Document XzKykMVwN18GponX1dXErKXnd

f\ p *^ *rv > ^ o^ *>ct V a o ifl o X5 O'. .J& X?OP -4lft 4 IT' * *S > r> O & 0 * <n v> s P . >BE.rOS INTERNATIONAL ASSOCIATION (Limited by Guarantee) 68 GLOUCESTER PLACE, LONDON WiH 3HL, ENGLAND MEMORANDUM TO: Medical Advisory Panel FROM: Director General OUR REF.: AIA/20/1/16/HAS 11 September 1985 Asbestos-related Disease from Exposure to Brake Dust The abstract of a paper by Dr. Paul Gross is circulated to you for advance information. Dr. Gross kindly forwarded this to me together with his paper. However, please note that the paper has just been submitted to the BJIM, and therefore at this juncture no use can be made of it. When news of publication is received, I will let you know. Sir Neville Stack cc Dr. P. Gross AIA/20/l/l 6/&AS AO 1 209 ASBESTOS-RELATED DISEASE FROM EXPOSURE TO BRAKE-DRUM, OR BRAKE-LINING DUST: THE PROBABILITY OF ITS OCCURENCE by Paul Gross, M.D. Yale University New Haven, Connecticut 06510 Connecticut Cancer Epidemiology Unit 30 College Street (203) 436-8904 J. WlSTER Meigs, M.D., Director October 13, 1980 Dr. Hilton C. Lewinsohn Raybestos-Manhatten, Inc. 100 Oakview Drive Trumbull, Connecticut 06611 Dear Dr. Lewinsohn, Please review and give me a call. I haven't \ yet included the sample of the listing. I haven't heard from Dr. Vidone yet. I outlined your section briefly. V^ry truly yours, JT:bav Enclosure Jane Teta, M.P.H. Research Associate A00588 gfcc Inducing ul OULupallTmal aM Euvliunwum.al AsbusTDLj - Bttpoourc an thi InuiJuutrc Lf Malignant Mesothelioma in Connecticut^ rss-1977 by H. C. Lewinsohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 A00569 The Iaflummw uf OuiupaLluual and Envliuamental Ac,bag tog- Exposure on thft Incidence af Malignant Mesothelioma In Connecticut^ H77 by H. C. Levinsohn, J. W. Meigs, and M. J. Teta I. Introduction and Alms Bruckman et al. (1977a) reported that "the combined sex age-adjusted mesothelioma incidence rate (AAR) per 100,000 Connecticut population has exhibited a possible ten-fold increase since 1935..." They ac knowledge that the available statistics might be subject to diagnostic error but, nevertheless, postulate that the rapid Increase in the State's mesothelioma incidence rate is closely related to the Increase In the State's "cumulative asbestos consumption", which includes asbestos emis sions from industrial sources, motor vehicles, and building demolition. One criticism of their study is the failure to make available complete occupational exposure histories for the 133 diagnosed (1935-1972) cases of mesothelioma drawn from the Connecticut Tumor Registry (CTR). The Air Compliance Unit of the Connecticut Department of Environmental Protection has monitored asbestos concentrations in Connecticut (Bruckman, 1977b; Bruckman, 1978) and proposed an ambient air standard for Connecticut 3 of 30ng/m , measured over a thirty-day interval. The rapid Increase in the State's mesothelioma incidence reported in 1977 is referred to as justifica tion for this proposal. A second criticism is the failure to Investigate the degree of certainty in these diagnoses and to institute a pathological review, if ifc^g warranted. The present imj study has been designed to A0052C re-examine the identified cases of malignant mesothelioma recorded in the CTR and attempt to determine the role of various etiological factors, Buch as occupational and environmental asbestos exposures. In view of the jmr- SugQcst .lyiiuiwlsdQnd possible diagnostic errors, which our results verify, a thorough review of available histological material is being undertaken. A0052 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). ------yvrphr,i npy nTf lu llm ILU-0 (WbllLi Health Ougnrltrnff tinj 1076) LlasjlfiLBLlwv^Medical, demo graphic, 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 Tandom sample of approximately 700 decedents (1935-75) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health. Descriptive epidemiology for this research pertains primarily to the forty- three year time interval. Future case-control comparisons will include^cases (215) diagnosed after 1954 (Table 1), and controls (604) whose deaths occurred during this save 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 o + awareness of mesothelioma associated with fehw^WSr time period (1935-19J/7. The Price and Lee City Directories were searched for job title and name of specific employer or industry for cases, controls and spouses at 1, 10, 20, 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 corresponding cases. The throe digt 1970 U. S. Census industrial and occupational codes (U. S. Dept, of Commerce, 1971) were assigned to the employment Information ascertained from medical histories, death certificates, and City Directories. A machine readable listing of job and industry titles has been developed for all cases, spouses, and controls. This will form the basis for classification of study subjects 'TAP>L 1 V-- \ v. nr. Table 1. Sex, age and diagnostic characteristics of cases of malignant mesothelioma and other pleural tumours diagnosed in Connecticut, 1935-1977 Diagnosis0 Pleural mesothelioma Pleural tiaoour (other than asothelioma) Peritoneal mesothelioma Mesothelioma at other sites 6 at unknown sites Total Kales Females Total Kean age 102 (94 24 (12) 45 (37) 14 (8) 147 (131) 38 (20) 61 (62) 62 (63) 20 08) 13 01) 33 (29) 58 (59) 29 (21) 175 (145) 20 (14) 92 (70) 49 (35) 267 (215) 52 (54) 59 (60) Percent 'positive'*' histology Percent autopyei (95)\ 93 71 (as) \ (38) y* 35 (37) /94 (97) \ 89 (88) 84 /86) (93) ' V33 V (41) (45) WHO (1976) ^SCCHi Wit Cadiitrield Niaaber 19 (US Department of Health, Education, and Welfare, National Cancer Institute (1976) f (Mu. HTWpr+e*jho. deceased) 100 Niaobers in brackets refer to the period 195S-1977 f A-9-&55-3 Into asbestos exposure categories for future case-control comparisons (sample from listing Fig. 1). A005S4 III. Results Descrlptlve Epidemiology The ugqflL Incidence rate for mesothelioma in Connecticut is 2.p/million for the years 1935-1977. i adjuulul lUL.tift.uu- j^ptes per 100,000 population (using the 1950 US population as a standard) 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. Qve/v^jL Survival time from date of diagnosis to date of death is approximately ten months. Ten cases were reported in an area (New London) where shipyards are located, and five 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 (1940-1977), the suggested urban effect may reduce to a factor of population density. These 5 large cities and New London are also centers of Labor Market Areas rJ r (LMA). All 6 areas exhibit a similarly increasing*'incidenceVfaith the Dridge port IitA Llai UlgUfctbL U Util dll1. The Stamford LMA's mesothelioma rate shows aA untf sharp increase since 1965 (Fig. 4). A0050b AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX RATE/100,000 -- ro 01 ^ oi o> oo o o o o CO GEOGRAPHICAL MAPPING 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 RATE/ 100,000 1935-44 45-54 55-64 65-74 75-77 A005 SLIDE REVIEW 2Jte.se. dUl.Cl.lptive~rLAu.LEL ewmli^te^uompleteness and accuracy ef ease -tAqnr-f f-frnt *"" tr 1 ty-r.il.............. mlirr-tup ).. Ill* .