Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses.

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

Mortality and lung function decline in patients who develop chronic pulmonary aspergillosis after lung cancer surgery.

BACKGROUND: Lung cancer surgery is reported as a risk factor for chronic pulmonary aspergillosis (CPA). However, limited data are available on its clinical impact. We aimed to determine the effect of developed CPA after lung cancer surgery on mortality and lung function decline. METHODS: We retrospectively identified the development of CPA after lung cancer surgery between 2010 and 2016. The effect of CPA on mortality was evaluated using multivariable Cox proportional hazard analyses. The effect of CPA on lung function decline was evaluated using multiple linear regression analyses. RESULTS: During a median follow-up duration of 5.01 (IQR, 3.41-6.70) years in 6777 patients, 93 developed CPA at a median of 3.01 (IQR, 1.60-4.64) years. The development of CPA did not affect mortality in multivariable analysis. However, the decline in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were greater in patients with CPA than in those without (FVC, - 71.0 [- 272.9 to - 19.4] vs. - 10.9 [- 82.6 to 57.9] mL/year, p < 0.001; FEV1, - 52.9 [- 192.2 to 3.9] vs. - 20.0 [- 72.6 to 28.6] mL/year, p = 0.010). After adjusting for confounding factors, patients with CPA had greater FVC decline (ß coefficient, - 103.6; 95% CI - 179.2 to - 27.9; p = 0.007) than those without CPA. However, the FEV1 decline (ß coefficient, - 14.4; 95% CI - 72.1 to 43.4; p = 0.626) was not significantly different. CONCLUSION: Although the development of CPA after lung cancer surgery did not increase mortality, the impact on restrictive lung function deterioration was profound.

Machine learning-based diagnostic method of pre-therapeutic 18F-FDG PET/CT for evaluating mediastinal lymph nodes in non-small cell lung cancer.

OBJECTIVES: We aimed to find the best machine learning (ML) model using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for evaluating metastatic mediastinal lymph nodes (MedLNs) in non-small cell lung cancer, and compare the diagnostic results with those of nuclear medicine physicians. METHODS: A total of 1329 MedLNs were reviewed. Boosted decision tree, logistic regression, support vector machine, neural network, and decision forest models were compared. The diagnostic performance of the best ML model was compared with that of physicians. The ML method was divided into ML with quantitative variables only (MLq) and adding clinical information (MLc). We performed an analysis based on the 18F-FDG-avidity of the MedLNs. RESULTS: The boosted decision tree model obtained higher sensitivity and negative predictive values but lower specificity and positive predictive values than the physicians. There was no significant difference between the accuracy of the physicians and MLq (79.8% vs. 76.8%, p = 0.067). The accuracy of MLc was significantly higher than that of the physicians (81.0% vs. 76.8%, p = 0.009). In MedLNs with low 18F-FDG-avidity, ML had significantly higher accuracy than the physicians (70.0% vs. 63.3%, p = 0.018). CONCLUSION: Although there was no significant difference in accuracy between the MLq and physicians, the diagnostic performance of MLc was better than that of MLq or of the physicians. The ML method appeared to be useful for evaluating low metabolic MedLNs. Therefore, adding clinical information to the quantitative variables from 18F-FDG PET/CT can improve the diagnostic results of ML. KEY POINTS: • Machine learning using two-class boosted decision tree model revealed the highest value of area under curve, and it showed higher sensitivity and negative predictive values but lower specificity and positive predictive values than nuclear medicine physicians. • The diagnostic results from machine learning method after adding clinical information to the quantitative variables improved accuracy significantly than nuclear medicine physicians. • Machine learning could improve the diagnostic significance of metastatic mediastinal lymph nodes, especially in mediastinal lymph nodes with low 18F-FDG-avidity.

Effects of Antithrombotic Treatment on Bleeding Complications of EBUS-TBNA.

