Document 8VyQEk0XN7jwjNmjnKBmmL6DK

it ]' "'aU;* Oir.fe. VE0PLAS1A AMONG INSULATION WOHKKRS IN Till-: ' UNITKD STATUS WITH SFUUIAL RUFKUKNCK TO 1NTUA-ALDOM INAL NKOPLASlA . -e E. C. Hammond 4 American Cancer Society, Note York, N. Y. I. J. Selikoff, J, Churg __ . The Mount Sinai Hospital. New York.N. Y. ' t Before presenting the findings in our study of insulation workers, we would like to discuss briefly some considerations which we believe to he important. Maiignant neoplasms produced by exposure to chemical agents or ioniz ing radiation typically have a long Intent period. That is to say, there is i long delay between first exposure and the appearance of the neoplasm, la the case of carcinogens which can be eliminated from the body, re lated contacts over a long pei-iod of time may be required. However, in she case of agents which are not eliminated, exposure of the tissues is -If continuous from time of first exposure. The probability that neoplasia will occur and how soon it appears generally depend upon the degree of exposure. jfow let us consider the effects of exposure to an agent which can pro- o"ce neoplasia but which can also produce some other type of disease. Here we are dealing with the problem of competitive risks. If exposure results in death from some other disease within ten or fifteen years, then, because of the long latent period, it is very unlikely that neoplasia will result from such exposure. In these situations, the outcome depends in part upon the time required to produce the other disease in relation to the time required for the de velopment of neoplasia; and this in turn depends upon the degree of ex posure. Of equal importance is whether or not the other disease can be cured, or death delayed. An historical review of the literature from this point nf view is most interesting. All of the early reports apparently concerned workers who were very heavily exposed to asbestos dust. This was long before the development of the sulfa drugs and antibiotics. Pulmonary diseases including tuber culosis and pneumonia were among the lending causes of death. Life ex pectancy in the general population was far shorter than it is today, and a datively small percentage of people lived to an age where the incidencs .. cancer becomes high. I-i 1906, Auribault reported the results of what was probably the first study of mortality among asbestos workers.1 His account is interesting. 519 iSSlMr Annuls New York Academy of Sciences In 1800 an asbestos spinning mill ami weaving factory was estaWisheci: e neighborhood of Conde^uv-Noiveau (Calvados). During the first yea)s of operation there was no artificial ventilation and the employ*# e: e eav*il\ exposed to dust from the looms. According to Auribnult, 5/7 W;. V.-.. .. oi 'firs ied during this five-ye.Tr period. Furthermore the director, vte?;'*previously owner of a cotton mill had recruited seventeen of his fora* .i empojces and "sixteen of them were wiped out by the Chalicosis." Sfvf. in ,918, Hoffmann was able to present some data from the Industrie - *.W** ' t experience of the Prudential Life Insurance Company.1 From 1S97 to I'-1-* there were 13 deaths of asbestos workers and three of these wen? W- tvibuU'd to pulmonary tuberculosis. It is of interest that nine of the.** '> si-.' ' asbestos workers died under the age of 44. This is in contrast with a rrc:- *ft'.*'. * older average age at death reported for potters, molders, marble worfctr*- 'vf: y<c\ and stone workers. Hoffmann notes that "in the practice of American 5-''- Canadian iife insurance companies, asbestos workers are generail}' ^ dined on account of the assumed healths'lljm-ious conditions of the it* dustry." He also quotes E. L. Collins (Annual Report of the Chief in spector of Factories and Workshops for England and Wales for 1910 ** having found five deaths in people having pulmonary tuberculosis sr. ' years among a staff of under 40 workers in a factor}' weaving asbe".c.c- Since Hoffmann s time, many authors have reported findings in of cases of asbestosis. Until after 1940. emphasis was placed upon v-* role oi secondary infections, particularly pulmonary tuberculosis bronchopneumonia. For example, Ifferewether7. writing in 1033 commentrC Usually, the fatal issue is determined by the onset of some acute infection with which the remaining undamaged tissue is quite un able to cope: tins is commonly a Ion* grade bronchopneumonia. The same year, Gloyne* stated that, "the writer has so far only seen asbestos patient recover from bronchopneumonia." In two series of cases reported by Wood and Gloyne' in 1934 and St-^.r in 1940. bronchitis, bronchopneumonia and pulmonary tuberculosis w* the commonest terminal complications of asbestosis. However, Wood sr/s Gloyne found two lung cancers and one cancer of the pleura in 2G de-*--' of