Prognostic analysis of the plasma fibrinogen combined with neutrophil-to-lymphocyte ratio in patients with non-small cell lung cancer after radical resection.

BACKGROUND: To investigate the correlation between the fibrinogen combined with neutrophil-to-lymphocyte ratio (F-NLR) and the clinicopathologic features of non-small cell lung cancer (NSCLC) patients who underwent radical resection. METHODS: This study reviewed the medical records of 289 patients with NSCLC who underwent radical resection. The patients were stratified into three groups based on F-NLR as follows: patients with low NLR and fibrinogen were group A, patients with high NLR or fibrinogen were group B, and patients with high NLR and fibrinogen were group C. Receiver operating characteristic curve and Youden index were used to determine the cutoff value of the NLR and fibrinogen. Survival curves were described by Kaplan-Meier method and compared by log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors. RESULTS: A value of 3.19 was taken as the optimal cutoff value of NLR in this study. A value of 309 was used as the optimal cutoff value of fibrinogen. Cox multivariate analysis showed that tumor, nodes, metastasis (TNM) stage and F-NLR were independent prognostic factors affecting the survival rate of patients. The first-, third-, and fifth-year survival rates in group A were 99.2%, 96.6%, and 95.0%, respectively. The first-, third-, and fifth-year survival rates in group B were 98.4%, 76.6%, and 63.2%, respectively. The first-, third-, and fifth-year survival rates in group C were 91.3%, 41.1%, and 22.8%, respectively. F-NLR was significantly correlated with overall survival in patients with NSCLC (p < 0.001). CONCLUSIONS: The F-NLR level is markedly related to the prognosis of patients with NSCLC undergoing radical surgery. Therefore, closer attention should be given to patients with NSCLC with a high F-NLR before surgery to provide postoperative adjuvant therapy.

Efficacy and safety of esophagectomy via left thoracic approach versus via right thoracic approach for middle and lower thoracic esophageal cancer: a multicenter randomized clinical trial (NST1501).

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC). Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test. Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs. 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96). Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy. Trial Registration: ClinicalTrials.gov NCT02448979.

Identified lung adenocarcinoma metabolic phenotypes and their association with tumor immune microenvironment.

BACKGROUND: Lung adenocarcinoma (LUAD), a subtype of non-small cell lung cancer (NSCLC), causes high mortality around the world. Previous studies have suggested that the metabolic pattern of tumor is associated with tumor response to immunotherapy and patient's survival outcome. Yet, this relationship in LUAD is still unknown. METHODS: Therefore, in this study, we identified the immune landscape in different tumor subtypes classified by metabolism-related genes expression with a large-scale dataset (tumor samples, n = 2181; normal samples, n = 419). We comprehensively correlated metabolism-related phenotypes with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in LUAD patients. RESULTS: And we confirmed tumors with activated lipid metabolism tend to have higher immunocytes infiltration and better response to checkpoint immunotherapy. This work highlights the connection between the metabolic pattern of tumor and tumor immune infiltration in LUAD. A scoring system based on metabolism-related gene expression is not only able to predict prognosis of patient with LUAD but also applied to pan-cancer. LUAD response to checkpoint immunotherapy can also be predicted by this scoring system. CONCLUSIONS: This work revealed the significant connection between metabolic pattern of tumor and tumor immune infiltration, regulating LUAD patients' response to immunotherapy.

A prospective study examining the impact of uniportal video-assisted thoracic surgery on the short-term quality of life in patients with lung cancer.

BACKGROUND: The aim of this study was to evaluate the effect of uniportal and three-portal VATS in lung cancer patients on the postoperative short-term quality of life (QOL). METHODS: A single-center, prospective, nonrandomized study was performed on patients who underwent uniportal or three-portal video-assisted thoracoscopic surgery (VATS) lobectomy and systemic mediastinal lymph node dissection. QOL was measured before surgery at baseline and at one, two, four, and eight weeks after the operation. The measured data of normal distribution were indicated by the mean ± standard deviation, the independent sample t-test was used among the groups, and the χ2 test was used to compare the counting. Non-normal distribution of the measurement data was carried out using the Mann-Whitney test. RESULTS: Preoperative functional areas, symptom areas and overall health scores were similar in the two groups. The physical, role, emotional and social functions and overall health status of the uniportal group were significantly higher than those of the three-portal group in postoperative time. The score of symptom field was higher in one week after operation, the score of two, four and eight weeks decreased gradually, but it was still above the preoperative level, and the fatigue and pain of the uniportal group were significantly lower than that of the three-portal group. CONCLUSION: The advantages of uniportal VATS include a shorter hospital stay, more rapid recovery and superior cosmetic results compared to three-portal VATS. Additionally, uniportal VATS is superior to three-portal thoracoscopic surgery in terms of the immediate postoperative short-term QOL.

