Document 2xDV8e8ZrOQLkkR6ZB2wg8nL

MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 (ANATOMIC PATHOLOGY SECTION) INTRODUCTION In any retrospective review of mesothelioma it is essential to include an objective review of all anatomic pathology material. This review should include all available reports and slides including cytology, surgical pathology and autopsy materials. It should be conducted by an experienced pathologist^with special expertise in the surgical pathology of tumors./'' ^nL ~ tt * I** 'A. * ^ a - *. *- ^ The object of this review should be to classify the cases relative to the certainty of diagnosis using well defined criteria for the diagnosis of mesothelioma. In the present study this^review is first being conducted with no knowledge of the occupational history or environmental exposure to asbestos. As the study progresses this data will be analyzed in relation to these factors. (Slide 1 Classification) On first review the cases in this study are being placed in one of six categories (see slide) which represent the relative certainty of the diagnosis of mesothelioma using anatomic criteria. This is being carried out on all available materials, including cytologic preparations, surgical pathology and autopsy reports and slides. As might be expected in a study of this type, the material available is quite variable. In all cases the diagnostic classification is based on autopsy materials, or iuNcson surgical pathology A0054h 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. (Slide 2 Preliminary Results) The preliminary results of the primary review of the first 106 cases are shown on this slide. As you can see 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 tn he 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 purposes of this review classifications 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. As broken down by percentage, there were 56.6% thought to be mesothelioma, 26.4% possibles and 10.3% not mesothelioma or excluded from the study. There were 6.6% that are still considered unknown. A00546 It should be pointed out that as further studies of this material are carried out, cases may be moving from one to another classification and this report should be considered only a preliminary report at this time. It also should be mentioned that less than half of the total number of cases in this study have been subjected to anatomic pathology review as of this time. I Discussion: The most striking histologic character of diffuse mesothelioma is the remarkable structu,,ral< variation that occurs from v, area to area even in the same case. As this portion of the study progresses, the* mesotheliomas will be categorized as to pleural, peritoneal or other, and an attempt will be made to categorize the histologic structure based on its predominant pattern, into (1) epithelia (tubulo-papillary and undifferentiated polygonal), (2) sarcomatous or mesenchymal and (3) mixed. As has been emphasized by others two problems become apparent on review of this material. The first is the separation of localized or nodular (and sometimes benign mesothelial reactions) from diffuse or malignant mesothelioma. In the present study this is a minor problem because of the selection of the material being reviewed, having been obtained from the Tumor Registry where the vast majority of these cases would have been reasonably carefully reviewed in their own institution and they would have had benefit of the ooupbo or progression of the diseaseA As is the practice in Connecticut, cases are occasionally reclassified or removed from the Tumor Registry by the local hospital when it is determined that they do not represent the malignancy originally reported. A0054 / The second and more important problem in the present study is the separation of mesothelioma from metastatic carcinoma. The finding at autopsy in the cases so evaluated are extremely valuable m this regard and 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 connective tissue stains jy/are valuable in this regard. It can be pointed out that as one gams experience m looking at large numbers of mesotheliomas, one begins to recognize a character istic pattern which has been well described by many workers in this field. This coupled with experience in surgical pathology of tumors enables one to categorize My of these cases m the proper class. ^ n nr 11 ~ i 1 ""'T' M>T r 'rr i i-vi `Mt nr*~ r 11,1 i is '^SniBi^le that with additional studies and special stains this classification should become more accurate. AU0548 addressed in the later anatomic pathology studies. There is variation in the literature on the classification of these tumors. The lines 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. rm descriptions which are not .mifiiCJTU 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 AU0 4 ; II. Methodology The CIR has Identified 229 cases of malignant mesothelioma as well as 38 other pleural tumors, not mesothelioma, which were diagnosed in the state between 1935 and 1977 (Table 1). Medical, demographic, and occupational data have been collected for the cases and for the respective spouses of cases diagnosed 1955-1977. Similar information has been gathered for a random sample of approximately 700 dece dents (1935-75) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health Services. Descriptive epidemiology for this research pertains primarily to the |W , 1-- -- <' ^ t~c (!'1 til- forty-three year time interval. Future case^-control comparlsions will in-- --elude cases (215) diagnosed after 1954 (Table 1), and controls (604) whose deaths occurred during this same time period. This procedure yields a case- control ratio of approximately 1:3, while reducing sources of error resulting from the limited occupational and medical data prior to 1955 and the lack of awareness of mesothelioma associated with this earlier time period (1935- 1954). The Price and-~iee City Directories were searched for job title and name of soecific 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 fftx fr, c f ~-t tat C --C* -ui ,!*>*> *" >97U, subject was less than twenty years ol<fP An occupational history search was attempted for spouses to coincide with these intervals for their correspond ing cases. 1970 U.S. Census industrial and occupational codes (U.S. Dept, of Corn erta* of merce,J'1971) were assigned to the employment information ascertained from - medical histories, death certificates, and City Directories. A computerized - j- A o o E =: 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**api*a*aB-JJ*4a>g^Fig. 1). III. Results Descriptive Epidemiology The following descriptive results are based upon the -information available jamv+fce CTR and will require adjustment following the completion A of slide review. Using the 1950 US population as a standard, the ageadjusted incidence rate for mesothelioma in Connecticut is 2.1/mllllon for the years 1935-1977. Rates per 100,000 population increased for both sexes, but there was a rapid rise from about 1960 for males (Fig. 2). The 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. -See- cases_. were reported in/.Vatf IiMA (Hew London) where shipyards are located, and -five of these were identified between 1975 and 1977 (Fig. 3). The geographical distribution of mesothelioma shows evidence of urban clusters in the 5 largest cities (Bridgeport, Hartford, Waterbury, Stamford , New Haven) where 30 % of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-302 of Connecticut's population (19401977), the suggested urban effect may reduce to a factor of population density. ai\ fc( LMfts. These 5 large cities and New London are a&eo centers fo -Labor Market Areas (LHA). All 6 areas exhibit a similarly increasing age-adjusted incidence rate for males. The Stamford LMA's mesothelioma rate shows an unexplained sharp increase since 1965 (Fig. 4). - V- Malignant SLIDE REVIEW L/i IK mesothelioma Is a very rare disease^ only 2 cases per million population expected annually. Resistance to the acceptance of mesothelioma as a disease entity persisted until the late I960'6. Vagner's widely pub licized association of mesothelioma with Cape Crocldollte asbestos exposure created the potential for the introduction of diagnostic bias '***^-*e rj Positive diagnosis of mesothelioma is often complicated by its confusion _ with other forms of cancer.. fVldone^discussion of simulators). --------- jnaayf The controversy.over criteria for positive diagnosis is well documented in *>" e-ri-r* , fl77) , the literature! Most experts agree, however, that a full autopsy is re quired to positively distinguish diffuse mesothelioma of the pleuryf' or perit oneum from other primary or secondary neoplasms. Ve examined, for all CTR reported cases of mesothelioma and for all pleural tumors other than mesothelioma (1935-77), the histological basis for diag nosis (Tables 2,3jT^For 12Z (32) of the cases, no tissue was examined at time of diagnosis, while the origin of available material varied. Overaflonly7Z4Z (105).af the 238 deceased, cases are known by the CTR to have been autopsied. b t-vx. c>^J~opii -c^ c ujerf c.vy f <>---*- , The percentages for all categories, except peritoneal mesothelioma, are low ranging from 33Z to 40%p-*< f i > *&., e> These results suggested the advisability of a fle review. Dr. Romeo Vidone, available cMi'uJ chief.pathologist of St. Raphael's Hospital, is presently studying the^medical records (except occupational data) and slides we have obtained for cases diagnosed after 1954. Cooperation was sought from 37 hospitals, of which 30 have thus far provided us with the materials requested. --(Sugmary of Djff- Findings) -(),(> (?) L& I>e5ujec^ <Au^ W^Jfax&JjU C^y^(UL . . --. UaJ&Ici4^ CEju^efeju ) U Wiv CAae4 o>e g^&t-euu^ , - . |cuj) &&*m &a*U oo aic.\qm udk auJ1 ^ w-fitr ud$L*iy ^laohx^e Onj! o. \trt%/ WiA-aCatfrrM'e Q& C#muJLKaju>e Slgju^S a* Lu^Vgf A^aXt/ruX's CUe i/'ftjuaAfc a,) u>f) TM ttua H^ay{l, ^ % [vuXj^t (Q U^(ujfcel$ ^&o he\u&$ 0*^ "tUj- fa VU-fta^ 3Jn|tu^ (U^XsXle^u cXi/xd(Lu tdjjkt& w it* fAMA4|ca^(e S^y^LuaaP (J*/ifuZ>rr tul* rflut \ t& emtea <ix&A w "tlti> &omv2 Ca*e. -As--(far -CEv3C--K*u-- ^yCV^&ljQj ft*\-------U< tUA^g--feb----bteqpw#--flu t jviiM ij (j jlir 1< ^^ l*/tea> (J) (L? / fij 'few oiml reaieu ua^ U? ti cJUmU %& &#& wJUiOJu^e tfa (Up uuxj u>e^-dUkw^r tnSViae ifcp djuSiMJuB^ ^ M<U^KilvvK4U . W io faM $ulu iu (fcl# ^Li-C&j^af ui-lP U&*a U^o \pj~faJ$Jiaj wi |ite QiAALheUU-4v<il \}ijP(_0Ln oJ e^Aj^u-e Qt&-e&ero. (jit UaW. Ik> OMeAvzd. tv> <>ej2A3L^) Xfc. tiw Sh&>( Ortilfr&a&j fLo cfiaCt ^^ CTC006269 I *acmSQ) The preliminary results of the primary review of the first 106 cases are shown thi'31 slide. Af--yw mil jll 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 faAc 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-put pubea oi tniyrrr^ffftw (classifications 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. As--broken down by--percenLage, \Vjuu9 tbe^^32SPe 56.6% thought to be mesothelioma, 26.4% possibllff and A /' f A 10.3% not mesothelioma or excluded from the study. Clasxrfte^ ,i o thert are still oonai^eiPDd unknown. 6.6% \vjttdl (&) In any retrospective review of mesothelioma it is essential to include an objective review of all anatomic pathology material. This review should include all available reports and slides including cytology, surgical pathology and autopsy materials. It should be VSitU fee Chaiccfrw.lbiu CV conducted by an experienced pathologist^ith special expertise in the surgical pathology of tumors. A00557 IV. Discussion Although this study was initially undertaken to discover whether it would be feasible to identify the environmental factors responsible for the in crease of malignant mesothelioma in the State of Connecticut, it has suffered from lack of detail in available records. Major deficiencies in the data are s-.-i t the low autopsy rate for the pleural mesotheliomata and the inadequacy ofA'* the pathological material available and used for diagnostic purposes. Felton has pointed out several -meeds for post-motem review. A problem may arise in workers' compensation adjudication where a decision has to be made, years to decades after initial work exposure, in those instances where death has resulted from pulmonary cancer or a thoracic or peritoneal mesothelioma. It is therefore important in such cases to be able to confirm by the presence of asbestos related effects that there has been exposure to respirable asbestos fibers^Fcf-to^ 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 ic ap- It has been our experience that occupational histories are not routinely ob-, , .Ajt*nr tained and Included in hospital ' J" *,,* rhrnig.h rrrrrdi itrrni Jr*--a J1 Xr*--'`ft* (c ^ p,r,. p-rv c r jt,\ i ** 'oL. recc'/f V*or*+. ++** G at the CTH (li>i hnrplmT rarnrrisjl. ws found jab tlslsu fui uulv ^Til! of LlTe Ci'fj mauuLlielluuiu uauea. 