An interesting dynamic retrograde His bundle potential during the transventricular-septal process for left bundle branch pacing in a patient with right bundle branch block: A case report.

A 67-year-old male presented with symptomatic bradycardia caused by atrial fibrillation and underwent His bundle pacing (HBP) and left bundle branch pacing (LBBP). Electrocardiography (ECG) revealed a complete right bundle branch block (RBBB). John Jiang's connecting cable was used during the transventricular septal process. An interesting dynamic retrograde His bundle potential (RHP) was recorded with uninterrupted lead screws.

[Exploration of the Perturbation of PKIG in Lung Squamous Cell Carcinoma and the Role in Tumor Microenvironment Based on Bioinformatics Method].

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and patients have limited survival benefits from traditional treatments such as surgery, radiotherapy and chemotherapy. As a new treatment for lung cancer, immunotherapy has significantly prolonged the overall survival (OS) of patients. However, only some patients can benefit from it. We need to explore immunotherapy biomarkers more deeply to screen for advantages. METHODS: The original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, and the immunological and prognostic genes of lung squamous cell carcinoma (LUSC) were screened using R software and TIMER database. The expression of target genes was studied in TCGA and GEO databases, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and correlation analysis with tumor immune characteristics were performed by R software and TISIDB database. RESULTS: We screened out a gene related to immunity and prognosis, cAMP dependent protein kinase inhibitor γ (PKIG), which is significantly differentially expressed in LUSC and normal tissues, and has important reference value for the diagnosis and prognosis assessment of LUSC. PKIG differential genes are mainly concentrated in the regulation of humoral immune response and other processes. The expression of PKIG was positively correlated with the infiltration level of regulatory T cells (Tregs) (r=0.340, P<0.001). In addition, the expression level of PKIG was positively correlated with the expression of chemokines/chemokine receptors such as chemokine C-C motif ligand 2 (CCL2) (r=0.503, P<0.001), CXC chemokine ligand 12 (CXCL12) (r=0.386, P<0.001) and CXC-chemokine receptor 4 (CXCR4) (r=0.492, P<0.001), and immunoinhibitors such as programmed cell death protein 1 (PDCD1) (r=0.359, P<0.001), cytotoxic T-lymphocyte associated antigen 4 (CTLA4) (r=0.375, P<0.001) and T cell immunoglobulin and ITIM domains (TIGIT) (r=0.305, P<0.001) in LUSC. CONCLUSIONS: The immunological and prognostic gene PKIG in lung squamous cell carcinoma was screened through bioinformatics analysis. PKIG is highly correlated with LUSC prognosis and immune microenvironment, and is expected to be a potential biomolecular marker for LUSC immunotherapy.

Short-term outcomes of robot-assisted versus thoracoscopic-assisted Mckeown esophagectomy.

BACKGROUND: Thoracoscopic-assisted and robot-assisted Mckeown esophagectomy are currently two common surgical methods, but there is no clear statement on the advantages and disadvantages of the two. METHODS: This study conducted a single-centre retrospective analysis of esophageal cancer patients diagnosed and treated at Lanzhou University Second Hospital from 1 February 2020 to 31 July 2022. According to the inclusion and exclusion criteria, 126 patients were finally included in the RAM group and 169 patients in the TAM group. RESULTS: There was no significant difference between the RAM and TAM groups in the number of lymph node dissections, operative time, the length of stay in the intensive care unit after surgery, the incidence of hoarseness, postoperative pulmonary complications, surgery-related complications, use of opioids after surgery, the length of postoperative hospital stay, and 30-day mortality. CONCLUSIONS: RAM is a minimally invasive alternative to TAM and has similar short-term oncological efficacy.

Genomic and immunogenomic analysis of three prognostic signature genes in LUAD.

