Advances in the treatment of hepatocellular carcinoma using drug-eluting beads

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor. Although radical surgery and liver transplantation are possible cures for the disease, most patients are beyond the optimum stage for radical treatment at the time of diagnosis. Transarterial chemoembolization (TACE) is the first choice of treatment for advanced HCC. Owing to the widespread use of conventional TACE (cTACE), the problems with this treatment cannot be ignored. Drug-eluting beads (DEBs), a new type of embolization material, appear to overcome the problems of cTACE, and they have other advantages such as synchronous controlled continuous drug release after chemotherapy and embolization and low blood concentrations after treatment. This review summarizes the recent advances in the use of DEB-TACE to treat HCC.     

Conventional versus drug-eluting bead transarterial chemoembolization: A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 ​cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.     

Double-contrast magnetic resonance imaging of hepatocellular carcinoma after transarterial chemoembolization

Background The purpose of this study was to assess the accuracy of double-contrast magnetic resonance (MR) imaging for the treatment response evaluation of hepatocellular carcinoma (HCC) in cirrhotic liver after transarterial chemoembolization (TACE). Methods Twenty-two patients with 30 HCC nodules treated by TACE underwent double-contrast MR imaging 1 month after treatment. MR images were obtained before and after the sequential administration of superparamagnetic iron oxide (SPIO) and gadopentetate dimeglumine contrast agent within the same imaging session. Two observers retrospectively assessed all treated nodules for evidence of residual viable tumor after TACE. The diagnostic performance of gadolinium-enhanced, SPIO-enhanced, and double-contrast enhanced images was calculated. Histopathological and angiographical findings served as standard of reference. Receiver operating characteristic curves and areas under the curves (A _z) were calculated. Results Double-contrast technique (A _z = 0.95) was significantly (p = 0.036) more accurate than SPIO-enhanced technique (A _z = 0.92) and gadolinium-enhanced technique (p = 0.005) (A _z = 0.81) in viable tumor detection after TACE. Double-contrast technique was significantly more sensitive (92%) than SPIO-enhanced technique (80%) and gadolinium-enhanced technique (68%). Kappa values for interobserver agreement ranged from 0.67 to 0.87 and were significantly different from zero (all p < 0.001). Conclusions Compared to gadolinium-enhanced and SPIO-enhanced techniques, double-contrast technique significantly improves the detection of viable tumor in HCC after TACE.     

Effects of combining transarterial chemoembolization with percutaneous microwave coagulation therapy for hepatocellular carcinoma abutting the diaphragm

Objective: This study aims to explore the clinical effectiveness of a combination therapy of transarterial chemoembolization (TACE) and percutaneous microwave coagulation therapy (PMCT) in treating hepatocellular carcinoma (HCC) abutting the diaphragm. Material and methods: Six cases with HCC were treated with TACE followed by PMCT one month later with the aid of artificial pneumothorax. Results: CT/MRI revealed complete necrosis in the tumor lesions and the treated tumor margins (≥5?mm). Serum alpha-fetoprotein (AFP) levels markedly declined in patients who originally had higher serum AFP levels. Postoperative complications such as fever, mild hepatic dysfunction and pleural effusion were alleviated within a short period of time. All patients were closely monitored through follow-up; all patients survived, except for one patient who received a liver transplantation. Conclusions: As lesions are either invisible or poorly visible in sonography, determining an effective treatment for HCC abutting the diaphragm remains a particular challenge. TACE and PMCT combined therapy with the aid of artificial pneumothorax proved to be an available treatment option.     

