Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

BACKGROUND: Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. METHODS: In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. RESULTS: Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). CONCLUSIONS: In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.

Chronic lung allograft dysfunction phenotype and prognosis by machine learning CT analysis.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used a machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared with radiologist scoring. METHODS: This retrospective study included all adult first double lung transplant patients (January 2010-December 2015) with CLAD (censored December 2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus and CLAD phenotype. RESULTS: 88 patients were included (57 bronchiolitis obliterans syndrome (BOS), 20 restrictive allograft syndrome (RAS)/mixed and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (area under the curve (AUC) 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC 0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (hazard ratio 1.23, 95% CI 1.05-1.44; p=0.01). CONCLUSIONS: Machine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.

Assessment of lateral costal artery with CT angiography: determination of prevalence and vessel length in the general population and its potential impact for coronary artery bypass grafting.

OBJECTIVES: Standard treatment for severe coronary artery disease (CAD) is coronary artery bypass grafting (CABG). An underreported branch of the internal mammary artery, the lateral costal artery (LCA), can cause a steal phenomenon after CABG, resulting in angina. The aim of this study was to determine the prevalence and length of LCA based on CT angiography (CTA). METHODS: This retrospective study included adult patients undergoing a thoracic CTA between January 2016 and August 2018. Exclusion criteria were prior CABG, insufficient clinical information, or inadequate image quality. Two blinded, independent readers reviewed all studies for the prevalence of the LCA. Positive cases were reviewed by two readers (R1/R2) for side distribution and vessel length, measured in intercostal spaces (ICS). Study indication, aortic size, and coronary calcification were noted. RESULTS: LCA was present in up to 42/389 (11%) of studies (60.3 ± 16.7 years, 30 males). The LCA was most commonly unilateral (n = 23, 55%). Median vessel length was 2 ICS (IQR 0; 3). Logistic regression was not significant in vessel distribution for sex (OR 0.6, 95% CI 0.28-1.15; p = 0.11). Inter-observer agreement in detecting LCA was substantial (kappa 0.71, 95% CI 0.59-0.83) and excellent for side/length distribution (kappa 0.94, 95% CI 0.82-1.0; ICC 0.96, 95% CI 0.93-0.98). CONCLUSION: The LCA is uncommon and most often unilateral and extends the third rib. Radiologists should be aware of this vessel and its potential role in angina after CABG, particularly when large. KEY POINTS: • LCA is an uncommon normal variant that is reported to cause angina pectoris after CABG. • CT angiography can reliably detect the LCA. It is most often unilateral and spans two intercostal spaces.

Significance of phenotype change after chronic lung allograft dysfunction onset.

Definitions for chronic lung allograft dysfunction (CLAD) phenotypes were recently revised (2019 ISHLT consensus). Post-CLAD onset phenotype transition may occur as a result of change in obstruction, restriction, or RAS-like opacities (RLO). We aimed to assess the prevalence and prognostic implications of these transitions. This was a single-center, retrospective cohort study of bilateral lung transplants performed in 2009-2015. CLAD phenotypes were determined per ISHLT guidelines. CLAD phenotype transition was defined as a sustained change in obstruction, restriction or RLO. We specifically focused on phenotype changes based on RLO emergence. Association of RLO development with time to death or retransplant were assessed using Kaplan-Meier and Cox proportional hazards models. Among 211 patients with CLAD, 47 (22.2%) experienced a phenotype transition. Nineteen patients developed RLO. Development of RLO phenotype after CLAD onset was associated with a shorter time to death/retransplant when considering the entire CLAD patient cohort (HR = 4.00, CI 2.74-5.83, P < 0.001) and also when restricting the analysis to only patients with a Non-RLO phenotype at CLAD onset (HR 9.64, CI 5.52-16.84, P < 0.0001). CLAD phenotype change based on emergence of RAS-like opacities implies a worse outcome. This highlights the clinical importance of imaging follow-up to monitor for phenotype transitions after CLAD onset.

Cardiothoracic Imaging for Outcome Prediction in Chronic Thromboembolic Pulmonary Hypertension after Pulmonary Endarterectomy or Balloon Pulmonary Angioplasty: A Scoping Review.