BACKGROUND: Searching for immunotherapy-related markers is an important research content to screen for target populations suitable for immunotherapy. Prognosis-related genes in early stage lung cancer may also affect the tumor immune microenvironment, which in turn affects immunotherapy. RESULTS: We analyzed the differential genes affecting lung cancer patients receiving immunotherapy through the Cancer Treatment Response gene signature DataBase (CTR-DB), and set a threshold to obtain a total of 176 differential genes between response and non-response to immunotherapy. Functional enrichment analysis found that these differential genes were mainly involved in immune regulation-related pathways. The early-stage lung adenocarcinoma (LUAD) prognostic model was constructed through the cancer genome atlas (TCGA) database, and three target genes (MMP12, NFE2, HOXC8) were screened to calculate the risk score of early-stage LUAD. The receiver operating characteristic (ROC) curve indicated that the model had good prognostic value, and the validation set (GSE50081, GSE11969 and GSE42127) from the gene expression omnibus (GEO) analysis indicated that the model had good stability, and the risk score was correlated with immune infiltrations to varying degrees. Multi-type survival analysis and immune infiltration analysis revealed that the transcriptome, methylation and the copy number variation (CNV) levels of the three genes were correlated with patient prognosis and some tumor microenvironment (TME) components. Drug sensitivity analysis found that the three genes may affect some anti-tumor drugs. The mRNA expression of immune checkpoint-related genes showed significant differences between the high and low group of the three genes, and there may be a mutual regulatory network between immune checkpoint-related genes and target genes. Tumor immune dysfunction and exclusion (TIDE) analysis found that three genes were associated with immunotherapy response and maybe the potential predictors to immunotherapy, consistent with the CTR-DB database analysis. CONCLUSIONS: From the perspective of data mining, this study suggests that MMP12, NFE2, and HOXC8 may be involved in tumor immune regulation and affect immunotherapy. They are expected to become markers of immunotherapy and are worthy of further experimental research.

Right subclavian vein approach for selective left bundle branch pacing: A case report.

We reported a 65-year-old man with symptomatic bradycardia caused by chronic atrial fibrillation who underwent pacemaker implantation by left bundle branch pacing (LBBP) via right subclavian vein (RSV) approach. A tricuspid valve annulus (TVA) angiography was performed, and a different connecting cable that can monitor electrocardiograms (ECG) and intracardiac electrograms (EGM) in real time was used during the process. By TVA angiography, we could easily find the ideal location of LBBP; a new connecting cable helped us avoid perforation and guide effective endpoint without the need to stop pacing. The case showed that it was feasible and safe to use the new method for LBBP through RSV route.

[Clinical Study of Artificial Intelligence-assisted Diagnosis System in Predicting the 
Invasive Subtypes of Early-stage Lung Adenocarcinoma Appearing as Pulmonary Nodules].

BACKGROUND: Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early­stage lung adenocarcinoma appearing as pulmonary nodules. METHODS: Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed. RESULTS: In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively. CONCLUSIONS: Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early­stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.

Consolidation treatments after chemoradiotherapy in patients with locally advanced inoperable non-small cell lung cancer: a systematic review and network meta-analysis protocol.

INTRODUCTION: Concurrent chemoradiotherapy (CCRT) is the standard of care for inoperable locally advanced non-small cell lung cancer. To further improve prognosis, the use of consolidation treatments after CCRT has been explored extensively. Although durvalumab is the only consolidation treatment recommended by national clinical practice guidelines, there have been many studies exploring the effectiveness of other agents. However, until now, no studies have compared all agents systematically, and no studies have provided evidence for the optimal combination of different CCRTs and consolidation treatments regimens. This systematic review will evaluate the comparative clinical efficacy of consolidation therapies after CCRT as well as various combinations of CCRTs and consolidation therapies. METHODS AND ANALYSIS: PubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE and ClinicalTrials.gov will be searched for relevant information. The estimated end date for the search will be 3 February 2022. Each stage of the review, including the study section, data extraction and risk of bias and quality of evidence assessments, will be performed in duplicate. We will include randomised controlled trials that included participants who received CCRT and consolidation treatment in at least one treatment arm. The primary endpoints will be overall survival and progression-free survival. Tumour response, health-related quality of life, disease-free survival and treatment-related toxicity will be presented as secondary outcomes. Both traditional meta-analysis and network meta-analysis (NMA) with the Bayesian approach will be conducted. Subgroup analyses and meta-regression will be completed to investigate heterogeneity, and sensitivity analyses will be conducted to assess the robustness of the findings. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required as this study is a meta-analysis based on published studies. The results of this study will be submitted to a peer-reviewed journal for publication. In case of any changes in the protocol, protocol amendments will be updated in PROSPERO and explanations of these modifications will be described in the final report of this review. The results of this systematic review and NMA will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42021239433.

