Search

Importance Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, –1.8% [95% CI, –10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration ISRCTN Identifier: ISRCTN47845793

Background Malignant pleural effusion affects more than 750,000 persons each year across Europe and the United States. Pleurodesis with the administration of talc in hospitalized patients is the most common treatment, but indwelling pleural catheters placed for drainage offer an ambulatory alternative. We examined whether talc administered through an indwelling pleural catheter was more effective at inducing pleurodesis than the use of an indwelling pleural catheter alone. Methods Over a period of 4 years, we recruited patients with malignant pleural effusion at 18 centers in the United Kingdom. After the insertion of an indwelling pleural catheter, patients underwent drainage regularly on an outpatient basis. If there was no evidence of substantial lung entrapment (nonexpandable lung, in which lung expansion and pleural apposition are not possible because of visceral fibrosis or bronchial obstruction) at 10 days, patients were randomly assigned to receive either 4 g of talc slurry or placebo through the indwelling pleural catheter on an outpatient basis. Talc or placebo was administered on a single-blind basis. Follow-up lasted for 70 days. The primary outcome was successful pleurodesis at day 35 after randomization. Results The target of 154 patients undergoing randomization was reached after 584 patients were approached. At day 35, a total of 30 of 69 patients (43%) in the talc group had successful pleurodesis, as compared with 16 of 70 (23%) in the placebo group (hazard ratio, 2.20; 95% confidence interval, 1.23 to 3.92; P = 0.008). No significant between- group differences in effusion size and complexity, number of inpatient days, mortality, or number of adverse events were identified. No significant excess of blockages of the indwelling pleural catheter was noted in the talc group. Conclusions Among patients without substantial lung entrapment, the outpatient administration of talc through an indwelling pleural catheter for the treatment of malignant pleural effusion resulted in a significantly higher chance of pleurodesis at 35 days than an indwelling catheter alone, with no deleterious effects.

Purpose The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. Patients and methods 18F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. 18F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from 18F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan–Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. Results PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan–Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with 18F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. Conclusions 18F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Pleural infection is increasing in incidence. Despite optimal medical management, up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial.A randomised controlled pilot study in which saline pleural irrigation (three times per day for 3 days) plus best-practice management was compared with best-practice management alone was performed in patients with pleural infection requiring chest-tube drainage. The primary outcome was percentage change in computed tomography pleural fluid volume from day 0 to day 3. Secondary outcomes included surgical referral rate, hospital stay and adverse events.35 patients were randomised. Patients receiving saline irrigation had a significantly greater reduction in pleural collection volume on computed tomography compared to those receiving standard care (median (interquartile range) 32.3% (19.6–43.7%) reduction versus 15.3% (−5.5–28%) reduction) (pSaline irrigation improves pleural fluid drainage and reduces referrals for surgery in pleural infection. A large multicentre randomised controlled trial is now warranted to evaluate its effects further.

Background: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Method: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Results: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. Conclusions: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