| nil 1 I I V W f 'ffTa p- --unsift-. Malignant mesothelioma is a very rare disease, expected in only 2 A persons for every million at risk. Resistance to acceptance of mesothelioma as a disease entity persisted until the late 1960's^ deep its WufcULi~*t> 1900 35 royoi l Uf ^"TilStmuglcall^ picnretr-cases of pleural mc.suLhullUIua associatea Wflgnevf with Capp dm Pi t r t r** TMs widely publiohod association o^mesothelioma with asbestos exposure^ ^mawr, created the pa/ fce ef" ^ /(pi potential fr-diagnostic bias# Tn ndriiHrtn tn Ifn rnrlty and thr mil i in*nI liiiV i f n iirmrir,-{positive diagnosis of mesothelioma is^complicated by its confusion with other forms of cancer. (Dr. Vidone's discussion of simulators.) The controversy over criteria for positive diagnosis is well-documented in the literature. Most experts agree, however, that without an autopsy it is difficult to distin guish mesothelioma from a metastasis from another primary site. In the light ef thooo dif fiaubtiegUi^ examined, for all CTR reported cases of mesothelioma and for all pleural tumors other than mesothelioma (1935-77), the histological basis for diagnosis (tables 2,3). For 12% (32) of the cases, no i-wnTir. at time of diagnosis, ft*. <XY^V\ #f **<*t& while available Bpeaineniii emy-feea biupaj LU D & C Llsauo. * cms-<<m) Overall only 44% (105) of the 238 deceased cases are known by the CTR to have been autopsled. The percentages for all categories, except peritoneal mesothelioma, are low,ranging from 33% to 40%. These results suggested the advisability of a case review, aehieh was Hm laifl* p,.wp^jwil off piiHamt / Vi n.in/I.Mn h-t ct-nl pg-f pal material at time ef diaguubigt Dr. Romeo Vldone, chief pathologist at St. A00599 sb*J'fi*4 Raphael's Hospital, is presentlyawv4audLg the medical records (except oc cupational data) and slides ve have obtained for cases diagnosed after 1954. SoujM- H.UJ At Cooperation was elicited from 37 hospitals, of which 30 have provided us A with the materials requested. (Dr. Vidone-Summary of Findings) A0060C 'T'AQl.B 2. l for C&-&<s c ^ T^W*>o{j^^7Vkt **fCA. /*5 Jr<3'C 0 tiij.'c* jf 'Vj ^ *--^T ft * s d TLaS t J P)**ir-*j ,v`v ^j w*e-c/'^ ^jV/^ 7 "?y -------- - -- -- .'k'^<j*ici<ts Cu -A r^jk c ^ ky^l'c/i i/t XzM% O/rvcJ- V/Vcf" . y^i.'c. M_*mhi/i bcai*j? tfaitULb***,- ~ - J^_... .. ___ . _. ___3_. ------ -- ------ J V. 77ii 'Yi \cjui f*OTu mAr *rcft*^ ..... . 21 ___ __ .31_ - - - *~ ... _, .. _....... . . L IT J/ tft-^ r s*"^^*>'3. S / --M i -- ... ... _ .... - ---- . ._ -------------- --_ "? 1 ......... ! . f. >1?^ ______ W:. 3 ____ ...... 2 , ... ^0 J 247 - * U.ti 0 -C/t?<) -f(VWv b/43S\Lj frf* Av^ >W''^cCtj ) ....CUiyfafti ^ -O.r. . ^..__ ._-- ------------ --- - A0060 1 f- ^ *\ " i /fys' -/<r?? / >ru*i **t5 '< / '7vi 6&S --------------------- (, i --------------- .................. - ' ( c/ T "777 "" "CS/......17j ..A1LQSQ2------------------------- > A j4,r S flr-&r i'^^J tTVf *o rc^zjf, ct I'KfA r-faL^-tv <. . jB "f ev-- &Z << *' Ce/u-^ye 3HJ A^4 l>is/el A.<*J7L0('/'0 '^ ^rf - Ti'M C4-^ < Vj'ta-i O C-C-t-^5 ____ G-cAVf'/SCLT ^ be b <~ 4? / ``>J ^ "fvt /u^' /'o-w. C7 ft p^^-f/Ap /> ^ erv* ^ / 7,1% r^N r^U ^ <<j- D^bit o "f , -I* f < e^<*c_ j cr 5>jWZtpsu. r-e_ j`-* /2.7"ji - "7Z_^ } ''ck-CtS j~t ^ /* *\ ^ar < Vu^ t -Qr* ,. AHpJV-C. -- / .5 7^J 2 <TL^*3 /f v-- <2 Ai4 . F-/'*^-^ <L77^ - ''./! /^'s-T-77 >/ v -. y' jp/&*<r</ ++<*s-orSj n Jb *+*zZ. j 77 ) A00-603 & References Bruekman, L., Rubino, R. A., and Christine, B. (1977*) Asbestos Mesothelioma in Connecticut. APCA Journal. 27, 121-126 Bruekman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: ]V>fMr^-Mons and Measurement Methods. Rational Bureau of Standards, Gaithersburg, Maryland truckman, 1. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 28, 1221-1226 Price and Lee Citv Directory (1890-1977) The Price and Lee Company, Rev Haven, Connecticut / B. S. Department 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 7&r *'1. World Health Organization: ICD-0 International Classification of Diseases for Oncology. (1976) Geneva, Switzerland Ellton C. LevinsobaCorporate Medical Director, Raybestos-Manhattan, Inc. and Lecturer, Tale School of Epidemiology and 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, Hev Haven, Connecticut 06^20, 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, D. S. A.) A0060b DISCUSSION Although this study was undertaken initially in an attempt to discover whether i: would be feasible to determine the environmental factors responsible for the increase of malignant mesothelioma in the State of Connecticut, it has suffered from the lack of detail in available records. Xabl-o II-ona III illuctf'Oba one af the. fed jor deficiencies in the data available for study, irons ly the low autopsy rate 0 for the pleural cesot'neliomata and the inadequacy of the types of ciooua- available and used for diagnostic purposes. It has been our experience that occupational histories are not routinely obtained and included in hospital records.. Smoking habits are not routinely recorded and _________________ -------------------- -A no inquiries are rase of patients admitted witn suspected malignant disease re garding their hobbies or part-time activities. In our search through the C. I. paper files (i.e. hospital records), we found job titles for only 17% of the mesothelioma cases. If we exclude from this group those merely designated as "retired", "housewife" or "student", the figure i6 re duced to 12%. We were only able to ascertain the type of industry in 7% of these cases. This data is applicable to 220 cases consisting of: 195 mesotheliomas in the Connecticut Registry, 1955 - 1977, 5 nesotneliomas from the Veterans Administration files, 