Jin Wook Moon

Impact of Environmental Tobacco Smoke on the Incidence of Mutations in Epidermal Growth Factor Receptor Gene in Never-Smoker Patients With Non–Small-Cell Lung Cancer

PURPOSE Active tobacco smoking has been associated with the incidence of epidermal growth factor receptor (EGFR) mutations. However, the impact of environmental tobacco smoke (ETS) on EGFR mutations has been unknown. We investigated an association between ETS exposure and EGFR mutations in never smokers with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS We enrolled 179 consecutive never smokers who were newly diagnosed with NSCLC. The history of ETS exposure was obtained with a standardized questionnaire that included exposure period, place, and duration. The nucleotide sequences of exons 18 to 21 on EGFR gene were determined using nested polymerase chain reaction amplification. RESULTS The incidence of EGFR mutations was significantly lower in patients with ETS exposure than in those without (38.5% v 61.4%; P = .008). In a logistic regression model that adjusted for sex and histology, an adjusted odds ratio (AOR) for the risk of EGFR mutations with exposure to ETS was 0.40 (95% CI, 0.20 to 0.81; P = .011). In quartile groups based on total smoker-year, the AORs for the lowest- to highest-quartile groups were 0.59 (95% CI, 0.23 to 1.49), 0.50 (95% CI, 0.17 to 1.50), 0.48 (95% CI, 0.20 to 1.18), and 0.22 (95% CI, 0.08 to 0.62; P(trend) = .028). Among the types of ETS exposure, adulthood ETS and household ETS were significantly associated with the incidence of EGFR mutations. Patients with ETS exposure showed a lower response rate to EGFR tyrosine kinase inhibitors than did patients without ETS exposure (24.6% v 44.8%; P = .053). CONCLUSION ETS exposure is negatively associated with EGFR mutations in never smokers with NSCLC.

Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

High tumor metabolic activity as measured by fluorodeoxyglucose positron emission tomography is associated with poor prognosis in limited and extensive stage small-cell lung cancer

Purpose: We investigated the prognostic effect of incorporating metabolic assessment by 18F-fluoro-2-deoxyglucose uptake on positron emission tomography/computed tomography (18F-FDG-PET/CT) into a conventional staging system in small-cell lung cancer (SCLC). Experimental Design: Seventy-six consecutive patients with pathologically proven SCLC were enrolled. All patients underwent standard treatment after pretreatment 18F-FDG-PET/CT scanning. The mean values of maximal standardized uptake values (meanSUVmax) of the malignant lesions upon 18F-FDG-PET/CT were calculated. The Cox proportional hazards model was used with performance status, lactate dehydrogenase, stage, and meanSUVmax. Results: Patients with high meanSUVmax were significantly related with the established poor prognostic factors, such as higher lactate dehydrogenase (P = 0.04) and extensive disease (ED; P = 0.01). Furthermore, in multivariate analysis, patients with high meanSUVmax were associated with poor survival outcomes compared with patients with low meanSUVmax [adjusted hazard ratio, 3.74; 95% confidence interval (95% CI), 1.67-8.37; P = 0.001, for death and adjusted hazard ratio, 2.25; 95% CI, 1.21-4.17; P = 0.01 for recurrence/progression]. In subgroup analysis, limited disease (LD) with high meanSUVmax showed significantly shorter overall survival than LD with low meanSUVmax [high versus low meanSUVmax, 20.1 months (95% CI, 7.9-23.2) versus 35.3 months (95% CI, 27.6-42.9); P = 0.02]. ED with high meanSUVmax had significantly shorter overall survival than ED with low meanSUVmax [high versus low meanSUVmax, 9.5 months (95% CI, 4.9-13.9) versus 17.7 months (95% CI, 12.0-20.1); P = 0.007]. These findings were replicated in progression-free survival analysis. Conclusions: In SCLC, tumor metabolic activity as assessed by FDG-PET is a significant prognostic factor and identifies subgroups of patients at higher risk of death in both LD and ED SCLC.

Frequent central nervous system failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors in Korean patients with nonsmall-cell lung cancer.

We investigated the risk of central nervous system (CNS) failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) in Korean patients with nonsmall‐cell lung cancer (NSCLC)

The Clinical Utility of Polymerase Chain Reaction for the Diagnosis of Pleural Tuberculosis

BACKGROUND There is no exact consensus about the usefulness of the Mycobacterium tuberculosis polymerase chain reaction (PCR) testing for the diagnosis of tuberculous pleural effusion because of the diverse PCR methods and the different diagnostic criteria that are described in other studies. METHODS We analyzed pleural effusion specimens obtained from 111 patients for whom the exclusion of the possibility of tuberculous pleural effusion was necessary. We performed M. tuberculosis PCR testing using the Cobas Amplicor MTB test (Roche Diagnostic Systems), which is fully automated and commercially available. RESULTS Results of the M. tuberculosis PCR test of pleural effusion specimens were positive for 7 (17.1%) of the 41 patients with confirmed pleural tuberculosis and for 3 (18.8%) of the 16 patients with probable pleural tuberculosis. The overall sensitivity and specificity of M. tuberculosis PCR testing of pleural effusion were 17.5% and 98.1%, respectively. The sensitivity of M. tuberculosis PCR testing for each group of patients with tuberculous pleural effusion detected by smear-positive results, smear-negative and culture-positive results, and culture-negative and pleural biopsy-positive results, was 100.0%, 33.3%, and 3.7%, respectively. Of the 57 patients with pleural tuberculosis, only 3 (5.3%) had positive results of M. tuberculosis PCR testing along with negative results of smearing, negative results of pleural pathological analysis, and a low level of adenosine deaminase. CONCLUSION For specimens such as pleural effusion, in which the bacillary load is very low, the clinical utility of PCR testing seems highly limited.