Background Bacterial pleural infection requires prompt identification to enable appropriate investigation and treatment. In contrast to commonly used biomarkers such as C-reactive protein (CRP) and white cell count (WCC), which can be raised due to non-infective inflammatory processes, procalcitonin (PCT) has been proposed as a specific biomarker of bacterial infection. The utility of PCT in this role is yet to be validated in a large prospective trial. This study aimed to identify whether serum PCT is superior to CRP and WCC in establishing the diagnosis of bacterial pleural infection. Methods Consecutive patients presenting to a tertiary pleural service between 2008 and 2013 were recruited to a well-established pleural disease study. Consent was obtained to store pleural fluid and relevant clinical information. Serum CRP, WCC and PCT were measured. A diagnosis was agreed upon by two independent consultants after a minimum of 12 months. The study was performed and reported according to the STARD reporting guidelines. Results 80/425 patients enrolled in the trial had a unilateral pleural effusion secondary to infection. 10/80 (12.5%) patients had positive pleural fluid microbiology. Investigations for viral causes of effusion were not performed. ROC curve analysis of 425 adult patients with unilateral undiagnosed pleural effusions showed no statistically significant difference in the diagnostic utility of PCT (AUC 0.77), WCC (AUC 0.77) or CRP (AUC 0.85) for the identification of bacterial pleural infection. Serum procalcitonin >0.085 μg/l has a sensitivity, specificity, negative predictive value and positive predictive value of 0.69, 0.80, 0.46 and 0.91 respectively for the identification of pleural infection. The diagnostic utility of procalcitonin was not affected by prior antibiotic use (p = 0.80). Conclusions The study presents evidence that serum procalcitonin is not superior to CRP and WCC for the diagnosis of bacterial pleural infection. The study suggests routine procalcitonin testing in all patients with unilateral pleural effusion is not beneficial however further investigation may identify specific patient subsets that may benefit. Trial registration The trial was registered with the UK Clinical Research Network (UKCRN ID 8960). The trial was approved by the South West Regional Ethics Committee (Ethical approval number 08/H0102/11). Electronic supplementary material The online version of this article (doi:10.1186/s12931-017-0501-5) contains supplementary material, which is available to authorized users.

Rationale: Evaluation of a pleural effusion has historically focused on establishing a single etiology. Pleural fluid may accumulate through multiple pathophysiological processes. The prevalence of multiple causes for pleural effusions has not been established. The identification of contributing processes may improve clinical outcomes. Objectives: The objective of this prospectively collected case series was to establish the prevalence and nature of multiple etiologies for a unilateral pleural effusion. Methods: Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited at a tertiary pleural center. Patients underwent a comprehensive structured diagnostic clinical evaluation and were followed up for a minimum of 12 months, after which one or more diagnoses were recorded independently by two experienced clinicians. Measurements and Main Results: One hundred thirty patients were recruited to the study over a 24-month period, and 126 patients completed follow up. Altogether, 88 patients (70%) had a single cause for their pleural effusion, and 38 (30%) had multiple causes. Serum N-terminal pro-brain natriuretic peptide (NT-pro BNP) greater than or equal to 1,500 pg/ml was predictive of multiple etiologies. NT-pro BNP had a sensitivity and specificity of 79 and 88%, respectively, for establishing heart failure as a primary or contributory cause. Thirteen patients with a malignant pleural effusion also had an NT-pro BNP greater than or equal to 1,500 pg/ml. Conclusions: This study is the first to estimate the prevalence of more than one identifiable cause for a unilateral pleural effusion. Out of 130 study subjects, 38 (30%) had multiple causes for an effusion. The identification of multiple pathologies underlying an accumulation of fluid in the pleural space may be important in determining optimum treatment and improving patients' symptoms.

The BTS pleural procedures audit collected data over a 2-month period in June and July 2011. In contrast with the 2010 audit, which focussed simply on chest drain insertions, data on all pleural aspirations and local anaesthetic thoracoscopy (LAT) was also collected. Ninety hospitals submitted data, covering a patient population of 33 million. Twenty-one per cent of centres ran a specialist pleural disease clinic, 71% had a nominated chest drain safety lead, and 20% had thoracic surgery on site. Additionally, one-third of centres had a physician-led LAT service.

The past decade has seen a dramatic rise in clinical and research interests in pleural disease in parallel with rising incidences of pleural cancers and infection worldwide. Development of specialist pleural services can streamline patient diagnosis and therapy, reduce health-care resource consumption, improve procedural training and safety and facilitate clinical research. Pleural ultrasound, pleuroscopy, indwelling pleural catheter services and pleural procedural education programmes for junior staff are important elements of most specialist pleural units. An integrated service including radiology, pathology, oncology and thoracic surgery input is pivotal to success. Establishing funding support and referral sources are the common initial hurdles. This article provides an overview of the need for specialist pleural disease units, the essential elements required and the likely challenges encountered in setting a service up.

