Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (<400 ng/ml) (Odds ratio=3.3) and PR as best response to TACE (Odds ratio=6.7) were significantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2.1% (one patient). CONCLUSIONS: DSM and Lipiodol were combined successfully in the palliative TACE treatment of advanced HCC resulting in high rates of tumor response and survival at limited toxicity. Favourable tumor response was associated with tumor extent and vascularization. TACE using DSM and Lipiodol can be considered a suitable palliative measure in patients who might not tolerate long acting embolizing agents.

Combination of repeated single-session percutaneous ethanol injection and transarterial chemoembolisation compared to repeated single-session percutaneous ethanol injection in patients with non-resectable hepatocellular carcinoma

瞄准：为病人评估经皮的乙醇注射(PEI ) 的治疗效果与先进， non-resectable HCC 与 transarterial chemoembolisation 的联合相比(不作声) 并且重复单个会议的 PEI，独自重复了单个会议的 PEI，重复不作声独自一个，或最好的支持的照顾。方法：在学习时期期间接受了 PEI 治疗的所有病人根据物理地位和肿瘤程度被包括并且成层到下列治疗形式之一：联合不作声并且重复单个会议的 PEI，独自重复了单个会议的 PEI，重复不作声独自一个，或最好的支持的照顾。包括Okuda分类，门静脉血栓的存在，腹水的存在，肿瘤的数字，最大的肿瘤直径，和假胆硷酯酶( CHE )的临床的参数的预示的价值，以及孩子呸上演， alpha-fetoprotein (法新社)，发烧，复杂并发症的发生在这些组之间被估计并且比较。幸存用 Kaplan-Meier 被决定，多，变量回归分析。结果：所有病人的 1 年、 3 年的幸存是 73% 和 47% 。在亚群分析，联合不作声， PEI (1 ) 与更长的幸存被联系(1- ， 3- ， 5 年的幸存：90% ， 52% ，和 43%) 与 PEI 治疗相比独自一个(2 )(1- ， 3- ， 5 年的幸存：65% ， 50% ，和 37%) 。(3 ) 在起始的层化以后的第二等的 PEI 产出可比较的结果不作声(1- ， 3- ， 5 年的幸存：91% ， 40% ，和 30%) 当在到最好的支持的照顾(4 ) 的层化以后的 PEI 与减少的幸存被联系时(1- ， 3- ， 5 年的幸存：50% ， 23% ， 12%) 。除了选择治疗形式，为更好的幸存的预言者是肿瘤数字(n 【 5 ) ，肿瘤尺寸(【 5 厘米) ，在 PEI 前的没有腹水，和在 PEI 以后的稳定的假胆硷酯酶(P 【 0.05 ) 。在在 PEI 以后的 2 wk 以内的死亡是 2.8%(n = 3 ) 。有 24 (8.9%) 主修在包括部分肝梗塞，焦点的肝坏死，和肝脓肿的 PEI 以后的复杂并发症。所有复杂并发症能非通过手术被管理。结论：重复单个会议的 PEI 在有以可接受、可管理的复杂并发症率的先进 HCC 的病人是有效的。病人们成层到联合不作声， PEI 能比那些独自成层到重复 PEI 期望更长的幸存。而且，有在好临床的地位的大或多重的肿瘤的病人可以也从联合获利不作声并且为第二等的 PEI 的再考虑。

Initial experience from a combination of systemic and regional chemotherapy in the treatment of patients with nonresectable cholangiocellular carcinoma in the liver

AIM: In nonresectable cholangiocellular carcinoma (CCC)therapeutic options are limited. Recently, systemic chemotherapy has shown response rates of up to 30%.Additional regional therapy of the arterially hyper vascularized hepatic tumors might represent a rational approach in an attempt to further improve response and palliation. Hence, a protocol combining transarterial chemoembolization and systemic chemotherapy was applied in patients with CCC limited to the liver.METHODS: Eight patients (6 women, 2 men, mean age 62 years) with nonresectable CCC received systemic chemotherapy (gemcitabine 1 000 mg/m2) and additional transarterial chemoembolization procedures (50 mg/m2cisplatin, 50 mg/m2 doxorubicin, up to 600 mg degradable starch microspheres). Clinical follow-up of patients, tumor markers, CT and ultrasound were performed to evaluate maximum response and toxicity.RESULTS: Both systemic and regional therapies were tolerated well; no severe toxicity (WHO Ⅲ/Ⅳ) was encountered. Nausea and fever were the most commonly observed side effects. A progressive rarefication of the intrahepatic arteries limited the maximum number of chemoembolization procedures in 4 patients. A median of 2 chemoembolization cycles (range, 1-3) and a median of 6.5 gemcitabine cycles (range, 4-11) were administered.Complete responses were not achieved. As maximum response, partial responses were achieved in 3 cases,stable diseases in 5 cases. Two patients died from progressive disease after 9 and 10 mo. Six patients are still alive. The current median survival is 12 mo (range, 9-18); the median time to tumor progression is 7 mo (range, 3-18). Seven patients suffered from tumor-related symptoms prior to therapy, 3 of these experienced a treatment-related clinical relief. In one patient the tumor became resectable under therapy and was successfully removed after 10 mo.CONCLUSION: The present results indicate that a combination of systemic gemcitabine therapy and repeated regional chemoembolizations is well tolerated and may enhance the effect of palliation in a selected group of patients with intrahepatic nonresectable CCC.