TACE联合抗肿瘤药物在原发性肝细胞癌治疗中的现状及进展

原发性肝细胞癌(HCC)是世界范围内的一种常见疾病,经导管动脉化疗栓塞术(TACE)已成为不能手术切除的中晚期肝细胞癌的首选治疗方法.但是,TACE有其本身的局限性,例如肿瘤复发率高、并发症较多等,且栓塞治疗后局部组织缺血、缺氧,促进了血管内皮生长因子的活化,进而促进新生血管形成,导致肿瘤复发,降低疗效.TACE联合抗肿瘤血管生成治疗能弥补对方的缺点,两者有良好的协同作用,明显降低肝细胞癌复发率,近年成为非手术治疗肝细胞癌的热点.     

TACE联合抗肿瘤药物在原发性肝细胞癌治疗中的现状及进展

原发性肝细胞癌(HCC)是世界范围内的一种常见疾病,经导管动脉化疗栓塞术(TACE)已成为不能手术切除的中晚期肝细胞癌的首选治疗方法.但是,TACE有其本身的局限性,例如肿瘤复发率高、并发症较多等,且栓塞治疗后局部组织缺血、缺氧,促进了血管内皮生长因子的活化,进而促进新生血管形成,导致肿瘤复发,降低疗效.TACE联合抗肿瘤血管生成治疗能弥补对方的缺点,两者有良好的协同作用,明显降低肝细胞癌复发率,近年成为非手术治疗肝细胞癌的热点.     

重组人血管内皮抑制素联合介入治疗肝癌

重组人血管内皮抑制素( rH-ES)是我国学者自主研发的抗血管生成类药物,对 肿瘤血管生成具有广谱抑制作用.动物实验及部分临床试验结果证明rH-ES对晚期非小细胞肺癌具有明显疗效[1],但目前rH-ES在晚期恶性复发肿瘤的应用报道较少.我们随机选择了一组中晚期肝癌,用rH-ES联合经导管肝动脉化疗栓塞术(TACE)治疗,观察患者在治疗过程的外周血自发微核形成、血管生长因子变化等生物学指标,探讨rH-ES联合TACE治疗肿瘤中生物学监测的意义.     

原发性肝癌TACE介入治疗前后血清VEGF和bFGF水平变化及临床意义

检测原发性肝癌患者肝动脉化疗栓塞(TACE)治疗前后血清血管形成因子(VEGF和bFGF)水平变化,了解介入治疗对肿瘤血管形成的影响。采用ELISA法检测肝癌患者血清VEGF、bFGF含量,比较TACE治疗前后的水平。30例肝癌患者血清VEGF及bFGF水平介入治疗后均较介入治疗前明显升高(P0.05)。TACE介入治疗使VEGF和bFGF增高表达,促进了残余肝癌组织新生血管的形成,可能是肝癌TACE治疗远期效果不理想的原因之一。     

肝外供血动脉栓塞在巨块型肝癌治疗中的价值

目的探讨经导管肝外供血动脉栓塞在治疗巨块型肝癌中的价值。方法对35例巨块型肝癌,首次行经导管肝动脉化疗栓塞术（TACE）,第2次及其后在肝动脉TACE基础上加行经右侧胸廓内动脉、右侧肋间动脉侧支供血动脉栓塞术。结果本组35例巨块型肝癌患者,发现肝外侧支49支,对46支使用微导管进行栓塞治疗,3支行超选择灌注化疗。初次TACE治疗时肝外血供多有膈下动脉参与,治疗过程中,随着肿瘤的增大或肝动脉的闭塞,胸廓内动脉、肋间动脉、胰十二支肠动脉弓等血管有可能参与。结论对肝外侧支血管应用微导管超选择栓塞或灌注化疗均能加强TACE在巨块型肝癌治疗中的作用,提高患者带瘤生存期。     

