Document 15DkQa5w4k56NXrDY8pobOZ1E

>.'214 25 July 1964 }9 cf tyfil nm9i U0ICJU. Jow*VH*4 . Diffuse Mesothelioma and Exposure'to Asbestos Dust . in the Merseyside Area : w. GLYN OWEN,*1 mjj., - - PLAINTIFF'S * EXHIBIT ! Brit, mea. J,, 106'!. 2. 114-213 [With SrsciAi. P?LlaA7S C/ - 3ooo tfL 1 Paticnrs suffering from pulmonary asbestosis show a high incidence of malignant-tumour formation. Particular attention has been given in the past to the occurrence of carcinoma of the lung. Doll (1955) assessed the average risk among men employed for 20 or more years at one asbestos factory as 10 times that among the general population. More recently a close association Isas been found to exist between exposure to asbestos and the development of diffuse mesothelioma. Wagner ct el. 0 960) described 33 examples of diffuse plcjral meso thelioma from the North Western Cape Province of South Africa. All but one of the patients had been exposed to asbestos and many had worked in the local asbestos mines. Later, Wagner (1962) described 75 eases of diffuse pleural meso thelioma together with three examples of diffuse peritoneal mesothelioma. - Occupational or environmental exposure to asbestos had occurred in ail but two of the patients. In the present investigation a study has been made of 17 examples of diffuse mesothelioma occurring in the Merseyside area. In each case evidence has been sought of exposure to asbestos dust. Subjects and Methods The series includes 16 examples of diffuse pleural* meso thelioma and on: example of diffuse peritoneal mesothelioma. Most of the names were collected from the files of the Liverpool Cancer Control Organisation and from those of the Liverpool Regional Thoracic Surgery Unit, which is based at this hospital. They cover a period of eight years from 1955 to 1963. A critical examination was made of all available histological material, and in only one instance was the diagnosis of diffuse mesothelioma accepted without histological reassessment. In this ease necropsy lud been performed in 1958, but none of the blocks or sections could be found. Tumour tissue was obtained at thoracotomy alone in six patients, at necropsy alone in eight patients, and from both these sources in three patients. The reports of 12 post-mortem examinations were available.' Evidence of exposure to asbestos was sought by taking careful occupational histories from the patients themselves or from their next of kin. In addition, lung tissue was examined micro scopically for the presence of asbestos bodies wherever it was possible to do so. No attempt was made to obtain information from factories or other industrial concerns where the patients had been employed. Results * Strong positive evidence of exposure to asbestos was obtained in 14 (82%) of the 17 eases studied. Each of the other three patients had been employed in places where they may have bandied asbestos, but there is no detailed information about die nature of their duties. Occupation of the Patients Eleven patients arc known to have handled asbestos during only, but had worked in the office of a factory where the 1 atmosphere is frequently contaminated by asbestos dust. Five patients gave- a negative or inconclusive occupational history. ; but in two of them asbestos bodies were seen in sections of lung tissue. ; Of those giving a clear history of exposure seven were con- ; cerned with fire-proofing or heat-insulation. I-'ive of these were j laggers employed by firms of insulation engineers and. were ; mainly engaged in the lagging cf steam-pipes. Two were sheet- j metal workers and boiler-makers. Both of these and three of < the laggers had worked in ship-repairers' yards. Only two ! . patients had worked in factories directly concerned with the ; processing of asbestos--one as a card-room operative for a j period of five years from 1914 to 1919, and the othcr.i.