SDF-1 promotes metastasis of NSCLC by enhancing chemoattraction of megakaryocytes through the PI3K/Akt signaling pathway.

Lung cancer (LC) is the leading cause of cancer-associated deaths worldwide, among which non-small-cell lung cancer (NSCLC) accounts for 80%. Stromal cell-derived factor-1 (SDF-1) inhibition results in a significant depletion of NSCLC metastasis. Additionally, SDF-1 is the only natural chemokine known to bind and activate the receptor CXCR4. Thus, we attempted to clarify the molecular mechanism of SDF-1 underlying NSCLC progression. Transwell migration, adhesion, and G-LISA assays were used to assess megakaryocytic chemotaxis in vitro and in vivo in terms of megakaryocytic migration, adherence, and RhoA activation, respectively. Western blotting was used to assess PI3K/Akt-associated protein abundances in MEG-01 cells and primary megakaryocytes under the indicated treatment. A hematology analyzer and flow cytometry were used to assess platelet counts in peripheral blood and newly formed platelet counts in Lewis LC mice under different treatments. Immunochemistry and flow cytometry were used to measure CD41+ megakaryocyte numbers in Lewis LC mouse tissue under different treatments. ELISA was used to measure serum TPO levels, and H&E staining was used to detect NSCLC metastasis.SDF-1 receptor knockdown suppressed megakaryocytic chemotaxis in Lewis LC mice. SDF-1 receptor inhibition suppressed megakaryocytic chemotaxis via the PI3K/Akt pathway. SDF-1 receptor knockdown suppressed CD41+ megakaryocyte numbers in vivo through PI3K/Akt signaling. SDF-1 receptor inhibition suppressed CD41+ megakaryocytes to hinder NSCLC metastasis. SDF-1 facilitates NSCLC metastasis by enhancing the chemoattraction of megakaryocytes via the PI3K/Akt signaling pathway, which may provide a potential new direction for seeking therapeutic plans for NSCLC.

Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis.

Advances in lung cancer research applying machine learning (ML) technology have generated many relevant literature. However, there is absence of bibliometric analysis review that aids a comprehensive understanding of this field and its progress. Present article for the first time performed a bibliometric analysis to clarify research status and focus from 2010 to 2021. In the analysis, a total of 2,312 relevant literature were searched and retrieved from the Web of Science Core Collection database. We conducted a bibliometric analysis and further visualization. During that time, exponentially growing annual publication and our model have shown a flourishing research prospect. Annual citation reached the peak in 2017. Researchers from United States and China have produced most of the relevant literature and strongest partnership between them. Medical image analysis and Nature appeared to bring more attention to the public. The computer-aided diagnosis, precision medicine, and survival prediction were the focus of research, reflecting the development trend at that period. ML did make a big difference in lung cancer research in the past decade.

3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma.

SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.

Alveolar macrophage modulation via the gut-lung axis in lung diseases.

Several studies have demonstrated great potential implications for the gut-lung axis in lung disease etiology and treatment. The gut environment can be influenced by diet, metabolites, microbiotal composition, primary diseases, and medical interventions. These changes modulate the functions of alveolar macrophages (AMs) to shape the pulmonary immune response, which greatly impacts lung health. The immune modulation of AMs is implicated in the pathogenesis of various lung diseases. However, the mechanism of the gut-lung axis in lung diseases has not yet been determined. This mini-review aimed to shed light on the critical nature of communication between the gut and AMs during the development of pulmonary infection, injury, allergy, and malignancy. A better understanding of their crosstalk may provide new insights into future therapeutic strategies targeting the gut-AM interaction.

cGAS-STING pathway in ischemia-reperfusion injury: a potential target to improve transplantation outcomes.

Transplantation is an important life-saving therapeutic choice for patients with organ or tissue failure once all other treatment options are exhausted. However, most allografts become damaged over an extended period, and post-transplantation survival is limited. Ischemia reperfusion injury (IRI) tends to be associated with a poor prognosis; resultant severe primary graft dysfunction is the main cause of transplant failure. Targeting the cGAS-STING pathway has recently been shown to be an effective approach for improving transplantation outcomes, when activated or inhibited cGAS-STING pathway, IRI can be alleviated by regulating inflammatory response and programmed cell death. Thus, continuing efforts to develop selective agonists and antagonists may bring great hopes to post-transplant patient. In this mini-review, we reviewed the role of the cGAS-STING pathway in transplantation, and summarized the crosstalk between this pathway and inflammatory response and programmed cell death during IRI, aiming to provide novel insights into the development of therapies to improve patient outcome after transplantation.

