Identifying potential targets for lung cancer intervention by analyzing the crosstalk of cancer-associated fibroblasts and immune and metabolism microenvironment.

BACKGROUND: Cancer-associated fibroblasts (CAFs) have been reported to play a crucial role in the tumor microenvironment and progression. METHODS: The data used in this study were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases, and all analyses were performed using R software. RESULTS: We first quantified the CAFs infiltration through single sample gene set enrichment analysis in the TCGA and combined GEO cohort (GSE30219, GSE37745, and GSE50081). Our result showed that patients with high levels of CAF infiltration were associated with worse clinical features and poor prognosis. Immune microenvironment analysis indicated that high CAF infiltration might result in increased infiltration of immune cells, including aDC, B cells, CD8+ T cells, cytotoxic cells, DC, eosinophils, iDC, macrophages, mast cells, neutrophils, NK CD56dim cells, NK cells, pDC, and T cells. Correlation analysis showed a significant positive correlation between CAFs and M2 macrophages, while a negative correlation was found between CAFs and glycerophospholipid metabolism. Kaplan-Meier survival curves indicated that glycerophospholipid metabolism was a protective factor against lung cancer. Biological enrichment analysis showed that pathways such as allograft rejection, epithelial-mesenchymal transition, KRAS signaling, TNF-α signaling, myogenesis, IL6/JAK/STAT3 signaling, IL2/STAT5 signaling were upregulated in the patients with high CAF infiltration. Moreover, patients with high CAF infiltration had a lower proportion of immunotherapy responders. Genome analysis showed that low CAFs infiltration was associated with high genome instability. We identified FGF5 and CELF3 as key genes involved in the interaction between CAFs, M2 macrophages, and glycerophospholipid metabolism, and further analyzed FGF5. In vitro experiments showed that FGF5 promoted the proliferation, invasion and migration of lung cancer cells and was primarily localized in the nucleoli fibrillar center. CONCLUSIONS: Our study provides novel insights into the roles of CAFs in lung cancer progression and the underlying crosstalk of tumor metabolism and immune microenvironment.

Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood. METHODS: We collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment. RESULTS: At baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72-14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression. CONCLUSIONS: The present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.

Pulmonary Function Recovery and Displacement Patterns After Anatomic Segmentectomy vs Lobectomy.

BACKGROUND: The functional benefit of segmentectomy compared with lobectomy remains controversial. This ambispective study characterizes the changes in pulmonary function as correlated to displacement patterns of residual lung after segmentectomies vs lobectomies. METHODS: Patients with normal preoperative pulmonary function and undergoing segmentectomy or lobectomy between 2017 and 2021 were considered. Pulmonary function testing was scheduled preoperatively and at least 3 months postoperatively. Differences in the proportions of the median forced expiratory volume in 1 second (FEV1) reduction between segmentectomy and lobectomy were calculated. Covariance analysis was used to estimate the adjusted postoperative FEV1 (apoFEV1) and compare the difference value (DV) in apoFEV1 between segmentectomy and lobectomy. RESULTS: The study enrolled 634 patients (334 lobectomies and 300 segmentectomies). Median difference in the proportions of the FEV1 reduction between segmentectomy and lobectomy was 4.58%, with maximal difference observed in right S6 (9.08%) and minimal difference in left S1+2+3 (2.80%). For resections involving the upper lobe, apoFEV1 was significantly higher after segmentectomy than after lobectomy (DV, 0.15-0.22 L), except for left S3 and S1+2+3 segmentectomies (DV, 0.08 L and 0.06 L, respectively). Compared with a lower lobe lobectomy, S6 segmentectomy conferred a higher apoFEV1, whereas S7+8 and S9+10 had a similar apoFEV1 (DV, 0.16-0.18 L, 0.07 L, and 0.00-0.06 L, respectively). Functional recovery after segmentectomy was associated with the number of intersegment planes (P < .01) and the presence of an adjacent nonoperated on lobe (P = .03). CONCLUSIONS: Basilar and left S3 segmentectomies did not preserve more pulmonary function compared with their corresponding lobectomies, possibly due to the presence of multiple intersegmental resection planes.

