Malignant Pleural, Peritoneal, and Pericardial Effusions and Meningeal Infiltrates
Rekha T. Chaudhary
Malignant pleural, peritoneal, and pericardial effusions and malignant meningeal infiltrates are uncommon early in the course of the malignancy. They occur more frequently with disseminated disease and often herald a poor prognosis. Although pleural and peritoneal effusions may initially have little adverse effect on quality of life, when progressive, they can result in incapacitating disability and death. Effusions can denote a poor prognosis; for example, the median survival after a diagnosis of a malignant pleural effusion is 4 months. It is therefore necessary for the clinician to have a high index of suspicion for these problems and to be prepared to take appropriate action and deliver palliative treatment promptly.
I. PLEURAL EFFUSIONS
A. Causes
Malignant pleural effusions arise in association with malignant cells lining the pleura, exuded into the pleural space, or blocking veins or
lymphatics. The most common malignancy associated with pleural effusions in women is carcinoma of the breast; in men, it is carcinoma of the lung. Other causes of malignant pleural effusions include lymphoma, mesothelioma, and carcinomas of the ovary, gastrointestinal tract, urinary tract, and uterus. Malignancy is not the only cause of effusions, even in patients with known neoplastic disease; therefore, it is important to attempt to exclude other possible causes such as congestive heart failure, infection, and pulmonary infarction.
B. Diagnosis
1. Clinical diagnosis. Effusions may be asymptomatic or may be suspected because of respiratory symptoms such as shortness of breath with exertion or at rest, orthopnea, paroxysmal nocturnal dyspnea, or occasionally chest pressure or cough. The patient may feel more comfortable when lying on one side when the effusion is unilateral. On physical examination, dullness to percussion, decreased tactile fremitus, diminished breath sounds, and egophony are typical signs over the area of the effusion.
2. A chest radiograph should be obtained to confirm the clinical impression. If fluid appears to be present, a lateral decubitus film must be obtained to help estimate the volume of the effusion and how free it is within the pleural space.
3. Diagnostic thoracentesis should be performed. Ultrasonographic guidance is helpful if loculation is present. Fluid should be obtained for bacterial, acid-fast, and fungal cultures, for cytologic examination, and for determining protein concentration (greater than 3 g/dL in most exudates), lactate dehydrogenase (LDH) level, specific gravity, and cell count. The cytologic examination is important, because if the results are positive, as in 50% to 70% of patients with malignant effusion, the diagnosis is established. Other parameters of the pleural fluid that may be helpful in establishing that the fluid is an exudate and not a transudate include a specific gravity of more than 1.015, protein concentration that is more than 0.5 times the serum protein concentration, LDH level more than 0.6 times the serum LDH level, and low glucose level. A cytologic examination of fluid from a newly discovered pleural effusion is wise, regardless of whether the patient is known to have malignancy, because for nearly half of all malignant effusions, this finding is the first sign of malignancy. Analyzing pleural fluid for carcinoembryonic antigen (CEA) may be helpful in some patients. Levels higher than 20 ng/mL are suggestive of adenocarcinoma, although they do not substitute for a tissue diagnosis in patients who have no history of malignancy. CEA elevations may be seen in adenocarcinomas from various primary sites including the breast, lung, and gastrointestinal tract. Elevated levels between 10 and 20 ng/mL
may reflect malignancy or benign disorders such as pulmonary infection. The role of assessing other tumor markers on a routine basis has not been established. Likewise, the utility of monoclonal antibodies and gene rearrangement studies in patients with lymphomas to distinguish reactive mesothelial or lymphocytic cells from malignant cells has yet to be determined. The routine use of a “panel of tumor markers” is costly, time-consuming, and not recommended.
4. Pleural biopsy may be helpful in establishing the diagnosis in up to 20% of patients for whom the pleural fluid cytology results are negative.
5. Thoracotomy or pleuroscopy with direct biopsy may be done in patients who have negative cytology and pleural biopsy results but in whom there is still high suspicion of malignancy.
C. Treatment
As malignant pleural effusions are generally a sign of systemic rather than localized disease, the best therapy is treatment that effectively treats the malignancy systemically. Unfortunately, effective systemic treatment is often not possible, particularly when the malignancy is commonly refractory to systemic treatment (e.g., in non-small-cell carcinoma of the lung) or in patients who have previously been heavily treated and in whom systemic therapy is no longer effective. In these circumstances, locoregional therapy is required for palliation of the patient’s symptoms.
1. Drainage. Many malignant pleural effusions recur within 1 to 3 days after simple thoracentesis; about 97% recur within 1 month. Chest tube drainage (closed tube thoracotomy) allows the pleural surfaces to oppose each other and, if maintained for several days, may result in obliteration of the space and improvement in the effusion for several weeks to months. It does not appear to be as effective when used alone as when a cytotoxic or sclerosing agent is added, and therefore, one of these agents is commonly instilled into the space while the chest tube is in place. Repeated thoracentesis is an option in patients who reaccumulate slowly (greater than 1 month).
