Malignant Pleural Effusion

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Pleural effusion is a common and devastating complication in patients with malignant neoplasms. It is usually caused by disturbance of the normal Starling forces regulating reabsorption of fluid in the pleural space, via obstruction of mediastinal lymphatics draining the parietal pleura. Tumors that metastasize frequently to these nodes, i.e. lung cancer, breast cancer, and lymphoma, cause most malignant effusions. Pleural effusion restricts ventilation and causes progressive shortness of breath. Pleural deposits of tumor cause pleuritic pain. Lymphangitic pulmonary metastases further worsen pulmonary function. Management is usually complicated by the presence of disseminated tumor, with bone, brain and other organ metastases. In addition, the patient is often malnourished and debilitated. Untreated, death usually ensues within a few months due to the primary disease or to complications related to the effusion.

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Diagnosis

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The new onset of a pleural effusion may herald the presentation of a previously undiagnosed malignancy, or more typically, complicate the course of a known tumor. The first step in management in almost all cases is thoracentesis. An adequate specimen should be obtained and sent for cell count, glucose, protein, LDH, pH, appropriate cultures and cytology. A negative cytology result is not uncommon, and does not rule out a malignant etiology. If no specific diagnosis is obtained after thoracentesis, and malignant disease is still suspected , pleural biopsy was previously the typical next step in the workup, with minimal diagnostic yield. Currently, thoracoscopic examination is emerging as a more reliable technique. It has a low complication rate and allows a comprehensive visualization of one pleural cavity with the ability to biopsy areas of disease. It also offers the opportunity for simultaneous treatment by pleurodesis or pleurectomy. This will provide definitive diagnosis and allow the pathologist to suggest possible sites of primary disease based on the histo-pathologic appearance of the tumor. This technique will also allow diagnosis and staging of malignant mesothelioma if this disease is the cause of the effusion.

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Treatment

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Malignant pleural effusion should be treated aggressively as soon as it is diagnosed. In most cases, pleural effusion will rapidly reform after treatment by thoracentesis or tube thoracostomy alone. If it is decided to treat the underlying primary malignancy with chemotherapy, in tumors such as breast cancer, lymphoma and small cell lung cancer, it is important to carefully follow the patient and treat immediately upon recurrence of effusion. If a malignant pleural effusion is left untreated, the underlying lung will become encased by tumor and fibrous tissue. Once encasement atelectasis has occurred, the underlying lung is "trapped" and will no longer re-expand after thoracentesis or tube thoracostomy. Characteristically the chest roentgenogram will show resolution of the pleural effusion after thoracentesis, but the underlying lung will remain partially collapsed. This is often misinterpreted by the inexperienced clinician as evidence of a pneumothorax, and a chest tube is placed. The air space persists and the lung remains unexpanded even with high suction and pulmonary physiotherapy. Allowing the chest tube to remain in place can worsen the situation by causing bronchopleural fistulization and empyema.

To avoid this disastrous complication, the pleural effusion should be treated definitively at the time of the initial diagnosis. Multiple physical techniques of producing adhesions between the parietal and visceral pleura, obliterating the space and preventing recurrence have been used, including open or thoracoscopic pleurectomy, gauze abrasion or laser pleurodesis. Surgical methods have not been demonstrated to have any advantage over simpler chemical pleurodesis techniques in the treatment of malignant effusions

Multiple chemical agents have been used. The largest experience in the U.S. has been with tetracycline. Tetracycline pleurodesis results in a lower incidence of recurrence , when compared with tube thoracostomy alone, but often causes severe pain and is no longer manufactured in the United States. Doxycycline has been recently advocated for the same indications and a single are retrospective study indicates that doxycycline is roughly equal to tetracycline in effectiveness. Intrapleural bleomycin in a dose of 60 units has been shown to be more effective than tetracycline, is not painful to the patient, but has a high cost. Absorption of the drug can result in systemic toxicity. Talc pleurodesis was first introduced by Bethune in the 1930s, but has not been widely used in the U.S. until the past decade. Numerous studies indicate that it is an effective method, preventing recurrent effusion in 80-90% of cases. It is less painful than tetracycline. Cost is minimal, but special sterilization techniques must be mastered by the hospital pharmacy. Talc can be insufflated in a dry state at the time of thoracoscopy or instilled as a slurry through a chest tube. The dose should be restricted to no more than 5 grams.

