Document X8aO4aYrdnKZL7QZQyja61oYw

37 587 & Mesothelioma and Its Association Maxwell Borow, MD, Alfred Conston, MD, Lawrence L. Uvomese, MD, and Xorbert chalet, MD Within a three-year period in a community hospital, 17 cases of mesothelioma, nine of the pleura and eight of the peritoneum, were found at surgery. Two of our eetie-its contracted this malignancy with only environ mental exposure consisting of living in a community adjacent to the asbestos mill. In the same hospital, there has been a high incidence of bronchogenic carcinoma w!;h esMstPJSis. A review of the gptonsy material of .the P3$t decade brought to light only one additional case, tt is our belief that the incidence of mesothelioma is increasing as is the incidence of asbestosis, with the increasing application of this product in many different industries. Primary tumors of the serosal surfaces are so. rare that for years they were considered to be pathologic curiosities. The first reference to such tu tors can lie found in a report by Von Rokitansky,' ho in 1654 described primary tumors of the peri toneum which he called "colloid cancer." During the next 100 years, there were sporadic reports of similar types of tumors. However, this entity re gained so ill defined that there was much doubt as t0 precise nature. Brown and Johnson' in 1951 wnsidered these mesothelial tumors (mesothelio- to be the end result of an inflammatory* projvss, with organization of the exudate. Willis" in *5atk`0fdc text made the following statement: * the present day accounts of supposedly primary "*"sai tumors continue to be descriptively inade `e and insufficiently critical, displaying a lack of 'tvness of the possible behavior of small unde ' carcinomas." end he also cautioned the reari - ' preserve an open mind regarding the exact "h'genesis Gf these tumors. In 1954. Ackerman4 --Uec that it was the majority opinion that nl- ash primary mesotheliomas are rare they do sh' I'.-j^ rlm e n U o f s u r w r v am i (vitholucv. S x i v r s f ! ! Is- NJ. ' ' 4 ' rM!a' ,s to S IS C hurch S t. H ound Brook. X J OS.'-W \ D r. exist. Since Godwin* in 1957 laid down strict cri teria for the diagnosis of pleural tumors and Wins low and Taylor in 1960 for ceritonenl tumors, the diagnosis of these neoplasms has become more common. The incidence of primary mesothelioma has varied statistically from .02% to .2% of ail autop sies. with a ratio of one to two in favor of the male. T h eJk st large series pf-cases o f diffuse meso thelioma was diagnosed histologically in 1957 at the Pneumoconiosis Research Unit at Johannesburg. South Africa. In trying to explain this mysterious epidemic, Wagner et aI,Tnoting that asbestos bodies could be found in the lunsrs of some of their pa tients, obtained detailed life histories of these pa tients. By 1960, they were able to establish an as sociation with the Cape of Good Hope asbestos fields, or the industrial use of asbestos, in 32 of 33 patients with histologically proven pleural meso theliomas. The maiority of these patients had not actually worked with asbestos but had lived in the vicinity of the mines and mills and some had left these areas of exposure as young children. The aver age period between exposure and development of the tumor was 20 to 40 years. 3 y 1962. Wagner et a!* had diagnosed a total of 67 pleural and two peritoneal mesotheliomas. In only two cases was it not possible to establish a history of exposure to the asbestos dust. Of these 67 cases, 12 had had industrial exposure and the remainder '-ad had en vironmental exposure from living in the vicinity of the mills and dumps. This association between mesothelioma and asbestosis was made even more intriguing when, in 1955. Bonser et aP described a series of 72 autopsies on patients with asbestos;,, in which four cases of peritoneal m.cothobk --.a were found. Subsequently. Maneuso and Corker found five peritoneal mesotheliomas in autopsies ou 1,495 asbestos workers, and Houriha.no. 