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Three Part Question

In patients [with a pneumothorax] does [talc pleurodesis] cause [long term adverse effects]?

Clinical Scenario

A 23 year man was due to undergo a VATS procedure with talc insufflation for recurrent spontaneous pneumothorax. While preparing the patient for theatre he asks you about how the talc that will be insufflated in the operation works. After explaining how the talc causes an inflammatory reaction that causes the pleura to adhere together, he asks that since the talc causes a reaction, can it cause any long term problems.

Search Strategy

Medline 1950 – June 2006 and Embase 1974 – June 2006 using the Dialog Datastar interface
[Pneumothorax.W..DE. OR PNEUMOTHORAX#.W..DE.] AND [Talc.W..DE.]. Limit to English. This search was repeated in Cochrane Central Register of Controlled Trials.

Search Outcome

A total of 181 papers were identified of which eight were deemed to be relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Cardillo et al, 2006, Italy	861 patients underwent VATS talc poudrage with/without bullectomy for PSP. Mean age 28.6 yrs. 26 patients with follow up of >60 months underwent RFTs.	Retrospective Cohort	26 patients (15 male, 11 female) had normal respiratory function (80% or more of predicted value) after 60 months 14 patients had recurrences (1.73%) after a mean follow-up of 52.5 months Statistically significant relationship (P0.037) with continuation of smoking	Lung function was normal in all 26 patients after 60 months Low recurrence rate after >50 month follow-up	Small no. of long-term follow ups that underwent RFTs Intermediate-term follow up completed in 805 (93%) patients, with follow up >60 months available in 285 (33%) patients No control group for talc usage 2g of Asbestos free talc (<50ìm fibres) used No ARDS reported
Ozcan et al, 2003, USA	32 VATS procedures performed on 22 children. Age range 9-21yrs, PSP in 9 & SSP in 13 patients (including CF) Talc used in 28 cases. Mean follow up 4 years (2.5 months to 14 years)	Retrospective Cohort	2 cases of partial recurrence of pneumothorax both in SSP (6.25%). One case following abrasion, one case following talc usage. Repeat talc pleurodesis performed on both.	3.6% rate of partial recurrence following talc usage. No other long term effects reported.	Small study No randomisation of patients into talc versus abrasion. 2g USP asbestos free pure talc used.
Tschopp et al, 2002, Switzerland	61 patients with PSP underwent medical VATS talc under LA vs. 47 patients with pleural ICD. Mean follow-up 60.5+/-34.3 vs. 54+/-33.2months	Prospective randomised comparison	3 out 59 cases (2 lost to follow up) developed recurrence of pneumothorax with VATS talc (5%) vs. 16 out of 47 cases for pleural drain (34%) after 5 years.	5% recurrence rate for talc compared to 34% recurrence for conservative treatment.	No blinding 2g Sterile asbestos free talc
de Campos et al, 2001, Brazil	614 patients underwent talc poudrage. Age range 1-96 yrs- 49 for spontaneous pneumothorax. Follow up of 24 to 60 months.	Retrospective Cohort	1 patient out of 49 developed a recurrent pneumothorax (occurred 15 days after op). No mortality or long-term adverse effects detected. 7 patients (of 614) developed ARDS & 12 patients re-expansion pulmonary oedema (none in PSP group)	2% recurrence rate in 49 patients. No long term adverse effects noted in PSP group.	This paper looked at all possible complications of talc poudrage but mainly for the treatment of malignant pleural effusions (N=457). Small number for recurrent pneumothorax with no age range given (N=49) 2g asbestos free sterilized talc (5-70ìm particle size)
