Degradable Starch Microspheres Research Articles

A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial

We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial. We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n = 15), TAI using DSM (DSM group, n = 15), and TAI using lipiodol and DSM (lipiodol + DSM group, n = 15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol + DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM. The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol + DSM group, respectively. The response rate tended to improve in the lipiodol + DSM group (lipiodol group vs. lipiodol + DSM group, P = 0.07). The median progression-free survival time was 177 days in the lipiodol group, 287 days in the DSM group, and 377 days in the lipiodol + DSM group. The progression-free survival in the lipiodol + DSM group was significantly better than those in the DSM group (P = 0.020) and the lipiodol group (P = 0.035). There were no serious adverse effects among the 3 groups. TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.

Abstract No. 171: Phase I Study of Transcatheter Arterial Chemoembolization with Cisplatin Powder and Degradable Starch Microspheres for Unresectable Hepatic Metastases from Colorectal Cancer

Abstract No. 171: Phase I Study of Transcatheter Arterial Chemoembolization with Cisplatin Powder and Degradable Starch Microspheres for Unresectable Hepatic Metastases from Colorectal Cancer

Treatment of Hepatocellular Carcinoma Using Arterial Chemoembolization with Degradable Starch Microspheres and Continuous Arterial Infusion of 5-Fluorouracil

Transcatheter arterial embolization (TAE) with gelatin sponge particles and iodized oil often yields poor results when used to treat unresectable multifocal hepatocellular carcinoma (HCC). The present study retrospectively investigated the utility of a novel combination chemotherapy regimen for treating multifocal HCC resistant to TAE. Thirteen consecutive patients with unresectable multifocal HCC and resistance to TAE were treated with combination chemotherapy consisting of arterial chemoembolization with degradable starch microspheres (DSM) (150-4500 mg on Day 1), mitomycin-C (4-8 mg on Day 1), continuous arterial infusion of 5-fluorouracil (1250 mg/120 h), cisplatin (25-50 mg/120 h) and l-leucovorin (125 mg/120 h) for 10-19 weeks. The response rate was 84.6%, with complete response in one patient and partial response (PR) in 10 patients. In four of 10 patients with PR, the tumor was not observable, although the tumor marker did not completely decline to the normal range. The 1-, 2- and 3-year survival rates were 100, 28.9 and 9.6% in all, and 100, 33.3 and 0% in six patients with portal vein tumor thrombosis (PVTT). The median survival was 22.1 months in all and 17.1 months in six patients with PVTT. Thrombocytopenia of Grade III or higher was observed in eight patients. Laparoscopic splenectomy was performed before therapy in four patients with platelet counts of <70,000/mm(3), and during therapy in five patients with severe thrombocytopenia. This novel chemotherapy regimen achieved favorable results and may be useful in treating patients with unresectable multifocal HCC resistant to TAE.

Synergistic antitumor effects of transarterial viroembolization for multifocal hepatocellular carcinoma in rats

Oncolytic virotherapy is a promising strategy for safe and effective treatment of malignancy. We have reported previously that recombinant vesicular stomatitis virus (VSV) vectors are effective oncolytic agents that can be safely administered via the hepatic artery in immunocompetent rats to treat multifocal hepatocellular carcinoma (HCC), resulting in tumor necrosis and prolonged survival. Though the results were encouraging, complete tumor regression was not observed, which led us to explore alternative approaches to further enhance the efficacy of VSV treatment. Transarterial embolization techniques have been shown to improve the efficiency and tumor selectivity of anticancer treatments. Degradable starch microspheres (DSM) are one such embolic agent that provides transient embolization of the therapeautic agent before being degraded by serum amylases. Here we demonstrate via dynamic contrast-enhanced magnetic resonance imaging that in our rat model of multifocal HCC, DSM injection into the hepatic artery results in a substantial reduction in tumor perfusion of systemically applied contrast agent. VSV, when administered in combination with DSM, results in enhanced tumor necrosis and synergistically prolongs survival when compared with VSV or DSM monotherapy. This regimen of viroembolization represents an innovative therapeutic modality that can augment the future development of transarterial oncolytic virus therapy for patients with advanced HCC.

Pharmacokinetics of intra-arterial applied liposomal encapsulated doxorubicin in liver metastases or hepatocellular carcinoma: A phase I study

