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Purpose The role of epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) in the management of persistent subsolid nodules (SSNs) is unclear. This study aimed to investigate the impact of EGFR-TKIs on concurrent SSNs in patients with stage IV non–small cell lung cancer (NSCLC).Materials and Methods Patients who received an EGFR-TKI for at least 1 month for stage IV NSCLC and had concurrent SSN(s) that had existed for at least 3 months on chest computed tomography were included in this retrospective study. Size change of each nodule before and after EGFR-TKI therapies were evaluated using a cutoff value of 2 mm; increase (≥ 2 mm), decrease (≤ –2 mm), and no change (–2 mm < size change < +2 mm).Results A total of 77 SSNs, 51 pure ground-glass (66.2%) and 26 part-solid nodules (33.8%), were identified in 59 patients who received gefitinib (n=45) and erlotinib (n=14). Among 58 EGFR mutation analysis performed for primary lung cancer, 45 (77.6%) were EGFR mutant. The proportions of decrease group were 19.5% (15/77) on per-nodule basis and 25.4% (15/59) on per-patient basis. Four SSNs (5.2%) disappeared completely. On per-patient based multivariable analysis, EGFR exon 19 deletion positivity for primary lung cancer was associated with a decrease after initial EGFR-TKI therapy (adjusted odds ratio, 4.29; 95% confidence interval, 1.21 to 15.29; p=0.025).Conclusion Approximately 20% of the concurrent SSNs decreased after the initial EGFR-TKI therapy. EGFR exon 19 deletion positivity for primary lung cancer was significantly associated with the size change of concurrent SSNs.

Rationale: While the history of pulmonary tuberculosis (PTB) is a risk factor for developing both chronic obstructive pulmonary disease (COPD) and lung cancer, it remains unclear whether the histor...

Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics.What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens?We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form.Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002]).Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD.

Background We investigated the clinicoradiopathological features and prognosis according to genomic alterations in patients with surgically resected lung adenocarcinoma. Methods Patients who underwent surgical resection for pathologic stage I, II, or IIIA lung adenocarcinoma between 2009 and 2016 and for whom results regarding EGFR mutation, ALK immunohistochemistry (IHC), and KRAS mutation were available were included. Clinicoradiopathological characteristics, genomic alterations, and disease-free survival were analyzed retrospectively. Results Of 164 patients, 86 (52.4%) were female and 94 (57.3%) were never-smokers. The most common imaging patterns were part-solid lesion (67.7%) followed by solid (26.2%) and non-solid (6.1%) lesions. EGFR mutation, ALK IHC, and KRAS mutation were positive in 95 (57.9%), 9 (5.5%), and 11 (6.7%) patients, respectively. EGFR mutation positivity was associated with female sex, never-smoker, subsolid pattern on radiological examination, and acinar or papillary predominant histologic subtype. ALK IHC positivity was associated with longer maximal diameter, advanced stage, solid pattern on radiological examination, solid predominant histologic subtype, and distant metastasis during follow-up. KRAS mutation positivity was associated with male sex, smoker, solid pattern on radiological examination, and invasive mucinous adenocarcinoma on histologic analysis. In multivariable analysis, ALK IHC positivity and lymph node involvement were independently associated with recurrence. However, solidity was not an independent risk factor for recurrence. Conclusions Genomic alterations are associated with clinicoradiopathologic features in patients with resected lung adenocarcinoma. Identifying genomic alterations could help to predict the prognosis of early-stage lung adenocarcinoma.

Background While there is an increasing number of early-stage non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD), there are no specific clinical guidelines for treating them. This study aims to evaluate different treatment modalities and corresponding clinical outcomes among early-stage NSCLC patients with COPD. Methods We retrospectively reviewed 692 patients with stage I and II NSCLC and COPD from January 2012 to June 2014. Patients were categorized into four groups according to primary treatment modality: surgery only group (n=442), surgery with adjuvant treatment group (n=157), radiotherapy (RT) group (n=48), and supportive care (SC)-only group (n=45). Results Overall, mortality rate was the highest in the SC-only group (35.7 deaths per 100 person-years), followed by RT group (21.5 deaths per 100 person-years), surgery with adjuvant treatment group (8.9 deaths per 100 person-years) and surgery only group (7.2 deaths per 100 person-years). The adjusted hazard ratios (HR) for all-cause mortality compared to the surgery only group were 1.18 (95% CI, 0.84-1.67) in surgery with adjuvant treatment group, 1.61 (95% CI, 1.01-2.57) in RT group and 3.23 (95% CI, 1.99-5.23) in SC-only group. Conclusions Surgical resection should be considered as the first choice for early-stage NSCLC with COPD. Despite poor lung function or general patient condition, RT rather than SC can be an alternative option if surgery is not feasible. A multi-disciplinary approach and active communication between patients and physicians might be helpful for adequate decision-making regarding treatment for patients with early-stage NSCLC and COPD.

