Malignant mesothelioma: A clinicopathological study of 76 cases with emphasis on immunohistochemical evaluation along with review of the literature.

INTRODUCTION: Malignant mesothelioma is an aggressive neoplasm arising from serosal lining and has a poor prognosis. Definite diagnosis requires confirmation through a biopsy; however, it is sometimes difficult on microscopic evaluation alone and requires the use of a wide panel of immunohistochemical markers. So, immunohistochemistry (IHC) is of paramount importance and must be routinely used for a definite diagnosis. Till date, very few studies on morphology and detailed IHC markers of mesothelioma have been reported from India. AIMS: To analyze the histomorphological findings of malignant mesothelioma, study the utility and role of the various immunohistochemical markers. MATERIAL AND METHODS: A total of 76 cases of mesotheliomas diagnosed at a tertiary cancer center in Udaipur were analyzed retrospectively from January 2015 to January 2020. Comprehensive data were analyzed including demographic, clinical, radiological, histopathological features along with a wide panel of IHC markers. RESULTS: Mesothelioma occurs over a wide age range from 40 to 70 years. It most commonly involved pleura in 68 cases (89.47%) with very few cases from the peritoneum. On computed tomography (CT) scan, nodular pleural or peritoneal thickening was present. On microscopy, the most common histopathological type was epithelioid mesothelioma (58 cases, 74.3%) followed by sarcomatous (9 cases, 12.8%), deciduoid (6 cases, 8.6%), and 3 cases of biphasic (4.3%). On IHC, WT1, mesothelin, and calretinin markers were positive in 85.91%, 80%, and 93.33% cases of mesothelioma, respectively. Other markers were helpful to rule out differential diagnosis in difficult scenarios. CONCLUSION: Therefore, the correlation of histopathology with clinico-radiological findings and judicious use of a panel of IHC markers is required for routine evaluation and definite diagnosis. IHC is also useful in situations with similar morphological spectrum in specific locations.

Pleuroparenchymal fibroelastosis in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: PPFE is characterized by fibrosis in the pleura and subpleural lung parenchyma in the upper lobes, while other types of ILD, mainly UIP, can be observed in about half of the patients in their lower lobes. The aim of this study was to evaluate the clinical significance of the radiologically defined PPFE in patients with IPF. METHODS: Clinical data and chest CT images were retrospectively analysed in 445 patients with IPF (biopsy-proven cases, n = 165). The radiological criteria of PPFE were defined as follows: (i) bilateral subpleural dense fibrosis with or without pleural thickening in the upper lobes, (ii) evidence of disease progression and (iii) no clinical evidence of identifiable aetiologies. RESULTS: The median follow-up period was 43.0 months. The mean age of the patients was 66.4 years and 76.4% were male. PPFE was identified in 28 patients (6.3%). The PPFE group showed lower BMI and lung function (FVC and TLC) at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow-up than the no-PPFE group. PPFE was an independent risk factor (HR = 2.953, 95% CI: 1.350-6.460, P = 0.007) for pneumothorax or pneumomediastinum, but not for mortality in patients with IPF. CONCLUSION: Among patients with IPF, the PPFE group, when compared to the no-PPFE group, showed lower BMI and lung function and showed more frequent complications and poorer survival during follow-up.

Radiographic Changes in Colombian Asbestos Factory Workers.

Background: Until recently, Colombia has been a country actively using asbestos. A major factory in Bogota manufactures friction products. Objective: To determine if the use of chrysotile asbestos in a friction products facility leads to workers developing disease. Methods: One hundred forty-eight factory workers, former workers, or retirees volunteered for X-ray and pulmonary function testing after informed consent. X-rays were read by two readers who needed to agree on positive findings. Results: Nineteen of the 148 X-rays had changes consistent with the known prior exposure to asbestos, mostly parenchymal in nature. Pulmonary function was not altered in most of the studied population. Conclusion: Asbestos disease is clearly present among Colombian asbestos factory workers, as is seen in other exposed populations around the world.