% fore- j man for most of. his working life. Two female-patient* i:r..: 5 spent many years as sorters of used sacking, being employed 1 by different firms of sackwarc manufacturers. Old sacks sun- | mined for repair contained traces cf their previous contents \ and usually were extremely dusty. In each of the factories! asbestos sacks were notorious for the fine dust which they I produced on handling. j The occupations of all the patients arc listed in Tabic I. } In every ease the first known exposure to asbestos had. occurred 1 1 many years before the development ot a tumour. The shortest I interval was 13 and the longest 66 years, with an average o: i 38.5. Length of exposure ranged from 5 to 55 years, and die ; interval terween the end of exposure and the development of ; tumour from a fc.v months to 40 years. LEGENDS TO SPECIAL PLATE 07. GLYN OWEN Ftc. l.- Cue S. TuRmur-lincri etch* vriihia a :";h:ous uimu. (H. me E. x SO.) Fie. 2. C-sc 3. An iru nf pipilu.-y tumour .'ormauoa. (K. and E. xSO.) r 1C. 3.--Ciie 9. Hifh-prwvcr view a.' -r. ires of papiILry tumour. (H. and E. X313.) Fie. aae 3. A sineic ubeuoi body lyir.e *iihin an livcaLar septum. (H. and c. xjlS.) ric. C-ac 6. A eroup of aacrti.n bouica in iur.; tissue. (H. aad . x 313.) C. E. DENT aad L. C A. V.WTSCN ?:c. I.--phalanccsi x-ray Sim* C) U August *\:) on 6 November 1953. Minimal icbpcnoaual erosion it visir;- or. ire !cfc margin o( the middle phaunx. ir.d :hcrc is a dawdle .Lr.e * me terminal tuft indicating further erosion there, limn changes have healed in the Later x-ray n**n cetomy. I?iC. I.--Phalanges! x-ray films (a) or. i-4 August X'/CZ me on 6 November 196X 4here is a particularly weiUnwLed erosion at (he a.uc of the middle pr.nianx (arrn**j wh*cn has heaied in the later x-ray film after :iio remove! of the para thyroid tusaour. * `\ i-; i!. i- : jir'rTA'^ ' uiv' 1'964 h` Mesothelioma--Oiscii flrrw 215 Clinical Features trying similarity is apparent in the presenting symptoms : the course of the illness in all patients. Of those with |L*y growths in the pleura all complained of breathlessness P'i but one of pain in the chest. Pain, felt deeply in the .all, was more often of dull aching character than of tic type and was frequently accompanied by pain in the .;er. Once established, both pain and breathlessness were ;:s;ngly persistent, becoming more severe with advance ': disease. Cough was not a prominent feature except secondary respiratory infection had occurred-. Eleven -v.s had pleural etTusions when first examined in hospital \ur developed efTusions later. Numerous aspirations were -1 'our, but rcaccur.tulation of fluid occurred with incteas. -pidity until such time as tumour tissue had grown to ::atc the pleural space. Loss of weight was invariable out ften delayed until the final months of the illness, gnosis remained in doubt in every ease until exploratory ;ocomy or posr-mortem examination was carried out. chcscopy had been performed on 12 patients. Three :J rigidity of the bronchial tree and one showed comprcsaf the left main bronchus. No bronchial tumour was seen no other abnormalities were recorded. age and sex of all patients and the duration of their * . es arc given in Table I, together with details of their -Rational histories. There were 12 male and five female :s. Only one is still alive. The average age was 5S years, vjngcsi patient being 46 and the oldest S2 at death. Rapid deterioration followed the onset of symptoms in eight eases. In the remainder the duration of symptoms ranged from or.c to six years, ar.d four patients suffered protracted illnesses of over two years' duration. None of the patients complained of symptoms suggestive of pulmonary asbestosis. All had been in good health until the onset of symptoms attributable to .the growth of tumour. Post-mortem Appcarar.ecs Post-mortem examinations were carried out on 12 subjects. The main findings are summarized in Table II. In ail cases extensive malignant growth was present, confined to Use lining layers of serous cavities. One example of diffuse peritoneal mesothelioma is included. In this subject large effusions were present in both pleural cavities but no primary or secondary tumours were seen within the thorax. The peritoneal cavity contained fluid loculaied between masses of tumourinfiltrated mesentery anti omentum. The growth had spread widely on the surface of the bowel and over both surfaces of the liver, bur no primary tumour could .be detected in these or in the other abdominal organs. The remaining examples were thought to be primary growths of the pleura, though very extensive involvement of the peritoneum had occurred in two of them. In nearly all instances the lung on the affected side was shrunken and encased in thick white rumeur tissue which extended deeply into the interlobar fissures. The pleural space - Table T.