Pathological Approach to Pleural Malignant Mesothelioma

Exposure to asbestos can lead to asbestosis or malignancy 10-40 years after initial exposure [1]. Although its use has been banned in multiple countries, past occupational exposure leads to most cases that we see in present time. Malignant mesothelioma is an insidious and rare neoplasm that can arise from mesothelial surface cells, being Malignant Pleural Mesothelioma (MPM) the most common type. Lifetime risk of developing mesothelioma among asbestos workers can be as high as 10 percent and latency period is approximately 30-40 years since time of exposure to development of disease [2]. Annual incidence in the united states is approximately 3,300 cases per year [3]. Median overall survival of patients with advanced unresectable disease is approximately 12 months [4]. Clinical suspicion should arise in patients with previous exposure to asbestos who present with pleural thickening and/or effusion with associated respiratory symptoms. Most symptoms are nonspecific such as chest pain, dyspnea, cough and night sweats. Initial evaluation includes chest x-ray, contrast enhanced CT of the chest to find pleural abnormalities, thoracentesis and closed pleural biopsy. However, difficulties establishing diagnosis have been illustrated on studies where thoracentesis and pleural fluid cytology only yields diagnosis in 26% of cases. The diagnosis, then, is established by morphologic and immunohistochemistry findings of cytologic and surgical specimens.

Computed tomography with 6-year follow-up demonstrates the evolution of HTLV-1 related lung injuries: A cohort study

Previous observational studies have demonstrated the development of pulmonary impairments in human T-lymphotropic virus type 1 (HTLV-1) infected individuals. The main observed lesions due to chronic inflammation of viral infection in situ are bronchiectasis and lung-scarring injuries. This lung inflammation may be the causal agent of restrictive and obstructive lung diseases, primarily in tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP-HAM) patients. We conducted a prospective cohort study to compare spirometry and high-resolution computed tomography (HRCT) findings among 28 HTLV-1-carrier patients over the course of 6 years (2014–2019) (male/female: 7/21; mean age: 54.7 ± 9.5, range: 41–68 years). Chest HRCT exams revealed the development and evolution of lung lesions related to TSP-HAM: including centrilobular nodules, parenchymal bands, lung cysts, bronchiectasis, ground-glass opacity, mosaic attenuation, and pleural thickening. Spirometry exams showed maintenance of respiratory function, with few alterations in parameters suggestive of obstructive and restrictive disorders primarily in individuals with lung lesions and TSP-HAM. The findings of the present study indicate that pulmonary disease related to HTLV-1 is a progressive disease, with development of new lung lesions, mainly in individuals with TSP-HAM. To improve clinical management of these individuals, we recommend that individuals diagnosed with PET-MAH undergo pulmonary evaluation.

Cyclical Learning Rates (CLR’s) for Improving Training Accuracies and Lowering Computational Cost

Prediction of different lung pathologies using chest X-ray images is a challenging task requiring robust training and testing accuracies. In this article, one-class classifier (OCC) and binary classification algorithms have been tested to classify 14 different diseases (atelectasis, cardiomegaly, consolidation, effusion, edema, emphysema, fibrosis, hernia, infiltration, mass, nodule, pneumonia, pneumothorax and pleural-thickening). We have utilized 3 different neural network architectures (MobileNetV1, Alexnet, and DenseNet-121) with four different optimizers (SGD, Adam, and RMSProp) for comparing best possible accuracies. Cyclical learning rate (CLR), a tuning hyperparameters technique was found to have a faster convergence of the cost towards the minima of cost function. Here, we present a unique approach of utilizing previously trained binary classification models with a learning rate decay technique for re-training models using CLR’s. Doing so, we found significant improvement in training accuracies for each of the selected conditions. Thus, utilizing CLR’s in callback functions seems a promising strategy for image classification problems.

High-Resolution Computed Tomography Based Comparative Analysis of Asbestosis vs. Fibrotic Hypersensitivity Pneumonitis

BackgroundAsbestosis and fibrotic hypersensitivity pneumonitis (FHP) are fibrotic interstitial lung diseases that develop secondary to inhalation exposure. The differential diagnosis is based on clinical evaluation of imaging findings, particularly in developing countries. We compared the imaging features between asbestosis and FHP to gain a better understanding of the differential diagnostic value of these conditions.MethodsThis comparative study included 204 patients with asbestosis and 74 patients with FHP. We compared patients’ clinical data and chest high-resolution computed tomography (HRCT) images obtained from a predesigned chart. The International Classification of HRCT for Occupational and Environmental Respiratory Diseases was used to categorize chest imaging findings in patients. Diagnostic tests were used to compare the imaging features of asbestosis and FHP.ResultsPatients with asbestosis were older and had a longer latent period until disease manifestation than those with FHP. Asbestosis was characterized by irregular and/or linear opacities, with lower lung preponderance, accompanied by ground-glass opacities and mosaic attenuation. Notably, 98.5% of patients with asbestosis showed benign pleural abnormalities, and >33% of these patients had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. Abnormalities of the mediastinal and diaphragmatic pleura were observed only in cases of asbestosis, and this finding showed high specificity for the diagnosis for asbestosis compared with that for FHP. Subpleural dots or diaphragmatic pleural abnormalities showed moderate sensitivity and high specificity for diagnosis of asbestosis compared with that for FHP. Interobserver reliability was good for evaluation of imaging findings including honeycombing, pleural calcification, lymphadenectasis, and lymph node calcification.ConclusionsHRCT-based imaging findings can distinguish between asbestosis and FHP to a certain extent, particularly with regard to subpleural dots and diaphragmatic pleural abnormalities that characterize the former.

