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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Propensity-matched analysis of patients with intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma and hepatocellular carcinoma undergoing a liver transplant
Ajacio Bandeira de Mello Brandão, Santiago Rodriguez, Alfeu de Medeiros Fleck Jr, Claudio Augusto Marroni, Mário B Wagner, Alex Hörbe, Matheus V Fernandes, Carlos TS Cerski, Gabriela Perdomo Coral
Ajacio Bandeira de Mello Brandão, Santiago Rodriguez, Claudio Augusto Marroni, Matheus V Fernandes, Gabriela Perdomo Coral, Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre 90050170, RS, Brazil
Ajacio Bandeira de Mello Brandão, Alfeu de Medeiros Fleck Jr, Claudio Augusto Marroni, Liver Transplantation Group, Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020090, RS, Brazil
Santiago Rodriguez, Department of Hepatology, Hospital Vozandes Quito-HVQ, Quito 170521, Ecuador
Mário B Wagner, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035002, RS, Brazil
Alex Hörbe, Interventional Radiology Unit, Santa Casa de Misericórdia de, Porto Alegre 90020090, RS, Brazil
Carlos TS Cerski, Department of Pathology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035002, RS, Brazil
Author contributions: All the authors solely contributed to this paper.
Institutional review board statement: The Institutional Review Board of Santa Casa de Misericórdia de Porto Alegre approved the study protocol (No. 4.250.889).
Informed consent statement: Informed consent was waived due to the non-interventional design of the study and retrospective nature of data collection. All investigators signed a data use agreement to ensure the ethical and secure use of the data.
Conflict-of-interest statement: All authors have no conflicts of interest to disclose.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement checklist of items, and the manuscript was prepared and revised according to the STROBE Statement checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Ajacio Bandeira de Mello Brandão, PhD, Academic Research, Graduate Program in Medicine: Hepatology, School of Medicine, Universidade Federal de Ciências da Saúde de Porto Alegre, R. Eng. Álvaro Nunes Pereira, 400/402, Porto Alegre 90050170, RS, Brazil. ajaciob@gmail.com
Received: April 8, 2022
Peer-review started: April 8, 2022
First decision: May 12, 2022
Revised: June 14, 2022
Accepted: July 11, 2022
Article in press: July 11, 2022
Published online: August 24, 2022
ARTICLE HIGHLIGHTS
Research background
Cholangiocarcinoma (CC) is a rare tumor that arises from the epithelium of the bile ducts. It is classified according to anatomic location as intrahepatic, perihilar, or distal. Intrahepatic cholangiocarcinoma (ICC) is rare in patients with cirrhosis due to causes other than primary sclerosing cholangitis. Mixed hepatocellular-cholangiocarcinoma (HCC-CC) is a rare neoplasm with histologic findings of both hepatocellular carcinoma (HCC) and ICC within the same tumor mass.
Research motivation
Because of difficulties in reaching the correct diagnosis, patients eventually undergo liver transplantation (LT) with a presumptive diagnosis of HCC on imaging when, in fact, they have ICC or HCC-CC.
Research objectives
To determine the prevalence of ICC or HCC-CC confirmed by explant pathology in patients who underwent LT with the presumptive diagnosis of HCC and to compare tumor recurrence (TR), recurrence-free survival (RFS), and overall mortality (OM) rates between these patients and LT recipients with HCC.
Research methods
This retrospective cohort study included patients aged ≥ 18 years with liver cirrhosis and imaging findings suggestive of HCC within the Milan criteria who underwent LT between June 1997 and July 2019. Patients were divided into three groups according to the diagnosis on explant pathology: (1) Patients with HCC; (2) Patients with ICC; and (3) Patients with mixed HCC-CC. The analyzed outcomes were TR, RFS, and OM. Propensity score matching was used to assess whether TR, OM, and RFS rates in patients with ICC or HCC-CC differed from those in patients with HCC. Additionally, hazard ratios (HRs) and their confidence intervals were calculated. Progression-free survival and OM rates were computed with the Kaplan-Meier method using Cox regression for comparison.
Research results
Over a 22-year period, 475 patients with the presumptive diagnosis of HCC underwent LT, and 15 (3.1%) were found to have either ICC (n = 8) or HCC-CC (n = 7) detected in the pathological examination of the explant. LT recipients with ICC had higher TR (46% vs 11%; P = 0.006), higher OM (63% vs 23%; P = 0.002), and lower RFS (38% vs 89%; P = 0.002) than those with HCC when matched for pretransplant tumor characteristics, as well as higher TR (46% vs 23%; P = 0.083), higher OM (63% vs 35%; P = 0.026), and lower RFS (38% vs 59%; P = 0.037) when matched for posttransplant tumor characteristics. Two pairings were performed to compare the outcomes of LT recipients with HCC-CC vs HCC. There was no significant difference between the outcomes in either pairing.
Research conclusions
Patients with ICC had worse outcomes than patients with HCC undergoing LT. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant options.
Research perspectives
This study reinforces the need for more accurate criteria: (1) To identify these rare tumors in pretransplant evaluation; and (2) To select patients who may benefit from LT.