'upon re-.'.-kng the necropsy tiles of the Loudo" l u - ' ,1 ~.un 1917 to 1962. found 34 cases of --eso: v .erne. 17 of the pleura and an equal number c. .be peri* , ^ *-'? " i. 1967 Vo! 201. No 8 3 'sa V.ESOTHE GWA AND AS3$T0S<3~BGRGW ET AL fmt Wm tor.ii:an. Ail of these patients had pulmonary &s- le$toris. even though in o' few there was no his tory* nf exposure to the asbestos dust. In the same year. Kniieknap and Smither1'1reported 11 cases of B'litoneal mesriihcHoma in patients exposed to m , Nttosut. In an attempt to determine whether mesotht-lio- ' -'nm of the serosal surfaces had any relationship with asbestos exposure in the United States, Selikoft et aF* studied 307 consecutive deaths among asbestos insulation workers in Northeastern United States. They found ten deaths caused by mesothelioma, four pleural and six peritoneal mesotheliomas. In mhim ^ -an rate attrioulnd to cancer of the stomach, ^ jetton, and rem uai Of the 307 deaths, 40.4% were attributed to cancer, 5.5% to asbestosis, and 54.1% to other causes. In a second study where they re viewed 26 consecutive autopsies of patients with . asbestosis, they found four mesotheliomas of the - pleura and three o f ih e peritoneum. , '"vjfe*of m (M j& I l i s hqd d ie unique experience of ''W hstimg, within &.^M t'lw0 years, on II patients ; proved. to have mpsothelioma. Six of these '' of the peritoneum and five of the pleura. These Sfsitff. added to those diagnosed previously made a of 17 cases o f mesothelioma, of which eight were pritoneal and nine were pleural mesotheliomas. AH "17 Cases were ciaghosd within the past three years. A review of the autopsy material at Somerset Hos- ' pita!, Somerville, N J, from 1948 through 1985 did not disclose any additional cases of mesothelioma. This high concentration of what is considered to be a f t ie tumor can be explained by the close proximity of a major asbestos mill. Approximately 75% of all mm asbestos fiber which is mined in North America ,,is convened to commercial use in an industrial fa cility which is located only two miles from Somerset ifiSapital. ' ' : . lir e association between pulmonary cancer and asbestosis has been recognized at this institution for many years. The number of patients admitted with thse conditions is difficult to determine, as in ear lier years many of them were diagnosed as pulmo nary fibrosis or silicosis. The only accurate statis tic* could be obtained from the autopsy material of 'm m t decade.rgM ^to! 5 , when 1,330 autop- thisgroup, there were 22 5 'llii^ -x rith pulmonary asbes- T iils of mesothelioma. An despite the fact also employed a t;:"th industrial many contracted as ~ ' there is , ........ ale w ith mesothelio- ma In our series. Ss |e never worked in the as~ plant but lived nearby. This experience is in it to o th er reportedseries, particularly those South Africa where there was a significant er of females affiicted with mesothelioma. Newhouse and Thompson," in studying the occu pational histories of S3 patients with mesothelio ma noted that 42 of these patients were female. We might invoiv-.; w ith this .. exposure work, However, other;afa^^.w m iM ..-n^3|b.tiitfeto this, as there a p p m ^ 0 ;- ^ - fjk4ftcsdencd of mesc- theliomas % iig . ir r ite 'mciiSiy the asbestos d q e^ j# ^ id u si# e M W i^ ris sari from Soadk. hia not been These people had to liv- ir.g in the The sta- tistics from by Newhouse and .th e same an c-n- is infor m ation, w&mem. similar circumstances p ' e s p e c i a l l y since there is a k rge asbestos durtip adjacent to a resi dential area. - ; . . ; Another interesting observation in our series is the fact that 16 of the 17 patients with mesothelio ma were diagnosed within the past three years. A re