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 7Z of these cases. The sample size for these statistics was 220 cases, whose diagnose^wsve between 1955 and 1977. A recently passed Ot. statute, whose method of implementation is under study, will hopefully alleviate the paucity of employment data from medical records. r - lr - A005 There* is. /4nother problem^hat has^arieen and, hope fit-H y will *e addressed,in tfce-1 anatomic pathology studies. There is variation in the literature on the classification of these tumors. The lines , <ne/f helic^o- between localized and diffuse are not always clear cut and the A 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 44nfiioni 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 A 0055 3 Two other areas of epidemiological interest which are not routinely recorded for patients admitted with suspected malignant disease are smoking habits and hobbles and or part-time activities. (Coamant-n' the significance of the Slide Review)^ IkflWvV G It is evident that until the physicians investigating cases of malignancy appreciate the importance of occupational aefcere-eit and environmental factors en-the-etiaiegy-af-these-dieeaeeflT-ne (lifestyle, habits, hobbies, part-time & actlvitiAs, de` a^tiled job histories) , amjp. attemptSto apportion blame to any particular factor for disease causation or promotion will be severely hampered. It is particular^ essential in the case of a rare tumor, which may present diagnostic difficulties, to obtain sufficient tissue for study before a diagno sis is made. Whenever a tumor is found and an association is suspected with a particular occupational or environmental factor, every attempt should be made to document all relevant facts and to subsequently verify the diagnosis by means of a full autopsy. A0056C Table 1. Sex, age and diagnostic characteristics of 229 cases of malignant mesothelioma and 38 other pleural tumours diagnosed in Connecticut, 1935-1977 Diagnosis* Pleural mesothelioma Pleural tumour (other than mesothelioma) Peritoneal mesothelioma Mesothelioma at other sites & at unknown sites Total Males 102 (94)b 24 (12) 20 (18) 29 (21) 175 (145) Females 45 (37) 14 (8) 13 (ID 20 (14) 92 (70) (1976) ^Numbers in brackets refer to the period 1955-1977 Total 147 (131) 38 (20) 33 (29) 49 (35) 267 (215) Mean age 61 (62) 62 (63) 58 (59) 52 (54) 59 (60) A0056 1 Table 2: Basis for Diagnostic Evaluation for cases of Malignant Mesothelioma and Pleural Tumors other than Mesothelioma Diagnosed in Connecticut, 1935-1977 Diagnosis* Pleural Mesothelioma Tissue Available 136 X (93) Pleural Tumor 27 (71) (other than mesothelioma) Peritoneal Mesothelioma 31 (94) Mesothelioma at other sites and unknown sites 41 (84) No Tissue Available X 11 (7) 11 (29) 2 (6) 8 (16) Total 235 (88) 32 (12) Total 147 38 X (100) (100) 33 (100) 49 (100) 267 (100) 'SfHO (1976) ''specimen from biopsy, frozen section, surgery, autopsy, D and C 400562 Table 3: Frequency o f Autopsy fo r Cases o f M alignant Mesothelioma and P le u ra l Tumors o th e r th a n M esotheliom a Diagnosed In C onnecticut, 1935-1977 00 O' M| O m co xua "4O)e1| z3 Q 'S' CO X3cGo co o aao, ZH *3< C\0M CO uo >aao>n co 4awo-1| 4J 0) <3 aA *>-,4-10 0) > H u o o (0 C 0) s c O. O Vi <U o ih a o 43J 43J "GO -->i **- < X M W O m >oGa3uO., UGoWO "0cuuaH) M> Co5 53c XX5J<VVJui u0uoea) 'CWM * J>ca0Jo,. <3 uCoCuOO Ts0Hu3) W> 0Uo) (e53 Vo-l >, w oa. *3<J a o ou OoM -c00uHa)) w> eo co CO o> oo n 00 CM co U0 CM CM CM CM M *r oo CCMO ucoo oo>o CM cooo ro CO in r--\ o *< 4 CD oQGoco<HO0c Va(HH30>* XJ-u0ao91OHHJ) 0* z 3uoSC OHaa H --4 XU W X-404J) Vt3l Xu1) Vo euHO*> B H44eOJ) XHH49O1J 7VV* (oOUo Q* Z o9sH aCaO JG0JO) 4oVaHJ CO X4-1 z0o1 jJuurJ o 5eo s a3 rJ<JJ9 HO CM c-s vO + a\ /*> w o 5 fCHO .aoo AU0 5 6 4 o CO 00 g A0 0 56 S o GO \in CM N o r~ s r- w mH H Ea 1a in * cn o o\ o ,--* rH <0 o <u E Eh Eh (0 (0 O< u U& H vo Eh U o U H iH W s "--' zo z 03 o < Eh u z PI < D z 03 H Z 63 o OS rtj s a >H o w OS Mw< <z wmH ss zEh H o o h3 cn H w w &H OS s < cu u Eh H Zb cM z 03 o 03 H< JJ 2 CJ HP HP vo HP VO <*> vo vo o VO in CN rH o o CO iH r- z vo CN <--f A1 A1 0 CM 00 00 vo in r- z cm cn CN id E 0 rl id id r--1 e E 03 0 0 X3 H H P rH iH O 0) 03 to id x: x: 03 g -p -p 2 0 00 H id (Q (0 P rH 0) <13 0 03 zc 0 S z x: 0 H -p rH rH 03 >i 0 P QJ i--( rH iH <0 C id x: X3 X3 fl 03 S o +j id H id 2 0 H 0 XI <0 c HH (0 o (0 0 -P rH 03 P o P 0 C 10 2 04 04 04 Z D 10 (0 f-H u r-l CN m xr m vo HP O O i-H VO O f--1 vo o 1--1 rH id P o Eh XZX4 <ttZjuiaao >(/> t/iu>3t loc O.ZZZZIUJ oa Ml(OM> xOJKQHXUi 1/1 Q <-!>---3 a. 33 --QOX JCX 30. o< 3333 < uaaaaua* >-(juuujf-a uu < 33 <za< Ml 130UUU>- uJ ufli/un 3333UOO M 03 XX 3 uQJJjx Qi>*aisai4 3>--0 3330C >*< 3 JO XZQ ~i ii ii iif N)^)(rthUUU>JZ< Oxi/ix3a3o`<'<<*x-o0o3o JujOO cooi/h/I'/k/iidx i i OaaDZJQttJZZ^ -x >*:><a.a.a. Cjat a. o 33 > -- * ujuiuJU^* UUUuJ ozaao.oaca3< xxxa.3 -o ^aaajou^kjoj x 3333303 IJO 0.0.0. 003 1--3 < UJOUIi/1 3333 < 1Z1Z >->>< *--3 uiaz 0X.1/Z1Z00Z0Z040 uii--a <</>o c?^Qr_j ZZ2 -- Oujujojuj OOOH.t 00 0000 30 --LO*--XhT-JX--O--' QOZ< roaax BJOlCi |f<hx os or>ooom/\or^or^o,-n aj *oooo *ac 333 3333 f -H- oo Li a x 003 <o. juJ-uo X 330-->i-<i-*--03 2 rin>-7Uij UU -Jo3h-> -- 3>-xo ''u.u.itu.^zat OO</H/1/Vy'f033 so ^ -*a i<--ar j<ottmZZuMiztkouo.ikouo.HrUoj>4 3 3u. u. u u. mi > 3 uj <ujxHttoca3j oacocou-Oi/ia. <juouj -^COCQ-Sf rox<M044i ori'Docoo crot^*'fnfl^.*o)mcooo ao oa to so o-oopx*> oojodi coo coo>aoaorx*oaooaos ciofaoof---ikm <n nj nj -i-- o*-o ao _______zzl>zIPz<1jn UiLU<X^Qt^< vHla.LO.tt co o >* ---<-- OOCt)>-i^OOOOOOwxHOOOOOOOO(VOOOOC1lMl'ltVN<MM<'J'll<MinJ'iflxxxHOJxx'M(MMMMMi*xx--O *333-- 33 <-'--ii'\ir\|<\l <\|i\lrnrOrn rn^n in *-g-n33333304333333 fNjf'jfvj'0rK<<f\jf\j(\j<\irM\j<.'`<^njr,*r'*^"r^r'< <rmmmnvn333<M(Ni<\j.ruT33,- 333J0<01HX| || li.|g>0>JlHg>Oyi Ii ti Ii 1.1. l|^xO>g(}'XO>HHOHgiX--0\XH(^iJO<a'q>q'><(f'xO>(>g0'g>g<XH>)0> iioOa'fMj'OQOOQff'O'O'nijio'jsiSoooOQovoo'd'O'OO'naa'oa'OOwrinBvOO'' ia'0'<j'0j'.f\0'X>o0'0'<jOQa> JSOOOCDiMCT'rfl^O'CT'--uCT'tfli/IOOJ' ^J'3'O' j*J>J3cT'iJ'3'(7'O'0>'XX Off' lOOOff'ff'ff'^DO304'Or'^'J'OCT'Cr'U'f'vjaOCO 0.0 3CT'>n J' J'CT' 'TJ'OOff'iOff' C."^ J'<'J'J<3'<rCff'Off'ff'ff'-nff'^ J'ff'ff'ff'O'ff> 30 Off mm .a j'O' jsn333.o j'u' j> oo' j'mu'O'O'mO'JSift jifr\>jr**r"0'OJ'f'vff' j>o* _i jijs ji j'Cf'sj'O'tj'3330 mOw\IUT330'--l33<\|OJt\j--r-3000<M<0'OOOmin3*3a'0`>MC'a'<'J<MO'0'3r\ji'gun>r,-0<-CT'<\Jina'iJ`f\l3.y33:\|inOCr'a'*a'` OffOj. ;offOO O'-*--* CC 03 003000 I iff* CJCT> O' 0<ff'CT'Ol''JC^(ff''^r J ;s>r3j3^ ^nj ufftf'CT'.--iO>JO O--r'-tff'J'CT'iff'O' us j'4Jf\nc<a'J'miff's/''r<M'\iruoji\4 mrnrnfn niff'jjf-j'j'j'jsr-^-^oooCT'C7'cr%ff' SC a C3 <3 o3 X3 o 3 --ac X3 3 < X c-- 3 3 jJ oU tt `ij UJ-il `33 'TO X (V -- V ><u X*-- U UllLUC JO ZT`U X <_l aj r< U* QC U.LU --'3 .V SC <*" TO UJ J 3 o o ko^ %f 0'/ XX #k iu3 C J JZjC xJ O 4 X XxX^" i J*> JlJv1<ZJ X->->/>33X 3 J OUI JO. r--i -- |-- (/) Jl-Ji X 3033 3 3 --4 3 X X XlXOjJ 3 3 30J N-T4u> mH/ OXOCX<<X<<<4X 3 03 X Z4JI4jJ4JCZiOXJ>-J < X JOJi-OOjO4>a:^>- --^ i_ _C .0030 iJoCXX uaJttZZZZJXJIJJO uouxiuia.jo'io.iojjujujujuoa.ta.iii- XjI -> J oo.-- 3 *- U->* 31-- 3 JZxiJ n. oo-a. * XX x4 JLiate r-X 3 /I Xi-- 4-*>uxZHiX 1'i.XO--4 --J O JiJ<OCC JOC ra y/<jcac.4 xx -JO Ox 30 aji O X3 03 33 o-- ii"r< J 3 3X33jT/1o<3 -JO u--jX >-JlvJXZ2u.^ --4 33>----r-/I JUOIXOOff n^rw.jojjcu O 3 > O -J a. ->XOxX'< 444XXi400It-i-P-i-r4-<4 X--*X O--<<X<3< << x--'3X44-.XX X XOO.-oX .no oasr-.i' JJ4/l2a..')f1/,/1/1V)4ljXlU.-i u i)n-o.r^.rfT.o j'Ovff'aiaii^JfiflnoitnxiJir'-CT'r^r^x ji JZXJ xX-JxOCXX 33-UoXi-- OxXoOX X'tif^nin n ;> r-- O' r (* nr* .7* > > i>. n rn cr O f-- 4lJ\ n j--o jj> o jjuj--jj'-'.nxijs-so' j> j'<3'3'-r J' fi.ii'no OOiOrt^Hrti'lOl'W'ffJ'OOOOJ'Cl'f <r O' .mf'jruO' O' o O' <- ^ x J* O' wMJ'iff' o O' inm.n< HHOrgHw-jO uffiivirjr* 'jiNjrgrrj.-'jo fMff:rur f^.'ursj*-* rjrj (\ir\j .u. gHiO--iu <^0-irJfg st.i>n o.j^j.no-jso ^.~j.n.n J-JSO in<jso >r-s js o ooo'jso o-n<un--> r-r~r~ hhh O'O jjOOdj.n.-n'nnx o jjo oro^i'-j'O'j' oT,mn.n --o-ooo *----wiv*i^'4->-< j'-^oo.oo oo-o - oooj'0'nrim.nfnfn.nooo^,^'^ounusjSaS-4-i'^^'^^ooOor^f**f^j^r^J'J'3'unxuso'fooooO'^jo*- .-U'-JiM J-O OOOOOOOO--IJOOO JOOO 5 J o 30 n - ' o^ffi j'r>.t^ ^ <* -05 E 2 II CD M i1 Oo <0 m ^ o 000*001/3Vd 11 oo to CM AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX n rt A 0056 / 0* > m to A ,vT> GEOGRAPHICAL MAPPING OF CASES OF MESOTHELIOMA (1 9 9 5 -1 9 7 7 ) BY TOWN OF RESIDENCE AND I9 6 0 LABOR MARKET AREA A00558 AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA FOR CONNECTICUT MALES BY YEAR OF DIAGNOSIS AND LABOR MARKET AREA 000*001/31VM Aoose 1935-44 45-54 55-64 65-74 75-77 Hilton C . Levins ohn. Corporate 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. 1.) J. Viater 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 06520, U. S. A.) Mary Jane Teta, Associate in Research, Connecticut Cancer Epidemiology Unit, Tale School of Epidemiology and Public Health (address: 30 College Street, Hev Haven, Connecticut 06520, D. S. A.) A0057C References Bruckman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop on Asbestos: Lefinitions and Measurment Methods, -Natuial Bureau of Standards, Gaithersburg, Maryland Bruckman, L. and Rubino, R.A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal, 28,1221-1226 Felton, J.S. (i960) Letter to the Editor. JAMA, 244,1675 Kannerstein, M., McCaug*3f. W.T.E., Churg.J. (1977) A Critique of the Criteria for the Diagnosis of Diffuse Malignant Mesothelioma. Mt.Sinai J. Med, N.Y. 44, 485-494 Price and Lee City Directory (1890-1977) The Price and Lee Company, New Haven, Connecticut U.S. Department of Conmerce, Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries and Occupations (l97?), Washington, D.C., U.S. Governemtn Printing Office Wagner, J.C., Sleggs, C.A., and Marchand, P. (1960) Diffuse Pleural Mesothelioma and Asbestos Exposure in the North Western Cape Province. British Journal of Industrial Medicine, 17, 260-271 World Health Organization: ICD-0 International Classification of Diseases for Oncology,(1976) Geneva, Switzerland He Cauafc'j y V4- (- G . (PiftI) ^ A0PF 7 i DISCI'S 5 UN Although this study was undertaken initially in an attempt to discover whether it 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. Tablo II <ng III illuct-ata sue. of.trie * ft to w4* -S' Irkjor deficiencies in the data available for study, noacty the low autopsy rate f faboltytif 0 \for the pleural cesotheliomata and the inadequacy of the types ef tiooue- 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 ------------ --------------------------- no inquiries are made of patients admitted witn suspected malignant disease re garding their hobbies or part-time activities, In our search through the C. T. ?. paper files (i.e. hospital records), we found job titles for only 172 of the mesothelioma cases. If we exclude from this group those merely designated as "retired", "housewife" or "student", the figure i6 re duced to 122. We were only able to ascertain the type of industry in 72 of these cases. This data is applicable to 220 cases consisting of: 195 mesotheliomas in the Connecticut Registry, 1955 - 1977, 5 mesotneliomas from the Veterans Administration files, 1955 - 1977, and mors, not mesothelioma, recorded 1955 - 1977. his disease ppeardd to /ntroent increase aften 1955. A00606 Comment on the significance of the findings or. the slide review. It is evident that until the physicians or hospitals investigating cases of 4r Ci- cm malignancy appreciate the importance of^environmental facts the etiology of these diseases, no attempt can be made to apportion the blame to any particular factor unless adequate histories are available containing complete information on lifestyle, habits, hobbies, part-tine activities and details of occupation and industry. It is also essential,particularly in the case of a rare tumor which may present diagnostic difficulties,to obtain sufficient tissue for study before 441 l'f MiAfaloal the final diagnosis is cade Whenever a tumor is found where m> association agists between it anc a particular occupational or environmental factor, every attempt should be made to fully doc ment all the eeereei facts and tc subsequently verify the diagnosis by means of a full autopsy. *00607  V he 5 t * c r v .;: r v* ."C * * !'. i .`-fe i'l* ;r*> t*i: :;* ucr o' wt.,T.*. it-?- r*c ir. uj'i'c* *io^rr r.a r.isi ;.! r.ac :-eer. Irta'.t-c iu- tnrunic r-c-*r:r z s - nov;:..- of thr i-ores with bexar.f-.'.iM-'jt ir. Dosages from 0.5 to 1.5 mg ci.ir. inurRittientiy for let' veari. Dur;rf this period. the skin of her fore arm! betamt extremely thin, and she experienced several episodes of subcola- s:t-atic r ce-.a- ::-t site u: a iota.met r.erps- s:mp<t;. ir.fcrtio: that had occurred or. my uppt' i:t and hac no: heaied for approximately one year. It was removed by a Mohs' surgical procedure at a local universi ty center, and a diagnosis of bascsquamous cell carcinoma was made t iS.-.rg c: trrr.v ir tr.os-. irstarues where ctair ra? resulted fro.T pulmonary canter - a tnoracic o* peritonea! mesotneliv-ma it is important to identify the t:ss,,aiueraticrs directly attributable to occupational contact with the respira ble asbestos fiber. neous extravasation of blood. again. At that time, the dermatolo As we have counseled family survi Or the fount hospital day, she was transported to the x-ray department, where it was noted that she had two superficial tears in the skin of the lei: forearm with gaping marpns Attempts were made if suiure the skin edges topetr,er. but the sutures tore througr the skin. The edges were htlc together with strips of steriie tape Or. one other occasion curing her hospi gist performing the chemosurgery mentioned how unusual the lesion was. inasmuch as there were no: supposed to be such things as bastsouamous carcinomas Both wounds healed without any unusual event. After the first occurrence, 1 con tacted Dr Herman Pinkos in Detroit, and he stated that there were about a vors of such persons dying of asbesitsis 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 all physicians or house staff caring for such patients urge relatives to permit the examination These procedures will Dot only aid the beneficiaries bu: tal stay, s.xi.ar iesiocs deveioped during dozen cases in the literature at that will also prove of worth to physicians the course of transport to anc from her bed for other diagnostic procedures. These lesions faiied lo heal during her hospital stat. and gross evidence of infection was no: noted Cormrunit--Transport by handling of the forearms, even though careful ly done, resulted in serious, poorly healing tears of the skin in this o\ era-eight, weak woman. Even though extra care was taken after the initial episode, there was recurrence Ir. this case there was no complaint or dissatisfaction expressed by the pa- I tier.: or the family, but such episodes hate the potential for risk of com pensable injur.. Certainly there have beer allegations of hospital-based lime. I saw him at a meeting shortly after the chemotherapy, and he com mented on the unusual nature of this condition occurring more that once, though he w-as more aware of its occurrence than, he had beer before. There is an embarrassing situation about this personally, and that is that 1 am a dermatologist. There were no other forms of ther apy used on these lesions with either surgery, antibiotics, or photodynamic inactivation, nor am 1 a smoker. 1 have had an occasional localized herpes simplex infection curing the past 20 years. Man* L CatOC VC 1 AlQPri U#OiS* Ce'DU? S~ | in familiarizing them with the find ings characterizing a greatly under diagnosed job-generated disease. Furthermore, such postmortem cats will aid in our knowing what actually happens to a worker under certain conditions of exposure anc will help to rectify the inaccurate conclusions drawx from the current underreporting of occupationally as sociated disease tw.*nr, o' Soul'**'*' C*mi9*tw! benoe p> topple** iu Anpoo* Safety of Ipecac Syrup 7c Du Eiucr-- On behalf of the injury with lesser justification. American Association of Poison C: r - h would be prudent for physicians nospitaltztng patients who have been receiving steroid therapy to place a warning note or the chart advising hospital personnel to use extreme The Aufopsy and Asbestos Exposure To Due Editor.--\z the article entitled i troi Centers. 1 am concerned about the titling of a recent J.4-A14 article, "Death Resulting From Ipecac Syrup Poisoning'' (242.1927, 29S0i. I am wor ried that the index skimmer or scan care when bathing, assisting, or "The Autopsy Past. Present, and ner--particularly if he is of the older iransotrting such patients. Lw T t. *<:. UC Zrjwrfy Cal'* Future*' by Aadersor. and cc-workers school reared in an era of gastric (242 ]05. 2P79i. the fall in the rate of j lavage for management of poison autopsies is decried. aDd several ings--may inadvertently conclude cogent reasons are presented for a that the typical emetic dose of syrup Carcinoma al the Site of He-pes Simplex Infection 7o u.