Background and Objectives: The application of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been markedly increased over the past decade. EBUS-TBNA is known to be a very safe and accurate procedure; however, the incidence of bleeding complications in patients who are taking antithrombotic agents (ATAs) is not well established. Materials and Methods: We conducted a retrospective analysis of a prospectively registered EBUS-TBNA cohort in a single tertiary hospital from May 2009 to December 2016. The patients were divided into two groups: an insufficient discontinuation group, defined as having a prescription for ATAs on the procedure day or only interrupting them for a short period of time, and a sufficient discontinuation group, defined as having prescription for ATAs during 30 days prior to the procedure and interrupting them for a sufficient period of time. Results: During the study period, a total of 4271 patients, after excluding 3773 patients who did not take ATAs at all, 498 patients were classified into the insufficient discontinuation group (n = 102) and the sufficient discontinuation group (n = 396). The baseline characteristics of patients and examined lesions between two groups were not significantly different, except insufficient discontinuation group had longer prothrombin times than the sufficient discontinuation group. In the insufficient discontinuation group, the most common reasons for prescriptions of ATAs were ischemic heart disease (48.0%) and cerebral vascular disease (28.4%), and half of the patients were taking two or more ATAs. Eventually, only one bleeding complication in the insufficient discontinuation group (1/102, 1.0%) and one event in the sufficient discontinuation group (1/396, 0.3%) occurred (p = 0.368). Conclusions: EBUS-TBNA is considered a safe procedure in terms of bleeding complications, even in patients with insufficient stopping of ATAs.

Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?

BACKGROUND: Guidelines recommend invasive mediastinal staging for centrally located tumours, even in radiological N0 nonsmall cell lung cancer (NSCLC). However, there is no uniform definition of a central tumour that is more predictive of occult mediastinal metastasis. METHODS: A total of 1337 consecutive patients with radiological N0 disease underwent invasive mediastinal staging. Tumours were categorised into central and peripheral by seven different definitions. RESULTS: About 7% (93 out of 1337) of patients had occult N2 disease, and they had significantly larger tumour size and more solid tumours on computed tomography. After adjustment for patient- and tumour-related characteristics, only the central tumour definition of the inner one-third of the hemithorax adopted by drawing concentric lines arising from the midline significantly predicted occult N2 disease (adjusted OR 2.13, 95% CI 1.17-3.87; p=0.013). This association was maintained after excluding patients with pure ground-glass nodules (adjusted OR 2.54, 95% CI 1.37-4.71; p=0.003) or only including those with solid tumours (adjusted OR 2.30, 95% CI 1.08-4.88; p=0.030). CONCLUSIONS: We suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC.

Clinical usefulness of routine AFB culture and MTB PCR of EBUS-TBNA needle rinse fluid.

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 < 0.001, P = 0.001 and P = 0.005, respectively). On addition of MTB PCR to histopathology, tuberculous lymphadenitis was diagnosed in 0.4%, 1.9% and 8.8%, respectively (Group C; P = 0.029). CONCLUSION: Routine AFB culture of needle rinse fluid was useful to increase the diagnostic yield of tuberculous lymphadenitis for all subjects who underwent EBUS-TBNA regardless of pre-procedural diagnosis in an intermediate tuberculosis (TB)-burden country. However, MTB PCR was only useful in subjects with pre-procedural diagnosis of benign pulmonary diseases.

Correction to: Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

Following publication of the original.

Are there differences among operators in false-negative rates of endosonography with needle aspiration for mediastinal nodal staging of non-small cell lung cancer?

BACKGROUND: Endosonography with needle aspiration (EBUS/EUS-NA) is recommended as the first choice for mediastinal nodal assessment in non-small cell lung cancer (NSCLC). It is important to maintain adequate negative predictive value of the procedure to avoid unnecessary additional surgical staging, but there are few studies on the influence of operator-related factors including competency on false negative results. This study aims to compare the false negative rate of individual operators and whether it changes according to accumulation of experience. METHODS: This is a retrospective study of NSCLC patients who were N0/N1 by EBUS/EUS-NA and confirmed by pathologic staging upon mediastinal lymph node dissection (n = 705). Patients were divided into a false negative group (finally confirmed as pN2/N3) and a true negative group (pN0/N1). False negative rates of six operators and whether these changed according to accumulated experience were analyzed. RESULTS: There were 111 (15.7%) false negative cases. False negative rates among six operators ranged from 8.3 to 21.4%; however, there were no statistical differences before and after adjustment for patient characteristics and procedure-related factors (P = 0.346 and P = 0.494, respectively). In addition, false negative rates did not change as each operator accumulated experience (P for trend = 0.632). CONCLUSIONS: Our data suggest that there would be no difference in false negative rates regardless of which operator performs the procedure assuming that the operators have completed a certain period of observation and have performed procedures under the guidance of an expert.

