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BACKGROUND Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) may be necessary for patients with incidental lung cancer during or after coronary intervention. Although EBUS-TBNA is quite safe, the safety in patients who recently received percutaneous coronary intervention (PCI) has not been demonstrated. The aim of this study was to assess the safety of EBUS-TBNA in patients with lung cancer who underwent PCI within one year. METHODS We retrospectively reviewed the medical records of 24 patients who underwent EBUS-TBNA within one year after PCI between May 2009 and June 2017. Cardiovascular complications (death, myocardial infarction, arrhythmia, and acute heart failure) were assessed as primary outcomes. Procedural-related complications were assessed as secondary outcomes. RESULTS The coronary artery diseases requiring PCI were: myocardial infarction (n = 10), unstable angina (n = 10), stable angina (n = 2), and silent ischemia (n = 2). The median interval between PCI and EBUS-TBNA was 125 days (interquartile range: 66-180). Atrial fibrillation with a rapid ventricular response temporarily occurred in one patient after EBUS-TBNA. No other significant cardiovascular complications were encountered. Fifteen patients were administered an anti-thrombotic agent the day of EBUS-TBNA, while four had ceased taking the agent < 4 days before EBUS-TBNA, however, there was no significant bleeding among those patients. CONCLUSION EBUS-TBNA was safe and did not cause serious adverse events in patients with lung cancer who required tissue confirmation or mediastinal staging within one year after PCI. Incidental lung cancer found during or after a coronary intervention should be actively evaluated by EBUS-TBNA.

Objectives The relationship between transthoracic needle biopsy (TTNB) and pleural recurrence of cancer after curative lung resection remains unclear. We aimed to assess whether TTNB increases the ipsilateral pleural recurrence (IPR) rate and identify other potential risk factors for pleural recurrence after surgery. Materials and methods This retrospective study included 392 patients with p-stage I non-small cell lung cancer with solid or part-solid nodules after curative lung resection in 2009–2010. Imbalances among the characteristics were adjusted using an inverse probability-weighted method based on propensity scoring. Multivariate Cox’s regression analysis and the Kaplan-Meier method were used to determine independent risk factors for IPR. Results A total of 243 (62%) patients received TTNB, while 149 (38%) underwent an alternate, or no, diagnostic technique. IPR was significantly more frequent in the TTNB group (p = 0.004), while total recurrence was similar between the groups (p = 0.098). After applying the weighted model, diagnostic TTNB (hazard ratio [HR], 5.27; 95% confidence interval [CI], 1.49–18.69; p = 0.010), microscopic visceral pleural invasion (HR, 2.76; 95% CI, 1.08–7.01; p = 0.033) and microscopic lymphatic invasion (HR, 3.25; 95% CI, 1.30–8.10; p = 0.012) were associated with an increased frequency of IPR. Among patients who received TTNB, microscopic lymphatic invasion was a risk factor for IPR (HR, 2.74; 95% CI, 1.10–6.79; p = 0.030). Conclusions The diagnostic TTNB procedure is associated with pleural recurrence but may be unrelated to overall recurrence-free survival in early lung cancer. Moreover, microscopic lymphatic invasion could be a risk factor for pleural recurrence. TTNB should be carefully considered before lung resection and close follow-up to detect if pleural recurrence is needed.

To evaluate clinical presentations, treatment modalities, and outcomes of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma by stage strata.We retrospectively reviewed 51 patients diagnosed with pulmonary MALT lymphoma between January 2003 and December 2015. To compare treatment modalities and outcomes, we stratified the patients into low-stage (IE/IIE) and high-stage (IIIE/IVE) groups using modified Ann Arbor staging. Progression-free survival was estimated using Kaplan-Meier curves, and differences were compared using the log-rank test. A hazard ratio of progression by stage strata, adjusted for other clinical variables, was determined using a Cox adjusted proportional hazards model.The majority of patients had stage IE disease (76.5%; 39 of 51). With advancing stage, patients were more likely to have respiratory and B symptoms and higher International Prognostic Index scores. The most common treatment modality was surgical resection in low-stage patients (33 of 43) and chemotherapy in high-stage patients (7 of 8). At a median follow-up of 40.7 months, progression-free survival was longer for low-stage patients (median, 40.7 months vs 24.9 months; P .001), and high-stage patients were 9.2 times more likely to progress (hazard ratio, 9.24; 95% confidence interval, 1.93-44.36). Among 30 patients with surgically resected stage IE disease, 8 with central lesions were treated via lobectomy and 22 with peripheral lesions were treated via lobectomy (n = 8) or limited resection (n = 14). One of these patients, with a central lesion, experienced disease recurrence.Our findings suggest that the clinical course of low-stage pulmonary MALT lymphoma, for which the mainstay of treatment is surgical resection, might be indolent.

Mycobacterium avium complex (MAC) was originally composed of 2 species, M. avium and M. intracellulare. However, several new species closely related to M. intracellulare have recently been identified. In addition, M. avium has been further subdivided into 4 subspecies. The aim of this study was to determine the proportion of different MAC species recovered from respiratory specimens and to elucidate the clinical relevance of these species. Clinical isolates, from 219 patients, that had been initially identified as M. avium or M. intracellulare by non-sequencing methods were reidentified using multilocus sequence typing, and the clinical significance of the identified species was then investigated. Of 91 isolates originally identified as M. intracellulare, 75 (82%) were confirmed to be M. intracellulare, 8 (9%) isolates were identified as M. chimaera, and 4 (4%) isolates each were identified as "M. indicus pranii" and M. yongonense. The 128 isolates originally designated as M. avium were determined to be M. avium subsp. hominissuis. Of the 219 patients, 146 (67%) met the diagnostic criteria for MAC lung disease, and for each MAC species, the proportion of patients meeting these criteria was as follows: M. intracellulare (54/75, 72%), M. chimaera (3/8, 38%), "M. indicus pranii" (3/4, 75%), M. yongonense (2/4, 50%), and M. avium subsp. hominissuis (84/128, 66%). In summary, multilocus sequence typing of respiratory isolates initially identified as MAC revealed that, although most isolates were M. avium subsp. hominissuis or M. intracellulare, approximately 7% were newer MAC members, with clinical evidence supporting their potential pathogenicity for humans.

