Approximately 50% of pleural effusions, which are a common clinical problem, are malignant. Although most of these patients have advanced disease with a poor prognosis, some patients could have a relatively prolonged survival. Thus, specific treatments of pleural effusions are justifiable in an attempt to palliate symptoms. However, only a minority of patients with malignant pleural effusions (MPE) benefit from suitable systemic treatment. Pulmonologists, therefore, must treat these chronic pleural effusions, which recur rapidly and are disabling for patients.
Most patients with MPE are symptomatic and their quality of life is affected. Complaints are usually dyspnea, cough, chest pain, and treatment is focused on relieving these symptoms. Tumor seldom responds to chemotherapy; therefore, the first step in management is thoracentesis. When thoracentesis is repeated frequently to relieve dyspnea, the resulting discomfort, as well as depletion in ions, fluid, and proteins, contributes to deterioration of the patient's general condition and other options must be considered. Because open thoracotomy with pleurectomy or pleuroperitoneal shunting is a very aggressive therapy, 1 chemical pleurodesis through a chest tube or under thoracoscopic guidance is usually proposed as the “gold standard” for management of recurrent MPE. 2 The literature on treatment of MPE has focused on the comparative efficacy of specific sclerosing agents in favor of talc. There has also been interest in the use of less invasive techniques of fluid drainage and sclerosing, including the use of a small-bore catheter in lieu of larger tubes 3 and the management on an outpatient basis in comparison to standard hospitalization for pleural symphysis. 4,5 Such trends arise from consideration of the patient's quality of life and the cost of available treatments for MPE. 6
This article summarizes several therapeutic approaches for MPE and outlines advantages of management on an inpatient basis for talc pleurodesis, in particular, under medical thoracoscopy.
PATHOGENESIS AND ETIOLOGY OF MPE
Based on the existing literature, most pleural metastases arise from tumor emboli to the visceral pleural surface with secondary seeding to the parietal pleura. Other possible mechanisms include direct tumor invasion (in lung cancers, chest wall neoplasms, and breast carcinoma), hematogenous spread to parietal pleura, and lymphatic involvement. However, it is usually impossible in a given clinical situation to predict the real mechanism of an MPE and, consequently, the involvement of the visceral and parietal pleura; these are important prognostic factors, as previously shown in clinical and experimental situations. 7,8 Although all neoplasms have been reported to involve the pleura, lung carcinoma is the most common, accounting for approximately one third of all malignant effusions. Breast carcinoma is the second most common. Lymphomas, including both Hodgkin disease and non-Hodgkin lymphoma, are also an important cause of MPE. Tumors less commonly associated with MPE include ovarian and gastrointestinal carcinomas. In 5% to 10% of malignant effusions, no primary tumor is identified. 9
TREATMENT: INDICATIONS AND CONTRAINDICATIONS
When the malignancy is refractory to chemotherapy, the first step for management of patients with MPE should be the evaluation of symptoms, general condition, functional status, and expected survival. The major indication for palliative treatment is relief of dyspnea, which is dependent on several factors such as the volume of the effusion and the underlying condition of the lungs and pleura. Further therapeutic strategy is dictated by the relief of breathlessness and rate and degree of recurrence after thoracentesis. If dyspnea is not relieved by thoracentesis, other causes should be investigated such as lymphangitic carcinomatosis, atelectasis, thromboembolism, and tumor embolism. After thoracentesis, complete lung expansion should be obtained to eliminate a mainstem bronchial occlusion (careful analysis of the mediastinal shift on the chest radiograph is required) or trapped lung resulting from extensive pleural tumor infiltration. The measurement of the pleural pressure is a simple and effective method for the diagnosis of trapped lung. 10 Then, chemical pleurodesis is an accepted palliative treatment of patients with recurrent, symptomatic MPE and with no trapped lung.
