Document B51GNJeXVxVZmop3B9B5OBpD4

MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 - 1977 7>y H . C . Levin s ohn J . W. Meigs M . J . Tet a A00623 PrcacnlaliOTi--trc--Ore--gonno oticirt--Ihsvacic--Society-,--NovenrtreT UCC 010170 2 Malignant Mesothelioma in Connecticut 1935-1977 by H. C. Levinsohn, J. W. Meigs, and M. J. Teta I. Introduction and Aims The combined sex age-adjusted mesothelioma incidence rate for Connecticut was reported in 1977 to have increased ten-fold since 1935- Although available statistics might be subject to diagnostic error, the apparent rise was attributed to the increase in the State's 'cumulative asbestos consumption'. Complete occupational histories for the cases of mesothelioma were not presented. A detailed review of the available pathological material by an independent pathologist to investigate the degree of diagnostic certainty was not undertaken (Bruckman 1977; Bruckman 1978). The present study attempts to determine the role of various etiological factors, such as occupational and environmental asbestos exposures, and includes a review of available pathological material. XI. Methodology SU3)c The CTR#has identified 229 cases of malignant mesothelioma as well as 38 other pleural tumors, not mesothelioma, which were diagnosed in the state between 1935 and 1977 (Table l). Medical, demographic, and occupational data have been collected for the cases and for the respective spouses of cases diagnosed 1955-1977. Similar information has been gathered -for a random sample of approximately 700 decedents (1935-75) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health Services. ^Connecticut Tumor Registry A0063C UCC 010171 3 Descriptive epidemiology for this research pertains primarily to the forty-three year time interval. The case-control comparisons vill comprise cases (215) diagnosed after 195^ (Table l), and controls (6oH) whose deaths occurred during this same time period. This procedure yields a case-control ratio of approximate ly 1:3, while reducing sources of error resulting from the limited occupational and medical data prior to 1955 and the lack of awareness of mesothelioma associated with this earlier time period (1935-195*0. City Direc tories were searched for job title and name of specific employer or industry for cases, controls and spouses at 1, 10, 20, 25, 30, HO and 50 years prior to date of diagnosis, death or until the subject was less than twenty years old (The Price and Lee Company, 1890-1977)- An occupational history search was attempted for spouses to coincide with these intervals for their corresponding cases. 1970 U. S. Census industrial and occupational codes (u. S. Dept, of Commerce, Bureau of the Census, 1971) were assign ed to the employment information ascertained from medical histories, death certificates, and City Directories. A computerized list of job and industry titles has been de veloped for all cases, spouses, and controls (1955-1977). This will form the basis for classification of study subjects into asbestos exposure categories for future case-control comparisons (Fig. l). UCC 010172 A0063 1 -kIII. Results SltDiT bu9C Descriptive Epidemiology The following descriptive results are based upon avail able CTR information and will require adjustment following the completion of the slide review. Using the 1950 U.S. population as a standard, the age-adjusted incidence rate for mesothelioma in Connecticut is 2.1/million for the years 1935-1977. Fates per 100,000 population increased for both sexes, but there was a rapid rise from about i960 for males (Fig. 2). The male-female ratio is approximately 2:1; the mean age at diagnosis is 59 years. Average survival time from date of diagnosis to date of death is ten months. 