肝移植治疗肝内胆管细胞癌临床疗效的多中心研究

Clinical efficacy of liver transplantation for intrahepatic cholangiocarcinoma: a multicenter study

  • 摘要:
    目的 探讨肝移植治疗肝内胆管细胞癌(ICC)的临床疗效。
    方法 采用回顾性队列研究方法。收集2005年9月至2021年12月吉林大学第一医院等国内5家医学中心收治的22例行肝移植ICC患者的临床病理资料;男18例,女4例;年龄为57(38~71)岁。观察指标:(1)ICC患者临床病理特征。(2)随访情况。(3)预后情况。偏态分布的计量资料以M(范围)表示。计数资料以绝对数或百分比表示。采用Kaplan‑Meier法绘制生存曲线,Log‑Rank检验进行生存分析。
    结果 (1)ICC患者临床病理特征。22例患者中,20例移植前确诊ICC;7例有乙型病毒性肝炎病史,1例有原发性硬化性胆管炎病史;7例移植前有肿瘤治疗史;肝功能Child‑Pugh分级A、B、C级分别为7、6、9例;16例术前CA19‑9>40 U/mL;14例肿瘤数目为单发;11例肿瘤位于右半肝、6例位于左半肝+右半肝、5例位于左半肝;9例肿瘤侵犯脉管;肿瘤均为中、低分化;9例有肝硬化改变;4例发生淋巴结转移;10例肿瘤负荷满足米兰标准;22例患者肿瘤长径为4.5(1.5~8.0)cm。(2)随访情况。22例患者均获得随访,随访时间为15(3~207)个月。22例患者中,9例肿瘤复发,8例死亡。(3)预后情况。22例ICC患者肝移植后1年总生存率、1年无瘤生存率分别为72.73%、68.18%。亚组分析结果显示:10例满足米兰标准和12例超出米兰标准ICC患者肝移植后总生存、无瘤生存情况比较,差异均有统计学意义(风险比=0.13,0.26,95%可信区间为0.03~0.53,0.08~0.82,P<0.05)。进一步分析结果显示:12例超出米兰标准ICC患者中,5例术前行肿瘤降期治疗和7例未行肿瘤降期治疗患者肝移植后总生存、无瘤生存情况比较,差异均有统计学意义(风险比=0.18,0.14,95%可信区间为0.04~0.76,0.04~0.58,P<0.05)。
    结论 满足米兰标准ICC患者肝移植预后效果明显优于超出米兰标准患者,而对超出米兰标准ICC患者积极行肝移植前降期治疗可显著改善患者预后。

     

    Abstract:
    Objective To investigate the clinical efficacy of liver transplantation for intra-hepatic cholangiocarcinoma.
    Methods The retrospective cohort study was conducted. The clinico-pathological data of 22 patients with intrahepatic cholangiocarcinoma who underwent liver trans-plantation in the 5 medical centers, including First Hospital of Jilin University, et al, from September 2005 to December 2021 were collected. There were 18 males and 4 females, aged 57(range, 38‒71)years. Observing indicators: (1) clinicopathological characteristics of patients with intrahepatic cholangiocarcinoma; (2) follow-up; (3) prognosis. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to draw survival curves. The Log-Rank test was used for survival analysis.
    Results (1) Clinicopathological characteristics of patients with intrahepatic cholangio-carcinoma. Of the 22 patients, 20 cases were diagnosed as intrahepatic cholangiocarcinoma before liver transplantation, 7 cases had viral hepatitis type B, 1 case had primary sclerosing cholangitis, 7 cases had tumor treatment before liver transplantation, 7 cases, 6 cases and 9 cases were classified as grade A, grade B and grade C of the Child-Pugh classification, 16 cases had preoperative CA19-9 >40 U/mL, 14 cases had single tumor, 11 cases with tumor located at right lobe of liver, 6 cases with tumor located at both left and right lobe of liver, 5 cases with tumor located at left lobe of liver, 9 cases with tumor vascular invasion. All 22 patients were diagnosed as moderate-poor differentiated tumor. There were 9 cases with liver cirrhosis, 4 cases with tumor lymph node metastasis, 10 cases with tumor burden within Milan criteria. The tumor diameter of 22 patients was 4.5(range, 1.5‒8.0)cm. (2) Follow-up. All 22 patients were followed up for 15(range, 3‒207)months. Of the 22 patients, 9 cases had tumor recurrence and 8 cases died. (3) Prognosis. The 1-year overall survival rate and 1-year disease-free survival rate of the 22 patients was 72.73% and 68.18%, respectively. Results of subgroup analysis showed there were significant differences in overall survival and disease-free survival between the 10 patients with tumor burden within Milan criteria and the 12 patients with tumor burden beyond Milan criteria who underwent liver transplantation (hazard ratio=0.13, 0.26, 95% confidence interval as 0.03‒0.53, 0.08‒0.82, P<0.05). Results of further analysis of the 12 patients with tumor burden beyond Milan criteria showed there were significant differences in overall survival and disease-free survival between the 5 patients with preoperative tumor down-staging treatment and the 7 patients without preoperative tumor down-staging treatment (hazard ratio=0.18, 0.14, 95% confidence interval as 0.04‒0.76, 0.04‒0.58, P<0.05).
    Conclusions Intrahepatic cholangiocarcinoma patients with tumor burden within Milan criteria have a better prognosis than patients with tumor burden beyond Milan criteria after liver transplantation. For patients with tumor burden beyond Milan criteria, active tumor down-staging treatment before liver transplantation can improve the prognosis.

     

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