肝动脉化疗栓塞联合血管内皮抑制素介入治疗原发性肝癌的疗效和安全性

目的:观察肝动脉化疗栓塞联合血管内皮抑制素介入治疗原发性肝细胞癌的疗效及其安全性.方法:50例原发性肝细胞癌患者接受肝动脉化疗栓塞联合血管内皮抑制素介入治疗.观察治疗后不良反应和近期疗效,以评价治疗的安全性和有效性.结果:50例原发性肝细胞癌患者接受肝动脉化疗栓塞联合血管内皮抑制素介入治疗后,主要不良反应包括Ⅰ～Ⅱ度骨髓抑制以及谷丙转氨酶和谷草转氨酶的升高,未发生严重的治疗相关不良反应.近期疗效显示,50例患者中部分缓解3例,疾病稳定40例,疾病进展7例,疾病控制率为86.0%.结论:肝动脉化疗栓塞联合血管内皮抑制素介入治疗原发性肝细胞癌是安全而有效的.     

经肝动脉化疗栓塞术联合化疗治疗原发性肝癌的临床研究

目的:了解化疗联合肝动脉化疗栓塞术(TACE)治疗肝癌的疗效、毒副反应、生化改变以及对生存时间的影响.方法:经肝动脉化疗栓塞术(TACE):经肝动脉造影(DSA)明确肿瘤供血动脉,先给予碘化油15ml-20ml 平阳霉素8mg混合液栓塞,然后灌注顺铂60mg 健择800mg/m2,最后以明胶海绵颗粒栓塞.全身化疗:TACE治疗2周后开始给予GP方案化疗:吉西他滨800-1000mg/m2 d1,d8,顺铂75mg/m2 d2,外周静脉滴注,21天为1周期,共4周期.对患者术前、术后临床表现、肝功能、AFP进行比较,随访生存时间.结果:化疗联合TACE治疗后患者症状、体征明显改善,AFP下降者25例,恢复正常者12例.1年生存期80.9%、2年50.O%、3年31.0%、4年以上16.7%.结论:化疗联合肝动脉化疗栓塞术操作简便,并发症少.可重复进行,可明显提高肝癌患者的生活质量,延长生存期.     

索拉非尼对原发性肝癌TACE后血管内皮生长因子水平影响的研究

为了探讨索拉非尼对肝细胞癌患者TACE后血清VEGF水平的影响,选取50例初治的肝细胞癌患者,30例单行TACE治疗,20例行TACE后联合索拉非尼治疗。于TACE术前1d、术后1d及术后28d用双抗体夹心酶联免疫吸附试验法检测两组患者血清VEGF的水平。TACE术后1d两组患者血清VEGF浓度均较术前升高,差异有统计学意义(TACE组,P=0.02;索拉非尼组,P=0.00);术后28d,两组患者VEGF水平均降低,TACE联合索拉非尼患者血清VEGF浓度较单纯TACE组降低更明显,差异有统计学意义,P=0.00。初步研究结果提示,索拉非尼可降低原发性肝癌TACE后的VEGF水平。     

内皮抑素基因抑制兔VX2肝癌肝动脉栓塞后肿瘤血管生成的实验研究

目的:研究内皮抑素基因治疗对介入栓塞后兔VX2肝肿瘤血管生成的抑制作用.方法: 建立兔VX2肝癌模型,分为栓塞(TAE)组,肝动脉注射(IHA)组和瘤内注射(IT)组.三组动物均经肝动脉注入超液化碘油进行肝动脉栓塞.IHA组在栓塞的同时,经肝动脉注入携带内皮抑素基因的真核表达质粒pCEP-Pu,IT组在栓塞的同时直接瘤内注射pCEP-Pu.测定栓塞前后血清谷丙转氨酶(ALT)含量.栓塞后第7天处死动物,计算抑瘤率.免疫组化方法检测肿瘤微血管密度(MVD)及血管内皮生长因子(VEGF)蛋白的表达,Western印迹杂交测定VEGF蛋白表达,逆转录聚合酶链反应(RT-PCR)检测VEGF mRNA的表达.结果: IHA组和IT组MVD分别为(16.5±5.7)和(18.8±7.4),显著低于TAE组MVD(28.6±10.6)(P<0.05).组化及Western印迹杂交结果均显示IHA组和IT组VEGF蛋白表达显著低于TAE组. RT-PCR结果显示IHA组和IT组VEGF165 mRNA表达显著低于 TAE组(P<0.01),分别为(2.03±0.42),(2.01±0.39)和(2.58±0.42).三组栓塞前后血清ALT水平无差异(P>0.05). 三组栓塞后肿瘤体积差异无显著性 (P>0.05).结论: 介入栓塞的同时经肝动脉注射内皮抑素基因可方便、有效地阻止栓塞后残留肿瘤的血管生成,无明显的肝脏毒性.     

