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The purpose of this study was to compare the ability of multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) to evaluate treatment results after transarterial chemoembolization (TACE), with a special focus on the influence of Lipiodol on calculation of tumor necrosis according to EASL criteria. A total of 115 nodules in 20 patients (17 males, 3 females; 69.5 ± 9.35 years) with biopsy-proven hepatocellular carcinoma were treated with TACE. Embolization was performed using a doxorubicin-Lipiodol emulsion (group I) or DC Beads loaded with doxorubicin (group II). Follow-up included triphasic contrast-enhanced 64-row MDCT (collimation, 0.625 mm; slice, 3 mm; contrast bolus, 120 ml iomeprol; delay by bolus trigger) and contrast-enhanced MRI (T1 native, T2 native; five dynamic contrast-enhanced phases; 0.1 mmol/kg body weight gadolinium-DTPA; slice thickness, 4 mm). Residual tumor and the extent of tumor necrosis were evaluated according to EASL. Contrast enhancement within tumor lesions was suspected to represent vital tumor. In the Lipiodol-based TACE protocol, MDCT underestimated residual viable tumor compared to MRI, due to Lipiodol artifacts (23.2% vs 47.7% after first, 11.9% vs 31.2% after second, and 11.4% vs 23.7% after third TACE; p  = 0.0014, p  < 0.001, and p  < 0.001, respectively). In contrast to MDCT, MRI was completely free of any artifacts caused by Lipiodol. In the DC Bead-based Lipiodol-free TACE protocol, MRI and CT showed similar residual tumor and rating of treatment results (46.4% vs 41.2%, 31.9 vs 26.8%, and 26.0% vs 25.6%; n.s.). In conclusion, MRI is superior to MDCT for detection of viable tumor residuals after Lipiodol-based TACE. Since viable tumor tissue is superimposed by Lipiodol artifacts in MDCT, MRI is mandatory for reliable decision-making during follow-up after Lipiodol-based TACE protocols.

Objectives The pharmacokinetic profile after hepatic arterial embolization with superabsorbent microspheres (QuadraSpheres) loaded with doxorubicin was studied. Methods Rabbits with hepatic VX2 tumors were treated with intra-arterial administration of QuadraSpheres loaded with doxorubicin, or transarterial chemoembolization (TACE) using doxorubicin, Lipiodol and Embospheres, or hepatic arterial infusion (HAI) of doxorubicin. Tumor specimens were evaluated by fluorescence microscopy, and plasma and tumor concentrations of doxorubicin were measured. Results The peak plasma concentration of doxorubicin was lower in the QuadraSphere group (309.9 ng/ml) than in the HAI (673.4 ng/ml) or TACE (360.5 ng/ml) groups, suggesting higher tumor retention in the QuadraSphere group. Intratumoral doxorubicin levels declined to negligible levels at 1 and 3 days after treatment, respectively, in the HAI and TACE groups. In the QuadraSphere groups, intratumoral doxorubicin level declined after day 1, but was still detectable at 14 days after treatment and was higher than that in the other groups at 1, 3, and 7 days. Intratumoral doxorubicin fluorescence was detected at all time points in the QuadraSphere group, but only at 1 day after treatment in the TACE group. Conclusions Hepatic arterial administration of doxorubicin-loaded QuadraSpheres enables the sustained release of doxorubicin to hepatic tumors.

Purpose To clarify the efficacy of transcatheter hepatic sub-subsegmental, subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who had been treated using subseg/seg lip-TACE alone were retrospectively examined. Materials and Methods Subjects comprised 199 patients with HCC (T1/2/≥3 = 30/108/61; Child–Pugh A/B/C = 115/52/32; Japan Integrated Staging [JIS] score ≤1/2/≥3 = 88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed with an anticancer drug followed by injection of gelatin sponge particles. Each patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7-, and 10-year cumulative survival rates were calculated. Subgroup analyses were performed by stratifying the population according to T-factor, Child–Pugh classification, and JIS score. Results Median duration of follow-up was 3.8 years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7- and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS ≤1, respectively. Significant survival differences were found across two subgroups of staging systems (T2 vs. T3≤ [ P  = 0.0012] and JIS score ≤1 vs. 2 [ P  = 0.0036]). Conclusion This study demonstrated that subseg/seg lip-TACE is a feasible treatment for obtaining prolonged survival in patients with localized HCC showing rich vasculature. Outcomes are influenced by both tumor stage and liver function, as seen in the best prolonged survival in patients with JIS score ≤1.