大视野对比常规视野锥形束CT在经动脉化疗栓塞术中的应用

目的比较数字减影血管造影(digital substraction angiography, DSA)大视野(field-of-view, FOV)锥形束计算机断层扫描(cone-beam computed tomography, CBCT)与常规FOV CBCT在经动脉化疗栓塞术(transarterial chemoembolization, TACE)中的应用价值。方法 选择2021年10月至12月接受TACE治疗的肝癌患者37例,随机分为大视野组(n=20)和对照组(n=17)。大视野组在术中行大FOV CBCT扫描;对照组行常规CBCT扫描。对两组患者的影像学资料、透视和曝光时间及辐射剂量进行分析,比较两组图像质量和辐射剂量。结果 大视野组3D图像质量达优率为90%,高于对照组的58.82%(P=0.028)。大视野组与对照组平均曝光次数、平均累计透视时间、平均累计曝光时间和空气比释动能差异均无统计学意义。大视野组单位时间剂量面积乘积(dose area product,DAP)低于对照组[(26.852±6.430)μGymm²/s vs (53.12...     

Conventional versus drug-eluting bead transarterial chemoembolization: A better option for treatment of unresectable hepatocellular carcinoma

Transarterial chemoembolization (TACE) is a minimally invasive procedure involving intra-arterial catheter-based chemotherapy to selectively administer high doses of cytotoxic drugs to the tumor bed along with ischemic necrosis induced by arterial embolization. Chemoembolization forms the essential core of management in patients with hepatocellular carcinoma (HCC) who are not suitable for curative therapies such as transplantation, resection, or percutaneous ablation. TACE of hepatic cancer(s) has proven to be helpful in achieving local tumor control, and has supported the ability to prevent tumor progression, prolong patient life, and manage patient symptoms. Recent data have demonstrated that, in patients with single-nodule HCC ≤3 ​cm without vascular invasion, the 5-year overall survival with TACE was found to be comparable with hepatic resection and radiofrequency ablation. Used for several years, Lipiodol continues to play a vital role as a tumor-seeking and radiopaque drug delivery vector in interventional oncology. Efforts have been made to enhance the administration of chemotherapeutic agents to tumors. Compared with conventional TACE, drug-eluting bead TACE is a fairly new drug delivery embolization technique that permits fixed dosing and has the ability to provide sustained release of anticancer agents over a period of time. The present review discusses the basic procedure of TACE and its properties, and the effectiveness of conventional and drug-eluting bead chemoembolization systems currently available or presently undergoing clinical evaluation.     

药物洗脱微球经导管动脉化疗栓塞术治疗肝细胞癌进展

肝细胞癌(HCC)是最常见的原发性肝癌之一。经导管动脉化疗栓塞术(TACE)一直被用为中期HCC患者的一线治疗方法,而药物洗脱微球TACE(DEB-TACE)的临床应用近年来亦不断增加。本文对DEB-TACE的药物代谢动力学、微球选择、适应证和禁忌证及疗效评估进展进行综述。     

Current concepts in transarterial chemoembolization of hepatocellular carcinoma

Transarterial chemoembolization (TACE) has the potential to improve survival in patients with intermediate stage hepatocellular carcinoma (HCC). Careful selection of patients is mandatory to gain survival benefit and safe quality of life. Basic principles of TACE in HCC include selective treatment via intrahepatic and extrahepatic arteries, proper management of side effects and continuation of treatment guided by imaging. After conventional TACE, based on delivery of cytotoxic drugs emulsified in iodized oil and embolization of various types of particles, has been used for more than 20 years, the new concept of drug-eluting microspheres has been introduced. This technology effectively combines enhanced local drug delivery and ischemic embolization effects. Clinical studies showed intensified local necroses and reduced systemic toxic side effects compared to conventional TACE. Embolization of HCC with sub-100 μm particles penetrating deeply into the tumor vascular bed is another promising new option. Very effective devascularization of HCC nodules has been shown after 40 μm bland embolizations, however, potential risks like passage of particles into hepatic veins and systemic circulation have to be considered. Today the indication for TACE in intermediate stage HCC patients is widely accepted; however, there is no clear methodical standard so far. Further studies are necessary to define how to adapt various available methods to individual HCC and patients characteristics.     

