手术切除后混合型肝癌、肝细胞癌及肝内胆管细胞癌的临床特征及预后分析：倾向性匹配分析

摘要/Abstract

摘要： 目的：探讨混合型肝癌（mHCC）与肝细胞癌（HCC）、肝内胆管细胞癌（ICC）患者术后临床病理特征异同以及预后影响因素。
方法：回顾性分析2015年1月至2023年12月就诊于北京大学人民医院肝胆外科收治的317例肝脏恶性肿瘤患者的临床资料。在肿瘤分化程度、淋巴结转移情况以及第8版AJCC分期方面,经倾向性匹配后150例患者被分别纳入2个独立的匹配队列:mHCC与HCC患者各43例,mHCC与ICC患者各32例。比较组间患者临床特征和预后情况。正态分布连续变量使用Student t检验或单因素方差分析,不符合正态分布连续变量应用Wilcoxon 秩和检验。分类变量使用χ²检验。Kaplan-Meier 方法评估中位总生存时间和中位无病生存时间。采用单因素和多因素Cox回归分析评估预后影响因素。
结果：mHCC患者年龄、性别、肝硬化程度与HCC、ICC患者相似,乙型肝炎患病率低于HCC患者,但与ICC患者相当。mHCC患者甲胎蛋白水平明显高于ICC患者,糖类抗原19-9水平低于HCC患者,而癌胚抗原水平明显高于HCC、ICC患者。mHCC患者病理特征中微血管侵犯率、淋巴结转移率高于HCC患者且与ICC患者相当。mHCC患者中位生存时间差于HCC患者（19.6个月∶70.8个月,P<0.001）,与ICC患者相当（19.6个月∶40.6个月,P=0.07）。mHCC患者无病生存时间差于HCC患者且与ICC患者相当。多因素Cox分析显示淋巴结转移、低分化肿瘤、肿瘤分期、病理类型及饮酒史是总生存时间的影响因素,低分化肿瘤及肿瘤分期是无病生存时间的影响因素;在2个匹配队列中多发肿瘤均是预后影响因素。
结论：mHCC患者临床特征及预后与HCC、ICC并不一致,是一种恶性程度较高、极易复发的罕见病理类型,应当被视为原发性肝癌中一个独特的肿瘤类型进行诊疗。mHCC患者长期生存时间比HCC差、与ICC相当,淋巴结转移、低分化肿瘤、肿瘤分期及饮酒史是预后影响因素,匹配后多发肿瘤与预后相关。

关键词: 混合型肝癌, 肝细胞癌, 肝内胆管细胞癌, 手术切除, 倾向性匹配分析, 预后

Abstract: Objective: To compare the clinicopathological features and prognosis of mixed hepatocellular carcinoma (mHCC), hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) after surgical resection.
Methods: The clinical data of 317 patients diagnosed with liver malignant tumors who were admitted to the Department of Hepatobiliary Surgery, Peking University People's Hospital from January 2015 to December 2023 were retrospectively analyzed. After propensity matching with 1:1 in the degree of tumor differentiation, lymph node metastasis and AJCC (8th edition) stage, 150 patients were enrolled in two independent matching cohorts: mHCC and HCC 43 cases each, mHCC and ICC 32 cases each. The clinical characteristics and prognosis of patients were compared between groups. Normally distributed continuous variables were compared using Student's t-test or one-way ANOVA, and non-normally distributed continuous variables were compared using Wilcoxon rank sum statistics. Chi-square test is used to compare categorical variables. The Kaplan-Meier method assesses median survival and median disease-free survival.
Results: The age, sex, and degree of cirrhosis of mHCC patients were similar to those of HCC and ICC patients, and the prevalence of hepatitis B was lower than that of HCC patients but comparable to that of ICC patients. mHCC patients had significantly higher levels of AFP than those of ICC patients, lower levels of CA19-9 than those of HCC patients, and significantly higher levels of CEA than those of the other two pathological types. mHCC's pathological features of microvascular invasion rate and lymph node metastasis rate were higher than those of HCC and comparable to those of ICC.The median survival of mHCC patients was worse than that of HCC patients (19.6 months vs. 70.8 months, P<0.001) and comparable to that of ICC patients (19.6 months vs. 40.6 months, P=0.07). mHCC patients had a worse disease-free survival than that of HCC patients and comparable to that of ICC patients. Multifactorial Cox analysis showed that lymph node metastasis, poorly differentiated tumor, tumor stage, pathological type and history of alcohol consumption were independent risk factors associated with prognosis, and that poorly differentiated tumor and tumor stage were independent risk factors for disease-free survival; multiple tumors were an independent risk factor affecting postoperative prognosis in both 1:1 matched cohorts.
Conclusions: The clinical features and prognosis of mHCC are not consistent with those of HCC and ICC, and it is a rare pathological type with a high degree of malignancy that is highly susceptible to recurrence, and it should be treated as a unique tumor type in primary hepatocellular carcinoma. The mHCC has a poorer long-term survival than HCC, and it is comparable to that of ICC, and lymph node metastasis, poorly differentiated tumors, tumor stage, and a history of alcohol consumption are prognostically relevant independent risk factors, luminal surgery was a prognostically relevant independent insurance factor, and poorly differentiated tumors and tumor stage were independent risk factors for disease-free survival. The multiple tumors were found to be associated with poor prognosis and recurrent metastases in mHCC after propensity matching.

Key words: Mixed hepatocellular carcinoma, Hepatocellular carcinoma, Intrahepatic cholangiocarcinoma, Surgical resection, Propensity match analysis, Prognosis

朱润泽, 穆少伟, 李照, 朱继业, 高杰. 手术切除后混合型肝癌、肝细胞癌及肝内胆管细胞癌的临床特征及预后分析：倾向性匹配分析[J]. 肝癌电子杂志, 2024, 11(3): 25-32.

Zhu Runze, Mu Shaowei, Li Zhao, Zhu Jiye, Gao Jie. Clinical features and prognosis analysis of combined mixed hepatocellular carcinoma, hepatocellular carcinoma and intrahepatic cholangiocarcinoma after surgical resection: propensity match analysis[J]. Electronic Journal of Liver Tumor, 2024, 11(3): 25-32.

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