1955 - 1977, and 20 pleural--tumors. not mesothelioma, recorded 1955 - 1977. A00606 Comment on the significance of the findings or. the slide review. It is evident that until the physicians or hospitals investigating cases of OOaptW ^ malignancy aooreciate the importance of environmental facts A' the etiology of these diseases, no et:enpt can be cade to apportion the blame to any particular factor unless adequate histories are available containing complete information on lifestyle, habits, hobbies, part-time activities and details of occupation anc industry. It is also essential.particularly in the case of a rare tumor which may present diagnostic cifficulties,to obtain sufficient tissue for study before the final diagnosis is made. VThenever a tumor is found where e association g?:ists between it enc a particular occupational or environmental factor, every attempt should be made to fully document all the geijze.1 facts and tc subsecuer.tlv verify AOO60? }. TTr" -A T'-;, I'.'.rg the pe*t a s.r.t.a* v . ' C - a t..' t y. -; - i -1 '. v ; t .* t.- r o:rr.;:,v. i .c:i .ta io- ;r>t-s; :t'- s::_atit: cr-ei.-prc a- tot st* of e lie: o' wt .T.; it-?- ar.c a.-. aio-m r.i. rr.iii 5:.e r.ac :-err. IrtateC fur cnrvnic rctuvir f s -nov;'.:.- of the kneet w;:r, oexa- n.ei.'.is-f.'it ir. Ousape? from 0.5 ic 1.5 mp ciii;- intermittently for let years. Liur.nf ibis period. lie skit of her fore arms became extremely thin, and she experienced several episodes of subcuta lo: aimed r.trpef s:mp/tx :n;'crtio: th.E: had occurrec or. my uppf ii: and had not heated fur a; proximate;;. ODe year. It was removed by a loons' surgical procedure a: a local universi ty cemer, and a diagnosis of bascsouamous cell carcinoma was made it. tnos-. irsianit? where ctatr r as resu.ttz from, pulmonary caret: t* a thoracic or peritoneal mesotnehoma it is important to identify the t;ss_aiteraticns directly attributable to occupational contact with the respira ble asbestos fiber. neous extravasation of biood. again. At that time, the dermatolo As we have counseled family survi Or the fourth hospital day, she was gist performing the chemosurgery vors of such persons dying of asbesto- transported to the x-ray department, where i: was noted that she had two superficial tears in the skin of the left forearm with papmp margins Attempts were made to suture the skit copes togeu.er. but the sutures tore throupr the skin. The edges were held together with strips of sler.ie tape. Or. one other occasion during her hospi mentioned how unusual the lesion was, inasmuch as there were not supposed to be such things as bastsquamous carcinomas Both wounds healed without any unusual event. After the first occurrence, I con tacted L'r Herman Pinkus in Detroit, and he stated that there were about a sis or its related disease states, or both, to request a necropsy to lend substance to a worker's compensation claim, it is strongly suggested that ali physicians or house staff caring for such patients urge relatives to permit the examination These procedures will not only aid the beneficiaries but tal stay, s.miiar lesions developed during the course of transport to and from her bed for other diagnostic procedures. These lesions faiieo to heal during her hospital stay. and gross evidence of infection was do: noted Comir.eTiL-- Transport by handling of the forearms, even though careful ly done, resulted in serious, poorly healing tears of the skin in this overweight, weak woman. Even though extra care was taken after the initial episode, there was recurrence ]r. this case thtre was no complaint or dissatisfaction expressed by the pa tient or the family, but such episodes hate the potential for risk of comper.ssbit injury. Certainly there have been allegations of hospital-based dozen cases in the literature at that lime. 1 saw him at a meeting shortly after the chemotherapy, and he com mented on the unusual nature of this condition occurring more than once, though be was more aware of its occurrence than he had been before. There is ar. embarrassing situation about this personally, and that is that 1 am a dermatologist. There w ere no other forms of ther apy used on these lesions with either surgery, antibiotics, or photodynamic inactivation, nor am I a smoker. 1 have had an occasional localized herpes simplex infection curing the past 20 years L WZ AliPO- M9iJ O'OUr SC will also prove of worth to physicians in familiarizing them with the find ings characterizing a greatly under diagnosed job-generated disease. Furthermore, such postmortem data will aid in our knowing what actually happens to a worker under certain conditions of exposure anc will help to rectify the inaccurate conclusions crawx from the current underreporting of occupationally as sociated disease. m: e* Co mom* benso o* <**oi9m+ Lot Anpow* Safety of Ipecac Syrup 7r Tu Editor--Or behalf of the inju-.' with lesser justification. Crncopc American h ssociatior cf Poison C tr- 1; would be prudent for physicians i:ospitaltntng patients who have been receiving steroid therapy to place a warning note on the chart advising hospital personnel to use extreme care when bathing, assisting, or transporting such patients. i ;>* T *-*: MS Cob* Carcinoma at the Site of He-pes Simplex Infection To ii,' Editor -- The Joprval recently published a letter entitled "Carcino ma al the Site of Herpes SimplexInfection'' (243.2296, 1980). My letter is to note further the occurrence of such a situation. 1 personally had bast-squamous carcinoma develop on two occasions. The first occurrence "a? approximately five or six years ago at the site of a vaccination for imall pox that 1 had received for traveling. After the vaccination site did not heal for oDe year, I became J-Vc/cious and had it excised at the i troi Centers. 1 am concerned about The Autopsy the titling of a recent J.4JtL4 article, and Asbestos Exposure "Death Resulting From Ipecac Syrup Poisoning" (243:1927,19SDf. I am wor To iii Editor.--In the article entitled ried that the index skimmer or scan "The Autopsy- Past. Present, and j ner--particularly if he is of the older Future" by Anderson and co-workers school reared in an era of gastric (242 IC'56. 