Retrospective Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2020; 12(11): 1020-1030
Published online Nov 27, 2020. doi: 10.4254/wjh.v12.i11.1020
Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma
Tomoki Sempokuya, Eric A Wien, Robert J Pattison, Jihyun Ma, Linda L Wong
Tomoki Sempokuya, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States
Eric A Wien, Robert J Pattison, Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, United States
Jihyun Ma, Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, United States
Linda L Wong, Department of Surgery, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96817, United States
Author contributions: Sempokuya T contributed to study design, data collection, statistical analysis; Sempokuya T, Wien E and Pattison R contributed to the literature review, manuscript drafting, and editing; Ma J contributed to study design and statistical analysis; Wong L contributed to study supervision, manuscript drafting and editing; and all of the authors approved the final version of the manuscript.
Institutional review board statement: Since we utilized publicly available de-identified database, review by our institutional review board was not required.
Informed consent statement: Informed consent was not required to conduct this study.
Conflict-of-interest statement: LW is a speaker bureau for Eisai. Other authors do not have any conflict of interest.
Data sharing statement: All the data used in this analysis is available from SEER database.
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: Tomoki Sempokuya, MD, Doctor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, 982000 Nebraska Medical Center, Omaha, NE 68198, United States. tsempoku@hawaii.edu
Received: April 15, 2020
Peer-review started: April 15, 2020
First decision: June 4, 2020
Revised: July 25, 2020
Accepted: October 12, 2020
Article in press: October 12, 2020
Published online: November 27, 2020
Abstract
BACKGROUND

Combined hepatocellular and cholangiocarcinoma (HCC/CC) is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature. Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis. Given the rarity of HCC/CC, an analysis of large national cancer database was needed to obtain larger number of HCC/CC cases.

AIM

To identify associated factors for 5-year survival of HCC/CC.

METHODS

We conducted a retrospective study of The Surveillance, Epidemiology, and End Results (SEER) database obtained from SEER*Stat 8.3.6 software. Previously defined histology code 8180 for the International Classification of Disease for Oncology, 3rd edition was used to identify HCC/CC cases from 2004 to 2015. We collected demographics, American Joint Committee on Cancer (AJCC) stage, treatment, tumor size, and survival data. These data were converted to categorical variables. The Shapiro-Wilk normality test was used to assess normal distribution. Mann-Whitney U test was used to compare continuous variables without normal distribution, and t-test was used to compare continuous variables with a normal distribution. The Kaplan-Meier survival curve analyzed 5-year survival. Univariate and multivariate logistic regression model was used to analyze factors associated with 5-year survival. Multivariate Cox proportional hazard regression was done on 5-year survival. We defined P < 0.05 was statistically significant.

RESULTS

We identified 497 patients with the following characteristics: Mean age 62.4 years (SD: 11.3), 149 (30.0%) were female, racial distribution was: 276 (55.5%) white, 53 (10.7%) black, 84 (16.9%) Asian and Pacific Islander (API), 77 (15.5%) Hispanic, and 7 (1.4%) others or unknown. Stage I/II disease occurred in 41.5% and tumor size < 50 mm was seen in 35.6% of patients. Twenty-four (4.8%) received locoregional therapy (LRT), 119 (23.9%) underwent resection, and 50 (10.1%) underwent liver transplantation. The overall median survival was 6 mo [Interquartile range (IQR): 1-22]. After multivariate logistic regression, tumor size < 50 mm [Odds ratios (OR): 2.415, P = 0.05], resection (OR: 12.849, P < 0.01), and transplant (OR: 27.129, P < 0.01) showed significance for 5-year survival. Age > 60, sex, race, AJCC stages, metastasis, and LRT were not significant. However, API vs white showed significant OR of 2.793 (CI: 1.120-6.967). Cox proportional hazard regression showed AJCC stages, tumor size < 50 mm, LRT, resection, and transplant showed significant hazard ratio.

CONCLUSION

HCC/CC patients with tumor size < 50 mm, resection, and transplant were associated with an increase in 5-year survival. API showed advantageous OR and hazard ratios over white, black.

Keywords: Combined hepatocellular and cholangiocarcinoma, Surveillance, Epidemiology, and End Results database, Survival, Race, Hepatobiliary cancer, Transplant

Core Tip: Combined hepatocellular and cholangiocarcinoma (HCC/CC) is a rare primary hepatic malignancy which carries a poor prognosis due to its aggressive nature. Few centers have enough cases to draw definitive conclusions and there is limited understanding of prognosis. This analysis of Surveillance, Epidemiology, and End Results database comprised of 497 patients. HCC/CC patients with tumor size < 50 mm, resection, and transplant were associated with an increase in 5-year survival. Asian and Pacific Islander (API) showed advantageous odds ratios and hazard ratios over white, black. Elucidation of better prognosis on API are needed in the future studies.