Search

Contains fulltext : 196781.pdf (Publisher’s version ) (Open Access), INTRODUCTION: Lung cancer presenting as subsolid nodule (SSN) can show slow growth, hence treating SSN is controversial. Our aim was to determine the long-term outcome of subjects with unresected SSNs in lung cancer screening. METHODS: Since 2005, the Multicenter Italian Lung Detection (MILD) screening trial implemented active surveillance for persistent SSN, as opposed to early resection. Presence of SSNs was related to diagnosis of cancer at the site of SSN, elsewhere in the lung, or in the body. The risk of overall mortality and lung cancer mortality was tested by Cox proportional hazards model. RESULTS: SSNs were found in 16.9% (389 of 2303) of screenees. During 9.3 +/- 1.2 years of follow-up, the hazard ratio of lung cancer diagnosis in subjects with SSN was 6.77 (95% confidence interval: 3.39-13.54), with 73% (22 of 30) of cancers not arising from SSN (median time to diagnosis 52 months from SSN). Lung cancer-specific mortality in subjects with SSN was significantly increased (hazard ratio = 3.80; 95% confidence interval: 1.24-11.65) compared to subjects without lung nodules. Lung cancer arising from SSN did not lead to death within the follow-up period. CONCLUSIONS: Subjects with SSN in the MILD cohort showed a high risk of developing lung cancer elsewhere in the lung, with only a minority of cases arising from SSN, and never representing the cause of death. These results show the safety of active surveillance for conservative management of SSN until signs of solid component growth and the need for prolonged follow-up because of high risk of other cancers.

Contains fulltext : 193523.pdf (Publisher’s version ) (Open Access), OBJECTIVES: The aim of this study was to compare computer-aided diagnosis (CAD) and visual reading for the detection of subsolid nodules (SSNs) in volumetrl measuremic low-dose computed tomography (LDCT) for lung cancer screening. MATERIALS AND METHODS: Prospective visual detection (VD) and manuaent of SSN were performed in the 2303 baseline volumetric LDCTs of the Multicenter Italian Lung Detection trial. Baseline and 2- and 4-year LDCTs underwent retrospective CAD analysis, subsequently reviewed by 2 experienced thoracic radiologists. The reference standard was defined by the cumulative number of SSNs detected by any reading method between VD and CAD. The number of false-positive CAD marks per scan (FP/scan) was calculated. The positive predictive value of CAD was quantified per nodule (PPV) and per screenee (PPV). The sensitivity and negative predictive value were compared between CAD and VD. The longitudinal 3-time-point sensitivity of CAD was calculated in the subgroup of persistent SSNs seen by VD (ratio between the prevalent SSNs detected by CAD through 3 time points and the total number of persistent prevalent SSNs detected by VD) to test the sensitivity of iterated CAD analysis during a screening program. Semiautomatic characteristics (diameter, volume, and mass; both for whole nodule and solid component) were compared between SSN detected CAD-only or VD-only to investigate whether either reading method could suffer from specific sensitivity weakness related to SSN features. Semiautomatic and manual diameters were compared using Spearman rho correlation and Bland-Altman plot. RESULTS: Computer-aided diagnosis and VD detected a total of 194 SSNs in 6.7% (155/2,303) of screenees at baseline LDCT. The CAD showed mean FP/scan of 0.26 (604/2,303); PPV 22.5% (175/779) for any SSN, with 54.4% (37/68) for PSN and 19.4% for NSN (138/711; P < 0.001); PPV 25.6% (137/536). The sensitivity of CAD was superior to that of VD (88.4% and 34.2%, P < 0.001), as well as negati

