Document G5EnqqO54y5jbERa14ddmjDY7

DRAFT MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935-1977 by H. C. Lewinsohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 UCC 010115 Aor Malignant Mesothelioma in Connecticut 1935-1977 by H C Lewinsohn, J.W. Meigs, and M.J. Teta 1.Introduction and Alms The combined sex age-adjusted mesothelioma incidence rate for Connecticut vas reported in 1977 to have Increased ten-fold since 1935. Although available statistics might be subject to diagnostic error, the apparent rise was attri buted to the increase in the State's 'cumulative asbestos consumption'. Com plete occupational histories for the cases of mesothello^ were not presented. A derailed review of the available pathological material by an Independent pathologist to investigate the degree of diagnostic certainty was not under let /f 77 > taken? 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. -iUCC 010116 A0055 1 II. Methodology 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 1). 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 dece dents (1935-75) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health Services. Descriptive epidemiology for this research pertains primarily to the _ i-- --<' i'lX- forty-three year time interval. Future casejf-control comparisons will i- --elude cases (215) diagnosed after 1954 (Table 1), and controls (604) whose deaths occurred during this same time period. This procedure yields a casecontrol ratio of approximately 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 1954). The Price -and Lee City Directories were searched for job title and name of snecific employer or industry for cases, controls and spouses at 1, 10, 20,25, 30, 40 and 50 years prior to date of diagnosis, death or until the subject was less than twenty years ol<fT An occupational history search was attempted for spouses to coincide with these intervals for their correspond ing cases. 1970 U.S. Census industrial and occupational codes (U.S. Dept, of Com- v, TV*.(few merce.^1971) were assigned to the employment information ascertained from medical histories, death certificates, and City Directories. A computerized - ?UCC 010117 A005E: list of job and industry titles has been developed 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 4eeipi*asaah^lei*4ng^Fig. 1). UCC 010118 Aan- III. Results Descriptive Epidemiology The following descriptive results are based upon Che information t available Jwmbe CTR and will require adjustment following the completion A,, of slide review. Using the 1950 US population as a standard, the age- adjusted incidence rate for mesothelioma in Connecticut is 2.1/million for the years 1935-1977. Rates per 100,000 population increased for both sexes, but there was a rapid rise from about 1960 for males (Fig. 2). The male- female ratio is approximately 2:1; the mean age at diagnosis is fifty nine years. Average survival time from date of diagnosis to date of death is ten months. Tam cases were reported in^af Nat('l.HA) (New London) where shipyards are lo cated, and -five of these were identified between 1975 and 1977 (Fig. 3). The geographical distribution of mesothelioma shows evidence of urban clusters in the 5 largest cities (Bridgeport, Hartford, Waterbury, Stamford , New Haven) where 30 X of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-30% of Connecticut's population (1940 1977), the suggested urban effect may reduce to a factor of population density. <\|\ fcr LMAs. These 5 large cities and New London are triLoo center's fo hobor Market Areas (LHA). 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). - V- UCC 010119 A 0 0' SLIDE REVIEW Malignant mesothelioma Is a very rare disease^ 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 pub licized association of mesothelioma with Cape Crocidolite asbestos exposure created the potential for the introduction of diagnostic blas rj Positive diagnosis of mesothelioma Is often complicated by its confusion with other forms of cancer.. (Vidone^discussion of simulators). r--------- UkAS** _ The controversy.over criteria for positive diagnosis is well documented in *77). the literature? Most experts agree, however, that a full autopsy is re quired to positively distinguish diffuse mesothelioma of the pleur^ or perit oneum from other primary or secondary neoplasms. We examined, for all CTR reported cases of mesothelioma and for all pleural tumors other than mesothelioma (1935-77), the histological basis for diag nosis (Tables 2,3jT^For 12% (32) of the cases, no tissue was examined at time of diagnosis, while the origin of available material varied. Overatl^onIy7Z4% (105) ,,of the 238 deceased, cases are known by the CTR to have been autopsied, y-iLe. lAje-rf t'K f, The percentages for all categories, except peritoneal mesothelioma, are low ranging from 33% to 40%n--< f v p % raji., e** These results suggested the advisability of a eilll review. Dr. Romeo Vidone, , available cJiAiCaJ chief,pathologist of St. Raphael's Hospital, is presently studying thelmedleal records^(except occupational data) and slides we have obtained for cases diagnosed after 1954. Cooperation was sought from 37 hospitals, of which 30 have thus far provided us with the materials requested. --(Siamary of Djf- y-idnne1 Findings) (f) - b- UCC 010120 Aon? 5 0 yo ib JU^euL^JU t>elusc^ duuJ \ueJfcx2&tU CMftw~G1NL . 