Erratum: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

An erratum was issued for: Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion. The Authors section was updated from: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation to: Uffe Bodtger1,2 José M. Porcel3 Rahul Bhatnagar4,5 Nick Maskell4,5 Mohammed Munavvar6,7 Casper Jensen1 Paul Frost Clementsen1,8 Daniel Bech Rasmussen1,2 1Respiratory Research Unit PLUZ, Department of Respiratory Medicine, Zealand University Hospital 2Institute of Regional Health Research, University of Southern Denmark 3Pleural Medicine Unit, Department of Internal Medicine, Hospital Universitari Arnau de Vilanova, IRBLleida 4Respiratory Department, Southmead Hospital, North Bristol NHS Trust 5Academic Respiratory Unit, University of Bristol 6Lancashire Teaching Hospitals 7University of Central Lancashire 8Centre for HR and Education, Copenhagen Academy for Medical Education and Simulation.

Ultrasound in the Diagnosis of Non-Expandable Lung: A Prospective Observational Study of M-Mode, B-Mode, and 2D-Shear Wave Elastography.

BACKGROUND: Non-expandable lung (NEL) has severe implications for patient symptoms and impaired lung function, as well as crucial implications for the management of malignant pleural effusion (MPE). Indwelling pleural catheters have shown good symptom relief for patients with NEL; hence, identifying patients early in their disease is vital. With the inability of the lung to achieve pleural apposition following thoracentesis and the formation of a hydropneumothorax, traditionally, chest X-ray and clinical symptoms have been used to make the diagnosis following thoracentesis. It is our aim to investigate whether ultrasound measurement of lung movement during respiration can predict NEL before thoracentesis, thereby aiding clinicians in their planning for the optimal treatment of affected patients. METHODS: A total of 49 patients were consecutively included in a single-centre trial performed at a pleural clinic. Patients underwent protocolled ultrasound assessment pre-thoracentesis with measurements of lung and diaphragm movement and shear wave elastography measurements of the pleura and pleural effusion at the planned site of thoracentesis. RESULTS: M-mode measurements of lung movement provided the best diagnostic ROC-curve results, with an AUC of 0.81. Internal validity showed good results utilising the calibration belt test and Brier test. CONCLUSION: M-mode measurement of lung movement shows promise in diagnosing NEL before thoracentesis in patients with known or suspected MPE. A validation cohort is needed to confirm the results.

Local Anesthetic Thoracoscopy for Undiagnosed Pleural Effusion.

Local anesthetic thoracoscopy (LAT) is a minimally invasive diagnostic procedure gaining recognition among chest physicians for managing undiagnosed pleural effusions. This single-port procedure is conducted with the patient under mild sedation and involves a contralateral decubitus position. It is performed in a sterile setting, typically a bronchoscopy suite or surgical theater, by a single operator with support from a procedure-focused nurse and a patient-focused nurse. The procedure begins with a thoracic ultrasound to determine the optimal entry point, usually in the IV-V intercostal space along the midaxillary line. Lidocaine/mepivacaine, with or without adrenaline, is used to anesthetize the skin, thoracic wall layers, and parietal pleura. A designated trocar and cannula are inserted through a 10 mm incision, reaching the pleural cavity with gentle rotation. The thoracoscope is introduced through the cannula for systematic inspection of the pleural cavity from the apex to the diaphragm. Biopsies (typically six to ten) of suspicious parietal pleura lesions are obtained for histopathological evaluation and, when necessary, microbiological analysis. Biopsies of the visceral pleura are generally avoided due to the risk of bleeding or air leaks. Talc poudrage may be performed before inserting a chest tube or indwelling pleural catheter through the cannula. The skin incision is sutured, and intrapleural air is removed using a three-compartment or digital chest drainage system. The chest tube is removed once there is no airflow, and the lung has satisfactorily re-expanded. Patients are usually discharged after 2-4 h of observation and followed up on an outpatient basis. Successful LAT relies on careful patient selection, preparation, and management, as well as operator education, to ensure safety and a high diagnostic yield.

