Document 2j7MOde14Z0yga31oweDa55NR

559 Mesothelioma and Asbestos Exposure Jan Lieben, MD, and Harry Pistaiuha, MD, Harrisburg, Pa WITHIN the past five years several arti cles have called attention to the association between mesotheliomas of the pleura and peritoneum with asbestos exposure.1'3 Wagner et al4 studied 33 cases of meso thelioma. All but one had probable exposure to^^idcbte, the blue asbestos. . I^^Fstos has become a ubiquitous materi al in our civilization. Cauna et al3 reported that asbestos bodies were found in the lung smears of 41% of 100 consecutive autopsies at the `Presbyterian University Hospital in Pittsburgh. Similar findings were reported bv Thompson0'7 in 500 consecutive lung `moors from Capetown, South Africa, and Miami, Fla. Asbestos bodies were found in `;0% of the men and 20% of the women. As bestos bus been conclusively associated with increased incidence of lung cancer and other malignancies3'0 and an increasing number* of studies associate its presence with malig nant mesothelioma or the pleura and perito neum. Pathology Mesotheliomas of the pleura and perito neum are rare neoplasms. Controversy in volves histological types, nomenclature, ori gin, and their very existence. Recently, mesotheliomas as an entity have become generally accepted. Their morphologic vari ability makes classification difficult and dif ferentiation from other malignancies is often a problem. Submitted for publication June 6, 3966; accepted Sept 13. ------ - From the Division of Occupational Health, De partment of Health, Harrisburg, Pa, Dead before the Ninth International Cancer Con gress, Tokyo, October 1966. Meprint requests to PO Box 90, Harrisburg, Pa H320 <Dr. f.ieben). Sacconi and Coblenz10 give the incidence of pleural mesotheliomas as 1.1 cases per 1,000 autopsies. Campbell reported four cases of pleural mesotheliomas m 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 left 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 complete 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 the relationship of asbestos exposure with mesothelioma diagnosed in southeast ern Pennsylvania. 1967 Lieben y&t .v b;-- `AC'-v.-tV .. 'oV. _ ' V:-*. l 530 MESOTHELIOMA--LIEDEN & PISTAWKA Method Table 1.--Readings of Consultant Pathologist One hundred and sixty-two hospitals serving a population of 6*4 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 was 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, ten had 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 asbestos exposure could be elicited on direct questioning or no survivor could be located. Case No. Mesothelioma Asbestos Bodies 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 l-Q 2-Q 4-Q 5-Q 6-Q 7-Q 8-Q 9-Q 10-Q 1-X 2-X 3-X 4-X 5-X 6-X 7-X 8-X 9-X 10-X Yes Not acceptable Probably not Yes Probably not Probably not Yes Yes Probably not Not acceptable Yes Yes Yes Yes Probably not Yc 5 Yes Probably yes Not acceptable Yes Yes Probably not May be Metast Yes Yes Not acceptable Not acceptable Anaplastic malignancy Probably not No epithelial cells Mesothelioma must be proven Probably not Yes Yes No lung tissue Yes No lung tissue Yes Yes No lung tissue Yes No lung tissue No lung tissue No lung tissue No lung tissue No lung tissue No lung tissue No lung tissue No lung tissue Yen, No No No No lung tissue No No No Yes No lung tissue No lung tissue Mo lung tissue No No No lung tissue No JunG tissue No lung tissue Yes Exposure of Ten Mesothelioma Patients V/l'o Worked With Asbestos,--Patient 1-0 worked 35 years in the textile department of a large as bestos plant. Patients 2-0, 3-0, and 4-0 worked more than 20 years in asbestos insulation plants and pa tient 5-0 worked in ar. insulation plant for only one year. Patient 6-0 worked 15 years in a plant manu facturing acoustic tile and linoleum. Patient 7-0 was a boiler maker in a railroad yard where, for 25 years, he worked on insula tion of steam engines. Patient 8-0 built bakery, ovens in which large amounts of asbestos insulation were used. Patient 9-0 was a certified accountant who worked more than 30 years in the office of an asbestos textile plant. ' Patient 10-0 was a plasterer who came in contact with a large amount' of asbestos in his wor k. Of these ten men, patients 1-0, o-O, and 10-0 had mesotheliomas of the peritoneum; the oth er seven rnen had pleural mesotheliomas. Neighborhood Cases.