Gallbladder Cancer and Cholangiocarcinoma. Yuman Fong, MD Upper Gastrointestinal Cancer Seminar Copenhagen, Denmark 2009

Transcription

1 Gallbladder Cancer and Cholangiocarcinoma Yuman Fong, MD Upper Gastrointestinal Cancer Seminar Copenhagen, Denmark 2009

2 A.A. Blalock, Johns Hopkins Hosp. Bull. 35:391, 1924 "...in malignancy of the gallbladder, when a diagnosis can be made without exploration, no operation should be performed, inasmuch as it only shortens the patient's life."

3 Gallbladder Cancer Natural History 5,836 patients in literature ( ) 1978) Overall 5-year 5 survival of 4.1% Resection resulted in 16.5% 5-year 5 survival One 5-yr 5 survivor out of 2,115 non-resected patients Overall mean survival months Piehler, SG&O, 147:929, 1978 (collected review)

4 Gallbladder Cancer Epidemiology 90% of cases in patients over 50 Male:Female ratio of 1: % of cases associated with gallstones 1% of cholecystectomy for gallstones 10% of porcelain gallbladders Approximately 2000 cases/ year

5 Gallbladder Cancer Histologic Subtypes Histologic Type Carriage and Hanson, Cancer, 1995 Fong et al., Ann Surg, 2000 Adenocarcinoma 89% 91% Papillary 6% 3% Mucinous 5% 2% Squamous 2% 2% Other 8% 7% Sarcoma 0.2% 0.2%

6 Gallbladder Cancer Symptoms Burdette (1957) Thorbjarnarson (1959) Perpetuo (1978) Chau (1991) Fong (2000) Pain 82% 86% 97% 54% 64% Jaundice 50% 23% 44% 46% 37% Weight loss 47% 35% 77% 28% 10%

7 Gallbladder Cancer Presentation RUQ discomfort RUQ mass c/w distended gallbladder

8 Gallbladder Cancer Radiologic Findings

9 Radiologic Presentation of Gallbladder Cancer

10 Gallbladder Cancer Questions What is the appropriate extent of resection? Is a radical resection necessary for early stage disease? Is a radical resection justified for advanced disease? When patients present after simple cholecystectomy, is a re-operative radical resection necessary and justified?

11 Gallbladder Cancer Surgical Options Simple cholecystectomy Extended cholecystectomy Extended hepatic resection Hepatic resection and pancreaticoduodenectomy

12 Gallbladder Cancer Major Hepatic Resection as Therapy Treated by right lobectomy,, node dissection Three cases: two after previous exploration One One patient died peri-operatively One One died of disseminated recurrence One One alive NED at two years Wound implantation noted in one case on re- exploration Pack et al., Ann. Surg., 142:6, 1955

13 Gallbladder Cancer Major Hepatic Resection as Therapy First to advocate right lobectomy, lymph node dissection First report of wound implantation of tumor Pack et al., Ann. Surg., 142:6, 1955

14 Gallbladder Cancer Presentation after Cholecystectomy T-stage GB involvement Tis T1 T2 T3 T4 In situ Mucosal Not through serosa Through serosa >2 cm beyond gallbladder

15 Gallbladder Cancer Simple Cholecystectomy for Stage I Author 5-yr Survival Donohue, % Gall, % Shirai, % Yamaguchi, % Shirai, % Oertli, %

16 Author Gallbladder Cancer Stage II Disease Source Shirai, 1992 Ann Surg, 216:565 40% Yamaguchi, 1992 Am J Surg, 163:382 36% Oertli, 1993 Eur J Surg, 159:415 24% Author Simple Cholecystectomy Extended Resection Source Matsumoto, 1992 Am J Surg, 163: % Shirai, 1992 Ann Surg, 216:565 90% Bartlett, 1996 Ann Surg, 224:639 88% 5-yr Survival 5-yr Survival