view of the autopsy material for the previous decade brought to light only one additional case which initially had been misdiagnosed. Since the refine ment of the asbestos fiber \a s been one of the ma jor industries in this geographic area for over. 6u years, ftj* d g fc g t Jo mw aware of this disease. One possible explanation is that in our group of patients, once the diagnosis was suspected, an intensified effort was made to obtain an autopsy when the patient died. However, prior to our recognition of this entity, patients with mesothelioma were m ost likely diagnosed as having a generalized carcinomatosis and little effort was made to obtain an autopsy when they did. Regard- less whether this reasoning is correct or not. it is our distinct impression that there has been a defi nite increase in incidence of this malignancy within the last few years* il * it* V ho" No ( b iia An of t 1. Tubulopapillary type ..... slightly reduced from x!2Q). (ease 1, -----Lf- - - -539 2. Asbestosis of the long (case 1, X l20). Report of Cases t C*SE I.--A 52-year-old white man was admitted to the ; with increasing constipation, an enlarged abdomen one month's deration, and an ill-defined abdominal pain. i'i" had been retired with a medical disability from pulmo- mry asbestosis after working 23 years a t an asbestos mill. Ho suffered a myocardial infarction two years before ad- n'kskm. He smoked only occasionally. Physical examination revealed a slightly emphysematous Vst with harsh breath sounds and abdominal distention. - N<>intra-abdominal masses could be palpated at that time. *'i--*t x-ray of the lungs demonstrated basilar fibrosis, U'aterally, interpreted as most likely due to asbestosis. "Ah Mtbp8(bfier xirayflhn, -without -ecertirast-material, the abdomen demonstrated a ground glass appearance -i:-restive of ascites. Some attenuation of the rectosig- >d on the x-ray film taken after evacuation of the ' runn enema raised the possibility of a pelvic mass. A 'K-entesis yielded approximately 1,500 cc of straw-col- 1 fluid. Surgical exploration revealed the visceral and i'.trictal serosal surfaces to be studded with fine papillary, granular-like, projections. A diagnosis of papilloma ri^iitheliosna was made from a biopsy specimen (Fig 1). Foliowing an intraperitoneal injection of gold AU-193, It remained symptom free and ascitic free for nine ' "ruhs. Fourteen months after surgery he died from a mvoeartliai infarction. ' . Autopsy examination revealed pleural cavities to be i fire of tumor. Pleural plaques were present a t the bases -ei.l there were multiple adhesions. The lungs demonstrat- *<1 bullae emphysema with an irregular delicate fibrosis throughout. The heart was enlarged with old scarring and * fie*h infarct. The peritoneal cavity yielded 1,000 cc of 'htl.v mucoid yellowish fluid, and all the coelomie cav- rgans as well as the parietal peritoneum were cov- 1'>! with white hard nodules, varying from 5 mm to 5 cm i:*''nutter and having a mucoid appearance on the cut ' In many areas there was a tendency for these viil.-s to coalesce' to form larger tumor masses. The tu- did -not jK-nctratc for any appreciable distance be -- Serosal tumor encasing loops of bowel (case 2). * ! i j i 9*9! l$p"!V neatb the surface, and all other organs were unremarkable. Microscopic examination demonstrated an extensive in terstitial fibrosis of the lungs with many asbestos bodies (Fig 2). The hypertrophied heart showed areas of fibrosis and acute necrosis. The tumor was characteristic of meso thelioma with cuboidal cells showing some p'eomorphism and superficial papillation. Case 2.