13523 Background: Doxorubicin has been one of the most widely used anti-neoplastic agents as a single-agent systemic therapy for HCC. Doxorubicin is also used in locoregional therapy approaches. Caelyx (Doxil) is a doxorubicin formulation of polyethylene glycol-coated liposomes. For this new form of doxorubicin, a superior pharmacokinetic profile over that of free doxorubicin is postulated. Blood flow reduction by micro embolization with degradable starch microspheres (DSM; e.g. Spherex, EmboCept) is effective in HCC and liver metastasis. Purpose: Evaluation of the pharmacokinetics (PK) of the encapsulated as well as the released fraction of doxorubicin in addition to the determination of the maximum tolerated dose of intra-arterially applied liposomal encapsulated doxorubicin (Caelyx) in HCC and liver metastases in combination with DSM. Methods: All patients with histologically proven HCC or liver metastases had shown progressive disease when previously treated with systemic chemotherapy. Six dose escalation steps from 15 mg/m2 to 100 mg/m2 were performed with two or three patients in each dose group. Each patient received one single application of Caelyx/DSM. The distribution of Caelyx depended on the tumor size in the left and right liver lobe. For the quantification of Caelyx, doxorubicin, and doxorubicinol, a validated RP-HPLC method with fluorometric detection (excitation wavelength: 470 nm, emission wavelength: 550 nm) was used. Results: PK was calculated for 13 out of 14 treated patients. The mean (terminal) half life for Caelyx was calculated as 3 days, mean residence time about 5 days, the Vss 1.5 l, clearance was determined to be less than 1 ml/min. The increase in peak plasma concentration as well as AUC was linear between 15 and 100 mg/m2 Caelyx. The MTD was reached at a single dose of 100 mg/m2 due to WHO- grade 3 myelosuppression in two patients without further SAE. Conclusions: These first results indicate that hepatic intra arterial chemotherapy with Caelyx in combination with DSM is well tolerated and achieved encouraging responses in patients with liver metastases or HCC. The main PK parameter for Caelyx in combination with DSM did not significantly differ from those obtained after systemic intravenous infusion. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Essex Pharma GmbH, PharmaCept GmbH

Repetitive transarterial chemoembolization (TACE) of liver metastases from renal cell carcinoma: Local control and survival results

The purpose was to evaluate the effectiveness of transarterial chemoembolization (TACE) in local tumor control and survival in patients with hepatic metastases from renal cell carcinoma (RCC). Prospective evaluation of TACE treatment outcome in 22 patients recruited from 1999 and 2005 was performed. The chemotherapeutic agent used was mitomycin only in 45% of the patients and mitomycin together with gemcitabine in the other 55%. The embolizing materials used in all of the patients were iodized oil (lipiodol) and degradable starch microspheres. Local response was evaluated by MRI and judged according to Response Evaluation Criteria in Solid Tumors (RECIST). Mean and median survival and survival probability after diagnosis and treatment were both calculated by Kaplan-Meier method. Partial response was achieved in 13.7%, stable disease in 59% and progressive disease in 27.3% of patients. Survival time from the diagnosis of metastases ranged from 18 to 307 months and from 2.2 to 35 months from the start of TACE treatment. The median and mean survival times from the date of diagnosis were 68.6 and 102.9 months, respectively. The median and mean survival times from the start of TACE were 8.2 and 11.7 months, respectively. Survival probability from the start of treatment was 31% after 1 year and 6% after 2 years. TACE can result in a favorable local tumor response in patients with hepatic metastases from RCC, but survival results are still limited.

Hepatic Arterial Infusion of Mitomycin C with Degradable Starch Microspheres for Unresectable Intrahepatic Cholangiocarcinoma

Aims With no effective chemotherapy, the prognosis of unresectable intrahepatic cholangiocarcinoma is extremely poor. Hepatic arterial infusion of mitomycin C with degradable starch microspheres has been reported to be an effective treatment for unresectable liver metastasis. We retrospectively evaluated the efficacy and safety of this chemotherapy for treating unresectable intrahepatic cholangiocarcinoma. Materials and methods Hepatic arterial infusion chemotherapy through an implanted port system was carried out in 20 patients with unresectable intrahepatic cholangiocarcinoma. Degradable starch microspheres mixed with mitomycin C and contrast media were injected until either embolisation of the hepatic artery or influx to the gastroduodenal system was confirmed. This treatment was repeated weekly. Results Hepatic arterial infusion chemotherapy was carried out 204 times. The response rate was 50.0%. Twelve patients experienced transient epigastralgia and four experienced gastroduodenal ulcer. The time to progression was 8.3 months and the median survival time was 14.1 months. Conclusions This chemotherapy was effective and feasible for patients with unresectable intrahepatic cholangiocarcinoma. Further study with a larger number of patients is warranted.

肝細胞癌に対するDegradable starch microspheres（DSM）を用いた新たな肝動脈塞栓療法の試み

We evaluated the efficacy and safety of a novel transarterial chemoembolization using degradable starch microspheres (DSM) for hepatocellular carcinoma. Twelve patients were enrolled. According to tumor vascularization and distribution, a mixture of cisplatin and iodized oil were administered. Next, DSM was injected. Final response rate was 83% (CR5, PR5), and final complete response rate was 42%. Although thrombocytopenia was observed in five patients, and ALT elevation was elevated in three patients, these data were improved in 2 weeks after treatment. Our developed transarterial chemoembolization using DSM for hepatocellular carcinoma is both safe and effective therapy.

