CHEST / 142 / 1 / JULY 2012 17journal.publications.chestnet.org

10 . Kennedy L , Sahn SA . Talc pleurodesis for the treatment of pneumothorax and pleural effusion . Chest . 1994 ; 106 ( 4 ): 1215 - 1222 .

11 . Campos JR , Werebe EC , Vargas FS , Jatene FB , Light RW . Respiratory failure due to insuffl ated talc . Lancet . 1997 ; 349 ( 9047 ): 251 - 252 .

12 . Maskell NA , Lee YC , Gleeson FV , Hedley EL , Pengelly G , Davies RJ . Randomized trials describing lung infl ammation after pleurodesis with talc of varying particle size . Am J Respir Crit Care Med . 2004 ; 170 ( 4 ): 377 - 382 .

13 . Janssen JP , Collier G , Astoul P , et al . Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospec-tive cohort study . Lancet . 2007 ; 369 ( 9572 ): 1535 - 1539 .

14 . Shaw P , Agarwal R . Pleurodesis for malignant pleural effusions . Cochrane Database Syst Rev . 2004 ; 1 ( 1 ): CD002916 .

15 . Tan C , Sedrakyan A , Browne J , Swift S , Treasure T . The evi-dence on the effectiveness of management for malignant pleural effusion: a systematic review . Eur J Cardiothorac Surg . 2006 ; 29 ( 5 ): 829 - 838 .

16 . Dresler CM , Olak J , Herndon JE II , et al ; Cooperative Groups Cancer and Leukemia Group B ; Eastern Cooperative Oncol-ogy Group ; North Central Cooperative Oncology Group ; Radia-tion Therapy Oncology Group . Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion . Chest . 2005 ; 127 ( 3 ): 909 - 915 .

17 . Stefani A , Natali P , Casali C , Morandi U . Talc poudrage ver-sus talc slurry in the treatment of malignant pleural effusion. A prospective comparative study . Eur J Cardiothorac Surg . 2006 ; 30 ( 6 ): 827 - 832 .

18 . Crnjac A , Sok M , Kamenik M . Impact of pleural effusion pH on the effi cacy of thoracoscopic mechanical pleurodesis in patients with breast carcinoma . Eur J Cardiothorac Surg . 2004 ; 26 ( 2 ): 432 - 436 .

19 . Lee YC , Baumann MH , Maskell NA , et al . Pleurodesis prac-tice for malignant pleural effusions in fi ve English-speaking countries: survey of pulmonologists . Chest . 2003 ; 124 ( 6 ): 2229 - 2238 .

20 . Heffner JE , Nietert PJ , Barbieri C . Pleural fl uid pH as a pre-dictor of pleurodesis failure: analysis of primary data . Chest . 2000 ; 117 ( 1 ): 87 - 95 .

21 . Aelony Y , Yao JF . Prolonged survival after talc poudrage for malignant pleural mesothelioma: case series . Respirology . 2005 ; 10 ( 5 ): 649 - 655 .

22 . Nasreen N , Mohammed KA , Dowling PA , Ward MJ , Galffy G , Antony VB . Talc induces apoptosis in human malignant mesothelioma cells in vitro . Am J Respir Crit Care Med . 2000 ; 161 ( 2 pt 1 ): 595 - 600 .

23 . Lee P , Sun L , Lim CK , Aw SE , Colt HG . Selective apopto-sis of lung cancer cells with talc . Eur Respir J . 2010 ; 35 ( 2 ): 450 - 452 .

24 . Nasreen N , Mohammed KA , Brown S , et al . Talc mediates angiostasis in malignant pleural effusions via endostatin induc-tion . Eur Respir J . 2007 ; 29 ( 4 ): 761 - 769 .

25 . Tremblay A , Michaud G . Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleu-ral effusion . Chest . 2006 ; 129 ( 2 ): 362 - 368 .

26 . Van Meter ME , McKee KY , Kohlwes RJ . Effi cacy and safety of tunneled pleural catheters in adults with malignant pleu-ral effusions: a systematic review . J Gen Intern Med . 2011 ; 26 ( 1 ): 70 - 76 .

27 . Olden AM , Holloway R . Treatment of malignant pleural effu-sion: PleuRx catheter or talc pleurodesis? A cost-effectiveness analysis . J Palliat Med . 2010 ; 13 ( 1 ): 59 - 65 .

