Great Debates & Updates in GI Malignancies March 28-29, 2014 Biliary Tract Cancers: Standards of Care and Emerging Therapies The Role of Surgery Michael A. Choti, MD Department of Surgery UT Southwestern Medical Center

Disclosures none

LOCATION Peripheral Hilar Distal Cholangiocarcinoma 7-20% Intrahepatic mass Cirrhosis uncommon Etiology unknown 40-60% Biliary confluence Most common 20-30% 10-15% of peripancreatic tumors

Trends in Incidence of Cholangiocarcinoma in the United States SEER: Shaib et al. Semin Liver Dis (2004)

Assessment of Surgical Resectability Intrahepatic Cholangiocarcinoma Assessment of Surgical Resectability Capability to remove all gross disease (R0 resection) and leave an adequate inflow, outflow, and remnant liver volume

Prognosis Following Resection Intrahepatic Cholangiocarcinoma Prognosis Following Resection Satellitosis 5-year: 33% MVI + Nodes MDACC (2006)

Controversies Regarding Surgical Resectability Intrahepatic Cholangiocarcinoma Controversies Regarding Surgical Resectability Multifocal disease and satellitosis Intraoperative findings of positive perihepatic nodes Preoperative findings of nodal involvement Role of hilar lymphadenectomy

Distal Cholangiocarcinoma Surgical Management Distal Cholangiocarcinoma Pancreaticoduodenectomy (Whipple)

Assessment of Surgical Resectability Distal Cholangiocarcinoma Historic Method Current Method

Assessment of Surgical Resectability Distal Cholangiocarcinoma More likely locally resectable than pancreatic adenoCa Patients often present with a distal CBD stricture and no mass Brushings and biopsies can be negative Ca19-9 elevation Consider resection in patient with stricture and no mass

Hilar Cholangiocarcinoma Gerald Klatskin, MD (Yale University) Thirteen cases reported in 1965 Adenocarcinoma at hepatic duct bifurcation Klatskin, G. American Journal of Medicine (1965) 38: 241-256

Hilar Cholangiocarcinoma Treatment Complete resection is the only effective therapy Outcomes after R0 resection: 5-year overall survival of 25-40% DFS of 15-25% The minority of patients are resectable R1 resections are common Palliating the effects of biliary obstruction is often the primary treatment objective

CRITERIA OF UNRESECTABILITY Hilar Cholangiocarcinoma CRITERIA OF UNRESECTABILITY Patient-Related Factors Medical contraindication to major abdominal surgery Cirrhosis or insufficient remnant hepatic volume Metastatic Disease N2 lymphadenopathy Distant metastases

CRITERIA OF UNRESECTABILITY Hilar Cholangiocarcinoma CRITERIA OF UNRESECTABILITY Local Tumor-Related Factors Tumor extension to secondary biliary radicles bilaterally Encasement or occlusion of the main portal vein proximal to its bifurcation Unilateral tumor extension to secondary bile ducts with contralateral vascular encasement or occlusion Atrophy of one hepatic lobe with contralateral portal vein encasement or secondary biliary extension

Complete Tumor Excision with Negative Margins Hilar Cholangiocarcinoma Goal of Resection: Complete Tumor Excision with Negative Margins Recommended ESTABLISHED: Excision of supraduodenal bile duct Cholecystectomy Restore bilioenteric continuity LESS CONTROVERSIAL: Routine hepatectomy/caudate (left resections) Portal lymphadenectomy Selected major vascular reconstruction MORE CONTROVERSIAL: Routine PV resection (Neuhaus)

Controversies Regarding Surgical Resectability Hilar Cholangiocarcinoma Vascular reconstruction of portal vein and/or hepatic artery Hilar lymph node involvement and role of lymphadenectomy Small remnant volume and use of preoperative right portal vein embolization

Neoadjuvant Chemoradiation Therapy Followed By Liver Transplantation for Hilar CholangioCa Murad et al. Gastroenterology 2012

Neoadjuvant Chemoradiation Therapy Followed By Liver Transplantation for Hilar CholangioCa Murad et al. Gastroenterology 2012

Gallbladder Cancer

QUESTIONS How extensive of a preoperative evaluation is required? Gallbladder Cancer QUESTIONS How extensive of a preoperative evaluation is required? When is radical surgery indicated? How extensive of surgical resection is required? What is the role of adjuvant therapy?

Outcomes Following Resection for T2 Gallbladder Cancer Radical resection Cholecystectomy Fong et al. Ann Surg 232:557 (2000)

EXTENDED RESECTION FOR T2-T3 Gallbladder Cancer EXTENDED RESECTION FOR T2-T3 ESTABLISHED: Liver resection of gallbladder bed Hilar lymphadenectomy CBD resection/reconstruction if cystic duct margin + Selected use of more major resection SOMEWHAT CONTROVERSIAL: Routine segment 4/5 liver resection Routine CBD resection/reconstruction Routine trocar site excision MORE CONTROVERSIAL: Routine trisectorectomy Routine radical lymphadenectomy

Hilar Cholangiocarcinoma and Gallbladder Cancer LAPAROSCOPIC STAGING Most useful to rule out metastatic disease Less helpful for cholangiocarcinoma than GB Ca Consider in locally advanced cases.

Hilar Cholangiocarcinoma and Gallbladder Cancer STAGING LAPAROSCOPY 100 patients with potentially resectable biliary cancer hilar cholangioca = 56 gallbladder ca = 44 All underwent staging laparoscopy prior to surgical exploration RESULTS: Overall 69% were unresectable (HC = 59%, GB = 82%) Laparoscopy yield: 48% in patients with gallbladder cancer (56% in those w/o previous cholecystectomy) 25% in patients with hilar cholangiocarcinoma Most useful at detecting peritoneal or liver metastases. Weber et al. Ann Surg 235:392 (2002)

Hilar Cholangiocarcinoma and Gallbladder Cancer Role of FDG-PET Not useful for infiltrating cholangiocarcinoma False negatives due to low volume metastases False positives due to stents or recent cholecystectomy Anderson et al. J Gastrointest Surg 8:90 (2004)

Surgical Management of Biliary Cancer Summary Bile duct cancers are uncommon malignancies with a rising incidence and poor prognosis. In particular, intraheptic cholangiocarcinoma is increasing in incidence. Surgery remains the only curative therapy, and curative resection is the most important prognostic factor. Controversial indications for surgery include satellitosis and nodal involvement Transplantation combined with neoadjuvant therapy is an emerging therapy in unresectable hilar CCC.