was poorly differentiated adenocarcinoma with positive for thyroid transcription factor-1 (TTF-1) and PE10 by the examination of immunostaining. Thus, he was diagnosed as primary lung cancer with metastasis to the small intestine. The patient was treated with 4 cycles of cisplatin and pemetrexed combination chemotherapy. Gastrointestinal symptoms were absent throughout the course. The pulmonary disease was not changed. Re-examination by DBE showed decrease of the lesion in the upper jejunum after the chemotherapy, resulting in reduced anemia despite no blood transfusions. Conclusion. This is the first report indicating that DBE is useful for the diagnosis and observation of metastatic small intestine tumors in patients with lung cancer.

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Background. The efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) depends on EGFR-mutation status in patients with non-small cell lung cancer (NSCLC). According to some reports, NSCLC patients with EGFR-wild-type tumor have a favorable clinical response to EGFR-TKI erlotinib. However, erlotinib has not been reported to control EGFR-wild-type tumors completely for the long periods, following discontinuation. Case. A 81-year-old man with an EGFR-wild-type adenocarcinoma of lung (pathological stage I) was treated by some undetermined kind of chemotherapy for recurrent foci of the lung. They responded to erlotinib well and disappeared completely on a computerized tomography imaging. The adverse reactions resulted in the discontinuation of erlotinib, but the survival time from discontinuation was 30 months. Conclusion. Erlotinib is a treatment option for EGFR-wild-type NSCLC.

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Background. von Recklinghausen disease is an autosomal-dominant hereditary disorder sometimes accompanied by carcinoma but rarely by hamartoma. Case. A 66-year-old man with von Recklinghausen disease was found to have an abnormal shadow in the right upper lung field during a routine health check. The chest computed tomography demonstrated a 69×41 mm nodule invading the chest wall in the right upper lobe and a 20-mm nodule in the right S⁶. Transbronchial biopsy revealed non-small cell lung cancer which was classified as cT3N0M0. Resection of the right upper lobe with chest wall and partial resection of the right S⁶ was performed. Postoperative histological examination revealed the tumor in S⁶ was a hamartoma. Although von Recklinghausen disease is a risk factor for various malignant tumors and is often accompanied with pulmonary bullae, von Recklinghausen disease with lung cancer is rare. On the other hand, pulmonary bullae and hamartoma can be associated with lung cancer. To the best of our knowledge, no case of synchronous pulmonary hamartoma and lung cancer in patients with von Recklinghausen disease has been reported. Conclusion. We report a very rare case of von Recklinghausen disease with lung cancer and pulmonary hamartoma.

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The clinical indications of MRI for neoplastic lesions in the chest are limited at the current time; however, when MR examinations are performed with appropriate sequences and, for appropriate purposes, they can play an important role in the clinical scenario. In particularly, current technical progress enables us to obtain various information concerning the living body without any invasive procedures. Additionally, whole body MRI and lymph node-specific contrast materials will be introduced in the diagnosis of lung cancer in the developed countries except for Japan. Unfortunately, we cannot access these 2 novel technical developments because of the problems in the medical systems in Japan.

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I commented on lung cancer cases for low dose CT screening in the seminar.

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The present WHO classification (3rd edition) has 2 critical problems. Bronchioloalveolar carcinoma is classified in the invasive adenocarcinoma category, even though its 5-year survival rate is 100%. Since the WHO adopted "mixed subtype" in invasive adenocarcinoma classification, over 90% of invasive adenocarcinoma was diagnosed as "mixed subtype". Recently, the IASLC proposed a multidisciplinary adenocarcinoma classification. "Adenocarcinoma in situ" is added in preinvasive lesion. Invasive adenocarcinomas are divided into 5 histological subtypes, based on their predominant structure.

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