[A Rare Case of Lung Adenocarcinoma with EGFR L833V/H835L Co-mutation 
and Literature Review].

Epidermal growth factor receptor (EGFR) mutations are the most common driver genes in the development of non-small cell lung cancer (NSCLC), of which mutations in exons 18-21 are frequent, especially the loss of exon 19 and exon 21 L858R mutation are the most frequent. Other rare gene mutations are rare. Simultaneous occurrence of two or more rare EGFR mutations are extremely rare in lung cancer, and the incidence of EGFR L833V/H835L rare gene compound mutations is very low, and there is little clinical data and evidence of relevant treatment methods. Some EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are effective in treating lung cancer patients with rare gene mutations. In this article, we reported a case of NSCLC patient with a rare gene compound mutation EGFR L833V/H835L, who responded to Afatinib in combination with Anilotinib treatment well after 5 months of treatment, and computed tomography (CT) showed shrinkage of lung lesions. Meanwhile, we also compiled previously reported NSCLC patients with EGFR L833V/H835L rare gene compound mutation and summarized the characteristics of this group of patients and the effect of applying different kinds of EGFR-TKIs treatment.
.

The diagnosis interval influences risk factors of mortality in patients with co-existent active tuberculosis and lung cancer: a retrospective study.

BACKGROUND: Previous studies reported that tuberculosis (TB) is associated with an increased risk of lung cancer or the survival and mortality of lung cancer. However, the impact of coexisting TB on the survival of lung cancer patients was controversial. We aimed to identify risk factors on the survival rate of patients with co-existent active TB and lung cancer. METHODS: One hundred seventy-three patients diagnosed with active TB and lung cancer from January 2016 to August 2021 in Shanghai pulmonary hospital were selected and divided into two groups (≤ 6 months, > 6 months) according to the diagnosis interval between active TB and lung cancer (the order of diagnosis is not considered). The clinical characteristics and survival were analyzed. Univariate and multivariate logistic regression analyses were used to identify the risk factors for overall survival (OS). RESULTS: One hundred seventy-three patients were diagnosed with lung cancer and active TB. The study population exhibited a median age of 64 years, with a majority of 81.5% being male, 58.0% of patients had a history of smoking. Among those involved, 93.6% had pulmonary TB, 91.9% were diagnosed with non-small cell lung cancer (NSCLC), 76.9% were Eastern Cooperative Oncology Group (ECOG) 0-2 and 12.7% were ECOG 3-4. We observed better survival in the > 6 months group compared with the ≤ 6 months group (hazard ratio [HR] 0.456, 95% confidence interval [CI]:0.234-0.889, P = 0.017). The 1-, 3-, and 5- year OS rates were 94.2%, 80.3%, and 77.6%, respectively, in the > 6 months group and 88.3%, 63.8%, and 58.5%, respectively, in the ≤ 6 months group. Surgery (HR 0.193, [95% CI, 0.038-0.097]; P = 0.046) and ECOG Performance Status (HR 12.866, [95% CI, 2.730-60.638]; P = 0.001) were independent prognostic factors in the > 6 months group. CONCLUSIONS: Patients diagnosed with lung cancer and active TB for more than half a year have a significantly better prognosis than those diagnosed within half a year. ECOG Performance Status and surgery might possibly affect the outcomes of patients with co-existent active TB and lung cancer.

Effects of spray cryotherapy on cough receptors and airway microenvironment in a canine model of chronic bronchitis.

The aim of this study was to explore the effects of spray cryotherapy (SCT) on cough receptors and airway microenvironment in a canine model of chronic bronchitis. We examined the expression of transient receptor potential vanilloid 1/4 (TRPV1/4) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) at the gene and protein levels before and after SCT. In addition, we explored whether TRPV1/4 could regulate inflammatory factors via mediator adenosine triphosphate (ATP). The levels of ATP and cytokines in alveolar lavage fluid and cell supernatant were measured using ELISA. SCT effectively downregulated the expression of TRPV1/4 and SP/CGRP in canine airway tissues with chronic bronchitis and reduced the levels of inflammatory mediators and cytokines that affect cough receptor sensitivity, achieving cough relief. TRPV1/4 - ATP - inflammatory cytokines axis has been demonstrated at the cellular level, which in turn modulate the milieu of the airways and promote the formation of a cough feedback loop. Our study has fully revealed the specific mechanism of SCT in treating cough in a canine model of chronic bronchitis, providing a solid theoretical basis for future clinical treatment.

