Surgical Management of Intrahepatic Cholangiocarcinoma in the Modern Era: Advances and Challenges

Ioannis T. Konstantinidis; Nikolaos Arkadopoulos; Cristina R. Ferrone

Disclosures

Chin Clin Oncol. 2016;5(1) 

In This Article

Abstract and Introduction

Abstract

Intrahepatic cholangiocarcinoma (ICC) is one of the few gastrointestinal cancers with increasing incidence and mortality worldwide. Unlike hepatocellular carcinoma (HCC) which arises usually in a cirrhotic environment ICC frequently arises in the context of normal hepatic parenchyma. Surgical resection represents the mainstay of curative treatment, with minimally invasive approaches being increasingly utilized. Despite good surgical outcomes, most patients suffer from disease recurrence and eventually succumb to their disease. Effective adjuvant treatments are therefore needed. For unresectable disease hepatic artery utilization techniques are becoming more widely used. New treatments for non metastatic disease such as proton beam therapy (PBT) are also emerging. Systemic chemotherapy is also changing and targeted biologic agents are being added to conventional chemotherapeutic agents.

Introduction

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and it has been increasing in incidence and mortality.[1,2] This increase can be at least partially attributed to our improved ability to accurately diagnose ICC and differentiate it from other adenocarcinomas.[3]

Unlike hepatocellular carcinoma (HCC) which arises in the setting of chronic liver disease [i.e., from viral hepatitis, alcohol abuse, and/or nonalcoholic steatohepatitis (NASH)[4]], ICC often occurs in patients with no existing risk factors. Therefore, the application of prevention or screening strategies is not feasible. Consequently, unlike HCC where the status of the underlying liver parenchyma condition is crucial in the selection between resection versus transplantation, ICC usually does not appear in a cirrhotic environment making surgical resection the mainstay of treatment.

Hepatic resections can now be performed safely in tertiary centers with minimal mortality and acceptable morbidity.[5,6] The 5-year survival rate for patients who undergo resection with curative intent however is only 21% to 35% in the largest series.[7–10] Most patients suffer from disease recurrence, and the majority of these recurrences occur within the liver itself.[11] Due to the lack of phase 3 trials there is no established adjuvant treatment. Extrapolating treatment strategies from advanced biliary cancer, gemcitabine based regimens are usually utilized in the adjuvant setting, most often as a doublet with cisplatin or oxaliplatin.[12,13]

The technique of hepatic resection itself is changing. Minimally invasive hepatic resections are increasingly being utilized for the treatment of primary and metastatic liver cancer. Their advantages of faster recovery, decreased pain and better cosmetic outcome coupled with comparable morbidity, mortality and oncologic outcomes has made minimally invasive hepatic resection a desirable option.

For advanced ICC, locoregional treatments are increasingly being utilized in an effort to control the liver disease. However, their application has never been studied in phase 3 clinical trials making their use limited. Small studies have described varying degrees of effectiveness.[14–16] New treatment modalities such as proton beam therapy (PBT) have started to emerge in an effort to control liver disease effectively.

Even though the changes in systemic chemotherapy are not a primary aim of this article, highlighting some recent changes is important. After the introduction of the gemcitabine/cisplatin doublet as a gold standard for advanced biliary cancer[12] our increasing knowledge of the genetics of biliary cancer helps us adopt a targeted approach and introduce new agents to the existing gemcitabine based regimens for improved outcomes.[17]

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