> Eci:c'.~Ths Jofp.NAt recently :>uhi:shrd a letter er.titied "Carcino ma ai the Site of Herpes Simplex Infection" (243.2296, 19S0). My letter return to the previous high number of such examinations, a goal formerly pursued by dedicated house officers. One additional need for postmor tem revjew-s has been given emphasis in recent years by the epidemiologic and clinical information gathered in of ipecac was responsible. In reality, the dose was three to four bottles per day for three months--thus repre senting a long-term poisoning. As noted by the authors, syrup of ipecac as an emetic agent has a remarkable safety record; its current is to note further the occurrence of connection with the asbestos-related availability over-the-counter and in such a sit cation. I personally had disease. Because workers are now the home permits an enormous saving hasoscuamous carcinoma develop on two occasions. The first occurrence was approximately five or six years ago at the site of a vaccination for small pox that I had received for traveling. After the vaccination site did not heal for oDe year, I became suspicious and had it excised at the local ur.iwrsity hospital. I was ap proximately 55 years old at that time. beginning lopresent radiological and altered physiological evidciivt of the effects of the inhalation of free asbes tos fiber, years to decades after initial work exposure, a problem in work er's compensation adjudication has arisen. The changes elicited through clinical study, although present, most often do not have accompanying symptoms, er yet. nor have they caused any disability, as yet There of needles? visits to emergency rooms for the treatment of accidental inges tions 1 think that it would be unfor tunate indeed were the inference drawn that single emetic doses were risky. MummO fi30**S3* MD Ctvio *-i * Ono:-H3>c Hr*r*o eiC M0icc* C*n*0> AttOtiBWO* * Fo'ftpft Control Contort SellUt JAM A. Oct 10. 1930 --Vol 244. No. 15 A00608 Letters 1675 i i I DRAFT 10/17/80 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935-1977 by H. C. Leviasohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 A00572 Malignant Mesothelioma in Connecticut 1935-1977 by H C Lewinsohn, J.W. Meigs, and M.J. Teta I.Introduction and Aims The combined sex age-adjusted mesothelioma incidence rate for Connecticut was reported in 1977 to have Increased ten-fold since 1935r"Although available statistics might be subject to diagnostic error, the apparent rise wa^ attri buted to the increase in the State's 'cumulative asbestos consumpt ion '^Com plete occupational histories for the cases of mesothelio^ were not presented. A de/tailed 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. II. Methodology The CTR has identified 229 cases of malignant mesothelioma as well as 38 other pleural tumor6, not mesothelioma, which were diagnosed in the state between 1935 and 1977 (Table 1). Medical, demographic, and occupational data have been collected for the cases and for the respective spouses of cases diagnosed 1955-1977. Similar information has been gathered for a random sample of approximately 700 dece dents (1935-75) aged 20 to 98 years from the Division of Health Statistics of the Connecticut Department of Health Services. Descriptive epidemiology for this research pertains primarily to the forty-three year time interval. Future case^-control comparislons will in dwde cases (215) diagnosed after 1954 (Table 1), and controls (604) whose deaths occurred during this same time period. This procedure yields a casecontrol ratio of approximately 1:3, while reducing sources of error resulting from the limited occupational and medical data prior to 1955 and the lack of awareness of mesothelioma associated with this earlier time period (1935- 1954). The Price and Lee City Directories were searched for job title and name of 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 correspond ing cases. 1970 U.S. Census industrial and occupational codes (U.S. Dept, of Com- merce, 1971)(Sw> ere assigned to the employment information ascertained from -- medical histories, death certificates, and City Directories. - "> . A computerized A0n574 Table 1. Sex, age and diagnostic characteristics of 229 cases of malignant mesothelioma, and 38 other pleural tumours diagnosed in Connecticut 1935-1977 Diagnosis Males Females Pleural mesothelioma Pleural tumour (other than mesothelioma) Peritoneal mesothelioma Mesothelioma at other sites & at unknown sites 102 (94)b 24 (12) 20 (18) 29 (21) 45 (37) 14 (8) 13 (ID 20 (14) Total ^0 (1976) ^ 175 (145) 92 (70) `'Numbers in brackets refer to the period 1955-1977 Total 147 (131) 38 (20) 33 (29) 49 (35) 267 (215) Mean age 61 (62) 62 (63) 58 (59) 52 (54) 59 (60) A0057S list of job and industry titles has been developed for all cases, spouses, and controls <1955-1977). This will form the basis for classification of study subjects into asbestos exposure categories for future case-control comparisons (sample from listing Fig. 1). III. Results Descriptive Epidemiology table The following dr^-rfrt1~~r results are based upon -the faifernation l<v Vx>^.Uv > ii fi iiiii < In CTR and will require adjustment following completion A Kc of euv slide review. Using the 1950 US population as a standard, the age- adjusted incidence rate for mesothelioma in Connecticut is 2.1/million for the years 1935-1977. Rates per 100,000 population increased for both sexes, but there was a rapid rise from about 1960 for males (Fig. 2). The male- female ratio is approximately 2:1; the mean age at diagnosis is fifty-nine years. Average survival time from date of diagnosis to date of death is ten months. __ (Lfffl) cases were reported in where shipyards are lo- cated, and tove of these were identified between 1975 and 1977 (Fig. 3). A The geographical distribution of mesothelioma shows evidence of urban clusters in the 5 largest cities (Bridgeport, Hartford, Waterbury, Stamford , New Haven) where 30 % of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-30% of Connecticut's population (1940- 1977), the suggested urban effect may reduce to a factor of population density. LH<HThese 5 large cities and New London are aimo centers foTtiObo>r Mttoarrkket Areas (Mtt*. All 6 areas exhibit a similarly increasing age-adjusted incidence rate for males. The Stamford LMA's mesothelioma rate shows an unexplained sharp increase since 1965 (Fig. 4). A00577 AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX oj 01 f 3 m$7 RATE/100,000 fO o CtJ o * o Ol o T T t--------- r Oi O T H El S CD *n s o a> D -I CD Ul Oi a> o> Ol <G _ a> s01 I . . J l l . Li .O' -- i *? A00578 6E06RAPHICAL 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 O Cl Q. or 3 CD wz ro o o ^-r ro o T O 3 $ RATE/100,000 Oi CO o OOo TT oa T fO o 1935-44 45-54 55-64 65-74 75-77 SLIDE REVIEW Uifo Malignant mesothelioma is a very rare disease, only 2 cases per million (, population expected annually. Resistance to the acceptance of mesothelioma as a disease entity persisted until the late 1960's. Wagner's widely pub licized association of mesothelioma with Cape Crocidolite asbestos exposure created the potential for the introduction of diagnostic bias.^J Positive diagnosis of mesothelioma is often complicated by its confusion with other forms of cancer..(Vidone discussion of simulators). The controversy over criteria for positive diagnosis is well documented in 10 the literature. Most experts agree, however, that a full autopsy is re quired to positively distinguish diffuse mesothelioma of the pleural or perlt- h oneum from other primary or secondary neoplasms. We examined, for all CTR reported cases of mesothelioma and for all pleural tumors other than mesothelioma (1935-77), the histological basis for diag nosis (Tables 2,3). For 12% (32) of the cases, no tissue was examined at time of diagnosis, while the origin of available material varied. 0verailj^onIy^2<W (W5) 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% a- ^ i ., c**^* These results suggested the advisability of a sitll review. Dr. Romeo Vidone, chief pathologist of St. Raphael's Hospital, is presently studying the medical records (except occupational data) and slides we have obtained for cases diagnosed after 1954. Cooperation was sought from 37 hospitals, of which 30 have thus far provided us with the materials requested. (Summary of Dr. Vidone's Findings) A A0058 1 Table 2: Basis for Diagnostic Evaluation for cases of Malignant Mesothelioma and Pleural Tumors other than Mesothelioma Diagnosed in Connecticut, 1935-1977 Diagnosis8 Pleural Mesothelioma Tissue Available 136 2 (93) Pleural Tumor 27 (71) (other than mesothelioma) Peritoneal Mesothelioma 31 (94) Mesothelioma at other sites and unknown sites 41 (84) No Tissue Available 2 11 (7) 11 (29) 2 (6) 8 (16) Total 235 (88) 32 (12) Total 147 38 2 (100) (100) 33 (100) 49 (100) 267 (100) aWHO (1976) ^specimen from biopsy, frozen section, surgery, autopsy, D and C A 0058 2 o' i o + O' N> on + U> + + Ln 5e c3o5 0rH3r f0t3 faot* r1a rHmr fODt Pa9 QrAODrX IIr-3aOBa*** Br9t Ira5aSOOhtArX-'M I(rrHao3nBB-r1 IIr-3oaaHoBr"* B r3Or" ir|b r3ar" 9 >eHaAiMeH r5C| raoArX Ho* rc|a O' 03 CDOB9 CD co la (l) 3HHOA--* I-a* aa Table 3: Frequency o f Autopsy fo r Cases o f M a lig n a n t M esotheliom a and P le u ra l Tumors o th e r than Mesothelioma Diagnosed In C onnecticut, 1935-1977 M H* ( i) (2) (3) (A) (5) Autopsy, M icroscopic Evidence o f Cancer A u to p s y , Gross Evidence o f Cancer Autopsy Gross E v id e n c e , Unknown Whether Cancer Autopsy, but only In d ire c t Evidence o f Cancer Autopsy, no Report (6) No Autopsy HW A3 62 8 13 (7) (8) Number Unknown | Dead | 18 134 11 37 21 2 1 28 11 21 5 39 ---------- ------1 83 12 98 35 238 - 00 > c CD cc UU>> V00O LUn O N r |H rCoDO? o* IV. Discussion Although this study was initially undertaken to discover whether it would be feasible to identify the environmental factors responsible for the in crease of malignant mesothelioma in the State of Connecticut, it has suffered from lack of detail in available records. Major deficiencies in the data are *.*>.-I the low autopsy rate for the pleural mesotheliomata and the inadequacy of the A pathological material available and used for diagnostic purposes. fth r Feltonhas pointed out several needs for post-motem review. A problem may arise in workers' compensation adjudication where a decision has to be made, years to decades after initial work exposure, in those instances where death has resulted from pulmonary cancer or a thoracic or peritoneal mesothelioma. It is therefore important in such cases to be able to confirm by the presence t> of asbestos related effects that there has been exposure to respirable asbestos fibers. A further need for autopsy arises to confirm the diagnosis of malignant meso thelioma made on limited biopsy material obtained during life. This is im portant for workers' compensation purposes and also to improve the epidemiolo gical data required to investigate the etiological factors involved with this disease. Valuable information can be gained from a comparison between radiographic apperances and histological changes in the lung. Such Information will help to eliminate present diagnostic uncertainties. It has been our experience that occupational histories are not routinely ob tained and Included in hospital records. In our search through records stored at the CTR (i.e. hospital records), we found job titles for only 17Z of the mesothelioma cases. If we exclude 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 72 of these cases. The sample size for these statistics was 220 cases, whose diagnoses were between 1955 and 1977. A recently passed Ct. statute, whose method of implementation is under study, will hopefully alleviate the paucity of employment data from medical records. A U 0 5.. 4 Two other areas of epidemiological interest which are not routinely recorded for patients admitted with suspected malignant disease are smoking habits and hobbies ead or part-time activities. (Comment on the significance of the Slide Review) It is evident that until the physicians investigating cases of malignancy appreciate the Importance of occupational faetere-en and environmental factors en-ehe-etielegjr-ef-these-diseasesT-BO (lifestyle, habits, hobbles, part-time e. . actlvltis, deatiled job histories) , any attempt to apportion blame to any particular factor for disease causation or promotion will be severely hampered It is particular^ essential in the case of a rare tumor, which may present diagnostic difficulties, to obtain sufficient tissue for study before a diagno sis is made. Whenever a tumor is found and an association is suspected with a particular occupational or environmental factor, every attempt should be made to document all relevant facts and to subsequently verify the diagnosis by means of a full autopsy. A0056b i- Referenced Brockman, L., Rubino, R. A., end Christine, B (1977*) Asbestos wfl Mesothelioma in Connecticut. APCA Journal. 27# 121-126 Bruckman, L. (1977b) A Study of Airborne Asbestos Fibers in Connecticut. Faper presented at the Workshop on Asbestos? nations and Measurement Methods. National Bureau of Standards, Gaithersburg, Maryland ^Bfruckman, L. 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, Jfov Raven, Connecticut U. S. Department of Cornerce. Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries and Occupations (1971)# Washington, D. C., U. S. Government Printing Office World Health Organisation: ICD-0 International Classification of Diseases for Oncology. (1976) Geneva, Svltserland --- A 0 u b i b &' Hilton C . LevinaohniCorporate Medical Director, Raybestos-Mianhattan, Inc. and Lecturer, Tale School of Epidemiology and Public Health (addreaa: Raybestoa-Manhattan, Inc., 100 Oakviev Drive, Trumbull, Connecticut 06611, U. S. 1.) J. Viater Meigs, Director, Connecticut Cancer Epidenlology Unit and Clinical Professor of Epidemiology, Tale School of Epidemiology and Public Health (address: 30 College Street, Hev Haven, Connecticut 06520, U. S. A.) Mary Jane Teta, Associate In Research, Connecticut Cancer Epidemiology Unit, Tale School of Epidemiology and Public Health (address: 30 College Street, Hev Haven, Connecticut 06520, U. S. A.) AowDl/ 73m. iBfflueHUE ul OCCBp^^^orrai 3R^"15nvttwinndffH4""Asbc^^^6-- Bwpoouge an the--twe4aagg=^ Malignant Mesothelioma in Connecticut^ WIS-iW by H. C. Levinsohn J. V. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 A0058 9 The Ieflwanoa of~Oc.Lupm.luual and Environmental Aobastos Exposure on ,th> laoidcnee of Malignant Mesothelioma In Connecticut^ It- H77 by H. C. Levinsohn, J. V. Meigs, and M. J. Teta I. Introduction and Aims Brockman 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 (Brockman, 1977b; Brockman, 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 it Ae warranted. The present study has been designed to A 0 0 5 ij C re-examine the identified cases of malignant mesothelioma recorded in the - I- CTR and attempt to determine the role of various etiological factors, such as occupational and environmental asbestos exposures. In view of the mbt- Suggsrf.lpwwlsdgnd possible diagnostic errors, which our results verify, a thorough review of available histological material is being undertaken. A005C 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). p,<-------- "0T --A n-a Lu Llm 1LD-U CffSllLl Umltb OfgaaiaaAAafcy--W^1) ulmsulf icBt4up,^Medicai, 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 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. c a*. Descriptive epidemiology for this research pertains primarily to the forty- three year time interval. Future case-control cosparlsons will include^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 |oc-A o "t occupational and medical data prior to 1955 and the 4aMWM4ag awareness of mesothelioma associated with fch^^WWr time period (1935-19J^5. 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 fchses digfrt 1970 D. 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 \ A<bL 1 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 timeur (other than mesothelioma) Peritoneal mesothelioma mesothelioma at other sites 6 t unknown sites Total Hales Females Total Mean age 102 (94)* 24 (12) 45 (37) 14 (8) 147 031) 38 (20) 61 (62) 62 (63) 20 (18) 13 (11) 33 (29) 58 (59) 29 (21) 175 (US) 20 (14) 92 (70) 49 (35) 267 (215) 52 (54) 59 (60) Perrtnt 'positive'^ histology Percent autops>ed' (9S)\ 93 71 (85) \ (38) /f 35 (37) y94 (97) \ 89 (88) 84 /a6) (93) ' <33 (41) \ (45) WHO (1976) SECni ield Ntaaber 19 (US Department of Health, Education, and Welfare, National Cancer Institute (1976) f (hu. lidfhw. deceased) >100 Ntaabers In brackets refer to the period 1955-1977 4 A005S3 Into asbestos exposure categories for future case-control comparisons (sample from listing Fig~. 1). A00524 r- III. Results Descriptive Epidemiology ..</j-i The Wafli Incidence rate for mesothelioma in Connecticut is 2.I/million for the years 1935-1977. arijuulud lULllft-ULL flutes 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. 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 302 of the cases resided at time of diagnosis (Fig. 3). Since these locations have comprised 20-302 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 -y --Jj ft' far (LMA). All 6 areas exhibit a similarly increasing* incidence^tfith the Bridge pert LHA Lilli lllgllUbL uvuialt. The Stamford LMA's mesothelioma rate shows aA cite* sharp increase since 1965 (Fig. 4). A005GS AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR OF DIAGNOSIS AND SEX 9 RATE/100,000 -- ro oi ^ oi o> oo o o o o CO CD 3 *1 AGE-ADJUSTED INCIDENCE RATES OF MESOTHELIOMA FOR CONNECTICUT MALES BY YEAR OF DIAGNOSIS AND LABOR MARKET AREA ro oo AY T r\> o T t------- 1-------- r-------r T oo 0> <& oo RATE/100,000 ro * o 'o 1935-44 45-54 55-64 65-74 SLIDE REVIEW Jhe.se. dliucfiptlve "re&ulCS"'WM$3^te^coinp-lctenesa and accuracy of case ldintlfic nfl-- gal uy pi**- 7-<*j ^7 fu. <. .uiuitii|i i,- >ii gnus n p hf snap- ouuuml*^ --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's9 despite Wu gun's ropoet-Of 'hlMLUluglLallj proven cases of pleural uiejuLliellUBia associatea Wo^M^T with Capr,r-----'.dollto asbestos fleldo in Be. Aflra. Ms widely publiohod y*lc>(<a`z.ej Cmp\ liuMiNIl Gaf* ^Tr> association o^mesothelloma with asbestos exposure/^aMwer, created the pw be rvhoduth** ^ potential i**- diagnostic bias* In addition to its rarity and the subsu.que.uU laLk'of awueanasc,epositlve ofa* diagnosis of mesothelioma is^complicated by its confusion with other forms of cancer. (Dr. Vldone'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. the light sf-thooe-'diffiaul-tieyUt^ 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) A < csue '*aJ txa m<*td of the cases, no *-- at time of diagnosis, sf fnoi&uJ 94it while available speelmeHS mTyfren blupsj UTT3 & e Llsauu. Overall only 44% (105) of the 238 deceased cases are known by the CTR to have been autopsied. The percentages for all categories, except peritoneal mesothelioma, are low,ranging from 33% to 40Z. These results suggested the advisability of a case review* -which was faaa<h1 h pi ttf pat--f pitt M Bf-nl nylral n .f Dr. Romeo Vldone, chief pathologist at St. -- /<->- A00593 Raphael'6 Hospital, Is presentlyjbviewing the medical records (except oc cupational data} and slides ve have obtained for cases diagnosed after 1954. oujM~ Cooperation was eilaitad from 37 hospitals, of which 30 have provided us A with the materials requested. (Dr. Vldone-Summary of Findings) A0060C c ~J * <; for Cos-*-* 6 ^ s Tf ^ <-* j . C. J. KM u*/-. /Vv __T ft[<r s -TW. vw^. o-t. J Pfau.rvJt kW> cc ^ fc'/fwIiV/* ^ t' 7 _.'... J_3 _.. _... . 3>__ _ 3__ v tVzrh fa.'c. 1 -n. UnfaCS&A /<rt -- -J V... .. ... _L._ -- 1 -3* _ . _ 3 / _.. .. 1 1 *s*A4t*s ct~ jh-*r c*,`4k S' ..... yy..... 1 h --, -- .... J -- .... .--_._ -- - - - - ---------- / -- Jj . f. -r$ ( . . .. TL-fe? _____________ W:., "^ 5 --------- ~ " 3 ....I_______ Jl..... 2 Xo 2C1 _--... W M.&. -C/f7c) S <-l r g . - a^ob^ >) . ...o.r pS y ,t^ VMy ^ *<- D-- ................ ........ f `J j A0060 1 /^ r ^ "V c*. `--4 sw*xe^' ^jt /f3*~ "/f'77 Y%.-.- **lC<^ ,V| *" *- <i f*^C ' ------------------------- (,> "T` "" cv" - "TV/ ^-) r77--" ~<^/ " nj ar AiLdEC-2._____________ 9 \ S /A^ A* I o f ar *o r i ?/ A/f / 'V J> S f "faL^-tC. C . -tf o- to & y < < *' Ccv-^jfl'lc^i. > KV~~ .................................... iuu4* Ii kt'es ** jr*rf--rt*** o-c/iv,'/'/'^ bet tf. fes-rf * / j~f C_ / `aes.S ^4 titter* /'O'W. Ci / R p-Y</" *f / f^c^r^5 j <o*- crvi Ctj / 7j% o "f 6cie-S, // -^4 'F*r~ *+* e& g/+*JLz__ r^N r^JL ^ L*^"^(5* tw < V* , C* rWa-/ i*-* /*. f^^ji - ~TL*- p-erc-ev*-/*^ 4V^c<^-e -f^) j j-r ^ i' * fvr*<MM i'/^ '`3 *&*?%, /Hp jv-c. t' t ^ 7$J 2 "2-0 ^T" oLO " -4. ^ r // **-- jp/&^r<f t-l* *^rj^ KiJf ***lS. j /7ST-77 ^ / //-- A00603 References Bruckman, L., Rubino, R. A., end Christine, B. (1977*) Asbestos wfl Mesothelioma In Connecticut. APCA Journal. 27, 121-126 Brucknan, L. (1977b) A Study of Airborne Asbestos Fibers In Connecticut. Paper presented at the Workshop on Asbestos: jufMrHMons and Measurement Methods. National Bureau of Standards, Gaithersburg, Maryland .-Bruckman, 1. and Rubino, R. A. (1978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 28, 1221-1226 Price and Lee Cltv Directory (1890-1977) The Price and Lee Coopany, New Haven, Connecticut XL S. Department of Cornerce, Bureau of the Census: 1970 Census of the Population. Alphabetical Index of Industries and Occupations (1971) Washington, D. C., TJ. S. Government Printing Office . .f World Health Organization: ICD-O International Classification of Diseases for Oncology. (1976) Geneva, Svitserland AOQqq4 .VswiSiSS1 M- Hilton C. Levineohn. Corporate Medical Director, Raybestos-Manhattan, Inc. Lecturer, Tale School of Epidemiology and Public Health (addreaa: Raybestos-Manhattan, Inc., 100 Oakviev Drive, Trumbull, Connecticut 06611, U. S. i.) J. Viater Meigs, Director, Connecticut Cancer Epidemiology Chit and . Clinical Profesaor of Epidemiology, Tale School of Epidemiology and Public Health (addreaa: 30 College Street, Hev Haven, Connecticut 06320, 17. S. A.) Mery Jane Teta, Associate in Research, Connecticut Cancer Epidemiology Unit, Tale School of Epidemiology and Public Health (address: 30 College Street, lev Haven, Connecticut 06520, U. S. A.) A0060S //_ 1 MALI Gl'i ANT MESOTHELIOMA' IN CONNECTICUT 1935 - 1977 by H . C . Lewinsohn J. W. Meigs M. J. Teta A00629 Prescii laliuu Lu tile fro tin ct icut--T li o r a c i c--6-oe-iety ,--Nuu amber k , -i960 2 Malignant Mesothelioma in Connecticut 1935-1977 by K. C. Levinso'nn, J. W. Meigs, and M. J. Teta I. Introduction and Aims The combined sex age-adjusted mesothelioma incidence rate for Connecticut was reported in 1977 to have increased ten-fold since 1935- 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 1972). 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 SUT>C The CTR*h as 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 Ao063c 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 195H (Table l), and controls (6oH) 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 (1935-195M. City Direc tories were searched for job title and name of specific employer or industry for cases, controls and spouses at 1, 10, 20, 25, 30, HO 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). AG063 1 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, 19&0 ) 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 A006 3 3 6 in the same case. For 12? (.32) of the cases, no tissue was examined at time of diagnosis , while the origin of available material varied. Overall (.1935-77) only 1*1*? (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 1*0? 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. 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, in cluding 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 ce 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. U% are possibly mesothelioma and 10.k% not mesothelioma or excluded from the study. 6.6> are still classified as "unknown". A 0O G 3 h 8 TV. Discussion Although this study was initially undertaken to discover whether it would 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 low autopsy rate for the pleural mesotheliomata and the inadequacy of some of the pathological material available and used for diagnostic purpos es. 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 ft 0 0 6 3 6 9 stored at the CTE (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 12JE. 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 80-1^3) 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 A0063 7 /. X 1V- \Li < \ @ \-G.u` i c 1 ! /"7{ j ll 3' 1 r*,., K K-v V_- v/3c/fc C3; V il., 7/>3/5- r r: . r (3' V'->; 7j^ ?jO L L_ i ' ti / \A, , L-'-i O L:- .3 r O' / i\ \^ U) M ^^ \ L^.; G/.V^i ^U)UrO, v\ t;Q^A 3 - v- ^1 > --mJ ' ' ^Jjl3sc - V \1 ^<L.|_^rX>'Or' XAuaj*^* ',;^A_ 3 '"'^J ^uXxj v^-juAU L{ |\/"7-/ f ! _- 1 | ((7 i^ i j 33 1 ' "7;/32. /k I 11 ' , \`'- 1: vl-,. a 3>< l^rAt-w - s~ v -----" O -^!' V' U--U.U. 1\ . ?v u_ 3) ; 3 *> ^-UUvh. O <3' J 1 j^O J |&Xww c7 ;(^/: 3 <o >eu /---\ Oy 1^-3 S A00638 r'T? 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 apnreciate 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. A0063 3 New London Labor Market Area Town Old Lyme East Lyme Montville Ledyard Groton Hew London I.D. Occupation Dx Sex Site & Histology 675092 At home spouBe-atty (1966) F Pleural mesothelioma 711723 Clothing merchant (1971) M Peritoneal mesothelioma 781723 E.B. Safety Nuclear Eng. (1976) M Pleural mesothelioma 792536 Architect, retired eng. Past exposure to some asbestos long ago (1977) M Pleural mesothelioma 793335 - Housewife spouse-truck driver paper 6 board co. (1977) F Pleural mesothelioma 761292 Painter-glazer sub-base (1975) M Pleural mesothelioma 200401 Landscaper-Gardiner (1939) M Pleural mesothelioma 501121 At home (1950) F Pleural mesothelioma 693627 Supt.-E.B. machlnest (1968) (3 time periods) M Pleural mesothelioma 779762 Rigger-E.B. erector-E.B. stevedorerailway (1976) (2 time periods) (1 time period) M Pleural mesothelioma 10 Cases 9 Pleural 1 Peritoneal A0064 C 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 066ll , U.S.A. J . W i s t e r 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. 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 - c. Beferencer Brucknan, 1. (2977b) A Study of Airborne Asbestos Fibers in Connecticut. Paper presented at the Workshop op Asbestos Definitions and Measurement Methods, Rational Bureau of Standards, Gaithersburg, Maryland Brucknan, L. and Bubino, B. A. (2978) Monitored Asbestos Concentrations in Connecticut. APCA Journal. 26.1221-1226 Felton, J. (1980) Letter to tbe Editor. JAMA. 2hl ,1675 Kannerstein, M. , McCaughey. V.T.E., Churg, J. (1977) A Critique of tbe Criteria for tbe Diagnosis of Diffuse Malignant Mesothelioma. Mt. Sinai J. Med, E.Y. , L 8 5-- L 9 L . McCaughey, W. T. E. (1965) Criteria for Diagnosis of Diffuse Mesothelial Tumors. Anpals of the Rev York Academy of Sciences, 132 (Art.2) 603-613- Price and Lee City Directory (1890-1977) Tbe Price and Lee Compare , Rev haven, Connecticut Public Act 80-1^3 effective January 1, 1981 U. S. Department of Commerce, Bureau of tbe Census:3 970 Census of the Ponul at i or.. Alphabetical Index of Industries and Occupations (1971). Washington, D. C., U. . Government Printing Office Vagner, J. C., Sleggs, C. A., and Marcband, P. (i960) Diffuse Pleural Mesothelioma and Asbestos Exposure in tbe 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, Svitzerland 40064.' 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. Table II-ana III illustrate ene. ef trie jor i'ej deficiencies in the data available for study, mnTa9cty the low autopsy rate 7 fabcltfibif 9 AggrNfor the pleural nesotheliomata and the inadequacy of the types ef 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 no inquiries art made of patients admitted with 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 is 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 mesotneliomas from the Veterans Administration files, 1955 - 1977, and mors, not mesothelioma, recorded 1955 - 1977. his disease , A ppear< d to /nt :o- ent increase aftern 1955, A00606 Comment on the significance of the findings or. the slide review. It is evident that until the physicians or hospitals investigating cases of 00*f*tfcMJ * of oh malignancy aooreciate the importance of environmental facts A the etiology of these diseases, no attempt can be cade to apportion the blame to any particular factor unless adequate histories are available containing complete information or. lifestyle, habits, hobbies, part-tine activities and details of occupation anc industry. It is also essential,particularly in the case of a rare tumor which nay present diagnostic cifficulties,to obtain sufficient tissue for study before 44V, |V mjxfaclaal the final diagnosis is cade VTnenever a tumor is found where m> association ?nrsms between it and a particular occupational or environmental factor, ever}- attempt should be cade to fully coc cent all the lULirt'tl facts and tc subsequently verify :ne ciapros is tv rears o: full autopsy. 40060? * t- :rr.::t.v. I .'-it If ;r\ e;-. sit-atu: cr-ei.'t-rc t:-t site of a t.ai.-tnr cf ::m.u lit,r f wt . iff- a:,C a:. up;>i" iito.iff-. iotal.cef r.erpt? simpjtx tr.tertior ir. trust instant e? where ctat: has r.i. r.tii 5 .it- hac :-err trtatrc for cnronic s. novr.:.- of the i.nee? with oexa- r.