Vitamins are known to be associated with immunity and nutrition. Moreover, vitamin deficiency can affect host immunity to various infectious diseases, including tuberculosis. Although patients with tuberculosis often have vitamin D deficiency, little is known about the levels of other vitamins. Here, we aimed to investigate the status of vitamins A, BWe performed a case-control study to investigate the serum vitamin concentrations in 152 patients with tuberculosis and 137 control subjects. The concentrations of vitamin A, vitamin D, vitamin E, homocysteine, and methylmalonic acid were measured using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. Patient demographic data and other biochemical parameters were also analyzed.The serum concentrations of vitamins A, D, and E were significantly lower in patients with tuberculosis than in control subjects (1.4 vs. 2.0 μmol/L, P 0.001; 10.6 vs. 19.3 ng/mL, P 0.001; and 22.8 vs. 30.6 μmol/L, P 0.001, respectively). In contrast, the methylmalonic acid levels were higher in patients with tuberculosis (134.9 vs. 110.8 nmol/L, P 0.001). The prevalences of vitamin deficiencies were significantly higher in patients with tuberculosis. Moreover, multiple vitamin deficiencies were only observed in patients with tuberculosis (22.4% of all patients with tuberculosis vs. 0% of all control subjects). Positive correlations among vitamin A, D, and E concentrations were observed (vitamins A and D, r = 0.395; vitamins D and E, r = 0.342; and vitamins A and E, r = 0.427, P 0.001). Body mass index, total cholesterol, low-density lipoprotein, iron, and total iron-binding capacity all showed positive correlations with vitamin A, D, and E concentrations.Vitamin deficiencies are common in patients with tuberculosis. Further research investigating the clinical importance of vitamin and nutritional status in patients with tuberculosis is needed.

Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.

We aim to examine how season and temperature levels affect physical activity using a wearable device among patients scheduled to undergo surgical resection of lung cancer. Physical activity (PA) data from the wearable device were analyzed by seasons for 555 preoperative lung cancer patients from the CATCH-LUNG cohort study. The seasons were divided into spring, summer, autumn, and winter using the study enrollment date before surgery. The overall mean (SD) age was 61.1 (8.9) years, and the mean (SD) daily steps at each season were 11,438 (5922), 11,147 (5065), 10,404 (4403), and 8548 (4293), respectively. In the fully-adjusted models, patients in the winter season had 27.04% fewer daily steps (95% CI = &minus, 36.68%, &minus, 15.93%) and 35.22% less time spent performing moderate to vigorous physical activity (MVPA) compared to patients in the spring. The proportion of participants with over 8000 steps and duration of MVPA were significantly lower in the winter than the spring. In particular, daily steps had a negative linear association with wind chill temperature in patients who lived in Seoul. In conclusion, PA was significantly lower in the winter and it was more robust in patients who had a low cardiorespiratory function.

Although treatment success for multidrug-resistant tuberculosis (MDR-TB) in Korea has increased owing to a national TB program and insurance coverage, Korea still has the highest TB incidence and associated mortality among the OECD Countries. Further, the final treatment outcome with bedaquiline in Korea has not been evaluated. In the present study, we compared the safety and efficacy of bedaquiline in Korean population, with advanced resistant profile, with those of the total population of the C209 trial to obtain valuable information. In the C209 trial, patients with MDR-TB received bedaquiline for 24 weeks in combination with optimized background regimen and all patients were followed up for 96 weeks after the last administration of bedaquiline. A subgroup analysis was performed in 21 Korean patients enrolled in the C209 trial. The baseline characteristics were similar between the two groups, except the drug-susceptibility pattern. The proportion of patients with pre-extensively drug resistant (XDR)/XDR-TB was 61.9% and 35.2% in the Korean population and total C209 population, respectively. Aminoglycosides, later generation fluoroquinolones, cycloserine, and linezolid were the most frequent drugs concomitantly used during bedaquiline treatment. The culture conversion rate was similar at the end of bedaquiline treatment (80% vs. 79.5%) and at 120 weeks (75% vs. 72.2%). The frequency and type of adverse events were similar between the two groups. In conclusion, bedaquiline showed similar efficacy and safety in Korean patients with MDR-TB despite their advanced drug-resistant profile, likely due to the effective companion drugs such as linezolid and later generation fluoroquinolones.

Objectives Recent practice guidelines recommend endosonography for patients with radiological N0 non-small cell lung cancer (NSCLC) when the primary tumors are >3 cm in diameter or centrally located. However, any role for endosonography remains debatable. We evaluated the utility of endosonography in patients with radiological N0 NSCLC based on tumor centrality, diameter and histology. Materials and methods Patients who underwent staging endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with or without transesophageal bronchoscopic ultrasound-guided fine needle aspiration (EUS-B-FNA) for radiological N0 NSCLC were retrospectively investigated using prospectively collected endosonography data. The radiological N0 stage was defined by node diameter as evident on computed tomography images and 18F-FDG uptake using integrated positron emission tomography-computed tomography. Results In total of 168 patients, the median size of the primary tumor was 39 mm, and 41 % of tumors were centrally located. The prevalence of occult mediastinal metastases was 11.3 % (19/168). The sensitivity of endosonography in terms of diagnosing occult mediastinal metastases was only 47 % (9/19); 6 of 10 patients with false-negative endosonography data exhibited metastases in accessible nodes. The diagnostic performance of endosonography did not differ by tumor centrality or diameter. Patients with adenocarcinoma histology showed higher prevalence of occult mediastinal metastases and higher false-negative results in endosonography compared with those with non-adenocarcinoma histology. Conclusion Not all patients with radiological N0 NSCLC benefit from endosonography, given the low prevalence of occult mediastinal metastases and the poor sensitivity of endosonography in this population. The strategy of invasive mediastinal staging needs to be tailored considering the histology of the tumor in this population.