A Stepwise Approach for Performing Ultrasound Guided Transthoracic Lung Biopsy.

Diagnosing patients with radiological lung lesions, especially those suspected of having primary lung cancer, is a common and critical clinical scenario. When selecting the most suitable invasive procedure to establish a diagnosis in these cases, a delicate balance must be struck between achieving a high diagnostic yield, providing staging information, minimizing potential complications, enhancing the patient experience, and controlling costs. The integration of thoracic ultrasound as a routine clinical tool in respiratory medicine has led to increased awareness and utilization of ultrasound-guided invasive techniques in chest procedures, including transthoracic biopsies. By following a systematic and stepwise approach, transthoracic ultrasound-guided lung biopsy emerges as a safe, cost-effective procedure with a remarkable diagnostic accuracy. These attributes collectively position it as an ideal invasive technique when technically feasible. Consequently, in patients presenting subpleural lung lesions suspected of malignancy, transthoracic ultrasound-guided lung biopsy has become a standard procedure in the realm of modern invasive pulmonology.

Clinical characteristics of chylothorax: results from the International Collaborative Effusion database.

Background: Chylothorax is an uncommon medical condition for which limited data are available regarding the contemporary aetiology, management and outcomes. The goal of this study was to better define these poorly characterised features. Methods: The medical records of adult patients diagnosed with chylothorax at 12 centres across Europe, America and South Africa from 2009-2021 were retrospectively reviewed. Descriptive and inferential statistics were performed. Results: 77 patients (median age 69 years, male to female ratio 1.5) were included. Subacute dyspnoea was the most typical presenting symptom (66%). The commonest cause of chylothorax was malignancy (68.8%), with lymphoma accounting for 62% of these cases. Other aetiologies were trauma (13%), inflammatory/miscellaneous conditions (11.7%) and idiopathic cases (6.5%). At the initial thoracentesis, the pleural fluid appeared milky in 73%, was exudative in 89% and exhibited triglyceride concentrations >100 mg·dL-1 in 88%. Lymphangiography/lymphoscintigraphy were rarely ordered (3%), and demonstration of chylomicrons in pleural fluid was never ascertained. 67% of patients required interventional pleural procedures. Dietary measures were infrequently followed (36%). No patient underwent thoracic duct ligation or embolisation. Morbidity included infections (18%), and thrombosis in malignant aetiologies (16%). The 1-year mortality was 47%. Pleural fluid protein >3.5 mg·dL-1 (sub-distribution hazard ratio (SHR) 4.346) or lactate dehydrogenase <500 U·L-1 (SHR 10.21) increased the likelihood of effusion resolution. Pleural fluid protein ≤3.5 mg·dL-1 (HR 4.047), bilateral effusions (HR 2.749) and a history of respiratory disease (HR 2.428) negatively influenced survival. Conclusion: Chylothoraces have a poor prognosis and most require pleural interventions. Despite the standard recommendations, lymphatic imaging is seldom used, nor are dietary restrictions followed.

The randomised thoracoscopic talc poudrage+indwelling pleural catheters versus thoracoscopic talc poudrage only in malignant pleural effusion trial (TACTIC): study protocol for a randomised controlled trial.