中晚期肝癌的介入治疗

中晚期肝癌介入治疗包括经血管介入治疗和影像导向经皮穿刺病灶消融。血管介入治疗即经动脉化疗栓塞术（transcatheter arterial chemoembolization，TACE）。1975年，Goldstain首先创立了经导管肝动脉栓塞术（TAE）治疗肝脏恶性肿瘤。随后，在Wallace，VP Chuang等人的不懈努力下，创立并发展了TACE，它已经成为中晚期肝癌介入治疗最为经典的方法。     

TACE联合其他手段治疗肝癌发展现状

经血管介入治疗肝癌兴起于20世纪70年代，肝动脉化疗栓塞术（transcatheter hepatic arterial chemoembolization, TACE）是其中最为经典的治疗方式。当时除外科手术切除外，肝癌治疗缺乏其他有效手段，然而以TACE为代表的经血管介入治疗方法的出现为肝癌的临床治疗开辟了全新的途径，因此在短时间内发展迅猛，临床应用极为广泛，技术、     

沙利度胺对原发性肝癌介入栓塞术后血管生长因子的影响

目的 本研究旨在评价沙利度胺对原发性肝癌介入栓塞术后血管生长因子的影响,探索以介入治疗为主的中晚期肝癌的综合治疗模式.方法 以肝动脉栓塞术前1周内及术后30天血管内皮生长因子水平为观察终点指标,并观察沙利度胺的不良反应.采用前瞻性随机对照研究,对2006年2月～2006年8月就诊我科的68例原发性肝癌患者随机分为治疗组和对照组,治疗组给予沙利度胺200 mg/d口服1～6个月联合TACE,对照组单纯行TACE.TACE用药选用吉西它滨0.4～1.6 g、奥沙利铂100～200 mg、氟脲嘧啶脱氧核苷 0.5～1.0 g, 栓塞剂选用碘化油、明胶海绵.以双抗夹心ELISA法检测血VEGF水平.结果 介入治疗后两组患者的VEGF水平均有升高,但联合沙利度胺组VEGF升高幅度明显低于单纯介入栓塞组,两组有显著性差异(P《0.05).结论 口服沙利度胺可降低原发性肝癌介入栓塞术后的血管内皮生长因子水平,提示沙利度胺联合TACE可能进一步提高原发性肝癌介入栓塞治疗的效果.     

TACE治疗原发性肝癌后并发肝脓肿的影响因素

目的 观察TACE治疗原发性肝癌后并发肝脓肿的影响因素。方法 采用倾向性评分匹配法回顾性收集99例接受TACE治疗的原发性肝癌患者,其中26例TACE后并发、73例未并发肝脓肿;根据治疗方式将其分为传统TACE(cTACE)组(n=48)和药物栓塞微球TACE(DTACE)组(n=51)。比较并发肝脓肿与未并发肝脓肿患者临床资料的差异,以logistic回归分析筛选TACE治疗原发性肝癌后并发肝脓肿的影响因素。结果 TACE治疗原发性肝癌后并发与未并发肝脓肿患者之间,肿瘤供血血管数目、碘油量及栓塞剂种类差异均有统计学意义(P均<0.05)。cTACE组内并发与未并发肝脓肿患者血糖及栓塞剂种类差异有统计学意义(P均<0.05);DTACE组内并发与未并发肝脓肿患者碘油量差异有统计学意义(P<0.05)。TACE治疗原发性肝癌后并发肝脓肿的保护因素为患者年龄<55岁、无靶向药物联合免疫检查点抑制剂治疗史(靶免史)、仅栓塞1支肿瘤供血动脉、碘油量少及仅使用1种栓塞剂,TACE次数≥3则为危险因素(P均<0.05)。结论 患者年龄、靶免史、TACE次数、肿瘤供血血...     

