Clinical course of COVID-19 pneumonia in a patient undergoing pneumonectomy and pathology findings during the incubation period.
- 作者列表："Çınar HNU","İnce Ö","Çelik B","Saltabaş F","Özbek M
BACKGROUND:The cause of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical information about patients undergoing lung resection while infected with this virus and pathological information about early COVID-19 pneumonia are still scarce. CASE PRESENTATION:A 69-year-old male patient underwent a right pneumonectomy for squamous cell lung carcinoma. Until the fourth postoperative day, the patient, who had minor radiological changes on chest x-ray, was asymptomatic. From this day, the COVID-19 test, which was performed after the appearance of symptoms such as fever and shortness of breath, lymphopenia and diffuse ground glass opacity in the left lung on computed tomography, was reported to be positive. The patient was given NIMV (non-invasive mechanical ventilation), and hydroxychloroquine, favipiravir and azithromycin in isolation intensive care, with the diagnosis of severe pneumonia. He was discharged on the 17th postoperative day with healing of the lung lesions. The pathology specimen of the patient, who was found to have been infected with SARS-CoV-2 before the day of surgery, was examined retrospectively. Irregular and severe pneumocyte hyperplasia, interstitial thickening, oedema, pronounced protein exudates, diffuse enlargement of the alveolar walls, macrophage infiltration and fibroblastic proliferation, which is an indicator of early organisation, were detected. CONCLUSION:We believe that the clinical course and pathology findings obtained after right pneumonectomy in a patient with pre-symptomatic COVID-19 pneumonia will guide the diagnosis and treatment of patients infected with SARS-CoV-2.
背景: 冠状病毒疾病 2019 (新型冠状病毒肺炎) 的病因是新型冠状病毒冠状病毒 2 (SARS-CoV-2)。感染这种病毒时接受肺切除术的患者的临床信息和早期新型冠状病毒肺炎肺炎的病理信息仍然很少。 病例报告: 一名 69 岁男性患者因肺鳞状细胞癌行右全肺切除术。直到术后第 4 天，胸部x光检查有轻微影像学改变的患者无症状。从这一天开始，新型冠状病毒肺炎测试，这是在计算机断层扫描显示左肺出现发热和呼吸急促、淋巴细胞减少症和弥漫性磨玻璃影等症状后进行的，报告为阳性。患者接受NIMV (无创机械通气)，以及羟氯喹、法匹拉韦和阿奇霉素的隔离重症监护，诊断为重症肺炎。患者于术后第 17 天出院，肺部病灶愈合。对患者的病理标本进行回顾性检查，该患者在手术前发现SARS-CoV-2 感染。检测到不规则和严重的肺细胞增生、间质增厚、水肿、明显的蛋白渗出、肺泡壁弥漫性扩大、巨噬细胞浸润和成纤维细胞增生，这是早期组织的指标。 结论: 我们认为的临床及病理资料，获得后右全肺切除患者症状前新型冠状病毒肺炎肺炎将指导诊断和治疗的感染患者SARS-CoV-2.
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.