Transarterial Radioembolization Agents: a Review of the Radionuclide Agents and the Carriers

Liver tumors, both primary and secondary to metastatic disease, remain a major challenge, with an increasing incidence. In this context, taking advantage of the dual blood supply of the liver, and the fact that liver tumors derive majority of their blood supply from the hepatic artery, intraarterial therapies are gaining popularity. Intraarterial liver-directed therapy (IALDT) is the option when the surgery is not feasible due to the number of metastases or for other reasons. Transarterial radioembolization (TARE) is a specific type of IALDT, where a carrier particle/microsphere is labeled with a radioactive substance and then is injected into hepatic artery for therapeutic purposes. As this field is rapidly evolving, with multiple agents being investigated and being introduced into clinical practice, it is hard for the practitioners and researchers to encompass all the available information concisely. This article aims to present a comprehensive review of the prominent TARE technologies.     

转移性肝癌的介入治疗

目的探讨转移性肝癌的介入治疗方法及疗效。方法收集我院2004年8月至2008年4月介入治疗的62例转移性肝癌,其中胃肠道肿瘤肝转移40例,肺癌肝转移10例,胰腺癌肝转移4例,鼻咽癌肝转移3例,胆总管癌肝转移3例,膀胱癌肝转移1例,前列腺癌肝转移1例。62例中,病灶为富血供27例,中等血供15例,乏血供20例,对于病灶为富血供、中等血供者进行肝动脉化疗栓塞;乏血供病灶进行置管持续灌注化疗,导管保留1周,间隔3～4周,次。介入治疗后,分析其临床症状体征及生存期。结果介入治疗后,所有患者临床症状体征不同程度地减轻,未发生与操作有关的严重并发症,通过随访,生存率0．5a96．8％,1a61．3％,2a41．9％,3a12．9％。结论对于不能手术的转移性肝癌依其不同血供选择合适的介入治疗方式,可达到较好的临床效果。     

分期手术联合射频消融和化疗栓塞治疗结肠癌肝转移12例

目的探讨分期手术联合射频消融、肝动脉化疗栓塞治疗结肠癌术后双叶肝转移的临床价值。方法 2004年12月—2007年12月我科选择性接收并采取分期手术治疗结肠癌术后双叶肝转移患者12例。Ⅰ期手术,结扎横断大多数结肠癌转移灶隶属肝叶的门静脉Ⅰ级分枝(左:右=1:11),射频消融残余肝叶内转移灶,并经胃十二指肠动脉植入肝动脉化疗泵;术后通过化疗泵行3个疗程化疗栓塞。Ⅱ期手术,全部化疗疗程结束后4周行半肝切除术。随访30月,记录术后并发症、化疗客观疗效和毒副作用、残余肝和肝外发现转移瘤时间以及实际生存时间。结果围术期内患者无死亡和肝功能衰竭,呼吸道感染/尿道感染/切口感染(2/2/2,例)是主要的术后早期并发症。患者化疗后无CR,PR 83.3%(10/12),主要不良反应为白细胞减少/血小板减少/贫血(6/3/3,例次)。2例患者术后10月残余肝内发现转移灶(超声引导下射频消融),4例患者术后17月发现肝外转移(肺2例,骨2例;立体定向R-刀治疗)。1、2年总体实际生存率分别为100%和75%,中位生存期26个月。结论分期手术联合射频消融、肝动脉化疗栓塞治疗部分结肠癌术后双叶肝转移患者近期疗效满意,不良反应可耐受,且能增加患者肝转移癌切除率、提高生活质量和生存期,是治疗结肠癌术后双叶肝转移的较好模式之一。     

Interventional radiology for advanced hepatocellular carcinoma: comparison of hepatic artery infusion chemotherapy and transcatheter arterial lipiodol chemoembolization