Pleural effusions are a common medical problem with more than 50 recognised causes including disease local to the pleura or underlying lung, systemic conditions, organ dysfunction and drugs.1 Pleural effusions occur as a result of increased fluid formation and/or reduced fluid resorption. The precise pathophysiology of fluid accumulation varies according to underlying aetiologies. As the differential diagnosis for a unilateral pleural effusion is wide, a systematic approach to investigation is necessary. The aim is to establish a diagnosis swiftly while minimising unnecessary invasive investigations and facilitating treatment, avoiding the need for repeated therapeutic aspirations when possible. Since the 2003 guideline, several clinically relevant studies have been published, allowing new recommendations regarding image guidance of pleural procedures with clear benefits to patient comfort and safety, optimum pleural fluid sampling and processing and the particular value of thoracoscopic pleural biopsies. This guideline also includes a review of recent evidence for the use of new biomarkers including N-terminal pro-brain natriuretic peptide (NT-proBNP), mesothelin and surrogate markers of tuberculous pleuritis. The history and physical examination of a patient with a pleural effusion may guide the clinician as to whether the effusion is a transudate or an exudate. This critical distinction narrows the differential diagnosis and directs further investigation. Clinical assessment alone is often capable of identifying transudative effusions. Therefore, in an appropriate clinical setting such as left ventricular failure with a confirmatory chest x-ray, such effusions do not need to be sampled unless there are atypical features or they fail to respond to treatment. Approximately 75% of patients with pulmonary embolism and …

Background: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. Methods: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. Findings: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR

Background In order to estimate utilities for cancer studies where the EQ-5D was not used, the EORTC QLQ-C30 can be used to estimate EQ-5D using existing mapping algorithms. Several mapping algorithms exist for this transformation, however, algorithms tend to lose accuracy in patients in poor health states. The aim of this study was to test all existing mapping algorithms of QLQ-C30 onto EQ-5D, in a dataset of patients with malignant pleural mesothelioma, an invariably fatal malignancy where no previous mapping estimation has been published. Methods Health related quality of life (HRQoL) data where both the EQ-5D and QLQ-C30 were used simultaneously was obtained from the UK-based prospective observational SWAMP (South West Area Mesothelioma and Pemetrexed) trial. In the original trial 73 patients with pleural mesothelioma were offered palliative chemotherapy and their HRQoL was assessed across five time points. This data was used to test the nine available mapping algorithms found in the literature, comparing predicted against observed EQ-5D values. The ability of algorithms to predict the mean, minimise error and detect clinically significant differences was assessed. Results The dataset had a total of 250 observations across 5 timepoints. The linear regression mapping algorithms tested generally performed poorly, over-estimating the predicted compared to observed EQ-5D values, especially when observed EQ-5D was below 0.5. The best performing algorithm used a response mapping method and predicted the mean EQ-5D with accuracy with an average root mean squared error of 0.17 (Standard Deviation; 0.22). This algorithm reliably discriminated between clinically distinct subgroups seen in the primary dataset. Conclusions This study tested mapping algorithms in a population with poor health states, where they have been previously shown to perform poorly. Further research into EQ-5D estimation should be directed at response mapping methods given its superior performance in this study. Electronic supplementary material The online version of this article (doi:10.1186/s12955-014-0196-y) contains supplementary material, which is available to authorized users.

