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Lung cancer is one of the deadliest cancers, in which non-small cell lung cancer (NSCLC) accounting for 85% and has a low survival rate of 5 years. Dysregulation of microRNAs (miRNAs) can participate in tumor regulation and many major diseases. In this study, we found that miR-199a-3p/5p were down-expressed in NSCLC tissue samples, cell lines, and the patient sample database. MiR-199a-3p/5p overexpression could significantly suppress cell proliferation, migration ability and promote apoptosis. Through software prediction, ras homolog enriched in brain (Rheb) was identified as a common target of miR-199a-3p and miR-199a-5p, which participated in regulating mTOR signaling pathway. The same effect of inhibiting NSCLC appeared after down-regulating the expression of Rheb. Furthermore, our findings revealed that miR-199a can significantly inhibit tumor growth and metastasis

OBJECTIVES Oesophagectomy was always recommended after noncurative endoscopic resection (ER). And the optimal time interval from ER to oesophagectomy remains unclear. This study was to explore the effect of interval on pathologic stage and prognosis. METHODS We included 155 patients who underwent ER for cT1N0M0 oesophageal cancer and then received subsequent oesophagectomy from 2009 to 2019. Overall survival and disease-free survival (DFS) were analysed to find an optimal cut-off of interval from ER to oesophagectomy. In addition, pathologic stage after ER was compared to that of oesophagectomy. Logistic regression model was built to identify risk factors for pathological upstage. RESULTS The greatest difference of DFS was found in the groups who underwent oesophagectomy before and after 30 days (P = 0.016). Among total 155 patients, 106 (68.39%) received oesophagectomy within 30 days, while 49 (31.61%) had interval over 30 days. Comparing the pathologic stage between ER and oesophagectomy, 26 patients had upstage and thus had worse DFS (hazard ratio = 3.780, P = 0.042). T1b invasion, lymphovascular invasion and interval >30-day group had a higher upstage rate (P = 0.014, P CONCLUSIONS It was the first study exploring the relationship between time interval and prognosis in oesophageal cancer. The longer interval between noncurative ER and additional oesophagectomy was associated with a worse DFS, so oesophagectomy was recommended performed within 1 month after ER. Older age, T1b stage, lymphovascular invasion and interval >30 days were significantly associated with pathologic upstage, which is related to the worse outcome too.

Background Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. Methods From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. Results ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. Conclusions For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

In the eighth edition TNM staging, the T3N0M0 category represents a heterogeneous group of non-small cell lung cancers (NSCLC). This study aims to compare the oncologic outcomes associated with individual T3 features. We performed a single-institution, retrospective analysis of 280 consecutive patients with pT3N0M0 NSCLC. Multivariate regression models were used to estimate associations of clinical factors with oncologic outcomes. The patients were grouped according to their T3 features into 4 prognostic groups: chest wall infiltration (CWI-PG), largest diameter5 cm and ≤7 cm (Size-PG), presence of a satellite nodule (SN-PG), and all other T3 features. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and Cox proportional hazard analyses. Tumors were most often classified as T3N0M0 by size (156 patients, 55.7%), and the highest rate of incomplete resection occurred in patients with CWI (n = 7, 25.9%). In multivariate analysis, CWI (hazard ratio [HR] 2.45, 95% confidence interval [CI] 1.36, 4.44), incomplete resection (HR 3.01, 95% CI 1.29, 7.05), and age65 (HR 1.6; 95% CI 1.08, 2.38) were independently associated with worse OS, and female sex was associated with better OS (HR 0.6, 95% CI 0.42, 0.87). The CWI-PG had poorer OS when compared with each of the other prognostic groups (P0.05), and the Size-PG had inferior OS when compared with the SN-PG (P = 0.039). This single-center study demonstrated significant differences in OS and PFS between patients with different T3 classifying features and suggest that further subdivision of the T3 category should be considered.

