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Malignant pleural effusion


Table of Contents

DISEASE DESCRIPTION

DISEASE DESCRIPTION

Malignant pleural effusions are caused most commonly by carcinomas of the breast, lung, gastrointestinal tract or ovary and by lymphomas. In male patients about half of malignant effusions are caused by lung cancer, 20% by lymphomas or leukemia, 7% from gastrointestinal primaries, 6% from genitourinary primaries, and 11% from tumors of unknown primary site. In female patients, about 40% of malignant effusions are caused by breast cancer, 20% from tumors arising in the female genital tract, 15% from lung primaries, 8% from lymphomas or leukemia, 4% from gastrointestinal tract primaries, 3% from melanoma, and 9% from tumors of unknown primary site.[1] Effusions may be secondary to impaired pleural lymphatic drainage from mediastinal tumor (especially in lymphomas) and not due to direct pleural invasion.

Effusions may be the presenting sign of cancer or they may develop after the cancer is diagnosed. Only 50% of the effusions that develop in cancer patients during the course of their illness are malignant. Correct diagnosis of the cause of pleural effusions is the necessary first step in their management.

Pleural effusions are caused principally by congestive heart failure, malignancy, and infection. Patients present with the symptoms of cough, dyspnea, decreased exercise tolerance, and chest pain. While larger effusions may be detected on physical examination, effusions as small as 100 milliliters may be detected by decubitus chest radiographs, ultrasound, or computerized tomography of the chest. A diagnostic thoracentesis should be performed early in the course of investigation. In markedly symptomatic patients, removal of pleural fluid can provide immediate, albeit temporary, relief; generally 1 liter or more must be removed to improve symptoms. Pleural fluid analysis should include protein, LDH, glucose and pH determinations, cell counts, cell block, cytology, and smears and cultures for bacteria, fungi, and mycobacteria. At least 250 milliliters of pleural fluid is necessary for adequate cytologic examination.

Pleural effusions are classified as transudative or exudative. Most often, transudative effusions are caused by congestive heart failure, cirrhosis, nephrotic syndrome, or occasionally by lymphatic blockade produced by cancer. Exudative effusions are caused by infection or malignancy. In the absence of infection, an exudative pleural effusion, especially if it is bloody, strongly suggests a malignant etiology. An exudative pleural effusion in a patient with a current or past cancer is very likely caused by the cancer. Effusions due to lymphoma or mediastinal involvement by any tumor may be chylous and cytologically negative. About half of effusions ultimately diagnosed as malignant will have a positive cytology from the initial thoracentesis.

Two different approaches can be used to attempt to diagnose the etiology of pleural effusions if the initial cytologic examination does not show malignant cells. Repeat thoracenteses and pleural biopsy will confirm malignancy in 80% to 90% of malignant effusions.[2] The pleural biopsy has a higher complication rate but a higher yield than thoracentesis. Determinations of pleural fluid CEA and amylase may be helpful in selected cases. Despite thoracenteses and pleural biopsy, 10%-20% of patients with malignant pleural effusions will still not have a diagnosis.[2,3] In such patients, thoracoscopy will be needed for diagnosis.[2-4] Although thoracoscopic biopsy requires local or general anesthesia, it increases the diagnostic yield greatly compared to thoracentesis.

The alternative diagnostic approach to patients with pleural effusions whose initial cytologic examination does not show malignant cells is to go directly to thoracoscopy with biopsy of visually identified abnormal areas of the pleura. The diagnostic yield of a malignancy using this approach exceeds 90% if the effusion is caused by cancer.[2-4]

Once the diagnosis of malignant pleural effusion has been made, treatment depends on the tumor type and prior antineoplastic therapy.[2,3,5] About 25% of effusions do not require therapy; the effusions are small and stable. Malignant effusions caused by lymphomas, breast cancer, small cell lung cancer, or ovarian cancer may respond to systemic chemotherapy or hormonal therapy. Repeated percutaneous draining of effusions may lead to tumor growth along the needle track and through the chest wall. Patients who have received extensive prior systemic therapy and those with chemotherapy-resistant tumors, like non-small cell lung cancer, are not likely to respond to systemic therapy. Palliative approaches to the management of malignant pleural effusions are necessary in such patients.

Patients with symptomatic malignant pleural effusions whose underlying cancer is unlikely to respond to systemic treatment should have their pleural fluid drained. Patients with relatively large (>1,000 milliliters) recurrent effusions whose symptoms resolve with drainage and whose lung can fully expand are candidates for palliation. Two general approaches to the palliative management of symptomatic pleural effusions are chest tube drainage with installation of a sclerosing agent and thoracoscopic drainage of the pleural effusion under local or general anesthesia with intraoperative sclerosis of the pleural space.