Dual-targeting peptides@PMO, a mimetic to the pro-apoptotic protein Smac/DIABLO for selective activation of apoptosis in cancer cells.

The refractoriness of tumor cells to apoptosis represents the main mechanism of resistance to chemotherapy. Smac/DIABLO mimetics proved to be effective in overcoming cancer-acquired resistance to apoptosis as a consequence of overexpression of the anti-apoptotic proteins XIAP, cIAP1, and cIAP2. In this work, we describe a dual-targeting peptide capable of selectively activating apoptosis in cancer cells. The complex consists of a fluorescent periodic mesoporous organosilica nanoparticle that carries the short sequences of Smac/DIABLO bound to the αvß3-integrin ligand. The dual-targeting peptide @PMO shows significantly higher toxicity in αvß3-positive HeLa cells with respect to αvß3-negative Ht29 cells. @PMO exhibited synergistic effects in combination with oxaliplatin in a panel of αvß3-positive cancer cells, while its toxicity is overcome by XIAP overexpression or integrin ß3 silencing. The successful uptake of the molecule by αvß3-positive cells makes @PMO promising for the re-sensitization to apoptosis of many cancer types.

Integrative learning in developing an immunologic lncRNA signature as a consensus risk-stratification tool for lung adenocarcinoma.

Background: In the tumor immune microenvironment, the contribution of innate and adaptive immune cells to tumor progression has been consistently demonstrated. However, reliable prognostic biomarkers for lung adenocarcinoma (LUAD) have not yet been identified. We thus developed and validated an immunologic long noncoding RNA (lncRNA) signature (ILLS) to facilitate the classification of patients with high and low risk and provide potential "made-to-measure" treatment choices. Methods: The LUAD data sets were obtained and processed from public databases of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The abundance of immune infiltration and its related pathways were calculated through consensus clustering, weighted gene coexpression network analysis (WGCNA), and an integrated ImmLnc to identify immune-related lncRNAs and extract immune-related prognostic lncRNAs. Based on the integrative procedure, the best algorithm composition was least absolute shrinkage and selection operator (LASSO) and stepwise Cox regression in both directions to develop the ILLS in the TCGA-LUAD data set and validate the predictive power of 4 independent data sets, GSE31210, GSE37745, GSE30219, and GSE50081 through survival analysis, receiver operating characteristic (ROC) analysis, and multivariate Cox regression. The concordance index (C-index) analysis was transversely compared with 49 published signatures in the above 5 data sets to further confirm its stability and superiority. Finally, drug sensitivity analysis was conducted to explore potential therapeutic agents. Results: Patients from the high-risk groups consistently had worse overall survival (OS) compared to the low-risk groups. ILLS proved to be an independent prognostic factor with favorable sensitivity and specificity. Among the 4 GEO data sets, compared to those reported in the other literature, ILLS maintained stable prediction ability and was more suitable as a consensus risk-stratification tool. However, The Cancer Immunome Atlas and IMvigor210 data sets demonstrated practical utility in recognizing target populations with effective immunotherapy, while the high-risk group exhibited potential targets for certain chemotherapy drugs, such as carmustine, etoposide, arsenic trioxide, and alectinib. Conclusions: ILLS demonstrated superior and stable prognostic prediction ability and thus has potential as a tool for assisting in risk classification and clinical decision-making in patients with LUAD.

The outcome of lung transplantation for end-stage pulmonary diseases with pulmonary hypertension: a single-center experience.

Background: Lung transplantation is a treatment for end-stage lung disease. The optimal transplant strategy for patients with end-stage lung disease complicated by pulmonary hypertension (PH) is controversial. The aim of this study is to review this experience and analyze the outcomes of lung transplantation for PH. Methods: This retrospective study collected data on patients with PH undergoing lung transplantation between March 2016 and December 2019 at a single center in China. The perioperative features and short- and medium-term outcomes between single-lung transplantation (SLT) and double-lung transplantation (DLT) were compared. Kaplan-Meier methods were used to analyze overall survival across a variety of transplantation procedures, age, mean pulmonary artery pressure (mPAP), body mass index (BMI), and indications of transplantation. Results: A total of 63 patients with PH were finally included in the analysis. The mean age, mean BMI, and mPAP were 56.37 years, 19.56 kg/m2, and 35.4 mmHg respectively. The overall 1-, 2-, and 3-year survival was 70%, 63%, and 60%, respectively. Five (7.94%) patients died within 30 days after surgery and nine patients (14.3%) died from infection during the followed-up period. There were no significant differences in the short- and medium-term survival outcomes of SLT and DLT, but postoperative pulmonary function was better in DLT. Patients older than 60 years of age had worse survival (P=0.01). Conclusions: The short- and medium-term survival outcomes between SLT and DLT are similar in selected patients with PH. DLT provides better pulmonary function. Patients older than 60 years are associated with worse survival.

