Document XMbrxLzqD81rXVoZ5OE7BQXB

DRAFT 10/17/80 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935-1977 by H. C. Lewlnsohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 UCC 004937 A00572 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 though available statistics might be subject to diagnostic error, the apparent rise was attri buted to the increase In the State's 'cumulative asbestos consumption*T7Com plete occupational histories for the cases of mesothelioQt were not presented. jj A derailed review of the available pathological material by an independent ' pathologist to investigate the degree of diagnostic certainty was not under 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. UCC 004938 AQ0573 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. CO f*. |p Descriptive epidemiology for this research pertains primarily to the forty-three year time interval. Future case^-control comparisions will in ,, aimde cases (215) diagnosed after 1954 (Table 1), and controls (604) whose deaths occurred during this same time period. This procedure yields a case- control 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 specific employer or industry for cases, controls and spouBes 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 old. 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- <s> merce, 1971) were assigned to the employment information ascertained from medical histories, death certificates, and City Directories. A computerized UCC 004939 -- A0Q574 Table 1. Sex, age and diagnostic characteristics of 229 cases of malignant mesothelioma and 38 other pleural tumours diagnosed in Connecticut, 1935-1977 Diagnosis Males Females Pleural mesothelioma Pleural tumour (other than mesothelioma) Peritoneal mesothelioma Mesothelioma at other sites & at unknown sites 102 (94)b 24 (12) 20 (18) 29 (21) 45 (37) 14 (8) 13 (ID 20 (14) Total 175 (145) 92 (70) *WHO (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 004940 A 005 7 5 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 (sample from listing Fig. 1). .. . c UCC 004941 -3- A00576 III. Results Descriptive Epidemiology c*v<ylaW The following dffficriplrivo results are based upon -Oho infermotion (p. > jva 11 foe CTR and will require adjustment following <She completion ^ of ew 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. ^ do) i Ww cases were reported in ' 0b^ (m) 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 % 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. all _ LMflv These 5 large cities and New London are ais: centers foTtabor Marfeet Areas 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). -US 004942 A 00 57 7 AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX 8Z900V 000*001/31VH UCC 004943 *-- to i O to o> in in oo CM I in -- 10 ^ O) ^ mm io to ocvtonarm uA L MAFMN6 OF CASES OF MESOTHELIOMA (1 9 3 5 -1 9 7 7 ) BY TOWN OF RESIDENCE AND 1960 LABOR MARKET AREA AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA FOR CONNECTICUT MALES BY YEAR OF DIAGNOSIS AND LABOR MARKET AREA O CM CM -- o OO " ooo'ooi/3iva UCC 004945 to ^ CM 1935-44 45-54 55-64 65-74 75-77 SLIDE REVIEW Lito & ^Malignant mesothelioma Is a very rare disease.. only 2 cases per million population expected annually. Resistance to the acceptance of mesothelioma g as a disease entity persisted until the late 1960's. Wagner's widely pub licized association of mesothelioma with Cape Crocldollte asbestos exposure created the potential for the introduction of diagnostic blas.^1 Positive diagnosis of mesothelioma is often complicated by its confusion with other forms of cancer..(Vidone discussion of simulators). The controversy over criteria for positive diagnosis is well.documented in to the literature. Most experts agree, however, that a full autopsy is re quired to positively distinguish diffuse mesothelioma of the pleural or peritx 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 2,3). For 12% (32) of the cases, no tissue was examined at time of diagnosis, while the origin of available material varied. Gveraflj^only^i^ tu" e** "7 ranging from 33% to 40%n- ^ ii , These results suggested the advisability of a efe review. Dr, Romeo Vidone, chief pathologist of St, Raphael's Hospital, is presently studying the medical 