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Akito Hata,
Nobuyuki Katakami,
Hiroshige Yoshioka,
Kei Kunimasa,
Shiro Fujita,
Reiko Kaji,
Kenji Notohara,
Yukihiro Imai,
Ryo Tachikawa,
Keisuke Tomii,
Yohei Korogi,
Masahiro Iwasaku,
Akihiro Nishiyama, Tadashi Ishida
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ABSTRACT: : Epidermal growth factor receptor (EGFR) mutations are found mostly in adenocarcinoma, and rarely in squamous cell carcinoma (SQC). Little is known about SQC harboring EGFR mutations.
: Between April 2006 and October 2010, we investigated the incidence of EGFR activating mutations in SQC of the lung using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) was retrospectively evaluated in patients with EGFR-mutated SQC. Further pathologic analyses were performed using immunohistochemistry.
: Thirty-three of 249 patients with SQC (13.3%) had EGFR mutations, including exon 19 deletion (19 of 33 patients, 58%), L858R point mutation in exon 21 (12 of 33, 36%), and G719S point mutation in exon 18 (2 of 33, 6%). Twenty of these 33 patients received EGFR-TKI therapy, and five of these 20 responded to EGFR-TKIs with a response rate of 25.0% (95% confidence interval [CI], 8.7%-49.1%). The patients' median progression-free survival and median overall survival were 1.4 months (95% CI, 0.7-5.8 months) and 14.6 months (95% CI, 2.9-undeterminable months), respectively. Approximately one third of the EGFR-mutated SQC patients achieved progression-free survival for longer than 6 months. Some of these patients had high carcinoembryonic antigen levels or a history of never smoking, or were positive for thyroid transcription factor-1.
: Although EGFR-TKIs seem to be generally less effective in EGFR-mutated SQC than in EGFR-mutated adenocarcinoma, some EGFR-mutated SQC patients can obtain clinical benefit from EGFR-TKIs. To better identify these patients, not only EGFR mutation status, but also clinical factors and pathologic findings should be taken into consideration.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2013; 8(1):89-95. · 4.55 Impact Factor
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Kei Kunimasa, Tadashi Ishida,
Soichiro Kimura,
Maki Tanaka,
Yuichi Kouyama,
Shigeki Yamashita,
Mitsunori Morita,
Hiromasa Tachibana,
Fumiaki Tokioka,
Akihiro Ito,
Chisato Sumi,
Kazuhiro Tateda
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2012; 7(5):942-3. · 4.55 Impact Factor
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ABSTRACT: Gefitinib and erlotinib are first-generation small molecular inhibitors of EGFR tyrosine kinase activity. To the best of our knowledge, to date, two reports have stated that patients with NSCLC who develop severe hepatotoxicity secondary to gefitinib treatment can be safely switched to erlotinib. However, the reverse situation has not been reported. Here, we present the first case with non-small cell lung cancer harboring EGFR mutation who developed grade 3/4 hepatotoxicity after initiation of erlotinib, which resolved when therapy was changed to gefitinib. As far as we know, this is the first report showing the efficacy of gefitinib for a non-small cell lung cancer patient who developed severe hepatotoxicity while under erlotinib therapy.
Internal Medicine 01/2012; 51(4):431-4. · 0.94 Impact Factor
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Internal Medicine 01/2012; 51(6):685-6. · 0.94 Impact Factor
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ABSTRACT: Lenalidomide is a second-generation immunomodulatory drug that has been approved to treat relapsed or refractory multiple myeloma. Here, we describe a patient who was treated with a low dose of lenalidomide (5 mg/day on days 1-21 of a 28-day cycle) because the standard dose of bortezomib was too toxic and adverse events persisted. However, he developed fever, dyspnea, hypoxia and pulmonary infiltrates. The results of an extensive workup for other causes including infections were negative and the final diagnosis was lenalidomide-induced interstitial pneumonitis. This is the first case report of lenalidomide-induced pneumonitis in a Japanese patient.
