Egyptian Journal of Chest Diseases and Tuberculosis (2012) 61, 115120

The Egyptian Society of Chest Diseases and Tuberculosis

Egyptian Journal of Chest Diseases and Tuberculosis

www.elsevier.com/locate/ejcdt www.sciencedirect.com

ORIGINAL ARTICLE

Chemical pleurodesis for malignant pleural eusion

W. Shouman
a b c

a,b,c,*

, A. Elgazzar a, R.M. Hussien a, M. ElShaaray b, R.W. Light

Chest Department, Zagazig University, Egypt Cardiothoracic Surgery, Zagazig University, Egypt Chest and Critical Care Medicine, Vanderbilt University, USA

Received 5 May 2012; accepted 15 May 2012 Available online 15 March 2013

KEYWORDS Malignant pleural effusion; Pleurodesis; Tetracycline; Talcslurry; Iodopovidone; Bleomycin

Abstract Background and Objectives: Malignant pleural effusion is a common complication of primary and metastatic pleural malignancies. It is usually managed by drainage and pleurodesis, but there is no consensus as to the best method of pleurodesis, this study was designed to compare the effectiveness, side effects, and cost of different chemical pleurodesis agents used in patients with malignant pleural effusion. Methods: Seventy-ve patients with malignant pleural effusion were assigned into ve groups each of 15 patients, Talc slurry 5 gm, Tetracycline500 mg, Bleomycin1 IU/kg, Iodopovidone (2%) and patients underwent tube drainage only. Tube thoracotomy was performed in all patients and agents were administered through the chest tubes. Results: Tetracycline, talc slurry, iodopovidone andbleomycin, resulted inan insignicantly different success rates of 80%, 80%, 66.6%.73.3%, at 30 days and, 66.6%, 73.3%, 60%, 66.6%, at 60 days respectively while tube alone was much lower, 40% and 26.7% respectively. Chest tubes were removed after an average of 7.2 1.4 days for tetracycline, 7 0.8 days for talc slurry, 7.6 0.9 days for iodopovidone and 6.4 1.5 days for bleomycin which did not differ signicantly. Chest pain was more common in the tetracycline group, dyspnea was more common in the talc group, and fever was more common in the iodopovidone group. Conclusion: Since tetracycline, talc slurry, iodopovidone, andbleomycin achieved comparable success rates in this study, we suggest that the drug availability and cost are important factors in choosing a sclerosing agent in developing countries.
2012 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. All rights reserved.

* Corresponding author at: Chest Department, Zagazig University, Egypt. Tel.: +20 1005085302. E-mail address: [email protected] (W. Shouman). Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis.

Introduction Although the real incidence of malignant pleural effusion is not established, it is one of the most common problems that pulmonologists and oncologists face in their daily practice [1]. In one autopsy series metastatic pleural involvement was found in 29% of 191 cases of malignancy, but pleural effusion was present in only slightly more than half of these cases. Therefore, the

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0422-7638 2012 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ejcdt.2012.10.013

