Association between Physical Activity and Reduced Mortality in Inoperable Lung Cancer.

We examined device-measured physical activity (PA) and sedentary behaviour at the time of diagnosis in people with inoperable lung cancer and investigated their associations with 12-month mortality. The people with inoperable lung cancer wore an accelerometer for seven days prior to the treatment commencement. The analysed PA/sedentary behaviour variables included light-intensity PA, moderate-to-vigorous-intensity PA (MVPA), step count, the total time spent sedentary, and the usual sedentary bout duration. The data on the disease stage, clinical covariates and 12-month mortality were extracted from medical records. Cox regression models were used to estimate the association between the PA measures and 12-month mortality, and the sedentary behaviour measures and 12-month mortality. The models were adjusted for the stage and neutrophil-to-lymphocyte ratio. All the PA and sedentary behaviour variables were dichotomised at their medians for analysis. Eighty-nine participants (70 ± 10 years; 55 [62%] males) contributed valid data. The twelve-month mortality was 30% (n = 27). Compared to the participants who spent ≤4.6 min/day in MVPA (n = 45), those who spent >4.6 min/day (n = 44) had a relative risk of 12-month mortality reduced by 60% (hazard ratio, 0.40; 95% CI, 0.16 to 0.96; 18 versus nine deaths, respectively). The other variables of PA/sedentary behaviour were not associated with 12-month mortality. Higher device-measured MVPA was associated with reduced 12-month mortality in people who were newly diagnosed with inoperable lung cancer.

Sedentary Behaviour, Physical Activity, and Their Associations with Health Outcomes at the Time of Diagnosis in People with Inoperable Lung Cancer.

This study aimed to examine sedentary behaviour (SB), physical activity (PA) and their associations with health-related measures at the time of diagnosis in people with inoperable lung cancer. People newly diagnosed with inoperable lung cancer were invited to participate in the study and asked to wear an accelerometer for seven consecutive days. Variables analysed included time spent in SB, light intensity PA (LIPA) and moderate-to-vigorous intensity PA (MVPA). Daily steps were also recorded. Data on symptoms, health-related quality of life (HRQoL), hand grip force, comorbidities and lung function were collected. Of the 120 patients referred to the study, 89 (74%) consented to participate, and SB/PA data were available for 79 (age 71 ± 11 years; 29 females). Participants spent 71% of their waking time in SB, 28% in LIPA and 1% in MVPA. Regression models demonstrated that increased SB was associated with more symptoms of fatigue and dyspnoea (p ≤ 0.02 for both), poorer HRQoL (general health and physical component score; p ≤ 0.02 for all) and lower hand grip force. For PA variables, higher daily step count was associated with better scores in all health-related measures (p < 0.05 for all). LIPA was associated with more health-related outcomes than MVPA. These findings may guide future interventions in this population.

Pneumothorax: Classification and Etiology.

Pneumothorax is a common problem worldwide. Pneumothorax develops secondary to diverse aetiologies; in many cases, there may be no recognizable lung abnormality. The pathogenetic mechanism(s) causing spontaneous pneumothorax may be related to an interplay between lung-related abnormalities and environmental factors such as smoking. Tobacco smoking is a major risk factor for primary spontaneous pneumothorax; chronic obstructive pulmonary disease is most frequently associated with secondary spontaneous pneumothorax. This review article provides an overview of the historical perspective, epidemiology, classification, and aetiology of pneumothorax. It also aims to highlight current knowledge and understanding of underlying risks and pathophysiological mechanisms in pneumothorax development.

Widespread pulmonary invasion by malignant pleural mesothelioma: an important diagnostic consideration.

We report a rare case of early and extensive pulmonary invasion of malignant pleural mesothelioma (MPM) in a 70-year-old woman. She first presented with a hydropneumothorax and subsequent workup, including video-assisted thoracoscopy (VAT), confirmed MPM. After VAT, she developed dyspnoea, cough, and widespread pulmonary infiltrates of uncertain aetiology. These infiltrates progressed over the following months, failed to respond to antibiotics, and were strongly fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET). Bronchoalveolar lavage (BAL) yielded extremely viscous fluid containing mesothelioma cells. These cells were also found in the sputum when nebulized deoxyribonuclease (DNase) was trialled to enhance clearance of the pulmonary fluid. The patient deteriorated rapidly with progressive mediastinal and contralateral MPM involvement and died one month later. This case highlights the importance of including tumour invasion as a differential diagnosis of non-resolving pulmonary infiltrates in patients with MPM.