The Valuable Prognostic Impact of Regional Lymph Node Removed on Outcomes for IIIA N0 NSCLC Patients.

Background: Regional lymph nodes (RLNs) removed combined with surgery is a standard option for patients at stage I to IIIA NSCLC. The objective of the study is to clarify the effect of removing different number of RLNs on survival outcomes for patients at stage IIIA N0 NSCLC. Methods: Patients at stage IIIA N0 NSCLC from 2004 to 2015 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Prior propensity score method (PSM), survival time was compared among different number (0, 1-3 and ≥4) of RLNs removed groups. After PSM, lung cancer-specific survival (LCSS) and overall survival (OS) were compared. Kaplan-Meier analysis and Cox regression analyses were used to clarify the impact of the factors on the prognosis with hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 11,583 patients at stage IIIA N0 NSCLC were included. Prior PSM, survival indicators including 1-year mortality rate, 5-year mortality rate, median survival time (MDST) and mean survival time (MST) from good to bad were all: ≥4, 1-3 and none RLNs removed group. After PSM, Kaplan-Meier survival analyses and univariate Cox regression analyses on OS and LCSS revealed a statistically significance on survival curve (P<0.001) between each two of the three groups (none, 1-3 and ≥4 RLNs removed group). Multivariable Cox regression analyses on OS and LCSS showed an independent association of RLNs removed with higher OS (HR, 0.275; 95% CI, 0.259-0.291; P<0.001) and LCSS (HR, 0.239; 95% CI, 0.224-0.256; P<0.001) compared with none RLN removed and no statistical difference with OS (HR, 1.118; 95% CI, 0.983-1.271; P=0.088) and LCSS (HR, 1.107; 95% CI, 0.954-1.284; P=0.179) between 1-3 RLNs removed and ≥4 RLNs removed. Conclusions: Removing RLNs was beneficial to survival outcomes of patients at stage IIIA N0 NSCLC. Compared with 1-3 RLNs removed, ≥4 RLNs removed could bring a better survival time but not an independent prognostic factor (P>0.05).

Comprehensive Analysis of Circular RNA Expression Profiles in Gefitinib-Resistant Lung Adenocarcinoma Patients.

Introduction: Gefitinib is a selective epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) widely used in lung adenocarcinoma (LUAD) patients harboring sensitive EGFR mutations. Although it has a good initial efficacy, acquired resistance to gefitinib is eventually inevitable. Studies have shown that circular RNA (circRNA) is involved in the development of acquired resistance to different anti-cancer drugs, but the comprehensive analysis of its expression profile and functions on acquired gefitinib resistance remains poor. Methods: To explore the aberrant circRNAs expression profiles, we collected peripheral plasma samples from 4 gefitinib-sensitive and 4 gefitinib-resistant patients for performing microarray analysis. Candidates of differentially expressed circRNAs were used and analyzed by bioinformatics modalities including gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and a constructed circRNA-microRNA RNA network. The differential expression of selected circRNAs was verified by quantitative real-time PCR (qRT-PCR). Results: A total of 2571 circRNAs with significantly different expression between the groups were identified by microarray analysis. GO, KEGG, and pathway enrichment analyses reveal that these differentially expressed circRNAs (DECs) were complicated in many biological pathways that may be related to EGFR-TKI resistance such as ABC transporter and PI3K-Akt pathways. A circRNA-microRNA network was constructed by 10 circRNAs potentially involved in EGFR-TKI resistance togethering with their corresponding microRNAs (miRNAs). Consistent with the results of microarray assay, hsa_circ_0030591 and hsa_circ_0040348 were validated to be upregulated in gefitinib-resistant patients by qRT-PCR. Conclusions: Our study provides valuable data on circRNAs expression profiles detected in liquid biopsy for LUAD patients with acquired gefitinib resistance, and we validate that upregulations of hsa_circ_0030591 and hsa_circ_0040348 may play key roles in EGFR-TKI resistance and thus serving as candidates for biomarker.

The Clinical Characteristics and Treatments for Large Cell Carcinoma Patients Older than 65 Years Old: A Population-Based Study.

