Bonev, S.

Dimitrova, V.

Draganov, K.

Rusenov, D.

Taneva, I.

Tonev, S.

Tosheva, E.

English

Varna Medical University Press: Journals

MA LIG NANT TU MORS OF THE EXTRAHEPATIC BILE DUCTS – DO THEY RE MAIN A CHAL LENGE?V. Dimitrova, K. Draganov, S. Bonev, I. Taneva, E. Tosheva, D. Rusenov, S. TonevClinic of Gen eral, Liver and Pan cre atic Sur gery, Uni ver sity Hos pi tal “Alexandrovska”, So fiaRe viewed by: Assoc. Prof. R. Madjov, MD, PhDAB STRACTBack ground/ Aim: Though there is an im prove ment in the di ag nos tics and treat ment of extrahepatic bile duct car ci noma (EHBDC) the post op er a tive re sults are still un sat is fac tory. The aim of the study was to ana lyse theex pe ri ence of the au thors’ in sti tu tion in the treat ment of EHBDC and to com pare the re sults ac cord ing to thetu mor’s lo ca tion and stage and the sur gi cal pro ce dure per formed. Ma te rial and meth ods: From Jan.,1989 toJan.,2005, 1024 pa tients with EHBDC (incl. periampular ones)re ceived sur gi cal treat ment. The study was ret -ro spec tive based on clin i cal, lab o ra tory, in stru men tal, intraoperative and patho log i cal data. Re sults: Themale/fe male ra tio was 3/2 and 44.53% of all pa tients were above 60 years of age. Most of the EHBDC’s werelo cated in the dis tal part – 680 cases (66.41%). Klatskin tu mors ranked sec ond – 144 cases (14.06%). Rad i cal,pal lia tive and explorative pro ce dures were per formed in 28.42%, 66.11% and 5.47% re spec tively. Rad i calresectability showed de pend ence on the tu mor’s lo ca tion and stage. The early mor bid ity and mor tal ity rateswere 31.84% and 14.16% re spec tively. The me dian long-term sur vival (in months) af ter rad i cal pro ce dureswas 24 for Klatskin tu mors, 17 for car ci noma of the mid dle EHBD and 40 for periampullary tu mors and thesefig ures were sig nif i cantly worse af ter pal li a tions. Con clu sions: 1. EHBDC is ob served more of ten in pa tientsabove 60 years of age, it has ag gres sive bi ol ogy and poor prog no sis; 2. Re li abil ity of US, ERCP, CT-scan andMRI in cases of EHBDC ex ceeds 95%; 3. More than 70% of the pa tients with EHBDC are di ag nosed in stageIII and IV lim it ing rad i cal resectability; 4. EHBDC’s of the mid dle and dis tal parts are more of ten suit able forrad i cal re sec tions than prox i mal tu mors. Keywords: car ci noma, extrahepatic bile ducts, ob struc tive jaun dice, sur gi cal treat mentIN TRO DUC TIONThe first def i ni tion of bile duct can cer is cred ited to Fardal(1840). (1) But more than a cen tury af ter that G. Klatskin(1963, New Ha ven, Con nect i cut) pub lished the first pro -found and de tailed study on 13 cases of ma lig nant tu morsof the prox i mal part of the extrahepatic biliary tree. (2) Theau thor de scribed this type of can cer as small, lo cal ized andstrictly con fined to the com mon hepatic duct, rarelymetastasizing, and in some cases lead ing to pu ru lentcholangitis and/or acute hepatocellular fail ure. (2)Now a days tu mors of the extrahepatic bile ducts (EHBD) areclas si fied ac cord ing to their lo ca tion af ter W.P.Y. Longmire(Fig.1). (3) The clas si fi ca tion of Bis muth and Cor lette is par -tic u larly used for car ci no mas of the prox i mal part of theEHBD – the so called “Klatskin” tu mors (Fig.2). (4)The in ci dence rate of extrahepatic bile duct can cer(EHBDC) in creases per ma nently dur ing the last three de -cades but this might be a re sult of im proved di ag nos tics.(1,5,6,11) Treat ment of EHBDC has also marked a prog -ress due to ad vanced sur gi cal tech niques, en do scopicbiliary stenting, interventional ra di ol ogy and chemo- and105Scripta Scientifica Medica, vol. 37 (2005), pp 105-109 Copyright © Med i cal Uni ver sity, VarnaAd dress for cor re spon dence:Kiril Draganov, Clinic of General, Liver and Pancreatic Surgery(First surgical clinic), University Hospital "Alexandrovska", 1, G.Sofiyski str., 1431, Sofia, Bul gariaE-mail: kiril_draganov2000@hotmail.comFig. 