A deep learning model (LCP CNN) for the stratification of indeterminate pulmonary nodules (IPNs) demonstrated better discrimination than commonly used clinical prediction models. However, the LCP CNN ...score is based on a single timepoint that ignores longitudinal information when prior imaging studies are available. Clinically, IPNs are often followed over time and temporal trends in nodule size or morphology inform management. In this study we investigated whether the change in LCP CNN scores over time was different between benign and malignant nodules. This study used a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design. Subjects with incidentally or screening detected IPNs 6-30 mm in diameter with at least 3 consecutive CT scans prior to diagnosis (slice thickness ≤ 1.5 mm) with the same nodule present were included. Disease outcome was adjudicated by biopsy-proven malignancy, biopsy-proven benign disease and absence of growth on at least 2-year imaging follow-up. Lung nodules were analyzed using the Optellum LCP CNN model. Investigators performing image analysis were blinded to all clinical data. The LCP CNN score was determined for 48 benign and 32 malignant nodules. There was no significant difference in the initial LCP CNN score between benign and malignant nodules. Overall, the LCP CNN scores of benign nodules remained relatively stable over time while that of malignant nodules continued to increase over time. The difference in these two trends was statistically significant. We also developed a joint model that incorporates longitudinal LCP CNN scores to predict future probability of cancer. Malignant and benign nodules appear to have distinctive trends in LCP CNN score over time. This suggests that longitudinal modeling may improve radiomic prediction of lung cancer over current models. Additional studies are needed to validate these early findings.
Nonspecific pleuritis (NSP) is a frequent diagnosis after parietal pleural biopsy, but the clinical significance of this finding and need for further follow-up have not been firmly established. ...Previous reports suggest that 5% to 25% of patients with NSP are subsequently diagnosed with pleural malignancy.
Our pathology database was queried for patients with histologic evidence of NSP from January 01, 2001, to December 31, 2012 (n = 413). Patients with less than 1 year of follow-up after biopsy, diagnosis of empyema, tuberculous pleuritis, active systemic connective tissue disease or vasculitis, or active malignancy were excluded (n = 327). The remaining patients were included and their medical records were reviewed.
Eighty-six patients were included. Mean follow up was 1,824 ± 1,032 days (range, 409 to 4,599 days). Three of the 86 patients with NSP (3.5%) were subsequently diagnosed with pleural malignancy. All 3 patients were found to have mesothelioma with a mean time from biopsies to diagnosis of 205 ± 126 days (range, 64 to 306 days). Twenty-two of 86 patients (25.5%) had a possible identifiable cause of pleural inflammation (benign disease). After exclusion of these 22 patients, the incidence of malignancy was 3 of 64 (4.7%).
The incidence of subsequent pleural malignancy (mesothelioma) among patients found to have NSP based on pleural biopsy was 3.5%. Occult mesothelioma in patients with NSP will most likely be diagnosed within 1 year of the initial pleural biopsy; therefore, these patients should be followed for a minimum of 1 year to allow for timely detection of occult pleural malignancy.
High-resolution chest computed tomography (HRCT) is essential in the characterization of interstitial lung disease. The HRCT features of some diseases can be diagnostic. Longitudinal monitoring with ...HRCT can assess progression of interstitial lung disease; however, subtle changes in the volume and character of abnormalities can be difficult to assess. Accuracy of diagnosis can be dependent on expertise and experience of the radiologist, pathologist, or clinician. Quantitative analysis of thoracic HRCT has the potential to determine the extent of disease reproducibly, classify the types of abnormalities, and automate the diagnostic process.
Novel software that utilizes histogram signatures to characterize pulmonary parenchyma was used to analyze chest HRCT data, including retrospective processing of clinical CT scans and research data from the Lung Tissue Research Consortium. Additional information including physiological, pathologic, and semiquantitative radiologist assessment was available to allow comparison of quantitative results, with visual estimates of the disease, physiological parameters, and measures of disease outcome.
Quantitative analysis results were provided in regional volumetric quantities for statistical analysis and a graphical representation. These results suggest that quantitative HRCT analysis can serve as a biomarker with physiological, pathologic, and prognostic significance.
It is likely that quantitative analysis of HRCT can be used in clinical practice as a means to aid in identifying a probable diagnosis, stratifying prognosis in early disease, and consistently determining progression of the disease or response to therapy. Further optimization of quantitative techniques and longitudinal analysis of well-characterized subjects would be helpful in validating these methods.
To assess the frequency and clinical implications of positive autoimmune serologies in patients with biopsy-confirmed idiopathic pulmonary fibrosis (IPF).
We reviewed the records of patients at our ...institution with biopsy-confirmed usual interstitial pneumonia (UIP) from January 1, 1995, through December 31, 2010, for frequency and distribution of autoimmune serologies. Patients with IPF with and without positive serologies were compared.