Milanz et al, 1994, Brazil and USA	18 patients with recurrent spontaneous pneumothorax (>2 recurrences) treated with talc pleurodesis. Mean follow up 38.5 months, range 4 to 89 months.	Prospective Cohort	Only 1 patient had a recurrence in the follow up period. 12 patients with no recurrence were followed up for 2 years. 6 with no recurrence were followed up for 5 years.	5.6% recurrence rate in 18 patients. No long-term adverse effects of talc were detected.	This paper looked at all complications, however sample size was small. 2g sterile asbestos free talc used. Similar author group as [Tschopp] - same patients? Not stated
Viskum et al, 1989, Denmark	99 PSP patients between the years of 1954 and 1964 had VATS talc pleurodesis. Re- investigated in 1985. 4 had emigrated, 26 had died, 4 did not participate, 15 had telephone interviews, 50 had CXR and lung functions performed.	Retrospective cohort	In the 26 who died, 6 due to pulmonary disease, 1 due to alveolar carcinoma on contra lateral side, 2 of planocellular carcinoma within 2-yrs of pleurodesis, 3 due to pulmonary insufficiency present at time of procedure. 2 of 50 had bilateral pronounced pleural thickening on CXR. 1 patient had moderate restrictive function on RFTs. 2 out of 99 had recurrence of PSP.	MPM not reported in any patients No significant restrictive lung pattern noted apart from 1 patient before her treatment with talc pleurodesis had a contralateral PSP treated with hypertonic glucose infusion to the pleural space.	This paper looked at all complications, Dose of asbestos free talc between 0.5 to 4g (average of 3g)
Lange et al, 1998, Denmark	114 patients with treated pneumothorax were studied 22-35 years after the first pneumothorax with measurement of static and dynamic lung function. 80 were treated with talc, 34 with simple drainage.	Retrospective Cohort	17 out of 114 had died, 3 from lung cancer but none of the remaining from respiratory failure or MPM. 2 emigrated, 75 participated fully, 14 completed postal questionnaire & 6 did not respond. TLC 89% predicted in those treated with talc. 96% treated with simple drainage. 1 patient had severe reduction, 58%. No subjects developed MPM.	Talc causes mild restrictive impairment of lung function and pleural thickening on chest x-rays. No evidence of MPM.	Did not state what talc used. Same author group as [Milanz] – same patients? Not stated
Chappell et al, Research Committee 1979, UK	210 patients from 3 centres underwent iodized talc or kaolin pleurodesis 14 to 40 years previously.	Retrospective Cohort	152 patients were contacted and were alive. 2 were untraced but believed alive. 9 had emigrated or were untraced. 47 deaths, 3 from lung cancer (2 had tumour on opposite side to pleurodesis, 1 died from small cell ca 32 years after pleurodesis.	No increased incidence of lung cancer and no case of MPM in series of 152 patients. 88 patients had been followed 15 to 30 years, 75 patients for 30 to 40 years.	Subject years method used for comparison. Talc or kaolin used. Other cases as well as pneumothorax.

