Document DM6kjZjOEz75m2dkgZ2bakoYQ

FILE NAME Brakes BRK DATE 1984 Sept DOC BRK087 DOCUMENT DESCRIPTION Journal Article - Malignant Mesothelioma - Clinical and Epidemiological Features Reprinted from the SA Medical Journal Vol 66 15 September 1984 pp 407 - 412 Malignant mesothelioma epidemiological features A report of 80 cases K. SOLOMONS clinical and The clinical epidemiological of malignant mesothelioma as proved by examination ~ specimens referred clinic at of biopsy to the the for National Centre Occupational Health between January 1977 and June 1983 are reviewed There was ' a positive history of asbestos exposiun r89e of death cas Theemes an survival time diagnosdieasth was 8,6 months and from the onset of symptomtso death 13,6 months Survival time was unaffected symptoms presence treatment histological side of stage of the tumour smokingstatus presenting absence of effusion and asbestosis features or . lesion ~~ source of exposure and lag period from first exposure oe to diagnosis The duration ofsurvival was significantly - affected by age at diagnosis duration of asbestos exposure and the number rather than the type of treatment regimens used Caution is advocated in interpreting these data since the numbeorf cases was : , small and the study design was retrospective A. same reference group of 546 cases notified over the =Kees oa ae toed eet ene Nn Department of Occupational Medicine National Centre for Occupational Health Johannesburg K. SOLOMONS M.B. CH.B. available million year from per was calculated the underestimate data for South Africa This figure is an because not all diagnosed cases are reflected and more important significant numberosf cases are The never diagnosed extent is which the compen- sation machinery functions mentioned at South African mines produced 249 187 metric tons of asbestos in 1979 of which 53 was crocidolite 31 chrysotile and 16 amosite Exports accounted for 95 of the total production the remaining % being used locally While the 12 050 miners Table I who mined this tonnage are at risk of developing asbestosinduced diseases it is not possible at present to estimate the numbers of people in the rest of the population who are at a similar risk from either occupational or environmental exposure Almost 100 new cases of mesothelioma are confirmed nationwide by the South African Asbestos Tumour Reference Panel referred to as the Panel each year This figure which excludes asbestos tumours other than pleural and peritoneal meso- theliomas underestimates the true incidence of mesothelioma in the country 407 408 SA MEDIESE TYDSKRIF DEEL 66 15 SEPTEMBER 1984 Miners TABLE 1. ASBESTOS MINING DATA Asbestos production metric tonnes Year 1977 1978 1979 1980 1981 1982 Total 23 367 13311 12050 12626 11316 724 White 1096 718 678 706 617 649 Coloured and Black 271 593 11372 11920 699 10075 Totalf 380 164 257 325 249 187 276734 235 943 - Amosite - 39 058 - 56 834 - Chrysotile - 828 - 76772 --- Crocidolite - 118 301 - 102 337 --- * Bulletin of Statistics Pretoria Central Statistical Services 1979 1982 1983 South African Statistics Pretoria Central Statistical Services 1982 117 South African Mining and Engineering Yearbook Johannesburg Jim Emery 1981 16 1982 21 Value R1000 R1000 137779 682 048 102 148 335 --- Most cases diagnosed in the Witwatersrand area are referred for an exposure history to the clinic attached to the National Centre for Occupational Health Between 1972 and June 1983 150 documented cases of meso- thelioma were seen at the clinic A report on the first 70 cases was published by Cochrane and Webster in 1978. This article reviews the findings in the subsequent 80 cases The objectives of the review are to examine the epidemiology of mesothelioma in South Africa and the value of clinical and epidemiological features as prognostic indices for survival Subjects and methods All cases of malignant mesothelioma proven histologically from biopsy specimens and seen by the clinic between January 1977 and June 1983 were included in the study group Data on each subject were collected from the clinic's files Where the records were incomplete additional data were obtained from general practitioners thoracic surgeons hospitals the Panel the Workmen's Compensation Commissioner the South African Transport Services the Medical Bureau of Occupational Diseases employers and family members All cases of mesothelioma confirmed by the Panel over the same period excluding those in the study group were also evaluated Only basic data on age sex race and exposure history were available for this group and they were not followed up for survival data The