Internal Medicine 01/2012; 51(9):1081-5. · 0.94 Impact Factor
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Internal Medicine 01/2012; 51(24):3445-6. · 0.94 Impact Factor
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Kei Kunimasa,
Machiko Arita,
Takashi Nakazawa,
Maki Tanaka,
Kazuya Tsubouchi,
Satoshi Konishi,
Yasushi Fukuda,
Mika Saigusa,
Hiroaki Nakagawa,
Satoshi Ubukata,
Yohei Korogi,
Takao Fujii,
Tsuneyo Mimori, Tadashi Ishida
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ABSTRACT: We herein report the clinical and laboratory characteristics of two anti-OJ (anti-isoleucyl-tRNA synthetase) autoantibody-positive interstitial lung disease patients with polymyositis/dermatomyositis (PM/DM). We compared these characteristics with previously published findings. Previous reports and our present cases show that anti-OJ autoantibody-positive interstitial lung disease (ILD) patients with PM/DM lack the manifestations of Raynaud's phenomenon and sclerodactyly and show good prognoses and responses to glucocorticoid therapy. These results indicate that the presence of anti-OJ autoantibodies may be useful for predicting the prognosis of ILD and its clinical course in PM/DM patients.
Internal Medicine 01/2012; 51(24):3405-10. · 0.94 Impact Factor
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2012; 7(1):257. · 4.55 Impact Factor
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Case Reports 01/2012; 2012.
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Kei Kunimasa, Tadashi Ishida,
Soichiro Kimura,
Maki Tanaka,
Yuichi Kouyama,
Shigeki Yamashita,
Mitsunori Morita,
Hiromasa Tachibana,
Fumiaki Tokioka,
Akihiro Ito,
Chisato Sumi,
Kazuhiro Tateda
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ABSTRACT: This report presents a case of fulminant community-acquired Pseudomonas aeruginosa necrotizing pneumonia in a previously healthy young man, including an analysis of the virulence of the P.aeruginosa isolated from the patient. The patient was successfully treated with intensive care and antibiotic treatment. This study analyzed the pathogenicity of the isolated strain both in vivo (using a mouse pneumonia model) and in vitro (using biofilm production), but could not explain how an otherwise healthy young man developed such severe community-acquired P.aeruginosa pneumonia. Although rare in community-acquired pneumonia, P.aeruginosa infection should be considered in patients with severe rapidly progressive pneumonia.
Internal Medicine 01/2012; 51(17):2473-8. · 0.94 Impact Factor
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ABSTRACT: Objective The aim of this study was to describe the epidemiology, clinical features, antimicrobial treatment, and outcomes of patients with nursing and healthcare-associated pneumonia (NHCAP); a new category of pneumonia proposed by the Japanese Respiratory Society. Methods We conducted a retrospective analysis of a prospectively collected database of patients with NHCAP and community-acquired pneumonia (CAP) hospitalized at a single center between January 2008 and December 2010, and compared their clinical characteristics. The criteria for NHCAP were as follows: (1) residence in a nursing home or an extended-care ward, (2) a discharge from a hospital in the preceding 90 days, (3) an elderly or handicapped patient who needs long-term care, (4) a patient who regularly requires vascular access in an outpatient setting. Results A total of 442 NHCAP patients and 451 CAP patients were evaluated. The NHCAP patients were older and had a higher frequency of underlying diseases. Aspiration was thought to be associated with the NHCAP in 63% of patients. Streptococcus pneumoniae was the leading pathogen in both groups, whereas the frequency of multidrug-resistant pathogens was higher in the NHCAP patients. The most frequently used antimicrobials in NHCAP patients were penicillins with beta-lactamase inhibitors. The in-hospital mortality and recurrence rates were significantly higher in NHCAP patients than in CAP patients (13.1% vs. 5.1%, p<0.001 and 18.8% vs. 5.5%, p<0.001). Conclusion The clinical picture of NHCAP is consistent with that of HCAP described in the past. It is thought to be of benefit to modify the healthcare-associated pneumonia (HCAP) criteria considering the healthcare and social health insurance system in Japan.
