Malignant pleural effusion (MPE) is a pleural effusion caused by a malignant tumor originating in the pleura or a malignant tumor metastasizing to the pleura from other sites. At present, there is a lack of epidemiological research data on MPE at home and abroad. According to statistics, the annual number of patients with MPE in the United States is more than 150,000.
Almost all malignant tumors can develop MPE. lung cancer is the most common cause, accounting for about 1/3 of MPE, followed by breast cancer, lymphoma is also an important cause of MPE, while ovarian cancer and gastrointestinal cancer are also common. 5-10% of MPE cannot find the primary tumor lesion.
The presence of MPE indicates that the tumor has spread or progressed to an advanced stage, and the patient’s life expectancy is significantly reduced; the median survival for MPE is 3-12 months from the time the diagnosis is established, depending on the type and stage of the primary tumor. It has been shown that patients with MPE due to lung cancer have the shortest survival, those with MPE due to ovarian cancer have the longest survival, and those with MPE where the primary site cannot be found have an intermediate survival.
1. Clinical manifestations combined with adjuvant examinations to clarify the diagnosis
First of all, the “gold standard” for the diagnosis of MPE is to find malignant cells in the pleural effusion or to observe the pathological changes of malignant tumor in the pleural biopsy tissue.
Clinical manifestations: Clinical manifestations can be an important clue for the diagnosis of MPE. Most patients with MPE have clinical symptoms, but about 25% of patients may also be asymptomatic and have MPE detected incidentally by physical examination or X-ray chest radiography. dyspnea is the most common symptom.
Imaging: Most patients with MPE have moderate to large pleural effusions, usually 500-2000 ml, on chest X-ray, with about 10% of patients showing large pleural effusions (more than half of one side of the chest) and about 15% of patients with pleural effusions < 500 ml. CT helps to detect small amounts of MPE in patients with malignancy, helps to determine whether MPE is associated with mediastinal lymph node metastases, and allows assessment of underlying parenchymal lung lesions. CT is useful in detecting small amounts of MPE in patients with malignancy.
Magnetic resonance imaging (MRI) has limited diagnostic value for MPE, but MRI may be useful in assessing the extent of tumor invasion of the mediastinum or chest wall. Preliminary studies have shown that fluorodeoxyglucose positron emission CT scan (PET-CT) has good predictive value for MPE, but more evidence-based medical evidence is needed to support this.
Diagnostic thoracentesis: There are no absolute contraindications to performing thoracentesis, and relative contraindications include low pleural fluid volume (unilateral recumbent pleural fluid plane <1 cm from the chest wall), bleeding tendency, and being on anticoagulation and mechanical ventilation. The vast majority of MPEs are exudate, with a predominantly lymphocytic cellular classification; however, a very small number are leaky.
Pleural fluid cytology is the easiest way to diagnose MPE, and its diagnostic rate fluctuates from 62% to 90% depending on the type of primary tumor and its degree of differentiation. Multiple cytologic examinations may increase the positive rate. Certain tumor markers such as carcinoembryonic antigen, cytokeratin fragment 21-1, and glycoantigens (e.g., CA125, CA15-3, CA19-9, etc.) are helpful in the diagnosis of MPE. Combination of multiple tumor markers can improve the diagnostic rate.
Closed pleural biopsy: The sensitivity of closed pleural biopsy for MPE diagnosis is lower than cytology, and its diagnostic rate is 40-75%. If CT reveals pleural abnormalities (e.g., mesothelioma), a percutaneous closed pleural biopsy guided by ultrasound or CT is recommended.
Endoscopic thoracoscopy: Endoscopic thoracoscopy is mainly used for the differential diagnosis of unexplained exudative pleural effusion; it can also be used to treat MPE by endoscopic spraying of talcum powder for pleural fixation. endoscopic thoracoscopy is better than closed pleural biopsy for earlier diagnosis, histological classification and clinical staging of pleural malignancies because it can obtain larger and more representative lesions.
Surgical biopsy: Surgical biopsy can be performed in two ways: thoracoscopic or open chest. Surgical thoracoscopic biopsy usually requires general anesthesia and double-lumen tracheal intubation. Since the lungs are ventilated unilaterally during surgery, the visualization range of surgical thoracoscopy is wider than that of medical thoracoscopy, and both diagnostic and therapeutic operations can be performed simultaneously. The patient’s inability to tolerate single-lung ventilation is a contraindication to surgical thoracoscopic biopsy, and open-chest biopsy should be considered at this time.
Bronchoscopy: When intrapulmonary occupancy, hemorrhage, pulmonary insufficiency, bronchial mucosal lesions or large pleural effusion without mediastinal shift are suspected, then bronchoscopy should be performed.
2.Multiple treatment means should be chosen reasonably
Once the diagnosis of MPE is clear, palliative treatment should be considered as early as possible. A comprehensive assessment of the patient’s symptoms, general condition and expected survival time should be conducted before formulating a treatment plan. The main goal of treatment is to alleviate the symptoms of dyspnea.
