Document Rb6gQN4eamj33bq63b5QdVyz

Anti i')m Oncol (CCT) WA}:1)3^317.1W, ' Malignant Peritoneal Mesothelioma After Thorotrast Exposure Clawiia Stey, m.d., Ursula Laodolt-Wcber, M.D., Wilhelm Vetter, M.D., Christian Sauter, RE)., and BorytMarincek, m.d, A case ofa malignant peritoneal mesothelioma in a 63-year- old male patient with a history ofexposure to ThorotTMt in 1945 is presented. `There was. no history of exposure to as bestos. The clinical manifestation was a serosal effusion, which required weekly ascites puncture: until therapy: with iotraperitooeaIbleomycittwas:initiate<LThe;lattertreatmeitt ledto a significant reduction ofascites without any influence on tumor progression:; Unfortunately, intraperitonea)..Mso- roycin was accompanied by pulmonary toxicity, but at a higher, total dose than known for intravenous administration. Three: years after diagnosis the patient is still alive, without relapse of ascites production after bleomycin bad to be stepped, Consderiagthe risk ofpulmonary fibrosis with high* : dose: intraperitonea) bleomycin and<the lack of efficacy on tumor reduction, bleomycin seems to offer no advantage with respect to cisplatin. . Key Words; Computed tomography--Peritoneal roesolhe. lioma--Therapy--Thorotrast malignancies. From the Departments of imer^l Medicine (C.Sl.. W.V, C.S*.), Pathology (UiU-W;). and Radlelogyfb.M.), Uruvstiity Hospital, . Zurich,SwitwHand. Address correspondence and reprint requests to Dr. Claudia $t*y. Department of Internal Medicine, University Hospital of Zurich, Ramistraue 100, 8091 ZUrich, Swit2eiluid. < : - CASE REPORT A. 63-year-old man noticed an increase in abdominal circumference in September 1990, and was admitted to hospital because ofmassive ascites and a right-sided pleural eflbsion. The patient reported in his history an injury dining World War II, which led to a cubital angiography with Thorotrast in 1945. On physical examination, the patient was in good condition (176 cm, 83 kg), without fever, lymphoadenopathy, or signs of cholestasis. Erythrocyte sedi mentation rate was 25 mm/h, hematologic, laboratory values were normal. Creatinine, ALT, AST, alkaline phosphatase, PTT, serum albumin, amylase, and al ; pha-fctoprotcin were in the normal range. Serological tests for hepatitis revealed only previous exposure toHAV. Chest radiograph showed a right pleural effusion but normal heart size and lung parenchyma. Abdominal . ultrasound confirmed massive ascites with floating fi brinous bodies. Uver and spleen were diminished in size. Diagnostic paracentesis yielded a bloody, muci nous exudate (protein content 45,7 g/L). Microscopic examination ofthe exudate revealed tumor cells, sug gesting an adenocarcinoma (Fig. 1), In addition, com puted tomography.(CT) demonstrated characteristic findings of long-standing thorotrast-induced changes (fig. 2a,B). The Ever exhibited a subtle reticular pat tern of metallic densities, which were most appttfeftl in subcapstilar areas of the tight lobe. The peripancreatip and splenichilar lymph nodes also had metallic density, Metallic deposits were greatest in the spleen, which was small and homogeneously involved. Also evident were ascites and irregular soft tissue strands infiltrating the omental fat, indicative ofa peritoneal neoplasm. There was no obvious primary tumor. Up per and lower gastrointestinal tract endoscopy revealed 313 : "?' F) NOTlCi.?; :*v rx?A'-y(-v ! {-`-7 ti. ::ai PF.,0 u$} 314 C. STEY BT AL FK3, i. High collulatfty in smear* Of the aspirated And centrifugated ascites fluMt. floondoaUfeoates of tumor ceHsmorphologically not to he differentiated from ceils of ctn adsnocardnoma. Rapanlpofsou stain, xsoo. no abnormalities. Immuhostainmg with aptj-Lu-5, -CEA, -B12, and -vimentin antibodies of the ascites' cells and identical cells, which have been found later in an abdominal subcutaneous metastasis, were bu-5 and vimentin-positiv^ but negative for Bl2 and CEA. This is an unusual combination for adenocarcinoma. Diagnosis of a well-differentiated peritoneal mesothe lioma was made (Figs. 3 and 4), In view of the poor prognosis Conservative treatment with diuretics and periodic removal of the ascitic fluid was considered adequate, During the first year, weekly paracentesis with al bumin replacement was necessary, and the patient was stable, apart from weight loss. Because of increasing pleural effusion, a pksurodesis had to be performed in May 1992, Thoracoscopy showed tumor infiltration of the parietal and diaphragmatic pleura and the histologic appearance ofthe biopsy specimen wasidentical to the < ascites. Subsequently, the patient got tired of the par acenteses and they were stopped. Within 1-2 weeks increasing ascites Caused paid and dyspnea. In September 1992, weekly chemotherapy with 30 ffKS,..2. (AiBl Upperalxtomlhaf CT Secoodary changes 45:year's after, thorium dktxkle in jection: Reticular pettem of metallic paneltie* in the liver, most apparent In subcapsular areas of the right lobe (arrowhead). Homogeneous metallic density of the spleen, which is small <S). MetaKle deposits in peripanematic lymph nodes (open arrow). ApcHes (A). Omental inflf* tration Secondary to malignant peritoneal mesothelioma (curved arrow). AmJ Clin Oaedt (CCT), Vot. IS. Ha. 4. Ml T PERITONEAL MESOTHELIOMA AFTER TEOROTRAST 315 PtQ.a,Asptrtdcol(sof the &b-; nominal well tumor, immuiwytochemfcal stflinlngwtth tbs keratin antibody Lu-5 shows the positive reaction Id cells of the epfthelW type of mesothelioma. .....tsv -::,c .'