10 cases were reported in New London Labor Market Area {LMA) where shipyards are located, and 5 of these were identified between 1975 and 1977 (Fig. 3). The geo graphical distribution of mesothelioma shows evidence of urban clusters in the 5 largest cities (Bridgeport, Hartford, Waterbury , Stamford, New Haven) where 30% of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-30% of Connecticut's population (19^+0-1977) the suggested urban effect may reduce to a factor of population density. These 5 large cities and New London are all centers for LMA's. All 6 areas exhibit a similarly increasing age-adjusted incidence rate for males. The Stamford LMA's mesothelioma rate shows an unexplained sharp increase since 1965 (Fig.4). UCC 010173 k 0 0 6 31 5 SLIDE REVIEW Malignant mesothelioma is a very rare disease with only 2 cases per million population expected annually. Resistance to the acceptance of mesothelioma as a disease entity persisted until the late 1960's. Wagner's widely publicized association of mesothelioma with Cape Crocidolite asbestos exposure created the potential for the introduction of diagnostic bias (Wagner, i960 ) . Positive diagnosis of mesothelioma is often complicated by its confusion with other forms of cancer. It is im portant to differentiate between mesothelioma and metastatic carcinoma. Autopsy findings in such cases are extremely helpful in this regard. The use of special stains such as Alcian Blue with and without hyaluronidase , PAS with and without Diastase and to a lesser extent Mucicarmine and corrective tissue stains on surgical materials are valuable as well in this regard. The controversy over criteria for positive diagnosis is well documented in the literature (Kannerstein, 19TT)Most experts agree, however, that a full autopsy is required to positively distinguish diffuse mesothelioma of the pleura or peritoneum,from other primary or secondary neoplasms. S>upe Surpii We examined, for all CTR reported cases of mesothelioma and for all plueral tumors other than mesothelioma (1935-77), the histological basis for diagnosis (Tables 2, 3). Whitwell has pointed out that the most striking histologic character of diffuse mesothelioma is the remark able structural variation that occurs from area to area even UCC 010174 A00633 6 in th.e same case. For 12$ (.32) of the cases, no tissue vas examined at time of diagnosis, while the origin of available material varied. Overall (.1935-77) only kk% (105) of the 238 deceased cases are known by the CTR to have been autopsied, but only 83 (79$) of the autopsied cases were microscopically continued. The percentages for all categories, except peritoneal mesothelioma, are low ranging from 33$ to 1*0$ autopsied. These results suggested the advisability of a case re view. Dr. Romeo Vidone, chief pathologist of St. Raphael's Hospital, is presently studying the available clinical records in the CTR (except occupational data) and slides we have obtained for cases diagnosed after 195k. Cooperation was sought from 37 hospitals, of which 30 have thus far provided us with the materials requested. The object of the case review will be to classify the cases relative to the certainty of diagnosis using welldefined criteria for the diagnosis of mesothelioma. In the first phase of the review the pathologist will have no