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经皮冷冻消融联合无水酒精注射治疗70岁以上老年肝细胞癌患者的效果及安全性分析
DOI: 10.3969/j.issn.1001-5256.2022.02.021
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：罗婧和吕采红参与了研究数据的获取分析过程；杨永平参与了研究的思路设计。
Clinical efficacy and safety of percutaneous cryoablation combined with percutaneous ethanol injection in elderly patients with hepatocellular carcinoma aged 70 years or older
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摘要:
目的 探讨经皮冷冻消融(CRYO)联合无水酒精注射(PEI)对早期老年肝细胞癌患者的疗效和安全性。 方法 回顾性纳入解放军总医院第五医学中心2014年1月—2018年1月收治的92例老年肝细胞癌患者，其中单一CRYO治疗组46例，CRYO联合PEI(联合治疗)组46例。比较两种治疗方式的效果，不良反应及治疗前后肝功能相关指标的变化，并随访患者肿瘤的复发及生存预后情况。正态分布的计量资料两组间比较用t检验；非正态分布的计量资料两组间比较采用Mann-Whitney U秩和检验。计数资料两组间比较采用χ2检验。两组的生存时间采用Kaplan-Meier方法进行生存分析，并用log-rank检验生存曲线的差异；通过Cox回归法确定影响生存预后的独立危险因素。 结果 联合治疗组和CRYO组初次消融的有效率分别为89.1%和73.9%，组间差异无统计学意义(P＞0.05)。CRYO组和联合治疗组患者术后总生存率和无瘤生存率间的差异均无统计学意义(P值均＞0.05)，但联合治疗组患者术后第1、2和3年局部肿瘤进展率分别为20%、21%和21%，明显低于CRYO组的30%、46%、46%(χ2=4.187，P＜0.05)。多因素Cox回归分析提示行单一CRYO治疗可能是局部肿瘤进展率的独立危险因素(HR=2.206，95%CI: 1.003~4.850, P=0.049)。在不良反应的发生率上两组间差异没有统计学意义(P＞0.05)，但CRYO组有3例严重不良反应，联合治疗组未出现严重不良反应。 结论 对于早期老年肝细胞癌患者，CRYO联合PEI治疗较单纯CRYO治疗安全有效，能明显降低局部肿瘤进展率。 Abstract:Objective To investigate the clinical efficacy and safety of percutaneous cryoablation combined with percutaneous ethanol injection (PEI) in elderly patients with early-stage hepatocellular carcinoma aged 70 years or older. Methods A retrospective analysis was performed for the clinical data of 92 elderly patients with hepatocellular carcinoma who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2014 to January 2018, among whom 46 underwent cryoablation alone (CRYO group) and 46 underwent cryoablation combined with PEI (combination therapy group). The two groups were compared in terms of clinical outcome, adverse reactions, and changes in liver function parameters after treatment, and the patients were followed up to observe tumor recurrence and survival. The t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison of survival curves. The Cox regression analysis was used to identify the independent risk factors for survival and prognosis. Results There was no significant difference in the response rate of initial ablation between the combination therapy group and the CRYO group (89.1% vs 73.9%, P > 0.05). There were no significant differences between the CRYO group and the combination therapy group in overall survival time and tumor-free survival rate after surgery (P > 0.05), and compared with the CRYO group, the combination therapy group had significantly lower 1-, 2-, and 3-year local tumor progression rates (20%/21%/21% vs 30%/46%/46%, χ2=4.187, P < 0.05). The multivariate Cox regression analysis showed that cryoablation alone might be an independent risk factor for local tumor progression(HR=2.206, 95%CI: 1.003-4.850, P=0.049). There was no significant difference in the incidence rate of adverse reactions between the two groups (P > 0.05), but 3 patients in the CRYO group experienced serious adverse reactions, while no patients in the combination therapy group experienced such reactions. Conclusion For elderly patients with early-stage hepatocellular carcinoma, cryoablation combined with PEI is safer and more effective than cryoablation alone and can significantly reduce local tumor progression rate. -
Key words:
- Carcinoma, Hepatocellalar /
- Catheter Ablation /
- Ethanol /
- Injections Intralesional
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表 1 2组早期老年HCC患者临床特征比较
