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Management of Cholangiocarcinoma – Before Surgery

Management of Cholangiocarcinoma – Before Surgery. Charing Chong Alice Ho Miu Ling Nethersole Hospital / North District Hospital. Background. Before Surgery . . . . . . Before Surgery . . . . . . . Resectability. Diagnosis. Liver Function Assessment. Pre-operative Biliary Drainage.

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Management of Cholangiocarcinoma – Before Surgery

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  1. Management of Cholangiocarcinoma – Before Surgery Charing Chong Alice Ho Miu Ling Nethersole Hospital / North District Hospital

  2. Background

  3. Before Surgery . . . . . .

  4. Before Surgery . . . . . . Resectability Diagnosis Liver Function Assessment Pre-operative Biliary Drainage Portal Vein Embolization

  5. Diagnosis

  6. Diagnosis B l o o d T e s t s – T u m o u r M a r k e r s CA 19-9 • Increase in 50 – 70% of patients with biliary tract cancer CEA • Increase in 40 - 70% of patients with biliary tract cancer No specific and sensitive tumour markers for biliary tract cancer are available Improved diagnostic ability can be achieved with a combination of tumour markers and other imaging Patel AH, Harnois DM, Klee GG, at al. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol 2000;95:204–7. Nichols JC, Gores GJ, LaRusso NF, et al. Diagnostic role of serum CA 19-9 for cholangiocarcinoma in patients with primary sclerosing cholangitis. Mayo Clin Proc 1993;68:874–9. Pasanen PA, Eskelinen M, Partanen K, et al. Clinical value of serum tumor markers CEA, CA50 and CA242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis: results from a prospective study. Anticancer Res 1992;12:1687–93.

  7. Diagnosis I m a g i n g – c h o l a n g i o g r a m ERCP/PTC • Invasive • Therapeutic • Cytologic diagnosis : accuracy 30% • Increase by 40-70% by using brush biopsy MRCP • Site of bile duct stricture • Extension of invasion • Sensitivity in differentiating benign and malignant stricture : 70-96% Romagnuolo J, Bardou M, Rahme E,et al. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med 2003;139:547–57. Park MS, Kim TK, Kim KW, et al. Differentiation of extrahepatic bile duct cholangiocarcinoma frombenign stricture: fi ndings at MRCP versus ERCP. Radiology 2004;233:234–40. Romagnuolo J, Bardou M, Rahme E, et al. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med 2003;139:547–57. Park MS, Kim TK, Kim KW, et al. Differentiation of extrahepatic bile duct cholangiocarcinoma frombenign stricture: findings at MRCP versus ERCP. Radiology 2004;233:234–40..

  8. Resectability

  9. Resectability W h a t a r e t h e u n r e s e c t a b l e f a c t o r s ? Poor General condition: • Major surgery is often needed • Functions of liver, heart, lung, kidney and performance status Presence of metastasis (liver, lung, peritoneum, distant lymph nodes): • Lymph node in hepatoduodenal ligament (N1): resectable • Peripancreatic lymph node (N2): unresectable • Para-aortic and exptraperitoneal lymph nodes (Distant): unresectable Weber SM, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR.Staging laparoscopy inpatients with extrahepatic biliary carcinoma: analysis of 100 patients. Ann Surg2002;235:392–9.

  10. Resectability W h a t a r e t h e u n r e s e c t a b l e f a c t o r s ? Local extension of tumour: • Encasement or occlusion of main portal vein • Tumour extension to secondary biliary branches bilaterally • More aggressive surgical approaches like resection and reconstruction of the portal vein and/or hepatic artery have been reported Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz BS J, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001;234: 507–17. Roder JD, Stein HJ, Siewert JR. Carcinoma of the periampullary region: who benefi ts from portal vein resection? Am J Surg 1996;171:170–4. Kondo S, Hirano S, Ambo Y, Tanaka E, Kubota T, Katoh H. Arterioportal shunting as an alternative to microvascular reconstruction after hepatic artery resection. Br J Surg 2004;91:248–51. No consensus to date on local extension factors in unresectable cases

