Integrated whole-exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground-glass nodules.

OBJECTIVE: The genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC. METHODS: Thirty-five patients with ground-glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole-exome sequencing (WES) and transcriptome sequencing (RNA-Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA-Seq were subsequently analyzed. RESULTS: The findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co-mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD. CONCLUSIONS: Our findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.

A Novel Methylation-based Model for Prognostic Prediction in Lung Adenocarcinoma.

Objectives: Specific methylation sites have shown promise in the early diagnosis of lung adenocarcinoma (LUAD). However, their utility in predicting LUAD prognosis remains unclear. This study aimed to construct a reliable methylation-based predictor for accurately predicting the prognosis of LUAD patients. Methods: DNA methylation data and survival data from LUAD patients were obtained from the TCGA and a GEO series. A DNA methylation-based signature was developed using univariate least absolute shrinkage and selection operators and multivariate Cox regression models. Results: Eight CpG sites were identified and validated as optimal prognostic signatures for the overall survival of LUAD patients. Receiver operating characteristic analysis demonstrated the high predictive ability of the eight-site methylation signature combined with clinical factors for overall survival. Conclusion: This research successfully identified a novel eight-site methylation signature for predicting the overall survival of LUAD patients through bioinformatic integrated analysis of gene methylation markers used in the early diagnosis of lung cancer.

Ivermectin induces nonprotective autophagy by downregulating PAK1 and apoptosis in lung adenocarcinoma cells.

INTRODUCTION: LUAD (Lung adenocarcinoma), the most common subtype of lung carcinoma and one of the highest incidences and mortality cancers in the world remains still a substantial treatment challenge. Ivermectin, an avermectin derivative, has been traditionally used as an antiparasitic agent in human and veterinary medicine practice during the last few decades. Though ivermectin has been shown to be effective against a variety of cancers, however, there is few available data reporting the antitumor effects of ivermectin in LUAD. METHODS: The effect of ivermectin on cell viability and proliferative ability of LUAD cells was evaluated using CCK-8 and colony formation assay. Apoptosis rate and autophagy flux were detected using flow cytometry based on PI/Annexin V staining and confocal laser scanning microscope based on LC3-GFP/RFP puncta, respectively. Western blotting experiment was conducted to verify the results of changes in apoptosis and autophagy. LUAD-TCGA and GEO databases were used to analyse the expression and predictive value of PAK1 in LUAD patients. Xenograft model and immumohistochemical staining were used for verification of the inhibitor effect of ivermectin in vivo. RESULTS: Ivermectin treatment strikingly impeded the colony formation, and the viability of the cell, along with cell proliferation, and caused the apoptosis and enhanced autophagy flux in LUAD cells. In addition, ivermectin-induced nonprotective autophagy was confirmed by treating LUAD cells with 3-MA, an autophagy inhibitor. Mechanistically, we found that ivermectin inhibited PAK1 protein expression in LUAD cells and we confirmed that overexpression of PAK1 substantially inhibited ivermectin-induced autophagy in LUAD cells. Based on TCGA and GEO databases, PAK1 was highly expressed in LUAD tissues as compared with normal tissues. Furthermore, LUAD patients with high PAK1 level have poor overall survival. Finally, in vivo experiments revealed that ivermectin efficiently suppressed the cellular growth of LUAD among nude mice. CONCLUSION: This study not only revealed the mechanism of ivermectin inhibited the growth of LUAD but also supported an important theoretical basis for the development of ivermectin during the therapy for LUAD.

Nomogram Predicting the Prognosis of Patients with Surgically Resected Stage IA Non-small Cell Lung Cancer.

