Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2022; 28(36): 5351-5363
Published online Sep 28, 2022. doi: 10.3748/wjg.v28.i36.5351
Early extrahepatic recurrence as a pivotal factor for survival after hepatocellular carcinoma resection: A 15-year observational study
Jae Hyun Yoon, Sung Kyu Choi, Sung Bum Cho, Hee Joon Kim, Yang Seok Ko, Chung Hwan Jun
Jae Hyun Yoon, Sung Kyu Choi, Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
Sung Bum Cho, Department of Gastroenterology and Hepatology, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
Hee Joon Kim, Department of Surgery, Chonnam National University Hospital and College of Medicine, Gwangju 61469, South Korea
Yang Seok Ko, Department of Surgery, Hwasun Chonnam National University Hospital and College of Medicine, Hwasun 58128, South Korea
Chung Hwan Jun, Department of Internal Medicine, Mokpo Hankook Hospital, Mokpo 58643, South Korea
Author contributions: Yoon JH wrote the manuscript; Choi SK, Cho SB, and Jun CH designed the concept of the study; Yoon JH, Kim HJ, and Ko YS collected and analyzed the data on baseline patient characteristics and recurrence of HCC; Yoon JH interpreted the data; Choi SK, Cho SB, and Jun CH supervised the project.
Supported by Research Supporting Program of the Korean Association for the Study of the Liver and the Korean Liver Foundation, No. KASLKLF2019-06; and Chonnam National University Hospital Biomedical Research Institute, No. BCRI121007.
Institutional review board statement: This study was approved by the Institutional Review Board of Chonnam National University Hospital (IRB No. CNUH-2019-203).
Informed consent statement: Owing to the retrospective design of our study and the use of de-identified data, the requirement for informed consent was waived under the approval of the Institutional Review Board of Chonnam National University Hospital.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: Data available on additional request.
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: Sung Kyu Choi, MD, PhD, Professor, Department of Gastroenterology and Hepatology, Chonnam National University Hospital and College of Medicine, Jebongroe 42, Gwangju 61469, South Korea. choisk@jnu.ac.kr
Received: May 11, 2022
Peer-review started: May 11, 2022
First decision: August 1, 2022
Revised: August 11, 2022
Accepted: September 8, 2022
Article in press: September 8, 2022
Published online: September 28, 2022
ARTICLE HIGHLIGHTS
Research background

Surgical resection is one of the most widely used modalities for the treatment of hepatocellular carcinoma (HCC). Early extrahepatic recurrence (EHR) of HCC after surgical resection is considered to be closely associated with poor prognosis.

Research motivation

Data regarding risk factors and survival outcomes of early EHR after surgical resection remain scarce.

Research objectives

We decided to investigate the clinical features and risk factors of early EHR and elucidate its association with survival outcomes.

Research methods

From January 2004 to December 2019, we enrolled treatment-naïve patients who were ≥ 18 years and underwent surgical resection for HCC in two tertiary academic centers. After excluding patients with tumor types other than HCC and/or ineligible data, this retrospective study finally included 779 patients. Surgical resection of HCC was performed according to the physicians’ decisions and the EHR was diagnosed based on contrast-enhanced computed tomography or magnetic resonance imaging, and pathologic confirmation was performed in selected patients. Multivariate Cox regression analysis was performed to identify the variables associated with EHR.

Research results

Early EHR within 2 years after surgery was diagnosed in 9.5% of patients during a median follow-up period of 4.4 years. The recurrence-free survival period was 5.2 mo, and the median time to EHR was 8.8 mo in patients with early EHR. In 52.7% of patients with early EHR, EHR occurred as the first recurrence of HCC after surgical resection. On multivariate analysis, serum albumin < 4.0 g/dL, serum alkaline phosphatase > 100 U/L, surgical margin involvement, venous and/or lymphatic involvement, satellite nodules, tumor necrosis detected by pathology, tumor size ≥ 7 cm, and macrovascular invasion were determined as risk factors associated with early EHR. After sub-categorizing the patients according to the number of risk factors, the rates of both EHR and survival showed a significant correlation with the risk of early EHR. Furthermore, multivariate analysis revealed that early EHR was associated with substantially worse survival outcomes (hazard ratio, 6.77; 95% confidence interval, 4.81-9.52; P < 0.001).

Research conclusions

Early EHR significantly deteriorates the survival of patients with HCC, and our identified risk factors may predict the clinical outcomes and aid in postoperative strategies for improving survival.

Research perspectives

Further studies are warranted to investigate characteristics and risk factors for early EHR in patients with diverse chronic hepatitis by using a standardized study protocol. Using an accurate tool for the prediction of early EHR, the prognosis of patients with a high risk of early EHR may be improved with the utilization of adjunctive post-operative therapy.