Boksoon Chang

Natural History of Pure Ground-Glass Opacity Lung Nodules Detected by Low-Dose CT Scan

BACKGROUND Although focal ground-glass opacity (GGO) lung nodules are generally reported to grow slowly, their natural course is unclear. The purpose of this study was to elucidate the natural course of screening-detected pure GGO lung nodules in patients with no history of malignancy. METHODS We retrospectively reviewed the database of subjects who had undergone screenings involving low-dose CT scans. We included patients with pure GGO lung nodules who were followed for > 2 years after the initial screening. RESULTS Between June 1997 and September 2006, 122 pure GGO nodules were found in 89 patients. The median nodule size was 5.5 mm (range, 3-20 mm) in the largest diameter on initial low-dose CT scan. The median follow-up period per patient was 59 months. On a per-person basis, the frequency of growth was 13.5% (12 of 89 patients). On a per-nodule basis, the frequency of growth was 9.8% (12 of 122 nodules). Nodule growth was significantly associated with initial size and new development of an internal solid portion. The median volume doubling time was 769 days for growing pure GGO nodules. A total of 11 growing nodules were surgically validated, and all lesions were confirmed as primary lung cancer. CONCLUSIONS About 90% of the screening-detected pure GGO lung nodules did not grow during long-term follow-up in subjects with no history of malignancy and most growing nodules had an indolent clinical course. A strategy of long-term follow-up and selective surgery for growing nodules should be considered for pure GGO lung nodules.

Increasing Recovery of Nontuberculous Mycobacteria from Respiratory Specimens over a 10-Year Period in a Tertiary Referral Hospital in South Korea

Background The number of patients with pulmonary disease caused by nontuberculous mycobacteria (NTM) has been increasing worldwide. The aim of this study was to evaluate long-term trends in the NTM recovery rate from respiratory specimens over a 10-year period in a tertiary referral hospital in South Korea. Methods We retrospectively reviewed the records of mycobacterial cultures of respiratory specimens at Samsung Medical Center from January 2001 to December 2011. Results During the study period, 32,841 respiratory specimens from 10,563 patients were found to be culture-positive for mycobacteria. These included 12,619 (38%) Mycobacterium tuberculosis and 20,222 (62%) NTM isolates. The proportion of NTM among all positive mycobacterial cultures increased from 43% (548/1,283) in 2001 to 70% (3,341/4,800) in 2011 (p<0.001, test for trend). The recovery rate of NTM isolates from acid-fast bacilli smear-positive specimens increased from 9% (38/417) in 2001 to 64% (1,284/1,997) in 2011 (p<0.001, test for trend). The proportion of positive liquid cultures was higher for NTM than for M. tuberculosis (p<0.001). The most frequently isolated NTM were Mycobacterium avium-intracellulare complex (53%) and Mycobacterium abscessus-massiliense complex (25%). Conclusion The recovery rate of NTM from respiratory specimens in South Korea has increased steadily.

Severe vitamin D deficiency is associated with non‐tuberculous mycobacterial lung disease: A case‐control study

Previous studies have found evidence of an association between tuberculosis and vitamin D deficiency (VDD). However, the association between VDD and infection caused by non‐tuberculous mycobacteria (NTM) has never been studied. This study evaluated the prevalence and severity of VDD in NTM lung disease and attempted to identify predictive factors.

Nontuberculous Mycobacterial Lung Disease Caused by Mycobacterium lentiflavum in a Patient with Bronchiectasis

We report a rare case of lung disease caused by Mycobacterium lentiflavum in a previously healthy woman. A 54-year-old woman was referred to our hospital due to chronic cough and sputum. A computed tomography scan of the chest revealed bilateral bronchiectasis with bronchiolitis in the right middle lobe and the lingular division of the left upper lobe. Nontuberculous mycobacteria were isolated twice from three expectorated sputum specimens. All isolates were identified as M. lentiflavum by multilocus sequence analysis based on rpoB, hsp65, and 16S rRNA fragments. To the best of our knowledge, this is the first documented case of M. lentiflavum lung disease in an immunocompetent adult in Korea.

Clinical significance of a single isolation of pathogenic nontuberculous mycobacteria from sputum specimens.

A single sputum culture positive for nontuberculous mycobacteria (NTM) could be an early sign of NTM lung disease. We found that 14% of patients with a single sputum culture positive for pathogenic NTM were diagnosed with NTM lung disease during the median follow-up period of 16 months.

Loculated Tuberculous Pleural Effusion: Easily Identifiable and Clinically Useful Predictor of Positive Mycobacterial Culture from Pleural Fluid

Background Isolation of M. tuberculosis (MTB) is required in cases of Tuberculous pleural effusion (TBPE) for confirming diagnosis and successful therapy based on drug sensitivity test. Several studies have focused on predictors of MTB culture positivity in TBPE. However, the clinical role of loculated TBPE as a predictor of MTB cultivation from TBPE remains unclear. The aim of this study was to examine possible predictors including loculation of TBPE of MTB culture positivity in TBPE. Methods We retrospectively examined associations between clinical, radiological, microbiological, and laboratory characteristics and positive MTB culture from TBPE to determine a potent predictor of culture positivity. Results From January 2011 to August 2015, 232 patients with TBPE were identified. Of these, 219 were finally analyzed. Among them, 69 (31.5%) were culture positive for MTB in TBPE and 86 (39.3%) had loculated TBPE. In multivariate logistic regression analysis, the loculation of TBPE was independently associated with culture positivity for MTB in TBPE (adjusted odds ratio [OR], 40.062; 95% confidence interval [CI], 9.355–171.556; p<0.001). In contrast, the lymphocyte percentage of TBPE (adjusted OR, 0.934; 95% CI, 0.899–0.971; p=0.001) was inversely associated with culture positivity for MTB in TBPE. Conclusion In clinical practice, identification of loculation in TBPE is easy, reliable to measure, not uncommon and may be helpful to predict the possibility of positive mycobacterial culture.

