Abstract: Prognostic changes of three pathological types of hepatocellular carcinoma during the past decade and the relationship with tumor diameter and lymph node metastasis: a long-term prognosis analysis of 10 672 patients based on SEER database        YAO Qing,ZHANG Xing,LIU Chang,et al. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061，China
Corresponding authors:QU Kai,E-mail：qukaixjtu@163com;LIU Chang,E-mail：eyrechang@126.com
Abstract  Objective To analyze and compare the prognosis of patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC) after hepatectomy. Methods    The clinicopathologic data and follow-up results of 9044 patients with HCC, 1421 patients with ICC and 207 patients with CHC who underwent liver resection from 2004 to 2015 registered in the American SEER database were retrospectively analyzed. All these total 10 672 patients of primary liver cancer (PLC) had complete information about surgical resection, TNM stage and survival outcomes. The differences of overall survival and long-term survival after resection between 3 types of PLCs were compared. Furthermore, total 10 672 patients were divided into subgroups by N stage and tumor size, and prognostic differences between 3 carcinomas were compared for each subgroup. Kaplan-Meier survival curve and Log-rank test were employed for comparison. Landmark analysis was further performed for crossed survival curves. Results    For patients undergoing liver resection, 3-year survival rates of HCC, ICC and CHC all raised from 2004 to 2015. The overall survival of patients with HCC was significantly better than CHC and ICC. What’s more, despite that the prognosis within 40 months were similar between CHC and ICC(P>0.05), the long-term survival after 40 months of CHC was significantly better than ICC(P=0.014). In general, although the survival between CHC and ICC showed no significant difference, ICC had the worst prognosis in N0 subgroup and tumor-size-<5cm subgroup while CHC had the worst prognosis in N1 subgroup and tumor-size->5cm subgroup, and HCC showed the best prognosis in all subgroups. Conclusion    For PLCs patients undergoing liver resection, overall prognosis of HCC was the best of 3 pathologic types of PLC, and short-term prognosis within 40 months was similar between CHC and ICC. However, long-term survival after 40 months of CHC was significantly better than ICC. Moreover, the surgical outcome of CHC with tumor size > 5 cm and N1 stage was worse than HCC and ICC, which might due to stronger stem cell features.

Key words: hepatocellular carcinoma, intrahepatic cholangiocarcinoma, combined hepatocellular-cholangiocarcinoma, prognosis, tumor size, lymph node metastasis

摘要： 目的    分析比较肝细胞癌（HCC）、肝内胆管癌（ICC）和混合型肝癌（CHC）病人术后的预后差异。方法    回顾性分析SEER数据库2004—2015年间接受手术治疗的原发性肝癌10 672例，其中包括HCC病人 9044例，ICC 病人1421例，CHC病人 207例。所有病人包括完整的TNM分期、手术、生存时间及生存状态等信息。比较3种肿瘤术后总体生存（OS）情况及长期预后差异。同时观察N分期亚组（N0组、N1组）及肿瘤直径亚组（0~＜2 cm组，2~5 cm组，>5 cm组）中3种肿瘤病人的预后差异，绘制生存曲线并进行多因素cox回归分析校正，进一步行交叉生存曲线Landmark分析。结果    自2004—2015年3种病理学类型肝癌病人的3年存活率均有不同程度提高。其中，HCC病人术后总体生存明显优于ICC与CHC。ICC与CHC病人术后的早期预后（<40个月）虽差异无统计学意义，但CHC病人的长期预后（>40个月）显著优于ICC病人（P=0.014）。对影响肿瘤分期的肿瘤直径及淋巴结分期行进一步亚组分析显示，在所有亚组中，HCC病人的预后均优于ICC与CHC，而在N0期亚组以及肿瘤直径<5 cm的亚组中，ICC预后最差；而N1期亚组及肿瘤直径>5 cm的亚组中，CHC预后最差。结论    3种病理学类型肝癌病人中，HCC预后最佳，而CHC与ICC在早期（40个月内）虽无预后差异，但CHC的长期预后（40个月以后）明显优于ICC。此外，肿瘤直径>5 cm及N1分期的CHC病人预后差于其他两类肝癌，可能与其具有较强的肿瘤干细胞特性有关。

关键词: 肝细胞癌, 肝内胆管癌, 混合型肝癌, 预后, 肿瘤直径, 淋巴结转移