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 Mycobacterium avium, 53/57 M. intracellulare, 49/52 M. kansasii, 22/64 M. abscessus, and 57/67 M. massiliense). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 M. abscessus, 9/9 M. massiliense, 0/1 M. avium, and 1/1 M. intracellulare). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, p = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.

BACKGROUND: The eighth edition of the TNM classification for lung cancer does not provide a definite guideline for pulmonary lymphangitic carcinomatosis. The purpose of this retrospective case-control study is to evaluate the prognosis of pulmonary lymphangitic carcinomatosis in patients with non-small cell lung cancer compared with those with intrapulmonary metastases. METHODS: Non-small cell lung cancer (NSCLC) patients with pulmonary lymphangitic carcinomatosis detected on chest computed tomography scan during staging evaluation between 2000 and 2016 were included. The extent of pulmonary lymphangitic carcinomatosis was classified as being around the primary tumor (cLy1), at a distance from the tumor but confined to the same lobe (cLy2), in other ipsilateral lobes (cLy3), or affecting the contralateral lung (cLy4). Overall survival rates of the subjects were compared with those with intrapulmonary metastases. RESULTS: A total of 103 subjects with pulmonary lymphangitic carcinomatosis were analysed. The 5-year overall survival rates of the subjects with pulmonary lymphangitic carcinomatosis (n=103) and intrapulmonary metastases (n=111) were 33% and 21%, respectively. The 5-year overall survival rates of cLy1 (n=28), cLy2 (n=40), cLy3 (n=26) and cLy4 (n=9) were 54%, 35%, 12% and 11%, respectively. On multivariable analyses after adjusting for possible confounders, the subjects with cLy1 and cLy2 had better overall survival (adjusted hazard ratio for death, 0.34 and 0.49; 95% confidence interval, 0.24–0.73 and 0.30–0.80; P

Background Information about the natural history of nontuberculous mycobacterial pulmonary disease (NTM-PD) is limited. The purpose of this study was to evaluate the long-term natural history of non-cavitary nodular bronchiectatic NTM-PD and the factors associated with treatment initiation and the frequency of spontaneous sputum culture conversion after diagnosis of NTM-PD. Methods We evaluated 1,021 patients with newly diagnosed non-cavitary nodular bronchiectatic NTM-PD caused by Mycobacterium avium complex or M. abscessus between 2003 and 2013. Results Of 1,021 patients, 562 (55%) initiated antibiotic treatment and 459 (45%) did not. Young age (adjusted hazard ratio [aHR] = 0.99; 95% confidence interval [CI] = 0.98–0.99), low body mass index (aHR = 0.96; 95% CI = 0.93–0.99), previous history of tuberculosis (aHR = 1.23; 95% CI = 1.01–1.50), respiratory complaints such as cough (aHR = 1.36; 95% CI = 1.05–1.75) and sputum production (aHR = 1.47; 95% CI = 1.13–1.91), and high number of involved lobes on high-resolution computed tomography (aHR = 1.22; 95% CI = 1.14–1.31) were associated with treatment initiation. Of 459 patients who did not initiate treatment, 157 (34%) showed spontaneous sputum culture conversion. None of the clinical factors was associated with spontaneous conversion. After spontaneous culture conversion, 26 of 157 (17%) showed redeveloped NTM-PD caused by a species different from the original species. Conclusions The natural history of non-cavitary nodular bronchiectatic NTM-PD is variable. After diagnosis, the decision to initiate antibiotic therapy should be individualized based on consideration of the risk factors for disease progression. However, for patients who do not start antibiotic therapy, continuous and lifetime follow-up is recommended to manage underlying bronchiectasis and the possibility of late progression of NTM-PD.