INTRODUCTION: Malignant pleural effusion (MPE) is common, with 50 000 new cases per year in the UK. MPE causes disabling breathlessness and indicates advanced disease with a poor prognosis. Treatment approaches focus on symptom relief and optimising quality of life (QoL). Patients who newly present with MPE commonly require procedural intervention for both diagnosis and therapeutic benefit.Thoracoscopic pleural biopsies are highly sensitive in diagnosing pleural malignancy. Talc poudrage may be delivered at thoracoscopy (TTP) to prevent effusion recurrence by effecting pleurodesis. Indwelling pleural catheters (IPCs) offer an alternative strategy for fluid control, enabling outpatient management and are often used as 'rescue' therapy following pleurodesis failure or in cases of 'trapped lung'. It is unknown whether combining a TTP with IPC insertion will improve patient symptoms or reduce time spent in the hospital.The randomised thoracoscopic talc poudrage + indwelling pleural catheters versus thoracoscopic talc poudrage only in malignant pleural effusion trial (TACTIC) is the first randomised controlled trial (RCT) to examine the benefit of a combined TTP and IPC procedure, evaluating cost-effectiveness and patient-centred outcomes such as symptoms and QoL. The study remains in active recruitment and has the potential to radically transform the pathway for all patients presenting with MPE. METHODS AND ANALYSIS: TACTIC is an unblinded, multicentre, RCT comparing the combination of TTP with an IPC to TTP alone. Co-primary outcomes are time spent in the hospital and mean breathlessness score over 4 weeks postprocedure. The study will recruit 124 patients and aims to define the optimal pathway for patients presenting with symptomatic MPE. ETHICS AND DISSEMINATION: TACTIC is sponsored by North Bristol NHS Trust and has been granted ethical approval by the London-Brent Research Ethics Committee (REC ref: 21/LO/0495). Publication of results in a peer-reviewed journal and conference presentations are anticipated. TRIAL REGISTRATION: ISRCTN 11058680.

Investigation and outcomes in patients with nonspecific pleuritis: results from the International Collaborative Effusion database.

Introduction: We present findings from the International Collaborative Effusion database, a European Respiratory Society clinical research collaboration. Nonspecific pleuritis (NSP) is a broad term that describes chronic pleural inflammation. Various aetiologies lead to NSP, which poses a diagnostic challenge for clinicians. A significant proportion of patients with this finding eventually develop a malignant diagnosis. Methods: 12 sites across nine countries contributed anonymised data on 187 patients. 175 records were suitable for analysis. Results: The commonest aetiology for NSP was recorded as idiopathic (80 out of 175, 44%). This was followed by pleural infection (15%), benign asbestos disease (12%), malignancy (6%) and cardiac failure (6%). The malignant diagnoses were predominantly mesothelioma (six out of 175, 3.4%) and lung adenocarcinoma (four out of 175, 2.3%). The median time to malignant diagnosis was 12.2 months (range 0.8-32 months). There was a signal towards greater asbestos exposure in the malignant NSP group compared to the benign group (0.63 versus 0.27, p=0.07). Neither recurrence of effusion requiring further therapeutic intervention nor initial biopsy approach were associated with a false-negative biopsy. A computed tomography finding of a mass lesion was the only imaging feature to demonstrate a significant association (0.18 versus 0.01, p=0.02), although sonographic pleural thickening also suggested an association (0.27 versus 0.09, p=0.09). Discussion: This is the first multicentre study of NSP and its associated outcomes. While some of our findings are reflected by the established body of literature, other findings have highlighted important areas for future research, not previously studied in NSP.

Additional Up-Front Thoracic Ultrasound in the Workup of Patients with Unilateral Pleural Effusion: A Prospective Observational Pilot Study.

BACKGROUND: In patients with pleural effusion, specific ultrasound characteristics are associated with pleural malignancy. OBJECTIVES: This study aimed to evaluate the added value of an additional, up-front, systematic thoracic ultrasound (TUS) to standard imaging in patients with unilateral pleural effusion of unknown cause in a clinical setting. METHODS: In a prospective observational pilot study, patients referred for workup and thoracentesis of a unilateral pleural effusion received up-front TUS following a set protocol in addition to available imaging and US guiding the thoracentesis or diagnostic puncture. The primary outcome was the proportion of cases where systematic TUS changed the planned diagnostic workup. Follow-up took place 26 weeks after inclusion. RESULTS: From February to December 2020, 55 patients were included. Thirty-six (65%) patients had other chest imaging available before TUS. Twenty-one (38%) were diagnosed with malignant pleural effusion. Three patients (5%) had clinically relevant changes in the diagnostic workup after additional systematic TUS. CONCLUSIONS: Additional up-front, systematic TUS had limited clinically relevant effect on the planned diagnostic workup in patients with unilateral pleural effusion in a setting where chest CT scans often are available at referral.