116 incidence of malignant pleural effusion in patients dying of malignancy in this particular series was 15% [2]. About 75% of malignant pleural effusions are secondary to malignancies of the lungs, breast or lymphoma [1]. In the United States more than 150,000 new cases of malignant pleural effusion are estimated to occur each year, with 75% being due to lung or breast cancers [3].The presence of a malignant pleural effusion indicates that the patient has advanced disease with an ominous prognosis, and with a very small chance of long-term survival. Many patients with malignant pleural effusion have dyspnea which limits the quality of their life. Tube thoracostomy with bedside pleurodesis has become the most common approach to palliate symptoms related to the effusion [1]. Pleurodesis is the obliteration of the pleural space by fusion of the visceral and parietal pleurae with brous tissue. Recurrent symptomatic pleural effusions and pneumothoraces are indications for pleurodesis. Most of the agents used for pleurodesis injure the pleura and cause an inammatory reaction together with a pleural effusion. Subsequently, the local activation of the coagulation system and the production of brogenic cytokines such as transforming growth factor lead to the production of collagen that can result in a pleurodesis.[4]. Tetracycline, doxycycline, bleomycin, and talc have been the agents most commonly used to produce pleurodesis [5] .Tetracycline has been replaced by doxycycline because the former is no longer available for parenteral use in most countries. Talc can be administered as either poudrage during thoracoscopy or as slurry via tube thoracostomy, with similar success rates [6]. Talc slurry is less expensive when the cost of the thoracoscopic procedure is considered [7]. The aim of this study was to compare the efcacy of tetracycline, talc slurry, Iodopovidone, bleomycin, and chest tube alone in producing pleurodesis in patients with malignant pleural effusions. Patients and methods The study protocol was approved by chest department, faculty and university councils including the Institutional Review Board at Zagazig University Hospitals. The study was performed in the chest, cardiothoracic surgery, oncology and radiotherapy departments between June2003 and September 2005. Initially, 125 patients were enrolled in the study. However, we encountered great difculty in getting follow-up for all patients because many patients did not return for their visits, did not have telephones and lived a long way from the hospital. Accordingly, we continued the study until we had 60 day follow-up in 15 patients in each group. The patients with malignant pleural effusion met the following inclusion criteria. 1. Malignancy as proven by positive pleural uid cytology, needle biopsy of the pleura or thoracoscopic biopsy. 2. A pleural effusion which was massive (occupying more than three quarters of the hemithorax or extending beyond the second rib anteriorly in the PA chest radiograph) or rapidly reaccumulating (dyspnea necessitating thoracenteses every 3 days or less). 3. Subjective improvement of patients dyspnea following thoracocentesis. 4. Total re expansion of the lung after uid drainage. 5. Pleural uid pH > 7.2. The following were exclusion criteria: 1. 2. 3. 4.

W. Shouman et al.

Atelectasis due to endobronchial obstruction. Pleural uid pH < 7.2 Prior intrapleural therapy Any radiotherapy to the affected hemithorax.

All patients included in the study signed an informed consent which was approved by the Institutional Review Board, after which a new chest Xray was obtained and a diagnostic thoracentesis was performed to conrm that the patient still met the inclusion criteria. The following investigations were done for pleural uids: - Pleural uid glucose, protein concentration, LDH (the upper limit of normal for serum was 480 IU/L, using the Dimension RXL Machine: DADE Behring.DIAMOND DIAGNOSTICS Holliston, MA, USA. - Pleural uid total and differential WBCs (CELL-DYN. ABBOTT, TEXAS, USA.) - Pleural uid pH using arterial blood gas machine ;(OMNI-C, ROCH, DIAMOND DIAGNOSTICS Holliston, MA, USA.) All patients underwent tube thoracotomy using large bore chest tubes (30 French). The patients were assigned to one of the following ve groups. Every fth patient received the same treatment. The intrapleural injections were done once the pleural uid output through the chest tube was less than 150 ml/day. Lidocaine 20 cc of 2% (AstraZeneca, London, UK) was installed intrapleurally 30 minutes before any chemical agent was injected. Group1: Intrapleural injection of 500 mg of tetracycline (Pzer, MiddleEast, Cairo, Egypt) mixed with 100 ml of sterile saline. [8].this low dose of tetracycline was intended to lessen the pain; it was used before by Wallach [9]. Group2: Intrapleural injection of 5 g of talc (mixed particles, sized from1045lm in maximum diameter) (Algomhorya .co. Ltd, Zagazig, Egypt), in 100 ml of normal saline. The slurry was made by mixing 5 gm of talc with normal saline and agitated gently [10]. Group3: Intrapleural injection of 20 ml 10% iodopovidone (NilePharmaceutical Co, 10th Ramadan City, Egypt) mixed with 80 ml normalsaline [11]. Group4: Intrapleural injection of 1 IU/kg bleomycin (Nippon Kayaku Co., Ltd. Tokyo, Japan), in 100 ml normal saline [3]. Group5: Chest tube only with no intrapleural injections. In the rst four groups whom received chemical agents, the tube was clamped immediately after injection of the pleurodesing solution and remained clamped for 2.5 h. During this time the patient was turned to the supine, prone, right and left lateral decubitus and sitting positions so that the chemical substance could come in contact with all pleural surfaces. The patient was kept in each position for 30 min. - After 2.5 h, the chest tube was unclamped. - Follow up chest radiographs were done every 24 h until the tube was removed.