Identification of the Signature Genes and Network of Reactive Oxygen Species Related Genes and DNA Repair Genes in Lung Adenocarcinoma.

Reactive Oxygen Species (ROS) are present in excess amounts in patients with tumors, and these ROS can kill and destroy tumor cells. Therefore, tumor cells upregulate ROS-related genes to protect them and reduce their destructing effects. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. The present study aimed to identify the signature genes of and regulating network of ROS-related genes and DNA repair genes in lung adenocarcinoma (LUAD) using transcriptomic data of public databases. The LUAD transcriptome data in the TCGA database and gene expressions from Gene Expression Omnibus (GEO) were analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes namely NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby balancing the level of ROS. Therefore, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX, and PFKP). The risk score obtained from our survival prognostic model could be used as an independent prognostic factor in LUAD patients.

Identification of Signature Genes and Characterizations of Tumor Immune Microenvironment and Tumor Purity in Lung Adenocarcinoma Based on Machine Learning.

The implication of the Estimation of Stromal and Immune cells in Malignant tumor tissues using expression data (ESTIMATE) method to determine the tumor microenvironment (TME) and tumor immune score including tumor purity represents an efficient method to identify and assess biomarkers for immunotherapy response in precision medicine. In this study we utilized a machine learning algorithm to analyze the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) lung adenocarcinoma (LUAD) transcriptome data to evaluate the association between TME and tumor purity. Furthermore, we investigated whether fewer TME components or a few dominant genes can infer tumor purity. The results indicated that the 29 immune infiltrating components determined by the ssGSEA method could screen the 5 TME components [chemokine C-C-Motif receptor (CCR), T-helper-cells, Check-point, Treg, and tumor-infiltrating lymphocytes (TIL)] that significantly contributed the most to tumor purity prediction through regression tree and random forest regression methods. The findings revealed that higher activity of these five immune infiltrating components significantly lowered the tumor purity. Moreover, 5 TME components contributed significantly to the improvement of Mean Square Error (MES); therefore, we selected these five sets' genes and analyzed survival data to establish a prognostic model. We screened out 11 prognostic-related genes and constructed a risk model comprising 11 genes with good predictive value for patients' prognosis. Furthermore, we obtained four genes (GIMAP6, CD80, IL16, and CCR2) that had predictive advantages for tumor purity using random forest classification and random forest regression. The comprehensive score of genes for tumor purity prediction (CSGTPP) was obtained by least absolute shrinkage and selection operator (LASSO) regression indicated that four genes could be successfully used to classify high and low CSGTPP samples and that tumor purity was negatively correlated with CSGTPP. Survival analysis revealed that the higher the CSGTPP, the better the prognosis of patients. The association between a cluster of differentiation 274 (CD274) and CSGTPP revealed a higher expression of CD274 in the high CSGTPP group. Collectively, we speculated that CSGTPP could serve as a predictor of the response to immunotherapy and a promising indicator of immunotherapy effect.

DUS4L Silencing Suppresses Cell Proliferation and Promotes Apoptosis in Human Lung Adenocarcinoma Cell Line A549.