This study aimed to propose a revised ypN (r-ypN) classification based on lymph node ratio (LNR) and to examine its prognostic value in postneoadjuvant esophageal cancer.A new postneoadjuvant pathologic (ypTNM) staging classification has been introduced for esophageal cancer. However, the ypN classification currently defined by the number of positive lymph nodes is influenced by the extent of lymphadenectomy.Data on 7195 esophageal cancer patients receiving neoadjuvant chemoradiation were extracted from the National Cancer Database (NCDB). Four r-ypN stages were defined by 3 LNR thresholds (0%, 10%, and 20% using X-tile software). A revised ypTNM (r-ypTNM) classification was developed by solely changing N categories. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses. Akaike information criterion (AIC) and Harrell's concordance index (C-index) were used to compare the predictive performance of the current and the revised classification. External validation was performed using an independent cohort from the NEOCRTEC5010 clinical trial.Both ypN (P0.001) and r-ypN (P0.001) were independent prognostic factors of overall survival (OS) for esophageal cancer patients. Kaplan-Meier curves demonstrated a better discrimination with r-ypN than ypN categories. Within each ypN category (except ypN3), OS was significantly different comparing r-ypN strata; however, there were no differences between ypN strata within each r-ypN category (except r-ypN3). r-ypN (AIC: 60752 vs 60782; C-index: 0.591 vs 0.587) and r-ypTNM (AIC: 60623 vs 60628; C-index: 0.613 vs 0.610) showed better predictive performance than the current staging system, with a lower AIC (better calibration) and higher C-index (improved discrimination). This advantage was also confirmed by external validation using the NEOCRTEC5010 cohort.LNR showed better performance than ypN in predicting OS of esophageal cancer patients after neoadjuvant chemoradiation and may be an improvement on the current staging system.

Background Air leak is the most common complication after lung resection and leads to increased length of hospital (LOH) stay or patient discharge with a chest tube. Management by autologous blood patch pleurodesis (ABPP) is controversial because few studies exist, and the technique has yet to be standardized. Methods We retrospectively reviewed patients undergoing ABPP for prolonged air leak (PAL) following lobectomy in three centers, between January 2014 and December 2019. They were divided into two groups: Group A, 120 mL of blood infused; Group B, 60 mL. Propensity score-matched (PSM) analysis was performed, and 23 patients were included in each group. Numbers and success rates of blood patch, time to cessation of air leak, time to chest tube removal, reoperation, LOH, and complications were examined. Univariate and multivariate analysis of variables associated with an increased risk of air leak was performed. Results After the PSM, 120 mL of blood is statistically significant in reducing the number of days before chest tube removal after ABPP (2.78 vs. 4.35), LOH after ABPP (3.78 vs. 10.00), and LOH (8.78 vs. 15.17). Complications (0 vs. 4) and hours until air leak cessation (6.83 vs. 3.91, range 1–13) after ABPP were also statistically different (p Conclusion In our experience, 120 mL is the optimal amount of blood and the procedure can be repeated every 24 hours with the chest tube clamped.

Background Currently, there are no randomized trials on the effect of antiangiogenic therapy in patients with esophageal squamous cell carcinoma (ESCC). The following study investigated the efficacy and safety of anlotinib in patients with advanced ESCC who were previously treated with chemotherapy. Methods This randomized, placebo‐controlled, double‐blind phase 2 trial (NCT02649361) was conducted in 13 Chinese hospitals. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC who were previously treated with chemotherapy, and were randomly assigned (2:1) to receive oral anlotinib 12 mg or placebo on days 1–14 (repeated every 21 days). The primary endpoint was progression‐free survival (PFS). Results One hundred and sixty‐five patients were randomly assigned to the anlotinib (n = 110) or the placebo (n = 55) arm. Median PFS was 3.02 months (95% CI 2.63–3.65) in the anlotinib group and 1.41 months (95% CI 1.38–1.41) in the placebo group (hazard ratio 0.46 [95% CI 0.32–0.66]; p, Anti‐angiogenic multi‐target inhibitor anlotinib significantly improved PFS and DCR compared with placebo in this study. Our findings demonstrated that angiogenesis targeting therapy might be an efficient therapeutic target in advanced or metastatic ESCC.

Thoracoscopic lobectomy has become the preferred approach for surgical management of early stage lung cancer, but the potential higher operative costs limit its widespread use. Theoretically, higher direct costs may be significantly counterbalanced by lower indirect costs, resulting in lower overall costs for thoracoscopic than for open lobectomy. To support this hypothesis, we reviewed the literature until May 2020, analyzing all papers comparing the cost of thoracoscopic versus open lobectomy.A total of 20 studies provided the most applicable evidence to evaluate this issue. In all the studies apart from one, thoracoscopic lobectomy was associated with higher operative costs due to the increased use of disposable instruments, and prolonged operative time. By contrast, in 17 studies the increased operative costs were significantly offset by indirect costs which were lower in thoracoscopic than in open lobectomy due to fewer postoperative complications, faster recovery, and lower readmission rates. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar costs in seven, and higher in three, despite the lower hospitalization costs. The low bed fees and high prices of disposable instruments in these three studies may explain the discordance. The careful use of disposable instruments, and the minimizing hospitalization costs can reduce the total costs of thoracoscopic lobectomy to levels similar or to below those of open lobectomy. The worry that video‐assisted thoracoscopic surgery lobectomy (VATSL) might be associated with an increased overal cost is thus not warranted, and should not be used as an excuse against the use of VATS in surgery for early stage lung cancers., Is video‐assisted thoracoscopic lobectomy associated with higher overall costs compared with open surgery? A review of the literature until May 2020 was performed, and 20 studies provided the most applicable evidence to evaluate this issue.Thoracoscopic lobectomy was associated with higher operative costs than open lobectomy, but lower indirect costs. It translated into lower overall costs for thoracoscopic than for open lobectomy in 10 studies, similar in seven, and higher in three studies.The worry that thoracoscopic lobectomy might be associated with increased total cost is thus not warranted, and should not be used as an excuse against the use of thoracoscopy in surgery for early stage lung cancers.

