Review on transarterial chemoembolization in hepatocellular carcinoma: Palliative,combined, neoadjuvant,bridging, and symptomatic indications

The current review provides an overview on the palliative, combined, neoadjuvant, bridging, and symptomatic indications of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). It is based on an analysis of the current literature and the experience of the authors on the topic. Chemoembolization combines the infusion of chemotherapeutic drugs with particle embolization. Tumor ischemia raises the drug concentration compared to infusion alone, extends the retention of the chemotherapeutic agent and reduces systemic toxicity. Palliatively, TACE is performed to control symptoms and prolong survival in HCC patients; in some indications TACE allows a local tumor control of 18–63%. For combined indications, excellent results were achieved by combined therapies, such as percutaneous ethanol injection (PEI)/TACE, radiofrequency ablation (RF)/TACE, and laser-induced thermotherapy (LITT)/TACE. As a neoadjuvant therapy prior to liver resection TACE showed 70% tumor control. Though debatable, TACE still plays a role as a bridging tool before liver transplantation. Symptomatic indication of TACE in ruptured HCC showed 83–100% control of bleeding but survival was poor. Thus, TACE represents an important therapeutic tool against HCC in general in addition to its special role in cases of unresectable HCC.     

Selective and sequential transarterial chemoembolization: survival in patients with hepatocellular carcinoma

Purpose

To assess the survival time of patients with HCC following transarterial chemoembolization performed in a highly selective and sequential way.

Patients and methods

124 HCC patients (102 male, 22 female; mean age 63 ± 11 years) treated with selective and sequential chemoembolization at a single center were included. Selective chemoembolization was performed through a coaxially introduced microcatheter in a segmental or subsegmental hepatic artery. Treatment was stopped after complete stasis of the blood flow in the tumor-feeding vessel. The primary endpoint of the study was overall survival.

Results

The median overall survival of the entire patient population was 27.2 months (mo) (±8.9 mo, 95% CI 9.8 mo, 44.6 mo). When stratified according to liver function the median survival was 46.1 mo (±9.0 mo; 95% CI 28.5 mo, 63.7 mo) for Child-Pugh A and 11.1 mo (±4.3 mo; 95% CI 2.7 mo, 19.5 mo) for Child-Pugh B (p < .001). The median survival was 46.1 mo (±16.6 mo; 95% CI 13.5 mo, 78.7 mo) for BCLC stage A, 19.7 mo (±2.6 mo; 95% CI 14.6 mo, 24.8 mo) for BCLC stage B, and 14.4 mo (±5.0 mo; 95% CI 4.5 mo, 24.3 mo) for BCLC stage C (p < .01).

Conclusion

Selective and sequential chemoembolization offers long survival times in patients with HCC. Those patients with preserved liver function benefit more than patients with limited liver reserve.     

Single-session combined radiofrequency ablation and transarterial chemoembolization in the treatment of hepatocellular carcinoma

Aim of the study

To evaluate the efficacy of the combined use of both transarterial chemoembolization (TACE) and percutaneous radiofrequency ablation (RFA) in a single session for the treatment of large (≥3?cm in diameter) hepatocellular carcinoma.

Radiofrequency thermal ablation (RFA) after transarterial chemoembolization (TACE) as a combined therapy for unresectable non-early hepatocellular carcinoma (HCC)

The treatment of unresectable “non-early” (according to the BCLC classification) hepatocellular carcinoma (HCC) in cirrhotic patients with transcatheter arterial chemoembolization (TACE) followed by radiofrequency ablation (RFA) is retrospectively evaluated and possible prognostic factors of this combined therapy are investigated. Forty-six consecutive cirrhotic patients (Child-Pugh class A or B) with solitary or oligonodular HCC underwent RFA after TACE. The treated lesions were 51 overall (size 30–80 mm, mean 48.9). RFA was performed by a multitined expandable electrodes device after one TACE administration. Local efficacy was evaluated with multiphasic computed tomography (CT) performed an average of 2 months after treatment and then during follow-up. Patient survival rate was also evaluated (follow-up time 1–51 months, mean 15 months). Technical success (defined as complete devascularization during the arterial phase) was achieved in 34/51 lesions (66.7%) at the first CT check and in 29/51 (56.9%) during the succeeding follow-up. Among the considered prognostic factors, only lesion diameter (< or >=50 mm) was statistically significant in the Fisher's exact test in terms of local control (85.2 vs. 45.8% at first CT, p=.0065; 70.4 vs. 41.7% during follow-up, p=.051). There were two major complications (6.5%): one hepatic failure and one death. A Kaplan-Meier analysis showed survival rates of 89.7% at 12 months and 67.1% at 24 months. Combined therapy for non-early HCC shows a relatively high complete local response (especially in lesions less than 5 cm in diameter) and promising mid-term clinical success. Its overall usefulness has yet to be established by a larger series and risk-benefit analysis.     