PURPOSE: This study aims to investigate the potential role of DUS4L (dihydrouridine synthase 4 like) in lung adenocarcinoma (LUAD) and explore its associated pathways in human LUAD. METHODS: Firstly, we evaluated the relationships between clinicopathological characteristics and DUS4L expression via analysis of TCGA RNA sequencing data and other publicly available databases. Then, DUS4L was effectively silenced in LUAD cell line A549 using the lentiviral shRNA (short-hairpin RNA) transfection to assess its effects on cell proliferation, cycle and apoptosis in LUAD cells. RNA-seq technology was applied to shDUS4L and shCtrl-transfected cells to generate the corresponding gene expression profiles. Differentially expressed genes (DEGs) were identified using the DESeq2 program package. Also, DEGs were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis to explore the associated molecular signaling pathways and relevant biological functions. RESULTS: Analysis of TCGA data revealed that DUS4L was highly upregulated in LUAD tissues which was related to clinical T and TNM stages of LUAD. The knockdown of DUS4L effectively inhibited cell proliferation and promoted apoptosis in A549 cells. Furthermore, the DEGs between the shDUS4L and shCtrl A549 cells were mainly enriched in biological processes associated with spliceosome, ribosome, RNA catabolic process, ncRNA (non-coding RNA) processing, and p53 signaling pathway. CONCLUSION: Altogether, our results suggest that DUS4L is significantly associated with tumorigenesis and could be utilized as a novel biomarker and therapeutic target for LUAD.

Effects of ALOX5, IL6R and SFTPD gene polymorphisms on the risk of lung cancer: A case-control study in China.

BACKGROUND: ALOX5, IL6R and SFTPD are all immune related genes that may be involved in the development of lung cancer. We sought to explore the effect of polymorphisms of these genes on the risk of lung cancer. METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped using a MassARRAY platform in a case-control cohort including 550 patients with lung cancer and 550 healthy controls. RESULTS: The rs4845626-T and rs4329505-C alleles were associated with a decreased risk of lung cancer (p < 0.001), while the rs745986-G and rs2245121-A alleles were correlated with an increased risk of lung cancer (p < 0.01). The rs4845626-GT/GG and rs4329505-TC genotypes were protective against lung cancer (p < 0.001). However, the rs745986-AG and rs2245121-AG/AA genotypes were associated with an increased risk of lung cancer (p < 0.01). Stratification analysis showed that the rs4845626 and rs4329505 polymorphisms of IL6R were associated with a reduced risk of lung cancer in both smokers and nonsmokers (p < 0.05). However, rs892690, rs745986 and rs2115819 of ALOX5 were associated with an increased risk of disease in nonsmokers, while rs2245121 of SFTPD was correlated with a higher risk of disease in smokers (p < 0.05). CONCLUSION: Our results provide candidate SNPs for early screening for lung cancer and new clues for further study of the pathogenesis of the disease.

Screening for differential genes of the esophageal squamous cell carcinoma after DDX46 knockdown and bioinformatics analysis of their interaction / 中国胸心血管外科临床杂志

@#Objective    To explore the mechanism of DDX46 regulation of esophageal squamous cell carcinoma. Methods    Picture signals of fluorescence in gene array were scanned and differential expression of gene in two groups (a DDX46-shRNA-LV group and a control-LV group) were compared by GCOSvL.4 software. These differential expressed genes were analyzed by bioinformatics methods finally, and validated by quantitative real time polymerase chain reaction (qRT-PCR) analysis. Results    According to the screening criteria of fold change ≥2 and P<0.05, 1 006 genes were differentially expressed after DDX46 knockdown, including 362 up-regulated and 644 down-regulated genes. Bioinformatics analysis and gene co-expression network building identified that these differentially expressed genes were mainly involved in cell cycle, proliferation, apoptosis, adhesion, energy metabolism, immune response, etc. Phosphatidylinositol 3-kinase (PI3K) was the key molecule in the network. The results of RT-qPCR were completely consistent with the results of gene microarra. Conclusion    Bioinformatics can effectively exploit the microarray data of esophageal squamous cell carcinoma after DDX46 knockdown, which provides a valuable clue for further exploration of DDX46 tumorigenesis mechanism and helps to find potential drug therapy.

Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion.

Macrophages constitute one of the most common components of immune cells, which penetrate tumors and they have a key role in tumor prognosis. Here, we identified an unrecognized macrophage subpopulation, which favors tumorigenesis. These macrophages express programmed cell death protein 1 (PD1) in a constitutive manner and accumulates in esophageal squamous cell carcinoma (ESCC) in advanced stage of the disease and is negatively associated with the survival of ESCC patients. The PD1+ tumor-associated macrophages (PD1+ TAMs) displayed surface pattern and function akin to M2: a substantial enhancement in CD206 and IL-10 expression; a specific reduction in HLA-DR, CD64, and IL-12 expression; and a significant increase in the ability to inhibit CD8+ T-cell proliferation. Triggering of PD1 signal is effective in increasing PD1+ TAM function. Moreover, exosomal HMGB1 obtained from tumors are efficient in triggering differentiation of monocytes into PD1+ TAMs, which display phenotypic and functional properties of M2. Overall, our work is the first finding to confirm that exosomal HMGB1 obtained from ESCC can successfully trigger clonal expansion of PD1+ TAM. Further, as the macrophages exhibit an M2-like surface profile and function, thereby creating conditions for development of ESCC. Thus, effective methods of treatment include combining immunotherapy with targeting PD1+ TAMs and tumor-derived exosomal HMGB1 to resuscitate immune function in individuals suffering from ESCC.

Current state of lung cancer with chronic obstructive pulmonary disease in China: A bibliometrics analysis / 中国胸心血管外科临床杂志

@#Objective To explore the research state and topics of lung cancer with chronic obstructive pulmonary disease (COPD) in China using the visualization methods. Methods Literature about lung cancer with COPD was searched through WanFang, CNKI, CBM, PubMed, The Cochrane Library and EMbase databases from inception to March 2018 by computer. We used BICOMS software to analyze the main information and produce co-word matrix, gCLUTO software to cluster, and NetDraw and Cytoscape software to draw the pictures. Results There were 304 studies related to lung cancer with COPD which originated from 173 journals including 23 indexed by Chinese Science Citation Database (CSCD) with 42 articles published, accounting for 13.8% of the total number of studies. There were 37 articles from 24 journals indexed by Science Citation Index (SCI) accounting for 12.2% of the total number of studies. The studies grew rapidly since 2012. The study involved 32 provinces, municipalities, and autonomous regions, among which Beijing, Sichuan, Shanghai, Guangzhou and Jiangsu provinces and cities were the main research areas. Sixty-nine high-frequency keywords were obtained with frequency 2 as the threshold, which was clustered into 5 categories by dual cluster analysis. Among them, topic 0 showed pathogenesis and radiological diagnosis of lung cancer with COPD, topic 1 was about the clinical characteristics of different pathological types of lung cancer with COPD and Chinese medicine treatment, topic 2 aimed at the impact of risk factors on surgical complications and the relationship between chemotherapy or targeted therapies and patient survival prognosis, topic 3 involved the pigenetic correlation between lung cancer and COPD and topic 4 was about clinical studies of perioperative comprehensive management of lung cancer patients with COPD. Conclusion The bibliometrics results show that there are considerable-amount achievements on lung cancer combined with COPD in China, and the researches have gradually increased since 2012. Horizontal research topics are extensive, and the focus of the study is to explore the perioperative comprehensive management and basic research of lung cancer with COPD, but the longitudinal themes need to be further studied. The results of some studies have not yet reached a consensus. There are few high-quality multi-center studies and a lack of clinical-directed achievement.

