Dose escalation and pharmacokinetic study of carboplatin plus pemetrexed for elderly patients with advanced nonsquamous non-small-cell lung cancer: Kumamoto thoracic oncology study group trial 1002.

OBJECTIVES: This study was designed to determine the recommended dose of carboplatin and pemetrexed for elderly (≥70-year-old) chemotherapy-naïve patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of pemetrexed. METHODS: The patients were treated with 4-6 cycles of carboplatin plus a fixed dose of pemetrexed (500 mg/m(2)) every 3 weeks; the dose of carboplatin was escalated [from area under the curve (AUC) 4 to AUC 6]. To examine the pharmacokinetics of pemetrexed, blood samples were collected before and after pemetrexed infusion, and the blood levels of pemetrexed were measured by liquid chromatography-mass spectrometry. RESULTS: Grade 3 infection as a dose-limiting toxicity was observed at a carboplatin dose of AUC 6. We therefore determined a carboplatin dose of AUC 5 and a pemetrexed dose of 500 mg/m(2) as the recommended doses from this study. The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance. CONCLUSIONS: For elderly chemotherapy-naïve patients with advanced nonsquamous NSCLC, the combination of carboplatin AUC 5 plus pemetrexed 500 mg/m(2) is recommended as a promising regimen; however, a reduction of the pemetrexed dose may be required for patients with renal dysfunction because of the high risk of hematotoxicities.

[A case of systemic IgG4-related disease with bilateral pleural effusions].

An 85-year-old man was admitted for non-productive cough and bilateral pleural effusion on a chest X-ray film. Although his pleural effusion was exudative and showed an increased number of lymphocytes and a high level of adenosine deaminase, Mycobacterium tuberculosis infection, even with a microbiological culture, PCR and interferon-gamma release assay, was unverifiable. Cytology of his pleural effusion demonstrated plasmacytoid-like large atypical cells. Immunological tests showed high levels of IgG and IgG4 in both his serum and pleural effusion. A fluorodeoxyglucose-positron emission tomography (FDG-PET) scan showed uptake of FDG in orbital lesions, salivary glands, gastric wall, biliary system and lymph nodes (cervical, supraclavicular, axillary, hilar, mediastinal, along the lesser gastric curvature). Histological examination of an orbital pseudotumor and gastric mucosal biopsy revealed that numerous numbers of mostly IgG4 positive plasma cells, had accumulated. Based on these findings, systemic IgG4-related disease was diagnosed. Corticosteroid therapy was started and the volume of pleural effusion markedly declined. We report a rare case of IgG4-related disease accompanied by pleural effusion with a high level of ADA.

[A case of AIDS with Pneumocystis jirovecii pneumonia which required differentiation from ANCA-related lung disease].

A 41-year-old man with fever, diarrhea and skin rash received a diagnosis of drug-induced lupus. He was given corticosteroids for 3 months and was subsequently admitted to a local hospital due to dyspnea. Pneumonia was then diagnosed and he was given a new quinolone antibacterial agent. Despite this treatment, his symptoms and signs gradually worsened and he was referred to our hospital. High resolution CT (HRCT) of the chest showed diffuse ground-glass opacities, reticular shadows, parenchymal abnormalities, traction bronchiectasis, a subpleural curvilinear shadow and septal lines. Serological examinations were positive for anti-myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) and subsequent HRCT findings were consistent with ANCA-related lung disease. However, the patient had complications such as previous syphilis infection, oral candidiasis, herpes zoster, hepatitis B virus and cytomegalovirus infection. Additionally, his serum was positive for HIV antibody and HIV-1 RNA, and therefore we diagnosed AIDS. His bronchoalveolar lavage fluid revealed Pneumocystis jirovecii. It is known that HIV infection is associated with many types of autoantibodies including MPO-ANCA. Therefore, in HIV/AIDS patients with interstitial lung diseases, it is important to differentiate opportunistic Pneumocystis pneumonia infection from collagen vascular disease-associated interstitial lung diseases.

Diagnostic usefulness of endobronchial ultrasound-guided transbronchial needle aspiration in a case with malignant pleural mesothelioma.

A 74-year old man was admitted to our hospital with right diffuse pleural thickening and effusion and with subcarinal lymph node swelling. The effusion obtained by thoracentesis showed no malignant cells, although positron emission tomography showed abnormal uptake in the right pleural thickening and subcarinal lymph node. Histopathological examination of the lymph node specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration showed a sheet of epithelioid-like large atypical cells. The tumor cells were immunohistochemically positive for calretinin and cytokeratin 5/6, and negative for CEA and TTF-1. Therefore, malignant pleural mesothelioma of epithelioid type was diagnosed.

[A case of primary posterior mediastinal chordoma].

A 49-year-old man, with a tumor shadow overlapping the heart on chest X-ray film was followed for 5 years. He was admitted because the tumor shadow enlarged. Chest CT scan showed a 6 x 7 cm in diameter extrapulmonary tumor at the Th8 and Th9 level, and a defect of the anterior margin of the thoracic vertebra is observed. Because thoracic CT-guided needle biopsy was not successful, total resection combined with thoracic vertebrae was performed. The tumor was under the parietal pleura and did not involve into the intrathoracic organs. Histological examination showed small round cells arranged in sheets and cord-like fashion in a mucinous stroma. On immunohistochemistry, the tumor cells were positive for S-100 protein, vimentin, AE1/3. CAM5.2, EMA and Alcian blue staining. Thus, we confirmed the diagnosis of chordoma. Chordoma is a rare malignant bone tumor that originates from notochordal remnants and accounts for about 1-4% of all malignant bone tumors. Intrathoracic mediastinal chordomas is extremely rare, representing only 3% of all chordomas.