Edward T.H. Fysh

Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score

Background Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Methods Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Results Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228–549; n=43), 130 days (47–467; n=129) and 44 days (22–77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). Conclusions The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion

BACKGROUND Patients with malignant pleural effusion (MPE) have limited prognoses. They require long-lasting symptom relief with minimal hospitalization. Indwelling pleural catheters (IPCs) and talc pleurodesis are approved treatments for MPE. Establishing the implications of IPC and talc pleurodesis on subsequent hospital stay will influence patient choice of treatment. Therefore, our objective was to compare patients with MPE treated with IPC vs pleurodesis in terms of hospital bed days (from procedure to death or end of follow-up) and safety. METHODS In this prospective, 12-month, multicenter study, patients with MPE were treated with IPC or talc pleurodesis, based on patient choice. Key end points were hospital bed days from procedure to death (total and effusion-related). Complications, including infection and protein depletion, were monitored longitudinally. RESULTS One hundred sixty patients with MPE were recruited, and 65 required definitive fluid control; 34 chose IPCs and 31 pleurodesis. Total hospital bed days (from any causes) were significantly fewer in patients with IPCs (median, 6.5 days; interquartile range [IQR] = 3.75-13.0 vs pleurodesis, mean, 18.0; IQR, 8.0-26.0; P = .002). Effusion-related hospital bed days were significantly fewer with IPCs (median, 3.0 days; IQR, 1.8-8.3 vs pleurodesis, median, 10.0 days; IQR, 6.0-18.0; P < .001). Patients with IPCs spent significantly fewer of their remaining days of life in hospital (8.0% vs 11.2%, P < .001, χ(2) = 28.25). Fewer patients with IPCs required further pleural procedures (13.5% vs 32.3% in pleurodesis group). There was no difference in rates of pleural infection (P = .68) and protein (P = .65) or albumin loss (P = .22). More patients treated with IPC reported immediate (within 7 days) improvements in quality of life and dyspnea. CONCLUSIONS Patients treated with IPCs required significantly fewer days in hospital and fewer additional pleural procedures than those who received pleurodesis. Safety profiles and symptom control were comparable.

Clinical Outcomes of Indwelling Pleural Catheter-Related Pleural Infections: An International Multicenter Study

BACKGROUND Indwelling pleural catheters (IPCs) offer effective control of malignant pleural effusions (MPEs). IPC-related infection is uncommon but remains a major concern. Individual IPC centers see few infections, and previous reports lack sufficient numbers and detail. This study combined the experience of 11 centers from North America, Europe, and Australia to describe the incidence, microbiology, management, and clinical outcomes of IPC-related pleural infection. METHODS This was a multicenter retrospective review of 1,021 patients with IPCs. All had confirmed MPE. RESULTS Only 50 patients (4.9%) developed an IPC-related pleural infection; most (94%) were successfully controlled with antibiotics (62% IV). One death (2%) directly resulted from the infection, whereas two patients (4%) had ongoing infectious symptoms when they died of cancer progression. Staphylococcus aureus was the causative organism in 48% of cases. Infections from gram-negative organisms were associated with an increased need for continuous antibiotics or death (60% vs 15% in gram-positive and 25% mixed infections, P = .02). The infections in the majority (54%) of cases were managed successfully without removing the IPC. Postinfection pleurodesis developed in 31 patients (62%), especially those infected with staphylococci (79% vs 45% with nonstaphylococcal infections, P = .04). CONCLUSIONS The incidence of IPC-related pleural infection was low. The overall mortality risk from pleural infection in patients treated with IPC was only 0.29%. Antibiotics should cover S aureus and gram-negative organisms until microbiology is confirmed. Postinfection pleurodesis is common and often allows removal of IPC. Heterogeneity in management is common, and future studies to define the optimal treatment strategies are needed.

Risk reduction in pleural procedures: sonography, simulation and supervision.