Background Lung cancer is a common comorbidity of idiopathic pulmonary fibrosis (IPF) and has poor outcomes. The incidence and clinical factors related to development of lung cancer in idiopathic pulmonary fibrosis (IPF) are unclear. The aim of this study was to elucidate the cumulative incidence, risk factors, and clinical characteristics of lung cancer in IPF. Methods In this retrospective study, we analyzed clinical data for 938 patients who were diagnosed with IPF without lung cancer between 1998 and 2013. Demographic, physiologic, radiographic, and histologic characteristics were reviewed. Cumulative incidence of lung cancer and survival were estimated by the Kaplan-Meier method. Risk factors of lung cancer development were determined by Cox proportional hazard analysis. Results Among 938 IPF patients without lung cancer at initial diagnosis, lung cancer developed in 135 (14.5%) during the follow-up period. The cumulative incidences of lung cancer were 1.1% at 1 year, 8.7% at 3, 15.9% at 5, and 31.1% at 10 years. Risk factors of lung cancer were male gender, current smoking at IPF diagnosis, and rapid annual decline of 10% or more in forced vital capacity (FVC). Patients who developed lung cancer were mostly elderly men with smoking history. Squamous cell carcinoma followed by adenocarcinoma was the most common histologic type. Lung cancer was frequently located in areas abutting or within fibrosis. Survival was significantly worse in patients with lung cancer compared to patients with IPF alone. Conclusion Lung cancer frequently developed in patients with IPF and was common in current-smoking men with rapid decline of FVC. Electronic supplementary material The online version of this article (10.1186/s12890-019-0905-8) contains supplementary material, which is available to authorized users.

We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii . However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus , M. abscessus subsp. massiliense , and M. kansasii .

There has been limited evidence for the association between chronic obstructive pulmonary disease (COPD) and the incidence of lung cancer among never smokers. We aimed to estimate the risk of lung cancer incidence in never smokers with COPD, and to compare it with the risk associated with smoking. This cohort study involved 338 548 subjects, 40 to 84 years of age with no history of lung cancer at baseline, enrolled in the National Health Insurance Service National Sample Cohort. During 2 355 005 person-years of follow-up (median follow-up 7.0 years), 1834 participants developed lung cancer. Compared with never smokers without COPD, the fully-adjusted hazard ratios (95% CI) for lung cancer in never smokers with COPD, ever smokers without COPD, and ever smokers with COPD were 2.67 (2.09 to 3.40), 1.97 (1.75 to 2.21), and 6.19 (5.04 to 7.61), respectively. In this large national cohort study, COPD was also a strong independent risk factor for lung cancer incidence in never smokers, implying that COPD patients are at high risk of lung cancer, irrespective of smoking status.

The understanding of species distribution and inducible macrolide resistance in the Mycobacterium fortuitum complex (MFC) is limited. Of 90 mostly respiratory MFC clinical isolates, half were M. fortuitum , followed by M. peregrinum , M. porcinum , M. septicum , and M. conceptionense .

Background The final treatment outcomes of Korean multidrug-resistant tuberculosis (MDR-TB) patients treated with bedaquiline in the C209 trial have not yet been reported. Therefore, a subgroup analysis of the Korean population from the C209 trial was performed, and the results were compared with those of the overall C209 study population. Methods In the C209 trial, MDR-TB patients were treated with bedaquiline for 24 weeks in combination with background anti-TB drugs, and were followed-up until week 120 after bedaquiline treatment initiation. Results With the exception of drug susceptibility patterns, the baseline clinical characteristics of both groups were similar. The proportions of pre-extensively drug-resistant TB to extensively drug-resistant TB (pre-XDR-TB/XDR-TB) were 61.9 and 35.2% in the Korean and the overall C209 populations, respectively. Aminoglycosides, later-generation fluoroquinolones, cycloserine, and linezolid were the most common concomitant drugs used during bedaquiline treatment. The culture conversion rates of both groups were similar at week 24 (end of bedaquiline treatment; 80.0% vs. 79.5%) and 120 (75.0% vs. 72.2%). Additionally, the frequency and type of adverse events during treatment were similar in both groups, and 1 patient (5.0%) died due to a cause unrelated to bedaquiline treatment. Conclusions Bedaquiline showed similar efficacy and safety in Korean patients with MDR-TB, despite their advanced drug-resistance profiles, possibly due to other concomitant drugs such as linezolid.

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows:Mycobacterium avium(n=655),M. intracellulare(n=487),M. abscessus(n=129) andM. massiliense(n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality:M. intracellularehad an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03–1.91;M. abscessushad an aHR of 2.19, 95% CI 1.36–3.51; andM. massiliensehad an aHR of 0.99, 95% CI 0.61–1.64, compared toM. avium. Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12–2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57–3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.

BACKGROUND: We evaluated the role played by surgery in the diagnosis and treatment of pulmonary cryptococcosis (PC) in immunocompetent subjects. METHODS: We retrospectively studied 53 immunocompetent patients who were pathologically diagnosed with PC between January 2000 and December 2016 in a tertiary referral center. We compared the radiological presentations of, and diagnostic modalities used to evaluate, patients diagnosed both surgically and non-surgically. We also compared the treatment outcomes of patients who underwent surgical resection alone and those who received additional antifungals following surgical resection. RESULTS: Of the 53 patients, 30 (57%) were diagnosed via non-surgical modalities including percutaneous needle biopsy (PCNB) (n=29) and transbronchial lung biopsy (TBLB) (n=1); and 23 (43%) were diagnosed by surgical modalities including video-assisted thoracoscopic wedge resection (n=22) and lobectomy (n=1). An initial clinical suspicion of a lung malignancy was associated with the use of surgical diagnostic approaches (P

Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease.Seventy-one patients received oral macrolides, along with an initial 4-week (n = 28) or 2-week (n = 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24 months (4-week IV group) or for at least 12 months after negative sputum culture conversion (2-week IV group).Total treatment duration was longer in the 4-week IV group (median, 23.9 months) than in the 2-week IV group (15.2 months; P .001). The response rates after 12 months of treatment were 89% for symptoms, 79% for CT scanning, and 100% for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100% (P = .057), 91% (P = .177), and 91% (P = .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense.Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease.ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.

// Jung Min Bae 1, * , Ji Yun Jeong 2, * , Ho Yun Lee 1 , Insuk Sohn 3 , Hye Seung Kim 3 , Ji Ye Son 1 , O Jung Kwon 4 , Joon Young Choi 5 , Kyung Soo Lee 1 , Young Mog Shim 6 1 Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 2 Department of Pathology, Kyungpook National University Medical Center, Kyungpook National University School of Medicine, Daegu 702-210, Korea 3 Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 4 Division of Respiratory and Critical Medicine of the Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 5 Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea 6 Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea * These authors contributed equally to this work Correspondence to: Ho Yun Lee, email: hoyunlee96@gmail.com Young Mog Shim, email: youngmog.shim@samsung.com Keywords: lung adenocarcinoma, heterogeneity, radiomics, texture analysis, dual energy CT Received: June 29, 2016 Accepted: November 14, 2016 Published: November 21, 2016 ABSTRACT Purpose: To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results: Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i -uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods: A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions: Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma.

