Genome-wide expression of the residual lung reacting to experimental Pneumonectomy

Background Acute or chronic irreversible respiratory failure may occur in patients undergoing pneumonectomy. Aim of this study was to determine transcriptome expression changes after experimental pneumonectomy in swine model. Experimental left pneumonectomy was performed in five pigs under general anaesthesia. Both the resected and the remaining lung, after 60 post-operative completely uneventful days, underwent genome-wide bulk RNA-Sequencing (RNA-Seq). Results Histological analysis showed dilation of air spaces and rupture of interalveolar septa. In addition, mild inflammation, no fibrosis, radial stretch of the bronchus, strong enlargement of airspaces and thinning of the blood supply were observed. Bioinformatic analyses of bulk RNA-Seq data identified 553 Differentially Expressed Genes (DEGs) at adjusted P-value below 0.001, between pre- and post-pneumonectomy. The top 10 up-regulated DEGs were Edn1, Areg, Havcr2, Gadd45g, Depp1, Cldn4, Atf3, Myc, Gadd45b, Socs3; the top 10 down-regulated DEGs were Obscn, Cdkn2b, ENSSSCG00000015738, Prrt2, Amer1, Flrt3, Efnb2, Tox3, Znf793, Znf365. Leveraging digital cytometry tools, no difference in cellular abundance was found between the two experimental groups, while the analysis of cell type-specific gene expression patterns highlighted a striking predominance of macrophage-specific genes among the DEGs. DAVID-based gene ontology analysis showed a significant enrichment of “Extrinsic apoptotic signaling pathway” (FDR q = 7.60 × 10− 3) and “Response to insulin” (FDR q = 7.60 × 10− 3) genes, along with an enrichment of genes involved as “Negative regulators of DDX58/IFIH1 signaling” (FDR q = 7.50 × 10− 4) found by querying the REACTOME pathway database. Gene network analyses indicated a general dysregulation of gene inter-connections. Conclusion This translational genomics study highlighted the existence both of individual genes, mostly dysregulated in certain cellular populations (e.g., macrophages), and gene-networks involved in pulmonary reaction after left pneumonectomy. Their involvement in lung homeostasis is largely supported by previous studies, carried out both in humans and in other animal models (under homeostatic or disease-related conditions), that adopted candidate-gene approaches. Overall, the present findings represent a preliminary assessment for future, more focused, studies on compensatory lung adaptation, pulmonary regeneration and functional reload.

Investigation of the mechanisms of VEGF-mediated compensatory lung growth: the role of the VEGF heparin-binding domain

Morbidity and mortality for neonates with congenital diaphragmatic hernia-associated pulmonary hypoplasia remains high. These patients may be deficient in vascular endothelial growth factor (VEGF). Our lab previously established that exogenous VEGF164 accelerates compensatory lung growth (CLG) after left pneumonectomy in a murine model. We aimed to further investigate VEGF-mediated CLG by examining the role of the heparin-binding domain (HBD). Eight-week-old, male, C57BL/6J mice underwent left pneumonectomy, followed by post-operative and daily intraperitoneal injections of equimolar VEGF164 or VEGF120, which lacks the HBD. Isovolumetric saline was used as a control. VEGF164 significantly increased lung volume, total lung capacity, and alveolarization, while VEGF120 did not. Treadmill exercise tolerance testing (TETT) demonstrated improved functional outcomes post-pneumonectomy with VEGF164 treatment. In lung protein analysis, VEGF treatment modulated downstream angiogenic signaling. Activation of epithelial growth factor receptor and pulmonary cell proliferation was also upregulated. Human microvascular lung endothelial cells (HMVEC-L) treated with VEGF demonstrated decreased potency of VEGFR2 activation with VEGF121 treatment compared to VEGF165 treatment. Taken together, these data indicate that the VEGF HBD contributes to angiogenic and proliferative signaling, is required for accelerated compensatory lung growth, and improves functional outcomes in a murine CLG model.

Case Report: COVID-19 Pneumonia Following Left Pneumonectomy for Lung Cancer Complicated by Empyema and Bronchopleural Fistula

Background: Venous and arterial thromboembolism is commonly reported in critically ill COVID-19 patients, although there are still no definitive statistical data regarding its incidence.Case presentation: we report a case of a patient who fell ill with Covid during hospitalization for a pneumonectomy complicated by empyema and bronchopleural fistula. The patient, despite being cured of COVID, died after 14 days for pulmonary thromboembolism.Conclusion: Our case strengthens the suggestion of adequate thromboprophylaxis in all hospitalized COVID patients and of increasing prophylaxis in critically ill patients even in the absence of randomized studies

Lung metastasis after pneumonectomy. Is there a place for surgery?

The choice of patient for a single lung resection is challenging for the surgeon. This report is presenting our experience in surgical treatment for patient with metastatic synovial sarcoma who initially underwent total left pneumonectomy and to identify possible predictors for the selection of patients who may undergo surgical treatment.

An Uncommon Cause of Dysphagia: Postpneumonectomy Syndrome

Objective. Dysphagia after pneumonectomy is uncommon but concerning. The purpose of this paper is to present a case of dysphonia secondary to postpneumonectomy syndrome. Case Report. A 66-year-old female with stage IIIa adenocarcinoma of the lung was treated with a left pneumonectomy. Three years later, she presented with severe dysphagia, dyspnea, and dysphonia. Esophagram demonstrated severely deviated esophagus to the left of midline, attributed to prior left-sided pneumonectomy, without clear evidence of any external compression. Chest CT scan showed associated leftward mediastinal shift. This patient was treated with voice therapy and an exclusion diet, as the patient elected not to have surgery. Conclusion. This is the first reported case of dysphonia accompanying severe dysphagia following left pneumonectomy. While postpneumonectomy syndrome is rare, a high degree of clinical suspicion is recommended when treating patients with history of pneumonectomy.

Left pneumonectomy for primary lung cancer with Trousseau’s syndrome

Trousseau’s syndrome is a paraneoplastic syndrome and a pathological condition that causes cerebral stroke symptoms due to hypercoagulation associated with malignant tumours. There have been many cases of advanced lung cancer, but few reports have described surgery for lung cancer with Trousseau’s syndrome. We encountered a 76-year-old man suspected of having Trousseau’s syndrome associated with lung cancer. He was transferred to our hospital on the second day after the onset. After admission, he was treated with heparin and edaravone, and his condition improved. On the 12th day after the onset, we performed left pneumonectomy and lymph node dissection (ND2a-2). The final pathological results were adenocarcinoma, pathological stage was T4 (tumour size: 77 mm, pulmonary artery invasion) N1(#11, #12u) M0, stage IIIA. He has been recurrence free for 23 months since the surgery. In the future, we need to follow his condition carefully.