Document jmKjvx4VmMa1qJrMe9GRvBzXR

FILE NAME Brakes BRK DATE 1974 DOC BRK307 DOCUMENT DESCRIPTION 1967-68 Mesothelioma Register J. 7 motor mechanic mechanic Br Indust Med 31 91-104 1974 1974 ee : 91-104 Med 896 Mesothelioma Register 1967-68 wpe ee TS Sage ge care MORRIS GREENBERG and LLOYD DAVIES 1-13 Chepstow Place Medical Advisory Service Department of Employment Employment ; London W2 pirometer pirometer PEFR in MVV lume st a minute For further information please contact SANDOZ PRODUCTS Medical Equipment Division Somers Road Industrial Estate Somers Road RUGBY Telephone Telephone No. No. Rugby Rugby 7812781121 M. and Lloyd Davies T. A. 1974 British Journal of Industrial Medicine 31 Greenberg of mesothelioma cases is maintained by 91-104 Mesothelioma Register 1967-68 A rSeegrivsitceers Division now Employment Medical the Department of Employment Medical of 413 notifications to the Register Advisory Service This paper describes an investigation pathological in 1967-68 from England and Wales and Scotland had been Cases were regarded as definite when histological confirmation of diagnosis obtained either by hospital pathologists or by the UICC Panel of Pathologists to whom material was submitted whenever possible Two hundred and forty cases definite and 76 cases were regarded as definitely not mesothelioma The were accepted as insufficient pathological material Ihnty of remainder were classified as undecided ohrad nevertheless been so described on death certifi- the 76 cases definitely not mesothelioma cates carried out covers clinical aspects survival and evidence of exposure to The investigation of definite mesotheliomata were of peritoneal origin The age asbestos Twelve per cent mesothelioma occurred at an earlier age than range was 21 to 87 years but in general tumours in the Registrar General's statis- carcinoma of bronchus and lung or all malignant deduced study Evidence cannot tical mortality tables ; of asbestos bodies or pleural plaques occurred as Concomitant asbestosis and the finding in confirmed cases in those cases classified as definitely not mesothelioma as frequently found in 68 of definite cases apparently signifi- Occupational exposure to asbestos was mesothelioma but there was observer cantly more frequently thafnirsitnexthpoosseurdeefainnidtedleyatnhotfrom mesothelioma exceeded 25 years in varied bias The interval between The duration of exposure of cases but was only three and a half years in one case 85 it under five years The type of asbestos could be ascertained in widely in 12 of cases was r^leof crocidolite in actiology There were 38 so few cases that it was impossible to assess the could be obtained definite cases in which no history of amnayrkeexdpocsluursetetroinagsbienstaorseas where there is substantial Definite mesotheliomataWhsehtohweerd this should be interpreted as evidence of causation or an is industrial use of asbestos in these be from this heightened effect of thaawtatrheeneosbsserved annauraelasincidence of approximately 120 definite mesothethe true prevalence qluioomtaetdasiunggEenstgilnagnd Scotland and Wales may considerably understate enquiry For in the mesothelioma and Marchand 19 , gave impetus impetus to the enquiry For Diffuse Diffuse or malignant malignant mesothelioma of the pleura the Pneumoconiosis Unit of the Medical peritoneum although rare has been sought for some years Council had recorded cases of mesothe- ' ; decade The reported associa- Research By 1966 a register of som increasingly past rea Sloans and lio ' reported to them i we h os ee ea abe owe (Ore poy Po Hae a A Se 5 ante nf ae - - - - ght-- - - - 92 Morris Greenberg and A. Lloyd Davies 200 cases which had been diagnosed in Britain in the previous 15 years with histological confirmation of diagnosis was in their possession with the help of information resulting from an enquiry Smither Gilson and Wagner 1962 In that year the register was handed over to the Medical Branch of HM Factory Inspectorate now Employment Medical Advisory Service Department of Employment The objects of the register were stated in the Senior Medical Inspector's Advisory Panel Memorandum 1968 i to record the annual number of deaths from mesothelioma of the pleura or peritoneum associated with asbestos exposure il to ascertain trends in the prevalence rates to discover if possible tumours occurring without any exposure to known or suspected occupational causes iv to provide part of the evidence on ventive measures should be based which pre- and of necropsy findings The histological and histochemical features of mesothelial tumours have been discussed by UICC panel pathologists Wagner Munday and Harington 1962 Hourihane 1964 McCaughey 1965 Whitwell and Rawcliffe 1971 and the criteria employed by the UICC panel to derive a consensus opinion appears in the Appendix Where material could not be borrowed the reports of consultant pathologists were examined Where several pathologists gave varying opinions on a section and it was not possible to refer material to the UICC panel the majority decision was taken The occupational history was often sought after the histological diagnosis had been made by the nonpanel pathologists Diagnoses made by these pathologists were allocated to the following groups Definite where in the view of the pathologist based on adequate histological material supported by the gross appearance at thoracotomy laparotomy or necropsy mesothelioma was the diagnosis This paper presents the results of investigations into cases notified to the register from England and Wales and from Scotland for the period 1 January 1967 to 31 December 1968. Preliminary results have been - published elsewhere Lloyd Davies 1970 and the present report relates to information available to May 1972 Plan of investigation The Registrars