Promoter −202 A/C polymorphism of insulin-like growth factor binding protein-3 gene and non-small cell lung cancer risk

Insulin‐like growth factor binding protein‐3 (IGFBP‐3) inhibits the mitogenic and antiapoptotic activity of insulin‐like growth factor (IGF) by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP‐3 can enhance the activity of IGF by protecting IGF from degradation. More than half of the interindividual variations in IGFBP‐3 levels are known to be genetically determined by the polymorphism at −202 locus of IGFBP‐3 gene. Therefore, we attempted to ascertain whether the A−202C polymorphic variation of IGFBP‐3 gene constitutes a risk factor for non‐small cell lung cancer (NSCLC). Our study included 209 NSCLC patients and 209 age‐, gender‐ and smoking status‐matched control subjects. The frequencies of each polymorphic variation in the control population were as follows: AA = 95 (45.5%), AC = 91 (43.5%) and CC = 23 (11.0%). In the NSCLC subjects, the genotypic frequencies were as follows: AA = 131 (62.7%), AC = 73 (34.9%) and CC = 5 (2.4%). We detected statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p < 0.05, Pearsons chi‐square test). The NSCLC risk correlated significantly with AA genotype. Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 2.45 (95% CI = 1.17–5.40) and that for the ones with AA genotype was 4.58 (95% CI = 2.17–10.30). These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC and a potential target for novel antineoplastic therapies and/or preventative strategies in high‐risk groups.

Screening for latent tuberculosis infection in South Korean healthcare workers using a tuberculin skin test and whole blood interferon-γ assay

Abstract This study compared the results of a tuberculin skin test (TST) and a whole-blood interferon-γ release assay (IGRA) to screen latent tuberculosis (TB) infection (LTBI) according to risk of TB exposure in South Korea. A cross-sectional comparison of 82 healthcare workers (HCWs) was performed from June 2009 to January 2010. Participants were grouped according to their risk for TB exposure: group 1, frequent and direct contact with active TB patients (n = 35); group 2, no known history of direct contact with active TB patients (n = 47). For the TST (10-mm induration cut-off), the positive response rate was 42.9% in group 1 and 34.0% in group 2 (p = 0.42). For the IGRA, the positive response rate was 40% in group 1 and 10.6% in group 2 (p = 0.002). Results obtained from the TST and the IGRA were not in significant agreement. The working duration of HCWs in TB-related departments was the only significant risk factor for LTBI (odds ratio 1.03; p = 0.031). Further, the IGRA can more accurately discriminate LTBI compared to the TST, based on the risk of TB exposure. These results suggest that the IGRA is diagnostically useful for LTBI in South Korean HCWs.

Computed tomographic fluoroscopy-guided needle aspiration biopsy as a second biopsy technique after indeterminate transbronchial biopsy results for pulmonary lesions: comparison with second transbronchial biopsy.

Objective: The purpose of this study was to compare the diagnostic performance of computed tomographic (CT) fluoroscopy-guided percutaneous transthoracic needle aspiration biopsy (NAB) and transbronchial lung biopsy (TBLB) after indeterminate bronchoscopy in patients with suspected malignant pulmonary lesions. Methods: We included 77 patients who underwent CTF-NAB (n = 53) or TBLB (n = 24) as a second biopsy for pulmonary lesions because of inconclusive pathologic results on initial TBLB. Sensitivity, specificity, and diagnostic accuracy were calculated and compared between the 2 groups using the Fisher exact test. Sensitivity and diagnostic accuracy were also compared according to lesion depth (central vs peripheral), lesion location (upper vs lower), and lesion size (<2 vs 2-3 vs >3 cm). Results: There were 50 (65%) malignant and 27 (35%) benign lesions. The overall sensitivity, specificity, and accuracy for diagnosing pulmonary lesions were 84%, 100%, and 91% for NAB and 50%, 100%, and 63% for TBLB. The sensitivity and accuracy for diagnosing pulmonary lesions were significantly different between the 2 groups (P = 0.019, and P = 0.008). The sensitivity and accuracy of TBLB for diagnosing lesions was significantly different according to the lesion size (P = 0.025, and P = 0.048). Conclusion: A second biopsy using CT fluoroscopy-guided NAB is a useful diagnostic modality for exact diagnosis of pulmonary lesions in cases of inconclusive pathologic results on initial TBLB.