经导管动脉化疗栓塞治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效观察

目的观察经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效。方法回顾性分析2010年7月—2013年11月东南大学附属中大医院江北院区收治的肝细胞癌合并门静脉癌栓患者107例,符合入组条件的40例中,21例接受TACE联合索拉非尼治疗（联合治疗组）,19例接受单纯TACE治疗（TACE组）,观察患者生存时间及严重并发症发生率。结果联合治疗组和TACE组的中位生存时间分别为8.4个月和5.7个月（P<0.001）,疾病无进展生存期分别为7.3个月和4.3个月（P=0.002）,2组严重并发症发生率分别为19.1%和15.8%（P=0.559）。结论TACE联合索拉非尼较单纯TACE治疗肝细胞癌合并门静脉癌栓未增加严重并发症发生率,并可有效延长患者生存时间。     

CT-guided radiofrequency ablation after with transarterial chemoembolization in treating unresectable hepatocellular carcinoma with long overall survival improvement

Purpose

To assess the time to disease progression (TTP), long-term survival benefit and safety of patients with unresectable hepatocellular carcinoma (HCC) treated with computed tomography (CT)-guided radiofrequency ablation (RFA) with transarterial chemoembolization chemoembolization (TACE).

Methods

This study was approved by the institutional review board. We reviewed the records of patients with intermediate and advanced HCC treated with CT-guided RFA with TACE between January 2000 and December 2009. Median TTP, overall survival (OS) and hepatic function were analyzed with the Kaplan–Meier method and log-rank tests.

Results

One hundred and twenty-two patients (112 men and 10 women, mean age 53 years, range 18–86 years) were included in the study. The median follow-up time was 42 months (range 6–89 months), TTP was 6.8 months, the median OS was 31 months, and the 1-, 3-, and 5-year OS were 88.5%, 41.0%, and 10.7%. The results of the univariate analysis revealed that intrahepatic lesion, AJCC stage, and Child-Pugh stage were predictors of OS (P < 0.01). In the multivariate analysis, the AJCC stage system showed a statistically significant difference for prognosis. Procedure-related death was 0.21% (1/470) within 1 month, and a statistical difference was found between the TACE and RFA of liver decompensation and Child-Pugh stage (P < 0.05).

Conclusions

The survival probabilities of OS increased with CT-guided RFA with TACE, as observed in randomized studies from Europe and Asia. The longest TTP was observed for the intermediate stage HCC. The procedures were well tolerated with acceptable minor and major complications in unresectable HCC patients.     

经导管肝动脉化疗栓塞术联合微波消融治疗肝癌的精准护理研究

目的：探讨精准护理在经导管肝动脉化疗栓塞术（TACE）联合微波消融（MWA）治疗肝癌患者中的应用效果。 方法：将我院介入血管外科2016年11月至2017年10月收治60例TACE联合MWA治疗的肝癌患者,按前后时间顺序分为对照组（30例）和观察组（30例）,对照组采取常规护理,观察组在对照组的基础上,采用精准护理方法,对比两组患者术后尿储留、恶心呕吐、腰酸背痛、失眠发生率,健康知识知晓率和护理满意率。 结果：观察组患者的术后尿储留、恶心呕吐、腰酸背痛、失眠发生率明显低于对照组（P<0.05）;健康知识知晓率和护理满意率高于对照组（P<0.05）。 结论：精准护理方法运用于TACE联合MWA治疗肝癌患者中,可显著降低术后不良反应的发生,增加介入治疗术后整体舒适度,提高健康知识知晓率和护理满意率。     

Sequential transarterial chemoembolization for unresectable advanced hepatocellular carcinoma

Purpose The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of sequential transarterial chemoembolization (TACE) for patients with unresectable advanced hepatocellular carcinoma (HCC). Methods Twenty-one consecutive patients with unresectable T3 and T4 HCC were treated by sequential TACE (median time interval between treatments 7 weeks) up to six times with an emulsion of lipiodol, epirubicin, and cisplatin. All TACE procedures were performed as unilobar or whole-liver chemoembolization. Results An average of 3.9 TACE procedures were performed per patient. One primary and two secondary technical failures occurred. No procedural death was observed. After exclusion of the patient with the primary technical failure and 3 patients with extrahepatic disease, the survival rates for the remaining 17 patients at 6, 12, 18, and 24 months were 70.6%, 52.9%, 44.1%, and 33.1%, respectively. Conclusion Sequential TACE is a safe procedure in patients with unresectable advanced HCC and feasible in most cases. It seems to prolong the survival time compared with historical series of untreated patients.     

