Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma

AIM:To evaluate the efficacy of transarterial chemoembolization(TACE) using a suspension of a finepowder formulation of cisplatin(DDPH) in lipiodol(LPD) in the treatment of hepatocellular carcinoma(HCC).METHODS:The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension.The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD.TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected.These patients received additional TACE using the same agent.TACE was repeated until complete regression of the tumor was obtained.The primary efficacy endpoint of the current study was the objective early response rate.Secondary efficacy endpoints were progression-free survival(PFS) and overall survival.RESULTS:The objective early response rate was 43.6%.Cumulative PFS rates were 56.7% at 6 mo,23.1% at 12 mo,13.4% at 18 mo,and 10.5% at 24 mo.The median PFS was 6.6 mo.Cumulative survival rates were 90.6% at 6 mo,81.9% at 12 mo,70.5% at 24 mo,and 58.8% at 36 mo.Median survival time was 46.6 mo.All adverse reactions were controllable by temporary suspension of treatment.No serious complications or treatment-related deaths were observed.CONCLUSION:TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.     

胆囊动脉供血肝癌TACE治疗45例

目的:评估经导管动脉内化疗栓塞术(transcatheter arterial chemoembolization,TACE)治疗不能切除的、由胆囊动脉供血肝细胞癌(hepatocellular carcinoma,HCC)的安全性、插管成功率及其疗效.方法:收集我院45例经TACE治疗的由胆囊动脉供血的肝癌患者.36例患者以前曾行2-8次TACE术(平均4次),自初次治疗后的存活期为4-69 mo(平均24 mo).9例患者在首次血管造影时即发现胆囊动脉寄生.TACE技术只有在微导管能插入肿瘤供血动脉分支,并且造影不出现胆囊壁染色时才能进行.我们对其治疗效果及并发症作了回顾性分析.结果:28个肿瘤完全由胆囊动脉供血,17个由肝动脉及胆囊动脉共同供血.60%(n=27)的患者可以观察到肝动脉的变细或闭塞.32例患者(71%)成功地进行了栓塞治疗而无严重并发症出现.28例患者(62%)有足够的碘油聚集.这28例患者在平均随访18mo后仅有6例(21%)肿瘤局部进展.对于栓塞不成功的13例(29%)患者,分别给予经皮注射无水乙醇治疗(n=6),放疗(n=4)以及胆囊切除术后的TACE(n=3).结论:71%的患者经胆囊动脉行TACE治疗是安全可行的.如果肿瘤能获得足够的碘油聚集,理想的治疗效果还是值得期待的,本组有62%(n=28)的患者获取良好的碘油聚集.     

120例原发性肝癌的肝动脉化疗栓塞术疗效观察

目的 观察中晚期原发性肝癌经导管肝动脉化疗栓塞术(TACE)治疗的疗效。方法自1990-2003年共有120例中晚期肝癌患者，接受TACE介入治疗，评估和随访治疗前后的疗效。结果经过治疗，79．2％(95／120)的患者临床症状缓解；88．3％(55／120)肿块缩小；78．2％(79／101)AFP明显下降；生存期延长，1、2、3年生存率分别为80．8％(87／120)、48．3％(58／120)和1130％(36／120)。结论TACE治疗是中晚期肝癌的有效手段，使不能手术切除的肝癌成为适应手术治疗，延长了患者的生命，提高了生活质量。     

索拉非尼联合肝动脉化疗栓塞术治疗中晚期肝细胞癌疗效观察

目的观察经导管肝动脉化疗栓塞术(TACE)与靶向治疗药相结合治疗中晚期肝细胞癌的疗效和安全性。方法 2008年1月至2012年12月我院收治的中晚期肝细胞癌患者60例,均采用TACE治疗,其中37例术后口服索拉非尼(400 mg,2次/d),根据不良反应调整用量,定期复查腹部CT。根据m RECIST标准进行疗效评价,观察患者的肿瘤进展时间和总生存期,并记录索拉非尼不良反应和TACE前后的肝功能变化。结果 37例应用TACE联合索拉非尼治疗患者的中位生存期为(13±0.98)m,显著长于23例单纯TACE治疗组[(7.3±1.20)m,P=0.001],肿瘤进展时间为(7.5±1.21)m,显著长于单纯TACE治疗组[(5±0.62)m,P=0.001];在随访结束时,联合治疗组疾病控制率为48.6%,显著高于单纯TACE组的17.4%(P0.01);多因素分析显示有无联合应用索拉非尼、有无门脉癌栓、是否抗病毒治疗是显著影响生存时间的风险因素;索拉非尼治疗主要的相关不良反应为手足皮肤反应。结论 TACE联合索拉非尼治疗可延长中晚期肝细胞癌患者的疾病进展时间及总生存期,安全性好。     

