Management of Malignant Pleural Effusions and Malignancy-Related Ascites

Malignant Pleural Effusions

Background

Pleural effusion is the accumulation of fluid within the pleural space. Malignant pleural effusion (MPE) is one resulting directly from tumor in the pleural space or elsewhere in the thoracic cavity. When tumor directly invades the pleura itself, this results in increased permeability of the pleural vasculature and capillary beds. Additionally, if tumor metastasizes to or invades lymph nodes or the lymphatics, it may cause decreased fluid resorption. Both ultimately result in excess pleural fluid.[1] The diagnosis of MPE is definitively made by either cytological analysis of the pleural fluid or direct biopsy of a pleural lesion.

Lung and breast cancers are the most common causes of MPE accounting for 50 to 65% of cases. However, other malignancies and tumor of the pleura itself (mesothelioma) are also involved.[2] [3] MPEs cause more than 125,000 hospital admissions per year in the United States and are estimated to incur over $5 billion per year in inpatient charges.[4]

The development of MPE often represents advanced or incurable metastatic disease with the average survival after diagnosis estimated between 3 and 12 months.[5] [6] [7] This makes the goal of management primarily palliative and targeted toward symptomatic relief.

Treatment Options

Multiple treatment options are available with the goals of fluid removal and/or prevention of fluid reaccumulation. These include repeat thoracentesis, chemical pleurodesis through a chest tube or thoracoscopy, indwelling pleural catheter (IPC) placement, or less commonly pleuroperitoneal shunt.[8] [9] The two most widely used and more definitive methods of treatment are chemical pleurodesis and IPC placement, which will be discussed in more detail later. One caveat to consider is the presence of “trapped” or “untrapped” lung. Trapped lung occurs when the lung parenchyma cannot reexpand even after fluid is removed. This is most often caused by tumor or loculations in the pleura itself or endobronchial obstruction. In some cases, MPEs caused by lymphoma, small cell lung cancer, and germ cell tumors may respond to systemic therapy without the need for direct therapy.

Pleurodesis is a procedure that induces inflammation and scarring within the pleural space in hopes of eliminating the potential space for fluid to accumulate. Chemical pleurodesis accomplishes this by using a chemical irritant. Talc is most commonly used with tetracycline, doxycycline, bleomycin, and silver nitrate and silver nitrate being less commonly used alternatives. A systematic review published in the Cochrane Database suggests using talc can achieve pleurodesis in more than 90% of patients.[10] One disadvantage of this procedure is that a chest tube is typically required to remain in place 4 to 5 days to keep the pleural space collapsed.[10] [11] As mentioned, pleurodesis offers a potential cure by eliminating the pleural space. Interestingly, pleurodesis has been found to occur idiopathically (“auto pleurodesis”) in patients with IPCs after ongoing repeated drainage, although it occurs more rapidly after direct talc instillation.[12] [13]

A commonly used IPC is the PleurX Catheter (CareFusion, Illinois). The catheter consists of a fenestrated silicone catheter with a one-way valve mechanism and polyester cuff that can be attached to wall suction, a vacuum bottle, or capped when not in use ([Fig. 1]). It is inserted percutaneously into the pleural space through a subcutaneous tunnel ([Fig. 2]). This is easily performed in an outpatient setting under ultrasound guidance with or without fluoroscopy and often requires only local anesthetic with minimal sedation.[14] [15] The risk of complications is low and includes bleeding, cellulitis, catheter blockage, catheter fracture, infection within the pleural space, and reexpansion pulmonary edema (RPE).

Fig. 1 (a) PleurX Catheter kit supplied by Becton Dickinson, New Jersey. (b) Fenestrated catheter with cuff and one-way valve, and disposable vacuum bottle.

Fig. 2 Malignant pleural effusion in an 82-year-old woman with breast cancer. (a) Ultrasound demonstrating left pleural effusion. (b) Spot radiograph after PleurX Catheter placement (arrow).