Mechanism research of miR-34a regulates Axl in non-small-cell lung cancer with gefitinib-acquired resistance.

BACKGROUND: To investigate the regulatory mechanism behind miR-34a-altered Axl levels in non-small-cell lung cancer (NSCLC) with gefitinib-acquired resistance. METHODS: The expression of miR-34a, Axl, Gas6 and related downstream signaling proteins in the EGFR mutant NSCLC cell lines were determined by qRT-PCR and Western blot; PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells were established by transfecting the parent cells with a miR-34a overexpressing virus, then the expression of Axl, Gas6 and the downstream channel-related proteins were also compared in PC9-Gef-miR-34a and HCC827-Gef-miR-34a and drug-resistant strains. The survival rate of the cells were measured by CCK8 assay. A luciferase reporter detected whether Axl was the target of miR-34a. Finally, a tumor-bearing nude mouse model was established to verify the relationship between the expression of miR-34a, Axl and Gas6 mRNA in vivo. RESULTS: The expression levels of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream proteins in PC9-Gef and HCC827-Gef cell lines were higher than those in PC9 and HCC827 parental cell lines, while the expression of miR-34a was lower than it was in the parental cell lines (P < 0.05). The expression of Axl mRNA and protein, Gas6 mRNA and protein, and related downstream signaling proteins in PC9-Gef and HCC827-Gef cell lines was higher than the expression in PC9-Gef-miR-34a and HCC827-Gef-miR-34a cells, which overexpressed miR-34a (P < 0.05). CONCLUSION: The miR-34a regulation of Axl plays an important role in NSCLC-acquired gefitinib resistance, and their expression is inversely correlated, which suggests that they can be used as prognostic markers or potential therapeutic targets for NSCLC.

Systematic mediastinal lymph node dissection outcomes and conversion rates of uniportal video-assisted thoracoscopic lobectomy for lung cancer.

BACKGROUND: To evaluate the systematic mediastinal lymph node (LN) dissection outcomes and conversion rates of uniportal video-assisted thoracoscopic surgery (UVATS). METHODS: Patients with non-small-cell lung cancer who underwent video-assisted thoracoscopic surgery (VATS) and systematic mediastinal LN dissection between January 2015 and January 2017 were retrospectively reviewed. We categorized the patients into two groups according to the different surgical approaches. Patients' clinical data were collected and compared. The index of estimated benefit from LN dissection was used to evaluate the therapeutic value of LN dissection for each station. RESULTS: A total of 453 patients underwent VATS, including 197 patients in the UVATS group and 256 patients in the triportal VATS (TVATS) group. There were no significant differences in the 1-, 2- and 3-year survival rates of these two groups (P > 0.05). There were no statistically significant differences in the operative time, numbers and stations of LNs, numbers and stations of N2 LNs, conversion rate or postoperative complications. The UVATS group had less intraoperative blood loss, a shorter duration of hospital stay, less chest tube drainage and a shorter duration of chest tube drainage than the TVATS group (P < 0.05). The conversion rates in the UVATS and TVATS groups were 5.1% and 4.3%, respectively, and the difference was not significant. The same degree of LN sampling was achieved in both groups. CONCLUSION: UVATS permits the same degree of LN sampling as TVATS without a difference in the conversion rate.

Analysis of factors related to chronic cough after lung cancer surgery.