外照射配合肝动脉栓塞治疗不能手术切除的原发性肝癌的临床研究

Objective: This study evaluated the therapeutic effect of external beam radiotherapy(RT)combined with transcatheter arterial chemoembolization(TACE)on the patients with unresectable hepatocellular carcinoma(HCC).Methods: From June 1994 to April 2002, 114 patients with unresectable HCC were nonrandomized prospectively stepped into our study.All patients received TACE as initial therapy, except 54 also received combination therapy with external beam therapy.Survival failure patterns were analyzed and compared between the two groups.Results: Overall survival rates in the patients in the radiotherapy group were 65%, 47%, 38% at 1, 2, 3 years, respectively, improved over the non-radiotherapy group rates of 54%, 36.5%, 18% at 1, 2, 3 years, respectively.There was significant difference between two groups(P＜0.05).The survival rates correlated with tumor size, number of tumors, and portal vein embolus.Conclusion: TACE combined with RT is a more effective treatment than TACE alone in patients with unresectable HCC.     

金米冲剂联合化疗栓塞治疗原发性肝癌的疗效观察

目的观察金米冲剂(Star-1)联合化疗栓塞(TACE)治疗原发性肝癌的疗效,及对血清血管内皮生长因子(VEGF)表达的影响。方法将60例原发性肝癌患者随机分为金米冲剂加TACE组与单纯TACE组,所有病例于TACE术前、术后7天及1个月时分别采集空腹血,应用ELISA法测定血清中VEGF表达水平。结果金米冲剂加TACE组术后第7天血清VEGF水平较术前无明显升高(P>0.05),术后1个月血清VEGF水平较术前略有下降(P>0.05)。而单纯TACE组术后第7天血清VEGF水平较术前明显升高,差异有统计学意义(P<0.05),术后1个月血清VEGF水平逐渐下降,与术前相比,差异无明显统计学意义(P>0.05)。结论金米冲剂可降低原发性肝癌患者血清中VEGF的表达水平,提示金米冲剂对肝癌的肿瘤血管生成具有一定地抑制作用。     

放疗联合肝动脉栓塞化疗治疗原发性肝癌的研究进展

放疗和介入是目前不能切除的晚期原发性肝癌(PHC)患者的主要治疗方法,但由于各自适应证的限制影响其有效率.放疗技术的进步,特别是放疗联合肝动脉栓塞化疗(TACE)在肝癌治疗中的应用,为患者提供了更佳的治疗手段.     

肝动脉化疗栓塞联合灌注三氧化二砷治疗原发性肝癌初步观察

探讨三氧化二砷肝动脉灌注治疗原发性肝癌的临床疗效。对62例和56例原发性肝癌患者分别采用常规药物联合三氧化二砷和单纯常规药物介入治疗,分析治疗效果。结果常规药物联合三氧化二砷组1年生存率优于单纯常规药物组,P=0·017,P<0·05,半年生存率及近期疗效差异无统计学意义,P>0·05。初步研究结果提示,原发性肝癌患者肝动脉常规药物联合三氧化二砷介入治疗能提高1年生存率。     

