Intrahepatic Cholangiocarcinoma: expert consensus statement

Abstract

An American Hepato-Pancreato-Biliary Association (AHPBA)-sponsored consensus meeting of expert panellists met on 15 January 2014 to review current evidence on the management of intrahepatic cholangiocarcinoma (ICC) in order to establish practice guidelines and to agree on consensus statements. The treatment of ICC requires a coordinated, multidisciplinary approach to optimize survival. Biopsy is not necessary if the surgeon suspects ICC and is planning curative resection, although biopsy should be obtained before systemic or locoregional therapies are initiated. Assessment of resectability is best accomplished using cross-sectional imaging [computed tomography (CT) or magnetic resonance imaging (MRI)], but the role of positron emission tomography (PET) is unclear. Resectability in ICC is defined by the ability to completely remove the disease while leaving an adequate liver remnant. Extrahepatic disease, multiple bilobar or multicentric tumours, and lymph node metastases beyond the primary echelon are contraindications to resection. Regional lymphadenectomy should be considered a standard part of surgical therapy. In patients with high-risk features, the routine use of diagnostic laparoscopy is recommended. The preoperative diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) by imaging studies is extremely difficult. Surgical resection remains the mainstay of treatment, but survival is worse than in HCC alone. There are no adequately powered, randomized Phase III trials that can provide definitive recommendations for adjuvant therapy for ICC. Patients with high-risk features (lymphovascular invasion, multicentricity or satellitosis, large tumours) should be encouraged to enrol in clinical trials and to consider adjuvant therapy. Cisplatin plus gemcitabine represents the standard-of-care, front-line systemic therapy for metastatic ICC. Genomic analyses of biliary cancers support the development of targeted therapeutic interventions.

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

“…The most frequent imaging patterns displayed by iCCA in the cirrhotic liver are a progressive homogeneous contrast uptake until the delayed (around 5ʹ) phase (MRI, CT) or an arterial peripheral-rim enhancement (CT) 198,199 . Currently, identifi cation of rare primitive liver cancers -such as HCC with stem cell features (CK19 + HCC), cholangiolocellular carcinoma and combined HCC-CCA -by imaging procedures is still a challenge 17,201 . After excluding HCC in cirrhosis, or in the context of a nodule in non-cirrhotic liver, biopsy is necessary 4,5 .…”

“…On the other hand, photodynamic therapy can improve survival in patients with unresectable CCA [259][260][261] . The role of radiation therapy in CCA is still not clearly outlined, but radiation with concurrent chemotherapy has been recommended in margin-positive and node-positive iCCA and pCCA, and in unresectable pCCA ineligible for liver transplantation 201,217 . Thus, although results have been promising from the various locoregional types of therapy, conclusive evidence for efficacy in patients with CCA is still lacking and larger prospective randomized studies are warranted.…”

Current Status on Cholangiocarcinoma and Gallbladder Cancer

“…Surgical indication for ICC with multiple intrahepatic tumors remains controversial [9]. Several case series have shown that the presence of multiple tumors, found in up to 44% of the patients, is one of the strongest negative prognostic factors.…”

Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

“…Metastases are a contraindication for surgery [109] . Recurrence free survival (RFS) rates at 3 and 5 years after surgery are 6-47 and 2-39%, respectively [105,106,110] , and the median [80] CREB5 [95] RFS is 14 months [105] .…”

“…Radiotherapy may also have a role in treatment of large tumors [105] . Consensus statements recommend the use of AT in high risk cases (R1 and N1 disease) [109] . Resection of local intrahepatic recurrence has only been shown to provide a modest survival benefit [102] .…”