Document 9JNZOqGX7wbnXwyK3Gk4y93pV

FILE NAME: Talc (TALC) DATE: 1979 DOC#: TALC141 DOCUMENT DESCRIPTION: Medical Journal Article - Survey of the Long-Term Effects of Talc and Kaolin Pleurodesis >sis should )sy should specimen, d biopsy. preliminary of pleural 106. of pleural icans. Nig, 1. B r.y . Dis. Chest (1979) 73, 285 A SURVEY OF THE LONG-TERM EFFECTS OF . TALC AND KAOLIN PLEURODESIS Research C ommittee of the B ritish T horacic A ssociation a n d the M edical R esearch C ouncil P neum oconiosis U n it * Summary Of 210 patients who underwent pleurodesis with iodized talc or kaolin 14 to 40 years previously, all but 11 were traced. There was no increased incidence of lung cancer and no case of mesothelioma. ' Introduction Exposure to high concentrations of talc dust in mining and processing in the USA has been shown to cause pulmonary fibrosis and a four-fold increase in the incidence of malignant tumours of the lung and pleura (Kleinfeld et al. 1967). However, this dust contained other silicates including tremolite and anthophyllite and the incidence of these malignant tumours fell and approached the expected mortality when dust levels were reduced (Kleinfeld et al. 1974). In a controlled study of Italian talc miners and millers exposed to a very pure type of talc Rubino et al. (1976) were able to show a lower than expected incidence of lung cancer, although the mortality rate amongst the miners exceeded the norm because of the high incidence of pneumoconiosis (silicosis) with or without tuberculosis. In Great Britain Henderson et al. (1971) described talc particles in association with carcinoma of the ovary and cervix, confirmed later by analytical electron microscopy (Henderson & Griffiths 1975). Jackson and Bennett (1973) reported a chest wall tumour of adenocarcinomatous type developing within three years of iodized talc pleurodesis for recurrent spontaneous pneumothorax but it is unlikely that the talc played any causative role in the development of this tumour. Animal studies using inhalation and intrapleural injection of an Italian cosmetic talc have failed to demonstrate a carcinogenic effect (Wagner et al. 1977). Talc, which is mainly a hydrated magnesium silicate, is marketed in different grades, the higher grade being used for cosmetic and pharmaceutical purposes and the others in industry (Hildick-Smith 1976). Cosmetic talc consists of flake-like particles and is largely free of the long thin fibres of asbestos-like minerals (such as tremolite, actinolite and anthophyllite) which are closely related to it in the natural state. These contaminate some industrial talcs, however, and are possibly responsible for the fibrogenic and car cinogenic effects already referred to. In Britain talc has been used by intrapleural poudrage since 1935 to induce pleurodesis, usually for treatment of recurrent spontaneous pneumo thorax. A follow-up of such patients should reveal any possible carcinogenic effects of talc and a subcommittee was set up by the British Thoracic Association and Medical Research Council Pneumoconiosis Unit to organize a survey. * Members of the subcommittee were A. G. Chappell (chairman), A. Johnson (coordinator), J- Charles, J. C. Wagner, R. M . E. Seal, G . Berry and D . Nicholson. 286 British Thoracic Association/MRC Methods . In order to obtain a large number o f index cases 11 thoracic centres were approached but only three were able to participate: Sully, Brompton and Harefield Hospitals. At each centre medical record indexes and surgical registers were reviewed and the notes scrutinized to identify patients who had received pleurodesis with talc or a like mineral such as kaolin (china clay, hydrated aluminium silicate) before January 1961 so that a minimum observation period o f 14 years was possible. Tracing the patients proved a difficult and lengthy task. M ethods used included direct written approaches to patients and general practitioners, family practitioner committees, the Office of Population Censuses and Surveys (OPCS) and foreign embassies. A large number of patients would have remained untraced without further assistance from two `field' workers with experience of epidemiological studies who cross-checked information for accuracy and made visits to discover the present