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FILE NAME: Kaiser Gypsum (KG) DATE: 1967 Apr DOC#: KG096 DOCUMENT DESCRIPTION: Journal Article - Mesothelioma and Asbestos Exposure ,4 - it 559 Mesothelioma and Asbestos Exposure Jan Lichen, AID, and Harry Pistauiha, AID, Harrisburg, Pa W i t h i n the past five years several arti cles have called attention to the association between mesotheliomas of the pleura and u-.-ritoneum with asbestos exposure,1- Wagner et al4 studied 33 cases of meso thelioma. All but one had probable exposure tc^Mradclite, the blue asbestos. I^ ^ stos has become a ubiquitous materi al in our civilization. Oauna et al5 reported that asbestos bodies were found in the lung j-mears of 11% of 100 consecutive autopsies at the Presbyterian University Hospital in Pittsburgh. Simitar findings were reported by Thompson-7 in 500 consecutive lung 'aicars from Capetown, South Africa, and .-iaini, Via. Asbestos bodies were found in '/.% of the men and 20% of the women. AsIn-fins has been conclusively associated with increased incidence of lung cancer and other lyiaiignancies'0 and an Increasing number of studies associate its presence with malig nant mesothelioma of the pleura and perito neum. Pathology Mesotheliomas of the pleura and perito'.cum are rare neoplasms. Controversy inolves histological types, nomenclature, oriin, and their very existence. Recently, xsolheliomas as an entity have become enerally accepted. Their morphologic varibilitv makes classification difficult and difrrentiation from other malignancies is often problem. Submitted for publication June 6, 3966; accepted i)> t 3 3 . ----------- From the Division ol Occupational Health, De triment o{ Health, Harrisburg, Pa, head before the Ninth International Cancer Con es1;, Tokyo, October 1966. heprini re^ruesis to PO I3ox 90, Hnr.-bburg, Pa J20 (Dr. l.lelxm). Sacconi and Coblenz1give the incidence of pleural mesotheliomas as 1.1 cases per 1,000 autopsies. Campbell reported four cases of pleural mesotheliomas iti 3,533 con secutive autopsies.11 Mesothelioma occurs primarily in adults and is twice as common in males as in fe males.10-12 Pleural mesotheliomas occur equally on the right and loft though Weissman feels that pleural mesothelioma occurs on the right more frequently than on the left side.12 The criteria for diagnosis of pleural meso thelioma are presence of a firm pleural mass encasing the lung, histological structure compatible with mesothelioma, and absence of a demonstrable primary malignant neo plasm elsewhere. The histologic architecture may be mesenchymal, "epithelial," or mixed. A compiete autopsy is necessary for une quivocal diagnosis, but for the purpose of this study, criteria were made less rigid in that unautopsied cases were accepted if a definite diagnosis of pleural mesothelioma had been made by biopsy, and malignancy elsewhere had been excluded clinically; chest x-ray examination, bronchoscopy, and cytologic studies of sputum or bronchial washing assisted in excluding the presence of bronchial carcinoma. Primary tumors of the peritoneum are among the rarest of tumors. Generally called mesotheliomas, they form large spreading masses over the peritoneum and histologi cally appear the same as pleural mesothe liomas. As with pleural mesotheliomas, ex clusion of a primary tumor is necessary. This study is an attempt to learn the ex tent of tire relationship of asbestos exposure with mesothelioma diagnosed in southeast ern Pennsylvania. Arch Environ Health-- Voi 14, April 1967 ` -:y-Ai -Api'7`. hy 1967, Lieben It& i A-'- .v h'-D1!>?