Document Ozxvragz1aq4LQ6Xx64OJeqoM

PLAINTIFF'S EXHIBIT UC-4874 -1- 11-3-80 COUSECTICU'C 1935 19TT tiy H. C- Levinsohn J. V. Meigs M. J. Teta Conne cticut presentat ion to tbe November *cic Society, I960 A0230 2 Malignant Mesothelioma in Connecticut 1935-1977 "by H. C. Levinsohn, J. V. 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; Bruc .man 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. 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 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. 402303 'X4I3283 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 1951* tVfetalm ^) , and controls (6oM 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 lacfc of awareness of mesothelioma associated with this earlier time period (1935-1951*) City Direc tories were searched for Joh title and name of specific employer or industry for cases, controls and spouses at 1, 10, 20, 25, 30, U0 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). X 413284 \ III. Results Descriptive Epidemiology The following descriptive results are based upon avail able CTR information and will require adjustment folloving 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. Rates 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 eases were reported in Hew London Labor Market Area (LMA) where shipyards are located, and 5 of these vere 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, Hew Haven) where 30$ of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-30$ of Connecticut's population (191*0-1977), the suggested urban effect may reduce to a factor of population density. These 5 large cities and Hew 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.l). A0230b 5 SLIDE REVIEW Malignant mesothelioma is a very rare disease vith 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 vilely publicized association of mesothelioma vith Cape Crocidollte asbestos exposure created the potential for the introduction of diagnostic bias (Wagner, I960 ) . Positive diagnosis of mesothelioma is often complicated by its confusion vith 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 Alclan Blue with and vithout byaluronidase , PAS vith and vithout Diastase and to a. lesser extent Mucicarmine and corrective tissue stains on surgical materials are valuable as veil in this regard. The controversy over criteria for positive diagnosis is veil documented in the literature (Kannerstein, 197T). Most experts agree, hovever, that a full autopsy is required to positively distinguish diffuse mesothelioma of the pleura or peritoneum from other primary or secondary neoplasms. 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 5, 3)l. Whltvell 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 402306 X 41 3286 6 in the itae case. For 129 (.32) of the cases, so tissue vas examined at time of diagnosis, vhile the origin of available material varied. Overall (.1935-77) only bb? (105) of the 238 deceased cases are known by the CTH to have been autopsied, but only 83 (79?) of the autopsied cases vere microscopically con&ffiwKd. The percentages for all categories, except peritoneal mesothelioma, are lov ranging from 33? to bO? autopsied. These results suggested the advisability of a case re view. Or. Romeo Vidone, chief pathologist of St. Raphael's Hospital, is presently studying the available clinical records in the CTR (except occupational data) and slides ve have obtained for cases diagnosed after 195b. 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. On first review the cases in this study are being placed in one of six categories (3mMMfc-*3), 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 cytologic preparations, surgical pathology and autopsy reports and slides. In all cases the A02307 x 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 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 U and 5 were also added together since these were considered not to be mesotheliomas. Thus 56.6% are thought to be mesothelioma, 26.1*1 are possibly mesothelioma and 10.US not mesothelioma or excluded from the study. 