Right Sleeve Pneumonectomy for Local Recurrent Lung Cancer Following Right Sleeve Upper Lobectomy With Bronchoplasty: A Case Report.

Background:Salvage surgery has been frequently performed, increasing the opportunity to actively perform surgery for recurrence after a function-preserving operation. However, re-operation after airway reconstruction surgery on the proximal side and the effect of prior treatment, such as radiotherapy and/or chemotherapy, make the operation more difficult. In addition, cases of sleeve pneumonectomy after sleeve lobectomy with bronchoplasty are uncommon.Case presentation:A 71-year-old lung cancer patient underwent right upper sleeve lobectomy with bronchoplasty combined with perioperative chemotherapy in 2007. A new undiagnosed right hilar mass that appeared 9 years post-operation showed a temporary response to radiotherapy but progressed thereafter. Sleeve pneumonectomy was completed 14 months after radiotherapy by the following procedures: dividing the right pulmonary artery at the proximal site under median sternotomy and then reconstructing the bronchus by telescoping the left main bronchus into the distal trachea after pneumonectomy under posterolateral thoracotomy.Conclusions:Sleeve pneumonectomy for recurrent lung cancer could be safely performed under good vision using a two-stage approach as salvage surgery, even in high-risk patients who received various treatments and proximal airway reconstruction

Impact of fractional exhaled nitric oxide on the outcomes of lung resection surgery: a prospective study.

Background:Fractional exhaled nitric oxide (FeNO), which is representative of airway inflammation, is an indicator of chronic lung disease. However, its effect on the outcome of lung resection is unknown. The aim of this prospective study was to evaluate FeNO in patients who underwent lung resection, to analyze the perioperative dynamics, and clarify the impact on postoperative complications.Methods: We measured FeNO using NIOX VERO® once before and on days 1, 3, 5–7 after surgery in participants who were candidates for lung cancer surgery. The primary endpoint was the relationship between postoperative morbidity and preoperative FeNO. The secondary endpoint was the relationship between postoperative FeNO and additional treatment, including readmission.Results:We enrolled 105 patients between September 2017 and March 2019. Anatomical lung resection was the predominant treatment (87%) for primary lung cancer. Postoperative pulmonary complications developed in 16 patients. Multivariate analysis revealed that preoperative FeNO was a significant predictor of postoperative pulmonary complications (P=0.002, OR: 1.004, 95% CI: 1.016–1.074). FeNO levels increased significantly after surgery (P=0.011). Postoperative FeNO was a significant predictor of the need for additional medical treatment within 30 days of surgery (P=0.001, OR: 1.068, 95% CI: 1.028–1.110).Conclusions: Perioperative FeNO was a significant predictor of surgical outcome among patients who underwent lung resection. The measurement of FeNO is expected to be a simple and useful method for preventing subsequent deterioration in these patients

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

Impact of thoracic esophageal displacement after lobectomy on the continuity of oral adjuvant chemotherapy.

Background:Adjuvant tegafur-uracil therapy has prolonged postoperative survival in patients with non-small cell lung cancer. Some patients experience treatment discontinuation due to gastrointestinal disorders such as anorexia, and the associated factors and the impact of lobectomy remain unclear. This study aimed to assess the postoperative esophageal displacement after lobectomy and to clarify its impact on the continuity of tegafur-uracil treatment.Methods:Patients who received adjuvant tegafur-uracil therapy after lobectomy between April 2009 and March 2019 were retrospectively analyzed. Patient background, perioperative characteristics, treatment findings, and the degree of esophageal displacement measured by computed tomography were compared between the treatment completion group and the discontinuation group. A subgroup comparative analysis was further performed in the groups divided according to the degree of esophageal displacement.Results:A total of 68 patients were reviewed, including 41 males and 27 females with a mean age of 66.2 years old. A total of 41 patients completed the 2-year adjuvant treatment and 27 patients discontinued it. The overall survival and relapse-free survival between the two groups were statistically significant (p = 0.027, p = 0.010). The degree of esophageal displacement at the Th7 level was a significant predictor of treatment discontinuation (p = 0.046, odds ratio [OR]: 1.138, 95% confidence interval [CI]: 1.002-1.291). Among the patients with a high degree of esophageal displacement above the baseline determined from the receiver operating characteristic curve, the cause of discontinuation was anorexia, which was significant in multivariate analysis (p = 0.013, OR: 14.72, 95% CI: 1.745-124.2).Conclusions:Our study suggested that anatomical displacement of the esophagus after lobectomy may affect the discontinuation of oral adjuvant chemotherapy in patients with lung cancer