A case of advanced hepatocellular carcinoma with portal vein tumor thrombus refractory to epirubicin that showed marked decrease in tumor markers after transcatheter arterial infusion with miriplatin

Miriplatin, a cisplatin derivative with a high affinity for iodized ethyl esters of fatty acids from poppy seed oil, is a novel chemotherapeutic agent designed for use in the transarterial treatment of hepatocellular carcinoma (HCC). Here, we describe transcatheter arterial infusion (TAI) using miriplatin to treat a case of advanced HCC with portal vein tumor thrombus (PVTT) refractory to TAI with epirubicin. A 66-year-old man with advanced hepatitis C virus-related HCC with PVTT in the right lobe of the liver was treated with TAI with epirubicin suspended in iodized oil; however, tumor marker levels (alpha-fetoprotein and des-gamma-carboxy protein) did not decrease. Next, he was treated twice with TAI with miriplatin suspended in iodized oil. The tumor marker levels markedly decreased to a nearly normal range and the size of the main tumor was markedly reduced according to dynamic computed tomography. No serious adverse events occurred during the course of treatment with TAI and miriplatin. Therefore, we suggest that TAI with miriplatin is a safe and effective treatment option for advanced HCCs refractory to TAI with epirubicin.     

Transarterial "pile-up" infusion therapy of cisplatin and lipiodol emulsion in hepatic malignancies without TAE (transcatheter arterial embolization)]

We developed a modified transcatheter arterial infusion method using anticancer agents to treat hepatic malignancies; intermittent injections of iodized oil, lipiodol, containing adriamycin or epirubicin during the arterial infusion of cisplatin (75-200 mg/body) in order to achieve a higher concentration and longer retention of these anticancer agents in the tumor tissue. Fourteen patients with hepatocellular carcinoma (HCC) and five patients with metastatic liver cancer were treated with this "pile-up" arterial infusion therapy by anticancer agents without gelatin sponge TAE. In HCC patients, 50% or greater reduction in tumor size was obtained in 7 of 14 patients (50%). Serum AFP levels decreased by more than 75% in 6 of 7 patients in whom pretreatment serum levels of AFP were more than 200 ng/ml. The one-year and two-year survival rates were estimated at 55% and 27.5%, respectively, by the Kaplan-Meier method. Significant reduction in tumor size was not observed in 5 cases with metastatic liver cancer. Concerning the adverse effects, alimentary symptoms and fever were noted for a few days in many cases, but they were temporary and tolerable in almost all of the patients. Severe adverse changes in laboratory data were not observed. Thus this "pile-up" infusion therapy of anticancer agents without TAE may be a useful therapy for HCC.     

超早期肝动脉栓塞抢救肝癌破裂出血的临床意义

目的研究经导管肝动脉栓塞(TAE)抢救肝细胞肝癌(hepatocellular carcinoma,HCC)自发性破裂出血的方法及效果。方法对15例HCC自发性破裂出血患者行急诊肝动脉插管,联合运用明胶海绵,碘油,真丝线段,弹簧钢圈作出血动脉分支栓塞治疗。结果15例行TAE后出血均得到完全控制。除1例术后第5天死于严重肝肾功能衰竭外,其余14例均存活3月以上,1例随访30个月仍存活。结论用多种栓塞剂行急诊TAE治疗可使HCC自发性破裂出血立即止血。其适应症宽,创伤小,是安全、可靠、简便的抢救手段,且明显优于外科方法。     

中晚期肝癌508例的化疗栓塞疗效及影响因素分析

目的：探讨中晚期肝癌化疗栓塞治疗的疗效及影响生存的因素。方法：对1990年1月－2000年10月间508例中晚期肝癌行选择性肝动脉插管灌注化疗和（或）栓塞治疗共2025次,其中行选择性肝动脉插管灌注化疗栓塞治疗448例,单纯灌注化疗60例。结果：选择性肝动脉插管灌注化疗栓塞一、二、三年生存率分别为81．3％、38．6％、21．6％;单纯灌注化疗一、二、三年生存率分别为54．3％、21．3％、9．6％。肿瘤分类、门静脉是否有癌栓、侧支循环的形成、碘油沉积情况以及栓塞技术是否得当是影响疗效的主要因素。结论：选择性肝动脉插管灌注化疗栓塞可作为中晚期肝癌的常规治疗,远期疗效明显优于单纯灌注化疗。     

Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC.     

