敷和备化方联合肝动脉化疗栓塞术治疗肝郁脾虚型原发性肝癌患者的近期疗效及其对血浆血管生成因子水平的影响研究

背景　肝动脉化疗栓塞（TACE）术虽是目前中晚期不可手术的原发性肝癌患者的首选局部治疗措施，但TACE术后仍存在较多问题亟待解决，中医药治疗作为重要的辅助手段，联合TACE术能使原发性肝癌患者获得更大的治疗收益。目的　探讨敷和备化方联合TACE术治疗肝郁脾虚型原发性肝癌患者的近期疗效及其对血浆血管生成因子水平的影响。方法　选取2018年1-6月广西中医药大学第一附属医院肿瘤科及肝病科收治的肝郁脾虚型原发性肝癌患者90例，采用随机数字表法分为对照组和治疗组，每组45例。在常规对症支持治疗基础上，两组患者均行亚肝段动脉末梢水平TACE术，治疗组患者连续服用敷和备化方12周。比较两组患者近期（治疗12周后）疗效、无进展生存时间（PFS）及治疗前后血清甲胎蛋白水平、Karnofsky（KPS）评分、中医症候积分、血浆血管生成因子〔包括血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、血小板衍生生长因子（PDGF）〕，并观察两组患者毒副作用和/或并发症发生情况。TACE术后当天开始进行电话随访，随访截止时间为患者出现疾病进展或完成整个疗程（12周）。结果　两组患者均完成整个疗程及随访，无一例脱落或失访。两组患者总有效率（ORR）、疾病控制率（DCR）比较，差异无统计学意义（P>0.05）。平均随访（207.5±28.4）d，两组患者PFS的Kaplan-Meier生存曲线比较，差异有统计学意义（P<0.05）。治疗组患者治疗后血清甲胎蛋白水平，腹痛腹胀、纳呆食少、情志抑郁、恶心呕吐、神疲乏力、口苦咽干评分及中医症候积分，血浆VEGF、bFGF、PDGF水平均低于对照组，而KPS评分高于对照组（P<0.05）。两组患者毒副作用和/或并发症发生率比较，差异无统计学意义（P>0.05）。结论　敷和备化方联合TACE术能在一定程度上延长肝郁脾虚型原发性肝癌患者PFS，同时能有效改善患者临床症状及肿瘤相关血管微环境，降低血清肿瘤标志物及血浆血管生成因子水平，有利于提高患者生活质量，且安全性较高。

Short-term Curative and Plasma Angiogenic Responses to Fuhe Beihua Decoction with Transcatheter Arterial Chemoembolization in Primary Liver Cancer Patients with Liver Depression and Spleen Deficiency Syndrome

Background　Although transcatheter arterial chemoembolization（TACE）is the preferred local treatment for inoperable intermediate and advanced primary liver cancer at present，there are many problems which demands prompt solution after TACE.To improve the treatment benefits from TACE，TCM treatment may be used as an appropriate adjuvant therapy.Objective　To investigate the short-term curative and plasma angiogenic responses to Fuhe Beihua Decoction with TACE in primary liver cancer patients with liver depression and spleen deficiency syndrome.Methods　From January to June 2018，90 primary liver cancer patients with liver depression and spleen deficiency syndrome were selected from Oncology Department and Liver Disease Department，the First Affiliated Hospital of Guangxi University of Chinese Medicine，and were equally divided into control group and treatment group by random number table method.Both groups underwent TACE at the distal portion of the subsegmental hepatic artery plus routine symptomatic and supportive therapies.The treatment group additionally received Fuhe Beihua Decoction for 12 consecutive weeks（started on the completion day of TACE）.Short-term（12 weeks after treatment）curative response，progression-free survival（PFS），pre- and post-treatment serum alpha-fetoprotein（AFP）level，Karnofsky（KPS）score，TCM syndrome score，plasma angiogenesis factors〔including vascular endothelial growth factor（VEGF），basic fibroblast growth factor（bFGF），platelet-derived growth factor（PDGF）〕were compared between the two groups.Toxic and side effects and/or complications occurred in both groups were also compared.Patients in the two groups were followed up by telephone after TACE until to the occurrence of progress of disease or the end of course of treatment（12 weeks）.Results　All the patients completed the whole course of treatment and follow-up with complete data.The overall response rate and disease control rate were not significantly different between the two groups（P>0.05）.At average of （207.5±28.4）d of follow-up，Kaplan-Meier analysis revealed that PFS differed significantly between the groups（P<0.05）.Compared to control group，post-treatment serum AFP level，score of abdominal pain and distention，inappetence，depression，nausea and vomiting，fatigue，bitter mouth and dry throat，TCM syndrome score，as well as plasma levels of VEGF，bFGF and PDGF were significantly lowered in treatment group，but KPS score increased（P<0.05）.The incidence of toxic and side effects and/or complications was not significantly different between the groups（P>0.05）.Conclusion　In primary liver cancer patients with liver depression and spleen deficiency syndrome，Fuhe Beihua Decoction combined with TACE may improve prolong the PFS to some extent，relieve the clinical symptoms，improve the tumor vascular microenvironment，and reduce the levels of serum tumor markers and plasma angiogenic factors，which is helpful to improve the patients' quality of life with relatively high safety.