Joint effect of airflow limitation and emphysema on postoperative outcomes in early-stage nonsmall cell lung cancer.

This study aims to evaluate the joint effect of severity of airflow limitation and emphysema on postoperative pulmonary complications (PPCs) and overall survival after complete resection in patients with early-stage nonsmall cell lung cancer (NSCLC).We retrospectively studied 413 male patients with pathologic stage I or II NSCLC between 2007 and 2009. Severity of airflow limitation was defined based on forced expiratory volume in 1 s. Emphysema was defined by ≥5% low attenuation area at -950 HU.In multivariable-adjusted analyses, the adjusted odds ratio (aOR) for any PPC, comparing patients with moderate-to-severe airflow limitation to those without airflow limitation, was 2.23, and the aOR comparing patients with emphysema to those without emphysema was 1.77. However, the joint effect of airflow limitation and emphysema was much higher than expected from the independent effects of both factors (aOR 8.90). Moreover, patients with coexisting moderate-to-severe airflow limitation and emphysema had significantly poorer overall survival than any other group.Patients with moderate-to-severe airflow limitation and emphysema had almost nine times the risk of PPCs and poorer survival than patients with neither of these conditions. Integrated assessment of airflow limitation severity and emphysema is necessary for the optimal selection of candidates for lung resection surgery of early-stage NSCLC.

Comparison of operational characteristics for binary tests with clustered data.

Although statistical methodology is well-developed for comparing diagnostic tests in terms of their sensitivity and specificity, comparative inference about predictive values is not. In this paper, we consider the analysis of studies comparing operating characteristics of two diagnostic tests that are measured on all subjects and have test outcomes from multiple sites with varying number of sites among subjects. We have developed a new approach for comparing sensitivity, specificity, positive predictive value, and negative predictive value with simple variance calculation and, in particular, focus on comparing tests using difference of positive and negative predictive values. Simulation studies are conducted to show the performance of our approach. We analyze real data on patients with lung cancer, based on their diagnostic tests, to illustrate the methodology.

Fibrotic airway stenosis following radiotherapy in patients with adenoid cystic carcinoma.

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.

Clinical value of endobronchial ultrasound findings for predicting nodal metastasis in patients with suspected lymphadenopathy: a prospective study.

We evaluated whether sonographic findings can provide additional diagnostic yield in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), and can more accurately predict nodal metastasis than chest computed tomography (CT) or positron emission tomography (PET)/CT scans. EBUS-TBNA was performed in 146 prospectively recruited patients with suspected thoracic lymph node involvement on chest CT and PET/CT from June 2012 to January 2013. Diagnostic yields of EBUS finding categories as a prediction model for metastasis were evaluated and compared with findings of chest CT, PET/CT, and EBUS-TBNA. In total, 172 lymph nodes were included in the analysis: of them, 120 were malignant and 52 were benign. The following four EBUS findings were predictive of metastasis: nodal size ≥10 mm, round shape, heterogeneous echogenicity, and absence of central hilar structure. A single EBUS finding did not have sufficient diagnostic yield; however, when the lymph node had any one of the predictive factors on EBUS, the diagnostic yields for metastasis were higher than for chest CT and PET/CT, with a sensitivity of 99.1% and negative predictive value of 83.3%. When any one of predictive factors is observed on EBUS, subsequent TBNA should be considered, which may provide a higher diagnostic yield than chest CT or PET/CT.