Pulmonary artery pseudoaneurysm after a left upper sleeve lobectomy.

A 55-year-old man was re-admitted for persistent hemoptysis and high fever three weeks after an initial left upper sleeve lobectomy for a central squamous lung cancer tumor. Pulmonary artery pseudoaneurysm and pulmonary infection were confirmed by multidetector computed tomography angiography and subsequent emergency completion pneumonectomy. The development of pulmonary artery pseudoaneurysm, secondary to post-operative pulmonary infection and pulmonary vascular manipulation, is rare and prompt surgical manipulation is mandatory.

Changes in pulmonary function in lung cancer patients after segmentectomy or lobectomy: a retrospective, non-intervention, observation study.

OBJECTIVES: Pulmonary segmentectomy (SE) became an increasingly popular method for resection of early-stage lung cancer. This study aims to compare the impact of single SE (SSE), multiple SE (MSE) and lobectomy (LE) on postoperative pulmonary function in patients with NSCLC. METHODS: Medical records of a total of 1284 patients who underwent LE (n = 493), SSE (n = 558) and MSE (n = 233) at Shanghai Pulmonary Hospital from January 2013 to October, 2020 were retrospectively analysed. Pulmonary function tests (PFTs) were performed preoperatively and 12 months after surgery. RESULTS: SSE was associated with a significantly smaller decline in the PFT values compared to MSE and LE. There was a poor consistency between the observed and expected (O/E) loss of pulmonary function in all study groups (P < 0.05). Both LE and SE resulted in similar O/E ratios of all PFT parameters (P > 0.05). CONCLUSIONS: Overall loss of pulmonary function was much greater after LE than after both SSE and MSE. MSE was associated with higher postoperative pulmonary function decline compared to SSE but was still beneficial over LE. Both LE and SE groups had similar PFT loss per segment (P > 0.05).

Carbon Dioxide Blower Facilitates Visceral Pleurectomy in Malignant Pleural Mesothelioma.

Pleurectomy and decortication serves as a major component of therapy for malignant pleural mesothelioma (MPM), but the procedure is time consuming. We tentatively applied a carbon dioxide (CO2) blower into pleurectomy and decortication for a patient with local relapse of MPM. The blower can help increase the potential subpleural place thanks to the positive pressure by CO2, while the mist of saline could clean the potential bleeding to increase visibility. Thereby, the procedure was greatly facilitated in a more precise manner, with blood loss of 100 mL and acceptable postoperative air leak and thorax drainage. Therefore, a CO2 blower may be considered in pleurectomy and decortication for MPM.

Primary pulmonary synovial sarcoma.

Objective: Primary pulmonary synovial sarcoma (PPSS) is extremely rare. This study aims to identify the clinicopathologic and therapeutic factors determining survival in PPSS. Methods: We performed a retrospective analysis of 121 patients from the Surveillance, Epidemiology, and End Results Database as well as 12 patients from our own institution diagnosed with PPSS. Patient survival was evaluated using the Kaplan-Meier method. Results: The median survival time for 12 PPSS patients in our institution was 78 months. Postoperative chemotherapy (P = .027 for overall survival and P = .035 for disease-specific survival) was associated with superior survival, whereas pneumonectomy (P = .011 for overall survival and P = .006 for disease-specific survival) was associated with worse survival. Single lobe involvement (P = .022) and the absence of lymph node involvement (P = .045) were associated with improved disease-specific survival and overall survival, respectively. In the Surveillance, Epidemiology, and End Results Database, the median survival time was 23 months. Significantly superior survival was observed in patients with earlier American Joint Committee on Cancer stage (Ⅰ-Ⅱ) (P < .001 for both overall survival and disease-specific survival). Patients who were diagnosed within the recent decade did not achieve a better survival (P = .599 for overall survival and P = .596 for disease-specific survival). Conclusions: PPSS was aggressive with a very poor prognosis. The seventh American Joint Committee on Cancer stage might aid in predicting survival. Pneumonectomy and lymph node involvement might be associated with worse survival, whereas single lobe involvement and postoperative chemotherapy might be associated with improved survival.

Proteomic analysis of plasma exosomes in patients with non-small cell lung cancer.

