EBUS-centred versus EUS-centred mediastinal staging in lung cancer: a randomised controlled trial.

BACKGROUND: The impact of procedure sequence and primary procedure has not been studied in the combined application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in lung cancer staging. METHODS: In a randomised controlled trial, 160 patients with histologically confirmed or strongly suspected potentially operable non-small cell lung cancer were enrolled (Group A, n=80, EBUS-centred; Group B, n=80, EUS-centred). EBUS-TBNA and EUS-FNA with an ultrasound bronchoscope were used as the first procedures in Groups A and B, respectively, and secondary procedures (EUS-FNA in Group A, EBUS-TBNA in Group B) were added. RESULTS: Diagnostic values were evaluated in 148 patients (74 in each group). In Groups A and B the diagnostic accuracy (93.2% (95% CI 87.5% to 99.0%) vs 97.3% (95% CI 93.6% to 101.0%), p=0.245) and sensitivity (85.3% (95% CI 68.9% to 95.0%) vs 92.0% (95% CI 74.0% to 99.0%), p=0.431) in detecting mediastinal metastasis were not statistically different. In Group A, adding EUS-FNA to EBUS-TBNA did not significantly increase the accuracy (from 91.9% to 93.2%, p=0.754) or sensitivity (from 82.4% to 85.3%, p=0.742). In group B, adding EBUS-TBNA to EUS-FNA increased the accuracy (from 86.5% to 97.3%, p=0.016) and sensitivity (from 60.0% to 92.0%, p=0.008). There were no intergroup differences in procedure time, cardiorespiratory parameters during procedures, complications or patient satisfaction. CONCLUSIONS: Using a combination of EBUS-TBNA and EUS-FNA in mediastinal staging, we found that diagnostic values and patient satisfaction were not different between the EBUS-centred and EUS-centred groups. However, the necessity for EBUS-TBNA following EUS suggests that EBUS-TBNA is a better primary procedure in endoscopic mediastinal staging of potentially operable lung cancer. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT01385111.

A case of human pulmonary dirofilariasis in a 48-year-old Korean man.

Dirofilariasis is a rare disease in humans. We report here a case of a 48-year-old male who was diagnosed with pulmonary dirofilariasis in Korea. On chest radiographs, a coin lesion of 1 cm in diameter was shown. Although it looked like a benign inflammatory nodule, malignancy could not be excluded. So, the nodule was resected by video-assisted thoracic surgery. Pathologically, chronic granulomatous inflammation composed of coagulation necrosis with rim of fibrous tissues and granulations was seen. In the center of the necrotic nodules, a degenerating parasitic organism was found. The parasite had prominent internal cuticular ridges and thick cuticle, a well-developed muscle layer, an intestinal tube, and uterine tubules. The parasite was diagnosed as an immature female worm of Dirofilaria immitis. This is the second reported case of human pulmonary dirofilariasis in Korea.

Vitamin D deficiency and changes in serum vitamin D levels with treatment among tuberculosis patients in South Korea.

BACKGROUND AND OBJECTIVE: Vitamin D deficiency has been reported to be associated with the development of active tuberculosis (TB), but many discrepancies exist among studies. The aims of this study were to compare the frequency of vitamin D deficiency in a Korean population of TB patients and control subjects, and to monitor the changes in vitamin D levels during TB treatment. METHODS: Patients with newly diagnosed TB were prospectively enrolled. In addition, healthy volunteers or patients with diseases other than TB were enrolled as controls. Baseline serum 25-hydroxyvitamin D (25-OHD) levels were measured in both groups and compared. In the TB patients, measurements of serum 25-OHD were repeated 1 month after the initiation of treatment and again after completion of treatment. RESULTS: In total, 116 patients with TB and 86 control subjects were recruited. The median 25-OHD concentration was not different in TB patients at diagnosis (13.9 ng/mL; interquartile range (IQR) 8.80-21.8) compared with control subjects (13.2 ng/mL; IQR 9.6-19.3) (P = 0.97). The frequency of vitamin D deficiency (≤ 10 ng/mL) was also not different in TB patients (36.2%) compared with controls (27.3%) (P = 0.21). In TB patients, the median 25-OHD concentration decreased significantly during treatment, to 12.5 ng/mL at 1 month and 11.0 ng/mL on completion of treatment (P = 0.01). CONCLUSIONS: Vitamin D levels do not appear to be associated with the development of TB in the Korean population. The median 25-OHD concentration decreased after treatment for TB.