--/tgc, Sex, Duration of Illnesi, and Details of Occupations! History in 17 Cases Duration Time Since Length Interval from 01* First Possible ot End of Exposure Sex Ace Symptom* Exposure Exposure to Development 1 in Montru io Atnestos a Yean* inYes:i* of Tumour ia Years Occupation P S2 IS M Si s (66) 03) Si 19 J * At 57 4 . OO) M 57 72 37 7 M M - 4JO6 72 10 (35) (18) 1 At 71 5 i M 60 5 _ M 56 12 n 23 *1 At 50 24 t > P 56 15 : 4 P Alive 53 15 (55) (45) 4J 45 35 42 36 (55) (13) * n 1 ?) 00) 1 5 32 (35) 1 08) l (53) .05) 43 5 35 20 .13 ' I* 1 1 40 l 22 23 Sorter in saekware factory tniuliucd factory plant) hnoum to have handled asbestos fbc: asbetto* boc;e presets. Ilwhbr*th6c factory. Football poois cheeper. Gun-on.lmj *94v--tS. T jsse: T-arcer Ljrtetr Larr*<2river for sHsp-rcpairera. ?rooab6 environmental ts;otu/c. AnVpifi bodies presentShcct*mctl worker in slsifwepaircra* yard Lacner (thip^utldme) Asbestos factory* fffeman) AsdPtM factory Ceaed*rnnm operative^ Ilotler>.*naker (.ihiphuld*r.p) Sorter in mekware factory OiTtcc worker Cor concrete manufacturers--users of atbestoa cement , % M 63 . j M 65 ; 6 \i .Vi t 3S Corel eitA mm -- *. CUtr -- *f Er^rrvrr M A ihdttai Ikiiler-msker fship*ouU-!ir.p) _ Apprenticed to imp-repairers and ship-otter? for 7 years. Later store* man ar corporation suer depanmeat --* Dock railway porter ; -jm in ;uuutau ui ipproiisuu. " .:e . . 5 i i 3 .; Main Tumour Sue Rijnt pleura Let** pUura u:l: pleura Kichi and left pleura Highi and left pleura Left pleura Left pleura Riche pleura Peritoneum Left picu/a Hieht pteurs ILnht pleura Table II.--Main Pathological Findings a: Post-mortem Examination ir. 12 Cases Lymph-cade Deposits Distant Mccastasea tr.vnivcnicm of Other 5<rou* Cavities J Predominant Histological 1 , Tumour Type Axillary, internal mammary Asiliary, cervical, mcduatiaxl Mediasunai None -- Livu -- -- Mediastinal PcnearJicm. IVriionrum--!iver surface ?<rw.Nlium r,e;:w.;*6w.;t Hot it pleural cav;:ics. Pcr:nneum-v*%l r..utrwc(nmv nr, i,vn;atl<htmii sac, sue* face ni pancreas Doth pieurai cavities Und.Tvrcntisted ground L:ndi.Tercnuated growth Mixed Muvil t Mixed Xoac Axillary, mcdiaitianl. xbdosanal None 7 None None None * Richi plcvral cavity Sarcomatous .Vritincun--mescr.icrieddposiu ?e?8<.tr Jiuru Mixed Peritoneum--covcrm; ail organa _ None -- None -- Pericardium. Mi.ve-i - PapdUry No biio'o^*cL material ?(fi)7tfifum*tu,*ftce of over, ^ >84#face oi adrenal Xo Sarcomatous -- Heih pleural cavities. Mixed Peno/dtunu Peritoneum--covering LI organ* Aibcites "aiiui ia Lui: T;a;uss w w W W Cuni.'ui No .a; Na tunp tissue No t;t:ue S.r.sii irspment only lur.; ja '25 July 1964 Mcsochcl ic;nu--Owen was often obliterated so that no distinction could be mad: showing papillary end tubular endothelial structures mit.vd between the visceral and parietal layers. In other cam plea with areas of fibrosarcoma. Typical examples cl usmnur-tined \ / loculatcd collections of fluid were present, aod in one instance clefts and papillary growth arc shown in Figs. 1, 2, ar.J 3 | the pleural surfaces were separated by a large elusion though (Special Plate). y^ both layers were completely replaced by growth measuring up to 2 em. in thickness. Thickest tumour was generally seen on the surface of th: diaphragm and over the lung bases. Meyer and Chaffee (19>!0) showed the presence of hyaluronic acid in the serous ettusions of eases of mesothelioma. Its presence in the endothelial component of tumour tissue provides an additional diagnostic feature of mcsoihclioma and has been demon- ' \ \ Infiltration of inrercosral tissues and mediastinal structures strated histochcmicslly by Wagner c: si. (1962). Tn all 16 rases ; was noted in all eaten, with a tendency to penetrate the Cheat wliielt they examined MOtretliUt was present wltieii stuincd ; wall at the site of previous thoracotomy. Bilateral pleural mctaehromaticaily with azure " A " and which gave a positive involvement was unusual, being noted on only three occasions, reaction with aician blue