Spontaneous ventilation video-assisted thoracic surgery for mediastinal tumor resection in patients with pulmonary function deficiency.

BACKGROUND: Whether non-intubated spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) is a safe procedure remains controversial for mediastinal tumor patients with impaired lung function. Herein, we assessed feasibility of SV-VATS in lung function deficiency patients underwent mediastinal tumor resection. METHODS: From December 2015 to February 2020, 32 mediastinal tumor patients with impaired lung function (preoperative forced expiratory volume in 1 second <70% of the predicted value) were retrospectively collected. Patients were divided into two groups: SV-VATS group and mechanical ventilation VATS (MV-VATS) group. Intraoperative and postoperative variables were compared between two cohorts. RESULTS: Fifteen patients (46.88%) underwent SV-VATS and 17 patients (53.12%) were performed with MV-VATS. The most common causes of lung function deficiency were smoking (81.25%) and COPD (71.88%). Patients in the SV-VATS group had similar blood loss (20.63 vs. 18.76 mL, P=0.417) with MV-VATS group. The anesthesia time (217.51 vs. 197.76 min; P=0.343) and surgery time (141.23 vs. 132.36 min; P=0.209) were also similar between groups. Five people suffered postoperative complications in each group, in which 1 patient underwent MV-VATS was transferred to intensive care unit (ICU) because of prolonged extubation owing to hypoxia. There was no difference on chest tube removal time (2.6 vs. 2.3 days; P=0.172) or hospital duration (5.03 vs. 4.74 days; P=0.297) in patients underwent SV-VATS and MV-VATS. CONCLUSIONS: SV-VATS is safe and provides similar short-term results to MV-VATS for mediastinal tumor resection in patients with limited pulmonary function.

Downregulation of Hsa_circ_0000735 Inhibits the Proliferation, Migration, Invasion, and Glycolysis in Non-small-cell Lung Cancer by Targeting miR-940/BMPER Axis.

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and the major cause of cancer-related deaths worldwide. The increasing studies have demonstrated that circular RNA (circRNA) was involved in the progression of various cancers, including non-small-cell lung cancer (NSCLC). This study was designed to assess the expression, roles and functional mechanisms of circ_0000735 in NSCLC. MATERIALS AND METHODS: The expression levels of circ_0000735, miR-940 and bone morphogenetic protein binding endothelial cell precursor-derived regulator (BMPER) were estimated by the real-time quantitative polymerase chain reaction (RT-qPCR). The biological behaviors of NSCLC cells such as proliferation, migration and invasion were analyzed by cell counting kit-8 (CCK-8), colony-forming assays and transwell assay, respectively. Furthermore, extracellular acid ratio and lactate production were tested to assess glycolysis levels of NSCLC cells. The interaction relationship among circ_0000735, BMPER and miR-940 was analyzed by bioinformatics database and dual-luciferase reporter assay. The protein expression level of BMPER was assessed by Western blot assay. Tumorigenesis assay was established to clarify the functional roles of circ_0000735 in vivo. RESULTS: Circ_0000735 was upregulated and significantly correlated with overall survival in patients with NSCLC. In addition, the loss-of-functional experiments revealed that knockdown of circ_0000735 repressed proliferation, migration, invasion and glycolysis of NSCLC cells and tumor growth in vivo, which was overturned by overexpression of BMPER. Similarly, overexpression of circ_0000735 enhanced proliferation, migration, invasion, and glycolysis of NSCLC cells. In addition, we also confirmed that overexpression of miR-940 impeded proliferation, migration, invasion, and glycolysis of NSCLC cells. Furthermore, overexpression of BMPER abolished si-circ_0000735 induced effects on NSCLC cells. CONCLUSION: Circ_0000735 regulated proliferation, migration, invasion, and glycolysis in NSCLC cells by targeting miR-940/BMPER axis.

Endosonography with lymph node sampling for restaging the mediastinum in lung cancer: A systematic review and pooled data analysis.

