Document g26z3kpwGVy6Jz3dbGzg03nEq

il expo- 1 (7 \ ' 55) by cou rant No. tion, US i Gases; ?h Intern I i i Mesothelioma and Asbestos Exposure Jan Lieben, MD, and Harry Pislawha, MD, Harrisburg, Pa Gas V o \ - i W I T H I N the past five years several arti Sacconi and Coblenz10 give the incidence ermanent cles have called attention to the association of pleural mesotheliomas as 1.1' cases per mer Rev between mesotheliomas of the pleura and 1,000 autopsies. Campbell reported four it Gases y g 5:3i)0, i peritoneum with asbestos exposure.13 cases of pleural mesotheliomas in 3,533 con Wagner et al4 studied 33 cases of meso secutive autopsies.11 thelioma. All but one had probable exposure Mesothelioma occurs primarily in adults ulmonary ant and 933. nes, Proc Ciironic ing, Med i i i i t to crocidolite, the blue asbestos. Asbestos has become a ubiquitous materi al in our civilization. Cauna et alr>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 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 in Brook- by Thompson0 " in 500 consecutive lung The criteria for diagnosis of pleural meso spiratory soning, J smears from Capetown, South Africa, and thelioma are presence of a firm pleural mass Miami, Fla. Asbestos bodies were found in encasing the lung, histological structure in Effects Resp Dis i 30% of the men and 20% of the women. As compatible with mesothelioma, and absence bestos has been conclusively associated with of a demonstrable primary malignant neo increatjed in c id e n c e of lung cancer and other plasm elsewhere. The histologic architecture y InsufTiAmer J malignancies89 and an increasing number may be mesenchymal, "epithelial," or of studies associate its presence with malig mixed. s cn the ven: Yale i nant mesothelioma of the pleura and perito A complete autopsy is necessary for une neum. quivocal diagnosis, but for the purpose of this study, criteria were made less rigid in 'ulmonary , Amer J J Pathology that unautopsied cases were accepted if a \ definite diagnosis of pleural mesothelioma erimental 1947. vergiftumj j i j Mesotheliomas of the pleura and perito neum are rare neoplasms. Controversy in had been made by biopsy, and malignancy elsewhere had been excluded clinically; led Wschr ' volves histological types, nomenclature, ori chest x-ray examination, bronchoscopy, and ipathologv 1. 1964. latch, T.: ?ne, Arch j I t 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. 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 t masses over the peritoneum and histologi Submitted for publication June 6, 1966; accepted cally appear the same as pleural mesothe Sept 13. liomas. As with pleural mesotheliomas, ex ng to comthat ilpha From the Division of Occupational Health, D e partment of Health, Harrisburg, Pa. Read bcfoie the Nintli International Cancer Con gress, Tokyo, October 1966. Reprint requests to PO Box 90, Harrisburg, Pa 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 17120 (Dr. Lieben). ern Pennsylvania. Arch Environ Health--Voi 14, April 1967 560 M ESO THELIO M A--TAEBEN & PIS T AW K A Method Table 1.-- Readings of Consultant Pathologist O ne hundred and sixty-two hospitals serving a p o p u la tio n of 6]/2 m illio n p eo p le w e re r e quested to rep o rt all m esotheliom as diagnosed betw een 1958 a n d 1963. R eplies w ere received from 152 hospitals. H ospital records of 62 re ported cases v ere reviewed and only m esothe liom as confirmed by operation, biopsy, o r a u topsy w ere included in the study. Forty-tw o cases satisfied o u r critera. T h e re w ere 34 m eso theliom as of th e pleura and eight of the perito neum . Am ong the pleural m esotheliom as there was a definite preponderance for occurrence on the rig h t side of th e chest. O f 34 p leu ral m eso theliom as only seven occurred on th e left side, 25 on th e rig h t side, an d two w ere n o t stated. Sections of as m any of the tum ors and lungs as possible w ere borrow ed an d review'ed by a single consultant pathologist fam iliar w ith m es o thelio m as. I n th e 15 in sta n c e s in w h ich lu n g sections were available, they were exam ined for th e presence of asbestos bodies. All slides w ere reviewed w ithout the benefit of th e com plete history an d autopsy protocol available to the pathologists who m ade the original diagnosis. R esults of th e 33 cases review ed (T able) by our pathologist agreed w ith those of the outside p a th o lo g ists in 17 cases; h e re je c te d sever, cases as unacceptable histologically, had serious doubts in nine cases (of these one slide was read as m etastasis and one slide as anaplastic m a lig n a n c y ). O f th e 15 cases in w hich lu n g tis sue was