The American Joint Committee on Cancer (AJCC) 8th stage system was limited in accuracy for predicting prognosis of stage IA non-small cell lung cancer (NSCLC) patients. This study aimed to establish and validate two nomograms that predict overall survival (OS) and lung cancer-specific survival (LCSS) in surgically resected stage IA NSCLC patients. Postoperative patients with stage IA NSCLC in SEER database between 2004 and 2015 were examined. Survival and clinical information according to the inclusion and exclusion criteria were collected. All patients were randomly divided into the training cohort and validation cohort with a ratio of 7:3. Independent prognosis factors were evaluated using univariate and multivariate Cox regression analyses, and predictive nomogram was established based on these factors. Nomogram performance was measured using the C-index, calibration plots, and DCA. Patients were grouped by quartiles of nomogram scores and survival curves were plotted by Kaplan-Meier analysis. In total, 33,533 patients were included in the study. The nomogram contained 12 prognostic factors in OS and 10 prognostic factors in LCSS. In the validation set, the C-index was 0.652 for predicting OS and 0.651 for predicting LCSS. The calibration curves for the nomogram-predicted probability of OS and LCSS showed good agreement between the actual observation and nomogram prediction. DCA indicated that the clinical value of the nomograms were higher than AJCC 8th stage for predicting OS and LCSS. Nomogram scores related risk stratification revealed statistically significant difference which have better discrimination than AJCC 8th stage. The nomogram can accurately predict OS and LCSS in surgically resected patients with stage IA NSCLC. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01700-w.

A novel enemy of cancer: recent investigations into protozoan anti-tumor properties.

Cancer remains a significant global health issue, despite advances in screening and treatment. While existing tumor treatment protocols such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have proven effective in enhancing the prognosis for some patients, these treatments do not benefit all patients. Consequently, certain types of cancer continue to exhibit a relatively low 5-year survival rate. Therefore, the pursuit of novel tumor intervention strategies may help improve the current effectiveness of tumor treatment. Over the past few decades, numerous species of protozoa and their components have exhibited anti-tumor potential via immune and non-immune mechanisms. This discovery introduces a new research direction for the development of new and effective cancer treatments. Through in vitro experiments and studies involving tumor-bearing mice, the anti-tumor ability of Toxoplasma gondii, Plasmodium, Trypanosoma cruzi, and other protozoa have unveiled diverse mechanisms by which protozoa combat cancer, demonstrating encouraging prospects for their application. In this review, we summarize the anti-tumor ability and anti-tumor mechanisms of various protozoa and explore the potential for their clinical development and application.

Construction of PEI-EGFR-PD-L1-siRNA dual functional nano-vaccine and therapeutic efficacy evaluation for lung cancer.

BACKGROUND: PD-1/PD-L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-SiRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer in this study. METHOD: In this study, PEI lipid nanoparticles (PEI-LNP)/siRNA complex (EPV-PEI-LNP-siRNA) with the therapeutic function of PD-L1-siRNA and EGFR short peptide/PD-L1 double immune-enhancing function were constructed for the prevention and treatment of EGFR-positive lung cancer and functional evaluation was conducted. RESULTS: On the basis of the construction of the composite nano-drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV-PEI-LNP were tested in vitro, and the downregulation effect of PD-L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non-small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy. CONCLUSION: Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD-L1, realizing the tumor-specific expression of immune-stimulating cytokines, which is a highly efficient and safe targeted therapy nano-vaccine.

A novel mTOR-associated gene signature for predicting prognosis and evaluating tumor immune microenvironment in lung adenocarcinoma.

BACKGROUND: The mechanistic target of rapamycin (mTOR) was proven to have great impact on apoptosis, cell proliferation, autophagy, and many other fundamental cellular processes; moreover, it closely correlates with tumor occurrence and development. However, few studies have constructed signatures based on mTOR-associated genes to assess multiple indicators of prognosis in lung adenocarcinoma (LUAD) patients. METHODS: mTOR-associated gene sets, whole mRNA expression matrices, and clinical information of LUAD patients in training and validation cohorts were obtained from multiple public databases. Multiple methods were used to screen candidate genes, construct signatures, validate internally and externally, and conduct further studies: differentially expressed gene analysis, LASSO Cox regression analysis, Cox regression analysis, risk factor analysis, nomogram analysis, functional enrichment analysis, analyses in tumor immune microenvironment, and therapy. RESULTS: A prognostic signature containing 8 genes (LDHA, SLA, WNT7A, PLK1, CCT6A, BTG2, TXNRD1, and DDIT4) was constructed. It performed well in both internal and external validation. Subsequent analysis found that the prognostic signature was of great significance in evaluating the tumor immune microenvironment and could guide the treatment of patients with LUAD to a certain extent. CONCLUSION: The constructed mTOR-associated gene signature accurately predicted the prognostic pattern of patients with LUAD and is expected to be extremely useful in guiding LUAD therapy.

Plasmodium Circumsporozoite Protein Enhances the Efficacy of Gefitinib in Lung Adenocarcinoma Cells by Inhibiting Autophagy via Proteasomal Degradation of LC3B.