2P79/. the fall ir. the rate of j lavage for management of poison autopsies is decned. aDd several ings--may inadvertently conclude cogent reasons are presented for a that the typical emetic dose of syrup return to the previous high number of of ipecac was responsible. In reality, such examinations, a goal formerly the dose was three to four bottles per pursued by dedicated house officers. day for three months --thus repre One additional need for postmor senting a long-term poisoning. tem review-s has been given emphasis As Doled by the authors, syrup of in recent years by the epidemiologic ipecac as an emetic agent has a and cliDica! information gathered in remarkable safety record; its current connection with the asbestos-related availability over-the-counter and in disease. Because workers are now the home permits ar. enormous saving beginning to present radiological and I of needless visits to emergency rooms altered physiological evidence of the for the treatment of accidental inges effects of the inhalation of free asbes tions I think that it would be unfor tos fiber, years to decades after initial tunate indeed were the inference work exposure, a problem in work drawn that single emetic doses were er's compensation adjudication has risky. arisen. The changes elicited through clinical study, although present, most Wet mm D Kmi '{> MD Ch.iO e*> fr Hrtprto' k';. university hospital. 1 was ap- kr-- civ 55 v ears old at that time often do not have accompanying symptoms, cs pci, nor have they caused any disability, as yet There onC Mfd.p*' Crti#r Air>ri;*r Ai tr>n<oi>o* e* Po'or> Control Conor* SoalMO JAMa. . 10. 1990 --Vol 2A<. No. 15 A006C8 Leners 1675 1 I 1 II The Influence of Occupational and Environmental Asbestos Exposure on the Incidence of Malignant Mesothelioma in Connecticut by H. C. Levinsohn J. W. Meigs M. J. Teta A00603 The Influence of Occupational and Environmental Asbestos Exposure on the Incidence of Malignant Mesothelioma in Connecticut. by H. C. Lewinsohn, J. V. Meigs, and M. J. Teta Introduction Bruckman et al. (1977a) reported that "the combined sex ageadjusted mesothelioma incidence rate (AAR) per 100,000 Connecticut population has exhibited a possible ten-fold increase since 1935* They acknowledge that the available statistics might be subject to diagnostic error but, nevertheless, postulate that the rapid increase in the State's mesothelioma incidence rate is closely related to the increase in the State's "cumulative asbestos consumption", which includes asbestos emissions from industrial sources, motor vehicles, and building demolition. One criticism of their study is the failure to make available complete occupational exposure histories for the 133 diagnosed (19351972) cases of mesothelioma drawn from the Connecticut Tumor Registry (CTR). The Air Compliance Unit of the Connecticut Department of Environmental Protection has monitored asbestos concentrations in Connecticut (Bruckman, 1977b; Bruckman, 1978) and proposed an ambient air standard for Connecticut of 30ng/m^, measured over a thirty-day interval. The rapid increase in the State's mesothelioma incidence 2. reported in 1977 is referred to as justification for this proposal. The present study has been designed to re-examine the identified cases of malignant mesothelioma recorded in the CTR and attempt to determine the role of various etiological factors, such as occupational and environmental asbestos exposures. In view of the acknowledged possible diagnostic errors, which our results verify, a thorough review of available histological material will be undertaken. Methodology The CTR has identified 267 cases of malignant mesothelioma of the pleura (147) and peritoneum (33)> other mesotheliomas, including breast, ovary, synovial membrane, testis, spermatic cord, perivesical tissue, cervical glands, brain, esophagus, bone and sternum (49), and other pleural malignant tumors, not mesothelioma (38), which were diagnosed in the State between 1935 and 1977 (Table 1). Disease topology and morphology are coded according to the ICD-0 (World Health Organization, 1976) classification. Medical, demographic, and occupa tional data have been collected for the cases and for their respective spouses. Similar information has been gathered for a random sample of approximately 700 decedents (1935-76) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health (Table 2). Descriptive epidemiology for this research pertains primarily to the forty-three year time interval. Statistical modeling and future 4 006 I 1 3. case-control comparisons include cases (215) diagnosed after 195^+ (Table 1), and controls (605) 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 increasing awareness of mesothelioma associated with the later time period (1955-1977) The Price and Lee City Directories, utilized as an occupational data source for the three populations, were available for approximately sixty-six percent of Connecticut towns from 1890 to date ( with the exception of smaller towns). Directories were searched for job title and name of specific 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 old. An occupational history search was attempted for spouses to coincide with these intervals for their corresponding cases. The three-digit 1970 U. S. Census industrial and occupational codes (U. S. Dept, of Commerce, 1971) were assigned to the employment information ascertained from medical histories, death certificates, and City Directories. Industrial coding was determined on the basis of product descriptions for each specific employer which were found in the manufacturing directories of Connecticut, published by the State Department of Labor (1957, 1966, 1973) and from the Price and Lee Directories for non-manufacturing industries. From the complete listing of job and industrial codes a subset was selected by H. C. Lewinsohn, utilizing published sources indicating occupations A006 1 2 h. and products associated with asbestos (Hutchison, 1976; Levine, 1978; Weston, 1976). This will form the basis for probable asbestos expsoure classifications. The City Directory data over five decades provides information on duration of exposure. With a categorical response variable of occupational asbestos exposure, two fundamental research interests can be tested: 1. Whether cases and controls differ significantly with respect to job-related asbestos exposure (Relative Risk) and 2. The nature of the relative contributions of occupation, spouse occupation and geo graphical residence to the incidence of mesothelioma in Connecticut (Logistic Regression). In addition, the health experience of spouses of occupationally exposed cases and spouses of non-exposed cases can be