Pleural Plaques and the Risk of Lung Cancer in Asbestos-exposed Subjects.

Rationale: Asbestos exposure is associated with a dose-dependent risk of lung cancer. The association between lung cancer and the presence of pleural plaques remains controversial.Objectives: To define the relationship between pleural plaques and lung cancer risk.Methods: Subjects were from two cohorts: 1) crocidolite mine and mill workers and Wittenoom Township residents and 2) a mixed-asbestos-fiber, mixed-occupation group. All subjects underwent annual review since 1990, chest X-ray or low-dose computed tomography scan, and outcome linkage to national cancer and mortality registry data. Cox regression, with adjustment for age (as the underlying matching time variable), was used to estimate hazard ratios (HRs) for lung cancer incidence by sex, tobacco smoking, asbestos exposure, presence of asbestosis, and pleural plaques.Measurements and Main Results: For all 4,240 subjects, mean age at follow up was 65.4 years, 3,486 (82.0%) were male, 1,315 (31.0%) had pleural plaques, and 1,353 (32.0%) had radiographic asbestosis. Overall, 3,042 (71.7%) were ever-smokers with mean tobacco exposure of 33 pack-years. In total, 200 lung cancers were recorded. Risk of lung cancer increased with cumulative exposure to cigarettes, asbestos, and presence of asbestosis. Pleural plaques did not confer any additional lung cancer risk in either cohort (cohort 1: HR, 1.03; 95% confidence interval, 0.64-1.67; P = 0.89; cohort 2: HR, 0.75; 95% confidence interval, 0.45-1.25; P = 0.28).Conclusions: The presence of pleural plaques on radiologic imaging does not confer additional increase in the risk of lung cancer. This result is consistent across two cohorts with differing asbestos fiber exposures and intensity.

Preoperative Detection of Pleural Adhesions Using Ultrasonography for Ipsilateral Secondary Thoracic Surgery Patients.

BACKGROUND/AIM: Video-assisted thoracic surgery (VATS) for ipsilateral reoperations is challenging because of the potential for pleural adhesions. Insertion of the initial port can lead to lung injury because of the blinded intrathoracic area. We assessed the usefulness of ultrasonography before VATS to reduce the incidence of lung injury at the time of the initial port insertion during secondary ipsilateral VATS. PATIENTS AND METHODS: Thirty-three patients who underwent repeat VATS for ipsilateral pulmonary lesions were included. All patients underwent preoperative ultrasonography to assess the possible presence of pleural adhesions using the lung sliding sign. RESULTS: Seven adhesions were found at the VATS ports. Two of these adhesions were not evaluated as pleural adhesions using ultrasonography; however, they were loose. All initial ports were inserted without lung injury. There were no major complications. CONCLUSION: Preoperative detection of pleural adhesions using ultrasonography can determine the best initial port for secondary ipsilateral VATS.

Frecuencia, tipo y predictores de complicaciones pleuropulmonares en los primeros treinta días del postoperatorio de pacientes pediátricos intervenidos de cirugía cardiovascular sin apoyo de circulación extracorpórea / Frequency and type of pleuropulmonary complications and their predictors during the first thirty days after cardiopulmonary bypass surgery in children