28 . Langer CJ , Besse B , Gualberto A , Brambilla E , Soria JC . The evolving role of histology in the management of advanced non-small-cell lung cancer . J Clin Oncol . 2010 ; 28 ( 36 ): 5311 - 5320 .

Counterpoint: Should Thoracoscopic Talc Pleurodesis Be the First Choice Management for Malignant Pleural Effusion? No

Malignancy is one of the most common causes of exudative pleural effusion, with approximately

200,000 cases occurring annually in the United States. 1 Many patients with malignant effusions have the quality of their life diminished by shortness of breath. If the shortness of breath is relieved with a therapeutic thoracentesis, then consideration should be given to proceeding with a procedure that will prevent the accumulation of pleural fl uid. If the patient is not symptomatic from the pleural effusion, no treat-ment is recommended. Most patients who have small effusions that do not produce symptoms never become symptomatic. 2

The best way to prevent the accumulation of pleural fl uid is not known. In general, the two main proce-dures available are the implantation of an indwell-ing pleural catheter and the creation of a pleurodesis. A pleurodesis is created when an infl ammation-producing material is injected into the pleural space. This can be done either through a chest tube or at the time of thoracoscopy. Agents used to produce the pleural infl ammation include talc, tetracycline deriv-atives, silver nitrate, povidone, and antineoplastics.

In general, there are three components to this edi-torial. First, is pleurodesis superior to the implanta-tion of an indwelling pleural catheter? Second, is pleurodesis in conjunction with thoracoscopy superior to pleurodesis done with tube thoracostomy? Third, is talc superior to the other agents in producing a pleurod esis?

Is pleurodesis superior to the implantation of an indwelling pleural catheter? The original study con-cerning the indwelling pleural catheter randomized 144 patients with symptomatic pleural effusions to receive an indwelling pleural catheter with intermit-tent drainage every 48 h, or doxycycline pleurodesis. 3 These authors concluded that the indwelling pleural catheter was advantageous because it did not neces-sarily require hospitalization. Tremblay et al 4 subse-quently reported a series of 250 tunneled pleural catheter insertions in 223 patients. Most of the cath-eters were inserted on an outpatient basis, and 90.1% of the patients required no further ipsilateral pleu-ral procedures. 4 They concluded that the indwelling catheter should be considered a fi rst-line treatment option in the management of patients with malignant pleural effusion. 4 Warren et al 5 reported a series of 231 indwelling catheters in 202 patients, of which

Downloaded From: http://journal.publications.chestnet.org/ by a Pontificia Universidad Javeriana User on 11/01/2012

18 Point/Counterpoint Editorials

210 catheters were inserted as outpatients. They reported that they were able to remove 58% of the catheters, and reaccumulation of pleural fl uid occurred in only fi ve of these 134 patients (3.8%). 5 Van Meter et al 6 recently reviewed 19 studies with 1,370 patients who were treated with tunneled pleu-ral catheters for malignant pleural effusion. They reported that symptomatic improvement occurred in 95.6% of patients, and spontaneous pleurodesis occurred in 45.6%. Serious complications were rare and included empyema in 2.85%. They concluded that prospective randomized studies comparing the tunneled indwelling catheter with pleurodesis are needed before the indwelling catheter can be recom-mended defi nitively as a fi rst-line treatment of malig-nant pleural effusion. A recent study compared the number of in-hospital days in 34 patients who elected to receive the indwelling catheter and 31 patients who elected talc pleurodesis. 7 They reported that the median number of hospital days was signifi cantly greater in the pleurodesis group (18 days) than in the indwelling pleural catheter group (6.5 days). Moreover, the median number of hospital days related to the effusions was signifi cantly greater in the pleurodesis group (10 days) than in the indwelling pleural catheter group (3 days). The patients in the indwelling catheter group also spent a smaller per-centage of their remaining lives (8.0%) in the hos-pital, compared with the pleurodesis group (11.2%). Thus, it appears that implantation of an indwelling catheter is a viable option for the treatment of a malig-nant pleural effusion.

