A patient-centred approach to malignant pleural effusion

Rebuttal From Dr Lee

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.

AMBULATORY PLEURODESIS: SUCCESSFUL USE OF TALC WITH INDWELLING PLEURAL CATHETER FOR MANAGEMENT OF BILATERAL MALIGNANT PLEURAL EFFUSIONS

Background: Patients with Malignant Pleural Effusions are offered both inpatient (talc pleurodesis) and outpatient (Indwelling Pleural Catheter (IPC)) treatment options as palliative therapeutic relief. There is a paucity of data regarding the patient experience of either of these treatments. Aim: To evaluate patient satisfaction with both inpatient and outpatient treatment options for MPE. Results: Patients treated with talc pleurodesis (n=18) had an extended inpatient hospital stay (> 3 days) following their procedure. The majority of IPC patients were discharged the same day (n=7/8)). There was a clear preference in the talc pleurodesis group for inpatient treatment, with over half reporting that they would not consider IPC management. Four-fifths of those surveyed believed outpatient management would have either no effect or a negative effect on their quality of life (n=12, 80.0%). Patients who had the IPC reported generally positive outcomes, with the majority experiencing no discomfort and 87.5% of participants rated the overall experience as positive. All but one of the IPC patients surveyed were receiving support at home with their IPC from a domiciliary nurse (n=7, 87.5%) Conclusion: Talc pleurodesis patients report longer inpatient stays than IPC patients, however most would not consider a switch to outpatient management beneficial. The majority of surveyed IPC patients receive assistance at home from a health professional and report positive outcomes. Our results suggest the importance of collecting patients’ experience information for improving MPE management.

BackgroundDay-case local anaesthetic thoracoscopy (LAT) decreases length of stay and is safe.1 However, there is variation in current practice between inserting an indwelling pleural catheter (IPC) alone or IPC insertion...

