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Background: In advanced non-small cell lung cancer (NSCLC), small biopsy specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are often the only available material from cancer tissue for the analysis of programmed death ligand-1 (PD-L1) expression. We aim to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PD-L1 expression at ≥ 1% and ≥ 50% on EBUS-TBNA samples compared with their corresponding surgically resected tumor., Methods: We retrospectively reviewed all patients who underwent EBUS-TBNA followed by surgical resection of NSCLC between July 2006 and September 2016. Demographic information and periprocedural/surgical data were collected. The archived specimens were retrieved and assessed for PD-L1. A positive PD-L1 stain was defined using two separate cutoff points: ≥ 1% and ≥ 50% of tumor cell positivity. EBUS-TBNA aspirates were compared with the surgically resected specimen to calculate the sensitivity, specificity, PPV, and NPV., Results: Sixty-one patients were included. For PD-L1 ≥ 1%, the sensitivity, specificity, PPV, and NPV were 72%, 100%, 100%, and 80%, respectively. For PD-L1 ≥ 50%, the sensitivity, specificity, PPV, and NPV were 47%, 93%, 70%, and 84%, respectively. The concordance rates for PD-L1 ≥ 1% and ≥ 50% were 87% and 82%, respectively., Conclusions: A PD-L1 cutoff of ≥ 1% on EBUS-TBNA has a strong correlation with resected tumor specimen. For PD-L1 ≥ 50%, there is a significant decrease in the sensitivity and PPV of EBUS-TBNA specimen when compared with resected tumor. When analyzing for PD-L1 expression using a cutoff of ≥ 50%, EBUS-TBNA specimens may misclassify the status of PD-L1., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Multifocal lung cancer is an increasingly common clinical scenario, but there is lack of high-level evidence for its optimal treatment. Thus, we surveyed members of the interdisciplinary International Association for the Study of Lung Cancer on their therapeutic approaches and analyzed the resultant practice patterns., Methods: We described the clinical scenario of an otherwise healthy 60-year-old man with bilateral pulmonary nodules and asked the 6373 members of the International Association for the Study of Lung Cancer whether they would recommend surgery, and if so, the extent of surgery. We also asked what other measures would be recommended to complete the staging and whether radiation therapy or chemotherapy would be suggested., Results: We received 221 responses (response rate 3.5%) from multiple specialists. Most respondents (140 [63%]) recommended surgery for this scenario. Surgeons were significantly more likely to recommend surgery than were those in other specialties. Of those who recommended surgery, most would obtain a PET/CT scan to rule out distant metastases and a magnetic resonance imaging scan to rule out brain metastases; but in the absence of radiographic lymph node involvement, most would not stage the mediastinum by bronchoscopy or mediastinoscopy before resection. When surgery was not recommended or declined, respondents commonly recommended radiation., Conclusions: This survey suggests that therapeutic recommendations for multifocal lung cancer are influenced to a large extent by physicians' specialty training, probably because of the lack of high-level evidence for its standard treatment. Ongoing systematic and multidisciplinary approaches with robust short-term and long-term patient outcomes may improve the quality of evidence for the optimal management of this clinical entity., (Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