Prediction of Time to Next Therapeutic Thoracentesis and Identification of Risk Factors of Rapid Pleural Fluid Recurrence: A Prospective Observational Study.

BACKGROUND: The value of pre-booked repeated thoracentesis in patients with recurrent pleural effusion is reliant on the estimation of time to next drainage. Identifying factors associated with rapid pleural fluid recurrence could be supportive. OBJECTIVE: We aimed to evaluate the ability of the patient and physician to predict the time to next therapeutic thoracentesis and to identify characteristics associated with rapid pleural fluid recurrence. METHOD: In a prospective, observational study, patients with recurrent unilateral pleural effusion and the physician were to predict the time to next symptom-guided therapeutic thoracentesis. Primary outcome was difference between days to actual thoracentesis and days predicted by the patient and the physician. Factors associated with pleural fluid recurrence within 60-day follow-up were assessed using Cox regression analysis. RESULTS: A total of 98 patients were included, 71% with malignant pleural effusion. Patients' and physicians' predictions numerically deviated by 6 days from the actual number of days to re-thoracentesis (IQR 2-12 and 2-13, respectively). On multivariate analyses, factors associated with increased hazard of pleural fluid recurrence included daily fluid production (HR 1.35 [1.16-1.59], p > 0.001) and large effusion size (HR 2.76 [1.23-6.19], p = 0.01). Septations were associated with decreased hazard (HR 0.48 [0.24-0.96], p = 0.04). CONCLUSION: Patients and physicians were equally unable to predict the time to next therapeutic thoracentesis. Daily fluid production and large effusion size were associated with increased risk of rapid pleural fluid recurrence, while septations were associated with a decreased risk. This may guide patients and physicians in when to expect a need for therapeutic thoracentesis.

Silver Nitrate-coated versus Standard Indwelling Pleural Catheter for Malignant Effusions: The SWIFT Randomized Trial.

Rationale: Tunneled, indwelling pleural catheters (IPCs) have been demonstrated to be an effective method of managing malignant pleural effusions. However, they allow pleurodesis and can therefore be removed in only a subset of patients. A novel, silver nitrate-coated IPC was developed with the intention of creating a rapid, effective chemical pleurodesis to allow more frequent and earlier catheter removal. This study represents the pivotal clinical trial evaluating that catheter versus the standard IPC. Objectives: To compare the efficacy of a novel silver nitrate-eluting indwelling pleural catheter (SNCIPC) with that of a standard, uncoated catheter. Methods: The SWIFT [A Pivotal Multi-Center, Randomized, Controlled, Single-Blinded Study Comparing the Silver Nitrate-Coated Indwelling Pleural Catheter (SNCIPC) to the Uncoated PleurX® Pleural Catheter for the Management of Symptomatic, Recurrent, Malignant Pleural Effusions] trial was a multicenter, parallel-group, randomized, controlled, patient-blind trial. Central randomization occurred according to a computer-generated schedule, stratified by site. Recruitment was from 17 secondary or tertiary care hospitals in the United States and 3 in the United Kingdom and included adult patients with malignant pleural effusion needing drainage, without evidence of lung entrapment or significant loculation. The intervention group underwent insertion of an SNCIPC with maximal fluid drainage, followed by a tapering drainage schedule. The control group received a standard, uncoated catheter. Follow-up was conducted until 90 days. The primary outcome measure was pleurodesis efficacy, measured by fluid drainage, at 30 days. Results: A total of 119 patients were randomized. Five withdrew before receiving treatment, leaving 114 (77 SNCIPC, 37 standard IPC) for analysis. The mean age was 66 years (standard deviation, 11). More patients in the SNCIPC group were inpatients (39% vs. 14%; P = 0.009). For the primary outcome, pleurodesis rates were 12 (32%) of 37 in the control group and 17 (22%) of 77 in the SNCIPC group (rate difference, -0.10; 95% confidence interval, -0.30 to 0.09). Median time to pleurodesis was 11 days (interquartile range, 9 to 23) in the control group and 4 days (interquartile range, 2 to 15) in the SNCIPC group. No significant difference in treatment-related adverse event rates was noted between groups. Conclusions: The SNCIPC did not improve pleurodesis efficacy compared with a standard IPC. This study does not support the wider use of the SNCIPC device. Clinical trial registered with www.clinicaltrials.gov (NCT02649894).