Effect of DDX46 gene on the growth of xenografted tumor of esophageal squamous cell carcinoma in nude mice / 中国胸心血管外科临床杂志

@#Objective To observe the growth of xenografted tumor in nude mice after DDX46 expression decreased, and to further study the role of DDX46 in the development and progression of esophageal squamous cell carcinoma. Methods DDX46-shRNA mediated RNAi was applied to silencing DDX46 in Eca-109 cells. Twenty-five female BALB/c nude mice were divided into 3 groups: an experiment group (DDX46-shRNA-LV, n=10), a control group (Control-LV, n=10) and a blank control group (Het-1A, n=5). The prepared Eca-109 cells of DDX46-shRNA-LV and Control-LV were subcutaneously injected into the right armpit of mice (4×106 cells per mouse), while Het-1A cells were subcutaneously injected into the bilateral armpits of mice (4×106 cells per side). Tumor growth was monitored twice a week on the 14th day after injection. Tumor volume was measured with calipers, in vivo imager to observe the fluorescence of each group. Further, western blotting analysis was used to detect the changes of apoptosis signaling molecules in xenografted tumor after DDX46 silence. Results The growth of xenografted tumor in nude mice was significantly slower in the DDX46-shRNA-LV group than that in the Control-LV group throughout the study period (P<0.001). Western blotting analysis showed that silencing DDX46 effectively suppressed the expression of DDX46, and upregulated the expression of cleaved Caspase-3 and cleaved PARP-1 in xenografted tumor (P<0.01). Conclusion DDX46 is involved in the development and progression of esophageal squamous cell carcinoma, and the silence of DDX46 expression can inhibit the growth of esophageal squamous cell carcinoma, which probably by positive regulation of apoptosis signaling pathway.

Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: A meta-analysis.

BACKGROUND: The impact of high body mass index (BMI, >23/25 kg/m) on surgical outcomes and prognosis in patients with esophageal carcinoma (EC) after undergoing esophagectomy remains controversial. We herein conducted a systematic review and meta-analysis to determine the relationship between high BMI and surgical outcomes and prognosis in patients undergoing esophagectomy for EC. METHODS: The study search was conducted by retrieving publications from the PubMed, Embase, Web of Science, and CNKI (up to September 8, 2017). Nineteen studies with 13,756 patients were included in this meta-analysis. RESULTS: We found that high BMI was closely associated with a higher incidence of wound infection (odds ratio [OR]: 1.41, 95% confidence interval [CI]: 1.02-1.97, P = .04), cardiovascular complications (OR: 2.51, 95% CI, 1.65-3.81, P < .0001), and anastomotic leakage (OR: 1.50, 95% CI, 1.21-1.84, P = .0002), but a lower incidence of chylous leakage (OR: 0.59, 95% CI, 0.40-0.88, P = .01) when compared with normal BMI. The high BMI group was not associated with better or worse overall survival (OS) (hazard ratio [HR]: 0.95, 95% CI, 0.85-1.07, P = .4) and disease-free survival (HR: 0.95, 95% CI, 0.72-1.25, P = .72) than the normal BMI group. However, in the subgroup analysis, the pooled result of HRs generated from multivariate analyses suggested that high BMI could improve OS in EC patients (HR: 0.84, 95% CI, 0.76-0.93, P < .01). CONCLUSIONS: Overweight patients with EC should not be denied surgical treatment, but intraoperative prevention and careful postoperative monitoring for several surgical complications must be stressed for this population. Besides, high BMI might be a prognostic predictor in EC patients; further studies are warranted.

Expression and potential mechanism of metabolism-related genes and CRLS1 in non-small cell lung cancer.

