- Email: [email protected]
Talc pleurodesis
Talc pleurodesis Experience with 360 patients Talc was used intrapleurally for the creation of pleural adhesions in 360 patients. The indications for use were malignant pleural effusion in 169 patients, benign effusions in 41, recurrent pneumothorax in 122, empyema in 19, and chylothorax in 9. Of 336 patients available for foUow-up, exceUent results (complete pleurodesis) were achieved in 284 patients (84.5 %~ fair results in 28 (8.3% ~ and poor results (no adhesions) in 24 (7.2%). The results were best in empyema (100%) and better in pneumothorax than in pleural effusions. With repeat talc insufflation, the results were improved to exceUent in more than 90% of the patients. Talc is the most effective and least expensive agent for creation of pleural adhesions. Its use is simple and easily tolerated by the patients. Because-of the carcinogenic effect of asbestos, purified talc that is free of asbestos fibers must be used. (J 'fHORAC CARDIOVASC SURG 1993;106:689-95)
Dov Weissberg, MD, FRCSC, FACS, FCCP, and Ilan Ben-Zeev, MD,
Uliteration of the pleural space by adhesions is indicated when recurrent accumulations of liquid (effusion, chyle, or any other) or recurrent episodes of pneumothorax prevent complete expansion of the lung. Methods for creation of pleural adhesions include pleurectomy, pleural abrasion, and intrapleural instillation ofvarious agents capable of stimulating inflammatory reaction. Many irritating substances have been tried including bleomycin, various cytostatic agents, and talc, which are the few that remain in use today. It has long been known that talc causes adhesions of serosal surfaces. Since 1935, talc has been used therapeutically for intrapleural insufflation, to prevent recurrent spontaneous pneumothorax, and for control ofmalignant pleural effusions. After the original report of Bethune, I various methods of talc instillation have been described.v" Although the results were satisfactory, talc has not been universally accepted because of its alleged potential for complications. Febrile reactions, granuloma, Fromthe Departmentof ThoracicSurgery,Tel Aviv University Sackler Schoolof Medicine, E. Wolfson Medical Center, Holan, Israel. Received for publication Aug. 4, 1992. Accepted for publication Dec. 11, 1992. Address forreprints:DovWeissberg, MD, E. Wolfson MedicalCenter, Holan 58100,Israel. Copyright w 1993 by Mosby-Year Book, Inc. 0022-5223/93$1.00 +.10 12/1/45058
Holon, Israel
flbrothorax.l adult respiratory distress syndrome.P and, most important, malignant mesothelioma and bronchogenic carcinoma7,8 were mentioned among the possible complications of its use. We have been using talc for obliteration of the pleural space since 1974. This article summarizes our experience with 360 patients.
Patients and methods Between 1974 and 1991 talc was used intrapleurally in 360 (211 male and 149 female) patients, ranging in age from 14 to 84 years. The indications for use were control of malignant pleural effusion in 169 patients, benign effusions of various origins in 41, recurrent spontaneous pneumothorax in 122, empyema in 19, and chylothorax in 9. Before introduction of talc, the pleural cavity is emptied of all fluid,and complete lung expansibility is assured. When the lung is not fully expansible, talc is not introduced. Two grams of sterile iodized talc are used in each procedure. Talc is instilled by one of two methods. In patients who undergo pleuroscopy, talc is insufflated at the end of the procedure through the lumen of the mediastinoscope, under vision, with a bulb syringe. During the insufflation, the direction of the mediastinoscope is changed frequently to assure even distribution of talc over the entire pleural surface. A thoracostomy tube is inserted into the pleural cavity through a separate stab wound incision and is connected to an underwater seal with suction of 10 to 20 em H 20 . This method was used in 272 patients. In 88 patients in whom pleuroscopy was not indicated, suspensionof talc was instilled through the pleural drain. With this method, all liquid or air is evacuated through an intercostal
6R9
690
The Journal of Thoraclcand Cardiovascular Surgery October 1993
Weissberg and Ben-Zeev
Table I. Results ofpleural poudrage in 336 patients No. ofpatients (%) Indications Malignant effusion (n = 169) Benign effusions (n = 41) Pneumothorax (n = 122) Empyema (n = 19) Chylothorax (n = 9) Total (n = 360)
Died within 1 month 12
Lost to follow-up 3 9
12
12
drain, and completeexpansion of the lung is verified by radiography. A suspension of 2 gm talc in 30 ml normal salinesolutionisinjectedthroughthe tube drain intothe pleuralcavity,and the drain is flushed with another 20 ml of saline solution. The drain is then clamped for 2 hours, and the patient is instructed to change bodypositionfrequently, thus aidingin evendistribution of talc. After 2 hours,the tube is reconnected to the underwater seal with suctionfor 3 or 4 days. If, after 3 days,the chest roentgenogram shows complete lung expansion, the tube is removed. On severaloccasions, when expansion of the lung at the control roentgenogram was not complete, a suspension of talc was instilled through the chest tube again, and suctionwas continued for another 4 days.
Results Twelve patients died before the results could be evaluated. None of the deaths were related to poudrage, although one patient died several hours after the insufflation. The cause of death in this case was massive pulmonary embolism. Twelve other patients were lost to followup. The results were evaluated in 336 patients (Table I). Our evaluation of results was subjective, depending to a large extent on the physician's judgment and interpretation of radiographic findings. However, in practice, it proved satisfactory and correlated well with the patients' symptoms. Results were classified as excellent if complete pleurodesis was achieved without any evidence of fluid accumulation or pneumothorax at follow-up examinations (Fig. 1). The results were considered fair if most of the lung became adherent to the chest wall and marked symptomatic and radiographic improvement occurred. Patients with small, usually loculated accumulations of fluid and residual, sealed-off pockets of air were included in this category (Fig. 2). The outcome was considered poor if no adhesions or only minor adhesions formed without practical beneficial effect. Excellent results were achieved in 284 patients (84.5%), fair in 28 (8.3%), and poor in 24 (7.2%). The results were uniformly excellent in patients with empyema and were better in patients with
Results Evaluated 154 41 113 19 9 336
Excellent 130 30 98 19 7 284
(84.4) (73.2) (86.8) (100) (77.8) (84.5)
Fair
Poor
12 (7.8) 6 (14.6) 10 (8.8)
12 (7.8) 5 (12.2) 5 (4.4)
28 (8.3)
2 (22.2) 24 (7.2)
pneumothorax than in those with pleural effusions (Table I).