function of this reference group was to act as a body to which clinical findings in the study group could be generalized if it resembled the study group in significant features and to provide a broader population from which epidemiological data could be gathered Diagnosis was either made by the Centre's pathologists or subsequently corroborated by them The tumour type and the presence or absence of parenchymal asbestosis were also determined on histological examination of biopsy material which was usually obtained at open thoracotomy exposure histories were taken from all patients or their families at the request of the attendant thoracic surgeon or the Centre's pathologists Exposure history was considered positive if the patient recalled working with or being environmentally exposed to asbestos Environmental exposure included childhood domestic neighbourhood or any other definite exposure which was not occupational Possible exposure was recorded if the patient had no recall of specific asbestos exposure but when she had either worked in an industry or spent time in an environment where asbestos contamination was likely Exposure was considered negative if neither positive nor possible exposure were recorded Negative exposure means that no exposure history was elicited not that exposure had never occurred exposure could have occurred in infancy or childhood or been negligible or obscure Patients were staged retrospectively from data obtained from surgeons operative findings and notes at the time of diagnosis according to the system advocated by Mattsonstage I - ipsilateral pleura and lung only stage II - chest wall invasion mediastinal or pericardial involvement contralateral lung or pleural involvement stage III extrathoracic extension a nodes outside chest b diaphragmatic penetration to perito- neum stage IV - distant metastases It must be emphasized that staging was not an active process and that no standard staging system was used by the different surgeons Treatment was broadly divided into the major modality used rather than specific agents and regimens since these varied widely largely because treatment was not carried out at a single centre with standardized regimens The data were analysed statistically by a variety of techniques including analysis of variance and product survival analysis Percentages have been rounded off to the nearest point Results The study group comprised 80 subjects The mean age at the time of diagnosis was 57,2 years and the range 24 - 87 years The male female ratio was 10 the group consisting of 73 men 91 and 7 women % There were 64 Whites 80 13 Blacks 16 and 3 Coloureds % One subject had a primary peritoneal mesothelioma but the pleura was the primary site in the rest These mesotheliomas arose on the left side in 37 cases 46 and on the right side in 40 50 No data were available in the remaining 2 cases In 72 of cases 58/80 Panel had confirmed the diagnosis of malignant mesothelioma 3 patients had never been submitted and 19 patients had been submitted but not yet examined since submission of this article the diagnosis of mesothelioma was confirmed by the Panel in these latter 19 patients A positive history of previous asbestos exposure was obtained from 71 subjects 89 4 % gave a history of possible exposure and in 5 % no history of prior exposure was elicited Similar studies in the past have found between 18 and 97 positive exposure histories. In 59 cases 74 there was a history of only occupational exposure 7 % had a history of only environmental exposure and 5 % had a history of both occupational and environmental exposure The remaining 9 11 had either no exposure or only possible exposure The 4 subjects with possible exposure had possible occupational exposure one as a boilermaker another as a fitter and turner on naval ships one handling construction material and the fourth as a market agent handling hessian sacks which had previously been used to transport asbestos Among those 68 subjects with occupational exposure 15 22 were exposed in the mining industry 15 22 on the SA MEDICAL JOURNAL VOLUME 66 15 SEPTEMBER 1984 409 railways 8 12 in the construction industry 6 % in the engineering industry 2 each in the electrical engineering and battery industries 7 10 in the primary asbestos manufacturing industry and 11 16 in other assorted industries Table II The activities among those subjects occupationally exposed included lagging of boilers and pipes in 23 cases 34 underground mining in 8 12 surface mining jobs in 5 % and transport of raw asbestos in a further 6 cases % Drilling cutting and sawing of asbestos products