knowledge of the occupational history or environ mental exposure to asbestos. As the study progresses this data will be analyzed in relation to these factors. SulDS On first review the cases in this study are being placed in one of six categories (Table h) , which re present the relative certainty of the diagnosis of mesothelioma using anatomic criteria. This is being carried out on all available materials, in cluding cytol_ogic preparations, surgical pathology and autopsy reports and slides. In all cases the A00634 UCC 010175 7 diagnostic classification is based on autopsy materials, or surgical pathology material, in no case was cytology alone used to place a patient in category 1, 2 or 3. As the study progresses, attempts will be made to obtain the original blocks for additional special stains such as PAS with and without Diastase , Alcian Blue with and without hyaluronidase , Mucicarmine , Reticulin and Masson stain as indicated. It should be mentioned that in a number of the cases already reviewed some of the above mentioned stains were available. The preliminary results of the primary review of the first 106 cases are shown in Table 5. 22 cases were considered to be mesothelioma, 38 probable mesothelioma and 28 possible mesothelioma. The 28 possible meso theliomas, based on the material reviewed, might also possibly be some other condition such as metastatic carcinoma. Also on the basis of this first review, 6 cases were considered probably not mesothelioma and 5 were considered definitely not mesothelioma, 7 were considered unknown since no diagnostic classification could be arrived at based on the materials reviewed. Classifications 1 and 2 were added together since these represent probable or definite mesotheliomas. Classifi cations h and 5 were also added together since these were considered not to be mesotheliomas. Thus 56.6% are thought to be mesothelioma, 26.k% are possibly mesothelioma and 10.k% not mesothelioma or excluded from the study. 6.6% are still classified as "unknown". UCC 010176 A0063b 8 IV. Discussion Although this study vas initially undertaken to discover whether it would he feasible to identify the environmental factors responsible for the increase of malignant meso thelioma in the State of Connecticut, it has suffered from lack of detail in available records. Major defi ciencies in the data are the low autopsy rate for the pleural mesotheliomata and the inadequacy of some of the pathological material available and used for diagnostic purposes. Felton has pointed out several reasons for post-mortem review. A problem may arise in workers' compensation adjudication where a decision has to be made, years to decades after initial work exposure, in those instances where death has resulted from pulmonary cancer or a thoracic or peritoneal mesothelioma. It is therefore important, in such cases, to be able to confirm by the presence of asbestos related effects that there has been exposure to respirable asbestos fibers (Felton, 1980). A further need for autopsy arises to confirm the diag nosis of malignant mesothelioma made on limited biopsy material obtained during life. This is important for workers' compensation purposes and also to improve the epidemiological data required to investigate the etio logical factors involved with this disease. It has been our experience that occupational histories are not routinely obtained and included in hospital records. Although Job information was obtained for 99% of the cases from all three sources (City Directory, Death