Biliary Tract Cancers: Standards of Care and Emerging Therapies

Michael A. Choti, MDDepartment of Surgery

UT Southwestern Medical Center

Great Debates & Updates in GI MalignanciesMarch 28-29, 2014

The Role of Surgery

Disclosures

none

LOCATIONPeripheral

• 7-20%• Intrahepatic mass• Cirrhosis uncommon• Etiology unknown

Hilar

• 40-60%• Biliary confluence• Most common

Distal

• 20-30%• 10-15% of

peripancreatic tumors

Cholangiocarcinoma

SEER: Shaib et al. Semin Liver Dis (2004)

Trends in Incidence of Cholangiocarcinoma in the United States

Assessment of Surgical Resectability

Intrahepatic Cholangiocarcinoma

• Capability to remove all gross disease (R0 resection) and leave an adequate inflow, outflow, and remnant liver volume

5-year: 33%

Prognosis Following ResectionIntrahepatic Cholangiocarcinoma

Satellitosis

MVI

+ Nodes

MDACC (2006)

Controversies Regarding Surgical Resectability

Intrahepatic Cholangiocarcinoma

1. Multifocal disease and satellitosis

2. Intraoperative findings of positive perihepatic nodes

3. Preoperative findings of nodal involvement

4. Role of hilar lymphadenectomy

Pancreaticoduodenectomy (Whipple)

Surgical ManagementDistal Cholangiocarcinoma

Assessment of Surgical Resectability

Historic Method Current Method

Distal Cholangiocarcinoma

Assessment of Surgical ResectabilityDistal 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

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

• 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

Hilar Cholangiocarcinoma

Treatment

Patient-Related Factors • Medical contraindication to major abdominal surgery • Cirrhosis or insufficient remnant hepatic volume

Metastatic Disease • N2 lymphadenopathy• Distant metastases

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

Hilar Cholangiocarcinoma

CRITERIA OF UNRESECTABILITY

ESTABLISHED:• Excision of supraduodenal bile duct• Cholecystectomy• Restore bilioenteric continuity

Hilar Cholangiocarcinoma

Goal of Resection: Complete Tumor Excision with Negative Margins

LESS CONTROVERSIAL:• Routine hepatectomy/caudate (left resections)• Portal lymphadenectomy• Selected major vascular reconstruction

MORE CONTROVERSIAL:• Routine PV resection (Neuhaus)

Rec

omm

ende

d

Controversies Regarding Surgical ResectabilityHilar Cholangiocarcinoma

1. Vascular reconstruction of portal vein and/or hepatic artery

2. Hilar lymph node involvement and role of lymphadenectomy

3. 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

1. How extensive of a preoperative evaluation is required?

2. When is radical surgery indicated?

3. How extensive of surgical resection is required?

4. What is the role of adjuvant therapy?

Gallbladder Cancer

QUESTIONS

Fong et al. Ann Surg 232:557 (2000)

Radical resection

Cholecystectomy

Outcomes Following Resection for T2 Gallbladder Cancer

ESTABLISHED:• Liver resection of gallbladder bed • Hilar lymphadenectomy• CBD resection/reconstruction if cystic duct margin +• Selected use of more major resection

Gallbladder Cancer

EXTENDED RESECTION FOR T2-T3

SOMEWHAT CONTROVERSIAL:• Routine segment 4/5 liver resection• Routine CBD resection/reconstruction• Routine trocar site excision

MORE CONTROVERSIAL:• Routine trisectorectomy• Routine radical lymphadenectomy

• Most useful to rule out metastatic disease

• Less helpful for cholangiocarcinoma than GB Ca

• Consider in locally advanced cases.

Hilar Cholangiocarcinoma and Gallbladder Cancer

LAPAROSCOPIC STAGING

STAGING LAPAROSCOPYHilar Cholangiocarcinoma and Gallbladder Cancer

Weber et al. Ann Surg 235:392 (2002)

100 patients with potentially resectable biliary cancer hilar cholangioca = 56gallbladder 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.

Role of FDG-PETHilar Cholangiocarcinoma and Gallbladder Cancer

Anderson et al. J Gastrointest Surg 8:90 (2004)

• Not useful for infiltrating cholangiocarcinoma• False negatives due to low volume metastases• False positives due to stents or recent cholecystectomy

SummarySurgical Management of Biliary Cancer

1. Bile duct cancers are uncommon malignancies with a rising incidence and poor prognosis.

2. In particular, intraheptic cholangiocarcinoma is increasing in incidence.

3. Surgery remains the only curative therapy, and curative resection is the most important prognostic factor.

4. Controversial indications for surgery include satellitosis and nodal involvement

5. Transplantation combined with neoadjuvant therapy is an emerging therapy in unresectable hilar CCC.