BACKGROUND: In this study, we investigated the relationship between chronic cough and clinicopathological features in postoperative patients with non-small cell lung cancer (NSCLC) and evaluated the effectiveness of acupuncture therapy for the treatment of postoperative chronic cough in patients with NSCLC. METHODS: We retrospectively evaluated 171 patients with NSCLC who received lobectomy at our center between September 2017 and February 2018. The Mandarin Chinese version of the Leicester Cough Questionnaire (LCQ-MC) was used to evaluate the degree of cough in patients. Postoperative cough was assessed by a visual analog scale (VAS). RESULTS: The total LCQ-MC score for the whole group was 19.79 ± 0.53 before surgery and 18.40 ± 0.70 after surgery (p < 0.001). Logistic regression analysis showed that right lung cancer, difficult airway, acute cough and history of COPD were independent predictors of chronic cough. Of the 68 patients diagnosed with chronic cough, 41 received acupuncture therapy (acupuncture therapy group), and 27 received no acupuncture therapy (no therapy group). No significant difference was found between the two groups in terms of their LCQ-MC scores at eight weeks after surgery (p = 0.756). However, the acupuncture therapy group had a significantly higher LCQ-MC score than the no therapy group at 10 weeks after surgery (p = 0.002). CONCLUSIONS: Right lung cancer, difficult airway, acute cough, and history of COPD are independent predictors of chronic cough after surgery. For patients with chronic cough, acupuncture therapy can shorten the recovery time and improve quality of life after surgery.

Correlation of pulmonary venous circulating tumor cells with clinicopathological parameters in patients with early-stage lung adenocarcinoma.

BACKGROUND: Tumor recurrence following the surgical resection of lung cancer (LCa) reduces long-term disease-free survival rates. This study aimed to investigate the association of pulmonary venous blood (PVB) circulating tumor cells (CTCs) with the clinicopathological features of patients with early-stage lung adenocarcinoma. METHODS: A total of 120 cases were enrolled, including 24 healthy controls, 36 patients with lung benign tumors, and 60 early-stage lung adenocarcinoma patients. Cells displaying a profile of human chromosome 8 specific sequence (CEP8)+/4',6-diamidino-2-phenylindole (DAPI)+/leukocyte-specific antibodies (CD45)‒ were regarded as CTCs, and counts of ≥2 CTCs per 3.2 mL of PVB were considered positive. The association of CTC counts with clinical parameters were analyzed. RESULTS: The number of CTCs were significantly higher in early-stage lung adenocarcinoma patients compared to benign or normal control group. Moreover, increased CTCs in lung adenocarcinoma was closely associated with tumor invasion, pathological staging and the epidermal growth factor receptor (EGFR) mutations (P<0.05), whereas no significant difference was observed between CTC counts and age, sex, smoking history, pathological cell morphology or immunohistochemical indicators (P>0.05). Univariate and multivariate Cox's proportional hazards regression confirmed that CTC counts were an independent indicator for the prediction of tumor invasion, pathological staging, and EGFR mutations. CONCLUSIONS: Our data suggest that CTC counts correlate with tumor invasion, pathological staging, and EGFR mutations. CTCs therefore represent promising biomarkers for the surveillance of lung adenocarcinoma progression.

Value of the preoperative neutrophil-to-lymphocyte ratio as a prognostic factor for long-term survival in postoperative esophageal squamous cell carcinoma patients.

BACKGROUND: This study investigated the relationship between the neutrophil-to-lymphocyte ratio (NLR) and clinicopathological features and prognosis in patients with postoperative esophageal squamous cell carcinoma (ESCC). METHODS: The preoperative NLR was evaluated in 419 patients who underwent esophagectomy for ESCC. A receiver operating characteristic (ROC) curve was plotted to verify the accuracy of the NLR for predicting survival. Correlation between the NLR and clinicopathological characteristics was analyzed using the χ2 test. Prognostic influence was calculated by using the Kaplan-Meier method and the difference was assessed by log-rank test. Multivariate Cox regression models were applied to evaluate the independent prognostic value. RESULTS: The cutoff value of the NLR was 2.998, the area under the curve was 0.735, and the sensitivity and specificity were 69.3% and 69.3%, respectively. Tumor length (P = 0.0317), lymph node metastasis (P = 0.0352), pathological tumor node metastasis (pTNM) stage (P = 0.0271), and postoperative radiotherapy (P = 0.0385) were significantly different between the groups. Multivariate analysis showed that pTNM stage (P = 0.0098), lymph node metastasis (P = 0.001), and NLR (P = 0.0022) were independent prognostic factors for survival. Moreover, when patients were stratified by TNM stage, the adverse effects of preoperative NLR on cancer-specific survival were greater in patients with stage II and III ESCC and in patients with lymph node metastasis. CONCLUSIONS: The preoperative NLR is significantly correlated with long-term prognosis in postoperative patients with ESCC, particularly in patients with lymph node metastasis and stage II and III ESCC.

