Hyaluronic acid in viscous malignant mesothelioma pleural effusion

© 2020 The Authors. Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology Malignant pleural effusion (MPE) is common with mesothelioma. We report two cases of extraordinarily viscous MPEs associated with mesothelioma. The viscosity prohibited spontaneous gravity-dependent drainage via indwelling pleural catheters. Our ex vivo experiments found very high hyaluronic acid (HA) content within the fluid. Treatment of the fluid with hyaluronidase, but not with deoxyribonucleases, significantly reduced fluid viscosity. The results provide proof that HA can contribute to high viscosity of pleural fluid in mesothelioma. Research into strategies of counteracting HA properties in the management of MPEs may provide further insight

BAP1 loss by immunohistochemistry predicts improved survival to first-line platinum and pemetrexed chemotherapy for patients with pleural mesothelioma: A validation study

Introduction: Pleural mesothelioma (PM) is an aggressive malignancy with no identified predictive biomarkers. We assessed whether tumor BAP1 status is a predictive biomarker for survival in patients receiving first-line combination platinum and pemetrexed therapy. Methods: PM cases (n = 114) from Aalborg, Denmark, were stained for BAP1 on tissue microarrays. Demographic, clinical, and survival data were extracted from registries and medical records. Surgical cases were excluded. BAP1 status was associated with overall survival (OS) by Cox regression and Kaplan-Meier methods. Results were validated in an independent cohort from Perth, Australia (n = 234). Results: BAP1 loss was found in 62% and 60.3% of all Danish and Australian samples, respectively. BAP1 loss was an independent predictor of OS in multivariate analyses corrected for histological subtype, performance status, age, sex, and treatment (hazard ratio = 2.49, p \u3c 0.001, and 1.48, p = 0.01, respectively). First-line platinum and pemetrexed-treated patients with BAP1 loss had significantly longer median survival than those with retained BAP1 in both the Danish (20.1 versus 7.3 mo, p \u3c 0.001) and Australian cohorts (19.6 versus 11.1 mo, p \u3c 0.01). Survival in patients with BAP1 retained and treated with platinum and pemetrexed was similar as in those with best supportive care. There was a higher OS in patients with best supportive care with BAP1 loss, but it was significant only in the Australian cohort (16.8 versus 8.3 mo, p \u3c 0.01). Conclusions: BAP1 is a predictive biomarker for survival after first-line combination platinum and pemetrexed chemotherapy and a potential prognostic marker in PM. BAP1 in tumor is a promising clinical tool for treatment stratification

Pleural fluid investigations for pleural infections

Over 1.5 million patients are admitted to hospital with pneumonia in the United States each year. Up to 50% of them can develop a parapneumonic effusion which is associated with higher mortality. The incidence of pleural infection continues to rise, particularly in the elderly and those with comorbidities. Parapneumonic effusions cover a spectrum of presentations from a free-flowing \u27simple parapneumonic effusion\u27 to a septated \u27complicated parapneumonic effusion\u27 (CPE) (usually from bacterial pleural invasion) and \u27empyema\u27 (presence of pleural pus). Pleural infection is defined as either CPE or empyema, and usually requires evacuation of the infected fluid. Laboratory investigations play an essential part of the diagnosis and management of pleural infection. A parapneumonic effusion is typically a neutrophil-rich exudate. Presence of bacteria from culture of the fluid defines pleural infection but conventional culture methods have a low yield. Surrogate pleural fluid markers are often employed to confirm a CPE, including low pleural fluid pH ( \u3c 7.2) or glucose ( \u3c 3.3 mmol/L) and elevated lactate dehydrogenase (LDH). Measurement of pleural fluid triglyceride and chylomicrons (for chylothorax) and cholesterol (for pseudochylothorax) may be needed to separate lipid pleural effusions from empyema. Tuberculous pleural effusions usually result from a hypersensitivity pleuritis and are lymphocyte predominant with elevated pleural fluid adenosine deaminase (ADA) and interferon gamma levels. Culture yield of mycobacteria is typically low. Caseating granulomas on pleural tissue biopsy is often considered diagnostic. Common organisms for community-acquired pleural infection include Streptococcus pneumoniae, Streptococcus anginosus group bacteria and Staphylococcus aureus. Hospital-acquired pleural infections have higher mortality and are often polymicrobial which can include S. aureus, Enterobacteriaceae and anaerobes. Antibiotics and evacuation of the infected fluid, usually by chest tube drainage, remain the mainstay of treatment. Intrapleural fibrinolytic and deoxyribonuclease therapy, or occasionally surgical drainage, may be required