available, asbestos bodies w ere iden tified in seven. T he discrepancies betw een the original pathological diagnosis and th at of our patholo gist a re rep o rted to illu strate th e difficulties and disagreem ents w hich are so frequent in the diagnosis of this tum or. F or inclusion in this study the diagnoses of the originally reporting pathologists have been accepted and cases re ported by them w ere investigated. E fforts w ere m ade to obtain a com plete em ploym ent and residence history for each p a tient. In q u iry w as also m ade into the em ploy m ent history of fam ily contacts. D ata were obtained from the individual if alive, from fam ily m em bers, or em ployers. Of the 42 patients, ten had definite occupa tional exposure to asbestos during lifetim e, three w ere fam ily contacts of asbestos workers, eight either lived in the im m ediate neighbor hood of asbestos plants or had been em ployed next to an asbestos plant. T en patients had a questionable asbestos exposure and, in the o th er 11 patients, either no asbestos exposure could be elicited on direct questioning or no survivor could be located. Case No. M e so th e lio m a Asbestos B o d ie s 1-0 3-0 4-0 5-0 6-0 90 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 8Q ,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 Yes Yes Probably yes Not acceptable Yes Yes Probably not May be Metast Yes Yes Not acceptable Not acceptable A naplastic malignancy Probably not No epithelial cells M esotheliom a m ust 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 Yes No No No No lung 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 E xposure of T en M esotheliom a P atients W ho W orked W ith Asbestos.-- P a tie n t 1-0 w orked 35 years in the textile departm ent of a large as bestos plant. P a tie n ts 2-0, 3-0, a n d 4-0 w orked m ore th a n 20 y e a rs in asbestos in s u la tio n p la n ts a n d p a tie n t 5-0 w orked in a n insu latio n p la n t for only one year. P a tie n t 6-0 w o rk ed 15 y e a rs in a p la n t m a n u facturing acoustic tile and linoleum . P a tie n t 7-0 was a boiler m aker in a railro a d y a rd w here, for 25 years, h e w orked o n in su la tion of steam engines. P a tie n t 8-0 b u ilt bakery ovens in w hich large am ounts of asbestos insulation w ere used. P a tie n t 9-0 was a certified acco u n tan t who w o rk ed m o re th a n 30 y e a rs in th e office of a n asbestos textile plant. P a tie n t 10-0 w as a p lastere r who cam e in contact w ith a large am ount of asbestos in his w ork. Of th ese te n m en, p a tie n ts 1-0, 8-0, a n d 10-0 had m esotheliom as of the peritoneum ; the o th er seven m en had pleural m esotheliom as. N eighborhood Cases.-- P atien t 1-N was a 55year-old woman who never had any oecupa- Arch Environ Health--Vol 14, April 1967 i ! , ; _ 1 ' ! , , 1 ; ' tional secret of 8, bestof patici ag e oi from for 1. Pat death besto h e li\ of th and 1 ing Pa besto his d th e s in tl Pa strer com Pi tribi faini with plan mes' P stor plai no plaj best cast P tien pier tact yea ' eng tha am all> 1 an th( pic WO nc ha an an \v t yo gist s issue issue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue ssue Who id 35 ? as- than pa- only anu- road ula- arge who f an e in i his 10-0 oth- i 55upa- MESOTHELIOMA-IJEBEN & PISTAWKA 5G1 tional asbestos exposure. H er work was alw ays P atients 1-F and 3-F had peritoneal and p a secretarial; she was born and lived u ntil the age tien t 2-F pleural m esotheliom as. of 8, in th e im m ed iate n eig h b o rh o o d of a n a s M eso th e lio m a P a tie n ts W ith Q u estio n ab le bestos textile and friction m aterial plan t w here Asbestos Exposure.-- A study of these ten m en p a tie n t 1-0 h ad w orked for 35 years. F ro m th e elicited e ith e r a relatively m in o r or q u e stio n t age of 18 she lived for 30 y ears across th e street ab le exposure to asbestos. fro m th e p la n t w h e re p a tie n t 6-0 h a d w o rk ed P a tie n t 1-Q w as a w elder for 35 y ears. A c for 15 years. c o rd in g to a com m on re fe re n c e ,13 e ig h t o u t of ! P a tie n t 2-N , a clergym an from 1935 u n til his 12 w elding electrodes co n tain asbestos, w hich is d eath in 1961, never had an y occupational a s used as a filler. i bestos exposuie. P rio r to becoming a m inister P a tie n t 2-Q was a self-em ployed Sw iss-born h e lived for 19 y ears w ithin one h alf of a m ile Sw iss cheesem aker. A tho ro u g h stu d y of th e of th e insulation p la n t w here p atien ts 3-0, 4-0, processes of Swiss cheese m an u factu re revealed and 5-0 h ad w orked as insulation m an u factu r no use of asbestos. D uring the study of the ing workers. m anufacturing