A Novel Intergenic Region (chr2: 30,316,870)-ALK Fusion in a Patient with Lung Adenocarcinoma Responding to Crizotinib Combined with Pemetrexed Treatment: A Case Report.

Background: Anaplastic lymphoma kinase (ALK) rearrangements have been reported as an important oncogenic driver in 5-7% non-small cell lung cancer (NSCLC) patients. Reports about the intergenic region (IGR) as an ALK fusion partner are rare. In this study, we report a novel IGR (chr2: 30,316,870)-ALK fusion in an advanced lung adenocarcinoma patient that responded effectively to crizotinib combined with pemetrexed. Case Presentation: A 68-year-old Chinese female was diagnosed with stage IV right lung adenocarcinoma (cT3N3M1c). The targeted next-generation sequencing (NGS) of 14 cancer-related genes identified an IGR (chr2: 30,316,870)-ALK fusion. Her lung lesions have been successfully converted from a partial response to a complete response after administrating crizotinib for 1 year combined with 6 cycles of chemotherapy with pemetrexed. So far, her progression-free-survival has reached 21 months. Conclusion: In this case, we firstly report a novel IGR (chr2: 30,316,870)-ALK fusion by using targeted NGS, and highlight the efficacy of crizotinib combined with pemetrexed to reduce unbearable gastrointestinal adverse reactions. It provides valuable clinical guidance for the treatment of similar cases in the future.

[Results of EGFR Mutations Detected in Pleural Effusion and Its 
Clinical Significance in 132 Patients with Advanced Non-small Cell Lung Cancer: 
A Retrospective Study in A Single Center].

BACKGROUND: The lack of pathological quality control standard in detecting epidermal growth factor receptor (EGFR) gene mutation in malignant pleural effusion leads to confusion in the interpretation of detection results and the clinical use of EGFR-tyrosine kinase inhibitor (TKI). Therefore, it is very important to propose quality control standards and guide the detection of EGFR mutation in pleural effusion. The aim of this study is to retrospectively analyze the results of EGFR gene mutation in pleural effusion sediment section according to strict pathological quality control standards, and the therapeutic effect of EGFR-TKIs guided by this detection results. METHODS: From January 2012 to June 2018, the clinical data of patients with pleural effusion collected from Department of Pathology of Peking Union Medical College Hospital were analyzed retrospectively. Among them, 132 patients with relatively complete clinical data and with EGFR gene mutation detection of paraffin-embedded pleural effusion sediment section according to the established quality control standard were included. According to the results of EGFR gene mutation, it was divided into positive group and negative group, and the efficacy of EGFR-TKIs in different groups was compared. RESULTS: After the centrifugation of pleural effusion, the sediment was embedded in paraffin, sectioned, and observed under the microscope after HE staining. If the number of tumor cells ≥100, it met the pathological quality control standard, and it could be used for subsequent EGFR gene mutation detection. EGFR gene mutations were detected in 72 (54.5%) of 132 patients. EGFR-TKIs were used in 69 of 72 mutation positive patients. Of 60 EGFR mutation negative patients, only 15 used EGFR-TKIs. In EGFR mutation positive group, the disease control rate (DCR) was 95.8%, and the median progression-free survival (PFS) was 11 months. In EGFR mutation negative group, the DCR was 0%, and the median PFS was 1 month. The DCR and PFS were significantly different between the two groups (P<0.05). CONCLUSIONS: According to the pathological quality control standards, the embedded section of pleural fluid sediment can be used to detect EGFR gene mutation, and the results can be used to guide the clinical use of EGFR-TKIs.

Endocan, a Risk Factor for Developing Acute Respiratory Distress Syndrome among Severe Pneumonia Patients.

Background: Severe pneumonia (SP) has been widely accepted as a major cause for acute respiratory distress syndrome (ARDS), and the development of ARDS is significantly associated with increased mortality. This study aimed to identify potential predictors for ARDS development in patients with SP. Methods: Eligible SP patients at admission from January 2013 to June 2017 were prospectively enrolled, and ARDS development within hospital stay was identified. Risk factors for ARDS development in SP patients were analyzed by univariate and multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was performed for the predictive value of endocan for ARDS development. Results: A total of 145 SP patients were eventually enrolled into the final analysis, of which 37 developed ARDS during the hospital stay. Our final multivariate logistic regression analysis suggested plasma endocan expression as the only independent risk factor for ARDS development in SP patients (OR: 1.57, 95% CI: 1.14-2.25, P=0.021). ROC curve analysis of plasma endocan resulted in an AUC of 0.754, 95% CI of 0.642-0.866, a cutoff value of 11.6 ng/mL, a sensitivity of 78.7%, and a specificity of 70.3%, respectively (P < 0.01). Conclusions: Endocan expression at ICU admission is a reliable predictive factor in predicting ARDS in patients with SP.

Invasive-noninvasive Sequential Ventilation for the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

BACKGROUND: The study aimed to evaluate the efficacy and safety of invasivenoninvasive sequential ventilation versus invasive ventilation in the treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD). METHODS: PubMed, Cochrane, Embase, Wanfang, CNKI, VIP database were searched by the index words to identify the qualified RCTs, and relevant literature sources were also searched. The latest research was conducted in June 2017. Relative Risks (RR), and Mean Difference (MD) along with 95% confidence interval (95% CI) were used to analyze the main outcomes. RESULTS: Twenty-nine RCTs were involved in this analysis of 1061 patients in the invasivenoninvasive sequential ventilation group (In-non group) and 1074 patients in the invasive ventilation group (In group). The results indicated that compared with the invasive ventilation, invasive-noninvasive sequential ventilation would significantly decrease the incidence of VAP (RR:0.20, 95%CI: 0.16-0.26), mortality (RR:0.38, 95%CI: 0.26-0.55), reintubation (RR:0.39, 95%CI: 0.27-0.55); and statistically reduced the duration of invasive ventilation (MD:-9.23, 95%CI: -10.65, -7.82), the total duration of mechanical ventilation (MD:-4.91, 95%CI: -5.99, -3.83), and the length of stay in the ICU (MD:-5.10, 95%CI: -5.43, -4.76). CONCLUSION: The results demonstrated that the application of noninvasive sequential ventilation after invasive ventilation at the pulmonary infection control window has a significant influence on VAP incidence, mortality, and the length of stay in the ICU, but further well-designed, adequately powered RCTs are required to validate the conclusion.