© 2015 Clive et al. Introduction: Animal studies have shown Zoledronic Acid (ZA) may diminish pleural fluid accumulation and tumour bulk in malignant pleural disease (MPD). We performed a pilot study to evaluate its effects in humans. Methods: We undertook a single centre, double-blind, placebo-controlled trial in adults with MPD. Patients were randomised (1:1) to receive 2 doses of intravenous ZA or placebo, 3 weeks apart and were followed-up for 6 weeks. The co-primary outcomes were change in Visual Analogue Scale (VAS) score measured breathlessness during trial follow-up and change in the initial area under the curve (iAUC) on thoracic Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) from randomisation to week 5. Multiple secondary endpoints were also evaluated. Results: Between January 2010 and May 2013, 30 patients were enrolled, 24 randomised and 4 withdrew after randomisation (1 withdrew consent; 3 had a clinical decline). At baseline, the ZA group were more breathless, had more advanced disease on radiology and worse quality of life than the placebo group. There was no significant difference between the groups with regards change in breathlessness (Adjusted mean difference (AMD) 4.16 (95%CI -4.7 to 13.0)) or change in DCE-MRI iAUC (AMD -15.4 (95%CI -58.1 to 27.3). Two of nine (22%) in the ZA arm had a >10% improvement by modified RECIST (vs 0/11 who received placebo). There was no significant difference in quality of life measured by the QLQ-C30 score (global QOL: AMD -4.1 (-13.0 to 4.9)), side effects or serious adverse event rates. Conclusions: This is the first human study to evaluate ZA in MPD. The study is limited by small numbers and imbalanced baseline characteristics. Although no convincing treatment effect was identified, potential benefits for specific subgroups of patients cannot be excluded. This study provides important information regarding the feasibility of future trials to evaluate the effects of ZA further. Trial Registration: UK Clinical Research Network ID 8877 ISRCTN17030426 www.isrctn.com.

BACKGROUND: Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system.METHODS: Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated.RESULTS: Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228-549; n=43), 130 days (47-467; n=129) and 44 days (22-77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, pCONCLUSIONS: The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

Mesothelin has been proposed as a useful tool in the diagnosis of malignant pleural mesothelioma (MPM). We aimed to examine its diagnostic utility and the impact of renal impairment on results. We prospectively recruited 230 patients with new undiagnosed pleural effusions, testing serum (n=216) and pleural fluid (n=206) mesothelin (by ELISA) during the initial consultation. 28 (12%) out of 230 patients had MPM. Serum mesothelin gave sensitivity 59.3%, specificity 64.7%, negative predictive value (NPV) 91.2%, positive predictive value (PPV) 20.5%, and pleural fluid sensitivity 72.0%, specificity 87.5%, NPV 95.5%, PPV 46.2% for distinguishing effusions due to MPM. In a matched comparison, diagnostic characteristics of pleural fluid mesothelin were superior to serum (p=0.0001). Serum mesothelin levels in patients without MPM were higher in patients with renal impairment (p=0.007) while pleural fluid levels were unaffected. 19 (54%) out of 35 patients with a benign pleural effusion and an estimated glomerular filtration rate ≤59 mL·min −1 had a false-positive serum mesothelin result. The diagnostic accuracy of pleural fluid mesothelin is superior to that of serum and is unaffected by renal function. In patients with a low pre-test probability of mesothelioma, a negative mesothelin test could be reassuring, because of its high NPV. Routine use of mesothelin testing in undiagnosed pleural effusions at presentation appears to be unhelpful.

Expanded abstract Citation Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ: N Engl J Med 2011, 365:518-26. PMID: 21830966, available on www.pubmed. gov Background More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is the key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial therapy (Multicenter Intrapleural Sepsis Trial [MIST1]). Methods Objective: To evaluate the efficacy and safety of intrapleural DNase alone, alteplase alone, or the combination of both, to improve pleural drainage. Design: Multicenter, double-blind, double-dummy, 2 × 2 factorial randomized trial. Setting: Eleven centers in the United Kingdom (UK). Subjects: Adult patients (mean age 59 years, 72% men), who had clinical evidence of infection, and pleural fluid that had macroscopic purulence, a positive culture or Gram stain for bacteria, or a pH < 7.2. Intervention: Patients were assigned to 1 of the 4 study interventions for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. Outcomes: The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. Results The mean (± SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5 ± 23.3% vs. -17.2 ± 19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P = 0.005). The change observed with t-PA alone and with DNase alone (-17.2 ± 24.3 and -14.7 ± 16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006). Hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. Conclusions Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of hospital stay. Treatment with DNase alone or t-PA alone was ineffective.