General for England and Wales and for Scotland forwarded copies of a death certificates which included a diagnosis of mesothelioma of pleura or peritoneum and b Cancer Bureaux registrations with a diagnosis of malignant mesothelioma Pneumoconiosis Medical Panels also notified cases of mesothelioma which were subject to claims for benefit under the National Insurance Acts or otherwise came to their notice Information about ofelection Undecided where the material examined and other features while compatible with a diagnosis of mesothelioma did not permit the pathologist to make a firm diagnosis this corresponds to the category undecided finally employed by UICC pathologists Insufficient histological material where the pathologist was dissatisfied with the material or where neither histological nor necropsy material were ever examined Definitely not where a definite alternative diagnosis was made by the pathologist When tumour was present in both thorax and abdomen the site stated in the analysis is that given by the pathologist as the primary site Where the death certificate differed from the necropsy report the latter was accepted other cases was received from chest physicians surgeons pathologists and coroners The majority of cases were notified from two or more sources The Central Ethical Committee of the British Medical Association agreed that tracing of cases by medical advisers should take place only after the prior approval of the patient's medical attendant In the event approval was given in all cases Where possible histological slides or blocks of histological material were obtained these were submitted to the Union International contre le Cancer UICC Panel of Pathologists see Appendix Asbestos exposure history Where possible living subjects were interviewed but for deceased subjects the relatives were interviewed in the first instance Occupational histories were also sought from coroners and from former employers and workmates The initial classification was made by the investigating medical adviser who may or may not have been aware of the interim diagnosis and was rarely aware of the final diagnosis The final classification was made by a second medical adviser in consultation with the first and often this took place before the final diagnosis had been received Diagnostic criteria A definitive diagnosis was made only when histological proof was available Borrowed material was referred to the UICC Panel of Pathologists together with an abstract of occupational and clinical histories Occupational exposure Occupational exposure to asbestos was defined as follows Definite where the job involved time or intermittent handling of asbestos or asbestos- CO WO tos P. im sus N OCC > no bef in figu Don Don't a com obta Hobb Hobi hola sawir outh Neigh Neig jects shipy expo Othe Asb evide at n Total All Sce t- ind have gner 964 1971 el to ndix ports here on al to ken r the nontrese ups ogist ried iparnosis and sis of t to the ICC the Kor erial itive but wed 10 ers ide or osis mal Iser ook J. as or 105- Mesothelioma register 1967-68 93 containing compounds or where the subject worked in an atmosphere contaminated by asbes- tos dust Possible where the job description was too imprecise to be certain but there was a strong suspicion of exposure to asbestos None where after exhaustive enquiry no occupational exposure could be presumed Unknown where adequate industrial details were not forthcoming If possible the duration of exposure was recorded and the length of time before death that exposure ceased The duration in intermittent exposures is presented as a cumulative : figure Domestic exposure Domestic exposure was considered as positive when a history that members of a subject's family had come home visibly contaminated by asbestos was obtained Hobby exposure Hobby exposure was recorded in several householders or smallholders who gave a history of sawing asbestos sheeting for the construction of outhouses garages and chicken houses or fibres had been demonstrated by light microscopy in sputum lung sections or fluid expressed from the cu surface of the lung The reported finding of plural plaques at operation or necropsy or evidence of plaques on the chest radiograph was regarded as suggestive of asbestos exposure Results For the years 1967 and 1968 a total of 413 cases was reported to the mesothelioma register Of these 168 were first notified by death certificate as having died in those years and a further 166 were notified in life and died during this period Seventy subjects notified survived the period of study Death certificates were the most important source of notification comprising 53.5 of all notifications in 1967 and 77.8 in 1968. In the absence of death certifications further notifications were received from cancer bureaux 45 26.5 in 1967 and 33 13.6 in 1968. Further groups of cases were reported exclusively by other sources physicians surgeons and pathologists 31 18.2 in 1967 and 18 7.4 in 1968. Three other cases otherwise unreported were reported in each year by the Pneumoconiosis Medical Panels A total of 170 notifications were made in 1967 and 243 in 1968 Neighbourhood exposure Neighbourhood exposure was recorded when subjects lived within one mile of an asbestos factory or shipyard using asbestos but had no occupational exposure Other evidence of asbestos exposure Asbestos exposure was presumed in cases showing evidence of asbestosis either on chest radiograph or at necropsy and in those in whom asbestos bodies Pathological diagnosis In Table 1 the notifications are shown categorized according to the criteria of diagnosis The correlation between histological diagnosis and the diagnosis given on the death certificate was weak Of the 246 cases accepted as definite only 186 were so des- cribed on death certificates