Background Radial probe endobronchial ultrasound (R-EBUS), is effective for tissue diagnosis of lung lesions. We evaluated the diagnostic performance of R-EBUS both a guide-sheath and fluoroscopy and identified factors associated with accurate diagnosis. The feasibility of molecular and genetic testing, using specimens obtained by R-EBUS, was also investigated. Methods The study retrospectively reviewed 211 patients undergoing R-EBUS without a guide-sheath and fluoroscopy, June 2016-May 2017. After excluding 27 patients of which the target lesion was not reached, 184 were finally included. Multivariate logistic regression was used, to identify factors associated with accurate diagnosis. Results Among 184 patients, R-EBUS-guided biopsy diagnosed malignancy in 109 patients (59%). The remaining 75 patients (41%) with non-malignant results underwent additional work-ups, and 34 were diagnosed with malignancy. Based on final diagnosis, diagnostic accuracy was 80% (136/170), and sensitivity and specificity for malignancy were 76% (109/143) and 100% (27/27), respectively. In multivariate analysis, peripheral location (adjusted odds ratio [aOR], 3.925; 95% confidence interval [CI], 1.203-12.811; p=0.023), and central position of the probe (aOR, 2.435; 95% CI, 1.424-7.013; p=0.035), were associated with accurate diagnosis of malignancy. Molecular and genetic analyses were successful, in all but one case, with inadequate specimens. Conclusion R-EBUS-guided biopsy without equipment, is effective for tissue diagnosis. Peripheral location and central position of the radial probe, were crucial for accurate diagnosis. Performance of molecular and genetic testing, using samples obtained by R-EBUS, was satisfactory.

Background Mycobacterium kansasii is a major pathogen associated with nontuberculous mycobacterial pulmonary disease. For treatment of M. kansasii pulmonary disease, daily therapy with isoniazid, rifampin, and ethambutol is traditionally recommended. Although a regimen containing a macrolide, instead of isoniazid, has been recently recommended, supporting data are limited. We compared the treatment outcomes of a macrolide-containing regimen (macrolide group) and an isoniazid-containing regimen (isoniazid group) on patients with M. kansasii pulmonary disease. Methods A total of 49 patients were identified between January 2002 and December 2016. Treatment outcomes for the isoniazid group (n = 24) and the macrolide group (n = 25) were compared. Results Baseline characteristics of the isoniazid and macrolide groups were similar. Favorable outcomes did not differ between the isoniazid group (79%, n = 19) and macrolide group (88%, n = 22, P = 0.463). Total treatment duration (median 17.9 months vs. 15.4 months; P = 0.712) and time to culture conversion (median 2.0 months vs. 1.2 months; P = 0.838) were also similar between the isoniazid and macrolide groups. Five patients who completed three-times-weekly intermittent treatment containing a macrolide for non-cavitary M. kansasii pulmonary disease achieved negative sputum culture conversion within 12 months of treatment. Only one patient experienced recurrence of M. kansasii pulmonary disease in the isoniazid group. Conclusions A macrolide-containing regimen appears to be as effective as an isoniazid-containing regimen for treatment of M. kansasii pulmonary disease. Additionally, intermittent therapy containing a macrolide could be an alternative treatment option for non-cavitary M. kansasii pulmonary disease.

BACKGROUND AND OBJECTIVE We evaluated the usefulness of acid-fast bacilli (AFB) culture and Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) needle rinse fluid for diagnosing tuberculous lymphadenitis. METHODS EBUS-TBNA needle rinse fluid was routinely used for AFB culture and MTB PCR. The patients were categorized according to the pre-procedural diagnosis (Group A, suspected/histology-confirmed lung cancer; Group B, extrapulmonary malignancy; and Group C, other benign diseases). RESULTS Of the 4672 subjects, 104 (2.2%) were diagnosed with tuberculous lymphadenitis; 1.0%, 4.6% and 12.7% of Group A, B and C, respectively. Tuberculous lymphadenitis was diagnosed in 0.2%, 1.0% and 4.5% Group A, B and C patients, respectively, by histopathology. On addition of AFB culture to histopathology, tuberculous lymphadenitis was diagnosed in 1.0%, 4.4% and 10.3% of Group A, B and C patients, respectively (P

