外科理论与实践 ›› 2022, Vol. 27 ›› Issue (03): 221-228.doi: 10.16139/j.1007-9610.2022.03.008
尹彦江, 罗治文, 陈晓, 张业繁, 黄振, 赵宏, 赵建军, 李智宇, 周健国, 蔡建强, 毕新宇()
收稿日期:
2021-03-09
出版日期:
2022-06-25
发布日期:
2022-08-03
通讯作者:
毕新宇
E-mail:beexy1971@163.com
基金资助:
YIN Yanjiang, LUO Zhiwen, CHEN Xiao, ZHANG Yefan, HUANG Zhen, ZHAO Hong, ZHAO Jianjun, LI Zhiyu, ZHOU Jianguo, CAI Jianqiang, BI Xinyu()
Received:
2021-03-09
Online:
2022-06-25
Published:
2022-08-03
Contact:
BI Xinyu
E-mail:beexy1971@163.com
摘要:
目的:分析肝脏手术切缘对肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)病人预后的影响,并探索ICC切缘推荐距离。方法:收集2011年1月至2017年1月北京肿瘤医院肝胆外科ICC病人的临床病理资料。用单因素和多因素Cox分析影响ICC预后的危险因素,并用Kaplan-Meier方法制作无复发生存(recurrent free survival,RFS)期和总生存(overall survival,OS)期曲线。采用限制性立方样条(restricted cubic spline,RCS)分别探索R0切缘距离与OS期和RFS期的关系,并探索手术切缘推荐距离。结果:本研究共71例病人,随访2~107个月,中位RFS期8个月,中位OS期17个月。1、3、5年的RFS率分别为35%、20%、10%,OS率分别为68%、38%、23%。Cox回归分析发现,美国癌症联合委员会(American Joint Committee on Cancer,AJCC)分期、手术切缘、甲胎蛋白(alpha-fetoprotein,AFP)、糖类抗原19-9(carbohydrate antigen 19-9,CA19-9)是ICC病人预后的独立危险因素。共R0切除59例(83%),R1切除12例(17%)。比较R0与R1切除病人的术前临床病理因素,发现肿瘤单发、AJCC分期或日本肝癌研究组(Liver Cancer Study Group of Japan,LCSGJ)分期处于Ⅰ期、Ⅱ期时,R0切除的可能性更大。本研究原始数据为病理切缘,考虑到病理标本制作存在缩水,将病理切缘换算为手术切缘。RCS和Kaplan-Meier法分析发现,宽切缘组(0.5 cm<X1<2.8 cm)与窄切缘组(0.1 cm<X2≤0.5 cm)相比,RFS期更长。结论:R1切除是ICC病人预后的独立危险因素。对于肿瘤单发、AJCC分期或LCSGJ分期处于Ⅰ期、Ⅱ期的ICC病人,行肝切除术时,R0切除的可能性更大。至少实现0.5 cm以上手术切缘,以改善预后。
中图分类号:
尹彦江, 罗治文, 陈晓, 张业繁, 黄振, 赵宏, 赵建军, 李智宇, 周健国, 蔡建强, 毕新宇. 肝内胆管癌病人肝脏手术切缘与预后的关系[J]. 外科理论与实践, 2022, 27(03): 221-228.
YIN Yanjiang, LUO Zhiwen, CHEN Xiao, ZHANG Yefan, HUANG Zhen, ZHAO Hong, ZHAO Jianjun, LI Zhiyu, ZHOU Jianguo, CAI Jianqiang, BI Xinyu. Relationship between surgical margin and prognosis of patients with intrahepatic cholangiocarcinoma[J]. Journal of Surgery Concepts & Practice, 2022, 27(03): 221-228.