Pleural effusions and pneumothorax: Beyond simple plumbing: Expert opinions on knowledge gaps and essential next steps.

Pleural diseases affect millions of people worldwide. Pleural infection, malignant pleural diseases and pneumothorax are common clinical challenges. A large number of recent clinical trials have provided an evidence-based platform to evaluate conventional and novel methods to drain pleural effusions/air which reduce morbidity and unnecessary interventions. These successes have generated significant enthusiasm and raised the profile of pleural medicine as a new subspecialty. The ultimate goal of pleural research is to prevent/stop development of pleural effusions/pneumothorax. Current research studies mainly focus on the technical aspects of pleural drainage. Significant knowledge gaps exist in many aspects such as understanding of the pathobiology of the underlying pleural diseases, pharmacokinetics of pleural drug delivery, etc. Answers to these important questions are needed to move the field forward. This article collates opinions of leading experts in the field in highlighting major knowledge gaps in common pleural diseases to provoke thinking beyond pleural drainage. Recognizing the key barriers will help prioritize future research in the quest to ultimately cure (rather than just drain) these pleural conditions.

Management of Indwelling Tunneled Pleural Catheters: A Modified Delphi Consensus Statement.

BACKGROUND: The management of recurrent pleural effusions remains a challenging issue for clinicians. Advances in management have led to increased use of indwelling tunneled pleural catheters (IPC) because of their effectiveness and ease of outpatient placement. However, with the increase in IPC placement there have also been increasing reports of complications, including infections. Currently there is minimal guidance in IPC-related management issues after placement. RESEARCH QUESTION: Our objective was to formulate clinical consensus statements related to perioperative and long-term IPC catheter management based on a modified Delphi process from experts in pleural disease management. STUDY DESIGN AND METHODS: Expert panel members used a modified Delphi process to reach consensus on common perioperative and long-term management options related to IPC use. Members were identified from multiple countries, specialties, and practice settings. A series of meetings and anonymous online surveys were completed. Responses were used to formulate consensus statements among panel experts, using a modified Delphi process. Consensus was defined a priori as greater than 80% agreement among panel constituents. RESULTS: A total of 25 physicians participated in this project. The following topics were addressed during the process: definition of an IPC infection, management of IPC-related infectious complications, interventions to prevent IPC infections, IPC-related obstruction/malfunction management, assessment of IPC removal, and instructions regarding IPC management by patients and caregivers. Strong consensus was obtained on 36 statements. No consensus was obtained on 29 statements. INTERPRETATION: The management of recurrent pleural disease with IPC remains complex and challenging. This statement offers statements for care in numerous areas related to IPC management based on expert consensus and identifies areas that lack consensus. Further studies related to long-term management of IPC are warranted.

Use of indwelling pleural/peritoneal catheter in the management of malignant ascites: a retrospective study of 48 patients.

BACKGROUND: Patients suffering from malignant ascites usually require repeated large volume paracentesis (LVP) for symptomatic relief. This often requires hospital admission and has inherent risks. AIMS: To report the first Australian experience of placing tunnelled indwelling peritoneal catheters (IPeC) for management of recurrent malignant ascites. METHODS: A retrospective study was conducted of tunnelled IPeC use in patients with symptomatic malignant ascites in four hospitals in Western Australia (from 2010 to 2018). Procedure data, success rate and safety profile were collected from a database. RESULTS: Forty-eight patients (median age 65 years; female 56%) underwent 51 peritoneal catheter insertion procedures that were performed mostly by pleural specialists. The majority of patients (96%) had prior LVP (median two drainages, interquartile range (IQR) 1-4) before IPeC insertion. The IPeC was inserted successfully under ultrasound guidance in all patients. The median length of hospital stay for IPeC insertion and initial ascites drainage was 2 days (IQR 2-3 days) and most patients (96%) did not require further paracentesis after IPeC placement. The majority (96%) of patients experienced relief from ascites symptoms after catheter insertion. Most IPeC-related adverse events were self-limiting, including pain (in 25% cases), transient hypotension after initial fluid drainage (10%), peritoneal fluid leakage (10%), bacterial peritonitis (8%), fluid loculation (2%) and catheter dislodgement (2%). Six (12%) patients had IPeC removed. All patients with bacterial peritonitis responded to antibiotics and one required catheter removal. CONCLUSIONS: Use of tunnelled IPeC improves symptoms and can minimise further invasive drainage procedures in patients with symptomatic malignant ascites. Placement of IPeC was associated with a low rate of adverse events, most of which could be managed conservatively.

