Document dYjv1NkmN5ZMoQGJ8OpZ1V6oq

Original article Results of treatment of 33 patients with peritoneal mesothelioma , G. Sebbag, H. Yan*, B. M. Shmookler*, D, Changf attd P,, H* Sngafbaker Washington Cancer Uutjtntt and 'Department of Pathology, Washington Hospital Center, Wnbingten, DC and TWerai, Rockville, Maiyknd, Corrapmitfct tt: Dr P. :H;.Sn^bjke'rt::W^Mhiipon C<uic*r:Institute, tiPIrving S&eifrKW^ WiiJ-tfngiori,:PC 2Wi6, iJSA,;:. ! i:;:: j'j bokgnuidi Peritoneal mesothelioma is Bi rare : peritoneal malignancy, representing approproatcly one~third ofall mesotheliomas. It is regarded as tuniverwlly foul cancer with few treatment options. MoUtodwRecords of: 33: patients with peritoneal mesothelioma were : reviewed retrospectively. Demographic, clinical: and quantitattveprognostic indicators werecvaluateri and anafysedstatistiglly using survival as endpoint- Patients were treated by a uniform strategy iwolving cytoreductive surgery with peritoneotomy procedures and perioperative intruperitoneal chemotherapy (cisplatin, doxorubicin)...... ............. .... ........... ............... .... ReatiHei There were ten women and 23 men; mean age wS3>0 years-Asbestos exposure was recorded in five patients and a family history of cancer in 13. Presentation was mainly abdominal distension Mid pain. Median survival was 31,0 months; overall projected survival at 3 yean waa 56 per cent The most significant positive predictive factor* of survival were*, female sex (P0-003), low prior surgical score (? 0*002), completeness of cyttrreduetkm P* 0*0002) and second-look surgery (P 0*019). The morbidity rate for this combmed^iraatmeiit was 33 per cent and:the perioperative: mortalityrate was 3 percent, Conclusion: Although peritoneal: mesotheliomais rareiprogress in its managemcut b^s occurred- Survival has been extended and selection filters by which patients may be allocated to aggressive management strategies have been defined: Paprr accepted 13 May 3000 BritishJournal ofSurgery 2000,07,1587*1593 introduction Mesothelioma is 3 neoplasm originating from the mesothe- lial surface liinng cells of the serous human body cavities. MeSOtheliotna may involve the pleura, less frequently the peritoneum end* rarely, the pericardium, and the tunica yagjnal& cestis. Peritoneal mesothelioma is usually s rapidly: fatriperitoneal surface malignancywith a median survival of iessthan 1 year1. Itrepresents*boutone-third ofall forms of mesothelioma1*3;: Several articles have appeared; in the medical literature on the asbestos-mesothelioma aetiolo gies) liplr since Wagner ttalf" first described this important relationship in I960; Implication ofa$besto$exposureinthe : causation of peritoneal mesothelioma is far less obvious than in pleural mesothelioma1'*. This report describes an experience with 33 patients with peritoneal mesothelioma, and analyses their dbucopathoiogical features. Treatment consisted ofacombined approach of extensive cytoreduc- rive:,surgety:*ritb;:peritonectomyprocedures.and intraperitoneal perioperanve-i -chemotherapy^.. This- ? aggressive therapeutic approach:-resulted in: successful palliation of ascites and long-term survival was seen in some patients:A search was made for selection factors associated with an improvedquality oflife and a prolonged survival for patients with peritoneal mesothelioma. tatlinla and methods -Patients . The records of58patients-withprimary peritoneal- surface malignancy surgically treated between 1989 and 1999 were renewed retrospeerively. Thirty-seven patients with peri toneal mesothelioma were identified together with 13 patients withprimary peritoneal adenocarcinoma and eight padentswithpapillaryserouscarciiioma ofthe peritoneum.: -;ip^o66 .