patients with asbestosis. With the passage of time, pulmonary infections were found le.as quently and lung cancer was found more frequently in cases of asbe?t,,,<v`- He will not take the time to review the more recent literature, a part of which was written by people present at the Conference and quately covered by other papers in this Annul. It is sufficient to say s.nce the advent of the antibiotics, workers have generally been sawr. from death due to infectious pulmonary diseases resulting as a oomph"` tion of asbestosis. i hus they began to live long enough for the rreop-a-/,r effects of exposure to asbestos to become manifest. Our study differs from the early studies in two important resF*,'``,: V. .u ,U / i . . r i pi a m v j ,:r-J/.V.TIIU , Annals New York Academy of Sciences 11' The subjects had very liirht and intermittent exposure to asbestos dust as compared with the daily heavy exposure of subjects included in the old studies; and 12) Wo are reporting deaths which occurred after 1042; that is, alter antibiotics became available for the treatment of pneumonia arm after death rates from tuberculosis fiad been greatlv reduced in this coun try. It also differs front most other studies in that we were able to trace an entire group of workers including those who had retired and those who had left the trade. The data we are presenting here is an extension of data we publish last year.- Therefore, we will start by briefly reviewing our first report, the results of which are summarized in table 1. The data shown here are confined to the experience of 632 men. They composed the total membership of New York Local 12 and Newark Local 32 of the International Associa tion of Heat and Frost Insulators and Asbestos Workers as of January 1, 20-13. Ail of them were traced through December 31, 2 DG2 and 255 of them died during that period of time. Most of them had been first exposed to asbestos dust at least 20 years prior to 10-13. The remainder passed the 20-year point between 1943 and 1962; and we counted their experience only after they reached this point. ' Table 1 shows the total number of deaths and the number of deaths from selected causes during each of four successive 5-year periods. For comparison, we show the number of deaths which would have been expected ' among these asbestos workers had their age specific death rates been exactly the same as those reported for all white males in the United States during the same intervals of time. First note the total number of deaths. During the first five-year period, fewer deaths occurred among the asbestos workers than would have been expected on the basis of general U. S. death rates. This is accounted for by the fact that all of the workers were actively at work in 1943; and seriously ill men are unemployable. Thus their total death rates were low. This selective effect gradually wore off. During the last 5-vear period. SS of the workers died compared with 54.4 expected. During the entire 20year period. 255 asbestos workers died compared with 203.5 expected. .Vow' observe the number of deaths from cancer of the lung and pleura. During every 5-year period, far more than the expected number of as bestos workers died of this cause. Altogether there were 45 deaths from cancer of the Jung and pleura compared with 6.6 e.vpecteri; a mortality ratio of nearly 7 to 1. To our surprise, these asbestos workers also had extremely high death rates attributed to cancer of the stomach, colon and rectum. The'observed number of deaths from these cancers was 29 compared with an expected 9.4; a mortality ratio of 3 to 1. Hammond ci nl.: intra-nbdominal Xeopinsia II is uf interest that uul of a tola] of 2.'*f> deaths only 12 were attributed to asbestosis. As previously mentioned, our first report was based upon the-records of 622 men who were members of the two locals on December 31, 1942. An additional 890 men joined between January 1, 3943 and December 31, 1962. Thus a total of 1,522 were in the two locals at some time between 1943 and 1962. We have traced all of them through August 1964 and Dr. SeiikolF had medically examined'most of those who were living as of the end of 1962. Of the 1.522 men. 264 were dead as of January 1, 1963 and an additional 43 died between January 1, 1963 and August 31. 1964. The findings shown in table 2 are based upon these 307 deaths. Table 2 - N\ Y. C. Asbestos Insulation Wokkkks 307 Consecutive Deaths January 1, 1943 - August 31, 1964 Total deaths All neoplasia Bronchogenic carcinoma Mesothelioma G.I. carcinoma Upper respiratory Bladder Generalized carcinomatosis . All other Asbestosis All other causes 307 124 53 10 34 6 4 7 1C 17 166 40.4% 17.3% 3.3% . 