The aim of this study was to evaluate serum cytokines and natural antimicrobial peptide profiles in pulmonary tuberculosis, and compare them with levels in controls without tuberculosis, to explore the associations between these biomarkers and response to antituberculosis treatment. Serum levels of 10 biomarkers were measured using a Luminex bead array platform. Tuberculosis biosignatures were identified from the discovery cohort (n=148) and were validated in the independent cohort (n=148). Association between biosignatures and clinical outcome was investigated with negative conversion in follow-up sputum culture after 2months of treatment. Serum concentrations of eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 were significantly different between pulmonary tuberculosis patients and controls (P0.05). Serum concentrations of eotaxin and sIL-2Rα were higher in pulmonary tuberculosis patients than in controls, while those of MIP-1α and lipocalin 2 were lower (P0.05). Eotaxin concentrations were significantly higher in good responders to treatment (P0.05), indicating this immunomolecule may serve as a positive predictor for therapy response in pulmonary tuberculosis. The magnitude serum eotaxin, MIP-1α, sIL-2Rα, and lipocalin 2 are important indicators for pulmonary tuberculosis. These biomarkers alone or combinatorial detections have potential applicability in monitoring tuberculosis patients during antituberculosis treatment.Cytokines and endogenous antimicrobial peptides represent an important part of immune system and the identification of a pattern of differentially expressed those biomarkers (a "biosignature") could help to differentiate tuberculosis infection from the non-infected state which might eventually assist case identification and accelerate access to treatment. In this direction, cytokine analysis including multiple serum biomarkers to evaluate biosignatures of pulmonary tuberculosis would provide basic knowledge to aid understanding of the pathophysiology of tuberculosis infection and for the development of future diagnostic methods, treatments, and monitoring for pulmonary tuberculosis.

Current National Comprehensive Cancer Network guidelines recommend routine brain magnetic resonance imaging (MRI) screening in patients with stage II to IV non-small cell carcinoma, regardless of histological subtype. This recommendation might not be universally applicable, however, because brain metastasis (BM) is seen less frequently in patients with lung squamous cell carcinoma (SCC) than in those with a histological diagnosis of nonsquamous cell carcinoma.The cases of 564 patients with lung SCC in our institution between January 2012 and December 2013 were reviewed prospectively for comprehensive staging. All subjects' lung SCC, but not their BM, was staged on the basis of the seventh edition of the guidelines of the American Joint Committee on Cancer. We evaluated the incidence of BM across the stages and clinical factors associated with BM.Of the 564 patients, 28 (5.0%) had BM. BM did not occur in patients with stage Ia or Ib disease; however, it increased significantly as the disease progressed from stage IIa to IV (p0.001, trend test). Multivariate analysis showed that tumor involvement in N3 lymph nodes and distant metastasis other than BM (M1b) was independently associated with the development of BM.Routine brain MRI screening in patients with lung SCC in stage II to IV can help to evaluate asymptomatic BM. By contrast, we did not find any evidence supporting routine brain MRI screening in patients with stage I disease.

There are no studies evaluating the mechanisms driving linezolid resistance in nontuberculous mycobacteria. The novel mutations G2599A and A2137T in the 23S rRNA gene and mutations A439G and G443A in the rplD gene associated with linezolid resistance were identified in linezolid-resistant M. avium complex isolates.

Data on the frequency of gyrA and gyrB mutations in fluoroquinolone-resistant isolates of the Mycobacterium avium complex (MAC) and the Mycobacterium abscessus complex (MABC) are limited. In our analysis, we did not find any resistance-associated mutations in gyrA or gyrB in 105 MAC or MABC clinical isolates, including 72 moxifloxacin-resistant isolates.

Background: It has not been determined if adjuvant chemotherapy would be helpful for completely resected early-stage lung adenocarcinoma even with unfavorable genetic markers. As the positive anaplastic lymphoma kinase ( ALK ) rearrangement is associated with aggressive clinical feature in lung adenocarcinoma, we evaluated the treatment outcomes of completely resected stage IA lung adenocarcinoma according to initial ALK status. Methods: This is a retrospective cohort study including 309 patients with surgically resected stage IA lung adenocarcinoma from February 2010 to December 2013. Patients were screened for ALK rearrangement using immunohistochemistry. A positive ALK status was defined as an immunohistochemistry score of 2+ or more. Both disease-free survival (DFS) and the initial recurrence pattern were analyzed according to ALK status. Results: Twenty-three (7.4%) patients had ALK -positive adenocarcinoma. During the median follow-up of 35.8 months, recurrence developed in 34 (11.0%) patients. The patients with ALK -positive tumor had significantly lower 5-year DFS rate (62.4%) compared to those with ALK -negative tumor (86.5%; P=0.038). The multivariable analysis showed that ALK rearrangement was associated with a higher risk of disease recurrence (adjusted hazard ratio =2.64; 95% confidence interval, 1.08–6.44). In addition, patient with ALK -positive tumor showed more frequent recurrence in regional lymph nodes compared with those with ALK -negative tumor (83.3% vs . 28.6%; P=0.031). Conclusions: In patients with completely resected stage IA lung adenocarcinoma, ALK rearrangement was associated with unfavorable DFS and more frequent regional lymph node metastasis. Therefore, careful surveillance for recurrence should be performed in this subset of patients.