On the other hand of 76 cases definitely not mesothelioma death had been attributed to mesothelioma on the death TABLE 1 NOTIFICATIONS TO MESOTHELIOMA REGISTER ANALYSED BY DIAGNOSTIC CRITERIA AND SITE OF TUMOUR UICC Panel . Other pathologists Total All cases Site of - tumour Pleura Peritoneum Pleura Peritoneum Pleura Peritoneum Definite 118 -134 16 98 112 14 216 30 246 Diagnostic category,, Undecided Insufficient material 14 18 4) 26 28 2 40 6 12 13 1 32 32 0} 44 1 46 45 - Definitely 6 not 23 .30 23 42 .46 4) 2 = 21 Total 167 28 198 20 365 48 413 See text for definition c7 e. eapass Paes a NS OA Ratha, Ce prose . secre ty sid boob Floyd Floyd Davies { : in 35 The i certifiincsta ant ceses pathological diagnos peritoneal tumour represented 12.2 of all con- expe of in these 35 cases were firmed mesotheliomas Table2 This compares with orde Carcinoma of bronchus .. an - y proportions by five with a range of orde reported authors to 22 i Carcinoma origin unstated .. an 1) 3.7 of80 to 72.7 of cases Table 3 i adenocarcinoma primary distribution distribution distribution cases seen : Secondary adenocarcinoma primary From Table 2 it can be that the distribution of Age i unstated . . 3 cases between the sites was similar in the groups a no other diagnosis The 1 Not mesothelioma ! Myelomatosis of bladder Transitional carcinoma 4 confirmed by UICC pathologists and by other . I pathologists i The is pi feren of : Adenocarcinoma of thyroid _ 1 Sex distribution pi : Retroperitoneal fibroma or chordoma 1 Table 2 shows that the ratio of mesothelioma in men distr Asbestosis and tuberculosis 1 and women for both UICC and other pathologists distr Severe anaemia secondary to peptic ulcer 1 Malignant melanoma 1 As the concordance of diagnoses between the UICC was about 5 which is similar to that for all malignant neoplasms of the respiratory system Registrar General 1970 The sex difference in Genc death death death pathology panel and other pathologists was higher than 74 and the characteristics of the two groups are so similar for distribution of age at death Fig carcinoma of the bronchus in general is thought in part to be due to difference in smoking habits Hammond 1966 but tobacco is not known to play all . either either ) tumour site sex Table 2 and survival Figs 2 to 4 they can be treated as one In this study a role in the actiology of mesothelioma If it is assumed that mesothelioma is related to asbestos with ltiiomoana lioma carci 246 DEFINITE MESOTHELIOMAS ANALYSED BY SEX AND SITE OF TUMOUR Pathologists Site of tumour Males > " of all meso- thelial tumours Females % of all mesothelial tumours . Total UICC Pand nn .. . Pleural Peritoneal as in Other pathologists .. . Pleural Peritoneal a 96 14 12.8 re 22 2 8.3 - 118 16 11.9 81 10 1097 ~ 17 4 190 190 98 14 12.5 All .. ve vs Pleural Peritoneal - 177 24 : 12.0 39 6 13-300 13-300 216 30 12.2 TABLE 3 PREVALENCE OF PERITONEAL MESOTHELIOMA REPORTED BY VARIOUS AUTHORS Authors All mesotheliomas McEwen al 19701970 ve .. SO Te ee AshcArshocrfotft and Heppleston 1970 .- - 23 ce | ne Selikoff et al 1970 we a 22 Da Thomson 1970 : . . 17 Peritoneal mesotheliomas only Comment total 3 3.7 73 males and 7 females 2 males described as both sites Scotland ne [i 3 13-0) Tyneside . - -~ 16 727 Male insulation workers USA . 3 176 176 Cape Town Newhouse et al 1972 .- . i 49 5 454 oo 30 61.2 Females London Males from the same factory Present study oe . 246 30 12.2% England Wales and Scotland 1967-68 . In T. 167 : asbes eithe 30 20 20 % tc rot 30 20 % 10 ' FIG [ cones with mge of ble 3 tion of groups other men ogists or all .stem in The in abits play it is bestos Mesothelioma register 1967-6895 1967-6895 exposure it would be necessary to know the numbers of men and women at risk over the past 50 years in order to assess the relative susceptibility of the sexes to mesothelioma Age at death The distribution age at death of confirmed cases is presented in Fig : there is no significant difference between cases diagnosed by the two groups of pathologists mean age UICC 59.4 -0.9 other pathologists 60.2 - 1.3 For comparison the age distributions for all malignant neoplasms and for carcinoma of the bronchus and lung Registrar General 1970 are also shown The mean age at death from mesothelioma is significantly younger P < 0.05 than that for bronchial carcinoma and all neoplasms This may be due in part or in whole either to the greater chance of identifying occupational cancers within the working age compared with the retired or to earlier death from mesothe- lioma associated with occupational exposure to a : carcinogen . Exposure to asbestos In Table 4 it can be seen that of 246 confirmed cases 167 68 had definite occupational exposure to asbestos and a further 29 were possibly exposed either at work or at home There were however TABLE 4 NOTIFICATIONS TO MESOTHELIOMA REGISTER ANALYSED BY ASBESTOS EXPOSURE Asbestos exposure history No. of definite mesotheliomas No. undecided inadequate material or definite alternative diagnoses Definite occupational 167 35 exposure - . Possible occupational 16 35 exposure a an Neighbourhood domestic or hobby .. 332 258 Nonc oe os 332 258 Not obtained .. oe 12 20 still 38 15 for whom careful enquiry failed to elicit any exposure whatever In the remaining notifications undecided inadequate material definite alternative diagnosis nearly one third were without apparent exposure and those with definite occupational history formed only 38 of the total The differences between these groups are significant P < 0.001 but may be affected by bias towards 30- Definite mesotheliomas UICC panel ) Mean age 59.4 years 09 32 20 20 + 23 % 10 15 101 6 z == 2 ce) 15 35 40 45 Years 50 35 60.65 60.65 7075 7075 80 AS 30 All malignant neoplasms England & Wales 1968 204 % 104 30 Definite mesotheliomas Mean ag6e0 2years 13 Other pathologists ) . 