and with Hale's coiloidai-imn m/thnd. | but there were several examples of tumour extension to other These reactions were abolished or much reduced in all instances serous cavities. The pericardium was directly invaded in six after treatment of the tissues with testicular hyaluronidasc, in j instances, with extension of tumour on to the surface of the ' marked contrast to the behaviour of mucin in secreting adeno heart in three of these. Peritoneal deposits were presenr in carcinomas where the colours persist. In addition there was * six examples, four of which showed pericardial involvement consistent failure of the endothelial components ro stain with ; as well. the periodic-aeid-Schi;l.(?,,\.S.) reagent, whereas mucin was i Only one blood-borne metastasis was encountered. This was an isolated small nodule of rumour situated deeply within the aubatar.ca of the liver. Lymphatic spread was recorded much more frequently, axillary or mediastinal lymph-nede deposits demonstrated by this method in all examples of adenocarcinoma which they examined. Similar results were reported by Winslow and Taylor (1960) in a series of 12 eases of malignant peritoneal tncsotitclioma. ; * being present in half the eases. One patient showed extensive Similar methods were applied to ail available tissues in this j thoracic and abdominal lymph-node involvement togsthcr with series, mucicarminc being used in preference so P.A.S. for tlo.* i prominent IntrapuLmooary lymphangitsc spread of rumour. demonstration of mucin secretion. Positive reactions were All reports state that no primary carcinoma could ha found in the body, the organs examined being listed in most of them. Two of the post-mortem examinations were carried out Personally. No neoplasms other than the primary growths in the pleura were found after careful dissection of the bronchial tree and thorough examination of all organs, including breasts, thyroid, prostate, and testes. obtained with aician blue and with Hale's eoiioidal iron in every instance, and in each one a mcrieeJ reduction in intensity of colour followed treatment with hyaluronidasc. In only :*. of the specimens was the colour entirely abolished after IS hours' incubation, but persistence of strong colour was cemon strared consistently in control examples of normal mucinsecreting tissues and of mucin-secreting adenocarcinomas. Mucicarminc failed to give a reaction in all but one of : f i [ j die examples, and this gave only scanty and faint staining f . which was abolished by treatment with hyaiuronidaxc. Similar j Histological Appearances of Tumours reactions in the stromal elements were observed in several tumours, but these were regarded as non-specific, as hyaluronic J j Diffuse mesotheliomas of the pleura acd peritoneum ore **acid is known to be produced by rapidly growing connective 1 comparatively rare tumours and their histological diagnosis has _ tissues in oiher situations. \ occn the subject of controversy for many years, Robertson (1924) and Willis (1960) denying*their existence as a separate entity. Difficulty in diagnosis arises from the variation in structure shown by these tumours and from a similarity in Asbestos Bodies in Lung Tissue | many instances to secondary odcno-carcinoma cr to fibro sarcoma. Detailed descriptions of the microscopical features have been given by Klemperer and Rabin (1931), Campbell Vct7 little lung tissue had bean preserved for examination. most of the thoracotomy specimens and some of the necropsy material consisting only of tumour tissue. Blocks containing i ! (1950), Godwin (19J7), and McCaughey (195S). All these lung tissue were available in 10 eases and asliestos bodies were ; -.itthors emphasise the presence of a mixed structural pattern and attribute this to the dual potentiality of mcsothclium from which both endothelial and mesanebymatous elements mr.7 be identified in seven of these. Asbestos bodies are formed by the encrustation of inhaled asbestos Sores by cn iron-protein compies. They appear ns beaded structures of golden-brown colour j 5 j formed. Ciaractcristically, areas of endothelial proliferation in routine hscmatoxylin-snd-eosm preparations and give an > ioto papillary structures and into tumour-lined clefts within intensely