Malignant pleural effusion (MPE) refers to pleural effusion caused by malignant tumors originating from the pleura or malignant tumors metastasizing to the pleura from other sites. There is a lack of epidemiological investigation and research data of MPE at home and abroad. According to statistics, the number of patients with MPE is more than 150,000 in the United States every year.
MPE can occur in almost all malignant tumors; 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, and MPE is also common in ovarian cancer and gastrointestinal cancer. 5-10% of MPE cannot be found in the primary tumor lesion.
The presence of MPE indicates tumor dissemination or progression to advanced stages, and patients’ life expectancy will be significantly reduced. 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 a survival between the two.
1. Clinical manifestations combined with adjuvant examinations to clarify the diagnosis
First of all, the “gold standard” to determine the diagnosis of MPE is to find malignant cells in the pleural effusion cell precipitation 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 examination. dyspnea is the most common symptom.
Imaging: Most patients with MPE can be observed to have a medium to large amount of pleural effusion on chest X-ray, usually 500-2000 ml, with about 10% of patients showing large pleural effusion (pleural effusion accounting for more than half of one side of the chest cavity) and about 15% of patients with pleural effusion <500 ml. CT helps to detect a small amount of MPE in patients with malignancy and helps to determine whether MPE with mediastinal lymph node metastasis, and allows assessment of underlying parenchymal lung lesions.
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 a low volume of pleural fluid (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 simplest method to diagnose MPE, and its diagnostic rate is related to the type of primary tumor and its degree of differentiation, fluctuating from 62% to 90%. 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.) contribute to the diagnosis of MPE. Combined testing of multiple tumor markers can improve their diagnostic rate.
Closed pleural biopsy: The sensitivity of closed pleural biopsy for the diagnosis of MPE is lower than cytology, and its diagnostic rate is 40%-75%. If pleural abnormalities (e.g., mesothelioma) are found on CT, percutaneous closed pleural biopsy under ultrasound or CT guidance is recommended.
Endoscopic thoracoscopy: Endoscopic thoracoscopy is mainly used for the differential diagnosis of unexplained exudative pleural effusion; pleural fixation can also be performed through endoscopic thoracoscopic spraying of talcum powder for the treatment of MPE; because endoscopic thoracoscopy can obtain larger and more representative lesion tissues, it is more favorable than closed pleural biopsy for earlier diagnosis, histological classification and clinical staging of pleural malignancies.
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 made before the treatment plan is formulated. The main goal of treatment is to alleviate the symptoms of respiratory distress.
Clinical observation: Clinical observation means 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, a respiratory specialist needs to be consulted to decide whether to take observation alone.
Therapeutic thoracentesis: The recurrence rate of MPE within 1 month after thoracentesis drainage is high, therefore it is 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 the lungs are not significantly atrophied, pleural fixation should be performed after intercostal tube drainage to prevent recurrence of MPE. Patients with intercostal tube drainage alone without pleural fixation have a high recurrence rate of MPE, so intercostal tube drainage alone should be avoided.
Intercostal drainage tube caliber: Recent randomized controlled studies comparing the efficacy of large- and small-bore (10-14F) 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 common 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 compared to non-homogeneous talc and should be preferred. Injection of talc homogenate or spraying of talc powder to control MPE has comparable efficacy, typically 2.5-10.0 g per dose. bleomycin is another alternative sclerosing agent with moderate efficacy, typically 45-60 mg per dose. other alternative sclerosing agents include short rods, doxycycline, and tetracycline with variable efficacy.
Clamping and removal of intercostal drains: Intercostal drains can be clamped briefly (1h) after intrathoracic injection of sclerosing agents to prevent rapid outflow of drugs from the chest cavity. Since there is no study to confirm that prolonging the drainage time is better, and considering that prolonging the drainage time brings discomfort to the patient, it is recommended to remove the drainage tube within 24-48 h after injection of sclerosing agent.
The drainage tube should be removed within 24-48 h, provided that the chest X-ray confirms complete lung reopening and MPE drainage is <150 ml/d. If the indication for drainage is not met, the drainage time should be extended appropriately.
Failure of pleural fixation: Pulmonary atrophy is the most important cause of failure of pleural fixation. 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 the failure of pleural fixation. 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. Connecting the catheter to a vacuum drainage bottle for drainage at regular intervals can 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 recommended for the drainage of pleural effusion and pleural fixation in patients with confirmed MPE.
3.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 can be considered if there is no contraindication, along with combined thoracentesis or pleural fixation.
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.