Treatment of liver metastases by arterial injection of adriamycin/mitomycin C lipiodol suspension

Sixty-one patients with liver metastases were treated with hepatic arterial injection of Adriamycin/Mitomycin C oil suspension (ADMOS). The liver metastases originated from the gastrointestinal tract in 41 patients and from other organs in 20 patients. Sixty-nine liver tumors were analyzed in these 61 patients. Computed tomography (CT) after ADMOS injection (Lip-CT) gave more information in 19 cases (31%) than enhanced CT with a water-soluble contrast medium. With Lip-CT, Lipiodol tumor enhancement was observed in 64 of 69 lesions. The patterns of Lipiodol uptake in the tumors were classified into 4 types: Homogeneous accumulation (20%), heterogeneous accumulation (16%); accumulation with a central defect (57%); and no accumulation (7%). A tumor response was achieved in 41 of 69 lesions (59%). Anticancer effects were also shown as a decrease in serum CEA levels. The one year survival rate estimated by the Kaplan-Meier method was 43 per cent and the median survival time was 337 days. The results were better among patients who received multiple doses of ADMOS. Only minimal side effects were associated with ADMOS. The method is considered to be an excellent diagnostic and therapeutic procedure for liver metastases.     

Transarterial internal radiation therapy with I-131 lipiodol for multifoca hepatocellular carcinoma: Immediate and long-term results

Transarterial internal radiation with I-131 Lipiodol (TAIR) was performed in 21 patients with multifocal hepatic carcinoma. Eight patients were treated by TAIR alone and 13 by combination of TAIR and intraarterial infusion ofcis-diamminedichloroplatinum (CDDP) and/or adriamycin mitomycin C oil suspension (ADMOS). TAIR was found effective immediately and long-term. Serum α-fetoprotein (AFP) levels dropped to 50% or less in 7 of 14 patients. Eleven of 21 patients (52%) showed 50% or greater decrease in tumor size. The overall 1-year survival rate was 43% and 67% in patients who received 50 Gy or greater tumor dose. Lipiodol distribution pattern of the tumor indicated some difference in the prognosis between the scattered pattern and solid pattern. The solid pattern showed a statistically significant better survival rate. Patients treated with TAIR alone versus those treated with TAIR and chemotherapy showed no difference in their survival rate.     

Metastatic nodules of hepatocellular carcinoma: detection with angiography, CT, and US

Accurate detection of intrahepatic metastases, or daughter nodules, of primary hepatocellular carcinoma is of crucial importance. Due to the introduction of infusion hepatic angiography, computed tomography (CT) after Lipiodol (iodized oil) infusion, and intraoperative ultrasound (US), tumors less than 10 mm in diameter are now frequently found. We compared the diagnostic accuracy of these three modalities in the detection of nodules in 45 patients who had hepatocellular carcinoma (confirmed by biopsy). CT with Lipiodol was superior to hepatic angiography in demonstrating nodules when they were overlapped by the primary tumor or very small in size. Intraoperative US demonstrated nodules in four avascular or hypovascular hepatocellular carcinomas, which both hepatic angiography and CT failed to demonstrate. In cases associated with severe liver cirrhosis, differentiation of small nodules from regenerating cirrhotic nodules was sometimes difficult with intraoperative US. The combined use of these three modalities is indispensable for the accurate detection of small nodules of metastatic hepatocellular carcinoma.     

Liver intervention

Interventional radiology is now widely performed for the treatment of liver tumors, because surgery is sometimes limited by poor liver function. Transcatheter arterial chemoembolization(TACE) is an effective therapy for hepatocellular carcinoma. Lipiodol TACE shows a strong antitumor effect because of the overflow of excess iodized oil into the portal veins, and segmental TACE is recommended to avoid deteriorating liver function. Selective CT arteriography is performed in order to decide on the treatment area, and TACE under CT guidance leads to effective results in terms of dense accumulation of the chemotherapeutic drug in the individual tumors that are affected by the ischemic state and anticancer drugs. Percutaneous microwave or radiofrequency coagulation therapy is adequate for a few of the hypovascular tumors. Excessive coagulation through the needle tract is indispensable in these therapies, and precisely designed puncture is necessary to minimize damage to the liver parenchyma. Selective chemotherapy to the tumor-bearing organ is the first step in a number of liver tumors. Continuous intra-arterial infusion chemotherapy is performed for multiple liver metastases. The reservoir implantation technique is percutaneously achieved via the left subclavian artery under ultrasound guidance, without the exposure of an artery in the incision method, which can induce thrombus formation.     

