Liver Transplantation for Intrahepatic Cholangiocarcinoma: Ready for Prime Time?

Abstract

Cholangiocarcinoma (CCA) represents the second-most common primary liver malignancy after HCC and has risen in incidence globally in the past decades. Intrahepatic cholangiocarcinoma (iCCA) comprises 20% of all CCAs, with the rest being extrahepatic (including perihilar [pCCA] and distal CCA). Though long representing an absolute contraindication for liver transplantation (LT), recent analyses of outcomes of LT for iCCA have suggested that iCCA may be a potentially feasible option for highly selected patients.This has been motivated both by successes noted in outcomes of LT for other malignancies, such as HCC and pCCA, and by several retrospective reviews demonstrating favorable results with LT for a selected group of iCCA patients with small lesions. LT for iCCA is primarily relevant within two clinical scenarios. The first includes patients with very early disease (single tumor, ≤2 cm) with cirrhosis and are not candidates for liver resection (LR). The second scenario is patients with locally advanced iCCA, but where the extent of LR would be too extensive to be feasible. Preliminary single-center reports have described LT in a selected group of patients with locally advanced tumors who have responded to neoadjuvant therapy and have a period of disease stability. Currently, there are three prospective trials underway that will help clarify the role of LT in iCCA. This review seeks to explore the available studies involving LT for iCCA, the challenges of ongoing trials, and opportunities for the future.

Liver Transplantation for Intrahepatic Cholangiocarcinoma: What Are New Insights and What Should We Follow?

“…LT might serve as a viable option in cases as follows: (I) unresectable tumor restricted to 2 cm, whilst arisen in context of chronic liver diseases; (II) unresectable tumor locally advanced within the liver (single lesion more than 2 cm, or number of lesions ≥2; without extrahepatic metastasis or macrovascular invasion), but responses to tumor down-staging modality (namely, systemic neoadjuvant therapy and/or loco-regional therapy). The items are summarized as above, which were consistent with the insights raised by other researchers (5,20,28,29). Here, the optimized combination of "maximum size of single lesion" with/without "number of lesions" remained undefined, when compared with the Milan criteria.…”

“…I Patients with unresectable tumor restricted to 2 cm, whilst arisen in context of chronic liver diseases (10,15,20,29). II Patients with unresectable tumor locally advanced within the liver (single lesion more than 2 cm, or number of lesions ≥2), without extrahepatic metastasis or macrovascular invasion, but with responses to tumor downstaging (namely, systemic neoadjuvant therapy and/or loco-regional therapy) (5,11,17,29). Whereas, the optimized combination of "maximum size of single lesion" with/without "number of lesions" remained undefined.…”

The Role of Immunosuppression for Recurrent Cholangiocellular Carcinoma after Liver Transplantation

“…In this study, recurrence was significantly associated with higher UICC stage and N1 status at initial LT. N1 status was also associated with impaired overall survival in multivariate analysis for oncological parameters at LT, highlighting the importance of adequate staging before LT to identify eligible patients in times of organ donor shortage. Previous studies found tumor size, histological parameters, and differentiation to be associated with a high recurrence rate [ 29 ]. We did not analyze size or detailed histological findings, as the focus of our study was the course of patients after recurrence.…”

Clinical relevance of biomarkers in cholangiocarcinoma: critical revision and future directions

“…Although liver transplantation is already considered a potentially feasible option for highly selected patients with pCCA and iCCA,88 89 it is to be hoped that ongoing trials will help determine if tissue biomarkers are also associated with prognosis after transplantation.…”