6.6V are still classified as "unknown". A02308 *413288 - 8- IV. Discussion Although this study vts initially undertakes to discover vbetber it vould be feasible to identify the environmental factors responsible for the Increase of malignant meso thelioma in tbe State of Connecticut, it bas suffered from lack of detail in available records. Major defi ciencies in tbe data are tbe lov autopsy rate for tbe pleural mesotheliomata and the inadequacy of some of tbe pathological material available and used for diagnostic purposes. Felton has pointed out several reasons for post-mortem reviev. A problem may arise in workers' compensation adjudication where a decision has to be made, years to decades after initial work exposure, in tbose instances where death bas resulted from pulmonary cancer or a thoracic or peritoneal mesothelioma. It is therefore important, in such eases, to be able to confirm by tbe presence of asbestos related effects that there bas been exposure to respirable asbestos fibers (Felton, 1980). A further need for autopsy arises to confirm tbe diag nosis of malignant mesothelioma made on limited biopsy material obtained during life. This is important for workers' compensation purposes and also to improve tbe epidemiological data required to investigate tbe etio logical factors involved with this disease. It bas 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 A0230J X413289 5291 x 9 stored at the CTH (i.e., hospital records) produced job titles for only 17J of the mesothelioma cases. If ve exclude from this group those designated as "retired", "housewife", or "student", the figure is reduced to 12i. We were only able to ascertain type of industry in 7% of these cases. The saaple size for these statistics was 220 cases diagnosed between 1955 md 1977* A recently passed Connecticut Statute, (Public Act 80-ll3) whose method of iapleaentatlon 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 reviev of mesothelioma it is essential to include an objective review of all ana tomic pathology material. This reviev 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 microcsoplc characteristics of mesothelioma and vith 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 A023 J c X 4 1 3290 \ 3291 -9 stored at the CTR (i.e., hospital records) produced Job titles for only 179 of the mesothelioma cases. If ve exclude from this group those designated as "retired", "housevife", or "student", the figure is reduced to 129. We vere only able to ascertain type of Industry in 79 of these cases. The sample size for these statistics vas 220 cases diagnosed betveen 1955 and 1977. A recently passed Connecticut Statute, (Public Act 80-lb3) vhose method of Implementation is under study, vill hopefully alleviate the paucity of employ ment data from medical records. Tvo other areas of epidemiological interest vhich are not routinely recorded for patients admitted with sus pected malignant disease are smoking habits and hobbies or part-time activities. In any retrospective reviev 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 vith the gross and mierocsopic 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 4023 !c X413290 \ 10 to believe by reviev of the literature. In fact, there are discrepancies betveen some of the classic papers in this field regarding characteristics of these neoplasms, both gross and microscopic. This is not limited to grovth 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 vhich 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. X413291 i t *T able 1. 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P 2 jl a an Jj|| $*$ I S'*^vvA-: **55*SS c i ooo'ooi /aivu >0 /4?^98 1 18 19 i F ig u re 20 - Hilton C. Levinsohn, Director, Health and Safety Raybestos-Manhattan, Inc. and Lecturer, Tale School of Epidemiology and Public Health (Address: Raybestos-Manhattan, Inc., 100 Oakviev Drive Trumbull, CT 066ll, U.S.A. J. Vister Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Tale School of Epidemiology and Public Health 1 (Address: 30 College Street, Rev Haven, CT 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 Rev Haven. CT 06520. U.S.A. 32 1 *413301 ----------------------- 1 21 Reference! Bruekaan. 1. (197Tb) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos Definitions and Measurement Methods. Istional Bureau of Standards, Gaithersburg, Maryland Bruekaan, L. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 26.1221-1226 Felton, J. S. (1980) Letter to the Editor. JAMA. 2LI.1675 Kannerstein, M. , McCaughey. V.T.E., Cburg, J. (1977) A Critique of the Criteria for the Diagnosis of Diffuse Malignant Mesothelioaa. Mt. Sinai J. Med. B.7. hi, L85-L9L. McCaughey, V. I. E- (1965) Criteria for Diagnosis of Diffuse Mesothelial Tumors. Ann els of the Rev fori Academy of Sciences. 132 (ArtVl) 603-613. 1 Price and Lee City Directory (1890-1977) The Price and Lee Coapany , Jiev haven, Connecticut Public Act 60-1I43 effective January 1, 1981 U. S. Departaent of Commerce, Bureau of the Census : 1970 Census of the Population. Alphabetical Index of Industries and Occupations (1971). Washington, D. C., U. S. Government Printing Office Vagner, J. C. , Sleggs, C. A., and Mareband, P. (I960) Diffuse Pleural Mesothelioaa and Asbestos Exposure in the North Western Cape Province. British Journal of Industrial Mcdicine . 17, 260-271 World Bealtb Orgnaization: ICD-0 International Classi fication of Diseases for Oncology. (1976) Geneva, Switzerland * X413302 \