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不同肝切除手术对术后患者循环肿瘤细胞的影响:一项病例匹配对照研究。

Effect of various hepatectomy procedures on circulating tumor cells in postoperative patients: a case-matched comparative study.

作者信息

Lei YongRong, Wang XiShu, Tian YiChen, Xu Rong, Pei Jun, Fu YuNa, Sun Heng, Wang YaNi, Zheng Ping, Xia Feng, Wang JianHua

机构信息

Key Laboratory of Biorheological Science and Technology (Ministry of Education), College of Bioengineering, Chongqing University, Chongqing, China.

Key Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

出版信息

Front Med (Lausanne). 2023 Sep 28;10:1209403. doi: 10.3389/fmed.2023.1209403. eCollection 2023.

Abstract

BACKGROUND

The objective of this study is to elucidate the prevalence of systemic circulating tumor cells (CTCs) prior to and following resection of hepatocellular carcinoma (HCC), and to compare the disparities in postoperative CTCs in terms of quantity and classifications between the open liver resection (OPEN) and laparoscopic liver resection (LAP) cohorts.

PATIENTS MATERIALS AND METHODS

From September 2015 to May 2022, 32 consecutive HCC patients who underwent laparoscopic liver resection at Southwest Hospital were retrospectively enrolled in this study. The clinicopathological data were retrieved from a prospectively collected computer database. Patients in the OPEN group matched at a 1:1 ratio with patients who underwent open liver resection during the study period on age, gender, tumor size, number of tumors, tumor location, hepatitis B surface antigen (HBsAg) positivity, alpha-fetoprotein (AFP) level, TNM and Child-Pugh staging from the database of patients to form the control group. The Can-Patrol CTC enrichment technique was used to enrich and classify CTCS based on epithelial-mesenchymal transformation phenotypes. The endpoint was disease-free survival (DFS), and the Kaplan-Meier method and multiple Cox proportional risk model were used to analyze the influence of clinicopathological factors such as total CTCs and CTC phenotype on prognosis.

RESULTS

The mean age of the 64 patients with primary liver cancer was 52.92 years (23-71), and 89.1% were male. The postoperative CTC clearance rate was more significant in the OPEN group. The total residual CTC and phenotypic CTC of the LAP group were significantly higher than those of the OPEN group ( = 0.017, 0.012, 0.049, and 0.030, respectively), which may increase the possibility of metastasis ( = 0.042). In Kaplan-Meier analysis, DFS was associated with several clinicopathological risk factors, including Barcelona Clinical Liver Cancer (BCLC) stage, tumor size, and vascular invasion. Of these analyses, BCLC Stage [ = 0.043, HR (95% CI) =2.03(1.022-4.034)], AFP [ = 0.007, HR (95% CI) =1.947 (1.238-3.062)], the number of positive CTCs [ = 0.004, HR (95% CI) =9.607 (2.085-44.269)] and vascular invasion [ = 0.046, HR (95% CI) =0.475 (0.22-1.023)] were significantly associated with DFS.

CONCLUSION

In comparison to conventional OPEN technology, LAP technology has the capacity to augment the quantity of epithelial, mixed, and mesenchymal circulating tumor cells (CTCs). Following the surgical procedure, there was a notable increase in the total CTCs, epithelial CTCs, and mixed CTCs within the LAP group, indicating a potential drawback of LAP in facilitating the release of CTCs.

摘要

背景

本研究的目的是阐明肝细胞癌(HCC)切除术前和术后全身循环肿瘤细胞(CTC)的患病率,并比较开放肝切除术(OPEN)和腹腔镜肝切除术(LAP)队列在术后CTC数量和分类方面的差异。

患者材料与方法

2015年9月至2022年5月,对西南医院连续32例行腹腔镜肝切除术的HCC患者进行回顾性研究。临床病理数据从前瞻性收集的计算机数据库中获取。OPEN组患者与研究期间接受开放肝切除术的患者按1:1比例匹配年龄、性别、肿瘤大小、肿瘤数量、肿瘤位置、乙肝表面抗原(HBsAg)阳性、甲胎蛋白(AFP)水平、TNM和Child-Pugh分期,组成对照组。采用Can-Patrol CTC富集技术,根据上皮-间质转化表型对CTCs进行富集和分类。终点为无病生存期(DFS),采用Kaplan-Meier法和多因素Cox比例风险模型分析总CTC和CTC表型等临床病理因素对预后的影响。

结果

64例原发性肝癌患者的平均年龄为52.92岁(23 - 71岁),男性占89.1%。OPEN组术后CTC清除率更显著。LAP组的总残留CTC和表型CTC均显著高于OPEN组(分别为=0.017、0.012、0.049和0.030),这可能增加转移的可能性(=0.042)。在Kaplan-Meier分析中,DFS与几个临床病理风险因素相关,包括巴塞罗那临床肝癌(BCLC)分期、肿瘤大小和血管侵犯。在这些分析中,BCLC分期[=0.043,HR(95%CI)=2.03(1.022 - 4.034)]、AFP[=0.007,HR(95%CI)=1.947(1.238 - 3.062)]、阳性CTC数量[=0.004,HR(95%CI)=9.607(2.085 - 44.269)]和血管侵犯[=0.046,HR(95%CI)=0.475(0.22 - 1.023)]与DFS显著相关。

结论

与传统的OPEN技术相比,LAP技术能够增加上皮、混合和间质循环肿瘤细胞(CTC)的数量。手术后,LAP组的总CTC、上皮CTC和混合CTC显著增加,表明LAP在促进CTC释放方面存在潜在缺陷。

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