Background: Pulmonary large cell carcinoma, a type of non-small cell lung cancer (NSCLC), is a rare neoplasm with poor prognosis. In this study, our aim was to investigate the impact of radiation sequences with surgery for stage III/IV LCC patients between different age groups, especially in the elderly patients. Patients and Methods: The patients with LCC and other types of NSCLC in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2015 were retrospectively analyzed. Then we divided the LCC patients into two age groups: <65 years old group and ≥65 years old group. Propensity score method (PSM) was used to control potential differences between different groups. The overall survival (OS) of LCC patients and other types of NSCLC patients were evaluated by Kaplan−Meier analysis. Univariate and multivariate Cox regression analysis were employed to explore the independent risk factors of OS. The forest plots of HRs for OS were generated to show the above outcomes more visually. Results: In total, 11,349 LCC patients and 129,118 other types of NSCLC patients were enrolled in this study. We divided LCC patients into <65 years old group (4300) and ≥65 years old group (7049). LCC patients was more common in whites (81.4%), males (58.3%), elderly (≥65 years old: 62.1%), east regions (52.7%), upper lobe (51.6%), right-origin of primary (55.4%), with advanced grade (54.2%) or stage (76.7%). After PSM, Kaplan−Meier analysis and multivariate Cox analysis showed significantly worse survival prognosis for LCC patients compared to other types of NSCLC, especially in the group ≥65 years old (HR: 1.230; 95% CI: 1.171−1.291; p < 0.001). For LCC patients, there were some risk survival factors including whites, males, not upper lobe, advanced stage, elder age at diagnosis, bone metastasis, liver metastasis, singled status, no lymphadenectomy, no surgery, and no chemotherapy (p < 0.05). In LCC patients ≥65 years old, radiation after surgery had significantly better impact on overall survival outcomes (HR: 0.863, 95% CI: 0.765−0.973, p = 0.016), whereas radiation prior to surgery (HR: 1.425, 95% CI: 1.059−1.916, p = 0.019) had significantly worse impact on prognosis of patients. In LCC patients <65 years old, radiation sequences with surgery had no significant impact on the OS of patients (p = 0.580), but ≥4 LNRs had significantly survival benefits to prognosis (HR:0.707, 95% CI: 0.584−0.855). Elderly LCC patients had worse malignant tumors than young patients, of which the majority were diagnosed as stage III/IV tumors. Conclusions: Postoperative radiotherapy may achieve a better prognosis for stage III/IV LCC patients older than 65 years old compared to other radiation sequences with surgery.

Exploration of the optimal number of regional lymph nodes removed for resected N0 NSCLC patients: A population-based study.

Background: The aim of our study was to explore the optimal number of regional lymph nodes removed (LNRs) in resected N0 non-small cell lung cancer (NSCLC) patients and identify potential risk factors. Methods: Included in this study were 55,024 N0 NSCLC patients between 2004 and 2015 based on the Surveillance, Epidemiology, and End Results database (SEER). All the patients were divided into No LNR group (57.8%), 1-3 LNRs group (8.1%) and ≥4 LNRs group (31.4%). Relevant clinical and patient parameters including overall survival (OS), lung cancer-specific survival (LCSS), gender, race, year of diagnosis, primary site, T stage, AJCC stage, laterality, histological type, lymphadenectomy, radiation, chemotherapy, age at diagnosis, insurance status, marital status, family income. Results: Kaplan-Meier analysis demonstrated LNRs had significantly better OS and LCSS than No LNRs in all the N0 NSCLC patients with different T stages (Logrank p<.001). Univariate and multivariate analysis showed that both OS and LCSS in ≥ 4 LNRs group were better than those in <1-3 LNRs group (OS: ≥4 LNRs group: HR, 0.583; 95%CI, 0.556-0.610; P<.001 vs.1-3 LNRs group: HR, 0.726; 95%CI, 0.687-0.769; P<.001; LCSS: ≥4 LNRs group: HR, 0.514; 95%CI, 0.480-0.550; P<.001 vs.1-3 LNRs group: HR, 0.647; 95%CI, 0.597-0.702; P<.001). In addition, whites, males, not upper lobe, large cell carcinoma and others, advance T stage or AJCC stage, no surgery, no LNR, no radiation, no chemotherapy, elder age at diagnosis, singled marital status and low family income had negative impact on prognosis of N0 NSCLC patients. Conclusions: Our study suggests that ≥ 4 LNRs can yield better survival outcomes compared with 1-3 LNRs in N0 NSCLC patients.