The management of bronchopleural fistulas can be challenging. The initial treatment is usually conservative, but operative intervention with transposition of vascularized pedicled flaps may be required in refractory cases. We present the case of a 67-year-old man with stage IIIa squamous cell carcinoma of the lung who underwent a lower and middle bilobectomy after receiving neoadjuvant chemoradiation. His postoperative course was complicated by empyema and a bronchopleural fistula. Because of difficulty accessing the fistula, endobronchial-guided vascularized tissue flaps were successfully used to close the fistula., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Two-thirds of patients in the United States with newly diagnosed lung cancer would not meet the current U.S. Preventive Services Task Force (USPSTF) screening criteria, which suggests a need for amendment of the definition of high risk. To provide evidence of additional high-risk subpopulations and estimated gains and losses from using different criteria for screening eligibility, we conducted a two-step study using three cohorts., Methods: The two prospective cohorts comprised 5988 patients in whom primary lung cancer was diagnosed between 1997 and 2011 (the hospital cohort) and 850 defined-community residents (the community cohort); the retrospective cohort consisted of the population of Olmsted County, Minnesota, which was observed for 28 years (1984-2011). Subgroups of patients with lung cancer who might have been identified using additional determinates were estimated and compared between the community and hospital cohorts. The findings were supported by indirect comparative projections of two ratios: benefit to harm and cost to effectiveness., Results: Former cigarette smokers who had a smoking history of 30 or more pack-years and 15 to 30 quit-years and were 55 to 80 years old formed the largest subgroup not meeting the current screening criteria; they constituted 12% of the hospital cohort and 17% of community cohort. Using the expanded criteria suggested by our study may add 19% more CT examinations for detecting 16% more cases when compared with the USPSTF criteria. Meanwhile, the increases in false-positive results, overdiagnosis, and radiation-related lung cancer deaths are 0.6%, 0.1%, and 4.0%, respectively., Conclusions: Current USPSTF screening criteria exclude many patients who are at high risk for development of lung cancer. Including individuals who are younger than 81 years, have a smoking history of 30 or more pack-years, and have quit for 15 to 30 years may significantly increase the number of cases of non-overdiagnosed screen-detected lung cancer, does not significantly add to the number of false-positive cases, and saves more lives with an acceptable amount of elevated exposure to radiation and cost., (Copyright © 2015 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Indeterminate pulmonary nodules (IPNs) lack clinical or radiographic features of benign etiologies and often undergo invasive procedures unnecessarily, suggesting potential roles for diagnostic adjuncts using molecular biomarkers. The primary objective was to validate a multivariate classifier that identifies likely benign lung nodules by assaying plasma protein expression levels, yielding a range of probability estimates based on high negative predictive values (NPVs) for patients with 8 to 30 mm IPNs., Methods: A retrospective, multicenter, case-control study was performed using multiple reaction monitoring mass spectrometry, a classifier comprising five diagnostic and six normalization proteins, and blinded analysis of an independent validation set of plasma samples., Results: The classifier achieved validation on 141 lung nodule-associated plasma samples based on predefined statistical goals to optimize sensitivity. Using a population based nonsmall-cell lung cancer prevalence estimate of 23% for 8 to 30 mm IPNs, the classifier identified likely benign lung nodules with 90% negative predictive value and 26% positive predictive value, as shown in our prior work, at 92% sensitivity and 20% specificity, with the lower bound of the classifier's performance at 70% sensitivity and 48% specificity. Classifier scores for the overall cohort were statistically independent of patient age, tobacco use, nodule size, and chronic obstructive pulmonary disease diagnosis. The classifier also demonstrated incremental diagnostic performance in combination with a four-parameter clinical model., Conclusions: This proteomic classifier provides a range of probability estimates for the likelihood of a benign etiology that may serve as a noninvasive, diagnostic adjunct for clinical assessments of patients with IPNs.

Objectives: The objective of this article is to update previous evidence-based recommendations for evaluation and management of individuals with solid pulmonary nodules and to generate new recommendations for those with nonsolid nodules., Methods: We updated prior literature reviews, synthesized evidence, and formulated recommendations by using the methods described in the "Methodology for Development of Guidelines for Lung Cancer" in the American College of Chest Physicians Lung Cancer Guidelines, 3rd ed., Results: We formulated recommendations for evaluating solid pulmonary nodules that measure > 8 mm in diameter, solid nodules that measure ≤ 8 mm in diameter, and subsolid nodules. The recommendations stress the value of assessing the probability of malignancy, the utility of imaging tests, the need to weigh the benefits and harms of different management strategies (nonsurgical biopsy, surgical resection, and surveillance with chest CT imaging), and the importance of eliciting patient preferences., Conclusions: Individuals with pulmonary nodules should be evaluated and managed by estimating the probability of malignancy, performing imaging tests to better characterize the lesions, evaluating the risks associated with various management alternatives, and eliciting their preferences for management.

Introduction: Information is limited regarding health-related quality of life (QOL) status of long-term (greater than 5 years) lung cancer survivors (LTLCS). Obtaining knowledge about their QOL changes over time is a critical step toward improving poor and maintaining good QOL. The primary aim of this study was to conduct a 7-year longitudinal study in survivors of primary lung cancer which identified factors associated with either decline or improvement in QOL over time., Methods: Between 1997 and 2003, 447 LTLCS were identified and followed through 2007 using validated questionnaires; data on overall QOL and specific symptoms were at two periods: short-term (less than 3 years) and long-term postdiagnosis. The main analyses were of clinically significant changes (greater than 10%) and factors associated with overall QOL and symptom burden for each period and for changes over time., Results: Three hundred two (68%) underwent surgical resection only and 122 (27%) received surgical resection and radiation/chemotherapy. Recurrent or new lung malignancies were observed in 84 (19%) survivors. Significant decline or improvement in overall QOL over time were reported in 155 (35%) and 67 (15%) of 447 survivors, respectively. Among the 155 whose QOL declined, significantly worsened symptoms were fatigue (69%), pain (59%), dyspnea (58%), depressed appetite (49%), and coughing (42%). The symptom burden did not lessen among the 67 who reported improvement in overall QOL, suggesting that survivors had adapted to their compromised physical condition., Conclusions: LTLCS suffered substantial symptom burden that significantly impaired their QOL, indicating a need for targeted interventions to alleviate their symptoms.