Background: "Velcro-type" crackles on chest auscultation are considered a typical acoustic finding of Fibrotic Interstitial Lung Disease (FILD), however whether they may have a role in the early detection of these disorders has been unknown. This study investigated how "Velcro-type" crackles correlate with the presence of distinct patterns of FILD and individual radiologic features of pulmonary fibrosis on High Resolution Computed Tomography (HRCT). Methods: Lung sounds were digitally recorded from subjects immediately prior to undergoing clinically indicated chest HRCT. Audio files were independently assessed by two chest physicians and both full volume and single HRCT sections corresponding to the recording sites were extracted. The relationships between audible "Velcro-type" crackles and radiologic HRCT patterns and individual features of pulmonary fibrosis were investigated using multivariate regression models. Results: 148 subjects were enrolled: bilateral "Velcro-type" crackles predicted the presence of FILD at HRCT (OR 13.46, 95% CI 5.85-30.96, p < 0.001) and most strongly the Usual Interstitial Pneumonia (UIP) pattern (OR 19.8, 95% CI 5.28-74.25, p < 0.001). Extent of isolated reticulation (OR 2.04, 95% CI 1.62-2.57, p < 0.001), honeycombing (OR 1.88, 95% CI 1.24-2.83, < 0.01), ground glass opacities (OR 1.74, 95% CI 1.29-2.32, p < 0.001) and traction bronchiectasis (OR 1.55, 95% CI 1.03-2.32, p < 0.05) were all independently associated with the presence of "Velcro-type" crackles. Conclusions: "Velcro-type" crackles predict the presence of FILD and directly correlate with the extent of distinct radiologic features of pulmonary fibrosis. Such evidence provides grounds for further investigation of lung sounds as an early identification tool in FILD.

Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria—the Delphi items—for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as “essential”, “optional”, or “not relevant”. The items rated “essential” by < 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated “essential” by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated “essential” by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists

This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.

Aim: We studied the possible clinical significance of loss of heterozygosity (LOH) at key tumor suppressor genes loci in advanced renal cancer patients treated with nivolumab. Methods: LOH study was performed on 3p14.2 (FHIT gene); 3p21.3-21.2; 9p21 (BDMF gene); 9p22 (SH3GL2 gene). Results: Of 12 patients, 8 (67%) had LOH. The most affected gene was FHIT. All five patients with LOH at FHIT locus had good outcome, mean progression free survival of 6.8 months. The patients LOH negative at FHIT locus had mean progression free survival of 4 months, 67% were treatment refractory. Overall, 75% of patients with LOH of at least one gene had benefit; 75% of LOH negative cases were refractory. Conclusion: LOH at key tumor suppressor genes should be further investigated as predictive for immunotherapy.

Purpose. Interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary functional tests (PFTs) and semi-quantitative scores based on extent of ILD detectable on chest computed tomography (CT). CT quantitative indexes (QCTIs) are promising tools to assess extent of ILD. This study's aim is to evaluate the validity of QCTI compared with that of chest CT standard evaluation and PFTs. Moreover, QCTI differences between patients subgroups according to prognostic stratifications were investigated. Methods. ILD-SSc of patients from six rheumatological clinics was routinely assessed with chest CT and PFTs. Patients were clustered according to prognosis based on functional and/or radiological examinations. Finally, chest CTs were processed with OsiriX in order to obtain QCTI. Results. Two hundred fifty-seven SSc patients were enrolled. QCTI correlation between extent of ILD and PFTs range from - 0.60 to 0.58 and from - 0.54 to 0.52, respectively. The majority of QCTI have a different distribution in patients subgroups based on prognosis. Most of QCTI discriminate patients with an ILD severity leading to a poor prognosis. Conclusions. QCTI assessment of ILD-SSc is comparable to the evaluation based on chest CT and/or PFTs. QCTI values corresponding to severe ILD were identified. QCTIs are excellent candidates for a new and more reliable SSc-ILD assessment.

Contains fulltext : 174818.pdf (Publisher’s version ) (Open Access), Purpose To evaluate the added value of Lung CT Screening Reporting and Data System (Lung-RADS) assessment category 4X over categories 3, 4A, and 4B for differentiating between benign and malignant subsolid nodules (SSNs). Materials and Methods SSNs on all baseline computed tomographic (CT) scans from the National Lung Cancer Trial that would have been classified as Lung-RADS category 3 or higher were identified, resulting in 374 SSNs for analysis. An experienced screening radiologist volumetrically segmented all solid cores and located all malignant SSNs visible on baseline scans. Six experienced chest radiologists independently determined which nodules to upgrade to category 4X, a recently introduced category for lesions that demonstrate additional features or imaging findings that increase the suspicion of malignancy. Malignancy rates of purely size-based categories and category 4X were compared. Furthermore, the false-positive rates of category 4X lesions were calculated and observer variability was assessed by using Fleiss kappa statistics. Results The observers upgraded 15%-24% of the SSNs to category 4X. The malignancy rate for 4X nodules varied from 46% to 57% per observer and was substantially higher than the malignancy rates of categories 3, 4A, and 4B SSNs without observer intervention (9%, 19%, and 23%, respectively). On average, the false-positive rate for category 4X nodules was 7% for category 3 SSNs, 7% for category 4A SSNs, and 19% for category 4B SSNs. Of the falsely upgraded benign lesions, on average 27% were transient. The agreement among the observers was moderate, with an average kappa value of 0.535 (95% confidence interval: 0.509, 0.561). Conclusion The inclusion of a 4X assessment category for lesions suspicious for malignancy in a nodule management tool is of added value and results in high malignancy rates in the hands of experienced radiologists. Proof of the transient character of category 4X lesions at short-term follow-up could avoid u