Discussion Attempts at obliteration of the pleural space are often viewed with suspicion and have drawn criticism because of alleged interference with respiratory function. This suspicion is unfounded. It has never been shown that a free pleural cavity is necessary for the lungs to function properly. The presence of the pleural cavity is the result of a peculiar embryologic development in some species but not in others; its mere existence does not necessarily imply function and usefulness. For example, a pleural space does not exist in the elephant, but this does not in any way impair the animal's breathing capacity. It thus appears that obliteration of the pleural space can be done without harm and without significant long-term negative effects. The fibrosis caused by talc is related to the amount used. Use of excessive amounts of talc will result in excessive fibrosis of the pleura and trapping of the lung, affecting pulmonary function. However, a minimal dose of a fibrosing agent, barely sufficient for obliteration ofthe pleural space, does not have this effect and can be used safely. This has been demonstrated in the classic work of Paul, Beattie, and Blades? in 1951, who used talc intrapleurally for treatment of recurrent spontaneous pneumothorax with no untoward effect on pulmonary function. Their results were confirmed by Lange, Mortensen, and Groth.l'' who studied patients 22 to 35 years after intrapleural instillation of talc and found only a mild restrictive impairment. McGahren and associates 11 used talc for obliteration of the pleural space in growing pigs. The use of talc caused a temporary impairment in dynamic transpulmonary and transrespiratory compliance, but this resolved with time and growth. The longterm evaluation showed only minimal effects on pulmonary compliance. It is mandatory, however, to use the minimum amount of talc to avoid the intensification of
The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 4
Weissberg and Ben-Zeev
69I
Fig. 1. A, Massive idiopathic right pleuraleffusion in a 25-year-old woman. Because of recurrence, talc was insufflated at pleuroscopy. B, One-year follow-up. Excellent result of poudrage,
these effects. We have found our maximum dose of 2 gm of talc to be safe. Long-term results of pleural obliteration should be evaluated not only with regard to time but also in relation to underlying diagnoses. Most recurrences of pneumothorax occur within 6 months. Although we follow up our patients for as long as they keep appointments, often for 5 to 6 years or more, we have never seen recurrence beyond the first year. Accordingly, a I-year follow-up should be considered adequate. Inthe majority of patients
with malignant pleural effusion, the follow-up is virtually irrelevant because the median survival time is only 3V2 months. However, differences in survival exist among patients with various cancers. Although the median survival for patients with malignant pleural effusion because of bronchogenic carcinoma is only 2V2 months, patients with breast cancer and malignant pleural effusion survived a median of 7V3 months. Follow-up is obviously more important for patients with breast cancer and malignant pleural effusion than it is for patients with
692
Weissberg and Ben-Zeev
The Journal of Thoracic arid Cardiovascular Surgery October 1993
Fig. 2. A, Malignantpleuraleffusion as a resultof carcinomaof breast in a 72-year-old woman. B, Roentgenogram taken 3 months after poudrage, showing fair result. malignant pleural effusion because of bronchogenic carcinoma. Talc pleurodesis can fail for a number of reasons, including trapped lung as a result of thickened pleura, irregularly scattered adhesions preventing good lung expansion, loculation of the pleural space by fibrin and adhesions, loss of pulmonary elasticity, high liquid output interfering with creation of adhesions, and extensive pleural metastases. Some of these factors can be diagnosed ahead of time and should be regarded as contraindications for the use of talc.
Talc has several advantages over other agents capable of creating adhesions and obliterating the pleural space. Tetracycline gained great popularity in recent years and became the most widely accepted sclerosant. However, its use results in much pain, likened by Stephenson'? to scalding water injected through the chest tube. Therefore, it must be used in combination with either local anesthesia or heavy sedation; however, the pain is severe, and these measures are often inadequate. In addition, the effectiveness of tetracycline is only about 50%,13 whereas the average effectiveness of talc is 95%.14.15 The effec-
The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 4
tiveness of bleomycin is reported to be near 65%,13, 16 still far below that of talc. In addition, bleomycin is systemically absorbed, with a potential for systemic toxicity. Associatedalopecia and mucositishave been described by Siegel and Schiffman.!? In these days of cost-effectiveness, the high cost of bleomycin also cannot be disregarded. The use of quinacrine was successful in 80% of patients but was accompanied by a high complication rate, with fever for up to 10 days in nearly all patients and pain, nausea, vomiting, and hallucinations. I S-20 Tetracycline and quinacrine are no longer available. Objection to the use of talc has been expressed by Rinaldo, Owens, and Rogers" because of its alleged association with adult respiratory distress syndrome. In their experiencewith four patients, this syndrome occurred in the three who received 10 gm talc intrapleurally. The fourth patient received 5 grn talc, and adult respiratory distress syndrome did not develop. The reported complication was most likely dose related.i' We are not aware of any other reports linking talc with adult respiratory distress syndrome. It is possiblethat an excessive amount of talc is capable of inducing adult respiratory distress syndrome, and we have stressed repeatedly that no more than 2 grn should be used for obliteration of the pleural space.21-24 A much more widely publicized objection to the use of talc is its alleged association with pleural mesothelioma and bronchogenic carcinoma. Talc is a generic term that includes,in addition to the pure mineral talc, impure massive talcose rocks (soapstone). These may contain as little as 50% mineral talc. Mineral talc is hydrous magnesium silicate corresponding approximatelytotheformula3MgO . 