The Effect of Insect Repellent Exposure on Leukocyte Profile and Histopathologic Findings in Lungs

Organophosphate compounds in insect repellent have a role in contributing to mosquito mortality but have toxic effects for humans when exposed for a long time. The research is aimed to analyze the effect of insect repellent exposure in blood leukocyte profile and histopathologic findings in lungs. The study used thirty males Rattus novergicus, which were divided into three groups, such as electric liquid insect repellent (P1) with contain 0.031% dimefluthrin, anti-mosquito coils (P2) with 0.014% dimefluthrin, and electric mat mosquito repellent with 0.566% dimefluthrin for 8 hours in 20 days respectively. Leukocyte profiles were determined by using the blood smear method, and the lung’s health was identified by histopathologic findings. Based on the results study showed mosquito coils exposure increase the lymphocytes count. Meanwhile, the electric liquid-repellent increased the basophil’s numbers. The electric mat exposure had more eosinophils, neutrophils stab, neutrophils segment, and monocytes in the blood. The leukocyte profile of each group showed there were no statistically significant differences (P-value > 0.05). Based on histopathology, lung findings showed that the electric mat exposure contributed to cells degeneration 7.5% and pleural thickening 30%. The higher dimefluthrin concentrations in insect repellents could affect leukocyte profile and lungs health.

Rounded atelectasis after exposure to refractory ceramic fibres (RCF)

Background Refractory Ceramic fibres (RCF) are man-made mineral fibres used in high performance thermal insulation applications. Analogous to asbestos fibres, RCF are respirable, show a pleural drift and can persist in human lung tissue for more than 20 years after exposure. Pleural changes such as localised or diffuse pleural thickening as well as pleural calcification were reported. Result A 45 years old man worked in high performance thermal insulation applications using refractory ceramic fibres (RCF) for almost 20 years. During a occupational medical prophylaxis to ensure early diagnosis of disorders caused by inhalation of aluminium silicate fibres with X-ray including high-resolution computed tomography (HRCT), bilateral pleural thickening was shown and a pleural calcification next to a rounded atelectasis was detected. Asbestos exposure could be excluded. In pulmonary function test a restrictive lung pattern could be revealed. In work samples scanning electron microscopy (SEM) including energy dispersive X-ray analysis (EDX) classified used fibres as aluminium silicate fibres. X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) showed crystalline as well as amorphous fibres. Conclusions A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.

Pleural Involvement in IgG4-Related Disease: Case Report and Review of the Literature

Diagnostic work-up of IgG4-related disease (IgG4-RD) pleural involvement is a complex task, as there is a broad spectrum of differential diagnoses to consider. We report the case of a patient presenting with relapsing pleural effusion, discussing the main challenges for achievement of a definite diagnosis. A 63-year-old man was admitted for pleural effusion prevalent on the ride side, initially labeled as idiopathic non-specific pleuritis, based on tissue evaluation after a medical thoracoscopy. He was started on steroids with initial improvement, but a later CT scan showed a relapse of pleural effusion associated with diffuse pleural thickening; a subsequent surgical pleural biopsy revealed features suggestive for IgG4-RD, with a marked increase of IgG4 positive plasma cells. High IgG4 serum levels were also found. The present case underlines the importance of increasing awareness of this potential condition among physicians in order to properly guide the diagnostic work-up, as it is likely that IgG4-RD accounts for a proportion of patients with pleural effusions, labeled as idiopathic. In particular, in patients with unexplained pleural effusion, IgG4-RD should be included among differential diagnoses when lymphoplasmacytic infiltration is observed, and a multidisciplinary interaction between clinicians and pathologists appears crucial for an accurate diagnosis and an appropriate management.

A novel PDX modeling strategy and its application in metabolomics study for malignant pleural mesothelioma

Background Malignant pleural mesothelioma (MPM) is a rare and aggressive carcinoma located in pleural cavity. Due to lack of effective diagnostic biomarkers and therapeutic targets in MPM, the prognosis is extremely poor. Because of difficulties in sample extraction, and the high rate of misdiagnosis, MPM is rarely studied. Therefore, novel modeling methodology is crucially needed to facilitate MPM research. Methods A novel patient-derived xenograft (PDX) modeling strategy was designed, which included preliminary screening of patients with pleural thickening using computerized tomography (CT) scan, further reviewing history of disease and imaging by a senior sonographer as well as histopathological analysis by a senior pathologist, and PDX model construction using ultrasound-guided pleural biopsy from MPM patients. Gas chromatography-mass spectrometry-based metabolomics was further utilized for investigating circulating metabolic features of the PDX models. Univariate and multivariate analysis, and pathway analysis were performed to explore the differential metabolites, enriched metabolism pathways and potential metabolic targets. Results After screening using our strategy, 5 out of 116 patients were confirmed to be MPM, and their specimens were used for modeling. Two PDX models were established successfully. Metabolomics analysis revealed significant metabolic shifts in PDX models, such as dysregulations in amino acid metabolism, TCA cycle and glycolysis, and nucleotide metabolism. Conclusions To sum up, we suggested a novel modeling strategy that may facilitate specimen availability for MM research, and by applying metabolomics in this model, several metabolic features were identified, whereas future studies with large sample size are needed.