BACKGROUND: Mediastinal restaging after induction treatment is still a difficult and controversial issue. We aimed to investigate the diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration for restaging the mediastinum after induction treatment in patients with lung cancer. METHODS: Embase and PubMed databases were searched from conception to March 2019. Data from relevant studies were analyzed to assess sensitivity and specificity of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration, and to fit the hierarchical summary receiver operating characteristic curves. RESULTS: A total of 10 studies consisting of 558 patients fulfilled the inclusion criteria. All patients were restaged by endobronchial ultrasound-guided transbronchial needle aspiration, endoscopic ultrasound-guided fine-needle aspiration, or both. Negative results were confirmed by subsequent surgical approaches. There were no complications reported during any endosonography approaches reviewed. The pooled sensitivities of endobronchial ultrasound-guided transbronchial needle aspiration and endoscopic ultrasound-guided fine-needle aspiration were 65% (95% confidence interval [CI], 52-76) and 73% (95% CI, 52-87), respectively, and specificities were 99% (95% CI, 78-100) and 99% (95% CI, 90-100), respectively. The area under the hierarchical summary receiver operating characteristic curves were 0.85 (95% CI, 0.81-0.88) for endobronchial ultrasound-guided transbronchial needle aspiration and 0.99 (95% CI, 0.98-1) for endoscopic ultrasound-guided fine-needle aspiration. Moreover, for patients who received chemotherapy alone, the pooled sensitivity of endosonography with lymph node sampling for restaging was 66% (95% CI, 56-75), and specificity was 100% (95% CI, 34-100); for patients who received chemoradiotherapy, the results seemed similar with a sensitivity of 77% (95% CI, 47-92) and specificity of 99% (95% CI, 48-100). CONCLUSIONS: Endosonography with lymph node sampling is an accurate and safe technique for mediastinal restaging of lung cancer.

Potential of the glasses-free three-dimensional display system in shortening the learning curve of video-assisted endoscopic surgery: a self-controlled ex-vivo study.

BACKGROUND: One of the largest challenges in endoscopic surgical training is adapting to a two-dimensional (2D) view. The glasses-free three-dimensional (GF-3D) display system was designed to integrate the merits of both 2D and conventional 3D (C-3D) displays, allowing surgeons to perform video-assisted endoscopic surgery under a stereoscopic view without heavy and cumbersome 3D glasses. METHODS: In this study, 15 junior thoracic surgeons were divided to test one routine and one complex task three times each via traditional high-definition 2D (HD-2D) and GF-3D to determine whether there was any advantage when using the GF-3D system to acquire endoscopic skills. The duration, numbers of stitches, and distance between every two stitches were recorded for every procedure. RESULTS: Seven participants were enrolled in the HD-2D group and eight participants were enrolled in the GF-3D group. All 15 participants successfully completed porcine skin continuous suture and tracheal continuous anastomosis procedures three times each. For skin continuous suture, there was no significant difference between the two groups in terms of the learning curve for speed (P=0.683) and accuracy (P=0.556). For tracheal continuous anastomosis, there was a significant difference between the two groups in terms of the learning curve for speed (P=0.001), but no significant difference was observed between the two groups in terms of the learning curve for accuracy (P=0.211). CONCLUSIONS: In summary, both HD-2D and GF-3D display systems are efficient for routine and complex endoscopic surgery. With the help of GF-3D, surgeons can acquire new complex endoscopic skills faster than HD-2D and be free from burdensome polarized glasses. More comparative studies in a clinical setting are needed to further explore the feasibility, necessity, and economic aspects of the GF-3D display system.

Presence of intra-tumoral CD61+ megakaryocytes predicts poor prognosis in non-small cell lung cancer.

BACKGROUND: Lung is a reservoir for megakaryocytes (MKs). The relationship between intra-tumoral MKs and non-small cell lung cancer (NSCLC) is unknown. We investigate relationship between high intra-tumoral MKs with the recurrence of NSCLC. METHODS: The tissue sections of 629 patients with resected NSCLC were stained with hematoxylin, anti-CD61, anti-CD34 and stromal cell-derived factor-1 (SDF-1). CD61+ giant cells localized in CD34+ capillaries were identified as MKs. The impact of MKs and preoperative platelet count on disease-free survival (DFS) was investigated. RESULTS: Overall, 18.9% of patients were positive for the presence of MKs. In univariate analysis, the median DFS of the MK+ group was shorter than the median DFS of the MK- group (69.1 vs. 80.5 months; P=0.021). Multivariate analysis indicated that MKs in tumor tissue was an unfavorable prognostic factor for DFS (HR 1.351, P=0.065), the impact of which was more significant in non-squamous cell carcinoma (NSCC) (HR 1.710, P=0.008) and in patients with N0 (HR 1.883, P=0.009). Although systemic platelet count of the MK+ group was significantly higher than the MK- group (270.6×109 vs. 243.6×109/L, P=0.007), the stratified subgroup DFS curves (P=0.003) showed that the effect of MKs on prognosis was independent of the blood platelet count. CONCLUSIONS: Our results demonstrate that CD61+ MKs in tumor tissue predict unfavorable prognosis in NSCLC.