4Si02' H20.22,25-27Themost important contaminant of talc linked to carcinogenesis is asbestos. It consists of six naturally occurring minerals: chrysotile, crocidolite, amosite, anthophyllite, tremolite, and actinolyte. In carcinogenesis, the major determining factor is the diameter of the fiber: those with the lesser diameter are more carcinogenic. Fibers responsible for mesothelioma have a diameter of less than 0.25 ttm and probably a length greater than 5 ttm.2S The most significantcontaminant, tremolite, Ca2Mg5Sis022(OHh, consists of long, fibrous, needle-shaped particles that are 10 to 200 ttm long (50%) and irregularly shaped particles that are less than 10 ttm in greatest projected diameter (50%).25 These fine fibers oftremolite are responsible for its carcinogenic effect. Likewise,crocidolite (blue asbestos) and amosite (brown asbestos) are composed of tiny fibers. Tremolite, crocidolite, and amosite are most commonly implicated in carcinogesis.P'" No crysotile exposures with an exceptionally high risk of mesothelioma have been reported thus far. 32
Weissberg and Ben-Zeev
693
Talc must be free of all carcinogenic contaminants to be suitable for clinical use. Purified talc is finely powdered magnesium trisilicate, a physical irritant capable of creating adhesions and granuloma but not cancer.P This distinction has been shownvery convincinglyby Kleinfeld and associates.I" They studied the prevalence of cancer and respiratory diseases in talc miners and millers in the state of New York, where talc is heavily contaminated with amphiboles and free silica. Initially, talc was associated with an increased mortality as a result of mesothelioma and cor pulmonale. Later, according to the same authors.F' after dust levels had been reduced, the death rates for malignant diseases among the mine employees became similar to those in the United States in general. The results of their studies were confirmed conclusivelyin animal experiments by Wagner and associates.l" In their study, 48 rats received chrysotile asbestos intrapleurally. Mesothelioma developedin 18 animals. In another group of 48 rats exposedsimilarly to cosmetic (purified) talc, no mesotheliomas were found. These studies show clearly that the carcinogenic substance is asbestos, not purified talc. The purified talc that we use is produced in Israel by Frutarom, Inc. It corresponds with the requirements of the British Pharmacopoeia-S 27 and does not contain any asbestos. It isoften assumed that adhesionscaused by talc are the result of an inflammatory reaction. However, not every inflammatory reaction results in adhesions, and it is possible that the adhesions resulting from talc are caused not by an acute inflammatory reaction but by a different, fibrosis-stimulating mechanism. The problem of inflammation versus fibrosis-stimulating mechanism is a real one and is well demonstrated by our experience with empyema.V No one questions that empyema is an inflammatory process. As such, it should stimulate creation of pleural adhesions, and it often does. However, in certain patients with empyema, the fully expansible lung does not become adherent to the chest wall, and the pus continues to accumulate. Our experience includes 19such patients; all were eventually treated with talc, and all had excellent results (Table I). If inflammation, per se, were the only factor necessary for creation of adhesions, good pleurodesiswould be expected to develop in the course of empyema in all instances. Yet, in our 19 patients, adhesions did not form while persistent prolonged inflammation was present. Eventually, talc was introduced, and this resulted in prompt formation of adhesions, ending the problem in all patients within 4 days. The failures encountered before the use of talc were certainly not due to lack of inflammation, but only talc provided the new adhesion-stimulating factor, the nature of which has not
694
Weissbergand Ben-Zeev
been positively determined. An attractive hypothesis explaining this phenomenon is based on Thorsrud's" suggestion that the visceral mesothelium is protected from inflammatory reaction by a constant flow of fluid from the visceral pleura into the pleural space. This protective mechanism can be blocked only by destroying the visceral mesothelium, thus enabling creation of pleural symphysis if the pleural surfaces are kept in apposition.i" This concept is in accordance with what is known about the formation of intestinal adhesions by talcum powder. According to Grabowski and Malt,25 fibroplasia under those circumstances is a nonchemical reaction enhanced by mechanical trauma to the surface of the bowel. 25 Replacement of the mechanical trauma by a chemical agent causing injury to the visceral pleura, such as adding labile iodine to talc, may provide the necessary factor on which talc exerts its fibrogenic effect. Instead of a chemical agent, mechanical abrasion of the pleural surface fulfills the same requirement, breaching the visceral pleura and enabling the talc to initiate the process leading to pleural symphysis. We conclude that purified talc free of asbestos is safe for clinical use. It is the cheapest and most reliable substance in creating pleural adhesions, with effectiveness exceeding 90%. Its use in doses not exceeding 2 gm eliminates complications almost completely.
1.
2.
3. 4. 5.
6.
7. 8. 9.
10.
