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IntroductionCurrent 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.MethodsA 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.ResultsA 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, p2 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.ConclusionsAn 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.

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

BackgroundPleural infection (PI) is a major global disease with an increasing incidence, and pleural fluid (PF) drainage is essential for the successful treatment. The MIST2 study demonstrated that intrapleural administration of tissue plasminogen activator (t-PA) and DNase, or t-PA alone increased the volume of drained PF. Mouse model studies have suggested that the volume increase is due to the interaction of the pleura with the t-PA via the monocyte chemoattractant protein 1 (MCP-1) pathway. We designed a study to determine the time frame of drained PF volume induction on intrapleural delivery of t-PA±DNase in humans, and to test the hypothesis that the induction is mediated by the MCP-1 pathway.MethodsData and samples from the MIST2 study were used (210 PI patients randomised to receive for 3 days either: t-PA and DNase, t-PA and placebo, DNase and placebo or double placebo). PF MCP-1 levels were measured by ELISA. One-way and two-way analysis of variance (ANOVA) with Tukey’s post hoc tests were used to estimate statistical significance. Pearson’s correlation coefficient was used to assess linear correlation.ResultsIntrapleural administration of t-PA±DNase stimulated a statistically significant rise in the volume of drained PF during the treatment period (days 1–3). No significant difference was detected between any groups during the post-treatment period (days 5–7). Intrapleural administration of t-PA increased MCP-1 PF levels during treatment; however, no statistically significant difference was detected between patients who received t-PA and those who did not. PF MCP-1 expression was not correlated to the drug given nor the volume of drained PF.ConclusionsWe conclude that the PF volume drainage increment seen with the administration of t-PA does not appear to act solely via activation of the MCP-1 pathway.

Introduction Malignant Pleural Mesothelioma (MPM) is the only malignancy which develops primarily in the pleural space and is a common cause of a malignant pleural effusion (MPE). MPE associated with MPM is managed similarly to any other malignancy, but it is unclear if the underlying mechanisms of fluid accumulation are the same and whether different treatment strategies should therefore be employed. The TIME 1 trial enrolled patients with MPE who underwent pleurodesis. This post hoc analysis compares the outcomes of patients with MPM to the rest of the trial population. Methods 298 patients had available data on their final diagnosis. A number of different variables were compared, including pleurodesis success, systemic inflammation, the prevalence of trapped lung, total fluid volume drained and baseline pain Visual Analogue Score (VAS). Results Of the 298 patients included in the analysis 110 patients had mesothelioma (36.9%). Post pleurodesis, MPM patients had a significantly greater rise in CRP than those with other underlying pathologies but had a significantly lower rate of successful pleurodesis. Patients with MPM had a lower pain VAS score on enrolment. There was no significant difference in the rates of trapped lung, the total volume of pleural fluid drained or the change in White Cell Count (WCC) between the groups. Conclusion There are significant differences in the outcomes of patients with MPM and those with other MPE. Patients with MPM had a lower pleurodesis rate but a significantly greater change in C-reactive protein levels post pleurodesis, signifying a higher inflammatory response to pleurodesis, which has been assumed to associate with pleurodesis success. The mechanisms causing the increased inflammatory response in MPM are unclear. The basis for the lower rates of pleurodesis is unexplained, especially as there was no significant different in the rates of trapped lung. Patients with MPM had a lower level of pain VAS scores on enrolment but further analyses are needed to determine whether this is clinically relevant and reproducible. These data indicate that MPM behaves differently to other forms of MPE and treatment strategies should be tailored towards MPM as a separate entity.

Maged Hassan (MH): I would like to present three cases of patients who presented with symptoms of lower respiratory tract infection, fever and cough productive of small amount of sputum. The three patients had complained of symptoms for at least 2 weeks before presentation. The chest X-rays showed large encysted collections (figure 1A) which required chest CT to delineate the source of the abnormality. The CT studies (case 1: figure 1B, C; case 2: figure 2A and case 3: figure 2C) caused prolonged discussion between the treating clinicians with opinions divided on the nature of the lesion in each case being either an encysted empyema or a large peripheral lung abscess. Clinically, the differentiation between empyema and lung abscess was important because empyema is treated with tube drainage which is only resorted to in limited situations in lung abscess with the attendant risk of creating a bronchopleural fistula or extending the infection to the pleura. Figure 1 Case 1. (A) Chest X-ray shows right side cavity with air-fluid level. (B) Chest CT with contrast, axial cut, shows right side spherical lesion with air-fluid level causing lung collapse at the hilum (hollow arrow). Note pleural enhancement and extrapleural fat hypertrophy (arrowheads). (C) Chest CT, coronal reconstruction in lung window shows the acute angle the lesion makes with the chest wall and the pushed distorted airways proximal to the lesion (hollow arrow). (D) Thoracic ultrasound shows multiple hyperechoic shadows inside an echogenic collection. (E) Follow chest X-ray 48 hours after chest tube insertion (seen in situ) shows lung re-expansion. Figure 2 Case 2. (A) Baseline CT chest with contrast, coronal cut showing large left collection that is making an acute angle with chest wall (arrow) and uniformly thin wall with smooth inner margins (hollow arrows). (B) Chest X-ray following chest tube removal. Note thickened visceral pleura (hollow arrows). …

An 18-year-old man presented to the local hospital in Malta, with dyspnoea, cough, mild haemoptysis, chest pain and night sweats. CT revealed a right hilar mass. Pleural tap, bronchoscopy and open lung biopsy were inconclusive. Biopsies obtained at repeat bronchoscopy and endobronchial ultrasound (EBUS) revealed a likely diagnosis of inflammatory myofibroblastic tumour (IMT). The patient subsequently underwent right pneumonectomy, and histology revealed the presence of two further nodules apart from the main tumour. Follow-up with positron emission tomography (PET)/CT showed the development of a right basal paracardial lesion due to recurrence and the presence of lymph node, pleural and skeletal disease. Despite radiotherapy to the recurrent nodule and chemotherapy, there was skeletal disease progression. Treatment with an anaplastic lymphoma kinase inhibitor, ceritinib, resulted in very good metabolic response. This case report highlights the importance of keeping IMT in mind when the diagnosis of lung tumours is difficult, as delayed diagnosis may lead to worsened prognosis.

A 47-year-old asymptomatic man with no significant family history was referred to our faculty because of an abnormal chest X-ray (CXR). The CXR, similar to his CXR 10 years previously, showed bilaterally increased interstitial markings suggestive of pulmonary fibrosis. High-resolution CT (HRCT) showed multiple bilateral branching calcifications, mostly in the lung bases (figures 1 and 2), with ground-glass opacities in the lingula, and no enlarged mediastinal lymph nodes. A repeat HRCT after 4 months remained similar. After discussion at a multidisciplinary team meeting, a diagnosis of pulmonary alveolar microlithiasis (PAM) was reached., peer-reviewed