Role of thoracic ultrasonography in pleurodesis pathways for malignant pleural effusions (SIMPLE): an open-label, randomised controlled trial.

BACKGROUND: Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75-80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. METHODS: The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. FINDINGS: Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2-4]) than in the standard care group (3 days [2-5]; difference 1 day [95% CI 1-1]; p<0·0001). In the per-protocol analysis, thoracic ultrasonography-guided care was non-inferior to standard care in terms of pleurodesis failure at 3 months, which occurred in 27 (29·7%) of 91 patients in the intervention group versus 34 (31·2%) of 109 patients in the standard care group (risk difference -1·5% [95% CI -10·2% to 7·2%]; non-inferiority margin 15%). Mean time to chest tube removal in the intervention group was 2·4 days (SD 2·5) versus 3·1 days (2·0) in the standard care group (mean difference -0·72 days [95% CI -1·22 to -0·21]; p=0·0057). There were no significant between-group differences in all-cause mortality, symptom scores, or quality-of-life scores, except on the EQ-5D visual analogue scale, which was significantly lower in the standard care group at 3 months. Although costs were similar between the groups, thoracic ultrasonography-guided care was cost-effective compared with standard care. INTERPRETATION: Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. FUNDING: Marie Curie Cancer Care Committee.

Randomised trial of indwelling pleural catheters for refractory transudative pleural effusions.

OBJECTIVE: Refractory symptomatic transudative pleural effusions are an indication for pleural drainage. There has been supportive observational evidence for the use of indwelling pleural catheters (IPCs) for transudative effusions, but no randomised trials. We aimed to investigate the effect of IPCs on breathlessness in patients with transudative pleural effusions when compared with standard care. METHODS: A multicentre randomised controlled trial, in which patients with transudative pleural effusions were randomly assigned to either an IPC (intervention) or therapeutic thoracentesis (TT; standard care). The primary outcome was mean daily breathlessness score over 12 weeks from randomisation. RESULTS: 220 patients were screened from April 2015 to August 2019 across 13 centres, with 33 randomised to intervention (IPC) and 35 to standard care (TT). Underlying aetiology was heart failure in 46 patients, liver failure in 16 and renal failure in six. In primary outcome analysis, the mean±sd breathlessness score over the 12-week study period was 39.7±29.4 mm in the IPC group and 45.0±26.1 mm in the TT group (p=0.67). Secondary outcomes analysis demonstrated that mean±sd drainage was 17 412±17 936 mL and 2901±2416 mL in the IPC and TT groups, respectively. A greater proportion of patients had at least one adverse event in the IPC group (p=0.04). CONCLUSION: We found no significant difference in breathlessness over 12 weeks between IPCs or TT. TT is associated with fewer complications and IPCs reduced the number of invasive pleural procedures required. Patient preference and circumstances should be considered in selecting the intervention in this cohort.

Positron emission tomography-computed tomography (PET-CT) in suspected malignant pleural effusion. An updated systematic review and meta-analysis.

The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions. A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned. Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR + ) and negative likelihood ratio (LR-) of 9.9 (4.5-15.3) respectively 0.1 (0.1-0.2). There was considerable heterogeneity among studies. In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias. Clinical Trial Registration: The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020.