Resumen Objetivo: Determinar la frecuencia, tipo y predictores de complicaciones pleuropulmonares en los primeros 30 días de postoperatorio de pacientes intervenidos de cirugía cardiovascular sin apoyo de circulación extracorpórea. Métodos: Se realizó un estudio de cohorte retrospectivo durante el periodo comprendido del 1 de enero de 2013 al 31 de diciembre 2014. Incluyó a todos los pacientes portadores de cardiopatías congénitas intervenidos de cirugía cardiaca con abordaje esternal o torácico, sin soporte de circulación extracorpórea con ingreso registrado a Unidad de Cuidados Intensivos del Hospital de Pediatría del Centro Médico Nacional Siglo XXI, IMSS. Se cuantificó la frecuencia de eventos de las complicaciones pleuropulmonares y se realizó un análisis multivariado de regresión logística para identificar los factores de riesgo asociados a complicaciones pleuropulmonares, calculándose odds ratio (OR) e intervalos de confianza al 95% (IC 95%). Resultados: Se incluyeron un total de 139 pacientes, en los cuales la frecuencia de complicaciones pleuropulmonares fue del 42.4% (n = 59), y los tipos más frecuentes fueron atelectasia (28 eventos), neumonía asociada a ventilador (24 eventos), neumotórax (20 eventos), pudiéndose encontrar más de una complicación por paciente. Los predictores más significativos de complicaciones pleuropulmonares fueron las cardiopatías congénitas cianógenas (OR = 3.58; IC 95%: 1.10-7.50; p = 0.001), el abordaje por toracotomía (OR = 1.46; IC 95%: 1.18-1.12; p = 0.008) y el evento quirúrgico realizado de urgencia (OR = 3.46; IC 95%: 1.51-7.95; p = 0.002). Conclusiones: La principal complicación pleuropulmonar fue la atelectasia lo cual concuerda con lo reportado en la literatura internacional. Los pacientes que presenten alguno de los predictores identificados en el presente estudio deben ser monitorizados de manera especial para prevenir, detectar y/o tratar oportunamente las complicaciones pleuropulmonares tras cirugía cardiaca.

Abstract Objective: To determine the frequency and type of pleuropulmonary complications and their predictors in the first thirty postoperative days of patients undergoing surgery without cardiopulmonary bypass. Methods: A retrospective cohort study was carried out between January 2013 and December 2014. It included all patients with congenital heart disease who underwent cardiac surgery using a sternal or thoracic approach, without cardiopulmonary bypass with a registered admission to a Neonatal or Paediatric Intensive Care. The frequency of events of pleuropulmonary complications and logistic regression analysis was performed, and the adjusted odds ratio (OR) and confidence intervals at 95% (95% CI) were calculated. Results: A total of 139 patients were included. The frequency of pleuropulmonary complications was 42.4% (N = 59), and the most frequent types were atelectasis (28 events), ventilator-associated pneumonia (24 events), pneumothorax (20 events), with more than one complication per patient occasionally being found. Significant risk factors were cyanogenic congenital heart disease (OR = 3.58, 95% CI: 1.10-7.50, P =.001), thoracotomy approach (OR = 1.46, 95% CI: 1.18-1.12, P = .008), and an emergency surgical event (OR = 3.46, 95% CI: 1.51-7.95, P = .002). Conclusions: The main pleuropulmonary complication was atelectasis, which is consistent with that reported in the international literature. Patients with any of the predictors identified in the present study should be closely monitored in order to prevent, detect and/or treat pleuropulmonary complications in a timely manner after cardiac surgery.

[Asbestosis and pleural plaques].

Asbestos was used in numerous products until its total ban in Denmark in 1988. The prevalence of asbestosis and pleural plaques does not yet appear to be falling. Unfortunately the statistics are unreliable due to errors in the Danish translation of the ICD-10 codes of the disease. In this review, clinical and radiologic diagnostic criteria of asbestosis and pleural plaques and recommendations for follow-up of patients are described. Typical changes on a high-resolution CT scan combined with relevant asbestos exposure is essential for the diagnosis. Asbestosis and pleural plaques are both notifiable in Denmark.

An unusual presentation of pulmonary embolism leading to infarction, cavitation, abscess formation and bronchopleural fistulation.