-etkaaorit ir. ousape? from 0.5 u, 1.5 mg cair. imermitientlv for let' years. During this period, lie skit of her fortarms became enremely thin, and she . experienced several episodes of subcuta that ha: occurred or. my uppe* i:t resc.ce: from, iiuimor.ary cancer i * a and had not heaied to- a; proximate:: j the rack o* peritoneal ir.esotr.elit m.a one year. It was removed by a Mohs' i it is lrr.pcriar.: to identify tne i:ss_- surgical procedure at a local universi aiterations directly attributable to ty center, and a diagnosis of basc- I occupational contact with the respira squamous cell carcinoma was made 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 dymg of ashes te transported to the x-ray department, where it was noted that she had two superficial tears in the side of the left forearm with gaping n-.arpns Attempts were made to suture the skin edges topetr,er. but the sutures tore throupr the slue. The edpes were held U/pether with strips mentioned how unusual the lesion was. inasmuch as there were not supposed to be such things as bascsquamous carcinomas Both wounds heaied without any unusual event. After the first occurrence, 1 con sts 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 all physicians or house sta5 caring for such patients urge relatives to permit of ster,ie. tape tacted Dr Herman Pinkus in Detroit, the examination These procedures Or. one other occasion curing her hospi i and he stated that there were about a will not only aid the beneficiaries bu: tal stay, s.mbar iesions developed during dozen cases in the literature at that will also prove of worth to physicians the course of transport to and from her bed for other diagnostic procedures These iesions failed to heal during her hospital stay, and gross evidence of infection was do: noted Comment--Transport by handling of the forearms, even though careful ly done, resulted in serious, poorly time. I saw him at a meeting shortly in familiarizing them with the find after the chemotherapy, and he com ings characterizing a greatiy under mented on the unusual nature of this diagnosed job-generated disease. condition occurring more than once, Furthermore, such postmortem though he was more aware of its data will aid ir our knowing what occurrence than he had beer before. I actually happens to a worker under There is an embarrassing situation certain conditions of exposure and about this personally, and that is that I will help to rectify the inaccurate healing tears of the skin in this overweight, weak woman. Even though extra care was taken after the initial episode, there was recurrence Ir. this case there was no complaint or ]I dissatisfaction expressed by the pa tient or the family, but such episodes 3 am a dermatologist. I There were no other form? of ther- I apy used or these iesions with either [ surgery, antibiotics, or photodynamic : inactivation, nor air. 1 a smoker. 1 , have had an occasional localized ' herpes simpiex infection curing the j conclusions drawn from the current underreporting of occupationally as sociated disease. AM &**** F-r.'aa KC O' Camomi* fcenoe o' fct+oicsetr AO* An0tk ha'e the potential for risk of com pensable injury. Certainly there have beer allegations of hospital-based iriu*y wt:r. lesser justification. past 2(' years 1 Safety of Ipecac Syrup i u; I Allp3*T U0i4 G'our SC | Tc Eiuor--Os behalf of the CAicajJC Americas Association of Poison C:r- 1; would tie prudent for physicians hospitalizing patients who have been The Autopsy i troi Cemers. 1 am concerned about the titiing of a recent J.AJIi.4 article, receiving steroid therapy to place a warning note or the chart advising hospital personnel to use extreme care when bathing, assisting, or transporting such patients. LsaT c-*: m: and Asbestos Exposure "Death Resulting From Ipecac Syrup Poisoning" (243:1927,19S9). I am wor To Ot Editor.--In the article entitled ried that the index skimmer or scan "The Autopsy. Past. Present, and ner--particularly if he is of the older Future" by Ardersor. and co-workers | school reared in an era of gastric (242 1056. 19791. the fall in the rate of j lavage for management of poison Cal'' autopsies is decned. and several ings--may inadvertently conclude cogent reasons are presented for a that the typical emetic dose of syrup Carcinoma at the Site of He'pes Simplex Infection return lo the previous high number of such examinations, a goal formerly pursued hy dedicated house officers. of ipecac was responsible. In reality, the dose w as three to four bottles per day for three months --thus repre T(' ii.` Eci:o---The Jorp.NAL recently One additional need for postmor senting a long-term poisoning. pubbslrd a letter entitled "Carcino tem reviews has been giver, emphasis As noted by the authors, syrup of ma ai the Site of Herpes Simplex in recent years by the epidemiologic ipecac as an emetic agent has a Infection" (243.2396, 1980). My letter and clinical information gathered in remarkable safety record; its current is to note further the occurrence of connection with the asbestos-related availability o\er-tbe-coun1er and in such a situation. I personally had besoscuamous carcinoma develop on disease. Because workers are now the home pi.-nits ar. enormous saving beginning lo present radiological and I of needles? visits to emergency rooms to occasions The first occurrence was approximately five or six years altered physiological evidence of the effects of tie inhalation of free asbes for the treatment of accidental inges tions J think that it would be unfor ago at the site of a vaccination for small pox that I had received for traveling. After the vaccination site tos fiber, years to decades after initial work exposure, a problem in work er's compensation adjudication has tunate indeed were the inference drawn that single emetic doses were risky. did not heal for oDe year, I became suspicious and had it excised at the lota! ur.hf-sity hospital. I was ap proximately 55 years old at that arisen. The changes elicited through clinical study, although present, most oftfeD do not have accompanying symptoms, cs yet, dot have they Wumm 0 M3 nff M0isa' Ar.*n;#r AtanpiaiiO* c* Fouot* Control Camara tune. caused any disability, as yet There Soatlw JAMA. Oci 10. 19S0--Vol 244. No. 15 A006C8 Leflers 1675 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 1977- AU0 u 4 U IQ -*4 u a) 44 (0 2 O' in 0 u in H o < u 44 bo Cu CJ 2o M H EO E-> 44 < u <c0 M< tu t--t 4-1 tn 0 cn <5 0) u H > 0) OS c 0 s m a (0 _ l u 0 + w E O H m (0 i-4 E E a> 0 0 H H 44 rH O a) 0) w to <D E P 44 2 0 n0 O pH w 44 zE a> a> 022 H 0 a> 44 rH > 0) a) r-H -4 ^4 O m c a> s 4-> 0 m 0) 2 (0 O i-i & H (0 tt o cl to O l-i CL 2 44 z0 0c a; c D H fs m r in VO Table 1. Sax, age and d ia g n o s tic c h a ra c tc rla tlc s o f 229 caaea o f malignant eaothelloma and 38 o th e r p le u ra l tunoura diagnoaed In Connecticut 1935-1977 N^ co o cl e --O-v4 I lO 0 01 a. xt o 0u) V Xauu X e VO orv hwi X O x X i ea sv 9Vu i ui g & c moo & B .o6 o B i tTable tiaais lo r Diagnostic Evaluation fo r cased o f MallgtiOnt Mesothelioma specimen from biopsy! frozen section* surgery* autopsy* D and C xh CO 3 <5 r*. I WD Tbl J i P r e q u o n c r o f A u t o p o r f o r Caeca o t M a lig n a n t M eeotH eil afid P le u ra l Tuanre o th e r than H eanthelIn n a f)laanoee4 in Connect le n t, 1915-197; I-1 4 s s s ?? 4a ^ 9^ 9 f* CD <9 9 9b M 2~ JI ~ to* SI m m* 4 4Tb , J^ ^ JI SJ ** ^ * * 9 ie_Sil] --* o w S * 2 Si 2 SI 4 l 9 *> ** 4a 9 to* u u u s^ frs'-selae m* m* mo ** 9 9 C to to. xmw e K eb 99 U) b ^ e oj *"i e e c ** u V to 4a 5 9 e 4WS*S3 *** ___ ^ a - * --* ^ -- ^ 4a 99 6 64. u u 99 4frS a 4 99 4M < MO u arf fa K4 t 9 C It U ogee 0999 ^09 9 9 to ^ U to to 2" > --b tot 99 9 ^ mm ^ fl 9 -m 91 Vt toi 9* toM D to> m 1 -1 to 9 wm At X II rs 2 I 8| CD 3 <1 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 1977- Au o6 4 u M w (X >* u o -3 in o 0) X to E-* <u (X VO uo M wrH O E-i w < Eh Z <D W zW oa a >< ua w< <z CD M X zw oJ t-t W E-> D < tu CJ w tM X (0 < u dP dP dP dP VO VO dP VO VO O VO in (N rH 0 z o VO 00 (N rH rH A1 A1 0 z Psl CN 00 m 00 <N vo in r~ (0 E 0 H 0 <0 rH E 0 E 0 0) JZ H H HJ rH rH 0 0) V n 10 r J= 0> E 4J 0 4J 0 0 H 10 n to 4J E a> 0) o 0) c 0 O H z x: 4J iH rH V >1 0 4J 0) i-H rH rH m P 10 X xi xa J3 0) 5 u 4J H <0 0 H -H 0 XJ nO uP XI c n 0 4J M o iH 0 C n Cu a- cu z n a iH u ^H rsi r> in VO dP O O rH VO O rH vo o rH rH (0 P 0 Eh .J J - ............................ 1 ................................................... .... ` . . . 5z^3z3z3z3z3z3z3m33z3z3u33z3z3z3z8z3z3n3z83x3z3z3z3z3z3z3z3z33z3z3z3z3z3z3u3u33z3z3t3z3z3x3z3z3x3z3z3z3z3 00 3 <1 SSS or ^yguJ 3Z 1-0 o-- --z ugy AL.W> X =- ZZZ 53 g-aotooroat--^ xor A. -j gJ ^OAkLX liK U1 z TIZI3JZ uuggoK *>*r> Zj x*f iMogu *-Xs u o or OuOOiOU v WK-K^i N Ar'w^2.i^nXi_Ui X~i i XPMUb xz u--j*Cl ZZZZZXUO I^SooQmjS oooi ^IJUWJ^O txa Jww***uga-ri O 4*_ ggw i^-- Z4-- X "-- Oa-- lAiA^ <53oeOi'* mj *39 gO^k'k 4--"^U <1^4 &o --^4t Zt>ZkZOu.wa zofdzlcd:a-o#--^ --wizr- ODDZ< roooz *^aaa. UzoUaVu>w^ j*MjWjaMMutMMj 4U41rjOr*' 4gg<iXUrO.z*k^.:/QMsCA^zoruuU--JgUu; ockioctrocw^u*,UfU Xtf^OT4^rgMg 4mfI4f&S^S^SSM SMO.^OtkOtcZtOus4s^ sBPSSs-o1*s*e Ai e<swcwssAsfsibctskePs^a&o^ojg^geMs^NNNN*w*gierQo^c.a*ac.CaLc.aacor 0P>C-^0C3f00i^Or>r>^OOODfy^OOOONNfg<VW*V,vN<rv^lfta*------ w4**W*jcwy--.ww-- II I W n- -i --i f^MUMi ir'V^jnir j~w^--mi anjrii^tnjT ^r~i --1i--i----------~i ! n ninnji---------mm - --I 'g"0>Q4ff>0 in ....... 0>V<99>^^,*l*^^9>^9t9>^\8<SSOMOkA9>9>><4^m^4^C y9'W%tfl9'OOk*Ot9`Pk^9'-SOk9'O''00*P`SA(^ r* ^trgo^cgvgr*.^^nw>o^*iow%^orrfgvn.y*>* ** 0; U 3 fcu MZw_>A^mg2Zm 2aX-Jl-tAjJ3^..J7w_u_>^I>4*xXJ oe 3a Ww or or * ui a or u. 0C ib(k ^ Ta or +z-o* Kfryt or Mw*U^UU 4<0^g X*X*4j Xw-fi xu4(ZZ.zUXZz^iJlZyJiliZ<2to&jjxx^4_n*jiS_^~*4_dLw'-_OQr_5u_du.3_^lii_5%-M*I_I>:^_Mkz'>'MJi:'^uJijx">dx3o^^Uaj[_M<_^x&_;I>0g_jIa>_a0g^I>_<u2x__-^roIXaOukU-*--x-**Ili--*-jU.-w--Xja< ogt>r iJu --Oui uu -3S3 Z^-- _r _a .4wlr.m--bj).jl<4raX3i4iBi"jz--4x<< * g- x Mia * -# ** a5x"ao>*^^ooougw gg W^<^UJ*X***" uJ<sj*o4l 4^OIjaZii*j3.s"SS^tZiXo4ZJ^wyriMni<*|ij A. X .HOIVIO^" --*403!v3 ni4i itxi'QOSMlmmi^ln* ^wwwvi'ix rrn- I~"-- rwrynjr* #nKiV3* M<iw *w.<> iftv w.<wim3 --*.An<--ii>V Nx wMx~m-<x.v.v<1~>m^--n--n---J-->----M-----Aa^vr>*3\"f3te.3*7.BxtrcSvsv-x-A-*-ax-dW-xo-x<-Jx-X3-Sx-3M-x-J'B-Nx)--^*0'V>w.3.t*3iilr/w34i i^0wi/^>0v0i3*<-0--xJ>-4xr-.<-><--x-3M-n>-W-M-i>t3isMtr,f<vn.^rS.f<4j^-^U--^-.C---*j-r>m--x-9->-Mo^.mW^ru<.*-*.*nx-.*n"*'*mx-xnh.xnih,i^m9*..X>.*lwMx.*ar* 4 AoE-ADJUStED INCIDENCE RATES OF MESOTHELIOMA IN CONNECTICUT BY YEAR Of DIAGNOSIS AND SEX RATE/100,000 fe V 0 09 b* 00 1 ------1--------1----------1--------r a BBS i T3 t-**c "1 ro ro :55555555555555555555555555555555S nifmm 5555555555555555555555555555555555555555555555555555c c: r~* c~ -F*' \ (Sulv CC **<-* V- -- iT'- I--must apologize to you right--at the outset of-tM-s--^ba-lk. Bein^.-a erai-gner--I have been -4,-ivvolvod -in -something -e-aH-eh-FEEX - the Fffr|orni nf T.iflanjting--Examinations -Board-or some thing-and, I just finished the oxnms last week. This ic th? second time-I have taken bictrhrmi rrtrjr nnri nil__the., th-i r>gg th^i-bevn n,ppf>n-nra nn thic * no-no since X graduated. The time I have had to prepare this talk has not been very great and I apologize to yon because what I am going to 4*- Seod " a paper that was published this year in the British Journal of Industrial Medicine of which I was a co-author. I was only a e^ipio^ej co-author by virtue of the fact that I was able to4o in a factory in the United Kingdom which has preserved its personnel records ('>(' turn of the giuwn the/last century oiwamis and which has good medical records going late Ufusie back to the/19^01 s-early 1950' s + aimeL which had previously been studied by my predecessor, John Knox in association with Richard Doll who noi*i Kc *< J Z O-f:4 is the.Professor of Medicine at Oxford University whom I am sure ^A a Sir know of as a leading epidemiologist in thro field. It was Richard 7u'Ol-1 i Doll who^in 1955^based upon studies of the population I am about to describe to you^S- MU niLliBBP4^5555 proved that there was indeed an association between lung cancer and exposure to asbestos. Baffri ' i "nn i 1 111 I , I think it is always worthwhile to go through drnW tho old- pat bailing uiL"Clru44im"juu it? L^lliir^what asbestos qmJ <0Ne. tt-o r't'WisJ is well not oxaotly but just giving- you some idea of what vre are talking about, ^ali-ko-tfee-ghairman of Turner & Nepali} the company which....! .AMifikad fnr whioh was -large company with--gO-yOOO in--Ue United i.-ftgdoa"<>nd-many-suboidiarioe throughout thc-wor]-d inalwding iiii'ries'~iir "Ccgrada1,' _ , v/ou< boc^A5wncl oUfn will men be ( .. man Plato! and Southorn Rhodesia. and faetoriie< a in lay countries., fee Ssh c?r A A o o 9 o ;i of \'*\Vo^i h> i' *> Chairman who went out to Rhodesia to see for himself where the a asbestos came from and after breakfast said let's go and look at the plantation. If wc could just have--the first slide and the lights I then i-^euld rilujliafce tu just -bi'lefly that Asbestos is a ;lo> u fibrous mineral silicate and tiwt there are a number of varieties that are of commercial importance. I am not going to go into ai* the argument^ ipd t~v,~ about the differences in biological effects which exist between the various forms of asbestos. Chrysotile asbestos which comes from Canada, Southern Rhodesia, the Soviet Union, SuaaziI**1 A at J be is Cyprus, Couth Afriee-, United States,/the type of fiber which composes about 95% of the world's usage of this material. It is a hydrated % 5 rr> . r*. i magnesium silicate. Crocidolite^which is a blue .pallet fiber^aomoc' i's fipw South Africa at the present time from the Northwest Cape Province and from, the Northeast ad Transvaal. It efcused to be mined in Australia but that m-iftiftg no longer takes place and there was a H\e t'r>ode<Kfc disastrous experience there with regard to aaoeunfre of mesothelioma among the miners. ; CL , Amosite is not^an acceptable mineralogical term^ u o<\ aCtxr jt,oo because it merely yteaxik: for Asbestos (mines of South Africa X4 ^ f i IVx and that is unique in that it only comes from one part of the world \.<s-. r /' A the Northeast Transvaal. The amosite and crocidolite _ 'Cock from the Northeast Transvaal oftened occurn^d- in the same seam itr the A a*o-el: and therefore it possible teg--wy that amosite -s may be v\ct vf(a. Econtaminated with &oac crocidolite* That ic possible. There are deposits of amosite in India but I dorryy think they have been commercially exploited yet, hut there are-some there of that type ef fi-bor. Qft'o./c i flirt nf the eummintinate grunatlo (Jn series and just to digress for a moment the importance of the CG series (or the fact \that amosite is part of that series^became apparent when Reserve fining ^ompan found/ itself eahattled' with EPA, the State of AGO 9 04 3 tf. Minnesota and various others people regarding the dumping ofA tailings^ \a ror\ Vr .