Introduction: The National Lung Screening Trial has achieved a 7% reduction in total mortality with low-dose computed tomography (LDCT) screening as compared with in the chest radiography arm. Other randomized trials are under way, comparing LDCT screening with no intervention. None of these studies was designed to investigate the impact of smoking habits on screening outcome. In the present study, we tested the effect of stopping smoking on the overall mortality of participants undergoing repeated LDCT screening for many years. Methods: Between 2000 and 2010, 3381 smokers aged 50 years or older were enrolled in two LDCT screening programs. On the basis of the last follow-up information, subjects were divided into two groups: current smokers throughout the screening period and former smokers. Results: With a median follow-up time of 9.7 years and a total of 32,857 person-years (PYs) of follow-up, a total of 151 deaths were observed in the group of 1797 current smokers (17,846 PYs) versus 109 among 1584 former smokers (15,011 PYs), corresponding to mortality rates of 8.46 and 7.26 for every 1000 PYs, respectively. Compared with current smokers, former smokers had an adjusted mortality hazard ratio of 0.61 (95% confidence interval: 0.44-0.83), with a 39% reduction in mortality. A similar reduction in mortality was observed in the subset of 712 late quitters, with a hazard ratio of 0.65 (95% confidence interval: 0.44-0.96). Conclusions: Stopping smoking significantly reduces the overall mortality of smokers enrolled in LDCT screening programs. The beneficial effect of stopping smoking on total mortality appears to be threefold to fivefold greater than the one achieved by earlier detection in the National Lung Screening Trial.

BACKGROUND Delayed diagnosis of fibrotic interstitial lung disease (ILD) is characterized by significant repercussions for management and survival. A timely assessment of “velcro-type” crackles at lung auscultation might prompt a proper diagnostic process in these patients. The accuracy of objective, computerized methods in detecting ILD from respiratory sounds has not been systematically assessed in a clinical setting. We aimed to validate automatic detection of “velcro-type” crackles by comparing the results of lung sounds analysis with chest high resolution computed tomography (HRCT) scans. METHODS Lung sounds were recorded using an electronic stethoscope (Littmann 3200) from anatomically defined sites in 56 subjects (derivation cohort) undergoing a chest HRCT scan in Modena (Italy). Three-hundred anonymized, single-layer HRCT images corresponding to the sites of sound recording were reviewed by two radiologists with expertise in ILD and scored for the signs indicating lung fibrosis. All audio recordings were analyzed by extracting a set of global acoustic features from each file and different classification algorithms were employed on a subset of the best ranked features to classify the data into two groups. The gold standard used to label the ground truth for each sound file was based on the evidence of fibrosis in the corresponding HRCT image. Two ILD physicians were also asked to independently assess the sound files for the presence of “velcro-type” crackles. The results were validated in a further cohort of 59 patients (validation cohort) undergoing chest HRCT in Parma (Italy). Three-hundred nineteen HRCT images and corresponding sound files were obtained. RESULTS In the derivation cohort, accuracy of 74.4% was achieved in automatic detection of lung sounds associated with fibrotic HRCT images. However, although specificity was high (87.3%), sensitivity was lower (48.5%). The two respiratory physicians showed comparable performance, with accuracy 71.6%, spec