If a pleurodesis is attempted, are the results with thoracoscopy superior to those with tube thoracos-copy? The largest randomized controlled study on this subject was reported by Dresler et al. 8 In this multicenter study, 482 patients were randomized to receive 4 to 5 g of talc , either administered as a slurry in 100 mL saline through a chest tube or insuffl ated during thoracoscopy. The Kaplan-Meier curves for the proportion of patients with a recur-rence were essentially superimposable with a very slight advantage to the group that received the slurry ( Fig 1 ). 8 In this study, subgroup analysis showed that patients with lung or breast carcinoma who were treated with thoracoscopy had a lower recurrence rate (18%) at 30 days than did patients treated with tube thoracostomy (33%). The only other random-ized study 9 that I am aware of that compared thora-coscopy with tube thoracostomy also concluded that thoracoscopic talc insuffl ation was not superior to talc slurry in the management of symptomatic malig-nant pleural effusion. This smaller study randomized 57 patients to one of the two treatments and reported that there was no difference in recurrence, chest drainage duration, or complications between the

two groups. 9 Because talc insuffl ation requires more resources, they concluded that talc slurry should be considered as the procedure of choice in the treat-ment of symptomatic malignant pleural effusion in patients who do not have a trapped lung. 9 However, if the diagnosis of malignancy is made at thoracos-copy, then it is reasonable to inject a sclerosant in an attempt to create a pleurodesis.

If pleurodesis is attempted, what agent should be used? Talc is the sclerosing agent most commonly used for chemical pleurodesis by pulmonologists in English-speaking countries. 10 The reason that talc is the most popular agent is that it is widely available, inexpensive, and perceived to be effective. However, as seen in Figure 1 , talc is not overwhelmingly effec-tive, because by 50 days . 30% of the patients had a recurrence. Many different agents have been injected intrapleurally in attempts to create a pleurodesis, including the tetracycline derivatives, 1 silver nitrate, 11 iodopovidone, 12 and bleomycin. 1 There is no con-vincing evidence that talc is superior to other agents, because there have been very few randomized con-trolled studies comparing the different agents.

One concern about talc is that its intrapleural administration has been associated with the devel-opment of ARDS and death in some patients. The incidence of ARDS has varied markedly from series to series, and most of the reported cases have been from the United States. There were 13 respiratory deaths in the 449 patients (2.9%) in the study by Dresler et al 8 discussed previously. Maskell et al 13 randomized 20 patients with malignant effusions to receive 20 mg/kg tetracycline or 4 g of mixed talc,

Figure 1. Time to recurrence of malignant pleural effusion in patients receiving talc slurry and talc insuffl ation. Note that the lines are nearly superimposable, with talc slurry having a slight advantage. (Reproduced with permission from Dresler et al. 8 )

Downloaded From: http://journal.publications.chestnet.org/ by a Pontificia Universidad Javeriana User on 11/01/2012

CHEST / 142 / 1 / JULY 2012 19journal.publications.chestnet.org

with most particles , 15 m m. They reported that the patients who received mixed talc had a signifi cantly greater decrease in diethylene triamine pentaacetic acid clearance, a signifi cantly greater decrease in arterial oxygen saturation, and a signifi cantly greater increase in C-reactive protein. 12 It appears that acute lung injury depends on the size of the talc used. Maskell et al 13 randomized 48 patients to receive mixed talc or graded talc in which most particles , 15 m m had been removed. They reported that the patients who received the graded talc had a significantly smaller increase in the alveolar to arterial oxygen gradient, a signifi cantly smaller decrease in Pa o 2 , and a signifi cantly smaller increase in C-reactive protein. Janssen et al , 14 in a multicenter, open-label, prospec-tive cohort study of 558 patients who received 4 g calibrated French large-particle-sized talc for malig-nant effusion, reported that there were no instances of ARDS. However, seven patients did develop pul-monary infi ltrates, which they attributed to reexpansion pulmonary edema in two, cardiogenic pulmonary edema in one, and respiratory failure unrelated to talc in one. 13 I am not convinced that the pulmonary infi ltrates in some of these patients were not related to the talc. In general, if one elects to use talc as a pleurodesing agent, only large-sized talc should be used.

In summary, the indwelling pleural catheter is a reasonable alternative to pleurodesis in many patients and appears to be associated with fewer days in hos-pital. There is no good evidence that pleurodesis via thoracoscopy is any more effective than pleurodesis via tube thoracostomy. Talc is the agent used most commonly for pleurodesis, but only large-particle talc should be used. Reasonable alternatives to talc are the tetracycline derivatives, silver nitrate and iodopovidone. Randomized controlled studies are needed to iden-tify the optimal way to manage patients with symp-tomatic malignant pleural effusions.