Background: Almost all lung adenocarcinoma (LUAD) patients with EGFR mutant will develop resistance to EGFR-TKIs, which limit the long-term clinical application of these agents. Accumulating evidence shows one of the main reasons for resistance to EGFR-TKIs is induction of autophagy in tumor cells. Our previous study found that circumsporozoite protein (CSP) in Plasmodium can suppress autophagy in host hepatocytes. However, it is unknown whether CSP-mediated inhibition of autophagy could improve the anti-tumor effect of EGFR-TKIs. Methods: We constructed A549 and H1975 cell lines with stable overexpression of CSP (OE-CSP cells). CCK-8, Lactate Dehydrogenase (LDH), flow cytometry, and colony analysis were performed to observe the effect of CSP overexpression on cell viability, apoptosis rate, and colony formation ratio. The sensitizing effect of CSP on gefitinib was evaluated in vivo using a subcutaneous tumor model in nude mice and immunohistochemical assay. The role of CSP in regulation of autophagy was investigated by laser confocal microscopy assay and western blotting. A transcriptome sequencing assay and real-time polymerase chain reaction were used to determine the levels of mRNA for autophagy-related proteins. Cycloheximide (CHX), MG132, TAK-243, and immunoprecipitation assays were used to detect and confirm proteasomal degradation of LC3B. Results: OE-CSP A549 and H1975 cells were more sensitive to gefitinib, demonstrating significant amounts of apoptosis and decreased viability. In the OE-CSP group, autophagy was significantly inhibited, and there was a decrease in LC3B protein after exposure to gefitinib. Cell viability and colony formed ability were recovered when OE-CSP cells were exposed to rapamycin. In nude mice with xenografts of LUAD cells, inhibition of autophagy by CSP resulted in suppression of cell growth, and more marked apoptosis during exposure to gefitinib. CSP promoted ubiquitin-proteasome degradation of LC3B, leading to inhibition of autophagy in LUAD cells after treatment with gefitinib. When LUAD cells were treated with ubiquitin activating enzyme inhibitor TAK-243, cell viability, apoptosis, and growth were comparable between the OE-CSP group and a control group both in vivo and in vitro. Conclusion: CSP can inhibit gefitinib-induced autophagy via proteasomal degradation of LC3B, which suggests that CSP could be used as an autophagy inhibitor to sensitize EGFR-TKIs.

Significance of Parkinson Family Genes in the Prognosis and Treatment Outcome Prediction for Lung Adenocarcinoma.

Epidemiological investigations have shown that patients with Parkinson's disease (PD) have a lower probability of developing lung cancer. Subsequent research revealed that PD and lung cancer share specific genetic alterations. Therefore, the utilisation of PD biomarkers and therapeutic targets may improve lung adenocarcinoma (LUAD) diagnosis and treatment. We aimed to identify a gene-based signature from 25 Parkinson family genes for LUAD prognosis and treatment choice. We analysed Parkinson family gene expression and protein levels in LUAD, utilising multiple databases. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a prognostic model based on the TCGA-LUAD cohort. We validated the model in external GEO cohorts. Immune cell infiltration was compared between risk groups, and GEO data was used to explore the model's predictive ability for LUAD treatment response. Nearly all Parkinson family genes exhibited significant differential expression between LUAD and normal tissues. LASSO regression confirmed that our seven Parkinson family gene-based signature had excellent prognostic performance for LUAD, as validated in three GEO cohorts. The high-risk group was clearly associated with low tumour immune cell infiltration, suggesting that immunotherapy may not be an optimal treatment choice. This is the first Parkinson family gene-based model for the prediction of LUAD prognosis and treatment outcome. The association of these genes with poor prognosis and low immune infiltration requires further investigation.

Attenuated plasmodium sporozoite expressing MAGE-A3 induces antigen-specific CD8+ T cell response against lung cancer in mice.