Background: Currently, the prognosis of patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. This current study evaluated the relationship between histology of NSCLC and protein expression of exosomes in the plasma from NSCLC patients, and furthermore investigate the impact of the exosome profile on the tumor, node, metastasis (TNM) classification. Methods: Plasma samples were collected from 26 NSCLC patients before surgery. The exosomes were extracted from the plasma and liquid chromatography-mass spectrometry (LC/MS) was used to evaluate the expression of the proteins in the exosomes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the Cytoscape 3.8.2 software. Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to identify proteins which could effectively distinguish between lung adenocarcinoma and lung squamous cell carcinoma. The relationship between protein expression and the TNM stage was calculated using Spearman rank correlation. Results: The expression levels of ZSWIM9, FYB1, SERPINF1, C1orf68, MASP2, and IGHV3-72 were higher in patients with lung adenocarcinoma compared to patients with lung squamous cell carcinoma. MFGE8 was associated with the occurrence of squamous cell carcinoma. CORO1A was positively correlated with the TNM stage of the patients, and COL4A2 was negatively correlated with TNM stage. GO and KEGG analyses revealed that cholesterol metabolism was important in NSCLC development. Conclusions: Lung adenocarcinoma may be distinguished from squamous cell carcinoma by the molecular profile of exosomes in the plasma samples. And, proteomics analysis suggested that cholesterol metabolism may play an important role of cancer progress in NSCLC.

Extracorporeal membrane oxygenation support for lung transplantation: Initial experience in a single center in China and a literature review.

Background: Extracorporeal membrane oxygenation (ECMO) is a versatile tool associated with favorable outcomes in the field of lung transplantation (LTx). Here, the clinical outcomes and complications of patients who underwent LTx with ECMO support, mainly prophylactically both intraoperatively and post-operatively, in a single center in China are reviewed. Methods: The study cohort included all consecutive patients who underwent LTx between January 2020 and January 2022. Demographics and LTx data were retrospectively reviewed. Perioperative results, including complications and survival outcomes, were assessed. Results: Of 86 patients included in the study, 32 received ECMO support, including 21 who received prophylactic intraoperative use of ECMO with or without prolonged post-operative use (pro-ECMO group), while the remaining 54 (62.8%) received no external support (non-ECMO group). There were no significant differences in the incidence of grade 3 primary graft dysfunction (PGD), short-term survival, or perioperative outcomes and complications between the non-ECMO and pro-ECMO groups. However, the estimated 1- and 2-year survival were superior in the pro-ECMO group, although this difference was not statistically significant (64.1% vs. 82.4%, log-rank P = 0.152; 46.5% vs. 72.1%, log-rank P = 0.182, respectively). After regrouping based on the reason for ECMO support, 30-day survival was satisfactory, while 90-day survival was poor in patients who received ECMO as a bridge to transplantation. However, prophylactic intraoperative use of ECMO and post-operative ECMO prolongation demonstrated promising survival and acceptable complication rates. In particular, patients who initially received venovenous (VV) ECMO intraoperatively with the same configuration post-operatively achieved excellent outcomes. The use of ECMO to salvage a graft affected by severe PGD also achieved acceptable survival in the rescue group. Conclusions: Prophylactic intraoperative ECMO support and post-operative ECMO prolongation demonstrated promising survival outcomes and acceptable complications in LTx patients. Particularly, VV ECMO provided safe and effective support intraoperatively and prophylactic prolongation reduced the incidence of PGD in selected patients. However, since this study was conducted in a relatively low-volume transplant center, further studies are needed to validate the results.

Coagulation Status and Surgical Approach as Predictors of Postoperative Anemia in Patients Undergoing Thoracic Surgery: A Retrospective Study.