The objective of this study was to investigate the effect of transcatheter arterial embolization (TAE) with N-butyl-2-cyanoacrylate (NBCA)–Lipiodol mixture in patients with bronchial artery aneurysm (BAA). From January 2005 to January 2010, five patients presenting hemoptysis with six BAAs were treated with NBCA–Lipiodol mixture, including intra-aneurysm embolization (IAE) in one patient. Adjuvant embolization with spherical polyvinyl alcohol (PVA) embolic microparticles or NBCA was first performed to embolize the distal engorged bronchiectatic arteries. Bronchial arterial angiography showed six BAAs (four in the right lobe and two in the left lobe) and some engorged, tortuous bronchial arteries. TAE through microcatheter was successful in all cases. Postembolization angiogram demonstrated the NBCA cast and total occlusion of BAAs and bronchiectatic engorged vessels. After these procedures, hemoptysis completely disappeared in all patients. Follow-up computed tomography (CT) scan was performed at an average of 3 months (range 2 to 6), which showed no enhancement of BAAs and accumulation of NBCA. TAE is a minimally invasive, effective, and reliable approach for treatment for patients with BAA. NBCA–Lipiodol mixture provides a good choice for treatment of BAA, especially when catheterization of the efferent branches is impossible.

The purpose of this study was to correlate histopathological with CT findings in patients suffering from hepatocellular carcinoma (HCC) eligible for orthotopic liver transplantation (OLT), with a special focus on the antitumoral effect of transarterial chemoembolization (TACE) therapy. A total of 42 consecutive patients suffering from HCC had been treated prior to OLT by means of TACE. TACE was carried out with a mixture of Lipiodol (10–20 ml) and mitomycin C (max. dosage, 10 mg). TACE was performed at 6- to 8-week intervals. Follow-up investigation included contrast-enhanced multislice CT controls and laboratory control. Liver explants were evaluated macroscopically and microscopically to determine the number and size of the tumor lesions as well as the degree of tumor necrosis. Necrosis was investigated in H&E-stained sections. The degree of necrosis was classified as follows: 0–25%, 26–50%, 51–75%, 75–99%, and complete necrosis. Two hundred thirty-one TACE procedures (5.5 ± 2.9; range, 1–14) were performed. Mean tumor size in CT before and after TACE was 4.1 ± 2.4 (range, 1.0–12.0 cm) and 2.7 ± 1.2 (range, 1.0–6.0 cm; p  < 0.001). Mean tumor number before and after TACE in CT was 2.5 ± 1.5 ( n  = 105; range, 1–8) and 2.4 ± 2.0 ( n  = 103; range, 1–6; p  = 0.99). In the surgical specimen tumor size and tumor number were 2.8 ± 1.6 (range, 1.0–7.0 cm; p  = 0.78) and 1.9 ± 1.2 (range, 1–7; p  = 0.003). Mean tumor necrosis was 67.8% ± 28.1%. Tumor necrosis was subtotal or complete in 17 of 42 (40.5%) patients. Tumor necrosis correlated significantly with the degree of arterial devascularization in CT ( p  = 0.001), the amount of Lipiodol washout ( p  = 0.002), and the number of tumor lesions (i.e., unifocal vs. multifocal). Furthermore, elevated serum levels of bilirubin ( p  = 0.005) and decreased albumin ( p  = 0.004) affected the local antitumoral effect. A poor necrosis rate (< 25%) significantly correlated with the number of TACE procedures accomplished ( p  = 0.023). In conclusion, TACE provided an acceptable local antitumoral effect in patients scheduled for liver transplantation. Tumor necrosis depended significantly on the degree of arterial devascularization and the accumulation of Lipiodol within the HCC lesions. Unifocal tumors and preserved liver function were positive predictors for a more favorable local antitumoral effect. Poor necrosis rates were found in patients with significant Lipiodol washout and who received a limited number of TACE procedures.

