Rachelle Asciak

Churchill Hospital

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Najib M. Rahman

University of Oxford

Rachel Mercer

Churchill Hospital

Rob Hallifax

Oxford University Hospitals NHS Trust

Maged Hassan

Iraqi University

Ioannis Psallidas

AstraZeneca (United Kingdom)

Eihab O. Bedawi

University of Oxford

David McCracken

Piedmont HealthCare

Nikolaos I. Kanellakis

Oxford University Hospitals NHS Trust

Nick Maskell

University of Bristol

John Wrightson

Oxford University Hospitals NHS Trust

Cooperative Institutions

University of Oxford

106

Oxford University Hospitals NHS Trust

Churchill Hospital

Oxford Centre for Diabetes, Endocrinology and Metabolism

John Radcliffe Hospital

Mater Dei Hospital

National Institute for Health Research

Oxford BioMedica (United Kingdom)

National Health Service

University of Patras

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Clinical identification of malignant pleural effusions

Translational Oncology (2023)

Jianlong Jia Antonia Marazioti Apostolos Voulgaridis Ioannis Psallidas Anne‐Sophie Lamort

Pleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.A consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n = 238).Five variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count 〈 2,500/mm3, effusion protein 〉 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (P < 10-15) in the derivation cohort. The integrated discrimination improvement of MAPED scores showed an increase compared to cytology (p <0.001). Decision curve analysis indicated that the MAPED score generated net clinical benefit. In the validation dataset, the AUC of MAPED scores was 0.723 ( P = 3 × 10-9) for the MAPED score. Interestingly, MAPED correctly identified 33/42(79%) of cytology-negative patients that indeed had cancer.The MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures.Diagnostic markers for malignant pleural effusions remain uncertain. The MAPED score identifies malignant pleural effusions and complements cytology and confers no additional risk to the patient or cost to the healthcare system.

10.1016/j.tranon.2023.101800

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Citations (3)

Retrospective analysis of survival time in malignant pleural effusion requiring IPC insertion

Rachelle Asciak Rob Hallifax Rebecca Shakir Nikolaos I. Kanellakis Ioannis Psallidas

Background: Malignant pleural effusion (MPE) is a common cause of a recurrent pleural effusion, and a common indication for indwelling pleural catheter (IPC) insertion. The relationship between treatment time with IPC and survival has never been investigated in patients with MPE. Aim: To analyse survival times in patients with MPE from the date of symptomatic effusion requiring IPC insertion, according to when the IPC was inserted in the treatment course. Method: Details of patients who had IPC insertions for MPE between the years 2008-2015 were collected from our procedure database and analysed against the clinical records. Results: 146 cases (72 female; mean age 68 years) were studied. The commonest primary malignancies were lung (25%), breast (21%), and mesothelioma (20%). 34 cases were excluded due to incomplete data, 11 were still alive. In the remaining 101, 41.6% had a primary malignancy diagnosed prior to pleural effusion being diagnosed (Group A), 58.4% had the first pleural effusion diagnosed prior to the malignancy being diagnosed (Group B). 93% of the study population had died by January 2017. Overall survival time was a mean of 453 days after IPC insertion. In Groups A and B, there was a mean of 136.1 days and 214.9 days respectively between IPC insertion and death (p <0.05). Conclusion: Time between IPC insertion and death varies significantly between patient groups according to whether malignant effusion is diagnosed prior to the diagnosis of malignancy elsewhere or if MPE is the primary cause of diagnosis. Further analysis by tissue type, chemotherapy and performance status is required to identify factors that influence survival time in patients treated with IPC.

Group B

10.1183/1393003.congress-2017.pa1589

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S131 Novel model of indwelling pleural catheter in mice with malignant pleural effusion

Christopher Merrick Taylor P. Sherrill NI Kanellakis Rachelle Asciak GT Stathopoulos

Introduction

Malignant pleural effusion (MPE) is common and indicates advanced malignancy. Indwelling pleural catheters (IPC) are used in recurrent MPE. To date, there has not yet been a reliable mouse model of MPE utilising IPC, and such model would be useful especially since intrapleural therapy for malignancy is a burgeoning area of research, and IPC provides direct access to the pleural space with the potential of testing novel treatment agents.

Aim

To design the first experimental mouse model with IPC.

Method

250,000 Lewis lung carcinoma (LLC) cells were injected into the pleural space of anaesthetised C57BL/6 mice. 7–9 days are required for development of MPE from time of LLC intrapleural injection,¹ so on day 7, the IPCs were inserted: 3 punctures were made at distal end of a polyurethane tube (PU-40) to enhance catheter flow; a small puncture was made through the 7th rib space in mid-axillary line of the mice. PU-40 was advanced 1.5 cm into the pleural space. A 16G needle was used to puncture the dorsum between scapulae, and advanced through subcutaneous tissue towards catheter insertion site. Proximal end of PU-40 tube was then passed through needle and out between the scapulae, leaving IPC tunnelled through the subcutaneous space. MPE was drained while mice were still under anaesthesia.