应用海藻酸钠微球联合碘化油经导管 肝动脉化疗栓塞治疗肝癌

目的探讨海藻酸钠微球联合碘化油在经导管肝动脉化疗栓塞（TACE）治疗肝癌中的应用价值。方法应用海藻酸钠微球联合碘化油,采用TACE治疗136例原发性肝癌患者。结果TACE后,38例肿瘤完全消失,65例肿瘤缩小〉50%,25例肿瘤缩小25%～50%,8例肿瘤无明显变化。TACE后腹痛发生率47.79%（65/136）,其中80.00%为轻、中度,术后发热为41.18%（56/136）。术后肝功能损害轻微,无严重并发症。结论应用海藻酸钠微球联合碘化油TACE治疗原发性肝癌使用方便,能够克服碘油流失,增强栓塞血管的效应,提高治疗效果。     

经导管动脉化疗栓塞术后肝细胞癌残癌组织HIF-1α、VEGF及CD34的表达水平

目的探讨缺氧诱导因子-1α（HIF-1α）在经导管动脉化疗栓塞术（TACE）后肝细胞癌（HCC）残癌组织中的表达及其与肿瘤新生血管的相关性。方法取TACE后手术切除的HCC组织标本24份（TACE组）和未经任何治疗直接手术切除的HCC组织标本30份（单纯手术组）。采用免疫组化SP法,检测残癌组织HIF-1α、血管内皮生长因子（VEGF）表达水平和微血管密度[MVD（CD34标记）]。结果 HIF-1α和VEGF在TACE组阳性表达率分别为95.83%、91.67%,显著高于单纯手术组（66.67%、63.33%,P=0.008、0.016）;TACE组残癌组织中MVD值显著高于单纯手术组（P〈0.001）。TACE组残癌组织中HIF-1α与VEGF表达呈正相关（r=0.546,P=0.006）;HIF-1α、VEGF表达与MVD值变化呈正相关（r=0.512,P=0.010;r=0.793,P〈0.001）。结论 TACE后能明显上调HIF-1α的表达,HIF-1α/VEGF通路在血管新生过程中起重要作用,可能是HCC经TACE后残癌复发、转移的原因之一。     

明胶海绵微粒化疗栓塞肝细胞癌后外周血中血管内皮生长因子水平变化

目的通过观察肝细胞癌（HCC）患者外周血中血管内皮生长因子（VEGF）水平在GSPs化疗栓塞治疗前后的变化,探讨该方法对肿瘤血管生成的影响。方法应用ELISA双抗体夹心法检测30例原发性HCC患者（HCC组）GSPs化疗栓塞术前1天、术后4、7及28天和30名健康志愿者（对照组）外周血中VEGF水平。结果 HCC患者术前外周血中VEGF含量明显高于对照组（P〈0.05）。HCC患者术后4天[（232.56±119.40）pg/ml]、7天[（290.33±97.17）pg/ml]外周血中VEGF水平较术前1天[（106.79±55.85）pg/ml]明显增高（P均〈0.05）;术后28天[（233.54±106.60）pg/ml]低于术后7天[（290.33±97.17）pg/ml],但差异无统计学意义。结论 GSPs化疗栓塞治疗HCC术后VEGF规律性的变化可反映肿瘤血管生成状态,为术后抗血管内皮生长治疗提供理论依据。     

VEGF和MVD在术前接受过肝动脉栓塞化疗的肝癌组织中的表达及临床意义

目的探讨血管内皮细胞生长因子(VEGF)和平均微血管密度(MVD)在接受术前经导管肝动脉栓塞化疗(TACE)肝癌细胞中的表达和在二期切除肝癌复发预后中的意义。方法选取91例术前TACE和50例未行TACE肝癌手术切除标本,采用免疫组化方法检测两组标本VEGF、CD34的表达情况和MVD值。分析两组VEGF的表达情况和MVD值的差异,以及62例术前TACE后根治性切除的肝癌中VEGF的表达水平与复发的关系。结果 VEGF表达于肝细胞质中,CD34选择性表达于血管内皮细胞,术前TACE组和未行TACE组VEGF的表达(6.9±4.7vs5.1±4.4)和MVD值(62.0±35.4vs45.6±29.0)差异有统计学意义(P0.05)。术前TACE后根治性二期切除患者,复发组(45例)与未复发组(17例)肿瘤组织中VEGF阳性率分别为82.2%和41.2%,差异有统计学意义(P0.05)。VEGF阳性组1、3、5年无瘤生存率分别为50.9%、%、22.5%,VEGF阴性组分别为88.5%、68.2%、28.153.0%,差异有统计学意义(P0.05)。多因素分析表明治疗前存在播散结节及VEGF的表达水平是影响TACE后二期切除患者复发的独立危险因素。结论 TACE后残癌组织血管生成增多,术前TACE后二期根治性切除肝癌VEGF的表达与患者术后复发转移密切相关。     