204 06 4 20 ' 20 25 30 leors CT 35 40 45 SS 60 65 70 75 80 85 90 30 Carcinoma of bronchus lung England & Wales 1968 20 + r % 10 + 25 30 15 Years 40 45 50 55 60 65 70 75 80 85 90 95 100 HG 1. Age distributions at death OY 20 25 Years 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 peg ; i. vAK dat or Ba Ee) va TR aa RE nti ONT ater a ve Sa a Se aSRNSAB. <R7 igg heeatt Woe ne Dd can nk ss RS + a. re' 96 Morris Greenberg and T. A. Lloyd Davies underdiagnosis in areas without scale asbestos industry or to bias on the part of the intervieneinterrviesners who might have been more assiduous in pursuing an asbestos association history in cases of definitive mesothelioma Ideally it would have been desirable conceal intertv he di iage nosiw s ine indr ivids ual cases but on account of limited manpower the interviewer may have been responsible for identify- ing cases and arranging for confirmation ofdiagnosis On the other hand the number of notifications which were not subsequently fully confirmed but had TABLE 5 INDUSTRY OR JOB TITLE IN 167 DEFINITE MESOTHELIOMAS WITH DEFINITE OCCUPATIONAL EXPOSURE TO ASBESTOS Industry or job Shipworker .. oe . Asbestos factory worker - Insulation worker not marine .. Boiler house worker not marine Chemical worker .. os oe Docker . an Welding rod manufacture oe Building worker Electrician .. Sack cleaner repairer Welder plater : Battery box manufacture Electricity generating industry Gas worker Railway locomotive builder _ Motor mechanic .. an .. Refuse work .. . .. Number of mesotheliomas -. 75 oe 39 an 13 a 5 - .5 . 4 . 4 . -2 2NW w : -2 2NW w : -2 2NW w -2 2NW w ae -22NWw . -2 2NW w . -2 2NW w a -2 2NW w Le -2NWw . t known asbestos exposure may have been the result of diagnosis because of the known association of mesothelioma with this occupational history thus introducing a bias in the opposite direction The individual occupations of confirmed cases with industrial exposure are shown in Table 5. The degree of risk associated with these occupations cannot be computed because the population exposed over a period of 50 years is unknown and cannot even be guessed Table 6 lists those subjects with mesothelioma where a history of exposure to asbestos not occupational in origin was obtained Of those subjects with neighbourhood exposure the first four lived near the same asbestos factory in a district where chest physicians have a high awareness of mesothelioma The final four subjects listed had exposures that might be considered minimal and common experience In cases notified to the register by the Registrar General for England and Wales a control group was established from 1 January 1968 the next death registration matched for age and sex but not for area being notified to the register for comparison of occupation It was found however that as cases of mesothelioma were more commonly referred to coroners than were other subjects the job description was frequently qualified to indicate asbestos exposure for example plumber or fitter was further categorized as shipyard whereas no such qualification appeared in the controls Even housewife and widow were recorded as occupations with the discase attributed to asbestos exposure Ethical considerations prevented the interviewing of control subjects or their relatives though it is TABLE 6 OCCUPATIONAL ASBESTOS EXPOSURE HISTORIES OBTAINED IN CASES OF MESOTHELIOMA Case number EW 67/70 EW 68/174 EW '38 EW 68 86 $ 68,71 S 68'31 $ 68:23 EW 67/82 EW 67/115 EW 68/19 EW 68 88 EW 68 190 EW 68 186 EW 68/80 Duration of exposure 25 years 14 years 3 years 22 years Unknown 15 years 30 years Unknown 14 years Unknown 17 years 40 years 2 years Unknown 4 years 3 years 1 day Nature of exposure Resident within yards of an asbestos factory at school nearby school Resident close to an asbestos factory; probably went to both parents worked in asbestos factory nearby Worked next door to asbestos factory Resident 1 miles from same asbestos factory Hobby relining and relitting clutches and brakes Resident 200 yards from an asbestos factory Resident <4 mile from a shipyard Resident < nule from a shipyard Resident J mile from an asbestos using factory Resident < mile from an abestos factory Resident < | mile from asbestos factory Resident < mile from an asbestos factory Husband worked in an asbestos factory Lived in a house largely composed of asbestos cement sheeting Worked on and lived adjacent to chicken farm composed of asbestos cement buildings Intermittent exposure to brother's overalls contaminated with asbestos Sawing up asbestos cement sheets to construct two sheds C FIG asbe rece Mc kno OCC alt yea sig Chry Cro Am -- -- Mi Tyr Tot result of ociation ory thus ed cases e 5. The upations pulation own and thelioma -- --, subjects our lived ct where of meso- xposures common --- Registrar roup was Ext death not for arison of cases of erred to scription estos ex> further qualifica- wife and with the rviewing ugh it is UICC panel 30- 20 Number of cases 04 6 3 Mear 4 years 10 18 18 14 104 UICC panel 40 Number of cases 3687313356224 36873135624 36873135624 36873135624 36873135624 36873135624 36873135624 36873135624 36873135624 36873135624 304 % 204 (e] oa $ Years 10 15 20 25 30 35 40 45 So SS pothologists 30 Number of coses 01979 20 Mean 4 years 17 14 [| 21 % 10 10 fe) 0 5 Years 10 15 30 30 35 40 45 So 35 Other pathologists Number of cases 4 37 50 37 734182521 734182521 734182521 734182521 734182521 73418251 1 404 0 -- S Years 10 15 20 30 10 45 50 55 80 65 FIG 2. Definite mesotheliomas with definite occupational asbestos exposure survival after first exposure 30 _ % 20 recognized that this would have been desirable McEwen Finlayson Mair and Gibson 1970 Figures 2 3 and 4 illustrate time relationships with known asbestos exposure