$iii&iwLtd ' 'V: :: British Journal of Surgery 2600, 87, 1587*1393.... FI NOTICE: THIS MATHft'AU MAY BiT PHfcJECTED By OOf-yr;.^tar *W:(T:nti n* US.COOE) J - 1587 iSW Ptmonul mwethuilonw G. Scbbig, H, Yan, B. M. Shmtwlder, D. Chang H- Sugafbaker This reportwas restricted to 5 J patients with mesothelioma involving exclusively die peritoneum, free; from distant metasasis&tfoetimeofinitialtxeamjenratthisinstitodon. Pathology . Pathological procedures mduded^examination of haemstoxylin mdeasfo-stamtd actions; routine histochemistry . aftdjWheurequiredvspecialiMd imKiUnohistocheraicat tests for differentiation from other peritoneal surface maligium-. cits; The immunohistochemical stains included: mueicarmin aldan : blue, monoclonal antikeratin antibodies CAMS.2 and AE1/3, epithelial membrane antigen, carcinoembryogenic ajidgen (GEAi. cardntigenic antigen l^S (CA125), tiwootir-sssodared glycoprotein B72J, mono clonal antibody Ber-E?4, aniimyelomonocytic antibody Leu-Mi, placental alkaHne phosphatase and acid calciumconjugated S-tOO protein. - Clinical features analysed The following-data were retrievedfrom the patient records; and analysed for their impact on survival: age it surgery, sex, race, personal and familial medical history, exposure :to asbestos, and use of tobacto and akohol. Fromother institutions were gathered date and character of first presenting symptom, date of first diagnosis, previous surgery andadjuvanttreatments before referral. - - - : A scries of quantitative prognostic indicators for perito neal surface malignancy was used in an aitemptto identify selection factors for treatment: the prior surgical score, the peritoneal cancer index and the completeness ofeytoredoc: tion score. All these indicators used survival as an endpoint. The prior surgical score has been described previously9 and ranged from aero to 3 fO, no previous surgery; I, one abdominopelvic region dissected; 2, two to four regions dissected; 3y five or more abdominal regions). The . ^peritoneal cancerindexvisually flssessedthe mass oftumour present within the abdomen and pelvis at the time of abdonunal eaploranon.i:lt has :also been described pre-r viausly^. ft quantified die tumour in 13 abdominopehic regions by a lesion site score; the sire ofthe largest nodule and not the number of (esions: was scored. The lesion she was from zero to 3 fl ; lesion smaller than 0*5 cm; 2; lesion smaller than 5 cm; 3, lesion larger than 5 cm or layering of mesothelioma in the region); the maximum peritoneal Cancer index was 39 (3 X13). The completeness of cytoreductkm score is another quantitative visual assess ment of tumour volume left on the peritoneal surface8. In contrast to the peritoneal cancer index, which was scored during abdominal exploration, this scoring occurred alter the surgical efforts had been completed. The score ranged from zero to 3 (0; no tumour; 1, nodules smaller than; 0*2 5 cm; 2, nodules smaller than 2-5 cm; 3, nodules larger than 2*5 cm remaining after surgery qr confluent tumour}; complete cytoreduction was reflected by a score of 0 or 1. Performance statuswasassessed using tiieZubrod*-Eastem Co-operative Oncology Group(ECOG) scale fromzero to 5, with zero indicating a normal level of functionw- The following data were recorded