Cereblon contributes to the development of pulmonary fibrosis via inactivation of adenosine monophosphate-activated protein kinase α1.

Pulmonary fibrosis is a progressive and lethal lung disease characterized by the proliferation and differentiation of lung fibroblasts and the accumulation of extracellular matrices. Since pulmonary fibrosis was reported to be associated with adenosine monophosphate-activated protein kinase (AMPK) activation, which is negatively regulated by cereblon (CRBN), we aimed to determine whether CRBN is involved in the development of pulmonary fibrosis. Therefore, we evaluated the role of CRBN in bleomycin (BLM)-induced pulmonary fibrosis in mice and in transforming growth factor-beta 1 (TGF-ß1)-induced differentiation of human lung fibroblasts. BLM-induced fibrosis and the mRNA expression of collagen and fibronectin were increased in the lung tissues of wild-type (WT) mice; however, they were significantly suppressed in Crbn knockout (KO) mice. While the concentrations of TGF-ß1/2 in bronchoalveolar lavage fluid were increased via BLM treatment, they were similar between BLM-treated WT and Crbn KO mice. Knockdown of CRBN suppressed TGF-ß1-induced activation of small mothers against decapentaplegic 3 (SMAD3), and overexpression of CRBN increased it. TGF-ß1-induced activation of SMAD3 increased α-smooth muscle actin (α-SMA) and collagen levels. CRBN was found to be colocalized with AMPKα1 in lung fibroblasts. CRBN overexpression inactivated AMPKα1. When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of α-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-ß1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKα1 inactivation. Taken together, these data suggest that CRBN is a profibrotic regulator and maybe a potential target for treating lung fibrosis.

Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer.

PURPOSE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used for the diagnosis and staging of lung cancer. However, evidence of its usefulness for re-biopsy in treated lung cancer, especially according to the previous treatment, is limited. We evaluated the role of EBUS-TBNA for re-biopsy and its diagnostic values in patients with different treatment histories. MATERIALS AND METHODS: We reviewed the medical records of patients who underwent EBUS-TBNA for re-biopsy of suspicious recurrent or progressive lesions between January 2006 and December 2016 at the National Cancer Center in South Korea. Patients were categorized into three groups based on the previous treatment modalities: surgery, radiation, and palliation. RESULTS: Among the 367 patients (surgery, n=192; radiation, n=40; palliation, n=135) who underwent EBUS-TBNA for re-biopsy, the overall sensitivity, negative predictive value (NPV), and diagnostic accuracy of EBUS-TBNA in detecting malignancy were 95.6%, 82.7%, and 96.3%, respectively. The sensitivity was lower in the radiation group (83.3%) when compared with the surgery (95.7%, p=0.042) and palliation (97.7%, p=0.012) groups. The NPV was lower in the palliation group (50.0%) than in the surgery group (88.5%, p=0.042). The sample adequacy of EBUS-TBNA specimens was lower in the radiation group (80.3%) than in the surgery (95.4%, p < 0.001) or palliation (97.8%, p < 0.001) groups. EGFR mutation analysis was feasible in 94.6% of the 92 cases, in which mutation analysis was requested. There were no major complications. Minor complications were reported in 12 patients (3.3%). CONCLUSION: EBUS-TBNA showed high diagnostic values and high suitability for EGFR mutation analysis with regard to re-biopsy in patients with previously treated lung cancer. The sensitivity was lower in the radiation group and NPV was lower in the palliation group. The complication rate was low.