Objective: Postoperative anemia is a common complication after a major surgery. Our study aims to identify factors that are associated with higher risk of developing postoperative anemia after thoracic surgery. Methods: We conducted a retrospective study of 465 patients who underwent pulmonary surgery in 2017 in Shanghai Pulmonary Hospital, China. Of them, 191 patients underwent standard open thoracotomy (OT), and 274 patients underwent video-assisted thoracic surgery (VATS). A total of 350 patients were diagnosed with postoperative anemia, and 115 patients did not have anemia. Multiple logistic regression was used to compute odds ratios for predicting preoperative anemia. Results: Postoperative anemia was associated with significantly lower weight (p < 0.001) and height (p = 0.022) of the patients, as well as higher prothrombin time (PT), and international normalized ratio (INR) (p = 0.012). Open thoracotomy resulted in a 1.2-fold increase in the incidence of postoperative anemia compared to VATS (p = 0.002). Multiple logistic regression analysis identified INR [OR (95% CI) 24.46 (2.05-292.27; p = 0.012] and surgical approach [OR (95% CI) 0.48 (0.31-0.74); p < 0.001] as predictors of postoperative anemia and postoperative drop in hemoglobin (Hb). Conclusion: Postoperative coagulation status and surgical approach are statistically significant predictors of postoperative anemia in patients undergoing thoracic surgery. International normalized ratio and surgical approach are specifically associated with Hb drop immediately after the surgery.

[Treatment of delayed inhaled bronchial foreign bodies by pulmonary resection: 17 cases reports].

OBJECTIVE: To investigate and analyze the clinicopathological features and choice of treatment for delayed inhaled bronchial foreign bodies. METHODS: A retrospective review is presented of patients with delayed inhaled bronchial foreign bodies treated by pulmonary resection between January 1980 and June 2010. There were 17 patients (12 male and 5 female). Mean age was 36 years (ranging 10 to 66 years). The mean interval of onset was 2 years (ranging 3 months to 8 years). Confirmed diagnosis before surgery in 8 cases and 9 cases were misdiagnosed as other diseases. Surgical procedures included right lower lobectomy in 4 cases, right middle lobectomy in 3 cases, right lower and middle lobectomy in 1 case, right lobe lobectomy and rid resection drainage in 1 case, right lobe lobectomy and pleurectomy in 1 case, video-assisted right lobe partial resection in 1 case, left pneumonectomy in 4 cases, left lower lobectomy in 1 cases and left upper lobectomy in 1 cases. RESULTS: One case died of pulmonary infection and 2 cases complicated of BPF after operation. Foreign bodies were localized in the right bronchial tree in 11 cases, the left in 6 cases. The majority of the foreign bodies were vegetable origin. CONCLUSIONS: The diagnosis rate of delayed inhaled bronchial foreign bodies should be improved in order avoiding of pulmonary resection. It is necessary to perform pulmonary resection timely if the pulmonary infection is evident for fear that the infection progress into severe infection.

Clinicopathological and Prognostic Significance of EML4-ALK Rearrangement in Patients with Surgically Resected Lung Adenocarcinoma: A Propensity Score Matching Study.

OBJECTIVE: The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is a key oncogenic driver in non-small cell lung cancer (NSCLC). This study analyzed the clinicopathological characteristics and prognostic significance of EML4-ALK fusion gene in patients with surgically resected adenocarcinoma. METHODS: The clinicopathological characteristics of 1056 consecutive patients with surgically resected stage I-IIIA adenocarcinoma were collected from February 2014 to October 2014, and EML4-ALK rearrangement was detected using real-time polymerase chain reaction (RT-PCR) technology. To compare the imaging and pathological features, a propensity score matching (PSM) method was performed. The follow-up information was collected to evaluate the long-term outcomes of patients with EML4-ALK rearrangement. RESULTS: The prevalence of EML4-ALK rearrangement was 6.6% in 1056 consecutive patients. A total of 70 EML4-ALK-positive and 210 EML4-ALK-negative patients were identified after PSM. Imaging and pathological analyses showed that EML4-ALK rearrangement was significantly associated with less ground-glass opacity (GGO) (adjusted OR=1.38, 95% CI=1.03-1.85, Ptrend =0.029) and higher prevalence of non-invasive mucinous adenocarcinoma mucin-laden adenocarcinomas (non-IMA MLA, adjusted OR=6.79, 95% CI=2.69-17.17, P<0.001). EML4-ALK rearrangement was found to be an unfavorable prognostic factor for disease-free survival (DFS) in female patients (HR=2.26, 95% CI=1.13-4.53, P=0.021). CONCLUSION: Our results suggest that adenocarcinomas harboring EML4-ALK fusion gene exhibit specific radiological and pathological characteristics compared with EML4-ALK-negative adenocarcinomas. In female patients, EML4-ALK rearrangement was associated with shorter DFS.

