Document dar4ngzRdqEy1762L80xZmjzq

08/06/2003 WED 09:39 FAX 312 996 1899 UIC LHS CHICAGO @1002 oiled animal expothe literature. orted In part by eona part by grant No. >f Air Pollution, US 3te Common Gasea; y Tract, Arch Intern Effects of Gas Poi- z, W.C.: Permanent Warfare, Amer Rev of Irritant Gases l Indust Hyg 5:390, fence of Pulmonary to Vesicant and J 2:862, 1933. les and Fumes, Proc Gases and Chronic 610, 1954. ts of Gassing, Med i Accident in Brook- Respiratory >f cirtta Poisoning,. J e Long-term Effects Amer Reu Reap DU : Pulmonary Insuffis Disease, Amer J \ed Studies on the New Haven: Yale ing, H.: Pulmonary Phosgene, Amer J . es on Experimental h 28:1037,1947. > Masaenverglftung Oeutsch Med Wschr -G.: Histopathology ath 78:544,1964. !.; and Hatch, T.: iy Phosgene, Arch be willing to eas and cam e action that 'as of Alpha Mesothelioma and Asbestos Exposure Jan Lieben, MD, and Harry PUtaiuka, 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.1*3 Wagner et al* studied 33 cases of meso thelioma. All but one had probable exposure to crocidolite, the blue asbestos. Asbestos bas become a ubiquitous materi al in our civilization. Cauna et al8 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 Thompson6-7 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 malignancies8-6 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, 1960; accepted Sept 13. From the Division of Occupational Health, De partment of Health, Harrisburg, Pa. Head before the Ninth International Cancer Congreas, Tokyo, October 1966. Reprint requests to PO Box 90, Harrisburg, Pa 17120 (Dr. lieben). 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 form large .Bpreading 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 SC-ALL-12901 SCF-FA-5921 m 08/06/2003 WED 09:41/FAX 312 996 1899 UIC LHS CHICAGO @003 560 MESOTHELIOMA--UEBEN & PISTAWKA Method Table 1.--Readings of Consultant Pathologist One hundred and sixty-two hospitals serving ' Case Asbestos a population of 6% million people were re No. Mesothelioma Bodies quested to report all mesotheliomas diagnosed between 1958 and 1963. Replies were received from 162 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 enters. There were 34 meso 1-0 30 4.0 5-0 6-0 9-0 10-0 2-N Yes Not acceptable Probably not Yes Probably not Probably not Yes Yes No lung tissue Yes No lung tissue Yes Yes No lung tissue Yes No lung tissue 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 3-N Probably not 4-N Not acceptable 6-N Yes 1-F Yes 2-F Yes No lung tissue No lung tissue No lung tissue No lung tissue No lung tissue theliomas only seven occurred on the left aide, 26 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 dide as anaplastic 3-F l-Q 2-Q 4-Q S-Q 6-Q 7-Q 8-Q 9-Q 10-Q 1-X 2-X 3-X 4X 5-X 6-X 7-X 8-X 9-X 10-X 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 epithelial cells Mesothelioma must be proven Probably not Yes Yes ' No lung tissue No lung tissue Yes No No No No lung tissue No No No Yes No lung tissue No lungtlssue No lung tissue No No No lung tissue No lung tissue No lung tissue Yes 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 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, 8-0, and 4-0 worked more than 20 years in asbestos insulation plants and pa tient 6-0 worked in an insulation plant for only one year. Patient'6-0 worked 15 years in a plant manu facturing acoustic tQe and linoleum. Patient 7-0 was a boiler maker in a railroad yard where, for 26 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 bis work. next to an asbestos plant. Ten patients had a Of these ten men, patients 1-0, 8-0, and 10-0 questionable asbestos exposure and, in the oth had mesotheliomas of the peritoneum; the oth er 11 patients, either no asbestos exposure er seven men had pleural mesotheliomas. could be elicited on direct questioning or no Neighborhood Cases.--Patient 1-N was a 55- survivor could be located. year-old woman who never had any occupa- Arch Environ Health--Vol 14, April 1967 08/06/2003 WED 09:41 FAX 312 996 1899 UIC LHS CHICAGO @004 awl Pathologist Asbestos 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 tissue No lung tissue No lung tissue No lung tissue No lung tissue Yes Patients Who 1-0 worked 35 >f a large as- id more than ants and pa tent for only plant manuim. in a railroad d on insula- which large re used, untant who office of an to came in estos in his 0, and 10-0 I m; the oth- lio" x J a 65ay occupa- MESOTHELIOMA--LIEBEN & PISTAWKA 561 tional asbestos exposure. Her work was always secretarial; she was boro and lived until the age of 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 18 she lived for SO years across the street from 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 he 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. PatientB 5-N, a nurse, and 6-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 mesothe1 l>imas in thin study. Patiei. i 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 1V4 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 8-N had pleural mesotheliomas. Mesothelioma Patients With Family Con tacts Exposed to Adjestos.