BACKGROUND: We aim to establish neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) related nomograms based on the clinical data and peripheral blood markers to predict the survivals of patients with limited-stage small-cell lung cancer (LS-SCLC). METHODS: A total of 299 LS-SCLC patients after surgery were enrolled in this study. Univariate and multivariate analyses were conducted to select independent prognostic factors to develop the nomograms and then subjected to bootstrap internal validation. The optimal cutoff value of NLR and PLR before surgery was calculated by X-tile (version 3.6.1) and the overall survival (OS) was analyzed by Kaplan-Meier method and compared by log-rank test. RESULTS: According to the X-tile calculation, the NLR value and PLR cutoff values are 2.6 and 156.7, respectively. The prognosis of patients with elevated NLR or PLR value was significantly worse than patients with lower NLR (HR =1.798, 95% CI: 1.284–2.518, P=0.001) or PLR (HR =1.781, 95% CI: 1.318–2.407, P

Non-small cell lung cancer (NSCLC) is the most common form of cancer, resulting in cancer-related deaths worldwide. Exosomes, a subclass of extracellular vesicles, are produced and secreted from various types of cells, including cancer cells. Cancer-derived exosomes can deliver nucleic acids, proteins, and lipids to provide a favorable microenvironment that supports tumor growth through enhancing cell proliferation and metastasis. Our results showed that miR-224-5p was upregulated in NSCLC patient tissues and cell lines, with a tumor-promoting phenotype. Meanwhile, exosome-derived miR-224-5p induced cell proliferation and metastasis in NSCLC and human lung cells. Moreover, we characterized the androgen receptor (AR) as a direct target of miR-224-5p. Tumor xenograft assay experiments revealed that overexpression of miR-224-5p drove NSCLC tumor growth via the suppression of AR and the mediation of epithelial-mesenchymal transition (EMT). Collectively, our results suggest that miR-224-5p-enriched exosomes promote tumorigenesis by directly targeting AR in NSCLC, which may provide novel potential therapeutic and preventive targets for NSCLC., Graphical Abstract, Exosomes and microRNAs play important roles in tumorigenesis. In non-small lung cancer, the cancer-derived exosome miR-224-5p increased significantly. With exosomes transporting, miR-224-5p promoted the proliferation and metastasis ability of their receptor cells via targeting androgenic receptor. Consequently, exosomal miR-224-5p may have a promising prospect in lung cancer therapy.

Background Prognosis of patients with stage IIIA-N2 lung adenocarcinoma is still not optimistic. The aim of this study was to evaluate safety, feasibility, and outcomes of surgery after induction epidermal growth factor receptor–tyrosine kinase inhibitor therapy in a clinical trial setting. Methods Fourteen patients with IIIA-N2 lung adenocarcinoma and epidermal growth factor receptor mutation received erlotinib induction followed by surgery in a phase II clinical trial. Perioperative outcomes and survival results were compared with a control group of 15 patients receiving neoadjuvant chemotherapy during the same time period. Results Thirteen patients showed partial response to induction, whereas 16 patients remained stable. Serum carcinoembryonic antigen level in the erlotinib group was significantly higher than in the chemotherapy group before treatment but was reduced to similar levels after induction. Operation time, blood loss, resection extents, complete resection rates, postoperative drainage, complication rates, and length of hospital stay were all comparable between the 2 groups. Thoracoscopic resection was accomplished in 78.6% of patients in the erlotinib group and 80.0% of patients in the chemotherapy group (P = .924) but was higher in patients who responded to induction than those who did not (92.3% vs 68.8%, P = .119). A resection extent greater than lobectomy and incomplete resections were only seen in stable disease after induction. No significant difference was detected in 1-year and 3-year overall or disease-free survivals between the 2 groups. Conclusions Pulmonary resection is safe and feasible after induction treatment with erlotinib for stage IIIA-N2 lung adenocarcinomas. Better surgical and oncologic outcomes may be expected in patients who respond to effective induction therapies.

