Document bBgdY4aKz0dVeJx3nQ0NmpXQD

FILE NAME: Welding (WELD) DATE: 1984 Sept DOC#: WELD033 DOCUMENT DESCRIPTION: Journal Article - Malignant Mesothelioma - Clinical and Epidemiological Features Reprinted from the e'SA Medical Journal", Vol 66, 15 September 1984, pp 4 0 7 -4 1 2 Malignant mesothelioma -- clinical and epidemiological features A report of 80 cases K. SOLOMONS Summary The c inicdi arid epidemiological features of 80 cases of malignant mesothelioma ms proven by examination I n of biopsy specim ens refenoa to the clinic at the N<iti,,rial Centre Occupational Hea'th betwuer Januaiy 19"7 and June 1983 are reviewed There was a positu h'Stoiy of asbestos exposure in 8 9 ^ of cases The mean survival time from diagnosis to death was 8.d irontns, anJ from tne o rse t of syp'ptomo to death 1>*b nionths Survival time was unaffected by stage of the turnout, tieatnient histological teatuies smoking status presenting symptoms presence or absence or etfusioi i and -isbestosis side of the lesion, sotiice of exposure and lag period fiom fust exposure to diagnosis Tne duration of survival was significantly affected b . age at diagnusis, duration of asbestos pxpoau1- anti *he number ratner trap tne type of treatment regimens used. Caution is advocated in interpreting these data s.rce the numbei of cases was small ar d the study design was retrospective A tefeienca group of 546 cases notified ovei the same Department of Occupational Medicine, National Centre for Occupational Health, Johannesburg K. SOLOMONS, m b c h b period was drawn from the records of the South African Asbestos Turnout Reference Panel The 1 incompleteness of national mesothelioma incidence data was noted and an incidence figure of 7 pr mmion per vear was calculated from the best-avd'iable data for South Africa This figure is an underestimate because not si' diagnosed cases af*> reflected and, more important, significant numbers of cases are nevei diagnosed The e/tent to which tne compen sation machinery functions is mentioned S A frM e d J 1964 86.407 - 412 South An lean n u n c1' produced 2 W 187 m c lik tori', ol j*.bt">tos in 1079, or w hich S i . was a o c ijo lr tc , 31' c h i\so n ic and H>'am osite. E xports accounted fo r 95% o f th e total production, the rem aining 5% being used locally. W hile the 12 050 m iners (Table I) who mined this tonnage are at risk of developing asbestosinduced diseases, it is n o t possible at presen t to estim ate the num bers of people in the rest of the population who are at a similar risk from either occupational or environm ental exposure. A lm ost 100 new cases of m esotheliom a are confirm ed nation wide by the South African Asbestos Tum our Reference Panel (referred to as the Panel) each year. T his figure, which excludes asbestos tum ours other than pleural and peritoneal meso theliomas, underestim ates the true incidence of mesothelioma in the country. 407 408 SA MEDIESE TYDSKR1F DEEL 66 15 SEPTEMBER 1984 TABLE I. ASBESTOS MINING DATA Miners*______ __________________________ Asbestos production (metric tonnes) Year 1977 1978 1979 1980 1981 1982 Total 23367 13311 12050 12626 11316 10 724 White 1096 718 678 706 617 649 Coloured and Black 22271 12 593 11372 11920 10 699 10 075 Total) 380164 257 325 249187 276 734 235 943 -- Amositei -- 39 058 -- 56834 Chrysohlef -- -- 91 828 -- 76772 CrocidoMej -- -- 118301 -- 102337 *Butletin of Statistics Pretoria Central Statistical Services, 1979,1982,1983 tSoutfi 'African Statistics Pretoria Central, Statistical Services, 1982 11 7 JSoufh African Mining and Engineering YearbOQK Johannesburg Jim Emery, 1981 16,1982 21 Value) (R1 000) 137779 121682 107048 102148 117335 Most cases diagnosed in the Johannesburg/Witwatersrand area are referred for an asbestos-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 W ebster1 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 W orkmen's Compensation Commissioner, the South African Transport Services, the Medical Bureau of Occupational Diseases, employers and family members. All cases of meso thelioma 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 tum our type and the presence or absence of parenchymal asbestosis were also deter mined on histological examination of biopsy material which was usually obtained at open thoracotomy. Asbestos-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, b u t when he/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 M attson2 (stage 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 treatm ent was not carried out at a single centre with standardized regimens. The data were analysed statistically by a variety of techniques including analysis o fvariance and product-limit 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 10:1, the group consisting of 73 men (91%) and 7 women (9%). T here were 64 Whites (80%), 13 Blacks (16%) and 3 Coloureds (4%). One subject had a primary peritoneal mesothelioma, b u t 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 m 40 (50%). No data were available in the remaining 2 cases. In 72% of cases (58/80) the 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 (5%) gave a history of possible exposure and in 5 (6%) no history of prior exposure was elicited. Similar studies in the past have found between 18% and 97% positive asbestos-exposure histories.5 In 59 cases (74%) there was a history of only occupational exposure, 7 (9%) had a history of only environmental exposure and 5 (6%) 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 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 survived significantly longer from diagnosis than untreated patients (P < 0,0001). While patients treated with four modalities survived significantly longer than patients treated