Lymph Node Ratio Enhances Predictive Value for Treatment Outcomes in Patients with Non-Small Cell Lung Cancer Undergoing Surgery: A Retrospective Cohort Study.

Purpose: To compare the prognostic value of lymph node ratio (LNR) and pN in patients with non-small cell lung cancer (NSCLC) undergoing surgery. Materials and methods: NSCLC patients were investigated between 2004 and 2015 from the Surveillance, Epidemiology, and End Results databases. The X-tile software was used to determine LNR cut-off values. Kaplan-Meier analysis was employed to assess cancer-specific survival (CSS) and overall survival (OS). Results: The identified cut-off values of LNR were 0.19 and 0.73. Median CSS for LNR1 (LNR < 0.19), LNR2 (0.19 ≤ LNR ≤ 0.73), and LNR3 (LNR > 0.73) were 71, 41, and 17 months. Both LNR2 (HR = 1.46, 95% CI: 1.36-1.57; P < 0.001) and LNR3 (HR = 2.85, 95% CI: 2.58-3.15; P < 0.001) demonstrated poorer median CSS compared to LNR1. Similarly, median OS for LNR1, LNR2, and LNR3 were 50, 35, and 16 months. LNR2 (HR = 1.36, 95% CI: 1.27-1.45; P < 0.001) and LNR3 (HR = 2.60, 95% CI: 2.37-2.85; P < 0.001) exhibited worse median OS compared to LNR1. A revised pN (r-pN) classification incorporating LNR and pN demonstrated superior penalized goodness-of-fit and discriminative ability in predicting CSS and OS compared to both LNR and pN. Conclusion: LNR outperformed pN in predicting CSS and OS in NSCLC patients undergoing surgery, potentially leading to more precise adjuvant treatment decisions.

Postoperative radiotherapy in pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis.

BACKGROUND: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy. METHODS: Electronic databases (PubMed, Web of Science databases, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched to extract randomized control trials comparing PORT with observation in pIIIA-N2 non-small cell lung cancer patients until October 2021. Main outcomes were disease-free survival (DFS), overall survival (OS), and local recurrence. RESULTS: Three-phase 3 randomized control trials involving 902 patients were included: 455 patients in the PORT group and 447 patients in the observation group. The methodological quality of the 3 randomized control trials were high quality. The pooled analysis revealed that PORT decreased local recurrence rate (odds ratio = 0.56, 95% confidence interval [CI]: 0.40-0.76). However, PORT did not improve median DFS (hazard ratio = 0.84, 95% CI: 0.71-1.00) and OS (hazard ratio = 1.02, 95% CI: 0.68-1.52). CONCLUSIONS: PORT decreased the incidence of local recurrence. However, PORT did not improve DFS and OS.

Expert consensus on resection of chest wall tumors and chest wall reconstruction.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years.

[Effect of transcutaneous electrical acupoint stimulation on venous thrombosis after lung cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on venous thrombosis and quality of life after lung cancer surgery, basing on the conventional nursing and early functional exercise. METHODS: A total of 120 patients diagnosed as non-small cell lung cancer (NSCLC) and received radical resection of lung cancer surgery for the first time were randomized into a conventional nursing group, a rehabilitation training group and a TEAS group, 40 cases in each group. Conventional nursing was adopted in the conventional nursing group. Conventional nursing combined with early functional exercise were adopted in the rehabilitation training group, the exercise was taken 20 min each time, once in both morning and afternoon for 5 days. On the basis of the treatment in the rehabilitation training group, TEAS was applied at Zusanli (ST 36), Xuehai (SP 10), Sanyinjiao (SP 6), etc. in the TEAS group, with disperse-dense wave in frequency of 30 Hz/100 Hz and tolerable intensity, 30 min each time, once in both morning and afternoon for 5 days. The incidence of venous thrombosis in each group was observed at the 5th day after surgery. Before surgery and at the 5th day after surgery, the Caprini thrombus risk assessment was performed, the Karnofsky performance status (KPS) scale and the functional assessment of cancer therapy-lung (FACT-L) were used to evaluate the quality of life. RESULTS: At the 5th day after surgery, no thrombosis was found in the TEAS group, the incidence of venous thrombosis in the TEAS group was lower than 15.0% (6/40) in the conventional nursing group (P<0.05). At the 5th day after surgery, the Caprini scores were increased in the 3 groups (P<0.01), while that in the TEAS group was lower than the conventional nursing group (P<0.05); the KPS scores were decreased in the 3 groups (P<0.01), while those in the TEAS group and the rehabilitation training group were higher than the conventional nursing group (P<0.01, P<0.05); the total scores and the subitem scores of FACT-L were decreased in the 3 groups (P<0.05), while the total score of FACT-L and the subitem score of lung cancer specificity in the TEAS group were higher than those in the conventional nursing group (P<0.05). CONCLUSION: On the basis of the conventional nursing and early functional exercise, TEAS can reduce the incidence of venous thrombosis, effectively prevent thrombosis and improve quality of life.

