Impact of preoperative pathological confirmation on surgical and postoperative outcomes of lung resection for early stage lung cancer

Introduction: The frequency of detection of peripheral pulmonary lesion (PPL) in suspected early lung cancer has been increasing, and whether preoperative pathological diagnosis (PPD) for small PPLs should always be established before their surgical resection can become a worrisome problem for physicians. The aim of the study was to clarify the impact of obtaining PPD on surgical and postoperative outcomes of lung resection for early stage lung cancer.Material and methods: This was a retrospective review of cases that underwent surgical resection for known or suspected primary lung cancer presenting pathological stage 0 or I, enrolled from June 2006 to May 2016. The patients divided into two groups according to PPD group (n = 57) and non-PPD group (n = 157) were compared. The procedure, node dissection, operation time, amount of bleeding, postoperative complications, postoperative length of stay, and postoperative recurrences were analyzed.Results: Among the 214 patients, no significant differences in operation time (248.5 ± 88.6 versus 257.6 ± 89.0, min, mean ± SD, p = 0.328), amount of bleeding (195.3 ± 176.5 vs 188.1 ± 236.1, ml, p = 0.460), postoperative complication (5.2% vs 4.5%, p = 0.728), postoperative length of stay (10.6 ± 6.3 vs 10.4 ± 5.3, days, p = 0.827), or postoperative recurrences (21.0% vs 17.2%, p = 0.550) were seen between PPD and non-PPD groups.Conclusion: Therefore, PPD had less impact on surgical and postoperative outcomes of pathological stage 0 or I lung cancer; direct surgical resection without non-surgical biopsy would be acceptable with careful selection of cases

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

Predictive factors for a successful diagnostic bronchoscopy of ground-glass nodules

Introduction: Since the National Lung Screening Trial demonstrated the utility of low-dose computed tomography screening for lung cancer, the detection rate of ground-glass nodules (GGNs) has increased. Endobronchial ultrasound with a guide sheath (EBUS-GS) is widely performed to diagnose peripheral pulmonary lesions, but there are not enough reports on the predictive ability of EBUS-GS in diagnosing GGNs. The aim of this study is to investigate the predictive factors for a successful diagnostic bronchoscopy for GGNs. Methods: Consecutive patients who underwent diagnostic bronchoscopy for GGNs from September 2012 to January 2016 were enrolled in this study. From these, cases who underwent EBUS-GS were selected. They were reviewed and analyzed to examine the association between the diagnostic yield and the following clinical factors: lesion size, lobar position, location, consolidation-to-tumor ratio, visibility on X-ray, use of virtual bronchoscopy, bronchus sign, guide sheath size, and number of biopsies. Results: We enrolled 254 cases, of which 167 were diagnosed using EBUS-GS (65.7% diagnostic yield). Univariate analysis indicated that a positive bronchus sign was a significant factor for higher diagnostic yield (72.9% vs. 34.0%; P < 0.001). The use of virtual bronchoscopy also tended toward a higher yield, but the result was not significant (69.0% vs. 54.4%; P = 0.058). However, multivariate analysis indicated that both were significantly associated with higher diagnostic yield (P < 0.001, odds ratio [OR]: 5.35; P < 0.001, OR: 1.97, respectively). Conclusions: Our results suggest that a positive bronchus sign and the use of virtual bronchoscopy are positive predictive factors for successful diagnostic bronchoscopy of GGNs

Elimination of IL-13 Reverses Established Goblet Cell Metaplasia into Ciliated Epithelia in Airway Epithelial Cell Culture

Background: Interleukin (IL)-13 induces goblet cell metaplasia and plays an important role in mucus hypersecretion in asthma. We previously reported that IL-13 induced goblet cell differentiation along with less ciliated cell differentiation in guinea pig tracheal epithelial cells in vitro. In this study, we asked whether elimination of IL-13 could reverse the established goblet cell metaplasia into ciliated epithelia. Methods: Primary epithelial cells from guinea pig tracheas were cultured at an air-liquid interface with the medium containing human recombinant IL-13 for 14 days, and continuously cultured with IL-13-eliminated medium, or cultured under the condition of neutralization of IL-13 with anti IL-13 antibody. Results: 2 days after elimination of IL-13, the periodic acid-Schiff-positive area as well as MUC5AC protein level rapidly decreased. After 4 days, the number of goblet cells dramatically decreased, while that of ciliated cells inversely increased. The total number of epithelial cells did not change, and 5-bromo-2’-deoxyuridine uptake decreased after IL-13 elimination. Transitional cells with cilia and secretory granules increased after IL-13 elimination. Similarly, the neutralization of IL-13 with anti-IL-13 antibody for 5 days reversed the goblet cell metaplasia into ciliated epithelia, and transitional cells also increased. Conclusions: Elimination of IL-13 reverses goblet cell metaplasia into ciliated epithelia in vitro, and transition of goblet cells to other phenotypes, especially ciliated cells, may be involved in this phenomenon. IL-13 inhibition may be a therapeutic strategy of established goblet cell metaplasia in asthma

Blizzard Sign as a specific endobronchial ultrasound image for ground glass opacity: A case report

We report a case of lung adenocarcinoma presenting as pure ground glass opacity (GGO) and diagnosed by bronchoscopy with the use endobronchial ultrasound with a guide sheath (EBUS-GS). The lesion was indistinguishable by real-time fluoroscopy but simultaneous endobronchial ultrasound scanning of the involved lung segment showed a hyperechoic shadow that was subtly more intense than a typical snowstorm appearance when scanning normal alveolar tissue. Transbronchial biopsy from this area revealed adenocarcinoma with lepidic growth. On hindsight, it was the aforementioned ultrasound pattern that helped us decide the sampling site for EBUS-GS guided TBB when fluoroscopy was equivocal. We hypothesize that this pattern is specific for GGO and we name it the Blizzard Sign