  11. Assessment of Liver Function GOOD NO GOOD

  12. Assessment of Liver Function A n y e f f e c t i v e m e a s u r e ? • Liver failure is the main cause of mortality • The perioperative outcome of hepatic resection has improved remarkably in recent years with improved surgical techniques and perioperative care • As a result, the indications of hepatic resection have been extended to include patients with borderline liver function

  13. Assessment of Liver Function C T V o l u m e t r y CT Volumetry: • Measuring the ratio of the future remnant liver volume to the total liver volume • To assess effect of portal vein embolization • Percentage of residual liver volume around 40-50% should be safe in cirrhotic liver • 25% in normal liver Lee SG, Hwang S. How I do it: assessment of hepatic functional reserve for indication of hepatic resection. J Hepatobiliary Pancreat Surg. 2005; 12: 38 – 43 Zacharia et al. Assessment of future remnant liver regeneration after portal vein embolization using three-dimensional CT and MR volumetric analyses. Australias Radiol. 2006 ;50: 543-8. Tu R, Xia LP, Yu AL et al. Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT. World J Gastroenterol. 2007; 13: 2956 – 61.

  14. Assessment of Liver Function I C G c l e a r a n c e t e s t Indocyanine green (ICG) clearance test: • Generally used in pre-operative assessment of hepatic function reserve • Widely recognized as a predictor for post-operative death and the development of liver failure in patients with liver cirrhosis • Occurrence of cholangitis prior to resection have unfavourable impacts on post-operative results even in patients with good hepatic functional reserve Miyagawa S, Makuuchi M, Kawasaki S, Kakazu T. Criteria for safe hepatic resection. Am J Surg 1995;169:589–94. Kanai M, Nimura Y, Kamiya J, Kondo S, Nagino M, Miyachi M, et al. Preoperative intrahepatic segmental cholangitis in patients with advanced carcinoma involving the hepatic hilus. Surgery 1996;119:498–504.

  15. Pre-operative Portal Vein Embolization

  16. YES Portal vein embolization leads to right liver atrophy A significant increase in future liver remnant volume in 2 – 3 weeks NO Even in patients without portal vein embolization, the liver remnant becomes larger after right hepatectomy Rate of hypertrophy unclear ? Similar as in portal vein embolization Pre-operative portal vein embolization I s I t u s e f u l ?

  17. Pre-operative portal vein embolization I s I t u s e f u l ? No randomized controlled trials on whether pre-operative portal vein embolization contributes to a decreased incidence of post-operative morbidity and mortality in cholangiocarcinoma

  18. Prospective cohort study: No differences in the incidence of post-operative complications in 55 patients with right hepatectomy for HCC and metastatic liver cancer Significantly lower incidence of post-operative complications in patients with chronic liver diseases Pre-operative portal vein embolization I s I t u s e f u l ? Farges O, Belghiti J, Kianmanesh R, Regimbeau JM, Santoro R, Vilgrain V, et al. Portal vein embolization before right hepatectomy: prospective clinical trial. Ann Surg 2003;237:208–17.

  19. Retrospective review: 53 patients with hilar cholangiocarcinoma Use of portal vein embolization as a routine pre-operative procedures for patients undergoing major hepatectomy Post-operative mortality was significantly lower in the group with hypertrophy of the future liver after embolization than the group without hypertrophy Pre-operative portal vein embolization I s I t u s e f u l ? Hemming AW, Reed AI, Fujita S, Foley DP, Howard RJ. Surgicalmanagement of hilar cholangiocarcinoma. Ann Surg 2005;241:693–9.