Value of transbronchial needle aspiration combined with a rapid on-site evaluation of cytology in the diagnosis of pulmonary lesions.

Background: The diagnostic value of rapid on-site evaluation (ROSE) of cytology during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains controversial. The purpose of this study was to validate the value of ROSE during the EUBS-TBNA procedure in the diagnosis of pulmonary lesions (PLs). Methods: Enrolled in this study were 260 patients with nodules, masses, cavities, or inflammatory lesions on pulmonary CT images. They were assigned to undergo EBUS-TBNA with ROSE (n = 134) or without ROSE (n = 126). The diagnostic results of ROSE during EBUS-TBNA and the final pathologic reports were analyzed and compared by utilizing SPSS21.0 software to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, we further explored whether the ROSE method during EBUS-TBNA would improve the diagnostic yield and reduce the incidence of complications. Results: The overall diagnostic yield of EBUS-TBNA for malignant diseases in the ROSE and the non-ROSE group were 29.9 and 11.1%, respectively. The sensitivity, specificity, PPV and NPV of the ROSE method during EBUS-TBNA were 97.4, 96.9, 92.5, and 98.90%, respectively. The result of the chi-square test effectively proved that ROSE operation during EBUS-TBNA contributes to the diagnosis of malignancy compared with the non-ROSE group (χ2 = 13.858, P < 0.001). The number of punctures in the ROSE group was significantly lower than that in the non-ROSE group (P < 0.001). Conclusion: ROSE examination during EBUS-TBNA could effectively improve the diagnostic yield of malignant diseases compared with the non-ROSE group and reduce the number of intraoperative punctures, which is a clinical application worth popularizing.

Adjuvant chemotherapy is not a decisive factor in improving the overall survival of pulmonary sarcoma: A population-based study.

Objective: This study aimed to investigate the impact of adjuvant chemotherapy on overall survival (OS) for pulmonary sarcomatoid carcinoma (PSC) and non-small-cell lung cancer (NSCLC) cohorts and to identify its potential risk factors. Methods: A retrospective analysis was performed by querying the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed as having PSC (n=460) and NSCLC (n=140,467) from 2004 to 2015. The demographics, tumor characteristics, treatment modes, and survival were included in the scope of statistical analysis. Confounding factors were controlled by propensity score matching (PSM) analysis. Kaplan-Meier survival curves were performed to compare the effects of adjuvant chemotherapy on OS of the patients in the two cohorts (PSC vs. NSCLC). A multivariable Cox regression model was constructed, and Kaplan-Meier analysis on each variate was applied to predict risk factors associated with OS. Results: When adjuvant chemotherapy approach was applied in the treatment of patients with PSC or adjusted NSCLC, respectively, an improved OS could be observed in the NSCLC cohort (p=0.017). For the entire PSC cohort, 1-, 3-, and 5-year OS were 25.43%, 13.04%, and 6.96%, respectively, compared with 41.96%, 17.39%, and 10.00%, respectively, for the new adjusted NSCLC cohort after PSM, which were statistically significant difference (p<0.001). Multivariable Cox regression analysis was performed on OS covering prognostic factors such as primary site (p=0.036), first malignant indicator (p<0.001), age at diagnosis (p<0.001), marital status at diagnosis (p=0.039), and high school education (p=0.045). Additionally, patients with the following parameters had the worse impact on OS: a poorly differentiated pathology (Grade III/IV, p=0.023), older age (p<0.001), liver or lung metastasis (p=0.004, p=0.029), and the number of lymph nodes removed <4 (p<0.001). Conclusions: Adjuvant chemotherapy did not play a decisive role in improving the OS of PSC, while it was associated with improved OS of NSCLC.

Advanced age is not the decisive factor in chemotherapy of small cell lung cancer: a population-based study.