表1
基线特征
临床病理因素 | 病例数 | 临床病理因素 | 病例数 |
---|---|---|---|
年龄 | 57.8±9.2 | 淋巴结清扫数 | 4 |
性别 | 阳性淋巴结数 | 1 | |
男 | 40(56.3%) | 肿瘤最大径(cm) | 5.5±2.2 |
女 | 31(43.7%) | >5 | 35(49.3%) |
肝炎史 | ≤5 | 36(50.7%) | |
无 | 54(76.1%) | LCSGJa)分期 | |
乙型肝炎 | 16(22.5%) | Ⅰ | 31(43.7%) |
丙型肝炎 | 1(1.4%) | Ⅱ | 19(26.8%) |
肝硬化史 | 12(16.9%) | Ⅲ | 6(8.5%) |
胆系疾病史 | Ⅳ | 15(21.1%) | |
胆结石 | 8(11.3%) | 手术切缘状态 | |
胆囊炎 | 7(9.9%) | R0 | 59(83.1%) |
无 | 56(78.9%) | R1 | 12(16.9%) |
肿瘤数目 | 切缘距离(cm) | 0.4 | |
单发 | 66(93.0%) | 术中出血量(mL) | 200 |
多发 | 5(7.0%) | 术中输血 | 45(63.4%) |
分化程度 | 术中输液量(mL) | 2 200 | |
低 | 37(52.1%) | 手术时间(h) | 3.7±1.3 |
中 | 32(45.1%) | 术后发生并发症 | 4(5.6%) |
高 | 2(2.8%) | 术后住院时间(d) | 9 |
血管侵犯 | 27(38.0%) | CA19-9(U/mL) | 130 |
其他器官侵犯 | 6(8.5%) | ALT(U/L) | 28 |
T | AST(U/L) | 24 | |
T1 | 34(47.9%) | GGT(U/L) | 54 |
T2 | 20(28.2%) | AFP(μg/L) | 2.96 |
T3 | 10(14.1%) | CEA(μg/L) | 2.56 |
T4 | 7(9.9%) | TBIL(μmol/L) | 11.3 |
N | ALB(g/L) | 47.1±9.5 | |
N0 | 59(83.1%) | PT(s) | 12.1±1.7 |
N1 | 12(16.9%) | 腹腔积液 | |
AJCC分期 | 无 | 65(91.5%) | |
Ⅰ | 31(43.7%) | 少量 | 5(7.0%) |
Ⅱ | 19(26.8%) | 多量 | 1(1.4%) |
Ⅲ | 19(26.8%) | Child-Pugh分级 | |
Ⅳ | 2(2.8%) | A | 66(93.0%) |
淋巴结清扫 | 45(63.4%) | B | 5(7.0%) |
表2
OS期和RFS期的单因素Cox分析
变量 | OS期(月) | RFS期(月) | |||||
---|---|---|---|---|---|---|---|
P值 | HR | 95%CI | P值 | HR | 95%CI | ||
性别 | 0.872 | 0.953 | (0.533, 1.706) | 0.604 | 0.871 | (0.518, 1.466) | |
就诊年龄 | 0.892 | 0.998 | (0.968, 1.029) | 0.957 | 1.001 | (0.974, 1.028) | |
肝炎史 | 0.718 | 0.882 | (0.448, 1.739) | 0.952 | 1.019 | (0.563, 1.841) | |
肝硬化 | 0.579 | 0.796 | (0.355, 1.782) | 0.799 | 0.915 | (0.461, 1.817) | |
胆系疾病 | 0.629 | 0.828 | (0.386, 1.777) | 0.598 | 0.837 | (0.432, 1.621) | |
肿瘤数目 | 0.017a) | 1.980 | (1.701, 2.591) | 0.005a) | 1.424 | (0.510, 3.981) | |
分化程度 | |||||||
低 | |||||||
中 | 0.572 | 0.844 | (0.468, 1.521) | 0.413 | 0.801 | (0.471, 1.363) | |
高 | 0.794 | 0.766 | (0.104, 5.671) | 0.307 | 2.145 | (0.496, 9.284) | |
肿瘤最大径 | 0.039a) | 1.113 | (1.014, 1.256) | 0.322 | 1.058 | (0.947, 1.182) | |
其他器官侵犯 | 0.028a) | 2.962 | (1.127, 7.788) | 0.307 | 1.630 | (0.639, 4.162) | |
淋巴结转移 | 0.007a) | 2.776 | (1.330, 5.792) | 0.002a) | 3.129 | (1.525, 6.422) | |
LCSGJ分期 | |||||||
Ⅰ | |||||||
Ⅱ | 0.784 | 1.111 | (0.524, 2.335) | 0.147 | 0.610 | (0.313, 1.190) | |
Ⅲ | 0.202 | 1.946 | (0.700, 5.406) | 0.939 | 1.038 | (0.397, 2.716) | |
ⅣA、ⅣB | 0.056 | 3.073 | (1.434, 6.582) | 0.054 | 1.945 | (0.988, 3.829) | |
AJCC分期 | |||||||
ⅠA、ⅠB | |||||||
Ⅱ | 0.783 | 1.111 | (0.524, 2.356) | 0.146 | 0.609 | (0.313, 1.188) | |
ⅢA、ⅢB | 0.008a) | 2.600 | (1.277, 5.291) | 0.207 | 1.490 | (0.802, 2.769) | |
Ⅳ | 0.207 | 3.752 | (0.480, 9.296) | 0.008a) | 2.929 | (2.233, 5.323) | |
血管侵犯 | 0.874 | 0.953 | (0.526, 1.725) | 0.038a) | 1.657 | (1.377, 2.144) | |
手术切缘状态 | 0.008a) | 2.439 | (1.267, 4.696) | 0.011a) | 1.539 | (1.188, 1.894) | |
ALT | 0.689 | 1.001 | (0.997, 1.004) | 0.987 | 1.000 | (0.996, 1.003) | |