-' - l " --'vr- :v - -'W ? ,:.: ; . VX.f.' x IP x W x - t X< % V- ' .. ' ' ' '.yvV'jfi V - Z S ' ' -'''AgliS ...................... " ' K _ t t >:?; * - i/ <*' ^, ,VT,1, ' _*.,\N* di? S';'r,\vV ` ' ' '>: 'V.. T. -A i * >1; *`':i^ A ^ 3 'X ' ? W ip fe l ' -": - H ; -'Xj., y Z t ' - - 530 ME S OT HE L IOM A--L I ED E N & PISTAWKA Method One hundred and sixty-two hospitals serving a population of 6Vi million people were re quested to report all mesotheliomas diagnosed between 1958 and 1963. Replies were received from 152 hospitals. Hospital records of 62 re ported cases were reviewed and only mesothe liomas confirmed by operation, biopsy, or au topsy were included in the study. Forty-two cases satisfied our critera. There were 34 meso theliomas of the pleura and eight of the perito neum. Among the pleural mesotheliomas there was a definite preponderance for occurrence on the right side of the chest. Of 34 pleural meso theliomas only seven occurred on the left side, 25 on the right side, and two were not stated. Sections of as many of the tumors and lungs as possible were borrowed and reviewed by a single consultant pathologist familiar with mes otheliomas. In the 15 instances in which lung sections were available, they were examined for the presence of asbestos bodies. All slides were reviewed without the benefit of the complete history and autopsy protocol available to the pathologists who made the original diagnosis. Results of the 33 cases reviewed (Table) by our pathologist agreed with those of the outside pathologists in 17 cases; he rejected seven cases as unacceptable histologically, had serious doubts in nine cases (of these one slide was read as metastasis and one slide as anaplastic malignancy). Of the 15 cases in which lung tis sue vvas available, asbestos bodies were iden tified in seven. The discrepancies between the original pathological diagnosis and that of our patholo gist are reported to illustrate the difficulties and disagreements which are so frequent in the diagnosis of this tumor. For inclusion in this study the diagnoses of the originally reporting pathologists have been accepted and cases re ported by them were investigated. Efforts were made to obtain a complete em ployment and residence history for each pa tient. Inquiry was also made into the employ ment history of family contacts. Data were obtained from the individual if alive, from fam ily members, or employers. Of the 42 patients, ter, hail definite occupa tional exposure to asbestos during lifetime, three were family contacts of asbestos workers, eight either lived in the immediate neighbor hood of asbestos plants or had been employed next to an asbestos plant. Ten patients had a questionable asbestos exposure and, in the oth er 11 patients, either no asho-tos exposure could be elicited on direct questioning or no survivor could be located. Table 1.--loadings of Consultant Pathologist C ase No. M esoi heliom a A sbestos B o d ies 1-0 3-0 4 0 5-0 6 0 9 -0 10-0 2-N 3-N 4-N 6-N 1-F 2-F 3 -F 1-Q 2-Q 4-Q 5-Q 6-Q 7-Q S-Q 9-0 10-Q 1-X 2-X 3-X 4 X 5-X 6-X 7 X 8-X 9 X 10 X Yes Not accep tab le P ro b a b ly Yes P ro b a b ly not not P ro b a b ly not Yes Yes P ro b a b ly not Not accep tab le Yes Yes Yes Yes P ro b a b ly not Yes Yes P ro b ab ly yes Not accep tab le Yes Yes P ro b ab ly not M ay be M etast Yes Yes Not a cce p ta b le Not accep tab le A n a p la stic m alig n a n cy P ro b ab ly not N o e p ith elial cells M eso th elio m a m u st be proven P ro b ab ly not Yes Yes N o lu n g tissu Yes N o H l.lg Yes Yes tl SLU N o lu n g tissu. Ye* N o lu n g lisst.No 'ung t'S s j N o lu n g tissu. No lu n g tis E j, NO )UM tis s u . N o lu n g tissu N o lu n $ tissu N o lu n g tisiu - Y e r. No No No No lu n g tissu- No No No Yes N o lu n g tissu- N o lu n g tissu- N o lu n g tissu No No N o lu n g tissu No lu n g N o lu n g Yes tissu- Exposure of Ten Mesothelioma Patient.- \\T Worked With Asbestos.