Document MG38Bz96XKL14G3v3Q8E4pLKz

ARCHIVES OF environmental health PREVENTIVE MEDICINE--OCCUPATIONAL MEDICINEAEROSPACE MEDICINE VOLUME 14 J anuary through J une, 1967 American Medical Association Publication v- PoUutlOQ, Ug Mesothelioma and Asbestos Exposure Common Case*; Tract, Arch Intern Sects of Gas Poi. W.C.: PermsacDi ariartt. Amrr Kcu f Irritant Caeca !ndu*t Hyg 6:390, ice of Pulmonary o Vesicant an^ 2:862. 1933. and Fumes, Proc ses and Chronic ). 3954. of Gassing, Med .ccident in Brook. ome Respiratory J" -orun g, J , . ESecls it teip Die 'ulmonary InsuffiDisease, Arner J l Studite on the New Haven: Yale g. H.: Pulmonary 'hosgene, Amer J on Eiperimental 23:1037, 1947. Massenver(t if tung utich Med Wechr i 1.: His topathology h 78:54-4, 1964. and Hatch. T.: Phosgene, Arch a willing to J and cornaction that 1 of Alpha * Jan Lieben. MD. and Harry Pistawka. MD, Harrisburg. Pa WiITHIN the past five years several arti cles have called attention to the association between mesotheliomas of the pleura and peritoneum with asbestos exposure.13 Wagner et al4 studied 33 cases of meso thelioma. All but one had probable exposure to crocidolite, the blue asbestos. Asbestos 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 by Thompson0* in 500 consecutive lung smears from Capetown, South Africa, and Miami, Fla. Asbestos bodies were found in 30% of the men and 20% of the women. As bestos has been-conclusively associated with increased incidence of lung cancer and other malignancies3-9 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 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. 19G3: accepted Sept 13. From the Division of Occupational Healta, De partment of Health. Harrisburg. Pa. Read before the Ninth International Cancer Con gress. Tokyo. October 1966. Reprint requests to PO Bog 90. Harrisburg, Pa 17120 (Dr. Liebenl. Sacconi and Coblenz10 give the incidence of pleural mesotheliomas as 1.1 cases per 1,000 autopsies. Campbell reported four cases of pleural mesotheliomas in 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 term 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. - Arch Environ Health--Vol 14, April 1967 560 MKSOTHIUQMA--LIZBES & PISTA V-'KA Method Tabie I.--Readings ot Consultant Patnoiogist One hundred and sixty-two hospitals serving a population ol 6y; million people were re quested to report all mesotheliomas diagnosed between 195S and 1963. Replies were received from 152 hospitals. Hospital records of 62 re ported cases were reviewed and oniy 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 pieural mesotheliomas there was a definite preponderance for occurrence on the right side of the chest. Of 34 pieurai meso theliomas oniy 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 siides were reviewed without the benefit of the complete historyi and aiutoD*1sy, pr,otoco,l availa. ble to. the pathologists wnosnaae 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 siiae was read as metastasis and one slide as anaplastic malignancy). Of the 15 cases in which iung 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 anc, in the oth er 11 patients, either no asbestos exposure could be elicited on direct questioning or no survivor could be located. Ca se~ Nc. N*. Asbestos Bootes 1c 4-0 5-0 6-0 9 -C I 0-0 2-N 3-N 4-N 6-N IT 2-F 3-F 1-0 2-Q --Q 5-0 6-Q 7-0 8-0 9-0 10-Q 1-X 2-X 3-X 4-X 5-X 6-X 7-X 8-X 9-X 2 0-X Vts Not acceptable P r 0 D a D1 y net Ves > Probably not Prooably no*. Yes Yes Prooably noi Not acceptable Yes Yes * Yes Yes Probably not Yes Yes Probably yes Not acceptable Yes Yes Probably not May be Metast Yes Yes Not acceptable Not acceptable Anaplastic malignancy Probably not ' No epitheual cells Mesothelioma must be prover. Probably not Yes Yes No lung 'issue 'ICS No iung tissuYes 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 Yes No No No No iung tissue No No .. No Yes No lung tissue No lung tissue No lung tissue No NO No lung tissue No lung tissue No lung tissue Yes Exposure of Ten Mesothelioma Patients Who 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 an insulation plant for onlv one year. Patient 6-0 worked 15 years in a plant manu facturing acoustic tiie 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. Pa: ient 8-0 bufit bakery ovens in which large amounts of asbestos insulation were used. Patient 9-0 was 3 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 work. Of these ten men. patients 1-0, 8-0. and 10-0 had mesotheliomas of the peritoneum: the oth er seven men had pleural mesotheliomas. Neighborhood Cases.