Safety of minimally invasive liver resection for resectable hepatocellular carcinoma complica-ted with portal hypertension: a multicenter study
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摘要:目的
探讨微创肝切除术治疗合并门静脉高压症可切除性肝细胞癌的安全性。
方法采用倾向评分匹配及回顾性队列研究方法。收集2011年6月至2022年11月我国浙江大学医学院附属邵逸夫医院等8家医学中心收治的807例行微创肝切除术治疗可切除性肝细胞癌患者的临床病理资料；男670例,女137例；年龄为58（50,66）岁。807例患者中,173例合并门静脉高压症,设为门静脉高压症组；634例不合并门静脉高压症,设为非门静脉高压症组。观察指标：（1）倾向评分匹配情况及匹配后两组患者一般资料比较。（2）术中及术后情况。（3）亚组分析。倾向评分匹配按1∶1最近邻匹配法匹配,卡钳值设为0.001。偏态分布的计量资料以M（Q1,Q3）表示,组间比较采用秩和检验。计数资料以绝对数表示,组间比较采用χ²检验或Fisher确切概率法。等级资料比较采用非参数秩和检验。
结果（1）倾向评分匹配情况及匹配后两组患者一般资料比较。807例患者中,268例配对成功,门静脉高压症组和非门静脉高压症组各134例。倾向评分匹配后消除肿瘤最大径、机器人手术系统辅助手术因素混杂偏倚,具有可比性。（2）术中及术后情况。门静脉高压症组和非门静脉高压症组患者肝门阻断时间,术中输血,术后并发症,>Ⅱ级Clavien‑Dindo并发症,Clavien⁃Dindo分级（Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级）,肝脏相关并发症分别为27.0（15.0,43.0）min,33例,55例,15例,13、29、14、1例,37例和35.0（22.0,60.0）min,17例,25例,5例,14、9、4、1例,13例,两组患者上述指标比较,差异均有统计学意义（Z=-2.15,χ²=6.30,16.39,4.38,20.72,14.16,P<0.05）。（3）亚组分析。亚组分析结果显示：行大范围肝切除术患者中,门静脉高压症组和非门静脉高压症组手术时间、术中出血量、术后住院时间分别为243.5（174.6,296.3）min、200.0（150.0,600.0）mL、7.5（6.0,13.0）d和270.0（180.0,314.5）min、200.0（75.0,450.0）mL、7.0（5.5,10.0）d,两组患者上述指标比较,差异均无统计学意义（Z=-0.54、-1.73、-0.92,P>0.05）；行非大范围肝切除术患者中,门静脉高压症组和非门静脉高压症组手术时间、术中出血量、术后住院时间分别为170.0（120.0,227.5）min、100.0（50.0,200.0）mL、8.0（5.0,10.0）d和170.0（120.0,227.5）min、100.0（50.0,200.0）mL、7.0（5.5,9.0）d,两组患者上述指标比较,差异均无统计学意义（Z=-1.39,-0.10,1.05,P>0.05）；行解剖性肝切除术患者中,门静脉高压症组和非门静脉高压症组手术时间、术中出血量、术后住院时间分别为210.0（150.0,285.0）min、150.0（50.0,200.0）mL、8.0（6.0,9.3）d和225.5（146.3,306.8）min、100.0（50.0,250.0）mL、7.0（6.0,9.0）d,两组患者上述指标比较,差异均无统计学意义（Z=-0.75,-0.26,-0.91,P>0.05）；行非解剖性肝切除术患者中,门静脉高压症组和非门静脉高压症组手术时间、术中出血量、术后住院时间分别为173.5（120.0,231.5）min、175.0（50.0,300.0）mL、7.0（5.0,11.0）d和186.0（123.0,262.5）min、100.0（50.0,200.0）mL、7.0（5.0,9.5）d,两组患者上述指标比较,差异均无统计学意义（Z=-0.97,-1.12,-0.98,P>0.05）。
结论经过筛选的合并门静脉高压症肝细胞癌患者行微创肝切除术及大范围肝切除术安全、可行,但需注意术后并发症的防治。
Abstract:ObjectiveTo investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.
MethodsThe propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M(Q1,Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test.
Results(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups (Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups (Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups (Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups (Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups (Z=-0.97, -1.12, -0.98, P>0.05).
ConclusionMinimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.