--Patient 1-0 worked 3 years in the textile department of a large a: bestos plant. Patients 2-0, 3-0, and 4-0 worked more that 20 years in asbestos insulation plants and pa tient 5-0 worked in ar. insulation plant for oub One year. Patient 6-0 worked 15 years in a plant manu factoring acoustic tile and linoleum. Patient 7-0 was a boiler maker in a railroa; yard where, for 25 years, he worked on insula tion of steam engines. Patient 8-0 built bakery, ovens in which larg< amounts of asbestos insulation were used. Patient 9-0 was a certified accountant wh< worked more than 30 yecus in the office of a. asbestos textile plant. Patient 10-0 was a plasterer who came n contact with a large amount of asbestos in hi woi k. Of these ten nu n, patients 1-0, 3-0, and 10-1 had mesotheliomas of the peritoneum; the oil. cr seven rnon had pleural mesotheliomas. Neighburhood Casts.--Patient 1-N was a 55 year-old woman who never had nnv oeuipi Arch Environ Health--Vo! 14. April 7567 M E S O T H E L I O M A --L J K E E N Ji PISTAWKA 5(51 itoiial asbestos exposure. Her work was always Patients 1-F and 3-F bad peritoneal and pa secretarial; she was born and lived until the age tient 2-F pleural mesotheliomas. r n * ) . . : , j ! _ a ,, ,,_ _ : _ i . i t. _ _ j . t . . . _ . Oi o f ii i i h , i i m u r u t a t ' ' m i ^ n u u u i u u u v t iu *ia- Mesothelioma Patients With Questionable I'.-stos textile and friction material plant, where j Asbestos Exposure.---A study of these ten men patient 1-0 had worked (or 35 years. From the elicited either a relatively minor or question age of 18 she lived for 30 years across the street able exposure to asbestos. from the plant where patient 6-0 had worked fur 15 years. Patient 2-N, a clergyman from 1035 until his death in 1951. never had any occupational as bestos exposure. Prior to becoming a minister he lived (or 19 years within one half of a mile of the insulation plant where patients 3-0, 4-0, and 5-0 had worked as insulation manufactur ing workers. Patient 3-N never had any occupational as bestos exposure except that, 20 years prior to his death, he had woiked for one year across (he street from the insulation plant mentioned in the history ot patient 2-N. P atent 4-N worked for 26 years across the itrc^^fcmi the insulation plant mentioned in unmBIcm with patients 2-N and 3-N. Patients 5-N, a nurse, and 6-N, a meat disributor, had no occupational exposure nor nrnily contai t with asbestos. They both lived lithin three fourths of a mile of two asbestos dates in a town with the greatest incidence of nc-sotlwhomas in this study. l 'dtii-n(s 7-N and S-N were both foremen in a Image battery plant. A careful check of the ib-.nt and their employment, records revealed iO asbestos exposure, past nor present. The dant is located less than 1'/ ' miles from an asedos textile plant. The exposure of these two ns'-s is questionable. Patients i-N and 4-N had peritoneal and pa. o.is 2-N, 3-N. 5-N, 6-N, V-N, and 8-N had lout cl mesotheliomas. Mesothelioma Patients With Family Conwlj^^fcJosetl to Asbestos.--Patient 1-F, a 3ear^^^ehild, was the daughter of a ceramicJ ogineer who worked in an insulation planm at utilizes 400 tons of Canadian chrysotile nd 1,500 tons of South African amesite annu- Patient 1-Q was a welder for 35 years. Ac cording tc> a common reference,13 eight out of 12 welding electrodes contain asbestos, which is used as a filler. Patient 2-Q was a self-employed Swiss-born Swiss cliecsemaker. A thorough study of the processes of Swiss cheese manufacture revealed no use of asbestos. During the study of the manufacturing process a 500-gal boiler was no ticed. This boiler was covered with a friable as bestos insulation which tlaked off on contact. Patient 3-Q, a 14-year-old boy v-itb mesothe lioma, had no occupational contact with asbes tos nor did any of his family. On questioning, the boy's father told the authors that his boy had lived with him and had helped him while he had replaced most of the plaster board dur ing extensive remodeling of his house. Plaster hoard contains a high percentage of asbestos. Patient 4-Q is employed in industrial sales and never had any occupational asbestos expo sure. Extensive questioning revealed that, on two occasions sovoial years before, he applied ashestos insulation to boilers in his home, mix ing asbestos cement himself. His total exposure during these applications was only a matter of hours. Patient. 