OBJECTIVE: There is limited research on the impact of chemotherapy on the prognosis of different age group patients with small cell lung cancer (SCLC). The aim of this study was to explore the impact of chemotherapy on survival prognosis of elderly patients with SCLC. METHODS: Based on the Surveillance, Epidemiology and End Results (SEER) database, 57,460 SCLC patients between 2004 and 2015 were identified and divided into a ≤ 80 years group (n = 50,941) and a >80 years group (n = 6,519). Confounding factors were controlled by propensity score matching (PSM) analysis. Kaplan Meier (KM) analysis was performed to determine the impact of chemotherapy on overall survival (OS) and lung-cancer specific survival (LCSS) of the patients. Other variables that could affect survival of SCLC patients were also examined by COX analysis. RESULTS: KM analysis showed that both OS and LCSS were improved in chemotherapy group compared to those in non-chemotherapy group (log rank P < 0.001) in both age groups after PSM. Cox analysis demonstrated the survival benefit of chemotherapy in both ≤ 80 years group (OS: HR 0.435; 95% CI 0.424-0.447; LCSS: HR 0.436; 95% CI 0.424-0.448) and >80 years group (OS: HR 0.424; 95% CI 0.397-0.451; LCSS: HR 0.415; 95% CI 0.389-0.444). Additionally, the following parameters had a negative impact on survival of elderly patients: male sex, tumor location in main bronchus, increased stage, bilateral tumor, no surgery or radiation, and lower median household income. CONCLUSIONS: Elderly patients with SCLC should be encouraged to receive chemotherapy provided their general conditions permit.

Phosphorylation of CAP1 regulates lung cancer proliferation, migration, and invasion.

PURPOSE: Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Previous studies have shown that S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the role of CAP1 phosphorylation in lung cancer. METHODS: Massive bioinformatics analysis was applied to determine CAP1's role in different cancers and especially in lung cancer. Lung cancer patients' serum and tissue were collected and analyzed in consideration of clinical background. CAP1 shRNA-lentivirus and siRNA were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and de-phosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and de-phosphorylation in lung cancer A549 cells. RESULTS: CAP1 is a kind of cancer-related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group, higher serum CAP1 protein concentration correlated with shorter overall survival (OS) in NSCLC patients, and higher pCAP1 and CAP1 protein level were observed in lung cancer patients' tumor tissue compared with adjacent normal tissue. Knockdown CAP1 in A549 cells can inhibit proliferation and migration, and the effect is validated in H1975 cells. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo. When de-phosphorylated, these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial-mesenchymal transition (EMT). CONCLUSION: These findings indicated that CAP1 phosphorylation can promote lung cancer proliferation, migration, and invasion. Phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.

Impact of Type 2 Diabetes Mellitus on the Prognosis of Non-Small Cell Lung Cancer.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is the most common metabolic disease and is characterized by sustained hyperglycemia. The impact of T2DM on the survival of lung cancer patients remains controversial. The aim of this study was to investigate the associations of type 2 diabetes with lung cancer mortality. METHODS: From January 2019 to January 2020, 228 patients with non-small cell lung cancer (NSCLC) staging earlier than IIIA were included. RESULTS: In our study, we found that the overall survival (OS) and progression-free survival (PFS) of lung cancer patients with diabetes was longer than non-diabetes group. Diagnosed T2DM was associated with the prognosis of lung cancer after adjusting for age and covariates. The association between T2DM and OS was influenced by age, stage of cancer and cancer treatment, as well as whether taking metformin was associated with the OS of lung cancer. However, with the adjustment for age and covariates, the relation trended to lose statistical significance. CONCLUSION: T2DM is an independent prognostic factor for patients with NSCLC staging before IIIA. The patients with both NSCLC and T2DM trended to having a longer OS, possibly due to metformin.

Effects of bronchial thermoplasty and cryoablation on airway smooth muscle.

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM). METHODS: Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups. RESULTS: In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ±â€Š7.75 µm vs. 17.57 ±â€Š15.20 µm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ±â€Š11.02 µm), BT group and CBA group (13.41 ±â€Š4.40 µm and 4.81 ±â€Š4.44 µm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ±â€Š4.42 µm vs. 7.41 ±â€Š7.20 µm, P = 0.540). Compared with the control group (0.161 ±â€Š0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ±â€Š0.022, 0.072 ±â€Š0.012, 0.074 ±â€Š0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613). CONCLUSIONS: CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.

PARC/CCL18 is Associated with Inflammation, Emphysema Severity and Application of Inhaled Corticosteroids in Hospitalized COPD Patients.