Management of Malignant Pleural Effusions-What Is New.

Malignant pleural effusion (MPE) is a common and challenging problem. Patients affected by MPE have a poor prognosis and suffer from breathlessness and impaired quality of life. The management of MPE has barely changed for many decades; however, recent research has driven new paradigms in the diagnosis and treatment of MPE and stimulated novel concepts that are being evaluated in many ongoing studies. This review provides an overview of recent advances in the diagnosis of MPE, including new cytopathology and imaging techniques, and the landmark studies that provide a solid evidence base to support the use of indwelling pleural catheters as first-line treatment in MPE. Lingering management dilemmas, including optimal chest drainage tube and role of surgery in MPE, and key knowledge gaps that are the focus of ongoing research are also highlighted.

Exercise training for advanced lung cancer.

BACKGROUND: Patients with advanced lung cancer have a high symptom burden, which is often complicated by coexisting conditions. These issues, combined with the indirect effects of cancer treatment, can cumulatively lead patients to continued deconditioning and low exercise capacity. This is a concern as exercise capacity is considered a measure of whole body health, and is critical in a patient's ability to participate in life activities and tolerate difficult treatments. There is evidence that exercise training improves exercise capacity and other outcomes, such as muscle force and health-related quality of life (HRQoL), in cancer survivors. However, the effectiveness of exercise training on these outcomes in people with advanced lung cancer is currently unclear. OBJECTIVES: The primary aim of this review was to investigate the effects of exercise training on exercise capacity in adults with advanced lung cancer. Exercise capacity was defined as the six-minute walk distance (6MWD; in meters) measured during a six-minute walk test (6MWT; i.e. how far an individual can walk in six minutes on a flat course), or the peak oxygen uptake (i.e. VO2peak) measured during a maximal incremental cardiopulmonary exercise test (CPET).The secondary aims were to determine the effects of exercise training on the force-generating capacity of peripheral muscles, disease-specific global HRQoL, physical functioning component of HRQoL, dyspnoea, fatigue, feelings of anxiety and depression, lung function, level of physical activity, adverse events, performance status, body weight and overall survival in adults with advanced lung cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE (via PubMed), Embase (via Ovid), CINAHL, SPORTDiscus, PEDro, and SciELO on 7 July 2018. SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared exercise training versus no exercise training in adults with advanced lung cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the studies and selected those for inclusion. We performed meta-analyses for the following outcomes: exercise capacity, disease-specific global HRQoL, physical functioning HRQoL, dyspnoea, fatigue, feelings of anxiety and depression, and lung function (forced expiratory volume in one second (FEV1)). Two studies reported force-generating capacity of peripheral muscles, and we presented the results narratively. Limited data were available for level of physical activity, adverse events, performance status, body weight and overall survival. MAIN RESULTS: We identified six RCTs, involving 221 participants. The mean age of participants ranged from 59 to 70 years; the sample size ranged from 20 to 111 participants. Overall, we found that the risk of bias in the included studies was high, and the quality of evidence for all outcomes was low.Pooled data from four studies demonstrated that, on completion of the intervention period, exercise capacity (6MWD) was significantly higher in the intervention group than the control group (mean difference (MD) 63.33 m; 95% confidence interval (CI) 3.70 to 122.96). On completion of the intervention period, disease-specific global HRQoL was significantly better in the intervention group compared to the control group (standardised mean difference (SMD) 0.51; 95% CI 0.08 to 0.93). There was no significant difference between the intervention and control groups in physical functioning HRQoL (SMD 0.11; 95% CI -0.36 to 0.58), dyspnoea (SMD -0.27; 95% CI -0.64 to 0.10), fatigue (SMD 0.03; 95% CI -0.51 to 0.58), feelings of anxiety (MD -1.21 units on Hospital Anxiety and Depression Scale; 95% CI -5.88 to 3.45) and depression (SMD -1.26; 95% CI -4.68 to 2.17), and FEV1 (SMD 0.43; 95% CI -0.11 to 0.97). AUTHORS' CONCLUSIONS: Exercise training may improve or avoid the decline in exercise capacity and disease-specific global HRQoL for adults with advanced lung cancer. We found no significant effects of exercise training on dyspnoea, fatigue, feelings of anxiety and depression, or lung function. The findings of this review should be viewed with caution because of the heterogeneity between studies, the small sample sizes, and the high risk of bias of included studies. Larger, high-quality RCTs are needed to confirm and expand knowledge on the effects of exercise training in this population.

