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Increased expression of osteopontin (secreted phosphoprotein 1, SPP1) is associated with aggressive human lung adenocarcinoma (LADC), but its function remains unknown. Our aim was to determine the role of SPP1 in smoking-induced LADC. We combined mouse models of tobacco carcinogen-induced LADC, of deficiency of endogenous Spp1 alleles, and of adoptive pulmonary macrophage reconstitution to map the expression of SPP1 and its receptors and determine its impact during carcinogenesis. Co-expression of Spp1 and mutant KrasG12C in benign cells was employed to investigate SPP1/KRAS interactions in oncogenesis. Finally, intratracheal adenovirus encoding Cre recombinase was delivered to LSL.KRASG12D mice lacking endogenous or overexpressing transgenic Spp1 alleles. SPP1 was overexpressed in experimental and human LADC and portended poor survival. In response to two different smoke carcinogens, Spp1-deficient mice developed fewer and smaller LADC with decreased cellular survival and angiogenesis. Both lung epithelial- A nd macrophage-secreted SPP1 drove tumor-associated inflammation, while epithelial SPP1 promoted early tumorigenesis by fostering the survival of KRAS-mutated cells. Finally, loss and overexpression of Spp1 was, respectively, protective and deleterious for mice harboring KRASG12D-driven LADC. Our data support that SPP1 is functionally involved in early stages of airway epithelial carcinogenesis driven by smoking and mutant KRAS and may present an important therapeutic target. © 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: Journals.permissions@oup.com.

Background: The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. Research Question: Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. Study Design and Methods: Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. Results: A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. Interpretation: The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

Malignant pleural effusions are a common complication of advanced malignancy, have a poor prognosis and have a significant impact on quality of life. Treatment strategies include chest drain and pleurodesis, or insertion of an indwelling pleural catheter. Successful pleurodesis is thought to be due to the body’s inflammatory response resulting in pleural symphysis. This post hoc analysis of data from the TIME 1 was conducted to address assess whether there is a correlation between the pleurodesis and a systemic inflammatory response.

Aim: To audit the pleural on-call service referrals and outcome.

Malignant pleural effusion (MPE) is common with 1 new case annually for every 2,000 individuals, imposing a significant burden on patients and healthcare providers as a result. Most patients require definitive treatment, usually drainage and chemical pleurodesis, to relieve symptoms and prevent fluid recurrence. Pleurodesis is reported to have a success rate of around 70%, with no robust means of predicting which patients will suffer failure of the procedure. Thoracic ultrasound (TUS) has been shown to be capable of identifying the presence of pleural adhesions in other clinical scenarios, and could therefore have a role in predicting long-term pleurodesis success or failure in MPE.

Use of medical thoracoscopy by respiratory physicians is increasing. This survey of experienced thoracoscopists was conducted to establish current practice of medical thoracoscopy and physicians' opinion of theoretical cases using 20 video clips. Results suggest an increasing trend towards day‐case thoracoscopy but that caution is required when making diagnosis on macroscopic appearance: malignant and benign disease could only be differentiated in 59% of cases, and trapped lung is difficult to predict at thoracoscopy.

Introduction Malignant pleural effusion (MPE) is common and currently in UK there are an estimated 50 000 new cases of MPE per year. Talc pleurodesis remains one of the most popular methods for fluid control. The value of thoracic ultrasound (TUS) imaging, before and after pleurodesis, in improving the quality and efficacy of care for patients with MPE remains unknown. Additionally, biomarkers of successful pleurodesis including measurement of pleural fluid proteins have not been validated in prospective studies. The SIMPLE trial is an appropriately powered, multicentre, randomised controlled trial designed to assess ’by the patient bedside' use of TUS imaging and pleural fluid analysis in improving management of MPE. Methods and analysis 262 participants with a confirmed MPE requiring intervention will be recruited from hospitals in UK and The Netherlands. Participants will be randomised (1:1) to undergo either chest drain insertion followed by instillation of sterile talc, or medical thoracoscopy and simultaneous poudrage. The allocated procedure will be done while the patient is hospitalised, and within 3 days of randomisation. Following hospital discharge, participants will be followed up at 1, 3 and 12 months. The primary outcome measure is the length of hospital stay during initial hospitalisation. Ethics and dissemination The trial has received ethical approval from the South Central-Oxford C Research Ethics Committee (Reference number 15/SC/0600). The Trial Steering Committee includes an independent chair and members, and a patient representative. The trial results will be published in a peer-reviewed journal and presented at international conferences.

Pleural disease is a common health problem and it is estimated to affect over 3,000 people per million population. Pleural effusion is the most common condition among the group and in approximately 75% of cases the clinical history, physical examination, radiographic techniques and pleural fluid analysis will identify a cause for the pleural effusion, with the remaining 25% requiring further invasive diagnostic procedures. An increasing trend has been seen in the number of centres performing local anaesthetic thoracoscopy (LAT) as a gold-standard diagnostic and/or therapeutic procedure. There is previous evidence from a single site that the technique can be performed on a day-case basis without compromising its efficacy and safety. This is the first multicentre study assessing LAT as a day case procedure and includes data from 4 centres in the UK and 1 centre in the USA. The primary aim of this paper was to report data on safety, feasibility and outcomes of day-case LAT.

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutantKRASis important for MPE induction in mice. Pleural disseminated, mutantKRASbearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition,KRASmutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novelKRASinhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition.

Malignant pleural effusion (MPE) is a common but serious condition that is related with poor quality of life, morbidity and mortality. Its incidence and associated healthcare costs are rising and its management remains palliative, with median survival ranging from 3 to 12 months. During the last decade there has been significant progress in unravelling the pathophysiology of MPE, as well as its diagnostics, imaging, and management. Nowadays, formerly bed-ridden patients are genotyped, phenotyped, and treated on an ambulatory basis. This article attempts to provide a comprehensive overview of current advances in MPE from bench to bedside. In addition, it highlights unanswered questions in current clinical practice and suggests future directions for basic and clinical research in the field. © ERS 2016.