OBJECTIVES This study reports the results of an international expert consensus process evaluating the assessment of intraoperative air leaks (IAL) and treatment of postoperative prolonged air leaks (PAL) utilizing a Delphi process, with the aim of helping standardization and improving practice. METHODS A panel of 45 questions was developed and submitted to an international working group of experts in minimally invasive lung cancer surgery. Modified Delphi methodology was used to review responses, including 3 rounds of voting. The consensus was defined a priori as >50% agreement among the experts. Clinical practice standards were graded as recommended or highly recommended if 50–74% or >75% of the experts reached an agreement, respectively. RESULTS A total of 32 experts from 18 countries completed the questionnaires in all 3 rounds. Respondents agreed that PAL are defined as >5 days and that current risk models are rarely used. The consensus was reached in 33/45 issues (73.3%). IAL were classified as mild (400 ml/min; 74%). If mild IAL are detected, 68% do not treat; if moderate, consensus was not; if severe, 90% favoured treatment. CONCLUSIONS This expert consensus working group reached an agreement on the majority of issues regarding the detection and management of IAL and PAL. In the absence of prospective, randomized evidence supporting most of these clinical decisions, this document may serve as a guideline to reduce practice variation.

Comorbidity of lung cancer and chronic obstructive pulmonary disease (COPD) is very common. Surgical operation is the initial treatment of lung cancer. But surgery operation will aggravate the symptoms of COPD, such as shortness of breath, chest tightness. On the other side, the COPD also increase the perioperative complications. Besides, the COPD may also influence the anti-cancer treatment and long-term survival of lung cancer patients. At present, there are guidelines for pulmonary rehabilitation (PR) of COPD or lung cancer respectively, but there is no reference expert consensus on the PR of patients with lung cancer who are comorbidity of COPD. Primary care has to satisfy the patient's complex needs holistically, and single-disease guidelines are unsuitable. In view of this, we organized experts from respiratory department, thoracic surgery department, oncology department, nursing department, etc., to write the expert consensus. We discussed the contents of the expert consensus through literature review, expert correspondence, expert meeting and discussion. This expert consensus contain five parts: introduction, respiratory assessment, timing of PR, PR strategies, perioperative PR management strategies in lung cancer patients with COPD. This expert consensus focuses on patients with COPD comorbid lung cancer and undergoing surgery operation, highlighting the concept of whole process management. For clinical medical staff, this expert consensus will promote the practice of PR in and out the hospital for this specific patient; for patients, this expert consensus is helpful to better understand PR and improve the enthusiasm of participating in PR in the whole process.

Background Phrenic nerve injury (PNI) during lung cancer surgery, without apparent nerve section or damage, is still not well-studied. The aim of our study is to find an easy and objective way to evaluate a significant diaphragm elevation (SDE) suggestive of inadvertent PNI and its incidence and impact on lung cancer patients undergone video-assisted thoracoscopic surgery (VATS) lobectomy. Methods Extent of diaphragm elevation was first examined on chest X-ray in a cohort of patients with invasive thymoma in whom phrenic nerve was intentionally transected. The result was then used as the criterion to diagnose a SDE suggestive of PNI in another cohort of VATS lobectomy patients. Fluoroscopy test was used to validate the results. Spirometry test was repeated to evaluate pulmonary function loss after surgery. Results Diaphragm elevation was 24.24%±6.2% in 22 invasive thymoma-patients, with 30% elevation adopted as the criterion to diagnose SDE suggestive of PNI. In 753 VATS lobectomy patients, 56 (7.4%) were diagnosed of SDE. On Fluoroscopy test, diaphragm movement was significantly less in patients with diaphragm elevation >30% than those without (5.0 vs. 11.0 mm, P=0.003), together with a significantly smaller diaphragm movement ratio on the operation (OP) side than on the contralateral side (17% vs. 42%, P=0.018). Although no difference in postoperative complications was found, reduction in FEV1, FVC, and DLCO was significantly greater in patients with a SDE than those without (P=0.009). Conclusions Patients with more than 30% diaphragm elevation after VATS lobectomy is highly likely to have PNI and should undergo fluoroscopic validation. Inadvertent PNI during VATS lobectomy is an underestimated phenomenon and is associated with significantly greater loss of pulmonary function.

