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Satoshi Igawa,1 Masashi Kasajima,1 Taihei Ono,1 Takahiro Ozawa,1 Mikiko Kakegawa,1 Seiichiro Kusuhara,1 Takashi Sato,1 Yoshiro Nakahara,1 Tomoya Fukui,1 Masanori Yokoba,2 Masaru Kubota,2 Hisashi Mitsufuji,3 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4Kitasato University School of Medicine, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, JapanCorrespondence: Satoshi IgawaDepartment of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara-city, Kanagawa, 252-0374, JapanTel +81-42-778-8506Fax +81-42-778-6412Email igawa@kitasato-u.ac.jpBackground: The clinical outcomes of elderly patients with EGFR-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations.Patients and Methods: We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥ 75 years of age) with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered 80 mg/day osimertinib as initial treatment.Results: Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75– 90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥ 3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF.Conclusion: Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.Keywords: non-small cell lung carcinoma, chemotherapy-naïve patients, efficacy

Satoshi Igawa,1 Taihei Ono,1 Masashi Kasajima,1 Hideaki Manabe,1 Tomoya Fukui,1 Hisashi Mitsufuji,2 Masanori Yokoba,3 Masaru Kubota,3 Masato Katagiri,3 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-City, Kanagawa 252-0374, Japan; 2Kitasato University School of Nursing, Sagamihara-City, Kanagawa 252-0329, Japan; 3School of Allied Health Sciences, Kitasato University, Sagamihara-City, Kanagawa 252-0373, Japan; 4Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-City, Kanagawa 252-0374, JapanCorrespondence: Satoshi IgawaDepartment of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-Ku, Sagamihara-City, Kanagawa 252-0374, JapanTel +81 42 778 8506Fax +81 42 778 6412Email igawa@kitasato-u.ac.jpPurpose: Amrubicin (AMR) is an anticancer drug for patients with relapsed small-cell lung cancer (SCLC). However, the efficacy of AMR in elderly patients with relapsed SCLC after chemotherapy by carboplatin plus etoposide (CE) has not been sufficiently evaluated.Patients and Methods: The medical records of patients with relapsed SCLC who received AMR as second-line chemotherapy were retrospectively reviewed, and their treatment outcomes were evaluated.Results: Forty-one patients with a median age of 76 years were analyzed. The overall response rate was 26.8%. Median progression-free survival (PFS) and overall survival (OS) were 3.5 and 8.1 months, respectively. While the median PFS of 4.7 and 2.8 months in the sensitive relapse and the refractory relapse group differed significantly (P=0.043), respectively, the median OS of 10.7 and 6.8 months in the respective relapse groups did not indicate a statistically significant difference (P=0.24). The median PFS in a group with a modified Glasgow prognostic score (mGPS) of 0 and a group with a mGPS 1 or 2 were 4.5 and 1.6 months (P=0.052), respectively, and the median OS in the respective mGPS groups were 10.7 and 4.4 months (P=0.034). Multivariate analysis identified good performance status, limited disease, and mGPS 0 as favorable independent predictors of PFS and OS of AMR monotherapy. Grade 3 or higher neutropenia was observed in 23 patients (56%), and febrile neutropenia was observed in nine patients (22%). Non-hematological toxic effects were relatively mild, and pneumonitis and treatment-related deaths were not observed.Conclusion: AMR is an effective and feasible regimen for elderly patients with relapsed SCLC after CE therapy.Keywords: small-cell lung cancer, amrubicin, elderly, second-line chemotherapy, modified Glasgow prognostic score

Hisamitsu Omori,1 Noritaka Higashi,2 Takeshi Nawa,3 Toshiki Fukui,4 Toshihiko Kaise,5 Takeo Suzuki5 1Department of Biomedical Laboratory Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan; 2Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan; 3Department of Internal Medicine, Hitachi General Hospital, Hitachi, Japan; 4Center for Preventive Medical Treatment, Olive Takamatsu Medical Clinic, Takamatsu, Japan; 5Japan Development Division, GlaxoSmithKline K.K., Tokyo, JapanCorrespondence: Toshihiko KaiseJapan Development Division, GlaxoSmithKline K.K., 1-8-1 Akasaka, Minato-ku, Tokyo 107-0052, JapanTel +81 80 5927 9500Fax +81 3 4231 5993Email toshihiko.kaise@gsk.comPurpose: The purpose of this study was to estimate the prevalence of subjects with chronic cough and phlegm and describe their characteristics including the presence or absence of airflow limitation among the general population in Japan.Subjects and Methods: This was an observational cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited. The existence of chronic cough and phlegm, airflow limitation, and treatment for respiratory diseases were examined. Chronic cough and phlegm were defined as having both symptoms for at least 3 months of the year and for at least 2 consecutive years, or as receiving any treatment for chronic bronchitis at the time of recruitment. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) less than 0.7.Results: In a total of 22,293 subjects, 380 subjects (1.7%) had chronic cough and phlegm. Among these 380 subjects, 21.8% received treatment for a respiratory disease, and 11.6% had airflow limitation. Compared to subjects without both chronic cough and phlegm but with airflow limitation, subjects with chronic cough and phlegm without airflow limitation were younger, more likely to be current smokers (39.6%), and had higher total scores on a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Scores of CAT questions 1– 4 (cough, phlegm, chest tightness, breathlessness, respectively) were higher in subjects with chronic cough and phlegm regardless of airflow limitation.Conclusion: This study demonstrated that subjects identified to have chronic cough and phlegm in comprehensive health examination settings were symptomatic, while most of them did not receive any treatment for respiratory diseases and did not have airflow limitation. Screening subjects for chronic cough and phlegm in a comprehensive health examination followed by a detailed examination of screened subjects could be an effective approach for better management of chronic cough and phlegm. Smoking cessation should be included in the management, in consideration that around 40% of subjects with chronic cough and phlegm were current smokers.Keywords: respiratory disease, chronic bronchitis, spirometry, lung function, general population, health checkup