Surgery in Masaoka stage IV thymic carcinoma: a propensity-matched study based on the SEER database.

BACKGROUND: Thymic carcinoma is a type of rare and highly malignant tumor. Limited information was available on prognostic factors of late-stage thymic carcinoma. The aim of this study was to identify factors that impact prognosis and to define the relationship between survival and surgical intervention in patients with Masaoka stage IV thymic carcinoma. METHODS: From 1973 to 2015, a total of 311 consecutive patients were enrolled in this study with pathologic confirmed Masaoka stage IV thymic carcinoma from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier analyses, Cox-regression analyses and propensity score matching (PSM) were performed to evaluate prognosis. RESULTS: In the multivariate analysis, larger tumor size, distant metastasis and positive lymph node status were associated with poorer outcome. After PSM, no receipt of surgery was the prognostic factor indicating poorer survival [hazard ratio (HR) 1.985, 95% confidence interval (CI) 1.007-3.913, P=0.048 for overall survival (OS); HR 1.649, 95% CI: 1.009-2.697, P=0.046 for disease-specific survival (DSS)]. Subgroup analysis indicated that significantly improved survival with surgery was observed in patients who were <60 years (HR 0.48, 95% CI: 0.32-0.72), female (HR 0.37, 95% CI: 0.23-0.60), Caucasian (HR 0.56, 95% CI: 0.40-0.77), with larger tumor size (≥7.0 cm, HR 0.42, 95% CI: 0.25-0.69), with (HR 0.60, 95% CI: 0.39-0.90) or without distant metastasis (HR 0.46, 95% CI: 0.26-0.83), and node-positive (HR 0.56, 95% CI: 0.38-0.82). CONCLUSIONS: Surgical treatment could be beneficial in patients with Masaoka stage IV thymic carcinoma. This SEER based analysis revealed the role of surgical resection and the favorable effect of surgery in specific thymic carcinoma subgroups.

Alveolar macrophage - derived exosomes modulate severity and outcome of acute lung injury.

Severe acute lung injury (ALI) can cause death, and the survivals may develop acute respiratory distress syndrome (ARDS) due to fibrotic repair of the lung. Alveolar macrophages play a demonstrative role during the pathogenesis of ALI, and the timing and degree of differentially polarization of macrophages determine the severity of disease and outcome. Exosomes are important mediators of cellular communication and play critical roles during macrophage differentiation, proliferation and function. Nevertheless, the exact effects of alveolar macrophage - derived exosomes on ALI remain unknow. Here, we used lipopolysaccharide (LPS) to induce ALI in mice and analyzed the exosome population in bronchoalveolar lavage fluid (BALF) from macrophages, neutrophils and epithelial cells at different time points after treatment. Our data showed that macrophages were the major secretors for early secreted pro-inflammatory cytokines in the BALF-exosomes, which likely activated neutrophils to produce a variety of pro-inflammatory cytokines and IL-10. IL-10 by neutrophils in BALF-exosomes likely in turn polarized macrophages to M2c, which may be responsible for post-ALI fibrosis. Our study thus reveals a previous non-acknowledged role of BALF-exosomes as a mediator of inflammatory response and cell crosstalk during ALI.