--Patient 1-F, a 3year-old child, was the daughter of a ceramic engineer who worked in an insulation plant that utilizes 400 tons of Canadian chrysotile and 1,500 tons 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 who worked as insulators in a shipyard for six years. These sons lived at home until 15 years prior to their mother's death. Patients 1-F and 3-F had peritoneal and pa tient 2-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 1-Q was a welder for 35 years. Ac cording to a common reference,18 eight out of 12 welding electrodes contain asbestos, which is used as a filler. Patient 2-Q was a self-employed Swiss-born Swiss cheeaemaker. A thorough study of the processes of Swiss cheese manufacture revealed no use of asbestos. During the study of the manufacturing process a 600-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 pads.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 forger; 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 in a silk company Arch Environ Health--Vol 14, April 1967 08/06/2003 WED 09:43 FAX 312 996 1899 UIC LBS CHICAGO @005 MESOTHELIOMA--LIEBEN & PISTAWKA from 1925 to 1938, and later in a plastic fabri cation plant which utilized fiber glass; he also had been a welder for 25 yean. 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 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 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 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 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- Clergymon Patient 2-N tremel portec doubli of tb There diseas patter tacts, attack tween Ant pleurt frequt Tht was t came matel; and i These ing t neigh N) ai daugl Fo: ed fr od, v asbes were asbes work work patie work sumt after Nurse Patient 2-F Occupational, neighborhood, and family contact patients with mesothelioma associated with one insulation plant. Arch Environ Health--Vol 14, April 1967 08/06/2003 WED 09:43 FAX 312 996 1899 UIC LHS CHICAGO @006 d deal of circumny unanswered ; material used a generally realin the brewery, to the writers, ay others, os may be the for malignant cases described t the minimal duration of a "he occupationworkers or asjertainly many i those of the contacts. Simibeen reported leliomas is ex- t -At MESOTHELIOMA--LIEBEN & PISTAWKA 568 tremely low. Not all mesotheliomas were re tients no history of asbestos exposure could ported to us by the hospitals, but, even 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 L Newfcousa, M L., and Thompson, H.: Mesothe lioma of the Pleura and Peritoneum Following Ex posure to Asbestos in the London Area, Brit J Industr Med 22:261-269, 1966. 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. 2. Hourihane, P.O.: The Pathology of Mesotheliomata and an Analysis of Their Association With Asbestos Exposure, Thorax 19:268-277, 1964. 8. SelikoS, LJ.; Churgh, J.; and Hammond, C.: Exposure to Asbestos and Mesothelioma, NeOi Eng J Med 272:660-663 (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 Induatr Med 17:260-271, 1960. 5. Cauna, D.; Totten, R; and Gross, P.: Asbestos 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 Bodies in Human Lungs at Autopsies, JAMA 192:371-373 (May 3) 1963. C ' Thompson, J.G.; Kaschula, R.O.; and MacDon ald, _vR: Asbestos as a Modem Urban Hazard, 3 Afr Med J. 37:77-81 (Jan) 1963. 7. Thompson, J.G.: Asbestos and Urban Dweller, daughter of an insulation worker. Summary 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 IndustrMed 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 j 10. Sacconi, A., and Coblenz, A.: Endothelioma ot asbestos. Survivors or employers, or both, ' the Pleura, With Report of Two Cases, Amer J Clin Path 13:186-207, 1943. were questioned regarding the possibility of 11. Campbell, W.: Pleural Mesothelioma, Amer J asbestos exposure. Ten patients actually 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 12. Weisaman, H.: Primary Endothelia of the Pleura, Die Chest 12:562-670, 1946. 13. Lyman, T. (ed.): Metals Handbook: 1. Prop erties and Selection of Metals, ed 8, American Socie ty of Metals. 1961, p 6. - 14. Modern Chemical Processes, New York: Rein after prolonged questioning. In 11 other pa-; hold Publishing Co., 1952, vol 2, p 167. fur** 'at lent 2-F w le 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 rick, 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 14, April 1967 sif m