--Patient 1-N was a 55year-old woman who never had any occupa- Arch Environ Health--Vo! f-f. April 1967 MESOTHELIOMA--L1EBEN & PISTAWKA 561 i uclit Asbesloi Bodies 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 Yes No No No No lung tissue No No No Yes . No lung tissue No lung (issue No lung tissue No No ' :ssue h . ! .sue N Wssue Yes Patients Who -0 worked 35 f a large as- I 3 d more than ants and palant for only plant manuim. in a railroad d on insula I . which large re used. luntant who office of an ho came in >estos in his -0, and 10-0 im; the othnliomas. X wps a 55- tpa- lional asbestos exposure. Her work was always etarial: she was berr. and lived until the age 0f 8, in the immediate neighborhood of an as bestos textile and friction material plant where patient 1-0 had worked for 35 years. From the age of 13 she lived for 30 years across the street (rom the plant where patient 6-0 had worked for 15 years. Patient 2-N, a clergyman from 1935 until his death in 1961, never had any occupational as bestos exposure. Prior to becoming a minister be lived for 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 worked for one year across the street from the insulation plant mentioned in the history of patient 2-N. Patient 4-N worked for 26 years across the street from the insulation plant mentioned in connection with patients 2-N and 3-N. Patients 5-N, a nurse, amj..-3-N, a meat dis tributor, had no occupational exposure nor family contact with asbestos. They both lived within three fourths of a mile of two asbestos plants in a town with the greatest incidence of mesotheliomas in this study. Patients 7-N and 8-N were both foremen in a storage battery plant. A careful check of the plant and their employment records revealed no asbestos exposure, past nor present. The plant is located less than IV2 miles from an as bestos textile plant. The exposure of these two cases is questionable. Patients 1-N and 4-N had peritoneal and pa tients 2-N, 3-N, 5-N, 6-N, 7-N, and 6-N had pleural mesotheliomas. Mesothelioma Patients With Family Con tacts Exposed to Asbestos.--Patient 1-F, a 3year-old chiid, was the daughter of a ceramic engineer v,-ho worked in an insulation plant that utilizes 400 tons of Canadian chrysotile and 1,500 tens of South African amesite annu ally. Patient 2-F, a 40-year-old nurse, never had any occupational asbestos exposure, but her fa ther had worked for 35 years in the insulation plant where patients 3-0. 4-0, and 5-0 had worked and which was also credited with three neighborhood cases. The nurse's brother also had worked in this plant for one year. Patient 3-F, a 67-year-old woman, never had any asbestos exposure nor had she lived near an asbestos plant. She had two sons wffio worked as insulators in a shipyard for six years. These sons lived at home until 15 years prior to their mother s death. Patients TF and 3-F had peritoneal and pa tient ?-F pleural mesotheliomas. Mesothelioma Patients With Questionable Asbestos Exposure.--A study of these ten men elicited either a relatively minor or question able exposure to asbestos. Patient i-Q was a welder for 35 years. Ac cording to 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 cheesemaker. A thorough study of the processes cf 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 flaked off on contact. Patient 3-Q, a 14-year-old boy with 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 board 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 several years before, he applied asbestos 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 washed 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 forming machine where it is compressed at 89 to 90 pounds per square inch to form new filter pack.14" 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 forcer; and 8-Q a foreman and supervisor. In all cases the companies did not recall any as bestos exposure for these men. Pipe insulation containing asbestos is extensively utilized by steel companies. Patient 9-Q was a spinner ir a silk company Arch Environ Health--Vo! 7-f, April JGG7 I ft -V IESO7r. ELIOA/.4--LIEBE.V from 1325 to 193S. and later in a oiastir :.ar,. cation piamt which utilized fiber class- he also had been a weider ter 2; years. He lin.ini nrhas used asbestos but couid not recall w hen anc wherePatient 10-Q. a 