Certificates, CTR) , our search through records f A00636 UCC 010177 9 stored at the CTR (i.e., hospital records) produced jot titles for only IT% of the mesothelioma cases. If we exclude from this group those designated as "retired", "housewife", or "student", the figure is reduced to 12%. We were only able to ascertain type of industry in 7% of these cases. The sample size for these statistics was 220 cases.diagnosed between 1955 and 1977. A recently passed Connecticut Statute, (Public Act 80-1^3) whose method of implementation is under study, will hopefully alleviate the paucity of employ ment data from medical records. Two other areas of epidemiological interest which are not routinely recorded for patients admitted with sus pected malignant disease are smoking habits and hobbies or part-time activities. In any retrospective review of mesothelioma it is essential to include an objective review of all ana tomic pathology material. This review should include all available reports and slides including cytology, surgical pathology and autopsy materials. It should be conducted by an experienced pathologist thoroughly familiar with the gross and microcsopic characteristics of mesothelioma and with special expertise in the surgical pathology of tumors. Another problem has been recognized which should be addressed. There is variation in the literature on the classification of these tumors. The lines be tween localized and diffuse mesothelioma are not always clear cut and the separation of benign from malignant is not always as readily apparent as one would be lead A0063 7 UCC 010178 UCC 010179 10 to believe by review of the literature. In fact, there are discrepancies between some of the classic papers in this field regarding characteristics of these neoplasms, both gross and microscopic. This is not limited to growth patterns such as that in the pleura or peritoneum, but includes such important character istics such as metastatic patterns and certainly applies to histologic descriptions which are not uniform from paper to paper. It is hoped that as an outgrowth of this study some clarification of this aspect of the problem will be forthcoming. It is evident that until the physicians investigating cases of malignancy appreciate the importance of occu pational and environmental factors (lifestyle, habits, hobbies, part-time activities, detailed job histories), attempts to apportion blame to any particular factor for disease causation or promotion will be severely hampered. It is particularly essential in the case of a rare tumor, which may present diagnostic difficulties, to obtain sufficient tissue for study before a diag nosis is made. Whenever a tumor is found and an association is suspected with a particular occupational or environmental factor, every attempt should be made to document all relevant facts and to subsequently verify the diagnosis by means of a full autopsy. UCC 010180 A0063 9 New London Labor Market Area Town Old Lyme East Lyme Montville Ledyard Groton New London I.D. Occupation Dx Sex Site & Histology 675092 At home spouse-atty (1966) F Pleural mesothelioma 711723 Clothing merchant (1971) M Peritoneal mesothelioma 781723 E.B. Safety Nuclear Eng. (1976) M Pleural mesothelioma 792536 Architect, retired eng. Past exposure to some asbestos long ago (1977) M Pleural mesothelioma 793335 - Housewife spouse-truck driver paper 6 board co. (1977) F Pleural mesothelioma 761292 Painter-glazer sub-base (1975) M Pleural mesothelioma 200401 Landscaper-Gardiner (1939) M Pleural mesothelioma 501121 At home (1950) F Pleural mesothelioma 693627 Supt.