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化疗与转化生长因子-β1对结直肠癌患者肝切除术后肝脏再生的影响

The Impact of Chemotherapy and Transforming Growth Factor-β1 in Liver Regeneration after Hepatectomy among Colorectal Cancer Patients.

作者信息

Račkauskas Rokas, Lukšaitė-Lukštė Raminta, Stulpinas Rokas, Baušys Augustinas, Paškonis Marius, Kvietkauskas Mindaugas, Sokolovas Vitalijus, Laurinavičius Arvydas, Strupas Kęstutis

机构信息

Clinic of Gastroenterology, Nephrourology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Ciurlionio Str. 21, LT-03101 Vilnius, Lithuania.

Department of Radiology, Nuclear Medicine and Medical Physics, Institute of Biomedical Sciences, Faculty of Medicine, Vilnius University, LT-03101 Vilnius, Lithuania.

出版信息

J Pers Med. 2024 Jan 28;14(2):144. doi: 10.3390/jpm14020144.

Abstract

An ongoing debate surrounds the impact of chemotherapy on post-hepatectomy liver regeneration in patients with colorectal cancer liver metastases (CRLM), with unclear regulatory mechanisms. This study sought to delve into liver regeneration post-resection in CRLM patients, specifically examining the roles of hepatocyte growth factor (HGF) and transforming growth factor β1 (TGF-β1). In this longitudinal observational study, 17 patients undergoing major liver resection for CRLM and 17 with benign indications as controls were enrolled. Liver regeneration within 30 postoperative days was assessed via CT, considering clinicopathological characteristics, liver enzymes, liver stiffness by elastography, and the impact of HGF and TGF-β1 on liver regeneration. The results revealed that the control group exhibited significantly higher mean liver regeneration volume (200 ± 180 mL) within 30 days postoperatively compared to the CRLM group (72 ± 154 mL); = 0.03. Baseline alkaline phosphatase (AP) and TGF-β1 blood levels were notably higher in the CRLM group. Immunohistochemical analysis indicated a higher proportion of CRLM patients with high TGF-β1 expression in liver tissues compared to the control group ( = 0.034). Correlation analysis showed that resected liver volume, baseline plasma HGF, AP, and albumin levels significantly correlated with liver regeneration volume. However, in multivariable analysis, only resected liver volume (β: 0.31; 95% CI: 0.14-0.47, = 0.01) remained significant. In conclusion, this study highlights compromised liver regeneration in CRLM patients post-chemotherapy. Additionally, these patients exhibited lower serum TGF-β1 levels and reduced TGF-β1 expression in liver tissue, suggesting TGF-β1 involvement in mechanisms hindering liver regeneration capacity following major resection after chemotherapy.

摘要

关于化疗对结直肠癌肝转移(CRLM)患者肝切除术后肝脏再生的影响存在持续的争论,其调节机制尚不清楚。本研究旨在深入探讨CRLM患者肝切除术后的肝脏再生情况,特别研究肝细胞生长因子(HGF)和转化生长因子β1(TGF-β1)的作用。在这项纵向观察性研究中,纳入了17例因CRLM接受大肝切除的患者和17例具有良性指征的患者作为对照。通过CT评估术后30天内的肝脏再生情况,同时考虑临床病理特征、肝酶、弹性成像测量的肝脏硬度以及HGF和TGF-β1对肝脏再生的影响。结果显示,与CRLM组(72±154 mL)相比,对照组术后30天内的平均肝脏再生体积显著更高(200±180 mL);P = 0.03。CRLM组的基线碱性磷酸酶(AP)和TGF-β1血水平显著更高。免疫组织化学分析表明,与对照组相比,CRLM患者肝脏组织中TGF-β1高表达的比例更高(P = 0.034)。相关性分析显示,切除的肝脏体积、基线血浆HGF、AP和白蛋白水平与肝脏再生体积显著相关。然而,在多变量分析中,只有切除的肝脏体积(β:0.31;95%CI:0.14 - 0.47,P = 0.01)仍然具有显著性。总之,本研究强调了CRLM患者化疗后肝脏再生受损。此外,这些患者的血清TGF-β1水平较低,肝脏组织中TGF-β1表达降低,提示TGF-β1参与了化疗后大切除后阻碍肝脏再生能力的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e88/10890619/2701250acd99/jpm-14-00144-g001.jpg

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