AST | 0.925 | 1.000 | (0.993, 1.007) | 0.797 | 0.999 | (0.993, 1.005) | |
GGT | 0.273 | 1.001 | (0.999, 1.003) | 0.046a) | 1.002 | (1.000, 1.003) | |
AFP | 0.010a) | 1.007 | (1.002, 1.013) | 0.021a) | 1.006 | (1.001, 1.010) | |
CEA | 0.045a) | 1.005 | (1.000, 1.011) | 0.380 | 1.002 | (0.997, 1.007) | |
TBIL | 0.243 | 1.003 | (0.998, 1.009) | 0.154 | 1.004 | (0.999, 1.009) | |
ALB | 0.728 | 1.005 | (0.976, 1.036) | 0.763 | 0.996 | (0.968, 1.024) | |
PT | 0.424 | 1.067 | (0.911, 1.249) | 0.108 | 1.123 | (0.975, 1.295) | |
CA19-9 | 0.004a) | 1.768 | (1.198, 2.740) | 0.022a) | 3.377 | (1.507, 5.162) | |
腹腔积液 | |||||||
无 | |||||||
少量 | 0.278 | 0.456 | (0.110, 1.887) | 0.119 | 0.324 | (0.079, 1.337) | |
多量 | 0.953 | 0.942 | (0.129, 6.872) | 0.611 | 0.598 | (0.082, 4.352) | |
Child-Pugh分级 | |||||||
A | |||||||
B | 0.328 | 1.595 | (0.626, 4.065) | 0.555 | 1.321 | (0.525, 3.323) |
表3
OS期和RFS期的多因素Cox分析
变量 | OS期(月) | RFS期(月) | |||||
---|---|---|---|---|---|---|---|
P值 | HR | 95%CI | P值 | HR | 95%CI | ||
肿瘤数目 | 0.123 | 2.463 | (0.783, 7.749) | 0.329 | 1.806 | (0.551, 5.915) | |
肿瘤最大直径 | 0.371 | 1.077 | (0.919, 1.255) | ||||
其他器官侵犯 | 0.183 | 2.447 | (0.656, 9.135) | ||||
淋巴结转移 | 0.474 | 1.514 | (0.487, 4.708) | 0.402 | 1.631 | (0.520, 5.114) | |
AJCC分期 | |||||||
ⅠA、ⅠB | |||||||
Ⅱ | 0.876 | 0.935 | (0.405, 2.158) | 0.686 | 0.811 | (0.293, 2.244) | |
ⅢA、ⅢB | 0.443 | 1.537 | (0.513, 4.608) | 0.386 | 1.643 | (0.535, 5.040) | |
Ⅳ | 0.573 | 1.990 | (0.182, 2.779) | 0.026a) | 2.376 | (1.486, 3.375) | |
血管侵犯 | 0.242 | 0.586 | (0.239, 1.434) | ||||
手术切缘状态 | 0.041a) | 1.946 | (1.438, 2.464) | 0.044a) | 1.582 | (1.011, 2.474) | |
GGT | 0.301 | 1.001 | (0.999, 1.003) | ||||
AFP | 0.001a) | 1.010 | (1.004, 1.016) | 0.017a) | 1.006 | (1.001, 1.011) | |
CEA | 0.847 | 0.999 | (0.991, 1.007) | ||||
CA19-9 | 0.027a) | 2.310 | (1.263, 3.167) | 0.181 | 1.539 | (0.818, 2.894) |
表4
R0和R1切缘病人术前临床病理数据特征
变量 | R0切缘(n=59) | R1切缘(n=12) | P值 |
---|---|---|---|
年龄(岁) | 57.81 | 57.83 | >0.05 |
肝炎史[n(%)] | 43(73) | 11(92) | >0.05 |
肝硬化史[n(%)] | 48(81) | 11(92) | >0.05 |
胆系疾病史[n(%)] | 47(80) | 10(83) | >0.05 |
肿瘤数目(单发/多发)[n(%)] | 57(97)/2(3) | 10(83)/2(17) | <0.05a) |
分化程度(低/中、高)[n(%)] | 29(49)/30(51) | 8(67)/4(33) | >0.05 |
血管侵犯[n(%)] | 37(63) | 7(58) | >0.05 |
其他器官侵犯[n(%)] | 55(93) | 10(83) | >0.05 |
肿瘤最大径(cm) | 4.31 | 6.15 | >0.05 |
AJCC分期(Ⅰ、Ⅱ/Ⅲ、Ⅳ)[n(%)] | 45(76)/14(24) | 5(42)/7(58) | <0.05a) |
LCSGJ分期(Ⅰ、Ⅱ/Ⅲ、Ⅳ)[n(%)] | 45(76)/14(24) | 5(42)/7(58) | <0.05a) |
CA19-9(U/mL) | 85.42 | 164.9 | >0.05 |
ALT(U/L) | 62.95 | 84.75 | >0.05 |
AST(U/L) | 39 | 52.67 | >0.05 |
GGT(U/L) | 99.53 | 112.5 | >0.05 |
AFP(μg/L) | 12.56 | 11.43 | >0.05 |
CEA(μg/L) | 11.18 | 31.15 | >0.05 |
TBIL(μmol/L) | 19.62 | 19.93 | >0.05 |
ALB(g/L) | 45.55 | 44.34 | >0.05 |
PT(s) | 12.09 | 12.3 | >0.05 |
腹腔积液[n(%)] | 54(92) | 11(92) | >0.05 |
Child-Pugh分级(A/B)[n(%)] | 55(93)/4(7) | 11(92)/1(8) | >0.05 |
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