blue colour characteristic of iron in Peril's reaction. I fibrous stroma merge or mix with areas of fibroblastic activity, Examples arc shown in rigs. 4 and 5 (Special Plate). .A.:4:es:.v. often of sarcomatous appearance. McCaughey divides his bodies were numerous and easily detected in the lungs of II examples into those of mainly epithelial patters, those .if two patients but were scanty in the rest of the material, pro fibrous structure, mixed tumours, and anaplastic spindle-eel growths. longed search being necessary to find them. Only fragment' cf lung tissue attached to picurai tumour were evaiLbie for A mixed pattern was clearly, seer, in 11 of the 16 rumours examination in the three negative eases. In no instance -.vcrc examined in this series. Two Others-were prcdomir.ectly of asbestos bodies seen within rumour tissue. Some degree of sarcomatous appearance, one was predominantly papillary, aad two w^ere poorly differentiated growths composed of sheets of fibrosis was observed in ail samples of lung tissue, but its extent was minimal, being confined to the wails of respirator*.* malignant cells with several mukir.uclcatcd giant forms. None bronchioles. This degree of fibrous reaction was thought to of the tumours showing a predominance of oce strutrural be consistent with the absence of clinical features of pulntonery pettern was uniformly of one cell type, and in every example asbestosis in these patients. ksomc areas were present in which other features cf mesothelioma Fcould be distinguished. It can therefore be said that a mixed pattern was present to some degree in all the examples stuJici. t o demonstrate this it was necessary in a ;c*.v cases to study Blusarative Case Histories alecks of tissue from several different areas of tumour. The following short ease histories have been selected to only metastasis encountered -was entirely of Sbressreomatous :u*jc;urc. T*h^ *rv ^ ru - *T .......... ;st, :c points of environmental, clinical. and `-- ; L25 July 1564 Mesothelioma--0:-jch s* ^ <K 7 17 ; ' Case 1. Female. S2 years. Died 13G3 Occupational hi'toty in this case was given by the paticr.t'i daughter, who had worked for icvcr.il years in the same (actor/ i.i her mother. The patient had been employed from Id to 71 . yeors a( sec hy a firm of lockware manufacturers si a sorter of J uied sacking. Socks were received which had contained a grot variety of .materials and which had enme from all over the world. I Asbestos sacks were often handled aad were said to be exceptionally y duuy. . The patient was edotlucd to hospital lufTering from bronchopneumonia ar.d fractured neck of femur, and died three weeks later. She had been losing weight for IS months and had com plained of increasing breathlessness for over two years. At necropsy the right lung war encased in thick white tumour tissue which completely obliterated the pleural space. Growth had infiltrated intercostal (issues, mediastinal structures, and the peri cardium. A nodule of tumour' was present on the surface of the liver, where growth had penetrated the diaphragm, and there were deposits of tumour in axillary and internal mammary lymph nodes an the right side. The breasts, lungs, ovaries. ar.d gascro-intestinal tract were carefully examined, but no carcinoma was found in these or in any other organ in the body. Asbestos bodies were seen in smears made from the cut surfaces of the lungs and in histological sections, of lung tissue. Case G. Male. 50 years. Died 1953 This patient had worked for most of his life as a logger of steam pipes and boilers and had handled asbestos regularly. A few months h.