A prognostic index of the survival of patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its prognostic usefulness has not previously been clarified. METHODS: The authors reviewed all patients treated at their institution with TACE for unresectable HCC in order to analyze prognostic factors and to determine which patients might benefit from this treatment. One hundred forty-three patients were retrospectively studied. Pretreatment, treatment, and follow-up variables with possible prognostic significance were analyzed. A stepwise multivariate analysis was performed using the Cox regression model, and a prognostic index was obtained. RESULTS: According to univariate analysis, variables significantly associated with survival were alpha-fetoprotein (>400 U/L), tumor size (>50%), ascites, albumin (<30 g/L), Child-Pugh grade (Child C), Okuda stage (Okuda III), portal vein thrombosis, tumor greatest dimension larger than 5 cm, more than 3 nodules, bilobular involvement, and pattern of iodized oil uptake, tumor size reduction, and radiologic T classification on computed tomography scan performed 7 and 30 days after TACE. However, only ascites, alpha-fetoprotein (>400 U/L), tumor size (>50%), Child-Pugh grade (Child C), pattern of iodized oil uptake, and portal vein thrombosis were independent factors in multivariate analysis. Using the beta-coefficients of alpha-fetoprotein (>400 U/L), tumor size (>50%) and Child-Pugh score, a prognostic index was calculated, and according to this index patients were classified into 3 categories with different prognoses. Ascites was excluded from the analysis because it is included in Child-Pugh grade, and iodized oil uptake was excluded because it cannot be evaluated before treatment. CONCLUSIONS: This simple prognostic index can predict the survival of patients treated with TACE and can therefore be used to decide which patients with unresectable HCC should receive this therapy. TACE should not be administered to patients with one or more positive prognostic factors.     

Immunochemo-embolization therapy of hepatocellular carcinoma]

To increase antitumor effects of transcatheter arterial embolization therapy (TAE) for hepatocellular carcinoma (HCC), immunochemo-embolization therapy via hepatic artery was performed with a mixture of doxorubicin and iodized oil (LPD) following a mixture of gamma-IFN, OK-432 and gelatin sponge, and then a mixture of actinomycin D and gelatin sponge. Three patients with HCC were treated by this procedure. One patient had tumor thrombus in inferior vena cava (IVC). The serum alpha fetoprotein (AFP) levels before this procedure ranged from 66 ng/ml to 8,360 ng/ml. Following this procedure, the serum AFP levels began to decrease for 1-3 months, then increased for 3-6 months, and again suddenly decreased under 10 ng/ml in two cases after initial procedure. The serum AFP levels of two cases revealed under 10 ng/ml for 9-18 months. CT after 2 weeks to 3 months of this procedure showed a low-density area around LPD-uptaking tumor and after 1-8 months decreased tumor in size with diminishing of the low-density area. Therapy for the main tumor of one case with tumor thrombus of IVC proved to be effective, but it was not effective for tumor thrombus of IVC. The reasons that the serum AFP level increased after decreasing for 1-3 months and then fell below 10 ng/ml following this procedure, may be some kinds of immunological antitumor effects produced by endogenous cytokines.     

Radiofrequency ablation combined with transcatheter arterial chemoembolization for hepatocellular carcinoma--CT examination during the follow-up period

Radiofrequency ablation (RFA) combined with transcatheter arterial embolization (TAE) can increase the volume of coagulation necrosis to treat patients with hepatocellular carcinoma. Furthermore, in clinical practice, RFA combined with TAE using iodized oil and gelatin sponge often induced the sub-segmental or segmental necrosis toward the liver periphery of the ablated lesion. In this study, we compared the CT findings and histological characteristics of peripherally spreading necrosis induced by this combination therapy for 12 patients with hepatocellular carcinoma. In all cases, complete necrosis of ablated lesions and peripherally spreading necrotic areas were confirmed by CT examination. The histochemical (lactate-dehydrogenase, maleate-dehydrogenase, and NADPH-diaphorase) stained specimens, biopsies from ablated lesions and peripherally spreading necrotic areas, were absent suggesting a 100% cellular destruction. No incomplete local treatments after the therapy were obtained during the 4-26 months of follow-up periods. We conclude that RFA combined with TAE using iodized oil and gelatin sponge makes it possible to induce the segmental or sub-segmental necrosis including tumors.     