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad‐Cre, KrasG12D, and P53f/f). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual‐specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor‐promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target., ZNF251 promotes lung cancer by activating ERK signaling.

Objective: Our aim was to validate the prognostic relevance in NSCLC of potential residual tumor (R) descriptors, including the proposed International Association for the Study of Lung Cancer definition for uncertain resection, referred to as R(un). Methods: A total of 14,712 patients undergoing resection with full R status and survival were analyzed. The following were also evaluated: whether fewer than three N2 stations were explored, lobe-specific nodal dissection, extracapsular extension, highest lymph node station status, carcinoma in situ at the bronchial resection margin, and pleural lavage cytologic examination result. Revised categories of R0, R(un), R1, and R2 were tested for survival impact. Results: In all, 14,293 cases were R0, 263 were R1, and 156 were R2 (median survivals not reached, 33 months, and 29 months, respectively). R status correlated with T and N categories. A total of 9290 cases (63%) had three or more N2 stations explored and 6641 cases (45%) had lobespecific nodal dissection, correlated with increasing pN2. Extracapsular extension was present in 62 of 364 cases with available data (17%). The highest station was positive in 942 cases (6.4%). The pleural lavage cytologic examination result was positive in 59 of 1705 cases (3.5%): 13 had carcinoma in situ at the bronchial resection margin. After reassignment because of inadequate nodal staging in 56% of cases, 6070 cases were R0, 8185 were R(un), 301 were R1, and 156 were R2. In node-positive cases, the median survival times were 70, 50, and 30 months for RO, R(un) (p < 0.0001), and R1 (p < 0.001), respectively, with no significant difference between RO and R(un) in pN0 cases. Conclusions: R descriptors have prognostic relevance, with R(un) survival stratifying between R0 and R1. Therefore, a detailed evaluation of R factor is of particular importance in the design and analyses of clinical trials of adjuvant therapies. (C) 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

BackgroundThere are no optimal regimens for advanced thymic epithelial tumors (TETs) when front-line chemotherapy fails. In this study, we aimed to assess the activity of Bevacizumab in combination with routine chemotherapeutic regimen.MethodsPatients with advanced TETs who had failed after previous chemotherapy were enrolled in this study. Paclitaxel (160mg/m2) or cisplatin (70mg/m2) and carboplatin (area under the curve, 6) plus Bevacizumab (7.5mg/kg) were intravenously injected on day 1.The treatment was repeated every 3 weeks until the disease progressed or intolerable toxicities occurred.ResultsBetween March 2018 and August 2020, a total of 49 patients (21 thymoma and 28 thymic carcinoma) received the new treatment. There were 28 men and 21 women with a median age of 50 years (range: 21-73 years).The median number of cycles was 3 (range: 1-6) per patient. The objective response rate (ORR) for all patients was 43% (21/49). The ORRs for thymoma and thymic carcinoma were 24% and 57%, respectively. The median progression free survival for thymoma and thymic carcinoma were 6 and 8 months, respectively. Hematological toxicities were the main side effects.ConclusionsPaclitaxel and platinum plus Bevacizumab showed promising effect in refractory or relapsed advanced TETs without severe toxicity. Even applied as salvage therapy, this regimen resulted in better ORR than the front-line chemotherapy.

Objective To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT). Summary background data There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT. Methods The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified. Results A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27). Conclusions Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.

The surgical treatment of advanced non-small-cell-lung-cancer (NSCLC) invading mediastinal organs and great vessels is still controversial. The aim of this multicentre study is to analyse oncological outcomes, surgical outcomes and prognostic factors of patients with NSCLC involving heart and great vessels.362 patients treated surgically for locally advanced T4-NCSLC between 1990 and 2020 were retrospectively reviewed. Patients were divided into five subgroups: pulmonary artery(n = 129), left atrium(n = 82), superior vena cava(n = 80), aorta(n = 43), and multiple vascular structures(n = 28). Resection was complete in 327(90%) patients.Overall 90-day mortality was 8.8%, influenced by poly-transfusions, pneumonectomy, bronchopleural fistula and previous cardiovascular disease (4.5HR.p = 0.03, 3.7HR p = 0.01, 14.0HR.p 0.001 and 3.0HR p 0.01). One-, 3- and 5-year survival rates were 75%, 43%, 33%, respectively and there were significant differences among the five groups(p 0.001). Survival was significantly affected by induction radiotherapy, nodal status, pTNM-stage and radicality (3.8HR p = 0.03, 2.6HR p = 0.001, 1.6HR p 0.05 and 1.6HR p 0.05).Surgery provided acceptable results in selected patients with T4-NSCLC with major vascular infiltration in expert centres. Nodal-status and radicality influenced the overall-survival and disease-free survival. Neoadjuvant chemotherapy appears to have a positive effect on long-term results, particularly in N2-patients.