This study was designed to assess the safety of transcatheter arterial embolization (TAE) with n -butyl cyanoacrylate-lipiodol (NBCA-Lp) for the large bowel and to investigate the vital response to NBCA-Lp in a swine model. In nine swine, nine arteries nourishing the colon were embolized with NBCA-Lp (1 ml of NBCA mixed with 4 ml of lipiodol): sigmoid-rectal branch artery in six swine, right colic branch artery in two, and middle colic branch artery in one. The amount of NBCA-Lp was 0.1–0.4 ml. Sacrifice was conducted 3 days after TAE to identify histological infarction. Classification was conducted retrospectively: group A, vasa recta without NBCA-Lp embolization despite TAE; group B, three or fewer vasa recta with NBCA-Lp embolization; and group C, five or more vasa recta with NBCA-Lp embolization. In one swine in group A, no necrotic focus was observed. In group B, three of four swine experienced no ischemic damage. The remaining one swine experienced necrosis of mucosal and submucosal layers in one-fourth of the circumference. In group C, all four swine with marginal artery and five vasa recta or more embolized experienced total necrosis of mucosa, submucosa, and smooth muscle layers of the whole colonic circumference. Significant difference on the extent of ischemic damage was observed between groups B and C ( P  < 0.05). Microscopically, NBCA-Lp induced acute vasculitis. Embolization of three or fewer vasa recta with NBCA-Lp induced no ischemic damage or limited necrosis, whereas embolization of five or more vasa recta with NBCA-Lp induced extensive necrosis.

Purpose This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin–lipiodol suspensions. Methods Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration. Results At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point after the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits. Conclusions We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.

The purpose of this study was to retrospectively clarify the current status in Japan of TACE using Lipiodol together with anticancer agents to treat hepatocellular carcinoma (HCC). We retrospectively surveyed 4,659 (average annual total) procedures for HCC over the years 2002–2004 at 17 institutions included in the TACE Study Group of Japan. The survey included six questions that were related mainly to TACE and Lipiodol for HCC treatment. The most frequently applied among the 4,659 procedures at the 17 institutions were TACE (2,310; 50%) and local ablation (1,395; 30%). Five of the institutions applied 201–300 procedures and 4 applied 101–200. Lipiodol was used in “all procedures” and in “90% or more” at seven and nine institutions, respectively. Almost all institutions applied 4–6 (mean, 5) ml of Lipiodol during TACE to treat tumors 5 cm in diameter. In conclusion, this survey clarified that TACE using Lipiodol and anticancer agents is a popular option for HCC treatment in Japan.

Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 μm, N  = 9; and (B) 47–180 μm, N  = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5–76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) ( p  < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) ( p  < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47–180 μm) are superior to large ones (>180 μm).

Purpose The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin–Lipiodol emulsion at our institution. Materials and Methods Between January 2006 and March 2009, 51 patients with unresectable HCC underwent TACE using cisplatin. All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE using epirubicin–Lipiodol emulsion. TACE procedures consisted of arterial injection of a mixture of Lipiodol and cisplatin (30–100 mg [mean 57 ± 21]) ( n  = 29) or arterial infusion of cisplatin (30–100 mg [mean 87 ± 19]) solution ( n  = 22) followed by injection of 1-mm porous gelatin particles. Early tumor response was assessed by contrast-enhanced computed tomography (CT) according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver (EASL) criteria. Overall survival and progression-free survival was calculated using the Kaplan–Meier method. Toxicity was assessed according to NCI-CTCAE version 3 criteria. Results Response rates were 11.8 and 27.5% by RECIST and EASL criteria, respectively. Overall survival rates were 61.9, 48.2, and 28.9% at 1, 2, and 3 years, respectively, and the median survival time was 15.4 months. Progression-free survival rate was 35.2% at 1 year, and median progression-free survival time was 3.1 months. No major complications were observed, and the occurrence of postembolization syndrome was minimal. Grade 3 to 4 toxicities included thrombocytopenia (5.8%), increased aspartate aminotransferase (AST) level (35.3%), and increased alanine aminotransferase (ALT) level (23.5%). Conclusion Switching the TACE anticancer drug from epirubicin to cisplatin might be the feasible option for advanced HCC, even when considered resistant to the initial form of TACE.