WITHDRAWN:The Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Re-biopsy in Previously Treated Lung Cancer.

Ahead of Print article withdrawn by publisher.

Comparison of Epidermal Growth Factor Receptor Mutations between Metastatic Lymph Node Diagnosed by EBUS-TBNA and Primary Tumor in Non-Small Cell Lung Cancer.

INTRODUCTION: Although the use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is increasing for epidermal growth factor receptor (EGFR) testing in lung cancer, the discordance rate in EGFR mutations between lymph node (LN) samples obtained by EBUS-TBNA and primary tumor (PT) is not well known. Thus, we compared the EGFR mutation status of LN samples obtained by EBUS-TBNA and PTs to estimate the efficacy of using EBUS-TBNA specimens for EGFR testing in advanced, non-squamous, non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Using data of patients from the EBUS-TBNA database (N = 1914) obtained between January 2009 and January 2013, we identified 100 treatment-naïve, advanced, non-squamous NSCLC patients (stage 3 and 4) with matched LN specimens obtained by EBUS-TBNA and PT specimens. Of these, 74 patients with paired specimens were feasible for EGFR mutation analysis, which we performed using a direct sequencing method. RESULTS: Of the 74 cases, at least one major [exon 19 deleted (19del) and L858R] or minor (T790M, exon 20 insertion, and other point mutations) EGFR mutation was detected in 31 cases (41.9%), which included PT (n = 31, 41.9%) and LN (n = 28, 37.8%) specimens. Major mutations were detected in 25 PT (33.8%, 19del = 13, L858R = 12) and 22 LN (29.8%, 19del = 11, L858R = 11) specimens. The discordance rate in major mutations between matched PT and LN specimens was 4.1% (3/74). Among minor mutations, T790M was detected in LN specimen only in 2 cases with L858R in PT and LN. The discordance rate major and minor EGFR mutations combined between matched PT and LN specimens was 12% (9/74). CONCLUSIONS: We observed a high concordance rate of major EGFR mutations between matched LN specimens sampled by EBUS-TBNA and PTs, suggesting that LN samples obtained by EBUS-TBNA from advanced non-squamous NSCLC patients are effective for use in EGFR mutation testing.

Comparison of clinical characteristics between patients with ALK-positive and EGFR-positive lung adenocarcinoma.

BACKGROUND: The discovery of the chromosomal fusion product of anaplastic lymphoma kinase (ALK) with echinoderm microtubule-associated protein-like 4 (EML4) (EML4-ALK) has changed the treatment paradigm of lung cancer. In this study, we analysed the clinical characteristics, including bronchoscopic findings, of patients with EML4-ALK-positive adenocarcinoma and compared them with those of EGFR mutation-positive patients. MATERIALS AND METHODS: In this retrospective cohort study, the clinical characteristics and bronchoscopic findings of patients with ALK fusion-positive lung cancers were compared to patients with EGFR-mutant lung cancers. RESULTS: Among the 440 patients with adenocarcinoma of lung screened for this study, 46 (10.4%) harboured the EML4-ALK fusion, 90 (20.4%) harboured an activating EGFR mutation, and all had adenocarcinoma. In univariate analysis, ALK-positive patients were significantly younger than EGFR-positive patients (p = 0.004) and were more commonly male (p = 0.021). An initial status of stage IV metastatic cancer was more frequently noted in EML4-ALK-positive patients (p = 0.012), with initial brain metastasis frequently observed (p = 0.007). Compared with EGFR-positive patients, EML4-ALK-positive patients were significantly more likely to have positive bronchoscopic findings, which suggested a more centralized origin (p = 0.001). EML4-ALK patients also had significantly more positive bronchoscopic findings and were more commonly male in multivariate analysis. CONCLUSIONS: The EML4-ALK fusion defines a new molecular subset of NSCLC that has distinct clinical and bronchoscopic findings suggesting more proximal origin when compared to tumours harbouring EGFR mutations.