In-depth molecular pathogenesis of ground-glass nodular lung adenocarcinoma has not been well understood. The objectives of this study were to identify genomic alterations in ground-glass nodular lung adenocarcinomas and to investigate whether viral transcripts were detected in these tumors. Nine patients with pure (n = 4) and part-solid (n = 5) ground-glass nodular adenocarcinomas were included. Six were females with a median age of 58 years. We performed targeted exon sequencing and RNA sequencing. EGFR (n = 10), IDH2 (n = 2), TP53 (n = 1), PTEN (n = 1), EPHB4 (n = 1), and BRAF (n = 1) were identified as driver mutations by targeted exon sequencing. Vasculogenesis-associated genes including NOTCH4 and TGFBR3 expression were significantly downregulated in adenocarcinoma tissue versus normal tissue (adjusted P values

We sought to determine whether quantitative analysis of lung adenocarcinoma manifesting as a ground-glass opacity (GGO) nodule (GGN) on initial CT scans can predict further CT scanning change or rate of growth.This retrospective study included patients with lung adenocarcinoma manifesting as pure GGN on initial CT scans who were followed up with interval CT scanning until resection. All pure GGNs were classified based on CT scanning interval change in three subgroups as follows: group A (development of solid component), group B (growth of GGO component), and group C (no change in size). Nodule size, volume, density, mass, and CT scanning attenuation values were assessed from initial CT data sets.Fifty-four pure GGNs were enrolled and classified into group A (n = 9), group B (n = 25), and group C (n = 20). Nodule size, volume, mass, and density of the GGNs in each subgroup were not significantly different. The 97.5th percentile CT scanning attenuation value and slope of CT scanning attenuation values from the 2.5th to the 97.5th percentile were significantly different among the three subgroups (P = .02, P .00). Three of nine (33%) pure GGNs showing a new solid component developed a solid component within 6 months.The 97.5th percentile CT scanning attenuation value and slope of CT scanning attenuation values from the 2.5th to the 97.5th percentile could be helpful in predicting future CT scanning change and growth rate of pure GGNs. Pure GGNs showing higher 97.5th percentile CT scanning attenuation values and steeper slopes of CT scanning attenuation values may require more frequent follow-up than the usual interval of 6 months.

Introduction Recently, a new lung adenocarcinoma classification scheme was published. The prognostic value of this new classification has not been elaborated together with the value of imaging biomarkers including computed tomography (CT) and positron emission tomography (PET). Methods We reviewed pathologic specimens and imaging characteristics of primary tumors from 723 consecutive patients who underwent surgical resection for lung adenocarcinoma. On pathology, the predominant histologic subtype and pattern group were quantified. Tumor-shadow disappearance ratio (TDR) on CT and maximum standardized uptake value (SUVmax) on PET were assessed. The relationships between those variables and survival (overall survival [OS] and disease-free survival) were analyzed by using Kaplan–Meier curves and Cox regression analyses. Results The median follow-up period was 3.8 years. There were 137 patients (19%) with recurrence and 167 patients (23%) with metastasis after surgical resection. Among 723 patients, 35 patients (4.8%) had adenocarcinoma in situ, 34 patients (4.7%) had minimally invasive adenocarcinoma, 125 patients (17.3%) had lepidic predominant, 314 patients (43.4%) had acinar predominant, 65 patients (9.0%) had papillary predominant, 23 patients (3.2%) had micropapillary predominant, 113 patients (15.6%) had solid predominant, and 14 patients (1.9%) had variant adenocarcinomas. OS and disease-free survival rates were significantly different according to TDR on CT and SUVmax on PET, predominant subtypes, and pattern groups. On multivariate analysis, the SUVmax ( p p = 0.038), and pattern group ( p = 0.015) were independent predictors of OS. Conclusions TDR on CT, SUVmax on PET, and the new histologic classification schemes appear to be promising parameters for the prognostic stratification of patients with lung adenocarcinomas, allowing for the triage of patients who necessitate further staging workup and adjuvant therapy.

OBJECTIVES Fluoroquinolones (FQs) are the most important second-line drugs for MDR-TB treatment. Therapeutic options for FQ-resistant (FQ-R) MDR/XDR-TB are very limited. The purpose of the present study was to determine treatment outcomes and risk factors associated with unfavourable outcomes of MDR/XDR-TB, focusing on the impacts of FQ-R status and linezolid treatment. METHODS This was a retrospective cohort study of 337 MDR-TB patients, including 144 (42.7%) FQ-R MDR/XDR-TB cases. Treatment outcomes were evaluated according to WHO 2013 recommendations. RESULTS Later-generation FQs such as levofloxacin or moxifloxacin were given to 331 (98.2%) patients. Overall, favourable outcomes were achieved in 272 (80.7%) patients. FQ-R second-line injectable drug-susceptible MDR [adjusted OR (aOR) 4.299, 95% CI 1.239-14.916, P = 0.015] and XDR status (aOR 6.294, 95% CI 1.204-32.909, P = 0.024) were independently associated with unfavourable outcomes. However, FQ-susceptible (FQ-S) second-line injectable drug-resistant MDR status was not associated with unfavourable outcomes (aOR 1.814, 95% CI 0.314-10.485, P = 0.999). Favourable treatment outcomes were more frequent in FQ-R MDR/XDR-TB patients who received linezolid (82.8%) compared with those who did not receive linezolid (58.1%, P = 0.002). When FQ-R MDR/XDR-TB treatment without linezolid was used as a reference, the addition of linezolid was associated with favourable outcomes (aOR 4.081, 95% CI 1.237-13.460, P = 0.017), comparable to those for FQ-S MDR-TB (aOR 4.341, 95% CI 1.470-12.822, P = 0.005). CONCLUSIONS Later-generation FQs could improve treatment outcomes of patients with MDR-TB. Linezolid should be considered for inclusion in FQ-R MDR/XDR-TB treatment regimens.

Deficiencies in essential trace elements are associated with impaired immunity in tuberculosis infection. However, the trace element concentrations in the serum of Korean patients with tuberculosis have not yet been investigated. This study aimed to compare the serum trace element concentrations of Korean adult patients with tuberculosis with noninfected controls and to assess the impact of serum trace element concentration on clinical outcome after antituberculosis treatment. The serum concentrations of four trace elements in 141 consecutively recruited patients with tuberculosis and 79 controls were analyzed by inductively coupled plasma-mass spectrometry. Demographic characteristics were also analyzed. Serum cobalt and copper concentrations were significantly higher in patients with tuberculosis compared with controls, while zinc and selenium concentrations were significantly lower (p &lt, 0.01). Moreover, serum selenium and zinc concentrations were positively correlated (ρ = 0.41, p &lt, 0.05). A high serum copper concentration was associated with a worse clinical outcome, as assessed after one month of antituberculosis therapy. Specifically, culture-positive patients had higher serum copper concentrations than culture-negative patients (p &lt, 0.05). Patients with tuberculosis had altered serum trace element concentrations. Further research is needed to elucidate the roles of individual trace elements and to determine their clinical impact on patients with tuberculosis.

Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy ( n = 26) or intermittent therapy ( n = 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.

Recent data conflict on the clinical efficacy of later-generation fluoroquinolones, such as moxifloxacin or levofloxacin, for the treatment of multidrug-resistant tuberculosis (MDR-TB) that is resistant to ofloxacin but susceptible to moxifloxacin. The purpose of the present study was to evaluate whether later-generation fluoroquinolones can improve treatment outcomes in patients with ofloxacin-resistant, moxifloxacin-susceptible MDR-TB. A retrospective cohort study was performed on 208 patients with moxifloxacin-susceptible MDR-TB who were treated between 2006 and 2011. Later-generation fluoroquinolones were used for all patients. Overall, 171 patients (82%) had ofloxacin-susceptible, moxifloxacin-susceptible MDR-TB (ofloxacin-susceptible group), and 37 (18%) had ofloxacin-resistant, moxifloxacin-susceptible MDR-TB (ofloxacin-resistant group). Compared to the ofloxacin-susceptible group, the ofloxacin-resistant group was more likely to have a history of MDR-TB treatment ( P < 0.001) and cavitary lesions on chest radiography ( P < 0.001). In addition, the ofloxacin-resistant group was more likely than the ofloxacin-susceptible group to have resistance to the drugs pyrazinamide ( P = 0.003), streptomycin ( P = 0.015), prothionamide ( P < 0.001), and para-aminosalicylic acid ( P < 0.001). Favorable outcomes were more frequently achieved for the ofloxacin-susceptible group than for the ofloxacin-resistant group (91% [156/171] versus 57% [21/37], respectively [ P < 0.001]). In multivariable regression logistic analysis, the ofloxacin-susceptible group was about 5.36 (95% confidence interval, 1.55 to 18.53) times more likely than the ofloxacin-resistant group ( P < 0.001) to have favorable outcomes. Despite in vitro moxifloxacin susceptibility, the frequency of favorable treatment outcomes for ofloxacin-resistant MDR-TB was significantly lower than that for ofloxacin-susceptible MDR-TB, even when later-generation fluoroquinolones were used, indicating that more-aggressive therapies may be needed for ofloxacin-resistant MDR-TB.

Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology ( n = 48, 62%), followed by MAC ( n = 20, 26%) and mixed infections ( n = 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) ( P = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy ( P < 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections ( P = 0.009), a forced expiratory volume in 1 s of greater than 60% ( P = 0.008), and the absence of macrolide resistance ( P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity ( n = 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.

This study investigated the changes in the major etiologic organisms and clinical phenotypes of nontuberculous mycobacterial lung disease (NTM-LD) over a recent 15-year period in Korea. The increase of number of patients with NTM-LD was primarily due to an increase of Mycobacterium avium complex (MAC) lung disease (LD). Among MAC cases, the proportion of M. avium increased compared with M. intracellulare, whereas the incidence of M. abscessus complex and M. kansasii LD remained relatively stable. The proportion of cases of the nodular bronchiectatic form increased compared with the fibrocavitary form of NTM-LD., Graphical Abstract

Introduction Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non–small-cell lung cancer (NSCLC). The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with that of mediastinoscopy in patients with NSCLC. Methods A prospective trial was conducted in a tertiary referral center in Korea. Patients with histologically proven NSCLC and suspicion for N1, N2, or N3 metastasis were enrolled. Each patient underwent EBUS-TBNA followed by mediastinoscopy. Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy. Results In total, 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy. N2/N3 disease was confirmed in 59.1% of the patients. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value (NPV) of EBUS-TBNA on a per-person analysis were 88.0%, 100%, 92.9%, 100%, and 85.2%, respectively. The diagnostic sensitivity, specificity, accuracy, positive predictive value, and NPV of mediastinoscopy on a per-person analysis were 81.3%, 100%, 89.0%, 100%, and 78.8%, respectively. Significant differences in the sensitivity, accuracy, and NPV were evident between EBUS-TBNA and mediastinoscopy ( p Conclusions EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1–3 NSCLC. Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity, it should be the first-line procedure performed in patients with NSCLC.

Melanoma antigen (MAGE) genes are expressed in tumor cells, the testis and the placenta. The purpose of this prospective study was to investigate the sensitivity, specificity, and accuracy of the carcinoembryonic antigen (CEA), MAGE reverse transcriptase-nested polymerase chain reaction (RT-nested PCR), and cytology of pleural fluid in the diagnosis of malignant pleural effusion. Patients in whom unilateral pleural effusion was identified on chest radiography from January to December 2009 were included in the study. MAGE genes were analyzed by RT-nested PCR using MAGE A1-6 common primers. Of 81 enrolled patients, 46 were diagnosed as malignant pleural effusion, and 24 were diagnosed as benign pleural effusion. The diagnoses of 11 patients were not confirmed in this study. The diagnostic sensitivity, specificity, and accuracy of MAGE RT-nested PCR were 61.4%, 95.7%, and 73.1%, respectively. The diagnostic sensitivities of cytology and CEA (5 ng/mL) were 61.4% and 75.0%, respectively. Among 17 patients with negative cytology who had malignant pleural effusion, 12 and 10 patients were positive for CEA (5.0 ng/mL) and MAGE RT-nested PCR, respectively. However, of five patients with malignant pleural effusion that was not recognized by cytology and CEA, MAGE RT-nested PCR correctly predicted a malignant etiology in only one additional patient (20%). MAGE RT-nested PCR seems to add little on the combination of conventional methods in the diagnosis of malignant effusion.

Mycobacterium abscessus lung disease is difficult to treat due to inducible resistance to macrolides. However, 15%-20% of isolates are macrolide susceptible. In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved in 93% (13/14) following antibiotic therapy.