1. The classification of the main parts of theextrahepattc bile ducts after WPY Longmire (1973)ra di a tion ther apy.(1,7-17) How ever de spite these achieve -ments EHBDC re mains a chal lenge to all the spe cial istfrom the multidisciplinary team dealing with this problem.AIMTo study the ex pe ri ence of the au thors’ in sti tu tion in the di -ag nos tics and treat ment of pa tients with EHBDC and toana lyse the early and late post op er a tive re sults and their de -pend ence on the lo ca tion of the tu mor, its stage and the sur -gi cal procedure performed.MA TE RIAL AND METH ODSFrom 01/01/1989 to 01/01/2005, 1024 con sec u tive pa tients with EHBDC in clud ing also periampullary tu mors were di -ag nosed and treated at the Clinic of Gen eral, Liver and Pan -cre atic Sur gery, Uni ver sity Hos pi tal “Alexandrovska”, So -fia. The dis tri bu tion of cases ac cord ing to the lo ca tion of the pri mary tu mor is dem on strated on Table 1.The study was ret ro spec tive based on di ag nos tic and sur gi -cal meth ods and out pa tient fol low-up (once per threemonths dur ing the first year and twice a year af ter that). Dif -fer ences con cern ing mor bid ity and mor tal ity rates andlong-term sur vival were com pared us ing the chi-square test and Fisher’s ex act test. A “p”-value less than 0.05 wasconsidered significant. RE SULTS Among all the pa tients 619 (60.45%) were male and 405(39.55%) fe male. The male/fe male ra tio was ap prox i -mately 3/2 (p<0.001). The mean age of the whole groupwas 60.7 +/- 18.3 years, 61.9 and 58.7 for men and womenre spec tively (p>0.05). The age above 60 years was the most of ten seen (44.53%) while only 23.73% of the pa tientswere un der 50 (p<0.01).The anal y sis of data con cern ing the fre quency of dif fer entlo ca tions showed the prev a lence of periampullary tu mors -680 cases (66.41%). Klatskin tu mors ranked sec ond with anum ber of 144 cases (14.06%). Car ci noma of the mid dlepart of the EHBD was ob served in 53 pa tients (5.18%) andto tal in volve ment of the EHBD in only 37 pa tients (3.61%)(p<0,001).The lead ing clin i cal symp toms and syn dromes (Ta ble 2)and the lab o ra tory data (Table 3) were the typ i cal ones forma lig nant biliary ob struc tion. We used rou tinely ul tra sound (US), ERCP, com puted to -mog ra phy (CT)-scan, mag netic res o nance (MR)-cholangio-pancretaography and intraoperative106V. Dimitrova, K. Draganov, S. Bonev ...Clinical symptoms andsyndromesNo ofpatients%Obstructive jaundice 981 95,80Pain and dyscomfort in the righthypochondium868 84,76Epigastric pain, nausea, vomitting 496 48,43Weakness, loss of appetite and body weight192 18,75­T ° 171 16,70Other nonspecific symptoms 98 9,57Table 2. Clinical presentation of EHBDCLocation of the primary tumor No of cases %Upper part of the EHBD(Klatskin tumors)144 14,06Middle part of the EHBD 53 5,18Periampulary tumors:1. Distal common bile duct2. Ampullary and papillary     tumors3. Head of the pancreas4. Duodenum6803553585766,413,425,1857,130,68Total involvement of the EHBD 37 3,61Gall bladder cancer infiltratingthe hepato-duodenal ligament110 10,74Total 1024 100,00Table 1. Relative frequency of the location of EHBDCin our materialFig. 2. The classification of Klatskin tumors afterBismuth and Corlette (1975). Type I - common hepaticduct; Type II - common hepatic duct + bifurcation;Type III A - bifurcation + right hepatic duct; Type III Â-bifurcation + left hepatic duct; Type IV - totalcholangiography for es tab lish ing the fi nal di ag no sis with ahigh rate of re li abil ity, ex ceed ing 95% (Ta ble 4).Rad i cal sur gi cal pro ce dures were re ceived by 291 pa tients(28,42%), pal lia tive – by 677 pa tients (66,11%) and weper formed only explorative laparotomies in 56 cases(5,47%) (Ta ble 5). The type of the sur gi cal op er a tion cor re -sponded to the stage of the EHBDC. The in stru men tal andintraoperative data as well as the patho log i cal studyshowed that 792 tu mors (77,34%) were in stage ²²² and ²V. Resectability de pended also to the lo ca tion of the car ci -noma. Tu mors of the mid dle part of the EHBD were rad i -cally re moved in 69.81% (37 from all the 53 cases) and tu -mors of the dis tal com mon bile duct, the ampulla and thepa pilla of Vater (i.e. periampullary tu mors ex clud ing pan -cre atic and du o de nal can cer) – in 67.04% (59 from all the88 cases).There were 41 rad i cal re sec tions (22,05%) for Klatskin tu -mors and 24 of them (16,66%) in cluded liver and/or vas cu -lar re sec tions.The to tal num ber of duodeno-pancreatectomies in cases ofperiampullary tu mors was 193 (184 Whipple re sec tionsand 9 py lo rus pre serv ing Traverso-Longmire pro ce dures). The early post op er a tive mor tal ity rate was 14.16% (145cases) in the whole group. It was higher in explorativelaparotomies – 28.57% (p<0,05). The main cause for fa talout come was pro gres sion of the hepatic dys func tion lead -ing to hepatic failure.The mor bid ity rate was 31.84% (326 cases). The mostcom mon spe cific com pli ca tions were per sis tentcholangitis, biliary leak age and acute up per gas tro in tes ti naltract bleed ing, ne ces si tat ing re-op er a tion in 23 cases(2.25%). The me dian sur vival rates ac cord ing to the tu mor’s lo ca tion and the type of the sur gi cal pro ce dure are dem on strated onTa ble 6. The dif fer ences be tween these data af ter rad i caland pal lia tive op er a tions proved to be sta tis ti callysignificant (p<0.01). DIS CUS SIONThe main char ac ter is tic fea tures of EHBDC are those de -scribed by Klatskin. The tu mor ag gres sive ness is due to thetrend to vas cu lar in va sion and neu ral in fil tra tion but the ten -dency to metastasise is lit tle and some times even pal li a tions may of fer a sat is fac tory long-term sur vival.(1,7,8,10,11,19)107Ma lig nant Tu mors of the Extrahepatic Bile Ducts ...Type of theprocedure/Location of thetumorRadicalNo (%)PalliativeNo (%)ExplorationsNo (%)Total1. Klatskin  tumors41(28,47%)100(69,44%)3 (2,09%) 1442. Middle part  BDC37(69,81%)16(30,19%)0 533. Periampullary  tumors- ampulla, papilla, distal CBD*58(65,91%)30(34,09%)- 88- head of the pancreas129(22,05%)432(73,85%)24(4,10%)587- duodenum6(85,71%)1(14,29%)74. Totally  involved  EHBD031(83,78%)6(16,22%)37Table 5. Types of the surgical procedures according tothe location of EHBDCMethodTotal No of investigations/No of confirmed diagnosisReliability(%)US 1023/977 95,50ERCP 467/463 99,14Location of thetumorRadical procedure(survival in months)Palliative procedure(survival in months)Klatskin tumors 24 4,9Middle part 17 11,5Periampullarytumors incl. thedistal CBD40 10*CBD -com mon bile ductTable 6. Median survival according to the location ofthe tumor and the type of the surgical procedureLaboratory sign No of patients %­ serum bilirubin 994 97,07­ alkaline phosphatase 962 93,94­ GGT 853 83,30%­ ASAT; ­ ALAT 496 48,93Secondary anaemia 704 68,75Hypoalbuminemia 518 50,59Disturbed coagulation 498 48,63Table 3. Laboratory data in patients with EHBDCThe right ap proach to these cases and the way of ob tain ingmax i mum ben e fit and good qual ity of life are still con tro -ver sial. Now we shall fo cus on some cur rent de bat ableprob lems con cern ing EHBDC.Is it pos si ble to es tab lish the di ag no sis “EHBDC” early?The clin i cal signs of EHBDC are more or less spe cific butthey are late. Tu mor mark ers (CA 19-9 and CEA) are of tennor mal (5,6). The di ag nos tics have been sig nif i cantly im -proved due to the new meth ods rou tinely used in prac ticedur ing the last 25-30 years - US, ERCP, CT andMR-cholangiopancretaography. (6,8,11) How ever evennow a days about 70-75% of all cases are found in stage IIIand IV which de ter mines the low rate of rad i calresectability and poor prog no sis. (7,11,14,18-20)A pos si bil ity for early de tec tion of EHBDC ex ists in the ac -tive out pa tient fol low-up of cases with a pre-can cer con di -tion such as cys tic di la tion of the bile ducts, clonorchiasis,hepatolithiasis, sclerosing