The past decade has seen a dramatic rise in clinical and research interests in pleural disease in parallel with rising incidences of pleural cancers and infection worldwide. Development of specialist pleural services can streamline patient diagnosis and therapy, reduce health-care resource consumption, improve procedural training and safety and facilitate clinical research. Pleural ultrasound, pleuroscopy, indwelling pleural catheter services and pleural procedural education programmes for junior staff are important elements of most specialist pleural units. An integrated service including radiology, pathology, oncology and thoracic surgery input is pivotal to success. Establishing funding support and referral sources are the common initial hurdles. This article provides an overview of the need for specialist pleural disease units, the essential elements required and the likely challenges encountered in setting a service up.

Purpose of review T-cell interferon-gamma release assay (IGRA) use in tuberculosis (TB) contact screening and latent TB diagnosis is established and supported by American and European guidelines. However, questions remain regarding their clinical utility beyond conventional tests in the investigation of suspected active TB. We review the evidence base for IGRAs in the diagnosis or exclusion of pleural TB. Recent findings The specificity of IGRAs for diagnosis of active TB disease is limited by an inability to distinguish latent disease. The test's sensitivity when applied to the blood of patients with active TB is diminished by compartmentalizing of sensitized T cells at the disease site. To circumnavigate these problems, recent studies explore the value of applying IGRAs to pleural fluid. Results have varied between patient populations, but the strategy does not appear to completely eliminate false-positive results. Summary Accurate biomarkers of pleural TB are useful, particularly for their negative predictive value. IGRAs are technically more complicated and expensive than established biomarkers, and their diagnostic performance for active pleural TB is highly variable between studies and settings. Currently, there is inadequate evidence to support the use of IGRAs in the diagnosis or exclusion of active pleural TB, particularly in centres where adenosine deaminase and interferon-gamma assays are available.

INTRODUCTION: The management of recurrent malignant pleural effusions (MPE) can be challenging. Various options are available, with the most efficacious and widely used being talc pleurodesis. Talc can either be applied via a chest drain in the form of slurry, or at medical thoracoscopy using poudrage. Current evidence regarding which method is most effective is conflicting and often methodologically flawed. The TAPPS trial is a suitably powered, multicentre, open-label, randomised controlled trial designed to compare the pleurodesis success rate of medical thoracoscopy and talc poudrage with chest drain insertion and talc slurry. METHODS AND ANALYSIS: 330 patients with a confirmed MPE requiring intervention will be recruited from UK hospitals. Patients will be randomised (1:1) to undergo either small bore (

Background Outpatient management of undiagnosed pleural effusions is increasing. Payment for managing these patients is usually based on standard outpatient Healthcare Resource Group (HRG) codes. For 2013/14, a new Best Practice Tariff (BPT) of £1534 has been introduced to further disincentivize emergency inpatient management. We audited our service and examined what effects this tariff may have when applied. Methods Our well-established tertiary pleural service serves a local population of around 540,000. New patients are seen in a weekly pleural clinic or in a daily respiratory admission avoidance (Hot) clinic, which had standard 2012/13 tariffs of £223 and £334 respectively. The service sees approximately 150 new effusion patients per year in clinic and 3 new patients per week in Hot. Around 50 medical thoracoscopies and 60 indwelling pleural catheter insertions are performed each year. We audited randomly selected patients from our large, prospectively-maintained database. All audited patients were seen as new pleural effusion referrals between 2008 and 2012. Diagnosis was confirmed after a minimum of 12 months’ follow-up. Results 146 patients were audited. Median age 76(range 21–93), 71% male. Final diagnoses were mesothelioma (n = 28,19%), lung cancer (n = 10,7%), breast cancer (n = 13,9%), other cancer (n = 31,21%), pleural infection (n = 15,10%), benign pleuritis (n = 11,8%) and other (n = 38,26%). 92% of patients avoided direct admission following their initial clinic appointment. 115 patients (79%) underwent ultrasound-guided pleural aspiration at their initial appointment and 63(43%) patients underwent subsequent pleural biopsy. For patients with malignancy, diagnostic sensitivity on first fluid cytology was 27% (adenocarcinoma n = 15,80%; mesothelioma n = 21,5%), and 93%(25/27) for medical thoracoscopy biopsy. Histological/cytological diagnosis took a median of 20 days (IQR 10–33) from presentation. There were no significant procedural complications noted (bleeding, pneumothorax, empyema). 97%(58/60) of patients surveyed rated the service as either very good or excellent. Conclusions Ambulatory management of undiagnosed effusions is efficacious, avoids hospitalisation in the vast majority and is preferred by patients. The 2013/14 pleural effusion BPT promotes admission avoidance by encouraging appropriate outpatient management. Trust reimbursement for practising in this way should facilitate enough resource to enable new pleural services to be established where required.