Three hundred eighty-nine consecutive patients with biopsy-confirmed IPF underwent serologic testing, with positive serologic test results being found in 112 (29%). Of 2051 individual screening serologic tests performed, results of 163 tests were positive (8%), with antinuclear antibody being the most frequent (47%). There was no difference in age at biopsy (P=.21), gender (P=.21), or presenting radiologic features between those with or without positive serology. More frequent use of immunosuppressive treatment (P=.02) was noted in those with positive serology. No survival difference was observed (log-rank; P=.43). Median follow-up for the whole cohort was 43.5 months.
Positive autoimmune serology may occur in as much as one-third of the patients with biopsy-confirmed IPF with no associated clinical implication or survival advantage. Systematic use of autoimmune laboratory panels in patients without clinical features of connective tissue disease should be reconsidered in patients with suspected UIP on chest computed tomography scan or confirmed UIP on biopsy.
Lung adenocarcinoma (LUAD) is the predominant type of lung cancer in the U.S. and exhibits a broad variety of behaviors ranging from indolent to aggressive. Identification of the biological ...determinants of LUAD behavior at early stages can improve existing diagnostic and treatment strategies. Extracellular matrix (ECM) remodeling and cancer-associated fibroblasts play a crucial role in the regulation of cancer aggressiveness and there is a growing need to investigate their role in the determination of LUAD behavior at early stages. We analyzed tissue samples isolated from patients with LUAD at early stages and used imaging-based biomarkers to predict LUAD behavior. Single-cell RNA sequencing and histological assessment showed that aggressive LUADs are characterized by a decreased number of ADH1B
CAFs in comparison to indolent tumors. ADH1B
CAF enrichment is associated with distinct ECM and immune cell signatures in early-stage LUADs. Also, we found a positive correlation between the gene expression of ADH1B
CAF markers in early-stage LUADs and better survival. We performed TCGA dataset analysis to validate our findings. Identified associations can be used for the development of the predictive model of LUAD aggressiveness and novel therapeutic approaches.
The burden of a number of pleural diseases continues to increase internationally. Although many pleural procedures have historically been the domain of interventional radiologists or thoracic ...surgeons, in recent years, there has been a marked expansion in the techniques available to the pulmonologist. This has been due in part to both technological advancements and a greater recognition that pleural disease is an important subspecialty of respiratory medicine. This article summarises the important literature relating to a number of advanced pleural interventions, including medical thoracoscopy, the insertion and use of indwelling pleural catheters, pleural manometry, point-of-care thoracic ultrasound, and image-guided closed pleural biopsy. We also aim to inform the reader regarding the latest updates to more established procedures such as chemical pleurodesis, thoracentesis and the management of chest drains, drawing on contemporary data from recent randomised trials. Finally, we shall look to explore the challenges faced by those practicing pleural medicine, especially relating to training, as well as possible future directions for the use and expansion of advanced medical interventions in pleural disease.
ObjectivesRecurrent symptomatic effusions can be durably managed with pleurodesis or placement of indwelling pleural catheters. Recent pleurodesis trials have largely relied on lung re-expansion on ...post-thoracentesis radiograph as an inclusion criterion rather than pleural elastance as determined by manometry, which is an important predictor of successful pleurodesis. We investigated the association between lung re-expansion on post-pleural drainage chest imaging and pleural physiology, with particular attention to pleural elastance over the final 200 mL aspirated.DesignPost-hoc analysis of a recent randomised trial.Setting and participantsPost-results analysis of 61 subjects at least 18 years old with symptomatic pleural effusions estimated to be at least of 0.5 L in volume allocated to manometry-guided therapeutic thoracentesis in a recent randomised trial conducted at two major university hospitals in the USA.Primary outcome measuresThe primary outcome was concordance of radiographic with normal terminal pleural elastance over the final 200 mL aspirated. We label this terminal elastance ‘visceral pleural recoil’, or the tendency of the maximally expanded lung to withdraw from the chest wall.ResultsPost-thoracentesis chest radiograph and thoracic ultrasound indicated successful lung re-expansion in 69% and 56% of cases, respectively. Despite successful radiographic lung re-expansion, visceral pleural recoil was abnormal in 71% of subjects expandable by radiograph and 77% expandable by ultrasound. The sensitivity and positive predictive value of radiographic lung re-expansion for normal visceral pleural recoil were 44% and 24%, respectively.ConclusionRadiographic lung re-expansion by post-thoracentesis chest radiograph or thoracic ultrasound is a poor surrogate for normal terminal pleural elastance. Clinical management of patients with recurrent symptomatic pleural effusions guided by manometry rather than post-thoracentesis imaging might produce better outcomes, which should be investigated by future clinical trials.Trial registration numberNCT02677883; Post-results.
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