原发性肝癌根治术联合TACE术后肠道菌群变化特征观察

摘要/Abstract

摘要： 目的观察原发性肝癌根治术联合经肝动脉化疗栓塞(TACE)术后患者肠道菌群的变化。方法选择2020年1月—2023年1月西安交通大学第二附属医院收治的114例原发性肝癌患者,对照组(57例)接受肝癌根治术,观察组(57例)在肝癌根治术后联合TACE治疗。比较两组临床疗效,检测血清指标及乳杆菌、肠杆菌、酵母菌、双歧杆菌等菌群数量,相关性采用Pearson相关系数分析。结果两组疾病控制率分别为94.74%、80.70%,观察组较高(P<0.05);治疗后观察组血清甲胎蛋白(AFP)、肿瘤坏死因子α(TNFα)、白细胞介素-6(IL-6)水平分别为(581.64±47.32)ng/mL、(85.13±15.37)pg/mL、(124.39±15.73)pg/mL,均明显低于对照组[分别为(662.37±52.49)ng/mL、(92.53±19.84)pg/mL、(145.81±19.77)pg/mL],白细胞介素-2(IL-2)水平为(86.22±5.84)pg/mL,明显高于对照组的(80.26±7.33)pg/mL(P<0.05)。治疗后观察组乳杆菌、双歧杆菌数量分别为(10.52±1.77)、(10.84±2.25)lgCFU/g,均明显高于对照组[分别为(8.34±1.63)、(9.52±1.37)lgCFU/g],治疗后观察组肠杆菌、酵母菌数量分别为(9.93±2.71)、(5.91±1.37)lgCFU/g,均明显低于对照组[分别为(13.95±3.82)、(7.83±1.58)lgCFU/g],P<0.05。血清AFP表达与乳杆菌、肠杆菌、酵母菌、双歧杆菌数量存在一定相关性(r=-0.522、0.498、0.503、-0.518,P=0.034、0.041、0.039、0.034),血清TNFα表达与肠道菌群数量存在一定相关性(r=-0.637、0.622、0.574、-0.592,P=0.005、0.005、0.021、0.018),血清IL-2表达与肠道菌群数量存在一定相关性(r=0.536、-0.508、-0.529、0.564,P=0.032、0.039、0.034、0.023),血清IL-6表达与肠道菌群数量存在一定相关性(r=-0.613、0.572、0.603、-0.517,P=0.006、0.021、0.007、0.034)。结论原发性肝癌根治术后TACE治疗有利于提高疾病控制率,促进肠道菌群平衡,降低炎症因子水平。

关键词: 原发性肝癌, 肝癌根治术, 经肝动脉化疗栓塞, 肠道菌群

Abstract: Objective To analyze the changes in intestinal flora in patients with primary liver cancer following radical resection combined with transcatheter arterial chemoembolization (TACE).Methods A total of 114 patients with primary liver cancer treated in our hospital from January 2020 to January 2023 were included in the study. The control group (57 cases) underwent radical liver cancer surgery, while the observation group (57 cases) received combined TACE treatment after radical liver cancer surgery. The clinical efficacy of the two groups was compared, and serum indices as well as the number of lactobacillus, enterobacter, yeast, bifidobacterium and other bacteria were measured. The correlation between these factors was analyzed by the Pearson correlation coefficient.Results The disease control rates in the observation group and the control group were 94.74% and 80.70%, respectively. The observation group had a significantly higher disease control rate compared to the control group (P<0.05). After treatment, the serum levels of alpha-fetoprotein (AFP), tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the observation group were (581.64±47.32) ng/mL, (85.13±15.37) pg/mL, and (124.39±15.73) pg/mL, respectively, which were significantly lower than those of control group [(662.37±52.49) ng/mL, (92.53±19.84) pg/mL, (145.81±19.77) pg/mL, respectively]. The levels of interleukin-2 (IL-2) were (86.22±5.84) pg/mL, which was significantly higher than that in control group [(80.26±7.33) pg/mL, P<0.05]. After treatment, the number of lactobacilli and bifidobacteria in the observation group were (10.52±1.77) lgCFU/g and (10.84±2.25) lgCFU/g, respectively, which were significantly higher than those in the control group [(8.34±1.63) lgCFU/g and (9.52±1.37) lgCFU/g, respectively]. The number of Enterobacteriaceae and yeast in the observation group were (9.93±2.71) lgCFU/g and (5.91±1.37) lgCFU/g, respectively, which were significantly lower than those in the control group [(13.95±3.82) lgCFU/g and (7.83±1.58) lgCFU/g, P＜0.05]. Correlations were observed between serum AFP expression and the number of Lactobacillus, Enterobacter, yeast and bifidobacterium (r=-0.522, 0.498, 0.503, -0.518, P=0.034, 0.041, 0.039, 0.034). Furthermore, the expression of TNFα in serum was correlated with the numbe of intestinal flora (r=-0.637, 0.622, 0.574, -0.592, P=0.005, 0.005, 0.021, 0.018). The expression of serum IL-2 was also correlated with the number of intestinal flora (r=0.536, -0.508, -0.529, 0.564, P=0.032, 0.039, 0.034, 0.023). Similarly, the expression of serum IL-6 was correlated with the number of intestinal flora (r=-0.613, 0.572, 0.603, -0.517, P=0.006, 0.021, 0.007, 0.034).Conclusion TACE treatment following radical surgery for primary liver cancer can improve the disease control rate, promote intestinal microbiota balance, and reduce inflammatory factor levels.

