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FILE NAME Brakes BRK DATE 1972 DOC BRK038 DOCUMENT DESCRIPTION Journal Article - Peritoneal Mesothelioma GASTROENTEROLOGY Copyright '1972 by The Williams & Wilkins Co. CURRENT CLINICAL CONCEPTS = Vol 63 Na Printed in U.SAS U.SAS 7 August 1 and per Thomas R. Hendrix M.D. Current Clinical Concepts Editor The Johns Hopkins University School of Medicine Baltimore Maryland tos exp cupation bestos ti installat repair w With PERITONEAL MESOTHELIOMA mesothel umented known o CHARLES G. MOERTEL M.D. or demo Mayo Clinic and Mayo Foundation Rochester Minnesota significa A clin has come The filmy mesothelial layer that lines substantial the abdominal cavity and envelopes its real portion of this increase is contents is exceedingly vulnerable to The incidence of 3 - secondary involvement by a multitude of striking mesotheliomas has oc- neoplasms taking origin both within the ' relationship to the dominant abdomen and at distant sites The cupation of the population studied In only the cancer primary to the peritoneal surface Canada where a large proportion of populace is engaged in rural pursuits the however is the mesothelioma Recognition of this tumor seems to be average rate of occurrence is 0.1 case per unique to the latter half of the 20th century by virtue of 100,000 of population per years among heavy industry workers in Dutch either the astuteness or creativity of inces the rate is 1 prov prov our pathologists and also by virtue the Dutch shipyard per 100,000 and workers it is found in sometimes less than wholesome nature of 100 per 100,000.11 100,000.11 to be be our environment The remarkably rapid SWF increase The peritoneum is host to mesotheli in the rate of occurrence of these mesotheli tron of | bestos fi all three site chry equally ca The du widely in lated to a year to formly he period whi between : sured from exposure exposure rane neoplasms makes it seem likely that they nas cwihlalllbeengeantointchreeasingly frequent clinical single sources 257 cases were years ahead gastroenterologist in the the pleura 128 to the peritoneum and cases seemed to have tumors primary Incidence both surfaces 4. 6-9 12 From the stand Prior to the last decade reported cases mesotheliomas of peritoneal mesotheliomas were ex- reve ceedingly rare and in 1960 Winslow and Taylor were able to cull only 13 reason- point of incidence as well as etiology and pathology however should best be considered as a whole gardless of their site of origin - use of asbe century it years ahea alarming i mesothelio already wit It should theliomas ; the related to t clearly the evidence meso - ably documented cases from the literature Etiology In the 11 subsequent years up to this writing this total has swelled to at least With the possible exception of lung can 169 cases in the English literature alone 1-11 cer there is no malignant neoplasm for Much of this increase . which the relationship of environmental can undoubtedly be factors attributed to improved pathological carcinogenesis has been 0 recog- nition but retrospective studies established as in mesotheliom necropsy material of The first link in this chain of ~- ological criteria employing current path- was forged by Wagner and workers would also indicate that a who demonstrated a remarkable pre- Received dilection for the development 5. January 31 1972 Address theliomas among asbestos miners in Moertel requests for reprints to Dr. Charles G. South Africa Since then a number of Mayo Clinic Rochester Minnesota 55901 other studies have associated both pleural *, 346 particular et al.'s sti proportion + tn shipyard ative history the London pations w itive his als als Canad tients had -bestos -bestos and nts had n troi subjects ver unelucid can- 1 for ental , SO oma lence ters pre- neso- s in er of leural August 1972 1972 CURRENT CLINICAL CONCEPTS 347 and peritoneal mesothelioma with asbes- Particularly vulnerable oc- tos exposure cupations are shipyard workers asbestos textile manufacturing brake lining installation insulation workers and sack induce this neoplasm Of particular inter- est in this regard is the recent demonstra- tion by Chabot and associates of induction of typical mesotheliomas in the chicken by a strain of MC29 avian leu- kosis virus repair workers With specific regard to peritoneal mesotheliomas 54 of 84 adequately doc- umented 