compared. Results Of all cases diagnosed as pleural mesothelioma, twenty-one percent (31) had unknown staging (SEER, 1976) and sixty percent did not have an autopsy. The forty-nine cases of mesothelioma of other or unknown site have a mean age of fifty-two years and sixty-seven percent are without autopsies. The male-female ratio is approximately 1.5:1 (Table 3)* The question of the accuracy of classification of cases of malignant pleural tumors into mesothelioma and other pleural tumors naturally arises. The mean ages and the male-female ratios are similar for these two groups and the "other pleural tumor" A006 1 3 5. group exhibits weak diagnostic confirmation, i.e., seventy-one percent positive histology and only thirty-five percent autopsied. A discriminant function analysis of these two groups of cases (diagnosed after 1954) on the basis of age, sex, survival, time, stage, and number of tumors yields a sixty percent misclassification. This result suggests that: 1. Either these variables are not sufficiently powerful discriminators of pleural mesothelioma from other pleural tumors, or 2. The two groups, as a result of mis-assignment of a substantial number of cases to the incorrect category, now lack the heterogeneity one would expect from distinct categories. If consideration is limited to cases identified after 1954, when recorded clinical detail in general improved, as well as an increasing awareness of this form of cancer, the number of cases with solid diagnostic confirmation and characteristics consistent with the natural history of mesothelioma are strikingly few. Of the 131 cases classified as pleural mesothelioma, 124 (95$) bad histological material, (specimen from biopsy, frozen section, surgery, autopsy or D and C) examined and autopsies were performed on forty-five cases (38$) The proportion autopsied is disappointingly small. Table 4. shows the percentages of subjects with these two diagnostic critieria for mesothelioma cases of other or unknown site, for peritoneal mesothelioma, and cases of pleural tumors, not mesothelioma. A00Q H 6. As a result of these findings, it is imperative that a slide review and a re-examination of hospital clinical reports for all cases of mesothelioma and other pleural tumors be undertaken. A commitment has been received from an independent pathologist for this aspect of the study. The following data analyses are subject to change subsequent to this procedure. Descriptive Epidemiology Between 1935 and 1977, the CTR identified 229 cases of mesothelioma, 2.2. yielding an overall crude incidence rate of few per million. Age-adjusted incidence rates per 100,000 population (using 1950 U. S. population as a standard) for pleural and peritoneal mesothelioma consistently increase and exhibit a rapid rise beginning about 1955 ~ .04 (1935 - 44); .07 (1945 - 54); .18 (1955 - 64) (Figure 1.). We are in the process of generating these rates through 1977* Of these cases, 195 (85/6) were reported after 1954. The male-female ratio is approximately 2:1; the mean age at diagnosis is fifty-nine years. Survival time from date of diagnosis to date of death is approximately ten months. A logistic regression model of the form: Log ( JL- ) = A + B1 X1 + B2 X2 + Xy was fit in order to examine the incidence of pleural mesothelioma (binary response variable) as a function of the categorical explana tory variables - time, age and sex (X^, Xg, X^). Connecticut population figures supplied by the Connecticut State Department of Health were A used for denominator data in the estimate of disease probability (P). A006 1 S 7. The three and two-way interactions of time, age and sex were found to be unimportant and the main effects model provided a reasonably good fit (p> 0.1). A A /A From the estimates of the model parameters (B^, B^, B^), changes in relative risk (here approximated by the odds ratio) over time intervals, age categories, and sex groups are approximated. Persons exposed between 1975 - 77 carry 3.5 times the risk of pleural mesothelioma as those exposed between 1955 - 64. With progression across the age intervals: 45-54, 55-64, 65-74,...the individual risk of this disease is 1.5 times greater than in the preceding ten year age group. As one might expect, males have three times the risk of females. In assessing these results, the poor diagnostic confirmation outlined in Table 3 should be borne in mind. The geographical distribution of cases of mesothelioma throughout Connecticut shows evidence of urban clusters in the five largest cities where 30% of the cases resided at the time of diagnosis. Since these locations have comprised from 37% to 20% of Connecticut's population (1940 - 1977)> the suggested urban effect reduces to merely being a factor of population density. These five large cities are also centers of Labor Market Areas (LMA) of which there are eighteen in the State. Application of the CochranMantel-Haenszel Test of Average Partial Association (Landis et al., 1970) between these five LMA's and time of diagnosis (1935-77)> while controlling for population age differences, suggests the following: A0G6 16 8. 1. Incidence trends (i.e., the manner in which an area's cases distribute over given time intervals) are primarily the same for four out of five LMA's tested. One region suggests a greater proportion of its cases appearing in more recent years than the others (p=.04). This is readily explicable by the substantial in-migration experienced by this one area and its increasing industrialization as opposed to the other highly industrialized areas whose populations have gradually decreased over time and are, therefore, more comparable for analysis. 2. With the exclusion of this one LMA, the others indicate a similar distribution of their cases of mesothelioma over time (p=.17) This possibly implies similar patterns of asbestos exposure for the four large industrial regions of Connecticut. Until such time as the mesothelioma incidence has been adjusted for the previously mentioned diagnostic weaknesses and possible misclassifications and until the occupationally exposed cases have been identified, it is not possible to determine the role of environmental asbestos exposure, if any, in the remaining cases. Summary Medical, occupational, and demographic data were collected for 267 cases of malignant mesothelioma and other pleural tumors, their spouses, and 605 controls. Methodology was developed for classification of subjects into probable asbestos exposure categories on the basis of product and job descriptions. Although disease incidence rates exhibit a rapid increase from 1955 to 1977, there remains a serious question of diagnostic reliability. A case review will be undertaken. A00R 1 7 9Acknowledgements The authors wish to acknowledge the technical assistance of Linda Mowad of the Connecticut Cancer Epidemiology Unit and Kathleen Pinto of Raybestos44anhattan, Inc. A 006 18 .10 References Bruckman, L., Rubino, R. A., and Christine, B. (1977a) Asbestos and Mesothelioma in Connecticut. AFCA Journal. 