Erratum To: Short-term efficacy of transarterial chemoembolization with epirubicin-loaded superabsorbent polymer microspheres for hepatocellular carcinoma: comparison with conventional transarterial chemoembolization

Abdominal Radiology -     

Comparison of health-related quality of life after transarterial chemoembolization and transarterial radioembolization in patients with unresectable hepatocellular carcinoma

Abdominal Radiology - The purpose of this study was to compare quality of life (QoL) after two different transarterial therapies [transarterial chemoembolization (TACE) and transarterial...     

4D CT成像辅助引导经动脉精准化疗栓塞治疗原发性肝癌

目的 描述四维(4D)CT成像方法 ,并探究经动脉化疗栓塞(TACE)术前应用四维CT成像引导肝癌的化学栓塞治疗的价值。方法利用容积螺旋动态穿梭技术,前瞻性完成拟行TACE治疗的原发性肝细胞癌患者的增强CT扫描。扫描范围覆盖全肝,从动脉前期至静脉期动态研究肿瘤病灶。针对目标病灶的4D CT重组图与数字减影血管造影(DSA)图在肝动脉解剖、肿瘤供血血管、肿瘤血管显示以及肿瘤染色方面进行比较。栓塞效果经CT随访进行评价。结果本研究纳入了39位患者的46个孤立肝癌病灶。根据Michels分型,25位(64.1%)具备正常的肝动脉解剖,其余存在解剖变异。该信息为肝动脉插管造影提供了很好的依据,并经过DSA证实。4D CT成像无创性显示了病灶的肿瘤供血动脉(41/46),肿瘤血管(36/46),肿瘤染色(42/46)。因4D CT成像可以引导超选择性置入微导管,使得化学栓塞治疗成功完成。结论 四维CT成像可以有效地评价肝动脉解剖,定位肿瘤供血动脉,为肝癌介入化学栓塞提供影像引导。     

Comparison of radiation doses between hepatic artery infusion chemotherapy and transarterial chemoembolization for liver cancer

ObjectiveTo analyze the radiation dose received by patients during hepatic artery infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE) procedures and the related influencing factors.MethodsData of 162 cases in the HAIC group and 230 cases in the TACE group were collected. The included covariates were Age (<45/45–59/≥60 years), BMI levels (underweight/normal weight/obesity), focus Dye of tumor (present/absent), lesion size (<5cm/≥5cm), superselection (present/absent), hepatic vascular variation (present/absent). The endpoints were postoperative dose-area product (DAP), exposure time and Air kerma (AK).ResultsOf all included patients, the HAIC group patients were younger than those in the TACE group (P ​= ​0.028). The proportion of patients with large lesions in the HAIC group was higher than the TACE group (45.7% vs. 33.9%, P ​= ​0.019). The proportion of patients who had superselection was lower in the HAIC group as compared to the TACE group (61.7% vs. 82.2%, P ​< ​0.001). Generally, the HAIC group has lower DAP, exposure time and AK by 36.3% (P ​< ​0.001), 38.2% (P ​< ​0.001), and 41.3% (P ​< ​0.001) than the TACE group, respectively. Linear regression analysis showed the procedure method (HAIC/TACE, P ​< ​0.001), type of DSA machine (Pheno/FD20, P ​< ​0.001), BMI levels (P ​< ​0.001), age (P ​= ​0.021), lesion size (<5cm/≥5 ​cm, P ​= ​0.031) significantly correlated with low DAP. In the HAIC group, the type of DSA machine and BMI correlated with the radiation dose, while in the TACE group, the type of DSA machine, BMI, and lesion size correlated with the radiation dose.ConclusionCompared with TACE, HAIC enables doctors and patients to receive lower radiation doses. Obese patients in both HAIC and TACE groups increase the radiation exposure in interventional doctors and patients, but large lesions only affect the radiation dose in the TACE procedure.     