Introduction Blood and tissue lymphocyte subsets (LS) analysis are routinely used in the diagnosis of a number of haematological conditions. Samples cost £25 to process and are technically labour intensive. The 2010 BTS pleural guidelines suggest LS may be useful in cases of suspected lymphoma, but there is no evidence supporting their utility or position in pleural diagnostic algorithms. Methods Using a prospectively-maintained database of all undiagnosed pleural effusions, we analysed patients presenting to our service from 2009–2011. Fluid was initially sent for cytology and cell differential. Patients with ≥ 50% fluid lymphocytes at first sampling, with no definite cytological evidence of carcinoma, and who underwent a further pleural procedure, had a second sample sent for LS analysis. The cause of the original effusion was agreed by two independent consultants after a minimum 12 month follow-up period. Results 395 patients with undiagnosed effusions were seen, of which 124(31%) were found to be lymphocytic on initial examination. 35(28.2%) patients were excluded due to confirmed (non-haematological) malignancy (11 initial cytology, 24 biopsy). A further 46(37.1%) patients were excluded with confirmed benign diagnoses including inflammatory pleuritis, heart failure and pleural infection. 39/43 (90.7%) patients therefore had samples sent for LS analysis. 7/43 (16.3%) patients’ effusions were diagnosed at 12 months as primarily due to lymphoma, with 5 having a previous diagnosis of such. Their characteristics are described in the table below. LS analysis was diagnostic in 4 and negative in 35 cases. There were no false positive results. Therefore, based on these data, for determining whether there is haematological malignancy in lymphocytic pleural fluid, LS analysis has a sensitivity of 57.1%, a specificity of 100%, and a positive and negative predictive value of 100% and 91.4% respectively. Conclusions LS analysis appears useful in a selected subgroup of patients presenting with undiagnosed effusions. It should only be considered in those patients with a lymphocytic effusion which shows negative initial cytology and/or no firm diagnosis established on pleural biopsy, or those with a past medical history of a lymphoma. A negative LS result does not exclude the possibility of a haematological cause for the effusion.

Background Pleural infection remains common with an increasing incidence. It is associated with a high morbidity and mortality. Despite chest tube drainage and antibiotic therapy up to 30% of patients will die or require surgery. Case reports suggest that irrigation of the pleural space with saline may be beneficial but this has never been the tested in the form of a randomised controlled trial. Method Randomised controlled pilot study comparing saline irrigation (250ml normal saline intra-pleurally over one hour, 3 times a day for 3 days) plus best standard care, with best standard care alone, in patients with pleural infection (microbiology positive or pH Results 47 patients approached, 38 randomised, 3 excluded (drain fell out/no residual fluid on CT/removal of consent). Saline irrigation results in significant reduction in CT pleural collection volume compared to standard care – Irrigation group 29.15% reduction (95% CI 16.2–62) vs Standard care 13.9% (95% CI –4.1–26.3) p Conclusion Saline irrigation improves fluid drainage in pleural infection (as measured by volumetric CT), leading to reduction in referral for surgery. No change in hospital stay was noted. This study now needs to be repeated as a large multicentre RCT powered to look at mortality and length of hospital stay.

