Impact of hepatocellular carcinoma-related prognostic factors on combined hepatocellular cholangiocarcinoma: A surgical cohort study.

[INTRODUCTION] Combined hepatocellular cholangiocarcinoma (cHCC-CC) exhibits features of hepatocellular carcinoma (HCC) and cholangiocarcinoma. However, whether HCC-related prognostic factors are involved in cHCC-CC remains inconclusive. This study aimed to compare the pathophysiology and recurrence factors between cHCC-CC and HCC.

[MATERIALS AND METHODS] We retrospectively analyzed 1274 consecutive patients who underwent standard hepatectomy between January 2002 and November 2024 for preoperatively diagnosed cHCC-CC or HCC. Propensity score matching (1:2) yielded 80 patients with cHCC-CC and 160 patients with HCC for comparative analysis of clinicopathological characteristics and surgical outcomes.

[RESULTS] The 10-year overall survival was 11.3 % for cHCC-CC vs. 17.5 % for HCC (p < 0.001), whereas the 10-year disease-free survival was 10.0 % vs. 15.6 % (p = 0.012). Early recurrence occurred in 27.5 % of cHCC-CC cases vs. 12.5 % of HCC cases. Compared to HCC, cHCC-CC showed higher prevalence of high-grade tumors (55.0 % vs. 39.4 %, p = 0.031), lack of tumor encapsulation (2.3 % vs. 14.5 %, p = 0.031), tumor necrosis (58.3 % vs. 37.8 %, p = 0.02), vascular invasion (51.3 % vs. 39.3 %, p = 0.028), lymphovascular and perineural invasion (both p < 0.001), and lymph node metastasis (7.5 % vs. 1.3 %, p = 0.009). Early recurrence was significantly associated with a higher prevalence of tumor necrosis (p = 0.002), aggressive vascular invasion (p = 0.006), satellite nodules (27.3 % vs. 6.9 %, p = 0.009), and advanced tumor stage (T3-T4: 27.3 % vs. 10.3 %, p = 0.003).

[CONCLUSION] Our findings suggest that HCC-related prognostic factors significantly influence cHCC-CC progression and recurrence, emphasizing that cHCC-CC may represent an aggressive variant of HCC.