sheets boards cloth accounted for exposure in 11 cases 16 and the use of asbestos gloves blankets and aprons for another 3 cases % One of this latter group of 3 had further exposure from the asbestos present in asbestos welding rods The work activities of the remaining 12 18 were not specified The types of asbestos involved were predominently mixed although Cape crocidolite as the sole type was documented in 17 cases Amosite asbestos from the Penge mine was implicated as the sole type in 4 cases A fifth patient with only amosite exposure was excluded from the study group because the Panel diagnosed squamous carcinoma of the bronchus and not mesothelioma Similarly a patient with squamous carcinoma of the bronchus an amosite miner was excluded from the reference group The reference group included 8 cases of mesothelioma with amosite exposure No further data on asbestos type were available The mean duration of asbestos exposure was 13,6 years but ranged from 1 week to 47 years The mean lag period of time TABLE II SOURCE OF ASBESTOS EXPOSURE No. of patients Mining Mining Milling and sorting Transport sinking Railways Workshops Transport Construction Carpentry Construction site Plumbing Asbestos insulation spray Marine engineering Naval shipyards naval engine Engineering - Electricians Battery industry Manufacture Destruction Asbestos board and sheet manufacture Asbestos manufacturers agents Fitting and turning Brake repairs Stove manufacture Cement manufacture Mattress manufacture making asbestos belts and pad repair on conveyor belt Foundryman . Market agent contaminated hessian bags Environmental Nil known Total @ 2 1 11 11 3 1 a 3322 32 1 5 2 mr 1 1 1 580 from first exposure to diagnosis was 34,3 years In one case the lag period was as short as 4 years and in another as long as 68 years There is a possibility that the person with the year lag had environmental exposure to asbestos as a child but this could not be confirmed by a carefully taken history At the time of diagnosis 29 43 of the 68 subjects whose smoking status was known were still smoking 8 12 had stopped smoking within 10 years of their presentation 9 13 had stopped more than 10 years before their presentation and 22 32 were lifelong smokers The smoking status of the remaining 12 subjects was not established Dyspnoea and chest pain were the presenting symptoms in 75 of all cases dyspnoea alone in 23 cases 29 chest pain alone in 14 cases 18 and both in 22 cases 28 In 4 cases the tumour presented incidentally 3 at routine chest radiography and 1 at unrelated abdominal surgery The remaining cases presented in various ways including recurrent chest infections Horner's syndrome chest swelling abdominal mass and ascites Associated symptoms included weight loss cough tiredness and haemoptysis Pleural effusions detected clinically and radiologically were present in 42 cases 56 and absent in 33 44 Parenchymal asbestosis established on histological examination of lung tissue specimens was present in 18 cases absent in 42 and unknown in the remaining 20. The histological type of tumour was established in 36 cases 45 Of these 29 80 were epithelial 2 % were sarcomatous and 5 14 were mixed The stage of disease at diagnosis was ascertained in 50 cases 63 Of these 9 18 were in stage I 25 50 in stage II 14 28 in stage III and 2 % in stage IV A number of cases had evidence of haematogenous and distant tumour spread which confirms reports that malignant mesothelioma invades the bloodstream and metastasizes Table III In 5 of the 10 cases on which full autopsies were performed internal abdominal organs were affected by haematogenous spread In the 5 remaining cases spread was confined to intrathoracic organs The superior vena cava syndrome and Horner's syndrome were observed in 4 and 2 cases respectively TABLE III SITES OF SPREAD IN 52 CASES No. 32 Ipsilateral lung 26 Chest wall 11 Thoracotomy scar 12 Pericardium 3 Opposite pleura 12 Opposite lung Mediastinal structures lymph nodes 16 great vessels myocardium 14 Diaphragm 6 Peritoneum 5 Intestine 8 Liver 2 Kidney 1 Adrenals 1 Spleen 2 Mesentery 1 Abdominal wall 1 Scalp % 62 50 21 23 6 23 31 27 12 10 15 4 2 2422 2422 2422 2422 Information about treatment was known in 69 of the 80 cases A total of 5 different therapeutic modalities were employed either alone or in a variety of combinations These included radiotherapy in 22 cases systemic chemotherapy in 20 cases in 23 cases immunotherapy with BCG in 11 cases and sinutrrgaeprlyeural mustine in 26 cases In 29 cases only one of these 410 SA MEDIESE TYDSKRIF DEEL 66 15 SEPTEMBER 1984 methods of treatment was used In 19 