--A 51-year-old white man was admitted to Som erset Hospital because of abdominal pain. For 25 years he was an employee at an asbestos refining plant. He smoked less than one pack of cigarettes per day. Results of physical examination were normal, and all laboratory studies were unrevealing Chest x-ray showed a fibrotic infiltration of both lower lobes. An upper gastro intestinal roentgenographic series demonstrated duodeni tis and gastritis. He was discharged on a regimen for ul,,.*er convalescence only to he readmitted seven months later with postprandial abdominal pain and a 10-Ib weight loss. On palpation the abdomen appeared board-like, though there was no tenderness, and an extraluminal mass could be palpated through the anterior portion of the rectal wall. A barium enema demonstrated rigidity and narrowing of the sigmoid colon. At surgery, the abdominal cavity was found to be almost completely obliterated by large masses of neo plastic tissue which had enveloped the intra-abdominal or gans and was infiltrating the parietal peritoneum. A diag nosis of mesothelioma was made from a biopsy specimen. The patient died four months later. Pertinent findings at autopsy included numerous large plaques on the parietal pleura and congestion at the bases of both lungs. The peritoneal cavity was virtually obliterat ed by a large, yellowish-white hard tumor which was com pletely encasing the abdominal organs (Fig 3). Except for this surface involvement, the organs were unremark able. . Microscopic examination demonstrated bronchial pneu monia with a mild pulmonary fibrosis and many asbestos bodies. The tumor consisted of fusiform cells in a hyalinized stroma with papillary formation characteristic of mesothelioma (Fig 4). Case 3.--A 4"-year-old white man was admitted to the hospital with a nonproductive cough and ill-defined dis comfort in the right lower lobe of the lung. The initial chest x-ray film was normal, but a second one taken two days before admission demonstrated a small pleural effu sion in the right costophrenie angle. Though he had been an insurance agent and more recently a liquor salesman, he had worked as a stock boy in an asbestos refining plant for 18 months, 24 years ago. Physical examination and complete work-up were unre- vealing. including scalene node and two needle pleural biopsies. Thoracocentesis yielded 10C* cc of straw-colored fluid with some mesothelial cells. At exploratory thoraco tomy the patient was found to have a greatly thickened parietal and visceral pleura with encasement of a partial ly atelectatic lung. In certain areas the parietal and vis ceral pleura were intimately adherent to one another and could not be separated. There was no nodularity of the serosal surfaces. A diagnosis of pulmonary asbestosis and mesothelioma was made from a biopsy specimen. Postoperatively he re ceived steroids and cobalt radiation with a poor response, and he died ten riiontlis later with bilateral pleural in volvement. . . Clinical Features O ur patients w ith peritoneal mesothelioma pre sented themselves in one of two ways. Four had as cites of unknow n origin and the o:hov three com p lain ed o f vacile abdom inal pain an d w eigh: loss. I n th is la tte r g roup a n ill-damned roas-- was ne.-n'ly p alp a te d e ith e r th ro u g h th e abdom inal wall ov on rectal exam ination. L aboratory w o r k - v ana reent- ger.ographic ex am in atio n of .h a go . ' ' t t e s t h a l fel .. - . '% ! 5 5 0 MESOTHELiO.V.A AND AS EEL7C 5..S-- BOSOV/ ET AL tract v .r e r.r.revealing. T he diagnosis was made either r,y sm-tery or peritoneoscopy and biopsy. Those pane:::-- with ascites were found to have small papillary projections studding the visceral and parietal peritoneum. The ascitic fluid varied from a clear syrupy to a thin straw-colored consis tency. Those patients w ith the palpable masses were found on exploration to have complete ob literation of the peritoneal cavity by large tumor masses which were occupying m ost of the coelomic cavity and invading the parietal peritoneum. We believe that th is picture is but the end stage