Malignant pleural effusion (MPE) is a common clinical problem, which causes significant morbidity and has a variable prognosis. This is the largest series to date evaluating the survival of patients with MPE according to their underlying cell type. Methods We prospectively collected data on patients presenting with MPE from two large pleural services over a 3 year period. All patients gave written informed consent. Patients were followed up for a minimum of 9 months or until death or loss to follow up (whichever was sooner). For survival analysis, the log rank (Mantel-Cox) test was applied to Kaplan Meier survival curves. Results Data was collected on 466 patients. The median age of the patients was 71 (IQR 65–79) and 63% were male. 56% of effusions were right sided and 41% patients had an effusion occupying >50% of the hemithorax. 73% of patients had confirmation of pleural malignancy based on cytology or pleural biopsy, 21% had a presumed malignant effusion with confirmed malignancy elsewhere and 6% had a radiological diagnosis. Patients with a pleural effusion secondary to mesothelioma (n=148) had the longest median survival (MS) at 339 days. This is significantly longer than those effusions caused by lung cancer (n= 127, MS 71 days) (95% CI –0.56–4.45, p The Kaplan-Meier survival curve for the 3 largest groups is shown in the figure. Conclusions Selecting the most appropriate strategy for management of malignant pleural effusion depends on patient choice, their clinical condition and the perceived prognosis. This data confirms that the survival of patients with malignant pleural effusion varies widely depending on the site of their primary malignancy. Accounting for this may help to better inform patients of their prognosis and aid clinical decision making.

Measurement of serum NT-proBNP has been proposed in the investigation of pleural effusions, particularly in the diagnosis of cardiac failure in those misclassified as exudates by Light9s criteria. Studies have reported excellent diagnostic accuracy for the test but have included both bilateral and unilateral effusions and applied short follow-up periods. We prospectively examined the diagnostic utility of serum NT-proBNP in a consecutive series of unilateral pleural effusions with robust follow-up and diagnostic criteria. Method Consecutive patients presenting to a UK teaching hospital with an undiagnosed unilateral pleural effusion underwent clinical assessment including CXR, ECG, echocardiogram, thoracentesis (and CT when appropriate). Light9s criteria were applied. Serum NT-proBNP was measured using point of care ELISA. Patients were followed up to histological/microbiological diagnosis, radiographic resolution or 12 months. Echocardiograms were double reported and diagnosis determined independently by two respiratory consultants—all blind to NT-proBNP results. Results 118 patients. Median age 74 (42–95). 39 in patients, 79 outpatients. 18 transudates, 92 exudates. 30 large, 66 moderate, 22 small. Diagnoses: primary cardiac cause (PCC) 20/118, Malignant 57/118, PE 4/118, Non-cardiac transudate 3/118, other benign cause 30/118. The ROC curve for NT-proBNP discriminating effusions of PCC gave an AUC of 0.845 (0.774–0.934). At cut-off of age and sex adjusted 97.5th centile (healthy population) NT-proBNP had sensitivity 100%, Specificity 53%, PPV 30% and NPV 100% and all four cardiac exudates were correctly diagnosed. At an optimum cut-off of 1500 pg/ml—sensitivity 75%, specificity 76%, PPV 38% and NPV 94%. Co-morbid cardiac disease was common in patients without a PCC for effusion with 70% having significant abnormalities on echocardiogram but cardiac disease was considered to be contributing to effusion in only 9/98 of this group. Conclusion The excellent negative predictive value of NT-proBNP, particularly at an age and sex adjusted cut-off level gives the test utility to rule out a primarily cardiac cause in selected cases of unilateral pleural effusion. Co-morbid cardiac disease and associated NT-proBNP elevation is very common in patients with a non-cardiac origin of pleural effusion such that a positive test at baseline should not alter the initial investigation pathway, particularly amongst pleural exudates.