.'-iZ&ih; .v.r if-v mg intraperitoneal bleomycin was initiated and theascites decreased markedly within 4 weeks. The dose in tern! was prolonged to 14 days, because thecumulative dose for side effects (especially pneumonitis) with intraperitoaeal bleomycin is not .known. Bleomycin therapy was continued untit May 1993 (cumulative dose of 720 mg). At this time, the patient started suf fering from dyspnea and cough. CT ofthekmp showed interstitial fibrosis and cardiophrenic lymphadenopathy (Fig. 5>. In the abdomen there was evident pro gression of the peritoneal tumor, but ascites bad de creased (Fig, 6). Bleomycin was stopped, and so far no relapse in ascites production has occurred. Therapy with steroids and oxygen was started to mducedyspnea. Three years after diagnosis the patient is still alive. DISCUSSION . Malignant peritoneal mesothelioma is a rare neo plasm causing major diagnostic and therapeutic prob lems. Most eases are related to a$bfe$tn& exposure (J), In the case of a malignant tumor in an individual with a history of Thorottast exposure with typical deposits ofthorium dioxide, a causal relationship must be con sidered (2-4). In our patient, them was no other known FIG. 4. The partially ^poirttveGJnv munoreacdon of the- tumor ceils with: vfrnentlrr demonstrates the Nphaplc character of the meso- fheliomaluinorcete. . Am Jam Orient (CCT). Vti. iS, jVrt. *, tm 316 a stey et al. FIG. 5. Pulmonary Hbrosla after bleomycin; .GT shows Interstitial: fibrosis most merited in trie eaudad left lung. carcinogenic stimulus and no exposure to asbestos. The long latency period is characteristic. Malignant tumors occur alter a latency of 14-45 years <3>. Thorotrast accumulates in the reticuloendothelial system; - es pecially in the liver (60%) and in the spleen (20%), where alpha radiation is delivered in considerable quantities over prolonged period$,.because Thorctrast has an extremely long half-life (4-6). Its physical half life is about !,4 X 10,(h years and its biologic half-life is 400 years in human beings (7). Wherever the sub stance accumulates, fibrous tissue is formed. Beyond this fibrogenesis, Thorotrast is carcinogenic. A positive BGyU. progresalonofmalignant peritonealruMothe*wir{curved arrow):: folowlfig: imraperitObeUt With bleomycin, but regression of ascites - Am JCIIm Cm/ (CCD. Vat. IS, Nt>, 4 mS PERITONEAL MESOTHELIOMA AFTER TROROTRAST 217 correlation between dosage, tumor incidence, and la tency has been demonstrated in previous studies (6,8- H). The most frequent tumors are renal/pclvie card- nomas, sarcomas, leukemias, liver hemangfoendotiie- Jioma, hepatocIkdarcarcinorna,flnd cateinomaofthe bile ducts (4,12-16), Up to now Thorotmst-associated peritoneal mesothelioma has been reported only once (J 7). The mesothelioma in our case is not in a direct irradiated area, but there is a close topographic relation between,the tumor and the deposits ofthorium dioxide in the liver, the spleen, and the lymph nodes, s Histologic diagnosis of mesothelioma is oft diffi- cultbocausetnesothdial hyperplasiaor oftser raaJigOMit tumors may mimic mesothelioma. Therefore, immu- nohistochemical assays, demonstrating the coexpres sion of vimentin, keratin, and epithelial membrane antigens, are often necessary to establish the diagnosis (18), CT isa floninvaave imagingmodality in diagnosis and follow upin peritoneal mesothelioma (19); Ascites is usually present in moderate or large amounts. Omental infiltration is a prominent and valuable OT feature and the progression ofomental involvement is a notable change to discern on follow-up (19). Therapeutically, malignant peritonead mesothelioma is still a problem. It is known to be relatively refractory to conventional intravenous chemotherapy- A subset ofpatieots, principally those with small-volume disease, with and without surgical tumor debulking, can benefit from treatment with intraperitoneal chemotherapy, Most data available refer to cisplatin-based intraperi toneal chemotherapy (20,21). In our case, intraperi tonea) chemotherapy with bleomycin had an excellent eflfeet on ascites control, , but no effect on tumor pro gression. The cumulative dose fur intraperitoneal treatment which is not associated with side effects is unknown (22). Unfortunately, our patient developed pulmonary fibrosis after a cumulative dose of 720 mg, which is three to four times the total intravenous dose associated with pulmonary toxicity (23). Considering the side effect of pulmonary fibrosis and the lack of effect on tumor mass reduction, high-dose bleomycin given intraperitonealy seems to offer no advantage with respect to cispiatin. oE ' REFERENCES I. Aotman KH, Pass Hi, Recht A. benign and malignant raesoibelioma, ltij:Devita V?, NeUmann S, Rosenberg SA, eds. Can- ret,tpriimjfa'aMpwaiceii)onajlatni.^.Phitadel9hiKJ,(t:lsin-;- pineotU I989J399-417. . 2. Jammer ML, Miettinm OS, Flynn MJ. Effect of long-term Thoroutul exposure. RrWMofcy 1972;103:13-20, 3. :GondoS B, Late clinical and roentgen observations following Tfcorotmst administration. (?lin Radiol 1973:24:195-203. i, .- ; 4. Case Records of the Massachusetts General Hospital. Case 15: : t981. H EtigfjMedm (;304:893-899, 5. Cramp* O. Radiation injury with particular reference to Tho- - rotrasL Pathol Anna )971;6,'147-<>9. fi;:Vori .Kaiek C. Lorens37, Moth-H, KAtil;A Malignanricsin . 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