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.     

Intra-arterial injection of adriamycin/mitomycin C lipiodol suspension in liver metastases

Intra-arterial injection of a suspension of adriamycin and/or mitomycin C in Lipiodol was performed in 17 patients with hepatic metastases, which at angiography were poorly vascularized. Accumulation of Lipiodol in the tumors was demonstrated at computed tomography (CT) in 15 of 17 patients examined within one week. Follow-up with CT showed that Lipiodol remained in the tumor during the first month in 94 per cent, after 2 months in 31 per cent, and after 3 months in 17 per cent. In the non-tumor part of the liver Lipiodol disappeared earlier, and one month after injection it could no longer be traced on CT. In 8/17 cases (47%) CT, after intra-arterial injection of Lipiodol, gave superior information compared with CT after intravenous contrast enhancement. Tumor response was achieved in 9 of 16 cases. Particularly in metastases originating from cancer of the colon and stomach response was observed with a decrease in tumor size in 8 of 10 patients.     

肝转移性肿瘤DSA表现分析

目的 探讨肝转移瘤血供特点与原发性肝癌的鉴别以及和原发肿瘤的相关性。材料与方法 搜集５１例肝转移瘤ＤＳＡ影像,根据肿瘤血管的多少和肿瘤染色深浅分为多血供、中血供和少血供,原发肿瘤包括腺癌３８例,鳞癌８例,其他类型５例。结果 肝转移瘤血供来源主要为肝动脉,门静脉参与供血,多血供肝转移１２例,中血供７例,少血供３２例。累及肝右叶少血供转移２７例,腺癌转移多于动脉晚期及以后显示多或单发环状染色;鳞癌转移     

Hilar cholangiocarcinoma. An evaluation of subtypes with CT and angiography.

Sixty-seven patients had hilar cholangiocarcinomas which were divided into 3 types based on tumor morphology as observed on cholangiography and CT. The pathology, vascularity, and pattern of tumor spread of these types were compared. Most of the infiltrative tumors (n = 44) were scirrhous adenocarcinomas, which on CT showed poor or no contrast enhancement with frequent lymph node metastases and liver atrophy. At angiography, there was vascular encasement in 52%, in rare cases neovascularity, and tumor stain. The exophytic type (n = 19) was divided into 2 subgroups depending on the main location of the tumor. The nodular subtype (n = 16) was mainly inside the liver and somewhat hypervascular similar to peripheral cholangiocarcinoma, often with intrahepatic metastases. The periductal subtype (n = 3) was hypovascular, similar to the infiltrative cholangiocarcinoma, and had a tendency to spread along the portal vein. The intraductal type (n = 4) was observed as a filling defect on cholangiography. CT revealed an intraluminal low density mass. Histologically, they were papillary adenocarcinomas. The radiologic types of hilar cholangiocarcinoma showed different characteristics with regard to pathologic findings, vascularity, and pattern of spread.     

肝胆管细胞癌并发肝脓肿的MSCT诊断

目的:探讨肝胆管细胞癌并发肝脓肿患者的MSCT诊断价值。方法:收集15例肝胆管细胞癌合并肝脓肿患者的MSCT资料进行回顾性分析。结果:15例患者CT平扫图像上发现31处边界模糊的低密度病灶,包括15处肝内胆管细胞癌和16处肝脓肿。病灶位于肝右叶者12处,位于肝左叶者19处,其中10例患者肝胆管细胞癌和肝脓肿位于同一肝段或肝叶,5例患者肝胆管细胞癌和肝脓肿位于不同肝段或肝叶。15处肝胆管细胞癌中,肿块型5处,表现为肝实质内轻～中度环形强化结节,常不伴有周围胆管扩张;管周浸润型4例,表现为沿胆管纵轴生长的树枝状肿块,伴有周围胆管扩张;肿块并管周浸润型6例,表现为肝实质内轻～中度延迟强化结节,常伴周围胆管扩张。16处肝脓肿病灶动态强化CT图像上,表现为中央完全强化者3处;中央不完全强化者6处,其中表现为伴中央小范围不强化者2处,表现为花簇状、多间隔强化者4处;表现为中央不强化者7例,称为肝脓肿的典型表现,即周围环形强化而中央不强化。结论:肝内胆管细胞癌和肝脓肿有着不同的强化特征,因此动态增强CT对同时患有肝胆管细胞癌和肝脓肿的患者有重要价值。     