肝动脉化疗栓塞联合伽玛刀治疗原发性肝癌的临床观察

[目的]探讨肝动脉化疗栓塞(TACE)联合伽玛刀治疗原发性肝癌的疗效和不良反应。[方法]将2010年1月至2012年12月期间收治的原发性肝癌患者84例分为两组,联合治疗组共计47例患者,先给予TACE治疗,之后给予伽玛刀治疗,伽玛刀照射剂量以50%剂量线作为处方剂量,3~10Gy/次,总剂量40~60Gy,1~3周完成治疗;TACE治疗组共计37例患者,仅给予TACE治疗。[结果]联合治疗组和TACE治疗组总有效率分别为80.9%和51.3%,1年生存率分别为74.5%、45.9%,差异均有统计学意义(P<0.05);联合治疗组不良反应发生率稍高于TACE治疗组,但差异无统计学意义(P>0.05)。[结论]肝动脉化疗栓塞联合伽玛刀治疗原发性肝癌近期疗效满意且并发症发生率低,是中晚期肝癌患者安全有效的治疗方法之一。     

薏苡仁提取物联合经导管肝动脉化疗栓塞术治疗转移性肝癌的临床研究

 目的　研究薏苡仁提取物联合经导管肝动脉化疗栓塞术（TACE）对转移性肝癌的疗效以及治疗前后血清血管内皮生长因子 （VEGF）的变化。方法　转移性肝癌患者62例随机分为两组,每组各31 例。研究组：采用薏苡仁提取物+TACE术。对照组：单纯TACE术。薏苡仁提取物注射液缓慢静脉注射200 ml,1次/d,连用21 d,1个月为1个周期,至少连用2个周期。每位患者至少行TACE术2 次,并检测TACE术前1 周及术后3 周血清VEGF水平。结果　研究组有效率为61.3 ％（19／31）,对照组为45.2 ％（14／31）,两组差异无统计学意义（P＞0. 05）;研究组疾病控制率（DCR）为80.6 %（25／31）,对照组为54.8 ％（17／31）,两组差异有统计学意义（P＜0.05）;研究组1 年生存率为67.7 ％（21／31）,对照组为38.7 %（12／31）,两组差异有统计学意义（P＜0.05）;研究组中位无进展生存期（PFS）为7.0 个月,对照组为5.1 个月,两组间差异有统计学意义（P＜0.05）。血清VEGF研究组下降显著（P＜0.05）;对照组治疗前后血清VEGF水平差异无统计学意义（P＞0.05）;研究组治疗后血清VEGF水平较对照组治疗后水平明显低下,差异有统计学意义（P＜0.05）;两组不良反应均为Ⅰ～Ⅲ级,研究组乏力、食欲下降及右上腹疼痛症状较对照组轻,差异有统计学意义。结论　薏苡仁提取物联合TACE术治疗转移性肝癌能提高疾病控制率,并降低血清VEGF水平,延长无进展生存期及1年生存率,改善临床症状。     

Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Objective:To investigate the expression level of serum vascular endothelial growth factor(VEGF) in patients with unresectable hepatocellular carcinoma(HCC) and its relationship with the clinicopathological characteristics,and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization(TACE) treatments.Methods:Serum VEGF levels were measured using enzyme-linked immunosorbent assay(ELISA) in 60 random patients who underwent TACE or transarterial infusion(TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control.All patients’ clinicopathological features were retrospectively analyzed.Serum VEGF levels were correlated with clinicopathological features of the HCC patients.The patients’ survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test.The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results:The median serum VEGF level in the HCC patients was 285 pg/ml(range 14 1,207 pg/ml),significantly higher than that of healthy controls(P=0.021).The serum VEGF levels were significantly correlated with platelet counts(r=0.396,P=0.002) but not other clinicopathological features.Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml(P=0.002).By multivariate analysis,the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.     

经导管肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床观察

目的 观察经导管肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝细胞癌的有效性和安全性.方法 40例已接受过TACE治疗的中晚期肝细胞癌患者口服索拉非尼单药治疗,400mg,2次/d,直至病情进展或出现不可耐受的毒性反应.按照实体瘤疗效评价标准(RECIST)评价疗效,按照美国国立癌症研究所常见毒性事件标准(NCI-CTCAE)评价不良反应.结果 40例中晚期肝细胞癌患者中,获得完全缓解1例,部分缓解7例,疾病稳定19例,疾病进展13例,疾病控制率为67.5%.全组患者的生存时间为1～18个月,1年生存率为54.0%.主要不良反应为手足皮肤反应,其次是腹泻和血小板计数降低.结论 TACE联合索拉非尼治疗中晚期肝细胞癌是有效和安全的.     