-fiire he died he had changed to lighter work as the controller 1 of a machine for making asbestos net. lie began to have intermittent chest pain in 1957. nv 1959 he had become breathless bn exertion, and in December 1961 he was admitted :o hospital because of severe dyspnoea. A large, pleural cifuMon was present and aspiration of fluid was carried out through the sixth left intercostal space. Three months later a subcutaneous rumour ita.l farmed at the site of aspiration. This mass increased slowly in sine over the next 19 months but the parien: remained at work, lie then began to lose weight, became increasingly breath less, and suffered persistent pain in the chest and :a the left shoulder. He died a few days after rcadm.ission to hospital in Cewscr-1963. At necropsy a mass was present in subcutaneous tissues over the fifth arui sixth ribs on the left side. This was seen to be an extension of tumour from the parietal pleura, which was everywhere infiltrated hy malignant growth. A large pleural effusion .was present anj aspiration was carried out, together with needle biopsy of the pleura. Tumour had infiltrated the mediastinum, encasing part of the aorta". Fluid was present in the. peritoneal cavity and there were several small tumour nodules scattered over the mesen teries. No other growths were found. Asbestos bodies were present in profusion in the lungs. Case 7. Male. 46 years. Died 13S3 In this case there was no history of direct contact with asbestos. From I9v5 onwards the patient had worked as a lorry-driver for a firm of ship repairers ap.d fitters. His loads consisted mainly cf machine components, but he had carried powdered asbestos on a number of occasions. This material had always been contained in scaled bags, and he denied handling it himself, all loading and unloading being carried out by other workmen. He did not think that he had been exposed to asbestos dust inside the factory or at the docks, which he frequently visited. When admitted to hospital in July >963 he had been breathless for, six months and had complained of pain ir. the cheij fnr tv.o >weeks. A large left pleural cflusion was present. Uronch.iser.py . showed no abnormality. At thoracotomy tumour nodules were seza 6n both pleural surfaces. These were thickest over the lung base and on the surface of the diaphragm. Fluid reaeeumuiated pmioperatively and continued to ooze through the tkoracotor.-.y inci.suia. He remained in hospital for eight weeks and was later readmitted for short periods for picural aspirations to relieve breathlessness. He appeared mure ill at each sttcr.danee, losing weight and developing ascites. He was finally admitted in Deeember 1963, " and died three weeks later. At necropsy the left lung was encased in thick tumour tissue traced the cites* wall to form a sui'nitar.cotii mass deep to the eld thoracotomy sear and there were several skin nodules in the vieir.it/ . of the sear. The pericardium had been dirratly invaded and th: - .thoracic sort* was encased by tumour. Within the abdomen there wgj massive replacement of the mesenteries and the omentum. 'Growth had also filled the pelvic cavity, encasing the bladder, the; ureters, and the rectum. No primary growth cnuld he found in: these or in ar.y other organ in the body. Tumour deposits were: present in hepatic, panereatie, para-aortic, mediastinal, and axillary: lymph nodes. Asbestos bodies were present in smears made from Use cut surfaces of the lungs and in sections of lur.g tissue. < Case 12. Mrle. SO years. Died 1355 This man had been a boiler-maker and shect-mesal worker and: was employed all his life by a firm of ship repairers and fitters.. Kc sea* engaged in the construction of many insulated " boilers and was known to have handled asbestos. In addition he was. often exposed to asbestos dust during the mixing of materials fnr. the " magnesia " process. This method is used for the insulation cf large surfaces. Powdered asbestos anJ magnesium carbonate are mixed together and made into a paste with wstrr, thg moist material being applied to the surface requiring insulation. He was admitted to hospital in May 195-1 because of ineres'ir.; breathlessness over a period of six months. A large right plrura. effusion was aspirated several times, but fluid continued to accumu late. He was transferred to the thoracic surgery unit in July 155No abnormality was seen at bronchoscopy. Exploratory thoracotomy showed irregular patches of thickened pleura, mainly in the partita: layer and particularly over the surface of the diaphragm. Other; were present on the mediastinal surfaces. He remained :r. ho-;*;: for a further six weeks, and during mis time 16 separate aspirati-.n; of fluid were made. After discharge home, fluid continued accumulate ar.d to ooze persistently through the oper.iti.in j. s. He wns in constant pain, and his wife administered a