The prevalence of tumour markers in malignant pleural effusions associated with primary pulmonary adenocarcinoma: a retrospective study.

BACKGROUND: Oncological treatment of primary pulmonary adenocarcinoma (AC) includes drugs targeting the pathways involving programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK). The aim of the study was to report the prevalence of these tumour markers in pleural fluid with cytology positive for pulmonary AC and the potential influence of volume pleural fluid tested. METHODS: We retrospectively reviewed all thoracenteses performed in a two-year period at our interventional unit at Department of Respiratory Medicine at Zealand University Hospital Naestved, Denmark. ALK and PD-L1 testing was done using immunohistochemistry and EGFR testing using next-generation sequencing. We included pleural fluid specimens containing malignant cells originating from primary pulmonary AC and with at least one tumour marker requested by the clinicians. RESULTS: When screening 927 pleural fluid specimens, we identified 57 in accordance with the inclusion criteria. PD-L1, ALK and EGFR were obtained in 35/55 (64%), 38/57 (67%) and 26/47 (55%), respectively. The prevalence did not increase when analysing volumes > 50 mL (p = 0.21-0.58). CONCLUSION: Tumour markers in pleural fluid specimens containing cells from pulmonary AC can be demonstrated in more than half of the cases. Therefore, supplementary invasive procedures than thoracentesis could potentially await these analyses.

Breathlessness Predicts Survival in Patients With Malignant Pleural Effusions: Meta-analysis of Individual Patient Data From Five Randomized Controlled Trials.

BACKGROUND: Patients with malignant pleural effusions (MPEs) experience breathlessness and poor survival. Breathlessness is associated with poor survival in other conditions. RESEARCH QUESTION: Is breathlessness, measured using a visual analog scale for dyspnea (VASD), associated with survival in patients with MPE? STUDY DESIGN AND METHODS: Individual patient data from five randomized controlled trials of 553 patients undergoing interventions for MPE were analyzed. VASD was recorded at baseline and daily after intervention. Patients were followed up until death or end of trial. Univariate and multivariable Cox regression were used to identify factors associated with survival. RESULTS: Baseline VASD was significantly associated with worse survival, with a hazard ratio of 1.10 (95% CI, 1.06-1.15) for a 10-mm increase in VASD. On multivariable regression, it remained a significant predictor of survival. Mean 7-day VASD and mean total VASD were also predictors of survival (mean 7-day VASD: hazard ratio [HR], 1.26 [95% CI, 1.19-1.34]; total VASD: HR, 1.25 [95% CI, 1.15-1.37]). Other predictors of survival were serum C-reactive protein level and tumor type. Previous treatment with chemotherapy, performance status, pleural fluid lactate dehydrogenase, serum albumin, hemoglobin, serum neutrophil:lymphocyte ratio, and size of effusion were associated with survival on univariate but not multivariable analysis. INTERPRETATION: Breathlessness, measured using VASD at baseline and postprocedure, is a predictor of survival in patients with MPE.

Using creative co-design to develop a decision support tool for people with malignant pleural effusion.

BACKGROUND: Malignant pleural effusion (MPE) is a common, serious problem predominantly seen in metastatic lung and breast cancer and malignant pleural mesothelioma. Recurrence of malignant pleural effusion is common, and symptoms significantly impair people's daily lives. Numerous treatment options exist, yet choosing the most suitable depends on many factors and making decisions can be challenging in pressured, time-sensitive clinical environments. Clinicians identified a need to develop a decision support tool. This paper reports the process of co-producing an initial prototype tool. METHODS: Creative co-design methods were used. Three pleural teams from three disparate clinical sites in the UK were involved. To overcome the geographical distance between sites and the ill-health of service users, novel distributed methods of creative co-design were used. Local workshops were designed and structured, including video clips of activities. These were run on each site with clinicians, patients and carers. A joint national workshop was then conducted with representatives from all stakeholder groups to consider the findings and outputs from local meetings. The design team worked with participants to develop outputs, including patient timelines and personas. These were used as the basis to develop and test prototype ideas. RESULTS: Key messages from the workshops informed prototype development. These messages were as follows. Understanding and managing the pleural effusion was the priority for patients, not their overall cancer journey. Preferred methods for receiving information were varied but visual and graphic approaches were favoured. The main influences on people's decisions about their MPE treatment were personal aspects of their lives, for example, how active they are, what support they have at home. The findings informed the development of a first prototype/service visualisation (a video representing a web-based support tool) to help people identify personal priorities and to guide shared treatment decisions. CONCLUSION: The creative design methods and distributed model used in this project overcame many of the barriers to traditional co-production methods such as power, language and time. They allowed specialist pleural teams and service users to work together to create a patient-facing decision support tool owned by those who will use it and ready for implementation and evaluation.