17 Gallbladder Cancer Survival after Resection Author Source % Stage III/IV 5-yr Surv Nakamura, 1989 Surgery, 106: % Donohue, 1990 Arch Surg, 125: % Ogura, 1991 World J Surg, 15: % Shirai, 1992 Ann Surg, 216: % Ouchi, 1993 Surgery, 101: % Bartlett, 1996 Ann Surg, 224: % Fong, 2000 Ann Surg, 232: % Behari, 2003 J Am Coll Surg, 196: %

18 Gallbladder Cancer Goals of Resection Removal of gallbladder Removal of areas of liver invasion Portal lymph node dissection Remove and reconstruct areas of portal vein invasion Biliary reconstruction

19 Gallbladder Cancer Resection and Reconstruction

20 Gallbladder Cancer MSKCC Report July March 2000 n=410 M:F = 137:273 Median age (range) = 65 (28-87) 162 presented without prior surgery 248 presented after surgery 127 open cholecystectomy 85 laparoscopic cholecystectomy

21 Gallbladder Cancer Surgical Therapy and Outcome Survival.6.4 Resection.2 Cholecystectomy +/- bypass None P= Months

22 Gallbladder Cancer Extent of Resection and Outcome for T2 Tumors Radical Resection Survival Cholecystectomy P=0.04 Months

23 Gallbladder Cancer 1.0 T stage.8 T2 Survival.6.4 T3.2 T P=0.003 Months

24 Gallbladder Cancer Effect of Prior Exploration on Outcome 1.0 Survival Previous exploration No previous exploration P=NS Months

25 Gallbladder Cancer T-stage and Resectability Resected Lymph Node Metastases Peritoneal or Liver Metastases T2 58% 33% 16% T3 27% 58% 42% T4 13% 69% 79%

26 Gallbladder Cancer Node Status 1.0 Survival Node negative Node positive P=0.002 Months

27 Gallbladder Cancer Laparoscopically-discovered laparoscopic cholecystectomy 24 cancers found 3 3 cases of port site recurrence Yamaguchi et al., Arch Surg, 131:981, 1996

28 Gallbladder Cancer Laparoscopic Port Site Recurrence

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30 Gallbladder Cancer Summary Unresected gallbladder cancer is a rapidly fatal disease Radical resection is indicated for T2-T4 T4 disease Long-term survival can result from resection of T4 cancer Patients presenting after prior non-curative cholecystectomy should be considered for radical re-resection resection

31 Peripheral Cholangiocarcinoma Location Hilar Distal GB CBD D PD 10 20% Large mass Unknown 1 o 40 60% Biliary confluence Most common 20 30% 10% of periampullary tumors

32 Cholangiocarcinoma Demographics Uncommon: 1.2/100,000 < 2% of all cancers Disease of elderly: 2/3 over 65 years. 10/100,000 in octogenarians Death results from hepatic failure or sepsis Carriaga and Henson. Cancer Suppl. 1995;75:171

33 Hilar Cholangiocarcinoma Gerald Klatskin, MD Thirteen cases reported in 1965 Adenocarcinoma at hepatic duct bifurcation Klatskin, G. American Journal of Medicine 1965;38:

34 Cholangiocarcinoma Anatomical Considerations Portal vein involvement Lobar atrophy Tumor contact w/ distortion, narrowing, encasement/occlusion. Small, hypoperfused lobe w/ crowded, dilated ducts. Lobar atrophy implies portal venous involvement Common 60% have one or both findings Mandate hepatic resection

35 Cholangiocarcinoma Anatomical Considerations Principal caudate duct enters LHD in most patients Additional drainage of the right portion of the caudate and caudate process is via the RHD

36 Cholangiocarcinoma Goals of Resection R0 resection Leaving a well-perfused liver remnant With adequate biliary drainage. Remove bile duct Remove involved liver Portal lymphadenectomy Remove/reconstruct areas of portal vein invasion Biliary reconstruction

37 Hilar Cholangiocarcinoma MSKCC Results 279 Patients 1/91 11/03 Unresectable at Presentation 64 patients, 23% (metastases in 26) Explored for Cure 215 Patients, 77% Unresectable 109 Patients, 51% (metastases in 90) Resected 106 Patients, 49%