Cardiolipin (CL) is a phospholipid localized in the mitochondria, which is essential for mitochondrial structure and function. Human cardiolipin synthase 1 (CRLS1) is important in regulating phosphatidylglycerol (PG) remodeling and CL biosynthesis. However, the expression and distinct prognostic value of CRLS1 in neoplasms, including non-small cell lung cancer (NSCLC), is not well established. In the present study, the mRNA expression of CRLS1 was investigated using Oncomine analysis and the prognostic value was assessed using the Kaplan-Meier plotter database for patients with NSCLC. The results of the analyses indicated that the expression of CRLS1 in lung cancer was lower, compared with that in normal lung tissues. Notably, a high expression of CRLS1 was found to be associated with improved overall survival (OS) in all patients with NSCLC and lung adenocarcinoma (Ade). However, this was not observed in patients with squamous cell carcinoma (SCC). The results also demonstrated an association between the mRNA expression of CRLS1 and the clinicopathological parameters of patients with NSCLC, including sex, smoking status, tumor grade, clinical stage, lymph node status and chemotherapy. These results indicated that CRLS1 was associated with improved prognosis in patients with NSCLC, particularly at an early stage (T1N1M0). In addition, it was revealed that CRLS1 was co-expressed with well-known genes associated with metabolism using Gene Ontology term enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis also showed that tumor-related metabolism and the mitogen-activated protein kinase (MAPK) signaling pathways were enriched with CRLS1-co-expression genes. The results of the present study suggested that CRLS1 may be a novel tumor suppressor involved in regulating lipid and seleno-amino acid metabolism in the tumor microenvironment, and suppressing the MAPK signaling pathway during tumorigenesis and development. Comprehensive evaluation of the expression, prognosis and potential mechanism of CRLS1 is likely to promote an improved understanding of the complexity of the molecular biology of NSCLC.

Traditional and cumulative meta-analysis: Chemoradiotherapy followed by surgery versus surgery alone for resectable esophageal carcinoma.

The role of neoadjuvant chemoradiotherapy followed by surgery (CRTS) compared with surgery alone (SA) for resectable esophageal carcinoma has been established by several randomized controlled trials (RCTs). The present study aimed to investigate the difference in survival between the two treatments by a review of meta-analyses. Related research indicators were extracted from RCTs investigating CRTS or SA for resectable esophageal carcinoma by searching electronic databases for eligible articles. Outcomes were synthesized by adopting a fixed- or random-effects model with 95% confidence interval (CI). A total of 22 RCTs including 3,419 patients were selected. The odds ratio (OR) (95% CI, P-value), expressed as CRTS vs. SA, was 1.06 (0.94-1.19, P=0.348) for 1-year overall survival rate (OSR1y), 1.38 (1.20-1.58, P<0.001) for 3-year overall survival rate (OSR3y), and 1.42 (1.22-1.66, P<0.001) for 5-year overall survival rate (OSR5y). The R0 resection rate increased in patients treated by CRTS (OR=2.76, 95% CI: 2.15-3.53, P<0.001). CRTS lowered the locoregional cancer recurrence (OR=0.49, 95% CI: 0.36-6.65, P<0.001) and distant metastasis rate (OR=0.76, 95% CI: 0.60-0.97, P=0.02). However, the incidence of postoperative mortality was similar between the two groups (OR=0.97, 95% CI: 0.72-1.32, P=0.87). The subgroup analysis revealed that OSR3y and OSR5y for Asian, European and American populations were significantly higher in the CRTS group compared with those in the SA group (P<0.05). When comparing the OSR1y between the two groups for patients in all three continents, there was no significant difference (P>0.05). Histological subgroup analysis indicated that patients with esophageal adenocarcinoma may benefit from CRTS in terms of OSR1y (OR=1.55, 95% CI: 1.09-2.20, P=0.01), OSR3y (OR=1.77, 95% CI: 1.34-2.36, P<0.0001) and OSR5y (OR=1.92, 95% CI: 1.34-2.75, P=0.0004). The pooled OR of squamous cell carcinoma in terms of OSR3y and OSR5y between the two groups was 1.57 (95% CI: 1.21-2.04, P=0.0006) and 1.69 (95% CI: 1.32-2.16, P<0.0001), respectively, but there was no statistical difference in terms of OSR1y (OR=1.13, 95% CI: 0.88-1.45, P=0.35). Thus, neoadjuvant CRT followed by surgery may improve long-term survival and surgical parameters, and reduce locoregional cancer recurrence and distant metastasis.

A systematic review of pharmacoeconomic guidelines.