We report an unusual presentation of pulmonary embolism (PE) where a 58-year-old man first developed symptoms of community-acquired pneumonia. Despite antibiotic therapy, he remained unwell with rising inflammatory markers, general malaise and persistent cough. He developed stony dull percussion and absent breath sounds to his left mid to lower zones. Serial chest x-rays showed progression from lobar consolidation to a large loculated left-sided pleural collection. CT chest showed left-sided lung abscess, empyema and bronchopleural fistulation. Incidentally, the scan revealed acute left-sided PE and its distribution corresponded with the location of the left lung abscess and empyema. The sequence of events likely started with PE leading to infarction, cavitation, abscess formation and bronchopleural fistulation. This patient was managed with a 6-month course of rivaroxaban. After completing 2 weeks of intravenous meropenem, he was converted to 4-week course of oral co-amoxiclav and metronidazole and attained full recovery.

Pleural manometry in patients with pleural diseases - the usefulness in clinical practice.

Although pleural manometry is a relatively simple medical procedure it is only occasionally used to follow pleural pressure (Ppl) changes during a therapeutic thoracentesis and pneumothorax drainage. As some studies showed that pleural pressure monitoring might be associated with significant advantages, pleural manometry has been increasingly evaluated in the last decade. The major clinical applications of pleural pressure measurements include: the prevention of complications associated with large volume thoracentesis, diagnosis and differentiation between various types of an unexpandable lung and a possible prediction of the efficacy of chest tube drainage in patients with spontaneous pneumothorax. It is well known that the therapeutic thoracentesis might be complicated by cough, chest discomfort, and rarely, by a life threatening condition called reexpansion pulmonary edema (RPE). The serious adverse events of thoracentesis are related to pleural pressure drop rather than to the volume of removed pleural effusion. The use of pleural manometry during pleural fluid withdrawal enables the evaluation of the relationship between withdrawn pleural fluid volume, pleural pressure changes and procedure related complications. Pleural pressure measurement is also an important tool to study the different mechanism of pneumothorax complicating the thoracentesis. Pleural manometry is critical for measurement of pleural elastance, diagnosis of an unexpandable lung and differentiation between trapped lung and lung entrapment. This usually has significant clinical implications in terms of further management of patients with pleural effusion. The paper is a comprehensive review presenting different aspects of pleural pressure measurement in clinical practice.

Fibrin turnover and pleural organization: bench to bedside.

Recent studies have shed new light on the role of the fibrinolytic system in the pathogenesis of pleural organization, including the mechanisms by which the system regulates mesenchymal transition of mesothelial cells and how that process affects outcomes of pleural injury. The key contribution of plasminogen activator inhibitor-1 to the outcomes of pleural injury is now better understood as is its role in the regulation of intrapleural fibrinolytic therapy. In addition, the mechanisms by which fibrinolysins are processed after intrapleural administration have now been elucidated, informing new candidate diagnostics and therapeutics for pleural loculation and failed drainage. The emergence of new potential interventional targets offers the potential for the development of new and more effective therapeutic candidates.

Libby Amphibole Disease: Pulmonary Function and CT Abnormalities in Vermiculite Miners.

OBJECTIVE: This article describes radiologic and pulmonary function findings among miners exposed to Libby amphibole. Computed tomography (CT) permits the detection of the characteristic thin, lamellar pleural thickening (LPT). METHODS: Individuals who worked at the mine for a minimum of 6 months had chest CT and pulmonary function tests. RESULTS: Pleural thickening was noted in 223 (87%) of the 256 miners, parenchymal abnormalities in 49 (19%). LPT, found in 151 (68%), was associated with low values of forced vital capacity and diffusion capacity and significantly lower values in all pulmonary function tests when associated with parenchymal abnormalities. CONCLUSION: Eighty-seven percent of miners exposed to Libby Amphibole had pleural abnormalities on CT. LPT alone, and more so with parenchymal abnormalities, resulted in decreased pulmonary function. The importance of this easily missed LPT is demonstrated by its high frequency and significant functional effects.

Inhibition of angiotensin II and calpain attenuates pleural fibrosis.