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(muEuxttP t/XYUJEZ^ ttltl' 610**# \ ^W2A t& QJttO- <iK0A VM Hi> &0M<j2 COA4 t -ftl-----fo--COjX *CltoCa-- 44M&9--Q*\ ijAfl?--U*--*MtJLe feb --TZi^W oui^iuuuj t Tii r j^ fiftp vr11 A/ *J * '--^Xkw . \m^u) (l* sj lw Cflwe (tuieci t/tf? le tt> cjUa^U %p ^ k fop lufit^ dxS^*Mt^io UiUMj Uw>j%<jurP^'uduE^iJrvkv(A^^xr vtKwn\ ^0r*< l^fci> (fajZMJU&W A446-$L&le/VK4. , \*- lit? ^lo^o--LZ--o* TX^TlwM-10 U<ua? u^o iaA^v*k^iXL<. ^ D4o'i4l/ s^ij|.u-u^. ol "tU* 1 ^ A -A ` '" flJ&\JMMdyj j4cA-^XuU-C <2t&^4-&7, 6UAA*0n*tuiu*^y c~urv^o^i~-c -> UaCI !k> ou&htfjeX tv. *d2a5^n {> lx? |)UJ QtE&i ' \mAi)l (f) On first review the cases in this study are being placed in one of six categories (see slide) which represent the relative certainty of the diagnosis of mesothelioma using anatomic criteria. (XM* This is being carried out on all available materials, including cytologic preparations, surgical pathology and autopsy reports and slides. Ae_ miah-b-bo expected in a -study of thi-s type.--the material available 4-*t quite-variable. In all cases the diagnostic classification is based on autopsy materials, or in Jomc* caaej 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. Ac 1 n r UCC 010121 (\iAOiQ) The preliminary results of the primary review of the first t>w 1 106 cases are shown *sn this slide. 22 cases were considered to be mesothelioma, 38 probable mesothelioma and 28 possible mesothelioma. The 28 possible mesotheliomas, 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 ta^Ac 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. For-puipubes ot ^^assifications 1 and 2 were added 5w together since these represent probable or definite mesotheliomas. Classifications 4 and 5 were also added together since these were considered not to be mesotheliomas. As broken down by percentage, ~\W> t bhes^SEBape 56.6% thought to be mesothelioma, 26.4% possibly*.and A /' f A 10.3% not mesothelioma or excluded from the study. ,/ " trhot are still oonaidewod unknown. Tfce^^i^e 6.6% ' luJttJl (&) In any retrospective review of mesothelioma it is essential to include an objective review of all anatomic pathology material. This review should include all available reports and slides including cytology, surgical pathology and autopsy materials. It should be . foe conducted by an experienced pathologist^ith special expertise in the surgical pathology of tumors. UCC 010122 A00557 IV. Discussion Although this study was Initially undertaken to discover whether It would be feasible to identify the environmental factors responsible for the in crease of malignant mesothelioma in the State of Connecticut, it has suffered from lack of detail in available records. Major deficiencies in the data are the low autopsy rate for the pleural mesotheliomata and the Inadequacy ofA the pathological material available and used for diagnostic purposes. r Felton has pointed out several -msais for post-motem 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 casesI to be able to confirm by the presence of asbestos related effects that there has been exposure to respirable asbestos fibers4 F&f'k^ A further need for autopsy arises to confirm the diagnosis of malignant meso thelioma made on limited biopsy material obtained during life. This is im portant for workers' compensation purposes and also to improve the epidemiolo gical data required to investigate the etiological factors involved with this disease. runs It has been our experience that occupational histories are not routinely ob- . tained and included in hospital records j' o*' 1 <ut li Mill II ITB nf IfTo & f-i'rfes for / 7^0 e<f *-*- ^ x o +-v ! o.