OBJECTIVE: The prognosis of advanced hepatocellular carcinoma remains poor. The aim of this study was to compare the efficacy of hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization for treatment of advanced tumor. SUBJECTS AND METHODS. Thirty-seven patients with hepatocellular carcinoma and unresectable tumors were enrolled. In the hepatic artery infusion chemotherapy group (n = 16), cisplatin (10 mg/person, on days 1-5) and subsequent 5-fluorouracil (250 mg/person, on days 1-5) were administered for four serial courses. In the transcatheter arterial Lipiodol chemoembolization group (n = 21), an emulsion of Epirubicin (20-30 mg/person) and Lipiodol was administered every 3-4 weeks. RESULTS: The tumor response rates (complete response plus partial response for all cases) of the hepatic artery infusion chemotherapy and transcatheter arterial Lipiodol chemoembolization groups were 56.3% and 23.8%, respectively, showing the significantly higher rate in the former than in the latter group. The cumulative survival rates between the two groups were not significantly different; whereas in those patients whose tumors were classified as TNM stage IV or as having the maximal tumor size of greater than 5 cm, patients tended to have higher survival rates in the hepatic artery infusion chemotherapy group than in the transcatheter arterial Lipiodol chemoembolization group. Univariate analysis identified the serum aspartate aminotransferase value as solely significant. Patients' adverse reactions were successfully managed by treatment of symptoms. Adverse events, such as obstructions of the catheter or hepatic artery or infection around the catheter, rarely occurred. CONCLUSION: Hepatic artery infusion chemotherapy had a better antitumor effect than transcatheter arterial Lipiodol chemoembolization and may be a useful therapeutic option for more advanced hepatocellular carcinoma.     

选择性肝动脉化疗药物灌注及栓塞治疗肝转移癌

目的 探讨选择性肝动脉化疗药物灌注及栓塞治疗肝转移癌的价值。材料与方法对122例失去手术机会的肝转移癌患者，采用经股动脉穿刺，选择性肝动脉插管灌注化疗药物(ADM，MMC，CDDP，5-FU)，并用ADM及碘化油乳化后检塞肝动脉。结果近期疗效以CT检查结果作为评价标准，总有效率为54％(66／122)，平均生存期22．2个月。0．5、1、2、3年生存率分别是98．3％、80．4％、40．9％、10．6％。结论经肝动脉化疗药物灌注及栓塞治疗是失去手术机会的肝转移癌患者的一种安全、有效的姑息性治疗方法，其不仅能提高疗效，而且能改善患者的生活质量。     

经肝动脉栓塞治疗转移性肝癌的方法探讨及疗效分析

目的探讨经肝动脉化疗并栓塞治疗转移性肝癌的方法及效果。方法180例转移性肝癌患者经造影后根据血供情况分别采用单纯灌注化疗(HAI)、化疗并用稠度不同的碘油化疗药乳剂栓塞治疗(TACE),并观察其临床效果。结果临床效果以肝癌和直肠癌肝内转移最佳,有效率分别为87.5%、84.3%。少血管型化疗栓塞组有效率为86.3%,明显高于单纯灌注化疗组的73%(P<0.01)。结论经肝动脉化疗栓塞是治疗转移性肝癌的一种有效方法,对少血供型患者采用稀碘油化疗药乳剂适量栓塞可以明显提高治疗效果。     

Application of single-photon emission computed tomography (SPECT) with99mTc-MAA in evaluation of perfusion patterns during hepatic infusion chemotherapy

In 6 patients receiving hepatic artery infusion chemotherapy for liver metastases, planar and single-photon emission computed tomography (SPECT) images of the abdomen were obtained after intravenous injection of 99mTc-phytate, and intra-catheter injection of 99mTc-MAA in the same geometrical settings. With this method, the three-dimensional intra- and extra-hepatic distribution of the agents during hepatic artery infusion chemotherapy can be evaluated.     