Biochemical fingerprints of human papillomavirus infection and cervical dysplasia using cervical fluids: Spectral pattern investigation

The Pap smear is the primary screening tool for invasive cervical cancer resulting from a persistent infection with oncogenic human papillomavirus (HPV); however, there are the problems such as the inability to distinguish between HPV infection and cervical dysplasia and a low sensitivity remain. We present preliminary findings of a label‐free method to detect and classify HPV infection and cervical dysplasia using human cervical fluids. Three experimental groups, defined as normal, HPV‐positive, and cervical dysplasia, were evaluated through their Raman spectral patterns for noise‐independence, high reproducibility, and uniformity. Clinical diagnosis was performed through liquid‐based cervical cytology, HPV test, and cervical histologic examination. Healthy cervical fluids showed a strong Raman intensity at 877 cm−1 (symmetric C–C stretching), and at 963 cm−1 (phosphate), compared to a reference Raman peak at 1003 cm−1 (phenylalanine symmetric ring breath). The HPV‐positive cervical fluids showed a strong intensity of a Raman peak at 1448 cm−1 corresponding to C–H deformation vibration mode and the highest similarity between the central and ring zones among the three groups. The cervical dysplasia fluids showed the presence of strong peaks compared to the control and HPV‐positive groups. In addition, different Raman spectra were acquired according to HPV type. Therefore, all ranges of cervical fluid‐induced Raman spectra could be used to detect the presence of cervical pre‐cancer. Raman peak‐gated assessment provides a label‐free and nondestructive tool for the clinical diagnosis of HPV infection and cervical precancerous changes.

A Case of Pleural Paragonimiasis Confused with Tuberculous Pleurisy

Here, we report a case of pleural paragonimiasis that was confused with tuberculous pleurisy. A 38-year-old man complained of a mild febrile sensation and pleuritic chest pain. Radiologic findings showed right pleural effusion with pleural thickening and subpleural consolidation. Adenosine deaminase (ADA) activity in the pleural effusion was elevated (85.3 IU/L), whereas other examinations for tuberculosis were negative. At this time, the patient started empirical anti-tuberculous treatment. Despite 2 months of treatment, the pleural effusion persisted, and video-assisted thoracoscopic surgery was performed. Finally, the patient was diagnosed with pleural paragonimiasis based on the pathologic findings of chronic granulomatous inflammation containing Paragonimus eggs. This case suggested that pleural paragonimiasis should be considered when pleural effusion and elevated ADA levels are observed.

Selective cytotoxic effect of non-thermal micro-DBD plasma.

Non-thermal plasma has been extensively researched as a new cancer treatment technology. We investigated the selective cytotoxic effects of non-thermal micro-dielectric barrier discharge (micro-DBD) plasma in cervical cancer cells. Two human cervical cancer cell lines (HeLa and SiHa) and one human fibroblast (HFB) cell line were treated with micro-DBD plasma. All cells underwent apoptotic death induced by plasma in a dose-dependent manner. The plasma showed selective inhibition of cell proliferation in cervical cancer cells compared to HFBs. The selective effects of the plasma were also observed between the different cervical cancer cell lines. Plasma treatment significantly inhibited the proliferation of SiHa cells in comparison to HeLa cells. The changes in gene expression were significant in the cervical cancer cells in comparison to HFBs. Among the cancer cells, apoptosis-related genes were significantly enriched in SiHa cells. These changes were consistent with the differential cytotoxic effects observed in different cell lines.

NANOG as an adverse predictive marker in advanced non-small cell lung cancer treated with platinum-based chemotherapy

Purpose NANOG is a master transcription factor that regulates stem cell pluripotency and cellular reprograming. Increased NANOG expression has been associated with poor survival in several human malignancies. However, the clinical significance of NANOG overexpression in lung cancer has been scarcely evaluated. The aim of this study was to investigate whether NANOG levels are associated with clinical outcomes of patients with non–small cell lung cancer (NSCLC) who were treated with platinum-based chemotherapy. Methods NANOG levels were evaluated immunohistochemically using the histologic score (H-score) in tumor tissues from patients with advanced NSCLC who received platinum-based doublet treatment. We performed survival analyses according to the NANOG levels and evaluated the association between clinicopathological parameters and levels of NANOG. Results Multivariate analyses using 112 tumor specimens showed that high NANOG levels were independently associated with short progression-free survival (hazard ratio [HR] =3.09, 95% confidence interval [CI]: 2.01–4.76) and with short overall survival (HR =3.00, 95% CI: 1.98–4.54). Similar results were shown in the subgroup analyses for patients with adenocarcinoma and squamous cell carcinoma. NANOG expression was not associated with any clinicopathological parameter such as age, gender, smoking status, stage, differentiation, or histological subtypes. Conclusion NANOG overexpression was associated with poor response and short overall survival in patients with advanced NSCLC who were treated with platinum-based chemotherapy, suggesting that NANOG could be a potential adverse predictive marker in this setting.