Pleural fibrosis is associated with various inflammatory processes such as tuberculous pleurisy and bacterial empyema. There is currently no ideal therapeutic to attenuate pleural fibrosis. Some pro-fibrogenic mediators induce fibrosis through inflammatory processes, suggesting that blockage of these mediators might prevent pleural fibrosis. The MeT-5A human pleural mesothelial cell line (PMC) was used in this study as an in vitro model of fibrosis; and intra-pleural injection of bleomycin with carbon particles was used as an in vivo mouse model of pleural fibrosis. Calpain knockout mice, calpain inhibitor (calpeptin), and angiotensin (Ang) II type 1 receptor (AT1R) antagonist (losartan) were evaluated in prevention of experimental pleural fibrosis. We found that bleomycin and carbon particles induced calpain activation in cultured PMCs. This in vitro response was associated with increased collagen-I synthesis, and was blocked by calpain inhibitor or AT1R antagonist. Calpain genetic or treatment with calpeptin or losartan prevented pleural fibrosis in a mouse model induced by bleomycin and carbon particles. Our findings indicate that Ang II signaling and calpain activation induce collagen-I synthesis and contribute to fibrotic alterations in pleural fibrosis. Inhibition of Ang II and calpain might therefore be a novel strategy in treatment of pleural fibrosis.

[Frequency and type of pleuropulmonary complications and their predictors during the first thirty days after cardiopulmonary bypass surgery in children]. / Frecuencia, tipo y predictores de complicaciones pleuropulmonares en los primeros treinta días del postoperatorio de pacientes pediátricos intervenidos de cirugía cardiovascular sin apoyo de circulación extracorpórea.

OBJECTIVE: To determine the frequency and type of pleuropulmonary complications and their predictors in the first thirty postoperative days of patients undergoing surgery without cardiopulmonary bypass. METHODS: A retrospective cohort study was carried out between January 2013 and December 2014. It included all patients with congenital heart disease who underwent cardiac surgery using a sternal or thoracic approach, without cardiopulmonary bypass with a registered admission to a Neonatal or Paediatric Intensive Care. The frequency of events of pleuropulmonary complications and logistic regression analysis was performed, and the adjusted odds ratio (OR) and confidence intervals at 95% (95% CI) were calculated. RESULTS: A total of 139 patients were included. The frequency of pleuropulmonary complications was 42.4% (N=59), and the most frequent types were atelectasis (28 events), ventilator-associated pneumonia (24 events), pneumothorax (20 events), with more than one complication per patient occasionally being found. Significant risk factors were cyanogenic congenital heart disease (OR=3.58, 95% CI: 1.10-7.50, P=.001), thoracotomy approach (OR=1.46, 95% CI: 1.18-1.12, P=.008), and an emergency surgical event (OR=3.46, 95% CI: 1.51-7.95, P=.002). CONCLUSIONS: The main pleuropulmonary complication was atelectasis, which is consistent with that reported in the international literature. Patients with any of the predictors identified in the present study should be closely monitored in order to prevent, detect and/or treat pleuropulmonary complications in a timely manner after cardiac surgery.

Thoracic involvement in IgG4-related disease in a UK-based patient cohort.

IgG4-related disease (IgG4-RD) is a multi-system fibro-inflammatory disorder with classical histopathological findings, often in the context of elevated serum IgG4 levels. The thoracic manifestations of IgG4-RD are numerous and can mimic several common and better known conditions. The objective of this study was to outline the frequency and nature of thoracic involvement in a prospective cohort of IgG4-RD patients who met defined diagnostic criteria. Over 40% of IgG4-RD patients had clinicoradiological and/or histological evidence of thoracic involvement, predominantly mediastinal lymphadenopathy, the majority associated with multi-system disease outside the chest. Thoracic involvement was associated with a higher serum IgG4 level, potentially representing greater disease activity or spread. Our data highlight the diverse nature of thoracic IgG4-RD, and the importance of knowledge and recognition of the condition among respiratory physicians who are likely to encounter this disease entity on an increasing basis.