In 85 of cases death occurred more than 25 years after first exposure although the shortest period was three and a half years and the longest 53 years There was no significant difference in the distributions of years of 104 ie) 0 Years 10 15 20 25 30 35 40 45 50 SS 60 HG Definite mesotheliomas with definite occupational asbestos exposure survival after last exposure arby all Mos Dextos ~ rn TABLE 7 TYPE OF ASBESTOS INVOLVED IN OCCUPATIONAL ASBESTOS EXPOSURE rf Asbestos type to which exposed occupationally Histological diagnosis ae ~ Undecided and Definite mesothelioma insufficient material oo Definitely not mesothelioma we Chrysotile only Crocidolite only mm Amosite onl . : - Crocidolite and other asbestos Mixed asbestos without crocidolite Type not ascertamable Total 1 4 JOXNY 4 JOOXNY i 0 JOOXNY 1 JOOXNY 7 42 JOOXNY 2 0 117 JOOXNY 15 167 36 27 5 al Se OT Ee Pe r Sats sah ata ries EOSaf we SR bn, fs ape GRR Sa abt ii : TH: s e on fe Tae6. YF e ns,$F ater sghthutetses Bu Morris Greenberg and F. A. Lloyd Davies UICC panel Number of cases 20 13 973697365 5761 97367 5761 973656 761 97361 5761 97365761 small proportion of subjects Of the 50 subjects with definite mesotheliomas where the types of asbestos to which they were exposed were known 45 had been exposed to crocidolite Of the group of 12 subjects diagnosed as definitely not mesothelioma in which types of asbestos to which they had been exposed were known eight had been exposed to crocidolite G n S 10 15 20 25 JO 35 4 45 30 55 * Years There is no significant difference between these two groups In four cases of definite mesothelioma no exposure was known other than to chrysotile A Other patholo sta history of exposure to talc was obtained in seven subjects with definite mesotheliomas but six of Number of cases them had also been exposed to asbestos It was not 9 oe 20 7 10 6 5 4 possible to identify the nature of the tale to which re US ne 15 they had been exposed 0 tern REN 10 4 Other evidence of asbestos exposure hana 5 It is apparent that a history of occupational exposure MfdenE to asbestos is frequently associated with the presence oO of asbestosis asbestos fibre bodies asbestos fibres or Reta YearYesars $ 10 15 20 25 30 35 10 45 S Years pleural plaques observed at necropsy or radiologi- Bem ANT cally Table 8 Ashcroft and Heppleston 1973 FIG 4. Definite pleural mesothelioma duration of stress the importance of phase contrast microscopy m occupational exposure to asbestos oO and electron microscopy in searching for asbestos in tissues The presence of pleural plaques does not always indicate asbestos exposure Rous and survival after first exposure in the two groups mean Studeny 1970 It is not possible however to age UICC 37.4 years other pathologists 38-4 observe a significant difference of asbestos exposure years The interval between last handling asbestos between subjects with definite pleural mesotheliomas and death was under one year in about 40 cases and those subsequently categorized as definitely not aed but varied up to 52 years one case The duration pleural mesothelioma Great taeNe of exposure was more widely spread ranging from In four definite pleural mesotheliomas corrobora- Rest three weeks to over 50 years Twelve per cent of cases tive evidence of asbestos exposure was found in the had been exposed for under five years The man with absence of occupational exposure histories Of those only three weeks exposure died over half a century subjected to hobby or domestic exposure six later cases none showed corroborative features Of those Table 7 summarizes information regarding the with neighbourhood exposure eight cases two type of asbestos but this could be obtained in only a had asbestos bodies TABLE 8 CORROBORATIVE EVIDENCE OF ASBESTOS EXPOSURE RELATED TO OCCUPATIONAL EXPOSURE NOTIFICATIONS TO MESOTHELIoma Register Pleural TumoURS ONLY HISTORY AND Occupational Occupational asbestos exposure history Definite . . Possible . . None ascertainable Definite pleural mesothelioma wa eee ee - ~--t Corroborative evidence No corroborative evidence Not reported Definitely not pleural mesothelioma _ -- _ Corroborative Corroborative evidence No corroborative evidence Not reported 100 69 8 50 4 13 24 16 4 25 IS 569 27 15. 4 25 10 317 19 730 0 f 0 ( 3 129 3 60 6 33 4 15 2 40 12 67 Asbestosis asbestos bodies asbestos fibres or pleural plaques peas CS ne 9 , 4 rae sees a4 a Ree eese Bes, . ER 4 se . ae ars Es fei ey 3 mgt 2 es as e Bs us iret 4 : a 2 Cee cen ren cS Se : ao Mesothelioma register 1967-68 99 with -bestos 45 had of 12 lioma i been sed to these elioma titliele AA seven six of as not which posure posure resence bres or fiologi- fiologi- fiologi- 1973 oscopy .bestos oes not , and . wer , to posure liomas ly ly not obora- in the I those . -- SIX ~ those , two j AND ; oo y tteedd : y ) : . . Geographical distribution Tables 9a and 9b show the distribution and rate million per year of mesothelioma notifications and diagnoses in England and Wales and in Scotland The Registrar General's standard regions are employed for England and Wales Clydeside includes Dunbartonshire Renfrewshire Greenock Glasgow Hamilton and Motherwell The distributions are by no means related to population density South western England with a population of 3 652 thousands had a total of 22 definite cases a rate of with 22.97 .97 million million per year yet Plymouth Plymouth with a population of 000 had 13 cases all with histories of occupational exposure to asbestos The remainder of the region with nearly 3 million population produced nine mesotheliomas of which which only four had a history of occupational exposure to asbestos a rate of 1-5 million per year As uming Assuming that Plymouth hospitals serve a population of twice that number the rate would be 26 million per year Merseyside