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梁霄：研究设计；郑俊浩：统计分析及文章撰写；梁霄、麻勇、尹大龙、李建伟、张志波、黄纪伟、高强、张起帆：患者评估及手术实施；郑俊浩、杨广超、孟展志、蔡伟、曹利、吴旭坤、刘烨东、廖明恒、施杰毅、王鑫、李尧：数据收集及录入所有作者均声明不存在利益冲突郑俊浩, 杨广超, 孟展志, 等. 微创肝切除术治疗合并门静脉高压症可切除性肝细胞癌安全性的多中心研究[J]. 中华消化外科杂志, 2023, 22(4): 481-488. DOI: 10.3760/cma.j.cn115610-20230311-00104.
http://journal.yiigle.com/LinkIn.do?linkin_type=cma&DOI=10.3760/cma.j.cn115610-20230311-23104
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表 1 倾向评分匹配前门静脉高压症组和非门静脉高压症组肝细胞癌患者一般资料比较
Table 1 Comparison of general data of patients with hepatocellular carcinoma in the portal hypertension group and the non⁃portal hypertension group before propensity score matching
组别 例数 性别（例） 年龄[M（Q1,Q3）,岁] 体质量指数[M（Q1,Q3）,kg/m2] ASA分级（例） 男 女 Ⅰ级 Ⅱ级 Ⅲ级 Ⅳ级 门静脉高压症组 173 142 31 57（51,64） 23.7（21.4,25.9） 36 71 63 3 非门静脉高压症组 634 528 106 58（50,66） 23.0（21.0,25.3） 104 353 174 3 统计量值 χ²=0.14 Z=-0.67 Z=-1.30 Z=-1.26 P值 0.732 0.504 0.192 0.207 注： 门静脉高压症组为肝细胞癌患者合并门静脉高压症；非门静脉高压症组为肝细胞癌患者不合并门静脉高压症；ASA为美国麻醉医师协会；肝前叶单段包括肝S2、S3、S4b、S5、S6段；肝后叶单段包括肝S1、S7、S8、S4a段；扩大右半肝为肝右三叶；扩大左半肝为肝左三叶；肝右后叶为肝S6+S7段；肝中叶为肝S4+S5+S8或肝S5+S8段
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表 2 倾向评分匹配后门静脉高压症组和非门静脉高压症组肝细胞癌患者一般资料比较
Table 2 Comparison of general data of patients with hepatocellular carcinoma in the portal hypertension group and the non⁃portal hypertension group after propensity score matching
组别 例数 性别（例） 年龄[M（Q1,Q3）,岁] 体质量指数[M（Q1,Q3）,kg/m2] ASA分级（例） 男 女 Ⅰ级 Ⅱ级 Ⅲ级 Ⅳ级 门静脉高压症组 134 112 22 57（50,64） 23.8（21.3,25.8） 28 60 44 2 非门静脉高压症组 134 115 19 58（50,65） 23.5（21.1,26.6） 17 69 48 0 统计量值 χ²=0.26 Z=-0.28 Z=-0.17 Z=-0.93 P值 0.367 0.778 0.864 0.352 注： 门静脉高压症组为肝细胞癌患者合并门静脉高压症；非门静脉高压症组为肝细胞癌患者不合并门静脉高压症；ASA为美国麻醉医师协会；肝前叶单段包括肝S2、S3、S4b、S5、S6段；肝后叶单段包括肝S1、S7、S8、S4a段；扩大右半肝为肝右三叶；扩大左半肝为肝左三叶；肝右后叶为肝S6+S7段；肝中叶为肝S4+S5+S8或肝S5+S8段
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表 3 门静脉高压症组和非门静脉高压症组肝细胞癌患者行微创肝切除术的术中及术后结果比较
Table 3 Comparison of intraoperative and postoperative situations of patients with hepatocellular carcinoma who underwent minimally invasive liver resection in the portal hypertension group and the non⁃portal hypertension group
组别 例数 第一肝门阻断（例） 肝门阻断时间[M（Q1,Q3）,min] 术中出血量[M（Q1,Q3）,mL] 术中输血（例） 中转开腹（例） 门静脉高压症组 134 61 27.0（15.0,43.0） 174.0（50.0,300.0） 33 7 非门静脉高压症组 134 74 35.0（22.0,60.0） 100.0（50.0,200.0） 17 10 统计量值 χ²=2.34 Z=-2.51 Z=-1.16 χ²=6.30 χ²=1.59 P值 0.142 0.012 0.247 0.018 0.451 注： 门静脉高压症组为肝细胞癌患者合并门静脉高压症；非门静脉高压症组为肝细胞癌患者不合并门静脉高压症；“-”为此项无；a采用Fisher确切概率法
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