Histone deacetylase inhibitor SAHA-induced epithelial-mesenchymal transition by upregulating Slug in lung cancer cells.

SAHA, a member of histone deacetylase inhibitors (HDACIs), which emerged as a class of novel antitumor drug, has been used in clinical treatment of cancers. However, clinical experience of SAHA in solid tumors has been disappointing. Nevertheless, the underlying mechanism of this deficiency is not clearly understood. In the present study, we found that SAHA could induce epithelial-mesenchymal transitions (EMT) in lung cancer A549 cells, which was associated with increased migration capability and cellular morphology changes. We showed that SAHA decreased epithelial marker E-cadherin's expression and increased the expression of mesenchymal marker vimentin. SAHA upregulated the protein and mRNA expression of transcription factor Slug in a time-dependent manner and promoted its nuclear translocation. We further demonstrated that SAHA upregulated Slug expression by promoting Slug acetylation but not influencing the phosphorylation of GSK-3ß, a main kinase-controlled Slug expression. Finally, silencing of Slug by siRNA reversed EMT marker expressions and cellular morphology change induced by SAHA, suggesting that Slug plays a crucial role in SAHA-mediated EMT in A549 cells. Our research study provided a better understanding of treatment failure of SAHA in patients with solid tumors. Therefore, more attention should be paid to cancer treatment using SAHA and strategies for reversing EMT before using SAHA would be better if the value of SAHA in the treatment of solid tumors, especially lung cancer, is realized.

Minimally Invasive Ivor-Lewis Esophagectomy (MIILE): A Single-Center Experience.

With the development of minimally invasive procedures, minimally invasive Ivor-Lewis esophagectomy (MIILE) has been proposed as a safe and feasible surgical choice for the treatment of esophageal cancer. This retrospective study evaluated MIILE results from a single medical center. A total of 619 patients were selected as candidates for Ivor-Lewis esophagectomy from December 2011 to May 2015, in which 334 patients accepted MIILE and 285 patients accepted open Ivor-Lewis esophagectomy (OILE). General characteristics, surgical data, complication rates, and survival were analyzed. Differences in general characteristics between groups were not significant. Intraoperative blood loss (P < 0.01), postoperative volume of drainage for the first day (P < 0.01), time to drain removal (P ≤ 0.01), wound infection rate (P = 0.04), and length of hospital stay (P < 0.01) were significantly reduced in the MIILE group. There were no statistically significant differences in general morbidity (P = 0.56), the total swept lymph nodes (P = 0.47), mortality (P = 0.34), and survival rate at 3 years (P = 0.63). MIILE is a safe and feasible method for the treatment of esophageal cancer, in which good outcomes were reported and some advantages were found over the open procedure.

Prognostic significance of the number of lymph nodes examined in node-negative Siewert type II esophagogastric junction adenocarcinoma.

BACKGROUND: Involvement status of lymph node (LN) is one of the most important prognostic factors for esophagogastric junction (EGJ) adenocarcinoma. However, the prognostic value of the number of examined LNs remains unclear in node-negative (pN0) Siewert type II EGJ adenocarcinoma. METHODS: A cohort of 262 patients who underwent curative surgery for pN0 Siewert type II EGJ adenocarcinoma from January 2000 to August 2013 were retrospectively analyzed from high-volume center database. All enrolled patients were categorized into 3 groups according to the number of examined LNs (≤14, 15 to 21, ≥22). Kaplan-Meier curves were used for comparing the differences of cancer-specific survival among groups; Correlation between survival and the number of examined LNs were analyzed by using stratified, uni- and multivariate analyses. RESULTS: The hazard ratio for cancer-specific mortality decreased sequentially with increasing number of LNs examined. The 5-year cancer-specific survival rates were 45.1%, 58.4% and 65.7% for patients with ≤14 LNs, 15 to 21 and ≥ 22 LNs removed, respectively. The number of removed LNs was significantly correlated with survival in stratified analyses according to T stage. In multivariate model controlling for gender, age, surgical approach, tumor grade, and postoperative chemotherapy, the number of removed LNs and T stage were confirmed to be independent prognostic factors and significantly correlated with disease-specific survival. CONCLUSION: The number of examined LNs is an independent prognostic factor of survival for patients with pN0 Siewert type II EGJ adenocarcinoma. Adequate dissection of LNs (more than 15 LNs) is recommended for patients undergoing curative resection.

