Malignant pleural effusion, current and evolving approaches for its diagnosis and management

Summary

Malignant pleural effusion is a common and debilitating complication of advanced malignant diseases. This problem seems to affect particularly those with lung and breast cancer, contributing to the poor quality of life. Approximately half of all patients with metastatic cancer develop a malignant pleural effusion at some point, which is likely to cause significant symptoms such as dyspnea and cough. Evacuation of the pleural fluid and prevention of its re-accumulation are the main goals of management. Optimal treatment is controversial and there is no universally standard approach. Intervention options range from observation in the case of asymptomatic effusions through simple thoracentesis to more invasive methods such as chemical and mechanical pleurodesis, pleur-X catheter drainage, pleuroperitoneal shunting, and pleurectomy. The best results are reported with thoracoscopy and talc insufflation, with an acceptable morbidity. Development of novel methods to control malignant pleural effusion should be a high priority in palliative care of cancer patients. This article reviews the current, as well as, novel approaches that show some promise for the future. The aim is to identify the proper approach for each individual patient.

Introduction

Malignant pleural effusion (MPE) is a common and distressing condition seen at the advanced stage of various malignant diseases. There are more than 150,000 new cases of malignant pleural effusion in the United States yearly. The majority of malignant pleural effusions have exsudative character [1]. Pleural effusion might be the first presenting sign of cancer, suggestive of recurrent or advanced disease [2]. Primary or metastatic tumors may invade the visceral pleura, affecting the normal resorptive flow of fluid from the parietal to the visceral pleura [2] or causing increased capillary leaking and increased fluid production [3]. A blockage in lymphatic system anywhere between the parietal pleura and the mediastinal lymph nodes result in accumulation of fluid in the pleural space [4]. Intrapulmonary shunt is the main underlying reason for the arterial hypoxemia associated with a large pleural effusion [5]. Lung cancer including malignant pleural mesothelioma is the most common cause of malignant pleural effusion (MPE). In women it is followed by breast cancer [6]. However, almost all forms of cancer including cancer of ovary and stomach, lymphoma, Hodgkin's and non-Hodgkin's disease can cause malignant pleural effusion [7]. In a series of 120 patients with malignant pleural effusion 40% of patients were found to have lung cancer and 26% had breast cancer [8]. In a meta-analysis including 811 patients with MPE, 23% of effusions resulted from breast cancer and 35% from lung cancer [9]. In 5–10% of malignant effusions, no primary tumor is identified [10]. The presence of MPE is suggestive of end stage disease with very short life expectancy [12]. However, it also occurs in patients with long survival, such as in breast cancer, Hodgkin's disease, or lymphoma [13]. A hematogenous spread of tumor would likely cause contralateral effusions, while ipsilateral effusions might be caused by hematogenous spread or direct invasion of tumor through the chest wall, as well as tumor recurrence on the chest wall or lymph nodes. Raju and Kardinal [14] reported in a series of 122 patients with breast cancer and pleural effusion that 83% of effusions were ipsilateral, 9% contralateral, and 6% bilateral. On the other hand, in Fentiman et al.'s [13] series 48% of effusions were ipsilateral, 42% contralateral, and 10% bilateral.

Paramalignant effusions are associated with a known malignancy. They are not the direct result of neoplastic involvement of the pleura but are still related to the primary tumor. These effusions include postobstructive parapneumonic effusion caused by tumors compressing bronci, chylothorax following obstruction of the thoracic duct, pulmonary embolism, transudative effusions secondary to postobstruction atelectasis, and effusions due to low plasma oncotic pressures secondary to cachexia. Radiation and chemotherapy with some agents such as methotrexate, procarbazine, cyclophosamide and bleomycin can also cause pleural effusions [15].

Approximately 10% of malignant pleural effusions are due to lymphoma. The incidence of MPE in lymphoma patients ranges between 5 and 33% [16]. The pathogenesis of pleural effusion in these patients is obstruction of the lymphatic drainage by enlarged mediastinal lymph nodes (in Hodgkin's disease) or by direct tumor infiltration of the parietal or visceral pleura (in non-Hodgkin's lymphoma) [17]. Non-Hodgkin's lymphoma is the most common cause of chylothorax [18].