from patients1 chart? and follow-up notes: physical examination and operative find ings, surgical procedures, intraoperative and postoperative inmperironeal chemotherapy treatments, postoperative.;., course and treutJnentSMckding systemic chemotherapy and radiation, second-and third-look operative procedures, tumour marker levels, presence or absence of metastasis, survival status, date and cause ofdeath. - Treatments . The goal of the treatment was to use both surgery and regionalchemotherapy maximally: ineverypatient; to: the limits of patient tolerance11. Nine patients with extensive ascites were orated before surgery with induction intraperitoneal chemotherapy ttsfog oispJatin-'(Elating;: Bristol . Mj'ers Squib Cfompariy, PenningtotiyNew Jersey, USA.) at .; ISntg per m? per day and; tioxorubiein {Adriatnyetn; * BenVemie Laboratories, Bedford, Ohio, USA) atdmg per m? per day. Each cycle of treatment was for 5 consecutive days; given once a month for 3 months. After the induction . intraperitoneal chemotherapy the patients Went on to cytoreductive surgery. The other;: 24 patients' Initial , treatment at this institution was cytoreductive surgery, which included all or part Qf thefollowing five peritoneot omy procedures, which have been described previously', greaterand lesser omentectomy, right and left subphrecic iperitonectotny and complete pelvic peritoneotomy8. Visceral resections were often required for complete : :cyxofeduction, During the surgical procedure the patients had intraoperative intraperitoneal chemotherapy with risplatjn 50 mgAtl2 and doxorubicin 15 mg/m3, heated to . 41-41 S'C.11. Patients whohad a moderate-to-largevolume ofmesotheliorna left behind after surgerywere treatedwith additional cycles of postoperative intraperitoneal die-1 : mothenpy, with a similar dose and schedule to the induction treatment. Toxicity was recorded and graded accojding to the National Cancer Institute Common Toxicity Criteria15. Follow-up was updated until 15 August 1999. Statistical analysis ;. Survival was retained as endpoint for all statistical analysis, and was determined from the time of initid diagnosis. The : British Journal of Surgery 2OD0, 87,. 1587--l S03 www.bjs.co.ult itiiOtW. BldtWtll:SaMLCCil8: G- Sebbag, H. Van, fi, M. ShmeokJer, D- Ch*n and P. H, Sogarbaker * Auitortul maseUMjIttna 168* survival curves were obtained using the Kaplan-Mejer : jnethodandcompatisonofsurvival was bylog ranktestS'15.?; Two-tailed P< U-05 was considered statistically significant. Result Demographic and epidemiological data The significant data are summarized in TkMr h The mcan : age was 53-0 (range 17-79) years. There was a statistically : significant advantage in survival for women:: median 4i ?7i?rwl6monthsTbr:men(i,t0'003).Thirty-OnepatiMr5 were Caucasian; there was one African American and one Asian American,Twelve patientshad no historyofexposure to asbestos, five had a positive history (two worked in a shipyard* one in a cement faccorv, one with insulation and one as an electrician) and there were no data on Id patients. Sixpatients were tobacco userid Thealcoboleonsumption: rate was low (four patients) and no patient used recreational drugs, Thirteen pacientshad a famih'history ofcancer (in a . parent or: sibling), five: of whom had more than one first* degree relative with a malignancy. Symptoms, signs and diagnosis Tab)* i Significant epidemiological and: clinical data ott33 patients vdth peritoneal mesothelioma : ' 1 . _ j ' .riwvf. ` patent* .1 (months} 0:'4 Aq*(ynut) 1 *53 >83 Sex 'r'ih 17 28 . 