state of index cases not traced by letter. The results were assessed by comparing the number of observed deaths with the number expected by the subject-years method (Case & Lea 1955) multiplying years o f risk by death rates. T he death rates for England and Wales were taken from tables compiled for studies of this kind (Institute of Cancer Research 1976). These tables give age-specific death rates with age in five-year groups and also calendar year in five-year groups up to 1966-70. T he study extends beyond 1970 and the rates for 1966-70 were used for thq later years. Deaths from all causes and also from cancer of the lung and pleura have been considered. Excess mortality has been tested by treating the observed number as a Poisson variable with expectation equal to the expected number. Results Two hundred and ten cases were collected from the three centres (Table I). The Sully patients, many of whom had chronic lung disease such as chronic bronchitis, emphysema and pneumoconiosis, received intrapleural kaolin as treatment for spontaneous pneumo thorax between 1956 and 1960. All the Brompton and Harefield patients received intra pleural talc over half having been treated before 1945. In 22 Brompton and 70 Harefield patients iodized talc was used to produce pleurodesis in patients with bronchiectasis and other non-malignant disorders before lung resections. Hospital Sully Brompton Harefield No. of patients {males) 63 (50) 43 (24) 104 (54) 210 (128) Table I. Outcome o f the study Contacted, alive and well Untraced but believed alive 45 -- 26 -- 81 2 152 2 Emigrated and untraced -- 3 6 9 Dead {lung cancer in parentheses) 18 14 (1) 15 (2) 47(3) One hundred and fifty-two patients have been contacted and are well whilst a further two are thought to be alive (OPCS) but have not been traced (Table I). Follow-up data are available on nine emigrants for periods ranging from 14 months to 24 years but attempts to locate them have failed. There were 47 deaths including three from lung cancer (Table II). Two patients with lung cancer had a tumour on the side opposite to the pleurodesis with intervals of 18 months and 19 years between pleurodesis and death. The third case was a 61-year-old man with a carcinoma i radiotherap significant < patients we Table III patients, 36 three quinq the already for 21 of th This study Later repor contaminan of carcinort only in rec iched but only centre medical entify patients clay, hydrated f 14 years Was ncluded direct tees, the Office rer of patients ith experience its to discover a the number yy death rates. ;s of this kind ge in five-year s beyond 1970 o from cancer y treating the ber. ). The Sully emphysema tus pneumo:eived intra70 Harefield liectasis and Dead (lung cancer in parentheses) 18 14 (1) 15 (2) 47(3) 1st a further ow-up data 1 years but atients with irvals of 18 61-year-old Talc and Kaolin Pleurodesis 287 Table II . Observed and expected mortality Hospital Sex A ll causes* Obs. Exp. Lung cancerf Obs. Exp. Sully Brompton Harefield Men Women Men Women Men Women 18 9.1 0 0 .8 9 3 .4 5 4 .0 11 7.1 4 4 .6 0 0.84 0 0.03 1 0.36 0 0.06 2 0.72 0 0.13 Total *P<0.01. f P>0.3. 47 29 ' 3 2.14 man with an oat cell carcinoma who died 32 years after pleurodesis. The site of the carcinoma is not known and at autopsy no tumour was found, but he had received radiotherapy. Although lung cancer deaths were no greater than expected, there was a significant excess of observed over expected mortality for all causes (the two untraced patients were assumed to be alive for the purposes of this calculation). Table III shows that although follow-up was longer than 15 years in the majority of patients, 36 deaths occurred within 15 years of pleurodesis. The observed deaths in these three quinquennia were significantly more than expected. The probable explanation is the already high incidence of respiratory disease in these patients at the time of pleurodesis for 21 of the deaths were due to respiratory causes. Table II I. Duration of follow-up after pleurodesis Duration offollow-up (years) 0-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 Deaths 16 9 11 6 2 0 2 1 Others 4# 2* 5+ 70 7 3 45 "27 Total 47 163 * Emigrated, f Includes one emigrant. D iscussion This study was devised in 1974 because of