Sir, Malignant pleural effusion heralds a poor prognosis with a median survival ranging from 3 to 12 months. These patients are mostly candidates for palliative therapy which includes alleviation of dyspnoea and facilitating the patient to spend the rest of their life at home with minimal hospitalisations. There are three main modalities of management in malignant pleural effusion, namely, repeated needle thoracentesis, intercostal tube drainage with chemical pleurodesis, and indwelling pleural catheter (IPC). Chemical pleurodesis has always been the first-line approach for malignant pleural effusions, but it requires apposition of pleural surfaces and a mean duration of hospital stay of 4 days.[1] An IPC is a multi-fenestrated silicone tube which is inserted aseptically, allowing long-term access to pleural space. The catheter is tunnelled through a short section of subcutaneous tissue and has a cuff that acts as a focal point for fibrous growth to allow the drain to remain in place. The catheter has a one-way access valve designed to be attached to a proprietary vacuum drainage bottle or a suction machine. The pre-vacuumed bottles provide the advantage of home drainage of the pleural fluid and are calibrated to drain only one litre of fluid, which prevents re-expansion pulmonary oedema during unsupervised drainage at home. Even though there is large international data on the use and advantage of IPC, there is paucity of Indian data regarding the same with only one case report published to the best of our knowledge.[2] This is why we would like to report our early experience on managing poor performance malignant pleural effusion using IPC in the Indian population. We inserted IPC in six patients with malignant pleural effusion who either had a moderate to high risk as per LENT score (LDH level in pleural fluid, ECOG performance scale, neutrophil lymphocyte ratio, tumour type) or had a trapped lung. IPCs were inserted aseptically on an out-patient basis, and patients were followed up for 3 months [Figure 1]. For the initial 1-week, daily drainage of the pleural fluid was carried out on an out-patient basis using a low-pressure suction pump, following which symptom-guided home drainage of the pleural fluid was performed using vacuum bottles. The daily visual analogue score (VAS) score (0–100) was recorded for the first 1 week, followed by 3, 6, 9, and 12 weeks. Patients were reviewed on an out-patient basis every third week, during which their dyspnoea was assessed using VAS and the catheter was inspected for any complications. During the 3 months follow-up or follow-up till death (whichever was earlier), the number and duration of hospital admissions for pleural effusion-related complaints and the number of auto-pleurodesis (defined as less than 50 ml drain for 3 consecutive days with radiological apposition of the pleural surface and no evidence of loculated collection or catheter blockage) were noted.Figure 1: Steps of IPC insertionOut of six patients who were managed with IPC, three were male and three were female. Metastatic lung carcinoma was the most common cause of pleural effusion in this group of patients (n = 3, 50%). Other causes of malignant pleural effusion were carcinoma breast, hepatocellular carcinoma, and angiosarcoma. The mean age of patients was 59 years (SD 19 years). All patients had symptomatic malignant pleural effusion with moderate to high LENT scores (mean 5, SD 1). One patient had a trapped lung. Five patients had unilateral pleural effusion, whereas one had bilateral effusion. During follow-up, two patients died, two patients had the IPC removed at the sixth and seventh weeks post insertion because of auto-pleurodesis, one patient had IPC removed at the sixth week because of pleural space infection, and one patient continued draining through IPC for 3 months. The median duration of catheter drainage was 60 days. Five out of six patients did not require any hospital admission for effusion-related complaints. One patient was admitted for 3 days in hospital, and IPC was removed and replaced with a large bore inter-coastal drainage tube because of pleural space infection. The mean breathlessness on presentation as per VAS was 80.83. Post IPC insertion and drainage, VAS dropped to a mean value of 45.83. This relief of breathlessness was maintained throughout the study period [Table 1]. Two out of the six patients had auto-pleurodesis. The patients who achieved auto-pleurodesis were an 88-year-old male and a 66-year-old female, both of whom had an adenocarcinoma lung with malignant pleural effusion. Auto-pleurodesis was achieved after a mean duration of 7 weeks of drainage.Table 1: Degree of dyspnoea as per visual analogue scale before and after insertion of IPCThe main advantage of IPC over chemical pleurodesis is the reduced number of days spent in hospital. Randomised control trial by Putnam et al.[3] showed the mean duration of hospital admission in chemical pleurodesis patients to be 7 days, whereas IPCs could be safely used as an out-patient procedure requiring no hospital admission. The second therapeutic intervention in malignant effusion trial (TIME 2 trial) and Australian malignant pleural effusion trial (AMPLE trial) also showed fewer effusion related hospital admissions post IPC insertion. In our experience, we were able to replicate these results with five out of our six patients requiring no hospital admissions. Patients were able to self-drain the effusion when symptomatic while at the comfort of their home. Even though a tunnelled tract of IPC, a cuff, and a one-way valve are designed to prevent ascending infection, catheter-associated pleural space infection can complicate IPC. A large multi-centre review of 1021 patients with IPC found an infection rate of 4.8%.[4] In our experience, one out of our six patients (with hepatocellular carcinoma as the cause of malignant pleural effusion) developed pleural space infection requiring hospital admission, replacement of IPC with a wide bore inter-coastal drainage tube, and antibiotics. TIME 2 trial was the first to examine whether using an IPC or the instillation of talc slurry via a chest tube was effective at relieving dyspnoea. Dyspnoea improved in both groups, with no significant difference in the mean VAS. In our experience, all our patients had statistically significant symptom relief with IPC drainage which was maintained throughout the study with initial aggressive pleural fluid drainage and later symptom-guided pleural fluid drainage. In this way, IPCs offer the advantage of dyspnoea relief with symptom-guided at-home self-drainage using vacuum bottles. One of the major limiting factors of IPC is cost. The catheter is much costlier than routine inter-coastal drainage, and there is recurring cost of single use pre-vacuumed bottles. Interestingly, a Dutch analysis of cost of IPC showed a mean cost of IPC comparable with that of chemical pleurodesis.[5] This is because of the cost of in-patient care which is reduced in IPC drainage. There are no studies regarding the same in the Indian population. In conclusion, IPCs are a novel method for management of malignant pleural effusion which offers good symptom relief with the added advantage of reduced hospital admissions, the option of which should be offered to all patients with malignant pleural effusion. Further studies in the Indian population are required to assess the improvement in quality of life and cost effectiveness as compared to conventional management. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

IntroductionBritish Thoracic Society (BTS) guidelines suggest that Indwelling Pleural Catheters (IPCs) are the best treatment for malignant pleural effusion (MPE) associated with unexpandable lung (UL), where pleurodesis is contraindicated. Although,...