7 - it 'M 0403 F*nvto 19 41 y:- . :(:; Mala i'Mrl : : 1ft A*6*8torMpt*uf. -; . ;: . /;: ;04S ' - y*t ,5 18 Na 12 18. Unknown 16 83 ***** ft* 22^ 17 : .. ri: \ It 34 WMtoSnp 8 28 f'taopiCtvimottwapy Systemic Intrapaittooea] 7 a 34 35 ;0-65' Both 2 51 Pwfwminoa statu*'' >03 0-1 2t 2rA 12 IT ::|^::iM^l6*t:ici6M:''' 7;o^ 0 18 41 / :t-b; - '.iiir'.:: IB 18 -. .The commonestinitial complaints fof peritoneakdiesotheT. Homa, isolated or combined, were an increasing abdominal girth (2? patients), abdominal pain (nine) and weight loss: (six). Ascites was present at time of diagnosis in 22 patients .. and was debilitating in six(7oWe:/:). Unusual presentations. included aCuie abdomen (one) and rectal bleeding (one). . Thc tncan interval from onsetofsymptoms to diagnosis was ' 5 (range &r33) months. The mean interval from diagnosis tq definitive cytoreduction was 9 (range 1--48) months, Diagnosis of peritoneal mesothelioma was made by laparotomy in :18 :patients, by laparoscopy in ten, and by a bdominal puncture and cytology ip five patients. : : Treatments before definitive cytoreduction and :- : intraperitoneal chemotherapy '. Sixteeiipatientsreceivedchemotherapybefore cytoreduc* tive surgery: intraperitoneaj (nine), systemic (seven) and: both (two). These, chemotherapy treatments: before and : after cytoreductive:surgery were not part of ft: systematic perioperative approach, but reported as treatments received : at different iastitutions.:No patient underwent kradiation. Induction intraperitoneal chemodierapy was successfol in eight ofninepatients butthert was no significant impact on survival (TuWe 2). The performance status before cyto-. reduction w*s2eroor 1 in 2 (patients and 2r4in 12 patients; their median survival was;29 and: 17 months respectively (P - 0-02 9). The prior surgical score was zero ini 8 patients; and 1-3 in IS patients; the median survival was 41 and 16 months respectively (P-0'G02)(7hM> J). Treatment data Significant data regarding treatments are shown in TtfWr 2. Between 1989 and 1999,47 cytoreductive procedures were performed on 33 patients with peritoneal mesothelioma by the Same surgeotiv 33: as a firstprocedure , M as second-look and three as third*k>ok surgery. Twenty of die 33 patients had the first cytoreduction after 1993. Twenty patients received a major first cytnreduction involving four or more , abdominopelvie regions.Thirteefl patients, with high comorbidity or kreseetable peritoneal mesothelioma, had: a- less extensive defaulting procedure; a comparison of survival approached statistical significance in fjvour: of major cytpredbction (P-0-07), Mean operating time was <5-8 (range 2-13<5)h; mcamastiits volume was 24(rangt Os: 14) litres; mean blood requirement was 2 (range 0-8} units. For the initial 33 cytoreductions the mean peritoneal cancer index was 29. For patients with a score of 0-28 the median survival was 34momhs compared -with only Id months for patients with a score between 29 and 39; . #2000 Bladweil Science I>d: :' ' ::www-bjs.co.ui : British Journal of Surgery 2000,87, 1587-1591 15B0 PMttonul^nvMOthftUotna G> H. Yon, B.M.Shmoolfter, E>,\ Citing and. ?- H. Swgaxbikei: Tabki2 Significant treatment data on 33 patients -with peritoneal mesothdlotna ' m'' ..........w..... TaU*a Pathology of peritoneal mesothelioma .................. ""' """ ...... :''f :$% -iwerthd} V . -CWT ' T^^Maa^^iipiMg^niiifefe iW rr-M~^V ^ ;Sv 1; 'v`\ %Gtnrc:; ;iiy;4^:F -11 13 Ml. 28 .rfa' : > ;.