Historically, many chemical agents have been instilled into the pleural space and shown to have some effectiveness in controlling effusions, including tetracycline, doxycycline, minocycline, bleomycin, cisplatin, doxorubicin, etoposide, fluorouracil, mitomycin, mitoxantrone, interferon, Corynebacterium parvum, mepacrine, methylprednisolone, and talc.[6]

Chest tube drainage should be done by inserting the chest tube into the pleural cavity and draining the fluid. When the drainage reaches less than 50-100 milliliters in a 24 hour period, a sclerosing agent can be instilled.[2,5] Information on the recommended sclerosing agent is currently inconclusive. The few randomized studies on this topic are plagued by small numbers (all but one have fewer than 50 patients per arm), and relatively short follow-up. The single randomized study with more than 100 patients showed nearly twice as many patients had their pleural effusion controlled with bleomycin at 90 days (70%) than those treated with tetracycline.[7]

Large single-arm comparative studies [8-10] and very small randomized studies suggest advantages for talc as the sclerosing agent compared to tetracycline and bleomycin.[11,12] In these two randomized studies, thoracoscopy and insufflation of talc controlled the pleural effusions in twice as many patients as tetracycline or bleomycin (>90% versus 50%, respectively) in 63 patients with breast cancer. The comparative and single-arm studies suggest that talc provides control of approximately 90% of pleural effusions for 90 days or longer.[8-10] We await the results of two different large cooperative group randomized studies to help determine the appropriate sclerosing agent to use to treat patients with malignant pleural effusions. One compares intrapleural bleomycin, doxycycline, and talc as sclerosing agents.[13] Another compares the use of a talc slurry administered via chest tube to talc insufflated during thoracoscopy.[14] Another approach is appropriate for patients with a symptomatic malignant pleural effusion and good performance status (ECOG performance status of 0-2) who are capable of undergoing a procedure under local, regional, or general anesthesia. These patients can have thoracoscopy with biopsy of suspicious pleural lesions, lysis of adhesions, evaluation to see if the lung re-expands, and installation of the sclerosing agent during the same procedure.[4] This potentially shortens the hospitalization because the whole procedure can be done in the operating room in a single day.

Since tetracycline is no longer available and similar efficacy has been shown for doxycycline, doxycycline has been substituted for tetracycline in clinical trials.[15,16]

Pleural stripping (pleurectomy) via thoracotomy or thoracoscopy is nearly 100% effective in controlling malignant pleural effusions, but the morbidity is so severe that this procedure is rarely used.[4]

Treatment options:

1. After histologic confirmation of diagnosis, attempt to treat the underlying malignancy with systemic chemotherapy. Chylous effusions are not controlled with sclerosis.


2. Pleurodesis: Where systemic therapy is not feasible or fails to control the pleural effusion, drain the effusion with a surgical chest tube until daily output falls to 50-100 milliliters. Small-bore chest tubes have been used for drainage of the pleural effusion in small single-arm studies.[16-18] The smaller chest tubes are used because they cause less discomfort and do not limit patient mobility. Then instill either 5 grams of talc via insufflation during thoracoscopy or as a slurry via chest tube. An alternate agent is bleomycin 1.25 milligrams per kilogram (not to exceed 40 milligrams per square meter in elderly patients).


3. Thoracoscopic management of the pleural effusions: Patients with a symptomatic malignant pleural effusion and good performance status (ECOG performance status of 0-2) are candidates for this procedure. The procedure can be performed under local, regional, or general anesthesia. After appropriate anesthesia, the thoracoscope is introduced into the pleural cavity. The pleural fluid is evacuated, the adhesions are lysed, and the pleural cavity is inspected. Suspicious pleural lesions can be biopsied, particularly if the diagnosis of a malignant pleural effusion has not been made. An assessment is made to see if the lung re-expands. Three to 5 grams of talc are then uniformly sprayed onto the visceral and parietal pleural surface. After the talc is distributed, a chest tube is left in the chest and placed to suction. The chest tube can be removed after the drainage is less than 50 to 100 milliliters per 24-hour period.

Patients whose effusions are not controlled by talc or bleomycin
sclerosis should be considered for pleural stripping if the pleural
effusion represents the predominant active metastatic disease.