Results

Mean volume of fluid drained (n=19) was 188 ul (range 0–770 uL). Post-mortem dissection demonstrated bulky tumour with minimal residual MPE (n=17). Occasionally, IPC was enveloped by tumour, blocking MPE drainage, with resulting residual MPE within pleural space (n=2). IPC was also useful to allow intrapleural drug delivery. Potential agents could be injected through IPC using a 22G syringe by means of a syringe accessible port. A typical volume of 100 uL phosphate buffer solution was well tolerated by mice.

Discussion

This novel mouse model seeks to mimic MPE drainage using an IPC in humans, and allows MPE aspiration as well as drug delivery to the pleural space. This model will enable the testing of the use and effectiveness of intrapleural therapies in the treatment of MPE.

Reference

Stathopoulos GT, et al. AJRCMB2006;34(2):142–50.

Pleural cavity

Lewis lung carcinoma

Subcutaneous tissue

Chest tube

Thoracic cavity

10.1136/thorax-2018-212555.137

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Lung abscess or empyema? Taking a closer look

Thorax (2018)

Maged Hassan Rachelle Asciak Rana Rizk Hany Shaarawy Fergus Gleeson

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). …

Lung abscess

10.1136/thoraxjnl-2018-211604

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Citations (16)

ERS/ESTS statement on the management of pleural infection in adults

European Respiratory Journal (2022)

Eihab O. Bedawi Sara Ricciardi Maged Hassan Michael R. Gooseman Rachelle Asciak

Pleural infection is a common condition encountered by respiratory physicians and thoracic surgeons alike. The European Respiratory Society (ERS) and European Society of Thoracic Surgeons (ESTS) established a multidisciplinary collaboration of clinicians with expertise in managing pleural infection with the aim of producing a comprehensive review of the scientific literature. Six areas of interest were identified: 1) epidemiology of pleural infection, 2) optimal antibiotic strategy, 3) diagnostic parameters for chest tube drainage, 4) status of intrapleural therapies, 5) role of surgery and 6) current place of outcome prediction in management. The literature revealed that recently updated epidemiological data continue to show an overall upwards trend in incidence, but there is an urgent need for a more comprehensive characterisation of the burden of pleural infection in specific populations such as immunocompromised hosts. There is a sparsity of regular analyses and documentation of microbiological patterns at a local level to inform geographical variation, and ongoing research efforts are needed to improve antibiotic stewardship. The evidence remains in favour of a small-bore chest tube optimally placed under image guidance as an appropriate initial intervention for most cases of pleural infection. With a growing body of data suggesting delays to treatment are key contributors to poor outcomes, this suggests that earlier consideration of combination intrapleural enzyme therapy (IET) with concurrent surgical consultation should remain a priority. Since publication of the MIST-2 study, there has been considerable data supporting safety and efficacy of IET, but further studies are needed to optimise dosing using individualised biomarkers of treatment failure. Pending further prospective evaluation, the MIST-2 regimen remains the most evidence based. Several studies have externally validated the RAPID score, but it requires incorporating into prospective intervention studies prior to adopting into clinical practice.

Cardiothoracic surgery

Chest tube

10.1183/13993003.01062-2022

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Citations (60)

Pleural effusion

European Respiratory Society eBooks (2018)

Christopher Merrick Rachelle Asciak Anthony Edey Fabien Maldonado Ioannis Psallidas

10.1183/2312508x.10014817

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Citations (1)

P252 The role of a regional mesothelioma MDT in improving prognostication

DJ McCracken Eihab O. Bedawi M. Hassan Rachel Mercer Rachelle Asciak

Introduction

Malignant pleural mesothelioma (MPM) is primarily associated with asbestos exposure. Prognosis is poor, with median survival quoted as 6–12 months. Although uncommon, incidence has been steadily increasing and is predicted to peak in 2020. The National Lung Cancer Audit report on MPM (2015), demonstrated significant variation in management and outcomes across the UK and subsequently lead to the production of the British Thoracic Society Guideline for the investigation and management of MPM (2017). This included the recommendation for regional mesothelioma MDTs. We present the findings from the first 15 months of the regional MDT in Oxford and its impact on other recommendations contained within the guidelines.

Method

Complete follow up data was collected prospectively from all patients with MPM treated at the Oxford Pleural Unit since 2005. Following the establishment of a mesothelioma MDT in March 2017, 39 patients have been diagnosed and discussed at this meeting. These cases were compared with the 39 preceding cases to assess the impact of the introduction of a specialist MDT.