Objectives: Several studies have identified airflow obstruction as a risk factor for lung cancer independent of smoking history, but the risk associated with the presence of radiographic evidence of emphysema has not been extensively studied. We proposed to assess this risk using a quantitative volumetric CT scan analysis., Methods: Sixty-four cases of lung cancer were identified from a prospective cohort of 1,520 participants enrolled in a spiral CT scan lung cancer screening trial. Each case was matched to six control subjects for age, sex, and smoking history. Quantitative CT scan analysis of emphysema was performed. Spirometric measures were also conducted. Data were analyzed using conditional logistic regression making use of the 1:6 set groups of 64 cases and 377 matched control subjects., Results: Decreased FEV(1) and FEV(1)/FVC were significantly associated with a diagnosis of lung cancer with ORs of 1.15 (95% CI, 1.00-1.32; P = .046) and 1.29 (95% CI, 1.02-1.62; P = .031), respectively. The quantity of radiographic evidence of emphysema was not found to be a significant risk for lung cancer with OR of 1.042 (95% CI, 0.816-1.329; P = .743). Additionally, there was no significant association between severe emphysema and lung cancer with OR of 1.57 (95% CI, 0.73-3.37)., Conclusions: We confirm previous observations that airflow obstruction is an independent risk factor for lung cancer. The absence of a clear relationship between radiographic evidence of emphysema and lung cancer using an automated quantitative volumetric analysis may result from different population characteristics than those of prior studies, radiographic evidence of emphysema quantitation methodology, or absence of any relationship between emphysema and lung cancer risk.

Background: Although no study has prospectively documented the rate at which lung cancers grow, many have assumed exponential growth. The purpose of this study was to document the growth of lung cancers detected in high-risk participants receiving annual screening chest CT scans., Methods: Eighteen lung cancers were evaluated by at least four serial CT scans (4 men, 14 women; age range, 53 to 79 years; mean age, 66 years). CT scans were retrospectively reviewed for appearance, size, and volume (volume [v] = pi/6[ab(2)]). Growth curves (x = time [in days]; y = volume [cubic millimeters]) were plotted and subcategorized by histology, CT scan attenuation, stage, survival, and initial size., Results: Inclusion criteria favored smaller, less aggressive cancers. Growth curves varied, even when subcategorized by histology, CT scan attenuation, stage, survival, or initial size. Cancers associated with higher stages, mortality, or recurrence showed fairly steady growth or accelerated growth compared with earlier growth, although these growth patterns also were seen in lesser-stage lung cancers. Most lung cancers enlarged at fairly steady increments, but several demonstrated fairly flat growth curves, and others demonstrated periods of accelerated growth., Conclusions: This study is the first to plot individual lung cancer growth curves. Although parameters favored smaller, less aggressive cancers in women, it showed that lung cancers are not limited to exponential growth. Tumor size at one point or growth between two points did not appear to predict future growth. Studies and equations assuming exponential growth may potentially misrepresent an indeterminate nodule or the aggressiveness of a lung cancer.

Background: Pulmonary nodules are spherical radiographic opacities that measure up to 30 mm in diameter. Nodules are extremely common in clinical practice and challenging to manage, especially small, "subcentimeter" nodules. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer., Methods: We developed evidence-based clinical practice guidelines based on a systematic literature review and discussion with a large, multidisciplinary group of clinical experts and other stakeholders., Results: We generated a list of 29 recommendations for managing the solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter; small, subcentimeter nodules that measure < 8 mm to 10 mm in diameter; and multiple nodules when they are detected incidentally during evaluation of the SPN. Recommendations stress the value of risk factor assessment, the utility of imaging tests (especially old films), the need to weigh the risks and benefits of various management strategies (biopsy, surgery, and observation with serial imaging tests), and the importance of eliciting patient preferences., Conclusion: Patients with pulmonary nodules should be evaluated by estimation of the probability of malignancy, performance of imaging tests to characterize the lesion(s) better, evaluation of the risks associated with various management alternatives, and elicitation of patient preferences for treatment.