total of JGh s. (32.4 kg.) morphine under medical guidance over the next 14 month* He died in November 1955. Post-mortem ctamt.isuan wa r.i carried out. The specimens taker, a: thoracotomy consisted entire I; of tumour and there was no lung tissue available, for exsrr.tr.at.an Discussion The occurrence of lung esneer in eases of ashcato-vis has bet: frequently recorded since 1935, when correlation between :.n two conditions was suggested by Lynch and Smith (193 5, Gloync (1951) found lung cancer in 14.1% of 121 des:h associated with asbesrosis, and Mcrewcthtr (155-1) found 5 lung cancers in a srudy or 344 cases of asbustosis (16%). An association between mesothelioma ar.d asbestsr-is was lirs described by Wcdlcr (1943) in tjermany. Neal (19w,,; sra-.ite the records of 42 cases of ssbestosis st the London Hur.pitd Out of 23 women, four had died of lung cancer, one had died , ovarian carcinoma, and eight had diffuse peritoneal growth of uncertain origin. Out of 19 men, 10 had died of lung carta: and cr.e from probable diffuse mesothelioma of the pcrr.ar.eua Konig (1960) described nine lur.g rumours, four pleural meg; theliomas, and three peritoneal mcsothcliomaa in' su'o;ec exposed to asbestos. Conversely, exposure to asbestos had occurred :r. sit one of the 33 cares of diffuse pleural mesothelioma studied L Wagner d. ('.950) and in all but two o: the larv.-r sert. of 7S cases of pleural and peritonctu mesothelioma descril*. by Wagner (1962). Since then McCaughey e! cl. (1962) hm found asbestos bodies ir. the iur.gs in 13 out of ii caeca . diduse picural mesothelioma. Tbis very striking incidence asbestos workers is confirmed by the results of the p.-esc. investigation, ar.J ir is concluded thut exposure to asb<_;: is a major factor and possibly or. essential cr.e in ji^esusati: of diffuse mesothelioma. \D' No attempt has been made to identify the type of sabe.-; used by these patients. All the South African cases had r exposed to cracidolita. Chrysotile anc arnasite are oho * in Vv.r nnnn nf th wnrsrfi <*va' ....do ycvf iVdt' Mcsochdiof/ia- -Q'cai J( {.Wf >< .J these itbrca. On the other hand. Cartier (1952) mentioned two eases ci diffuse mesothelioma from a Canadian chrysotilc r.tyte. Tc is clear that evidence of exposure to asbestos may assist i the diagnostic of diffuse mesothelioma and that a careful occupational history should be obtained in eases of prolonged chest pain or recurrent pleural effusion of obscure origin. The nrcscnca of hyaluronic acid in serous effusions is said to provide confirmatory evidence, and a simple screening-test is available for the detection of this substance (Washer el af. (1962). No pleural or peritoneal fluids have been available for examination in this series. I ant grateful to the surgeons of the Liverpool Their-eic Surgtr/ Unit for permission :n itu.iy the mcoie.il records o: caw. under their care, anti- to Dr. Dditit M. McConnell for scarsiun,; the files of the Liverpool Canerr Control Organization. 1 am indebted tn Dr. H. MeCican, Dr. Rachel M. Ra-.vrl-:ic, Dr. P. J. Taylor, Sr. 11. E. Viewers, and Dr. A. S. Vvoadcrek for maltwi: avail-hic post-mortem retards and for sending blocks at tissue from their cases. My thanks are due to Dr. F. Whitwcil and Dr. J.. A. Campbell foe their constant encouragement, ar.J to Dr. J. C. .Wagner, of the M.R.C. Pneumoconiosis Research Unit, who ilrtt suggested the investigation and who has helped me at many stages. The wore could not have been carried out without the enthusiastic assistance of Mr. A. Robertson, wlw devoted much time to the preparation of the histological material. Summary Seventeen esses of diffuse mesothelioma occurring in the Merseyside area were investigated and evidence was sought of exposure to asbestos dusr. An account is given of die clinical features of diffuse meso thelioma, and in 12 eases the pathological, findings at post mortem examination arc described. Difficulties cl histological diagnosis arc discussed and the .'.istoicgicai appearance of the tumours described. Exposure to asbestos had occurred in 14 (32%) of the 17 eases examined, and asbestos bodies were seen in seven out of 1C specimens of lung tissue examined. It is concluded that exposure to asbestos is a major factor n ti'.e causation of diffuse mesothelioma. AsscNSU.m.