Up-regulation of circ_0000353 impedes the proliferation and metastasis of non-small cell lung cancer cells via adsorbing miR-411-5p and increasing forkhead box O1.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common malignant tumor worldwide. This work focuses on investigating the role of circ_0000353 in NSCLC and its potential mechanism of action. METHODS: The expression levels of circ_0000353 and miR-411-5p in NSCLC and their matched normal lung tissues were detected by real-time PCR (RT-PCR). The correlation between the circ_0000353 expression and the clinicopathological parameters of NSCLC patients was also analyzed. CCK-8, BrdU and colony formation assays were adopted to detect the role of circ_0000353 in the proliferation of NSCLC cells. The metastasis of NSCLC cells was measured by Transwell assay. The dual-luciferase reporter gene assay was used to confirm the targeting relationship between circ_0000353 and miR-411-5p. The expression level of FOXO1 was detected by western blot. RESULTS: Circ_0000353 was significantly down-regulated in NSCLC tissues and cell lines, and the decreased expression was significantly linked to the increased clinical stage, larger tumor volume, and metastasis. The circ_0000353 over-expression restrained the proliferation, migration, and invasion of NSCLC cells in vitro. Additionally, up-regulation of miR-411-5p was observed in NSCLC tissues and cell lines, and luciferase assay and RT-PCR assay showed that circ_0000353 over-expression could target miR-411-5p and suppress its expression. Further studies confirmed that circ_0000353 and miR-411-5p modulated the FOXO1 expression. CONCLUSION: Circ_0000353 repressed the proliferation, migration, and invasion of NSCLC cells via inhibition of miR-411-5p and up-regulation of FOXO1.

Surgical modality for stage IA non-small cell lung cancer among the elderly: analysis of the Surveillance, Epidemiology, and End Results database.

BACKGROUND: The appropriate surgical modality for early-stage non-small cell lung cancer (NSCLC) among the elderly remains controversial; identifying appropriate modalities will be helpful in clinical practice. METHODS: It's a cohort study and we explored the Surveillance, Epidemiology, and End Results (SEER) database for identifying patients aged ≥70 years with pathologic stage IA NSCLC. Three types of surgeries were compared (lobectomy, segmentectomy, and wedge resection) via survival and stratification analyses. RESULTS: Overall, 6,197 patients were enrolled. Among patients aged ≥76 years with tumor diameters ≤1 cm, significant differences in survival were noted for segmentectomy vs. lobectomy [hazard ratio (HR) =0.294, P=0.007] and wedge resection vs. lobectomy (HR =0.548, P=0.017) but not in those with tumors diameters >1 cm. Among patients aged 70-75 years with tumor diameters >1-2 cm, significant differences in survival were observed for segmentectomy vs. lobectomy (HR =0.671, P=0.037) and segmentectomy vs. wedge resection (HR =0.556, P=0.003) and for wedge resection vs. lobectomy (HR =1.283, P=0.003) among those with tumor diameters >2-3 cm but not in those with tumor diameters ≤1 cm. CONCLUSIONS: Both age and tumor size should be considered when selecting the surgical modality. Lobectomy is not recommended for lesions ≤1 cm among patients aged ≥76 years. Segmentectomy was associated with superior prognosis for tumor diameters >1-2 cm and survival favored lobectomy rather than wedge resection for NSCLCs >2-3 cm among patients aged 70-75 years. Surgeons could rely on personal experience to determine the appropriate surgical modality for NSCLCs >1 cm among patients aged ≥76 years and NSCLCs ≤1 cm among patients aged 70-75 years.

Differential expression and functional analysis of lung cancer gene expression datasets: A systems biology perspective.

There is an inherent need to identify differentially expressed genes (DEGs), characterize these genes and provide functional enrichment analysis to the publicly available lung cancer datasets, primarily coming from next-generation sequencing data or microarray gene expression studies. The risk of lung cancer in patients with smokers is manifold, and with chronic obstructive pulmonary disease (COPD) it is 2- to 5-fold greater, compared with smokers without COPD. In the present study, differential expression analysis and gene functional enrichment analysis of lung cancer gene expression datasets obtained from NCBI-GEO were performed. The result identifies a significant number of DEGs which have at least a 2-fold change in their expression. Among them, six genes were found to have a 4-fold change in the expression level, and 47 genes exhibited a 3-fold change in the expression. It was also observed that most of the genes were upregulated and few genes were downregulated.

Electrical restitution determined by epicardial contact mapping and surface electrocardiogram: its role in ventricular fibrillation inducibility in swine.