4. Insertion of a pleuroperitoneal shunt: The use of a pleuroperitoneal shunt has also been shown to control the dyspnea associated with malignant pleural effusions, although approximately 25% of shunts will become occluded during the lifetime of the patient.[19,20]

References:

  1. Johnston WW: The malignant pleural effusion: a review of cytopathologic diagnoses of 584 specimens from 472 consecutive patients. Cancer 56(4): 905-909, 1985.

  2. Fenton KN, Richardson JD: Diagnosis and management of malignant pleural effusions. American Journal of Surgery 170(1): 69-74, 1995.

  3. Pass HI: Malignant pleural and pericardial effusions. In: DeVita VT, Hellman S, Rosenberg SA, Eds.: Cancer: Principles and Practice of Oncology. Philadelphia: Lippincott-Raven Publishers, 5th ed., 1997, pp 2586-2598.

  4. Colt HG: Thoracoscopic management of malignant pleural effusions. Clinics in Chest Medicine 16(3): 505-518, 1995.

  5. Ruckdeschel JC: Management of malignant pleural effusions. Seminars in Oncology 22(2, Suppl 3): 58-63, 1995.

  6. Walker-Renard PB, Vaughan LM, Sahn SA: Chemical pleurodesis for malignant pleural effusions. Annals of Internal Medicine 120(1): 56-64, 1994.

  7. Ruckdeschel JC, Moores D, Lee JY, et al.: Intrapleural therapy for malignant pleural effusions: a randomized comparison of bleomycin and tetracycline. Chest 100(6): 1528-1535, 1991.

  8. Hartman DL, Gaither JM, Kesler KA, et al.: Comparison of insufflated talc under thoracoscopic guidance with standard tetracycline and bleomycin pleurodesis for control of malignant pleural effusions. Journal of Thoracic and Cardiovascular Surgery 105(4): 743-748, 1993.

  9. Viallat JR, Rey F, Astoul P, et al.: Thoracoscopic talc poudrage pleurodesis for malignant effusions: a review of 360 cases. Chest 110(6): 1387-1393, 1996.

  10. Weissberg D, Ben-Zeev I: Talc pleurodesis: experience with 360 patients. Journal of Thoracic and Cardiovascular Surgery 106(4): 689-695, 1993.

  11. Fentiman IS, Rubens RD, Hayward JL: A comparison of intracavitary talc and tetracycline for the control of pleural effusions secondary to breast cancer. European Journal of Cancer and Clinical Oncology 22(9): 1079-1081, 1986.

  12. Hamed H, Fentiman IS, Chaudary MA, et al.: Comparison of intracavitary bleomycin and talc for control of pleural effusions secondary to carcinoma of the breast. British Journal of Surgery 76(12): 1266-1267, 1989.

  13. Ruckdeschel JC, Eastern Cooperative Oncology Group: Phase III Randomized Study of Bleomycin vs Doxycycline vs Talc for Malignant Pleural Effusions (Summary Last Modified 12/96), E-8592, clinical trial, active, 11/06/1996.

  14. Olak J, Cancer and Leukemia Group B: Phase III Randomized Study of Sclerosis of Malignant Pleural Effusion by Talc Slurry vs Talc Thoracoscopy (Summary Last Modified 05/98), CLB-9334, clinical trial, active, 12/15/1994.

  15. Robinson LA, Fleming WH, Galbraith TA: Intrapleural doxycycline control of malignant pleural effusions. Annals of Thoracic Surgery 55: 1115-1122, 1993.

  16. Seaton KG, Patz EF, Goodman PC: Palliative treatment of malignant pleural effusions: value of small-bore catheter thoracostomy and doxycycline sclerotherapy. American Journal of Roentgenology 164(3): 589-591, 1995.

  17. Patz EF, McAdams HP, Goodman PC, et al.: Ambulatory sclerotherapy for malignant pleural effusions. Radiology 199(1): 133-135, 1996.

  18. Goff BA, Mueller PR, Muntz HG, et al.: Small chest-tube drainage followed by bleomycin sclerosis for malignant pleural effusions. Obstetrics and Gynecology 81(6): 993-996, 1993.

  19. Lee KA, Harvey JC, Reich H, et al.: Management of malignant pleural effusions with pleuroperitoneal shunting. Journal of the American College of Surgeons 178(6): 586-588, 1994.

  20. Reich H, Beattie EJ, Harvey JC: Pleuroperitoneal shunt for malignant pleural effusions: a one-year experience. Seminars in Surgical Oncology 9(2): 160-162, 1993.

Date Last Modified: 12/98



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