Management of perihilar cholangiocarcinoma in the era of multimodal therapy

Abstract

Perihilar cholangiocarcinoma (CCA) is the second most common primary malignant tumor of the liver. In the USA, there are approximately 3000 cases of CCA diagnosed annually, with approximately 50-70% of these tumors arising at the hilar plate of the biliary tree. Risk factors include advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, parasitic infection, inflammatory bowel disease, cirrhosis and chronic pancreatitis. Patients typically present with jaundice, abdominal pain, pruritus and weight loss. The mainstays of treatment include surgery, chemotherapy, radiation therapy and photodynamic therapy. Specific preoperative interventions for patients with perihilar CCA include endoscopic retrograde cholangiopancreatography, percutanteous transhepatic cholangiography and portal vein embolization. Surgical resection offers the only chance for curative therapy in perihilar CCA. R0 resection is of utmost importance and has been linked to improved survival. Major hepatic resection is needed to achieve both longitudinal and radial margins negative for tumor. Fractionated stereotactic body radiotherapy has shown promising results in CCA. Perihilar CCA typically presents with advanced disease, and many patients receive systemic therapy; however, the response to current regimens is limited. Orthotopic liver transplantation offers complete resection of locally advanced tumors in select patient groups.

Figure 1. Magnetic resonance cholangiopancreatography of hilar cholangiocarcinoma

(A) Magnetic resonance cholangiopancreatography and (B) MRI revealing a 1.9 × 1.6 cm hyperintense T2 lesion (arrow) that demonstrates delayed enhancement in the region of the porta hepatis. The mass causes moderate intrahepatic biliary ductal dilation and is a concern for Klatskin tumor.

Figure 2. Placement of left-sided percutanteous transhepatic cholangiography for preoperative biliary drainage (long arrow)

Note the stricture/obstruction at the level of the hilum (short arrow).

Figure 3. The Bismuth–Corlette classification system provides an anatomic description of the tumor location and longitudinal extension in the biliary tree

(A) Locations of cholangiocarcinoma in the biliary tree. (B) Morphological subtypes of cholangiocarcinoma. (C) Bismuth–Corlette classification of hilar cholangiocarcinoma. Reproduced with permission from [135].

Figure 4. Tumor depth may more accurately stratify patients with regard to long-term outcome in patients with perihilar cholangiocarcinoma

Reproduced with permission from [62].

Figure 5. Outcome of patients treated with systemic chemotherapy for cholangiocarcinoma

A randomized trial of 400 patients with unresectable cholangiocarcinoma showed an improvement in both overall (A) and disease-free (B) survival among patients who received gemcitabine plus cisplatin versus gemcitabine alone. (A)Hazard ratio for death: 0.64 (95% Cl: 0.52–0.80); p < 0.001. (B) Hazard ratio for disease progression: 0.63 (95% Cl: 0.51–0.77); p < 0.001. Reproduced with permission from [101].