Management of malignant pleural effusions.

PURPOSE OF REVIEW: Malignant pleural effusion (MPE) is a common cause of breathlessness indicative of advanced disease. Treatment approaches focus on relief of breathlessness and optimizing quality of life. A number of recent, high-impact publications give further insight into the advantages of different treatment options. This article provides a summary of the most up-to-date evidence in this area. RECENT FINDINGS: Recent publications have demonstrated comparable pleurodesis outcomes of talc slurry to talc poudrage and explore strategies to combine the advantages of indwelling pleural catheters (IPCs) with a chemical pleurodesis. A daily IPC drainage regime improves the chances of pleurodesis success and early IPC removal in patients without significant trapped lung. SUMMARY: MPE is a diverse condition, with no one strategy representing the 'best' approach for all. Management decisions should be made in conjunction with the patient, taking their views and preferences into consideration.

Thoracoscopy and talc poudrage compared with intercostal drainage and talc slurry infusion to manage malignant pleural effusion: the TAPPS RCT.

BACKGROUND: There are around 40,000 new cases of malignant pleural effusion in the UK each year. Insertion of talc slurry via a chest tube is the current standard treatment in the UK. However, some centres prefer local anaesthetic thoracoscopy and talc poudrage. There is no consensus as to which approach is most effective. OBJECTIVE: This trial tested the hypothesis that thoracoscopy and talc poudrage increases the proportion of patients with successful pleurodesis at 3 months post procedure, compared with chest drain insertion and talc slurry. DESIGN: This was a multicentre, open-label, randomised controlled trial with embedded economic evaluation. Follow-up took place at 1, 3 and 6 months. SETTING: This trial was set in 17 NHS hospitals in the UK. PARTICIPANTS: A total of 330 adults with a confirmed diagnosis of malignant pleural effusion needing pleurodesis and fit to undergo thoracoscopy under local anaesthetic were included. Those adults needing a tissue diagnosis or with evidence of lung entrapment were excluded. INTERVENTIONS: Allocation took place following minimisation with a random component, performed by a web-based, centralised computer system. Participants in the control arm were treated with a bedside chest drain insertion and 4 g of talc slurry. In the intervention arm, participants underwent local anaesthetic thoracoscopy with 4 g of talc poudrage. MAIN OUTCOME MEASURES: The primary outcome measure was pleurodesis failure at 90 days post randomisation. Secondary outcome measures included mortality and patient-reported symptoms. A cost-utility analysis was also performed. RESULTS: A total of 166 and 164 patients were allocated to poudrage and slurry, respectively. Participants were well matched at baseline. For the primary outcome, no significant difference in pleurodesis failure was observed between the treatment groups at 90 days, with rates of 36 out of 161 (22%) and 38 out of 159 (24%) noted in the poudrage and slurry groups, respectively (odds ratio 0.91, 95% confidence interval 0.54 to 1.55; p = 0.74). No differences (or trends towards difference) were noted in adverse events or any of the secondary outcomes at any time point, including pleurodesis failure at 180 days [poudrage 46/161 (29%), slurry 44/159 (28%), odds ratio 1.05, 95% confidence interval 0.63 to 1.73; p = 0.86], mean number of nights in hospital over 90 days [poudrage 12 nights (standard deviation 13 nights), slurry 11 nights (standard deviation 10 nights); p = 0.35] and all-cause mortality at 180 days [poudrage 66/166 (40%), slurry 68/164 (42%); p = 0.70]. At £20,000 per quality-adjusted life-year gained, poudrage would have a 0.36 probability of being cost-effective compared with slurry. LIMITATIONS: Entry criteria specified that patients must be sufficiently fit to undergo thoracoscopy, which may make the results less applicable to those patients presenting with a greater degree of frailty. Furthermore, the trial was conducted on an open-label basis, which may have influenced the results of patient-reported measures. CONCLUSIONS: The TAPPS (evaluating the efficacy of Thoracoscopy And talc Poudrage versus Pleurodesis using talc Slurry) trial has robustly demonstrated that there is no additional clinical effectiveness or cost-effectiveness benefit in performing talc poudrage at thoracoscopy over bedside chest drain and talc slurry for the management of malignant pleural effusion. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47845793. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 26. See the NIHR Journals Library website for further project information.