Aggressive versus symptom-guided drainage of malignant pleural effusion via indwelling pleural catheters (AMPLE-2): an open-label randomised trial.

BACKGROUND: Indwelling pleural catheters are an established management option for malignant pleural effusion and have advantages over talc slurry pleurodesis. The optimal regimen of drainage after indwelling pleural catheter insertion is debated and ranges from aggressive (daily) drainage to drainage only when symptomatic. METHODS: AMPLE-2 was an open-label randomised trial involving 11 centres in Australia, New Zealand, Hong Kong, and Malaysia. Patients with symptomatic malignant pleural effusions were randomly assigned (1:1) to the aggressive (daily) or symptom-guided drainage groups for 60 days and minimised by cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group [ECOG] score 0-1 vs ≥2), presence of trapped lung, and prior pleurodesis. Patients were followed up for 6 months. The primary outcome was mean daily breathlessness score, measured by use of a 100 mm visual analogue scale during the first 60 days. Secondary outcomes included rates of spontaneous pleurodesis and self-reported quality-of-life measures. Results were analysed by an intention-to-treat approach. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12615000963527. FINDINGS: Between July 20, 2015, and Jan 26, 2017, 87 patients were recruited and randomly assigned to the aggressive (n=43) or symptom-guided (n=44) drainage groups. The mean daily breathlessness scores did not differ significantly between the aggressive and symptom-guided drainage groups (geometric means 13·1 mm [95% CI 9·8-17·4] vs 17·3 mm [13·0-22·0]; ratio of geometric means 1·32 [95% CI 0·88-1·97]; p=0·18). More patients in the aggressive group developed spontaneous pleurodesis than in the symptom-guided group in the first 60 days (16 [37·2%] of 43 vs five [11·4%] of 44, p=0·0049) and at 6 months (19 [44·2%] vs seven [15·9%], p=0·004; hazard ratio 3·287 [95% CI 1·396-7·740]; p=0·0065). Patient-reported quality-of-life measures, assessed with EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L), were better in the aggressive group than in the symptom-guided group (estimated means 0·713 [95% CI 0·647-0·779] vs 0·601 [0·536-0·667]). The estimated difference in means was 0·112 (95% CI 0·0198-0·204; p=0·0174). Pain scores, total days spent in hospital, and mortality did not differ significantly between groups. Serious adverse events occurred in 11 (25·6%) of 43 patients in the aggressive drainage group and in 12 (27·3%) of 44 patients in the symptom-guided drainage group, including 11 episodes of pleural infection in nine patients (five in the aggressive group and six in the symptom-guided drainage group). INTERPRETATION: We found no differences between the aggressive (daily) and the symptom-guided drainage regimens for indwelling pleural catheters in providing breathlessness control. These data indicate that daily indwelling pleural catheter drainage is more effective in promoting spontaneous pleurodesis and might improve quality of life. FUNDING: Cancer Council of Western Australia and the Sir Charles Gairdner Research Advisory Group.

Air in the Pleural Cavity Enhances Detection of Pleural Abnormalities by CT Scan.

Detection of pleural abnormalities on CT scan is critical in diagnosis of pleural disease. CT scan detects minute parenchymal lung nodules, but often fails to detect similar-sized pleural nodularity. This is likely because the density of the visceral/parietal pleura and pleural fluid is similar. We hypothesize that an air-pleural interface enhances detection of pleural abnormalities. We describe six patients with pleural abnormalities that were not (or barely) detected on initial CT scan. However, pneumothorax (either ex vacuo or from a genuine air leak) after pleural fluid drainage permitted the visualization of small pleural abnormalities on CT scan, which would be amenable to imaging-guided biopsies. This case series provides proof-of-principle evidence that the sensitivity of CT scan detection of pleural abnormalities is dependent on adjacent tissue density and can be enhanced by intrapleural air. Future studies of the potential for artificial pneumothorax to improve the diagnosis of pleural disease are warranted.