Stabilization of a percutaneously implanted port catheter system for hepatic artery chemotherapy infusion

A port catheter system for hepatic artery infusion chemotherapy was implanted percutaneously via the left subclavian artery in 41 patients for treatment of unresectable liver metastases. The catheter tip was inserted into the gastroduodenal artery (GDA), the end hole was occluded with a guidewire fragment, and a side-hole for infusion was positioned at the bifurcation of the proper hepatic artery and the GDA. The GDA was embolized with steel coils around the infusion catheter tip via a transfemoral catheter. This procedure is designed to reduce the incidence of hepatic artery occlusion and infusion catheter dislocation.     

Reexamination of hepatic falciform artery: angiographic study]

Supraumbilical skin complication during hepatic artery infusion chemotherapy or transcatheter arterial chemoembolization (TACE) for liver tumor has been reported by some authors. This complication is thought to be caused by the flow of chemotherapeutic, agent and embolus into the hepatic falciform artery (HFA). It is important for angiographers to be aware of the presence of HFA to prevent possible supraumbilical skin complication. The rate of visualization of the HFA on angiography has been considered to be only about 2%. In a retrospective study of celiac angiograms performed in 200 patients, we found an incidence of 32/200 (16%). The proximal side of this artery may be tortuous. In all cases, the flow of the HFA is slower than that of the hepatic artery. The paraumbilical vein was visualized with the HFA in 18 cases. Chemotherapy or transcatheter arterial chemoembolization was performed in 10 patients, and there was no postprocedure supraumbilical skin complication.     

大肠癌肝转移的介入治疗

目的：探讨采用介入化疗并栓塞方法治疗大肠癌肝转移的疗效,并发症及生存期。材料与方法：治疗组３８例采用介入法肝动脉栓塞化疗,对照组２４例采用常规全身静脉化疗。结果：介入栓塞化疗组ＣＲ＋ＰＲ为８４．２％,全身静脉化疗组ＣＲ＋ＰＲ为３７．５％,两组比较,介入栓塞化疗组３８例中６、１２和２４个月的生存率分别为９４．７％、６４．５％和４１．７％,而单纯静脉人 组２４例中６、１２和２４个月的生存率分别为５９．     

外生性肝癌的血供特点及介入治疗

目的探讨外生性肝癌血供特点及经肿瘤供血动脉化疗栓塞术的疗效。方法5例外生性肝癌经股动脉插管,肿瘤供血动脉造影、化疗栓塞治疗,用榄香烯350 mg肿瘤血管内热灌注化疗和顺铂60～80 mg加碘油8～15 ml乳剂及明胶海绵化疗栓塞。结果5例患者共行10次经血管途径的化疗栓塞术。造影显示肿瘤供血动脉以肝外血管为主,肝动脉部分参与供血。5例患者术后瘤体缩小30%～50%,4例AFP下降。结论外生性肝癌有不同于肝内肝癌的血供特点,经肿瘤供血动脉化疗栓塞术对外生性肝癌同样有效,是可供选择的治疗方法之一。     

Minimally invasive catheter implantation for regional chemotherapy of the liver: A new percutaneous transsubclavian approach

Purpose Development of a percutaneously implantable catheter system for regional chemotherapy of liver metastases and its application in patients with surgically implanted but dislocated catheters. Methods Thirty-three patients with liver metastases of colorectal tumors were submitted to percutaneous puncture of the subclavian artery and insertion of a catheter whose tip was placed in the proper hepatic artery and whose end was subcutaneously connected with an infusion pump. Results The mean duration of therapy via the percutaneously inserted catheter was 27 weeks (±14 weeks). The most frequent complication was disconnection of the therapy catheter from the tube of the infusion pump. Eighty percent of all complications were corrected by reintervention. The therapy drop-out rate due to catheter-associated complications was 9%. Conclusion Percutaneous insertion of a catheter for regional chemotherapy of the liver is a relatively uncomplicated method with high patient acceptance and simple access for reintervention.     