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. (Summary of Dr. VidoneTs Findings) A UCC 004946 A0058 1 Table 2: Basis for Diagnostic Evaluation for cases of Malignant Mesothelioma and Pleural Tumors other than Mesothelioma Diagnosed in Connecticut, 1935-1977 g Diagnosis 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 I (100) (100) 33 (100) 49 (100) 267 (100) aWHO (1976) ^specimen from biopsy, frozen section, surgery, autopsy, D and C UCC 004947 A00582 T a b le 3: Frequency o f A u to p s jr f o r Cases o f M a llg n a ri t M e s o th e llc >ma and in P leur Connec a ti l c uTut m, ors cith e r 1931>--1977 th a n Me s o th e llo n u i D ia g n o s e d CO (D 00 IoaH e-H H (0 Hl-l *j4W-BoHi<4 H431 OO4B) Pi X (1) (2) (3) (4) (5) Autopsy, : Autopsy, M icro sco p ic Gross Evidence Evidence o f Cancer ! o f Cancer Autopsy Gross E v id e n c e , Unknown W hether Cancer Autopsy t 1 but only In d ire c t : Autopsy, E v id e n c e no o f Cancer Report 43 (6) (7) (8) No Autopsy 62 Unknown 1 18 Number Dead 134 A u to p s y ^ 40 cn fH 8 13 11 ; 37 35 <r 21 2 1 28 89 11 21 5 39 33 iH i--1 u ^3 34ff4l lM-l i-43>i pi a X44oM41 si XiH4O4-Jl) 4S) i--1 o 4c4o-1) iXT4-a44J> M4H> Oa4) Pi X UCC ,004948 4-> -a " Xi40aHO4OHB4>j X a -404H4B) Xw4t-1l 0 Ca0HUOB 5o 5 Q3 --M44 X) LO oo <4 1 1 86 GO 83 12 35 238 Ho m + /% "w** + m 00 oo CM1 r-. I 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 of the pathological material available and used for diagnostic purposes. A Feltonhas pointed out several needs 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 i in such cases/ to be able to confirm by the presence of asbestos related effects that there has been exposure to respirable asbestos fibers. 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. Valuable Information can be gained from a comparison between radiographic apperances and histological changes in the lung. Such Information will help to eliminate present diagnostic uncertainties. It has been our experience that occupational histories are not routinely ob tained and included in hospital records. In our search through records stored at the CTR (i.e. hospital records), we found job titles for only 17% of the mesothelioma cases. If ve 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, whose diagnoses were between 1955 and 1977. A recently passed Ct. statute, whose method of Implementation is under study, will hopefully alleviate the paucity of employment data from medical records. UCC 004949 - A00Bl 4 Two other areas of epidemiological interest which are not routinely recorded for patients admitted with suspected malignant disease are smoking habits and hobbies end 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 faefeeee-en and environmental factors en-fche-etielegy-ef-dheee-dieeaeesT-ne (lifestyle, habits, hobbies, part-time e ,a activiti^s, de*aAtiled job histories) , any attempt to 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 Bhould be made to document all relevant facts and to subsequently verify the diagnosis by means of a full autopsy. UCC 004950 A0058b References Bruekman, L. Rubino, R. A., and Christine, B. (1977a) Asbestos end Mesothelioma is Connecticut. APCA Journal. 27* 121-126 Bruekman, 1. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: JWtfMnations and Measurement Methods. National Bureau of Standards, Gaithersburg, Maryland * ^BTuckman, L. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journalt 28, 1221-1226 Price and lee Cltnr Directory (1890-1977) The Price and lee Company, Rev Haven, Connecticut ' U. S. Department of Connerce. Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries end Occupations (1971)* Washington, D. C-, H. S. Government Printing Office >fc ..A-* -- World Health Organisation: ICD-0 International Classification of Diseases for Oncology. (1978) Geneva, Switzerland Hilton C. Levinaohn,Corporate Medical Director, Raybestos-Manhattan, Inc. ad Lecturer, Tale School of Epidemiology and Public Health (addreae: Raybestos-Manhattan, Inc., 100 Oakviev Drive, Trumbull, Connecticut 06611, U, S. 1.) J. Viator Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Tale School of Epidemiology and Public Health (address: 30 College Street, Hew 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, Hev Haven, Connecticut 06520, U. S. A.) UCC 004952 AUi/bc 7