BACKGROUND: Pulmonary and activation-regulated chemokine (PARC) also named CC-chemokine ligand 18 (CCL18) is a lung-predominant inflammatory protein that is found in serum. The relationship of PARC/CCL18 with the chronic obstructive pulmonary disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC/CCL18 in COPD. METHODS: Ninety-eight hospitalized COPD patients and 60 healthy volunteers from January 2019 to December 2019 were recruited in this retrospective study. Gender, age, height, weight, disease duration, smoking status, blood cell classification and count, length of hospital stay (LOS), symptom score, including COPD Assessment Test (CAT) score, modified British Medical Research Council (mMRC) score, lung function and therapy were recorded and serum PARC/CCL18 was analyzed by ELISA. The correlation between symptom score, blood cell classification and count, CRP, lung function parameters and serum levels of PARC/CCL18 and ROC curves of PARC/CCL18 levels and inhaled corticosteroids (ICS) were accessed. RESULTS: It was found that serum PARC/CCL18 level in hospitalized COPD population was significantly higher than that in healthy people (p=0.003). COPD patients with emphysema had significantly higher serum level of PARC/CCL18 than those without emphysema (p=0.049). Total lung capacity (TLC) and residual volume (RV)/TLC had positive correlation with serum level of PARC/CCL18 (p=0.001, 0.020, respectively). Furthermore, serum PARC/CCL18 level was predictive for the application ICS (p=0.003) and related to C-reactive protein (p <0.0001) in hospitalized COPD patients. CONCLUSION: PARC/CCL18 is associated with the severity of inflammation and emphysema in COPD. Furthermore, PARC/CCL18 is a predictor of ICS application in the treatment of hospitalized COPD patients.

Segmentectomy or Wedge Resection in Stage IA Lung Squamous Cell Carcinoma and Adenocarcinoma?

Objectives: We performed this study to compare survival outcomes of segmentectomy (SG) and wedge resection (WR) in stage IA lung squamous cell carcinoma (SQCC) and lung adenocarcinoma (AD). Methods: Using the Surveillance, Epidemiology, and End Results registry (SEER), we identified 1529 and 4070 patients with stage IA SQCC and AD, respectively, who had complete clinical information between 2004 and 2015. We used Kaplan-Meier analysis to determine the propensity score for patients with limited resection based on the preoperative characteristics of patients. Lung cancer-specific survival (LCSS) was compared in patients treated with WR and SG after adjusting, stratifying, or matching lung cancer patients according to propensity score. Results: Kaplan-Meier analysis demonstrated that there was a statistically significant difference in survival curves (log rank P=0.01) for patients with stage IA SQCC between SG and WR. But there was no statistically significant difference in survival curves (log rank P>0.05) in patients with stage IA AD between the two limited resections. Compared with the WR, The hazard ratios (95% confidence intervals) of SG were 0.689 (0.519-0.914) and 0.896 (0.752-1.067) in patients with stage IA SQCC and AD, respectively. Conclusion: This study suggests that SG can yield superior survival outcome compared with WR in patients with stage IA SQCC. However, the survival outcomes of SG and WR are generally equivalent in patients with stage IA AD.

The impact of order with radiation therapy in stage IIIA pathologic N2 NSCLC patients: a population-based study.

BACKGROUND: The aim of this study was to investigate the optimal order of radiation therapy in patients affected by stage IIIA pathologic N2 (IIIA/N2) non-small-cell lung cancer (NSCLC) and to identify its potential risk factors. METHODS: 17,654 (8786 men and 8868 women) diagnosed with NSCLC stage IIIA-N2 from 2004 to 2015 patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Among the relevant clinical parameters, we evaluated overall survival (OS), lung cancer-specific survival (LCSS) and other variables such as age, sex and tumor size in patients who were treated with different combinations of surgery and radiotherapy strategies. RESULTS: We discovered that surgery benefit in younger IIIA/N2 NSCLC patients (age ≤ 75), and compared with surgery only, preoperative radiotherapy significantly improved the survival rate most (p < 0.001). When we performed the OS and LCSS analysis in the subgroup of patients' age > 75 years old, who underwent postoperative radiotherapy (PORT) had the highest survival rate (p < 0.001). Multivariate analyses showed that the following parameters had a negative impact on survival: female sex, older age, no chemotherapy, large tumor size, high tumor grade, no surgery or radiotherapy. CONCLUSIONS: In IIIA/N2 NSCLC patients, surgery, radiotherapy and chemotherapy were associated with improved OS and LCSS. Younger patients underwent surgical resection and chemotherapy, the main population we studied, benefited most from preoperative radiotherapy in all orders with radiation therapy (p < 0.001). In patients more than 75 years old, there was no clear benefit from only surgery, and PORT was recommended in case of having surgery.