Purpose: It is unclear whether (and, to what extent) radiologists look at and report cardiovascular abnormalities on non-cardio-synchronized standard chest computed tomography (CT). In this study, the frequency and the reporting rate of cardiovascular findings in chest CT examinations were retrospectively assessed. Materials and methods: This study was approved by the institutional review board of each participating center. Four academic centers provided data on 447 subjects who underwent non-ECG-synchronized chest CT examinations for evaluating pulmonary fibrosis (161/447, 36 %), suspected pulmonary embolism (140/447, 31.3 %), or lung cancer staging (146/447, 32.7 %). A total of 220/447 (53.7 %) and 227/447 CT (46.3 %) examinations were evaluated and reported by junior and senior chest radiologists, respectively. Two radiologists with training in cardiac imaging reviewed the same chest CT images looking for the presence of incidental cardiovascular abnormalities using a preformatted score sheet. Inter-observer agreement was assessed using the kappa coefficient of agreement (k). Results: Inter-observer agreement between the study reviewers was moderate to good (0.4–0.73) for most of the incidental cardiovascular findings. At least one incidental cardiovascular finding not documented in the original report was identified by the study reviewers in 225/409 (55 %) of chest CT examinations. A total of 168/266 (63.2 %) potentially clinically significant cardiovascular findings were unreported in the original reports of 177/447 (39.6 %) subjects (p < 0.0001). Senior radiologists tended to more frequently report coronary artery calcification (p = 0.0006), cardiac valves calcification (p = 0.0003), and ascending aorta enlargement (p = 0.01) compared to junior radiologists. Conclusions: Several cardiovascular abnormalities can be reliably identified on standard chest CT. Yet, they are often und

Background: Fibroblastic foci profusion on histopathology and severity of traction bronchiectasis on highresolution computed tomography (HRCT) have been shown to be predictors of mortality in patients with idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the relationship between fibroblastic foci (FF) profusion and HRCT patterns in patients with a histopathologic diagnosis of usual interstitial pneumonia (UIP), fibrotic non-specific interstitial pneumonia (NSIP) and chronic hypersensitivity pneumonitis (CHP). Methods: The HRCT scans of 162 patients with a histopathologic diagnosis of UIP or fibrotic NSIP (n = 162) were scored on extent of groundglass opacification, reticulation, honeycombing, emphysema and severity of traction bronchiectasis. For each patient, a fibroblastic foci profusion score based on histopathologic appearances was assigned. Relationships between extent of fibroblastic foci and individual HRCT patterns were investigated using univariate correlation analysis and multivariate linear regression. Results: Increasing extent of reticulation (P < 0.0001) and increasing severity of traction bronchiectasis (P < 0.0001) were independently associated with increasing FF score within the entire cohort. Within individual multidisciplinary team diagnosis subgroups, the only significant independent association with FF score was severity of traction bronchiectasis in patients with idiopathic pulmonary fibrosis (IPF)/UIP (n = 66, r2 = 0.19, P < 0.0001) and patients with chronic hypersensitivity pneumonitis (CHP) (n = 49, r2 = 0.45, P < 0.0001). Furthermore, FF score had the strongest association with severity of traction bronchiectasis in patients with IPF (r2 = 0.34, P < 0.0001) and CHP (r2 = 0.35, P < 0.0001). There was no correlation between FF score and severity of traction bronchiectasis in patients with fibrotic NSIP. Global disease extent had the strongest association with severity of traction bronchiectasis in patients with fi

Seven years after left hemicolectomy and radical lymph nodal dissection followed by adjuvant chemotherapy for colorectal cancer (histotype, adenocarcinoma; stage, pT3N2M0; grading, G2), a slight increase in carcinoembryonic antigen levels (6.2 ng/mL; range, 0-5 ng/mL) was detected in a 79-year-old man. He was a heavy smoker with history of an interstitial fi brotic lung disease with associated areas of emphysema.