Comparative Analysis of Clinical Characteristics and Prognosis Between Primary Lung Cancers Identified as Screening Detected and Incidentally Detected Pulmonary Nodules.

BACKGROUND/AIM: Although the importance of low-dose computed tomography (LDCT) screening is increasingly emphasized and implemented, many lung cancers continue to be incidentally detected during routine medical practices, and data on incidentally detected lung cancer (IDLC) remain scarce. This study aimed to investigate the clinical characteristics and prognosis of IDLCs by comparing them with screening-detected lung cancers (SDLCs). PATIENTS AND METHODS: In this retrospective study, subjects with cT1 (≤3 cm) pulmonary nodules detected on baseline computed tomography (CT), later pathologically confirmed as primary lung cancer in 2015, were included. Patients were categorized into IDLC and SDLC groups based on the setting of the first pulmonary nodule detection. RESULTS: Out of 457 subjects, 129 (28.2%) were IDLCs and 328 (71.8%) were SDLCs. The IDLC group, consisted of older individuals with a higher prevalence of smokers and underlying pulmonary disease, compared to the SDLC group. Adenocarcinomas were more frequently detected in SDLCs (87.5%) than in IDLCs (76.7%, p<0.001). The time to treatment initiation (TTI) and 5-year overall survival (OS) rates were similar. Multivariate analyses revealed underlying interstitial lung disease, DLCO, solidity of nodules and TNM stage as independent risk factors associated with mortality. Less than 30% of study participants would have been eligible for the current lung cancer screening program. CONCLUSION: The IDLC group was associated with older age, higher rate of smokers, underlying pulmonary disease, and non-adenocarcinoma histology. However, prognosis was similar to that of the SDLC group, attributable to the similarity in TNM stage, strict adherence to guidelines, and short TTI. Furthermore, less than 30% of the participants would have been suitable for the existing lung cancer screening program, indicating a potential need to reconsider the scope for screening candidates.

Clinical Effect of Endosonography on Overall Survival in Patients with Radiological N1 Non-Small Cell Lung Cancer.

PURPOSE: It is unclear whether performing endosonography first in non-small cell lung cancer (NSCLC) patients with radiological N1 (rN1) has any advantages over surgery without nodal staging. We aimed to compare surgery without endosonography to performing endosonography first in rN1 on the overall survival (OS) of patients with NSCLC. MATERIALS AND METHODS: This is a retrospective analysis of patients with rN1 NSCLC between 2013 and 2019. Patients were divided into 'no endosonography' and 'endosonography first' groups. We investigated the effect of nodal staging through endosonography on OS using propensity score matching (PSM) and multivariable Cox proportional hazard regression analysis. RESULTS: In the no endosonography group, pathologic N2 occurred in 23.0% of patients. In the endosonography first group, endosonographic N2 and N3 occurred in 8.6% and 1.6% of patients, respectively. Additionally, 51 patients were pathologic N2 among 249 patients who underwent surgery and mediastinal lymph node dissection (MLND) in endosonography first group. After PSM, the 5-year OSs were 68.1% and 70.6% in the no endosonography and endosonography first groups, respectively. However, the 5-year OS was 80.2% in the subgroup who underwent surgery and MLND of the endosonography first group. Moreover, in patients receiving surgical resection with MLND, the endosonography first group tended to have a better OS than the no endosonography group in adjusted analysis using various models. CONCLUSION: In rN1 NSCLC, preoperative endosonography shows better OS than surgery without endosonography. For patients with rN1 NSCLC who are candidates for surgery, preoperative endosonography may help improve survival through patient selection.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study.

Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Performances of prognostic scoring systems in patients with healthcare-associated pneumonia.

