Surgery and hepatic artery infusion therapy for intrahepatic cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma is an aggressive tumor that commonly presents at an advanced stage requiring multimodal treatment. Surgical resection remains the only curative option; however, only 20% to 30% of patients present with resectable disease as these tumors remain asymptomatic at an early stage. Diagnostic workup for intrahepatic cholangiocarcinoma includes contrast-enhanced cross-sectional imaging (eg, computed tomography, magnetic resonance imaging) to determine resectability and percutaneous biopsy for patients receiving neoadjuvant therapy or with unresectable disease. Surgical treatment of resectable intrahepatic cholangiocarcinoma is centered on complete resection of the mass with negative (R0) margins while preserving sufficient future liver remnant. Intraoperative measures that aid in ensuring resectability include diagnostic laparoscopy to rule out peritoneal disease or distant metastases and ultrasound to evaluate for vascular invasion or intrahepatic metastases. Predictors of survival after surgery for intrahepatic cholangiocarcinoma include margin status, vascular invasion, nodal disease, and tumor size and multifocality. Patients with resectable intrahepatic cholangiocarcinoma may also benefit from systemic chemotherapy in either the neoadjuvant or adjuvant setting; however, guidelines do not presently support the use of neoadjuvant chemotherapy outside of ongoing clinical trials. For unresectable intrahepatic cholangiocarcinoma, the combination of gemcitabine and cisplatin has been the first-line chemotherapeutic option, but recent advancements in triplet regimens and immunotherapies may offer novel strategies. Hepatic artery infusion presents an efficacious adjunct to systemic chemotherapy as it takes advantage of the hepatic arterial blood supply that feeds intrahepatic cholangiocarcinomas to deliver high-dose chemotherapy to the liver through a subcutaneous pump. Thus, hepatic artery infusion takes advantage of first-pass hepatic metabolism and provides liver-directed therapy while minimizing systemic exposure. In unresectable intrahepatic cholangiocarcinoma, using hepatic artery infusion therapy in conjunction with systemic chemotherapy has been associated with better overall survival and response rates when compared to systemic chemotherapy alone or other liver-directed therapies, such as transarterial chemoembolization and transarterial radioembolization. This review focuses on surgical intervention for resectable intrahepatic cholangiocarcinoma and the utility of hepatic artery infusion for patients with unresectable disease.