Introduction Non-expansile lung (NEL) is a common cause of talc pleurodesis (TP) failure in Malignant Pleural Effusion (MPE). NEL is frequently occult prior to drainage and is more effectively managed using an indwelling pleural catheter (IPC). Reliable pre-drainage detection of NEL would facilitate more informed MPE management. Elevated Pleural Elastance (PEL) is associated with NEL but technical challenges, a limited evidence base and low sensitivity during small volume aspiration have precluded clinical utilisation. Pre-EDIT is a randomised feasibility trial of Elastance-Directed Intra-pleural catheter or Talc Pleurodesis (EDIT) management of MPE, using a novel, purpose-built digital pleural manometer (DPM, Rocket Medical). Methods EDIT involves computation of PEL during a large volume aspiration. Patients are then directed to TP or IPC within 24 hours (see figure 1). In pre-EDIT, eligible patients (symptomatic MPE, no prior evidence of NEL or preference for IPC) are randomised 1:1 between EDIT and standard care (TP). The primary objective is to determine whether it is feasible to recruit and randomise 30 patients within 12 months (or 15 patients within 6 months). Secondary objectives include assessment of the safety of EDIT management, the aspiration volume required to detect abnormal PELand the proportion of patients in whom pneumothorax induction is required for subsequent TP/IPC. Additionally, a treatment preferences survey will assess factors important to patients when choosing a first-line intervention for symptomatic MPE. 4-D volumetric pleural Magnetic Resonance Imaging (MRI) is being used to explore mechanisms of symptoms during fluid aspiration, to validate an ultrasound estimate of pleural effusion volume (a proposed inclusion criterion) and the assumption that aspiration volume equals change in pleural cavity volume. Potential MRI biomarkers of NEL will also be explored. Results 23/30 patients have been recruited at the point of submission. The primary objective was met during 6 months between October 2017 and April 2018. Preliminary results relating to secondary objectives will be available for the Winter BTS Meeting 2018. Conclusion Pre-EDIT will address important areas of uncertainty regarding the design of a potential future Phase III trial regarding the efficacy of EDIT management. Recruitment has reached a pre-specified feasibility threshold.

BackgroundLittle is known about patient outcomes following treatment of malignant pleural effusions (MPE) in the real-world setting.Research questionWe aimed to compare post-procedure all-cause mortality between individuals who received indwelling pleural catheter (IPC) insertion versus chemical pleurodesis for managing MPEs.Study design and methodsWe performed a retrospective population-based study using provincial health administrative data (Ontario, Canada) of adults with a MPE who underwent IPC insertion or chemical pleurodesis between 2015 and 2019. Individuals were followed until death or March 31, 2021. Difference in post-procedure mortality was calculated using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazard regression analysis to balance potential confounders at baseline.ResultsWe identified 4,790 (77.3%) individuals who received an IPC and 1,407 (22.7%) who had chemical pleurodesis for MPE. IPC insertions are increasing and chemical pleurodesis procedures are decreasing. The majority of IPCs were inserted in outpatients (61%), by pulmonologists (64.2%) and at sites with higher annual IPC volume, while chemical pleurodesis procedures were generally done by thoracic surgeons (74%) and at sites with higher annual pleurodesis volumes. In unadjusted comparison median time from initial cancer diagnosis to intervention was significantly longer in the IPC group (244 days, interquartile range [IQR]:33–903) compared to pleurodesis group (81 days, IQR:10–737; p < 0.0001). Unadjusted median time from index procedure to death was significantly longer in the pleurodesis group (165[IQR:48–457] days vs. 81[IQR:29–256] days, p < 0.0001), however the difference between groups became insignificant after the IPTW was applied (HR 1.27, 95%CI 0.95–1.69). 35% of IPCs were removed prior to death or end of follow-up.InterpretationAfter adjusting for differences in baseline characteristics there was no difference in post-procedure mortality between IPC and chemical pleurodesis groups. In the real world, there are significant differences in the characteristics of patients who receive these two procedures and notable regional practice variation between procedure use. Future research should evaluate these variations in care and their effect on patient outcomes.

BACKGROUND: Malignant and paramalignant pleural effusions are important complications of many malignancies. The two main management options debated in the literature are: 1) insertion of an indwelling pleural catheter (IPC) to achieve chronic drainage of the effusion, or 2) hospitalization with tube thoracostomy and subsequent chemical pleurodesis (CP) with talc or doxycycline to prevent fluid reaccumulation. We aimed to describe a large series of patients with malignant pleural effusions managed with an IPC, identify and validate factors identified in the literature as predictors of spontaneous pleurodesis in the IPC group and compare the group managed with IPC to patients managed with CP. METHODS: We designed a retrospective cohort study comparing patients with malignant and paramalignant pleural effusions managed either with CP between March 1, 2003 and February 28, 2006 or IPC insertion between May 1, 2006 and April 1, 2009. The CP group was identified through the prescription of talc or doxycycline and the IPC group from the IPC clinic database. Data were collected from paper and electronic records and from the Government of Ontario. RESULTS: We identified 193 consecutive patients with an ECOG performance status of less than 4 (ECOG less than 4 means that the patient is not completely disabled and confined to bed or chair) having undergone IPC insertion and 168 who were managed with CP. None of the variables we tested were significant predictors of spontaneous pleurodesis in the IPC group. Pleural effusion control rates at 6 months were higher in the IPC group than in the CP