cholangitis, va ri et ies of thehepatic ar tery and its main branches caus ing com pres sionon the EHBD. (6)Rad i cal or pal lia tive pro ce dure should be pre ferred inEHBDC?Ac cord ing to the lit er a ture there is no agree ment yet aboutthe type of the sur gi cal pro ce dure. But any type of treat -ment (sur gi cal or other) is man da tory since life ex pec tancyranges from 2 to 5 months with out a re lief of ob struc tivejaun dice! (7)Cri te ria of resectability are ob tained pre-op er a tively by thetriad “cholangiogram + CT and/or MRI + se lec tiveangiogram”. (6) Rad i cal pro ce dure can be achieved by sim -ple bile duct re sec tion in a few cases. Most of them needalso a vas cu lar re sec tion and re con struc tion +/- liver re sec -tion +/- DHPE in or der to be la beled “rad i cal”. (19)Many au thors ad vo cate only pal li a tions in EHBDC bypoint ing the lack of sig nif i cant dif fer ences be tween the re -cur rence rates and me dian sur vival af ter rad i cal and pal lia -tive op er a tions on the one hand and the early post op er a tivemor bid ity and mor tal ity rates af ter rad i cal re sec tions aredra mat i cally higher than af ter pal li a tions. (8,11,12)Based on our ex pe ri ence we ap ply an in di vid ual ap proachto ev ery case of EHBDC and make the fi nal de ci sion aboutthe type of the pro ce dure af ter the intraoperative ex plo ra -tion – in spec tion, pal pa tion, in stru men tal (US,cholangiogram, choledochoscopy) and histological in ves ti -ga tion. We found sig nif i cant dif fer ences be tween the latere sults af ter rad i cal and pal lia tive pro ce dures in our ma te rial (Ta ble 6). That’s why we aim to be rad i cal when ever pos -si ble but with out tak ing se ri ous risks and pay ing at ten tionto all the lim it ing fac tors such as: (a) lo cally ad vanced tu -mors and/or dis tant metastases; (b) ad vanced age (above 70 but this is n’t ab so lute) and poor gen eral con di tion of the pa -tient (co-ex ist ing cardio-vas cu lar, re spi ra tory, he ma to log i -cal and nephrological diseases); (c) severe jaundice – totalserum bilirubin > 350 µmol/l.How should a pal lia tive pro ce dure be done?En do scopic in ser tion of a biliary stent and interventionalra dio log i cal pro ce dures (percutaneous ex ter nal biliarydrain age) of fer an al ter na tive to con ven tional sur gery. Inthe be gin ning of 1980’s en do scopic biliary stenting (EBS)was char ac ter ized by high mor bid ity and mor tal ity ratesand short me dian sur vival. (9,15) At pres ent EBS is char ac -ter ized by: (a) suc cess ful in stal la tion and ef fec tive ness (re -lease of jaun dice) in more than 90% of in di cated cases; (b)du ra tion of ef fec tive ness - about 3 months for plas tic and6-7 months for metal stents; (c) sur vival rates com pa ra bleto those of sur gery, but this type of treat ment is muchcheaper and the me dian hos pi tal stay is shorter. (13,17)In our prac tice we pre fer EBS only in cases of unresectablema lig nant biliary ob struc tion de tected pre op er a tively andlack of duodenostasis which in di cates gas tro-jejunostomy. Are chemo- and ra di a tion ther apy in di cated in BDC?Rescently most au thors em pha size on the fact that ap pro -pri ate treat ment of EHBDC needs to be multidisciplinaryin clud ing chemo- and radiationtherapy. (14,16) How everthere is no enough ex pe ri ence. Most of the re ports are onsin gle cases or small se ries. Though the ini tial re sults areprom is ing fur ther stud ies are nec es sary for mak ing finalconclusions. CON CLU SIONS1. EHBDC is ob served more of ten in pa tients above 60years of age, it has ag gres sive bi ol ogy and poorprog no sis;2. Re li abil ity of US, ERCP, CT-scan and MRI in cases ofEHBDC ex ceeds 95%. These meth ods are able toan swer the ques tion whether there is or there is n’tEHBDC quite sat is fac tory but they could n’t be used for early di ag no sis nei ther for screen ing. 3. Most of the pa tients with EHBDC all