38 Cholangiocarcinoma Operative Procedures and Operative Results All resections Complete gross resection 106 Concomitant liver resection 87 (82%) En bloc caudate resection 36 (41%) Vascular resection/reconstruction 11 (10%) Mortality 8 (7.5%)

39 Cholangiocarcinoma Survival after Resection Resection margin status R0, 43 months (n = 82) R1, 24 months (n = 24) Loc Adv, 16 months (n = 29) %.5 p< P= Time (months)

40 Cholangiocarcinoma Variables Associated with Survival after Resection p p (univariate) (multivariate) HR R0 Resection (82) Liver Resection (87) Well-Differentiated (35) Papillary Tumor (25) Node (-)( Variables not significant: Age, gender, AJCC stage, tumor size, vascular resection, en bloc caudate lobectomy

41 Cholangiocarcinoma Hepatic Resection and Margin Status %Hepatic %neg Author Resection Margin Tsao Cameron Gerhards Hadjis Jarnagin Klempnauer Neuhaus Nimura % Liver Resection R 2 = % Negative Magins

42 Morbidity and Mortality Resected Author Years (N) Morbidity Mortality Iwatsuki ( 96) * % Klempnauer ( 97) * % 10% Gerhards ( 00) % 18% Tabata ( 00) % 12% Gazzaniga ( 00) % Neuhaus ( 00) * % 8% Nimura ( 00) % 9% Jarnagin ( 01) % 10% Nagino ( 01) % 10% * - includes OLT in some patients.

43 Cholangiocarcinoma Hepatic Resections and Operative Mortality % 77% 78% 92% 40 Liver Resection Mortality % 10% (n = 30) (n = 40) (n = 36) 2.8%

44 Percutaneous Portal Vein Embolization

45 Pre-operative Biliary Drainage: Rationale Improve: Hepatic function Allow normal regeneration of liver remnant Decrease risk of post-operative hepatic failure Renal function, cell-mediated immunity, nutrition Indications: Sepsis Renal insufficiency Left dominant tumors Severe medical co-morbidity

46 Pre-operative Biliary Drainage Procedure-related complications Pancreatitis Biloma Biliary injury Hemorrhage Perforation

47 Summary Prolonged survival is possible after complete resection Advances in non-surgical therapy are needed Heightened awareness of intrahepatic cholangioca Hepatic resection required for hilar tumors Operative mortality has been high but is improving Points of ongoing debate: Pre-operative biliary drainage? Pre-operative portal vein embolization? Caudate resection for all patients? Extended lymphadenectomy?

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49 Chemotherapy for Biliary Cancers Regimen Response Median Survival 5-FU 10% 6-7 m 5-FU/ cisplatin 20-40% 6-12 m Gemcitabine 20-30% 6-12 m Gemcitabine/ 5-FU 10-35% 9-14 m Gemcitabine/ Cisplatin 20-35% 9-11 m Gemcitabine/ Oxaliplatin 20-50% m

50 Molecular Abnormalities in Biliary Cancers EGF/ EGFR HER-2 MAPK COX2 VEGF MUC-1/ MUC-4 K-RAS Cyclin-D1 TGF-b p53

51 Llovet and Bruix, Hepatology 2008

52 Targeted Agents In Development Hezel and Zhu, Oncologist 2008;13: Copyright 2008 AlphaMed Press

53 Incidence of Gallbladder Cancer Delhi: 22/100 K Quito: 13 Roi Et: 33 Cali: 10 N Mexico: 9

54 Etiology of Biliary Cancers Gallbladder Cancer Stones Environmental pathogens Cadmium, Chromium, Lead (Tanneries of Northern India) Infections Typhoid (Chile, Northern India, Scotland) Salmonella Helicobacter

55 Etiology of Biliary Cancers Meal of Koi-Pla: Fermented Uncooked Cyprinoid Fish Opisthorchis viverrini

56 Public Education Roi Et Province