Clydeside Tyneside the South East Lancashire conurbation and Greater London had on incidence of mesothelioma markedly greater than the national rate with deficits in the remainder of these regions They have in common the presence of heavy asbestos industries The geographical distributions of cases and of cases with occupational exposure are shown in Figures 5 and 6 Discussion Discussion The recognition of diffuse mesothelioma depends on awareness and acceptance of the tumour as a pathological entity The macroscopic appearance of a typical mesothelioma resulting from its propensity to infiltrate serosal membranes is best characterized by the developed pleural mesothelioma with permeation visceral metastatic permeationpermeation of visceral and parietal parietal surfasurfaces ces by a continuous continuous llaayyeerr of tumour HowHevoerwever metastatic metastatic tumour in the pleura usually from a primary adeno- GEOGRAPHICAL DISTRIBUTION oO OF NUMBERS TABLE 9 a AND DATES OF NOTIFICATIONS THELIOMA 1967-68 AND CONFIRMATIONS OF MESO- Region . 1967 1967 population . millions Notifications Notifications to Register 1967-68 eee me een ee eee eb No. million . Definite mesotheliomas 1967-68 ee a No. million year year Greater London i . a Rest of SE England .. : : Sova ee | SE Lancashire conurbation . . Merseyside conurbation . .: England 2. ew England eee - ee ee Tyneside .. . : : Rest of N England we . - W Yorkshire conurbation . Rest of Yorks & Humberside m , N Wales . SE Wales os : : . : , a 79 WW 703 58 93 40 2-04 18 ree me 2.5 fe re 723 4.20 en | eee 16 4 33 11-79 25 2.9 13 2.24 fe eb cee eee eee [eee ee 0.8 14 8.75 S meee 9 25 13 2.60 9 1.7 17 5.00 5.00 12 30 5 083 3 08 3 1.88 3 1.9 14 368 10 3.67 0.97 3.20 8.93 1:38 - _ 5-63 1.80 3.53 0-50 1-88 2-63 E Anglia .. nee a . .- Lp Clydeside Rest of Scotland rs ~ ee a oe oe smn |e SW England 6. wee 1.6 ee 1-7 3.5 ee een] 37 6 eee ee fe 1-88 ee = nef 43 12 65 18 2.57 rm rrr fn cere me men 30 05 3 2 ep 94 28 24 a 086 086 nes Porm ne 22 2-97 F Midlands . W Midlands conurbation Res oftW Midlands Som eee . : : ee . nee apee England Wales & Scotland _ 33 9 2.4 11 2 11 eee 536 4123 1.36 2.29 212 nn 3.84 366 366 366 245 0.45 1-25 1.15 2-29 Standard regions of Registrar General Ingland & Wales except Clydeside Dunbartonshire Renfrewshire Greenock Glasgow Hamilton Motherwell One subject who died in Australia not included ees Bia gue Zee t? Pak s3> ae : i ^' e ig RS, 2 a : i % 2 ie ee J, enr tt a, nprenmr scnetirtnat epmnare tensange sei ere eae hu enert Re Pi SalmnBane Mepraitent iplin Prent 6 AME OE RECE CL Seno PTE 100 Morris Greenberg and T. A. Lloyd Davies TABLE 9 b GEOGRAPHICal DistribuTION OF MESOTHELIOMAS MESOTHELIOMAS ASSOCIATED WITH OCCUPATIONAL ASBESTOS EXPOSURE AND THE PROPORTION OF THESE THESE CASES TO ALL CASES OF MESOTHELIOMA Region Mesotheliomas with definite occupational asbestos exposure No. Percentage of all mesotheliomas Greater London Rest of SE England SE Lancashire conurbation Merseyside conurbation Rest of NW England .. Tyneside . Rest of N England W Yorkshire conurbation Rest of Yorks & Humberside N Wales SE Wales te an a os oe we we oe . . . oe . o . oe 22 22 226 226 226 88 88 11 2 1 6 50 26 18 88 100 26 67 26 26 38 60 Clydeside os a . oe oe . a Rest of Scotland . - . ve a . 23 23 1282365 1282365 SW England 18 1282365 E Midlands .. W Midlands conurbation Rest of W Midlands 1 1282365 4 1282365 { 1282365 England Wales & Scotland ~ 167 68 Standard regions of Registrar General England & Wales except Clydeside Dunbartonshire Renfrewshire Greenock Glasgow Hamilton Motherwell . carcinoma can produce widespread sheet growth resembling late diffuse pleural mesothelioma Histologically the cellular intercellular characteristics can be highly equivocal The UICC patholo- gists panel criteria for reaching a decision were modified in the course of the survey see Appendix and have not finally been decided McCaughey and Oldham 1974 Willis 1952 cautioned against accepting the diagnosis of mesothelioma until by careful search alternative primary neoplasm had been excluded In a series of 771 necropsies Cameron Litton and Lyon 1961 found a prevalence of primary carcinoma multiplex of 2 In the present series there were three with additional primary neoplasms in the 246 definite cases one with carcinoma of the stomach another with carcinoma of the bronchus and the third with myelogenous leukaemia This represents a prevalence of carcinoma multiplex of 1.2 Sections referred to the UICC pathologists had previously been studied by other pathologists who had not necessarily made a diagnosis of mesothe- lioma In 182 cases where adequate histological material had been studied by UICC pathologists they made a diagnosis of mesothelioma in 134 74 were undecided in 10 and made an alternative diagnosis on 30 occasions 16 % concordance of diagnosis between UICC and other pathologists is greater in view of the fact that a number of sections were referred to the UIGC panelists for a second opinion when the other pathologists had said the condition was not mesothelioma but an asbestos occupation history had been obtained by the clinicians In those cases with adequate histological material not referred to the UICC panel 186 cases a pathological diagnosis of definite mesothelioma was made in 112 60 The submission of sections to the UICC panel varied in different parts of the country In Greater London 77 out of 111 cases were referred % compared with only 12 out of 61 cases in Scotland 20 The number of cases diagnosed is unlikely to be e Mesothelioma register 1967-68 101 sical vists tive 20f is ons and the stos the al was nel ter ) nd be -TYNESIDE CONURBATION 900 W YORKSHIRE CONURBATION rS MERSEYSIDE CONURBATION ? W MIDLANDS CONURBATION NOTTINGHAM <o0v E) D v CARDIFF 00 BRISTOL < v v SOUTHAMPTONV