项目 CRYO组(n=46) 联合治疗组(n=46) 统计值 P值 年龄(岁) 73(70~83) 72(70~81) U=833.500 0.107 男/女(例) 34/12 34/12 χ2=0.000 1.000 BMI(kg/m2) 22.28±0.51 23.52±0.43 t=1.859 0.066 ECOG PS评分(例) χ2=2.841 0.092 0 8 15 1 38 31 病因学(例) χ2=0.066 0.797 HBV 37 36 HCV 9 10 Child-Pugh分级(例) χ2=0.123 0.726 A级 42 41 B级 4 5 AFP(μg/L) 15.39(5.25~39.90) 17.00(4.63~85.75) U=1 014.000 0.731 Alb(g/L) 37.00(35.00~40.00) 37.00(33.00~41.00) U=1 054.500 0.978 TBil(μmol/L) 13.20(9.70~17.30) 13.20(10.50~16.95) U=1 113.500 0.665 ALT(U/L) 18.00(14.50~44.50) 24.00(16.50~40.00) U=1 166.500 0.397 AST(U/L) 27.00(22.00~44.00) 35.00(25.00~51.50) U=1 210.500 0.233 PLT(×109/L) 123.00(79.00~156.50) 114.00(77.50~168.00) U=1 076.000 0.888 ALP(U/L) 92.00(77.00~105.50) 89.00(75.00~109.50) U=1 051.000 0.956 GGT(U/L) 38.00(23.50~80.50) 29.00(20.00~49.50) U=867.500 0.137 肿瘤最大直径(cm) 2.07±0.15 2.20±0.17 t=0.445 0.658 肿瘤数目(例) χ2=0.522 0.470 单发 33 36 多发 13 10 高危部位肿瘤(例) 36 34 χ2=0.239 0.625 合并基础疾病(例) 肝硬化 21 18 χ2=0.401 0.527 糖尿病 9 9 χ2=0.000 1.000 高血压 21 15 χ2=1.643 0.200 心血管疾病 7 3 χ2=1.795 0.180 既往抗病毒治疗(例) 19 23 χ2=0.701 0.402 
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表 2 2组患者的生存预后情况
项目 CRYO组(n=46) 联合治疗组(n=46) 统计值 P值 中位随访期(月) 57(44~60) 67(46~72) χ2=3.247 0.072 完全消融[例(%)] 34(73.9) 41(89.1) χ2=3.536 0.060 LTP[例(%)] χ2=4.187 0.041 1年 14(30) 9(20) 2年 21(46) 10(21) 3年 21(46) 10(21) TFS[例(%)] χ2=3.346 0.067 1年 26(58) 27(59) 3年 6(13) 16(34) 5年 2(5) 11(25) OS[例(%)] χ2=0.000 0.989 1年 45(97) 42(91) 3年 35(76) 26(68) 5年 25(55) 28(61)
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表 3 影响患者LTP的Cox单因素回归分析
变量 HR(95%CI) P值 单一治疗方式 2.206(1.003~4.850) 0.049 Child-Pugh B级 0.629(0.149~2.645) 0.399 ECOG PS =1分 1.438(0.654~3.159) 0.245 男性 1.168(0.517~2.640) 0.739 年龄＞75岁 1.052(0.466~2.375) 0.406 BMI＞24 kg/m2 1.081(0.479~2.441) 0.831 HBsAg阳性 1.559(0.634~3.832) 0.282 抗-HCV阳性 1.678(0.584~4.822) 0.980 伴随合并症 1.014(0.489~2.101) 0.778 有门静脉高压 0.835(0.402~1.737) 0.251 规律抗病毒治疗 0.682(0.322~1.445) 0.522 高危部位肿瘤 0.600(0.229~1.574) 0.457 肿瘤直径＞3 cm 0.918(0.350~2.409) 0.906 肿瘤数量＞1个 1.031(0.456~2.329) 0.641 Alb＞35 g/L 0.669(0.304~1.469) 0.863 TBil＞17.1 μmol/L 1.383(0.629~3.038) 0.475 ALT＞40 U/L 1.148(0.508~2.592) 0.441 ALP＞150 U/L 1.314(0.397~4.345) 0.322 AFP＞20 ng/mL 1.237(0.597~2.566) 0.315
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表 4 影响患者TFS和OS的Cox单因素回归分析
变量 TFS OS HR(95%CI) P值 HR(95%CI) P值 单一治疗方式 1.529(0.958~2.441) 0.067 0.995(0.512~1.934) 0.989 Child-Pugh B级 1.289(0.639~2.603) 0.468 2.603(1.133~5.981) 0.019 ECOG PS =1分 0.617(0.371~1.024) 0.055 0.945(0.461~1.939) 0.878 男性 1.060(0.623~1.802) 0.827 1.082(0.509~2.302) 0.837 年龄＞75岁 1.009(0.618~1.648) 0.970 1.075(0.528~2.189) 0.841 BMI＞24 kg/m2 0.669(0.396~1.130) 0.123 1.767(0.896~3.482) 0.094 HBsAg阳性 1.804(0.986~3.300) 0.056 1.433(0.505~4.063) 0.494 抗-HCV阳性 0.661(0.370~1.182) 0.152 0.653(0.271~1.570) 0.335 伴随合并症 0.846(0.538~1.331) 0.461 0.791(0.407~1.538) 0.486 有门静脉高压 1.376(0.863~2.193) 0.170 1.397(0.722~2.703) 0.316 规律抗病毒治疗 0.920(0.584~1.449) 0.713 1.358(0.703~2.625) 0.358 高危部位肿瘤 0.773(0.450~1.329) 0.341 0.596(0.247~1.437) 0.242 肿瘤直径＞3 cm 1.367(0.785~2.380) 0.258 2.041(0.978~4.260) 0.049 8 肿瘤数量＞1个 1.501(0.904~2.493) 0.107 1.450(0.725~2.904) 0.289 Alb＞35 g/L 1.191(0.754~1.881) 0.445 0.475(0.245~0.921) 0.024 TBil＞17.1 μmol/L 1.405(0.839~2.352) 0.186 1.033(0.497~2.146) 0.931 ALT＞40 U/L 0.855(0.507~1.443) 0.551 0.910(0.427~1.937) 0.805 ALP＞150 U/L 0.900(0.411~1.972) 0.789 1.930(0.733~5.082) 0.173 AFP＞20 ng/mL 1.183(0.750~1.867) 0.462 1.804(0.929~3.504) 0.076
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