7-9 11 cases have had either to asbestos known occupational exposure or demonstration of asbestos bodies of significant number in lung tissue A clinching bit of etiological evidence has come from the induction of tumors of mesothelioma histology after inocula- tion of experimental animals with asbestos fiber Under these conditions all three varieties of asbestos amo- site chrysotile crocidolite proved equally carcinogenic has varied The duration of exposure widely in mesotheliomas presumed related to asbestos ranging from less than 1 uni- year to formly over 50 however years a very series There long averaged period period which in several series has 15 16 10 between 33 and 43 years induction mea- sured from the time initial asbestos exposure With the widespirnetahde imnidudst2r0itahl use of asbestos materials century it is entirely possible that the ahead may demonstrate a far more years of alarming increase in the occurrence mesothelioma than that which we are Pathology The histological appearance of the peritoneal mesothelioma is so variable - and in its variability it so closely simulates other recognized neoplasms that some have challenged the existence of this tumor as a pathological entity Indeed many pathologists will still only make the histological diagnosis of probable mesothelioma with confirmation resting on such factors as the failure to _ demonstrate some other primary neoplasm at autopsy or a history of occupa- tional exposure The pathological classification employed by Whitwell and Rawcliffe is quite typical of those used in other re- ~ ports 1. A papillary form These are quite similar to secondary adenocarcinomas and are characterized by branch- ing acini lined by low columnar or cu- boidal cells In contrast to adenocar- cinoma Mucicarmine stains seldom re- veal evidence of mucin production but staining reactions do demonstrate a hyaluronidase mucopolysaccharide around the tumor cells indicating the already witnessing It should be noted that not all meso- theliomas are related to asbestos expo- sure proportion of such patients is related to the occupational pattern of the particular region studied In McEwen et al.'s study of Scotland where a large proportion of the population is employed in shipyard industries 83 gave a posative history of occupational exposure in the London Hospital series where oc- cupations were more varied 38 gave a positive history and in MacDonald et als Canadian series only 20 of male patients had an occupational exposure to asbestos and female mesothelioma pa- tients had no greater exposure than control subjects It is apparent that other as yet unelucidated etiological factors may presence of hyaluronic acid A transition zone between normal and neoplastic mesothelium may provide convincing evi- dence of a peritoneal site of origin 2. An undifferentiated polygonal cell type Here uniform eosinophilic polygonal or round tumor cells occur in solid sheets resembling a medullary type of adenocarcinoma Mitotic figures however are quite rare 3. A sarcomatous type This variety may be indistinguishable from a fibrosar- coma or fibromyxosarcoma There is a spindle cell fibroblastic appearance with arrangements in bands or whorls and multinucleated giant cells may be seen 4. A mixed type This may contain any of the above elements and with this mix- ee tang ts Bam rocynegamDetwohe A=r amen t ae 2 an sabes nlael TAD. AP dudes hte oa t e Oe 99 tae weine aylonen ee cbs cheb pi, eS e bntANL a Netint2 tl vik tae Pees geen si dtTore Mabel p os anes RodGearmne aenine tadWen wevle Got oe Sie aati adntharsotlase 4 Sebrwnand es R woudlPOE TTte Rivest oe bed. meswnaa bhdebod ek tkELid cai pete peat PdiPere due, Sra a| eo!s2 iter.so at ary ror dhe Te TBamet A INTE AE Ce EUG ae ences estate MLAS AANA eR 348 CURRENT CLINICAL CONCEPTS Vol 63 No. 2 4 August 1972 ture histological diagnosis is simplified The only confusion that may exist is with a primary carcinosarcoma or a malignant cramping inal discomfort obstructive severe paroxysms Sometimes or ag pain is #@ aggravated by micturition or defecation-% &F without la biopsy alor ogist with a synovioma Grossly peritoneal mesotheliomas Severe weight loss is almost universal and usuallyby the time the patient seeks a 3 terpretatio Examina present in two basic forms One is with a medical assistance abdominal distention fluid may b large tumor mass