OBJECTIVE: Cancer vaccines that rely on tumor antigen-specific CD8+ T cell responses, are promising anti-cancer adjuvant immunotherapies. This study investigated whether genetically attenuated Plasmodium sporozoite (GAS) could be used as a novel vector to induce antigen-specific CD8+ T cell responses against lung cancer. METHODS: We constructed GAS/MAGE-A3, a recombinant GAS engineered to express the lung cancer-specific antigen, melanoma-associated antigen 3 (MAGE-A3), and assessed its therapeutic effects against lung cancer. RESULTS: Robust parasite-specific CD8αlowCD11ahigh and CD49dhighCD11ahigh CD4+ T cell responses as well as a MAGE-A3-specific CD8+ T cell response were induced in GAS/MAGE-A3-immunized mice. Adoptive transfer of GAS/MAGE-A3-induced CD8+ T cells from HLA-A2 transgenic mice into lung cancer-bearing nude mice inhibited tumor growth and prolonged survival. CONCLUSIONS: These findings demonstrate that GAS/MAGE-A3 induces a strong MAGE-A3-specific CD8+ T cell response against lung cancer in vivo, and indicate that GAS is a novel and efficacious antigen delivery vector for antitumor immunotherapy.

Dichloroacetate enhances the antitumor efficacy of chemotherapeutic agents via inhibiting autophagy in non-small-cell lung cancer.

BACKGROUND: Chemotherapy is still the primary adjuvant strategy of cancer therapy; however, the emergence of multi-drug resistance has been a cause for concern. Autophagy has been demonstrated to have a protective role against chemotherapeutic drugs in cancer cells, and autophagy inhibition is generally considered to be a promising therapeutic strategy. However, the paucity of effective and specific autophagy inhibitors limits its application. PURPOSE: The objective of this study was to explore the effect of DCA, small molecular anti-tumor agent, on the autophagy regulation and chemosensitization in NSCLC cells. METHODS: We investigated the autophagy regulation of dichloroacetate (DCA) by laser confocal microscopy and western blotting in A549 and H1975 cell lines. The MTT assay and flow cytometry was performed for explore the chemosensitization effectiveness of DCA. The results were verified with subcutaneous tumor model in nude mice and the immunohistochemistry was applied for assessing the level of cell apoptosis and autophagy in vivo post treatment. RESULTS: We found that DCA, which exhibited antitumor properties in various carcinoma models, induced apoptosis of non-small cell lung cancer cells (NSCLC) by inhibiting cancer cell autophagy. Furthermore, Perifosine, an AKT inhibitor, can greatly weaken the capacity of inducing apoptosis by DCA. The results indicate that the AKT-mTOR pathway, a main negative regulator of autophagy, is involved in the DCA-induced inhibition of autophagy. Then, we detected the effectiveness of autophagy inhibition by DCA. When used in co-treatment with the chemotherapeutic drug paclitaxel (PTX), DCA markedly decreased cell autophagy, enhanced apoptosis and inhibited proliferation in A549 and H1975 cells. The results of the xenograft experiment demonstrate that co-treatment of PTX and DCA can significantly decrease cell proliferation in vivo and prolong the survival of mice. CONCLUSION: Our results suggest that DCA can inhibit cell autophagy induced by chemotherapeutics, providing a new avenue for cancer chemotherapy sensitization.

Plasmodium circumsporozoite protein suppresses the growth of A549 cells via inhibiting nuclear transcription factor κB.

Blocking the activation of nuclear factor κB (NF-κB) is a promising strategy for the treatment of non-small cell lung cancer. The circumsporozoite protein (CSP), a key component of the sporozoite stage of the malaria parasite, was previously reported to block NF-κB activation in hepatocytes. Therefore, in the present study, the effect of CSP on the growth of the human lung cancer cell line, A549, was investigated. It was demonstrated that transfection with a recombinant plasmid expressing CSP was able to inhibit the proliferation of A549 cells in a dose-dependent manner and induce the apoptosis of A549 cells. A NF-κB gene reporter assay indicated that CSP and its nuclear localization signal (NLS) motif were able to equally suppress the activation of NF-κB following stimulation with human recombinant tumor necrosis factor (TNF)-α in A549 cells. Furthermore, western blot analysis indicated that NLS did not affect the phosphorylation and degradation of IκB, but was able to markedly inhibit the nuclear translocation of NF-κB in TNF-α stimulated A549 cells. Therefore, the data suggest that CSP may be investigated as a potential novel NF-κB inhibitor for the treatment of lung cancer.

High expression of DJ-1 promotes growth and invasion via the PTEN-AKT pathway and predicts a poor prognosis in colorectal cancer.