Acalculous cholecystitis complicating hepatic intraarterial lipiodol: Case report

Hepatic intraarterial injection of Lipiodol has been used by various authors to enhance the diagnostic accuracy of computed tomography in hepatic tumors. The technique appears safe and seems free from serious complications when used judiciously. We report a case in which injection of hepatic intraarterial Lipiodol precipitated acalculous cholecystitis requiring urgent laparotomy.     

Prognostic factors in liver metastases after transcatheter arterial embolization or arterial infusion

From January 1986 to December 1988, 85 patients (55 men and 30 women, mean age 59 years) with metastatic liver tumors were treated with hepatic artery embolization (TAE) or infusion (HAI). Sixty-eight patients with successful catheterization were treated with TAE using iodized oil (Lipiodol) mixed with anticancer agent (ACA). In 12 of 68 patients with hypervascular tumors gelatin sponge was added. Patients with unsuccessful catheterization were treated with hepatic artery infusion of ACA. Forty-three patients received oral chemotherapy following TAE or HAI. Overall, the 6-month, and 1- and 2-year survival rates were 69.5, 31.8 and 4.1 per cent, respectively (mean 233 days). A univariate analysis of prognostic factors showed that number of metastases, stage, treatment times and oral chemotherapy were all significant factors (p less than 0.05). Ascites, jaundice, percentage of hepatic replacement and treatment protocol also had some influence (p less than 0.1). Sex, age, primary site, elevation of tumor markers, other metastatic lesions, portal vein involvement and difference in anticancer agent had no prognostic significance. A multivariate analysis using Cox's proportional hazard model revealed that the number of treatments had the most important prognostic significance, followed by oral chemotherapy, stage and percentage of hepatic replacement.     

微导管在肝动脉化疗栓塞治疗原发性肝癌的临床应用

目的 评价3.0F微导管在肝动脉化疗栓塞治疗原发性肝癌中的临床应用价值，讨论其操作技术和使用适应证。资料与方法 32例原发性肝癌患者采用3.0F SP导管进行化疗栓塞治疗。使用SP导管的原因为：肿瘤肝外侧支供血（n=9)；肿瘤供养血管细小需超选择（n=16)；腹腔干和肝动脉解剖变异（n=6)；肝动脉痉挛（n=1)。结果 32例患者共使用SP导管42次，操作成功39次，失败3次，成功率为92.9%。治疗后AFP下降＞50％者27例（84.4%)，肿瘤病灶缩小＞50%者8例（25％），略有缩小者16例（50％），其余患者肿瘤无明显变化。2例成功进行肿瘤内科性亚肝段切除。全部患者术后均无严重并发症。结论 微导管操作简单、方便，超选择成功率高，特别适用于肿瘤供血动脉严重狭窄、细小，走行迂曲和容易痉挛的患者，在肝动脉化疗栓塞治疗原发性肝癌中有较高的应用价值。     

肝动脉化疗栓塞后碘油在肝癌内聚积、存留和消失的血管造影、CT与病理对照研究

用血管造影和ＣＴ对照分析肝动脉化疗栓塞后碘油在肝癌内的初期聚积特点，用ＣＴ动态观察碘油在肝癌内的存留和消失时间，同时与栓塞后切除标本行病理对照研究。结果表明：碘油能选择性聚积于多血供的肝癌内，且聚积量与肿瘤血供有关。少血供肝癌无或少有碘油聚积。碘油能选择性聚积并持续存留部是肿瘤栓后坏死区，一般存留２～６月甚至更长，伴肿瘤明显缩小；碘油虽能选择性聚积但逐渐消失部是肿瘤栓后存活区，一般１～２月消失，肿瘤缩小不明显或反增大。少量碘油在非癌肝实质一般２周消失。对碘油聚积、存留物消失问题的阐明，为肝癌的介入治疗提供了理论依据。     