Effect of an Indwelling Pleural Catheter vs Talc Pleurodesis on Hospitalization Days in Patients With Malignant Pleural Effusion: The AMPLE Randomized Clinical Trial.

Importance: Indwelling pleural catheter and talc pleurodesis are established treatments for malignant pleural effusions among patients with poor prognosis. Objective: To determine whether indwelling pleural catheters are more effective than talc pleurodesis in reducing total hospitalization days in the remaining lifespan of patients with malignant pleural effusion. Design, Setting, and Participants: This open-label, randomized clinical trial included participants recruited from 9 centers in Australia, New Zealand, Singapore, and Hong Kong between July 2012 and October 2014; they were followed up for 12 months (study end date: October 16, 2015). Patients (n = 146) with symptomatic malignant pleural effusion who had not undergone indwelling pleural catheter or pleurodesis treatment were included. Interventions: Participants were randomized (1:1) to indwelling pleural catheter (n = 74) or talc pleurodesis (n = 72), minimized by malignancy (mesothelioma vs others) and trapped lung (vs not), and stratified by region (Australia vs Asia). Main Outcomes and Measures: The primary end point was the total number of days spent in hospital from procedure to death or to 12 months. Secondary outcomes included further pleural interventions, patient-reported breathlessness, quality-of-life measures, and adverse events. Results: Among the 146 patients who were randomized (median age, 70.5 years; 56.2% male), 2 withdrew before receiving the randomized intervention and were excluded. The indwelling pleural catheter group spent significantly fewer days in hospital than the pleurodesis group (median, 10.0 [interquartile range [IQR], 3-17] vs 12.0 [IQR, 7-21] days; P = .03; Hodges-Lehmann estimate of difference, 2.92 days; 95% CI, 0.43-5.84). The reduction was mainly in effusion-related hospitalization days (median, 1.0 [IQR, 1-3] day with the indwelling pleural catheter vs 4.0 (IQR, 3-6) days with pleurodesis; P < .001; Hodges-Lehmann estimate, 2.06 days; 95% CI, 1.53-2.58). Fewer patients randomized to indwelling pleural catheter required further ipsilateral invasive pleural drainages (4.1% vs 22.5%; difference, 18.4%; 95% CI, 7.7%-29.2%). There were no significant differences in improvements in breathlessness or quality of life offered by indwelling pleural catheter or talc pleurodesis. Adverse events were seen in 22 patients in the indwelling pleural catheter group (30 events) and 13 patients in the pleurodesis group (18 events). Conclusions and Relevance: Among patients with malignant pleural effusion, treatment with an indwelling pleural catheter vs talc pleurodesis resulted in fewer hospitalization days from treatment to death, but the magnitude of the difference is of uncertain clinical importance. These findings may help inform patient choice of management for pleural effusion. Trial Registration: anzctr.org.au Identifier: ACTRN12611000567921.

Malignant pleural fluid from mesothelioma has potent biological activities.

BACKGROUND AND OBJECTIVE: Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma. METHODS: Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed. RESULTS: Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13-fold in six mesothelioma cell lines using scratch-wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm2 vs 28.0 cm2 at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed-induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs. CONCLUSION: This 'proof-of-concept' study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology.

Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters.

INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation. METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.

Histopathology of removed indwelling pleural catheters from patients with malignant pleural diseases.

BACKGROUND AND OBJECTIVE: Indwelling pleural catheters (IPC), used for management of malignant pleural effusions, are often left in situ for a long duration. This study reports for the first time the histological findings of IPCs removed from patients with underlying pleural malignancy. METHODS: Forty-one IPCs (in situ for median 126 days, interquartile range 43-226) that were removed over a 54-month period from a single centre were examined. RESULTS: Mesothelioma (n = 18) was the predominant underlying malignancy followed by breast, tubo-ovarian and lung carcinomas. The catheter tubing was fully intact macroscopically in all IPCs. There was no evidence of direct tumour invasion or cancer cell growth on the catheter surfaces in none of the 29 IPCs that were histologically examined. Malignant cells were seen within organizing fibrinous tissues in the lumen of 11 IPCs (27%). A foreign body giant cell reaction was present at the cuff site in all the 29 IPC in which the subcutaneous cuff was examined. Acute (n = 10) and/or chronic inflammatory changes were seen in the luminal contents in all 41 IPCs. CONCLUSION: Our study provides reassuring evidence that the IPC material does not support direct tumour growth or invasion even in the setting of high mesothelioma prevalence. See Editorial, page 787.