--Since this paper was submitted two further papers (Enticknap and Smithcr, 1964 ; Kourihanc, 1964) have teen published, both dealing with the subject of mesothelioma, and asbestos. iterunxcs* Campbell. W. S\ (1950). Amer. J. 7\a/u, 26. 472. Cartier. 7. (1952). Arelu inJutir. //ye.. S, 252. nail. 1L (1955). Brit. J. injuur. Mr*.. 12. SI. Entickr.ap, J. U.. srut Xr.iiiiier, W. J. (1964). Ibid., 21, 20. C.layac. S. R. (1951). Licer, t. StO. Godwin. M. C (19571. C:>rr (ritiia*.). 10. 298. Hourihanc. O. 0*11. (1904). Thanat, 19, 20$. Real. ti. E. (I5M). Unset. 2, 1211. Klemperer. P, and Rabin. C IS. (llJl). Arch, rssh.. II. 3SS, Rome. J. (1900). A'eit. Getesrbef.uh. Getccr.iciiv;.. IS, 15V. Lynch. K..M.. and Smith. W. A. (17)5). Amer. J. C.mcsr, 24. 50. MeCuwney, W. T. is. (193S5. J. .".tit. /Let.. 70. 517. ------ Wade. 0. L. anc Elates. P. C 0 902). Bn;. '., 2. 13J7. Merewether, E. R. A. (1934). Annual Report, Chic: Inspector at l-'aetoricv. K.ALS.G..-London. Meyer, K., and ChaeTee. c. (19-0). J. hiet. Chem., 122, S3. Robertson. H. E. (5924). 7. Center Ret., 3. 317. Wagner, J. C. (5902). "The Pa:holcc7 at Ast-esrmis in Saudi Africa." A thesis accepted by the University of the Vvitwaicrsrand' for the Degree of Doctor of Medicine. Monday, D. 1L, and Hartr.gton, J. S. (1962). 7- Peth. Bass., S4. 72. ---- Sieggs, C A-, and Marchand, P. (1900). Bris. J. insettr. A!**., 17, 260. Wt!cr, H. W. (1943). Dstek. me*. Warr..-.. 09, 575. WiUis, R. A. (I960). Peskaiocy a/ Ten-.aun, 3rd ed. 3utter.vcr-.5t. London. Winslow, D. J., and Taylor, K. B. (1900). Censer (Phils*.). 12, 127. Hypcrparathyrcidisiri end Cancer C E. DENT,* m.d., F.s.s.; L. -C A. WATSON',* M.3., m.r.a.c.I). [Wit5I SrcciAL Plate] Ms. me*. 7.. I96-;, 2. 218-221 The muse of hypcrcalcacmia in a particular patient can usually be established with great certainty. This lias been emphasized in several reviews, including those of Albright and Rcifcnstcin (194SJ, Thomas el cl. (1959), and David et cl. (1962), and sued has been our experience in this unit. A difficult problem still arises in the differential diagnosis of ypercalczcmia when more than one of the known causes is present in the one patient, a situation which seems to occur more often tlian it should. .Case reports c:'these associations inalcde hyperparathyroidism and thyrotoxicosis (Dortz eg si.. 1961 y ` Jackson et cl., 1961), hyperparathyroidism and sarcatdcsis (Durr el cl., 1959), hyperparathyroidism and Paget's disease (Koitn and Myerson, 1961), and hyperparatltyroidism and cancer (Hcllsirom and Ivemark, 1962). We arc repeating our findings from a severely hyperaaica: tmic nisr.t, who proved to have both a primary carcinoma o: si r-.-b; uteri and primary hyperparathyroidism, due . to parathyroid adenoma. * Member et die Medical .Uni;, Univerii.-y College Hospital and Medical Sebooi, Londoo. Case Depot; A married woman aged 37 was admitted to University C-i'.'.ege Hospital in August 1962. Site was the mother of six children, whese aces tanged from 17 years to 3 .-nor.tlis. bhc had t'-.-v.- complaints. She had hern a little more tired than usual sir.:, the beginning of her sixth pregnancy and perhaps a little thirsty. six mont.ss pregnant she slipped and teti frnm a bus and .-.a.-, admitted to Red'ni'.l Hospital because s: abdominal pair.. <..iea r,uick!y settled down. She soon felt very wed but was found ! be anaemic, with a haemoglobin of t.bnu'. 50%. She giver, two blood transfusions, cacti of 2 pin:-, (1,1-50 mi.) and dMcharg.-d. Thrst months later sht ea.v.e into labour, which w..r. rather pro- longed, lasting about 25 hour: and terminating wi:5i the :c , f vacuum extraction. This was unusual far her, as she had prevt.i-.-.jly had tjuich and easy labours at heme. | ! | ; During the piterperium investigations revealed ihat the. plasma calcium level was rat.scd. as was the plasma alkaline phospn.-.tu w, while :hc plasma piiosphor.ia level was abnormally low. A: i.-.-s stage the patten: insisted that she was tree cf symptoms and eh..; she should be allowed tc, leave hospital in order to look after her family, in August she returned for a post-n.-.tai follow-up ctsminatten, when the S.H.O- (Mr. A. R. F. Williamsi i.houri-t t- -.r