-- ' ^ early } from its, mines in Silver Bay^into Lake .Superiory^d/DgT-'Selil&off A waltg'Od into -Minnesota and waltaod oat again aad really upset""the whole--apricot thore--and that balLlerTb still- going on with Ra-fre-rve Ifc-e fVfcCi in rrt +01 \,/v7 Milling. I am sure you are familiar with that story, ghat -was CG f H\ tlof Off.iHzvVf is similar to commercially used amosite. Apart from the fart / that a lot crf-the fibers--initially diooovorad were.Piatimalie eKuTgTb'nb /^nthophyllite isn't very widely used in industry. It's one of IcPcu-v the oldest aiaed asbestos fiber* particularly^ Finland where for thousands of years it's been incorporated in the building of j. a. baths -If you like to go lulu'that soil uf-oreupatioa. ffowavaj*, i-t isn't taiiibly important. Biologically it is^very vary- interesting CiW because no cases of mesothelioma have as yet been described with tho xOE 7 association anthophyllite exposure, and-wc ean forget a-bout -the t" O r iS remolite which isAoften found in commercial talc or industrial talc. Juot -to give-yeu oomo idoa--of really the fact___thai.-.fihrysnti la ...<wvoi4ollto/i-&--bluo ameai-ta--irs-aort of an in betwoon celnr. Thnse ara holh iron -oontaining -is various anthophylllt>e--wfr-i-ch--i-o -also An . 3 >Nt ->J -'QP. <0pcri a mine up "in Panada)ohawing-what hao happsdned to tho oount-ry aide. This is a composite slide aad-thio io what we did with asbestos "TrC S cros^cJ Qf\d in Rochdale in England, fhat'a a rock, it wwc sponod at the mine of A ^<? to some extent, TJ.t was further opened at the factory in the process i[ fvfmeJ into nf t Thrift iw called fiberizing. awd carding it wft8""Usod ao a sliver and ften o.: -spun into a yarn.and that ia tho prcoooe--and thonHEhe yarn would bo- ,s Car\ woven or sold to customers. Cloth A be used for various purposes OS r 4 OVOcW in>u!o-.0-"l Sef'Vo/f^ ls> *^1 Aohfj (/V -it! (yt fwh'en *>ra\eA iVs, V1Cvi'XW '-U. , Aamthar think I think you should appreciate -i-f -you will ro-ad in the pgpo-n -i-c yovi v.r,-,rQ ?vn + ^ rTra^ 11 1m the fact that in the United Kingdom, Regulations were made in 1931 which took affect AOOGCb 4 in 1933,,xl^*M&d ^rior to the making of those regulations^which were called the Asbestos Industry Regulations^ and whieh--theref ore only rrflHy tn that a 1 ^ p i a impn-rtant frnm the p~int nf view nf what happens ^nhsefiupntly hnweyer those rpgnl-q-M^ns Pculted aftwr a study whioh was conducted by M/irywhothcr and Price omJ \t became in 1929 and published in 1930 whieh is one-e-f the neg^ famous rfeudy the history of the ^ th-s g fi nlfi nnd- i n a milestone in/KHxkxxn: British asbestos industry. What they found was that in people who had been employed for 20 or Jpg-* more years, 8l% had pqUon3<V fibrosis. We are talking about a^hpgtn^yw^-itl.n i mpnnt.^nt, t.n vnmomlnr> w> tihut, ^wtnrir w a 20th Century disease. The first case of asbestosis was not described until the beginning of the Century in London by Koniac>ug - and therefore- this io-a 20th Ceiil/ury uccuyaliuna'l "di-seasw.-- The first evidence that exposure to asbestos was going to cause a problem to the health of w^*e workers was the finding of asbestosis and the regulations that were made in 1931 and that took affect in 1933 were designed to reduce the incidence of pulmonary fibrosis. Lung cancer was not associated with asbestos exposure apart from A speculative case histories that first began appearing in 1935* No epidemiological study was done to confirm this suspected zxxbb a association until the work of Richard Doll in 1955\ Although the Me^'W^i-cq ' same Morrywhether in 19^7 had shown that 13$ of asbestosis cases diagnosed in the United Kingdom wereodying of lung cancer or had died of lung cancer. That leads to another ~pr ml nti nri. npnin whi rh ^s-'' -- (fe Jpvf.it>>>' 1. flon-Mi intend .dwell up an and feha,t_|,s where asbestos is & a Car\ prerequisite for the development of lung cancer or 4)hat lung cancer occui in an asbestos workers without asbestosisio ne^orthotooo-an r^r,.a.an. "Tllj TIT TPHny fl V glliriT 111 ~ especially in view of the known multiplicative effect which cigarette^ zb smoking has on lung cancer in asbestos wo^k^^-.-jQ0 5 However-,-4--flkoy- LhaT~s Imply tirpulnl uul whal Lhe-situation was Ir 1*2*? ,, uj+v. -Poga-rH tn .ao^ogt.n^c!. 2kx Pulmonary fibrosis o*-. wsvv-^Vj crippling and killing pnnplo wntl 81% of thoseAwith more than 20 . years exposure, ir~r" finin ,'<. If in 1975 onlyO.77 or0.8$ of the, group A 1' *' By comparison .v \o?o compared with 26.2$ were found to have asbestosis and the 20 year and over.fcfce incidence w-s-re ic:.-s A down to 5%,\riinh obviously is still xh unacceptable but what you Ike <\ iKu par jV'ja havo-to romeffibcr i-s ^hab some of those cases^ were'in fact exposed (re 1^.2: L;n rK* os before regulations A 4ag and^this wxx a is a table of prevalence not incidence they were there w?<f i and counted. It does indicate quite dramatically that those regulations A had reduced the incidence of asbestosis. M wo go te tire / t-- W^Oif fnode' T<j <Sf>e>v> his co-hort that, we are describing rn the has been the subject of f 3 previous reports and the last of these i*9=s was published in 1968tho one prior to this andThey from dealt particulary with mortality x lung cancer and respiratory disease in workers exposed to the high dust levels which preceded the 1931 asbestos industry regulations. They attempted to examine the dependence of lung cancer incidence -p 0\e papef Thu >"`i 1 mu _jn 1968 the cohort was S) /'A . 'v / 0st>e:^ on t)><^ age and duration of exposure, A divided into 6 groups,wi<t^`th'c>CS ,^3 bwy ipoup 1 had more than 10 years of exposure Xanax groups 1, 2, 3 and 4 W 4-oVal ^ all had more than 20 years but group 1 had1" gruaLei Ilian K) yuar-p A ovpngn-po hafnrp ~IQ33 Group 2 had between 5 and 10 years exposure before 1933 when the regulations took affect. Group 0\ had less than 5 years exposure and Group 4 had had no exposure before 1933* Group 5 was all males and had had more than 10 years exposure but less than 20 with no exposure prior to 1933 and group 6 was all females and they hxx had all been exposed after 1933 for more than 10 years. Tw' - Cam.'. Wow' Wh(?"-yfm iiaok nt cancer of the lung and pleura, .-ymu sac thj ^ u>e^ / ohcervod was* 15 and tho ojcpoetock 1.6 so there i<6 about an 11) times A 0 U9t; 7 ui^***' 6 excess incidence of lung cancer in feinrt group which -be* had the longest exposure prior to the improvements which came with regulations As you gu down you ace that that diminiohos. When ywa get to thic-- (r\ y*j group hwe no exposure before 1933^ with pST^than 20 years^the difference is not statistically signified fibse/Vano* a. That was Avery i-ateresting but the authors were wise and Is hey pointst out that no f-gT-fctereT firm conclusions could be drawn because little carcinogenic effect kz would be expected for 20 years after first exposure and some of the follow-up had not been for long enough. -i-f we juct--go -rough t.wn more wl i dps ripaling with that. f.nhnrt^T- with thow-a -f-i-gureS- horo -wean have the men and women all exposed iia since 1933 and you fa can ooo-tfefti cancer of the lung and pleura xxx there was no statistically t-eGtlyC-e*- ay/! aujtdui significance difference and sn the women there was this diffpppnra- n,nlY 2 cases and it was not possible to state what the {tetiuu meaning of that was^ What we are dealing with here is men and women employed 10 years or longer since 1933* This is--the gerag group with-less Llietri yuai's or 16'to 3r9 jedis andOCT see no dfegence ia-ilie ubljyr veil Lu Lhe -ezperted xala. mil--inc id eraser of lung cancer. !*&' ^ r T In men employed 20 years^those who worked before 1933 as we have imc-h w*tv.\-J ^ Oae-t^' e>;ikLJ. sai-d-boforc 11 to O.&^tll to 1) and, all neoplasms 15 to 3 a4 chnee 1933 3^to 2.9 AA ^ wbr therefore yit appeard from this information. ' that people who had worked since 1933 were asw no longer at risk omJ WcauS* J if you accepted this^ that^the dust levels tiwrt had been brought dowinhad been achieved(^adisappeagce of the lung cance?}) Further more this was against a diminishing background of incidence of asbestosis and as yeaa-ww in 1975 the prevalence of asbestosis was only p0.8% in the factory population studied^ The report published in 1977 is concerns/with the po,a#^i<)33 'gitrpul the post-1932 population mainly^whichI oaid although exposed dust levels A00908 7 XJor^ higher than the present cbsmEsix permitted levels, was employed during the time of improving dust controls and plant modernization. The study is based on 1,106 men and women 28^ women/ and the cohorts ij*6 been roughly sub-divided in the same way except that you will see there are only 5 groups instead of 6ailtl fr-nm lliu p ITU vluu.a g,iwup 3 and 11 have. been eanbiwad. it 'I' think that's what happened. I-dwi't want to go into it tnn r? Tiro fully. A^in we got years in asbestos areas 20 or more, 10 jar-more before 1933 1h4 than 20 or more less than 10 we havs'-^aken" out the less than 5 group frba that and then we have^ysxH gone on so that will be from to 10 ins^a^ of just^J>^o^0 and then we go on to 20 or more with no exposure afte^x^33 and that's the group we are particularly xwx-fcg interestaeKin 10 to l^ai^d then females with 10 or more. Well there^may^be some lamia females whb-^iave done 20 years. We get 3rfi06 with a total of 16,000 person year's-, of observations. Re-examination of our personnel records since the lack last report in 1968 showed that a further 23 workers were eligible for inclusion Ko-' in cohorts 1 and 2 and in addition 205 workers who have completed 10 years employment since June 6 1966^were added to cohort^ 3 > *+ and 5* So the study comprised 822('men^nd 284 women and the followup was until the 31st of December 1974 using the factory personnel records and the National Health Service Central register. of workers could not be traced and 13 Tnrrt thmt 1 -^l 2%) Only 2% recorcfelin the National Health Service Central registery as having imigrated or were not currently registered with ttee GP. As you know everyone in the UK is registered with a r.P7 yrm + hrrrn tn hr; but moat pgnplm rue. Tfa-.im--n.< +h^t p vpry gmall percentage wl ireL. Esjx&ially among tho working population whrr are no1t1 "able p" .'p.-j *-~?"-t-Tnrnt- The remaining 1,071 ^6.8^have been A a0 903 8 followed-up to the end of 1971+- The number of deaths in each group which have b^er. attributed to lung cance-r^md lung cancer includes deaths due to mesotheliom^ami -feta-Brs-g nvmihar--of deaths in oech group att-fibutod- to lung unmoor other cancers, respiratory disease and other causes are shown in the next slide and although it looks the complicated it isn't really. If you simply loplr'at that column -ftf Jvhi ch ^^ the max cause of death, which > i-sA lung cancer and mesothelioma other cancers, respiratory diseases and^ther causes^, and if you will SKovJ 6 * <i' just look at the oneswhich statistically xgHKxxjcx significant^ EH'ji-e you will see that again n Group 1 [which wo know before p-c*a< - & we-had the 1S:0* \ observed to expected ratio) sss. in gxxxp the respiratory diseases again there is a 3-6 observed to expected ratio and all causes the ratio is about 2 to 1 so there is an excess mortality in this population which is largely attributable to lung cancer but some of which is attributable to other respiratory dise^kes which might reflect a xs residue of asbestosis in kx this population. The expected numbers ffer thooo of you who are1 intorooted were calculated from National death rates by 5 yeF periods and 5 Ou,Vpc<? ) year age groups. To insure that the expected 'members7 are not underestimated, imigrants and those lost to follow up were assumed to be alive on December 1, 1971+. Deaths before the 1st of January 1931 or after the jcexe age of 85 are ignored and expected members are calculated accordingly. In Rochdale itself lung cancer mortality risalef y was lower than the national average among tho men which is interesting, n that "This is the ixxt largest asbestos textile factory in the world. W lb Rochdale a population of about 80,000 people aw4 it had a lower than average lung'cancer mortality. It doesn't prove anything but jwu kH iLifi^ for thoji1 iiirl-in if asbestos is an environmental pollutant which is going to cause an excess incidence of lung cancer in the general population k^this doesn't seem to make sense. The A 00 3 1 0 fu n-;. |* standardized mortality ratio xx in Rochdale is 87Aand eigdlar for women ie4^thmfr`'.i, (j959 to 1963 Register ^general 1971/).Workers first exposed before 1933 1 ,e. 1 u ii.ii ak cohorts 1 and 2, suffered a* ---- - from excess of lung cancer and respiratory disease, Rxxxi AA J 0 .Particularly those with 10 or more years exposure prior to 33. 1 i-- ftCrr ^ cmh4 Ithere is also some excess mortality^lung cancer and mesothelioma ^36 observed and 19*^--expected^'Wre P thai*0.0^ and respiratory disease^35 observed^25yfexpectedj P ogiiais O.Ojj) in those who entered after the 1st of January 1933 frhert' s^cohorts 3>aH 4 and 5 combine^). You-eombino those--3, cohorts. This excess is very much less than in the first two cohorts. Wiul It lndtraltfb Is Hub Jui evenXn those people -villr longer follow up now thoaL._pjjasd* who were first exposed after 1933^the longer follow up indicates that there is still an excess mortality from lung cancer, mesothelioma and respiratory diseases. In the 1968 study there was a slight excess of circulatory disease in cohorts 3 and that hasn't increased (27 observed 20.6 were expected^ In cohorts 4 and 5 there was a matching deficit/50 observed,60.10 \ {ote<erce ^ expected. The in-oidiansc that this was probably a chance observation seemed confirmed. There were 16 deaths attributable to gastro intestinal cancer comapred with 15*7 expected. This cohort^ever since it has been formed and sA hao teog*i followed, has not yielded an excess incidence of g deaths from gastrointestinal carcinoma. It is also interesting that in a paper published in the same issue of the British Journal of Industrial Medicine^Elmes in Belfast,following up his insulation workers finds the incidence of gastro-intestinal carcinoma is declining as the gHgxi time goes by and inMie thinks that this might be due to improvements in earlier years, aew -^hcrt fec-is following luliu papula Li am fwrthor riuuiii uliLail i 11--Lime . However this excess incidence of gastro-intestinal carcinoma(Ln^/asbestos workers appears to be something that is related to th^ ,^0^ heavily $ 10 OJCtt . exposed gH groups.aarel Although this group of textile workers A in the earlier years was probably as heavily exposed as any, it has a<-' progressively been getting less and less exposure and tfea-s excess of gastro-intestinal carcinoma has fe never been found in Dcchdalg. think *** ymmp will oiy find that gastro-intestinal carcinoma ObV is associated with it in'-oomo way uiW* very severe exposures. * i*C-)<Vjr That is just my personal opinion. No excessAfor way of theso-4hat is statistical gastro-intestinal carcinoma approached/significanfce in any cohorts cd and no peritone** mesothelioma was reported. To distinguish exposure immediately after 1933 from that under present conditions cohorts 3, 4 and 5 were divided into those first entering or first s being exposed from 1933 to 1950 and those starting later. The reason we took 1950 was because in we regardEi as the start of the \_y -r A modern period in that factory.because J.t was the year in which t* routine dust sampling was initiated. Although -Merrywhether had> way back in the 1930's fcerd tried to give some indication as to what dvd level, he considered to be an unacceptable dusty the instrumentation and the techniques were not available to assess dustiness it rwiaerioally and to assess accurately. It was only in 1951 when the thermal p{e\'pivota percipitator came into use in that ^^imfr g,,,,v'g,^qnflntTy was followed by the long-running thermal pe^cipitator and then, in 1961^by the membrane filter method,that it was possible to attempt to measure wtet the exposure >990--of these people and to control the WSt'f't measurable environment aooopdang W/dust levels rather than aooogdiagic> vi's<'bit best achievable^results,vioifeiy. Observed and expeKted deaths for those first exposed between 1933 and 1950 are shown in Table 'One*.' t-think hofnrp wp pet there, no we got t.hpra . H'l'i 'mil ^nliinli Fi*t ka-pnqpd ~imi * i|'40^nr^hirvnr 1TO-PO - * 1951 nr iate.i`'iui't'g-oanaer .33-4iO 5Q gfr-obcorved "36 'expected" "16 'i.iLli in uo j. rduu. Here we find that the 1968 authors w4r6^ ^ L. wise to add a word of caution about the length of follow up. It had only been 20 years and 20 years may not be long enough because here % and we fead. emerging mu something they didn't find/that is a slight excess -ito by no moans--he gJm. oi-gnifioant g access of 11 to 3--that up havp V'qH p~"^TTi?nnly ^ rti'u.a-niigv* of lung cancer in those persons exposed between 1933 and 1950. What fW* 6 at" f0.6^ about 1951? Well we luiuu ll~sg*iJn. We at have a ratio of 1.9.