A complete response to one-shot hepatic arterial infusion of epirubicin in a patient with highly advanced hepatocellular carcinoma

A 61-year-old male was admitted for advanced hepatocellular carcinoma (HCC) with multiple lung metastases and tumor thrombus in the portal vein and superior vena cava. At first, we planned to perform transcatheter arterial embolization (TAE) to avoid the rupture of the liver tumor. But, due to the severe liver dysfunction, ie Child-Pugh C and 36% ICG R15, hepatic arterial infusion (HAI) of epirubicin 40 mg was performed. After that, the patient was followed at the outpatient ward and his general condition has gradually improved without a special treatment. At the present, one year and ten month after HAI, the serum alpha-fetoprotein (AFP) is almost within normal limits and CT scans show that HCC with multiple lung metastases, and tumor thrombus in the portal vein and superior vena cava almost disappeared. Although, spontaneous regression of HCC was a rare phenomenon, it might have played a major role in the good anticancer efficacy of this patient as well as high anti-cancer agent sensitivity of his liver tumor.     

HCC伴PVTT经肝动脉-门静脉联合化疗栓塞疗效观察

目的对原发性肝癌(HCC)伴门静脉癌栓(PVTT)的患者行肝动脉-门静脉联合化疗栓塞治疗后1年内的疗效进行观察。方法 选择符合纳入标准的HCC伴PVTT患者124例进行肝动脉-门静脉联合化疗栓塞治疗,观察治疗后在肿瘤及门脉癌栓变化、AFP变化、生存质量及生存率方面随访其1年内的疗效。结果 AFP变化,介入后转阴率为27.4%。治疗后肿瘤及门静脉癌栓变化,CR 6例(4.8%),PR 39例(31.5%),NC 45例(36.3%),PD 34例(27.4%)。治疗后1月、3月生存质量较前提高,两者比较差异有统计学意义(P<0.01),治疗后1年较前降低,两者比较差异有统计学意义(P<0.01)。生存率方面,治疗后1月、3月、6月和1年生存率分别100.0%、89.1%、71.6%和58.3%。结论 肝动脉-门静脉联合化疗栓塞治疗HCC伴PVTT患者改善生存质量、提高生存率方面均有较明显的短期疗效。     

Combined hepatic-artery and portal-vein chemoembolization for colorectal cancer metastatic to the liver

The purpose of the study was to evaluate the results of combined (hepatic artery and portal vein) oily chemoembolization (OCE) in patients with unresectable colorectal liver metastases. Courses of combined OCE were given to 45 patients (1990-2000). For arterial OCE (n = 150), 40-100 mg doxorubicin mixed with 10-15 ml iodized oil and gelatin sponge was used. OCE of the portal vein (n = 118) included injection of doxorubicin-in-oil without sponge. Response to treatment (partial tumor decrease or stabilization) was reported in 80%. Serious complications occurred in 3 patients (7%) but there was no mortality. The mean and median survival rates for those patients who died were 20.2 and 17 months, respectively. The 1-, 2-, and 3-year survival rates were 83, 40 and 14%, respectively. These results were significantly better than those for arterial OCE alone or hepatic arterial infusion. Combined (arterial and portal vein) OCE with doxorubicin appears the most effective locoregional treatment for unresectable colorectal liver metastases.     

