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.

Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. 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. 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<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients’ treatment response.

British Journal of Hospital MedicineVol. 76, No. 10 RegularsEvaluation of an ambulatory pleural service: costs and benefitsRebekah L Young, Rahul Bhatnagar, Andrew RL Medford, Nick A MaskellRebekah L YoungSearch for more papers by this author, Rahul BhatnagarSearch for more papers by this author, Andrew RL MedfordSearch for more papers by this author, Nick A MaskellSearch for more papers by this authorRebekah L Young; Rahul Bhatnagar; Andrew RL Medford; Nick A MaskellPublished Online:12 Oct 2015https://doi.org/10.12968/hmed.2015.76.10.608AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Department of Health Payment by Results Team (2013) Payment by Results Guidance for 2013-14. Department of Health, Leeds Google ScholarYim AP, Chan AT, Lee TW, Wan IY, Ho JK (1996) Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion. Ann Thorac Surg 62: 1655–8 Crossref, Medline, Google Scholar FiguresReferencesRelatedDetailsCited byPleural clinic: where thoracic ultrasound meets respiratory medicine11 October 2023 | Frontiers in Medicine, Vol. 10Impact of a Pleural Care Program on the Management of Patients With Malignant Pleural Effusions1 April 2023 | Journal of Bronchology & Interventional Pulmonology, Vol. 30, No. 2The Pathway to Definitive Palliation of Malignant Pleural EffusionsAnnals of the American Thoracic Society, Vol. 16, No. 5Outcomes of a Clinical Pathway for Pleural Disease Management: “Pleural Pathway”Pulmonary Medicine, Vol. 2018Diagnostic approach to pleural diseases: new tricks for an old trade17 July 2017 | F1000Research, Vol. 6 2 October 2015Volume 76Issue 10 ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 12 October 2015 Published in print 2 October 2015 Information© MA Healthcare LimitedPDF download

IntroductionBlood 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.MethodsUsing 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.Results395 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.ConclusionsLS 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.

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<0.0001). Cell types with an intermediate survival, included gynaecological malignancy (n=33; MS=268 days), urological cancer (n=11; MS=220 days), gastrointestinal malignancy (n=16; MS 268 days), haematological malignancy (n=27; median survival 204 days) and breast cancer (n=48; MS 204 days). Lung cancer, adenocarcinoma of unknown primary (n=9; MS 87 days) and sarcoma (n=6, MS 65.5 days) had the shortest survival. 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.

VEGF is a key mediator of tumour growth and metastasis and is considered central to the formation of exudative pleural effusions. This study examined the relationship between levels of VEGF and its soluble receptor, sVEGFR-1 in the pleural fluid and plasma of patients with malignant pleural effusions and their association with pleurodesis outcomes and survival.103 patients with malignant pleural effusions were recruited at their first presentation. Follow-up was to 6months or death. Survival and pleurodesis outcomes were robustly ascertained. VEGF and sVEGFR-1 were measured in pleural fluid and plasma by ELISA.VEGF and sVEGFR-1 were present in significantly higher concentrations in pleural fluid than plasma. There was no significant correlation between mediators within or between sample types. There was no association between baseline pleural fluid VEGF or sVEGFR-1 levels and pleurodesis failure.In both sample types, survival was inversely associated with sVEGFR-1 and within the non-small cell lung cancer sub-group (n=26), a highly significant association between increased pleural fluid VEGF and sVEGFR-1 and reduced survival was demonstrated (p=0.02 and 0.004 respectively).In conclusion, we have shown for the first time that sVEGFR-1 can be reproducibly measured in pleural fluid from malignant effusions. High levels at presentation in those with non-small cell carcinoma are strongly associated with poor outcomes.

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) (p<0.04). Significantly fewer patients in the irrigation group were referred for surgery (OR 7.1, 95% CI 1.23-41.0; p=0.03). There was no difference in length of hospital stay, fall in C-reactive protein, white cell count or procalcitonin or adverse events between the treatment groups, and no serious complications were documented.Saline 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.

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.