of sect an earlier stage. T h is is substantiated by the finding of papillary projections a t surgery in several of our patients who having presented with ascites and in whom obliteration of the peritoneal cavity with large tumor m asses developed later, as seen a t autopsy. . Patients with pleural mesotheliomas all present ' ed with varying degrees o f chest pain and pleural effusion. A work-up was likewise unrewarding with the exception of positive findings from a pleural biopsy in one patient. T ile ftuid in the pleural cavi ty varied from a gross bloody effusion to straw-col ored fluid, and the tum or involvement varied from papillary projections on the parietal and visceral pleura -ra generalized nfcadeened -pleura, -in areas the visceral and parietal pleura were intim itely ad- herent and could be separated only with difficulty. Treatment w ith cobalt radiation therapy, radio active gold and chromium, and chemotherapy, used alone or in com bination, had little effect on the course of this disease. F ifty percent of the patients suffering either from pleural or peritoneal meso thelioma died within one year and the remainder by the second year. Criteria for Diagnosis Although it is now accepted that mesothelial tumors of the serosal surfaces do exist and possess a number of characteristics which justify their seg regation as an en tity, th e criteria for the identifica tion of these tumors are still largely imprecise. The currently accepted criteria for the diagnosis of these tumors are that: (1 ) T h e diagnosis should be ap plied to those groups which how an unequivocal predilection to spread along the serosal membranes, with either none or on ly a shallow' invasion of the underlying organs. (2> A ll other sources for the tu mor have been excluded. (3 ) If m etastases are pres ent:. they should be lim ited to rite regional lymph nodes, rarely occurring in liver, bone, and lung. Special staining or histologic techniques may aid in a diagnosis o f th is disease. Wagner et al14 have suggested that metachxomatic staining (removable by exposure to hyaluroniaase) within a tumor is strong evidence for th e diagnosis of mesothelioma in a patient. Pathologic Characteristics.--In the earlier stages, the tumor is made up o f many small, rounded, firm nodules on the visceral and parietal surfaces. Later, " ' - ' < . * `" ' ,, r* .y; --- v- ' *' ' ...--.--_____ ... there is a coalescence of these nocu.es so tr.r. the terminal state usually consists of solid, `.vote, thick bands which encompass the viscera and fix them within a dense mass. Often the d-Lir.eati&r. between parietal and visceral peritoneum is lost, s: that the usual autopsy dissection is impossible dus to this encasem ent The tumor is generally white and firm and may have a mucinous appearance or. the cut surface. Histologic Characteristics.--We have seen two major histologic types of mesothelioma. The mos: common variety is the epithelial form where there .j^ c g h o id a l f^jJ^yhedral Is producing a tabulopapifiary appearance or a solid group of ceils with out a clear tubular formation. Usually there is a fair ly uniform cellular structure, but occasionally bizarre nucleated cells can be seen. Pathologic mito tic cells are rarely found, but doubly nucleate.: and muiiinucleated tumor cells are often seen. The other variety is the mesenchymal or fibrous type of mesothelioma in which spindle cells are arranged in an alm ost fascicular pattern within a stroma c: abundant hyaline collagen. Occasionally the cels may be arranged loosely in indistinct fasciculi or may occur in solid nests. The most striking histologic characteristic of mesothelioma is the structural variation which may occur from area to area withir. 