Louise Stadon

Outpatient Talc Administration by Indwelling Pleural Catheter for Malignant Effusion

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. (Funded by Becton Dickinson; EudraCT number, 2012–000599–40.)

Recurrence rates in primary spontaneous pneumothorax: a systematic review and meta-analysis

Primary spontaneous pneumothorax (PSP) recurrence rates vary widely in the published literature, with limited data describing the factors that influence recurrence. The aims of this systematic review were to determine an estimation of PSP recurrence rates and describe risk factors for recurrence. A systematic review was conducted of all studies reporting PSP recurrence. Electronic searches were performed to identify English language publications of randomised trials and observational studies. The population was adults with PSP, who underwent conservative management, pleural aspiration or chest drainage. The outcome of interest was recurrence. Articles were screened and data extracted from eligible studies by two reviewers. Of 3607 identified studies, 29 were eligible for inclusion, comprising 13 548 patients. Pooled 1-year and overall recurrence rates were 29.0% (95% CI 20.9–37.0%) and 32.1% (95% CI 27.0–37.2%), respectively. Female sex was associated with increased recurrence (OR 3.03, 95% CI 1.24–7.41), while smoking cessation was associated with a four-fold decrease in risk (OR 0.26, 95% CI 0.10–0.63). I2 for random effects meta-analysis was 94% (p<0.0001), reflecting high heterogeneity between studies. This systematic review demonstrates a 32% PSP recurrence rate, with greatest risk in the first year. Female sex was associated with higher risk, suggesting possible sex-specific pathophysiology. PSP has a 32% recurrence rate, with almost all the risk in the first year. Smoking cessation decreases this risk four-fold. Females may be at higher risk, possibly due to sex-specific pathogenic mechanisms. http://ow.ly/Mty730kPi9z

Randomised controlled trial to compare the diagnostic yield of positron emission tomography CT (PET-CT) TARGETed pleural biopsy versus CT-guided pleural biopsy in suspected pleural malignancy (TARGET trial)

Introduction Pleural malignancy, particularly malignant pleural mesothelioma (MPM) is increasing in incidence due to the long latency period from exposure to asbestos to development of the disease. MPM can be challenging to diagnose. For patients presenting without a pleural effusion, CT-guided biopsy remains the primary choice of biopsy, but the diagnostic sensitivity of this investigation is 70%–75%. Therefore, a proportion of patients will go on to require further biopsies. If the first biopsy is non-diagnostic, the chances of further non-diagnostic biopsies are high in MPM. Methods Target is a multicentre randomised controlled trial, aiming to recruit 78 patients over a 30-month period, from 10 centres in the UK. Patients will be randomised to either the standard arm which is a second CT-guided biopsy, or the interventional arm, a positron emission tomography-CT scan followed by a targeted CT-guided biopsy. Patients will be followed up for 12 months (patients recruited in the last 6 months of recruitment will have 6 months of follow-up). MPM biomarker mesothelin will be checked at baseline, 6 month and 12 month follow-up appointments where patients are able to attend these appointments. Ethics and dissemination Ethical approval for this trial was granted by the South West—Exeter research and ethics committee (reference number 15/SW/0156). Results of the trial will be published in a peer-reviewed journal and presented at an international conference. Trial registration number ISRCTN14024829; Pre-results.

S25 Eosinophilic pleural effusions – a large prospective study on aetiology and prognosis