Chemical pleurodesis for malignant pleural effusion Side effects were assessed as follows - Patients were said to have chest pain if they reported worse chest discomfort after the intrapleural injection. The patients had to volunteer that they had most chest discomfort; they were not asked specically about chest discomfort. - Patients were said to have fever if their temperature increased one or more degree Centigrade above what it had been anytime while they had the chest tube before the intrapleural injection - Patients were said to have dyspnea if they complained of dyspnea at a higher grade than was present before the procedure; The tube was removed when the amount of drainage was <150 cc/24 h in the groups that received the sclerosing agents, and when the amount of uid was less than 100 cc/24 h in the group that received only the chest tube. The smaller amount of drainage was required in the chest tube only group in order to increase the likelihood that it would be successful, after discharge the patient was followed by chest X-ray obtained monthly for the 2 month following pleurodesis. III- Assessment of the response: The effectiveness of pleurodesis was evaluated as follows: [12] - Complete response (success): Total resolution of pleural effusion, no recurrence of effusion on the chest X-ray during the period of follow up. - Failure: Recurrence of the pleural effusion on the chest X-ray, at any time during the follow up period. Statistical methods The values were presented as mean + SD. For comparison between groups, analysis of variance (ANOVA) was used for continuous variables and post hoc test or LSD was used to nd signicant differences between the groups. The chisquare test was used to compare the groups for the success rate of pleurodesis and the incidence of side effects. A p-value <0.05 was considered signicant. The EPI-INFO (2000) computer software package was used (WHO version). Results

117

Of the 75 patients who completed the study, 52 were male and 23 female. The age ranged from 31 to 70 years, the mean ages were comparable in the study groups. In addition there was no signicant difference in the distribution of the tumor types among the study groups, (Table 1). That there was no statistically signicant difference between groups regarding pleural uid parameters (WBCs, LDH, protein concentration, glucose level) (Table 2). The four sclerosing agents were all effective in producing pleurodesis. There was no signicant difference in the effectiveness of the chemical agents with complete responses occurring in 6780% in each group (Table 3), but there was a signicant difference between each of the agents and the control group (chest tube only group). There was no signicant difference in the duration of tube drainage after instillation of the four different chemical agents, but the group that received only tube thoracostomy had a signicantly longer period of chest tube drainage. The incidence of side effects following the intrapleural injection of the sclerosing agents were non signicant, dyspnea was most common in the talc slurry group occurring in ve of the patients while chest pain was the most common in the tetracycline group occurring in ve of the patients. Several patients in each group developed fever. There were no signicant differences in the incidences of any of the three side effects in the groups (Table 4). The presence of a positive pleural uid cytology was an indicator that the pleurodesis was less likely to be successful. The positivity of pleural uid cytology was 34% in successful patients, which was signicantly less than that of 88% in the patients who failed to achieve pleurodesis (Table 5). Discussion Our study demonstrates that tetracycline, talc slurry, iodopovidone and bleomycin, all resulted in comparable success rates of 80%, 80%, 66.6%, 73.3%, at 30 days and, 66.6%, 73.3%, 60%, 66.6% at 60 days respectively. Tube thoracostomy was the most inferior, yielding success rates of 40% and 26.7% at 30 and 60 days respectively. The duration of chest tube drainage was comparable in the four groups that received a sclerosing agent, but was longer in the chest tube only group. Chest pain was more common in the tetracycline group, dyspnea was more common in the talc group, and fever was more common in the iodopovidone group. The effectiveness of chemical pleurodesis in patients with recurrent, symptomatic malignant pleural effusions has been evaluated in many

Table 1

Cancer type distribution among study patients.