-E.B. machlnest (1968) (3 time periods) M Pleural mesothelioma 779762 Rigger-E.B. erector-E.B. stevedore railway (1976) (2 time periods) <1 time period) M Pleural mesothelioma 10 Cases 9 Pleural 1 Peritoneal UCC 010181 A0064C 20 Hilton C. Levinsohn, Director, Health and Safety Raybestos-Manhattan, Inc. and Lecturer, Yale School of Epidemiology and Public Health (Address: Raybestos-Manhattan, Inc., 100 Oakviev Drive Trumbull, CT 06611 , U.S.A. J. Wister Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Yale School of Epidemiology and Public Health (Address: 30 College Street, Hew Haven, CT 06520, U.S.A. Mary Jane Teta, Associate in Research, Connecticut Cancer Epidemiology Unit, Yale School of Epidemiology and Public Health (Address: 30 College Street New Haven, CT 06520, U.S.A. UCC 010182 A0064 1 21 Deferences Brucknaa, 1. (2977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop op Asbestos Definitions and Measurement Methods. Rational Bureau of Standards, Gaithersburg, Maryland Bruckman, L. and Bubino, B. A. (2978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 28,1222-1226 Felton, J. S. (2980) better to the Editor. JAMA, ,2675 Kannerstein, M. , McCaughey. V.T.E., Churg, J. (2977) A Critique of the Criteria for the Diagnosis of Diffuse Malignant Mesothelioma. Mt. Sinai J. Med, H.Y. h85-l<9ii. McCaughey, V. T. E. (1965) Criteria for Diagnosis of Diffuse Mesothelial Tumors. Annals of the Rev York Academy of Sciences, 132 (Art.l) 603-613. Price and Lee City Directory (1890-1977) The Price and Lee Company, Rev Eaves, Connecticut Public Act 80-1^3 effective January 1, 1981 U. S. Department of Commerce, Bureau of the Census: 1970 Census of the Population. Alphabetical Ipdex of Industries and Occupations (1972), Washington, D. C., U. . Government Printing Office Wagner, J. C., Sleggs, C. A., and Marchand, P. (i960) Diffuse Pleural Mesothelioma and Asbestos Exposure in the Borth Western Cape Province. British Journal of Industrial Medicine , 17, 260-271, World Health Orgnaization: ICD-0 International Classi fication of Diseases for Oncology. (1976) Geneva, Switzerland UCC 010183 A0064 Table 1* Sax, age and diagnostic c h a ra c te ria tic e o f 229 caaea o f aalignant aeaothelioma and 38 other p le u ra l tunoura dlagnoaed in Connecticut 1935-1977 O Nh CO o o -si & e s 1 M mbV X m VO s&e> Io> bo UCC 010184 o Cbk e o IMbe bw UCC 010185 i lTable lias la lo r D ia g n o s tic E va lu a tio n f o r cased o f M alighS nt Mesoth e Horn* and M e u rS l tum ori other than Mesothelioma Diagnosed in C onnecticut* 1935-1977 specimen from b io p s y , fro te n s e c tio n ) s u rg e ry , autopsy, tt and C r- I x> sf n#CO o o T*bl Jt Frequency of k u to rn j to r Case* at Hnllgnnnt Meeotheltoi Mil Neural Tumra other than Hennthettomn Maenoeed In Connecticut, 1915-1*77 -I1-1 SR SR 9* S~ iji4fil - fi SR R | RP e~ Jj | ^4 -p* 4TI r I bJ T4 S *j1 ' WS - 44 " 9s h-- Ik 9 *'I1 IS s*1c 4* 4 fc Mila !K* U U blj ^99 9m 4a *e- S9s e w 6. co 5 .c n 4U23c e> 4 e ** y V w b94 9 e - 4K ' *H T* 99 5 s Cl u ^ 9966 tl!3 w , 1!^ u * w * 9 9 9 C U V fK tits- * .