Purpose of review Complications from pleural drainage procedures are common, but their incidence is often underrecognized. Significant morbidity and mortality can arise, particularly as a result of poor procedural technique, lack of training and inadequate supervision. This review discusses safety considerations of common pleural procedures, methods for risk minimization and training issues. Recent findings Recent data have identified deaths and significant adverse events associated with pleural drainage procedures. Evidence suggests that significant risk reduction might be achieved by restricting the number of physicians authorized to perform a pleural aspiration to a smaller expert group who have had specific training and regularly perform the procedure. Pleural ultrasound has been shown to increase the accuracy of fluid localization and decrease the risk of postprocedure pneumothorax. Summary Strategies to improve physician training, reduce unnecessary pleural procedures and improve site selection (using pleural ultrasound) may reduce complication rates. Consequently, several international authorities have recently published updated guidelines and educational packages aimed at improving the safety of pleural intervention. Pleural ultrasound has the potential to significantly decrease adverse event rates, but requires specific training and has several possible pitfalls.

Catheter Tract Metastasis Associated With Indwelling Pleural Catheters

BACKGROUND Indwelling pleural catheters (IPCs) are commonly used to manage malignant effusions. Tumor spread along the catheter tract remains a clinical concern for which limited data exist. We report the largest series of IPC-related catheter tract metastases (CTMs) to date, to our knowledge. METHODS This is a single-center, retrospective review of IPCs inserted over a 44-month period. CTM was defined as a new, solid chest wall lesion over the IPC insertion site and/or the tunneled subcutaneous tract that was clinically compatible with a malignant tract metastasis. RESULTS One hundred ten IPCs were placed in 107 patients (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM often developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases had chest wall pain, and six received palliative radiotherapy to the CTM. Radiotherapy was well tolerated, with no major complications and causing no damage to the catheters. Longer interval after IPC insertion was the sole significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P = .0098) in the multivariate analyses. CONCLUSIONS IPC-related CTM is uncommon but can complicate both mesothelioma and metastatic carcinomas. The duration of interval after IPC insertion is the key risk factor identified for development of CTM. Symptoms are generally mild and respond well to radiotherapy, which can be administered safely without removal of the catheter.

Indwelling pleural catheter: Changing the paradigm of malignant effusion management

Malignant pleural effusions (MPEs) affect as many as 150,000 patients with cancer in the United States1 and 100,000 patients with lung cancer2 in Europe each year. Inpatient care alone for MPE costs US

Optimal chest drain size: the rise of the small-bore pleural catheter.

6 million per million population in Australia annually (data, the Western Australia Health Dept). The exciting advent of indwelling tunneled pleural catheters (IPCs) has critically challenged conventional approaches to MPE management, especially pleurodesis.3 IPCs offer ambulatory fluid drainage as the primary symptomatic therapy, thus prompting clinicians to redefine the goalposts of MPE care. Talc pleurodesis has been the mainstay of MPE management for decades, but its efficacy and safety have recently come under scrutiny.4 In the largest randomized trial in pleural disease (n 486),5 talc (poudrage or slurry) pleurodesis had a suboptimal success rate: only 75% of MPE patients at 1 month and 50% by 6 months had adequate fluid control. Adding the fact that many patients are unsuitable for pleurodesis (e.g., with trapped lungs), talc pleurodesis benefits only a subset of all MPE patients. Randomized trials have also shown that talc induces lung and systemic inflammation6 and killed 2.3% of patients in a Cancer and Leukemia Group B study through talc-induced respiratory failure.5 Although this acute lung injury can be avoided by using large particle size talc preparations,7 such products are not readily available in many countries, including the United States. These data have provoked debates and compelled the pleural community to revisit the principles of MPE care. The fundamental aim in MPE management is to improve dyspnea and quality of life, with minimal intervention and hospitalization. The timely introduction of IPCs which allow fluid evacuation from a single minimally invasive procedure serves exactly this purpose and explains its rapid rise in popularity (Suzuki et al estimated that 39,000 units sold in the United States per year8). Suzuki et al.8 in this issue of Journal of Thoracic Oncology reported the largest series of IPC (n 418) experience, providing corroborative evidence that IPCs are safe.9–12 A recent summary of all published reports on IPC complications revealed that most complaints were minor (e.g., mild pain after insertion).13 A systematic review including 1370 patients has confirmed that serious complications, e.g., infection were uncommon ( 3%).14 Other series have addressed specific concerns of IPC use: demonstrating safety records in patients undergoing chemotherapy15 and local radiotherapy16 with IPC in situ, and no significant protein loss results from regular drainage.17 IPC represents a new therapeutic ideology (not “yet another catheter”), and clinicians are still adapting to the specific changes needed to realize the full potential of this device. Suzuki et al.8 described a representative single-center review of IPC use, highlighting important contemporary issues of IPC management. First, the exact place of IPC in the paradigm of MPE management has yet to be defined. IPC is generally accepted for treatment of MPE patients in whom pleurodesis has failed or is contraindicated (especially trapped lungs).18 Many specialist centers now offer