6fi-year-old man. was a core-maker ail his life. He worked in two foun dries in one of which asbestos cement is used :r. small quantities but, according to the plant manager, the core-maker did not have sr._, con 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 tnat 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 il 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 omyiperitoneal mesothelioma. uomment This study presents a good deal cf circum stantial evidence and many unanswered questions. Asbestos is a ubiquitous material used 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 mav be the causative or trigger agent for malignant mesothelioma in some of the cases described above, we must admit that the minimal dose-enect relationship and duration of a latent period are unknow-n. The occupation al exposure of the insulation workers or as bestos textile workers were certainJy manv thousand times higher than those of the neighborhood cases or famiiy contacts. Simi lar findings have recently been reported from England.1 The attack rate for mesotheliomas is ex- C i tr qyno n Patient 2-N Patient 3-N 4 -N n Occupa:ir,ai. neiQriDorhooc. anc family cor.ta-i parent* witn mesotneiioma assccwMeo ytiih on? insulation plan:. Aich Lntiron Health -- Vo! 14, Apm 1967 MESOTHELIOMA--UZBEK & PISTAWKa 563 de^v >:.ircTJLnty unanswered { .p material used generally reali the brewery, to the writers. / others. s may be the for malignant ases described the minimal duration of a le occupationworkers or asirtainly many those of the o'ntacts. Simieen reported - . * J ~ i i . . I .'liomas is ex- ` / treruely low. Not all mesotheliomas were re ported to us by the hospitals, but, even if we double the incidence, only a minute fraction of the exposed population was affected. 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 attack rate, and a long latent period be tween exposure and onset of disease. Another question which arises is why pleural mesotheliomas are so much more frequent than peritoneal mesotheliomas. The most striking finding of this study was that of the 42 mesotheliomas which came from a geographical area of approxi mately 30,000 sq mi, six were clustered in and around 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 daughter of an insulatip^1 worker. Summary Forty-two cases of mesotheliomas report ed from 152 hospitals over a five-year peri 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 worked in asbestos plants; eight lived or worked dose to an asbestos industry; three patients were family members of asbestos workers. In ten patients a history of as sumed exposure to asbestos was obtained after prolonged questioning. In 11 other pa tients no history of asbestos exposure could be obtained. References 1. Newhouse. M L, and Thompson. H.: Mesothe lioma of the Pleura and Peritoneum Following Ex posure to Asbestos in the London Area. Brit J In dustr Med 22:261-269, 1965. 2. Hourihane, P.O.: The Pathology of Mesotheliomata and an Analysis of Their Association With Asbestos Exposure, Thorax 19:268-277, 1964. 3. SelikofT. I.J.; Churgh, J.; and Hammond, C.: Exposure to Asbestos and Mesothelioma, New Eng J Med 272:560-563 (March) 1965. 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.; Totten. R.; and Gross, P.: Asbestos Bodies in Human Lungs at Autopsies, JAMA 192:371-373 (May 3) 1963. 6. Thompson. J.G.; Kaschula. R.O.; and MacDon ald. R.R.: Asbestos as a Modem Urban Hazard. S Air Med J 37:77-81 (Jan) 1963. 7. Thompson, J.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 12:31, 1955. 9. Lieben, J-: Asbestos and Mabgnancy, Arch En viron Health 13:619-621 <Nov) 1966. 10. Sacconi. A., and Coblenz, A.: Endothelioma of the Pleura, With Report of Two Cases, Amer J Clin Path 13:186-207, 1943. 11. Campbell. W.: Pleural Mesothelioma. Amer J Path 26:473-487. 1950. 12. Weissman, H.: Primary Endothelia of the Pleura, Dis Chest 12:562-570. 1946. 13. Lyman, T. <ed.): Metals Handbook: 1. Prop erties and Selection of Meials. ed 8. American Socie ty of Metals, 1961, p 5. 14. Modern Chemical Processes, New York: Rein hold Publishing Co.. 1952. vol 2. p 167. 'ur* Client 2-F 1 *ith one ] 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, he recovered completely. When he returned to his village, he told the-store of his cure and thereafter cinchona bark 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 Phila 33:104-120 (Oct) 1965. Arch Environ Health--Vol M. April 19C'.'