REFERENCES Bethune N. Pleural poudrage: a new technique for the deliberate production of pleural adhesions as a preliminary to lobectomy. J THORAC SURG 1935;4:251-61. Pearson FG, MacGregor DC. Talc poudrage for malignant pleural effusion. J THORAC CARDIOVASC SURG 1966; 51:732-8. Bloomberg AE. Thoracoscopy in diagnosis of pleural effusion. N Y State J Med 1970;70:1974-7. Weissberg D. Talc pleurodesis:a controversial issue. Poumon-Coeur 1981;37:291-4. Gaensler EA. Parietal pleurectomy for recurrent spontaneous pneumothorax. Surg Gynecol Obstet 1956;102:293308. Rinaldo lE, Owens GR, Rogers RM. Adult respiratory distress syndrome followingintrapleural instillation of talc. 1 THORAC CARDIOVASC SURG 1983;85:523-6. Jackson JW, Bennett MH. Chest wall tumour following iodized talc pleurodesis. Thorax 1973;28:788-93. Jones RN. Asbestos exposures and thoracic neoplasms. Semin RoentgenoI1992;27:94-101. Paul lS, Beattie El, Blades B. Lung function studies in poudrage treatment of recurrent spontaneous pneumothorax. J THORAC SURG 1951;22:52-8. Lange P, Mortensen 1, Groth S. Lung function 22-35 years
The Journal of Thoracic 'and Cardiovascular Surgery October 1993
after treatment of idiopathic spontaneous pneumothorax with talc poudrage or simple drainage. Thorax 1988;43: 559-61. II. McGahren ED, Teague WG lr, Flanagan T, White B, Rodgers BM. The effects of talc pleurodesis on growing swine. 1 Ped Surg 1990;25:1147-51. 12. Stephenson LW. Treatment of pneumothorax with intrapleural tetracycline. Chest 1985;88:803-4. 13. Ruckdeschel lC, Moores D, Lee JY, et al. Intrapleural therapy for malignant pleural effusion:a randomized comparison of bleomycin and tetracycline. Chest 1991;100: 1528-35. 14. Weissberg D. Role of chemical methods to induce adhesive pleuritis. In: Deslauriers J, Lacquet LK, eds. Thoracic surgery: surgical management of pleural diseases. St. Louis: Mosby, 1990:130-1. 15. Chambers lS. Talc as a pleural sclerosant. Br 1 Surg 1991;78:1401. 16. Hamed H, Fentirnan IS, Chaudary MA, Rubens RD. Comparison of intracavitary bleomycinand talc for control of pleural effusionssecondary to carcinoma of the breast. Br J Surg 1989;76:1266-7. 17. Siegel RD, Schiffman Fl. Systemic toxicity following intracavitary administration of bleomycin. Chest 1'990;98: 507. 18. Gellhorn A, Zaidenweber 1, Ultmann 1, Hirschberg E. The use of Atabrine (quinacrine) in the control of recurrent neoplastic effusions. Dis Chest 1961;39:165-76. 19. Cattaneo SM, Sirak HD, Klassen KP. Recurrent spontaneous pneumothorax in the high-risk patient. J THORAC CARDIOVASC SURG 1973;66:467-71. 20. Larrieu AJ, Tyers GFO, Williams EH, O'Neill MJ, DerricklR. Intrapleural instillationof quinacrine for treatment of recurrent spontaneous pneumothorax. Ann Thorac Surg 1979;28:146-50. 21. Weissberg D. Talc and adult respiratory distress syndrome [Letter]. 1 THORAC CARDIOVASC SURG 1984;87: 474. 22. Weissberg D, Kaufman M, Zurkowski Z. Pleuroscopy in patients with pleural effusion and pleural masses. Ann Thorac Surg 1980;29:205-8. 23. Weissberg D, Kaufman M. Diagnostic and therapeutic pleuroscopy: experience with 127 patients. Chest 1980;78: 732-5. 24. Weissberg D. The surgical management of recurrent or persistent pneumothorax: pleuroscopy and talc poudrage. In: Kittle CF, ed. Current controversiesin thoracic surgery. Philadelphia: WB Saunders, 1986:46-50. 25. Grabowski EW, Malt RA. Tales for pleural poudrage: physical and chemical factors in therapeutic effect. 1 THORAC CARDIOVASC SURG 1968;56:760-4. 26. British pharmaceutical codex. London: Pharmaceutical Press, 1973:492. 27. Martindale W. The extra pharmacopoeia. 29th ed. London: Pharmaceutical Press, 1989:933.
The Journal of Thoracic and Cardiovascular Surgery Volume 106. Number 4
28. Wagner JC, Pooley FD. Mineral fibres and mesothelioma. Thorax 1986;41:161-6. 29. Webster I. Asbestos malignancy. S Afr Med J 1973;47: 165-71. 30. Wagner JC, Berry G, Pooley FD. Carcinogenesis and minerai fibres. Br Med Bull 1980;36:53-6. 31. Hobbs JST, WoodwardSD, Murphy B, MuskAW, Elder JE. The incidence of pneumoconiosis, mesothelioma and other respiratory cancer in men engaged in mining and milling crocidolite in Western Australia. In: Wagner JC, ed. Biological effects of mineral fibres. Vol. 2. New York: Oxford University Press, 1986:615-25. 32. Elmes PC. Mesotheliomas, minerals, and man-made minerai fibres. Thorax 1980;35:561-3. 33. Cosmetic talc powder (Editorial). Lancet 1977;1:1348-9.
Weissberg and Ben-Zeev
695
34. Kleinfeld M, Messite J, Kooyman 0, Zaki MH. Mortality among talc miners and millers in New York State. Arch Environ Health 1967;14:663-7. 35. Kleinfeld M, Messite J, Zaki MH. Mortality experiences among talc workers: a follow-up study. J Occup Med 1974; 16:345-9. 36. Wagner JC, Berry G, Cooke TJ, et al. Animal experiments with talc. Proceedings of the Fourth International Symposium on Inhaled Particles and Vapour; 1975;Sept 22-26 Edinburgh, Scotland. Oxford: Pergamon, 1977:647-54. 37. Weissberg D, Kaufman M. The use of talc for pleurodesis in the treatment of resistant empyema. Ann Thorac Surg 1986;41:143-5. 38. Thorsrud GK. Pleural reactions to irritants. Acta Chir Scand 1965;355(Suppl):I-74.