In this study, we aimed to retrospectively investigate and compare the drug susceptibility patterns of two major Mycobacterium abscessus complex (MABC) species; M. abscessus and M. massiliense. A total of 546 MABC respiratory isolates (277 M. abscessus and 269 M. massiliense) from 2011 to 2016 were analyzed in this study. We estimated minimum inhibitory concentrations (MICs) using the broth microdilution method, and we calculated MIC50 and MIC90 values from the MIC distribution. Both M. abscessus and M. massiliense were highly susceptible to amikacin and linezolid. For M. abscessus, the proportions of inducible and acquired resistance to clarithromycin were 68.6% and 12.3%, respectively. Only 15.2% of M. abscessus remained susceptible at day 14. On the other hand, none of the M. massiliense showed inducible resistance and 6.3% showed acquired resistance to clarithromycin. A total of 92.6% of the M. massiliense remained susceptible at day 14. The resistance rate of M. abscessus to moxifloxacin (90.3%) was significantly higher than that of M. massiliense (83.3%; p = 0.016). These susceptibility differences may explain the divergent treatment outcomes between patients with pulmonary disease caused by these two species.

Chronic obstructive pulmonary disease (COPD), an established risk factor for lung cancer, remains largely undiagnosed and untreated before lung cancer surgery. We evaluated the effect of perioperative bronchodilator therapy on lung function changes in COPD patients who underwent surgery for non-small cell lung cancer (NSCLC). From a database including NSCLC patients undergoing lung resection, COPD patients were identified and divided into two groups based on the use of bronchodilator during the pre- and post-operative period. Changes in forced expiratory volume in 1 s (FEV1) and postoperative complications were compared between patients treated with and without bronchodilators. Among 268 COPD patients, 112 (41.8%) received perioperative bronchodilator, and 75% (84/112) were newly diagnosed with COPD before surgery. Declines in FEV1 after surgery were alleviated by perioperative bronchodilator even after adjustments for related confounding factors including surgical extent, surgical approach and preoperative FEV1 (adjusted mean difference in FEV1 decline [95% CI] between perioperative bronchodilator group and no perioperative bronchodilator group; − 161.1 mL [− 240.2, − 82.0], − 179.2 mL [− 252.1, − 106.3], − 128.8 mL [− 193.2, − 64.4] at 1, 4, and 12 months after surgery, respectively). Prevalence of postoperative complications was similar between two groups. Perioperative bronchodilator therapy was effective to preserve lung function, after surgery for NSCLC in COPD patients. An active diagnosis and treatment of COPD are required for surgical candidates of NSCLC.

BACKGROUND Limited data are available regarding when to start treatment following a diagnosis of nontuberculous mycobacteria-pulmonary disease (NTM-PD) or regarding how achieving culture conversion affects NTM-PD outcomes. RESEARCH QUESTION Does the time between diagnosis and antibiotic initiation influence culture conversion or all-cause mortality in NTM-PD, and is there any association between achieving culture conversion after antibiotics and reduced all-cause mortality? STUDY DESIGN AND METHODS We evaluated 712 patients who received antibiotics for ≥ 6 months after diagnosis of NTM-PD between July 1997 and December 2013. Data on the waiting period, defined as the time interval between diagnosis and treatment initiation, and on outcomes such as culture conversion by six months or death were collected. Factors associated with outcomes were analyzed after adjusting for disease severity using the b ody mass index, a ge, c avity, e rythrocyte sedimentation rate and s ex (BACES) system. RESULTS Thirty-eight percent of study patients had mild disease, 48% had moderate disease, and 14% had severe disease. The median waiting period without antibiotics among all patients was 4.8 (interquartile range 1.3–20.8) months. After treatment initiation, 479 (67%) patients achieved culture conversion within six months, whereas 135 (19%) patients died. In univariate and multivariate models adjusted for BACES severity, no association between the waiting period and 6-month culture conversion or death was identified. However, 6-month culture conversion demonstrated a significant negative correlation with death (crude hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.33–0.65; adjusted HR 0.51, 95% 0.35–0.74). In the sub-group treated for ≥ 12 months, 12-month culture conversion was also associated with reduced death (adjusted HR 0.51, 95% CI 0.33–0.78). INTERPRETATION It may be reasonable to start antibiotics according to the ‘watchful waiting’ strategy for NTM-PD, but given the survival benefits, achieving culture conversion is an important goal for patients in need of treatment.