Arterial perfusion abnormalities of the liver after hepatic arterial infusion chemotherapy and their correlation with changes in the metastases: evaluation with CT and angiography

We studied the progress of hepatic arterial perfusion abnormalities in 50 patients receiving long-term arterial infusion chemotherapy for palliative treatment of liver metastases from colorectal cancers and correlated the findings with changes in the metastases. Intraarterially and IV enhanced CT scans and digital subtraction angiograms of the liver were made in all patients before chemotherapy and at 3-month intervals during chemotherapy for 1 year. Before the chemotherapy, all patients had normal hepatic arterial perfusion. Arterial perfusion abnormalities were detected in 30 patients (60%) after 6 months of chemotherapy and in 41 patients (82%) after chemotherapy for 1 year. After 6 months of chemotherapy, 36% of the regressive and 39% of the progressive metastases were located in areas with arterial perfusion abnormalities. After 1 year of chemotherapy, 54% of the regressive and 60% of the progressive metastases were situated in portions of the liver with perfusion abnormalities. Hepatic arterial perfusion abnormalities were found to be progressive during intraarterial infusion chemotherapy. No relationship between arterial perfusion abnormalities and tumor response to chemotherapy could be detected.     

肝癌的肝外动脉供血及其介入治疗

目的　探讨肝癌肝外动脉供血规律、插管技术及介入治疗。方法　总结７６ 例肝癌肝外动脉供血特征。７６ 例肝癌动脉栓塞术前常规腹腔动脉、肝总动脉、肠系膜上动脉造影,对位于膈顶部肿瘤还作膈动脉造影,发现肝外供血支进一步超选插管,并同时进行肝动脉、肝外动脉双动脉内化疗栓塞术。结果　７６ 例肝外供血支,由肝动脉闭塞引起侧支动脉供血达２１ 例,其余５５ 例为肝脏本身固有的寄生性供血。肝外供血与肿块部位、大小密切相关。Ｃｏｂｒａ、Ｙａｓｈｉｒｏ 导管配合ＳＰ 导管肝外动脉插管成功率为７２ ．４％ ,随访３６ 例,１、２ 年生存率分别为５２ ％ 和２１％ 。结论　１ ． 依据肿块部位积极寻找肝外供血支;２． 在介入治疗中,预防肝动脉闭塞,减少侧支供血形成至关重要;３． 对具有肝外动脉供血的肝癌采取双动脉内化疗栓塞是必要的、有效的     

Temporary indwelling catheter system via the left brachial artery: evaluation in 83 patients with hepatic tumors

OBJECTIVE: The purpose of our study was to evaluate retrospectively the usefulness and complications associated with a temporary indwelling catheter system through the brachial artery for patients with liver tumors. CONCLUSION: The temporary indwelling catheter system via the left brachial artery can be used not only for CO2-enhanced sonographically guided aspiration biopsy, radiofrequency ablation, and percutaneous ethanol injection, but also for short-term hepatic arterial infusion chemotherapy and transcatheter arterial chemoembolization.     

Indication for chemoembolization of liver tumors. An interdisciplinary concept and initial results]

We present a new concept after Schultheis which is based on the results of experimental studies on cell cultures. Local chemoembolization in liver tumours including liver metastases is usually performed via the angiographic route. Embolisation of the most peripheral branches of the hepatic artery prevents early formation of collateral vessels. The method also comprises the additional infusion of cytostatic agents via the portal vein. The procedure is usually repeated after an interval of about four weeks. In this paper we will describe our method in liver metastases and present the preliminary results obtained from 19 patients treated to date.     