肝动脉化疗栓塞术联合阿帕替尼治疗中晚期原发性肝癌疗效评价

  目的  评价肝动脉化疗栓塞术（transarterial chemoembolization,TACE）联合口服阿帕替尼治疗中晚期肝癌的近期疗效。   方法  收集2016年6月至2016年10月于首都医科大学附属北京友谊医院接受TACE联合口服阿帕替尼250 mg/d治疗的21例中晚期原发性肝癌（hepatocellular carcinoma,HCC）患者的临床资料;采用影像学中最新修订的实体瘤疗效评价标准（modified responseevaluation criteria in solid tumors,mRECIST）,回顾性分析联合治疗1个疗程（平均约28 d）后患者的治疗效果,并对不良反应进行分析。   结果  21例患者中,完全缓解（complete response,CR）3例（14.3%）,部分缓解（patial response,PR）6例（28.6%）,疾病稳定（stable disease,SD）5例（23.8%）。疾病控制率（disease control rate,DCR）为61.9%,客观缓解率（objective rate,ORR）为38.1%。疾病进展（progressive disease,PD）2例（9.5%）。21例患者治疗中出现的不良反应:乏力17例（94.4%）,胃肠道症状14例（66.7%）,手足综合征4例（19.0%）,血压升高4例（19.0%）,并出现不同程度的声音嘶哑、头痛头晕、蛋白尿等。   结论  TACE联合阿帕替尼对中晚期原发性肝癌的临床治疗近期效果满意,治疗过程中不良反应发生率较高,需给予积极处理。      

High serum levels of vascular endothelial growth factor predict poor response to transarterial chemoembolization in hepatocellular carcinoma: a prospective study

Vascular endothelial growth factor (VEGF) is an important mediator of tumor angiogenesis. A high serum VEGF level has been shown to predict poor response to chemotherapy and poor survival in several cancers, but its prognostic value in hepatocellular carcinoma (HCC) remains unknown. We conducted a prospective study to evaluate the prognostic significance of pretreatment serum VEGF levels on tumor response to treatment and survival of patients with HCC undergoing transarterial chemoembolization (TACE). Pretreatment serum VEGF levels were measured by an enzyme-linked immunosorbent assay in 80 patients with inoperable HCC undergoing TACE. Serum VEGF levels were correlated with clinical data, tumor response to TACE and survival results. The median serum VEGF level was 240 pg/ml (range 9-1730). Serum VEGF levels were positively correlated with the presence of venous tumor thrombus (P=0.011). Pretreatment serum VEGF levels were significantly higher in patients with progressive disease (median 434 pg/ml) than those with stable (median 176 pg/ml, P=0.010) or responsive disease (median 142 pg/ml, P<0.001) after TACE. Patients with serum VEGF >240 pg/ml had significantly worse survival than those with serum VEGF <240 pg/ml (median survival 6.8 vs. 19.2 months, P=0.007). In a Cox multivariate analysis, serum VEGF >240 pg/ml was an independent prognostic factor of survival. In conclusion, the results of this study suggest that serum VEGF level may be useful as a novel prognostic predictor of tumor response and survival of patients with inoperable HCC undergoing TACE treatment.     

原发性肝癌患者血清高水平VEGF的意义

目的:研究血清血管内皮生长因子(vascularendothelial growth factor, VEGF)水平与肝癌临床病理及肿瘤病理学之间的关系。方法:应用VEGF 165定量夹心ELISA法测定30 例正常人、30 例肝硬化和45例肝癌患者外周血清中VEGF的水平,并结合临床及肿瘤病理学的特点进行统计学分析。结果:正常人血清VEGF水平为(153±71)pg/mL,分布范围为(6~371) pg/mL;肝硬化患者血清VEGF水平为(158±67)pg/mL,分布范围为(4~352) pg/mL;45例肝癌患者血清VEGF为(312±206) pg/mL,分布范围为(34~968)pg/mL。肝癌患者的外周血VEGF水平显著高于正常人和肝硬化患者,P<0. 01。高水平的血清VEGF与肝癌的大小、包膜的不完整以及转移与复发有关, P<0. 01,而与肿瘤的分化程度无关, P>0 .01。当肿瘤发展到第Ⅳ期,血清VEGF水平显著升高, P<0. 01。结论:血清VEGF高水平是肝细胞肝癌具有血管侵犯和转移潜在危险的指标,预示不良的预后。     