-g. f > J , " 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 7X of these cases. The sample size for these statistics was 220 cases, whase diagnosed wave between 1955 and 1977. A (bnrttctiivV, (retwe***) recently passed Ot. statute, whose method of Implementation is under study, will hopefully alleviate the paucity of employment data from medical records. r ~ LUCC 010123 A00 A addressed,in the lJfrw Hiatomio pathology studies. %rh-AJU> k* c fully will There is variation in the literature on the classification of these tumors. The lines fwnflPt iflfc eje foeii ofo- between localized and diffuse are not always clear cut and the separation of benign from malignant is not always as readily apparent as one would be lead 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 characteristic such as metastatic patterns and certainly applies to histologic k,r-*n descriptions which are not -unfi-LOIli 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. RAV 10/28/80 UCC 010124 A0055 3 Two other areas of epidemiological interest which are not routinely recorded for patients admitted with suspected malignant disease are smoking habits and hobbles and or part-time activities. (Comment-on- the significance of the Slide Review)^ It is evident that until the physicians investigating cases of malignancy appreciate the importance of occupational f*etere-e*i and environmental factors ea-the-tieiegy-ef-thase-dieeesesT-ne (lifestyle, habits, hobbies, part-time 6A activities, de^tiled job histories) , aa^ attemptSto apportion blame to any particular factor for disease causation or promotion will be severely hampered. It is particular^ essential in the case of a rare tumor, which may present diagnostic difficulties, to obtain sufficient tissue for study before a diagno sis 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. 1- - UCC 010125 A0056C Table 1. Sex, age and- diagnostic characteristics of 229 cases of malignant mesothelioma and 38 other pleural tumours diagnosed in Connecticut, 1935-1977 Diagnosis* Pleural mesothelioma Pleural tumour (other than mesothelioma) Peritoneal mesothelioma Mesothelioma at other sites & at unknown sites Total Males 102 (94)b 24 (12) 20 (18) 29 (21) 175 (145) Females 45 (37) 14 (8) 13 (ID 20 (14) 92 (70) Smo (1976) ''Numbers in brackets refer to the period 1955-1977 Total 147 (131) 38 (20) 33 (29) 49 (35) 267 (215) Mean age 61 (62) 62 (63) 58 (59) 52 (54) 59 (60) UCC 010126 A0056 1 . Table 2: Baals for Diagnostic Evaluation for cases of Malignant Mesothelioma and Pleural Tumors other than Mesothelioma Diagnosed in Connecticut, 1935-1977 Diagnosis8 Pleural Mesothelioma Tissue Available 136 X (93) Pleural Tumor 27 (71) (other than mesothelioma) Peritoneal Mesothelioma 31 (94) Mesothelioma at other sites and unknown sites 41 (84) No Tissue Available X 11 (7) 11 (29) 2 (6) 8 (16) Total 235 (88) 32 (12) Total 147 38 X (100) (100) 33 (100) 49 (100) 267 (100) aWHO (1976) ^specimen from biopsy, frozen section, surgery, autopsy, D and C UCC 010127 A005B2 JO +><n0sj. h| 3 cd CO tH CD co 5C cd P Table 3: Frequency o f Autopsy f o r Cases o f M a lig n a n t Mesothelioma and P le u ra l Tumors o th e r than M esotheliom a Diagnosed in C o n n e cticu t, 1935-1977 (1) (2) (3) (4) (5) Autopsy, M icroscopic Evidence o f Cancer Autopsy, Gross Evidence o f Cancer Autopsy Cross E v id e n c e , Unknown Whether Cancer Autopsy, but only 1 In d ire c t Autopsy, Evidence no o f Cancer Report ci i--i 43 8 -a- 21 11 cm ^"1 t-i 00 83 12 wV"OI OS! 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Levins ohn,Corporate Medical Director, Raybestos-Manhattan, Inc. end Lecturer, Tele School of Epidemiology end Public Health (address; Raybestos-Manhattan, Inc., 100 Oakviev Drive, Trumbull, Connecticut 06611, U. S. A.) J. Vister Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Tale School of Epidemiology and Public Health (address: 30 College Street, lev Haven, Connecticut 06520, U. S. A.) Mary Jane Teta, Associate in Research, Connecticut Cancer Epidemiology Unit, Tale School of Epidemiology and Public Health (address: 30 College Street, lev Haven, Connecticut 06520, U. S. A.) UCC 010135 A0057C References Bruckman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: Definitions and MeaBurment Methods, -Natural Bureau of Standards, Gaithersburg, Maryland Bruckman, L. and Rubino, R.A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal, 28,1221-1226 Felton, J.S. (1980) Letter to the Editor. JAMA, 244,1675 Fannerstein, M., McCaugj*^. W.T.E., Churg.J. (1977) A Critique of the Criteria for the Diagnosis of Diffuse Malignant Mesothelioma. Mt.Sinai J, Med, N.Y. 44, 485-494 Price and Lee City Directory (1890-1977) The Price and Lee Company, New Haven, Connecticut U.S. Department of Comnerce, Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries and Occupations il97f), Washington, D.C., U.S. Governemtn Printing Office Wagner, J.C., Sleggs, C.A., and Marchand, P. (1960) Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape Province. British Journal of Industrial Medicine, 17, 260-271 World Health Organization: ICD-0 International Classification of Diseases for Oncology,(1976) Geneva, Switzerland (P<t-l) IS. UCC 010136 Aonc