Bound volumes available to subscribers Boundvolumes of THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY are availableto subscribers(only)for the 1993 issues from the Publisher,at a cost of $75.00 for domestic, $98.25 for Canadian, and $93.00 for internationalsubscribersfor Vol. 105 (JanuaryJune) and Vol. 106 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copiesare shippedwithin 60 days after publicationof the last issueof the volume. The bindingis durable buckram with the JOURNAL name, volumenumber, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Subscription Services, 11830 WestlineIndustrialDrive, St. Louis,Missouri63146-3318, USA; phone 1 (800) 453-4351 or (314) 453-4351. Subscriptions must be in force to quatify.Boundvolumes are not available in place of a regular JOURNAL subscription.
Dov Weissberg, MD, FRCSC, FACS, FCCP, and Ilan Ben-Zeev, MD,
Uliteration of the pleural space by adhesions is indicated when recurrent accumulations of liquid (effusion, chyle, or any other) or recurrent episodes of pneumothorax prevent complete expansion of the lung. Methods for creation of pleural adhesions include pleurectomy, pleural abrasion, and intrapleural instillation ofvarious agents capable of stimulating inflammatory reaction. Many irritating substances have been tried including bleomycin, various cytostatic agents, and talc, which are the few that remain in use today. It has long been known that talc causes adhesions of serosal surfaces. Since 1935, talc has been used therapeutically for intrapleural insufflation, to prevent recurrent spontaneous pneumothorax, and for control ofmalignant pleural effusions. After the original report of Bethune, I various methods of talc instillation have been described.v" Although the results were satisfactory, talc has not been universally accepted because of its alleged potential for complications. Febrile reactions, granuloma, Fromthe Departmentof ThoracicSurgery,Tel Aviv University Sackler Schoolof Medicine, E. Wolfson Medical Center, Holan, Israel. Received for publication Aug. 4, 1992. Accepted for publication Dec. 11, 1992. Address forreprints:DovWeissberg, MD, E. Wolfson MedicalCenter, Holan 58100,Israel. Copyright w 1993 by Mosby-Year Book, Inc. 0022-5223/93$1.00 +.10 12/1/45058
Holon, Israel
flbrothorax.l adult respiratory distress syndrome.P and, most important, malignant mesothelioma and bronchogenic carcinoma7,8 were mentioned among the possible complications of its use. We have been using talc for obliteration of the pleural space since 1974. This article summarizes our experience with 360 patients.
Patients and methods Between 1974 and 1991 talc was used intrapleurally in 360 (211 male and 149 female) patients, ranging in age from 14 to 84 years. The indications for use were control of malignant pleural effusion in 169 patients, benign effusions of various origins in 41, recurrent spontaneous pneumothorax in 122, empyema in 19, and chylothorax in 9. Before introduction of talc, the pleural cavity is emptied of all fluid,and complete lung expansibility is assured. When the lung is not fully expansible, talc is not introduced. Two grams of sterile iodized talc are used in each procedure. Talc is instilled by one of two methods. In patients who undergo pleuroscopy, talc is insufflated at the end of the procedure through the lumen of the mediastinoscope, under vision, with a bulb syringe. During the insufflation, the direction of the mediastinoscope is changed frequently to assure even distribution of talc over the entire pleural surface. A thoracostomy tube is inserted into the pleural cavity through a separate stab wound incision and is connected to an underwater seal with suction of 10 to 20 em H 20 . This method was used in 272 patients. In 88 patients in whom pleuroscopy was not indicated, suspensionof talc was instilled through the pleural drain. With this method, all liquid or air is evacuated through an intercostal
6R9
690
The Journal of Thoraclcand Cardiovascular Surgery October 1993
Weissberg and Ben-Zeev
Table I. Results ofpleural poudrage in 336 patients No. ofpatients (%) Indications Malignant effusion (n = 169) Benign effusions (n = 41) Pneumothorax (n = 122) Empyema (n = 19) Chylothorax (n = 9) Total (n = 360)
Died within 1 month 12
Lost to follow-up 3 9
12
12
drain, and completeexpansion of the lung is verified by radiography. A suspension of 2 gm talc in 30 ml normal salinesolutionisinjectedthroughthe tube drain intothe pleuralcavity,and the drain is flushed with another 20 ml of saline solution. The drain is then clamped for 2 hours, and the patient is instructed to change bodypositionfrequently, thus aidingin evendistribution of talc. After 2 hours,the tube is reconnected to the underwater seal with suctionfor 3 or 4 days. If, after 3 days,the chest roentgenogram shows complete lung expansion, the tube is removed. On severaloccasions, when expansion of the lung at the control roentgenogram was not complete, a suspension of talc was instilled through the chest tube again, and suctionwas continued for another 4 days.
Results Twelve patients died before the results could be evaluated. None of the deaths were related to poudrage, although one patient died several hours after the insufflation. The cause of death in this case was massive pulmonary embolism. Twelve other patients were lost to followup. The results were evaluated in 336 patients (Table I). Our evaluation of results was subjective, depending to a large extent on the physician's judgment and interpretation of radiographic findings. However, in practice, it proved satisfactory and correlated well with the patients' symptoms. Results were classified as excellent if complete pleurodesis was achieved without any evidence of fluid accumulation or pneumothorax at follow-up examinations (Fig. 1). The results were considered fair if most of the lung became adherent to the chest wall and marked symptomatic and radiographic improvement occurred. Patients with small, usually loculated accumulations of fluid and residual, sealed-off pockets of air were included in this category (Fig. 2). The outcome was considered poor if no adhesions or only minor adhesions formed without practical beneficial effect. Excellent results were achieved in 284 patients (84.5%), fair in 28 (8.3%), and poor in 24 (7.2%). The results were uniformly excellent in patients with empyema and were better in patients with
Results Evaluated 154 41 113 19 9 336
Excellent 130 30 98 19 7 284
(84.4) (73.2) (86.8) (100) (77.8) (84.5)
Fair
Poor
12 (7.8) 6 (14.6) 10 (8.8)
12 (7.8) 5 (12.2) 5 (4.4)
28 (8.3)
2 (22.2) 24 (7.2)
pneumothorax than in those with pleural effusions (Table I).