27 > 121-126 Bruckman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: Tlfifim'tions and Measurement Methods. National Bureau of Standards, Gaithersburg, Maryland Bruckman, L. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal, 28, 1221-1226 Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1957) Wethersfield, Connecticut Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1966) Wethersfield, Connecticut Connecticut Labor Department: Directory of Connecticut Manufacturing and Mechanical Establishments (1973) Wethersfield, Connecticut Cox, D. R. (1969) The Analysis of Binary Data: London; Methuen and Company, Ltd., pp. 14-29 Hutchison, M. K. (1976) A Guide to the Work-Relatedness of Disease. Washington, D. C., U. S. Department of Health, Education and Welfare (U. S. Government Printing Office) A006 1 3 11. Landis, R. J., Cooper, M. M., Kennedy, T., Koch, G. G. (1978) A Computer Program for Testing Average Partial Association in ThreeWay Contingency Tables (Parcat) Biostatistical Technical Report #18 Levine, R. J. (ed.) (1978) Asbestos: An Information Source, Washington, D. C., U. S. Department of Health, Education and Welfare (DREW Publication Humber (NIH) 79-1681) Price and Lee City Directory (1890-1977) The Price and Lee Company, New Haven, Connecticut D. S. Department 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 U. S. Department of Health, Education and Welfare, National Cancer Inst-ituts Cancer Surveillance Epidemiology and End Results Reporting. SEER Program (1976), Washington, D. C., U. S. Government Printing Office Weston, R. F. (1976) Technical Feasibility and Economic Impact of OSHA Proposed Revision to the Asbestos Standard, Prepared for the Asbestos Information Association/North America. Washington, D. C., Figure 2-1, p. 2-3. World Health Organization: ICD-0 International Classification of Diseases for Oncology. (1976) Geneva, Switzerland A0062C 12. Hilton C. Levinsohn,Corporate Medical Director, Raybestos-Manhattan, Inc. and Lecturer, Tale School of Epidemiology and Public Health (address: Raybestos-Manhattan, Inc., 100 Oakview Drive, Trumbull, Connecticut 06611, U. S. A.) J. Wister Meigs, Director, Connecticut Cancer Epidemiology Unit and Clinical Professor of Epidemiology, Tale School of Epidemiology and Public Health (address: 30 College Street, New 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, New Haven, Connecticut 06520, U. S. A.) A 0062 1 Figure 1. Age-adjusted Incidence Rates by Decade of Diagnosis, Pleural and Peritoneal Mesothelioma, Connecticut, 1935 - 1974 A00622 Table 1. CTR Reported Cases of Mesothelioma and Other Pleural Tumors Diagnosed Between 1935 and 1977 Table 2. Sources of Data and Variables Table 3- Sex, Age and Diagnostic Characteristics of Malignant Mesothelioma Cases and Other Pleural Tumors Diagnosed in Connecticut, 1935 - 1977 Table k Diagnostic Evidence for Disease Groups A 0062 3 c*- CD a4t o *o oo o oo -p* 03 fU ro ON o ro -p* DECADE OF DIAGNOSIS A00624 Table 1. Diagnosis Period 19^5-77 Primary Pleural Tumors (T6^) 185 Mesothelioma (M905) Other 147 38 Peritoneal Mesothelioma (T58, M905) Mesothelioma Elsewhere 33 49 Site not pleura or peritoneum Site unknown (T99) 37 12 Period 1955' 151 131 20 29 35 27 8 267 267 215 215 A0062b Source P opulation V ariables 1--1 a) 0 X c X rH O O X X -p CQ g O C w 0} X 0 r-i T3 a B O X X! a, ag a] 1 Gs bo 0 0X a5O rH O X X. X G TJ (h O CO G G O S O s O xX fn X CU OG U X bO -P O Qa) B T3 k X X a) X3 a X si OG mm GG si O O a. 0 t O X Xc a si B G > bO O 0 rH S a (X a 0 X X X O Cu as fu O X aas 0 X X O. X U O n (=1 um X 0 > G0 t3 rH 0 (JXH aa d cm 03 cd G *< 0 X X to E au cd X G *4 > O0 0 as X 0a G H3 a O &X 0 O bO * G 'O 5 rH O 0 JH G H a X -P O H X si G H G 'S 0 rH O G aG TT?5 H s X a a 1 G O C affsi T) O O *> U X eGg tJ G X 4\ ra TJ O O X 0"Q 0 0 00 0G 0O 0 CU O CO ra X 0 G X c 0 0 t 0 0 00 0G 0O 0a O CO V ro X 0 G X G O O k 0 0 00 0G 0O 0a O CO s CQ rH O (4 X G O O CQ S 0 CQ 0G 0O 0a O cq CQ X 0 G X c 0 0 m * 0 CQ 0G 0O 0a O us k 0 k X G O -P X Ga X 0G 0 a T3 C H c 0X G 0 as CG U ,---V O O m a, OGh X X X CO r-On X 0 X *4 4) Cu 0 X 0 a G a GG X 1 m on Os as as X (4 O X 0 u Eah) GG aG VX-- ' 0 X X a G Eh as --ra G 0 t*> . uX X CQ m as X X on X CD X bo OG G X00 Xa G O X 0 POn bo X 0 2Go CD X XX XX G5 X m t 0 X X X *4 G X t u 3 NO NO X On X xs G CQ -o G 0 0X G XX X G X k G 0X X G r- O o XX X > Ga as U G O G LfS G Os S rH X u a T3 G 0 rH 0 H -P 0 G TJ G H 0 00 G T3 0O GO 0 O rH 0 G CO O H -P E 0 a OG O On O XO CO CNJ CO o o -si /\ 0 0 6 2 7 Autopsy, i f T3 V5. S3 O JQ IT\ ON m co Vi. nn m ja-t "P ositive" * -Hp +r5a H *iH Wm. ON Vi. t" atON cb 03 K cVoi. co cut < c VO s03j 2 C\l CO VO LTV C\1 LTV m oO rM r--i 03 IT\ 03 B rH c- CD P=* m pH ON LTV OJ ON Of CM O CM CO\Jv LC--TV sOiJ -r3H" rn m -of VO CM ,--. <a rCHQ to tocu aHj Q aOH rH r--1 aVsi -jpz 3CD O03 rH 0) cv, s -OP SS3 C nt Ori r--1 r0-31 S3 Si 3 o03 rH 03 PH 2 rH SaO3 S3 *rHH -OGP J-PZ rH O Vi 03 PH 2 aas o c5o H rH -P H a 5 J-PZ U o m j-pz -PH 2 o OQ iH -P HO On VVi S TiH3 H \o oo Vr--O ON cawwos rH Table 4 Diagnosis Peritoneal Mesothelioma No. 29 Other mesothelioma (not pleural or peritoneal) 35 Pleural tumors, not mesothelioma 20 "Positive Histology" ` Autoosv . 96$ 88$ 88$ 40$ 85% 36$ 1. SEER, 1976, Code/Field Number 19 A00B28 Short and simple answers to difficult questions Medical and Physical questions I--C / 1. If it 1b not true that 1 fibre can kill a man, how much asbestos than is needed to kill a man 7 2. The limit value-of 2 f/ml protects workers from asbestosis risk. Is this value low enough to protect them also from lungcancer and mesothelioma ? 3. Supposing the 2 fiber /ml standard rules out the risk of asbestosis, how much Z of the workforce will die from other asbestos diseases in a factory operating at 2 f/ml ? A. Is it true that mesothelioma can occur after very short exposure to very high concentrations ? 