Management of solitary fibrous tumours of the pleura:a systematic review and meta-analysis

Background:Solitary fibrous tumours of the pleura (SFTP), or pleural fibromas, are rare tumours that generally, but not universally, follow a benign course. Surgical resection is the standard treatment, but there are no evidence-based guidelines regarding the management of these tumours. Methods:Five databases were searched from inception to April 1, 2019 for studies reporting on SFTP management. Results:Twenty-seven studies met the inclusion criteria (1542 patients, all non-comparative case series); 98% of these patients underwent resection and all SFTP included were pathologically diagnosed. 394 out of 1299 cases (30.5%, 95% CI 27.8-32.8%) were malignant with recurrence rates of between 0% and 42.9%. A pleural effusion was always associated with a negative outcome, but no other features were consistently reported to have negative associations. Preoperative biopsies incorrectly reported malignant histology in two studies. Over 25% of cases of recurrence occurred when a complete (R0) resection had been achieved. The first recurrence occurred >5 years after the initial resection in at least 23% of cases. Conclusions:There is strong evidence to support long-term surveillance after surgical resection of SFTP, even where a complete (R0) resection has been achieved; however, there is no clear evidence to inform clinicians regarding the selection of patients who should undergo resection. The rates of malignant SFTP and SFTP recurrence are higher than previously reported. Only those that were pathologically diagnosed or resected were included, which may bias the data towards more aggressive tumours. Data collection on radiologically diagnosed SFTP is required to draw conclusions regarding the timing and need for intervention

Critical analysis of the utility of initial pleural aspiration in the diagnosis and management of suspected malignant pleural effusion

INTRODUCTION:Current guidelines recommend an initial pleural aspiration in the investigation and management of suspected malignant pleural effusions (MPEs) with the aim of establishing a diagnosis, identifying non-expansile lung (NEL) and, at times, providing a therapeutic procedure. A wealth of research has been published since the guidelines suggesting that results and outcomes from an aspiration may not always provide sufficient information to guide management. It is important to establish the validity of these findings in a 'real world' population. METHODS:A retrospective analysis was conducted of all patients who underwent pleural fluid (PF) sampling, in a single centre, over 3 years to determine the utility of the initial aspiration. RESULTS:A diagnosis of MPE was confirmed in 230/998 (23%) cases, a further 95/998 (9.5%) were presumed to represent MPE. Transudative biochemistry was found in 3% of cases of confirmed MPE. Positive PF cytology was only sufficient to guide management in 45/140 (32%) cases. Evidence of pleural thickening on CT was associated with both negative cytology (χ2 1df=26.27, p<0.001) and insufficient samples (χ2 1df=10.39, p=0.001). In NEL 44.4% of patients did not require further procedures after pleurodesis compared with 72.7% of those with expansile lung (χ2 1df=5.49, p=0.019). In patients who required a combined diagnostic and therapeutic aspiration 106/113 (93.8%) required further pleural procedures. CONCLUSIONS:An initial pleural aspiration does not achieve either definitive diagnosis or therapy in the majority of patients. A new pathway prioritising symptom management while reducing procedures should be considered

A Pilot Feasibility Study in Establishing the Role of Ultrasound-Guided Pleural Biopsies in Pleural Infection (The AUDIO Study)

Background Pleural infection is a common complication of pneumonia associated with high mortality and poor clinical outcome. Treatment of pleural infection relies on the use of broad-spectrum antibiotics because reliable pathogen identification occurs infrequently. We performed a feasibility interventional clinical study assessing the safety and significance of ultrasound (US)-guided pleural biopsy culture to increase microbiological yield. In an exploratory investigation, the 16S ribosomal RNA technique was applied to assess its utility on increasing speed and accuracy vs standard microbiological diagnosis. Methods Twenty patients with clinically established pleural infection were recruited. Participants underwent a detailed US scan and US-guided pleural biopsies before chest drain insertion, alongside standard clinical management. Pleural biopsies and routine clinical samples (pleural fluid and blood) were submitted for microbiological analysis. Results US-guided pleural biopsies were safe with no adverse events. US-guided pleural biopsies increased microbiological yield by 25% in addition to pleural fluid and blood samples. The technique provided a substantially higher microbiological yield compared with pleural fluid and blood culture samples (45% compared with 20% and 10%, respectively). The 16S ribosomal RNA technique was successfully applied to pleural biopsy samples, demonstrating high sensitivity (93%) and specificity (89.5%). Conclusions Our findings demonstrate the safety of US-guided pleural biopsies in patients with pleural infection and a substantial increase in microbiological diagnosis, suggesting potential niche of infection in this disease. Quantitative polymerase chain reaction primer assessment of pleural fluid and biopsy appears to have excellent sensitivity and specificity.</p