There has been a rapid expansion in centers performing balloon pulmonary angioplasty (BPA) and pulmonary thromboendarterectomy (PTE) for chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of this scoping review was to identify cardiothoracic imaging predictors of outcomes and to identify gaps to address in future work. A scoping review was conducted using the framework outlined by Arksey and O'Malley and Levac et al. in MEDLINE and EMBASE. The study protocol was preregistered in OSF Registries and performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines. There were 1117 identified studies, including 48 involving pulmonary thromboendarterectomy (n = 25) and balloon pulmonary angioplasty (n = 23). CT was the most common preoperative imaging modality used (n = 21) and CT level of disease was the most reported imaging predictor of outcomes for pulmonary thromboendarterectomy. Although must studies evaluated hemodynamic improvements, imaging was of additional use in predicting clinically significant procedural complications after balloon pulmonary angioplasty, as well as mortality and long-term outcome after pulmonary endarterectomy. Predictors reported in MRI and digital subtraction angiography were less commonly reported and warrant multicenter validation. Cardiothoracic imaging may predict clinically significant outcomes after balloon pulmonary angioplasty and pulmonary thromboendarterectomy. Radiologists involved in the assessment of CTEPH patients should be aware of key predictors and future investigations could focus on multicenter validation and new technologies.

A radiographic score for human donor lungs on ex vivo lung perfusion predicts transplant outcomes.

BACKGROUND: Ex vivo lung perfusion (EVLP) is an advanced platform for isolated lung assessment and treatment. Radiographs acquired during EVLP provide a unique opportunity to assess lung injury. The purpose of our study was to define and evaluate EVLP radiographic findings and their association with lung transplant outcomes. METHODS: We retrospectively evaluated 113 EVLP cases from 2020-21. Radiographs were scored by a thoracic radiologist blinded to outcome. Six lung regions were scored for 5 radiographic features (consolidation, infiltrates, atelectasis, nodules, and interstitial lines) on a scale of 0 to 3 to derive a score. Spearman's correlation was used to correlate radiographic scores to biomarkers of lung injury. Machine learning models were developed using radiographic features and EVLP functional data. Predictive performance was assessed using the area under the curve. RESULTS: Consolidation and infiltrates were the most frequent findings at 1 hour EVLP (radiographic lung score 2.6 (3.3) and 4.6 (4.3)). Consolidation (r = -0.536 and -0.608, p < 0.0001) and infiltrates (r = -0.492 and -0.616, p < 0.0001) were inversely correlated with oxygenation (∆pO2) at 1 hour and 3 hours of EVLP. First-hour consolidation and infiltrate lung scores predicted transplant suitability with an area under the curve of 87% and 88%, respectively. Prediction of transplant outcomes using a machine learning model yielded an area under the curve of 80% in the validation set. CONCLUSIONS: EVLP radiographs provide valuable insight into donor lungs being assessed for transplantation. Consolidation and infiltrates were the most common abnormalities observed in EVLP lungs, and radiographic lung scores predicted the suitability of donor lungs for transplant.

Improving prognostic accuracy in lung transplantation using unique features of isolated human lung radiographs.

Ex vivo lung perfusion (EVLP) enables advanced assessment of human lungs for transplant suitability. We developed a convolutional neural network (CNN)-based approach to analyze the largest cohort of isolated lung radiographs to date. CNNs were trained to process 1300 longitudinal radiographs from n = 650 clinical EVLP cases. Latent features were transformed into principal components (PC) and correlated with known radiographic findings. PCs were combined with physiological data to classify clinical outcomes: (1) recipient time to extubation of <72 h, (2) ≥ 72 h, and (3) lungs unsuitable for transplantation. The top PC was significantly correlated with infiltration (Spearman R: 0·72, p < 0·0001), and adding radiographic PCs significantly improved the discrimination for clinical outcomes (Accuracy: 73 vs 78%, p = 0·014). CNN-derived radiographic lung features therefore add substantial value to the current assessments. This approach can be adopted by EVLP centers worldwide to harness radiographic information without requiring real-time radiological expertise.

Chronic thromboembolic pulmonary hypertension secondary to a vascular malformation: case report diagnosis by lung subtraction iodine mapping.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a challenging diagnosis that can occur even in the absence of a prior thrombotic event. The main screening test is ventilation-perfusion (VQ) scintigraphy. The gold standard treatment for CTEPH is pulmonary endarterectomy (PEA), however, balloon pulmonary angioplasty (BPA) is an emerging treatment, especially for CTEPH at the segmental level. We report on a case of a patient with segmental CTEPH diagnosed by lung subtraction iodine mapping (LSIM) in the context of a chest wall vascular malformation. CTEPH was treated with BPA and by embolization and ligation of their vascular malformation.