* vks.. ............ --' 1.,7^j;-ct; w=. ^ "fer tfvewftTttWMr.. OwHromowkie' n E2 - * 'i 21 .-- s 10 -15 23 1ft 35 17 SB 11 : 23 1ft MSB-; <M1 JV.O! itft(Siired:;ir^m dwwncipfiiiiagyDni; 'Jasg- fn|cirt the peritoneal cancer index wfts a statistically sijpiificant predictor of: survival (P-0-026), The completeness of: cytoreduetion score was 0-2 in 17 patients and 3 in 16 patients, with -a median survival of 41 and 13 months respectively (P -0-0002); Twenty-eight patients: received perioperative imraperitoneal chemotherapy (heated intra- Operative treatment, postoperative treatment orboth) and rive patients did not; their median survival was 28 and 18months respectively (P-0-1J), Eleven patients had a scheduled aecondelook cymreduction:6-?tnonthsafter.the first Operation, combined with perioperative incraperitoneal chemotherapy in ten. Three patients had a third-look operation;.Medtansurvival was 35,momhs inthetl patients: who hadsecond-Iook surgery compared with 1 S mooths in the other 22 patients; this was statistically significant (P-0-002), although the survival advantage may have resulted from selection factors inherent to that group of patients. Morbidity and mortality There were U patients with grade H3-4V complications, givingan overall morbidityrate of33 percent Fourpatients , MinnahiU-iMM#He.v.l '= w? ^Sgs.lft ;. : ,Z iTuWopapfti*.;: I?'?; /W4 ' -'--3 apnMbo :-SveitMrtW; :i:-- o 'Total:-; .MMK .' 3 ;*:&? . 77 02 01 1ft IB, requked reoperatioti for persistent bile leak from the liver surface (one), small bowel fistula (one) and late intra abdominal bleeding (two). There was one perioperative death from sepsis that occurred 33 days after surgery. Pathological features : Thirty-three patients retained a diagnosis of peritoneal mesothelioma {Tahiti)-. 30 malignant, two low-grade malignantmulticystic mesotheliomas and one multicenmc aggressive adenomatoid mesothelioma. The malignant mesothelioma subtypes were epithelial in 27 patients, subdivided into ten epithelioid and 17 tubulopapyiary lesions, biphasic or mixed in two patients and sarcomatous in one. AU three patients with mesothelioma of low malignant potential are freefrom disease; the three patients with an aggressive subtype have died from the disease, and patients with epicbelial histology showed mixed response to treatment. . Follow-up and survival The median follow-up after cytoreduetion was 21-3 (range 1-7?) months. No patient was lost to follow-up. During follow-up distant metastasejwerelater diagnosed in Seven patients-, liver (one), mediastinum (one), lung, (two) and pleural cavity (diree), All patients who developed distant metastasis havedied from the disease. Twenty-one patients had no metastasis and there were no data on five patients (Table 2), The occurrence of metastasis decreased survival significantly (P- C-001). , Fifteen padents:died -froteitbe disease and 18 patients are still alive (Tabit 2), Ten are alive withdisease and eight have no evidence of disease by imaging, tumour markers and second- or third-look surgery. The median survival: from diagnosis, was 31-Qmonthsi The KapJan-Meier survival curve forthis group is shown In Fg. 1, Theprojected overall survival at 1, 3 and Sycars is 77, 56 and 47 per cent respectively. SritUbJounuI of Surgery 2000,87, 1587-1S93 www.bjs.co.uk 2OO0 BIdfre8 Setnce Ltd G. Ssbbg, Ml Yu, S. M- ShmooUet, D; Chang sad P. H.Stlgubaker * p^fltanfctl nuidihtflWWi JWt 5*P and mAu, fhbtepa and bleomycin3 |2W7. More