Internal Medicine 01/2012; 51(18):2537-44. · 0.94 Impact Factor
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Akito Hata,
Nobuyuki Katakami,
Kei Kunimasa,
Hiroshige Yoshioka,
Shiro Fujita,
Reiko Kaji,
Ryo Tachikawa,
Keisuke Tomii,
Yukihiro Imai,
Masahiro Iwasaku, Tadashi Ishida
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ABSTRACT: Erlotinib has demonstrated survival benefit in patients with not only adenocarcinoma but also squamous cell carcinoma. Epidermal growth factor receptor-tyrosine kinase inhibitors are more effective in Asian populations, including the Japanese than in western populations. However, a higher incidence of interstitial lung disease has been reported as a fatal adverse event in the Japanese population. There is little data on erlotinib for Japanese patients with pretreated squamous cell carcinoma.
Between January 2004 and October 2010, we retrospectively evaluated the efficacy and toxicity of erlotinib administered as the first epidermal growth factor receptor-tyrosine kinase inhibitors for 41 Japanese patients with pretreated squamous cell carcinoma. Patients with pre-existing interstitial lung disease were carefully excluded by several examinations including high-resolution computed tomography.
The response rate and disease control rate were 9.7% [95% confidence interval: 2.7-23.1%) and 43.9% (95% confidence interval: 28.5-60.2%], respectively. Median time to treatment failure and overall survival were 2.2 months (95% confidence interval: 1.0-2.8 months) and 11.0 months (95% confidence interval: 5.7-15.7 months), respectively. Interstitial lung disease (Grade 5) was observed in one (2.4%) patient. Patients with Grade 0-1 skin rashes vs. patients with Grades 2-3 exhibited disease control rates of 28 vs. 83% (P = 0.0017), and median time to treatment failure of 1.2 months vs. 3.4 months (P = 0.0099).
Erlotinib has moderate efficacy for pretreated squamous cell carcinoma in Japanese patients. A higher grade of skin rash was associated with clinical benefit. Careful exclusion of pre-existing interstitial lung disease can minimize the occurrence of interstitial lung disease.
Japanese Journal of Clinical Oncology 11/2011; 41(12):1366-72. · 1.78 Impact Factor
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Thorax 09/2011; 66(9):830, 838. · 6.84 Impact Factor
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Akihiro Nishiyama, Tadashi Ishida,
Youhei Kourogi,
Satoshi Konishi,
Kazuya Thubouchi,
Chiya Iga,
Kei Kunimasa,
Masahiro Iwasaku,
Hajime Hukuyama,
Hiroaki Nakagawa,
Akihiro Itou,
Satoshi Ubukata,
Hiroshige Yoshioka,
Hiromasa Tachibana,
Machiko Arita,
Toru Hashimoto,
Junko Amemura-Maekawa
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ABSTRACT: Legionella pneumonia tends to be severe and is known to be fatal. Introduction of the urinary Legionella antigen test and changes in the Infectious Disease Law have led to increased numbers of reports, and milder cases are now occasionally seen. We experienced three cases demonstrating mild respiratory infections and one case demonstrating nosocomial pneumonia associated by Legionella pneumophila serogroup 3. Case 1 showed multiple ground-glass opacities on HRCT and productive cough. Cases 2 and 3 showed abnormal findings on chest X-ray, and chest CT findings in both cases suggested chronic respiratory infection. Case 4 experienced fever and hypoxia, and pulmonary edema was noted on X-ray. All of them four cases were diagnosed with respiratory infections isolated L. pneumophila serogroup 3 by culture results, and three of them cases were treated in the outpatient clinic. Thus, milder cases of Legionella pneumonia may be encountered during routine care, and tests for Legionella should be performed in such cases.
Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 07/2011; 85(4):373-9.
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Akito Hata,
Nobuyuki Katakami,
Hiroshige Yoshioka,
Shiro Fujita,
Kei Kunimasa,
Shigeki Nanjo,
Kyoko Otsuka,
Reiko Kaji,
Keisuke Tomii,
Masahiro Iwasaku,
Akihiro Nishiyama,
Hidetoshi Hayashi,
Satoshi Morita, Tadashi Ishida
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ABSTRACT: Recent reports have suggested that erlotinib therapy after gefitinib failure requires optimal patient selection to obtain clinical benefits in relapsed non-small cell lung cancer (NSCLC). However, insufficient evidence exists to determine which clinical factors best identify patients who benefit from erlotinib therapy.
One hundred twenty-five patients with relapsed NSCLC who had received erlotinib therapy after gefitinib failure were retrospectively evaluated between January 2008 and May 2009.