  20. Pre-operative portal vein embolization I s I t u s e f u l ? Pre-op PVE may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50-60% is planned, especially in jaundiced liver. Kondo S et al. Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment. J Hepatobiliary Pancreat Surg. 2008;15(1):41-54. Indications should be carefully considered especially in patients with normal liver or those with planned left hepatectomy since PVE-related complications had been reported

  21. Pre-operative Biliary Drainage

  22. YES Jaundice affects liver, kidneys, gastric mucosa, coagulation, immune system NO Risk of infection Invasive procedure No difference in post-operative morbidity and mortality Pre-operative biliary drainage I s I t n e c e s s a r y ?

  23. Randomized controlled trials : No significant difference in post-operative morbidity and mortality between patients who received pre-operative biliary drainage and those who did not Included mostly bypass surgeries and palliative small resections, few major procedures like hepatectomy Improvement in drainage procedure technique and outcome Pre-operative biliary drainage I s I t n e c e s s a r y ? Hatfi eld AR, Tobias R, Terblanche J, Girdwood AH, Fataar S, Harries-Jones R, et al. Preoperative external biliary drainage in obstructive jaundice. Lancet 1982:896–9. McPherson GAD, Benjamin IS, Hodgson HJF, Bowley NB, Allison DJ, Blumgart LH. Preoperative percutaneous biliary drainage:the results of a controlled trial. Br J Surg 1984;71: 371–5. Pitt HA, Gomes AS, Lois JF, Mann LL, Deutsch LS, Longmire WP Jr. Does preoperative percutaneous biliary drainage reduce risk or increase hospital cost? Ann Surg 1985;201:545–52.

  24. Retrospective cohorts: Pre-operative biliary drainage for all is unnecessary Except for patients with cholangitis or poor hepatic function and before extended hepatectomy Since mortality after extended hepatectomy is high Cause of death is mainly hepatic failure Pre-operative biliary drainage I s I t n e c e s s a r y ? Sewnath ME, Birjmohun RS, Rauws EA, Huibregtse K, Obertop H, Gouma DJ. The effect of preoperative biliary drainage on postoperative complications after pancreatoduodenectomy. J Am Coll Surg 2001;192:726–34. Martignoni ME, Wagner M, Krahenbuhl L, Redaelli CA, Friesss H, Buchler MW. Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy. Am J Surg 2001;181: 52–9. Pisters PW, Hudec WA, Hess KR, Lee JE, Vauthey JN, Lahoti S, et al. Effect of preoperative biliary decompression on pancreatoduodenectomy: associated morbidity in 300 consective patients. Ann Surg 2001;234:47–55

  25. Pre-operative biliary drainage I s I t n e c e s s a r y ? Pre-operative biliary drainage is recommended for patients with cholangitis or patients scheduled to undergo extended hepatectomy

  26. Pre-operative biliary drainage H o w ? • No RCTs compared percutaneous and endoscopic drainage as the most appropriate pre-operative drainage method in cholangiocarcinoma • Two RCTs on stent therapy for unresectable cases • Endoscopic procedure was superior to percutaneous stents and bypass surgery • For hilar lesion, endoscopic drainage is often difficult • Percutaneous drainage may be more effective and recommended Speer AG, Cotton PB, Russell RC, et al. Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice. Lancet 1987;330:57–62. Smith AC, Dowsett JF, Russell R,. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bile duct obstruction. Lancet 1994;344:1655–60.

  27. Pre-operative biliary drainage W h a t p r o c e d u r e s a r e a p p r o p r I a t e ? Percutaneous transhepatic or endoscopic, drainage can be used. The method that can be safely performed with the equipment and techniques available at each facility.

  28. Summary W h a t s h a l l w e d o ? Resectability • Poor general condition • Distant metastasis • Local extension Diagnosis • Tumour markers • Cytology Liver Function Assessment • CT volumetry • ICG test Pre-operative Biliary Drainage • Cholangitis • Extended hepatectomy • Percutaneous or endoscopic drainage Portal Vein Embolization • Right hepatectomy or more • Hepatectomy with a resection rate exceeding 50-60%

  29. Thank You

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