经导管动脉化疗栓塞术对原发性肝癌外周循环肿瘤细胞及血管内皮生长因子的影响

目的 探讨经导管动脉化疗栓塞术（TACE）对原发性肝癌患者外周循环肿瘤细胞（CTC）数量及血管内皮生长因子（VEGF）浓度的影响。方法 选择2011年至2013年50例原发性肝癌患者为研究对象,应用免疫磁珠分离技术及酶联免疫吸附法检测在TACE术前1天及术后1天、3天、30天CTC数量和VEGF浓度的变化。结果 TACE术前1天和术后1天、3天、30天的CTC阳性率分别为84.0％和66.0％、58.0％、78.0％,CTC检测数量分别为（2.38±1.65）个、（1.24±1.06）个、（0.86±0.83）个、（2.10±1.63）个,手术前后比较差异均有统计学意义（P＜0.05）;术前1天及术后1天、3天、30天的VEGF浓度分别为（304.98±33.94） pg／ml、（262.93±28.22） pg／ml、（258.40±27.55） pg／ml、（283.08±37.19） pg／ml,手术前后比较差异有统计学意义（P＜005）。对CTC数量及VEGF浓度在术后30天与术后3天两时段的差值进行相关分析,两者呈线性正相关（r=0.710,P＜0.05）。结论 TACE治疗原发性肝癌术后1～3天内可以有效减少血液VEGF浓度并阻止肿瘤细胞进入外周血循环。     

血管内皮生长因子在肝细胞癌血清中的表达意义

目的研究血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在肝细胞癌(HCC)患者周围血血清中的表达水平与肝癌临床病理特征及肝癌转移复发之间的关系.方法运用sandwich酶联免疫吸附测定法定量检测115例HCC、40例肝脏良性疾病患者和30例健康人血清中VEGF的含量.结果HCC组血清VEGF表达水平[(465.62±336.24)pg/ml]与肝脏良性疾病组[(159.54±120.58)pg/ml]、与健康人组[(123.53±51.84)pg/ml]比较,差异均有显著性(P值均=0.0001);VEGF表达阳性率分别为77.4%、25.0%和3.3%.HCC转移组患者血清VEGF表达水平与未转移组相比,差异有显著性(P=0.001).血清VEGF表达水平还与HCC合并门静脉瘤栓、肿瘤大小和TNM分期密切相关,VEGF含量随TNM分期升高而逐步升高.结论疗前HCC患者的血清VEGF表达水平,是反映HCC侵袭生长及转移潜能的有效生物学指标.     

Vascular endothelial growth factor in patients with hepatocellular carcinoma

The main aims of this study were to analyze the significance of serum vascular endothelial growth factor (VEGF) levels in the development of hepatocellular carcinoma, and the effect of transcatheter arterial embolization treatment on the production of VEGF. Serum VEGF levels in hepatocellular carcinoma were significantly higher than in liver cirrhosis (P<0.01) but not significantly different from normal controls. Serum VEGF levels in cirrhosis decreased gradually as the Pugh-Child grade increased in severity. In hepatocellular carcinoma serum VEGF levels were not related to the tumor stage or serum levels of the tumor markers, cr-fetoprotein and des-gamma-carboxy prothrombin. In 18 patients who underwent transcatheter arterial embolization, serum VEGF increased gradually and reached a peak at day 7, although serum interleukin-6 and hepatocyte growth factor levels peaked at days 1-3 and then decreased. VEGF levels were elevated significantly in patients who did not respond to transcatheter arterial embolization treatment as compared to those who responded to this treatment (P<0.05). Serum VEGF levels may be useful in the assessment of hepatocellular carcinoma patients and may indicate responsiveness to transcatheter arterial embolization.