Background Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. Methods All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. Results Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. Conclusions pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

Ba0.7Sr0.3TiO3 ceramic fibers were synthesized via the precursor linear self-assembly nonhydrolytic sol-gel (NHSG) method, taking TiCl4 as the titanium source, anhydrous barium acetate and strontium acetate as the barium source and strontium source, anhydrous ethanol and glycol as the oxygen donor and solvent, respectively. The NHSG method promotes the formation of Ba–O–Ti and Sr–O–Ti through heterogeneous condensation. The bimolecular association structure of the reaction intermediate (chlorotitanium ethoxide) between ethanol and titanium tetrachloride facilitates the self-linear assembly of precursors. It also enables linear colloidal particle formation and excellent spinnability of the sol. The novel Ba0.7Sr0.3TiO3 ceramic fibers would promote the flexibility of electronic products.

BACKGROUND: Thoracoscopic segmentectomy is increasingly used in the surgical treatment of early-stage non-small cell lung cancer. However, it remains unclear whether pulmonary function loss after thoracoscopic lung resection is in direct proportion to the number of resected segments, and thus intentional thoracoscopic segmentectomy has the function-preserving advantage over thoracoscopic lobectomy. METHODS: In this prospective observational study, spirometry tests were performed preoperatively and 6 months postoperatively. The observed functional loss was compared with the expected loss estimated by the segment counting method. Resection extent index was introduced as the number of resected segments to total number of segments in the corresponding lobe. Spirometry changes after thoracoscopic lobectomy and intentional thoracoscopic segmentectomy were compared using propensity score matching. RESULTS: There were 338 thoracoscopic lobectomies and 321 thoracoscopic segmentectomies. Overall, the observed pulmonary function loss after segmentectomy was significantly less than after lobectomy. But the observed functional loss was significantly greater than the expected loss after segmentectomy. And pulmonary function loss per segment resected was almost doubled after segmentectomy comparing to lobectomy. For segmentectomies with a resection extent index less than 0.5, especially single segmentectomies, pulmonary function loss was significantly less than after corresponding lobectomies. Otherwise, no significant differences in spirometry changes between lobectomies and segmentectomies were detected. CONCLUSIONS: Pulmonary function loss after thoracoscopic lung resection cannot be accurately evaluated by the number of resected segments. According to the resection extent index, intentional thoracoscopic segmentectomy may help preserve more pulmonary function than thoracoscopic lobectomy only when less than half of the corresponding lobe are resected.

Aortic invasion from non-small cell lung cancers (NSCLC) is a relative contraindication to surgery for oncological and technical reasons. Only a few studies have been published showing good results. Our aim was to evaluate short and long-term results of surgery for T4 NSCLC with aortic resection.This is a multicenter retrospective study including 47 patients (33 males and 14 females) who received a major lung resection with aortic surgery in our centers between January 2000 and December 2016.Adenocarcinoma was diagnosed in 31 patients (66.0%). Induction therapy was used in 14 patients. Pneumonectomy was performed in 34 patients (72.3%). A subadventitial dissection with or without endovascular stent graft was carried out in 40 patients (85.1%), a cardiopulmonary bypass was used in 3 patients and left heart bypass in 4. Intraoperatively, two patients had bleeding (4.3%) and one ventricular fibrillation (2.1%). Twenty-three patients (48.9%) experienced at least one postoperative complication. A radical resection was achieved in 39 patients (83.0%). Thirty-day and 90-day mortality were 2.1% and 4.3%. One-, 3- and 5-year overall survival were 85.1%, 57.4% and 53.2%. Overall and disease-free survivals were significantly influenced by pathological lymph node status and R status that were independent predictive factors for poorer survival at the multivariate analyses.Aortic resection during surgery for NSCLC is a challenging situation. Nevertheless, oncologic outcomes may be favorable in selected cases justifying a risky procedure that should be performed in experienced hands.

Background Indication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas. Methods We retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections. Results Comparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893). Conclusions Solid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.