TACE联合瘤内注药治疗中晚期肝癌的疗效观察

目的评价瘤内注射碘化油混悬液和无水乙醇联合肝动脉化疗栓塞术(TACE)治疗中晚期肝癌的疗效。方法 61例中晚期肝癌随机分为联合介入组(实验组)与TACE组(对照组),组间比例是1∶1,实验组采取瘤内注射碘化油混悬液和无水乙醇联合TACE术,对照组则单纯采取TACE术,比较两组之间的总有效率,无进展生存期,总生存率和不良反应。结果实验组的总有效率明显优于对照组(64.5%vs 40.0%,P=0.049);治疗和对照组中位无进展生存期(PFS)分别为10月和7月(χ2=4.821,P=0.028),中位生存时间(MST)分别为17月和14月(P=0.061)。两组均未出现严重的不良反应。结论瘤内注射碘化油混悬液和无水乙醇联合肝动脉化疗栓塞术(TACE)治疗可增加肿瘤有效率,延缓肿瘤进展时间,不良反应可耐受。     

Transcatheter arterial chemoembolization prolonged survival in a patient with advanced hepatocellular carcinoma accompanied by tumor thrombus of the portal vein trunk

A 50-year-old man having an advanced hepatocellular carcinoma (HCC) was admitted to our institution. An abdominal computed tomogram showed infiltrative mass in the right liver with tumor thrombus invading into the main trunk and contralateral branch of the portal vein. Repetitive transcatheter arterial chemoembolization reduced a tumor size and shrunken portal vein tumor thrombus. The tumor marker levels such as AFP and PIVKA-II decreased. During follow-up, he was diagnosed as having an impending rupture of HCC with acute abdominal pain. He was successfully treated with interventional technique. He died of liver failure 66 months after the first treatment. Although he had a highly advanced HCC with tumor thrombus of the portal vein, repetitive transcatheter arterial chemoembolization therapy may prolong survival.     

Effectiveness of Lipiodol in transcatheter arterial embolization of hepatocellular carcinoma

The effectiveness of Lipiodol (iodized oil) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC) was retrospectively evaluated using statistical analysis. A total of 343 HCC patients who underwent TAE at 5 institutions between 1984 and 1989 were divided into 2 groups: the GS-TAE group underwent TAE with Gelfoam sponge alone, whereas the LP-TAE group was given Lipiodol (LP) immediately before GS-TAE. The statisticalT value calculated for the LP-TAE group showed that the administration of LP, the tumor size, intrahepatic metastasis, portal vein infiltration, and serum total bilirubin and alpha-fetoprotein levels significantly (P<0.01) affected=" the=" patients'=" survival.=" both=" the=" cumulative=" survival=" determined=" using=" the=" kaplan-meier=" model=" and=" the=" cumulative=" hazard=" calculated=" using=" cox's=" proportional=" hazard=" model=" differed=" significantly=">P<0.01) between=" the=" gs-tae=" group=" and=" the=" lp-tae=" group=" (log-rank=" test).=" these=" results=" confirmed=" the=" effectiveness=" of=" lp=" used=" in=" combination=" with=" gelfoam=" sponge=" for=" tae=" of=">Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

Radiotherapy after transcatheter arterial chemoembolization for patients with hepatocellular carcinoma and portal vein tumor thrombus

Transcatheter arterial chemoembolization (TACE) is used in the treatment of hepatocellular carcinoma; however, it has limited effect on portal vein tumor thrombus (PVTT). The purpose of this study was to assess the feasibility and efficacy of radiotherapy targeting the PVTT after TACE for the tumor in the hepatic parenchyma. TACE was performed using epirubicin hydrochloride, iodized poppy seed oil, and gelatin sponge particles. Radiotherapy was performed targeting the PVTT to a total dose of 50 Gy in 25 fractions during 5 weeks. Twenty consecutive patients were treated with this combined treatment. Sixteen of 20 patients could complete the planned radiotherapy. Partial response was observed in 10, no change in 4, and progression in 6. The response rate was 50% (95% CI 28-72%). The 1-year overall survival rate was 25% (95% CI 6-44%), and the median survival time was 5.3 months. It was difficult to determine the late toxicities because of disease progression and additional TACE, and only one patient died without disease progression. Radiotherapy after TACE is feasible for patients with hepatocellular carcinoma and PVTT. The survival figure, however, is still dismal, and further investigation is needed to establish the best combination of treatment modalities.     