Current controversies in the management of malignant pleural effusions

Drainage of the pleural space is not a modern concept, but the optimal size of chest drains to use remains debated. Conventional teaching advocates blunt dissection and large-bore tubes; but in recent years, small-bore catheters have gained popularity. In the absence of high-quality randomized data, this review summarizes the available literature on the choice of chest drains. The objective data supporting the use of large-bore tubes is scarce in most pleural diseases. Increasing evidence shows that small-bore catheters induce less pain and are of comparable efficacy to large-bore tubes, including in the management of pleural infection, malignant effusion, and pneumothoraces. The onus now is on those who favor large tubes to produce clinical data to justify the more invasive approach.

Pleurodesis outcome in malignant pleural mesothelioma

Malignant pleural effusion (MPE) can complicate most malignancies and is a common clinical problem presenting to respiratory and cancer care physicians. Despite its frequent occurrence, current knowledge of MPE remains limited and controversy surrounds almost every aspect in its diagnosis and management. A lack of robust data has led to significant practice variations worldwide, inefficiencies in healthcare provision, and threats to patient safety. Recent studies have highlighted evolving concepts in MPE care that challenge traditional beliefs. Advancing laboratory techniques have improved the diagnostic yield from pleural fluid cytology, minimizing the need for invasive tissue biopsies, even in many cases of mesothelioma. Imaging-guided biopsy is comparable to thoracoscopy in suitable patients, if cytological examination was noncontributory. Cumulating evidence for the benefits of indwelling pleural catheters (IPCs) has led some centers to adopt this approach as first-line definitive management for MPE over conventional talc pleurodesis. The optimal technique of talc pleurodesis is still debated despite its use for many decades. Strategies combining pleurodesis and IPC are being studied. MPE consists of a heterogenous group of diseases and careful phenotyping of malignant effusion patients can provide important clinical information that will advance the field and allow better stratification of patients and planning of therapy accordingly. This review addresses the controversies in MPE diagnosis and management and exposes the deficits in knowledge of MPE that should be the focus of future research.

Matching positive end-expiratory pressure to intra-abdominal pressure improves oxygenation in a porcine sick lung model of intra-abdominal hypertension

Few data exist on the pleurodesis outcome in patients with malignant pleural mesothelioma (MPM). A retrospective review of the Western Australian Mesothelioma Registry over 5 years revealed 390 evaluable patients. Only a subset of patients (42.3%) underwent pleurodesis, surgically (n=78) or by bedside instillation of sclerosants (n=87). Surgical pleurodesis showed no advantages over bedside pleurodesis in efficacy (32% vs 31% failures requiring further drainage, p=0.98), patient survival (p=0.52) or total time spent in hospital from procedure till death (p=0.36). No clinical, biochemical or radiographic parameters tested adequately predict pleurodesis outcome.