recent reports show n more systematic approach to peritoneal mesothelioma, with debulking surgery and systemic: chemotherapy with paclitaxel, dsplatin alone ;or doxos rubidnJfrJS. A phase I trial with 1 patients repented a similar approach to the present one, with promising preliminary results51. The prognosisis grim after diagnosis Of peritoneal mesothelioma: survival of 7-13 *5 months and Only* few long-term survivors are reported1'5,24'52'53. The* : median: survival in-thjs ; group was M`ftmonths from diagnosis, with.a projected.3.-yearsurvival of S6 per cent These results need to be tempered by the relatively 6hott follow-up after cytoreduction, -: . In this study,>pnsitive predictive fectors of: survival were identified % univxriate.analysis: (1) female sex (2); good Nctaftfek 33 01 IS W 7 3 3 0 health status, (3) minimal previous surgery* (4) low Hfl. v Kaplaw-Meier survival euro ofJ J patients with peritoneal - peritoneal cancer index, (5> low completeness ofeytoreducmesythdiarnavMeJiin ;surMvaIfrta; diagnosiswasJl .Omornbs<: tjon score and (6) setOnd-look surgery (for selected - patients); these factors eomlated witbbnprovcd survival,:: There was a suggestion that partial debulldiigor resection of mesothelioma in the absence of intraperitoneal che Discussion . motherapy may jeopardize subsequent: treatment. Patients: who had a high prior surgical score were not as likely to Peritoneal mesothelioma has evolved over almost 100 years survive long teem. The peritoneal surface malignancy may from a clinical oddity to an established rare disease of ... be moved more rapidiy to an invasfve process ifanatomicai increasing importance. In 1908 Miller and Wynnls first defences are destroyed by surgery. In patients who had described1 `...a malignant tumour arising from: the en trocar-site tumoor progression, the abdominal wall masses dothelium oftheperitoneum and producing mucoid ascitic : progressed: roore rapidly^thaniresidtml itumour..in the. fluid,' In 19f)9 Adami)? first used die tetiumesothelioma to.:: abdomen, refer to a highfy malignant rumour of the serosal :: Patients: in whom major: resection of the mesothelioma membranes involving: mostly the pleura and the perito- : was possible, reflected by a lowcompletenese ofcytoreduc- nevun, end less often the pericardium and tunica: vaginalis tion score, survived statistically longer. Patients with testis. Mesothelioma. isnot specifietohiiriiansand i; also::. minimal or no progression of disease and no systemic found in other mammalian species, including horse, monkey, dogand cow19'". The linkbetween mesothelioma componentofmesothelioma were: candidates for a secondlook reoperation. In this selected group the survival was and exposure to asbestos is widely accepted; its incidence is: : significantly prolonged. These findingssuggest, but do not increasing: in the industrialiaed nattons*1^.. Peritoneal: confirm, thataggressive Cytoreductive surgery is ofvalue in mesothelioma represents 20-37 per cent ofall mesothelio this group ofpatients and should be recommended. mas1"5! because of its rarity and the small size of published : There was no stadsrical indication that intraperitoneal setfes, an estimation can onlybemade of200-400new cases chemotherapy resultedin survival benefit Ittspossibletfcat annually in the USA, Four histological types of malignant selection,factors:were importantitrthis evaluatiomibecause-. peritoneal mesothehoma are recognized: epithelial (75 per : patients with a large