Limitation of transcatheter arterial chemoembolization using iodized oil for small hepatocellular carcinoma. A study in resected cases.

The radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas (HCC), less than 2 cm in maximum diameter, after transcatheter arterial chemoembolization (TCE) using iodized oil. The effect of TCE on small HCC depended on the morphologic type of the tumors. When no extracapsular invasion of tumor cells occurred, TCE was extremely effective against encapsulated tumors. However, in nine of the 14 resected specimens, viable tumor cells remained in or around the tumor. The authors suggest that small HCC are not always curable with TCE alone and that a multi-disciplinary approach is necessary for patients with small HCC.     

Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors

A total of 100 patients with histologically proven hepatocellular carcinoma (HCC) underwent transcatheter arterial chemoembolization (TACE) and were followed for more than 1 year and 10 months. Portal vein branch thrombosis was diagnosed in 14 patients, and extrahepatic metastasis was noted in 11 subjects. The embolization material used was iodized oil (0.1–0.2 ml/cm tumor area at its maximal diameter), which was prepared by pumping with contrast agent and then mixed with anticancer drugs; Gelfoam particles measuring 1–2 mm in size were subsequently injected. The overall cumulative 0.5- 1-, 2-, and 3-year survival rates were 81%, 57%, 31%, and 21%, respectively. Patients with an intact capsule and those with solitary lesions, especially when the tumor diameter was <5 cm,=" achieved=" a=" higher=" survival=" rate.=" in=" contrast,=" incomplete=" tace,=" extrahepatic=" metastasis,=" and=" portal=" vein=" thrombosis=" were=" associated=" with=" the=" worst=" outcome.=" patients=" with=" positive=" hbsag=" and=" diffuse=" or=" multiple=" tumors=" also=" showed=" a=" poor=" outcome.=" early=" diagnosis=" and=" early=" treatment=" of=" hcc=" are=" the=" keys=" for=" the=" achievement=" of=" better=" clinical=">Presented at the Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 September 1991     

Three (3) cases of advanced hepatocellular carcinoma (HCC) treated successfully by transcatheter arterial infusion of cisplatin followed by gelatin particles

Hepatic artery chemotherapy with transarterial infusion (TAI) of a cisplatin formulation designed for intra-arterial injection (IA-call?) is recognized as an established treatment for advanced hepatocellular carcinoma (HCC). We experienced three patients whose multiple HCC(Stage III) was successfully treated by TAI using IA-call combined with embolization by porous gelatin particles (Gelpart?), after a series of treatments such as hepatectomy, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and TAI. Cisplatin-based TAI was not effective, but porous gelatin particles showed a therapeutic effect in one patient by reducing his hepatic arterial blood flow. The two other patients responded to combination therapy after the second treatment. Adverse events from the treatment were mild. This therapy has benefits even for multiple intra-hepatic lesions that are resistant to TACE and TAI because of its widespread effect on the entire liver, and it could be an effective treatment option for advanced HCC.     

根据大肝癌的血供特点确定介入治疗的碘油剂量

目的　探讨介入治疗时根据CT显示大肝癌血供的情况 ,确定个体较准确的碘油剂量的可行性。方法　对 10 0例大肝癌 (最大直径 >8cm)行多排螺旋CT 3期薄层扫描 ,根据血供特点分为 4型 :多血供、少血供、混合性血供和明显动静脉瘘。根据肿瘤大小和血供特点确定相应超液化碘油的剂量。经肝动脉行化疗栓塞 (TACE)时随机分为两组 ,第 1组按照术前制定剂量并根据实际情况以充满为止 ;第 2组仅以肿瘤最大直径为标准。观察两组肿瘤内碘油充填情况 ,比较两组符合率及有效率。结果第 1组和第 2组符合率分别为 82 .0 %和 36 .0 % ,有效率分别为 84 .0 %和 4 6 .0 % ,第 1组显著高于第 2组 ,差异具有非常显著性 (P <0 .0 1)。结论　根据CT图像对大肝癌肿瘤血供进行分类 ,确定灌注碘油的剂量 ,并在治疗中进行适当调整 ,可取得较好疗效。