IPCs require repeat drainage, often weekly, every other day, or even daily depending on the rate of reaccumulation and should be guided by patient symptoms. This can be performed at home by home care nurses, family members, and even patients themselves.

RPE is a known but rare complication following large volume thoracentesis. One to 1.5 L of fluid can usually be safely removed, but at levels greater than that the patient should be closely monitored for chest pain, which can be a sign of RPE. Intermittent cough is not abnormal during drainage and should not be confused for symptoms of RPE. Persistent cough, chest discomfort, frothy sputum, and dyspnea are more suggestive findings of RPE and classic signs are tachypnea, tachycardia, and unilateral crackles on the affected side. If this occurs, drainage should be stopped. Treatment is primarily supportive and often only oxygen supplementation is required. However, in severe cases, intubation and mechanical ventilation may be necessary. In addition to the signs and symptoms discussed earlier, classical imaging shows unilateral pulmonary edema.

Evidence Comparing the Options

Numerous studies have attempted to compare chemical pleurodesis and IPC placement in hopes of distinguishing a superior method, as both have become recognized as viable treatment options. The decision often depends on multiple factors, including life expectancy, performance status, local expertise, underlying disease, anatomy, and patient preference.

The TIME2 trial compared patients undergoing drainage and talc pleurodesis to patients who underwent IPC placement and found no statistical difference between the groups in symptomatic relief, with both groups reporting clinically significant improvement in dyspnea.[16] Likewise, the AMPLE study randomized patients to talc slurry pleurodesis or IPC, and both demonstrated clinically significant improvement in dyspnea after only 1 day and throughout an entire 12-month follow-up period.[17]

However, as an outpatient procedure, placement of IPCs has been shown to result in significantly fewer inpatient hospital days. Thus, the cost to the patient and overall health system compared with chemical pleurodesis is reduced. Lastly, IPC has equal or lower perioperative morbidity compared with chemical pleurodesis.[18] [19] [20] [21] One advantage of chemical pleurodesis is that it results in permanent obliteration of the pleural space. Although auto pleurodesis has been observed in patients undergoing repeat drainage through IPCs, it takes longer to achieve.[12] [13]

Guidelines and Recommendations

Guidelines for the management of MPE were first published in 2000 by the American Thoracic Society and in 2010 by the British Thoracic Society.[6] [22] In 2018, the American Thoracic Society collaborated with the Society of Thoracic Surgeons and the Society of Thoracic Radiology to publish new guidelines in an attempt to provide evidence-based recommendations.[23] [Fig. 3] outlines the treatment algorithm proposed for managing MPEs, and [Table 1] lists the consensus recommendations.

Table 1 Official ATS/STS/STR clinical practice guideline recommendations for management of malignant pleural effusions

Ultrasound should be used to guide pleural interventions

Pleural interventions should not be performed in asymptomatic patients with MPE

IPC or chemical pleurodesis can be utilized in symptomatic patients with suspected expandable lung

Initial large-volume thoracentesis should be performed to assess symptomatic response and lung expansion

Talc poudrage or talc slurry can be used for chemical pleurodesis

IPC should be utilized rather than chemical pleurodesis in patients with nonexpandable lung or failed pleurodesis

IPC-associated infections should be managed with antibiotics and not removal of the catheter

Abbreviations: ATS, American Thoracic Society; IPC, indwelling pleural catheter; MPE, malignant pleural effusion; STR, Society of Thoracic Radiology; STS, Society of Thoracic Surgeons.

Fig. 3 Management algorithm guiding treatment of MPEs. IPC, indwelling pleural catheter; MPE, malignant pleural effusion. (Reprinted with permission of the American Thoracic Society. Copyright © 2019 American Thoracic Society. Feller-Kopman DJ, Reddy CB, DeCamp MM, et al; Am J Respir Crit Care Med 2018;198:839–849. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.)

Disclosures

The authors have no conflict of interest.

Publication History

Article published online:
01 October 2020

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