D SOUTHAMPTONV SOUTHAMPTONV D D Qo v DOD DDDO01 noooo0vevev DODDO DDDDD OV 00000 DOOD DDDD DDDDDV DOO GREATER LONDON v v VV MAIDSTONE v DV HG 5. Geographical distribution of notifications and confirmations of mesothelioma 1967-68 standard regions employed by Registrar General except Clydeside which includes Dunbartonshire Renfrewshire Greenock Glasgow Hamilton and Motherwell D = definite mesothelioma Panel 0 = definite mesothelioma patho- logists V = other diagnoses : 5 nc a a 4 ae se as tia: he Serna ~ Pe a VBS Beatie. eo Be aceraneat, Me fe et i ! { { t { t ' t . i = ah Ths . eq i 4| st ig yi ia: fay 4 Aq i ot t fq i tA _d 4 by: 7} iy] i i & , 344 a. y a eq t : a4 eo ee 5UO US Sr SOD WEY Caer, nde a et eee ere a tae emt 102 Morris Greenberg and A. Floyd Davies IRVINE EDINBURGH IRVINE A. . CLYDESIDE CONURBATION MERSEYSIDE CONURBATION| W. MIDLANDS CONURBATION NOTTINGHAM SOUTHAMPTON DD 8 GREATER LONDON D PORTSMOUTH MAIDSTOMI og FIG 6. Geographical distribution of definite mesotheliomas and associated occupational asbestos exposure D = definite mesothelioma- -UICC Panel O = definite mesothelioma pathologists @@ definite occupational exposure overstate patholog underdiag These au group of 19 mesot patholog. only four The of in this 2 the reaso understa . The pr asbestos quoted : eographi showed . substantia 58 defini occupatio there we tumours In this asbestos < three wee - thelioma are safe Under I and Wa crocidolit not be du Planning . by all the . Employm ment of assistance the Regist land HN officers . Panels who sources o members the stand tumours departme slides to & and othe niosis Unt W. R. Le number Mr. M. Advisory > late Dr. D The follo undertook D. Bell T. W. Da M.D. Kip Tomblese Mesothelioma register 1967-68 103 overstated by the inclusion of diagnoses by other be pathologists as the tumour in general to underdiagnosed Newhouse Newhouse and Wagner 1969 These authors reviewed the causes of death in a of workers at an asbestos factory and found group 19 mesothelial tumours in 84 cases in which adequate pathological material was available but of which only four cases had previously been recognized The observed incidence of definite mesothelioma in this series was approximately 120 per year For the reasons stated above this figure may considerably understate the true incidence The proportion of mesothelial tumours in which asbestos exposure cannot be implicated has been quoted by Wagner et al 1971 as 10 to 15 The geographical distribution in the present series showed that in Greater London where there are substantial asbestos industries 29 50 of 58 definite mesotheliomas had no ascertainable occupational asbestos exposure Overall in the study there were 38 cases 15.0 of all mesothelial References Ashcroft 7 and Heppleston A. G. 1970 Mesothelioma and asbestos on Tyneside a pathological and social study In Proceedings of the InternatioendailteCdonfbeyrenHc.e o An . Pneumoconiosis Johannesburg 1969 Shapiro pp 177-179 Oxford University Press Cape Town sere ee 1973 The optical and electron microscopic determination of pulmonary asbestos libre concentration and its relation to the human pathological reaction Journal of Clinical Pathology 26 224-234 Cameron J. M. Litton A. and Lyon D. 1961 Primary carcinoma muluplex Journal of Clinical Pathology 14 Ham57m4o-n57d7 E. C. 1966 Smoking in relation to the death rates of one million men and women In Epidemiological to the Stiely of Cancer and Other Chronic ADpipsreoaascehseesdited by W. Haenszel p 127. National Cancer Institute Monograph No. 19. National Cancer Institute Bethesda Maryland U.S.A. - Hourihane D. O'B 1964 The pathology of mesotheliomata and an analysis of their association with asbestos expo- H.M.S.O. sure Thorax 19 268-278 Lloyd Davies T. A. 1970 Annual Report of H.M. Inspector of Factories 1969 p 57 Cmmd 4461. Chief tumours lacking evidence of asbestos exposure London of diffuse In this study the briefest occupational occupational exposure to McCaughey W. T. E. 1965 Criteria for diagnosis mesothelial tumours Annals of the New York Academy Academy asbestos associated with a mesothelial tumour was Sciences 132 603-613 but if asbestos was a cause of meso- of and Oldham P. D. 1974 Diffuse mesotheliomas three weeks - and histological criteria including could thelioma it cannot be assumed that lesser exposures morbid anatomical observer variation in histological diagnosis Proceedings relativare safe of the Working Group to review the Biological Effects of Under industrial conditions prevailing in England Asbestos International Agency for Research on Cancer and Wales and in Scotland the significance of W.H.O. Lyon in press crocidolite in the actiology of mesothelioma could McEwen J. Finlayson A. Mair A. and Gibson A. M. Mesothelioma in Scotland British Medical 1970 not be determined Journal 4 575-578 Newhouse Muriel L. Berry G. Wagner J. C. and Turok Mary E. 1972 A study of the mortality of female and field work were carried out asbestos workers British Journal of Industrial Medicine Planning administration by all the members of the Medical Services Division now 29 134-141 Validation of death certifi- Medical Advisory Service of the Depart- Employment 1967 and 1971. The ' and Wagner J. C. 1969 of Industrial cates in asbestos workers British Journal ment of Employment between Medicine 26 302-307 ie assistance of the following is gratefully acknowledged Registrar General 1970 Statistical Review of England and peardme the Registrars General for England and Wales and Scot- Wales the Year 1968 Part I Medical p 124. H.M.S.O. land HM coroners and their officers hospital records London ea reras and the staff of the Pneumoconiosis Medical Rous V. and Studeny J. 1970 Actiology of pleural cificers narPre: Panels who provided information and leads as to further the