>ct^ co^rei am; \ That io -o*ri.y 6 cases observed to 3-2 S expected. The numbers owe. might at this stage be. small and therefore this has to be followed ^ up jastA have to increase the numbers and fchE iangih xfl wo have - to but'.' |>. 4 ; j<:j lengthen the follow-up Bt? uiiiou people who first entered since J s Wiv-0 1951 up -fee 19^1 which-gives yeu(24 years still show this slight VA excess. Again the statistical significance is not as great as &v Oum~-K( for the other -half of the cohorts not garffgg exaet-ly tho half other 0/3 pprnTi mntnly -rf ^~h~ irh 'inh-r4"'j but here we have evidence that the lung cancer has not been totally eliminated in this population. There have been very few deaths among those first exposed in 1951 t or subsequently and if we look at table 4, one of the things that is going to crop a up about those 6 cases after 1951 is whether they smoked or not. M1 itr :,e important fop the"othoro tent Ui4 don't have &n He the information available in medical records but we do n for c'awnj S>'r"'e' -=&'*.Li a certain period of time whes- smoking histories were added. In fact, the lack of inforafati^n on cigarette smoking in the earlier studies was a serious on(issi/n, but there were no (Zccrfddt ^--s records kept in the medical records of g-eigaro-tto oaeking until w I WOftt"--tbOrO ift 1966 . x smoking-hafeg^s. ftfuui lliat unu Loirld jil Llmtjp 1976 if you broke the population into age groups smokers, ex-smokers and non- smokers I wont go into how thooo aro do fined-foe* puff-lee to &ajrQ 9 1 3 tfeatr-t-hfrt1 s~~the -way- thoy ware at tJao timo. "4here were 22$ who were hh non-smokers, 13$ who had given up smoking and fc&Ejc x there were 12 i.-et^dr^h 65%. who still smoked."end-phtfse yere comparable to the national ' <v figures,ifl a-way. This population was no different ikx x in its A smoking habits from the general population. Wlial do .yon du abuut sm^ki ng?--! don11 know Table f shows deaths . lung cancer'including mesothelioma^ in the men and ^p^ien first exposed 1933 to 1950 and men and women first exposed 1951 or later. They are distributed according to tho day- by-day firsstt and time since first exposure. If you look at that 10 to--lit years ..sdnre firnt i* iifirr-nre V5 tc-i'9, 0 years or T maae-the the 20 years or 0rCM[ more 2x1 the > : ' ratios is 2 to 1. In those-two groups it probably-4-s not si'gn-ifj^cairt^ Ir. Men and women first exposed 1951 or--lator 20 years or more if you tnkft nrTTrfxyp^xtEkg that + ^ 19 4-]-^ jng + about IQ yp-a-rq which is Cl0f=f> ^nmifT^ ^ ... ...... !* n 1 im lnurt-Mr O* / tKC 3 nn^ 0 y~" ep + 5 observed 1.8expected 0.7 ao yowe ratio of observed to expected^) The 6 employees who were first exposed after 1950 who died of lung cancer were all men and they were all smokers. 5 worked in areas where dust levels were high in 1951 and one of them may have been exposed to asbestos dust from 1925 to 1930 in a previous occupation. He was a welder in a shipyard. No case of----\ mesothelioma has occurred in the population first exposed aftag 1950^ a but that may not be long enough for follow up^ Although in view of the long latenl period, et would yet be expected. An approximately fV multiplicative effect of asbestos exposure and cigarette smoking x incidence on lung cancer/has been suggested. As you know, Selikoff has suggested that an asbestos worker who smokes has a 92 times greater chance of dying from lung cancer than a non-smokfeng non-asbestos worker pn+ n- + | -m--*- an asbestos worker w< an 8 times greater chance of dying from lung cancer than has x daar wot irmnlrn. But without detailed smoking histories which have been collected for the future, we can11 quantify what the k n0 9 1 * effect of smoking were in this particular study. Asbestosis wa's*'' 13 _ oA \r\ found by the Pneumoconiosis Medici^ Board at examination* of fc three of the six cases. They all came to postmorteym. All asbestos workers in Rochdale x who die^ have their x deaths reported^either by their doctors, frc tho ooronoor sr the hospital popogt to the ' ft*-".-to 8.v*r, ' C6MM*( or by the xsxx regie ter of^marriges and deaths. This has been done since 1930. The post mortey&i rate when I once looked rvecu 'y into it was acrely 70% of ewr eat aapwhichNfs pretty high#-ad I used to go to every post mortejlm that toolpplac^e. EffijOCaxa There is a lot of interesting work which wil3r~6ome out of the e post mortirtim work which was done in Rochdale. The numbers x are too small for the magnitude of excess of lung cancer in those first employed after 1950 to be estimated with any precision. The implementation of the asbestos industry regulations started a drive to improve dust levels and as I explained to you the pxxhisix-x process fiberizing the fiber came from the mines., kbx was opened mixed and thgpfr- wore certain operations such as mixing opening bag*slitting mechanical bagging. Than they wont on thaa to-phe carding ps process^ad if you are familiar with the textile industry the carding is simply a matter of teasing out the fibei^layering them all in one direction and you do this by passing them through two rollers moving in opposite directions with 5 he* i' *4-0 needle& projecting from tease_them out. and you /\ is q< --j-- g^t |4 fine web and then you take frhul iiulIi dlTfl ,yuu spin it and- there A Va/m is u4z> dot? are different grades of ynrn .fin# nr whitm^nr and than ymi brnning () at if ci winding s theand if you' -ovor "get pjnfuspH ui fbn TmmHn^--loom as tc 'wirel1 ll'ie"Tiief L and the wharp are the wheft goes from wfrref-t t&- white-and this whagp1 grrcL wliup -ind down and you k.can't forget-it.-that way and that's tfuwyuu weave. PIoi'TiAa o'::'1 Pitrthistg is obviously used for packings. low do things with platting 6Av ^ -aLLy )S VZiJ * >Ufciee impiegratirr&SwiAh gxaa grease or graphite and this .go-fr xtHKj W &i ^ m A TTQrvpc' m-iy Y-nn ran hege yaa.es--gOjyfrftv An; A~| r\ 3 \ b 1w I thinlc them: aro average--^eve Is ~aa& in those are .particles per cc and ,atcr 61 you -got the membrane filter--t-e-ehna^te--aa4--down to fihnr prr rr ''fa Shat operation, I'll show you in a moment, is totally closed. ~ Jury, ^ (jtf course that is the way to deal with fc-anything _lf you close it you got -0 AA no dust. Dut thooo gradully went dowg-4--fibor in 1061 to 3 In ?H-. She This factory population was used and studied by the British Occupational Hygiene k Society in 1966 eh and on the morbidity study which was done at /A K'yaij'r*' that time ant a et mortality but a morbidity-'-otudy [the ^present "standard for asbestos shh fiber was developed. &ftd ito hopper of the people who ft A /^s developed it became widely accepted throughout the world and/is how the US A y current standard<^or threshold limit valuefji asbestos of t 2 fiber/cc. Originally it was a cumulative standard of 100 fiber^ pxx years/cc, m> _if a man worked for 50 year in 2 fiber/cc he stood a 1% risk of k getting asbestosis. The standard was not designed for lung cancer. Although there faoV fta. ic<9evuc ii *s some indication ttrst I have shown you, if yeu reduce asbestosis you ^ o'co A alao--roduoo the incidence of lung cancer rrnt may ha.ve to reduce the aA exposure levels further still below 2 fiber/cc if we are going to eliminate the lung cancer. However no population in the world has been followed for long enough which has been purely ex^exee exposed to 2 fiber/cc or less. fet l>.o ** dm3;' No population has been followed tfe sa^ that 2 fiber/cc is or is not a A no effect level for lung cancer.and ao you lmew~^here is a lot of controversy about whether jthere is or isn't either a safe or no effect level for any carcinogen. As you can see, in certain operations dust QJ levels came down dramatically by 197*+ in the whole weaving operation --there were less than 1. ^ s'- i 1tr~ fti^ 1 lr'y-'Z + -,T"a-- -) . JIiy that weaving there has never been a case of lung cancer associated with r ' r JK ' exposurre that im know-of and asbestosis doesn't occur in that weaving shed. -and that'r why~^he old timers^ people who were involved in reporting the data to the British Occupational Hygiene Society in 1966^and some of them \ US I Mj if " had been at the factory for a long timej -Searig their gut feeling f^Lj^ q q ^ 0 that 2 fibers/cc was a reasonabl>level'because of the health experience of that weaving shed. 15 No singleL/population in the world ber'-. hasAfollowed-up for long enough at a 2 fiber/cc or-iaot less level to -wty^ based upon human expejience irifrothar this is/an adequate level or not. -fee-t-J-s look liable Jfr which 1 o the mean dusKtable anld the number of men exposed ovtr Tk p** v, to them. Fromi^S to A --------- dbV o-bviouoly I -to-M-you we didn`t have dust counts . _ uttf r oul**--<1. d:. s J- 1n t -T^nnr trrt" v. ^ th + counts^until 51that is' ________________ Mi][ but -it is 0ased on calculations made by the committee of the British Occupational Hygiene Society (a*wt the etattts id / N -station involved was Geoffrey Berry of the Medical Research Council'^ Pneumonociosis (Init in Penarth'lsufrd they arrived at a menas of aalculating iT^Trd + levels wh&t would be a reasonable estimate of exposure in those years when dust counts were not available. So jrou can aoo ao the yps-r.g by + h~ ^n i Tin, ftruir a .... ...hi ^ Again J 1952 *'V`t G^" ` the beginning of a modernization of the factory which wac completed in 6r; ffVO^y aboutlc[51+4 aifd pi lot' work was done a lot of jobs were changed^n- lot of 51 Ot(( VVO'ilo'U proces^were l&tsxa&d and theft resulted in a better environment. 1969 /\ A A new Regulations were made. Those x new regulations were called hE no longer x the (Asbestos Industry Regulations but the Asbestos Regulations A and they applied not only to the asbestos industry, but to anybody using asbestos where Ssxi asbestos dust was giving off in ^ concentrations iifiA as 46 liable to be harmful to the health of the exposed person. As opposed to the American method of doing it, the British See have not put a figure .+ in the asbestos stand'i rr+' in Um regulations there is no legally enforceable +0 * figure. The way it has been done is-fey-publishing as an addendum to the standard > yw li_ke guidelines for the benefit of those people xha..to whom ft? 4-lLjU^ (tu iijuutaL. ' Ttu Wdli Aes Mr^. gppi-ioc whioh indicate wwhat the current thinking of the A factory inspectorate is at tha procent time with regard to the levels be c*cX\e\K^ . they aje. going to enforce. That means1 lhat _Lf they want to ftrr level^t W mESxlt^E tumui'iow^and they have already changed them once since 19699)).^ all they have to do is aj+4M-&. ike ^xA-G-oLi-d diXMM..i pvtrrii.11 tthhJri piece uuff~Qppaapn<ar nut of A009 i cirravUofri an 7 Luliirc!! feUi^lher. It doesn't reauire an act of Parliament or any ^ C>` ccrt ^ o<ncultatod mechanisms to do this, although ex obviously tfee-y would ujftt- <*H Oj^eAf c* h'C ' - . consult before^"' It'realy makes it very much simplie,r to operate the ' regulations when you Haaan ' + gnt. a mimbr-- ,rV^` nb if i""' "fVi \S i Hpinw nr .1 ahnim~whi.-oh is the difference kx between the OSHA standard feE and the British standard. Howovog-y-that Eh juot -ghtyws 3zr j~rm thr ill mil ~"thi` 1---! r "1 n -i - You will see that the number -rf -men A gooc on--inoroaPMQQ anri than 44 atata dalinig and-eo-fchi-e-l-g -ohy-i-eusly j*>eing begmiHe fchg 'gHfcgg* to -.begin .tn trcrTE people-out--of--t>he~eohort peafyf G. nm.r nnri there are obviously fewer in 1972 who have been exposed for long AA period of time than there were in I960 because we are losing them. Ae you "im 'irr that Jin 1972 , 32$ &jie exposed at less than 2 fiber/cc. In i$5& 1936 100$ were exposed to gxESfext greater than 5 fiber/cc and only 3% now remain^ in ii 2 in 1972 who arc. exposed Mtas exe ExpEXEii to greater than 5 fiber/cc. What this is really allowing yotr is that with time the number of people drinfiig exposed to high concentrations is declining It is gewt interesting to present it that way. 