volume of mesothelioma after :cerLt)(sarcomatous,mixedorbiphasic:andpoorlydiffer-:: cytoreductiOh were usually not given intraperitoneal entiated; multicystie and multicentiic adenomatoid perito: neal mesothelioma has a malignant potential23'15. chemotherapy. However, it may be unwise to conclude that intraperitoneal chemotherapy may be eliminated from In a review of the literature no dominant therapeutic the treatmentregimen. Comparedwithpreviorjsexperience: . guideline forpcritonerimcsotheliorna was found* Few ::withthisdisease,the benefitsofmtraperitoneaichemothtr-: i-arrideswere: dinicopathologicalretrospiccdverevittvsand: apy inpaJlianoti were thought tube substantial,AlllnttOne: most were case reports compiling disparate and deceptive patient had no further symptoms from ascites* after therapeutic experiences, including use of systemic che tytoreduenon : and perioperativeintraperitQtieal chemo motherapy* whote abdomen irradiation, and intraperitoneal therapy. In the group of patients with resection of gross treatments with .compounds- such as colloidal radioactive disease (completeness of cytareduction score 1 or 2) 2000 BbdctreU Science Lei www.bjs.co.uk British Joum#lfSurgery 2000,87, 1587-1S93 13B2 Ptriteneif tneaothehWna G. S.cbbag, H. Van, B. M. Shmootler, D. Chang and P. H. Sugarbaker intreperitoneal chemotherapy may have bean an essential . component of the treaandnt that resulted in long-term survival. 'With die current state of knowledge, a recom mendationfor mtraperittneatwplatinand dastotubiem as a standard treatment forperitoneal mesorhebonja, Combined with cytoreductive surgery, m>' be worthy of considers- tion. - ' Reference* ' J SridlurKS; Dona R, Raub WAJr, Thottr RJ, Saldana jVL New V Istrategies an nexed in dilfo^naaligrianf:mesothelioma. >X' Canter Wl\7<hl969-n. 2 Ar)timn,ShtRuaRfRyia L,KItgarIi,OsteeiiK,HeftnanT - ettd, Malignant mesoftdioma: prognostic variables in a registry of 180 patients, the-Dam-I^rberCancerInstituteond:- - - -Brigham and Women's Kmpual.experienceovertwadecades, \%5~m5,JClinOnttn9B&\ 6; 147-J3, 3 Asensio JA-Goldblatt P.Thomford NR- Primary malignant peritoneal mesothelioma. A report of seven ca6es and a review : ofth.e:Iheratnre.^rcft S'Krg l99ri;.:125: 477-81. .?:;: 4: WagnerJC. Sleegs CA Mafchand P. Diffuse pleural . : > mesothelioma and asbestos arposurein the North Western :, CapeProvineeiBWwii'jrrwt7nr/-/'fodi.ittriaiMediemt l96(itl7i-., 260-71. : J PetersonJTJr, Greenberg SD, Baffler P,: Non-asbestos- :>: : related malignant mesothelioma. Areview; Canter 1984; 54: 951--6D. 6 SugarbakerPH. Peritoneotomy procedures; Ann Snrg 19951 .. 221* 2M2. '. 7 Sugarbaker PH; Ihtwpcritonealchemothcrapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosissnd sarconnatOsisiS'KTrmiScoy Onto! 199$; Ms 254-61. SJacquBiP^ugarbakerPH.ElinicalresearebinethQdobgiesin diagnosis and staging ofpatients wich perltoneal .; ' carcinomatosis. In: Sugarbaker PH, ed. Peritonea/ - CartinmOtansc Principles efManttgemenS, Bastion, Massachusetts: Kluwer AcademioPublishers; 1996:366*7... : 9Esquivel J, farinetti A Sugarbaker PH. Elective surgery in recuwentcoloricancervdthperitonealseeding: when to and when not to proceed- G C&tr 1999; 2ft 81-6. . 