OBJECTIVE: The roles of electrical restitution determined by epicardial contact mapping and surface electrocardiogram (ECG) in the inducibility of ventricular fibrillation (VF) were evaluated. METHODS: Ten epicardial unipolar electrograms using contact mapping and the surface ECGs were simultaneously recorded in 7 swine. Activation-recovery interval (ARI) and QT-interval restitution curves were constructed. Steady-state pacing protocol was performed to induce VF. Ventricular fibrillation threshold was defined as the longest pacing interval for inducing VF. Statistical correlation analysis was performed to determine the relationship between local ARI restitutions, QT-interval restitution, and ventricular fibrillation threshold. RESULTS: One hundred thirteen restitution curves were constructed (50 in left ventricular sites, 52 in right ventricular sites, and 11 in surface ECG lead II) from 11 steady-state pacing procedures. Statistical correlation between the slopes of the QT restitution curve and the slopes of regional ARI restitution curves was noted in several mapping sites. Ventricular fibrillation threshold significantly related to the local ARI restitution curve slope for the right ventricular apex (R = 0.752, P = .019) and the QT-interval restitution curve slope (R = 0.802, P = .005). CONCLUSION: There is a significant correlation between the local ARI restitutions and the QT-interval restitutions, both of which were associated with VF inducibility.

Surgery for advanced non-small cell lung cancer patient after epidermal growth factor receptor tyrosine kinase inhibitor neoadjuvant therapy.

BACKGROUND: This study aimed to evaluate the survival of the advanced non-small cell lung cancer (NSCLC) patients underwent salvage surgeries after EGFR-TKI neoadjuvant therapies. METHODS: From 2014 to 2016, 10 patients diagnosed as advanced stage NSCLC (N2 metastasis or great vessels invasion) who responded to EGFR-TKI neoadjuvant therapy were recruited in this study. All patients underwent surgeries and consented the follow-up study. RESULTS: All patients received successful radical surgeries (complete resection of the tumor with systematic lymphadenectomy). Among them, one patient passed away 7 days post-operatively due to respiratory failure. The pathology of the lesions and the lymph nodes suggested the replacement of tumors by fibrotic tissue, and concentration of focal residual tumors limited in areas of fibrous stroma and lymphocyte infiltration. Adjuvant therapy of EGFR inhibitor gefitinib for at least 6 months was applied to each patient. Each of the patients was followed up with contrasted CT scan, ultrasonography, bronchoscope and tumor markers for at least 8 months (8-30 months, median time: 24 months). The progression-free survival of these patients was 14 months since neoadjuvant therapy. CONCLUSIONS: EGFR-TKI neoadjuvant therapy is feasible and effective, along with surgery may improve the surgical rate and survival of advanced NSCLC patients. KEYWORDS: Non-small cell lung cancer (NSCLC); epidermal growth factor receptor tyrosine kinase inhibitor neoadjuvant therapy (EGFR-TKI neoadjuvant therapy); salvage surgery.

[A study on the relationship between the level of E-cadherin mRNA expression and pathological characteristics of non-small cell lung cancer].

BACKGROUND: E-cadherin is a subclass of the cadherin family that plays an important role in the maintenance of intercellular junctions in normal epithelium.Decreased expression of E-cadherin might be closely related to invasiveness and dedifferentiation in human cancers.There is increasing evidence that modulation of the E-cadherin-catenin cell-cell adhesion complex is an important step in the initiation and progression of human cancers.The aim of this study is to investigate the relationship between the level of E-cadherin mRNA expression and pathological grades and clinical stages of non-small cell lung cancer(NSCLC). METHODS: RT-PCR was used to measure the level of E-cadherin mRNA expression in 53 specimens of NSCLC,46 of para-cancer lung tissues,5 of benign nodal lung diseases,and the stages of disease was determined according to the results of surgery,pathology and imaging diagnoses.Then analyses were carried out between the level of E-cadherin mRNA expression and the clinical variables. RESULTS: 45.3%(24/53) and 45.7%(21/46) specimens of NSCLC and para-cancer lung tissue were positive for E-cadherin mRNA expression respectively(P > 0.05);NSCLC with low differentiation,advanced stages and nodal metastases showed a magnificantly lower expression of E-cadherin mRNA(P < 0.05).The median survival time for E-cadherin mRNA positive and negative patients were 15.5 months and 46 months,respectively,but the expression of E-cadherin mRNA did not correlate with patient's survival(P > 0.05). CONCLUSIONS: E-cadherin expression is related to the differentiation,lymph node metastasis and pathological staging of NSCLC,but probably does not effectively affect its prognosis.