In patients with cancer, fluid can build up in the space between the chest wall and lung, causing breathlessness. The fluid can be drained using a small tube inserted between the ribs under local anaesthetic. However, it often recurs. To avoid this, doctors usually inject talc powder (mixed into a slurry) back down the drainage tube to try to 'stick' the lung to the inside of the chest wall. If successful, this prevents the fluid reforming. This procedure is called pleurodesis. An alternative is to insert a camera into the chest under light sedation and local anaesthetic (a 'thoracoscopy') and spray talc directly onto the inside of the chest wall (poudrage). This may be more effective, although this has not been proven and it is a slightly more complex procedure. Therefore, this trial was conducted to see if poudrage was more effective than slurry. A total of 330 patients were recruited from 17 UK hospitals who had chest fluid due to cancer. They were divided evenly, with half receiving standard drainage and slurry and the other half receiving a thoracoscopy and poudrage. They were followed up for 6 months. We measured how many experienced a recurrence in fluid build-up 3 months after treatment, as well as other impacts, including if there was any difference in the long-term costs. No difference in clinical effectiveness was found between talc poudrage and talc slurry. Poudrage was unlikely to be cost-effective. In summary, the researchers conclude that slurry is likely to be the preferable method.

Manometry performed at indwelling pleural catheter insertion to predict unexpandable lung.

BACKGROUND: The finding of unexpandable lung (UL) at an early timepoint is of increasing importance in guiding treatment decisions in patients with malignant pleural effusion (MPE). Pleural manometry is the most common technique to delineate UL, however it has never been measured via an indwelling pleural catheter (IPC). To further the evidence base we analysed all patients in the IPC-PLUS study who had manometry performed during IPC insertion for the ability to predict substantial UL using manometry. METHODS: All patients enrolled in IPC-PLUS who had manometry performed at IPC insertion and radiographic assessment of UL at day 10 were included. Elastance curves were visually inspected for each patient. Initial pleural pressure, closing pleural pressure, and terminal elastance were analysed for their differences and predictive ability in those with substantial UL, defined as ≥25% entrapment on chest radiography. RESULTS: A total of 89 patients had manometry performed at IPC insertion with subsequent radiographic assessment of UL and interpretable elastance curves. Those with substantial UL had a significantly lower median closing pleural pressure (-15.00 vs. 0.00 cmH2O, P=0.012) and higher terminal elastance (12.03 vs. 8.59 cmH2O/L, P=0.021) compared to a combined group with no or partial UL. However, the predictive ability of these factors to discriminate substantial UL was poor, with areas under the receiver operating characteristic curves of 0.695 and 0.680 for closing pleural pressure and elastance respectively. CONCLUSIONS: Our results suggest that manometry is not useful in accurately predicting substantial UL when used via an IPC at the time of insertion.