Tetracycline N (%) Talc slurry N (%) 426.6 426.6 320.0 213.3 213.3 Iodopovidone N (%) 533.3 320.0 320.0 213.3 213.3 Bleomycin N (%) 533.3 426.6 320.0 16.6 213.3 Tube only N (%) 640 320 320 213 16.6 p 0.42 0.83 0.12 0.14 0.63 533.3 533.3 213.3 213.3 16.6

Lung cancer Lymphoma Breast cancer Met.ad.carcinoma Mesothelioma

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Table 2 WBCs, LDH, protein and glucose in the pleural uid among studied patients.
Tetracycline WBC Cells/mm3 LDH. IU/L Glucose mg/dl Protein. gm/dl pH 698 137 1710 546 70 20 4.4 0.6 7.32 .06 Talc slurry 683 196 1810 248 72 14 4.5 0.5 7.33 .04 Iodopovidone 644 151 1890 395 79 11 4.2 0.5 7.28 .06 Bleomycin 699 186 1860 395 79 12 4.2 + 0.3 7.29 .06

W. Shouman et al.

Tube alone 594 184 1410. 475 76 11 3.8 0.5 7.33 .08

P 0.41 0.26 0.26 0.56 0.33

Table 3

Success rate of different pleurodesis methods among studied patients.

Tetracycline (n = 15) NO. % Talc slurry (n = 15) NO. % 12 (80) 11 (73) Iodopovidone (n = 15) NO. % 10 (66.7) 9 (60.0) Bleomycin (n = 15) NO. % 11 (73.3) 10 (66.7) X2 P 7.60.1 Tube only (n = 15) NO.% 6 (40)

Success rate at 30 days Success rate at 60 days

12 (80) 10 (66.7)

8.47 07 4 (26.7)

Table 4

Complications encountered due to pleurodesis in different study groups.

Tetracycline No (%) 13% 33.3% 13% Talc slurry No 5 4 4 (%) 33.3% 26% 26% Iodopovidone No 1 2 5 (%) 6.5% 13% 33% Bleomycin No 1 4 4 (%) 6.5 26% 26% Tube only No 1 1 2 (%) 6.5% 6.5% 13% 0.14 0.36 0.63 P

Dyspnea Chest pain Fever

2 5 2

studies. However, there is still much debate about which agent is best. It is very difcult to compare the effectiveness of these agents between studies because different studies used varying doses of the sclerosing agents and different techniques for pleurodesis (tube size, duration for tube thoracostomy before and after the injection of the sclerosant and varying criteria for success) [13]. Currently, talc either in sufation or as slurry, tetracycline derivatives, mitoxantrone, bleomycin, silver nitrate and iodopovidone are the most commonly used sclerosing agents [5]. The goal of our current study was to compare the effectiveness of four of these agents in which the same pleurodesis procedure was used. Talc was the rst agent to be used for pleurodesis. In 1935 Bethune instilled talc intrapleurally in an attempt to create pleural adhesions after a lobectomy [14].In a survey of pleurodesis practices among English speaking pulmonologists in 2003, talc was the agent most commonly used [5]. Talc is commonly used because it is inexpensive, widely available and perceived to be very effective. However, in the largest study ever done with pleurodesis, talc either insufated or administered as slurry was not particularly effective [5]. In this prospective, randomized trial [6], with 482 patients reported by Dresler et al. [6], the success rate with insufated talc administered at thoracoscopy was comparable with that of talc slurry [6], The success rates at 30 days with insufated talc was (78%) and for talc slurry was (71%), which did not differ signicantly [6]. Most troublesome was the signicant mortality when talc was administered in either manner. Treatment-related mortality occurred in nine (3.7%) of patients receiving talc insufation and seven (2.9%) patients receiving talc slurry. Respiratory complications were more common following talc insufation than talc slurry (14% vs. 6%). Respiratory failure

was observed in 4% of talc slurry patients and 8% of talc insufation patients. Other studies with talc have reported higher success rates, Haddad et al. [15] reported a success rate of 85% for 71 patients treated with 4 gm talc slurry. Adler and Sayek [16] reported a success rate of 93% in 41 patients treated with 10 gm of talc. In the current study, the success rates of talc slurry were 80% after 30 days and 73.3% after 60 days, which are comparable to the results of Haddad et al. [15] and Dresler et al. [6]. But it was lower than that reported by Adler and Sayek, a possible explanation for the higher success ratesreported by Adler and Sayek is that, they used a higher dose of talc (10 gm) [16]. In the talc slurry group, the most common side effect was dyspnea which occurred in 33.3%. However, none of our patients developed ARDS. Tetracycline and its derivatives were the second most commonly used agent for chemical pleurodesis in the survey of pleurodesis practices among English speaking pulmonologists in 2003. In this survey, who used tetracycline or its derivatives

