Jiajun Teng

Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing intrathoracic tuberculosis.

BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has enabled mediastinal and hilar lymph node assessment with a high sensitivity, but its role in the diagnosis of intrathoracic tuberculosis (TB) has not been established. METHODS We prospectively studied 59 patients suspected of having TB with thoracic lymph node lesions or intrapulmonary lesions accessible by EBUS-TBNA at a clinical center for thoracic medicine from January 2010 to December 2011. Bronchoscopic findings, EBUS-TBNA procedures, pathologic findings, and microbiologic results were recorded. RESULTS Of 59 eligible patients, 41 patients had TB, 5 had lung cancer, 7 had inflammation, and 6 had sarcoidosis. Sensitivity was 85%, specificity was 100%, positive and negative predictive values were 100% and 75%, respectively, and accuracy was 90% by EBUS-TBNA for TB. Pathologic findings were consistent with TB in 80% of patients (33 of 41), and in 27% (11 of 41) the smear was positive. A total of 37 patients with TB had cultures, of whom 17 (46%) were positive. There were 80 mediastinal and hilar lymph nodes and 5 intrapulmonary lesions that were biopsied in the 41 patients with TB. Multivariate logistic regression revealed that short-axis diameter was an independent risk factor associated with positive pathology, smear, and culture (p < 0.05). Additionally, pathology showing necrosis was an independent risk factor associated with a positive culture. CONCLUSIONS Endobronchial ultrasound-guided transbronchial needle aspiration has a high diagnostic yield in the investigation of suspected intrathoracic TB by means of aspiration of intrathoracic lymph nodes and tracheobronchial wall-adjacent lung lesions.

Sonographic Features of Endobronchial Ultrasonography Predict Intrathoracic Lymph Node Metastasis in Lung Cancer Patients

BACKGROUND Intrathoracic lymph node sampling by endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) has become a standard of care in staging lung cancer. This study aimed to assess the efficacy of utilizing the individual sonographic features of lymph nodes for predicting metastasis in lung cancer patients. METHODS From January 2010 to May 2012, we retrospectively studied 459 metastatic lymph nodes in 298 lung cancer patients and 176 reactive lymph nodes in 90 patients with nonspecific inflammation. Digital videos of the lymph nodes were obtained during EBUS-TBNA and categorized according to the following characteristics: size, shape, margin, central hilar structure, echogenicity, necrosis sign, matting, calcification, and vascular patterns. The sonographic findings were compared with the final pathology results and clinical follow-up. RESULTS Multivariate analysis revealed five independent predictive factors for lymph node metastasis: long axis, round shape, absence of central hilar structure, presence of matting, and nonhilar vascular pattern perfusion. An aggregate score system based on the odds ratio was developed and reduced the criteria to four factors: presence of matting, nonhilar vascular pattern perfusion, absence of central hilar structure, and round shape. It showed at least two of four independent predictive factors could obtain the best performance for predicting metastatic lymph nodes and yield a high sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of 93.03%, 55.68%, 84.55%, 75.38%, and 82.68%, respectively. CONCLUSIONS Sonographic features of the EBUS images can differentiate metastatic from reactive lymph nodes, so it may help predict intrathoracic lymph nodes metastasis in lung cancer patients.

Determining Factors in Diagnosing Pulmonary Sarcoidosis by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

BACKGROUND Although the role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in pulmonary sarcoidosis has previously been investigated, the determining factors in diagnosing sarcoidosis by EBUS-TBNA without rapid on-site evaluation (ROSE) are unclear. METHODS Patients with clinically and radiographically suspected sarcoidosis underwent EBUS-TBNA without ROSE in a prospective study. Presence of non-caseating epithelioid cell granulomas was pathologic evidence of sarcoidosis. RESULTS The EBUS-TBNA was performed in 120 patients, 111 of whom had confirmed sarcoidosis. For the patients with sarcoidosis (62 stage I, 49 stage II) EBUS-TBNA provided sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.69%, 100%, 100%, 56.25%, and 94.17%, respectively, in the diagnosis of sarcoidosis. Diagnostic yield of EBUS-TBNA for sarcoidosis was associated with disease stage, but not associated with serum angiotensin converting enzyme level, number of lymph node stations sampled per patient, or total number of passes performed per patient. At EBUS-TBNA, 284 mediastinal and hilar lymph nodes were aspirated in 111 patients. Multivariate logistic regression revealed that short-axis diameter and more than 1 needle pass per lymph node were independent risk factors associated with positive pathology. No major procedure-related complications were observed. CONCLUSIONS Endobronchial ultrasound-guided transbronchial needle aspiration is a safe procedure with high sensitivity for diagnosing sarcoidosis, having a higher diagnostic yield in stage I than stage II. To obtain a higher diagnostic yield of EBUS-TBNA in pulmonary sarcoidosis without ROSE, operators should select the largest mediastinal or hilar lymph node accessible and puncture with 3 to 5 passes.

Endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of non-lymph node thoracic lesions

AIMS: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has shown excellent diagnostic capabilities for mediastinal and hilar lymphadenopathy. However, its value in thoracic non-lymph node lesions is less clear. This study was designed to assess the value of EBUS-TBNA in distinguishing malignant from benign thoracic non-lymph node lesions. METHODS: From October 2009 to August 2011, 552 patients underwent EBUS-TBNA under local anesthesia and with conscious sedation. We retrospectively reviewed 81 of these patients who had tracheobronchial wall-adjacent intrapulmonary or isolated mediastinal non-lymph node lesions. On-site cytological evaluation was not used. Immunohistochemistry (IHC) was performed to distinguish the origin or type of malignancy when necessary. RESULTS: EBUS-TBNA was performed in 68 tracheobronchial wall-adjacent intrapulmonary and 13 isolated mediastinal non-lymph node lesions. Of the 81 patients, 77 (95.1%, 60 malignancies and 17 benignancies) were diagnosed through EBUS-TBNA, including 57 primary lung cancers, 2 mediastinal tumors, 1 pulmonary metastatic adenocarcinoma, 7 inflammation, 5 tuberculosis, 3 mediastinal cysts, 1 esophageal schwannoma, and 1 focal fibrosis. There were four false-negative cases (4.9%). Of the 60 malignancies, there were 9 (15.0%) which originally had no definite histologic origin or type. Thus, IHC was performed, with 7 (77.8%) being subsequently confirmed. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in distinguishing malignant from benign lesions were 93.4% (60/64), 100% (17/17), 100% (60/60), 81.0% (17/21), and 95.1% (77/81), respectively. CONCLUSION: EBUS-TBNA is a safe procedure with a high sensitivity for distinguishing malignant from benign thoracic non-lymph node lesions within the reach of EBUS-TBNA, with IHC usually providing a more definitive diagnosis.

Comparison of plasma and tissue samples in epidermal growth factor receptor mutation by ARMS in advanced non-small cell lung cancer.

OBJECTIVE The aim of this study was to assess the effectiveness and accuracy of blood-based circulating-free tumor DNA on testing epidermal growth factor receptor (EGFR) gene mutations. METHODS In total, 219 non-small cell lung cancer patients in stages III-IV were enrolled into this study. All patients had tissue samples and matched plasma DNA samples. EGFR gene mutations were detected by the Amplification Refractory Mutation System (ARMS). We compared the mutations in tumor tissue samples with matched plasma samples and determined the correlation between EGFR mutation status and clinical pathologic characteristics. RESULT The overall concordance rate of EGFR mutation status between the 219 matched plasma and tissue samples was 82% (179/219). The sensitivity and specificity for the ARMS EGFR mutation test in the plasma compared with tumor tissue were 60% (54/90) and 97% (125/129), respectively. The positive predictive value was 93% (54/58) and the negative predictive value was 78% (125/161). The median overall survival was longer for those with EGFR mutations than for those without EGFR mutations both in tissue samples (23.98 vs. 12.16months; P<0.001) and in plasma (19.96 vs. 13.63months; P=0.009). For the 68 patients treated with EGFR- tyrosine kinase inhibitors (TKIs), the median progression-free survival (PFS) was significantly prolonged in the EGFR mutant group compared to the non-mutation group in tumor tissue samples (12.26months vs. 2.40months, P<0.001). In plasma samples, the PFS of the mutant group was longer than that of the non-mutant group. However, there was no significant difference between the two groups (10.88months vs. 9.89months, P=0.411). CONCLUSIONS The detection of EGFR mutations in plasma using ARMS is relatively sensitive and highly specific. However, EGFR mutation status tested by ARMS in plasma cannot replace a tumor tissue biopsy. Positive EGFR mutation results detected in plasma are fairly reliable, but negative results are hampered by a high rate of false negatives.

Serum dickkopf-1 as a clinical and prognostic factor in non-small cell lung cancer patients with bone metastases

