Document 3JNb7jDv64E55jG5XjGdR4gaD

DRAIT WttftO MALIGNANT MESOTHELIOMA IN CONNECTICUT 1933-1977 by H. C. Levinsohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 A0nC 5 X 416022 Malignant Mesothelioma In Connecticut 1935-1977 by H C Lewinsohn, 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 attri buted to the increase in the State's 'cumulative asbestos consumption'. Com plete occupational histories for the cases of mesothelio^g were not presented. A derailed review of the available pathological material by an independent pathologist to Investigate the degree of diagnostic certainty was not undertaken? 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. A0055 1 -1- X416023 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 eases 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 al-wde 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 Brice ami Lee City Directories were searched for job title and name of specific employer or industry for cases, controls and spouses at 1, -- -- ' ` '' '* ' he 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(isrtO'? merce.^1971) were assigned to the employment information ascertained from medical histories, death certificates, and City Directories. A computerized - J> - 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 4*aapia^ca>Ue*4mg^Pig. 1). Aon;55 X 416025 III. Results Descriptive Epidemiology The following descriptive results sre based upon the information svallsble javebt CTR and will require adjustment following the completion Ht A of ew slide review. Using the 1950 DS population as a standard, the ageadjusted 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 (Tig. 2). The malefemale 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. vo Lnbout NubjI'CWeo. (i-Hft) 9mt cases were reported in.atf UtA (Hew London) where shipyards are Id 'S" cated, and -five of these were identified between 1975 and 1977 (Tig. 3). The geographical distribution of mesothelioma shows evidence of urban clusters in the 5 largest cities (Bridgeport, Hartford, Waterbury, Stamford , New Haven) where 30 Z of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-30Z of Connecticut's population (19401977), the suggested urban effect may reduce to a factor of population density. l\ ft ( LMAs. These 5 large cities and New London are a&so centers fo Labor Market Areas -(-LMA). All 6 areas exhibit a similarly increasing age-adjusted Incidence rate foT males. The Stamford UlA's mesothelioma rate shows an unexplained sharp Increase since 1965 (Fig. 4). Aongc /, v4'<0?6 SLIDE REVIEW WfX Malignant mesothelioma la a very rare disease^ only 2 cases per million population expected annually. Eesistance to the acceptance of meaothelloma aa a dlaeaae entity peraiated until the late 1960's. Vagner's widely pub licized association of mesothelioma with Cape Crocldollte asbestos exposure created the potential for the introduction of diagnostic biasCVM*^erf Poaitlve diagnosis of meaothelloma is often complicated by its confusion with other forms of cancer..(9idona_dlecug8lon of simulators). -------- - I The controversy.over criteria foT positive diagnosis is veil documented in the literature! Moat experts agree, however, that a full autopsy is re quired to positively distinguish diffuse mesothelioma of the pleur^ or perit oneum from ocher primary or secondary neoplasms. Ve examined, for all CTR reported cases of meaothelloma and for all pleural tumors other than mesothelioma (1935-77), the histological baais for diag nosis (Tables 2,7 K.For 121 (32) of the cases, no tissue was examined at time of diagnosis, vhl\c. the origin of available material varied. Overail^only^^AI (105) nf the 238 deceased, cases are known by the CTR to have been autopsled. J3(n2*4- t-t-e exj-c/npC uUfc/'f. k* -'t (-/ <--*-& . The percentages for all categories, except peritoneal mesothelioma, are low ranging from 33Z to UOZ.p- e* C, / These results suggested the advisability of a eSfle review. Dr, Romeo Vidone, . . aitaiUblr cMitoJ chief.pathologist of St. Raphael's Hospital, is presently studying the^madical records^(except occupational data) and slides ve 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. --fg'TT--ry of ly, .y-iHnno'a Findings) (I) - i> - 40055s ^4 f 6027 0 vo ic, cL^eMuLkEr IxHtiia* ****+,LaJL/^ut auJ nitCvaZ*ttU CaOmLci**. . tliw CJu^afc^ fttitgjvrf) uii U-eiv c&a^> a^e 5**-eWy WUj^kj * 4< y <$Zlu4 ao QSC\9m (ue u.