The coronary artery calcification score (CACS), a strong predictor of cardiovascular events and mortality, can be assessed by nongated chest computed tomography (CT). The study aimed to determine whether CACS based on nongated CT is predictive of perioperative cardiovascular events during intermediate-risk lung cancer surgery.In this retrospective, single-center study, we used nongated CT images to evaluate CACS in 4491 patients with lung cancer who underwent intermediate-risk surgeries. Perioperative cardiovascular events were defined as in-hospital cardiac death, nonfatal myocardial infarction, heart failure, atrial and ventricular arrhythmia with hemodynamic compromise, and complete heart block. Risk factors of perioperative cardiovascular events were identified by multivariate logistic regression analysis.In total, 110 inpatients (2.5%) experienced perioperative cardiac events. Coronary calcification was observed on nongated CT in 1070 (23.8%) patients. CACS was significantly associated with the incidence of cardiovascular events and longer hospital stays. According to receiver operating characteristic curve analysis, the CACS cutoff value was set to 1. In the multivariate analysis, CACS ≥1 (odds ratio, 1.75; 95% CI, 1.14-2.68; P = .011) or the number of calcified vessels (odds ratio, 1.23; 95% CI, 1.01-1.50; P = .043), age, forced expiratory volume in 1 second/predicted, operation time, and thoracotomy were predictive of cardiovascular complications.CACS is an independent predictor of severe perioperative cardiovascular risk in patients undergoing intermediate-risk lung cancer surgery. CACS may represent a valuable tool for preoperative risk assessment of these patients.

Precise point positioning (PPP) is receiving increasing interest due to its cost-effectiveness, global coverage and high accuracy. However, its application in the urban environment is still full of challenges due to the satellite tracking sky-view. Thus, we presented a comprehensive positioning model by fusing the multi-GNSS (global navigation satellite system) combination, GNSS/INS (inertial navigation system) tightly coupled integration as well as the ionospheric and tropospheric augmentation in the undifferenced and uncombined PPP. The performance of this model in dual-frequency and single-frequency positioning was assessed with two experiments that denoted as T019 and T023, respectively, and both the experiments were carried out in a real urban environment. Particularly, the experiment T023 was carried out in the Second Ring Road of Wuhan city, which can be regarded as a typical downtown environment. Concerning the regional atmospheric augmentation, observations from 5 reference stations with an inter-station distance of about 40 km were also collected during the experimental time. The comparison between reference stations suggested that the regional tropospheric model had a precision of better than 0.6 cm in terms of zenith tropospheric delay, while the regional ionospheric model had a precision of around 0.5 total electron content unit in terms of Vertical Total Electron Content. It can be concluded that the GPS-only PPP can be improved significantly for urban vehicle navigation with these techniques, i.e., the multi-GNSS, INS tightly coupled integration and the atmospheric augmentation, through the positioning analysis, while INS tightly coupled integration makes the most contributions under the downtown environment, and the improvement of the regional atmospheric augmentation in single-frequency PPP is more significant since that single frequency is more sensitive to the ionospheric delay. In addition, it is proved that the regional atmospheric augmentation accelerates positioning convergence. The 3D positioning root-mean-square (RMS) with the comprehensive positioning model for dual frequency are 0.22 m and 0.77 m for T019 and T023, respectively. Concerning single-frequency PPP, the 3D RMS is 0.45 m and 1.17 m for T019 and T023, respectively. Moreover, taking the lane-level navigation under the downtown environment of T023 into consideration, we further presented the cumulative frequency of the horizontal positioning error less than 1 m, i.e., $$P\left( {\sqrt {{\text{d}}N^{2} + {\text{d}}E^{2} } < 1\;{\text{m}}} \right)$$ , and the best solution can be found with PPP by fusing all the techniques, in which $$P\left( {\sqrt {{\text{d}}N^{2} + {\text{d}}E^{2} } < 1\;{\text{m}}} \right)$$ is 99.0% and 93.2% for dual frequency and single frequency, respectively.

Background Histology is a traditional way to classify subtypes of thymoma, because of low cost and convenience. Yet, due to the diverse morphology of thymoma, this method increases the complexity of histopathologic classification, and requires experienced experts to perform correct diagnosis. Therefore, in this study, we developed an alternative method by identifying protein biomarkers in order to assist clinical practitioners to make right classification of thymoma subtypes. Methods In total, 204 differentially expressed proteins in three subtypes of thymoma, AB, B2, and B3, were identified using mass spectrometry. Pathway analysis showed that the differentially expressed proteins in the three subtypes were involved in activation-related, signaling transduction-related and complement system-related pathways. To predict the subtypes of thymoma using the identified protein signatures, a support vector machine algorithm was used. Leave-one-out cross validation methods and receiver operating characteristic analysis were used to evaluate the predictive performance. Results The mean accuracy rates were > 80% and areas under the curve were ≧0.93 across these three subtypes. Especially, subtype B3 had the highest accuracy rate (96%) and subtype AB had the greatest area under the curve (0.99). One of the differentially expressed proteins COL17A2 was further validated using immunohistochemistry. Conclusions In summary, we identified specific protein signatures for accurately classifying subtypes of thymoma, which could facilitate accurate diagnosis of thymoma patients.