BACKGROUND: There are limited data on the performance of the pneumonia severity index (PSI) and CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥65) score, which were originally developed for community-acquired pneumonia (CAP), for patients with healthcare-associated pneumonia (HCAP). METHODS: The performances of PSI and CURB-65 were retrospectively evaluated in patients with HCAP compared to patients with CAP using prospectively collected data between January 2008 and December 2010. RESULTS: In total, 938 patients hospitalized with pneumonia were eligible for this study, consisting of 519 (55%) with CAP and 419 (45%) with HCAP. The PSI and CURB-65 scores had similar trends of increasing mortality with worsening risk class in both the HCAP and CAP groups. In the HCAP group, however, the low-risk patients identified using CURB-65 had a higher aggregate 30-day mortality compared with the low-risk patients identified using PSI. Although the performances of PSI and CURB-65 in the HCAP group showed similar trends to those observed in the CAP group, the estimated areas under the receiver operating characteristic curve for PSI (0.679, 95% confidence interval [CI], .619-.739) and CURB-65 (0.599, 95% CI, .522-.675) in the HCAP group were significantly lower than those in the CAP group (0.835, 95% CI, .768-.759 for PSI and .686-.832 for CURB-65). CONCLUSIONS: The performances of PSI and CURB-65 for predicting 30-day mortality in patients with HCAP were comparable to those in patients with CAP. However, the discriminatory powers of PSI and CURB-65 for 30-day mortality were significantly lower in the HACP group than those in the CAP group.

Volume-based parameters of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography improve outcome prediction in early-stage non-small cell lung cancer after surgical resection.

OBJECTIVE: To evaluate the prognostic significance and predictive performance of volume-based parameters of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) in early-stage non-small cell lung cancer (NSCLC). BACKGROUND: Although surgical resection remains the optimal treatment for early-stage NSCLC, approximately 40% of patients with stage I and 60% of patients with stage II NSCLC relapse and die within 5 years after curative resection. Therefore, identification of additional prognostic biomarkers is needed to develop risk-adapted treatment strategies. METHODS: We retrospectively reviewed 529 consecutive patients with pathologically proven early-stage NSCLC who underwent preoperative F-FDG PET/CT. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumors were measured. Overall survival (OS) and disease-free survival (DFS) were assessed by the Kaplan-Meier method. The prognostic significance of PET parameters and other clinicopathological variables was assessed by Cox proportional hazards regression analysis. To evaluate and compare the predictive performance of PET parameters, time-dependent receiver operating characteristic (ROC) curve analysis was used. RESULTS: In the multivariate analyses, volume-based parameters of PET (MTV and TLG) that were analyzed as continuous variables were significantly associated with an increased risk of recurrence (P = 0.001 for MTV, P < 0.001 for TLG) and death (P = 0.009 for MTV, P = 0.007 for TLG), after adjusting for age, sex, histology, tumor stage, and type of surgery. SUVmax analyzed as a continuous variable was not a significant prognostic factor for both DFS (P = 0.056) and OS (P = 0.525). In the time-dependent ROC curve analysis, the volume-based parameter of PET showed better predictive performance than SUVmax (P < 0.001). CONCLUSIONS: The volume-based parameter of PET is an independent prognostic factor for survival in addition to pathological tumor-node-metastasis stage and a promising tool for better prediction of outcome in patients with early-stage NSCLC.

Repeated derecruitments accentuate lung injury during mechanical ventilation.

OBJECTIVES: The aim of our study was to assess whether repeated derecruitments induced by the repetitive withdrawal of high positive end-expiratory pressure could induce lung injury in a swine model. DESIGN: Prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Specific pathogen-free pigs (Choong-Ang Laboratory Animals, Seoul, Korea) weighing around 30 kg. INTERVENTIONS: After lung injury was induced by repeated saline lavage, pigs were ventilated in pressure-limited mode with the highest possible positive end-expiratory pressure with a tidal volume of 8 mL/kg and maximum inspiratory pressure of 30 cm H2O. With this initial ventilator setting, the control group (n = 5) received ventilation without derecruitments for 4 hours, and in the derecruitment group (n = 5), derecruitments were repeatedly induced by intentional disconnection of the ventilatory circuit for 30 seconds every 5 minutes for 4 hours. MEASUREMENTS AND MAIN RESULTS: After the initial increase in positive end-expiratory pressure, the PaO2 increased to greater than 450 mm Hg in both groups. The PaO2 remained at greater than 450 mm Hg in the control group persistently, but in the derecruitment group, PaO2 significantly decreased to 427.7 mm Hg (adjusted p = 0.03) after 2 hours and remained significant for the rest of the study. PaCO2, oxygenation index, and alveolar-arterial oxygen gradient also significantly increased after 2 hours compared with the control group. However, the variables of respiratory mechanics except for minute volume at 2-hour point showed no difference between the two groups for the duration of the study. Histologically, significant bronchiolar injury was observed in the dependent portion of the derecruitment group compared with the controls (p = 0.03), but not in the nondependent area of the lung. CONCLUSIONS: Repeated derecruitments exacerbated lung injury, particularly at the bronchiolar level in the dependent portion. Strategies to minimize this type of injury should be incorporated when designing optimal ventilator strategies in acute respiratory distress syndrome patients.