Although Candida species can cause invasive fungal diseases, such as disseminated infection and pneumonia, they rarely cause tracheobronchitis, which is often fatal. To identify the clinical characteristics of Candida tracheobronchitis, we retrospectively evaluated 8 patients who had pathologically proven Candida tracheobronchitis. Their median age was 64 (range: 51–70) years and 5 were females. Three patients had solid cancers and 5 had hematological malignancies. We classified tracheobronchitis into localized and diffuse types. Of the 8 patients, 5 had localized and 3 had diffuse tracheobronchitis. While all patients with diffuse tracheobronchitis had predisposing risk factors for invasive fungal disease, such as prolonged corticosteroid use, recent use of nucleoside analogues, or recent neutropenia (

The next diagnostic step in cases of indeterminate radial probe endobronchial ultrasound (radial EBUS)-guided biopsy results remains uncertain. This study aimed to identify risk factors for malignancy based on clinical findings, chest computed tomography (CT), and radial EBUS images, and to estimate the risk of malignancy in lung nodules that showed indeterminate radial EBUS-guided biopsy results by constructing a nomogram. This retrospective study included 157 patients with indeterminate results on an initial radial EBUS biopsy performed at the Samsung Medical Center from January 2017 to December 2018, but with a definitive final diagnosis. Medical records, chest CT, radial EBUS images, and the final diagnoses were reviewed. Patients were randomly divided into training and validation sets. Factors related to malignancy were identified through logistic regression analysis, and a nomogram was constructed using the training set and subsequently applied to the validation set. Six factors in univariable and multivariable analyses, including upper lobe location, spiculation, satellite nodules, echogenicity, presence of dots or linear arcs, and patency of vessels and bronchi predicted malignancy. A nomogram was constructed based on these predictors. The area under the curve (AUC) value of the nomogram was 0.858 using the chest CT factors, which improved to 0.952 when radial EBUS factors were added. The calibration curve showed good agreement between the actual and nomogram-predicted malignancy outcomes. The utility of radial EBUS images for revealing risk factors of malignancy was confirmed. Furthermore, our nomogram was able to predict the probability of malignancy in lung nodules with indeterminate radial EBUS-guided biopsy results.

Previous studies have demonstrated that endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) is an effective and safe method for diagnosis of sarcoidosis. However, it is not known whether there is a difference in diagnostic value among targeted mediastinal and hilar lymph nodes (LN). This was a retrospective observational study on consecutive patients who received EBUS-TBNA for suspected sarcoidosis at Samsung Medical Center between 2011 and 2019. During the study period, 305 consecutive patients received EBUS-TBNA for suspected sarcoidosis. Of those patients, 209 patients (478 LNs) were finally diagnosed with sarcoidosis while EBUS-TBNA providing a pathologically diagnosis in 185 (88.5%) patients. The sampled LNs were 2R in 10 (4.8%), 4R in 159 (76.1%), 7 in 178 (85.2%), 2L in 3 (1.4%), 4L in 47 (22.5%), 11R in 44 (21.1%), and 11L in 37 (17.7%) patients. The sensitivity of paratracheal LNs, subcarinal LN, and hilar LNs for diagnosis of sarcoidosis was 0.79 (139/176), 0.76 (136/178), and 0.92 (59/64). The result of paratracheal LNs, subcarinal LN, and hilar LNs was the sole mean of diagnosis in 18.2% (32/176), 12.4% (22/178), and 18.8% (12/64), respectively. Although no difference in sensitivity between paratracheal and subcarinal LNs (P = 0.596) was observed, there was a tendency of higher sensitivity of hilar LNs compared to that of paratracheal LNs (P = 0.065) or subcarinal LN (P = 0.021). EBUS-TBNA is an effective diagnostic method of sarcoidosis. Inclusion of hilar lymph node among other lymph nodes as biopsy targets may be helpful in increasing the sensitivity.