Defining the minimal important difference for the visual analogue scale assessing dyspnea in patients with malignant pleural effusions

BACKGROUND: The minimal important difference (MID) is essential for interpreting the results of randomised controlled trials (RCTs). Despite a number of RCTs in patients with malignant pleural effusions (MPEs) which use the visual analogue scale for dyspnea (VASD) as an outcome measure, the MID has not been established. METHODS: Patients with suspected MPE undergoing a pleural procedure recorded their baseline VASD and their post-procedure VASD (24 hours after the pleural drainage), and in parallel assessed their breathlessness on a 7 point Likert scale. FINDINGS: The mean decrease in VASD in patients with a MPE reporting a 'small but just worthwhile decrease' in their dyspnea (i.e. equivalent to the MID) was 19mm (95% CI 14-24mm). The mean drainage volume required to produce a change in VASD of 19mm was 760ml. INTERPRETATION: The mean MID for the VASD in patients with a MPE undergoing a pleural procedure is 19mm (95% CI 14-24mm). Thus choosing an improvement of 19mm in the VASD would be justifiable in the design and analysis of future MPE studies

Randomized controlled trial of urokinase versus placebo for nondraining malignant pleural effusion

Rationale: Patients with malignant pleural effusion experience breathlessness, which is treated by drainage and pleurodesis. Incomplete drainage results in residual dyspnea and pleurodesis failure. Intrapleural fibrinolytics lyse septations within pleural fluid, improving drainage. Objectives: To assess the effects of intrapleural urokinase on dyspnea and pleurodesis success in patients with nondraining malignant effusion. Methods: We conducted a prospective, double-blind, randomized trial. Patients with nondraining effusion were randomly allocated in a 1:1 ratio to intrapleural urokinase (100,000 IU, three doses, 12-hourly) or matched placebo. Measurements and Main Results: Co–primary outcome measures were dyspnea (average daily 100-mm visual analog scale scores over 28 d) and time to pleurodesis failure to 12 months. Secondary outcomes were survival, hospital length of stay, and radiographic change. A total of 71 subjects were randomized (36 received urokinase, 35 placebo) from 12 U.K. centers. The baseline characteristics were similar between the groups. There was no difference in mean dyspnea between groups (mean difference, 3.8 mm; 95% confidence interval [CI], −12 to 4.4 mm; P = 0.36). Pleurodesis failure rates were similar (urokinase, 13 of 35 [37%]; placebo, 11 of 34 [32%]; adjusted hazard ratio, 1.2; P = 0.65). Urokinase was associated with decreased effusion size visualized by chest radiography (adjusted relative improvement, −19%; 95% CI, −28 to −11%; P < 0.001), reduced hospital stay (1.6 d; 95% CI, 1.0 to 2.6; P = 0.049), and improved survival (69 vs. 48 d; P = 0.026). Conclusions: Use of intrapleural urokinase does not reduce dyspnea or improve pleurodesis success compared with placebo and cannot be recommended as an adjunct to pleurodesis. Other palliative treatments should be used. Improvements in hospital stay, radiographic appearance, and survival associated with urokinase require further evaluation. Clinical trial registered with ISRCTN (12852177) and EudraCT (2008-000586-26)