Chemoembolisation of hepatocellular carcinomas: personal experience

Transcatheter arterial chemoembolisation (TACE) using antiblastic agents in association with occlusion of tumour-feeding arteries seems currently to be the most suitable treatment for unresectable hepatocellular carcinomas (HCC) larger than 3 cm in diameter. From July 1989 to January 1991, 21 patients with HCC and a previous history of liver cirrhosis were treated by TACE. The drugs used were doxorubicin and mitomycin C mixed with Lipiodol UF. The arterial occlusion was obtained using Gelfoam or Spongostan particles; in 16 patients it was limited to tumour-feeding arteries to avoid diffuse parenchymal liver damage, while in 5 patients either the main right or left hepatic artery was embolised. Three patients were excluded from the study after TACE because of too short a follow-up; 4/18 died within 3–9 months and 14/18 are still alive with follow-up ranging from 3 to 19 months. A tumour size reduction of more than 50% was observed in 9 patients (50%), with a median survival of 9.8 months. Transient and well-controlled side effects (fever, abdominal pain, nausea and vomiting) were related to the post-embolisation syndrome and could be reduced by using a superselective occlusion procedure. Correspondence to: G. C. Ettorre     

Radiofrequency ablation combined with transarterial chemoembolization for subcapsular hepatocellular carcinoma: A prospective cohort study

Objective

This study evaluated the safety and efficacy of using radiofrequency ablation combined with transarterial chemoembolization to treat hepatocellular carcinoma in a subcapsular location, given the increased risk of complications when using radiofrequency ablation alone.

Materials and methods

From January 2000 to December 2011, 1213 patients with unresectable hepatocellular carcinoma (up to three nodules) were screened. Of these, 132 patients with 132 subcapsular nodules (mean size, 3.0 cm; range, 1.2–5.0 cm) were enrolled in the study. After transarterial chemoembolization, percutaneous radiofrequency ablation was performed under ultrasound or C-arm cone-beam computed tomography guidance, on the same day or within 3 days. Local recurrence and survival curves were obtained using the Kaplan–Meier method.

Results

Technical success of treatment was achieved in 130 patients (98.5%). Major complications, including pleural effusion, secondary peritonitis, and liver abscess, occurred in 3 patients (2.3%); the incidence of complications was associated with the number of needle insertions (1–2 vs. 3–4, P = 0.039, Fisher's exact test). No patients developed permanent sequelae, tumor seeding, or tumor bleeding. The 3-year local recurrence rate was 9.7%. Local recurrence was associated with the pretreatment serum des-gamma-carboxy prothrombin level (≤200 mAU/mL vs. >200 mAU/mL, P = 0.019, log-rank test). The 3-, 5-, and 7-year overall survival rates in treatment-naïve cases (n = 82) were 79.3%, 60.6%, and 50.9%, respectively.

Conclusion

Combination therapy using radiofrequency ablation and transarterial chemoembolization was a safe and useful therapeutic option for patients with subcapsular hepatocellular carcinoma.     

Radiomic advances in the transarterial chemoembolization related therapy for hepatocellular carcinoma

Radiomics is a hot topic in the research on customized oncology treatment,efficacy evaluation, and tumor prognosis prediction. To achieve the goal of mining the heterogeneity information within the tumor tissue, the image features concealed within the tumoral images are turned into quantifiable data features.This article primarily describes the research progress of radiomics and clinicalradiomics combined model in the prediction of efficacy, the choice of treatment modality, and survival in tran...     

Rab10通过介导肝癌细胞上皮间质转化促进肝癌转移

目的 探讨Rab10在肝细胞肝癌转移中的作用,为晚期肝癌的治疗提供新靶点.方法 利用美国癌症基因组图谱(Cancer Genome Atlas,TCGA)和基因表达汇编(Gene Expression Omnibus,GEO)数据库分析Rab10在肝癌组织和癌旁组织的表达及表达与肝癌患者的生存关系.Western Bl...     