Esophageal leiomyoma is the most common benign tumor of the esophagus, which usually arises from the muscularis propria or muscularis mucosae. Incidence of benign esophageal neoplasms was reported to be in the range of 0.005% to 7.9% in autopsy cases, while leiomyomas account for 70–80% of them (1). Options for management include surveillance for small-sized tumors and surgical or endoscopic resection for large or symptomatic ones. Leiomyoma is commonly located in the lower two-thirds of the esophagus. In open surgery, right-sided surgical approach is preferred for lesions in the middle and upper esophagus, and left-sided approach for those in the distal lower esophagus. Video-assisted thoracoscopic surgery (VATS) for esophageal leiomyoma was first described by Everitt in 1992 (2,3). As scattered researches reported, enucleation of benign esophageal tumors can be performed effectively and safely with low morbidity (4-6), mostly through right-sided approach. The major complication after the enucleation of esophageal leiomyomas is mucosal injury, which may lead to esophageal leakage or perforation. We hereby report a novel approach using combined thoracoscopy and endoscopy to facilitate tumor removal and prevent mucosal injury.

Background: The purpose of this study is to develop a predictive model to accurately predict the malignancy of solid solitary pulmonary nodule (SPN) by data mining methods. Methods: A training cohort of 388 consecutive patients with solid SPNs was used to develop a predictive model to evaluate the malignancy of solid SPNs. By using SPSS Modeler, we utilized logistic regression (LR), artificial neural network (ANN), k-nearest neighbor (KNN), random forest (RF), and support vector machines (SVM) classifiers to build predictive models. Another cohort of 200 consecutive patients with solid SPNs was used to verify the accuracy of the predictive model. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: There was no significant difference in patients’ characteristics between the training cohort and the validation cohort. The AUCs of LR, ANN, KNN, RF, and SVM models for the validation cohort were 0.874±0.0280 (P=0.605), 0.833±0.0351 (P=0.104), 0.792±0.0418 (P=0.014), 0.775±0.0400 (P=0.013), and 0.890±0.0323 (reference), respectively. The SVM algorithm had the highest AUC, and the best sensitivity (90.3%), specificity (80.4%), positive predictive value (93.9%), negative predictive value (71.2%) and accuracy (88.0%) for the validation cohort among the five models. Conclusions: Data mining by SVM might be a useful auxiliary algorithm in predicting malignancy of solid SPNs.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been increasingly used in the treatment of lung cancers. But it is still unclear whether mediastinal lymph node dissection (LND) under VATS is safe and feasible. The aim of this study is to figure out whether LND by VATS is safe and feasible. METHODS: Consecutive patients with primary resectable lung cancers referred for lobectomy and LND or sampling by VATS between January 2012 and December 2016 were retrospectively reviewed. Clinicopathological characteristics and perioperative results were collected for statistical analysis. RESULTS: Seven-hundred and seventy-three VATS lobectomy patients were included in this study, 494 received LND and 279 received lymph node sampling (LNS). There were more male patients, higher pathological T and N stage in the LND group than in the LNS group. Multivariate analysis suggested that clinical N stage higher than cN0 category and LND were independent risk factors for finding pN2 diseases in all lung cancers, while higher than cN0 category, solid or micropapillary component, and LND were independently related to finding pN2 stage in adenocarcinomas. Propensity-score matching rendered 279 pairs of patients with no significant difference in age, gender, co-morbidity, tumor location, or T stage. Although the LND group had longer operation time (128 vs. 114 minutes, P

Esophageal cancer (EC) is a highly prevalent malignancy in China. According to the data released by National Cancer Registry Center of China in 2015, the prevalence of EC was 21.17/100,000 in China in 2012, ranking fifth among all malignancies; the mortality rate was 15.58/100,000, ranking fourth. It is expected that there will be 477,900 new EC cases nationwide in 2015, whereas 375,000 people will die from EC (1,2). Worldwide, EC is the 8 th most common malignancy, with 416,000 new cases in 2012 (3). At present, EC treatment is based on multidisciplinary treatment, but surgery remains the most effective therapy in optimizing long-term prognosis in patients without metastatic disease. The ideal surgical approach is a matter of debate.