Limited data are available regarding optimal treatment for refractory Mycobacterium avium complex-pulmonary disease (MAC-PD). We evaluated outcomes of inhaled amikacin (AMK) with clofazimine (CFZ) regimens as an add-on salvage therapy for refractory MAC-PD. We retrospectively analyzed 52 patients with refractory MAC-PD, characterized by persistently positive sputum cultures despite &gt, 6 months of treatment. Thirty-five (67%) patients had M. intracellulare-PD, and 17 (33%) patients had M. avium-PD. Twenty-seven (52%) patients received the salvage therapy for &ge, 12 months, whereas 25 (48%) patients were treated for &lt, 12 months due to adverse effects or other reasons. Seventeen (33%) patients had culture conversion: 10 (10/27) in the &ge, 12-month treatment group and seven (7/25) in the &lt, 12-month treatment group (p = 0.488). Microbiological cure, defined as maintenance of culture negativity, was achieved in 12 (23%) patients, six (6/12) with accompanying symptomatic improvement were considered to have reached cure. Clinical cure, defined as symptomatic improvement with &lt, 3 consecutive negative cultures, was achieved in three (6%) patients. Overall, 15 (29%) patients achieved favorable outcomes, including microbiological cure, cure, and clinical cure. Inhaled AMK with CFZ may provide favorable outcomes in some patients with refractory MAC-PD. However, given the adverse effects, more effective strategies are needed to maintain these therapeutic regimens.

Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.The aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD.Among 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Molecular analyses of the 23S ribosomal RNA gene responsible for macrolide resistance and serial mycobacterial genotyping were performed using stored MAC isolates.The median duration of treatment was 32 months (interquartile range, 24-41 mo) in 72 patients. After treatment for a median of 33 months (interquartile range, 21-44 mo), macrolide resistance developed in 16 (22%) patients. Molecular analysis of isolates from 15 patients revealed that 80% (12 of 15) had a point mutation at position 2,058 or 2,059 of the 23S ribosomal RNA gene. Of the 49 patients who had stored pre- and post-treatment isolates, mycobacterial genotyping revealed that reinfection by new MAC strains occurred in 36 (73%) patients. New MAC strains were found in 24 (49%) patients, and mixed infections with original and new strains occurred in 12 (24%) patients. Only 13 (27%) patients had persistent infections with their original MAC strains.Refractory MAC-LD is commonly caused by reinfection with new strains rather than persistence of the original strain, which may explain the infrequent development of macrolide resistance in refractory MAC-LD. Clinical trial registered with www.clinicaltrials.gov (NCT00970801).

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 aim of this study was to evaluate whether rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB. Methods: A retrospective cohort study was performed on 76 patients with rifabutin-sensitive MDR-TB who were treated with or without rifabutin between 2006 and 2011. Results: Overall, 75% (57/76) of patients achieved favorable outcomes, including cure (53/76, 70%) and treatment completion (4/76, 5%). In contrast, 25% (19/76) had unfavorable treatment outcomes, which included treatment failure (6/76, 8%), death (2/76, 3%), loss to follow-up (4/76. 5%), and no evaluation due to transfer to other institutions (7/76, 9%). Rifabutin was given to 52 (68%) of the 76 patients with rifabutin-sensitive MDR-TB. Although favorable treatment outcomes were more frequent in patients who received rifabutin [81% (42/52)] than in those who did not receive rifabutin [63% (15/24)], this difference was not statistically significant (P = 0.154). However, in multivariable regression logistic analysis, use of rifabutin was significantly associated with favorable treatment outcomes in patients with rifabutin-sensitive MDR-TB (adjusted odds ratio = 9.80, 95% confidence interval = 1.65â58.37, P = 0.012). Conclusions: These results suggest that the use of rifabutin can improve treatment outcomes in patients with rifabutin-sensitive MDR-TB. Keywords: Multidrug-resistant tuberculosis, Extensively drug-resistant tuberculosis, Rifabutin, Treatment outcome

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.

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.

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.

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.

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.

IntroductionThe maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM.Materials and methodsMedical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used.ResultsAmong the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype.ConclusionsSUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.

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: 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

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 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.