process a 500-gal boder was no P atien t 3-N never had any occupational as ticed. T his boiler was covered w ith a friable as b esto s ex p o su re ex c e p t th a t, 20 y e a rs p rio r to b esto s in s u la tio n w h ich flak ed off o n co n ta c t. his death, he had worked for one year across P a tie n t 3-Q, a 14-year-old boy w ith m esothe the street from the insulation plant m entioned liom a, had no occupational contact w ith asbes in the history of p atient 2-N. tos nor did any of his fam ily. On questioning, P a tie n t 4 -N w orked fo r 26 y e a rs ac ro ss th e th e b o y 's fa th e r to ld th e a u th o rs th a t h is boy l t street from the insulation plant m entioned in had lived w ith him and had helped him w hile connection w ith patients 2-N and 3-N. he had replaced m ost of the plaster board dur i P a tie n ts 5 -N , a n u rse , a n d G-N, a m e a t d is in g ex ten siv e re m o d elin g of h is h o u se. P la s te r tributor, had no occupational exposure nor board contains a high percentage of asbestos. fam ily contact w ith asbestos. T hey both lived P a tie n t 4-Q is em ployed in in d u strial sales i w ithin th ree fourths of a m ile of two asbestos and never had any occupational asbestos expo plan ts in a tow n w ith th e greatest incidence of sure. E xtensive questioning revealed th at, on I m esotheliom as in this study. two occasions several years before, he applied P a tie n ts 7-N a n d 8-N w ere b o th fo rem en in a asb esto s in s u la tio n to boilers in h is h om e, m ix storage battery plant. A careful check of the ing asbestos cem ent him self. H is total exposure plant and their em ploym ent records revealed during these applications was only a m atter of no asbestos exposure, past nor present. T he hours. ! p lan t is located less th a n IV2 m iles from a n a s bestos textile plant. T h e exposure of these two cases is questionable. P atien ts 1-N and 4-N had peritoneal an d p a tien ts 2-N , 3-N , 5-N , 6-N, 7-N , a n d 8-N had pleural mesotheliom as. P a tie n t 5-Q was a brew ery w orker for 20 years. T he brew ery was no longer in business w hen the case was investigated. Reviewing th e literatu re of beer production th e following paragraph was discovered: I M esotheliom a P atients W ith Fam ily Con "W hen ready for packaging th e beer is fil ta c ts E x p o se d to A sbestos.-- P a tie n t 1-F, a 3- te re d th ro u g h p u lp filters co n sistin g e ss en tially year-old child, was the daughter of a ceram ic of cotton fibers and asbestos. A fter each filtra e n g in e e r w ho w o rk ed in a n in s u la tio n p la n t, tio n th is `F IL T E R M A S S ' is rem oved, m an g led , th at utilizes 400 tons of C anadian chrysotile and w ashed in clear, w arm w ater, then bleach a n d 1,500 to n s of S o u th A frican am esite a n n u ed an d sterilized a t 160 to 180 F w ith chlorine. ally. T he w ashed pulp then goes directly to a p ad I * P atien t 2-F, a 40-year-old nurse, never had any occupational asbestos exposure, but h er fa th e r h a d w orked for 35 y ears in th e in su latio n form ing m achine w here it is com pressed a t 89 to 90 pounds p er square inch to form new filter p a d s.14" p la n t w here p a tie n ts 3-0, 4-0, a n d 5-0 had A sbestos-containing p ipe insulation is used in w orked and w hich was also credited w ith three brew eries. n eig h b o rh o o d cases. T h e n u rs e 's b ro th e r also P a tie n ts 6-Q, 7-Q, a n d 8-Q w e re a ll steel had w orked in this plant for one year. w o rk ers. P a tie n t 6-Q w as a c ra n e o p e ra to r; 7-Q P a tie n t 3-F , a 6 7 -year-old w om an, n ev er h ad a forger; a n d 8-Q a fo re m a n a n d su p erv iso r. In any asbestos exposure nor had she lived near all cases th e com panies did n o t re -all an y as an asbestos plant. S he had two sons who bestos exposure for these m en. P ipe insulation w orked as insulators in a sh ip y ard for six containing asbestos is extensively u tilized by years. T h ese sons lived a t hom e u n til 15 y ears steel com panies. p rio r to th e ir m o th e r's d e a th . P a tie n t 9-Q was a spinner in a silk com pany Arch Environ Health-- Vol 14, April 1967 562 MESOTHELIOM A--LIEBEN & PISTA \VK A from 1925 to 1938, a n d la te r in a plastic fa b ri Comment tremel cation p lan t w hich utilized fiber glass; he also ported h a d b een a w elder for 25 years. H e th in k s he This study presents a good deal of circum double h as u sed asb esto s b u t could n o t recall w hen an d stantial evidence and many unanswered of the where. questions. There P a tie n t 10-Q, a 63-year-old m an, was a Asbestos is a ubiquitous material used diseas co re-m ak er al. his life. H