Table 5 Effect of positive pleural uid cytology on pleurodesis success in different patients group.
Positive PF cytology Positive PF cytologyin p in success group No (%) failed group No (%) Tetracycline 5/12 (41%) Talcslurry 4/12 (33.3%) Iodopovidone 3/10 (30%) Bleomycin 2/6 (33.3%) Tubeonly 3/10 (30%) TOTAL 17/50 (34%) 3/3 (100%) 3/3 (100%) 4/5 (80%) 8/9 (88.8%) 4/5 (80%) 22/25 (88%) 0.024 0.035 0.032 0.023 0.032 0.02

Chemical pleurodesis for malignant pleural effusion reported success rate sof 61 19% [5]. Sherman et al. [17] reported that tetracycline in a dose of 1,500 mg, effectively controlled malignant pleural effusion in 94.4% of 108malignant pleural effusions at 30 days. Another study reported that, pleurodesis was achieved with 500 mg tetracycline in (67%) of 356patients [9]. In the current study tetracycline achieved pleurodesis in 80% of patients at 30 days and in 66.7% at 60 days. Our results were consistent with the results reported by Wallach [9], but were less than those reported by Sherman et al. [17], possibly because of the high dose of tetracycline 1500 mg used in Sherman study compared to 500 mg used in our study. The most common side effect for Tetracycline in most studies has been chest pain. The intrapleural administration of tetracycline in patients with spontaneous pneumothorax was associated with intense chest pain in many patients [18]. In our study, tetracycline caused chest pain in 33%, dyspnea in 13% and fever in 13% of patients. A possible reason that patients in present study did not have more pain is that they received Lidocaine 2% intrapleurally and the dose of tetracycline was lower (500 mg). Bleomycin was the third most commonly used agent for creating pleurodesis in the survey of pleurodesis practices among English speaking pulmonologists in 2003. In this survey, physicians who used bleomycin reported success rates of 62 16% [5]. The popularity of bleomycin is due in part to the randomized controlled study by Ruckdeschel et al. [19] who compared 60 units of bleomycin and 1000 mg of tetracycline in 44 patients. In this study the success rate with bleomycin at 30 days (64%) was signicantly (p = 0.023) higher than that with tetracycline (33%) [19]. in a review of 199 patients treated with bleomycin for malignant pleural effusion, a complete response was achieved in 54% (108 patients) [20]. Subsequently, Diacon et al. [21], in a prospective, randomized comparison of bleomycin and talc slurry in 36patients reported that the complete response rate with bleomycin (59%) was insignicantly (p = 0.12) less than that for talc (87%) [21].In the current study bleomycin achieved pleurodesis in 73.3% of patients at 30 days and in 66.6% at 60 days, the response rates to bleomycin in the current study tended to be slightly higher than those reported in the literature. Although the general concept is that bleomycin is less effective than talc or tetracycline derivatives in producing pleurodesis [15], in the current study bleomycin achieved a success rate comparable to both talc and tetracycline. The disadvantages of bleomycin are its higher cost, compared with talc and tetracycline, but not a lower success rate at least in the present study. Few studies had compared the three agents, but in the survey of Lee et al. [5] comparing the perceived success rates of the most commonly used agents for creating pleurodesis, physicians who used talc poudrage reported a signicantly higher success rate (73 17%) of pleurodesis than those used talc slurry (68 17%), tetracycline and its derivatives (61 19%), and bleomycin (62 16%). Those who used talc slurry in turn reported a higher success rate than tetracycline derivatives and bleomycin [5]. Iodopovidone is a topical antiseptic which has been shown to be safe and effective when used for pleurodesis in several series, including multicenter studies [2224]. Olivares et al. [24] reported that iodopovidone is an effective, safe, readily available, and inexpensive alternative to achieve chemical pleurodesis in cases of recurrent, incapacitating effusions, regardless of etiology. In the prospective multicenter study of