Introduction and Objectives Eosinophilic pleural effusions (EPE) are a relatively uncommon finding in the investigation of undifferentiated pleural effusions. Traditionally defined as a cell count ≥10% eosinophils, it was initially felt to be a marker of benign disease, however, subsequent studies found malignancy to be the commonest aetiology,1 with other causes, including infection, blood/air and drug reactions less frequent. Our aim is to use prospective data to examine the relative incidence and aetiology of EPE, and its prognostic significance. Methods We recruited 803 consecutive patients presenting to a pleural service, between 03/2008 and 03/2015, with undiagnosed pleural effusions. Pleural biochemistry, cytology, thoracic USS, chest radiograph and CT scans were performed. Biopsies and thoracoscopy were performed as clinically indicated. Patients were followed-up for minimum duration of 12 months with final diagnosis decided by independent review by 2 respiratory consultants. Survival data was calculated from study entry to death and censored on 07/2017. Results Of the 803 patients, 398/803 (49.6%) had a malignant pleural effusion(MPE). 57 (7.1%) had eosinophil count (EC) ≥10%. With this threshold, MPE was the commonest cause, at 24/57 (42%), followed by infection 9 (16%) and inflammatory pleuritis (IP) 5 (9%). With higher thresholds of EC, the relative frequency of malignancy decreased. At ≥30% EC, malignancy accounted for 4/20 cases, infection 4/20, drug/toxin 3/20, unknown 3/20, benign asbestos pleural effusion 2/20, pulmonary embolism 2/20, IP 1/20 and heart failure 1/20. Mortality rates were lower in EPE relative to non-EPE, with 6 months and 1 year mortality rates for EPE 19%–33% respectively, with non-EPE 36%–50%. The higher the EC, the lower mortality, with hazard ratios compared to non-EPE at 0.6, 0.5, 0.3, 0.2, 0.2 for ≥10%,≥20%,≥30%,≥40% and ≥50% EC respectively (p<0.01). Conclusion Higher eosinophil counts are associated with decreased mortality and lower rates of malignant vs benign effusions. The threshold ≥10% is not helpful in differentiating MPE from benign disease. We suggest a higher threshold of ≥30% would hold greater clinical significance and therefore be a more useful definition for clinicians. Reference Rubins JB, Rubins HB. Aetiology and prognostic significance of eosinophilic pleural effusions: A prospective study. Chest 1996;110(5):1271–4. Abstract S25 Figure 1 Kaplan-meier survival curves for Eosinophilic vs Non-Eosinophilic effusions.

S21 A prospective study using serum mesothelin to monitor malignant pleural mesothelioma

Background Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients. Methods This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT scans were performed following the completion of chemotherapy, or from baseline in the BSC group. Changes in mesothelin were correlated with radiological progression and overall survival. Results Forty-one patients with MPM were recruited and followed up for a minimum of 12 months (range 12–21 months). The majority of patients (n=23) received chemotherapy with pemetrexed and cisplatin. Across the cohort a 10% rise in serum mesothelin could predict radiological progression with a sensitivity of 96% (IQR; 79–100) and specificity of 74% (IQR; 50–91) (figure 1). Sensitivity fell to 80% in sarcomatoid only disease. Patients with a rising mesothelin at 6 months had significantly worse overall survival (175 days) compared to stable/falling levels (448 days) (p=0.003). Conclusions This is the first study to assess serum mesothelin’s ability to detect progression of MPM following chemotherapy or during BSC. A 10% rise in serum mesothelin level showed excellent sensitivity at predicting progressive disease. Mesothelin measurement has several advantages over serial CT imaging including reducing hospital visits and cost. Abstract S21 Figure 1

Nonmalignant Pleural Effusions: A Prospective Study of 356 Consecutive Unselected Patients

Background Pleural effusion secondary to a nonmalignant cause can represent significant morbidity and mortality. Nonmalignant pleural effusion (NMPE) is common, with congestive heart failure representing the leading cause. Despite this, there are limited data on mortality risk and associated prognostic factors. Methods We recruited 782 consecutive patients presenting to a pleural service between March 2008 and March 2015 with an undiagnosed pleural effusion. Further analysis was conducted in 356 patients with NMPE. Pleural biochemical analysis, cytologic analysis, thoracic ultrasonography, and chest radiography were performed. Echocardiography, CT imaging, radiologically guided biopsy, and medical thoracoscopy were undertaken as clinically indicated. Patients were followed for a minimum duration of 12 months, with the final diagnosis decided through independent review by two respiratory consultants. Results Of the 782 patients, 356 were diagnosed with NMPE (46%). These patients had a mean age of 68 years (SD, 17 years) with 69% of them being men. Patients with cardiac, renal, and hepatic failure had 1‐year mortality rates of 50%, 46%, and 25%, respectively. Bilateral effusions (hazard ratio [HR], 3.55; 95% CI, 2.22‐5.68) and transudative effusions (HR, 2.78; 95% CI, 1.81‐4.28) were associated with a worse prognosis in patients with NMPE, with a 57% and 43% 1‐year mortality rate, respectively. Conclusions This is the largest prospectively collected series in patients with NMPE, demonstrating that cases secondary to organ dysfunction have extremely high 1‐year mortality. In addition, the presence of bilateral and transudative effusions is an indicator of increased mortality. Clinicians should be aware of these poor prognostic features and guide management accordingly.

