Atsuhiko Tada

Relationship between serum tumor necrosis factor-α and insulin resistance in obese men with Type 2 diabetes mellitus

Abstract We analyzed serum concentrations of tumor necrosis factor-α (TNF-α) for their role in insulin resistance in 12 obese men with untreated Type 2 diabetes mellitus and in 6 age-and BMI-matched obese controls. Insulin resistance was expressed using the homeostasis model assessment (HOMA-R). Six of the patients were insulin-resistant (HOMA-R>5.0), while six were not (HOMA-R≤3.0). Serum levels of TNF-α were higher in patients with insulin resistance (4.19±0.96 pg/ml) than in patients without insulin resistance (2.52±1.64 pg/ml) and in controls (2.03±1.21 pg/ml). Fasting serum concentrations of insulin and HOMA-R were higher in patients with insulin resistance (16.2±5.0 and 6.30±1.0 IU/ml, respectively) than in patients without insulin resistance (7.3±2.2 and 2.4±0.6 IU/ml) and in controls (8.0±2.9 and 1.8±0.6 IU/ml). These data suggest that high levels of serum TNF-α in patients with insulin resistance are related to high levels of fasting insulin and HOMA-R. We conclude that TNF-α may be involved in the pathogenesis of Type 2 diabetes mellitus in obese men. The importance of this investigation is that the subjects recruited in the study are BMI matched, because human obesity is associated with an increased TNF-α mRNA expression in adipose tissue.

Epstein-Barr Virus Associated Diffuse Large B-Cell Lymphoma Complicated by Autoimmune Hemolytic Anemia and Pure Red Cell Aplasia

A 53-year old man with systemic lymphadenopathy and hepatosplenomegaly was diagnosed with diffuse large B cell-lymphoma after inguinal lymph node biopsy. Anemia was noted, direct and indirect Coombs tests were positive, and the haptoglobin level was low. However, the bone marrow aspirate revealed erythroid aplasia. Co-existing autoimmune haemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were diagnosed. In situ hybridization with Epstein-Barr virus (EBV) encoded small RNA (EBER) showed positive findings in lymphoma cells. Southern blot hybridization revealed immunoglobulin heavy chain gene rearrangement and a clonal EBV terminal repeat, indicating monoclonal proliferation of EBV in infected B cells. The patient was treated with CHOP, resulting in a complete remission (CR). AIHA and PRCA subsided after 3 courses of chemotherapy. In conclusion, this case demonstrates not only the association of B-cell lymphoma with autoimmune disorders but also the involvement of EBV in these conditions.

Successful Treatment of a Patient with Severe Churg-Strauss Syndrome by a Combination of Pulse Corticosteroids, Pulse Cyclophosphamide, and High-Dose Intravenous Immunoglobulin

A 24-year-old woman with a 4-year history of bronchial asthma suffered from bloody sputum, numbness of the extremities, elevated eosinophil count, and hypoxemia. A diagnosis of alveolar hemorrhage was made by bronchoalveolar lavage. Echocardiogram revealed severe hypokinesis of the left ventricular wall. Her respiratory condition deteriorated despite administration of pulse corticosteroids. A second pulse corticosteroids and pulse cyclophosphamide followed by high-dose intravenous immunoglobulin brought about a dramatic improvement of alveolar hemorrhage, cardiac impairment, and peripheral neuropathy. Levels of antimyeloperoxidase-antineutrophil cytoplasmic antibodies, soluble thrombomodulin, soluble interleukin-2 receptor, eosinophil cationic protein were elevated and returned to the normal range in remission. The combination of pulse corticosteroids, pulse cyclophosphamide, and high-dose intravenous immunoglobulin seemed effective for the acute phase of severe Churg-Strauss syndrome.

Phase II study of irinotecan and amrubicin in patients with relapsed non-small cell lung cancer: Okayama Lung Cancer Study Group Trial 0402

Abstract Background. The survival advantage achieved by existing anti-cancer agents as second-line therapy for relapsed non-small cell lung cancer (NSCLC) is modest and further improvement of treatment outcome is desired. Combination chemotherapy with irinotecan and amrubicin for advanced NSCLC has not been fully evaluated. Methods. The primary endpoint of this phase II clinical trial was objective response. Patients with NSCLC who had been treated previously with one or two chemotherapy agents were enrolled. Irinotecan and amrubicin were both administered on Days 1 and 8 of a 21-day cycle, at doses of 100 mg/m2 and 40 mg/m2, respectively. Results. Between 2004 and 2006, 31 patients received a total of 101 courses; the median number of courses administered was three (range, one to six). Objective response was obtained in nine of the 31 patients (29.0% response rate; 95% confidence interval (CI), 12.1–46.0%). With a median follow-up time of 43.9 months, median survival time and the median progression-free survival time were 14.2 and 4.0 months, respectively. Myelosuppression was the most frequently observed adverse event, with grade 3/4 neutropenia in 51% of patients. Febrile neutropenia developed after nine courses (9%) and resulted in one treatment-related death. Cardiac toxicity and diarrhea, possibly specific for both agents, were infrequent and manageable. Conclusion. Combination chemotherapy with irinotecan and amrubicin is effective in patients with NSCLC but showed moderate toxicities in second- or third-line settings.

