Clinical characteristics and outcomes of patients with small cell lung cancer detected by CT screening

The present study was performed to evaluate the clinical characteristics and survival outcomes in patients with small cell lung cancer (SCLC) detected by low-dose computed tomography (CT). We retrospectively reviewed clinical records of patients with SCLC treated at our hospital between 1997 and 2011 and selected patients with SCLC detected by CT screening. We identified 12 patients (male/female 11/1; mean age 67.8 years old. Nine patients had limited disease (LD), and 3 had extensive disease (ED). Five LD patients underwent thoracic surgery, and the pathological staging information included stage IA (n = 1), IB (n = 1), IIA (n = 1), and IIIB (n = 2). Although 2 patients with pathological stages IA and IB had >10-year survival, the median survival times (MST) in LD and ED were 25 months (95 % CI 17.0-32.9) and 16 months (95 % CI; not evaluated), respectively. In addition, MST in 12 patients was not significantly different from that in SCLC patients in general care in our hospital. This analysis suggested that CT screening contributes to the detection of early-stage SCLC in patients that are potentially suitable for surgery, but it remains unclear how to improve clinical outcome in patients with SCLC.ArticleMEDICAL ONCOLOGY. 30(3):623 (2013)journal articl

An Unusual Case of Multicentric Castleman's Disease, Complicated by Pleural Effusion

Article信州医学雑誌 65(1): 51-56(2017)journal articl

Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptor-mutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group Study

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第939号）・立石 一成The final publication is available at www.springerlink.com.The clinical efficacy and outcomes of gefitinib therapy as a first-line treatment for elderly patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations were analyzed retrospectively. We analyzed chemotherapy-naive NSCLC patients aged 75 years or older who had EGFR mutations (exon 19 deletion mutation or L858R), who were initially treated with gefitinib (250 mg) once daily in Nagano Prefecture. A total of 55 patients (16 men, 39 women) with a median age of 81.1 years (range; 75-94 years) treated between April 2007 and July 2012 were analyzed. The overall response rate and disease control rate were 72.7 % (95 % confidence interval (CI); 59.5-82.9 %) and 92.7 % (95 % CI; 82.0-97.6 %), respectively. Median progression-free survival and overall survival from the start of gefitinib treatment were 13.8 months (95 % CI; 9.9-18.8 months) and 29.1 months (95 % CI; 22.4 months-not reached), respectively. Two-year survival rate was 59.5 % (95 % CI; 41.0-78.0 %). Major grade 3 toxicities were skin rash (1.8 %) and increased levels of aspartate aminotransferase or alanine aminotransferase (7.3 %). First-line treatment with gefitinib for elderly EGFR-mutated NSCLC patients was effective and well tolerated. The results suggest that first-line gefitinib should be considered as a preferable standard treatment in elderly patients with advanced NSCLC harboring EGFR mutations.ArticleMEDICAL ONCOLOGY. 30(1):45 (2013)journal articl

EGFR mutation and ALK fusion-positive non-small cell lung cancer: a multicenter prospective cohort study in Nagano Prefecture, Japan

Introduction. We prospectively examined current clinical practices in patients with inoperable epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion-positive (EGFR+ and ALK+, respectively) non-small cell lung cancer (NSCLC) in Nagano Prefecture, Japan.  Material and methods. The study population consisted of newly diagnosed patients with inoperable EGFR+ and ALK+ NSCLC in 14 hospitals in Nagano between May 2016 and March 2019. Both initial and subsequent treatment decisions were made at the discretion of the attending physician.  Results. A total of 281 patients with EGFR+ NSCLC (mean age, 74 years, 59.1% female) and 26 patients with ALK+ NSCLC (mean age, 66 years, 53.8% female) were included in the study. The study population consisted of 148/107/29/20/3 cases with performance status 0/1/2/3/4 and 6/2/31/194/75 cases with clinical stage I/II/III/IV/recurrence, respectively. First-line therapy with tyrosine kinase inhibitors was performed in 259 (92.2%) and 22 (84.6%) patients with EGFR+ and ALK+ NSCLC, respectively. The median overall survival rate was 41.2 months (95% CI 36.8–45.6 months) with EGFR+. It was not reached with ALK+ .  Conclusions. This observational analysis represents a valuable resource for evaluating the outcomes of treatment in patients with NSCLC

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Nonfibrotic Hypersensitivity Pneumonitis Complicated by Chronic Progressive Pulmonary Aspergillosis : A Case Report

Diagnosis of chronic pulmonary aspergillosis in patients with nonfibrotic hypersensitivity pneumonitis is difficult, especially after treatment with systemic corticosteroids has been initiated. Therefore, treatment for chronic progressive pulmonary aspergillosis (CPPA) is often delayed. Although the chief complaint of non-fibrotic hypersensitivity pneumonitis complicated by pulmonary aspergillosis is often fever, the fungus cannot be identified, even after repeated sputum culture tests. Herein, we report a case of pulmonary aspergillosis that developed after initiating treatment with systemic corticosteroids and was difficult to diagnose. The patient had a fever that continued after the introduction of steroids. CPPA was eventually diagnosed based on histopathological examination of a bronchoscopy sample. When CPPA is suspected in patients with hypersensitivity pneumonitis, bronchoscopy may improve their prognosis.Article信州医学雑誌 71(4) : 235-240, (2023)journal articl

Successful Concurrent Chemoradiotherapy with Cisplatin plus Vinorelbine for Locally Advanced Thymic Carcinoma

Little information is available about the usefulness of concurrent chemoradiotherapy for locally advanced thymic carcinoma due to a rare anterior mediastinal tumor. We experienced a case of locally advanced thymic carcinoma that responded well to concurrent thoracic radiotherapy combined with cisplatin plus vinorelbine chemotherapy. The patient showed remarkable tumor regression and has remained disease free for over 4 years following combined therapy. Concurrent chemoradiotherapy seems to be effective for locally advanced thymic carcinoma, and cisplatin plus vinorelbine could be an alternative chemotherapy regimen in combination with thoracic radiotherapy in patients with thymic carcinoma