Lung cancer (LC) causes the majority of cancer-related deaths. Circular RNAs (circRNAs) were reported to play roles in cancers by targeting pro- and anti-oncogenic miRNAs. However, the mechanisms of circRNAs in LC progression and their prognostic value of treatment response remain unclear. By using next generation sequencing (NGS) of LC cell lines’ transcriptomes, we identified highly overexpressed hsa_circ_0000190 and hsa_circ_000164 as potential biomarkers. By using the highly sensitive RT-ddPCR method, these circRNAs were shown to be secreted by cell lines and were detected in human blood. Clinical validation by RT-ddPCR was carried out on 272 (231 LC patients and 41 controls) blood samples. Higher hsa_circ_0000190 levels were associated with larger tumor size (p < 0.0001), worse histological type of adenocarcinoma (p = 0.0028), later stage (p < 0.0001), more distant metastatic organs (p = 0.0039), extrathoracic metastasis (p = 0.0004), and poor survival (p = 0.047) and prognosis. Using liquid biopsy-based RT-ddPCR, we discovered the correlation between increased hsa_circ_0000190 plasma level (p < 0.0001) and higher programmed death-ligand 1 (PD-L1) level in tumor (p = 0.0283). Notably, long-term follow-up of the immunotherapy treated cases showed that upregulated plasma hsa_circ_0000190 level correlated with poor response to systemic therapy and immunotherapy (p = 0.0002, 0.0058, respectively). Secretory circRNAs are detectable in blood by LB-based RT-ddPCR and may serve as blood-based biomarkers to monitor disease progression and treatment efficacy.

Oxidative stress elicited by reactive oxygen species (ROS) and chronic inflammation are involved both in deterring and the generation/progression of human cancers. Exogenous ROS can injure mitochondria and induce them to generate more endogenous mitochondrial ROS to further perpetuate the deteriorating condition in the affected cells. Dysfunction of these cancer mitochondria may possibly be offset by the Warburg effect, which is characterized by amplified glycolysis and metabolic reprogramming. ROS from neutrophil extracellular traps (NETs) are an essential element for neutrophils to defend against invading pathogens or to kill cancer cells. A chronic inflammation typically includes consecutive NET activation and tissue damage, as well as tissue repair, and together with NETs, ROS would participate in both the destruction and progression of cancers. This review discusses human mitochondrial plasticity and the glucose metabolic reprogramming of cancer cells confronting oxidative stress by the means of chronic inflammation and neutrophil extracellular traps (NETs).

Background: The tubeless technique, defined as non-intubated general anesthesia with omission of chest drainage after video-assisted thoracoscopic surgery (VATS), is a new concept to further minimize surgical trauma. However, there has been little investigation into the associated feasibility and safety. Minimization of postoperative pneumothorax is challenging. We set up a “tubeless protocol” to select patients for tubeless single-port VATS with monitoring of a digital drainage system (DDS). Methods: From November 2016 to September 2017, 50 consecutive non-intubated single-port VATS for pulmonary resection were performed. In our study, patients with small and peripheral pulmonary lesions indicated for sublobar resections, as diagnostic or curative intent, were included. After excluding patients having tumors >2 cm, or intrapleural adhesions noted during operation, or forced expiratory volume in the 1 second <1.5 L, 36 patients were selected for tubeless protocol. The clinical characteristics and perioperative outcomes of these patients are presented. Results: Among 36 cases, 5 patients had minor air leaks detected using the DDS and required intercostal drainage after wound closure. Among the remaining 31 patients in whom the DDS showed no air leak, the chest drainage was removed immediately after wound closure. A postoperative chest roentgenogram on the surgery day showed full expansion in all patients without pneumothorax. Only 7 (19.4%) patients developed minor subclinical pneumothorax on the first postoperative day without the need for chest drainage. All patients were discharged uneventfully without the need for intervention. Conclusions: Our tubeless protocol utilizes DDS to select patients who can have intercostal drainage omitted after non-intubated single-port VATS for pulmonary resection. Using objective DDS parameters, we believe that this is an effective way to reduce the rate of pneumothorax after tubeless single-port VATS in selected patients.

Nodal upstaging of lung adenocarcinoma occurs when unexpected pathological lymph node metastasis is found after surgical intervention, and may be associated with a worse prognosis. In this study, we aimed to determine the predictive factors of nodal upstaging in cT1a-bN0M0 primary lung adenocarcinoma. We retrospectively reviewed a prospective database (January 2011 to May 2017) at National Taiwan University Hospital and identified patients with cT1a-bN0M0 (solid part tumor diameter ≤ 2 cm) lung adenocarcinoma who underwent video-assisted thoracoscopic lobectomy. Logistic regression models and survival analysis were used to examine and compare the predictive factors of nodal upstaging. A total of 352 patients were included. Among them, 28 (7.8%) patients had nodal upstaging. Abnormal preoperative serum carcinoembryonic antigen (CEA) levels, solid part tumor diameter ≥ 1.3 cm, and consolidation–tumor (C/T) ratio ≥ 0.50 on chest computed tomography (CT) were significant predictive factors associated with nodal upstaging, and patients with nodal upstaging tended to have worse survival. Standard lobectomy is recommended for patients with these predictive factors. If neither of the predictive factors are positive, a less invasive procedure may be a reasonable alternative. Further studies are needed to verify these data.