Cancer cell invasion and unlimited proliferation are key factors in patients with colorectal cancer (CRC). Increased protein deglycase DJ-1 in cancer cells is known to promote tumor growth; however, its role in CRC progression is not well defined. In this study, we investigated 100 CRC patients with disease stages I-IV to determine whether DJ-1 could serve as a prognostic biomarker in CRC. These results showed that DJ-1 expression in CRC tissues was higher than that in normal colon tissues and was associated with the (Tumor Node Metastasis) TNM stage. CRC patients with low DJ-1 expression had a longer overall survival than those with high expression, and multivariate and univariate analyses indicated that DJ-1 expression was an independent prognostic factor for overall survival in CRC. Furthermore, DJ-1 overexpression in two colon cancer cell lines, HCT116 and SW480, activated protein kinase AKT and downregulated tumor suppressor PTEN, whereas DJ-1 knockdown upregulated PTEN expression and effectively suppressed CRC cell invasion and proliferation both in vitro and in vivo, revealing a mechanism underlying DJ-1 pro-oncogenic activity in CRC. Treatment of MK2206, the specific AKT inhibitor, significantly decreased DJ-1-mediated cell proliferation and mobility in vitro. Taken together, these results suggest that DJ-1 may be a novel prognostic biomarker and potential therapeutic target in human CRC.

Anastomotic reinforcement with omentoplasty reduces anastomotic leakage for minimally invasive esophagectomy with cervical anastomosis.

PURPOSE: Anastomotic leakage is the most feared postoperative complication after esophagectomy. Omentoplasty, wrapping the omentum around the alimentary tract anastomosis, is thought to decrease the anastomotic leakage rate. The purpose of this clinical study is to investigate the use of omentoplasty to reinforce cervical esophagogastrostomy after minimally invasive esophagectomy (MIE). PATIENTS AND METHODS: In this retrospective study, the data of 160 consecutive patients who underwent cervical esophagogastrostomy after MIE between September 2012 and May 2015 were analyzed, 87 who underwent omentoplasty (group A) and 73 who did not undergo omentoplasty (group B). The primary outcome was the incidence of anastomotic leakage and anastomotic strictures after the operation. Secondary outcomes were other complications and mortality rate. Univariate and multivariate analysis of variables associated with an increased risk for anastomotic leak was performed. RESULTS: The median age was 61 years (range, 37-82 years). The anastomotic leakage rates were 4.6% (4/87) in group A and 15.1% (11/73) in group B (P = 0.023). There was no statistical significance in anastomotic stricture rates between group A (6.9%) and group B (9.6%; P = 0.535). No difference was noted in other complications between the groups. There was a trend toward lower leak-associated mortality rates for group A (0%) compared with that for group B (4.1%). CONCLUSION: Cervical esophagogastrostomy with omentoplasty is more effective than esophagogastrostomy without omentoplasty for the prevention of anastomotic leakage in MIE with cervical anastomosis. Omentoplasty could be used as an adjunct technique to reduce the incidence of anastomotic leakage in cervical esophagogastrostomy following MIE.

Segmentectomy versus wedge resection for the treatment of high-risk operable patients with stage I non-small cell lung cancer: a meta-analysis.

BACKGROUND: Although lobectomy is still the preferred treatment for patients with stage I non-small cell lung cancer (NSCLC), segmentectomy or wedge resection is frequently performed on patients who cannot withstand the physiological rigors of lobectomy. The objective of this study was to compare the overall survival (OS), cancer-specific survival (CSS), and disease-free survival outcomes among patients with stage I NSCLC who have undergone these procedures. METHODS: A systematic electronic search in three online databases was conducted from their earliest publication dates to June 2015. The studies were evaluated according to rigorous, predefined inclusion criteria. The hazard ratio (HR) was used as the outcome measure for data combining. RESULTS: There were nine eligible studies. These studies included 1181 patients who underwent segmentectomy and 2003 patients who underwent wedge resection. Stage I NSCLC patients who underwent segmentectomy had significantly better OS (HR 0.80; 95% confidence interval [CI], 0.68-0.93; p = 0.004) and CSS (HR 0.42; 95% CI, 0.20-0.88; p = 0.02) rates than those who underwent wedge resection. However, there were no significant differences in OS (HR 0.39; 95% CI, 0.15-1.02; p = 0.06) and CSS (HR 1.87; 95% CI, 0.29-12.06; p = 0.51) rates between segmentectomy and wedge resection in patients with stage Ia NSCLC with tumor size ⩽ 2 cm. CONCLUSIONS: For patients with stage I NSCLC, segmentectomy results in higher survival rates than wedge resection, whereas the outcomes of wedge resection are comparable to those of segmentectomy for patients with stage Ia NSCLC with tumor size ⩽ 2 cm. Considering the limitations and heterogeneity of the included studies, this conclusion should be further confirmed by rigorous randomized clinical trials.

