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OBJECTIVESThe present study aimed to clarify the association between preoperative biopsy and surgical outcomes in clinical stage I non-small-cell lung cancer (NSCLC) with different proportions of ground-glass opacity (GGO).METHODSData on patients who underwent pulmonary resection for NSCLC from 2006 to 2016 were drawn from a prospective registered database and analysed retrospectively. Patient characteristics collected included tumour size, location and staging, surgical approach, consolidation–tumour ratio, histopathology and the presence or absence of preoperative biopsy to identify the independent prognostic factors of disease-free survival (DFS) and cancer-specific survival. A 1:1 propensity score matching was conducted between the preoperative biopsy and reference groups based on their baseline characteristics measured before the decision for preoperative biopsy.RESULTSA total of 1427 patients were collected to achieve an overall 5-year DFS as 84.5% (median follow-up: 67.3 months), stratified to be 99.5% in the GGO-dominant group (n = 430) and 78.2% in the solid-dominant group (n = 997). Only 2 patients (0.5%) in the GGO-dominant group experienced tumour recurrence. For solid-dominant tumours matched with propensity scores (279 in preoperative biopsy vs 279 in reference group), the independent predictors of DFS included preoperative biopsy, sublobar resection, pathological staging and angiolymphatic invasion. Preoperative biopsy was a predictor of cancer-specific survival in univariable analysis but was not in multivariable analysis. Significant differences were also found between matched groups in those with late-delay surgery, but not in patients receiving preoperative biopsy with early-delay surgery (≤21 days).CONCLUSIONPreoperative biopsy may worsen surgical outcomes in patients with clinical stage I, solid-dominant NSCLC.

Simple Summary Frequent high-dietary fat intake increases muscle lipid use and reduces muscle carbohydrate use, thereby inducing metabolic inflexibility. The latter term can be described as a poor muscle biochemical and molecular response to increased availability of insulin, which in the long term results in chronically excessive-high glucose levels in blood. Chronic hyperglycaemia is associated with many pathological conditions, including type 2 diabetes mellitus, which can cause severe health damages in humans. Here, we attempt to unravel the underlying mechanism and its associated factors behind the inhibition of muscle glucose use by a high-fat diet, thereby providing evidence for appropriate therapeutic intervention. Abstract The molecular mechanisms by which free fatty acids (FFA) inhibit muscle glucose oxidation is still elusive. We recently showed that C2C12 myotubes treated with palmitate (PAL) presented with greater protein expression levels of PDK4 and transcription factors PPARα and PPARδ and lower p-FOXO/t-FOXO protein ratios when compared to control. This was complemented with the hallmarks of metabolic inflexibility (MI), i.e., reduced rates of glucose uptake, PDC activity and maximal pyruvate-derived ATP production rates (MAPR). However, the relative contribution of these transcription factors to the increase in PDK4 and reduced glucose oxidation could not be established. Therefore, by using a similar myotube model, a series of individual siRNA gene silencing experiments, validated at transcriptional and translation levels, were performed in conjunction with measurements of glucose uptake, PDC activity, MAPR and concentrations of metabolites reflecting PDC flux (lactate and acetylcarnitine). Gene silencing of PPARα, δ and FOXO1 individually reduced PAL-mediated inhibition of PDC activity and increased glucose uptake, albeit by different mechanisms as only PPARδ and FOXO1 silencing markedly reduced PDK4 protein content. Additionally, PPARα and FOXO1 silencing, but not PPARδ, increased MAPR with PAL. PPARδ silencing also decreased FOXO1 protein. Since FOXO1 silencing did not alter PPARδ protein, this suggests that FOXO1 might be a PPARδ downstream target. In summary, this study suggests that the molecular mechanisms by which PAL reduces PDC-mediated glucose-derived pyruvate oxidation in muscle occur primarily through increased PPARδ and FOXO1 mediated increases in PDK4 protein expression and secondarily through PPARα mediated allosteric inhibition of PDC flux. Furthermore, since PPARδ seems to control FOXO1 expression, this may reflect an important role for PPARδ in preventing glucose oxidation under conditions of increased lipid availability.

Background Preoperative positron emission tomography/computed tomography (PET/CT) is recommended as a guideline for staging of lung cancer. However, for patients with pulmonary ground‐glass opacity (GGO) nodules who are supposed to have a relatively low risk of incidence of lymphatic metastasis, it remains uncertain whether PET/CT is more effective than consolidation‐to‐tumor ratio (CTR) in the prediction of regional lymphatic metastasis. Methods The data on patients who underwent surgery for lung cancer from 2011 to 2016 were collected retrospectively, which included CTR, results of PET/CT, and pathological characteristics. The patients who had undergone preoperative PET/CT were identified to find the risk factors for lymphatic metastasis. A receiver operating characteristic (ROC) curve and multiple logistic regression was utilized to clarify the predictive value of CTR and main tumor maximal standardized uptake value (SUVmax). Results Among 217 patients who had PET/CT before lobectomy, chest computed tomography revealed that 75 patients had CTR greater than 62%. The patients with lymphatic metastasis were shown to have higher CTR and higher main tumor SUVmax. Multiple logistic regression showed that younger age (, For lung cancer patients with a ground‐glass opacity (GGO) component, CTR was not inferior to main tumor SUVmax for the prediction of lymph node metastasis in a preoperative setting. PET/CT might not be necessary preoperatively in selected patients at low risk of incidence of lymph node metastasis.