Objectives: To evaluate experience with the flexible bronchoscopic management of tracheobronchial foreign bodies (TFBs) in children (age < or = 16 years)., Design: All pediatric bronchoscopies performed by the bronchoscopy section at Mayo Clinic Rochester from 1990 through June 2001 for the suspicion of TFBs were reviewed. Information analyzed included the types of bronchoscope (rigid vs flexible) and techniques used, success rates of extraction of TFBs, and complications., Results: Of the 94 children suspected of having TFBs, 39 children (28 boys and 11 girls; mean age, 47.3 months) were found to have 40 TFBs. The flexible bronchoscope was used exclusively to extract TFBs in 24 patients, and in 2 patients in whom the rigid bronchoscopic procedure was unsuccessful. Flexible bronchoscopy was performed through an endotracheal tube in 19 children. In the other five children, the procedure was accomplished through a laryngeal mask airway (LMA). In two additional patients in whom the rigid bronchoscopic procedure was unsuccessful, the instrument served as a conduit for the passage of the flexible bronchoscope. The extraction instruments employed included ureteral stone baskets and stone forceps. Since 1994, all extractions of TFBs were successfully accomplished with the flexible bronchoscope. Complications occurred in four patients who underwent rigid bronchoscopy, and included postbronchoscopy laryngeal edema manifested by stridor, cough, and respiratory distress. These resolved quickly with medical therapy., Conclusions: Flexible bronchoscopic extraction of pediatric TFBs can be performed safely with minimal risks and complications. In our experience, it was successful in all children in whom it was employed. Nevertheless, we caution that provisions be made to provide immediate rigid bronchoscopic management, should the attempts at flexible bronchoscopic extraction fail.

Background: Pulmonary emphysema, with or without chronic bronchitis, has emerged as the most common indication for successful single lung transplantation. Although gas exchange can be expected to improve after successful transplantation, such changes do not adequately explain the improvement in dyspnea experienced by these patients and resulting in improved quality of life., Methods: We prospectively studied the respiratory mechanics of 14 single lung transplantation recipients with pulmonary emphysema, of whom 10 have been followed up beyond 1 year. The mean age of the group was 48.8 years (range, 42 to 60 years) for the seven men and seven women. Average donor-predicted total lung capacity was 0.6 L (+0.2 [standard error]) greater than recipient-predicted total lung capacity. Comparison of pulmonary resistance, dynamic lung compliance, and static lung compliance were taken to examine the possible role of reduced airways resistance and of improved elastic recoil in the reduced work of breathing. Results were analyzed by means of a one-tailed paired Student t test and linear regression analysis (both stepwise and multivariate); results are tabulated by mean (+/- 1 [standard error])., Results: Between preoperative measurements and 12 months postoperatively, maximum lung elastic recoil increased from 8.1 (+/- 0.7) to 11.3 (+/- 1.0) cm H2O, p < 0.01; pulmonary resistance fell from 8.3 (+/- 0.8) to 5.4 (+/- 0.7) cm H2O sec/L, p < 0.01. Dynamic lung compliance fell from 0.23 (+/- 0.04) to 0.12 (+/- 0.02) L/cm H2O, p < 0.02, and static lung compliance fell from 0.66 (+/- 0.13) to 0.22 (+/- 0.05) L/cm H2O, p < 0.001., Conclusions: The decline in lung compliance after single lung transplantation reflects the importance of improvement in elastic recoil and reduced chest wall distention, improving the work of breathing. The 67% decline in static lung compliance (300% increase in elastic recoil) is probably the single most important mechanical factor leading to reduced dyspnea after single lung transplantation for emphysema.

Evolving strategies of pulmonary preservation, bronchial revascularization, immunosuppression, and infectious disease management were used in 15 initial consecutive patients undergoing lung transplantation for emphysema. There were 10 women and 5 men with a mean age of 49 years (range, 36 to 60 years). All patients required supplemental oxygen therapy. One bilateral, 9 left, and 5 right transplantations were performed. Mean preoperative forced expiratory volume in 1 second and total lung capacity were 16% and 146%, respectively, of predicted. Quadruple drug immunosuppression was used. Actuarial 1-year survival in this initial series is 93.3% +/- 6.4% (Kaplan-Meier) with one early cardiac death at day 71. Mean forced expiratory volume in 1 second and diffusing capacity for carbon monoxide at discharge were 43% and 62%, respectively, of predicted. Rehabilitation has been excellent, and all survivors are active and free of supplemental oxygen. During the study, the following treatment strategies have evolved: (1) University of Wisconsin solution has replaced Euro-Collins' solution for pulmonary preservation; (2) direct bronchial revascularization with the internal thoracic artery now is used; (3) an algorithm-based variable dose OKT3 induction regimen has resulted in a major reduction in dosage; and (4) infectious disease management focuses on the prophylaxis of cytomegalovirus and fungal infection using prolonged ganciclovir and early itraconazole therapy as well as the avoidance of Epstein-Barr virus mismatches. Single-lung transplantation for emphysema has excellent early results with continuing evolving management strategies.