Comparison of clinical outcomes after thoracoscopic sublobectomy versus lobectomy for Stage I nonsmall cell lung cancer: A meta-analysis.

BACKGROUND: Although lobectomy has long been considered the standard procedure for Stage I nonsmall cell lung cancer (NSCLC), the selection of sublobectomy for Stage I NSCLC remains controversial. Amidst growing enthusiasm for minimally invasive surgery, the comparison of clinical outcomes after thoracoscopic sublobectomy versus thoracoscopic lobectomy may be of immense value. OBJECTIVE: The present study aimed to compare the overall survival (OS) and disease-free survival (DFS) outcomes of patients who underwent thoracoscopic sublobectomy with those who underwent thoracoscopic lobectomy for Stage I NSCLC. METHODS: An electronic search was conducted using five online databases from their dates of inception to February 2014. Hazard ratio (HR) was used in this meta-analysis, calculated from the published survival data. RESULTS: Eight studies met the selection criteria, including a total of 1613 patients (463 patients underwent thoracoscopic sublobectomy, and 1150 patients underwent thoracoscopic lobectomy). From the available data, compared with thoracoscopic sublobectomy, there was a significant benefit of thoracoscopic lobectomy on OS (HR: 1.45; 95% confidence interval [CI]: 1.11-1.90; P = 0.007). However, in subgroup analysis of thoracoscopic segmentectomy and thoracoscopic lobectomy, there was no significant difference in OS (HR: 1.03; 95% CI: 0.76-1.39; P = 0.85) or DFS (HR: 1.19; 95% CI: 0.67-2.10; P = 0.56) between the two groups. In addition, compared with thoracoscopic wedge resection, there was a significant benefit of thoracoscopic lobectomy on OS (HR: 4.19; 95% CI: 2.19-8.03, P < 0.0001). CONCLUSION: For Stage I patients, thoracoscopic segmentectomy leads to survival rates comparable to thoracoscopic lobectomy. However, the overall several of thoracoscopic lobectomy is superior to that of wedge resection.

Single chest tube drainage is superior to double chest tube drainage after lobectomy: a meta-analysis.

BACKGROUND: In this meta-analysis, we conducted a pooled analysis of clinical studies comparing the efficacy of single chest tube versus double chest tube after a lobectomy. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of the PubMed, Embase, Cochrane Library and Web of Science databases to identify articles to include in our meta-analysis. A literature search was performed using relevant keywords. A meta-analysis was performed using RevMan© software. RESULTS: Five studies, published between 2003 and 2014, including 630 patients (314 patients with a single chest tube and 316 patients with a double chest tube), met the selection criteria. From the available data, the patients using a single tube demonstrated significantly decreased postoperative pain [weighted mean difference [WMD] -0.60; 95 % confidence intervals [CIs] -0.68-- 0.52; P < 0.00001], duration of drainage [WMD -0.70; 95 % CIs -0.90-- 0.49; P < 0.00001] and hospital stay [WMD -0.51; 95 % CIs -0.91-- 0.12; P = 0.01] compared to patients using a double tube after a pulmonary lobectomy. However, there were no significant differences in postoperative complications [OR 0.91; 95 % CIs 0.57-1.44; P = 0.67] and re-drainage rates [OR 0.81; 95 % CIs 0.42-1.58; P = 0.54]. CONCLUSION: Our results showed that a single-drain method is effective, reducing postoperative pain, hospitalization times and duration of drainage in patients who undergo a lobectomy. Moreover, the single-drain method does not increase the occurrence of postoperative complications and re-drainage rates.

The Effectiveness of Postoperative Radiotherapy in Patients With Completely Resected Thymoma: A Meta-Analysis.

