Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma

Tomoki Sempokuya; Eric A Wien; Robert J Pattison; Jihyun Ma; Linda L Wong

doi:10.4254/wjh.v12.i11.1020

Factors associated with 5-year survival of combined hepatocellular and cholangiocarcinoma

World J Hepatol. 2020 Nov 27;12(11):1020-1030. doi: 10.4254/wjh.v12.i11.1020.

Authors

Tomoki Sempokuya¹, Eric A Wien², Robert J Pattison², Jihyun Ma³, Linda L Wong⁴

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, United States. tsempoku@hawaii.edu.
² Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, United States.
³ Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE 68198, United States.
⁴ Department of Surgery, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96817, United States.

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; Hepatobiliary cancer; Race; Surveillance, Epidemiology, and End Results database; Survival; Transplant.