16层螺旋CT动脉造影对肝癌动脉供血血管显示效果及临床价值

目的:评价16层螺旋CT在肝癌动脉供血血管显示的价值。方法:对65例肝癌患者进行16层螺旋CT增强扫描,将动脉期序列原始扫描数据传至工作站利用容积重建、最大密度投影及多曲面重建法重建腹腔动脉的解剖和走行,观察肝癌病灶动脉供血血管来源情况,其中65例患者行动脉化疗栓塞术前进行了DSA检查,将65例DSA结果与CT血管造影进行对比。结果:65例肝癌患者中,47例肝动脉解剖正常,肝癌病灶动脉血供来源于正常的肝动脉;18例肝动脉解剖变异,肝癌病灶动脉血供来源于变异肝动脉。CTA显示肝动脉血管解剖及变异及肝癌动脉供血来源与DSA完全相同。结论:16层螺旋CT动脉造影对肝动脉血管解剖及变异及肝癌动脉供血血管能较好的显示,对肝癌的外科手术及介入治疗具有重要的指导作用。     

右肾包膜动脉化疗栓塞在原发性肝癌介入治疗中的安全性及有效性研究

目的右肾包膜动脉参与原发性肝癌供血发生率低,既往文献报道少。本研究回顾性分析其临床特点及影像学资料,并探究右肾包膜动脉化疗栓塞在原发性肝癌患者中的有效性及安全性。 方法2016年5月至2019年12月,共纳入13例右肾包膜动脉参与原发性肝癌供血病例,观察并分析其影像学资料、右肾包膜动脉造影及参与肿瘤供血特点、化疗栓塞术后并发症以及近期疗效。 结果患者肿瘤大小为2.4～15.6 cm,平均8.0±4.25 cm。所有患者肿瘤均位于Ⅴ、Ⅵ、Ⅶ段中一段或两段,其中,69.2%（9/13）患者肿瘤压迫或紧贴右肾。10例患者仅由肾包膜上动脉供血,2例患者仅由肾包膜中动脉供血,1例患者同时由肾包膜上动脉、中动脉供血,无肾包膜下动脉供血病例。术后1个月及3个月局部控制率分别为92.3%、84.6%。 结论对于肝肿瘤位于右后叶且肿瘤负荷较大时,可常规行右侧膈下动脉及右肾包膜动脉造影,明确是否参与肿瘤供血。右肾包膜动脉化疗栓塞安全有效,近期疗效确切。     

Arterial lipiodol chemoembolization of a left liver metastasis through the right internal thoracic artery]

The purpose of this article is to illustrate the efficacy of the chemoembolization in patients with hypervascular metastases and to describe the post-embolization change in vascularization pattern. Unusual collaterals may develop following embolization. A 59-year-old woman, followed for unresectable small bowel carcinoid tumor since 1991, underwent successful chemoembolization of several liver metastases. Only one liver lesion, located in segment IV, showed interval increase in size. This lesion was supplied by the right internal mammary artery. A branch of the right internal mammary artery was catheterized using a microcatheter and embolization was performed using doxorubicine-Lipiodol (Adriblastine, Lipiodol) and gelfoam (Spongel). No complications occurred after the procedure. The right internal mammary artery should be considered as a possible source of collateral arterial supply to the liver and should be evaluated in patients with local progression of disease.     

肝癌的规则性、变异性、寄生性供血及对TACE治疗的影响

目的探讨肝癌的规则性、变异性、寄生性供血情况,以提高TACE治疗肝癌的疗效。方法回顾分析经病理及影像资料证实的肝癌病灶52枚。行常规DSA造影,当发现肿瘤无染色或动脉期存在部分无血管区及实质期充盈缺损时,再分别行肠系膜上动脉、胃左动脉、膈下动脉、右肾上腺动脉、胸廓内动脉、肋间动脉DSA造影。结果肝癌的规则性供血病灶39枚,占75%;肝癌的变异性供血病灶13枚,占25%;肝癌的寄生性供血病灶11枚,占21%。结论肝癌病灶主要供养动脉来自肝动脉的规则性供血,但尚有25%的肝癌病灶存在变异性供血。积极地通过肝癌的规则性、变异性、寄生性供血动脉进行肝癌的化疗栓塞,能进一步提高疗效。