Results

Demographics between both groups were similar. Average age was 77.4 in the MDT group versus 73.8. Sex showed a male predominance in both groups of 82.5%. There was some variation in the distribution of histological subtypes within the groups, however there was an improvement in the number of patients with a clinical diagnosis, no histological subtype or those requiring post-mortem, although sample size was inadequate to achieve significance (table 1). There was no difference in the number of patients being considered for enrolment in clinical trials (33% versus 36%) however there were significant increases in the number of patients who had prognostic scores calculated (54% versus 0%) and those who had formal staging documented (56% versus 21%, p=0.001).

Discussion

Mesothelioma MDTs appear to improve documentation and communication of disease stage and prognosis. Further improvement in this area and in the consideration of enrolment in clinical trials may be possible with the introduction of an MDT proforma. Further work is required to assess the impact on diagnostic accuracy which might be best achieved by joint MDT working to obtain required numbers.

Guideline

10.1136/thorax-2018-212555.408

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Sex differences in the efficacy, safety, and tolerability of omalizumab after 1 year in Maltese patients with asthma

Annals of Allergy Asthma & Immunology (2017)

Caroline Gouder Rachelle Asciak Stephen Montefort

Omalizumab

Tolerability

Allergic asthma

10.1016/j.anai.2017.01.019

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P101 Inflammatory pleural effusions: differentiating the diagnosis

Dinesh Addala RM Mercer Qiang Lü G Shepherd Rebecca Varatharajah

Introduction

Diagnosing pleural infection can be challenging in the clinical setting. Positive microbiology is the gold standard, but pleural fluid culture requires days to establish and can be negative in 40% of patients with pleural infection. Rapid biomarker testing showing low pH, low glucose and very high LDH in pleural fluid is used to diagnose pleural infection in the correct clinical setting.

Objectives

To establish the diagnostic accuracy of low pH, low glucose and very high LDH in pleural fluid for pleural infection and establish the common alternative diagnoses leading to this biochemical pattern.

Methods

A retrospective analysis of pleural effusion results from a UK tertiary centre over a three year period. Pleural fluid results with either pH<7.2, Glucose <2.2 mmol/L or LDH>1000 IU/L (total 173) were assessed to establish the frequency of non-infective final diagnoses and the relative specificity of each parameter calculated for the diagnosis of pleural infection.

Results

Of effusions with either a low pH, low glucose or LDH>1000 (n=173), the most common causes were infective 51% (n=89), with the most frequent alternative diagnosis malignant pleural effusion (MPE) 31% (n=53). Of note 10% (n=19) had co-existing malignancy and infection. The most common causative MPEs were lung 51%, mesothelioma 32% and breast 16%. In all pleural effusions with a pH<7.2 (n=47), 13% were non infective diagnoses with 4% MPE. In all pleural effusions with glucose<2.2 (n=57), 53% were due to non-infective diagnoses, and 30% due to MPE. In the cohort with pleural fluid LDH>1000 (n=129), 47% were non infective in aetiology, 30% due to MPE. Table 1 illustrates further specific diagnoses within each cohort.

Conclusions

Pleural effusions with a low pH, low glucose or very high LDH often have a non-infective cause. While it may be appropriate to commence antimicrobial treatment, our results suggest that malignancy should be actively investigated. Pleural fluid pH<7.2 was the most specific marker for pleural infection. Further work is required to establish whether biomarkers such as fluid c-reactive protein and procalcitonin provide added value in diagnosing pleural infection, especially in the cohort of patients with malignancy.

Gold standard (test)

10.1136/thorax-2019-btsabstracts2019.244

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Are there geographical differences in the microbiology of pleural infection?

Maged Hassan Tamsin Cargill John Corcoran Eli Harriss Rachelle Asciak

Background: In the past decade, several reports have pointed towards the emergence of certain microbes as causative agents for pleural infection (e.g. Klebsiella in the Far East). We hypothesised that such differences in microbiology may be related to variation in ambient temperature. Methods: we performed a systematic review of papers reporting on pleural infection in humans on Embase and Medline databases between 2000-2017. Entries reporting on paediatric, post-operative and tuberculous empyemas were excluded. The cumulative incidence of different microbes was collated from all studies and presented by geographic regions. Results: Initial search returned 20980 papers that were screened by titles/abstracts. 275 papers were found relevant and full-texts were downloaded for analysis. 78 papers contained good quality microbiology data, which was extracted for analysis. Figure 1 shows the worldwide pattern of microbiology and a break-up of the microbiology pattern by region (Viridans Streptococci group comprises the Streptococcus milleri subgroup and other microaerophilic streptococci). Besides the organisms represented in the figure, TB was found in 184/2074 cases where it was reported among the culture results. As for fungi, it was reported in 91/3003 cases. Conclusion: Gram +ve cocci are predominant causes of pleural infections. There appears to be geographical differences in the incidence of different organisms.

Clinical Microbiology

10.1183/13993003.congress-2018.pa4686

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Citations (1)