Long-term follow-up of phase II trial of docetaxel and cisplatin with concurrent thoracic radiation therapy for locally advanced non-small cell lung cancer

Abstract Background. Chemoradiation improves survival for patients with locally advanced non-small cell lung cancer (NSCLC), but clinical outcomes beyond five years are rarely reported. The aim of the present study was to identify the long-term results of a phase II study of docetaxel and cisplatin with concurrent thoracic radiation. Methods. We previously reported short-term outcomes from the phase II study, which enrolled 42 patients (aged ≤ 75 years) with unresectable stage III NSCLC. We continued to follow these patients for long-term clinical outcomes. Results. At a median follow-up for all patients of 6.3 years (range: 5.2–7.1 years), the median survival time was 2.1 years and the actual five-year survival rate was 31%. Among 14 patients who were progression-free longer than two years, three patients died due to bacterial or fungal pneumonia and one died due to gall bladder cancer. Conclusions. Thirty-one percent of locally advanced patients having NSCLC treated with docetaxel and cisplatin and concurrent thoracic radiation survived beyond five years. Progression-free patients might be cautiously followed up taking precautions against emerging pneumonia.

Frequency of Brain Metastasis in Lung Cancer at the Time of Diagnosis.

Objective. To determine the frequency of brain metastasis in lung cancer at the time of diagnosis. Methods. The frequency of brain metastasis at the time of diagnosis was studied retrospectively in 31450 patients with lung cancer (27730 non-small cell carcinomas and 3720 small cell cacinomas) according to clinical tumor status (cT factor) and nodal status (cN factor) . Results. Brain metastasis was observed in 1104 (4.0%) patients with non-small cell carcinoma and in 279 (7.5%) patients with small cell carcinoma. In 653 patients with non-small cell carcinoma and 163 patients with small cell carcinoma, there was no other metastatic lesion except brain metastasis. Frequency of brain metastasis was 4.8% in adenocarcinoma, 2.5% in squamous cell carcinoma, 6.4% in large cell carcinoma and 1.7% in adenosquamous cell carcinoma. Frequency of brain metastasis was higher in advanced clinical tumor status and nodal status, especially in non-small cell carcinoma with advanced nodal status. Median survival time (MST) of patients with brain metastasis was 21.4 weeks in non-small cell carcinoma and 28.1 weeks in small cell carcinoma. MST in patients 1国 立 療 養所 南 岡 山病 院 内科;2国 立療 養 所 肺 が ん研 究 会. 別刷 請 求 先:多 田敦 彦,国 立療 養 所 南 岡 山病 院 内科,〒701-0304 岡 山県 都 窪 郡 早 島 町 早 島4066(e-mail:tadaa@s-okayama.hosp.go. jp). 1Department of Internal Medicine , National Minami-Okayama Hospital, Japan; 2National Chest Hospital Study Group for Lung Cancer, Japan. Reprints: Atsuhiko Tada, Department of Internal Medicine, National Minami-Okayama Hospital, 4066 Hayashima, Hayashima-cho, Tsukubo-gun, Okayama 701-0304, Japan (e-mail: tadaa@s-okayama. hosp.go.jp). Received November 12, 2002; accepted March 19, 2003. C 2003 The Japan Lung Cancer Society Japanese Journal of Lung Cancer-Vol 43, No 3, Jun 20, 2003-www.haigan.gr.jp 259 Frequency of Brain Metastasis in Lung Cancer-Tada et al with other metastatic lesions together with brain metastasis was significantly shorter than in patients without other metastatic lesion in both non-small cell carcinoma (24.0 weeks versus 18.4 weeks, p< 0.001) and small cell carcinoma (30.7 weeks versus 25.3 weeks, p< 0.05). Conclusion. Brain metastasis of lung cancer was observed in 4.0% of patients with non-small cell carcinoma and in 7.5% of patients with small cell carcinoma at the time of diagnosis. (JJLC. 2003;43:259264) KEY WORDS-Brain metastasis, Lung cancer, Frequency

Serum Soluble Interleukin-2 Receptor in Patients with Lung Cancer.

未治療の肺癌患者54症例を対象に血清可溶性インターロイキン2受容体 (sIL-2R) を測定し, その臨床的意義について検討した.肺癌患者の血清sIL-2Rの測定値は751±432U/mlであり, 37例 (69%) が530U/ml (健常人の平均値+2S.D.) 以上であった. 血清sIL-2Rは病期III/IV期では病期I/II期に比して有意に高値であった. 小細胞癌では同じ病期の非小細胞癌に比較して血清sIL-2Rは低値であった. 血清sIL-2Rと血清アルブミンおよび血清choline esteraseとの問には有意な負の相関関係, 血清sIL-2Rと血清CRPとの問には有意な正の相関関係が認められた. 非小細胞癌においては血清sIL-2R高値 (600U/ml以上) のものは予後不良の傾向が認められた.以上より, 血清sIL-2Rは肺癌患者, 特に非小細胞肺癌患者の腫瘍量の有用な指標であり, 予後因子となりうる可能性が示唆された.

Coexistence of Lung Cancer and Active Pulmonary Mycobacterial Disease.

過去10年間に当院で経験した肺癌と活動性肺抗酸菌症の合併例15例について臨床的検討を行った. 肺癌の組織型は, 扁平上皮癌9例, 腺癌4例, 小細胞癌2例, 抗酸菌種は, M. tuberculosis12例, M. avium complex3例であった. 9例は同一肺葉に肺癌病巣と抗酸菌病巣が認められた. 肺癌の経過中に肺抗酸菌症が発症した症例は6例であった. 肺抗酸菌症が先に発見され, その治療中に肺癌が診断された症例は9例であった. その9例について, 過去のレントゲン写真の検討を行ったが, 9例全例, 肺抗酸菌症治療の入院時には肺癌は存在しており, そのうち6例は, 肺癌の発生は肺抗酸菌症の発症よりも先行していたものと考えられた. 以上より, 肺抗酸菌症に肺癌が潜在している可能性を念頭に置いて診療に当たる重要性が示唆された.