The physiological consequences of different distributions of diffuse pleural thickening on CT imaging

OBJECTIVE Diffuse pleural thickening (DPT) refers to extensive visceral pleural fibrosis with adhesion formation to the parietal pleura obliterating the pleural space. The radiological definition of DPT remains controversial with most of the literature requiring the presence of an obliterated costophrenic angle (CPA) for defining DPT. We conducted a study to investigate the variable distributions of DPT and associated lung function deficit. METHODS 85 patients referred to a pleural clinic with suspected pleural thickening were screened for our study. Data were collected from 37 patients with DPT confirmed on CT by size criteria (≥3 mm thick, ≥5 cm wide and ≥8 cm in length), and 21 controls with pleural plaques but no other pleuroparenchymal pathology. 27 patients were excluded. Groups were matched to age, body mass index and smoking history. RESULTS The percentage of predicted forced vital capacity showed a gradual decline from 98.9% for the control group to 83.5% in the DPT without CPA obliteration group (p < 0.05), to 79.5% in the unilateral DPT group (p < 0.001) and 66.7% in the bilateral group (p < 0.001). Similar reductions were seen in the percentage of predicted total lung capacity in the DPT with no CPA obliteration group and the bilateral DPT group. CONCLUSION Our study shows an incremental reduction in the forced vital capacity and total lung capacity in DPT without CPA obliteration, unilateral and bilateral DPT when compared with a matched control group. Advances in knowledge: Different distributions of DPT including no CPA obliteration can cause respiratory impairment, with bilateral DPT being the worst affected.

Non-Malignant Pleural Effusions (NMPE)

Background Pleural effusion secondary to a nonmalignant cause can represent significant morbidity and mortality. Nonmalignant pleural effusion (NMPE) is common, with congestive heart failure representing the leading cause. Despite this, there are limited data on mortality risk and associated prognostic factors. Methods We recruited 782 consecutive patients presenting to a pleural service between March 2008 and March 2015 with an undiagnosed pleural effusion. Further analysis was conducted in 356 patients with NMPE. Pleural biochemical analysis, cytologic analysis, thoracic ultrasonography, and chest radiography were performed. Echocardiography, CT imaging, radiologically guided biopsy, and medical thoracoscopy were undertaken as clinically indicated. Patients were followed for a minimum duration of 12 months, with the final diagnosis decided through independent review by two respiratory consultants. Results Of the 782 patients, 356 were diagnosed with NMPE (46%). These patients had a mean age of 68 years (SD, 17 years) with 69% of them being men. Patients with cardiac, renal, and hepatic failure had 1‐year mortality rates of 50%, 46%, and 25%, respectively. Bilateral effusions (hazard ratio [HR], 3.55; 95% CI, 2.22‐5.68) and transudative effusions (HR, 2.78; 95% CI, 1.81‐4.28) were associated with a worse prognosis in patients with NMPE, with a 57% and 43% 1‐year mortality rate, respectively. Conclusions This is the largest prospectively collected series in patients with NMPE, demonstrating that cases secondary to organ dysfunction have extremely high 1‐year mortality. In addition, the presence of bilateral and transudative effusions is an indicator of increased mortality. Clinicians should be aware of these poor prognostic features and guide management accordingly.