Cerebral and pulmonary embolisms after transcatheter arterial chemoembolization for hepatocellular carcinoma

A cerebral lipiodol embolism is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma. We present a case of cerebral lipiodol embolism that occurred after the third arterial chemoembolization, report the clinical and radiological findings, and review the medical literature.     

Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. While curative therapies, including resection, liver transplantation, and percutaneous ablation (percutaneous ethanol injection and radiofrequency ablation), are applicable for only a portion of the HCC population, transcatheter arterial chemoembolization (TACE) has been recognized as an effective palliative treatment option for patients with advanced HCC. TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems. TACE has become widely adopted in the treatment of HCC. By using computed tomography-angiography, TACE is capable of performing diagnosis and treatment at the same time. Furthermore, TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment. In this review, we first discuss the history of TACE, and then review the previous findings about techniques of achieving a locoregional treatment effect (liver infarction treatment, e.g., ultra-selective TACE, balloon-occluded TACE), and the use of TACE as a drug delivery system for anti-cancer agents (palliative, e.g., platinum complex agents, drug-eluting beads) for multiple lesions.     

肝动脉化疗栓塞术中注入重组人血管内皮抑制素治疗中晚期肝癌的疗效及安全性分析

目的：观察重组人血管内皮抑制素经肝动脉灌注联合TACE治疗中晚期肝癌的近期及远期疗效。方法将64例中晚期肝癌患者分为对照组（n=30例),仅予以TACE治疗,和观察组（n=34例）,在行TACE治疗时,同时经肝动脉注入重组人血管内皮抑制素,比较两组近、远期疗效,观察治疗前后肿瘤直径、KPS评分及AFP变化,分析两组毒副反应。结果观察组治疗总有效率（64.7%）明显高于对照组（43.3%,P<0.05）;两组患者治疗后肿瘤直径[（4.0±1.2） cm和（4.9±1.3） cm]较治疗前[（6.7±2.0） cm和（6.6±2.2） cm]明显缩小（P<0.05）,KPS评分明显升高[（92.5±9.8）对（76.1±4.5）和（84.8±8.6）对（75.2±3.4）,P<0.05],AFP明显降低[（547.2±160.7）μg/L对（1275.3±316.8）μg/L和（558.5±176.4）μg/L 对（1218.8±337.9）μg/L,P<0.05],且观察组肿瘤直径[（4.0±1.2） cm、KPS评分（92.5±9.8）较对照组缩小（4.9±1.3） cm或升高（84.8±8.6）更为显著,P<0.05];两组毒副反应比较差异无显著性（P>0.05）;随访1年,观察组患者病死率（5.9%）和肝外转移率（14.7%）明显低于对照组患者（16.7%和26.7%, P<0.05）。结论在行TACE治疗时加用重组人血管内皮抑制素治疗中晚期肝癌患者可明显提高近期及远期疗效,缩小肿瘤直径和改善KPS评分,且不会加重毒副反应。     

在TACE术中应用奥沙利铂联合表柔比星治疗肝癌患者疗效观察

目的 探讨在经导管动脉化疗栓塞术（TACE）中应用奥沙利铂联合表柔比星治疗晚期肝癌患者的临床疗效。方法 78例晚期肝癌患者被分成两组,39例对照组在行TACE介入时应用奥沙利铂与吉西他滨治疗,39例观察组则应用奥沙利铂联合表柔比星治疗。两组患者均完成4个周期治疗,并于第4周期治疗完成后观察临床疗效。结果 观察组治疗有效率为84.62%,明显高于对照组的64.10%（x²=25.19,P<0.05）。在治疗4周期后,观察组死亡1例,对照组死亡2例; 观察组治疗前血清IL-2、TNF-α和IFN-γ水平分别为（52.9±6.1）μg/ml、（44.2±9.7） U/ml和（15.0±2.2） U/ml,治疗后则升高至（72.0±11.6） μg/ml、（65.6±13.2）U/ml和（26.1±5.9） U/ml （P<0.05）,对照组患者血清细胞因子水平有类似变化,但治疗后升高不及观察组明显;观察组不良反应发生率为43.59%,明显低于对照组71.79%（x²=26.22,P<0.05）。结论 相比奥沙利铂联合吉西他滨而言,奥沙利铂联合表柔比星治疗晚期肝癌患者能提高临床疗效,且不良反应少。     