Enhancing preoperative assessment in chronic thromboembolic pulmonary hypertension: A comprehensive analysis of interobserver agreement and proximity-based CT pulmonary angiography scoring.

Background: Surgical risk in chronic thromboembolic pulmonary hypertension (CTEPH) depends on the proximity of thromboembolism on CT pulmonary angiography (CTPA). We assessed interobserver agreement for the quantification of thromboembolic lesions in CTEPH using a novel CTPA scoring index. Methods: Forty CTEPH patients (mean age, 58 ± 16 years; 19 men) with preoperative CTPA who underwent pulmonary endarterectomy (PEA) (08/2020-09/2021) were retrospectively included. Three radiologists scored each CTPA for chronic thromboembolism (occlusions, eccentric thickening, webs) using a 32-vessel model of the pulmonary vasculature, with interobserver agreement evaluated using Fleiss' kappa. CT level of disease was determined by the most proximal chronic thromboembolism: level 1 (main pulmonary artery), 2 (lobar), 3 (segmental) and 4 (subsegmental), and compared to surgical level at PEA. Results: Interobserver agreement for CT level of disease was moderate overall (κ = 0.52). Agreement was substantial overall at the main/lobar level (κ, mean = 0.71) when excluding the left upper lobe (κ = 0.17). Though segmental and subsegmental agreement suffered (κ = 0.31), we found substantial agreement for occlusions (κ = 0.72) compared to eccentric thickening (κ = 0.45) and webs (κ = 0.14). Correlation between CT level and surgical level was strong overall (τb = 0.73) and in the right lung (τb = 0.68), but weak in the left lung (τb = 0.42) (p < 0.05). Radiologists often over- and underestimated the proximal extent of disease in right and left lung, respectively. Conclusions: CT level of disease demonstrated good agreement between radiologists and was highly predictive of the surgical level in CTEPH. Occlusions were the most reliable sign of chronic thromboembolism and are important in assessing the segmental vasculature.

Using Recurrent Neural Networks to Extract High-Quality Information From Lung Cancer Screening Computerized Tomography Reports for Inter-Radiologist Audit and Feedback Quality Improvement.

PURPOSE: Lung cancer screening programs generate a high volume of low-dose computed tomography (LDCT) reports that contain valuable information, typically in a free-text format. High-performance named-entity recognition (NER) models can extract relevant information from these reports automatically for inter-radiologist quality control. METHODS: Using LDCT report data from a longitudinal lung cancer screening program (8,305 reports; 3,124 participants; 2006-2019), we trained a rule-based model and two bidirectional long short-term memory (Bi-LSTM) NER neural network models to detect clinically relevant information from LDCT reports. Model performance was tested using F1 scores and compared with a published open-source radiology NER model (Stanza) in an independent evaluation set of 150 reports. The top performing model was applied to a data set of 6,948 reports for an inter-radiologist quality control assessment. RESULTS: The best performing model, a Bi-LSTM NER recurrent neural network model, had an overall F1 score of 0.950, which outperformed Stanza (F1 score = 0.872) and a rule-based NER model (F1 score = 0.809). Recall (sensitivity) for the best Bi-LSTM model ranged from 0.916 to 0.991 for different entity types; precision (positive predictive value) ranged from 0.892 to 0.997. Test performance remained stable across time periods. There was an average of a 2.86-fold difference in the number of identified entities between the most and the least detailed radiologists. CONCLUSION: We built an open-source Bi-LSTM NER model that outperformed other open-source or rule-based radiology NER models. This model can efficiently extract clinically relevant information from lung cancer screening computerized tomography reports with high accuracy, enabling efficient audit and feedback to improve quality of patient care.

Highlights from the International Chronic Thromboembolic Pulmonary Hypertension Congress 2021.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism. It is caused by persistent obstruction of pulmonary arteries by chronic organised fibrotic clots, despite adequate anticoagulation. The pulmonary hypertension is also caused by concomitant microvasculopathy which may progress without timely treatment. Timely and accurate diagnosis requires the combination of imaging and haemodynamic assessment. Optimal therapy should be individualised to each case and determined by an experienced multidisciplinary CTEPH team with the ability to offer all current treatment modalities. This report summarises current knowledge and presents key messages from the International CTEPH Conference, Bad Nauheim, Germany, 2021. Sessions were dedicated to 1) disease definition; 2) pathophysiology, including the impact of the hypertrophied bronchial circulation, right ventricle (dys)function, genetics and inflammation; 3) diagnosis, early after acute pulmonary embolism, using computed tomography and perfusion techniques, and supporting the selection of appropriate therapies; 4) surgical treatment, pulmonary endarterectomy for proximal and distal disease, and peri-operative management; 5) percutaneous approach or balloon pulmonary angioplasty, techniques and complications; and 6) medical treatment, including anticoagulation and pulmonary hypertension drugs, and in combination with interventional treatments. Chronic thromboembolic pulmonary disease without pulmonary hypertension is also discussed in terms of its diagnostic and therapeutic aspects.