Background: A ground-glass nodule (GGN) represents early-stage lung adenocarcinoma. However, there is still no consensus for preoperative staging of GGNs. Therefore, we evaluated the need for the routine use of positron emission tomography/computed tomography (PET)/computed tomography (CT) scans and brain magnetic resonance imaging (MRI) during staging. Methods: A retrospective analysis was undertaken in 72 patients with 74 GGNs of less than 3 cm in diameter, which were confirmed via surgery as malignancy, at the Samsung Medical Center between May 2010 and December 2011. Results: The median age of the patients was 59 years. The median GGN diameter was 18 mm. Pure and part-solid GGNs were identified in 35 (47.3%) and 39 (52.7%) cases, respectively. No mediastinal or distant metastasis was observed in these patients. In preoperative staging, all of the 74 GGNs were categorized as stage IA via chest CT scans. Additional PET/CT scans and brain MRIs classified 71 GGNs as stage IA, one as stage IIIA, and two as stage IV. However, surgery and additional diagnostic work-ups for abnormal findings from PET/CT scans classified 70 GGNs as stage IA, three as stage IB, and one as stage IIA. The chest CT scans did not differ from the combined modality of PET/CT scans and brain MRIs for the determination of the overall stage (94.6% vs. 90.5%; kappa value, 0.712). Conclusion: PET/CT scans in combination with brain MRIs have no additional benefit for the staging of patients with GGN lung adenocarcinoma before surgery.

Purpose The diagnosis of pulmonary fungal infections is challenging due to the difficulty of obtaining sufficient specimens. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid has become an emerging diagnostic material. This study evaluated the role of routine fungal culture from EBUS-TBNA needle rinse fluid, in addition to histopathologic examination and fungal culture of EBUS-TBNA core tissue, in the diagnosis of pulmonary fungal infections. Materials and methods Among patients who underwent EBUS-TBNA, those with results for at least one of three tests (histopathologic examination, fungal culture of EBUS-TBNA core tissue or needle rinse fluid) were included. Patients with a positive test were divided into two groups (clinical fungal infection and suspected fungal contamination) according to their clinical assessment and therapeutic response to antifungal. Results Of 6072 patients, 41 (0.7%) had positive fungal tests and 9 (22%) were diagnosed as clinical fungal infection. Of the 5222 patients who were evaluated using a fungal culture from EBUS-TBNA needle rinse fluid, 35 (0.7%) had positive results. However, only 4 out of 35 (11.4%) were classified as clinical fungal infection. Positive results were determined in 4 of the 68 (5.9%) evaluated by a fungal culture of EBUS-TBNA core tissue, and all were diagnosed as clinical fungal infection. Conclusion Routine fungal culture of EBUS-TBNA needle rinse fluid is not useful due to the low incidence of fungal infection and high rate of contamination. However, fungal culture of EBUS-TBNA core tissue and needle rinse fluid should be considered in patients with clinically suspected fungal infection.

Background and objective Radiotherapy is usually administered to the central airway in patients with unresectable adenoid cystic carcinoma (ACC). The purpose of this study was to describe the outcomes of endobronchial intervention in patients with airway stenosis following radiotherapy for ACC. Moreover, we investigated the incidence and contributing factors for airway stenosis following radiotherapy for ACC. Methods Forty-seven patients with ACC, who underwent radiotherapy of the tracheobronchial tree from January 1995 to December 2011, were reviewed retrospectively. Fibrotic airway stenoses were diagnosed using three-dimensional computed tomography, flexible bronchoscopy or both. Results Eleven (23%) of the 47 patients with ACC suffered fibrotic airway stenosis following radiotherapy and received bronchoscopic intervention. The median interval from radiotherapy to diagnosis of fibrotic airway stenosis was 7 months. Low forced expiratory volume in 1 s (FEV1), FEV1/forced vital capacity and brachytherapy were verified as factors contributing to radiotherapy-induced airway stenosis. Bronchoscopic intervention provided both symptomatic relief and improvement of lung function, and no procedure-related death or major complication was observed. Insertion of a straight silicone stent was required in 10 patients (91%), and 4 (36%) eventually received Y-shaped silicone stents. The stents, once implanted, could not be removed in any of the patients; stents were well-tolerated for a prolonged period in all patients. Conclusions Fibrotic airway stenosis following radiotherapy in patients with ACC is often found. Bronchoscopic intervention, including silicone airway stenting, was a safe and useful method for treating radiotherapy-induced fibrotic airway stenosis in patients with ACC.

Purpose The outcomes and predictors of mortality from Pneumocystis pneumonia (PCP) in HIV-negative patients requiring mechanical ventilation (MV) for respiratory failure were evaluated. Materials and Methods This retrospective observational study enrolled 48 patients with PCP requiring MV in the medical intensive care unit (ICU). Multiple logistic regression analysis was used to identify independent predictors of in-hospital mortality. Results The main conditions underlying the PCP were malignancies (60%) or post solid organ transplant (35%). Excluding four patients whose initial treatment was changed due to adverse reactions, 21 (44%) of 44 patients did not respond to the initial treatment. During the ICU stay, additional complications developed: shock in 22 (46%), ventilator-associated pneumonia in 16 (33%), and acute kidney injury in 15 (31%). Ultimately, 31 (65%) patients died while hospitalised. In multivariate analysis, hospital mortality was independently associated with severity of illness on ICU admission, failure of initial antimicrobial treatment for PCP, and newly developed shock during ICU stay. Conclusions PCP in HIV-negative patients requiring MV for respiratory failure remains a serious illness with high mortality. Failure of the initial antimicrobial treatment for PCP as well as severity of illness was independent predictors of poor outcomes.

Summary Background A serum galactomannan (GM) antigen test has been widely used to diagnose invasive pulmonary aspergillosis. However, there are limited data on the use of the serum GM antigen test for the serologic diagnosis of chronic pulmonary aspergillosis (CPA). Methods Data were collected from all consecutive patients with a clinical suspicion of CPA who underwent a serum GM antigen test. Results In total, 334 patients who were suspected to have CPA were eligible for this study and 168 (50%) patients were finally diagnosed with CPA. The serum GM antigen test was positive in 38 (23%) patients with CPA and in 25 (15%) patients without CPA. The sensitivity of the serum GM antigen test was 23% (95% confidence interval [CI], 17–30%), and its specificity was 85% (95% CI, 79–90%), with positive and negative predictive values of 60% (95% CI, 47–72%) and 52% (95% CI, 46–58%), respectively. The accuracy of the test was 54%. The area under the receiver operating characteristic curve was 0.538 (95% CI, 0.496–0.580). Conclusion The serum GM antigen test could not be used for the serologic diagnosis of CPA.