5. If mesothelioma can also be caused by very low concentrations, how can industry justify the sale of asbestos based householdgoods such as simmering pads? 6. How to explain that asbestos diseases are often diagnosed only when it is already too late to stop the disease from progressing ? 7. If the diagnosis of asbestos related diseases is so difficult and requires highly specialized and experienced doctors, does it not mean that many cases remain undetected and that much more people die from asbestos than the reported cases. 8. The fibres which are too fine to be seen by the optical microscope, are they not dangerous ? 9. There are much more asbestos fibres present in the air than those detectable by optical microscopy. How then can industry justify the use of optical microscopy to measure asbestos concentrations in the workplace ? 10. Industry is in favour of optical microscopy because it gives lower figures than the electronmicroscope. Or not ? 11. Asbestos is recognized as a proven human carcinogen. How than to explain th; we need not worry about ingestion of asbestos ? AO 1287 t / ) 12. If ingestion of asbestos it harmless, why than have some countries 4 banned asbestos filters for wine 7 13. If ingestion of asbestos is harmless, how than to explain the excess gastro-intestinal cancer risk among AC industry workers found in the Laquet - Lepoutre epidemiological study ? # 0 0 14 The conviction that ingestion of asbestos is harmless is based on animal experiments. Is this sufficient proof to claim that it is safe for humans. 15. The San Francisco Bay Area study proves that ingestion of asbestos is not harmless. What does industry answer to that 7 16. If the public is not at risk from asbestos in building*^ how than to explain that the US government has found it necessary to remove asbestos from schools? AO 1 288 if Non Mrc:cal questions I. The asbestos industry is opposed to substitution because it is a cheap raw material (Is it true that ...) 2. The use of asbestos is declining in"the western world and increasing in third world countries. Is this not a proof that the asbestos industry is taking advantage of the less severe or non existing worker protection or environment protection legislation in these countries ? 3. Can A.C. pipes he recommended for drinking water distribution in third world countries without any restriction ? 4. If asbestos cement is as safe a product as industry claims it to be, why then does industry find it necessary to warn its customers by labelling and why is it necessary to use special tools 7 5. It has been proven that drinking water liberates fibres from AC pipes, and that natural erosion liberates fibres from AC roofs. Is it right than to claim that asbestos fibres are "locked-in" in A.C. ? 6. Since asbestos fibres are virtually indestructible, is there no danger that they will accumulate in the environmental air and reach unacceptable proportio if the use of asbestos containing products is not prohibited ? fc01283 *\ , - the answers SHORT AND SIMPLE ANSWERS TO DIFFICULT QUESTIONS 1. Different individuals have different levels of resistance, but studies at mines (McDonald) and factories (Neuhouse) indicate that long term exposure to 2 f/ml does not statistically increase the risk. 2. The studies mentioned above indicate that 2 f/ml is a safe level for chrysotile Experience in asbestos-cement factories (Belgium and Austria for example) indicates that crocidolite can be used safely in asbestos-cement (wet processes at this level. 3. See answers to questions 1 and 2. 4. Some individuals are apparently more susceptible than others to mesothelioma, but lung tissue analysis shows that this disease is dose related. See also answer to question 2. 5. It is difficult to believe that domestic articles such as simmering pads could produce enough dust to cause disease. Asbestos can be used safely in factories (questions 1 and 2) at levels much higher than could ever normally be encountered from such articles. 6. It is unfortunately true that asbestos-related diseases have a long latent period during which no changes can be detected. 7. To some degree this is true, but not significantly so where there is good medical experience and expertise in diagnosis. 8. Generally the very fine fibres are too short to lodge in the lung. 9. The optical microscope is at present the only instrument able to provide the necessary speed and convenience in analysis. 10. No, but consistency of measuring methods is essential if standards are to be meaningful. 11. It is obviously not desirable to ingest any mineral material like asbestos, but studies so far indicate that ingestion of asbestos is not a hazard. 12. To be on the safe side only. this. There is no real evidence of the need for 13. The authors of this study explain that the findings referred to are not likely to be due to asbestos exposure. AO 1 2 Q P 14. No, it must be reinforced by human experience - as indeed it is in many studies of populations ingesting asbestos in drinking water. 15. There is considerable doubt about the validity of the statistical calculation used in this study as shown in Dr. Crump's recent analysis. 16. To be on the safe side^it is very doubtful whether there is justification for removal of material other than exposed or damaged sprayed asbestos insulation. Non Medical Questions 1. The economic value of asbestos products to the community is an important factor, but it is not true that industry is generally opposed to substitution. 2. It is not true, but this is an important consideration of which the industry is uell aware. 3. No, the special considerations necessary when aggressive water is involved must always be recognised. 4. Asbestos products are safe when they are used properly. The industry has a responsibility to provide the means for this. 5. The "locked-in" concept has limitations when all conditions of use are considered. The question of natural erosion must be studied separately. There is no evidence however that natural erosion of a/c products can ever produce dangerous concentrations of respirable asbestos dust. 6. Asbestos fibres settle out relatively rapidly from the air and are washed away or incorporated into the soil. 401291 11- 1 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 1977 by H. C. Levinsohn J . W. Meigs M. J. Tet a A00623 PrcncnlaLion--tro--Ore--fienno ct i cu4--Thoracic--Society ,--H o v e mh e i----i-9-8-0 2 Malignant Mesothelioma in Connecticut 1935-1977 by H. C. Lewinsohn, 1. V. Meigs, and K. 