cases a combination of two methods was used in 12 cases a combination of three methods and in 2 cases a combination of four different methods In 5 cases no anticancer therapy was given Radiotherapy and systemic chemotherapy were used in combination on their own and with a other methods in total of 18 cases Survival data were available in 80 of cases and recorded in months from diagnosis to death and from onset of symptoms to death The mean survival time from diagnosis to death was 8,6 months and ranged from 1 week to 64 months 85 of subjects died within 12 months of diagnosis The mean survival time from the onset of symptoms to death was 13,6 months and ranged from 3 to 64 months The mean duration of time from onset of symptoms to diagnosis was 5,5 months and ranged from 2 weeks to 21 months Only 23 of the subjects are on record as having been compensated for mesothelioma In terms of the legislation 25 of the subjects 31 were not eligible for compensation but the remaining 55 69 were all eligible Only 27 of these subjects are known to have claimed compensation 4 were turned down and the remaining 23 were compensated Compensation was awarded to 3 people who had both mesothelioma and asbestosis at a time when mesothelioma had not yet become a disease for which compensation was paid but when asbestosis was Compensation was paid to 6 miners 5 White 1 Black 11 railway workers all White and 6 industrial workers 5 White 1 Black It seems that White railway workers and miners receive compensation in a high percentage of cases but Black miners and railway workers and most industrial workers are less frequently compensated At the end of the survey period 15 of the subjects in the group were still alive 19 had been lost to follow and 66 had died Reference group The reference group comprised 546 cases in 505 of which the diagnosis of mesothelioma had already been confirmed by the Panel 41 were yet to be examined by the Panel The Panel had confirmed 481 of the 505 cases as definite mesothelioma and 24 as probable mesothelioma The mean age of the control group was 55,1 years and ranged between 20 and 90 years The sex of 14 subjects in the reference group was not known but of the remaining 532 the female ratio was 2,9 - 395 males 74 and 137 females 26 The racial classification of 14 cases was not known but of the remaining 532 Whites comprised 43 228 cases of the group Coloureds 20 107 cases and Blacks 37 197 cases Sketchy positive exposure histories were available in 307 cases 56 and possible exposure histories in a further 71 cases 13 No history was available for the remaining 168 cases 31 Occupational exposure occurred in 213 subjects 69 and environmental exposure in 94 31 of the 307 with a positive history of exposure Mixed environmental and occupational exposure was noted in 13 of these 307 cases % Mining accounted for exposure in 143 67 of the 213 occupational exposure cases and industrial exposure for the remaining 70 cases 33 The histological type of tumour was known in 89 cases 16 58 65 were epithelial 16 18 were sarcomatous and 15 17 were mixed Parenchymal asbestosis was documented in 41 cases % No further data on asbestosis were available since no parenchymal biopsy material was submitted for histological examination in the remaining cases It is not known how prevalent asbestosis was among the other 505 subjects Histories of cigarette smoking were available in 88 cases Sixty subjects a had positive history of smoking and the remaining 28 were smokers Results of statistical analysis The results of product survival analysis indicated that the outcome or duration of survival was unaffected by the stage of the disease treatment presenting symptoms smoking status side on which the lesion occurred presence or absence of asbestosis and pleural effusion lag period from first exposure to diagnosis histological type of tumour or source of asbestos exposure Table IV The number of cases may have been too small for significance to be detected in the latter two categories Significant differences in outcome were detected with regard to age at diagnosis duration of exposure to asbestos and the number of therapeutic modalities used in treatment The mean duration of survival from diagnosis in patients over 50 years of age was 14,9 months while that for patients under 50 years was 7,4 months P = 0,03 This difference disappeared however when survival was measured from the onset of symptoms P = 0,13 Similarly when survival from diagnosis to death was correlated with the duration of asbestos exposure patients with TABLE IV FACTORS PREDICTING OUTCOME P value - Factor P value - diagnosis to death onset of symptoms to deatht Histological tumour type Source of exposure Smoking Side of tumour Asbestosis Lag period Presenting symptoms Effusion Stage Therapy Age at diagnosis Duration of exposure No. of therapeutic modalities 0,0951 0,5023 0,6097 0,0522 0,3934 0,4702 0,2908 0,8232 0,9587 0,9423 0,0310 0,0340 0,0000 - 0,0003 - 0,2509 0,7747 0,1186 0,1440 0,1503 0,7563 0,2856 0,8180 0,8063 0,1341 2,2912 0,9845 Correlation between factor and survival time from diagnosis to death expressed as a P value Correlation between factor and survival time from onset of symptoms to death expressed as a P value #Numbers too small to exclude significance Tendency towards significance i.e subjects with sided pleural mesotheliomas had a tendency to survive longer than subjects with sided tumours - 15,4 months as opposed to 8,63 months respectively Significant P < 0,05 SA MEDICAL JOURNAL VOLUME 66 15 SEPTEMBER 1984 411 exposure of between 30 and 40 years survived for a mean of 22,1 months whereas patients with less than 1 year's exposure survived for a mean duration of 5,6 months P = 0,03 This difference disappeared when survival was measured from the onset of symptoms P = 0,29 Patients treated with one or more anticancer modalities whereby the available figures underestimate the true incidence The total number of miners in the study and reference groups including the 21 miners from the Medical Bureau for Occupational Disease records is 171. Of these 44 26 were White 40 24 Coloured and 87 51 Black The White to Coloured and Black ratio is therefore almost 3 The race survived significantly longer from diagnosis than untreated distribution of asbestos miners for the period 1977 - 1982 patients < 0,0001 While patients treated with four modalities averaged 1 White to nearly 18 Coloureds and Blacks Table I survived significantly longer than patients treated with one or The number of Coloureds and Blacks at risk from asbestos three modalities P = 0,01 and 0,03 respectively they had no mining exposure is therefore nearly 18 times the number of advantage as regards survival over patients treated with two Whites Since the average duration of employment of Black modalities P = 0,08 All these differences however disappeared miners is shorter and their rate of turnover higher than those of when survival was measured from the onset of symptoms the White miners it is likely that greater numbers and an even The number of cases was too small to permit testing of the higher proportion of Black miners are at risk effects of combinations of factors such as stage and treatment or While the evidence for a response relationship for stage treatment and histological type on outcome This drawback mesothelioma is not as strong as it is for lung cancer in relation to restricts the interpretation of both negative stage and therapy asbestos exposure it is reasonable to assume that people with and positive age and therapeutic modalities associations shorter durations of exposure have a lower relative risk of The study group resembled the reference group with regard to contracting mesothelioma than those with longer exposures.10 age 57,2 years and 55,1 years P = 0,16 and histological type of However most South African asbestos miners work on the tumour P = 0,21 but had significantly more Whites 80 mines for longer than 2 - 3 months and would therefore have an compared with 43 P < 0,0001 and fewer females % exposure greater than 2 - 3 years a level which compared with 26 P = 0,0006 than the reference group Nicholson et al regard as sufficient to impart a significant risk Furthermore fewer subjects in the study group were exposed for the development of asbestos disease It is beyond the scope of environmentally % compared with 30 and through mining this article to estimate the size of the risk population in South 22 compared with 46 but a higher proportion were exposed Africa or to put a figure to the true incidence of mesothelioma in industry 60 compared with 23 but it is clear from the above discussion that in spite of the ta e k These differences are explained by the fact that the study group came mostly from the industrial sector of the Witwaters- relatively large numbers of Black miners found to have mesothelioma significant numbers of cases must occur which are rand whereas the reference group was drawn from a nationwide never recognized or diagnosed The extent of underdiagnosis is selection and particularly included the populations at risk probably more marked in the mining industries Of all the because of asbestos mining Mining places large numbers of mesotheliomas arising from