5-Q was a brewery worker for 20 years. The brewery was no longer in business when the case was investigated. Reviewing the literature of beer production the following paragraph was discovered: "When ready for packaging the beer is fil tered through pulp filters consisting essentially of cotton fibers and asbestos. After each filtra tion this `FILTERMASS' is removed, mangled, and v/ashed in clear, warm water, then bleach ed and sterilized at 160 to 180 F with chlorine. The washed pulp then goes directly to a pad Patient 2-F, a 40-year-old nurse, never had\\ i.v occupational asbestos exposure, but her fa- \ ier had worked for 35 years in the insulation I ant where patients 3-0, 4-0, and 5-0 had I orked and which was also credited with three hghborhood cases. The nurse's brother also id worked in this plant for one year. Patient 3-F, a 67-year-old woman, never had\ forming machine where it is compressed at 89 to 90 pounds per square inch to form new filter pads.11" Asbestos-containing pipe insulation is used in breweries. Patients 6-Q, 7-Q, and 8-Q were all steel workers. Patient 6-Q was a crane operator; 7-Q a forger; and 8-Q a foreman and supervisor. In iv asbestos exposure nor had she lived near \ all eases the companies did not recall any as1 asbestos plant. She had two sons who | bestos exposure for these men, Pipe insulation 'rked as insulators in a shipyard for six / containing asbestos is extensively utilized by ars. These sons lived at home until 15 years/ steel companies. lor to their mother's death. / Patient 9-Q was a spinner in a silk company Arch Environ Health-- Vnl 14, A pril 10G7 562 M E S O T H E L I O M A --L I E B E S & P!ST AWK A from 1925 to 193S, and later in a plastic fabri cation plant which utilized fiber glass; he also had been a welder for 25 years. He thinks he has used asbestos but could not recall when and where. Patient 10-Q, a 63-year-old man, was a core-maker all his life. He worked in two foun dries in one of which asbestos cement is used in small quantities but, according to the plant manager, the core-maker did not have any coa-_ tact.with this material. The son stated that his father had used asbestos pipe insulation for pipes in the basement of their home several years prior to the onset of his illness and that he had done some sawing of this pipe insula tion material. All cases in this group had pleural mesothe liomas. Mesothelioma Patients Without Asbestos Exposure.'--In the other 11 patients (1-X to 11X) no occupational, familial or neighborhood asbestos exposure evidence could be elicited. Ten of these patients had mesothelioma of the pleura and one peritoneal mesothelioma. Comment This study presents a good deal of cireim standal evidence and many unanswere questions. Asbestos is a ubiquitous material uxxmuch more frequently than is generally rse ized. Some uses, such as in the brewery were not previously known to the writer: There.. are undoubtedly many, others. If we assume that asbestos may be th causative or trigger agent for malignan mesothelioma in some of the cases describee above, we must admit that the minima .dose-effect relationship and duration of ; latent period are unknown. The occupation al exposure of the; insulation workers or ?s bestos textile workers were certainly mam thousand times higher than those of tlu neighborhood cases or family contacts. Simi lar findings have recently been reported from England.1 The attack rate for mesotheliomas is ex Aiclt Environ Health--Vol Pi, April J9C7 MESOTHELIOMA-- LIEBEN & PSTAWKA 503 (icmoly low. Not ali mesotheliomas were re tients no history of asbestos exposure could prter! to us by the hospitals, but, even if wc bo obtained. double the incidence, only a minute fraction of the exposed population was affected. References There are precedents for this with beryllium disease which acts in a somewhat similar pattern; occupational disemes, familial con tacts. neighborhood cases plus a very low t. Ntwhmi.se, MX., and Thompson, H.: Mesothe lioma ot the Pleura and Peritoneum Following Ex posure to Asbestos in (ho London Area, Brit J Indaslr Med 22:261-269, 1905. attack rate, and a long latent period be 2. Hourihane, P.O.: The Pathology of Mesothe- tween exposure and onset of disease. Another question which arises is why pleural mesotheliomas are so much more liomata and an. Analysis of Their Association With Asbestos Exposure, Thorax 19:900-277, 1964. 