Stratification of portal vein-invaded hepatocellular carcinoma treated with transarterial chemoembolization monotherapy

PurposeThe study aimed to establish a prognostic prediction model and an artificial neural network (ANN) model to determine who will benefit from transarterial chemoembolization (TACE) monotherapy for patients with hepatocellular carcinoma (HCC) invading portal vein.MethodsTreatment-naïve patients with HCC and portal vein invasion who were treated with TACE monotherapy at hospital A as training cohort and hospital B as validation cohort were included. The primary endpoint was overall survival (OS). In training cohort, independent risk factors associated with OS were identified by univariate and multivariate analysis. The prognostic prediction (PP) and ANN models based on the independent risk factors were established to find out who will benefit most from TACE monotherapy. The type of portal vein tumor thrombosis was classified based on the Cheng’s Classification. The accuracy of the models was validated in validation cohort.ResultsTotally, 242 patients (training cohort: n ​= ​159; validation cohort: n ​= ​83) were included. The median OS was 7.1 and 8.5 months in training and validation cohort, respectively. In training cohort, the PP model was established based on the following five independent risk factors: Cheng’s Classification, Eastern Cooperative Oncology Group score, maximum tumor size, number of HCC nodules, and Child-Pugh stage. PP score of 17.5 was identified as cut-off point and patients were divided into two groups by PP score <17.5 and >17.5 in survival benefit and prognostication (8.8 vs. 5.5 months; P ​< ​0.001). These five factors were included and ranked based on the importance associated with OS in the ANN model. Both of the two models received high accuracy after validation.ConclusionsPortal vein invaded HCC patients with PP score <17.5 may benefit most from TACE monotherapy. For these patients, TACE monotherapy should be considered.     

CT灌注成像在肝癌TACE治疗中的应用价值

肝细胞癌(HCC)是慢性肝病患者中死亡率较高的恶性肿瘤,已成为一个主要的全球健康问题。对于失去手术切除机会的肝癌患者,肝动脉化疗栓塞(TACE)是有效的治疗方法。肝癌TACE治疗反应的评价是决定治疗成功和指导后续治疗的关键。CT灌注成像能够精确提供正常肝脏组织和局部病变的微循环信息,可以用于肝癌TACE治疗的评价。本文主要阐述CT灌注成像的基本概念及其在肝癌TACE治疗中的应用价值。     

Plain and gadolinium-DTPA-enhanced MR imaging of hepatocellular carcinoma treated with transarterial chemoembolization

Background: To assess unenhanced and gadolinium-enhanced magnetic resonance (MR) imaging patterns of hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). Methods: Thirty-two patients with 48 HCC lesions underwent MR imaging before and 15 days after TACE. Fifteen lesions were then surgically resected. The remaining 33 lesions were not removed and were followed up with MR imaging at 3, 6, 12, and 18 months after treatment. Spin echo (SE) T1- and T2-weighted and gadolinium-enhanced SE T1-weighted sequences were employed. Qualitative evaluation of signal intensity pattern of the treated lesions was performed in all cases. Histological evaluation and selective hepatic arteriography were considered the gold standard of the study for the 15 resected lesions and the 33 unresected lesions, respectively. Results: On follow-up enhanced T1-weighted images of the 15 resected lesions, seven showed no area of enhancement corresponding to complete necrosis at histologic examination. The remaining eight resected lesions showed areas of enhancement; in six of these cases, viable tumor tissue was found at histology; in the other two lesions, histologic examination revealed the presence of complete tumor necrosis. In the group of resected lesions, T2-weighted images showed no pattern characteristic of necrosis. In 24 of 33 unresected lesions, loss of enhancement on follow-up enhanced T1-weighted images was a characteristic finding, which correlated to devascularization at arteriography. Of these 24 lesions, 17 were completely hypointense on follow-up T2-weighted images; the remaining seven showed small foci of hyperintensity. The other nine unresected lesions showed enhanced portions on follow-up enhanced T1-weighted images, which corresponded to hyperintense areas on T2-weighted images. These findings correlated to persistence of hypervascular areas at arteriography. Conclusion: Gadolinium-enhanced T1-weighted MR imaging is a reliable method for evaluating the outcome of TACE treatment and is more accurate than unenhanced T2-weighted MR imaging. Received: 2 June 1995/Accepted: 18 July 1995     