e w orked in tw o fo u n much more frequently than is generally real pattei dries in one of w hich asbestos cem e n t is used in ized. Some uses, such as in the brewery, tacts, sm all quantities but, according to the plant m anager, the core-m aker did not have any con tact w ith this m aterial. T h e son stated th at his father had used asbestos pipe insulation for pipes in th e basem ent of th eir hom e several 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 attacl tween An pleur y e a rs p rio r to th e o n set of his illness a n d th a t mesothelioma in some of the cases described frequ h e h a d d one som e saw ing of th is p ip e in su la above, we must admit that the minimal Th tion m aterial. dose-effect relationship and duration of a was A ll cases in th is g ro u p h a d p le u ra l m eso th e latent period are unknown. The occupation I came liom as. al exposure of the insulation workers or as M eso th elio m a P a tie n ts W ith o u t A sbestos bestos textile workers were certainly many I r mate and E x p o su re.-- In th e o th e r 11 p a tie n ts (1-X to 11- thousand times higher than those of the Thes X ) no o ccu p atio n al, fam ilial o r neighborhood neighborhood cases or family contacts. Simi ing asbestos exp o su re evidence could be elicited. lar findings have recently been reported neigl T e n of th ese p a tie n ts h a d m esotheliom a of th e from England.1 N) ; pleura and one peritoneal mesotheliom a. The attack rate for mesotheliomas is ex- dauf ed f od, asix wer asb< wor wor pat woi sun aft' Occupatienal, neighborhood, and fam ily contact patients w ith mesotheliom a associated w ith one insulation plant. Arch Environ Health-- Vol 14, April 1967 i i i I ! I t :uinerecl jsed ealery, ters. the ant i!>ed mal if a ionasany the imirted ex- j i i i i j i ! ! i t t MESOTHELIOMA--LIEBEN & PISTAWKA 563 tremely low. Not all mesotheliomas were re tienls no history of asbestos exposure could ported to us by the hospitals, but, oven if we 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. Newhouse, M.L , and Thompson, H.: Mesothe lioma of the Pleura and Peritoneum Following Ex posure to Asbestos in the Eondon Area, Brit J In dustr Med 22:261-209, 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. SeliholT, I.J.; Churgh, 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 came from a geographical area of approxi mately 30,000 sq mi, six were clustered in 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. Caima, D.; Totten, R ; and Gross, P.: Asbestos and around an insulation plant (Figure). 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 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 Afr Med J 37:77-81 (Jan) 1963. 7. Thompson, J.G.: Asbestos and Urban Dweller, daughter of an insulation worker. read before the Conference on Biological Effects of Summary 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 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, were questioned regarding the possibility of asbestos exposure. Ten patients actually 10. Sacconi, A., and Coblenz, A.: Endothelioma of the Pieura, With Repott of Two Cases, Amer J Clin Path 13:186-207, 1943. 11. Campbell, W.: Pleural Mesothelioma, Amer J Path 26:473-487, 1950. worked in asbestos plants; eight lived or worked close 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- 12. Weissman, H.: Primary Endothlia of the Pleura, Dis Chest 12:502-570, 1946. 13. Lyman, T. (ed.): Metals Handbook: 1. Prop erties and Selection of Metals, 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. DISCOVERY OF QUININE t i M any of the drug sources known in ancient tim es were apparently discovered by acci I dent. F o r example, according to an old South A m erican Indian legend, the curative f power of cinchona bark (containing quinine) for m alaria was discovered by a sick, fe I verish Indian lost in the jungle. H e quenched his th irst by drinking from a pool of w ater. From the bitter taste of the w ater, he recognized th a t it was tainted w ith the poison from the quina-quina tree. A lthough he shared this fictitious belief, he drank deeply so as to bring about a quick dot th. T o his great surprise, he recovered com pletely. W hen he returned to his village, he told the store of his cure and th ereafter cinchona bark was used as a m edicine for the fever prevalent in th at region. T h e Incas later I ta u g h t th e S p a n is h c o n q u ista d o rs t h a t m a la ria could be c u re d w ith c in c h o n a e x tra c t.__ i R ossm an, R .E .: T he H istory and Significance of Serendipity in M edical Discovery, Trans i Coll Physicians Phila 33:104-120 (O ct) 1965. Arch Environ Health-- Vol 14, April 1967 i