OBJECTIVE: To review, summarize, and analyze both similarities and differences of pharmacoeconomic (PE) guidelines, to enable researchers to access their characteristics and the current state of PE guidelines; furthermore, to learn which methodological issues still remain contested and to promote the methodological development of PE guidelines. MATERIALS AND METHODS: The authors performed a search for PE guidelines using PubMed, the Cochrane library database, and the websites of the International Society for Pharmacoeconomics and Outcomes Research. Information of each guideline was extracted using a pre-designed extraction template, which included 22 aspects; the guidelines were summarized in the forms of charts, and their characteristics have been described. RESULTS: A total of 40 PE guidelines were studied. The most common methodological issues include the types of analysis, sources for effectiveness, use of quality-adjusted life-years (QALYs) to measure outcomes, and use of incremental cost effectiveness ratios to present results. The majority of the guidelines preferred a cost utility analysis with outcomes expressed in terms of QALYs. Most of the guidelines preferred meta-analysis or meta-analysis of the randomized controlled trials, and required a systematic review of all evidence. Issues that varied most in the guidelines were the choice of the comparator, recommended costs to be included, methods related to indirect cost calculations, methods of sensitivity analysis, and discounting rate. CONCLUSION: A comparison of these guidelines revealed that a number of differences exist among them in several key aspects, and some critical methodological issues still exist, for which no best solution is available. Furthermore, efforts need to be made to develop harmonious methods for the PE, and to improve the transferability of the outcomes of PE evaluations.

Pattern of lymph node dissection in non-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective To compare lymph node sampling (LN-S) and lobe-specific lymph node dissection (LSLD) in the clinical efficacy and safety for early-stage non-small cell lung cancer (NSCLC). Methods PubMed, Medline, EMbase, Web of Science and The Cochrane Library databases were searched up to March 2017 for English language studies. We collected randomized controlled trials (RCTs) and cohort studies (CS) which used the systematic mediastinal lymph node dissection (SMLD) and LN-S or L-SLD for the treatment of NSCLC. Direct meta-analysis was performed using RevMan 5.3 software and indirect meta-analysis with ITC software after two researchers screened the literature, extracted the data and evaluated the risk of bias independently. Results A total of 18 articles were included (4 RCTs and 14 CS, and 10 714 patients). Meta-analysis results showed that in the CS, compared with the the SMLD group, overall survival increased in the L-SLD group (HR=0.99, 95%CI 0.78 to 1.25, P=0.92), and overall survival decreased in the LN-S group with significant difference in CS (HR=1.43, 95%CI 1.17 to 1.75, P=0.000 4), but was not statistically significant in RCT (P=0.35). In terms of disease-free survival, there was no significant difference between the SMLD group and the LN-S group (HR=1.25, 95%CI 0.90, 1.62, P=0.10) as well as the L-SLD group (HR=1.15, 95%CI 0.92 to 1.43, P=0.23) in the CS. There was no significant difference in the local recurrence rate or distant metastasis rate between the non-systematic lymph node dissection (NSMLD) and SMLD in CS and RCTs (CS: P=0.43, P=0.39; RCT: P=0.43, P=0.10). There was no significant difference in the postoperative complications between NSMLD and SMLD in the CS (OR=0.79, 95%CI 0.58 to 1.09, P=0.15) and RCTs (OR=0.36, 95%CI 0.09 to 1.45, P=0.15). Indirect meta-analysis showed that risk of death decreased by 31% and risk of recurrence by 35% in the L-SLD group compared with the LN-S group (HR=0.69, 95% CI 0.51 to 0.95, P=0.46; HR=0.65, 95% CI 0.65 to 1.30, P=0.72), but the difference was not statistically significant. Conclusion For earlystage NSCLC, L-SLD is not statistically different from SMLD in terms of survival; however, the overall survival of LN-S is lower than that of systematic lymphadenectomy. Indirect meta-analysis shows that L-SLD reduces the risk of death and recurrence risk compared with LN-S. There is no evidence to support both direct comparison of the prognosis of LN-S and L-SLD, therefore further prospective studies are still needed to verify.