Comment(s)

The role of talc as the agent to achieve pleurodesis usually combined with a minimally invasive videothoracosopic approach (VATS) has become popular in treating patients with primary spontaneous pneumothorax (PSP) [Cardillo]. However, issues about the use of talc in young patients, the risk of carcinogenesis [Chappell], and the development of restrictive lung pathology persist [Viskum, Lange]. The review focuses on the long-term consequences of talc use in patients with PSP and will not consider early complications such as acute pneumonitits and ARDS or complications of talc used in older patients with malignant pleural effusions. Concerns about the carcinogenic effect of talc are likely to have come originally from early reports in miners and processors exposed to impurities in talc dust resulting in malignant tumours of the lung and pleura [Chappell]. In 1979 three centres in the UK retrospectively examined medical records to identify patients who had received pleurodesis with talc or kaolin at least 14 years earlier [Chappell]. 210 patients were identified. Once data was collated the authors concluded that there was no increased incidence of lung cancer (as compared to the general population) and no cases of MPM. Furthermore, they speculated that the early reports suggesting talc may be carcinogenic may be due to asbestos-like contaminants present in the talc used. No other study identified an association between intrapleural talc use and increased incidence of subsequent lung or pleural cancer [all other references] Two papers published in the late 1980's specifically examined patients for long term evidence of respiratory compromise following talc pleurodesis [Viskum, Lange]. One study measured static and dynamic lung function in PSP patients treated with talc pleurodesis or simple chest drainage. Patients who had undergone a talc pleurodesis some 22-35 years earlier showed a mild restrictive impairment of lung function (mean Total Lung Capacity, TLC 89% predicted) compared to those who had simple chest drainage (TLC 96%, predicted). One patient who had received talc pleurodesis had evidence of lung fibrosis and severe reduction in lung function (TLC, 58% predicted). No patient had developed MPM [Lange]. In a paper published a year later by the same group X-ray, changes in the pleura was moderate with some thickening but no significant restriction in lung function [Viskum]. Both studies concluded that in the long term talc pleurodesis did not produce significant adverse effects on lung function. More recently, the largest series of VATS treated PSP using primarily talc pleurodesis was reported [Cardillo]. It showed a high success rate (98%) at >50 months follow-up, and with no reported deterioration in lung function in 26 patients followed-up over 5 years. Apart from the recent report from Italy [Cardillo], the other studies reviewed [Ozcan, Tschopp, de Campos, Milanez] comment on the absence of no long term adverse effects without presenting any objective clinical, physiological or radiological evidence to support assertion. Despite evidence dating back 20-25 years that talc as an agent for pleurodesis is likely to be safe and has few long term adverse effects [Milanez, Viskum, Lange, Chappell], recently concerns about the role of intrapleural talc and the generation of a systemic inflammatory response with systemic dissemination of talc particles beyond the pleural cavity have been reported [Cardillo]. This work has focused mainly on the immediate adverse effects of talc pleurodesis and the influence of dose and particle size on pulmonary inflammation. However, what influence the dissemination of talc has on long term adverse effects remains unclear and no study dealing with this issue was identified.

Editor Comment

(Respiratory Function Tests = RFTs; Primary Spontaneous Pneumothorax = PSP; VATS = Video Assisted Thoracoscopy; Intercostal Drain = ICD; Adult Respiratory Distress Syndrome = ARDS; Secondary Spontaneous Pneumothorax = SSP, Cystic fibrosis = CF; Malignant Pleural Mesothelioma = MPM)

Clinical Bottom Line

Talc pleurodesis in young patients with a primary pneumothorax appears to have minimal long-term adverse effects.

References

1. Cardillo G, Carleo F, Giunti R, Carbone L, Mariotta S, Salvadori L, Petrella L, Martelli M. Videothoracoscopic talc poudrage in primary spontaneous pneumothorax: a single-institution experience in 861 cases. J Thorac.Cardiovasc Surg 131:322-328, 2006.
2. Ozcan C, McGahren ED, Rodgers BM. Thoracoscopic treatment of spontaneous pneumothorax in children. J Pediatr.Surg 38:1459-1464, 2003.
3. Tschopp JM, Boutin C, Astoul P et al. ESMEVAT team. (European Study on Medical Video-Assisted Thoracoscopy). Talcage by medical thoracoscopy for primary spontaneous pneumothorax is more cost-effective than drainage: a randomised study. Eur Respir J. 2002 Oct;20(4):1003-9.
4. de Campos JRM, Vargas FS, Werebe EdC, Cardoso P, Teixeira LR, Jatene FB, Light RW. Thoracoscopy Talc Poudrage : A 15-Year Experience. Chest 119:801-806, 2001.
5. Milanez JR, Vargas FS, Filomeno LT, Fernandez A, Jatene A, Light RW. Intrapleural talc for the prevention of recurrent pneumothorax. Chest. 1994 Oct;106(4):1162-5.
6. Viskum K, Lang P, Mortensen J. Long term sequelae after Talc pleurodesis for spontaneous pneumothorax. Pneumologie. 1989 43:105-6.
7. Lange P, Mortensen J, Groth S. Lung function 22-35 years after treatment of idiopathic spontaneous pneumothorax with talc poudrage or simple drainage. Thorax. 1988 Jul;43(7):559-61.
8. Research committee of the British Thoracic Association and the Medical Research Council Pneumonconiosis unit. A long term survey of the long term effects of talc and kaolin pleurodesis. Br. J Dis. Chest. 73; 1979: 285-88.