Global trends in chronic thromboembolic pulmonary hypertension clinical trials and dissemination of results.

Treatment options for chronic thromboembolic pulmonary hypertension (CTEPH) are rapidly expanding. The purpose of this study is to identify trends in CTEPH clinical trials and the publication of results. We performed a worldwide review of completed and ongoing clinical trials through searching the ClinicalTrials.gov database and the World Health Organization International Clinical Trials Registry Platform for "CTEPH" and related terms. Entries were classified as pharmaceutical/procedural interventions (Group 1), all other clinical trials (Group 2) and patient registries (Group 3). Trial characteristics and national affiliation were recorded. PubMed was searched for related publications. There were 117 clinical trials registry entries after removing duplicates and non-target records. Group 1 comprised 29 pharmaceutical, 15 procedural, and four combined interventions starting in 2005, 2010, and 2016, respectively. Riociguat and balloon pulmonary angioplasty were the most frequent pharmaceutical and procedural interventions, respectively. The proportion of procedural trials increased over time from 0% of those in 2005-2009 to 29% in 2010-2014 and 54% in 2015-2020. There were 56 entries in Group 2 and 13 in Group 3. Japan was the most frequent national affiliation and the most frequent participating country, present in 28% of all trials. The proportion of entries with published results was highest with Group 3 (62%) and lowest with Group 1 (27%). Thirty percent of all publications occurred in 2020. In conclusion, CTEPH clinical trials are increasingly procedural based, with growth largely attributable to Japan and balloon pulmonary angioplasty. Most trials have not published, but results from balloon pulmonary angioplasty clinical trials are anticipated soon.

Importance of computed tomography in defining segmental disease in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Radiological assessment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) is critical to decide whether patients should be treated with pulmonary endarterectomy (PEA). Although computed tomography pulmonary angiography (CTPA) is increasingly used for decision making in CTEPH, the value of CTPA to predict surgical findings and outcome has never been explored. METHODS: We retrospectively reviewed 100 consecutive patients with high-quality CTPA undergoing PEA for CTEPH between May 2015 and December 2017. The most proximal level of disease in the pulmonary artery on CTPA was classified by two blinded radiologists as level 1 (main pulmonary artery), 2a (lobar pulmonary artery), 2b (origin of basal segmental pulmonary artery), 3 (segmental pulmonary artery) or 4 (predominantly subsegmental pulmonary artery). RESULTS: CTPA demonstrated level 1 in 20%, level 2a in 43%, level 2b in 11%, level 3 in 23% and level 4 in 3%. A majority of males presented with level 1 (55%) and level 2 (57%), and a majority of females (83%) with level 3 (p=0.01). Levels 3 and 4 were associated with longer duration of circulatory arrest (p=0.03) and higher frequency of Jamieson type III disease at surgery (p<0.0001). Requirement for targeted pulmonary hypertension therapy after PEA was 28% at 3 years in level 2b/3/4 compared with 6% in level 2a and 13% in level 1 (p=0.002). Level 2b/3/4 was an independent predictor for targeted pulmonary hypertension therapy after PEA (hazard ratio 4.23, 95% CI 1.24-14.39; p=0.02). CONCLUSIONS: High-quality CTPA provides accurate evaluation of CTEPH patients. The level of disease on CTPA can help guide peri-operative planning and post-operative monitoring.

Advanced Technologies for Imaging and Visualization of the Tracheobronchial Tree: From Computed Tomography and MRI to Virtual Endoscopy.

Advanced imaging plays an increasingly important role in the evaluation of the trachea. The use of computed tomography (CT) has evolved to include multi-planar reconstructions and 3-dimensional reconstructions for the evaluation of benign and malignant disease of the trachea. Advanced applications of CT include dynamic expiratory imaging for the diagnosis of tracheomalacia and virtual endoscopy as a complementary or alternative examination to flexible bronchoscopy. MRI of the trachea has limited applications but may see increased use in the future.