Computed tomography perfusion imaging for monitoring transarterial chemoembolization of hepatocellular carcinoma

PurposeTo prospectively monitor changes in tumor perfusion of hepatocellular carcinoma (HCC) in response to doxorubicin-eluted bead based transarterial chemoembolization (DEB-TACE) using perfusion-CT (P-CT).Methods and materials24 patients (54–79 years) undergoing P-CT before and shortly after DEB-TACE of HCC were prospectively included in this dual-center study. Two readers determined arterial-liver-perfusion (ALP, mL/min/100 mL), portal-venous-perfusion (PLP, mL/min/100 mL) and the hepatic-perfusion-index (HPI, %) by placing matched regions-of-interests within each HCC before and after DEB-TACE. Imaging follow-up was used to determine treatment response and to distinguish complete from incomplete responders. Performance of P-CT for prediction and early response assessment was determined using receiver-operating-characteristics curve analysis.ResultsInterreader agreement was fair to excellent (ICC, 0.716–0.942). PLP before DEB-TACE was significantly higher in pre-treated vs non-treated lesions (P < 0.05). Mean changes of ALP, PLP and HPI from before to after DEB-TACE were −55%, +24% and −27%. ALP and HPI after DEB-TACE were correlating with response-grades (r = 0.45/0.48; both, p < 0.04), showing an area-under-the-curve (AUC) of 0.74 and 0.80 respectively for identification of complete response.ConclusionHigh arterial and low portal-venous perfusion of HCC early after DEB-TACE indicates incomplete response with good diagnostic accuracy.     

Angiographic evaluation of hepatic arterial damage after transarterial chemoembolization for hepatocellular carcinoma

PURPOSE: The aim of this study was to assess the incidence, degree, and predictors of hepatic arterial damage (HAD) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A total of 33 patients with unresectable HCC underwent TACE alone using a mixture of iodized oil, epirubicin, and gelatin sponge. A follow-up angiogram was available for 76 of 109 sessions, and HAD was evaluated at each subsegment of the hepatic artery using a three-grade scale (1, no or slight wall irregularity; 2, overt stenosis; 3, occlusion). Grades 2 and 3 were considered to indicate significant HAD. The predictors of HAD were analyzed by multivariate analysis. RESULTS: A total of 161 hepatic arteries were embolized from the lobar (n = 43), segmental (n = 40), subsegmental (n = 72), or more distal (n = 6) level. The follow-up period between the initial and last sessions ranged from 70 to 1505 days (median 497 days). Significant HAD occurred in 37 of 231 subsegmental hepatic arteries (16%) and in 16 of 33 patients (48%). The accumulated dose of epirubicin per artery (P = 0.001) and Child-Pugh score (P < 0.001) were significant predictors. CONCLUSION: TACE is more likely to induce HAD in cirrhotic patients with impaired liver function and when a high dose of the chemotherapeutic agent was used.     

Influence of copper on MRI of hepatocellular carcinoma

The purpose of this paper is to clarify whether copper accumulation in hepatocellular carcinoma (HCC) is a cause of high intensity signal pattern on T1-weighted images (T1-WI) by comparing the histologically proven copper accumulation with MR images. Forty-five surgically resected HCCs were analyzed. Distribution patterns of divalent copper by a modified Timm's method on their maximum cut surfaces were compared with signal patterns on corresponding T1-WI. The degree of copper accumulation in tumor compared with surrounding liver tissue was higher in 6 lesions, equal in 17 lesions, and lower in 22 lesions. High intensity pattern on T1-WI were observed in 3 of 6 lesions (50%), 10 of 17 lesions (59%), and 10 of 22 lesions (45%). Distribution patterns of copper were not correlated with intensity patterns on T1-WI. We conclude that the paramagnetic effect of divalent copper accumulation in HCC is insufficient to influence the MRI.     

Conventional versus doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma

Purpose

To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC).

Materials and Methods

Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival.

Results

In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival.

Conclusions

Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.     

肝癌介入治疗栓塞综合征对症治疗(附142例报告)

目的:探讨奥西康(奥美拉唑针剂)联合麦滋林颗粒、胃复安针、甲基强的松龙针对控制肝癌动脉化疗栓塞后胃区疼痛、栓塞热、呕吐反应的治疗效果。方法:对142例接受介入治疗肝癌患者的术后栓塞综合征治疗情况进行回顾性分析,对比奥西康针联合麦滋林颗粒组与雷尼替丁针组治疗介入术后胃黏膜损伤引起胃区疼痛的疗效差别,对比甲基强的松龙针与地塞米松针控制术后栓塞热的差别,对比胃复安针与欧贝针控制术后呕吐反应的差别。结果:奥西康针联合麦滋林颗粒、甲基强的松龙针、胃复安针对控制肝癌介入术后胃区疼痛、栓塞热、呕吐反应治疗效果好于雷尼替丁针、地塞米松针、欧贝针等对照组。结论:奥西康针加麦滋林颗粒、甲基强的松龙针、胃复安针分别控制胃黏膜损伤、栓塞热、呕吐疗效较好。     