Differentiation of pleural infection from other causes of pleural effusion, particularly pleural malignancy can be difficult. Clinical features and readily available tests are non-specific resulting in early over-diagnosis of pleural infection. Procalcitonin (PCT) is produced in response to acute bacterial infection and its measurement in serum has shown promise in directing and shortening antibiotic courses in lower respiratory tract infections. We prospectively examined the diagnostic accuracy of PCT in the investigation of unilateral pleural effusions. Methods Consecutive patients with a unilateral pleural effusion, referred to a UK teaching hospital were included. Baseline serum and pleural fluid PCT was measured by enzyme-linked-fluorescent-assay (Vidas BRAHMS PCT—BioMerieux) and results compared to final diagnosis. Clinical data were collected prospectively and the ultimate diagnosis agreed against established criteria by two respiratory consultants, blind to the PCT result. Patients were followed up to histological or microbiological diagnosis, radiographic resolution or for 12 months. Results 145 patients, median age 72 (31–96). 71 inpatients, 75 outpatients. Effusion diagnoses: Complicated parapneumonic (CPE) 26/145, Simple parapneumonic (SPE) 7/145, Malignant 73/145, Idiopathic pleuritis 4/145, TB 1/145, other benign cause 34/145. Four patients with symptomatic non-thoracic bacterial infection and four with frank empyema were excluded from analysis. The Receiver operating characteristic (ROC) curve for serum PCT distinguishing CPE from non-infective diagnoses gave an AUC of 0.779 (95% CI 0.658 to 0.899) and at an optimum cut-off of 0.09 ng/ml had sensitivity 73%, specificity 81%, PPV 44% and NPV 94%. The ROC curve for pleural PCT gave an AUC of 0.809 (95% CI 0.709 to 0.908) and at an optimum cut-off of 0.1 ng/ml had sensitivity 81%, specificity 78%, PPV 45% and NPV 95%. Sub-group analysis excluding patients with >48 h in patient stay or >48 h antibiotics further improved diagnostic accuracy. In patients with pleural fluid pH ≤7.2 serum PCT distinguished CPE from other effusions with an AUC of 0.808 (0.613–1.000). Conclusion Serum and pleural fluid procalcitonin have promising diagnostic characteristics in distinguishing complicated parapneumonic effusions (Abstract P63 Table 1) from unilateral effusions of non-infective origin, having particularly high negative predictive values. Procalcitonin could help the clinician to decide optimal management pathways for individual patients.

Integrated PET-CT scans and serum mesothelin measurement have shown early promise in predicting prognosis and evaluating treatment response in malignant pleural mesothelioma (MPM) but may be less reliable with sarcomatoid histology or prior talc pleurodesis. Dynamic Contrast Enhanced-MRI (DCE-MRI) with pharmacokinetic analysis is a novel metabolic imaging modality providing a measure of tumour blood flow and angiogenesis. We prospectively examined the relationship between pharmacokinetic parameters on DCE-MRI with PET-CT, serum mesothelin and histological sub-type in MPM patients at diagnosis. Method 30 pre-treatment patients with a histologically proven MPM underwent DCE-MRI and integrated PET-CT and serum mesothelin assay (MESOMARK) at a single visit. SUVmax and total glycolytic volume (TGV) were reported from PET-CT scans with TGV calculated using MIM software version 4.2.2 (MIMvista corp.). Gadolinium washout rate (GWR) on DCE-MRI was defined at a region of interest from a straight line fit to the kinetic curve data (CAD software—ViewForum R6.3 V1L3, Philips Medical Systems) between peak enhancement in the first 2 min and the last data point. Results 70% (21/30) epithelioid and 30% (9/30) sarcomatoid histology. 43% (13/30) had undergone prior talc pleurodesis. Histology did not statistically significantly affect SUVmax, TGV or GWR. Serum mesothelin was significantly greater in the epithelioid group (3.2 nM/l (2.0, 6.3) vs 0.6 nM/l (0.5, 0.8) p Conclusion Metabolic imaging has been proposed as an important component of the assessment and management of patients with malignant pleural mesothelioma. Gadolinium washout rate on DCE-MRI may be less sensitive to talc pleurodesis than PET-CT parameters and MRI is a cheaper, more readily available modality that involves shorter patient appointment times, warranting further study in MPM prognostic evaluation and treatment response monitoring.