--Patient 1-N was a 55year-old woman who never had any oeeup.i- Arch Environ Health--Vo! 14, April 1967 . '.Va^'V ''. .1 ik >' -;\> ' `V"-? ' H& ' A- y,- W~?rr ; MESOTHELIOMA--LIKEEN 71. PASTA7tA 561 lirmul asbestos exposure. Her work was always^ Patients 1-F and 3-F had peritoneal and pa secretarial; she was born and lived until the age tient 2-F pleural mesotheliomas. of o, iil tiiC irfiiuv'diatf't rririgiiboihoocl of An 5- Mesothelioma Patients With Questionable hestos textile and friction material plant where / Asbestos Exposure.--A study' of those ten men patient 1-0 had worked for 35 years. From the elicited cither a relatively minor or question age of 18 she lived for 30 years across the street able exposure to asbestos. from the plant wlu-re patient 6-0 had worked Patient 1-Q was a welder for 35 years. Ac for 15 years. cording to a common reference,1'1 eight out of Patient 2-N, a clergyman from 1935 until his 12 welding electrodes contain asbestos, which is death in 1961, never had any occupational as used as a filler. bestos exposure. Prior to becoming a minister lie lived for 19 years within one half of a mile of the ijisulcrion 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 Patient 2-Q was a self-employed Swiss-born Swiss checscmaker. 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 exposure except that, 20 years prior to bestos insulation which flaked off on contact. his death, he had worked for one year across Patient 3-Q, a 14-year-old boy v-ith mesothe the street from the insulation plant mentioned in the history of patient 2-N. Patmnt 4-N worked for 26 years across the stre^^m the insulation plant mentioned in comwiwon with patients 2-N and 3-N. Patients 5-N, a nurse, and 6-N, a meat dis tributor, had no occupational exposure nor 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 w ith him and had helped him while he had replaced most of the plaster hoard dur ing extensive remodeling of his house. Plaster board contains a high percentage of asbestos. family contact with asbestos. They both lived Patient 4-Q is employed in industrial sales within three fourths of a mile of two asbestos and never had any occupational asbestos expo plants in a town with the greatest incidence of sure. Extensive questioning revealed that, on mesotheliomas in this study. two occasions several years before, he applied Patients 7-N and S-N were both foremen in a asbestos insulation to boilers in his home, mix storage battery plant. A careful check of the ing asbestos cement himself. His iotal exposure plant and their employment, records revealed during these applications was only a matter of no asbestos exposure, past nor present. The plant is located Jess than V/> miles from an as bestos textile plant. The exposure of these two cas'-g is questionable. Patients 1-N and 4-N had peritoneal and pa tients 2-N, 3-N. 5-N, 6-N, 7-N, and S-N had pleura] m c sot hoJ iomas. 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: Mesothelioma Patients With Family Con- "V/hen ready for packaging the beer is fil a.ctg^k.'osed to Asbestos.--Patient 1-F, a 3- tered through pulp filters consisting essentially year^^Pchild, was the daughter of a ceramicj of cotton fibers and asbestos. After each filtra engineer who worked in an insulation plant'' tion this `FILTERMASS' is removed, mangled, that utilizes 400 tons of Canadian chrysotile and v/ashed in clear, warm water, then bleach and 1,500 tons of South African amesite annu ed and sterilized at 160 to ISO F with chlorine. ally. The washed pulp then goes directly to a pad Patient 2-F, a 40-year-old nurse, never had forming machine where it is compressed at S9 any occupational asbestos exposure, but her fa to 90 pounds per square inch to form new filter ther had worked for 35 years in the insulation pads.11" plant where patients 3-0, 4-0, and 5-0 had Asbestos-containing pipe insulation is used in worked and which was also credited with three breweries. neighborhood cases. The nurse.'s brother also Patients 6-Q, 7-Q, and 8-Q were all steel had worked 'in this plant for one year. workers. Patient 6-Q was a crane operator; 7-Q Patient 3-F, a 67-year-old woman, never had\ a forger; and 8-Q a foreman and supervisor. In any asbestos exposure nor had she lived near ' all cases the companies did not recall any as an asbestos plant. She had two sons who bestos exposure for these men. Pipe insulation worked as insulators in a shipyard for six containing asbestos is extensively utilized by years. These sons lived at home until 15 years steel companies. prior to their mother's death. Patient 9-Q was a spinner in a silk company Arch Environ Health--Vo! 14, April 