Pretreatment albumin/fibrinogen ratio as a promising predictor for the survival of advanced non small-cell lung cancer patients undergoing first-line platinum-based chemotherapy.

BACKGROUND: This study aimed to identify potential predictive factors for the survival of advanced non small-cell lung cancer (NSCLC) patients undergoing first-line platinum-based chemotherapy. METHODS: A total of 270 advanced NSCLC patients who underwent first-line platinum-based chemotherapy from June, 2011 to June, 2015 were enrolled. A receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the albumin-to-fibrinogen ratio (AFR) for overall survival (OS). The predictive factors for survival were evaluated by univariate and multivariate analyses via the Cox proportional hazards regression model. The OS and progression free survival (PFS) results were determined via the Kaplan-Meier method using the log-rank analysis. RESULTS: Based on the results of the ROC curve analysis, 8.02 was accepted as the cut-off AFR value for OS. The metastasis stage (M0 vs M1a/b, HR: 1.73, 95% CI: 1.15-2.59, P = 0.020) and AFR (≤8.02 vs > 8.02, HR: 1.80, 95% CI: 1.09-2.78, P = 0.025) were two independent risk factors for PFS by multivariate Cox regression analysis. The AFR (≤8.02 vs > 8.02, HR: 1.79, 95% CI: 1.11-2.59, P = 0.029) was a significant predictive factor for OS in advanced NSCLC patients. The PFS (P = 0.008) and OS (P = 0.003) in the high AFR group were significantly improved compared with those in the low AFR group via the Kaplan-Meier method using the log-rank analysis. CONCLUSIONS: The AFR could be a potential effective predictive factor for the survival in advanced NSCLC patients undergoing first-line platinum-based chemotherapy.

Circulating 25-hydroxyvitamin D level and prognosis of lung cancer patients: A systematic review and meta-analysis.

BACKGROUND: Previous studies suggested a possible influence of circulating 25-hydroxyvitamin D [25(OH)D] level on the prognosis of lung cancer patients, but conflicting findings were reported. A systematic review and meta-analysis was thus conducted to comprehensively assess the influence of circulating 25(OH)D level on the prognosis of lung cancer patients. METHODS: Prospective or retrospective cohort studies assessing the influence of circulating 25(OH)D level on the prognosis of lung cancer patients were considered eligible. Hazard Ratios (HR) were pooled using meta-analysis. RESULTS: Eight studies with 2166 lung cancer patients were included. Meta-analysis of unadjusted HRs from four studies showed low circulating 25(OH)D level was significantly correlated with poor overall survival in lung cancer (HR=1.30, 95%CI 1.08-1.55, P=0.004). Meta-analysis of adjusted HRs from eight studies suggested that low circulating 25(OH)D level was not significantly correlated with poor overall survival (HR=1.25; P=0.13). However, sensitivity analysis suggested an obvious change in the pooled HRs when excluding single study by turns. When the study by Liu et al. was omitted, low circulating 25(OH)D level was significantly correlated with poor overall survival (HR=1.34; P=0.04). CONCLUSION: The present systematic review and meta-analysis suggested a correlation between low circulating 25(OH)D level and poor overall survival in lung cancer. More studies are needed to further validate the finding above.

[Expression and bioinformatic analysis of ornithine aminotransferase 
in non-small cell lung cancer].

BACKGROUND: It has been proven that ornithine aminotransferase (OAT) might play an important role in the oncogenesis and progression of numerous malignant tumors. The aim of this study is to detect the mRNA and protein expression of OAT in non-small cell lung cancer (NSCLC), as well as to analyze the bioinformatic features and binary interactions. METHODS: OAT mRNA expression was detected in A549 and 16HBE cell lines by reverse transcription-polymerase chain reaction. OAT protein expression was determined in 55 cases of NSCLC and 17 cases of adjacent non-tumor lung tissues by immunohistochemical staining. The bioinformatic features and binary interactions of OAT were analyzed. Gene ontology annotation and signal pathway analysis were performed. RESULTS: OAT mRNA expression in A549 cells was 2.85-fold lower than that in 16HBE cells. OAT protein expression was significantly higher in NSCLC tissues than that in adjacent non-tumor lung tissues. A significant difference of OAT protein expression was existed between squamous cell lung cancer and adenocarcinoma (P < 0.05), but was not correlated with the gender, age, lymph node metastasis, tumor size, and TNM stages. Bioinformatic analysis suggested that OAT was a highly homologous and stable protein located in the mitochondria. An aminotran-3 domain and several sites of phosphorylation, which may function in signal transduction, gene transcription, and molecular transit, were found. In the 54 selected binary interactions of OAT, TNF and TRAF6 play roles in the NF-κB pathway. CONCLUSIONS: OAT may play an important role in the oncogenesis and progression of NSCLC. Thus, OAT may be a novel biomarker for the diagnosis of NSCLC or a new target for its treatment.