Background: The concept of healthcare-associated pneumonia (HCAP) exists to identify patients infected with highly resistant pathogens who are exposed to the healthcare environment. However, many studies have included immunosuppressed patients who were excluded from the original concept. Objectives: The risk factors of potentially drug-resistant (PDR) pathogens in patients with pneumonia developed outside the hospital were reevaluated after excluding the patients who had immunosuppression. Methods: This was a retrospective study of prospectively collected data from all consecutive patients with pneumonia who were admitted to hospital via the emergency department between January 2008 and December 2011. Results: Pathogens were isolated in a total of 315 patients with pneumonia from our cohort; 33% with PDR pathogens did not meet the criteria for HCAP, but 44% without PDR pathogens did meet the criteria. Variables independently associated with PDR included nursing home residency, hospitalization in the preceding 90 days, antibiotics in the 30 days prior to pneumonia, poor function status and chronic lung disease. The new predictive scoring system based on the logistic regression model had a higher predictive power for the risk of PDR pathogens than the presence of the risk factors or the HCAP criteria. Conclusions: Functional status, pulmonary comorbidity and previous exposure to the healthcare environment were significantly associated with acquiring PDR pathogens in immunocompetent patients with pneumonia that developed out of hospital. However, a risk stratification model was more accurate than the presence of the risk factors or the HCAP criteria for assessing the probability of PDR pathogens.

Background Initial complete resection is a powerful prognostic indicator of survival in thymic epithelial tumors (TETs), but is obviously related to tumor stage. Here, we report the results of a prospective study of neoadjuvant docetaxel/cisplatin in locally advanced TETs. Methods Patients with histologically proven, Masaoka stage III/IV TETs at presentation were enrolled in this open-label, phase II, nonrandomized study. Patients received docetaxel 75 mg/m 2 I.V, followed by cisplatin 75 mg/m 2 I.V on day 1 of every 3-week cycle. After three cycles, surgical resection was performed if the tumor was considered resectable. Results From March 2007 to July 2011, 27 patients were enrolled in the trial. Masaoka stage at presentation was III ( n = 8; 29.6%), IVA ( n = 17; 63.0%), and IVB ( n = 2; 7.4%). Histologic types were nine thymomas (33.3%) and 18 thymic carcinomas (66.7%). After completion of neoadjuvant chemotherapy, 17 patients (63.0%) achieved partial response and 10 (37.0%) had stable disease. Nineteen patients (70.4%) underwent surgery and eight did not because of surgeons' decision ( n = 5), patient refusal ( n = 2), or decision to undergo radiation therapy instead ( n = 1). Fifteen among the 19 patients achieved complete resection (78.9%), which yields 55.6% of complete resection rate with intent-to-treat analysis. The most common side effects of severity greater than grade 3 were neutropenia and diarrhea. With a median follow-up of 42.6 months, 4-year overall survival, and progression-free survival in all patients was 79.4 and 40.6%, respectively. Conclusion Neoadjuvant docetaxel/cisplatin is both feasible and well tolerated, and potentially improves surgical resectability in patients with advanced TETs.

The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P = 0.880). However, there were significant differences in OS according to the N (P < 0.001) and M (P < 0.001) descriptors and TNM stage grouping (P < 0.001). Hazard ratios for OS, adjusted for known prognostic factors, differed significantly according to the N and M descriptor, and TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC.

Moxifloxacin (MXF) has in vitro and in vivo activity against Mycobacterium avium complex (MAC) in experimental models. However, no data are available concerning its treatment effect in patients with MAC lung disease. The aim of this study was to evaluate the clinical efficacy of an MXF-containing regimen for the treatment of refractory MAC lung disease. Patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified from our hospital database. We identified 41 patients who received MXF for ≥4 weeks for the treatment of refractory MAC lung disease. A total of 41 patients were treated with an MXF-containing regimen because of a persistent positive culture after at least 6 months of clarithromycin-based standardized antibiotic therapy. The median duration of antibiotic therapy before MXF administration was 410 days (interquartile range [IQR], 324 to 683 days). All patients had culture-positive sputum when MXF treatment was initiated. The median duration of MXF administration was 332 days (IQR, 146 to 547 days). The overall treatment success rate was 29% (12/41), and the median time to sputum conversion was 91 days (IQR, 45 to 190 days). A positive sputum acid-fast-bacillus smear at the start of treatment with MXF-containing regimens was an independent predictor of an unfavorable microbiological response. Our results indicate that MXF may improve treatment outcomes in about one-third of patients with persistently culture-positive MAC lung disease who fail to respond to clarithromycin-based standardized antibiotic treatment. Prospective studies are required to assess the clinical efficacy of MXF treatment for refractory MAC lung disease.

Background and objective We evaluated effective treatments of broncholithiasis based on its radiographical and bronchoscopic features. Methods This retrospective study conducted at Samsung Medical Center, Korea enrolled patients who were suspected of having broncholithiasis based on chest computed tomography (CT). The broncholiths were classified as intraluminal, mixed (both intraluminal and extraluminal) and extraluminal based on chest CT and bronchoscopic findings. Results The study enrolled 46 patients between 1995 and 2009. Symptoms included cough (n = 21, 45.7%), hemoptysis (n = 19, 41.3%) and purulent sputum (n = 11, 23.9%). Cough was more common in intraluminal boncholiths than in other type of broncholiths (P = 0.03). Based on chest CT, there were 15 (32.6%) intraluminal, 15 (32.6%) mixed and 16 (34.8%) extraluminal broncholiths. All 15 intraluminal broncholiths were removed completely via flexible (n = 2) or rigid (n = 13) bronchoscopy. For the 15 mixed broncholiths, seven (46.7%) bronchoscopic interventions were performed, but complete removal of the broncholiths was not accomplished. Six (40%) mixed and four (25%) extraluminal broncholiths were treated by surgical resection for symptom control. None of the patients who underwent surgical resection suffered morbidity or postoperative mortality. Conclusions The treatment of broncholithiasis should be based on chest CT and bronchoscopic findings. Intraluminal broncholiths can be removed via bronchoscopy, while surgery should be considered for symptomatic mixed or extraluminal broncholiths.