Discussion Attempts at obliteration of the pleural space are often viewed with suspicion and have drawn criticism because of alleged interference with respiratory function. This suspicion is unfounded. It has never been shown that a free pleural cavity is necessary for the lungs to function properly. The presence of the pleural cavity is the result of a peculiar embryologic development in some species but not in others; its mere existence does not necessarily imply function and usefulness. For example, a pleural space does not exist in the elephant, but this does not in any way impair the animal's breathing capacity. It thus appears that obliteration of the pleural space can be done without harm and without significant long-term negative effects. The fibrosis caused by talc is related to the amount used. Use of excessive amounts of talc will result in excessive fibrosis of the pleura and trapping of the lung, affecting pulmonary function. However, a minimal dose of a fibrosing agent, barely sufficient for obliteration ofthe pleural space, does not have this effect and can be used safely. This has been demonstrated in the classic work of Paul, Beattie, and Blades? in 1951, who used talc intrapleurally for treatment of recurrent spontaneous pneumothorax with no untoward effect on pulmonary function. Their results were confirmed by Lange, Mortensen, and Groth.l'' who studied patients 22 to 35 years after intrapleural instillation of talc and found only a mild restrictive impairment. McGahren and associates 11 used talc for obliteration of the pleural space in growing pigs. The use of talc caused a temporary impairment in dynamic transpulmonary and transrespiratory compliance, but this resolved with time and growth. The longterm evaluation showed only minimal effects on pulmonary compliance. It is mandatory, however, to use the minimum amount of talc to avoid the intensification of
The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 4
Weissberg and Ben-Zeev
69I
Fig. 1. A, Massive idiopathic right pleuraleffusion in a 25-year-old woman. Because of recurrence, talc was insufflated at pleuroscopy. B, One-year follow-up. Excellent result of poudrage,
these effects. We have found our maximum dose of 2 gm of talc to be safe. Long-term results of pleural obliteration should be evaluated not only with regard to time but also in relation to underlying diagnoses. Most recurrences of pneumothorax occur within 6 months. Although we follow up our patients for as long as they keep appointments, often for 5 to 6 years or more, we have never seen recurrence beyond the first year. Accordingly, a I-year follow-up should be considered adequate. Inthe majority of patients
with malignant pleural effusion, the follow-up is virtually irrelevant because the median survival time is only 3V2 months. However, differences in survival exist among patients with various cancers. Although the median survival for patients with malignant pleural effusion because of bronchogenic carcinoma is only 2V2 months, patients with breast cancer and malignant pleural effusion survived a median of 7V3 months. Follow-up is obviously more important for patients with breast cancer and malignant pleural effusion than it is for patients with
692
Weissberg and Ben-Zeev
The Journal of Thoracic arid Cardiovascular Surgery October 1993
Fig. 2. A, Malignantpleuraleffusion as a resultof carcinomaof breast in a 72-year-old woman. B, Roentgenogram taken 3 months after poudrage, showing fair result. malignant pleural effusion because of bronchogenic carcinoma. Talc pleurodesis can fail for a number of reasons, including trapped lung as a result of thickened pleura, irregularly scattered adhesions preventing good lung expansion, loculation of the pleural space by fibrin and adhesions, loss of pulmonary elasticity, high liquid output interfering with creation of adhesions, and extensive pleural metastases. Some of these factors can be diagnosed ahead of time and should be regarded as contraindications for the use of talc.
Talc has several advantages over other agents capable of creating adhesions and obliterating the pleural space. Tetracycline gained great popularity in recent years and became the most widely accepted sclerosant. However, its use results in much pain, likened by Stephenson'? to scalding water injected through the chest tube. Therefore, it must be used in combination with either local anesthesia or heavy sedation; however, the pain is severe, and these measures are often inadequate. In addition, the effectiveness of tetracycline is only about 50%,13 whereas the average effectiveness of talc is 95%.14.15 The effec-
The Journal of Thoracic and Cardiovascular Surgery Volume 106, Number 4
tiveness of bleomycin is reported to be near 65%,13, 16 still far below that of talc. In addition, bleomycin is systemically absorbed, with a potential for systemic toxicity. Associatedalopecia and mucositishave been described by Siegel and Schiffman.!? In these days of cost-effectiveness, the high cost of bleomycin also cannot be disregarded. The use of quinacrine was successful in 80% of patients but was accompanied by a high complication rate, with fever for up to 10 days in nearly all patients and pain, nausea, vomiting, and hallucinations. I S-20 Tetracycline and quinacrine are no longer available. Objection to the use of talc has been expressed by Rinaldo, Owens, and Rogers" because of its alleged association with adult respiratory distress syndrome. In their experiencewith four patients, this syndrome occurred in the three who received 10 gm talc intrapleurally. The fourth patient received 5 grn talc, and adult respiratory distress syndrome did not develop. The reported complication was most likely dose related.i' We are not aware of any other reports linking talc with adult respiratory distress syndrome. It is possiblethat an excessive amount of talc is capable of inducing adult respiratory distress syndrome, and we have stressed repeatedly that no more than 2 grn should be used for obliteration of the pleural space.21-24 A much more widely publicized objection to the use of talc is its alleged association with pleural mesothelioma and bronchogenic carcinoma. Talc is a generic term that includes,in addition to the pure mineral talc, impure massive talcose rocks (soapstone). These may contain as little as 50% mineral talc. Mineral talc is hydrous magnesium silicate corresponding approximatelytotheformula3MgO . 