Is the Glasses-Free 3-Dimensional Display System More Effective for Complex Video-Assisted Thoracic Surgery? A Self-Controlled Study Ex Vivo.

Objective. Considering the demerits of a high-definition 2-dimensional (HD-2D) system, with its lack of stereopsis, and a conventional 3-dimensional (C-3D) system, which results in a dimmed image, we have recently developed a glasses-free 3-dimensional (GF-3D) display system for reconstruction surgeries such as video-assisted thoracic surgery (VATS) for tracheal reconstruction. Methods. Thoracic surgeons were invited to complete thoracoscopic continuous suture of a transected porcine trachea using the HD-2D, C-3D, and GF-3D systems on separate mornings in randomized order. The duration, numbers of stitches, and distance between every 2 stitches were recorded for every procedure. The surgeons' spontaneous eye blink rate was recorded for 5 minutes before the procedure and the last 5 minutes of the procedure. Results. Fifteen volunteers successfully completed the tracheal reconstruction procedures in this study. Both C-3D (0.403 ± 0.064 stitch/min, P < .001) and GF-3D (0.427 ± 0.079 stitch/min, P < .001) showed significant advantages in speed compared with HD-2D (0.289 ± 0.065 stitch/min). Both C-3D (2.536 ± 2.223 mm, P < .001) and GF-3D (2.603 ± 2.159 mm, P < .001) showed significant advantages in accuracy compared with HD-2D (3.473 ± 3.403 mm). Both HD-2D (1.240 ± 0.642, P < .001) and GF-3D (1.307 ± 0.894, P < .001) showed significant advantages in eye fatigue compared with C-3D (3.333 ± 1.44). Conclusions. All 3 available display systems are efficient for complex VATS. With the help of stereopsis, surgeons can achieve faster operation using C-3D and GF-3D systems in a thoracoscopic simulated setting. GF-3D may be a more effective display system for VATS reconstruction in terms of speed, accuracy, and eye fatigue during operations.

Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA).

Rational: LDCT screening can identify early-stage lung cancers yet introduces excessive false positives and it remains a great challenge to differentiate malignant tumors from benign solitary pulmonary nodules, which calls for better non-invasive diagnostic tools. Methods: We performed DNA methylation profiling by high throughput DNA bisulfite sequencing in tissue samples (nodule size < 3 cm in diameter) to learn methylation patterns that differentiate cancerous tumors from benign lesions. Then we filtered out methylation patterns exhibiting high background in circulating tumor DNA (ctDNA) and built an assay for plasma sample classification. Results: We first performed methylation profiling of 230 tissue samples to learn cancer-specific methylation patterns which achieved a sensitivity of 92.7% (88.3% - 97.1%) and a specificity of 92.8% (89.3% - 96.3%). These tissue-derived DNA methylation markers were further filtered using a training set of 66 plasma samples and 9 markers were selected to build a diagnostic prediction model. From an independent validation set of additional 66 plasma samples, this model obtained a sensitivity of 79.5% (63.5% - 90.7%) and a specificity of 85.2% (66.3% - 95.8%) for differentiating patients with malignant tumor (n = 39) from patients with benign lesions (n = 27). Additionally, when tested on gender and age matched asymptomatic normal individuals (n = 118), our model achieved a specificity of 93.2% (89.0% - 98.3%). Specifically, our assay is highly sensitive towards early-stage lung cancer, with a sensitivity of 75.0% (55.0%-90.0%) in 20 stage Ia lung cancer patients and 85.7% (57.1%-100.0%) in 7 stage Ib lung cancer patients. Conclusions: We have developed a novel sensitive blood based non-invasive diagnostic assay for detecting early stage lung cancer as well as differentiating lung cancers from benign pulmonary nodules.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

BACKGROUND: Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. METHODS: A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). RESULTS: Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). CONCLUSIONS: We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

The Optimal Treatment for Stage IIIA-N2 Non-Small Cell Lung Cancer: A Network Meta-Analysis.