over the world aswell as in Bul garia are di ag nosed lately - more than70% in stage III and IV. This de ter mines the lowresectability rate and the un sat is fac tory late re sults –post op er a tive sur vival of short me dian duration;4. EHBDC’s of the mid dle and dis tal parts are moresuit able for rad i cal re sec tions than prox i mal and to taltu mors. REF ER ENCES1. Blumgart LH, Benjamin R, Hadjis NJ,Beazley R. Sur gi cal ap proaches tocholangiocarcinoma at con flu ence of the hepaticducts. Lan cet. 1984; i:66.2. Klatskin G. Adenocarcinoma of the hepatic duct atits bi fur ca tion within the porta hepatic. An un usual tu -mor with dis tinc tive clin i cal and patho log i cal fea -tures. Am J Med. 1965; 38: 241-256.3. Longmire WPJ, McArthur MS, Bastounis EA, Hiatt J. Car ci noma of the extrahepatic biliary tract.Ann Surg. 1973; 178: 333-345. 4. Bis muth HL, Cor lette MB. Intrahepaticcholangioenteric anas to mo sis in car ci noma of thehilus of the liver. Surg Gynecol Obstetr. 1975; 149:170-178.108V. Dimitrova, K. Draganov, S. Bonev ...5. Acalovschi M. Cholangiocarcinoma: risk fac tors,di ag no sis and man age ment. Rom J In tern Med.2004;42(1):41-58. 6. Thuluvath PJ, Rai R, Venbrux AC, Yeo CJ.Cholangiocarcinoma: a re view. Gastroenterologist.1997;5(4):306-15.7. Al ex an der F, Rossi RL, O’BryanM et al. Biliary car ci noma: a re view of 109 cases. Am J Surg. 1984; 147:503.8. Cameron JL, Broe P, Zuidema PGD. Prox i malbile duct tu mors: sur gi cal man age ment with silastictranshepatic biliary stents. Ann Surg. 1982; 196:412.9. Cot ton PB. Duodenoscopic place ment of biliaryprohtesis to re lieve ma lig nant ob struc tive jaun dice. Br J Surg. 1982; 62:501. 10. Lygidakis NJ, Brummelkamp WH, Lub bersMJ et al.  A new sur gi cal ap proach for the man age -ment of car ci noma of the junc tion of the main hepaticducts. Surg Ann. 1986; 297.11. Lygidakis NJ, van der Heyde MN.  Sur gi calMan age ment of Ma lig nan cies of the Biliary Tree. InHepatobilibary and Pan cre atic Ma lig nan cies. Ed.Lygidakis NJ, Tytgat GNJ. Georg Thieme VerlagStuttgart. New York. 1989; 341-82. 12. Lygidakis NJ, van der Heyde MN, vanDongem RJAM ey al . Sur gi cal ap proaches forunresectable pri mary car ci noma of the hepatic hylus.Surg Gynecol Obstet. 1988; 166: 107-114.13. Arguedas MR, Heudebert GH, Stinnett AA,Wilcox CM. Biliary stents in ma lig nant ob struc tivejaun dice due to pan cre atic car ci noma: a cost-ef fec -tive ness anal y sis. Am J Gastroenterol.2002;97(4):898-904.14. Becker G, Momm F, Schwacha H et al.Klatskin tu mor treated by inter-dis ci plin ary ther a piesin clud ing stereotactic ra dio ther apy: A case re port.World J Gastroenterol. 2005; 11(31): 4923-6.15. Becker G, Momm F, Schwacha H et al.Klatskin tu mor treated by inter-dis ci plin ary ther a piesin clud ing stereotactic ra dio ther apy: A case re port.World J Gastroenterol. 2005; 11(31): 4923-6.16. Kamisawa T, Tu Y, Egawa N et al.Thermo-chemo-ra dio ther apy for ad vanced bile ductcar ci noma. World J Gastroenterol2005;11(27):4206-4209.17. Smith AC, Dowsett JF, Rus sell RCet al. Ran -dom ised trial of en do scopic stenting ver sus sur gi calby pass in ma lig nant low bileduct ob struc tion. Lan cet.1994;344(8938):1655-60.18. Isaji  S, Yanagiva T, Naganuma T et al.  Pro -posal of a new clas si fi ca tion for pan cre atic can cer.Gastroenterol. 1998; 45: 2048-2054.19. Lai ECS, Tompkins RK, Ros lyn JJ, MannLL. Prox i mal bile duct can cer: qual ity of sur vival.Ann Surg. 1987; 162:457.20. Weimann A, Oldhafer KJ, Nashan B et al .Intrahepatic bile duct car ci noma – re sults of re sec tionand trans plan ta tion. Hepatogastroenterol. 1998; 54(Suppl. II):CXCIX.109Ma lig nant Tu mors of the Extrahepatic Bile Ducts ...

Malignant tumors of the extrahepatic bile ducts - Do they remain a challenge?

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Malignant tumors of the extrahepatic bile ducts - Do they remain a challenge?

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