Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2021; 13(10): 1439-1449
Published online Oct 27, 2021. doi: 10.4254/wjh.v13.i10.1439
Clinical outcomes of patients with two small hepatocellular carcinomas
Anh Duy Pham, Karl Vaz, Zaid S Ardalan, Marie Sinclair, Ross Apostolov, Sarah Gardner, Ammar Majeed, Gauri Mishra, Ning Mao Kam, Kurvi Patwala, Numan Kutaiba, Niranjan Arachchi, Sally Bell, Anouk T Dev, John S Lubel, Amanda J Nicoll, Siddharth Sood, William Kemp, Stuart K Roberts, Michael Fink, Adam G Testro, Peter W Angus, Paul J Gow
Anh Duy Pham, Karl Vaz, Zaid S Ardalan, Marie Sinclair, Ross Apostolov, Sarah Gardner, Ning Mao Kam, Kurvi Patwala, Michael Fink, Adam G Testro, Peter W Angus, Paul J Gow, The Victorian Liver Transplant Unit, Austin Health, Heidelberg 3084, Victoria, Australia
Zaid S Ardalan, Ammar Majeed, John S Lubel, William Kemp, Stuart K Roberts, Department of Gastroenterology, Alfred Health, Melbourne 3000, Victoria, Australia
Marie Sinclair, Ammar Majeed, Niranjan Arachchi, Sally Bell, Anouk T Dev, Amanda J Nicoll, Siddharth Sood, William Kemp, Stuart K Roberts, Michael Fink, Adam G Testro, Peter W Angus, Paul J Gow, The Melbourne Liver Group, Melbourne 3000, Victoria, Australia
Marie Sinclair, Ross Apostolov, Sally Bell, Siddharth Sood, Michael Fink, Adam G Testro, Peter W Angus, Paul J Gow, The University of Melbourne, Parkville 3010, Victoria, Australia
Ammar Majeed, John S Lubel, William Kemp, Stuart K Roberts, Central Clinical School, Monash University, Melbourne 3004, Victoria, Australia
Gauri Mishra, Sally Bell, Anouk T Dev, Department of Gastroenterology and Hepatology, Monash Health, Clayton 3168, Victoria, Australia
Numan Kutaiba, Department of Radiology, Austin Health, Heidelberg 3084, Victoria, Australia
Numan Kutaiba, Department of Radiology, Eastern Health, Box Hill 3128, Victoria, Australia
Niranjan Arachchi, Department of Gastroenterology, Western Health, Footscray 3011, Victoria, Australia
Amanda J Nicoll, Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
Siddharth Sood, Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3050, Victoria, Australia
Author contributions: All authors contributed to data collection, drafting and/or review of the manuscript.
Institutional review board statement: Institutional ethics committee approval was obtained from participating sites prior to commencement at each centre.
Informed consent statement: No signed consent form was required from individual patients included in this study, as deemed by our institutional ethics board.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at karl.vaz@austin.org.au. Consent was not obtained but the presented data are anonymized and risk of identification is low.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Karl Vaz, MBBS, Doctor, The Victorian Liver Transplant Unit, Austin Health, 145 Studley Road, Heidelberg 3084, Victoria, Australia. karl.vaz@austin.org.au
Received: April 25, 2021
Peer-review started: April 25, 2021
First decision: June 15, 2021
Revised: June 19, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 27, 2021
ARTICLE HIGHLIGHTS
Research background

Hepatocellular carcinoma (HCC) is one of the most common malignancies world-wide, and is a growing cause for cancer-related mortality globally. Curative therapies include ablation for small tumors, surgical resection, and liver transplantation.

Research motivation

At present, there is clear evidence underpinning the guidelines for management of small tumors (≤ 3 cm in maximal diameter) and three small tumors (i.e., all ≤ 3 cm), however a scarcity of literature surrounding the optimal management of two small tumors. In addition, it is unclear if synchronous (i.e., occurring at the same time) and sequential (i.e., occurring at different points in time) tumors have differing prognoses.

Research objectives

This study aimed to assess the outcome of two small tumors (i.e., ≤ 3 cm in maximal diameter), and whether there was a difference in prognosis between those occurring synchronously and sequentially. This is to help guide future guidelines for management of two small HCCs.

Research methods

This was a retrospective multicenter study conducted in Victoria, Australia, including all patients diagnosed with two small HCCs between 1st January 2000 and 31st March 2018. Review of the medical record for patient demographics, liver disease, tumor-specific details, treatment and outcome was collected. Diagnosis of HCC was based on accepted radiographic and/or histologic criteria. Primary outcomes were overall survival (OS) and transplant-free survival (TFS).

Research results

One-hundred and four patients, majority male (n = 89, 86%), with a median age of 63 years-old (interquartile range 58-67.75), and predominantly suffering from viral chronic liver disease (n = 57, 55%) were included in the final analysis and followed up for a median of 2.54 years. There was a slight majority in those presenting synchronously (n = 59, 57%) compared with those diagnosed sequentially (n = 45, 43%), with the only difference between these two groups being more severe liver disease on the basis of model for end stage liver disease (MELD) (11 vs 8, P = 0.01). 1-, 3-, and 5-year OS was similar between the two groups (P = 0.41), however TFS was higher in the sequential group (1-, 3- and 5-year TFS 93.2%, 56.6% and 48.5%, compared with 68.5%, 37.3% and 29.7% in the synchronous group, P = 0.02). This difference did not persist in multivariate analysis (P = 0.24), with only MELD > 14 being predictive of mortality in the model (hazard ratio 2.51, 95%CI: 1.15-5.46, P = 0.02).

Research conclusions

Transplant-free survival in patients with two HCCs ≤ 3 cm is poor irrespective if diagnosed synchronously or sequentially, and so all patients with two small tumors should be assessed and considered for liver transplantation.

Research perspectives

Given limited availability of liver transplantation, future research should aim to define the molecular carcinogenetic signature in multifocal tumors, which can occur from multi-centric hepatocarcinogenesis or intrahepatic metastases, and whether this impacts recurrence, prognosis, and response to curative therapy.