BACKGROUND: This meta-analysis aimed to provide a pooled analysis of clinical studies correlating postoperative radiotherapy (PORT) with survival in patients with completely resected thymoma. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. An electronic search was conducted using online databases. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used in this meta-analysis and were calculated from published survival data. A meta-analysis was conducted to assess the impact of PORT in completely resected thymoma on overall survival (OS), disease-free survival (DFS). and disease-specific survival (DSS). We also performed a subgroup analysis for OS of patients with stage II and stage III thymoma. RESULTS: Fourteen studies, which included 3,823 patients (2,096 patients who received PORT and 1,727 patients who did not receive PORT), met the selection criteria. From the available data, the thymoma patients with PORT who did not undergo resection did not have significantly improved OS (HR 0.99; 95% CI 0.87 to 1.13; p = 0.87), DFS (HR 1.21; 95% CI 0.97 to 1.51; p = 0.09), or DSS (HR 0.66; 95% CI 0.39 to 1.13; p = 0.13) compared with the patients who did not undergo PORT. However, our subgroup analysis showed a significant difference in OS in patients with stage II thymoma (HR 0.57; 95% CI 0.41 to 0.80; p = 0.001) and patients with stage III thymoma (HR 0.73; 95% CI 0.59 to 0.90; p = 0.004). CONCLUSION: Our results showed that for completely resected thymoma, PORT had no advantage in the overall group of patients but increased OS in the patients with stage II and III thymoma after a complete resection. On the basis of this study, PORT is beneficial in patients with stage II and III patients after a complete resection.

Comparison of two different mechanical esophagogastric anastomosis in esophageal cancer patients: a meta-analysis.

OBJECTIVE: In this meta-analysis, we conducted a pooled analysis of clinical studies comparing Linear Stapled (LS) versus Circular Stapled (CS) esophagogastric anastomosis for esophageal cancer. METHODS: According to the recommendations of the Cochrane Collaboration, we established a rigorous study protocol. We performed a systematic electronic search of the PubMed, Embase, Cochrane Library, Web of Science, and Chinese Biomedical databases as well as Chinese scientific journals to identify articles to include in our meta-analysis. The primary outcomes compared were anastomotic leak, anastomotic stricture and 3-month mortality. RESULTS: Five controlled trials comprising 840 patients (523 LS vs. 317 CS) were included. Primary outcomes revealed a statistically significant decrease in anastomotic strictures [risk ratio (RR): 0.26, 95 % confidence interval (CI): 0.11-0.60, P = 0.002] compared with linear stapled anastomosis. However, there were no significant differences between the two groups with respect to anastomotic leakage [risk ratio (RR): 0.80, 95 % confidence interval (CI): 0.40-1.58, P = 0.52] and 3-month mortality [risk ratio (RR): 0.94, 95 % confidence interval (CI): 0.47-1.87, P = 0.85]. CONCLUSION: There were no statistical differences in the rate of 3-month mortality or anastomotic leakage between the two groups. However, the LS method contributed to a reduced rate of anastomotic strictures. This meta-analysis may offer some specific suggestions for esophagogastric anastomosis.

Hand-sewn vs linearly stapled esophagogastric anastomosis for esophageal cancer: a meta-analysis.

AIM: To compare the outcomes of hand-sewn (HS) and linearly stapled (LS) esophagogastric anastomosis for esophageal cancer. METHODS: Before beginning this study, a rigorous protocol was established according to the recommendations of the Cochrane Collaboration. Databases and references were searched for all randomized controlled trials and comparative clinical studies that compared LS with HS esophagogastric anastomosis for esophageal cancer. The primary outcomes compared were anastomotic leak and stricture. Subgroup analyses were performed according to site of anastomosis. RESULTS: Fifteen studies were used, comprising 3203 patients (n = 2027 LS and 1176 HS). Primary outcome analysis revealed a significant decrease in anastomotic leakage (RR = 0.51, 95%CI: 0.41-0.65; P < 0.00001) associated with LS anastomosis. A significantly reduced rate of anastomotic stricture associated with LS was also found (RR = 0.56, 95%CI: 0.49-0.64; P < 0.00001). A subgroup analysis according to the site of anastomosis revealed a significantly reduced rate of anastomotic stricture (P < 0.00001). Although there was no significant difference in the decrease in thoracic anastomotic leakage, there was a significant decrease in cervical anastomotic leakage associated with LS (P < 0.00001). CONCLUSION: This meta-analysis indicates that the LS technique contributes to a reduced rate of leakage and stricture compared with the HS method.