2. Cytotoxic and sclerosing agents or pleurodesis. The most widely used agents for intrapleural administration are bleomycin, doxycycline, and talc. Other agents, including fluorouracil, interferon-α, and methylprednisolone acetate, have been less commonly used. Randomized studies have suggested that bleomycin may be more effective than doxycycline (in part because doxycycline sometimes requires multiple dose administrations) and that talc is either equal to or slightly better than bleomycin in terms of recurrence. The agents vary in toxicity, ease of administration, and cost. Additionally, institutional experience often determines the agent utilized. Nevertheless, for optimal
effectiveness, drainage of pleural fluid as completely as possible is required before instillation.
a. Method of administration. The drug to be used is diluted in 50 to 100 mL of saline and instilled through the thoracostomy tube into the chest cavity after the effusion has been drained for at least 24 hours and the rate of collection is less than 100 mL/24 h. Throughout the procedure, care must be taken to avoid any air leak. The thoracostomy tube is clamped, and the patient is successively repositioned on his or her front, back, and sides for 15-minute periods during the next 2 to 6 hours. The tube is then reconnected to gravity drainage or suction for at least 18 hours to ensure that the pleural surfaces remain opposed and to prevent the rapid accumulation of any fluid in reaction to the instillation. Some clinicians repeat the instillation daily for a total of 2 to 3 days. For most of the agents, this has no proven benefit. Exceptions include methylprednisolone acetate and doxycycline, which appear to be more effective with additional doses. If the drainage is less than 40 to 50 mL over the previous 12 hours, the tube may be removed and a chest radiograph obtained to be certain that pneumothorax has not occurred during removal of the tube. If the thoracostomy tube continues to drain more than 100 mL/24 h after the last instillation, it may be necessary to leave it in place for an additional 48 to 72 hours to ensure that a maximum amount of adhesion between the pleural surfaces has taken place. Because the use of sclerotic agents can be painful, it is prudent for the clinician to consider the use of scheduled narcotic analgesia, particularly during the initial 24 hours.
b. Recommended agents. Efficacy, side effects, cost, and institutional (operator) experience must be considered when choosing a sclerosing agent. Bleomycin, in one prospective study, was shown to be more effective than tetracycline. It is also more expensive per dose than the other agents. Talc is the least expensive, but this must be balanced against the costs of related procedures, including thoracoscopy and anesthesia. Talc is probably superior to bleomycin in terms of recurrence rate of effusions at 90 days and later.
(1) Bleomycin 1 mg/kg or 40 mg/m2 has relatively little myelosuppressive effect and is highly effective.
(2) Talc 5 g is given typically as a powder (poudrage). It is highly effective but requires thoracoscopy and general anesthesia. Rarely, adult respiratory distress syndrome has been reported, primarily with doses greater than 10 g. If the patient is a high risk for general anesthesia, talc slurry may be administered at the bedside, though it is probably less effective than the thoracoscopic poudrage.
(3) Doxycycline 500 mg may cause pleuritic chest pain. An injection of 10 mL of 1% lidocaine (100 mg) through the chest tube may reduce this symptom.
c. Alternative agents
(1) Fluorouracil 2 to 3 g (total dose) may have a theoretical advantage in sensitive carcinomas, but whether that advantage has practical significance is not established. Pain is generally minimal. Occasional patients may experience a depressed white blood cell count, especially at the higher dose.
(2) Interferon-α 50 × 106 U typically causes influenza-like symptoms. Lower doses appear to be ineffective. Patients should be premedicated with acetaminophen 650 mg before and then 6 hours after interferon administration. Meperidine 25 mg intravenously by slow push may be given for rigors from interferon.
(3) Methylprednisolone acetate 80 to 160 mg appears to be well tolerated.
d. Responses. Chest tube drainage together with instillation of one of the agents discussed in Section I.C.2.b or c controls pleural effusions more than 75% of the time. The durations of response are often short, with a median between 3 and 6 months unless the patient’s systemic disease comes under adequate control. In that circumstance, the effusion may not recur for years or at least until the systemic disease once more emerges.
e. Side effects common to most agents include chest pain, fever, and occasional hypotension. These effects are usually not severe and may be controlled by standard symptomatic management. Fever after pleurodesis is usually not due to infection.
3. Indwelling pleural catheter placement is another option for patients who have recurrent pleural effusions. It involves placement of a soft, flexible, valved catheter connected to a drainage kit into the pleural space. Patients must be willing to care for the catheter on an outpatient basis but in contrast to a standard chest tube and pleurodesis, it allows the patient to be treated as an outpatient. It has similar efficacy to pleurodesis, but carries an added risk of infection owing to the indwelling catheter. Spontaneous pleurodesis may occur after 1 month or more of pleural catheter placement.
4. Thoracotomy and pleural stripping may be tried subsequently for effusions refractory to other medical treatment, when the prognosis is otherwise good.
II. PERITONEAL EFFUSIONS
A. Causes
Malignant peritoneal effusions usually occur in association with diffuse seeding of the peritoneal surface with small malignant deposits.Related posts:
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