the suggestion that talc might be carcinogenic. Later reports quoted in the introduction have not supported this view and asbestos-like contaminants were possibly responsible for the early reports of an increased incidence of carcinoma. Strict standards for the manufacture of cosmetic talc have been adopted only in recent years (Editorial, 1977). We have been able to ascertain that talc B.P. 288 British Thoracic Association!MRC was used at Brompton and Harefield Hospitals even before 1945. Indian Finex has been used extensively for this preparation in the past and is unlikely to have contained any fibrous amphiboles but we have no idea of the composition of other B.P. talcs over the past 40 years (Pooley 1978). It was decided to include patients treated with kaolin because of its chemical similarity to talc and its propensity for producing pulmonary fibrosis after prolonged and heavy exposure, even though no carcinogenic effect has been ascribed to the mineral. All the Sully patients received kaolin rather than talc for their pleurodesis, but even if they are excluded from the analysis of lung cancer deaths (Table II) the ratio of the observed to expected incidence is still not significant (P=0.14). Tracing of patients proved very difficult, particularly those from Brompton and Harefield cases, over half of whom were treated prior to 1945. No attempt was made to examine or X-ray the patients, who were scattered throughout the country. It was felt that this would prolong the study and prove unrewarding as very few asymptomatic cases of mesothelioma would have been expected, for Elmes and Simpson (1976) in their study of 327 cases found a mean interval between onset of symptoms and arrival at hospital of only 3.4 months. We have therefore found no increased incidence of lung cancer and no case of meso thelioma in the series of 210 patients, 88 of whom have been followed for between 15 and 30 years and 75 for 30-40 years after pleurodesis. A cknowledgements We are grateful to Miss C. Exall and M rs B. Norman-Smith for their painstaking work in tracing many `missing' patients, and Mrs B. Gamble .and Mrs I. Speck for secretarial assistance. R eferences Case, R. A. M. & Lea, A. J. (195S) Mustard gas poisoning, chronic bronchitis, and lung cancer. Br. y . prev. soc. Med. 9, 62. ' Editorial (1977) Cosmetic talc powder. Lancet 1, 1348. Elmes, P. C. & Simpson, M . J. C. (1976) T he clinical aspects o f mesothelioma. Q.jfl M ed. 45, 427. H enderson, W. J. & Griffiths, K. (1975) Identifications of particles in ovarian tissue. In Gynae cological Malignancy : Clinical and Experimental Studies, ed. M . G . Brush and R. W . Taylor, pp. 225-40. London: Baillire Tindall. H enderson, W. J., J oslin, C. A ., T urnbull, A. C. & G riffiths, K. J. (1971) Talc and carcinoma o f the ovary, and cervix. J . obstet, gynaec. Br. Commonw. 78, 266. H ildick-Smith, G. Y. (1976) T he biology of talc. Br. J . indust. Med. 33, 217. Institute of Cancer Research (1976) Serial M ortality Tables-- Neoplastic Diseases, Vol. 1. Deaths and Death Bates by Sex, Age, Site and Calendar Period. London. Jackson, J. W. & Bennett, M . H . (1973) Chest wall tumour following iodised talc pleurodesis. Thorax 28, 788. K leinfeld, M ., M essite, J., K ooynar, Cf. & Zaki, M . H . (1967) Mortality among talc miners and millers in N ew York State. Archs envir. H lth 14, 663. K leinfeld, M ., M essite, J. & Zaki, M . H . (1974) M ortality experiences among talc workers: a follow-up study. J . occup. Med. 16, 345, P ooley, F. D . (1978) Personal communication. Rubino, G. F., Scansetti, G ., P iolatto, G . & R omano, C. A . 61976) Mortality study of talc miners and millers, y . occup. Med. 18, 186. ' W agner, J. C., Berry, G ., C ooke, T . J., H ill, R. J., P ooley, F. D . & Skidmore, J. W . (1977) Animal experiments w ith talc. In Inhaled Particles I V , ed. W . H . Walton, pp. 647-54. Oxfor and N ew York: Pergamon. u Electron mic that the turn matory cells Fibroblasts relationship 1 Since the fii (1963) and ". manifestatioi cally differer cell granuloi paper the ca not followed A 27-year-old solitary lesion tom-free and 1 a sharply defir on. the bronc cytology reve Protein was 81 The patiew an oval-shape Was well-enca Was no abnor necrotic areas hospital in M radiograph.