肝动脉化疗栓塞联合经皮射频治疗老年中晚期肝癌的疗效

目的 分析肝动脉化疗栓塞（TACE）联合经皮射频消融（RFA）治疗老年中晚期原发性肝癌（HCC）的疗效,为HCC的临床治疗提供参考.方法 按照随机数字表法将80例患者分为TACE联合RFA治疗组（观察组）和RFA治疗组（对照组）,比较两组治疗效果.结果 观察组肿瘤瘤体缩小率高于对照组,两组比较,差异具有统计学意义（P＜0.05）;甲胎蛋白下降超过50％者,观察组（85.7％）与对照组（55.6％）比较差异具有统计学意义（P＜0.05）.两组不良反应发生情况差异无统计学意义（P＞0.05）;术后24个月随访,观察组生存率27例（67.5％）,对照组生存率17例（42.5％）,两组比较差异具有统计学意义（P＜0.05）.结论 HCC患者对TACE联合RFA治疗的耐受性较好,联合治疗的安全性和可行性较好.     

Successful management of postoperative recurrence of hepatocellular carcinoma with p53 gene therapy combining transcatheter arterial chemoembolization

Transcatheter arterial chemoembolization (TACE) has become the standard treatment for unresectable hepatocellular carcinoma (HCC). But this method has some shortages. p53 gene, which was found to be mutant in many human tumors, has been proved with broad spectrum anti-tumor effects. We reported a 23-year-old patient with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this patient. We injected percutaneously and infused transcatheterally p53 gene (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow-up, the patient was in good clinical condition with normal liver function and no recurrence was identified. The case report proposed that recurrent HCC could be successfully treated with p53 gene therapy combining TACE.     

Meta-analysis of radiofrequency ablation in combination with transarterial chemoembolization for hepatocellular carcinoma

AIM: To compare radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) with RFA monotherapy in hepatocellular carcinoma (HCC). METHODS: We searched PubMed, Medline, Embase and Chinese databases (CBMdisc and Wanfang data) for randomized controlled trails comparing RFA plus TACE and RFA alone for treatment of HCC from January 2000 to December 2012. The overall survival rate, re-currence-free survival rate, tumor progression rate, and safety were analyzed and compared. The analysis was conducted on dichotomous outcomes and the standard meta-analytical techniques were used. Pooled odds ratios (ORs) with 95%CIs were calculated using either the fixed-effects or random-effects model. For each meta-analysis, the χ2 and I2 tests were first calculated to assess the heterogeneity of the included trials. For P<0.05 and I 2>50%, the assumption of homogeneity was deemed invalid, and the random-effects model wasused; otherwise, data were assessed using the fixed-effects model. All statistical analysis was conducted us-ing Review manager (version 4.2.2.) from the Cochrane collaboration. RESULTS: Eight randomized controlled trials were identified as eligible for inclusion in this analysis and included 598 patients with 306 treated with RFA plus TACE and 292 with RFA alone. Our data analysis indicated that RFA plus TACE was associated a sig-nificantly higher overall survival rate (OR 1-year=2.96, 95%CI: 1.84-7.74, P<0.001; OR 2-year=3.72, 95%CI: 1.24-11.16, P=0.02; OR 3-year=2.65, 95%CI: 1.81-3.86, P<0.001) and recurrence-free survival rate (OR 3-year=3.00, 95%CI: 1.75-5.13, P<0.001; OR 5-year=2.26, 95%CI: 1.43-3.57, P=0.0004) vs that of RFA alone. The tumor progression rate in patients treated with RFA alone was higher than that of RFA plus TACE (OR=0.60, 95%CI: 0.42-0.88, P=0.008) and there was no significant difference on major complications between two different kinds of treatment (OR=1.20, 95%CI: 0.31-4.62, P=0.79). Additionally, the meta-analysis data of subgroups revealed that the     