Choice of Treatment for Stage IA Non-small Cell Lung Cancer Patients Ineligible for Surgery: Ablation or Stereotactic Body Radiotherapy?

Purpose: To compare the survival outcomes of ablation and stereotactic body radiotherapy (SBRT) in inoperable patients with stage IA non-small cell lung cancer (NSCLC). Patients and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 6,395 patients with stage IA NSCLC who had complete clinical information from 2004 to 2015. Kaplan-Meier analysis was performed to determine the propensity score based on the clinical characteristics of patients with stage IA NSCLC. Overall survival (OS) was compared between patients with stage IA NSCLC who were treated with ablation and SBRT after adjusting, stratifying, or matching. Results: Kaplan-Meier analysis demonstrated no significant difference in survival curves (log-rank, p>0.05) between the ablation and SBRT groups. Compared with the SBRT group, the hazard ratio (HR) (95% confidence interval [CI]) of OS was 0.930 (0.817-1.058, p=0.269) in the ablation group on univariate analysis. On multivariate analysis, similar effects on OS (HR: 0.974, 95% CI: 0.858-1.105, p=0.680) were seen in patients with stage IA NSCLC in both the groups. Conclusions: This study suggests that survival does not differ significantly between patients with stage IA NSCLC treated with ablation and SBRT. These results will be helpful for patients with stage IA NSCLC who are ineligible for surgery.

Role of surgery in patients with early stage small-cell lung cancer.

PURPOSE: Currently, systemic chemotherapy combined with thoracic radiation is the standard treatment for patients with small-cell lung cancer (SCLC). However, the treatment of early stage SCLC remains controversial. This study evaluated the survival outcomes of surgical treatments and the effect of adjuvant chemotherapy and radiotherapy on lung cancer-specific survival (LCSS) in patients with early stage SCLC. METHODS: Using the Surveillance, Epidemiology, and End Results registry, we identified 2,453 patients with early stage SCLC (1,295 women and 1,158 men) who had complete clinical information between 2004 and 2015. The Kaplan-Meier analysis was used to determine the propensity score based on the characteristics of patients with early stage SCLC. LCSS was compared between patients treated with surgery and non-surgery after adjusting, stratifying, or matching patients with early stage SCLC. In addition, we compared the effects of chemotherapy and radiotherapy on LCSS in patients with early stage SCLC. RESULTS: Overall, 687 (28.0%) and 1,766 (72.0%) patients with early stage SCLC did and did not undergo surgery, respectively. Kaplan-Meier analysis demonstrated a statistically significant difference in survival curves between the surgery and non-surgery groups (log-rank p<0.001). Compared with the non-surgery group, the LCSS of the surgery group was better (hazard ratio [HR]:0.494, 95% confidence interval [CI]:0.415-0.587, p<0.001) in patients with early stage SCLC when using a Cox model for multivariate analysis. There was no statistically significant difference (p=0.847) in LCSS between patients with early stage SCLC with and without chemotherapy in the multivariate analysis. Radiotherapy had favorable effects on LCSS (HR: 0.579, 95% CI: 0.500-0.671, p<0.001) in patients with early stage SCLC using multivariate analysis. CONCLUSIONS: Our study results suggest that LCSS conferred by surgery was higher than that conferred by non-surgery and that radiotherapy is associated with better survival in patients with early stage SCLC. This study findings should be confirmed in prospective studies.

Adenylyl cyclase­associated protein 1­targeted nanoparticles as a novel strategy for the treatment of metastatic non­small cell lung cancer.

Non­small cell lung cancer (NSCLC) is one of the most fatal cancers worldwide. Adenylyl cyclase­associated protein 1 (CAP1) belongs to a family of cyclase­associated proteins that are involved in the development of cancerous tumors. A previous study by our group confirmed the association between CAP1, lung cancer and the metastasis of cancer cells. In the present study, poly(lactic­polyglycolic acid; PLGA)/CAP1­small interfering (si)RNA nanoparticles were prepared and delivered into A549 cells. The performance of PLGA/siCAP1­siRNA nanoparticles for siRNA delivery was measured based on the results of migration assay and animal experiments. The multifunctional nanoparticles were determined to be capable of inhibiting CAP1 expression, which reduced NSCLC metastasis in vitro and in vivo. Therefore, the findings of the current study highlighted the potential use of PLGA/siCAP1­siRNA nanoparticles for the treatment of NSCLC metastasis.