Loco‐regional interventional treatment of hepatocellular carcinoma: techniques,outcomes, and future prospects

Loco‐regional interventional treatments continue to evolve and to play a major role in the therapeutic management of hepatocellular carcinoma (HCC). Image‐guided ablation is established as the treatment of choice for patients with early‐stage HCC when transplantation or resection is precluded. Recent refinements in technique have substantially increased the ability of radiofrequency ablation to achieve sustained complete response of target tumors in properly selected patients, and new alternate thermal and nonthermal methods for local tumor treatment are currently under investigation. Transarterial chemoembolization (TACE) is the standard of care for patients with multinodular disease at the intermediate stage. The introduction of drug‐eluting beads – that enhance drug delivery to the tumor and reduce systemic exposure – appears to improve anticancer activity and safety profile of TACE compared with conventional regimens. Despite these advances, the long‐term outcomes of patients treated with loco‐regional therapies remain unsatisfactory because of the high rate of tumor recurrence. The introduction of molecular targeted therapies that inhibit tumor proliferation and angiogenesis has opened new prospects in this regard. Clinical trials focused on combining interventional treatment with systemically active drugs are ongoing. The outcomes of such studies are eagerly awaited, as they have the potential to revolutionize treatment of HCC.     

Transcatheter arterial chemoembolization with or without radiofrequency ablation in the management of patients with advanced hepatic malignancy

Transcatheter arterial chemoembolization (TACE) is efficacious against hepatic malignancies by rendering tumors ischemic while delivering high-dose chemotherapy. The added benefit of radiofrequency ablation (RFA) has not been determined. We sought to review our experience with TACE with or without RFA in the treatment of hepatocellular carcinoma and colorectal liver metastases in patients not amenable to resection. TACE and RFA were undertaken in 13 patients with hepatocellular carcinoma (n = 7) or colorectal liver metastases (n = 6). Concurrently 24 patients underwent TACE alone for hepatocellular carcinoma (n = 15) or colorectal liver metastases (n = 9). Patients undergoing TACE with or without RFA were similar in age, gender, and diagnosis. Overall follow-up was 9.1 months +/- 7.1. One-year survival was greater in patients undergoing TACE with RFA than with TACE alone (100% vs 67%, P = 0.04). Mean survival was longer after TACE with RFA compared with TACE alone (25.3 months +/- 15.9 vs 11.4 months +/- 7.3, P < 0.05). No patients suffered significant complications. The addition of RFA to TACE improves survival in patients with unresectable primary or metastatic hepatic malignancies. RFA with TACE should be in the armamentarium of surgeons caring for patients with malignant liver lesions.     

肝动脉化疗栓塞及无水酒精注射联用治疗中晚期肝癌

目的 比较中晚期肝癌单纯肝动脉化疗栓塞（ＴＡＣＥ）及加用经皮局部无水酒精注射（ＰＥＩ）的临床疗效。方法 回顾性分析了１９９２年１月至１９９７年３月不能一期手术切除的中晚期肝癌病人１９３例,其中行ＴＡＣＥ１１５例,ＴＡＣＥ并Ｂ超引导下ＰＥＩ７８例。结果 两组近期有效率（ＷＨＯ标准）分别为１２．２％和２５．６％;治疗后获得手术切除者两者分别有４．３％和１４．１％;半年、１年和２年生存率ＴＡＣＥ组盒为６     

Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis

Transarterial chemoembolization (TACE) has gained wide acceptance as a bridge to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Aim of this analysis was to compare long‐term results with and without neoadjuvant TACE and to identify subgroups, which particularly benefit from TACE. Patients with HCC transplanted at our center were retrospectively analyzed. The following were excluded to increase consistency: incidental‐HCC, Child‐C, living‐related‐LT, other HCC‐specific‐treatment. Of 336 patients, 177 were subject of this analysis, 71 received TACE and 106 no HCC therapy. Patients with and without TACE showed similar five‐yr survival (73/67%) and recurrence rates (23/29%). Progression on the waiting list was associated with a higher recurrence rate in the TACE (50 vs.12%) and the non‐TACE group (40 vs. 22%). HCC recurrence was reduced in patients inside Milan (0.053) and UCSF (0.037) criteria by neoadjuvant TACE but not outside UCSF (0.99). Also a trend towards an improved survival was seen within these criteria. Our large single center experience suggests that TACE lowers the HCC recurrence rate in patients inside the Milan and UCSF criteria. Moreover, the response to TACE is a good indicator of low recurrence rates. The effect of TACE might be more pronounced in patients with longer waiting time than in this cohort (mean, 4.6 months).     

Combination of transcatheter arterial chemoembolization using cisplatin-lipiodol suspension and percutaneous ethanol injection for treatment of advanced small hepatocellular carcinoma

BACKGROUND: We evaluated the long-term efficacy of the combination of transcatheter arterial chemoembolization (TACE) using cisplatin-lipiodol suspension and percutaneous ethanol injection (PEI) for treatment of advanced small hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Sixty-nine patients with HCC less than 3 cm in diameter and at most three lesions were enrolled in this study. HCC nodules were confirmed to be hypervascular by angiography. Thirty-two patients were treated with a combination of TACE and PEI (TACE/PEI group) and 37 patients with TACE alone (TACE group). RESULTS: The 5-year survival rates were 50% for the TACE/PEI group and 22% for the TACE group. The TACE/PEI group had a slightly but not significantly better survival than the TACE group. The 5-year survival rates of patients with solitary HCC were 61% for the TACE/PEI group and 24% for the TACE group. Although the two therapeutic groups both had high rates of recurrence, the rates in the TACE/PEI group were significantly lower than those in the TACE group (P <0.05). Severe complications such as intraperitoneal bleeding and segmental hepatic infarction were observed at low incidence, and recovered with supportive treatment. CONCLUSIONS: The combination of TACE and PEI appears to prolong survival, compared with TACE alone. This combination therapy can thus be a valuable form of treatment for unresectable advanced small HCC.     

Repeat Transarterial Chemoembolization (TACE) for Progressive Hepatic Carcinoid Metastases Provides Results Similar to First TACE

Background Transarterial chemoemobolization (TACE) is commonly used to treat metastatic carcinoid tumors; however, the management of progressive disease is less clear. We sought to determine if patients with disease progression after TACE would benefit from repeat TACE. Methods The records of 27 patients undergoing repeat TACE for radiologic or symptomatic progression after TACE for metastatic carcinoid were reviewed and compared to 122 undergoing first TACE. Overall and progression-free survivals were estimated by the Kaplan–Meier method. Results Mean disease-free interval after first TACE was 11.8 months. Radiologic response was observed in 61% compared to 82% after first TACE (p = 0.058); hormone response in 64% compared to 80% (p = 0.159); and symptomatic response in 77% compared to 92% (p = 0.053). The complication rate after repeat TACE was lower than after first TACE (p = 0.03). Median overall survival was similar after repeat (28.1 months) and first TACE (33.3 months) (p = 0.53). Progression-free survival was shorter after repeat TACE but not significantly so. No factor examined could predict survival after repeat TACE. Conclusion Repeat TACE for patients with hepatic carcinoid metastases failing first TACE or having evidence of disease progression is safe and offers a viable treatment option. Presented at the 48th Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, DC, May, 2007.