耳穴点压治疗肝癌介入术后呃逆的临床观察

目的　研究耳穴点压法治疗肝癌介入术后呃逆的疗效。方法　将 84例在行肝癌介入术后出现呃逆的患者随机分为耳穴点压组 (观察组 )和利他林肌内注射组 (对照组 ) ,观察组用持续点压耳部“膈肌”穴 5min的方法治疗 ,对照组用利他林 2 0mg肌内注射的方法治疗 ,对其有效率、生效时间和副作用进行观察。结果　有效率 :观察组 85 .71% ,对照组 83.33% ,两组比较 ,P >0 .0 5 ,无显著性差异 ;生效时间 :观察组为 1.6± 1.8min ,对照组为 15 .4± 4.6min ,两组比较 ,P <0 .0 1,有显著性差异 ;副作用 :观察组无副作用 ,对照组有 6例出现副作用。结论　耳穴点压治疗肝癌介入术后呃逆具有无损伤、无副作用、起效迅速的特点。     

原发性肝癌切除术后早期行肝动脉造影和肝动脉栓塞化疗对发现和治疗残癌的价值

目的:探讨肝动脉造影和肝动脉栓塞术在防治肝癌切除术后残癌的应用价值。方法:在原发性肝癌切除术后的2mo,对69例原发性肝癌切除术后患者(其中根治性性手术51例、姑息性手术18例)进行肝动脉造影和肝动脉栓塞化疗,比较了肝动脉造影和B超在诊断术后残癌的敏感性,观察了肝动脉栓塞化疗治疗残癌的临床效果。结果:69例原发性肝癌切除术后患者中发现残癌26例,其中姑息性手术者残癌的发生率为100％(18/18),根治性手术者15.7％(8/51)。残癌的平均直径为2..71±2.16cm,直径≤1cm占23.1％(6/26),≤2cm为65.4％(17/26),但多为多发性,占69.2％(18/26)。比较同期的B超和肝动脉造影发现残癌的敏感性,B超阳性者占38.5％(10/26),肝动脉造影阳性者占92.0％(23/25),肝动脉造影敏感性高于B超(p<0.005)。26例残癌经肝动脉栓塞化疗,其1a,2a生存率分别为90.0％和78.0％。结论:肝动脉造影能够早期发现术后残癌,原发性肝癌切除术后有残癌倾向者,特别是姑息性手术者应进行肝动脉栓塞化疗。     

肝动脉化学栓塞序贯适形放疗治疗中晚期原发性肝癌

目的 探讨肝动脉化学栓塞(TACE)联合三维适形放射治疗(3-DCRT)对中晚期原发性肝癌的疗效.方法 确诊的中晚期原发性肝癌67例分为两组,A组38例行肝动脉化学栓塞(TACE)后序贯三维适形放疗(3-DCRT),B组29例单用TACE.比较两组的近期疗效和毒性反应.结果 A组完全缓解(CR)4例,部分缓解(PR)21例,总有效率(CR PR)为65.8%;B组CR 0例,PR 11例,总有效率为37.9%,A组近期疗效优于B组,差异有显著性(P＜0.05).而两组治疗前后毒性反应无明显差异(P＞0.05).结论 肝动脉化学栓塞后序贯三维适形放疗能提高中晚期原发性肝癌的近期疗效,但不增加毒副作用.     

Current status of the combination therapy of transarterial chemoembolization and local ablation for hepatocellular carcinoma

Abdominal Radiology - To review the current status and ideal time interval of the combination therapy of transarterial chemoembolization (TACE) and local ablation for patients with HCCs. In recent...