原发性肝癌介入治疗后急性肾功能衰竭的预防及治疗

目的：探讨原发性肝癌介入治疗后急性肾功能衰竭的风险因素、预防及治疗措施。方法：回顾性分析4例原发性肝癌介入治疗后发生急性肾功能衰竭的临床表现及治疗情况。结果：4例患者均为巨块型肝癌,首次行介入治疗,术前肝功能ChildA级,肾功能正常,介入后72h内发生急性肾功能衰竭,2例经血液透析后恢复,1例经补液利尿治疗后恢复,1例合并糖尿病、高血压的年老患者死于心力衰竭。结论：介入后发生急性肾功能衰竭是少见而严重的并发症,对于高风险的患者应采取有效的防范措施。     

全肝CT灌注扫描对于介入术后肝肿瘤活性的观察

目的经动脉导管化疗栓塞术(transarterial chemoembolization,TACE)治疗后患者进行全肝灌注扫描,比较增强CT、全肝灌注扫描和DSA三种检查技术对TACE治疗后肝癌瘤灶活性的检出率。方法 17例经过穿刺病理或血清学证实的肝细胞癌患者曾经行TACE介入治疗:患者于介入术后4周行全肝脏CT灌注扫描。明确经过碘油栓塞治疗的病灶44个被列入观察中。肝脏灌注分数(hepatic arterial fracture,HAF)灌注图高参数信号作为判定术后瘤灶存有活性的标准。分别采用增强CT、全肝CT灌注成像和DSA判定介入治疗后肿瘤活性,最后对不同影像技术的肿瘤活性检出率进行比较。结果 DSA造影的肿瘤活性检出率最高,达86.36%,CTP的检出率84.09%,而增强CT扫描的检出率70.45%最低。并且与前两者相比有显著性差异(P=0.016和0.031)。结论作为无创性检查手段,CTP的肿瘤活性检出力明显强于增强CT,并且接近DSA造影。因此,全肝CT灌注扫描是一种有价值的观测肝癌介入治疗疗效的无创医疗技术。     

In vivo proton magnetic resonance spectroscopy of large focal hepatic lesions and metabolite change of hepatocellular carcinoma before and after transcatheter arterial chemoembolization using 3.0-T MR scanner

PURPOSE: To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of large focal hepatic lesions and to measure the metabolite change of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using 3.0-T scanner. MATERIALS AND METHODS: In this prospective study, 43 consecutive patients with large (not less than 3 cm in diameter) hepatic tumors and eight normal volunteer were included. MRS of the lesions in addition to uninvolved liver parenchyma was carried out using a whole-body 3.0-T scanner. Among the patients with proven HCC, eight lesions were evaluated before and two to five days after TACE. The choline-to-lipid (cho/lipid) ratio was measured by dividing the peak area of choline at 3.2 ppm by the peak area of lipid at 1.3 ppm. The sensitivity and specificity profiles of MRS in the diagnosis of malignant hepatic tumors were determined by plotting empirical receiver operating characteristic (ROC) curve. The mean cho/lipid ratios in different groups before and after TACE were also measured. RESULTS: The technical success rate for MRS was 90% (53/59). The ROC curve showed proton MRS has moderate discriminating ability in diagnosing malignant hepatic tumors, although the sensitivity was less than 50% while 1-specificity was less than 20%. The area under the curve was 0.71 (P < 0.05). The mean +/- 1 standard error (SE) of cho/lipid ratios for uninvolved liver (N = 8), benign tumor (N = 8), and malignant tumor (N = 21; 19 HCC, one angiosarcoma, and one lymphoma) were 0.06 +/- 0.02, 0.02 +/- 0.02, and 0.17 +/- 0.05, respectively. A significantly statistical difference (ANOVA planned contrast test, P = 0.01 and Games-Howell procedure, P = 0.03) was achieved in the mean cho/lipid ratio between malignant and benign tumors. The mean cho/lipid ratios were significantly decreased from 0.23 +/- 0.11 before TACE to 0.01 +/- 0.00 after the treatment (t = 2.01, P < 0.05, one-tail paired t-test; z = -2.37, P < 0.05, Wilcoxon Signed Ranks Test). CONCLUSION: In vivo proton MRS is technically feasible for the evaluation of focal hepatic lesions. The technique has potential in the detection of early metabolite change in malignant liver tumors after TACE but limitation still exists in clear differentiation between normal liver and benign and malignant tumor.