4Si02' H20.22,25-27Themost important contaminant of talc linked to carcinogenesis is asbestos. It consists of six naturally occurring minerals: chrysotile, crocidolite, amosite, anthophyllite, tremolite, and actinolyte. In carcinogenesis, the major determining factor is the diameter of the fiber: those with the lesser diameter are more carcinogenic. Fibers responsible for mesothelioma have a diameter of less than 0.25 ttm and probably a length greater than 5 ttm.2S The most significantcontaminant, tremolite, Ca2Mg5Sis022(OHh, consists of long, fibrous, needle-shaped particles that are 10 to 200 ttm long (50%) and irregularly shaped particles that are less than 10 ttm in greatest projected diameter (50%).25 These fine fibers oftremolite are responsible for its carcinogenic effect. Likewise,crocidolite (blue asbestos) and amosite (brown asbestos) are composed of tiny fibers. Tremolite, crocidolite, and amosite are most commonly implicated in carcinogesis.P'" No crysotile exposures with an exceptionally high risk of mesothelioma have been reported thus far. 32
Weissberg and Ben-Zeev
693
Talc must be free of all carcinogenic contaminants to be suitable for clinical use. Purified talc is finely powdered magnesium trisilicate, a physical irritant capable of creating adhesions and granuloma but not cancer.P This distinction has been shownvery convincinglyby Kleinfeld and associates.I" They studied the prevalence of cancer and respiratory diseases in talc miners and millers in the state of New York, where talc is heavily contaminated with amphiboles and free silica. Initially, talc was associated with an increased mortality as a result of mesothelioma and cor pulmonale. Later, according to the same authors.F' after dust levels had been reduced, the death rates for malignant diseases among the mine employees became similar to those in the United States in general. The results of their studies were confirmed conclusivelyin animal experiments by Wagner and associates.l" In their study, 48 rats received chrysotile asbestos intrapleurally. Mesothelioma developedin 18 animals. In another group of 48 rats exposedsimilarly to cosmetic (purified) talc, no mesotheliomas were found. These studies show clearly that the carcinogenic substance is asbestos, not purified talc. The purified talc that we use is produced in Israel by Frutarom, Inc. It corresponds with the requirements of the British Pharmacopoeia-S 27 and does not contain any asbestos. It isoften assumed that adhesionscaused by talc are the result of an inflammatory reaction. However, not every inflammatory reaction results in adhesions, and it is possible that the adhesions resulting from talc are caused not by an acute inflammatory reaction but by a different, fibrosis-stimulating mechanism. The problem of inflammation versus fibrosis-stimulating mechanism is a real one and is well demonstrated by our experience with empyema.V No one questions that empyema is an inflammatory process. As such, it should stimulate creation of pleural adhesions, and it often does. However, in certain patients with empyema, the fully expansible lung does not become adherent to the chest wall, and the pus continues to accumulate. Our experience includes 19such patients; all were eventually treated with talc, and all had excellent results (Table I). If inflammation, per se, were the only factor necessary for creation of adhesions, good pleurodesiswould be expected to develop in the course of empyema in all instances. Yet, in our 19 patients, adhesions did not form while persistent prolonged inflammation was present. Eventually, talc was introduced, and this resulted in prompt formation of adhesions, ending the problem in all patients within 4 days. The failures encountered before the use of talc were certainly not due to lack of inflammation, but only talc provided the new adhesion-stimulating factor, the nature of which has not
694
Weissbergand Ben-Zeev
been positively determined. An attractive hypothesis explaining this phenomenon is based on Thorsrud's" suggestion that the visceral mesothelium is protected from inflammatory reaction by a constant flow of fluid from the visceral pleura into the pleural space. This protective mechanism can be blocked only by destroying the visceral mesothelium, thus enabling creation of pleural symphysis if the pleural surfaces are kept in apposition.i" This concept is in accordance with what is known about the formation of intestinal adhesions by talcum powder. According to Grabowski and Malt,25 fibroplasia under those circumstances is a nonchemical reaction enhanced by mechanical trauma to the surface of the bowel. 25 Replacement of the mechanical trauma by a chemical agent causing injury to the visceral pleura, such as adding labile iodine to talc, may provide the necessary factor on which talc exerts its fibrogenic effect. Instead of a chemical agent, mechanical abrasion of the pleural surface fulfills the same requirement, breaching the visceral pleura and enabling the talc to initiate the process leading to pleural symphysis. We conclude that purified talc free of asbestos is safe for clinical use. It is the cheapest and most reliable substance in creating pleural adhesions, with effectiveness exceeding 90%. Its use in doses not exceeding 2 gm eliminates complications almost completely.
1.
2.
3. 4. 5.
6.
7. 8. 9.
10.