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, ana includes a review of available pathological material. II. Methodology SUl>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 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 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 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* (Table l) , and controls (6 0 U) 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 (1935-1951*). City Direc tories were searched for job title and name of specific employer or industry for cases, controls and spouses a*. 1, 10, 20, 25, 30, Uo 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). A0063 1 -h- III. Result s Descriptive Epidemiology S uj)iT 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. 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 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.L). AQ0632 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, 1977). 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. 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 A00633 6 in th.e same case. For 12* (.32) of the cases, no tissue vas examined at time of diagnosis, vhile the origin of available material varied. Overall (.1935-77) only (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 ^05? 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 195^. 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. L (]) On first review the cases in this study are being placed in one of six categories (Table 1*), which re- present the relative certainty of the diagnosis of mesothelioma using anatomic criteria. This is being carried out on all available materials, i n- eluding cytoLogic preparations, surgical pathology and autopsy reports and slides. In all cases the A00634 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 k and 5 were also added together since these were considered not to be mesotheliomas. Thus 56.6# are thought to be mesothelioma, 26.U# are possibly mesothelioma and 10.k% not mesothelioma or excluded from the study. 6.6# are still classified as "unknown". A0063S 6 IT. Discussion Although this study vas initially undertaken to discover vhether it vould 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 lov 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 A00636 9 stored at the CTR (i.e., hospital records) produced job 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 80-11+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 A00637 Q; lv_j o @ VS L * 1/7ci (f; K- /t-v/ J 3/3o/&j (0-2 * C. , 7/53/^c L_-' (by; Lc.:C ,'-/ Kvy 7/53/Sb !i) L bUy. t( n/ - LUX Lt-UV i.Y\ .7 ( Ll >` U'X5>' -- C-G-!< r \V- , \ (x~: Uxvi " Oi> -yj' LCilHi; t; M -!' v - ^ ' U ;au i \ [c? ^ k J 0> ,/^) W^` f j(C^y =2 'c^ty l^-Jdtr 3 g) t '^l0^Cr - vVUM^i Vj^i t/' 'Ol~^>/vjL' ic\jKM)f' r k*7-MA /i ^ A00638 p (T" y ^sT) {2y^u|>-^(x^v^/ \U V iCf L^iciM/ lUAn4 ' - fc,cr* *X~ * -* *. i v ** 'O i 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. A00G39 New London Labor Market Area Town Old Lyme East Lyme Montvilie Ledyard Groton New London I.D. Occupation Dx 675092 At home spouse-atty (1966) 711723 Clothing merchant (1971) 781723 E.B. Safety Nuclear Eng. (1976) 792536 Architect, retired eng. Past exposure to some asbestos long ago (1977) 793335 - Housewife 6pouse-truck driver paper & board co. (1977) 761292 Painter-glazer sub-base (1975) 200401 Landscaper-Gardiner (1939) 501121 At home (1950) 693627 Supt.-E.B. machinest (1968) (3 time periods) 779762 Rlgger-E.B. erector-E.B. stevedore railway (1976) (2 time periods) (1 time period) Sex Site & Histology F Pleural mesothelioma M Peritoneal mesothelioma M Pleural mesothelioma M Pleural mesothelioma F Pleural mesothelioma M Pleural mesothelioma M Pleural mesothelioma F Pleural mesothelioma M Pleural mesothelioma M Pleural mesothelioma 10 Cases 9 Pleural 1 Peritoneal 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, Nev 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. A0064 1 21 Referen cer Srucknan, 1. (2977b) A Study of Airborne Asbestos Fibers in Connecticut- Paper presented at the Vorhshon on Asbestos Definitions and Measurement Methods, Rational Bureau of Standards, Gaithersburg, Maryland Brucbman, L. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 2,1221-1226 Felton, J. S- (I960) Letter to the Editor. J AMA, 2M; ,1675 Kannerstein, M. , McCaughey.. V.T.E., Churg, J. (1977) A Critique of the Criteria for the Diagnosis of Diffuse Malignant Mesothelioma. Mt. Sinai J. Med, E.Y. , L B5-^9^- McCaughey, V. T. E. (2965) Criteria for Diagnosis of Diffuse Mesotbelial Tumors. Appals of the Rev York Academy of Sciences, 132 (Art.l) 603-613- Price and Lee City Directory (1890-1977) The Price and Lee Companj', Rev Raven, Connecticut Public Act 80-ll<3 effective January 1, 198l U. S. Department of Commerce, Bureau of the Census:3 970 Census of the Population. Alphabetical Index of Industries and Occupations (1971 ) Washington, D. C., U- S. Government Printing Office Wagner, J. C., Sleggs, C. A., and Marchand, P. (i960) Diffuse Pleural Mesothelioma and Asbestos Exposure in the Rorth 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 A00642 Table 1. Sax, age and d ia g n o stic c h a ra c te ris tic s o f 229 cases o f malignant mesothelioma and 38 o th e r p le u ra l tumoura diagnosed In Connecticut tc ee X Ho w 5 ni o 6 ^4CD O O * ioH> mI in o D. V X um 0h1 0) Xu *O* "eH \ wH hi X o6 c su jj:j o m 9 & B -A. C TJ -5 iri\ ul ec & v B O .BoB o B W Table 2i Easis lo r Diagnostic Evaluation Cor cased o f M alignant Meaotheliomd specimen from biopsy* fro z e n s e c tio n * su rg e ry* autopsy* b and C sfsh CO O o <1 9> I .a Tbl J i Frequency o f Autopsy fo r Cases o t H a lig n a n t M esothalioi slid in P leura Connect ll e Tnut n , nrs 19 o th e r 15-19; th a n Heaothel Iona Diagnosed ; !- S -2 * S 2! pk o| ^ m < J r* tn 1 ~ ^ 6] K fi ^4 JI Aft 5J **<* *- ^ O 1 40 ^ CH fj| Ik k| oj w . g 1-*d -s *' -* 1* k +* m m uuu & C 6 C O A* 4 A wO 0 O s a fele *- MO >K e w u Id j &. a oe 9c ox c * c o ^ Ad fe ^^sss Id * s U U c c 34 0 030 Ad la d -SUJ2 u A* Id KOI C CJ <k k u e c e ^ ^ A* 03 O 9 ^ U tea 2" a-i t - m aN a* fd #9 3D *< ft N A* 2 n w + 7 + m hi -1 *d iU SSS s 22 9 JJ CD O MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 1977- AU0 6 4 6 H u 0) p z<0 >1 CP cn 0 w CO iHo o< x: P (0 ot. 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