10 Zubrod CC, Schneiderman M, Frei EHI, Brindley Ci Gold LG; Sbnider B ctal Appraisal of methods far the study of - chemotherapy ofcancer in man: comparative therapeutic trial : ; . : ofnitrogen mustard and triethvlene thiophosphoramide. . ] Chronic Dis I960; lit 7-JJ, ' 11 Averbach AM, Sugarbaker PH. Peritoneal mesothelioma: ; : :trtatment approachbased on naturalhisiorv. Canerr-Trttr Rts 1996;81:193-211. ' 12 Stephens AD,Bdliveau JF, Sugarbaker PH. Intraoperative : hyperthermiclavagewith dsplatm for peritoneal eardnmttanm and sarcomatoris. Iht Sugarbaker PH, d; Peritoneal Cardnemttsk Drugs and Disuses. Boston,: ! S AfassachusettieKhiwcr Academic Publishers, 199.6:15--30: 13 National Cancer Institute J SouthwestOncology Group - ;: gtiideirnesior grading toxicity. &: Haskell; GM; BerelcJS, eds; Canter Treatsneni. IVth ed, Philadelphia, Pennsylvania: WB Saunders, 1995; 1164-9, .!- H'lilapi^nEL-.Meire.'P.Nun-parameiticestjitiationfor : . incomplete observations..?Am SfatAsset 1958; S3; 457-81, 15 Peto. R, PetoJ. Asymptotically efficient rack invariant test procedures.,? Serf Sot-41972) 135:185-98. 3 6 MillerJ, Wynn WH.A malignant tumor arising from the: : endothelium ofthe peritoneum, and producing a mucoid -<- asdticfUnd,.? Pathol Bemeritl 190S; 12:267-78. 17 Whitaker D, Manning LS, Robinson BWS, ShiOtin KB. The pathobjologyofthe mtsothelium. In; HendersonHW, Shllkirt KB, La nglois SLP, Wbitaker D, eds. Malignant Mtfathelima. New Yorlo Hemisphene Publishing, i$9?:25-68, 18 Harps 0,BnMnhardJ,Bartnunn CP, HinrichslI. Ascites as a :: result ofperitoneal mesotheliomas In a horse. Tierarxsl Prax ~ 1996;24:270-4. . 19 Chandra M; Mansfield KG. Spontaneous pericardial ntcsothdioitwln a rhestas monfceyi^Af*dPrinMtaf:1999r3Sr;: . HvH, ||P' ' MM' 20 Clasa JM, Font A MascortJ.: Pericardial mesothelioma iit;a: - a : dog: long.tenn survival after pericardjcctomy in combination with chemotherapy, 1999; 40: 383-6. : - 21 1'ates DH, Gofrin B, StidofphpN, BnownefC Afalignant mesothfiliornain southetst England: clinicopathoJogica! : experience of272 cases. Thorax 1997; 52:507-12, 22- Price B.Analyas ofeurrent trends: United States- : mesothelioznainadence.rimJit!iiiflwa/i997;;I4J::2H-I8;: 25 Battifaea H. McCaugheyrWTEv&ifiuse mriignant :. mesothelioma. InvRosaiJ, Sobin LH,eds.ririmgf7suw Pathohgf. Ttonmtftbe Stnsal Mtmhrmes, Washington, DG*. Armed Forces1Institute ofPatholCrgjrPublieationsi!l99St:3.1-2. 24 Kass ME.Pathology of peritotieil mesotheiiofna, In; .- - - SugarbakerPH, ei PerittmealCarcmtmsaSasir. Drug eng : Distasts. .BostoA;Massatdmsetri:KIuwerAcademic-Publishers, - ^ :r:::i:99dT:2l3")(6.;;- MM 25 Battifora H^McGaughey W I t, Other tumors and lesions of : : tnesodteUalorigkuIp^RosaiJ, Sobin EH, eds.ritlar ofTurner Petbsieg?, Tmars ofthe$tnsnlMmhraner, Washington, DC: .. Atmed Forces Institute of Pathology Publications, 1995: .;. 94kCI.--;'::' ||' 26 fcagoffEE, Hiliris BS, HuvoS AG. Long-term survival in :;. patients wills malignant peritoneal mesodielioma treated with irradiation. CSmrrr i973; 32? 656-64. 27. Rose RG, PalmerJDiLougheedMN; Treatment ofperitoneal mesotheliomawith radioactive colloidal gofd. Reportofa case, : ^j(Wri.955;8t478-8J.'.;;: ' 7:^;:;';^ '77: .'||i .57 28 EitabbakhGH,P>''erMS,HcinpIingRHfBcdoFOl,Iiitangeu . : MSkGHnical pionre, response to therapy,and surrivatof-: : :::. woilten wiA diflnse malignant peritoneal mesothelioma. fSnrg Oncol 1999; 70:6-12. 29. Mirfctnati3d,KeIsenD,:Efi6cacyofcisplatiu-based1 , .. intraperitoucal chemotherapy as treatment ofmalignant : peritoneal tnesatheb'oma;J' GinwrPer Clin Ontol 199i)itl8> 547-50. BritishJonnul of Surgery 2000,87,1587-1593 www.bjs.soaw Mi- : : ' ';:V.: ' .C^!2pOO:SJji.ci3^ffcU  (** ,***'* o*s w r**r &** z&g&ss&t," ~*S S^ss^ ***#**"?jUSe*6* Vi* ^^CCl,\fc