Additional role of second washing specimen obtained during single bronchoscopy session in diagnosis of pulmonary tuberculosis.

BACKGROUND: Flexible bronchoscopy with bronchial washing is a useful procedure for diagnosis of pulmonary tuberculosis (TB), when a patient cannot produce sputum spontaneously or when sputum smears are negative. However, the benefit of gaining serial bronchial washing specimens for diagnosis of TB has not yet been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens for the diagnosis of pulmonary TB in suspected patients. METHODS: A retrospective analysis was performed on 174 patients [sputum smear-negative, n = 95 (55%); lack of sputum specimen, n = 79 (45%)] who received flexible bronchoscopy with two bronchial washing specimens with microbiological confirmation of pulmonary TB in Samsung Medical Center, between January, 2010 and December, 2011. RESULTS: Pulmonary TB was diagnosed by first bronchial washing specimen in 141 patients (81%) out of 174 enrolled patients, and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli (AFB) was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p < 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p = 0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p = 0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the first and second bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p < 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p < 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p = 0.004]. CONCLUSIONS: Obtaining an additional bronchial washing specimen could be a beneficial and considerable option for diagnosis of TB in patients with smear-negative sputum or who cannot produce sputum samples.

Outcome and predictors of mortality in patients requiring invasive mechanical ventilation due to acute respiratory failure while undergoing ambulatory chemotherapy for solid cancers.

PURPOSE: Acute respiratory failure that requires invasive mechanical ventilation is a leading cause of death in critically ill cancer patients. The aim of this study was to evaluate the outcome and prognostic factors of patients requiring invasive mechanical ventilator for acute respiratory failure, within 1 month of ambulatory chemotherapy for solid cancer. METHODS: A retrospective observational study of patients who underwent ambulatory chemotherapy at Samsung Medical Center, between January of 2007 and April of 2009, was employed for this study. RESULTS: A total of 51 patients met the inclusion criteria and were included in the study. The median age was 65 years (25-87) and the majority of the patients were male (n = 38, 74.5%). There were 42 patients (82.3%) with lung cancer. The most common cause of acute respiratory failure was pneumonia (n = 24, 47.1%), followed by acute respiratory failure due to extra-pulmonary infection, drug-induced pneumonitis, alveolar hemorrhage, and cancer progression. The intensive care unit (ICU) mortality was 68.6% and the most common cause of death in the ICU was uncorrected cause of acute respiratory failure. Before adjustment for others factors, prechemotherapy Eastern Cooperative Oncology Group (ECOG) Performance Scale (PS) (P = 0.03), Sequential Organ Failure Assessment score (P = 0.01), and anemia (P = 0.04) were significantly associated with ICU mortality. However, when adjusted for age, sex, and Acute Physiologic and Chronic Health Evaluation II score, only poor ECOG PS (≥2) was significantly associated with ICU mortality [OR 6.36 (95% CI (1.02-39.5))]. CONCLUSIONS: The outcome of patients with acute respiratory failure needing invasive mechanical ventilation during ambulatory chemotherapy for solid cancer is poor. Prechemotherapy performance status is an independent predictor of mortality.