An Analysis of EGFR Mutations among 1506 Cases of Non-Small Cell Lung Cancer Patients in Guangxi, China.

An association between epidermal growth factor receptor (EGFR) and clinical characteristics of non-small cell lung cancer (NSCLC) was reported ten years ago. In addition, a different type of relationship was seen in different ethic races. However, the relationship between these factors is not well understood in the Guangxi province. Up to now, there are only very limited data on the association of TTF1/EGFR protein positivity and EGFR mutation status in NSCLC. This study aims to investigate the role of EGFR gene mutation status on the clinical characteristics and the relationship with TTF-1/EGFR protein positivity of patients with NSCLC in Guangxi, China. 1506 samples from different patients with NSCLC were detected by amplification refractory mutation system for 29 hotspot mutations. Analysis of the relationship between clinical characteristics and EGFR mutation status was performed by using the crosstabs Chi-square and SPSS 21.0 software. Of 1506 samples, 537 (35.7%) revealed tyrosine kinase inhibitor (TKI) sensitive EGFR mutations with 27 (1.8%) cases harboring TKI resistant EGFR mutations or union co-existing EGFR-TKIs sensitive mutations. EGFR-TKIs sensitive mutations were not significantly associated with age and TNM-M stage (P = 0.863; P = 0.572, respectively). However, they were significantly associated with p-stage, TNM-T stage and TNM-N stage (P = 0.011, P < 0.001, P = 0.036, respectively). Immunohistochemical studies revealed that TTF-1 and EGFR protein expression level were all associated with EGFR mutation status (P < 0.001, P = 0.002, respectively). Of the 537 EGFR-TKIs sensitive mutation cases, the rates of exon 19-del, 18 G719X point, exon 21 L858R and L861Q points were 54.6, 0.9, 42.3 and 0.9%, respectively. EGFR TKI-sensitive mutations commonly occur in female, non-smoking and adenocarcinoma patients. The p-stage, TNM-T stage, TNM-N stage, EGFR and TTF-1 protein expression levels have close relationships with EGFR mutation status.

Casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells.

OBJECTIVE: To assess if casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells. METHODS: Human non-small-cell lung carcinoma cell lines H460, A549 and H157 were cultured in vitro. The cytotoxic activities were determined using MTT assay. The apoptotic cells death was examined by flow cytometry using PI staining and DNA agarose gel electrophoresis. The activities of caspase-3, -8 and -9 were measured via ELISA. Cellular fractionation was determined by flow cytometry to assess release of cytochrome c and the mitochondrial transmembrane potential. Bcl-2/Bcl-XL/XIAP/Bid/DR5 and DR4 proteins were analyzed using western blot. RESULTS: The concentrations required for a 50% decrease in cell growth (IC(50)) ranged from 1.8 to 3.2 µM. Casticin induced rapid apoptosis and triggered a series of effects associated with apoptosis by way of mitochondrial pathway, including the depolarization of the mitochondrial membrane, release of cytochrome c from mitochondria, activation of procaspase-9 and -3, and increase of DNA fragments. Moreover, the pan caspase inhibitor zVAD-FMK and the caspase-3 inhibitor zDEVD-FMK suppressed casticin-induced apoptosis. In addition, casticin induced XIAP and Bcl-XL down-regulation, Bax upregulation and Bid clearage. In H157 cell line, casticin increased expression of DR5 at protein levels but not affect the expression of DR4. The pretreatment with DR5/Fc chimera protein effectively attenuated casticin-induced apoptosis in H157 cells. No correlation was found between cell sensitivity to casticin and that to p53 status, suggesting that casticin induce a p53-independent apoptosis. CONCLUSIONS: Our results demonstrate that casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells.