4he same-tumor,<so that in one .area the growth may have epithelial structure, while in another a purely mesenchymal appearance or in between combina tions. Pathogenesis The mode of action of asbestos in producing neo plasia is at present poorly understood. Furtnermore. a puzzling feature has been the presence o: meso thelioma in one mining area, while in another min ing area a few miles distant, the disease has as ye: to be identified. There are two major mining dis tricts in the Republic of South Africa. In none west Cape of Good Hope province, crocidolite is the fiber mined, whereas in the Transvaal asbestos field, both crocidolite and more importantly amosite are mined. Up to the present time there has been a 4. Spindle cell type mesothelioma (case 2, xD). 'f MES0THEL10VA AND ASBESTOSIS--BOROV/ ET AL 591 - -*hiTO `, '.-, 40 ,-T- ,-V -0* ..1 - h!d ;../ V- C 1C e! y v . iK .4 high prevalence of mesothelioma of the pleura and peritoneum in northwest Cape of Good Hope. On the other hand no case as yet has been reported from the Transvaal asbestos area or its surround ings. Sluis-Cremer* has studied the geographical and environmental differences in these two areas and has come to the conclusion that none of the fac tors examined explained satisfactorily the absence of mesothelioma in the Transvaal region. Other than for the mineralogic difference between the two areas, he found no variation in the intensity or length of production of these fields or in the extent of the environmental pollution and incidence of pul monary. asbestosis. Norths America, chrysotile, is the main fiber mined although crocidolite and amo site are present in lesser amounts. Both pleura and peritoneal mesothelioma have been found in work ers exposed to these fibers. Wagner' in 1962 induced mesothelioma bv inocu lating various dusts into the pleural cavity of rats. Pleural tumors developed in those inoculated with crocidolite, chrysotile, and a finely divided silicon powder (99.9'v: silicon dioxide). Recently Skidmore and W agner8 showed that crocidolite, chrysotile, silica powder, and to a lesser extent, amosite, all induced pleural mesotheliomaia in guinea pigs after interpleural injection. Peacock and Peacock18 in duced malignant tumors in fowls with crocidolite -and -amosite.--A-number of-hypotheses toeicplain the pathogenesis o f this disease have been proposed, but none of them have been widely accepted. The first theory' was that of physical irritation due to the presence of asbestos fibers deposited in the ter minal lymphatics of the serosal surfaces or due to the migration of the asbestos fiber from the lung following inhalation or from the gut as a result of ingestion. Fibers have been demonstrated in a num ber of tissues, including parietal pleura, gastric mu cosa. and spleen, but there have been no reports of fibers in the peritoneal surfaces. . Another concept is the auto-immune theory in which the presence of asbestos bodies in the lung is said to elicit the production of an abnormal globu lin. Up to the present time, there is little positive evidence for this concept. The serum of patients with either asbestosis or neoplasia shows only a slightly raised titer for the rheumatoid factor, and immunofiuorescent staining has not shown evidence of an antigen-antibody aggregate. Recently, Harington and Roe'"suggested that the carcinogenicity of asbestos may he related to the presence of nat ural and contaminated oils associated with the as bestos fiber or to certain carcinogenic metals or metal complexes in.he., fibers. They found that crocidolite and amosite contained appreciable amounts of natural oils. Furthermore, all the as bestos fibers, including chrysotile, may contain sec ondary oils as a result of an addition of oil to the asbestos during the processing or as a result of con tamination. Furthermore, almost universally, the asbestos is transported and stored in jute bags and the oil from the jute fiber is absorbed to a great ex tent