mining industry 87 occurred ' people at risk especially women and children through environ- mental contamination Thus 52 of the 71 women 73 in the reference group with known exposure sources were exposed environmentally and more than half of those exposed environ- among Whites and only 13 among Coloureds and Blacks The ratio of Blacks to Whites is not as high in mining industry as in the mining industry but is still high enough to expect that greater numbers of mesotheliomas would occur among Coloured mentally were women 57 as opposed to 43 of the men It is and Black workers The Black : White ratio in the two industries not possible to comment on the clinical implications of these where most mining mesotheliomas arose in this study the epidemiological features since the numbers in the study group construction industry and the railways is 6,5 and 1,3 were too small to indicate the effect if any that the source of respectively A similar situation applies as regards the environ- asbestos exposure might have on survival mentally exposed cases where 45 of all cases detected occurred among Whites and 55 among Coloureds and Blacks From the mean figure of 96,3 new cases of mesothelioma per Discussion year found in this study an annual incidence figure ageadjusted to the 1980 US population of 7,2 million population Mesothelioma is a rare tumour Its incidence has been reported was derived Table V As has been shown even this figure as 1 and million per annum in Canada and the USA underestimates the true incidence - further research is needed respectively The reporting of cases in South Africa is unfortunately unreliable Mesothelioma was only coded separately as a specific cause of death by the Department of Statistics in 1977. In 1978 a total of 5 deaths were officially recorded as due ee to mesothelioma in the study group alone 4 deaths occurred in that year The most recent official data available on causes of Cet death are dated 1978 for Whites Coloureds and Asians with 4 deaths from mesothelioma all in Whites and 1979 for Blacks in which year 18 deaths from mesothelioma were recorded In these circumstances the most reliable mesothelioma inci- to arrive at more reliable estimates The most plausible explanation for the South African incidence being more than three times higher than that found in the US is that asbestos is not mined or milled there in any major quantity whereas these activities are central to the South African asbestos industry The Canadian incidence rate is much lower than the South African rate presumably because although much mining and milling is carried out in Canada only chrysotile is worked in Canada whereas South Africa mines crocidolite and amosite as well both of which are considered to be more carcinogenic in man than dence data at present come from the Panel records Unfortu- nately not even the Panel records all diagnosed mesothelioma cases since there is no statutory obligation for cases to be reported to the Panel or any other centre Over the year period 1980 - 1982 only 57 of the 78 mesothelioma cases diagnosed and compensated by the Medical Bureau for Occupational Diseases were reported to the Panel unpublished records of the MBOD 1980 1983 In addition to these 21 unreported cases there are 3 from the study group which were also not reported to the Panel There is also cause to believe that significant numbers of cases occur which are never diagnosed particularly among Blacks.,, These unrecognized cases contribute further to the extent chrysotile. Another area of interest in the context of mesothelioma in South Africa is compensation Mesothelioma was made an occupational disease sufferers of which were eligible for compensation in the mining sector in 1979 although it has been compensated in the mining industry under a provision for compensation of pneumoconiosis since 1962. In this series of 48 industrially exposed mining subjects fewer than half 38 of all those eligible have been compensated The situation in the mining industry is much better and 88 subjects were compensated by the mines over the study period Even so only 1 of the 8 Black miners from the study is known to have been compensated to 412 SA MEDIESE TYDSKRIF DEEL 66 15 SEPTEMBER 1984 TABLE V. ADJUSTMENT TO US POPULATION 1980 FOR ANNUAL AVAILABLE SOUTH AFRICAN MESOTHELIOMA INCIDENCE RATE Age group yrs No. of cases 1977 - 1983 Adjusted No. of cases 1977 - 1983 Annual specific incidence million population Annual adjusted agespecific incidence rate million population 0-19 20 - 29 30 - 39 40 - 49 50 - 59 60 - 69 70 _- 12 42 106 144 129 68 _ 15 52 130 177 158 84 0,5 2,5 