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Nobuhiro Kanaji,1 Akira Tadokoro,1 Kentaro Susaki,1 Saki Yokokura,1 Kiyomi Ohmichi,2 Reiji Haba,2 Naoki Watanabe,1 Shuji Bandoh,1 Tomoya Ishii,1 Hiroaki Dobashi,1 Takuya Matsunaga11Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan; 2Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, JapanPurpose: No lung cancer xenograft model using non-obese diabetic (NOD)-scid Il2rg-/- mice has been reported. The purpose of this study is to select a suitable mouse strain as a xenogenic host for testing tumorigenicity of lung cancer.Materials and methods: We directly compared the susceptibility of four immunodeficient mouse strains, c-nu, C.B-17 scid, NOD-scid, and NOD/LtSz-scid Il2rg-/- (NSG) mice, for tumor formation from xenotransplanted lung cancer cell lines. Various numbers (101–105 cells/head) of two lung cancer cell lines, A549 and EBC1, were subcutaneously inoculated and tumor sizes were measured every week up to 12 weeks.Results: When 104 EBC1 cells were inoculated, no tumor formation was observed in BALB/c-nu or C.B-17 scid mice. Tumors developed in two of the five NOD-scid mice (40%) and in all the five NSG mice (100%). When 103 EBC1 cells were injected, no tumors developed in any strain other than NSG mice, while tumorigenesis was achieved in all the five NSG mice (100%, P=0.0079) within 9 weeks. NSG mice similarly showed higher susceptibility to xenotransplantation of A549 cells. Tumor formation was observed only in NSG mice after inoculation of 103 or fewer A549 cells (40% vs 0% in 15 NSG mice compared with others, respectively, P=0.0169). We confirmed that the engrafted tumors originated from inoculated human lung cancer cells by immunohistochemical staining with human cytokeratin and vimentin.Conclusion: NSG mice may be the most suitable strain for testing tumorigenicity of lung cancer, especially if only a few cells are available.Keywords: NOD-scid Il2rg(null), tumorigenicity, xenotransplantation, xenograft, mouse model

Study Objectives: To assess the diagnostic accuracy and safety of flexible bronchoscopy with multiplanar reconstruction (MPR) images and ultrafast Papanicolaou (UFP) stain in evaluating solitary pulmonary nodules (SPNs).Design: Prospective study of bronchoscopies performed between June 2000 and June 2002.Patients: One hundred consecutive patients with SPNs underwent bronchoscopy with MPR and UFP (MPR and UFP group). The data on historical control were collected in a retrospective fashion, between July 1997 and June 2000.Method: All information obtained from MPR regarding the leading bronchus of the SPNs was used to guide biopsy. Samples obtained by curette biopsies were stained with UFP and evaluated by a cytopathologist during the bronchoscopy procedure.Results: There were 88 malignant and 12 benign lesions in the MPR and UFP group, and 97 malignant and 3 benign lesions in the historical control group. The total diagnostic accuracy of bronchoscopy in the MPR and UFP group (91%) was significantly higher compared with the historical control group (58%) [p < 0.05]. Although the yield of bronchoscopy was significantly related to the lesion size in the historical control group (p < 0.05), there was no significant association between the diagnostic yield and lesion size in the MPR and UFP group. The diagnostic yield for SPNs < 4.0 cm in the MPR and UFP group was significantly higher compared with the historical control group (p < 0.05). In addition, the diagnostic yield in both upper lobes in the MPR and UFP group was significantly higher compared with the historical control group (p < 0.05). On the contrary, the complication rate was significantly lower in the MPR and UFP group (2%) compared with the historical control group (13%) [p < 0.05].Conclusion: Combined use of the MPR image and UFP during flexible bronchoscopy improved diagnostic accuracy and safety in evaluating SPNs using a double-hinged curette. [ABSTRACT FROM AUTHOR]