Background The study was designed to evaluate the association between serum dickkopf-1 (DKK1) and non-small cell lung cancer (NSCLC) bone metastases. Materials and Methods Serum DKK1 levels were quantified in 470 NSCLC patients, 140 with osseous metastases, 178 with extraosseous metastases, and 152 with early stage in complete remission. The Receiver Operating Characteristic (ROC) curve enabled us to identify a threshold value to distinguish patients with bone metastases. Results Serum DKK1 levels in patients with osseous metastases were significantly higher than in the other 2 groups (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 pg/ml (area under curve 0.791, 95% confidence interval 0.739–0.843, sensitivity 77.1% and specificity 71.4%). Of interest, serum DKK1 correlated with the number of bone lesions (P = 0.042) and associated with the poor survival in NSCLC patients with osseous metastases (P = 0.029). Conclusions Our data shows that serum DKK1 can be used for the detection of NSCLC bone metastases. More importantly this is the first report to show that serum DKK1 is a good predictor of poor prognosis in NSCLC patients with bone metastases.BACKGROUND The study was designed to evaluate the association between serum Dickkopf-1(DKK1)and non-small cell lung cancer(NSCLC) bone metastases. MATERIALS AND METHODS Serum DKK1 levels were quantified in 470 NSCLC patients, 140 with osseous metastases, 178 with extraosseous metastases, and 152 with early stage in complete remission. The Receiver Operating Characteristic (ROC) curve enabled us to identify a threshold value to distinguish patients with bone metastases. RESULTS Serum DKK1 levels in patients with osseous metastases were significantly higher than in the other 2 groups (P < 0.001). ROC curves showed that the optimum cutoff was 311.8 pg/ml (area under curve 0.791, 95% confidence interval 0.739-0.843, sensitivity 77.1% and specificity 71.4%). Of interest, serum DKK1 correlated with the number of bone lesions (P = 0.042) and associated with the poor survival in NSCLC patients with osseous metastases (P = 0.029). CONCLUSIONS Our data shows that serum DKK1 can be used for the detection of NSCLC bone metastases. More importantly this is the first report to show that serum DKK1 is a good predictor of poor prognosis in NSCLC patients with bone metastases.

Community-based lung cancer screening with low-dose CT in China: Results of the baseline screening

OBJECTIVES To investigate whether low-dose computed tomography (LDCT) screening is capable of enhancing the detection rate of early-stage lung cancer in high-risk population of China with both smoking and non-smoking related factors. METHODS From 2013-2014, eligible participants with high-risk factors of lung cancer were randomly assigned to a screening group or a control group with questionnaire inquiries. Any non-calcified nodules or masses with longest diameters of ≥4 mm identified on LDCT images were considered as positive. RESULTS A total of 6717 eligible participants were randomly enrolled to a study group (3550 to LDCT screening and 3167 to standard care). 3512 participants (98.9%) underwent LDCT screening, and 3145 participants (99.3%) received questionnaire inquiries. A positive screening result was observed in 804 participants (22.9%). In the two-year follow-up period, lung cancer was detected in 51 participants (1.5%) in the LDCT group versus 10 (0.3%) in the control group (stage I: 48 vs 2; stage II to IV or limited stage: 3 vs 8), respectively. Early-stage lung cancer was found in 94.1% vs 20%, respectively. CONCLUSIONS Compared to usual care, LDCT led to a 74.1% increase in detecting early-stage lung cancer. This study provides insights about the non-smoking related risk factors of lung cancer in the Chinese population.

Utility of endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing non-specific inflammatory intrathorcacic lymphadenitis

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has emerged as a minimally invasive technique for diagnosing intrathoracic malignancies and some benignancies; however, there are no data available on the utility of EBUS‐TBNA for the diagnosis of non‐specific inflammatory intrathoracic lymphadenitis.

Potential Antitumor Activity of SIM-89 in Non-Small Cell Lung Cancer Cells.

Purpose c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. Materials and Methods Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. Results c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC50 values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. Conclusion In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting its potential antitumor activity.

Lentivirus-mediated knockdown of CTDP1 inhibits lung cancer cell growth in vitro.

AbstractBackground CTDP1 catalyzes serine phosphorylation and dephosphorylation of the mobile carboxy-terminal domain of the RNA polymerase II. It is conserved among eukarya and is essential for cell growth for its ability in regulation of transcription machinery. However, its function in the process of tumorigenesis is unclear. In the present study, we aim to explore the roles of CTDP1 in the progression of human lung cancer. To our knowledge, this is the first study that reports the functions of CTDP1 in human lung cancer.Methods We first detected the expression level of CTDP1 in four human lung cancer cell lines: H-125, H1299, LTEP-A-2 and NCI-H446 by semiquantitative RT-PCR. We compared the expression level of CTDP1 in lung cancer tissues and paired adjacent normal tissues on 29 pathologically confirmed patients by real-time quantitative PCR. To further explore the effect of CTDP1 on cell proliferation, a lentiviral vector expressing CTDP1 short hairpin RNA (shRNA) was constructed and infected into human lung cell lines H1299. Interference efficiency was determined by western blot analysis and real-time quantitative PCR. The effects of knockdown of CTDP1 on cell growth, cell cycle and apoptosis and cell colony formation were explored by Cellomics, fluorescence-activated cells sorting and fluorescence microscopy, respectively.ResultsCTDP1 was expressed in all four human lung cancer cell lines. The expression of CTDP1 in tumor tissues was significantly higher than paired adjacent normal tissues in 29 patients with lung cancer. The expression of CTDP1 was markedly reduced in cells infected with lentivirus delivering shRNA against CTDP1. Inhibition of CTDP1 expression significantly suppressed cell growth, induced G0/G1 phase arrest and repressed cell colony formation.ConclusionsOur results demonstrated that CTDP1 was upregulated in human lung cancer tissues. In addition, it implied that CTDP1 played an important role in cell proliferation and may be a useful therapeutic target in human lung cancer.