Liver transplantation for unresectable intrahepatic cholangiocarcinoma: an Italian experience

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive form of primary liver cancer treated exclusively with surgery. Its incidence in the western world is growing lately [1] and the overall 5-year survival is poor due to late diagnosis, since patients rarely present a jaundice differently from patients affected by perihilar cholangiocarcinoma. Ideally liver resection and regional lymphadenectomy are the best treatments; however, these are unfortunately connotated by a 75% recurrence rate 5 years after surgery. Systemic chemotherapy offers a minimal response, as well as loco-regional therapy such as selective internal radiotherapy (SIRT), with a survival varying from 11 to 15 months between the two therapies. However, there is an ongoing trial that combines the two approaches [2]. In this scenario, interest has been documented about liver transplantation (LT) for unresectable iCCA which, on the contrary, was characterized by a poor 5-year post-transplant survival in the early series. Interpreting literature is not simple, because early studies include both iCCA and the perihilar form. Moreover, the large majority of data relates to incidental pathologic diagnosis of the explanted native liver, where a mixed form of iCCA and hepatocellular carcinoma (HCC) is present. Most recently, two Spanish retrospective reports [3, 4] showed that incidentally diagnosed iCCA or mixed iCCA and HCC had a 5-year post-transplant survival similar to that of HCC alone, even reaching a 73% overall 5-year post-transplant survival if the tumor was ≤ 2 cm. Based on this background, more liver transplant programs have started collecting data prospectively and neo-adjuvant protocols have been investigated. In a similar setting, an impressive finding of an 83% 5-year post-transplant survival was reported by Lunsford et al. [5] in locally advanced iCCA confined to the liver and transplanted after neo-adjuvant treatment. In our series of 1401 LTs, 14 (1%) were performed for iCCA. While 12 of 14 cases were incidentally diagnosed on pathologic examination, most of them (11 out of 12) developed on cirrhotic livers with 9 out of 12 being a mixed form of iCCA and HCC; two recent transplants were performed for locally advanced unresectable iCCA (Table 1). In these two LTs for iCCA we adopted a strategy of neoadjuvant treatment with SIRT followed by a short period (1–3 months) of follow-up to check the stability of the disease, and then LT within 3 months from the intra-arterial radio embolization. Kaplan–Meier overall survival for the incidentally diagnosed group was 69.4% at 5 years, while the two non-incidental cases are alive after 19 and 2 months, respectively. In transplant oncology it is necessary to achieve a posttransplant survival not inferior to that of patients transplanted for a non-cancer-related indication. According to the latest Italian National Transplant Center (CNT) report, in 2020 a total of 1202 liver transplants were performed in Italy and 978 patients were listed for liver transplantation. Mortality rate on the list was 4.1% and drop-out rate was 4.3%. Moreover, in Italy there is a highly variable rate of deceased donations: northern regions have an average of 45 donors per million people, whereas our southern region, Sicily, has an * Salvatore Gruttadauria [email protected]