The response rate (RR), disease control rate (DCR), and median progression-free survival (PFS) for all patients were 9% (95% confidence interval [CI], 5-15%), 44% (95% CI, 35-53%), and 2.0 months (95% CI, 1.4-2.5 months), respectively. The median survival time was estimated to be 11.8 months (95% CI, 6.4-16.0 months). Using multivariate analysis, good performance status (PS), EGFR mutation-positive status, and benefit from prior gefitinib therapy were identified as significant predictive factors for disease control. Using a proportional hazards model, benefit from prior gefitinib therapy, good PS, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies emerged as significant predictive factors for longer PFS. Thirty-two patients with concomitant PS 0/1, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies benefitted more from erlotinib therapy: RR, 25% (95% CI, 12-43%); DCR, 72% (95% CI, 53-86%); and median PFS, 3.4 months (95% CI, 2.4-4.9 months).
Higher efficacy of erlotinib after gefitinib failure can be achieved with proper patient selection criteria, including good PS, benefit from prior gefitinib therapy, and insertion of cytotoxic chemotherapies between gefitinib and erlotinib therapies.
Lung cancer (Amsterdam, Netherlands) 04/2011; 74(2):268-73. · 3.14 Impact Factor
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ABSTRACT: Several scoring systems have been derived to identify patients with severe community-acquired pneumonia (CAP). Recently, España et al (Am J Respir Crit Care Med 174:1249-1256, 2006) developed a clinical prediction rule that predicts hospital mortality, the need for mechanical ventilation, and risk for septic shock. We assessed the performance of this rule and compared it with other published scoring systems.
A prospective study was conducted of patients with CAP who were hospitalized at our hospital from April 2007 till May 2009. Clinical and laboratory features at presentation were recorded and used in order to calculate España rule, the pneumonia severity index (PSI), CURB-65, A-DROP, the 2007 Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) prediction rule and SMART-COP. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were compared for adverse outcomes. We also assessed the association of the España rule criteria and adverse outcomes.
A total of 505 patients were enrolled in the study. The overall in-hospital mortality rate was 6.5%, and 6.3% of patients were admitted to the intensive care unit (ICU). Sixty-two (12.3%) patients were defined as having severe CAP (in-hospital death or need for mechanical ventilation or septic shock). España rule achieved highest sensitivity and NPV in predicting severe CAP. When ICU admission was the outcome measure, the IDSA/ATS rule and SMART-COP were regarded to be good predictors.
España rule performed well in identifying patients with severe CAP. As a result, each of the severity scores has advantages and limitations for predicting adverse outcomes.
Internal Medicine 01/2011; 50(18):1917-22. · 0.94 Impact Factor
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ABSTRACT: A 50-year-old man with a 30-year occupational history of welding presented with low-grade fever, fatigue and persistent dry cough. Computed tomography (CT) of the chest revealed interlobular septal thickening and bilateral non-segmental patchy ground-glass opacities except in the sub-pleural zone. He revealed that he had inhaled nickel fumes 3 days previously at work. These findings suggested a diagnosis of pneumonitis induced by inhalation of nickel fumes. Fewer reports describe pneumonitis associated with the inhalation of nickel compared with zinc fumes. Although nickel compounds are particularly pernicious among the transition metals and more toxic than zinc compounds, nickel fume inhalation rarely induces lethal acute respiratory distress syndrome. Our patient was successfully treated with corticosteroid.
Internal Medicine 01/2011; 50(18):2035-8. · 0.94 Impact Factor
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ABSTRACT: Hypereosinophilic syndrome (HES) encompasses both myeloproliferative and lymphoproliferative diseases. We encountered a rare case of lymphocytic HES followed by malignant T cell lymphoma, who was diagnosed as eosinophilic pneumonia upon the first visit. During the clinical course, the transition of the chest CT findings from bilateral multifocal ground-glass opacities and consolidations to bilateral scattered multiple small nodules was impressive and suggestive. Given the increased risk of developing T-cell lymphoma, patients with HES (especially lymphocytic-HES) should be monitored on a regular basis to detect this complication as early as possible.
Internal Medicine 01/2011; 50(20):2417-21. · 0.94 Impact Factor
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Internal Medicine 01/2011; 50(22):2865. · 0.94 Impact Factor