by all three types of asbestos fiber. Both chrysotile and amosite have a significant ferrous content, particularly of certain macromolec ular complexes of Iron, such as iron-clextran which is knows to be highly carcinogenic in animals. The iron content of chrysotile is much lower than the other <t?w-fibers. I-t is proposed by Karington and Roe3" that the carcinogenic agent or agents may not be the fiber themselves but either the natural oil or secondary' oils which are present on the fiber and or possibly the iron complex. The authors are currently performing biologic tests for the carcino genicity of these materials. However, these studies were in a preliminary form at the time of the report. Generic and Trade Names of Drug Gold Au 12& -Aurcoloid-19S. Aureo:ope*Au 19$. A w e o tc a a -lS i. Radiogold Colloidal A u 19S, Aurcotope. References 1. Rokitansky. C. Von: M anuel of Path. Anat. Sydenham Soc. Trans_ London p 263, 1834. - 2. Broun. W J - and Johnson, L.C.: P ost Inflammatory `T u - mcrs" of Pleura: 3 e a ses of Pleural Fibroma o f Interlobar Fissure. Mili; urg 109:415-425 (Oct* 1951. 3. Willis. R-A: Pathology o f Tum ors. W ashington, DC: Butler- orth Inc_ I960, p 1.-5. ? 4. Ai-fcerman. L.V.: ; A tla s o f Tumor P athology. Washington. IX?; Armed Forces In stitute o f Patho'ogv. section 6. part 23. 1956. r ico. 5. Gcdwin. M.C.: D iffuse M esotheliom as With Comment in TVir Re1.,:ion to lax-eb /ed Fibrous M esotheliom as. Concur 10: March-April* 1957. Window. D.8.. and Taylor, H-B.; Malignant Peritoneal *;S>;V:ioIu3s, Cancer 13:12?-136 (Jan-Feb* ISVt*. :n,-r. J.C.: S h -trs. C-A.; and Marchand, I1.: Diffuse Pleu* Mesothelioma ami A sbestosis Exjxsstire in North Western ' r P rm nce. H n t J la d u s tr M e d 17:260-271 < C V :' 19-'A. -s V\.-r e . , , t . l '; E p id e m io lo g y o f D itit,se M osotho*::' T u m o rs : ' .'-v . ; .hi W .s-in tion From Studies in South . W e : ami ' A.! ;d V-m W A cad Sa, 132:575-576 ,lV c 8 1 > IsVCv ` iw-r. C. V ; ' aa'd*. J.S.; ami Stewart. M.,?.: ( V w n lio n a l , N 1'.'a M:-r in l*>os;u!?s 0;era!ives anil o' 1 : a in 1 -' - ' V. a-'.ers ami Iron Ore Minos. - c a r J i P a t h - ' ! `4 y, > p , ' ?1"le .i.i,. T . K . : vsI C ,m ite r. R .J .; M e th o d o lo g y >n I n d u s tria l Stihl es. *m Karirom H ealth & 210-226 ,F e 'a* ' -1 Hoi,! ' ' a M O : T h e P a th o lo g y o f M e s c ` i.ve-.i: a m i an Analvsis of Their Association W ith Asbestos Exposure. Thorax 19:266-278 (May? 1964. 12. Enticknap. J.B .. and Smither. W.P.-L: Peritoneal Tumors in Asbestosis. Brtf J Industr M ed 21:20-31 t j a n ' 1964. 13. Seliltoff. I.J.: Chtirg. J.; and Hammond. F.C.: Relations Between Exposure to Asbestos and M esothelioma. .Ve:c E n g J M ed- 272:300-565 tM atch* *>68. 14. Newhouse, 31.L . sn<| Thompson. H.t Epidemiology of M sothlial Tum ors in the London Area. Ann X T A cxd Sei 132: 579-5S8 (D ec 31* 1963, 15. Wagner. J.G : M onday. D.E.: and Karinptort. 7.S.; Histo- rhemiral Demonstration o f Hvalurenie Acid in Pleura! M eso theliomas, J P ath B eet 84:78-78 .July* l i ' t l 16. Slnis-Cretner. G.K.: A sbestosis in South Africa. Certain Geograplsteal and Environmental Cens1!- nions. .4.rt .VI' Aeail Sri 1,-42:215-284 , Deo 31* 1965, 17. Wagner. J.C.: Kvperi men ta! IV ster' bn o l M sothlial Tu mours of the l'leura I'V i)-<:p*.m:a'on o: 1Y.sts in ~.'aara'ar\ Animals. .V:.'.-.-c I96:15.M8! tlV i 16' 1:' ;2. IS. Wagner. an! Skidmore. .'.W.: V lv s a-- TVs! l\-''s:- !P,AW, .and Retention in Rats. A m .VI' ..v .i 132:'' 6 ; .I'Ve 81' lYaeook. A., and !Vav-k. P R ' -:,vj '* .. ` in abstracts. Filth At,:', ' ,1 M i. ' ; Br - A--a.-a:;.--. fr t'.v w r . Svt'.,n: U. S. aV.'.abte. -. ' !. 2\ l .trin-;.n, *1.S.. anl Roa. P..t i ' a i aes . ''a-e-'-o.:::,'- of Aslvwliw 1-V.vrs an!'l'hoir Nat,t-,i! t * ?. aa .'a. 1.'2: 4.tt> 4 M' t 1\ h- 81 ' liV *- "--MiUUJiaaM--S.V 2 t