Effect of preoperative transcatheter arterial chemoembolization on proliferation of hepatocellular carcinoma cells

AIM To evaluate the effect of preoperative transcatheter arterial chemoembolization (TACE) on proliferation of hepatocellular carcinoma (HCC) cells.METHODS A total of 136 patients with HCC underwent liver resection. Of 136 patients, 79 patients received 1 to 5 courses of TACE prior to liver resection (TACE group),who were further subdivided into four groups Group A (n = 11) who received 1 to 4 courses of chemotherapy alone; Group B (n = 33) who received 1 to 5 courses of chemotherapy combined with iodized oil; Group C (n = 23) who received 1 to 3 courses of chemotherapy combined with iodized oil and gelatin sponge; and Group D (n = 12) who received 1 to 3 courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge.The other 57 patients only received liver resection (nonTACE group). The expressions of Ki-67 and proliferating cell nuclear antigen (PCNA) protein were detected in the liver cancer tissues by immunohistochemical method.RESULTS The Ki-67 protein expression was significantly lower in Groups C and D as compared with non-TACE group (31.35% ± 10.85% vs 44.43% ± 20.70%,30.93% ± 18.10% vs 44.43% ± 20.70%, respectively, P ＜ 0.05). The PCNA protein expression was significantly lower in Groups C and D as compared with non-TACE group (49.61% ± 15.11% vs 62.92% ± 17.21%, 41.16% ± 11.83% vs 62.92% ± 17.21%, respectively, P ＜ 0.05).The Ki-67 protein expression was significantly higher in Group A as compared with non-TACE group (55.44% ± 13.72% vs 44.43% ± 20.70%, P ＜ 0.05). The PCNA protein expression was significantly higher in Groups A and B as compared with non-TACE group (72.22% ± 8.71% vs 62.92% ± 17.21%, 69.91% ± 13.38% vs 62.92% ± 17.21%, respectively, P ＜0.05).CONCLUSION Preoperative multi-material TACE suppresses the proliferation of HCC cells, while a single material embolization and chemotherapy alone enhance the proliferation of HCC cells.     

经导管肝动脉化疗栓塞术治疗肝细胞癌疗效及复发预测

目的 探讨肝细胞癌(HCC)患者经导管肝动脉化疗栓塞术(TACE)前、术后脱γ-羧基凝血酶原(DCP)、甲胎蛋白异质体(AFP-L3)、甲胎蛋白(AFP)的变化及其与预后关系.方法 纳入96例接受TACE作为初始治疗的HCC患者,分别于术前,术后4～5周及术后6～12个月检测血清DCP、AFP-L3、AFP等水平.根据...     

吉西他滨联合奥沙利铂经肝动脉化疗栓塞防治肝癌术后复发

目的:探讨吉西他滨联合奥沙利铂经肝动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)在防治肝癌高危患者术后复发中的价值.方法:回顾性分析肝癌术后复发高危患者120例,88例术后3-6wk接受TACE治疗为TACE组,其中43例采用吉西他滨联合奥沙利铂组成的GEMOX方案(GEMOX组),45例使用传统化疗药物方案(对照组);32例因其他原因未接受TACE治疗作为为单纯手术组.通过6mo、12mo的随访,比较各组6mo、12mo术后复发率.结果:TACE组术后6mo、12mo肝内复发率(20.5%、43.8%)明显低于单纯手术组(37.5%、59.4%),两者均有统计学意义(χ2=6.512、4.573,P<0.05).在TACE组中,GEMOX组6mo术后复发率(11.6%)较对照组(28.9%)低,差异有统计学意义(χ2=4.026,P<0.05),两组12mo术后复发率无明显差异(χ2=0.876,P>0.05);在TACE不良反应中,GEMOX组白细胞减少及恶心、呕吐发生率较对照组低,差异有统计学意义(Z=-2.156、-2.295,P<0.05).结论:对肝癌术后复发高危患者进行预防性TACE有助于减少或延缓术后近期复发率,吉西他滨联合奥沙利铂方案疗效更佳.     

Complete response with sorafenib and transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma

Patients with advanced hepatocellular carcinoma(HCC) showing portal vein tumor thrombosis(PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization(TACE) showing complete histological response. Two months after induction with sorafenib, a significant decrease in serum alpha-fetoprotein level was observed and computed tomography imaging showed a significant decrease in tumor size. Because of remaining PVTT, TACE and curative resection were performed. The combination of sorafenib and TACE may be an effective treatment for HCC patients with PVTT.     