\i* aui bhfiiW' ^uiixOuJlAt j PAS' uXif OhjS u/Sh+dr ~b\oer'a** axlJ> ^ c* __ \&ve/ W&uJ- Hucca<or><n* cui c*mu<Jlw teuue $u*J a* lu*iu*l t**L**-tStz Qjh 'fbiuaVLi to \Mlfi ** tlu* , [***/ (T) US&ijfc*fi0 tivJZarf "thd- "$Lf w^aP'' cWr*elC dJuge tnud&&-*** iU> MCoa$ciHa tiVnuSLureD UKrtUlZ** tuJ- n\ t& 4J>m. toe* wi JixP S^Mxa cat*. -As---"fer---CC*a*--r >wiaj-- +ul&--Q*\ *sHSfnwftr|l' (jfg--Im--H*Ji* to ^fr tugftnf (Wjiftln tE |MVliun<nU/ --paTiim . \muJ (S) ^Iu fcWj/ s| *ku CAM- ttvMui W\flP lb 1l cl`^jr\ %> ttSaJUu# c^UaI^1 *CA A MAMfrt# ttodt&dhtHA . \* I n "'miiiM i' I? OcnM (jWUc( -tu thtu p^uH i*aJC Wj*C (mv W^*-UiU-t S>l "tu> Oui<h*isSr*Q ol QjUiT-kvA&JiiP 6hAjD4**e tfe Qab&-Etn. Qj ~Ij pyOjyeucu 6iv> dlsCt u^l W oxxeSxxAtti. to\ 'U W (V) theOn first review 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.(TUtt This is being carried out on all available materials, including cytologic preparations, surgical pathology and autopsy reports and slides. Vs. might- hn erpeuLi.d in a--study nf. Mitv twei fm material m'laMa ta ignite variable. In all cases the diagnostic classificatior is based on autopsy materials, or in inisn i nin 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 Hasson 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 *416(128 I *AOiiQ) The preliminary results of the primary review of the first iVk 106 cases are shown<n this -slide. jui 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 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 puiputfcil or tni assifications 1 and 2 were added together since these represent probable or definite mesotheliomas. Classifications 4 and 5 were also added together since these were considered not to be mesotheliomas. A-o broken down by peicei'iLage, tin. iisULU'l 56.6% thought to be mesothelioma, 26.4% possible*.and A /' f A 10.3% not mesothelioma or excluded- from the study. C.\ass,ie4 *& u theL are still oonei4--d unknown. 6.6% 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 aiitnnsv ma+prial s. Tt- phnuld be conducted by an experienced pathologistj^iith special expertise in the surgical pathology of tumors. A 0055 7 X416029 IV. Discussion Although this study vss 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 S; '* of" the low autopBy rate for the pleural mesothelloaata and the inadequacy of the pathological material available and used for diagnostic purposes. Felton has pointed out several hmsAs 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, la such cases to be able to confirm by the presence of asbestos related effects that there has been exposure to respirable asbestos fibers(,p^(W; 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 It has been our experience that occupational histories are not routinely ob- . Ax talned and Included in hospital << tkf-rufVra*'*HIr* i<nnp<f ,.. Dr\ CTj**.*A. e*.>n.'** in nr. at >TliJl ) *<<' j'ub fi'rus fcr <'`^17^0 o-< -- r t C+"** ( !>. - f ~ te , manthrt ............. . TIff we relude from this group those designated as "retired", <? "housewife", or "student", the figure is reduced to 12Z. We' were only able to ascertain type of Industry in 71 of these cases. The sample size for these statistics was 220 cases, whaae diagnose^m Ci.wcetvV between 1955 and 1977. A recently passed Ot. ktatute, whose method of implementation is under study, will hopefully alleviate the paucity of employment data from medical records. Aon1 *4lA;n3n (ywM* fskjJU! Thw is Another problem^het has^asieen ind- hopefully will *e addressed,in Uhu 1 !*anatomio pathology .studios. There is variation in the literature on the classification of these tumors. The lines tffic ***** belief*^ 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 characteristics such as metastatic patterns and certainly applies to histologic descriptions which are not iiOTu 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 A00559 X4I603I Two other areas of epidemiological Interest which are not routinely recorded for patients admitted with suspected malignant disease are smoking habits and hobbles sad or part-time activities. (Commentrsa--'the -significance of the Slide It is evident that until the physicians investigating cases of malignancy appreciate the importance of occupational feetors-om and environmental factors en-the-etielegy-ed-fehese-ddseegesT-ae (lifestyle, habits, hobbies, part-time 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. A0056C X&UC32 -1 I Table 1. Sex, age and dlagnoatic 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) Total 147 (131) 38 (20) 33 (29) 49 (35) 267 (215) *WHO (1976) ^Numbers in brackets refer to the period 1955-1977 Mean age 61 (62) 62 (63) 58 (59) 52 (54) 59 (60) A00561 v/ 1 z' n 7 7