*> U 2h " 9 ** ,, M r* ~4 N PK w4 > m 3 ! j si -1 ill 9 V4 e- x -* < j 9 1 h Ex m $ ! S sItl SH3i1 ti Z* 111 Ztl m 2 I6 *S J _o -JCO 3 < UCC 010186 -MALIGNANT MESOTHELIOMA IN CONNECTICUT 1 9 3 5 1977 CD CD 3 <1 UCC 010187 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1 9 3 5 1977- ^ 0 0 6' 4 7 tfp so so in *> * t cs <#> o rH SD so o o 05 8 10 o s <u m fl) <u & so o Z o E-i CA < Z< 3 oz CA W a: a wa w < a zo M zw MW (X < 04 U (A (A 3 o zo o so CO (N AI A1 o Z CM CO cm m 00 cm SO in Ifl (0 (0 E E a> 0 0 H H P pH pH 0 (D 11) 01 Ifl P 0 P 0 (D z E 0 H 10 0} CO p c E 0 zQ) za> zo 0) 0 H P <0 Pt pH 0) >s V pH pH >1 pH P Om <D c 3 0 P <0 Pi i0 Z 0 H U-l pC nn 0n <U z 0 P 04 (0 n 0 04 0 u 04 P z0 c AC c D (0 pH u H CM CO * in so SO o so o 10 P o fc< UCC 010188 * . -J 1 . J U 1 1 ... . a i 1 -i 1 d . . ._ l.-i 1 . - 1 * 1 * , ' * 1 . J . . . . p , . > A 1 -t-.I A-* A d -i_ J * SSiSSSS!iSS3i^!ll393939Ua33a339933933SS333333a33 cO TD <1 -g w 0*A*vi atx L ' MtOC VI iv-- fWVHLAVi fOZopOo ^5" MM. If w oXz t-O u -A -- U.U 33 Ss XX & O 4JJ yyyg 4MHUJ izVVftVIVk M44J X uz 4&OD^ *ftflCtt4 li.-- .in u^ rttfUT o s X a. ftW Z- XV AA UA 40 U 4 o X MAtAM IA H TZZX3UC UUUUOK IM440UJ ^XCClB -- U A. 4C Ot>Ol$L* VIA ttK *-* Wi O.ZZXZXU4 oSSSBmjS - wgyii^u^o XX OO yg IA ^>X XUVU* UOMM 4rt g XX A IV-- BCI^ IAMB --^ KB AA SXM <4 KBS SSexx ZA PxWJ^ Of * M ^M(AiAO &D-J3>03S Ai* LJJXQ3U ZZZJ 003K yyj JJJM A44WI vayK U A Ui z*ftzUzUu-' g .............>^ZSZ4 ^^ j*. eU^AB04 I^333a U.DC XJCXfO _ ifcKVVbA_AAA--_3_*_*_! __U__W_--_ D033lJPtt jxt> *40 X--* Z*tKtf^IOMCVo&r^V^B>f4t*|MVUy*Vy*Vi4>W4BxC BfiMMMMAU I I &itB iZB &^aA4tUski--uoy^**af^t AkSfcO ^OTKJ SZZ -- U^UaUtg torasena^cOahcj v>Ti*r-^o ODO?< XOOOZ t_f.A\--^So--o* c><nj\^N. O^ gj>UIW*i>jomungU*i?* j4jw4Z^J4XX,i/ZUnU* ocuBfltacuAuuwu AnIo__p^Dr_X_Ms__Xs-M*-wA?SfrcwO'*MfMcO.ui*OM..f-uc-O-t^-.----t-XA4-t--/V-y-ei-AZ-^-e--f--fs-u.-.B-.4u.-Js.c-m3.-n.a.-.io-'.inov..^_aa.*.^_.^.a.V_cve_\ii_AAf4_*_iWO*_f^v_tf_.*ocU_Va_j_si^u__sj4f_O_is4u_f_ir4s_*f_tvk_fu_iUq_B.__a*4_t_NA>_t_S>_*H_*_Bt04_tO9v_y0_agSi_iisP>W_0pp(JJ^Nw__N_Megv3i^s0_zB)&&*S40.K&-B^0c.Ao-r pPC.Q--r*Op0eiO*">w4*><*`>n*iC00O>M;>0C>0fAv^fy*fW*yur4trwMf----m3 ----*,sarMl^Mry<y~a i ^imw i MNNOll%4r44r#4Wfy^Nrv*c44#Mr^M>#r4 >tww^y>^i in. i i i--no ^K44r*l4r4fw mp<^ OOp0^OOOOO0kO'P'n9>9^^OOjgOaO^^O9>ClO9>O9>O3nr>^D9`'a^9<^OIh<nCh9>IM>*^CjUO VS>SBV0t^9`Ch:>i9tptr'ADatJUjft>4Oi*>?k99kA^:DX>O'tf19' A*ffnN.",4ff*v9>M>9^^0^9>9*9>^>d030> J'?- ^tr>X*OTv>*vrV'-'^W9b9tmfrt^iA?ru0'vr)9trri?>>p7F1*d* WNrf\^^w4^NN3300ClM^OOiWViP>Mff>NM0**<NiV\4PNAN<4--^WOa*^y P9*o* .2^ a. A,!,*-**-:>-4--*>^'p.r%^>e---<3*^ Vi9*NA*tfl*4C0^4NVw^iyf*in4|fnmANB9'9*it^>^M4tfl4V4|in9sur*^9'VWN4#gOy^^ OJ L, 3 bC 3 u or * O D O t*J oc fc Tu X UIWC J * U1 Wu; .XA4ou.2 uKnriajrYj^Jx u_}..-J lllliO --uj --j .J_; >u.u. J.u.4t^g u_w__t_^z** --^w*_--i S 032 C^wZ "--" --i__,i _Jw---/ XJu_i_OS._: xuxjxjujt.uktf.t_.jjdaii-io.unj.uujautuzuzuzi<z_joxa..JaZt<JL.a4--o t43>#4X-___________ 444XZa4a0ZZ^4^4*Z4ZC4 x z XJ 3<l-3 jz j^ A oaa. *-* V lu tiJ 4J U J O ---- * *0^0 --r o v> *-- UkJ4dor 4^ ^^74444 4Hl4i<4 A* U4 X j ^:/l Za* UO * x-y 5^4^4 44 _ >^441 gl ^4 J OO jxJpxzyuM am k ift7M.JU.VAi u444AS.^X3*ZU4X4XuJ1*A4X A X #i^J44)Anr4i4lA4\^rt>ffl --IWNV* NN*" f4*l4v^vg 4*i MNN4 4*^y#4iy MA*fVtM#4MNfW i 4c<r4v/bVk<^ *^iw* rf^KMntt ^ ^ N>^rm44444<0?vJa^3o9rV0'v3x0r^0.^0^t3^^JkUy^2ig3.M3fxrviVJCJAC/iy<Ro1^^J^8y9jy*4*vv 4-vp^-w.4^ 4.^yyf4 4*** ******+*****&0**;*3Nft*+4**4*'ft *'*< 4ft <** AoE-ABJUSttO INCIDENCE RATES OR MESOTHtUOMA IN CONNECTICUT SY YEAR OR DIAGNOSIS ANO SEX F ig u re I 1 i_ h oi CM "d- JD O ZD <1 -J________I________I________I________I________L oo o oo o . *n <4 - 000*001 /31VM UCC 010190 GEOGRAPHICAL MAPPING OP CASES OP MESOTHELIOMA (1936-ter?) 6y town op residence and teso labor market area UCC 010191 AoE-AbJUSTEb INclOENcE RATES OF MESOTHELIOMA For CONNECTICUT MALES SY YEAR OF btAONOSIS ANO LAROR MARKET AREA F ig u re UCC 010192