Puncture injection of para-toluenesulfonamide combined with chemoembolization for advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is difficult to eradicate due to its resilient nature. Portal vein is often involved in tumors of large size, which exclude the patient from surgical resection and local ablative therapy, such as percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) because they were considered neither effective nor safe. Currently, there is almost no effective treatment for HCC of such condition. As a unique antitumor agent in form of lipophilic fluid for local injection, para-toluenesulfonamide (PTS) produces mild side effects while necrotizing the tumor tissues quickly and efficiently. Being largely different from both PEI and RFA therapies, PTS can disseminate itself in tumors more easily than other caustic agents, such as alcohol. So PTS may offer additional benefit to HCCs with vascular involvement. We herein describe a 70-year-old HCC patient who was treated with the combination of PTS injection and transcatheter arterial chemoembolization, resulting in a significantly improved clinical prognosis.     

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells

AIM： To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization （TACE） on angiogenesis of hepatocellular carcinoma （HCC） ceils. METHODS： A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients （TACE group）, in which one to four courses of chemotherapy alone were performed in 11 patients （group A）; one to five courses of chemotherapy combined with iodized oil were performed in 33 patients （group B）; one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients （group C）, one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients （group D）. The other 57 patients only received liver resection （non-TACE group）. The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor （VEGF） protein were detected by immunohistochemical methods. RESULTS： The mean microvessel density （MVD） in HCC cells was significantly higher in groups A, B, C and D than in the nonACE group （P 〈 0.05）. The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group （P 〈 0.05）. MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. CONCLUSION： Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.     

Combined treatment of hepatocellular carcinoma with partial splenic embolization and transcatheter hepatic arterial chemoembolization

AIM: To prospectively evaluate the effi cacy and safety of partial splenic embolization (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC). METHODS: Fifty patients suffering from primary HCC associated with hypersplenism caused by cirrhosis were randomly assigned to 2 groups: group A receiving PSE combined with TACE (n = 26) and group B receiving TACE alone (n = 24). Follow-up examinations included calculation of peripheral blood cells (leukcytes, platelets and red blood cells) and treatment-associated complications. RESULTS: Prior to treatment, there was no signifi cant difference in sex, age, Child-Pugh grade, tumor diameter, mass pathology type and peripheral blood cell counts between the 2 groups. After treatment, leukocyte and platelet counts were significantly higher in group A during the 3-mo follow-up period (P < 0.05), but lower in group B (P < 0.05). Severe complications occurred in 3 patients (11.5%) of group A and in 19 patients (79.2%) of group B (P < 0.05), and there was no significant difference in symptoms of post-embolization syndrome, including abdominal pain, fever, mild nausea and vomiting between the 2 groups (P > 0.05). CONCLUSION: PSE combined with TACE is more effective and safe than TACE alone for patients with HCC associated with hypersplenism caused by cirrhosis.     

Phase I/II study of a fine‐powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

Aim: The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine‐powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine‐powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods: Fine‐powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m² (level 1) and increased to 65 mg/m² in 10 mg/m² increments. Results: Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m²), the recommended dose was 65 mg/m². The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions: TACE with a fine‐powder formulation of CDDP at a dose of 65 mg/m² is well tolerated in patients with unresectable HCC.     

Pulmonary embolism after arterial chemoembolization for hepatocellular carcinoma: An autopsy case report

We report an extremely rare case of pulmonary lipiodol embolism with acute respiratory distress syndrome(ARDS) after transcatheter arterial chemoembolization(TACE) for hepatocellular carcinoma(HCC). A 77-yearold man who was diagnosed with a huge HCC wasadmitted for TACE. Immediately after the procedure, this patient experienced severe dyspnea. We suspected that his symptoms were associated with a pulmonary lipiodol embolism after TACE, and we began intensive treatment. However, his condition did not improve, and he died on the following day. A subsequent autopsy revealed that the cause of death was ARDS due to pulmonary lipiodol embolism. No cases have been previously reported for which an autopsy was performed to explain the most probable mechanism of pulmonary lipiodol embolism; thus, ours is the first report for such a rare case.