REFERENCES Bethune N. Pleural poudrage: a new technique for the deliberate production of pleural adhesions as a preliminary to lobectomy. J THORAC SURG 1935;4:251-61. Pearson FG, MacGregor DC. Talc poudrage for malignant pleural effusion. J THORAC CARDIOVASC SURG 1966; 51:732-8. Bloomberg AE. Thoracoscopy in diagnosis of pleural effusion. N Y State J Med 1970;70:1974-7. Weissberg D. Talc pleurodesis:a controversial issue. Poumon-Coeur 1981;37:291-4. Gaensler EA. Parietal pleurectomy for recurrent spontaneous pneumothorax. Surg Gynecol Obstet 1956;102:293308. Rinaldo lE, Owens GR, Rogers RM. Adult respiratory distress syndrome followingintrapleural instillation of talc. 1 THORAC CARDIOVASC SURG 1983;85:523-6. Jackson JW, Bennett MH. Chest wall tumour following iodized talc pleurodesis. Thorax 1973;28:788-93. Jones RN. Asbestos exposures and thoracic neoplasms. Semin RoentgenoI1992;27:94-101. Paul lS, Beattie El, Blades B. Lung function studies in poudrage treatment of recurrent spontaneous pneumothorax. J THORAC SURG 1951;22:52-8. Lange P, Mortensen 1, Groth S. Lung function 22-35 years
The Journal of Thoracic 'and Cardiovascular Surgery October 1993
after treatment of idiopathic spontaneous pneumothorax with talc poudrage or simple drainage. Thorax 1988;43: 559-61. II. McGahren ED, Teague WG lr, Flanagan T, White B, Rodgers BM. The effects of talc pleurodesis on growing swine. 1 Ped Surg 1990;25:1147-51. 12. Stephenson LW. Treatment of pneumothorax with intrapleural tetracycline. Chest 1985;88:803-4. 13. Ruckdeschel lC, Moores D, Lee JY, et al. Intrapleural therapy for malignant pleural effusion:a randomized comparison of bleomycin and tetracycline. Chest 1991;100: 1528-35. 14. Weissberg D. Role of chemical methods to induce adhesive pleuritis. In: Deslauriers J, Lacquet LK, eds. Thoracic surgery: surgical management of pleural diseases. St. Louis: Mosby, 1990:130-1. 15. Chambers lS. Talc as a pleural sclerosant. Br 1 Surg 1991;78:1401. 16. Hamed H, Fentirnan IS, Chaudary MA, Rubens RD. Comparison of intracavitary bleomycinand talc for control of pleural effusionssecondary to carcinoma of the breast. Br J Surg 1989;76:1266-7. 17. Siegel RD, Schiffman Fl. Systemic toxicity following intracavitary administration of bleomycin. Chest 1'990;98: 507. 18. Gellhorn A, Zaidenweber 1, Ultmann 1, Hirschberg E. The use of Atabrine (quinacrine) in the control of recurrent neoplastic effusions. Dis Chest 1961;39:165-76. 19. Cattaneo SM, Sirak HD, Klassen KP. Recurrent spontaneous pneumothorax in the high-risk patient. J THORAC CARDIOVASC SURG 1973;66:467-71. 20. Larrieu AJ, Tyers GFO, Williams EH, O'Neill MJ, DerricklR. Intrapleural instillationof quinacrine for treatment of recurrent spontaneous pneumothorax. Ann Thorac Surg 1979;28:146-50. 21. Weissberg D. Talc and adult respiratory distress syndrome [Letter]. 1 THORAC CARDIOVASC SURG 1984;87: 474. 22. Weissberg D, Kaufman M, Zurkowski Z. Pleuroscopy in patients with pleural effusion and pleural masses. Ann Thorac Surg 1980;29:205-8. 23. Weissberg D, Kaufman M. Diagnostic and therapeutic pleuroscopy: experience with 127 patients. Chest 1980;78: 732-5. 24. Weissberg D. The surgical management of recurrent or persistent pneumothorax: pleuroscopy and talc poudrage. In: Kittle CF, ed. Current controversiesin thoracic surgery. Philadelphia: WB Saunders, 1986:46-50. 25. Grabowski EW, Malt RA. Tales for pleural poudrage: physical and chemical factors in therapeutic effect. 1 THORAC CARDIOVASC SURG 1968;56:760-4. 26. British pharmaceutical codex. London: Pharmaceutical Press, 1973:492. 27. Martindale W. The extra pharmacopoeia. 29th ed. London: Pharmaceutical Press, 1989:933.
The Journal of Thoracic and Cardiovascular Surgery Volume 106. Number 4
28. Wagner JC, Pooley FD. Mineral fibres and mesothelioma. Thorax 1986;41:161-6. 29. Webster I. Asbestos malignancy. S Afr Med J 1973;47: 165-71. 30. Wagner JC, Berry G, Pooley FD. Carcinogenesis and minerai fibres. Br Med Bull 1980;36:53-6. 31. Hobbs JST, WoodwardSD, Murphy B, MuskAW, Elder JE. The incidence of pneumoconiosis, mesothelioma and other respiratory cancer in men engaged in mining and milling crocidolite in Western Australia. In: Wagner JC, ed. Biological effects of mineral fibres. Vol. 2. New York: Oxford University Press, 1986:615-25. 32. Elmes PC. Mesotheliomas, minerals, and man-made minerai fibres. Thorax 1980;35:561-3. 33. Cosmetic talc powder (Editorial). Lancet 1977;1:1348-9.
Weissberg and Ben-Zeev
695
34. Kleinfeld M, Messite J, Kooyman 0, Zaki MH. Mortality among talc miners and millers in New York State. Arch Environ Health 1967;14:663-7. 35. Kleinfeld M, Messite J, Zaki MH. Mortality experiences among talc workers: a follow-up study. J Occup Med 1974; 16:345-9. 36. Wagner JC, Berry G, Cooke TJ, et al. Animal experiments with talc. Proceedings of the Fourth International Symposium on Inhaled Particles and Vapour; 1975;Sept 22-26 Edinburgh, Scotland. Oxford: Pergamon, 1977:647-54. 37. Weissberg D, Kaufman M. The use of talc for pleurodesis in the treatment of resistant empyema. Ann Thorac Surg 1986;41:143-5. 38. Thorsrud GK. Pleural reactions to irritants. Acta Chir Scand 1965;355(Suppl):I-74.
Bound volumes available to subscribers Boundvolumes of THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY are availableto subscribers(only)for the 1993 issues from the Publisher,at a cost of $75.00 for domestic, $98.25 for Canadian, and $93.00 for internationalsubscribersfor Vol. 105 (JanuaryJune) and Vol. 106 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copiesare shippedwithin 60 days after publicationof the last issueof the volume. The bindingis durable buckram with the JOURNAL name, volumenumber, and year stamped in gold on the spine. Payment must accompany all orders. Contact Mosby, Subscription Services, 11830 WestlineIndustrialDrive, St. Louis,Missouri63146-3318, USA; phone 1 (800) 453-4351 or (314) 453-4351. Subscriptions must be in force to quatify.Boundvolumes are not available in place of a regular JOURNAL subscription.