Richard W. Light , MD, FCCP Nashville, TN

Affi liations: From the Division of Allergy, Pulmonary, Immunology and Critical Care, Vanderbilt University . Financial/nonfi nancial disclosures: The author has reported to CHEST the following confl icts of interest: Dr Light has been on the advisory board of and is a consultant to CareFusion, which makes the Pleurx indwelling catheter, and CareFusion has pro-vided support for some of his speaking engagements . Correspondence to: Richard W. Light, MD, FCCP, Vanderbilt University, 2201 W End Ave, Nashville, TN 37235 ; e-mail: rlight98@yahoo.com © 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details. DOI: 10.1378/chest.12-1087

References 1 . Light RW . Pleural Diseases . 5th ed . Baltimore, MD : Lippincott,

Williams and Wilkins ; 2007 .

2 . Tremblay A , Robbins S , Berthiaume L , Michaud G . Natural his-tory of asymptomatic pleural effusions in lung cancer patients . J Bronchol . 2007 ; 14 ( 14 ): 98 - 100 .

3 . Putnam JB Jr , 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 ( 10 ): 1992 - 1999 .

4 . Tremblay A , Michaud G . Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleu-ral effusion . Chest . 2006 ; 129 ( 2 ): 362 - 368 .

5 . Warren WH , Kalimi R , Khodadadian LM , Kim AW . Manage-ment of malignant pleural effusions using the Pleur( x ) catheter . Ann Thorac Surg . 2008 ; 85 ( 3 ): 1049 - 1055 .

6 . Van Meter ME , McKee KY , Kohlwes RJ . Effi cacy and safety of tunneled pleural catheters in adults with malignant pleural effu-sions: a systematic review . J Gen Intern Med . 2011 ; 26 ( 1 ): 70 - 76 .

7 . Fysh ETH , Waterer GW , Kendall P , et al . Indwelling pleural catheters reduce inpatient days over pleurodesis for malignant pleural effusion [published online ahead of print March 8, 2012] . Chest . doi:10.1378/chest.11-2657 .

8 . Dresler CM , Olak J , Herndon JE II , et al ; Cooperative Groups Cancer and Leukemia Group B ; Eastern Cooperative Oncology Group ; North Central Cooperative Oncology Group ; Radiation Therapy Oncology Group . Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion . Chest . 2005 ; 127 ( 3 ): 909 - 915 .

9 . Yim AP , Chan AT , Lee TW , Wan IY , Ho JK . Thoracoscopic talc insuffl ation versus talc slurry for symptomatic malignant pleural effusion . Ann Thorac Surg . 1996 ; 62 ( 6 ): 1655 - 1658 .

10 . Lee YC , Baumann MH , Maskell NA , et al . Pleurodesis prac-tice for malignant pleural effusions in fi ve English-speaking countries: survey of pulmonologists . Chest . 2003 ; 124 ( 6 ): 2229 - 2238 .

11 . Paschoalini M da S , Vargas FS , Marchi E , et al . Prospective randomized trial of silver nitrate vs talc slurry in pleurodesis for symptomatic malignant pleural effusions . Chest . 2005 ; 128 ( 2 ): 684 - 689 .

12 . Neto JD , de Oliveira SF , Vianna SP , Terra RM . Effi cacy and safety of iodopovidone pleurodesis in malignant pleural effu-sions . Respirology . 2010 ; 15 ( 1 ): 115 - 118 .

13 . Maskell NA , Lee YC , Gleeson FV , Hedley EL , Pengelly G , Davies RJ . Randomized trials describing lung infl ammation after pleurodesis with talc of varying particle size . Am J Respir Crit Care Med . 2004 ; 170 ( 4 ): 377 - 382 .

14 . Janssen JP , Collier G , Astoul P , et al . Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study . Lancet . 2007 ; 369 ( 9572 ): 1535 - 1539 .

Rebuttal From Dr Lee

Malignant pleural effusions (MPEs) treated with simple aspiration and intercostal tube drain-

age without instillation of a sclerosant are associ-ated with high rates of recurrence. According to a survey of . 800 physicians who collectively per-formed . 8,000 pleurodesis, thoracoscopic talc pou-drage (TTP) was preferred over tube talc slurry (TS). 1 Cochrane database and systematic reviews have also shown better outcome with TTP than tube TS. 2,3 Although overall success rates in the phase III inter-group study comparing TTP and tube TS were sim-ilar, TTP provided more comfort and safety and was more effective than slurry for breast and lung

Downloaded From: http://journal.publications.chestnet.org/ by a Pontificia Universidad Javeriana User on 11/01/2012