Clinical observation: Clinical observation is defined as no therapeutic intervention for MPE itself and is recommended for patients with MPE whose primary tumor is well defined but asymptomatic. For patients with symptomatic MPE, consultation with a respiratory specialist is required to decide whether to take observation alone.
Therapeutic thoracentesis: The recurrence rate of MPE within 1 month after thoracentesis drainage is high and is therefore not recommended for patients with a life expectancy of more than 1 month. Repeated therapeutic thoracentesis may temporarily relieve dyspnea and allow some patients with short survival expectancy and poor physical status to avoid hospitalization, and is indicated for frail and end-stage patients.
Intercostal tube drainage and pleural fixation: Repeated thoracentesis is generally not recommended for patients with very short life expectancy, and a small-diameter drainage tube can be placed in the rib cage to drain pleural fluid to relieve dyspnea. If there is no significant atrophy of the lungs, pleural fixation should be performed after intercostal tube drainage to prevent recurrence of MPE. Patients with intercostal drainage alone without pleural fixation have a high recurrence rate of MPE, so intercostal drainage alone should be avoided.
Intercostal drainage tube size: Recent randomized controlled studies comparing the efficacy of large- and small-bore (10-14 F) drains for MPE control have found similar results. The success rate of injecting commonly used sclerosing agents via small-bore thoracentesis drains is comparable to that of large-bore drains with minimal discomfort. Ultrasound-guided placement of small-bore intercostal drains is recommended for drainage of pleural effusion and pleural fixation.
Analgesia and preoperative medication: Intrathoracic injection of sclerosing agents can cause pain, and local anesthetic injection through the drainage tube prior to pleural fixation can reduce discomfort. Lidocaine is the most commonly used local anesthetic for thoracic injection, which has a rapid onset of action and should be administered immediately before the injection of sclerosing agent. The usual dose of lidocaine is 3 mg/kg, with a maximum dose of 250 mg at a time.
Choice of sclerosing agent: Several studies have shown that talcum powder is the most effective sclerosing agent for pleural fixation. Homogeneous talc reduces the risk of hypoxemia due to pleural fixation and should be preferred over non-homogeneous talc. Injections of talc homogenate or sprays of talc powder have comparable efficacy in controlling MPE, typically at 2.5-10.0 g. Bleomycin is another alternative sclerosing agent with moderate efficacy, typically at 45-60 mg per dose. other alternative sclerosing agents include short rods, doxycycline, and tetracycline, with varying efficacy.
Clamping and removal of intercostal drains: Intercostal drains can be clamped briefly (1 h) after intrathoracic injection of sclerosing agents to prevent rapid outflow of drugs from the chest cavity. Since no study has confirmed that prolonged drainage time is more effective, and considering the discomfort caused by prolonged drainage time, it is recommended that the drainage tube be removed within 24-48 h of sclerosing agent injection, provided that chest X-ray confirms complete lung reopening and MPE drainage <150 ml/d. If the indication for drainage is not met, the drainage time should be extended appropriately.
Pleural fixation failure: Pulmonary atrophy is the most common cause of pleural fixation failure. There is no reliable method to predict the failure of pleural fixation, and there are no studies to suggest what the next step should be after pleural fixation failure. Continued drainage of the pleural effusion is recommended, and the decision to repeat pleural fixation or intercostal drainage is based on pulmonary resuscitation.
Metastatic tumor cell implantation at intercostal drainage access: Prophylactic radiation therapy should be given at the site of large-bore chest drain placement, at the site of thoracoscopic manipulation, and at the surgical incision in patients with suspected or proven malignant pleural askew tumors; there is no evidence to support the need for such treatment at the site of thoracentesis or pleural biopsy.
Outpatient long-term indwelling chest drains: Indwelling chest drains are an effective way to control recurrent MPE, especially in patients with pulmonary atrophy or those who wish to shorten their hospital stay. The catheter is connected to a vacuum drainage bottle for drainage at intervals to promote pulmonary resuscitation and thoracic atresia, and most drains can be removed after a short stay.
Intrathoracic injection of fibrinolytic agents: For patients with multiatrial MPE and poor drainage effect alone, intrathoracic injection of fibrinolytic agents such as urokinase and streptokinase is recommended to reduce pleural adhesions and improve MPE drainage to relieve dyspnea symptoms.
Transthoracoscopic treatment: For patients in good physical condition, it is recommended for the diagnosis of suspected MPE and also for the drainage of pleural effusion and pleural fixation in patients with confirmed MPE.
Other treatments.
Systemic therapy: MPE due to pleural metastases from certain tumors such as small cell lung cancer may respond better to chemotherapy, and systemic therapy in combination with thoracentesis or pleural fixation may be considered if there are no contraindications.
Surgical treatment: Due to insufficient evidence-based medical evidence, pleurodesis is not recommended to replace pleural fixation or indwelling thoracic catheter for recurrent pleural effusion or pulmonary atrophy at this time.
Intrathoracic treatment: There is not enough evidence-based medical evidence to support intrathoracic treatment.