plaques Thorax 25 270-284 Selikoff I. J. Hammond F. C. and Churg J. 1970 pathologists sources of information the including of asbestos insulation workers In ate members of the British panel of UICC pathologists for Mortality experience Proceedings of the International Conference on Pneumo- mesothelial the standardization of the diagnosis of contosis Johannesburg 1969 edited by H. A. Shapiro tumours Dr. K. F. W. Hinson and members of his 180-186 Oxford University Press Cape Town at the Brompton Hospital who circulated Senipopr Medical Inspector's Advisory Panel Memorandum | department slides to the panel Dr. J. C. Gilson Dr. J. C. Wagner 1968 Problems arising from the Use of Asbestos and other members of the staff of the MRC PneumocoC. Elmes and Professor H.M.S.O. London W. J. Gilson J. C. and Wagner C. 1962 Smither British Medical riosis Unit Penarth Professor who read the draft manuscript and made a Mesotheliomas and asbestos dust letter W. Lee Mr. R. V. Hayball and Journal 2 1194-1195 of malig- number of helpful suggestions Medical Thomson J. G. 1970 The pathological diagnosis In Mr. M. T. E. Houghton of the Employment nant mesothelioma of the pleura and peritoneum Advisory Service for their meticulous record keeping the Proceedings of the International Conference on Pneumo- late Dr. D. C. Lindars who assisted with the final draft coniosis Johannesburg 1969 edited by H. A. Shapiro The following members of the Medical Services Division of tracing 150-154 Oxford University Press Cape Town pp JC Gilson J. C. Berry M. and Timbrell V. undertook the laborious yet delicate work Catton H. J. Davies Wagner British Medical 1971 Epidemiology asbestos cancers D. Bell E. S. Blackadder M. T W. Davies A. T. Doig K. J. Dunlop L. E. Euinton Bulletin 27 71-76 and Harington J. S 1962 Histo- G. L. Ritchic G. F. Smith B. L. M.D. Kipling West R. Whitelaw Munday D. E. ---, chemical demonstration of hyaluronic acid in pleural Tombleson D. G. Trott G. 3 { i aeRY 5 : i i z : * vais + L, r; Pag ob SN PESas ty REC oe Sineos g + eS weal a eentane rnades Pere 104 Morris Greenberg and 1. A. Lloyd Davies British J mesotheliomas Journal of Pathology and Bacteriolog . 84 73-77 +, Sleggs C. A. and Marchand P. 1960 Diffure pleural mesothelioma and asbestos exposure in North Western Cape Province British Journal of Industrial Medicine 17 260-271 Whitwell F. and Rawcliffe Rachel M. 1971 Diffuse malignant pleural mesothelioma and asbestos exposure Thorax 26 6-22 Willis A. 1952 The Spread of Tumours in the Human Body 2nd ed p 55. Butterworths London Received for publication May 17 1973 Accepted for publication July 20 1973 If the two opinions lead to a blank entry above then the specimen should be sent to the two other readers and a combined diagnosis made on the basis of four readings There are many possibilities from four readings but the combined diagnosis should follow the majority if there is a clear one and other- wise be undecided The following rule is sufficient to determine all cases of four readings score a definite as 1 point probable as 1 possible as 0 not as 1 then add up the four scores and if the total is greater than or equal to 1 the diagnosis is Definite between and +1 inclusive it is Undecided less than or equal to 1 is Not mesothelioma Addendum APPENDIX The Mesothelioma Register which in 1967 and 1968 recorded cases from all available sources has since continued with notifications of deceased cases only The following table gives details of notifications subject to confirmation for the years up to 1971 figures for the years 1967 and 1968 being included on similar basis for comparison The UICC Panel of Pathologists and diagnostic criteria A British panel of pathologists specializing in the diagnosis of mesothelial tumours was formed unofficially in 1963 and consisted of Dr. K. F. W. Hinson Dr. F. Whitwell Professor W. F. E. McCaughey and Dr. J. C. Wagner From 1963 to 1967 all cases were examined by all members of the panel and a majority opinion was arrived at Subsequently the panel was constituted as a UICC panel From 1967 panellists decided whether the diagnosis was definitely mesothelioma definitely not mesothelioma or whether there was insufficient histological material only referring material to another member or members of the panel in case of doubt After 1968 the policy was adopted that all cases referred to the panel should be seen by at least two members and that if there was a difference of opinion a third opinion should be sought In 1971 the following protocol was designed for combined panel diagnosis Two opinions are necessary for diagnosis and these two opinions should be combined as below NOTIFICATIONS TO THE MESOTHELIOMA DEATH CASES 1967-71 REGISTER Sources of notification Death certificate Cancer Registry Industrial injury`injury` data Other . Total 1967 1968 91 189 39 28 3 3 30 13 163 1969 126 20 6 S 157 1970 165 11 3 5 184 1971 124 11 _ 3 138 Not so certified at death Not on death certificate or cancer registration In the short period studied it is not possible to observe a significant trend The large number of cases notified in 1968 may have resulted from the publicity and vigilance generated by the survey If the impression of a falling off in notifications is confirmed then whether this will be due to a change in the prevalence of the disease or to a change in vigilance will require to be evaluated First opinion Definite mesothelioma Probable mesothelioma Possible mesothelioma Not a mesothelioma Definite Definite Definite Second opinion Probable Possible Definite Undecided Undecided _ -- Undecided Undecided Not Not _ - Not Not Mo pop min Departm _, Cancer It has be in harmi different pleural c Some ev from othe digestive Selikoff 1965 C. the possi from var asbestos the world difference various | Newhou type of as