usually in the upper ab- is also evident Nausea and vomiting Occasional domen and discrete smaller nodules bowel obstruction and fever are less com- thelioma p scattered over larger areas of the visceral mon complaints . me: viscid C and parietal peritoneum The other form is that of diffuse nodules and plaques The most common physical sign is as- ee cites which has been observed in almost 34 usually re thelial cell that coat the abdominal cavity and envelope and matt together the abdominal viscera There is characteristically a striking contrast between the massive abdominal involvement and the minimal 90 of reported cases A palpable abdomi- nal mass is a much less frequent present- # ing finding 16 Occasionally the disease-- # is first evidenced as an extrarectal or + < pelvic mass and rarely it has been 2 first this findi and wo high acid sterile fluic strongly visceral invasion and metastatic dissemination When invasion does occur it is usually only superficial and tends to fol- diagnosed incidentally on pathological ex- patients amination of a hernia sac Many : will have respiratory signs and digital club-- approach sufficient c nostic valu low fascial planes Large tumors in the abdomen may invade through the dia- bing associated asbestosis with their pulmonary : ; phragm and involve the diaphragmatic pleural surface Frequently death occurs as a result of abdominal involvement alone before there is any detectable metastasis Nodal metastasis is uncommon and is essentially never observed with the pure sarcomatous form When metas- other- In company with a variety of mesenchymal tumors the mesothe- lioma has been found rarely to be asso- ciated with symptomatic hypoglycemi#a 19 Thirteen such cases have been reported : and in 5 the primary tumor has been if peritoneal In some of these however f Unfortur cessfully has lagged etiology an instances and presur been recor tasis occurs from the mixed histological the precise diagnosis of mesothelioma always wel variety the metastatic lesions are usually may be challenged under today's 5 at the tim DALIANA pathologi 3% DALIANA of the papillary architecture Ob- cal criteria It has been evident in these : apy syster DALIANA syndromes served sites of blood metastatic patients that the hypoglycemic : lation of va ... spread have included most commonly the are not related to increased levels of cir the perito liver and lungs and more infrequently thyroid the adrenals and bone kidneys pancreas Clinical Presentation and Diagnosis hypogly culating insulin and some other cemic factor is probably involved As is ; cell 8 true with most of the other islet : hypoglycemic tumors this factor or fac f tors has not been clearly identified 2% tempted in and all ha In view of Incidence ganized th Among 118 reported cases of peritoneal 2. 3. 5-8 - mesothelioma where sex is stated Prominent theories include production of an insulin substances by the tumor seem to be in regions - men outnumbered women at a ratio of 67:51 The proportion of men tended to be higher in regions where occupational expo- irritation of splachnic nerves excessive consumption of glucose by the tumor and. an induced disorder of hepatic glycogenoly-- endemic Palliative marily of sure seemed to play a strong etiological sis aah Heve ascite role The median age at diagnosis was 53 years with a range of from 13 to 92 years of Diagnosis age Sixty per cent of cases occurred between ages 45 and 65 The most frequent initial symptom is abdominal pain which may be specified as epigastric or right upper quadrant burning vague and nonlocalized abdom- There are no specific laboratory or roentgenological findings which charac terize the peritoneal mesothelioma and although a clinical impression of ab- # dominal carcinomatosis is usually reached the specific diagnosis cannot be made Although vivals hav sothelio follows a gressive ir quent con or irac- and abhed nade August 1972 CURRENT CLINICAL CONCEPTS 349 without laparotomy or autopsy Needle biopsy alone will not provide the pathol- ogist with adequate tissue for definitive in- Death has uniformly been reported to occur in less than 12 months after the diagnosis is established terpretation Examination of aspirates of peritoneal fluid may be of some diagnostic assistance Occasionally the ascitic fluid in mesothelioma patients has been described as viscid Cytological examination will usually