Key words: Primary liver cancer, Radical resection of liver cancer, Transcatheter arterial chemoembolization, Intestinal microbiota

任宏涛, 王玉婷, 尹佳锋, 苏王辉. 原发性肝癌根治术联合TACE术后肠道菌群变化特征观察[J]. 肝脏, 2023, 28(12): 1450-1454.

REN Hong-tao, WANG Yu-ting, YIN Jia-feng, SU Wang-hui. Changes of intestinal flora after radical resection of primary liver cancer combined with TACE[J]. Chinese Hepatolgy, 2023, 28(12): 1450-1454.

参考文献

[1] 皮丽娜, 候艳莹, 张维. 肠道菌群失调、炎症因子变化、维生素缺乏与肝癌患者根治术后复发的关系[J]. 现代肿瘤医学,2019,27(17):3078-3081.
[2] Ohtani N, Hara E. Gut-liver axis-mediated mechanism of liver cancer: A special focus on the role of gut microbiota[J]. Cancer Sci.2021,112(11):4433-4443.
[3] Tilg H, Adolph TE, Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications[J]. Cell Metab.2022,34(11):1700-1718.
[4] 邓代安, 罗坤, 李祖丁, 等. 肿瘤切除术后肝动脉介入化疗栓塞术治疗原发性肝癌患者的血清肿瘤标志物和生存情况研究[J]. 中国肿瘤临床与康复,2020,27(1):62-64.
[5] 蒋锐沅, 满婷婷, 覃艳春, 等. 敷和备化方联合TACE术对原发性肝癌患者血清炎性因子及临床疗效观察[J]. 中国中医基础医学杂志,2021,27(1):102-106.
[6] 中国抗癌协会肝癌专业委员会, 中华医学会肝病学分会肝癌学组, 中国抗癌协会病理专业委员会, 等. 原发性肝癌规范化病理诊断指南(2015年版)[J]. 临床肝胆病杂志,2015,31(6):833-839.
[7] Wang R, Tang R, Li B, et al. Gut microbiome, liver immunology, and liver diseases[J]. Cell Mol Immunol.2021,18(1):4-17.
[8] Rao Y, Kuang Z, Li C, et al. Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis[J]. Gut Microbes.2021,13(1):1-19.
[9] 金志成, 张齐, 朱海东, 等. 肝癌根治性切除术后辅助性TACE治疗的研究进展[J]. 中华肝脏病杂志,2022,30(3):340-344.
[10] 匡悦, 张锡武. 肝癌根治术后行TACE治疗对微血管侵犯患者的生存影响的相关研究[J]. 解放军预防医学杂志,2019,37(10):42-43.
[11] Feng L, Zhang W, Shen Q, et al. Bile acid metabolism dysregulation associates with cancer cachexia: roles of liver and gut microbiome[J]. J Cachexia Sarcopenia Muscle.2021,12(6):1553-1569.
[12] 张群, 王宪波. 肠道菌群在门静脉高压发病机制中的作用. 临床肝胆病杂志,2020,36(3):673-676.
[13] 辛海荣, 李喜, 孙瑞芳, 等. 原发性肝癌患者内毒素与肠道菌群变化的相关性研究[J]. 中华普通外科杂志,2019,34(8):686-688.
[14] 施长生, 刘开才, 吕维富, 等. 肝细胞性肝癌TACE后血清内毒素、TOLL样受体4和肠道微生态改变的实验观察[J]. 蚌埠医学院学报,2022,47(2):219-222,226.
[15] 李科志, 韦家康, 韩志伟, 等. 肝动脉化疗栓塞术后原发性肝癌患者的肠道菌群变化[J]. 临床肝胆病杂志,2020,36(5):1043-1049.
[16] Gao J, Guo X, Wei W, et al. The Association of Fried Meat Consumption With the Gut Microbiota and Fecal Metabolites and Its Impact on Glucose Homoeostasis, Intestinal Endotoxin Levels, and Systemic Inflammation: A Randomized Controlled-Feeding Trial[J]. Diabetes Care. 2021 ,44(9):1970-1979.
[17] 赵阳, 郭瑛, 黄娜, 等. 肝硬化患者肠道菌群损伤小鼠肠黏膜屏障促肝硬化发展[J]. 中华实验外科杂志,2021,38(8):1567-1570.
[18] 汤莉, 吴伶莉. 原发性肝癌患者肠道菌群变化与内毒素和炎性因子水平的关系[J]. 中国微生态学杂志,2021,33(10):1162-1165.
[19] 冯锦凯, 陈振华, 武宇轩, 等. 肠道菌群在慢性肝病和肝细胞癌中的作用及临床意义[J]. 第二军医大学学报,2020,41(11):1246-1249.
[20] 刘尚伟, 李兴红. 益生菌对肝硬化患者肠道菌群和肠道屏障功能的影响[J]. 中国微生态学杂志,2021,33(3):326-330.