The impact of lifestyle behaviors on the acquisition of pandemic (H1N1) influenza infection: a case-control study.

PURPOSE: The purpose of this study was to evaluate the effects of lifestyle behaviors and health habits on the risk for acquiring pandemic influenza (H1N1) virus infection. MATERIALS AND METHODS: We conducted a case-control study in a secondary care hospital in South Korea between November 2009 and August 2010. We enrolled patients with H1N1 infection, as confirmed by a positive result of the real-time reverse transcriptase polymerase chain reaction assay; for each patient, we enrolled 4 age- and gender-matched controls with no history of H1N1 infection or severe acute respiratory illness during the H1N1 pandemic in South Korea (1:4 match). RESULTS: During the study period, 33 cases and 132 age- and gender-matched controls were enrolled. The case group had a higher percentage of current smokers (p<0.01), fewer subjects reporting regular physical activity (p=0.03), or regular vitamin supplementation (p<0.01), and more subjects reporting a higher annual incidence of the common cold (p=0.048) as compared to the control group. In the multivariable analysis, 2 factors were independently associated with the acquisition of H1N1 infection: current smoking [adjusted odds ratio (OR)=5.53; 95% confidence interval (CI), 1.60-19.16; p<0.01] and a higher annual incidence of the common cold (adjusted OR=1.24; 95% CI, 1.002-1.53; p=0.048). CONCLUSION: A current smoking status and a history of frequent colds were associated with an increased risk of acquiring H1N1 infection.

Technical aspects of endobronchial ultrasound-guided transbronchial needle aspiration.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is becoming a standard method for invasive mediastinal staging and for the diagnosis of paratracheal and peribronchial lesions. It is essential to understand the technical aspects of EBUS-TBNA to ensure safe and efficient procedures. In this review, we discuss the practical aspects to be considered during EBUS-TBNA, including anesthesia, manipulation of equipment, understanding mediastinal ultrasound images, target selection, number of aspirations needed per target, sample handling, and complications.

Adverse pulmonary reactions associated with the use of monoclonal antibodies in cancer patients.

BACKGROUND: The incidence and clinical characteristics of adverse pulmonary reactions resulting from anticancer monoclonal antibody (mAbs) therapy have not been well described. We determined the incidence and clinical characteristics of adverse pulmonary reactions in patients treated with anticancer chemotherapy including mAbs. METHODS: A retrospective cohort study was performed including patients who were treated with a chemotherapeutic regimen that included rituximab, trastuzumab, cetuximab, or bevacizumab at Seoul National University Hospital between January 1, 2004 and December 31, 2008. Rates of adverse pulmonary reactions classified as non-infectious and infectious complications were compared with those among patients treated with comparable regimens without mAbs. RESULTS: In total, 1078 patients were included (418 for rituximab, 329 for trastuzumab, 122 for cetuximab, 209 for bevacizumab). Adverse pulmonary reactions were identified in 36 patients (3.5%) and the incidence differed among agents: cetuximab (9%), rituximab (5.3%), trastuzumab (0.6%), bevacizumab (0.5%). Infectious pulmonary complications occurred in 28 patients, and eight patients experienced non-infectious pulmonary complications, most commonly interstitial lung disease (6 patients). In a multivariate analysis, low serum albumin level was associated with the development of pulmonary complications. The incidence of overall adverse pulmonary reactions did not differ between the mAbs users and the 1012 patients treated with comparable regimens other than mAbs (3.5% vs. 2.8%, P=0.53). CONCLUSIONS: Infectious and non-infectious adverse pulmonary reactions occur in patients with cancer who are administered a regimen including mAbs. Clinicians should be alert for the possibility of pulmonary adverse reactions, particularly among patients with low serum albumin levels.