经动脉灌注端粒酶抑制剂AZT对大鼠Walker-256肝肿瘤的影响

目的:观察经动脉灌注端粒酶抑制剂AZT对大鼠种植型walker-256肝癌的影响,探讨采用经动脉介入法应用端粒酶抑制剂治疗肝脏恶性肿瘤的可能性。方法:36例walker-256荷瘤大鼠分为两组,AZT组大鼠在显微镜下经肝动脉灌注端粒酶抑制剂AZT,对照组大鼠采用同样方法灌注等量生理盐水。7天后分别测定各组肿瘤组织端粒酶活性、细胞凋亡率及肿瘤体积的变化。结果:两组大鼠处理前端粒酶活性差异无统计学意义,处理后第7天AZT组肿瘤组织端粒酶活性(A值)明显低于对照组(AZT组0.384±0.131、对照组0.739±0.156,P<0.05),而肿瘤细胞凋亡率与对照组比较则明显升高[AZT组(14.218±0.913)%、对照组(4.025±0.287)%,P<0.05],两组肿瘤体积比较AZT组明显小于对照组[AZT组(371.665±25.298)mm3、对照组(772.943±52.221)mm3,P<0.05]。结论:经动脉灌注AZT能明显降低大鼠肝脏walker-256肿瘤组织的端粒酶活性、提高肿瘤细胞凋亡率、抑制肿瘤生长,采用经动脉灌注端粒酶抑制剂治疗肝脏恶性肿瘤是一种可能应用于临床并值得进一步深入研究的新方法。     

Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion

Transarterial chemoembolization with Lipiodol (Lipiodol TACE), also called conventional TACE, was developed in the early 1980s and widely adopted worldwide after randomized control trials and meta-analysis demonstrated superiority of Lipiodol TACE to best supportive care. Presently, there is no level one evidence that other TACE techniques are superior to Lipiodol TACE for intermediate stage hepatocellular carcinoma (HCC), which includes patients with preserved liver function and nonsurgical large or multinodular HCC without distant metastases. In addition, TACE is part of the treatment for progressive or symptomatic liver metastases from gastroenteropancreatic neuroendocrine tumors. When injected into the hepatic artery, Lipiodol has the unique property of selective uptake and retention in hyperarterialyzed liver tumors. Lipiodol/drug emulsion followed by particle embolization has been demonstrated to improve the pharmacokinetic of the drug and tumor response. Radio opacity of Lipiodol helps to monitor treatment delivery, with retention of Lipiodol serving as an imaging biomarker for tumor response. For 30 years, Lipiodol TACE has been inconsistently referenced in many publications with various levels of details for the method of preparation and administration, with reported progressive outcomes following improvements in the technique and the devices used to deliver the treatment and better patient selection. Consequently, there is no consensus on the standard method of TACE regarding the use of anticancer agents, embolic material, technical details, and the treatment schedule. In order to develop an internationally validated technical recommendation to standardize the Lipiodol TACE procedure, a worldwide panel of experts participated in a consensus meeting held on May 10, 2014 .     

Liver metastases from colorectal cancers: detection with CT during arterial portography

A total of 45 metastases to the liver from colorectal cancer were resected in 22 patients. The detectability of these lesions with the following modalities was determined: real-time ultrasound (US), computed tomography (CT), selective celiac arteriography (SCA), infusion hepatic angiography (IHA), CT during arterial portography (CTAP), and CT following intraarterial injection of iodized poppyseed oil (Lipiodol). The total detection rate (sensitivity) was 58% for US, 63% for CT, 27% for SCA, 50% for IHA, 84% for CTAP, and 38% for CT with iodized oil. Ten of 18 lesions less than 15 mm in largest diameter were demonstrated preoperatively by CTAP only. CTAP is useful in clarifying the locations of the lesions in the liver and should always be performed before liver metastases from colorectal cancer are resected.     

Dense parenchymal accumulation of Lipiodol after transarterial chemoembolization.