CHEMICAL PLEURODESIS BY TALC
Despite lack of adequate assessment of the efficacy of specific chemical agents in the literature, talc was found to be superior to that of other agents with a more than 90% success rate for talc pleurodesis in the treatment of recurrent pleural effusions. 2 Talc is an inexpensive and highly effective sclerosing agent when administered intrapleurally for symphysis. However, a controversy arose about the possible role of asbestos-free talc in inducing respiratory failure as a result of systemic distribution of particles after intrapleural injection. 11,12 It is not clear so far whether the method of administration (slurry vs. poudrage) plays a major role in the development of respiratory failure; further experimental studies are needed to answer this question. However, recent publications have pointed out the importance of the quality of talc and the size of talc particles in the safety of pleural symphysis. 13–15
Talc-slurry pleurodesis is a widely reported method of talc instillation into the pleural cavity for palliative treatment of MPE. Although the slurry preparation and talc slurry procedure are not very well defined (various volumes of saline, different amounts of talc, different chest tube size, various duration with clamped chest tube, patient rotation or not, level of the suction after unclamping the chest tube, parameters for chest tube removal, and so on), the rationale for using this procedure is based on the simplicity of the blind bedside technique and also the lack of experience of pulmonologists to perform thoracoscopy. The results of the study conducted by the North American Cooperative Oncology Group are pending, but currently there are no data available from a randomized clinical comparative study assessing the efficacy of pleural symphysis by slurry versus poudrage. Talc-slurry administration does not allow the talc to be distributed over the pleural surface. Most of the talc, in fact, is eventually eliminated through the chest tube with saline solution. Experimental studies have shown that fibrosis and inflammation of the pleura occurred mostly in gravity-dependent areas, and that pulmonary to costal adhesions are very rare with this technique in comparison with the talc poudrage procedure. 16,17
Talc poudrage pleurodesis can be performed by medical thoracoscopy under local anesthesia with conscious sedation or general anesthesia. Usually the procedure is performed in patients with spontaneous breathing. 18 Several technical details should be taken into account to achieve good pleurodesis and to avoid complications. All pleural fluid should be removed before insufflating talc. Fluid removal is easily done under visual control during thoracoscopy as air is entering the pleural cavity without insufflation. This creates equilibrium in pressure. Complete collapse of the lung allows a good view of the pleural cavity and a careful analysis of visceral and parietal pleuras, as well as the opportunity to biopsy suspicious lesions and, at the end of the procedure, permits a wide distribution of the talc on dry tissue. Usually less than 5 g of sterile, asbestos-free, calibrated talc is recommended to obtain symphysis in patients with MPE. Thoracoscopy allows repeated pleural inspection at the end of the procedure after talc insufflation to assure that the powder is distributed over the pleural surface.
The aim of the management of MPE is the selection of optimal treatment of patients with limited life expectancy, disabling symptoms such as dyspnea, and poor general condition. Efforts to palliate symptoms, optimize function, shorten hospitalization, and reduce end-of-life medical care costs are required.
Dedicated-talc pleurodesis is the safest and best procedure for achieving symphysis and, consequently, relieving dyspnea in patients with no trapped lung and improving the quality of life. Talc fits the criteria for an ideal pleurodesis agent: high efficacy, ease of administration, low cost, and freedom from severe adverse effects. 19 However, several studies attributing part of the cost to the performance of a sclerosing agent, which affected length of hospital stay, personnel costs, diagnostic costs, and the risk of adverse effects, found that the second major contributor to cost-effectiveness appeared to be procedural costs. 6 The highly sophisticated procedures, ie, medical thoracoscopy, required to administer talc makes the overall treatment expensive, despite the low cost and efficacy of the treatment itself.
In an attempt to reduce these costs, outpatient (ambulatory) management of MPE using pleurodesis with talc has been done. 20 The feasibility of such procedures is reported for a few patients with a very short 30-day response rate similar to that reported for inpatient drainage therapy and consequently with a lower cost. However, if further studies in this field are required, the need for expensive supplies could temper the use of such outpatient pleural symphysis management. 21
Conversely, ambulatory management is suitable in case of pleurodesis failure, which usually occurs soon after attempted pleurodesis as a result of suboptimal techniques or inappropriate patient selection (patient with a trapped lung or mainstem bronchial occlusion). Small-bore, indwelling pleural catheters for home drainage can be inserted into the pleural cavity. Despite catheter occlusions and infections, this method provides a convenient, effective alternative to the procedures currently in use, allowing good symptomatic relief. 5,22
The major drawback of out- or inpatient talc-slurry pleurodesis is the lack of adequate assessment of efficacy. Reported trials have evaluated only small numbers of patients, used different techniques, used conflicting success criteria, and/or monitored subjects for various periods of time. Moreover, progression of disease is variable and the precise pleural status of the patients at the time of pleurodesis, ie, visceral and parietal pleural involvement, is unknown. Medical thoracoscopy conversely offers the possibility to carefully explore the pleural cavity to evaluate pleural layers and perform biopsies for diagnosis. It facilitates pleural symphysis by talc and proper placement of the chest tube for optimal drainage. Immediate talc poudrage can be done in cases of macroscopic or histologic evidence of malignancy and ineligibility of the patient for trials of intrapleural treatment. The safety and quality of such talc pleurodesis depends on the type of talc used, as well as the drainage technique and the time when pleurodesis is performed. 13,18 The chest tube must be inserted as low as possible in the thorax, directed posteriorly toward the costovertebral gutter, and as close to the apex as possible for optimal drainage of residual fluid. Waiting for pleurodesis is detrimental to the patient because parietal nodules and/or cancerous thickening of the visceral pleura, which increase with time, can prevent adhesion of the lung to the chest wall, this being a prerequisite for pleurodesis. Conversely, pleural pH value has no practical impact for the management of MPE by talc poudrage pleurodesis because low pleural pH in MPE seems to be associated with advanced disease and trapped lung, which is a contraindication to pleural symphysis. 23,24
Therefore, patients with MPE are good candidates for thoracoscopy and talc pleurodesis if they meet the following criteria: 1) failure or unavailability of specific treatment; 2) dyspnea that improves after large-volume thoracentesis with subsequent and rapid recurrence of the pleural effusion; and 3) absence of trapped lung as evidenced by previous thoracenteses and control of intrapleural pressures.