Complications of indwelling pleural catheter use and their management.

The growing utilisation of indwelling pleural catheters (IPCs) has put forward a new era in the management of recurrent symptomatic pleural effusions. IPC use is safe compared to talc pleurodesis, though complications can occur. Pleural infection affects <5% of patients, and is usually responsive to antibiotic treatment without requiring catheter removal or surgery. Pleural loculations develop over time, limiting drainage in 10% of patients, which can be improved with intrapleural fibrinolytic therapy. Catheter tract metastasis can occur with most tumours but is more common in mesothelioma. The metastases usually respond to analgaesics and/or external radiotherapy. Long-term intermittent drainage of exudative effusions or chylothorax can potentially lead to loss of nutrients, though no data exist on any clinical impact. Fibrin clots within the catheter lumen can result in blockage. Chest pain following IPC insertion is often mild, and adjustments in analgaesics and drainage practice are usually all that are required. As clinical experience with the use of IPC accumulates, the profile and natural course of complications are increasingly described. We aim to summarise the available literature on IPC-related complications and the evidence to support specific strategies.

Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions.

BACKGROUND: Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology. METHODS: We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95 days (median, range 0-735 days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-α; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model. RESULTS: Significant decreases were observed over time in pleural fluid protein by 8 g/L per 100 days (SE, 1.32; P < .0001) and pH (0.04/100 days; SE, 0.02; P = .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100 days (SE, 0.02; P = .04). MPEs from mesothelioma (n = 63) had lower pleural fluid glucose (P = .0104) at baseline and a faster rate of decline in glucose (P = .0423) when compared with non-mesothelioma effusions (n = 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100 days; SE, 0.13; P = .0046), but not of other cytokines, was observed. CONCLUSIONS: MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE.

Intrapleural Fibrinolysis for the Treatment of Indwelling Pleural Catheter-Related Symptomatic Loculations: A Multicenter Observational Study.

BACKGROUND: Indwelling pleural catheters (IPCs) are an effective option in the management of malignant pleural effusion. Up to 14% of patients with IPCs develop symptomatic pleural loculations causing ineffective fluid drainage and breathlessness. To our knowledge, this is the first study to describe intrapleural fibrinolytic therapy for IPC-related symptomatic loculations. METHODS: All patients who received intrapleural fibrinolytic therapy for symptomatic loculations between January 1, 2002, and June 30, 2014, in four established IPC centers were retrospectively included. Patient outcomes, treatment effectiveness, and adverse events were recorded. RESULTS: Sixty-six patients (mean age, 64.7 ± 14.2 years; 52% women) were included. Lung cancer (31.3%) and malignant pleural mesothelioma (20.3%) were the most common malignancies. Fibrinolytic instillation was performed in outpatient (61%) and inpatient settings. Tissue-plasminogen activator (n = 52), urokinase (n = 12), and streptokinase (n = 2) were used. The majority (69.7%) received only one fibrinolytic dose (range, one to six). Pleural fluid drainage increased in 93% of patients, and dyspnea improved in 83% following therapy. The median cumulative pleural fluid volume drained at 24 h posttreatment was 500 mL (interquartile range 300-1,034 mL). The area of opacity caused by pleural effusion on chest radiograph decreased from (mean, SD) 52% (14%) to 31% (21%) of the hemithorax (n = 13; P = .001). There were two cases of nonfatal pleural bleed (3%). CONCLUSIONS: Intrapleural fibrinolytic therapy can improve pleural fluid drainage and symptoms in selected patients with IPC and symptomatic loculation, but it carries a small risk of pleural bleeding. There is significant heterogeneity in its use currently, and further studies are needed to determine patient selection and optimal dosing regimen and to define its safety profile.