BACKGROUND: The optimal treatment for stage IIIA-N2 non-small cell lung cancer (NSCLC) is controversial. We aimed to address this important issue through a Bayesian network meta-analysis. METHODS: We performed a search of electronic databases for randomized controlled trials comparing the following treatments: surgery, radiotherapy, chemotherapy, and their multiple combinations before March 25, 2018. Pooled data on overall survival and treatment-related deaths were analyzed within the Bayesian framework. RESULTS: Eighteen eligible trials reporting 13 treatments were included. In terms of overall survival, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy, which tended to be consistent (hazard ratio [HR] 1.14, 95% credible interval [CrI] 0.21 to 5.93), ranked superior to other treatments. Notably, neoadjuvant chemotherapy followed by surgery and adjuvant radiotherapy was significantly more effective in prolonging survival than surgery alone (HR 0.38, 95% CrI 0.18 to 0.81), surgery plus adjuvant radiotherapy (HR 0.51, 95% CrI 0.29 to 0.92) and potentially surgery plus adjuvant chemotherapy (HR 0.49, 95% CrI 0.23 to 1.05). Overall, with 29% as the highest possibility of causing the fewest treatment-related deaths, neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy was the safest treatment option. CONCLUSIONS: Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy or radiotherapy has the greatest possibility to be the optimal treatment with the best overall survival and fewest treatment-related deaths for stage IIIA-N2 NSCLC.

Three-Dimensional Versus Two-Dimensional Video-Assisted Endoscopic Surgery: A Meta-analysis of Clinical Data.

BACKGROUND: There have been no studies to systematically evaluate the two display (3D vs. 2D) systems regarding both laparoscopic and thoracoscopic surgeries in clinical settings; thus, we conducted one to evaluate the safety and efficacy of different visualization systems (two-dimensional and three-dimensional) during endoscopic surgery (laparoscopy or thoracoscopy) in clinical settings. METHODS: A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (laparoscopy vs. thoracoscopy, prospective vs. retrospective study, malignant vs. benign diseases) were examined. Meta-regression was conducted to explore the source of heterogeneity. RESULTS: Twenty-three articles were considered in this analysis, of which 7 were thoracoscopic and 16 were laparoscopic surgeries. A total of 2930 patients were recorded, of which 1367 underwent 3D video-assisted surgery and 1563 underwent 2D display. Overall, significantly shorter operating time (SMD -0.69; p = <0.001), less blood loss (SMD -0.26; p = 0.028) and shorter hospital stays (SMD -0.16; p = 0.016) were found in the 3D display group. Meanwhile, the perioperative morbidity (OR 0.92; p = 0.487), retrieved lymph nodes (SMD 0.09; p = 0.081), drainage duration (SMD -0.15; p = 0.105) and drainage volume (SMD 0.00; p = 0.994) were similar between the two groups. Comparison of the overall outcomes in each subset showed consistency in all groups. CONCLUSIONS: This up-to-date meta-analysis reveals that the 3D display system is superior to the 2D system in clinical settings with significantly shorter operating time, less blood loss and shorter hospital stay. These findings suggest that, in laparoscopic or thoracoscopic surgeries, 3D endoscopic system is preferable when condition permits. Future efforts should be made on decreasing the side effects of 3D display and increasing its cost-effectiveness.

Comprehensive targeted super-deep next generation sequencing enhances differential diagnosis of solitary pulmonary nodules.

BACKGROUND: A non-invasive method to predict the malignancy of surgery-candidate solitary pulmonary nodules (SPN) is urgently needed. METHODS: Super-depth next generation sequencing (NGS) of 35 paired tissues and plasma DNA was performed as an attempt to develop an early diagnosis approach. RESULTS: Only ~6% of malignant nodule patients had driver mutations in the circulating tumour DNA (ctDNA) with >10,000-fold sequencing depth, and the concordance of mutation between tDNA and ctDNA was 3.9%. The first innovative whole mutation scored model in this study predicted 33.3% of malignant SPN with 100% specificity. CONCLUSIONS: These results showed that lung cancer gene-targeted deep capture sequencing is not efficient enough to achieve ideal sensitivity by simply increasing the sequencing depth of ctDNA from early candidates. The sequencing could not be evaluated hotspot mutations in the early tumour stage. Nevertheless, a larger cohort is required to optimize this model, and more techniques may be incorporated to benefit the SPN high-risk population.

Liquid biopsy for early stage lung cancer.

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.