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Ann Thorac Surg 1996;62:1003-1004
© 1996 The Society of Thoracic Surgeons
DR JOSÉ RIBAS MILANEZ CAMPOS (São Paulo, Brazil): First of all, I congratulate Dr Cohen for the paper and his presentation.
At the University of São Paulo in Brazil, we have been using 2 g of talc as an agent to promote pleurodesis, delivering it through a thoracoscopic approach since 1983, with effective results of 94.6%. We have used this technique in more than 230 patients with malignant pleural effusion when it is established that the lung will fully expand.
A few months ago, we used this technique in a breast cancer patient. Two days later, talc crystals were noted in her bronchoalveolar lavage. Later on, this patient died, and her autopsy revealed talc emboli in pulmonary vessels and cerebral arteries.
Concerned about this finding, we went to the laboratory and, working with a rat model using 0.002 g, we were able to detect adhesions in the pleural space and talc emboli in the contralateral lung. We also found emboli of talc in the liver, spleen, kidney, and the brain in almost 100% of the animals that were killed 48 to 96 hours after the pleural application of talc.
In our opinion, these issues about talc—how to use it, the amount to be used, and the collateral effects it can cause—deserve much more research.
DR COHEN: Doctor Campos, thank you very much for your comments.
We did not specifically look for the presence of talc in other organs, and we only saw it occasionally in the lungs in the studies that we did. I agree that most people's experience would confirm that the side effects and toxicity from talc in the pleural space are probably dose related. We had 1 patient who had what appeared to be an anaphylactic reaction; we had used 10 g in that patient. We have used 5 g very safely, and it seems that 5 g seems to be the dose of choice among most surgeons.
DR CAROLYN M. DRESLER (Philadelphia, PA): I found this paper very interesting because of some ongoing trials looking at talc. A couple of things may be a problem in working with immature pigs. The problem in humans is malignant pleural effusions. The issue that the current trial is investigating malignant pleural effusions, and most surgeons think that video-assisted thoracic surgery is probably most useful because you can get a good circumferential look at the lung, you can break down the adhesions, and you can create a reexpanded lung. Lack of reexpansion and adhesions would not have been a problem with the immature pig. I noted in 1 of your pigs that you did have a problem because of the position of the lung, so perhaps this points out a problem in getting a good circumferential distribution of the talc.
One of the things you had said is that talc slurry was probably going to be better; however, when you looked at the 11 pigs, the pig that did the best was the one that had video-assisted thoracic surgery. It was this pig that had the most dense adhesions, versus 1 other pig that had talc slurry and that did not do as well. So I think the question is still unanswered about whether talc slurry or the video-assisted thoracic surgery talc procedure is going to be best. No doubt the cost is going to be considerably different, but in the human patient with a malignant pleural effusion, the answer is still unknown.
The question I would like to address to the last discussant is whether the use of talc is still of concern to physicians? As you implied, the dosage is not at all known. There are no good studies exploring appropriate dosages. Doctor Sahn, who is a pulmonologist and has looked at this issue of talc toxicity, definitely has found talc particles in multiple other organs in animal models. I think we need to be addressing this question in humans.
This was an excellent presentation.
DR COHEN: I agree with Dr Dresler that our study was performed in young animals with normal pleural spaces. The reason is that the real rationale for the study was to see how well the two modalities would distribute the talc. I also agree that there are patients who have loculated or complex effusions who are good candidates for thoracoscopy, because you can take these down and get a better pleurodesis. However, I also think that when you put a chest tube in and get good lung inflation, the majority of patients are candidates for talc slurry. I think you can get a similar result without having to expose them to the morbidity of a general anesthetic and thoracoscopic talc poudrage. I must say that we learned that lesson the hard way: We have seen some substantial morbidity and some deaths by not selecting our patients well in terms of which ones with malignant pleural effusions were going to tolerate general anesthesia.
In regard to the fact that 1 pig had a better result with one technique over the other, I think that it is hard to make assumptions based on only 1 animal. Eight of the 10 pigs had almost identical results with both modes. I suspect that there was a delivery problem with the talc slurry in that animal, though we were not able to ascertain that for sure.
DR LEWIS WETSTEIN (Freehold, NJ): Doctor Campos' comments are extremely distressing. Nevertheless, putting them aside for a second, do you have any preliminary clinical data? Do you use this technique for pneumothoraces? If you do, do you use the talc slurry for an initial pneumothorax, or do you use it only for recurrent pneumothoraces?
DR COHEN: We are reluctant to use talc at all for patients with benign disease. However, I think that there is a group of patients who are older and have chronic obstructive pulmonary disease with recurrent pneumothoraces who are not candidates for transplantation but are candidates for talc pleurodesis, with good results.
DR WETSTEIN: If you do not use talc, do you use any other modality for pneumothorax, or none at all?
DR COHEN: I do not use anything other than talc now, no.
DR JOSEPH LoCICERO III (Boston, MA): This was an excellent paper. I think this area needs a lot more study. I want to caution people who are going to be using talc slurry. Maybe Dr Cohen would want to comment on his own clinical application. We have found that this is a suspension in which the talc comes out of solution extremely fast. Because of this, the old traditional techniques of placing tetracycline or doxycycline in the chest, clamping the tube, and rolling the patient around for several hours really do not matter. So placing it in through a small needle in the tube over a long period of time and allowing the patient to be at bed rest for a long time really is not the appropriate method. We place the talc slurry in very rapidly and release the chest tube immediately, because it is going to come out of suspension right into the lung immediately.
DR COHEN: In our experimental model, we duplicated the technique that was described by Watts Webb in 1992 because of his excellent results, and I certainly agree that you have to make sure that the talc is in solution and that you give it and flush the talc quickly.
DR SEPPO E. RAPO (Hyannis, MA): Do you have any experience with or any comments on the now experimentally available aerosolized talc?
DR COHEN: Our experience is limited. I have found that the jet on the commercial talc, because it comes through a very small tube, is difficult to distribute; you really have to paint the lung with it. In addition, the cost is many times more than just having your pharmacy sterilize 5 g of USP talc.
DR STEVEN M. SCHWARTZ (Campbell, CA): Your last comment brings up the question of how you go about sterilizing the talc. The only approved way that I know is dry heat sterilization, which is not widely available commercially. As far as I know, the only commercially sterile preparation of talc that is available is the aerosolized can. I would like to hear your comments about how you prepare it.
DR COHEN: I believe our talc is heat sterilized. Early on, they were culturing it every few weeks to make sure that it was sterile, but sterility has not been a problem.
DR DRESLER: I was recently at the Food and Drug Administration's ODAC evaluation looking at the question of talc, because the Bryan Corporation, which makes the aerosolized talc, has been trying for the past year to get Food and Drug Administration approval. First of all, there is no approved method for sterilizing talc. There are three recommended methods, for which I would refer you to a 1995 article in Chest (107:1032–4). Talc is readily available from a large number of chemical companies. The Bryan Corporation talc may or may not be approved in the future. There still is the question of toxicity, which must be answered. At present, however, it is the only talc commercially available as an investigational new drug with the Food and Drug Administration.
Related Article
Ann. Thorac. Surg. 1996 62: 1000-1002.
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