Liver transplantation in the management of cholangiocarcinoma: Evolution and contemporary advances

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the biliary epithelium. It may occur at any location along the biliary tree with the perihilar area being the most common. Prognosis is poor with 5-year overall survival at less than 10%, typically due to unresectable disease at presentation. Radical surgical resection with clear margins offers a chance of cure in patients with resectable tumours, but is frequently not possible due to locally advanced disease. On the other hand, orthotopic liver transplantation (LT) allows for a radical and potentially curative resection for these patients, but has been historically controversial due to the limited supply of donor grafts and previously poor outcomes. In patients with perihilar CCA, within specific criteria and following the implementation of a protocol combining neoadjuvant chemoradiation and LT, excellent results have been achieved in the last decades, resulting in its increasing acceptance as an indication for LT and the standard of care in several centres with significant experience. However, in intrahepatic CCA, the role of LT remains controversial and owing to dismal previous results it is not an accepted indication. Nevertheless, more recent studies have demonstrated favourable results with LT in early intrahepatic CCA, indicating that, under defined criteria, its role may increase in the future. This review highlights the history and contemporary advances of LT in CCA, with particular focus on the improving outcomes of LT in intrahepatic and perihilar CCA and future perspectives.

Tumour stage and overall survival in patients with intrahepatic cholangiocarcinoma and primary sclerosing cholangitis – a retrospective cohort study

“…Altogether, these results argue against the efficacy of imaging-based screening for iCCA in patients with PSC and, consequently, emphasise the need for new screening modalities, e. g., anti-glycoprotein (GP) 2-IgA, bile and urine proteome analysis, next-generation sequencing, or protein biomarkers containing serum extracellular vesicles [4,14,15,16]. Whereas liver transplantation in carefully selected patients with pCCA, e. g., patients with unresectable tumours or tumours in PSC, with a diameter < 3 cm, after neoadjuvant therapy, and in the absence of intrahepatic or extrahepatic metastasis may be considered a therapeutic option, iCCA is widely considered a contraindication for liver transplantation because of high recurrence rates and reduced long-term survival [17,18]. Overall and recurrence-free survival was 38 % and 42 %, respectively, 5 years after liver transplantation, according to a recent meta-analysis [19].…”

Tumour stage and overall survival in patients with intrahepatic cholangiocarcinoma and primary sclerosing cholangitis – a retrospective cohort study

“…Whereas liver transplantation in carefully selected patients with pCCA, e. g., patients with unresectable tumours or tumours in PSC, with a diameter < 3 cm, after neoadjuvant therapy, and in the absence of intrahepatic or extrahepatic metastasis may be considered a therapeutic option, iCCA is widely considered a contraindication for liver transplantation because of high recurrence rates and reduced long-term survival [17,18]. Overall and recurrence-free survival was 38 % and 42 %, respectively, 5 years after liver transplantation, according to a recent meta-analysis [19].…”

Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease

“…Notably, it must be mentioned that even though OLT is largely considered contraindicated for the management of intrahepatic CCA, in recent years, there has been a number of studies with excellent outcomes. Consequently, the European Network for the study of CCA issued a consensus statement recommendation that OLT should be considered especially in patients with very early stage unresectable intrahepatic CCA (≤ 2 cm) and underlying cirrhosis, as a potentially curative option[ 109 , 114 ]. It appears plausible that such cases may indeed arise in the context of hepatolithiasis.…”