'Shore-a^..a rmmhor eif always in tVn - typp - f tlllTir the regulations were relaxed. Worl-4--War took- plaoo and Jzuring the uaf A Factory inspector's didn't care too much l/a-y about what the levels were. The government wanted production asbestos OmJ {?xAxuiJ9 ^ ' was essential it had to be oastde.Overtime worked kee women were brought in to work instead of men and long hours^ blackout restrictions made it impossible to operate fff ^hinf- Yeu have IV* fchi-g--period- in-World War-whioh I don't know what effect that is going Kojjp 1 i' to . to on the follow up. IIIt is difficult to interpret the relevance of ' / p<iM^dy the results which I have reported to you to mrimm condixtions. What H* <Ww It we are looking at is a hoto ohpath of bad conditions in the past and a continued exposure of the same population to changing conditions. What we need is a long term follow up of people exposed eventually at thre 4-o a lavol-dftops less than 2 fiber/cc for 20 or 30 years. //Dust levels don't come down in a day. wad that is It takes a long time to get down to less than 2 fibers/pc Q {*' AbUo I O a- plot at of ia the way in which the levels in the factory have been coining down. 17 Ur oC Even people exposed after 1950 re having substantially higher levels of exposure than are at the present time permitted by law. The thing to remember is that what we are interested in is diseases wither ii\Ci'deni Of l excess mortality. Shut yuui. fete bury liiaji be build here and--S'tart--p-reducing A gflurf * , hoT-o and + -I g ^.rVion y^n g-t-gj-t- -Ti-nn ffc^i rhnt. YOU &X&H don't begin tO / see any difference in mortality experience , you may gag a olight- i, & Utat \XA>xf ot fPjf'f after 20 years but you may have to ge 30, 40 or 50 years A ''' oetupe^or-j.1 co^:ef with occupational ^anoors before hat excess mortality becomes apparent. *fo A This is why it is important tha-t .yrm keep records of medical findings^, --f-o ymt keep personnel records which are accurate with regard to data date of employment and types of employment and if possible the type of materials kh to which people s&e exposed,whioh- arc haaardous or-1 which rrry in t.iip fyl-pirn mui thnti y mi Mn j n t Ti n a strict control of your environmental monitoring and dust sampling and that you beatific record these meticulously varying in mind that some time they will have to be related to the health experience of a group of people. It is only if you are meticulous about all that^ that in the future we will clear up a lot of the arguments and lot of the mess which we are in at the present time^ simply because our pxmixxK predecesors had no concept of this type of approach h to occupational medicine. Occupational medicine iw the 1 past for manv-yeans was the transfer of general practice into the factory .a-fc wift a captive population ami you could treat.ttaw*. Wliafc 14 is Z> my opinion that^ part of it fchat ' a a fringe benefit what -io fitore important to me to etVtb'* *'<' to is to establish a system of keeping records abstract from these records flad 4 information analyze it statistically arrd obtain an idea as to how iVui ^ w'to btffrs population compares with another population or the general population. a-j" CaA do all tkU' Will oat- y^tirijugfry A j.f you rn ifehat you hnvffi n idea whether ^ou age an in any way in igpe.doing or i-gparing the health of -Wwe employed peroon I promised WOu' ^ a4- Roctd!* that I show you that improvement had taken place -w&d^ITiat doesn't show nb A Ar very well, that's a man and those are his legs and what he fcww is a pitchfork, AA * 'i n ' n 18 ^ floor there is a hole in the ground and he is standing on a big wooden drum . "^his is asbestos and he is xhxh using his pitchfork to blend it on a open 's blowing floor throwing it up in the air and letting it settle.and ihxExxHg t about te p the have all over the place. That was taken place in # factory that I xxx just xhBXKxymi talked about until 195^ and in some American factories that I fke* visited in 1970 I saw that *4f41 taking place and in some American A factories that I visited in 1976 something very similar in was still taking place. And therefore that is another Youx have got to be very careful when you read the world literature because working when conditions in different countries vary and xfexi some jse people xxa SaxKxikiHg ax describe the horror and the disease associated with asbestos^ theyx conditions under which those' people worked have to be taken into account. I could show you lots of horror slides. I have been around the world and^ seen conditions and I^got slides to demonstrate the differences between the U.Ssomewhere like Ham f- --- South Africa, __ -___________ Uenbasa, India, Britain, and Jit depends upon the degree of sophistication of Regulation and of dust control as to what is going to happen to those people but authors of papers describing the effects seldom pay attention to that, and they xeh will talk about asbestos or asbestos textiles or asbestos cement and never show the pictures of the factory or tell you what the conditions ex were like.awd tliTrt uru> 1971! tmd jo^ fw OSHA or NIOSH to say that the Rochdale population was always exposed to 2 fiber/cc and hence the 2 fiber/cc standard is no good because they are still getting lung cancer is a lot of "well there /A are ladies present/yy That' s what happened to y*e jobit was totally enclosed. The drum is now in--thorc end jt revolves ad there is a \>V$<ebv tt> ^ fibev ? - bag opening procedure the bagcare fed on a conveyor belt and am* into (niV.-A, ,f A *^ the drum tips it into another bin down on the floor and thcrt is q\so A- Sbou'd b? all enclosed and there je. no dust, tbir vny it irm in 1951' When I walked into that factory in 1966 I was taken on a tour and tke^ /\ 0 0 c 2 omJ looked at 'fcfce umf< uold vhere do you waet to start. A at the beginning where the fiber comes in.J 19 _! u- I said i111 start e& -ft %mn I take urn" ontnerr nni I. took my camera and that's what I found. This of + course is very good fiber, tfeert is the best fiber in the world^it comes from Rhodesia. Turner & Newall owned the mines in kRhodesia and since rot UDI they have not had any of that fiber. They have had any of the profits / and they have been cut off from their mines because of Qgitioh sanctions % I x3tH wasn't allowed to visit Rhodesia while I worked for Turner & Newill. However in in .jiayEfeo tec1 factories there is plenty of this stuff. The United States hasn't bothered about sanctions. Anyway this was 1966 these were polish-*ap bags. Every now and then you could see holes in them. Shippers used to love this stuff because it was-kaaf beautiful bttU<LSf. balae&d. They could put a few bags in a corner here and a few bags -and a .a tamer in a hole there and they could trim their ships^*d that's the way it used to arrive in loose bags. The dockers had no respect A for these bags.they had big hooks and the way they lifted thet ii-ic to V th. ;v / fr.-. plunge a hook into the bags'swinging over their sholders KkK `fehtrek art over the side to someone else.and liaue & horrible mess and these things used to arrive at the factory sh*4 the chaps in the warehouse they did not have ** * * Hvfi<s quite as big hooks so the little holes are there aird A 1-1 + pnl1 thpge tbanfrf raf.f and hIhiL fuiaih waj, a stack like thul mid'Umt mo i ck ou can't imagine the size of this warehouse, huge warehouse heldl A full f of i fiber stacked to the ceiling. It 18 months supply because 6i3)I they knew % was coming and so they brought at as much as they could and as much as they could stuff .into the warehouse. There were bags bursting, there was fiber all over the place, fEKk that's what you found^t was an impossible situation and it was very very bad. That's the Vvcnf & i'S 0< polyefoyie>.*.t wha4- you find today. The bags are now polyprophylene or polythyno <S+<i they are pressuret-packed at the mines. These are all hjud- they ere like bricks, they are palletized and very often they are covered with an S e*c>f fibw r* _ .. &00321 if^ i' in the 2 mines,* there is one in North British Columbia and one in TTowa. oJt CV*k. ~-- Territoty^# Clinton goop writ's a nice part of the world to go to )h in January# //What we have is a story that is unfolding#ad phis is rather ItojjJ A A old slide an it tells you about asbestosis beginning at the beginning of the century. The incidence declinafjaSgl in textile workers from 1930 onwards. I haven't mentioned insulation workers at all but the lung cancer incidence noted to be increasing in the late 50's early 60's c (*- J [pcxl^fy 4-t> a if' or t. Asbestosis and lung cancer overall increasing this in the U.K. vvK;!r 14 ouv\ of> * fev/(< ^A Mesothelial tumors Liirg recognized in association with asbestos in the late 1950's-early I9601 s.aii^ work- produotian. taken off like tht during eyfeet* the War and a ae.oederating afterwards so that asbestos became a .I ')- widely- used material. It was cheap, hx easy to find and not expensive to mine and it was used in just about everything you could think of. With regard to mesothelioma in case you think we haven't had any in that factory, we have%ad I don't want to get into a long argument about it but that factory did also process crocidolite fiber and in my opinion crocidolite fiber is the most hazardous type of fiber and the one mostly associated with mesothelioma#-a*d Mii le I was there I collected S& 27 cases of mesothelioma^ a*d.Z hadn't seen any in anybody exposed after 1950. The average lapsed interval was long. At the present time Prof. Doll s o. stuWy b1 /vnt'io'fr.e-! \f'c,clt<nce o-t Tt?v just before I left we completedgoing through our personnel record cards \C\ fecorti of back to #18 and collected something like atfhLy 30,000 people who had A ever been employed. The group in Oxford are now going to check through those. They will probably take a random sample to start with and them to see what they can find with regard to mesothelioma .whether Via ve K'c underestimated our experience. an -fitrd, .ne^hat is .the next study which is going to emerge from this 7 particular group in Oseferd. I have taken up a lot of your time. I think it's over the hour and I must apologize. That is all I have to say. A00222 MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935 (ANATOMIC PATHOLOGY SECTION) 1977 INTRODUCTION In any retrospective review of mesothelioma it is essential to include an objective review of all anatomic pathology material. This review should include all available reports and slides including cytology, surgical pathology and autopsy materials. It should be conducted by an experienced pathologist^jwith special expertise in the surgical pathology of tumors, K* t ^ ** ^nL. 4 * ^ * '* tf * 't *1- The object of this review should be to classify the cases relative to the certainty of diagnosis using well defined criteria for the diagnosis of mesothelioma. In the present study this^review is first being conducted with no knowledge of the occupational history or environmental exposure to asbestos. As the study progresses this data will be analyzed in relation to these factors. (Slide 1 Classification) On first review the cases in this study are being placed in one of six categories (see slide) which represent the relative certainty of the diagnosis of mesothelioma using anatomic criteria. This is being carried out on all available materials, including cytologic preparations, surgical pathology and autopsy reports and slides. As might be expected in a study of this type, the material available is quite variable. In all cases the diagnostic classification is based on autopsy materials, or iiuMM^spi surgical pathology A0054h 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. (Slide 2 Preliminary Results) The preliminary results of the primary review of the first 106 cases are shown on this slide. As you can see 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 trfrmtoc' 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 purposes of this rcv4asw classifications 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. As broken down by percentage, there were 56.6% thought to be mesothelioma, 26.4% possibles and 10.3% not mesothelioma or excluded from the study. There were 6.6% that are still considered unknown. A00546 It should be pointed out that as further studies of this material are carried out, cases may be moving from one to another classification and this report should be considered only a preliminary report at this time. It also should be mentioned that less than half of the total number of cases in this study have been subjected to anatomic pathology review as of this time. Discussion: The most striking histologic character of diffuse mesothelioma is the remarkable structural variation that occurs from area to area even in the same case. As this portion of the study progresses, the mesotheliomas will be categorized as to pleural, peritoneal or other, and an attempt will be made to categorize the histologic structure based on its predominant pattern, into (1) epithelial (tubulo-papillary and undifferentiated polygonal), (2) sarcomatous or mesenchymal and (3) mixed. As has been emphasized by others two problems become apparent on review of this material. The first is the separation of localized or nodular (and sometimes benign mesothelial reactions) from diffuse or malignant mesothelioma. In the present study this is a minor problem because of the selection of the material being reviewed, having been obtained from the Tumor Registry where the vast majority of these cases would have been reasonably carefully reviewed in their own institution and they would have had benefit of the aoureo or progression of the diseased As is the practice in Connecticut, cases are occasionally reclassified or removed from the Tumor Registry by the local hospital when it is determined that they do not represent the malignancy originally reported. A0054 7 The second and more important problem in the present study is the separation of mesothelioma from metastatic carcinoma. The finding at autopsy in the cases so evaluated are extremely valuable in this regard and 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 connective tissue stains^are valuable m this regard. It can be pointed out that as one gains experience in looking at large numbers of mesotheliomas, one begins to recognize a character istic pattern which has been well described by many workers in this field. This coupled with experience in surgical pathology of tumors enables one to categorize BUMvy of these cases m the proper class. n nnt nn..l!ii IhiUIUUUI r MU fm Hw I !' i ) fcVrir mb pnf i y, eomo nf fhn -- 1 M' + is payable that with additional studies and special stains this classification should become more accurate. AU0548 There is another problem that has arisen and hopefully will be addressed in the later anatomic pathology studies. There is variation in the literature on the classification of these tumors. The lines 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, rm descriptions which are not 4*ufiiWU 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 AU04 J DRAFT H)/tT MALIGNANT MESOTHELIOMA IN CONNECTICUT 1935-1977 by 3. C. Lewinsohn J. W. Meigs M. J. Teta Presentation to the Connecticut Thoracic Society, November 4, 1980 Malignant Mesothelioma in Connecticut 1935-1977 by H C Lewinsohn, J.W. Meigs, and M.J. Teta I.Introduction and Aims The combined sex age-adjusted mesothelioma incidence rate for Connecticut vas reported in 1977 to have increased ten-fold since 1935. Although available statistics might be subject to diagnostic error, the apparent rise vas attri buted to the increase in the State's 'cumulative asbestos consumption'. Com plete occupational histories for the cases of mesothello^ were not presented. A derailed review of the available pathological material by an Independent pathologist to investigate the degree of diagnostic certainty was not undertakenf 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. A005b 1 -1-