Background: Malignant pleural effusions indicate advanced stage of cancer and making the treatment decisions difficult for the treating physicians. There are multiple treatment options for the treatment of malignant pleural effusion including pleurodesis, thoracocentesis, indwelling pleural catheters (IPCs), and pleural decortication surgeries. However, there is a considerable number of patients who are not candidates for either pleurodesis or have repeated thoracocentesis, these patients can be carefully selected for management with IPCs. Aims and Objectives: To establish the use of indwelling pleural catheter in malignant pleural effusions. Materials and Methods: Patients who are not candidates for either pleurodesis or have repeated thoracocentesis, these patients can be carefully selected for management with IPCs. This is a prospective study of 23 patients with underlying trapped lung or recurrent pleural effusions who have been treated with IPCs from January 2021 to December 2022. We have used Rocket pleural catheter in this study. Results: The common primary malignancy was from lungs with the most common histologic type being adenocarcinoma type. We had good improvement in symptoms and have observed minor complications in about 21% of the individuals. Conclusion: IPC can be considered a good treatment option for patients with malignant pleural effusion with trapped lungs and patients with recurrent pleural effusions.

Quality-Adjusted Survival Following Treatment of Malignant Pleural Effusions With Indwelling Pleural Catheters

The Optimal Treatment of Malignant Pleural Effusions A Continuing Dilemma

<b>Introduction:</b> Local Anaesthetic Thoracoscopy (LAT) has a role in the work-up of undiagnosed pleural effusions. If non-expandable lung is suspected, an indwelling pleural catheter (IPC) can be inserted at LAT. Incidence of subcutaneous emphysema (SCE) following this is unclear. It is unknown whether SCE reduces when the IPC is placed through a separate incision to the thoracoscopy port. We aim to establish the incidence of SCE when IPC is placed at time of rigid LAT and whether the site of IPC insertion influences this. <b>Methods:</b> Retrospective analysis of LAT electronic records and chest radiographs over a six-year period was undertaken at a tertiary centre. SCE was assessed at day 1 and discharge imaging and graded 0-4 [0 none; 1 IPC site; 2 ipsilateral chest wall; 3 neck; 4 contralateral chest wall]. <b>Results:</b> Between 2014-2019, there were 36 dual LAT and IPC procedures. Median length of stay post-LAT was 3 days. 28 patients had IPC sited through the LAT port incision and 8 were sited through a separate incision. Incidence of any subcutaneous emphysema on day 1 was 22/28 (79%) through port site and 4/8 (50%) through separate incision. At discharge, incidence was 79% and 62% respectively. No patients required additional intervention. Combined incidence of subcutaneous emphysema of Grade ≥2 only occurred in 10/36 (27%) on day 1 and 13/36 (36%) at discharge. For patients with IPC via separate incision, incidence of Grade ≥2 was 12.5% and 25% respectively compared with 32% and 40% for IPCs via LAT port site. <b>Conclusions:</b> Placement of IPCs through a separate incision to the LAT site may reduce the incidence of subcutaneous emphysema in rigid LAT.

Malignant pleural effusions (MPE) are a common complication of advanced malignancy. The treatment of MPE should be focused on palliation of associated symptoms. The traditional approach to MPE has been to attempt pleurodesis by introducing a sclerosant into the pleural space. A more recent development in the treatment of MPE has been the use of indwelling pleural catheters (IPC) for ongoing drainage of the pleural space. Controversy exists as to which approach is superior. Pleurodesis approaches will have the advantage of a time-limited course of treatment and high pleurodesis rate at the cost of a more invasive procedure requiring a general anaesthetic or conscious sedation (for thoracoscopic approaches) and an inpatient hospital stay. Use of IPC will allow the patient to be treated on an outpatient basis with a minimally invasive procedure, at the cost of long-term need for catheter drainage and care. Symptom control appears similar between techniques. Complication rates between the two approaches cannot be easily compared, but studies suggest more frequent severe complications such as respiratory failure, arrhythmias and even mortality following pleurodesis, with infection rates similar between the two approaches. IPC will likely see increasing utilization in the future but patient preference and local resources and expertise will continue to play a significant part in treatment decisions. Randomized trials directly comparing the two approaches are needed and some are underway. Novel combination approaches utilizing both IPC and pleurodesis agents have the potential to further improve the care of these patients.