Prognosis analysis and strategies selection in liver transplantation for intrahepatic cholangio-carcinoma
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摘要:
肝内胆管细胞癌（ICC）是一种复杂的恶性肿瘤,预后差。早期,ICC患者肝移植后预后差,导致其曾一度被视为肝移植的禁忌证。但近年越来越多的研究对上述传统观点提出挑战,在合理选择受者或联合新辅助治疗条件下,肝移植在ICC患者中已取得较好预后。与手术切除等其他治疗措施比较,肝移植可改善ICC患者预后。与ICC肝移植预后相关的因素包括新辅助治疗、肿瘤整体负荷、肿瘤生物学行为以及移植后综合治疗措施等。基于目前临床研究,笔者针对ICC肝移植预后情况、ICC肝移植及其他治疗措施预后比较、ICC肝移植预后相关因素、ICC肝移植受者选择策略、ICC肝移植治疗的进步与挑战进行深入阐述。
Abstract:Intrahepatic cholangiocarcinoma (ICC) is a complex malignant tumor with poor prognosis. Historically, the prognosis of ICC patients after liver transplantation is poor, which led to that it is once regarded as a contraindication of liver transplantation. However, in recent years, results of multiple studies challenge the above view. These emerging studies demonstrate that under the condition of reasonable selection of recipients or combined with neoadjuvant therapy, liver trans-plantation has achieved considerable prognosis in patients with ICC. In addition, compared with surgical resection and other treatments, liver transplantation can improve the prognosis of patients with ICC. The factors related to the prognosis of ICC patients who underwent liver transplantation include neoadjuvant therapy, overall tumor burden, tumor biological behavior and comprehensive treatment after transplantation, et al. Based on the results from currently existing clinical studies, the authors make a deep elaboration on the prognosis of ICC patients after liver transplantation, prognosis comparison between liver transplantation and other treatment measures for ICC, factors related to the prognosis of ICC patients who underwent liver transplantation, and the selection strategy of recipient of liver transplantation for ICC, and advance and challenge of liver transplantation for ICC.
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所有作者均声明不存在利益冲突吕国悦, 孙大伟. 肝内胆管细胞癌肝移植治疗的预后分析与策略选择[J]. 中华消化外科杂志, 2023, 22(2): 187-194. DOI: 10.3760/cma.j.cn115610-20221123-00707.
http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20221123-22707
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表 1 肝内胆管细胞癌患者肝移植治疗预后情况文献汇总
Table 1 Summary of literatures on prognosis of patients with intrahepatic cholangiocarcinoma after liver transplantation
作者 年份 国家 例数 病理学特征 降期治疗策略 总生存率（%） 无复发生存率（%） 1年 3年 5年 1年 3年 5年 O′Grady等[4] 1988 英国 13 NA NA 38.4 10 0 NA NA NA Pichlmayr等[5] 1997 德国 24 NA NA 19.4 4.9 0 NA NA NA Shimoda等[9] 2001 美国 16 TNM分期Ⅰ/Ⅱ/Ⅲ/Ⅳ期（2例/2例/3例/9例）,>2处病灶（12例）,血管侵犯（3例）,淋巴结转移（2例） NA 62 39 NA 70 35 NA 张彤等[10] 2010 中国 11 TNM分期Ⅰ/Ⅱ/ⅢA/ⅢC期（3例/2例/3例/3例）,血管侵犯（3例）,淋巴结转移（4例） 局部区域治疗（8例） 50.5 50.5 NA 51.9 51.9 NA Hu和Yun[11] 2011 中国 20 TNM分期Ⅰ/Ⅱ/Ⅲ期（4例/4例/12例）,≥2处病灶（11例）,大血管侵犯（12例）,微血管侵犯（16例）,淋巴结转移（9例）,肿瘤分化差（11例） NA 84.2 32.7 21.8 55.6 28.8 18.8 Vallin等[12] 2013 法国 4 进展期（4例）,血管侵犯（1例） NA 75 75 NA 75 75 NA Sapisochin等[13] 2014 西班牙 29 进展期（21例）,大血管侵犯（2例）,微血管侵犯（3例） 局部区域治疗：TACE（8例）,射频消融治疗（3例）,PEI（2例） 79 61 45 89 71 71 Takahashi等[14] 2016 美国 13 肿瘤长径为1.0~3.3 cm,血管侵犯（1例）,肿瘤分化差（0例）,淋巴结转移（1例） 局部区域治疗：TACE（4例）,RFA（1例） NA NA NA 67 42 NA Sapisochin等[6] 2016 国际多中心 48 进展期（33例）,大血管侵犯（2例）,微血管侵犯（11例）,肿瘤分化差（6例） 局部区域治疗：TACE（12例）,消融治疗（8例）,TACE+消融（3例） 83.3 47.9 31.3 75% 41.7 27.1 Lunsford等[7] 2018 美国 6 进展期（6例）,大血管侵犯（0例）,微血管侵犯（2例）,淋巴结转移（2例）,肿瘤分化差（3例） 新辅助治疗：顺铂为基础的化疗,联合吉西他滨（6例） 100 83.3 83.3 50 50 50 McMillan等[15] 2022 美国 18 进展期（18例）,淋巴血管侵犯（6例） 新辅助治疗：吉西他滨为基础的化疗,联同放射治疗和（或）局部区域治疗（18例） 100 71 57 70 52 NA Hara等[16] 2021 日本 19 术后病理学检查偶然发现 TACE（1例） 79 45 45 79 63 46 Hue等[18] 2021 美国国家癌症数据库 74 非转移性 新辅助治疗（52例） 89.4 53.0 40.8 NA NA NA Kim等[19] 2022 美国国家癌症数据库 66 TNM分期Ⅰ~Ⅲ期 新辅助治疗（25例） NA NA 36.1 NA NA NA Lee等[17] 2022 美国国家癌症数据库 62 早期（单发肿瘤长径<3 cm） NA 88.9 72.9 67.9 NA NA NA 注： TACE为经导管肝动脉化疗栓塞术；RFA为射频消融术；PEI为经皮酒精注射；进展期为肿瘤长径>2 cm和（或）肿瘤数目≥2个；NA为信息缺失
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表 2 1 093例早期肝内胆管细胞癌患者不同治疗方式预后比较
Table 2 Comparison of prognosis of 1 093 patients with early intrahepatic cholangiocarcinoma treated by different methods
治疗方式 例数 1年总生存率（%） 3年总生存率（%） 5年总生存率（%） 肝移植 62 88.9 72.9 67.9 手术切除 464 89.0 67.5 55.9 消融治疗 113 89.1 54.3 33.2 其他治疗 454 49.4 20.3 12.9
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表 3 肝内胆管细胞癌肝移植手术适应证及禁忌证
Table 3 Indications and contraindications of liver trans⁃ plantation for intrahepatic cholangiocarcinoma
适应证 禁忌证 （1）慢性肝病基础不适宜肝切除,单发病灶、肿瘤长径≤2 cm （1）肝移植后肿瘤复发 （2）局限于肝内的局部进展期（单发肿瘤、肿瘤长径>2 cm；肿瘤数目≥2个）,不伴有肝外转移,不伴有大血管侵犯,同时肿瘤对降期治疗（吉西他滨为基础的化疗方案,联合或不联合局部治疗措施）敏感 （2）移植等待期间肿瘤进展（肿瘤长径>2 cm、新发肿瘤灶、血管侵犯、CA19‑9显著升高、肝外转移）
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