11.1% 1.9% 1.3% 2.3% 2.2% 5.5% 54.1% Of the 307 deaths, 124 (40.4 per cent' were attributed to cancer, 17 f5.5 per cent) were attributed to asbestosis and 166 C34.1 per cent'' were attributed to various other causes. The Table shows the 124 neoplastic deaths classified by type of neoplasm. Fifty-three for 43 per cent of the cancer deaths) were attributed to bronchogenic carcinoma. Ten were attribu'od to mesothelioma. 31 Co gastrointestinal carcinoma. 6 to upper respiratory cancer. 4 to cancer of the bladder. 7 lo generalized carcinoma tosis and 10 to various other cancers. In studies of this type, accuracy of diagnosis is of prime importance. Of the 53 deaths attributed to bronchogenic carcinoma. 34 occurred in Annals Ney York Academy of Sciences hospitals. In 18 the diagnosis was based upon post-mortem examination and in 15 the diagnosis was based upon histologic examination of opera tive specimens. The remaining 20 were based upon clinical evidence or information reported on death certificates. J. Churg has personally ex amined specimens from 15 of these 53 cases. J. Churg has also personally examined sections on all of the 10 deaths attributed to mesothelioma. Four of the 10 were pleural mesotheliomas and six were peritoneal mesotheliomas. Of the 34 deaths attributed to gastrointestinal cancer (cancer of the stomach, colon and rectum plus one cancer of the esophagus), 20 occurred in hospitals. Six of the diagnoses were based upon post-mortem examina tion. 19 were based upon operative specimens and nine were based upon less reliable evidence. J. Churg personally reviewed sections from 12 of these cases. . Of the 27 other cancer deaths, 16 occurred in hospitals. Fifteen of the diagnoses were based upon autopsy or operative specimens, and 12 were based upon less reliable evidence. Of the 17 asbestosis deaths. 6 diagnoses were based upon post-mortem evidence and II upon ciinicai evidence only. In most prospective epidemiological studies, the investigators are forced to be content with information from death certificates plus a little addi tional information. We think it fair to say that in this study we were able to obtain a reliable diagnosis on cause of death in the majority of cases. This does not imply that all of the cases were correctly diagnosed. For example, the diagnosis is certainly open to question in those cases where it was based upon clinical evidence or death certificate information only. This is particularly true in the case of deaths attributed to generalized carcinomatosis (with primary site unknown), and deaths attributed to stomach cancer or liver cancer. Furthermore, it is not unlikely that a few mesotheliomas were missed. Indeed, in addition to the 10 deaths attributed to mesothelioma there is one lesion which looks suspiciously like this dis ease. but the diagnosis is not certain. Taken at face vaiue. it would appear that asbestos workers have an abnormally high risk of dying of gastrointestinal cancer. However, we will refrain from drawing conclusions on this matter at the present time. Returning to the subject of pulmonary neoplasms, TABLE 3 shows the lapsed time from onset of exposure to time of death of 57 of our subjects who died of cancer of the lung and pleura. (A few recent cases are not included here. > Not a singie one of these deaths occurred in less than 20 years after first exposure. The majority did not occur until after 30 years and many did not occur until after 40 years. Obviously, light exposure to asbestos dust does not lead rapidly to pulmonary' neoplasia. Kqually obviously, this disease is unlikely to appear Hammond ct nL: lntni-nbdominal Neoplasia Tahu: 3 Carcinoma of Lunu and Pu:cra in 57 Ashkstos Workers Lapsed time from onset of exposure to death 525 Years Less than 20 20 - 24 25 - 29 30 - 34 35 - 39 40+ ____ _ . Number 0 3 7 16 11 20 57 if workers die at a young- age due to some other effect of asbestos ex posure. However, with light exposure and the availability of antibiotics for the treatment of infectious disease, neoplasia is a major cause of death of such workers. References 1. AujubauLT, M. 1906. Observation regarding the hygiene and safety of workers in asbestos spinning anti weaving mills. Bull. Insp. Travail : 19G. 2.. Hoffmann, N. & L. Frederick. 1918. Mortality from respiratory dis. in dusty trades. Inorganic dusts. Bull. U.S. Bureau of Labor Statistics . No. 231 (Industrial Accidents and Hygiene Series: No. IT). Washington, D.C. 3. Merewether, E. R. A. 1933. A memorandum on asbestosis. Tubercle 15: 109-118. 4. Glovne, S. R. 1933. The morbid anatomy and histology of asbestosis. Tu bercle 14: 550-558. 5. Wood, W. B. & S. R. Glovne. 1934i-Puimonary Asbestosis, a review of one hundred eases. Lancet 2: 13S3-13S5. 6. Stone, J. J. 1940. Clinicai studies, in asbestosis. Am. Rev. Tuber. 41: 12-21. 7. Selikoff,- I. J., J. Churc & E. C.Hammond. 1964. Asbestos exposure and neoplasia. J. Am. Med. Assnr. 188: 22-26.