Short-term outcomes of minimally invasive Ivor-Lewis esophagectomy for esophageal cancer.

BACKGROUND: Esophagectomy represents the gold standard in the treatment of resectable esophageal carcinoma. This retrospective study evaluated the significance of minimally invasive Ivor-Lewis esophagectomy (MIILE) for the treatment of esophageal carcinoma. METHODS: We retrospectively evaluated 269 patients with esophageal carcinoma who received Ivor-Lewis esophagectomy in our center between October 2011 and January 2013. Of those 269 patients, 106 underwent MIILE and 163 underwent open Ivor-Lewis esophagectomy (OILE). The clinicopathologic factors, operational factors, and postoperative complications were compared. RESULTS: The two groups were similar in terms of age, sex, smoking history, American Society of Anesthesiologists grade, tumor location, preoperative staging, and incidence of comorbidities. The MIILE approach was associated with a significant decrease in surgical blood loss (p=0.04), chest tube duration (p=0.02), and postoperative stay (p=0.02) relative to the OILE approach. The postoperative in-hospital mortality and total morbidity did not differ between the two groups. The MIILE approach was associated with significantly fewer wound infections than the OILE approach (p=0.04). There were no significant differences between the two groups in the number of total lymph nodes dissected (p=0.69) or the locations of the total lymph nodes dissected (p=0.42). CONCLUSIONS: Our MIILE technique can be safely and effectively performed for intrathoracic anastomosis during esophageal operations with favorable early outcomes.

[Video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in thoracic cavity: analysis of 60 cases].

OBJECTIVE: To investigate the feasibility and safety of video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. METHODS: The clinical data of 120 patients who underwent esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity from March to December 2011 was analyzed retrospectively. In the video-assisted thoracoscopic surgery group, there were 60 patients [41 male and 19 female patients with aver age of (62 ± 7) years old] who underwent video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. In the routine thoracotomy group, there were 60 patients [39 male and 21 female patients with aver age of (62 ± 9) years old] who underwent routine thoracotomy esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity. Operation time, intra-operative blood loss, postoperative total thoracic drainage in 3 days, total number of harvested lymph nodes, hospitalization, cost of hospitalization and complications were compared between the two groups. RESULT: The operations were carried out successfully in two groups. There was no perioperative death in all patients. There was no statistical difference in intra-operative blood loss, postoperative total thoracic drainage and cost of hospitalization between the two groups. Operation time of rideo-assisted thoracoscopic surgery group was significantly longer than that of thoracotomy group ((188 ± 38) minutes vs. (138 ± 50) minutes, t = 6.171, P = 0.000), but postoperative hospitalization was significantly lower ((14 ± 3) d vs. (18 ± 6) d, t = -4.093, P = 0.000) and total number of harvested lymph nodes was lower (17 ± 9 vs. 21 ± 11, t = -2.058, P = 0.042). There was significantly statistical difference in total postoperative main complication (25.0% vs. 48.3%, χ(2) = 7.033, P = 0.008). And postoperative incisional infection of VATE group patients was significantly lower than that of thoracotomy group patients (6.7% vs. 25.0%, χ(2) = 7.566, P = 0.006). CONCLUSIONS: Video-assisted thoracoscopic esophagectomy for esophageal carcinoma and gastro-esophageal anastomosis in right thoracic cavity is technically feasible and safe, with minimized trauma and quick recovery. The recent result is satisfactory.