RATIONALE. Interstitial lung disease (ILD) is a well-recognized complication of rheumatoid arthritis (RA) and can present with different patterns on high-resolution computed tomography (HRCT) of the chest. It has been recently shown that a definite HRCT usual interstitial pneumonia (UIP) pattern is highly specific and moderately sensitive for a histopathologic UIP pattern. The aims of the present study were: i) to evaluate the prevalence of the UIP pattern on HRCT in patients with RA-ILD, as compared with patients with idiopathic pulmonary fibrosis (IPF) and ii) to assess the level of agreement between two experienced chest radiologists in detecting the UIP pattern in the two groups of patients. METHODS. 30 patients with RA and at least one chest HRCT showing interstitial changes were retrospectively identified from a single-center cohort of RA patients. Fifty-two patients with IPF based on current diagnostic criteria served as diseased controls. For patients who had more than one HRCT the more recent HRCT was selected. Two experienced thoracic radiologists (radiologist A and B) blinded to patient diagnosis scored all HRCT images independently. Radiologic patterns were categorized as definite UIP, possible UIP or inconsistent with UIP according to the most current international guidelines. The prevalence of the different patterns was assessed for both groups and compared by using the chi square test. The concordance between radiologists was determined using the Cohen kappa score. RESULTS. Radiologist A detected 4 definite UIP (13%), 10 possible UIP (33%) and 16 inconsistent with UIP patterns (53%) among patients with RA-ILD and 16 definite UIP (30%), 24 possible UIP (46%) and 12 inconsistent with UIP patterns (23%) among patients with IPF (chi square 0.016). Radiologist B identified 6 definite UIP (20%), 9 possible UIP (30%) and 15 inconsistent with UIP patterns (50%) in the RA-ILD group and 23 definite UIP (44%), 16 possible UIP (30%) and 13 inconsistent with UIP p

RHEUMATOID ARTHRITIS RELATED INTERSTITIAL LUNG DISEASE. RADIOLOGICAL PATTERNS AND CORRELATIONS WITH CLINICAL, SEROLOGICAL AND DEMOGRAPHIC FEATURES OF DISEASE

Background: In 2002 the American Thoracic Society/European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs)definedseven specific entities, andprovided standardized terminology anddiagnosticcriteria. Inaddition, thehistorical "gold standard" of histologic diagnosiswas replaced by amultidisciplinary approach. Since 2002 many publications have provided newinformation about IIPs. Purpose: The objective of this statement is to update the 2002 ATS/ ERS classification of IIPs. Methods: An international multidisciplinary panel was formed and developed key questions that were addressed through a review of the literature published between 2000 and 2011. Results: Substantial progress has been made in IIPs since the previous classification. Nonspecific interstitial pneumonia is now better defined. Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute exacerbation of IIPs is now well defined. A substantial percentage of patients with IIP are difficult to classify, often due to mixed patterns of lung injury. A classification based on observed disease behavior is proposed for patients who are difficult to classify or for entities with heterogeneity in clinical course. A group of rare entities, including pleuroparenchymal fibroelastosis and rare histologic patterns, is introduced. The rapidly evolving field of molecular markers is reviewed with the intent of promoting additional investigations that may help in determining diagnosis, and potentially prognosis and treatment. Conclusions: This update is a supplement to the previous 2002 IIP classification document. It outlines advances in the past decade and potential areas for future investigation. Copyright © 2013 by the American Thoracic Society.

Background: Factors determining the shape of the human rib cage are not completely understood. We aimed to quantify the contribution of anthropometric and COPD-related changes to rib cage variability in adult cigarette smokers. Methods: Rib cage diameters and areas (calculated from the inner surface of the rib cage) in 816 smokers with or without COPD, were evaluated at three anatomical levels using computed tomography (CT). CTs were analyzed with software, which allows quantification of total emphysema (emphysema%). The relationship between rib cage measurements and anthropometric factors, lung function indices, and %emphysema were tested using linear regression models. Results: A model that included gender, age, BMI, emphysema%, forced expiratory volume in one second (FEV1)%, and forced vital capacity (FVC)% fit best with the rib cage measurements (R2 = 64% for the rib cage area variation at the lower anatomical level). Gender had the biggest impact on rib cage diameter and area (105.3 cm2; 95% CI: 111.7 to 98.8 for male lower area). Emphysema% was responsible for an increase in size of upper and middle CT areas (up to 5.4 cm2; 95% CI: 3.0 to 7.8 for an emphysema increase of 5%). Lower rib cage areas decreased as FVC% decreased (5.1 cm2; 95% CI: 2.5 to 7.6 for 10 percentage points of FVC variation). Conclusions: This study demonstrates that simple CT measurements can predict rib cage morphometric variability and also highlight relationships between rib cage morphometry and emphysema.