119 Olivares and coworkers [24] 100 ml of 2% iodopovidone was instilled intrapleurally in 52 patients. In this study a complete response (no reaccumulation of the uid during the follow-up), was obtained in 50 patients (96.1%). Echavarria et al. [22]reported a complete response in all 15 patients with malignant pleural effusion who underwent pleurodesis with iodopovidone. The efcacy of iodopovidone in a prospective study by Ritech et al. [25] in which pleurodesis was performed with iodopovidone 2% solution infused through a chest tube and left in the pleural cavity for 4 h. was86.5% [25]. In another study by Garcia et al. [26], successful pleurodes is was achieved in 9 of 14 patients (64.2%) by iodopovidone through tube thoracostomy [26]. In the current study, the success rate of iodopovidone 2% was 66.7% at 30 days and 60% at 60 days which did not differ signicantly from the other agents (tetracycline, talc slurry, bleomycin). Our results were similar with those of Garcia et al. [26], but lower than those of Olivares et al. [24] possibly because thoracoscopy was used in most patients in the latter study. Our results were also inconsistent with Ritech et al. (86.5%) [25], It should be noted that in this study of Ritech et al. [25], the solution was left in the pleural cavity for a long period (4 h), and the 64 patents included in this study 37 of them had malignant pleural effusion and 27 had pneumothorax, this may explain the higher success rate in this study [25], compared to our success rate (66.7%).The reported side effects of iodobovidone in our study were dyspnea 6.5%, chest pain 13% and fever33%. An interesting nding in our study was that most of patients who failed to achieve pleurodesis had positive pleural uid cytology for malignancy 22 of 25 (88%), while only 17 of 50 (34%) with successful pleurodesis had positive cytology. We hypothesize that the lower rate of pleurodesis inpatients with positive cytology is due to the fact that they have a larger tumor burden which covers a higher percentage of the pleural surfaces. Accordingly, the mesothelial cells are covered with the tumor and cannot respond to the pleurodesis agents in the usual manner. Conclusion Chemical pleurodesis is a widely accepted method of treatment for recurrent symptomatic malignant pleural effusions. The agent of choice should be safe, easy to apply, readily available, inexpensive, and associated with a high rate of success. Since in this study comparing talc slurry, tetracycline, iodopovidone, and bleomycin no agent was signicantly better than the others, we suggest that economic costs, drug availability and medical skill should be considered in the choice of a sclerosing agent. References
[1] R.W. Light, Y.C. Lee, Textbook of Pleural Diseases, Arnold Publisher, London, 2003, pp. 97 chapter 22. [2] F. Rodriguez-Panadero, F. Borderas Naranjo, J. Lopez- Mejias, Pleural metastatic tumours and effusions: frequency and pathogenic mechanisms in a post-mortem series, Eur. Respir. J. 2 (1989) 366369. [3] American Thoracic Society, Management of malignant pleural effusions, Am. J. Respir. Crit. Care Med. 162 (2000) 19872001. [4] R.W. Light, Pleural Diseases, fourth ed., Lippincott, Williams and Wilkins, Philadelphia, PA, 2001, pp. 120123.