Understanding pneumothorax: epidemiology, physiology and predicting outcome

Contrary to traditional teaching, patients with Primary Spontaneous Pneumothorax (PSP) do not have normal lungs. Emphysema-like change (ELC) and inflammation are common. However, the natural history of ELC and its significance in terms of future disease is not known. Current management of pneumothorax is generic and not personalised. This thesis updates the UK epidemiology of pneumothorax, describes the use of two novel methods to examine the lungs, a method of predicting early treatment failure, the association of CT findings and recurrence, and a systematic review of chemical pleurodesis to reduce recurrence. Analysis of fifty yearsâ data on ~150,000 admissions demonstrated that the incidence of pneumothorax is increasing, and established a method to identify primary from secondary pneumothoraces and their relative risk of recurrence. Reduced ventilation of hyperpolarised Xenon on enhanced-Magnetic Resonance Imaging (MRI) was seen in those PSP patients with greater low attenuation areas on Computed Tomography (CT) and with reduced pulmonary function. A model of lung inhomogeneity found that metrics of lung ventilation distinguished pneumothorax patients from healthy volunteers and Chronic Obstructive Pulmonary Disease (COPD) patients. This may represent subtle or mild disease, not identified on standard testing, which may be exacerbated by smoking. CT scanning found that mild emphysema and cystic airspaces were common in PSP patients. Ex- or current smokers had more (and larger) cysts. Emphysema was more common in smokers and patients with a history of previous pneumothorax: who were at higher risk of recurrence. However, variation in number and size of cysts were seen in both those patients with and without recurrence. As such, no single algorithm to predict recurrence was identified. Airflow measurement early in the patient pathway has the potential to identify those likely to fail treatment, potentially allowing early triage to surgery. The addition of talc or minocycline as an adjunct to surgery provides the lowest recurrence rates, but physician-led talc poudrage may be similarly effective. Those in whom surgery is not suitable, chemical pleurodesis could be offered via chest drain. Data presented in this thesis thus provides insights into the underlying abnormalities in PSP and lays the groundwork for strategies to fundamentally alter the management paradigm.</p

Understanding pneumothorax: epidemiology, physiology and predicting outcome

Contrary to traditional teaching, patients with Primary Spontaneous Pneumothorax (PSP) do not have normal lungs. Emphysema-like change (ELC) and inflammation are common. However, the natural history of ELC and its significance in terms of future disease is not known. Current management of pneumothorax is generic and not personalised. This thesis updates the UK epidemiology of pneumothorax, describes the use of two novel methods to examine the lungs, a method of predicting early treatment failure, the association of CT findings and recurrence, and a systematic review of chemical pleurodesis to reduce recurrence. Analysis of fifty years’ data on ~150,000 admissions demonstrated that the incidence of pneumothorax is increasing, and established a method to identify primary from secondary pneumothoraces and their relative risk of recurrence. Reduced ventilation of hyperpolarised Xenon on enhanced-Magnetic Resonance Imaging (MRI) was seen in those PSP patients with greater low attenuation areas on Computed Tomography (CT) and with reduced pulmonary function. A model of lung inhomogeneity found that metrics of lung ventilation distinguished pneumothorax patients from healthy volunteers and Chronic Obstructive Pulmonary Disease (COPD) patients. This may represent subtle or mild disease, not identified on standard testing, which may be exacerbated by smoking. CT scanning found that mild emphysema and cystic airspaces were common in PSP patients. Ex- or current smokers had more (and larger) cysts. Emphysema was more common in smokers and patients with a history of previous pneumothorax: who were at higher risk of recurrence. However, variation in number and size of cysts were seen in both those patients with and without recurrence. As such, no single algorithm to predict recurrence was identified. Airflow measurement early in the patient pathway has the potential to identify those likely to fail treatment, potentially allowing early triage to surgery. The addition of talc or minocycline as an adjunct to surgery provides the lowest recurrence rates, but physician-led talc poudrage may be similarly effective. Those in whom surgery is not suitable, chemical pleurodesis could be offered via chest drain. Data presented in this thesis thus provides insights into the underlying abnormalities in PSP and lays the groundwork for strategies to fundamentally alter the management paradigm.</p

Pleural abnormalities predating the development of mesothelioma

Mesothelioma is an aggressive tumour of the pleura that is closely related to asbestos exposure. Asbestos is known to cause benign pleural thickening, effusion and plaques and the majority of patients with these abnormalities do not develop mesothelioma. It has been noted, however, that asbestos-exposed patients who have pleural plaques are at increased risk of mesothelioma. This study aimed to describe the range of pleural abnormalities seen on CT done at some time before the diagnosis of mesothelioma was made