Background: We aimed to determine the reasons for the high rate of asthma mortality in Kagawa Prefecture, Japan, by analyzing death certificates., Methods: We analyzed the death certificates between 2009 and 2011 in a demographic survey. Of 1187 patients with documented disease names suggesting bronchial asthma, analysis was performed on 103 patients in whom the cause of death was classified as asthma based on ICD-10 Codes. The patients were then classified into the following 4 groups: asthma death, asthma-related death, non-asthma death, and indistinguishable death. Based on this classification, consistency between ICD-10-based asthma death and asthma/asthma-related deaths was examined for each age group as well as for the site of death., Results: Of 103 asthma deaths based on the ICD-10 classification, 30 (29%) were classified as asthma death, 44 (43%) as asthma-related death, 16 (16%) as non-asthma death, and 13 (13%) as indistinguishable death. Asthma death based on our classification correlated with that of ICD-10-based classification as a cause of death in patients younger than the median age (87 years), but correlation was not observed in patients aged older than 87 years. Deaths occurred outside the hospital in 45% of patients, and many ICD-10-based deaths reported at nursing homes and geriatric health care facilities were classified as non-asthma deaths in this survey., Conclusion: Re-examination of the death certificate revealed that asthma deaths were reported incorrectly on the death certificates of elderly patients who died outside the hospital., (Copyright © 2019 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: We aimed to determine the presepsin concentration in pleural fluid from patients with pleural effusions of different aetiologies and to compare its diagnostic value with that of pleural fluid C-reactive protein (CRP) and procalcitonin (PCT)., Methods: We enrolled 132 patients with pleural effusion who underwent diagnostic evaluation, and we classified them into six categories: empyema, parapneumonic effusion, tuberculous effusion, malignant effusion, paramalignant effusion, and transudate effusion. Additionally, all pleural effusions were categorised as infectious or non-infectious effusions., Results: Receiver operating characteristic analysis was used to evaluate diagnostic performance. When diagnosing empyema, the marker with the highest sensitivity was pleural fluid presepsin (cut-off: 754 pg/mL; sensitivity: 90.9%, specificity: 74.4%) and that with the highest specificity was pleural fluid CRP (cut-off: 4.91 mg/dL; sensitivity: 63.6%, specificity: 89.3%). Pleural fluid PCT tended to be lower in patients with empyema than in those with parapneumonic effusion, but this was not useful for the diagnosis of empyema. When diagnosing infectious pleural effusion, a combination of pleural fluid CRP (cut-off: 2.59 mg/dL) and presepsin (cut-off: 680 pg/mL) produced the highest diagnostic accuracy (83.3%)., Conclusions: Pleural fluid presepsin was found at high levels in patients with empyema and parapneumonic effusion. This pattern closely resembles the previously reported pattern of pleural fluid CRP. Some combinations of pleural fluid inflammatory markers may be more clinically useful than these markers in isolation.

Small-cell lung cancer (SCLC) is intractable due to its high propensity for relapse. Novel agents are thus needed for SCLC treatment. Lemongrass essential oil (LG-EO) and its major constituent, citral, have been reported to inhibit the proliferation and survival of several types of cancer cells. However, the precise mechanisms through which LG-EO and citral exert their effects on SCLC cells have not been fully elucidated. SCLC cells express Src and have high levels of Src-tyrosine kinase (Src-TK) activity. In most SCLC cell lines, constitutive phosphorylation of Stat3(Y705), which is essential for its activation, has been detected. Src-TK can phosphorylate Stat3(Y705), and activated Stat3 promotes the expression of the anti-apoptotic factors Bcl-xL and Mcl-1. In the present study, LG-EO and citral prevented Src-TK from phosphorylating Stat3(Y705), resulting in decreased Bcl-xL and Mcl-1 expression, in turn suppressing the proliferation/survival of SCLC cells. To confirm these findings, the wild-type-src gene was transfected into the LU135 SCLC cell line (LU135‑wt-src), in which Src and activated phospho-Stat3(Y705) were overexpressed. The suppression of cell proliferation and the induction of apoptosis by treatment with LG-EO or citral were significantly attenuated in the LU135-wt-src cells compared with the control LU135-mock cells. The signal transducer and activator of transcription 3 (Stat3) signaling pathway is also associated with intrinsic drug resistance. LU135-wt-src cells were significantly resistant to conventional chemotherapeutic agents compared with LU135-mock cells. The combined effects of citral and each conventional chemotherapeutic agent on SCLC cells were also evaluated. The combination treatment exerted additive or more prominent effects on LU135-wt-src, LU165 and MN1112 cells, which are relatively chemoresistant SCLC cells. These findings suggest that either LG-EO or citral, alone or in combination with chemotherapeutic agents, may be a novel therapeutic option for SCLC patients.