9,0 18,3 26,8 30,0 0,090131 0,347906 0,9042165 1,8843363 2,2322845 1,534977 80 - 89 90+ Total 7 1 509 9 1 626 11,2 5,2 0,2238565 7,2177078 * Adjusted for cases with unknown age on proportional basis South African 1980 population figures source Year Estimates Republic of South Africa 1980 Statistical News Release Pretoria Central Statistical Services December 1982 US 1980 population figures source 1980 Census of Population US Department of Commerce Washington DC Bureau of the Census 1981 3 . date Attending medical practitioners shoulder a large portion of the responsibility for ensuring that details of all patients eligible for compensation are submitted to the appropriate centres Under the Occupational Diseases in Mines and Works Act there is a legal obligation on medical practitioners to notify all cases of mesothelioma in people employed at mines or controlled works to the Director of the Medical Bureau for Occupational Diseases No such provision exists with regard to industrial workers The obligation on medical practitioners to apply for compensation from the Workmen's Compensation Commissioner in these industrial cases is even more crucial since the responsible employer on whom the onus for reporting accidents and diseases and initiating compensation claims normally rests is often no longer in business Significant numbers of subjects in both the study and the reference groups were exposed to asbestos environmentally % and 30 respectively At present these persons have no recourse to compensation since existing compensation laws only cover persons exposed occupationally No other provision is made to cover them or their families against losses suffered as a result of the disease Malignant mesothelioma affects a relatively young population in South Africa It is noteworthy that % of all the subjects in the study contracted the disease before reaching the age of 40 | years and 31 before reaching 50 years of age Of the 54 subjects under 40 years of age 16 30 had been exposed environmentally presumably from an early age Half of the women 12/24 under 40 years of age were environmentally exposed Large controlled random prospective cohort studies as advocated by Hillerdal are necessary to advance our knowledge of treatment and other factors which may ultimately lead to a better outlook for patients with this disease which has such a dismal prognosis With a mean lag period of 34 years as found in this study and with the continuing mining manufacturing and consumer utilization of asbestos and asbestos products in South Africa even today medical practitioners should be seeing cases of mesothelioma well into the next century and should have ample opportunity to study the disease more comprehensively I thank Dr G. Reinach of the Institute for Biostatistics for statistical help and Dr J. C. Cochrane of the National Centre for Occupational Health for his support and advice Thanks are also due to Professor I. Webster of the South African Asbestos Tumour Reference Panel and Dr H. Faure of the Medical Bureau for Occupational Diseases for making their records freely available REFERENCES 1. Cochrane JC Webster I. Mesothelioma in relation to asbestos fibre exposure a J review of 70 serial cases S Afr Med 1978 54 279-281 2. Mattson K. Natural history and clinical staging of malignant mesothelioma Becklake Eur Respir Dis 1982 63 suppl 124 87 3. Becklake MR Asbestos related diseases of the lung and other organs their epidemiology and implications for clinical practice Am Rev Respir Dis 1976 114 187-227 4. Parkes WR Asbestos disorders Br J Dis Chest 1973 67 261-300 5. McDonald AD Harper A El Attar OA McDonald JC Epidemiology of primary mesothelioma tumors in Canada Cancer 1970 26 914-919 6. Brenner J Sordillo PP Magill GB Golbey RB Malignant mesothelioma of the pleura review of 123 patients Cancer 1982 49 2431-2435 7. 7. South African Department of Statistics Deaths of Whites Coloureds and Asians Report No. 07-03-17 Pretoria Government Printer 1978 131 8. 8. South African Department of Statistics Deaths of Blacks Report No. 07-05- 01 Pretoria Government Printer 1978 85 9.9. South African Department of Statistics Deaths of Blacks Report No. 07-05- 02 Pretoria Government Printer 1979 91 10. Nicholson WJ Perkel G Selikoff IJ Occupational exposure to asbestos population at risk and projected mortality - 1980 - 2030. AmJ Ind Med 1982 : 259-311 11. Central Statistical Services South African Statistics Pretoria Government Printer 1982 7.4 12. Hillerdal G. Prognostic factors and treatment results of 4225 patients with diffuse malignant mesothelioma EurJ Respir Dis 1982 63 suppl 124 89