Satoshi Igawa,1 Taihei Ono,1 Masashi Kasajima,1 Mikiko Ishihara,1 Yasuhiro Hiyoshi,1 Seiichiro Kusuhara,1 Noriko Nishinarita,1 Tomoya Fukui,1 Masaru Kubota,1 Jiichiro Sasaki,2 Mitsufuji Hisashi,3 Masanori Yokoba,4 Masato Katagiri,4 Katsuhiko Naoki11Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa 252-0373, JapanPurpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation.Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation.Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.Keywords: EGFR genotype, non-small cell lung carcinoma, osimertinib, efficacy

Satoshi Igawa,1 Noriko Nishinarita,1 Akira Takakura,1 Takahiro Ozawa,1 Shinya Harada,1 Seiichiro Kusuhara,1 Hideyuki Niwa,2 Shinji Hosotani,1 Hideyuki Sone,1 Yoshiro Nakahara,1,3 Tomoya Fukui,1 Hisashi Mitsufuji,4 Masanori Yokoba,5 Masaru Kubota,1 Masato Katagiri,5 Jiichiro Sasaki,6 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan; 2Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Aichi, Japan; 3Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Kanagawa, Japan; 4Kitasato University School of Nursing, Sagamihara 252-0329, Kanagawa, Japan; 5School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan; 6Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan Background: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. Patients and methods: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. Results: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59–83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. Conclusion: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD. Keywords: interstitial lung disease, non-small-cell lung cancer, carboplatin, nab-paclitaxel

Masayuki Shirasawa,1,* Tomoya Fukui,1,* Seiichiro Kusuhara,1 Yasuhiro Hiyoshi,1 Mikiko Ishihara,1 Masashi Kasajima,1 Yoshiro Nakahara,1 Sakiko Otani,1 Satoshi Igawa,1 Masanori Yokoba,2 Hisashi Mitsufuji,3 Masaru Kubota,1 Masato Katagiri,1 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan; 2Department of Medical Laboratory, Kitasato University School of Allied Health Sciences, Kanagawa, Japan; 3Fundamental Nursing, Kitasato University School of Nursing, Kanagawa, Japan; 4Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan *These authors contributed equally to this work Background: Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear.Methods: This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016.Results: According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4–22.2) months in the M1b group vs 7.3 (95% CI 5.7–8.9) months in the M1c group (P

Objective: Health locus of control (HLC) is associated with health behaviours. We aimed to investigate the difference of HLC to understand the potential gap in health beliefs between physicians and the general public. Design and setting: Physicians and the general public were surveyed in Japan using a cross-sectional survey. Data on the Japanese version of the HLC scale (HLCS-J) from 2194 members of the general public and 895 physicians were available. Method: Multi-group structural equation modelling analysis was used for examining differential item functioning (DIF) in the HLCS-J between the groups. Results: Uniform DIF was identified for the dimensions of internal, professional control and control by spiritual powers. Mean score for chance control (17.2) among physicians was greater than that (14.9) among the general public (adjusted p less than 0.001), while mean score for family control (21.7) among physicians was lower than that (22.1) among the general public (adjusted p less than 0.001). Conclusion: Physicians are more likely to have a higher chance control but lower family control than the general public. Further studies are needed to evaluate the relationships between individual physicians' HLC and their health behaviours. (Contains 4 tables.)

Background: Sulfhydryl (SH) compounds are essential in maintaining mucosal integrity in the gastrointestinal tract. A decrease in colonic mucosal SH compounds affects the redox status of the mucosa, resulting in [...]

Background and aim: Long term Helicobacter pylori infection leads to atrophic gastritis but the relation between H pylori infection and autoimmune related atrophic gastritis (AIG) remains unclear. We studied the [...]