reveal an abundance of meso- thelial cells with some atypical forms but this finding is nonspecific Thompson and workers have suggested that a high acid mucopolysaccharide level in sterile fluid with a nondiagnostic cytology strongly suggests mesothelioma This approach however has yet to be put to sufficient clinical trial to prove its diag- : nostic value Treatment Unfortunately our ability to treat suc- cessfully the peritoneal mesothelioma has lagged far behind our knowledge of its etiology and epidemiology Although some instances of surgical cure of localized and presumed benign mesotheliomas have been recorded the malignant variety is always well beyond any hope of resection at the time of diagnosis Radiation therapy systemic chemotherapy and instillation of various cytotoxic substances into the peritoneal cavity have all been attempted in a rather haphazard fashion and all have conspicuous failures In view of the apparent rapid increase in incidence of this neoplasm more organized therapeutic trial programs would seem to be clearly indicated particularly in regions where the mesothelioma is endemic Palliative management consists pri- marily of analgesia and measures to re- lieve ascites REFERENCES 1. Winslow DJ Taylor HB Malignant peritoneal mesothelioma A clinico pathological analysis of 12 fatal cases Cancer 127-136 1960 2. Cicero A Aguirre J Tamayo R Malignant peritoneal mesothelioma Am J Clin Pathol 417-426 1961 3. Enticknap JB Smither WJ Peritoneal tumours in asbestosis Br J Industr Med 20-31 1964 4. Godwin MC Diffuse mesotheliomas Cancer 298-319 1957 5. Mann RH Grosh JL O'Donnell WM Mesothe <~ lioma associated with asbestosis Cancer , 521-526 1966 : 6. McDonald AD Harper A. ElAttar OA et al Epidemiology of primary malignant mesothelial tumors in Canada Cancer 914-919 1970 7. Newhouse ML Thompson H Mesothelioma of pleura and peritoneum following exposure to asbestos in the London area Br J Ind Med 261 2619965 8. Roberts GH Irvine RW Peritoneal mesothelioma Br J Surg 645-650 1970 9. Selikoff IJ Churg J Hammond EC Relation between exposure to asbestos and mesothe- lioma N Engl J Med 560-565 1965 10. Smith PG Higgins P McR Park WD Peri- toneal mesothelioma presenting surgically Br J Surg 681-684 1968 . 11. Stumphius J Epidemiology of mesothelioma on Walcheren Island Br J Ind Med 59-66 1971 12. Roberts GH Diffuse pleural mesothelioma A clinical and pathological study Br J Dis Chest 201-211 1970 13. Wagner JC Slaggs CA Marchand P Diffuse pleural mesothelioma and asbestos exposure in the Northwestern Cape Province Br J Ind Med 260-271 1960 14. Wagner JC Berry G Mesothelioma in rats following inoculation with asbestos Br J Cancer 567-581 1969 15. Whitwell F Rawcliffe RM Diffuse malignant pleural mesothelioma and asbestos exposure Prognosis Thorax 6-22 1971 an 16. Elmes PC The epidemiology and clinical fea- Although occasional long term sur- vivals have been reported with pleural mesotheliomas the peritoneal variety follows a more virulent course with pro- gressive inanition and debility and frequent complicating bowel obstruction tures of asbestosis and related diseases Postgrad Med J 623-629 1966 17. McEwen J Finlayson A Mair A et al Meso- thelioma in Scotland Br Med J 575-578 1970 18. Chabot JF Beard D Langlois AJ et al Mesotheliomas of peritoneum epicardium ey cas) Hse SF ae TAG uf TORT Petr Aj TT? te AT ale as SEMI She fast aki ait ch,4 dawiar Sa b ; a tee deta nies AA oak ob seed Sa , ... ... heel ... LUD Lananetet ER sau Eke ab cuca: 4 BI * . CURRENT CLINICAL CONCEPTS and pericardium induced by strain of MC29 avian leukosis virus Cancer Res 1287-1308 1970 19. 19. Laurent J Derby G Floquet J Hypoglycaemic tumours Amsterdam Excerpta Medica 1971 p 87-119 20. Thompson ME Bromberg PA Amenta JS Acid mucopolysaccharide determination a usea ful adjunct for the diagnosis of malignant mesos thelioma with effusion Am J Clin Pathol 335 339 1969 in Se 2 a * PENTER PENTER PENTER TO CAN There ! idly acce and prok gastrointe HH! years tiberscope above to th low to th struments photograpi lection lection T ments is the forwa amination Tract The models off turers duri facturer strument representin Bent over bsolescenc bsolescenc endoscopist Chasing n eten me decide y se instru marily for proc dure and ar aar r pa casual presentatio and his as versity pul d d could 4 serio scopsicocpic scopic pr pr Tete at the arly p