Thoracoscopic talc poudrage is a safe and efficient procedure for the management of patients with recurrent MPE. Performing medical thoracoscopy in an endoscopy suite instead of an operating room can reduce the cost of the procedure. Despite the costs incurred by the technical procedure, it must be the treatment of choice for patients with this disabling disease. 25
1. Bernard A, de Dompsure BR, Hagry O, et al. Early and late mortality after pleurodesis for malignant pleural effusion. Ann Thorac Surg. 2002; 74:213–217.
2. Walker-Renard P, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med. 1994; 120:56–64.
3. Parulekar W, Di Primio G, Matzinger F, et al. Use of small-bore vs large-bore chest tubes for treatment of malignant pleural effusions. Chest. 2001; 120:19–25.
4. Putnam Jr, JB Light RW, Rodriguez RM, et al. A randomized comparison of indwelling pleural catheter and doxycycline pleurodesis in the management of malignant pleural effusions. Cancer. 1999; 86:1992–1999.
5. Pollak JS. Malignant pleural effusions. Treatment with tunneled long-term drainage catheters. Curr Opin Pulm Med. 2002; 8:302–307.
6. Belani CP, Pajeau TS, Bennet CL. Treating malignant pleural effusions cost consciously. Chest. 1998; 113:78S–85S.
7. Boutin C, Rey F, Gouvernet J, et al. Thoracoscopy in pleural malignant mesothelioma: a prospective study of 188 consecutive patients. Part 2: prognosis and staging. Cancer. 1993; 72:394–404.
8. Astoul P, Colt HG, Wang X, et al. `Patient-like' nude mouse metastatic model of advanced human pleural cancer. J Cell Biochem. 1994; 56:9–15.
9. Antony VB, Loddenkemper R, Astoul P, et al. Management of malignant pleural effusions. ERS/ATS statement. Eur Respir J. 2000; 18:402–419.
10. Lan RS, Lo SK, Chuang ML, et al. Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion. Ann Intern Med. 1997; 126:768–774.
11. Light RW. Talc for pleurodesis? Chest. 2002; 122:1506–1508.
12. Werebe EC, Cazetti R, Milanez de Campos JR, et al. Systemic distribution of talc after intrapleural administration in rats. Chest. 1999; 115:190–193.
13. Fraticelli A, Robaglia-Schlupp A, Helene Riera H, et al. Distribution of calibrated talc after intrapleural administration: an experimental study in rats. Chest. 2002; 122:1737–1741.
14. Ferrer J, Villarino MA, Tura JM, et al. Talc preparation used for pleurodesis vary markedly from one preparation to another. Chest. 2001; 119:1901–1905.
15. Ferrer J, Montes JF, Villarino MA, et al. Influence of particle size on extrapleural talc dissemination after talc slurry pleurodesis. Chest. 2002; 122:1018–1027.
16. Colt HG, Russack V, Chiu Y, et al. A comparative of thoracoscopic talc insufflation, slurry, and mechanical abrasion pleurodesis. Chest. 1997; 111:442–448.
17. Jerram RM, Fossum TW, Berridge BR, et al. The efficacy of mechanical abrasion and talc slurry as methods of pleurodesis in normal dogs. Vet Surg. 1999; 28:322–332.
18. Viallat JR, Rey F, Astoul P, et al. Thoracoscopic talc poudrage for malignant effusions. A review of 360 cases. Chest. 1996; 110:1387–1393.
19. Sahn SA. Talc should be used for pleurodesis. Am J Respir Crit Care Med. 2000; 162:2023–2024.
20. Saffran L, Ost D, Fein AM, et al. Outpatient pleurodesis of malignant pleural effusions using a small-bore pigtail catheter. Chest. 2000; 118:417–421.
21. Putnam Jr. JB Malignant pleural effusions. Surg Clin North Am. 2002; 82:867–883.
22. Pien GW, Gant MJ, Washam CL, et al. Use of an implantable pleural catheter for trapped lung syndrome in patients with malignant pleural effusion. Chest. 2001; 119:1641–1646.
23. Aelony Y, King RR, Boutin C. Thoracoscopic talc poudrage in malignant pleural effusions. Effective pleurodesis despite low pleural pH. Chest. 1998; 113:1007–1012.
24. Sanchez-Armengol A, Rodriguez-Panadero F. Survival and talc pleurodesis in metastatic pleural carcinoma, revisited: report of 125 cases. Chest. 1993; 104:1482–1485.
25. Cardillo G, Faciolo F, Carbone L, et al. Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent effusions. Eur J Cardiothorac Surg. 2002; 21:302–305.