3. Sclikoff. I.J.; Churgh. J.; and Hammond, C .`. Exposure to Asbestos and Mesothelioma, Neu) Eng frequent than peritoneal mesotheliomas. J Med 272:500-563 (March) 1965. The most striking finding of this study was that of the 42 mesotheliomas which : a ^ ^ frrom a geographical area of approxi- 30,000 sq mi, six were clustered in 4. Wagner, J.C.; Sleggs, C-A ; and Marchand, P.: Diffuse Pleural Mesothelioma and Aslrestos Expo sure in N.W. Cape Province, Brit J Industr Med 17:200-27), 1960. 5. Cauna, D.;-Totten, R.; and Gross, P.: Asbestos amnd^-aarrcound an insulation plant (Figure). These included two insulation manufactur ing workers (Cases 2-0 and 3-0), three neighborhood cases (Cases 2-N, 3-N, and 4N) and one family contact (Case 2 - F) -- the Bodies in Human Lungs at Autopsies. JAMA 192:371-373 (May 3) 1903. 6. Thompson, J.G.; Kaschula, R.O ; and MacDon ald, R.R.: Asbestos as a Modem Urban Hazard, S Ajr Med J 37:77-81 (-Jan) 1963. 7. Thompson, .T.G.: Asbestos and Urban Dweller, daughter of an insulation worker. read before the Conference on Biological Effect* of Asbestos, New York, Oct 19, 1904. Summary 8. Doll, 13.: M oitalilv From Lung Cancer in As bestos Workers, n t J Industr Med 12:81, 1955. Forty-two cases of mesotheliomas report 9. Lieben, J.: Asbestos and Malignancy, Arch En ed from 152 hospitals over a five-year peri viron Health 13:619-621 (Nov) 1966. od, were studied with regard to exposure to asbestos. Survivors or employers, or both, wore questioned regarding the possibility of asbestos exposure. Ten patients actually 10. Sac-coni, A., and Coblenz, A.: Endothelioma of the l-lcura, With Report of Two Cases, Amer J Clin rath 13:186-207, 1913. 11. Campbell, W.: Pleural Mesothelioma, Amer J Path 20:473-487, 1950. worked in asbestos plants; eight lived or 12. Weis-man, H.: Primary Eudothclia of thu worked close to an asbestos industry; three Pleura, Die Chest 12:562-570, 1946. paU fl^ were family members of asbestos^ ert1i3e.s LanydmSanel,ecTt.ion(eeolf.):MMeteatlas,lsedH8a,nAdbmoeorki:caJn- SPorcoipe wcS^Pe. In ten patients a history of as ty of Metals, 1961, p 5. sumed exposure to asbestos was obtained 14- Modern Chemical Processes, New York: Rein after prolonged questioning. In 11 other pa- hold Publishing Co., 1552, vol 2, p 167. L i \.~i. .- - i ) t I ! i i i DISCOVERY OF QUININE Many of the drug sources known in ancient times were apparently discovered by acci dent. For example, according to an Old South American Indian legend, the curative power of cinchona bark (containing quinine) for malaria was discovered by a sick, fe verish Indian lost in the jungle. He quenched his thirst by drinking from a pool of water. From the bitter taste of the water, he recognized that it was tainted with the poison from the quina-quina tree. Although he shared this fictitious belief, he drank deeply so as to bring about a quick death. To his great surprise, ho recovered completely. When he returned to his village, he told the store of his euro and thereafter cinchona hark was used as a medicine for the fever prevalent in that region. The Incas later taught the Spanish conquistadors that malaria could be cured with cinchona extract..-- Rossman, R.E.: The History and Significance of Serendipity in Medical Discovery, Trans Coll Physicians PhtUi 33:101-120 (Oct) 1965. Arch Environ Health-- Vol 14, April 3967