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[5] Y.C. Gary Lee, Michael H. Baumann, Nick A. Maskell, Grant W. Waterier, Tam E. Eaton, et al, Pleurodesis practice for malignant pleural effusions in ve English-speaking countries, survey of pulmonologists, Chest 124 (2003) 22292238. [6] C.M. Dresler, J. Olak, J.E. Herndon 2nd, et al, Phase III inter group study of Talc Poudrage vs. Talc Slurry Sclerosis for malignant pleural effusion, Chest 127 (2005) 909915. [7] A.P. Yim, A.T. Chan, T.W. Lee, et al, Thoracoscopic talc insufation versus talc slurry for symptomatic malignant pleural effusions, Ann. Thorac. Surg. 62 (1996) 16551658. [8] M.J. Moffett, J.C. Ruckdeschel, Bleomycin and tetracycline in malignant pleural effusions: a review, Semin. Oncol. 19 (Suppl5) (1992) 5963. [9] H.W. Wallach, Intrapleural tetracycline for malignant pleural effusions, Chest 68 (1975) 510512. [10] P.W. Zimmer, M. Hill, K. Casey, E. Harvey, D.E. Low, Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions, Chest 112 (1997) 430434. [11] E. Martinez-Moragon, J. Aparicio, M.C. Rogado, J. Sanchis, F. Sanchis, et al, Pleurodesis in malignant pleural effusions: a randomized study of tetracycline versus bleomycin, Eur. Respir. J. 10 (1997) 23802383. [12] Farouk abd el kader, Esamgoda, Shadiaabd el aziz, Comparative study of different modalities of chemical pleurodesis in management of malignant pleural effusion after a period of follow up, Egy. J. Chest Dis. Tub. 49 (2) (2000). [13] Dalokay Kilic, Hadi Akay, Sevket Kavukc u, Hakan Kutlay, AytenKayi Cangir, et al, Management of recurrent malignant pleural effusion with chemical pleurodesis, Surg. Today 35 (2005) 634638. [14] N. Bethune, Pleural poudrage: new technique for deliberate production of pleural adhesions as preliminary to lobectomy, J. Thorac. Cardiovasc. Surg. 4 (1935) 251261. [15] F.J. Haddad, R.N. Younes, J.L. Gross, et al, Pleurodesis in patients with malignant pleural effusions: talc slurry or bleomycin? Results of a prospective randomized trial, World J. Surg. 28 (2004) 749752. [16] R.H. Adler, I. Sayek, Treatment of malignant pleural effusion: a method using tube thoracostomy and talc, Ann. Thorac. Surg. 22 (1976) 815.

W. Shouman et al.
[17] S. Sherman, K.P. Ravikrishnan, A.S. Patel, et al, Optimum anesthesia with intrapleural Lidocaine during chemical pleurodesis with tetracycline, Chest 93 (1988) 533536. [18] R.W. Light, V.S. OHara, T.E. Moritz, A.J. McElhinney, R. Butz, et al, Intrapleural tetracycline for the prevention of recurrent spontaneous pneumothorax. Results of a department of veterans affairs cooperative study, JAMA 264 (17) (1990) 22242230, Nov 7. [19] J.C. Ruckdeschel, D. Moores, J.Y. Lee, et al, Intrapleural therapy for malignant pleural effusions. A randomized comparison of bleomycin and tetracycline, Chest 100 (1991) 15281535. [20] P.B. Walker-Renard, L.M. Vaughan, S.A. Sahn, Chemical pleurodesis for malignant pleural effusions, Ann. Intern. Med. 120 (1994) 5664. [21] A.H. Diacon, C. Wyser, C.T. Bolliger, M. Tamm, M. Pless, A.P. Perruchoud, et al, Prospective randomized comparison of thoracoscopic talc poudrage under local anesthesia versus bleomycin instillation for pleurodesis in malignant pleural effusions, Am. J. Respir. Crit. Care Med. 162 (2000) 14451449. [22] A. Echavarria, V. Pinzon, J.P. Bares, E. Fernandez, Intracavitary treatment of malignant pleural effusion with iodine-povidone, Rev. Med. Panama 16 (1991) 6974, in Spanish. [23] O. Brissaud, L. Desfrere, R. Mohsen, M. Fayon, J.L. Demarquez, Congenital idiopathic chylothorax in neonates: chemical pleurodesis with povidone-iodine (Betadine), Arch. Dis. Child. Fetal Neonatal. Ed. 88 (2003) F531F533. [24] C.A. Olivares-Torres, R. Laniado-Laborin, C. Chavez-Garcia, C. Leon-Gastelum, A. Reyes Escamilla, R.W. Light, Iodopovidone pleurodesis for recurrent pleural effusions, Chest 122 (2002) 581583. [25] A. Ritesh, N. Ashutosh, G. Dheeraj, Efcacy and safety of iodopovidone pleurodesis through tube thoracostomy, Respirology 11 (2006) 105108. [26] J. Kelly-Garcia, J.F. Roman-Berumen, C. Ibarra-Perez, Preliminary report: iodopovidone and bleomycin pleurodesis for effusions due to malignant epithelial neoplasms, Arch. Med. Res. 28 (1997) 583585.