[Isolation and identification of side population cells in human lung adenocarcinoma cell line A549].

OBJECTIVE: To isolate and characterize the side population cells (SP cells) in the lung adenocarcinomas cell line A549. METHODS: The protein expression of ABCG2 in human lung adenocarcinoma cell line A549 was detected by immunohistochemistry. SP and NSP cells in the cell line A549 were isolated by FACS, and their differentiation was analysed. ABCG2 expression in the two cell subsets was detected by RT-PCR. The cell growth curves, cell division indexes, cell cycles, plate clone formation tests, migration and invasion assays, chemotherapeutic susceptibility tests, tests of the intracellular drug levels, and the tumor cell implantation experiments on nude mice were applied to study the biological properties of the two cell subsets. The expression of ABCG2 in the transplanted tumor in nude mice was detected by immunohistochemistry and RT-PCR. RESULTS: The positive rate of ABCG2 expression in the A549 cells by immunohistochemistry was 2.13%. SP and NSP cells were isolated by FACS. The SP cells could produce both SP and NSP cells, while NSP cells only produced NSP cells. SP cells expressed ABCG2, but NSP cells did not. The proliferation and migration abilities of the two cell subsets were similar, but the invasion and tumorigenic ability of SP cells was significantly higher than that of NSP cells. The susceptibilities to DDP and its intracellular levels of the two cell subsets were similar, but the susceptibilities to 5-FU, VP16, NVB and GEM and their intracellular levels of NSP cells were significantly higher than those of the SP cells. CONCLUSIONS: SP cells in the human lung adenocarcinomas cell line A549 is enriched with tumor stem cells. An effective way to get lung adenocarcinomas stem cells is to isolate SP cells by FACS.

[Relationship between combined multigene detection and response to adjuvant chemotherapy in early-stage non-small cell lung cancer].

OBJECTIVE: To evaluate the relationship between combined multigene detection and response to adjuvant chemotherapy and prognosis in early-stage non-small cell lung cancer (NSCLC). METHODS: Tissue microarray was prepared from samples of 86 cases of early-stage NSCLC who received adjuvant chemotherapy after radical surgery. The expressions of caspase-3, Fas, bax, bcl-2, survivin, PCNA, Ki67, MGMT, p53, p63, p73, p16, p27, VEGF, nm23, P-gp, MRP, LRP, GST-pi, Topo II, c-myc, cyclin-D1, Her-2, Cox-2, Ku70, Ku80, DNA-PKcs, ERCC1, MSH2, BCRP proteins were detected using immunohistochemical two-step method. RESULTS: The positive rate of the 30 genes in lung cancer tissue were 27.9% - 91.9%, respectively. By univariate analysis, the expression of 8 genes was shown to be related with SCLC adjuvant chemotherapy. The cases with higher expression of survivin, P-gp, LRP, Ki67, p53, ERCC1 and lower expression of bax,VEGF had worse prognosis. By logistic regression analysis, the ERCC1, survivin, bax and VEGF were a marker group. Multivariate analysis showed the predict value of the response to adjuvant chemotherapy in early-stage NSCLC was 96.5%. CONCLUSION: Survivin, ERCC1, bax and VEGF are an ideal marker group to predict the effect of adjuvant chemotherapy in early-stage NSCLC.