1967 562 MESOTHELIOMA--LIFEE.V & PISTAWKA 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 c.on-_ tact.with this material..The-son-stated that.his father had used asbestos pipe insulation for pipes in the basement of their home seyeral 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 II patients (1-X to 11X) no occupational, familial or neighborhood asbestos exposure evidence could be elicited. Ten of these patients bad mesothelioma of the pleura and one peritoneal mesothelioma. Comment This study presents a good deal of circum stantial evidence and many unanswered questions. Asbestos is a ubiquitous material much more frequently than is generally real ized. Some uses, such as in the brewery, were not previously known to the writers. There, are undoubtedly many others. . ., If we assume that asbestos may be the causative or trigger agent for malignant mesothelioma in some of the cases described above, we must admit that the minimal dose-effect relationship and duration of a latent period are unknown. The occupation al exposure of the insulation workers or as bestos textile workers were certainly many thousand times higher than those of the neighborhood cases or family contacts. Simi lar findings have recently been reported from England.1 The attack rate for mesotheliomas is ex Occup-jtienal, neighborhood, and family contact patients with mesothelioma assoc:v one insulation plant. Arch Environ Health--Vol Id, April 19C7 .11KSO7HE110,11A--TJEIiEN & PISTAWKA 563 tremely low. Not all mesotheliomas were re tients no history of asbestos exposure could ported to us by the hospitals, but, even if wc be 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 diseases, familial con tacts, neighborhood cases plus a very low 1. Newhnuse, M.L., and Thompson, H.: Mesothe lioma of (lie Pleura and Peritoneum Following Ex posure to Asbestos in the London Area, Brit J Industr Med 22:261-269, 1965. 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 frequent than peritoneal mesotheliomas. liomata and an. Analysis of Their Association With Asbestos Exposure, Thorax 19:268-277, 1964. 3. Sclikoff. I.J.; Chuigh, J.; and Hammond, C.: Exposure to Asbestos and Mesothelioma, New Eng J Med 272:560-563 (March) 1965. The most striking finding of this study was that of the 42 mesotheliomas which cara^rom a geographical area of approxi- 30,000 sq mi, six were clustered in an^arourid an insulation plant (Figure). 4. Wagner, J.C.; Sleggs, C.A.; and Marchand, P.: Diffuse Pleural Mesothelioma and Asbestos Expo sure in N.W. Cape Province, Brit J Industr Med 17:260-271, 1960. 5. Cauna, D.pTolten, R.; and Gross, P.: Asbestos Bodies in Human Lungs at Autopsies, JAMA 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 daughter of an insulation worker. Summary 192:371-373 (May 3) 1963. 6. Thompson, J.G.; Knschula, R.O.; and MacDon ald, R.R.: Asbestos as a Modem Urban Hazard, S Air Med J 37:77-81 (Jan) 1963. 7. Thompson, .T.G.: Asbestos and Urban Dweller, read before the Conference on Biological Effects of Asbestos, New York, Oct 19, 1964. 8. Doll, R: Mortality From Lung Cancer in As bestos Workers, Brit J Industr Med 12:81, 1955. Forty-two cases of mesotheliomas report 9. Lieben, J.: Asbestos end Malignancy, Arch En ed from 152 hospitals over a five-year peri viron Health 33:619-621 tNcv) 1963. od, were studied with regard to exposure to asbestos. Survivors or employers, or both, were questioned regarding the possibility of asbestos exposure. Ten patients actually 10. Siuconi, A., and CobJenz, A.: Endothelioma of the pleura, With Report of Two Cases, Amcr J Clin Bath 13:186-207, 1943. 11. Campbell, W.: Pleural Mesothelioma, Amcr J Bath 20:473-487, 1950. worked in asbestos plants; eight lived or 12. Weis.sman, H.: Primary Eudolbelia of the worked close to an asbestos industry; three Pleura, Die Chest 12:562-570, 1946. wUe. were family members of asbestos^. In ten patients a history of as 13. Lyman, T. (od.): Metals Handbook: I. Prop erties and Selection of Metals, r-d 8, American Socie 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., 1952, vol 2, p 167. i l if 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 bid South American Indian legend, the curative power of cinchona bark (containing quinine) for malaria was discovered by a sick, fe verish Indian lost in tire 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 cure 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, I'lans Coll Physicians Phila 33:101-120 (Oct) 1965. Arch Environ Health--Vol 14, April 1967