with one or three modalities (P = 0,01 and 0,03 respectively), they had no advantage as regards survival over patients treated with two modalities (P = 0,08). All these differences, however, disappeared when survival was measured from the onset of symptoms. ' The number of cases was too small to permit testing of the effects of combinations of factors such as stage and treatm ent or stage, treatment and histological type on outcome. This drawback restricts the interpretation of both negative (stage and therapy) and positive (age and therapeutic modalities) associations The study group resembled the reference group with regard to age (57,2 years and 55,1 years, P --0,16) and histological type of tumour (P = 0,21), but had significantly more Whites (80% compared with 43%, P < 0,0001) and fewer females (9% compared with 26%, P = 0,0006) than the reference group. Furthermore, fewer subjects in the study group were exposed environmentally (9% compared with 30%) and through mining (22% compared with 46%), but a higher proportion were exposed in industry (60% compared with 23%). These differences are explained by the fact that the study, group came mostly from the industrial sector of the Witwatersrand, whereas the reference group was drawn from a nationwide selection and particularly included the populations at risk because of asbestos mining. Mining places large numbers of 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 mentally were women (57% as opposed to 43% of the men). It is not possible to comment on the clinical implications of these epidemiological features since the numbers in the study group were too small to indicate the effect, if any, that the source of asbestos exposure might have on survival. Discussion Mesothelioma is a rare tumour. Its incidence has been reported as 1 and 2,2/miIlion per annum in Canada and the USA respectively.3,6 The reporting of cases in South Africa is unfortunately unreliable. Mesothelioma was only coded sepa rately as a specific cause ofdeath bythe Department of Statistics in 1977. In 1978 a total of 5 deaths were officially recorded as due to mesothelioma; in the study group alone 4 deaths occurred in that year. The most recent official data available on causes of 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).7' 9 In these circumstances the most reliable mesothelioma inci 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 3-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.1 These unrecognized cases contribute further to the extent whereby the best-available figures underestimate the true inci dence. 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 1:3.. The race distribution of asbestos miners for the period 1977 - 1982 averaged 1 White to nearly 18 Coloureds and Blacks (Table I). The number of Coloureds and Blacks at risk from asbestos mining exposure is therefore nearly 18 times the number of Whites. Since the average duration of employment of Black miners is shorter and their rate ofturnover higher than those of the White miners, it is likely that greater numbers and an even higher proportion of Black miners are at risk. While the evidence for a dose-response relationship for mesothelioma is not as strong as it is for lung cancer in relation to asbestos exposure, it is reasonable to assume that people with shorter durations of exposure have a lower relative risk of contracting mesothelioma than those with longer exposures.10 However, most South African asbestos miners work on the mines for longer than 2 - 3 months and would therefore have an exposure greater than 2 - 3 fibre-years/ml, a level which Nicholson et al.10regard as sufficient to impart a significant risk for the development of asbestos disease. It is beyond the scope of this article to estimate the size of the at-risk population in South Africa or to put a figure to the true incidence of mesothelioma, but it is clear from the above discussion that in spite of the relatively large numbers of Black miners found to have meso thelioma, significant numbers of cases must occur which are never recognized or diagnosed. The extent of underdiagnosis is probably more marked in the non-mining industries. Of all the mesotheliomas arising from non-mining industry, 87% occurred among Whites and only 13% among Coloureds and Blacks. The ratio o f Blacks to Whites is not as high in non-mining industry as in the mining industry, but is still high enough to expect that greater numbers of mesotheliomas would occur among Coloured and Black workers. The Black: White ratio in the two industries where most non-mming mesotheliomas arose m this study, the construction industry and the railways, is 6,5:1 and 1,3:1 respectively.11A similar situation applies as regards the environ 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 year found in this study, an annual incidence figure, agead)usted to the 1980 US population, of 7,2 per million population was derived (Table V). As has been shown, even this figure underestimates the true incidence -- further research is needed to arrive at more reliable estimates. The most plausible explana tion 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 chrysotile.3 Another area of interest in the context of mesothelioma m South Africa is compensation. Mesothelioma was made an occupational disease, sufFerers of which were eligible for compen sation in the non-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 non-mining subjects, fewer than half (38%) of all those eligible have been compensated. The situation m the mining industry is much better and 88 subjects were compensated by the mines over the study period. Even so only 1of the 8 Black miners from the study is known to have been compensated to