The mechanisms behind the reduction in muscle pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation during chronic high-fat dietary intake are poorly understood, as is the basis of CHO oxidation restoration during muscle contraction. C2C12 myotubes were treated with (300 &mu, M) palmitate or without (control) for 16 h in the presence and absence of electrical pulse stimulation (EPS, 11.5 V, 1 Hz, 2 ms). Compared to control, palmitate reduced cell glucose uptake (p &lt, 0.05), PDC activity (p &lt, 0.01), acetylcarnitine accumulation (p &lt, 0.05) and glucose-derived mitochondrial ATP production (p &lt, 0.01) and increased pyruvate dehydrogenase kinase isoform 4 (PDK4) (p &lt, 0.01), peroxisome proliferator-activated receptor alpha (PPAR&alpha, ) (p &lt, 0.01) and peroxisome proliferator-activated receptor delta (PPAR&delta, 0.01) proteins, and reduced the whole-cell p-FOXO1/t-FOXO1 (Forkhead Box O1) ratio (p &lt, 0.01). EPS rescued palmitate-induced inhibition of CHO oxidation, reflected by increased glucose uptake (p &lt, 0.01), PDC activity (p &lt, 0.01) and glucose-derived mitochondrial ATP production (p &lt, 0.01) compared to palmitate alone. EPS was also associated with less PDK4 (p &lt, 0.01) and PPAR&delta, (p &lt, 0.01) proteins, and lower nuclear p-FOXO1/t-FOXO1 ratio normalised to the cytoplasmic ratio, but with no changes in PPAR&alpha, protein. Collectively, these data suggest PPAR&delta, and FOXO1 transcription factors increased PDK4 protein in the presence of palmitate, which limited PDC activity and flux, and blunted CHO oxidation and glucose uptake. Conversely, EPS rescued these metabolic events by modulating the same transcription factors.

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

Tubeless technique is a new concept to further enhance patient recovery after thoracoscopic surgery. Here we report our method to prevent pneumothorax after tubeless single port thoracoscopic lung resection by digital drainage system. At the end of the procedure, a single 16-Fr pigtail catheter was placed into the pleural cavity and connected to an electronic digital chest drainage system. The lung was re-expanded fully under thoracoscopic vision and the pigtail catheter was removed after confirming zero air flow. Our method utilizes electronic digital drainage system to select patients for tubeless thoracoscopic procedures. Full expansion of lung and zero air leakage were ensured at the end of procedure. The advantages include: (I) digitalized evaluation for air leaks in deciding whether to remove the catheter; (II) constant negative pressure during lung re-expansion; and (III) controllable inflation of lung without recruitment maneuvers by anesthesiologist. We believe it’s safer and more scientific to avoid chest tube after tubeless single port thoracoscopic lung surgery.

OBJECTIVES We aim to evaluate the prognostic value of metastatic lymph node number (MLN) and ratio (MLR) in oesophageal squamous cell carcinoma (OSCC) patients with or without neoadjuvant chemoradiation. METHODS Two thousand one hundred and fifty-one OSCC patients receiving oesophagectomy with (n = 850) or without (n = 1301) neoadjuvant chemoradiation were included. The MLN was categorized into 0 (N0), 1-2 (N1), 3-6 (N2) and more than 7 (N3); the MLR was categorized into 0, 0-0.2 and >0.2. The prognostic value was evaluated with survival analysis using the Cox proportional hazards regression model and the Kaplan-Meier method. RESULTS In patients without neoadjuvant chemoradiation, the 3-year overall survival rates were 54.8, 34.4, 21.8 and 6.5% with MLN = 0, 1-2, 3-6 and more than 7, respectively (P < 0.001). The 3-year overall survival rates were 54.7, 31.2 and 14.2% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). In patients with neoadjuvant chemoradiation, the 3-year overall survival rates were 49.0, 28.4, 12.5 and 0.0% with MLN = 0, 1-2, 3-6 and more than 7, respectively (P < 0.001). However, the survival curves of MLN = 3-6 and MLN ≥7 overlapped on the Kaplan-Meier plots. In contrast, MLR demonstrated good ability to show the survival differences on the Kaplan-Meier plots. The 3-year overall survival rates were 48.9, 27.3 and 0.0% with MLR = 0, 0-0.2 and more than 0.2, respectively (P < 0.001). CONCLUSIONS Both MLN and MLR were significant prognostic factors in OSCC patients regardless of neoadjuvant chemoradiation. But in patients with neoadjuvant chemoradiation, the survival rates were similar between ypN2 and ypN3 patients, suggesting that there was no necessity of separating patients into ypN2 and ypN3 stages.