Dense accumulation of Lipiodol in hepatic segmental parenchyma was studied by computed tomography (CT) after transarterial chemoembolization (TACE) for hepatic tumor. Six patients showed dense accumulation of Lipiodol in hepatic segmental parenchyma on CT two weeks after TACE. Four of the six showed parenchymal accumulation of Lipiodol as dense as that in a tumor at three weeks after TACE. Therefore, it was considered that evaluation with CT should be performed after one month or more in order to differentiate between Lipiodol accumulation in tumors and that in non-neoplastic liver parenchyma.     

Capsular retraction of the liver in malignant tumor of the biliary tract MRI findings

Retraction of the liver capsule adjacent to a hepatic tumor is an unusual feature that has received little attention in radiological literature. We report two patients with pathologically proved malignant tumor of the biliary tract (one cholangiocarcinoma and one gallbladder cancer) in whom magnetic resonance imaging (MRI) showed retraction of the liver capsule to the tumors. MRI was performed at 1.0 T using a spin-echo (SE) technique, with T1 (TR/TE = 450/15 msec) and T2 (TR/TE = 2000/45 to 90 msec)-weighted images. Capsular retraction was seen on both T1- and T2-weighted SE MRI. Although capsular retraction of the liver adjacent to hepatic tumors is highly suggestive for epithelioid hemangioendothelioma, these two cases confirm that retraction of the liver capsule adjacent to hepatic tumors can be associated with other types of tumor, and especially with malignant tumors of the biliary tract.     

Transcatheter arterial chemoembolization with paclitaxel-lipiodol solution in rabbit VX2 liver tumor

PURPOSE: To evaluate the antitumor effects of transcatheter arterial chemoembolization (TACE) with a solution of an anticancer drug (Paclitaxel; Bristol-Myers Squibb, Princeton, NJ) and iodized oil (Lipiodol; Laboratoire Gurerbet, Aulnay-Sous-Bois, France) (hereafter, the solution), as well as intratumor concentration and hepatotoxicity, in experimentally induced liver tumor. MATERIALS AND METHODS: VX2 carcinoma was grown in livers of 30 rabbits. In 18 rabbits, TACE was performed with the high-dose solution (4 mg anticancer drug and 0.4 mL iodized oil, n = 6), the low-dose solution (1 mg anticancer drug and 0.4 mL iodized oil, n = 6), or iodized oil alone (0.4 mL, n = 6) in a control group. One week later, the growth ratio and residual viable proportion of the tumors were calculated on the basis of findings at spiral computed tomography and histopathologic examination. Hepatic and hematologic toxicities were evaluated by means of biochemical analysis. Differences between the three groups were statistically assessed with the Kruskal-Wallace and Mann-Whitney U tests. The remaining 12 animals were treated with the high-dose solution and serially sacrificed for clarification of chronologic change of concentration of the anticancer drug in liver tissues. RESULTS: Growth ratios and residual viable proportions of the tumors were significantly lower in the solution groups (high dose, 3.3% +/- 6.2 [mean +/- SD] and 2.8% +/- 3.6, respectively; low dose, 18.7% +/- 7.4 and 12.7% +/- 6.1, respectively) than in the control group (68.3% +/- 12.7 and 31.1% +/- 8.8, respectively) (P <.05). Hepatotoxicity was transient in all but one rabbit, which died 2 days after TACE with substantial biochemical changes. The anticancer drug accumulated in tumor where the concentration peaked at day 3 and returned to levels comparable to those for normal hepatic parenchyma at 7 days after TACE. CONCLUSION: TACE with the Paclitaxel-Lipiodol solution has dose-dependent antitumor effects without major toxicities in VX2 liver tumor.     

Hepatic artery infusion and chemoembolization in the management of liver metastases

Hepatic metastases rather than the primary neoplasm usually dictate the course of the disease and the patient's survival. For unresectable disease, intraarterial infusion of chemotherapy, embolization, and chemoembolization are viable alternatives. Intraarterial therapy for hepatic metastases is based on the dual blood supply of the normal liver (portal vein, 75%, and hepatic artery, 25%) and that of the tumors (hepatic artery, 90%). Intraarterial infusion delivers a higher concentration of chemotherapy, whereas chemoembolization adds ischemia and increased contact time with the tumor. Selective vascular occlusion for infusion, redistribution of the blood supply and pulsatile flow enhance the delivery of therapeutic agents to the liver.