With any form of pleurodesis, a 24-32F tube should be inserted through a lower intercostal space and placed on underwater seal suction drainage until the pleural drainage is minimal. Because severe lung damage can be produced by improper chest tube placement, it is imperative to prove the presence of free fluid by preliminary needle tap and enter the pleural space gently with a blunt clamp technique, rather than by a blind trochar insertion. In the case of large effusions, especially those that have been present for some time, the fluid should be drained slowly, to avoid reexpansion pulmonary edema. If doxycycline or talc is to be used, the patient should be pre-medicated with narcotics. Intrapleural instillation of 20cc of 1% lidocaine before the chemical agent may help reduce pain. Following instillation of the chemical agent, the chest tube should remain clamped for at least two hours. During this time, the patient should be encouraged to role into prone, supine and both lateral decubitus positions in order to bring the drug into contact with the entire pleural surface. If high volume drainage persists, the treatment can be repeated. The chest tube can be removed after two or three days, if drainage is less than 300 ml/day. Follow up films at monthly intervals are important to assess the adequacy of treatment and to allow early retreatment in case of recurrence.

If encasement atelectasis is found at thoracentesis or thoracoscopy, then tube thoracostomy and pleurodesis are futile and contraindicated. Surgical decortication has been advocated for this problem. This is a potentially dangerous procedure that may result in severe complications such as bronchopleural fistula and empyema. Placement of a pleuro-peritoneal shunt may be helpful in some cases, but obstruction of the system by fibrinous debris is a potential problem. Intermittent thoracentesis, as needed to relieve symptoms, is probably the best option in patients with a limited survival. A pleural "spigot" has been created by inserting a peritoneal dialysis catheter and connecting it to a closed system drainage bag. The patient then merely unclamps the catheter and drains the fluid in response to dyspnea due to reaccumulation of fluid. Experience with this technique is limited. Fourteen published cases experienced good palliation. with no major complications reported. Sterile technique is important, as infection of the pleural space would worsen an already bad situation.

Radiation therapy may be indicated in some patients with lymphoma but has limited effectiveness in other types of tumors. It is problematic because of the potential for lung damage in a patient who is usually already dyspneic. Chemotherapy options will depend on the cell type of the tumor and the general condition of the patient.

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REFERENCES

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• 1. Black LF. The pleural space and pleural fluid. Mayo Clin Proc 1972;47:493-506. A good general review of the physiology and pathophysiology of the pleura and pleural effusion.
• 2. Ruckdeshel JC, Moores D, Lee JY, Einhorn LH, Mandelbaum I, Koeller J, Weiss GR, Losada M, Keller JH. Intrapleural therapy for malignant pleural effusions: a randomized comparison of bleomycin and tetracycline.Chest 1991;100:1535. A multi-institution, randomized comparison of intrapleural bleomycin vs. tetracycline demonstrated the greater effectiveness of bleomycin.
• 3. Fentiman IS, Rubens RD, Hayward JL. A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer. Eur J Cancer Clin Oncol 1986;22:1079-81. A randomized trial of intrapleural talc vs. tetracycline showed the superior effectiveness of talc.
• 4. Hamed H, Fentiman IS, Chaudary MA, Rubens RD. Comparison of intracavitary bleomycin and talc for control of pleural effusions secondary to carcinoma of the breast. Br J Surg 1989;1266-7. A randomized study demonstrated intrapleural talc to be superior in effectiveness to bleomycin.
• 5. Aelony Y, King R, Boutin C. Thoracoscopic talc poudrage pleurodesis for chronic recurrent pleural effusions. Ann Intern Med 1991;115:778-82. A prospective single arm study demonstrated the efficacy of talc insufflation during thoracoscopy in preventing recurrent pleural effusion.
• 6. Lee KA, Harvey JC, Reich H, Beattie EJ. Management of malignant pleural effusions with pleuroperitoneal shunting. J Am Col Surg 1994;178:586-588. The technique is illustrated and long term effectiveness in 75% of cases of malignant pleural effusion is documented.
• 7. Robinson RD, Fullerton DA, Albert JD, Sorensen J, Johnston MR. Use of pleural Tenckhoff catheter to palliate malignant pleural effusion. Ann Thorac Surg 1994;57:286-8.

Another source for malignant pleural effusion information is Malignant pleural effusion

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