Improving laser-induced thermotherapy of liver metastases – Effects of arterial microembolization and complete blood flow occlusion

Introduction A prerequisite for an oncologically curative application of laser-induced thermotherapy (LITT) of liver metastases is complete tumor destruction. This increased effectiveness was achieved experimentally by combining LITT with interrupted hepatic perfusion. The aim of this study was to evaluate whether an interventional selective arterial microembolization might be as effective as complete blood flow occlusion using an open Pringle's maneuver. Patients and methods We included patients with unresectable colorectal liver metastases. LITT was performed without interrupted hepatic perfusion (control group) compared to LITT in combination with interrupted perfusion either by embolization of intraarterial degradable starch microspheres (DSM) (percutaneous access) or by complete hepatic inflow occlusion (Pringle's maneuver; open access). Online monitoring was performed using intraoperative ultrasound or MRI. Volumetric techniques were used to assess metastases and postinterventional lesions. Results Fifty-six patients with 104 metastases (control group (25), DSM (37), and Pringle (42)) were treated. The preinterventional tumor volumes were significantly smaller than the postinterventional lesion volumes (control group: 9.8 vs. 25.3 cm 3; DSM: 9.5 vs. 65.4 cm 3; Pringle: 12.9 vs. 76.5 cm 3). The morbidity rate was 21.4% without treatment-related mortalities. After 6 months follow-up, tumor recurrence was diagnosed in 6 patients (control group (4), LITT with DSM (1), and Pringle (1)). Conclusions Combinig LITT with blood flow occlusion leads to a significant increase in lesion size. The application of DSM offers a safe and effective alternative to the open access with Pringle's maneuver. Compared to LITT-monotherapy, this modality achieves significantly larger thermal lesions with the need of fewer applications.

Formulation and Characterization of Formaldehyde Cross-linked Degradable Starch Microspheres Containing Terbutaline Sulfate

ABSTRACTPreparation of starch microspheres using epichlorohydrin is a time consuming method and requires around 18 hr for cross-linking reaction. To reduce reaction time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were prepared using formaldehyde as the cross-linking agent. All microspheres were spherical in shape and had a porous, rough surface with a mean particle size of 18–24 μm. Whatever the cross-linking time, it was seen that the release of the TBS was not complete during the release experiments. The influence of enzyme on the degradation of microspheres was moderate. Following intravenous administration, initial uptake of microspheres by the lung was higher than those of other organs.

Radiofrequency Ablation of Normal Lungs after Pulmonary Artery Embolization with Use of Degradable Starch Microspheres: Results in a Porcine Model

The present study was performed to evaluate the effect of pulmonary artery embolization on radiofrequency (RF) ablation of normal porcine lungs. RF ablation zones (n=34) were created in the normal lungs of five domestic pigs (five zones in each of the first two pigs and eight zones in each of the remaining three pigs) with an expandable multitined electrode with use of bilateral thoracotomy. RF ablation was performed without pulmonary artery embolization (group 1, n=8), immediately after embolization (group 2, n=11), 15 minutes after embolization (group 3, n=7), and 30 minutes after embolization (group 4, n=8) with degradable starch microspheres. Among them, 12 ablation zones were excluded from this study because they were considerably limited by the presence of the pleura or large bronchi. The remaining 22 zones were included (n=7, n=5, n=4, and n=6 in groups 1, 2, 3, and 4, respectively). Coagulation necrosis volumes in the ablation zones were measured and compared among the groups. Coagulation necrosis volumes were 0.9+/-0.5 cm3, 2.1+/-0.4 cm3, 2.1+/-1.0 cm3, and 1.9+/-0.6 cm3 in groups 1, 2, 3, and 4, respectively. Groups 2-4 showed significantly larger coagulation volumes than group 1 (P=.012, P=.023, and P=.010 in groups 2, 3, and 4, respectively). Pulmonary artery embolization contributed to larger volumes of coagulation necrosis after RF ablation of normal lungs.

Transarterial Therapy for Hepatocellular Carcinoma: Which Technique Is More Effective? A Systematic Review of Cohort and Randomized Studies

Chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, or whether embolization (TAE) alone gives the same survival advantage, is not known. To evaluate whether specific patient characteristics and/or radiological transarterial techniques result in better outcomes. A PubMed search was carried out for cohort and randomized trials (n = 175) testing transarterial therapies; meta-analysis was performed where appropriate. Anticancer drugs were used as sole agent in 75% of cases (double 15% and triple 6%): doxorubicin (36%), cisplatin (31%), epirubicin (12%), mitoxantrone (8%), mitomycin (8%), and SMANCS (5%). Embolizing agents used were: gelatin sponge particles (71%), polyvinyl alcohol (PVA) particles (8%), degradable starch microspheres (DSM) (4%), and embospheres (4%). Sessions per patient were 2.5 +/- 1.5 (interval: 2 months). Objective response was 40 +/- 20%; survival rates at 1, 2, 3, and 5 years were: 62 +/- 20%, 42 +/- 17%, 30 +/- 15%, and 19 +/- 16%, respectively, and survival time was 18 +/- 9.5 months. The post-TACE complications were: acute liver failure, 7.5% (range 0-49%); acute renal failure, 1.8% (0-13%); encephalopathy, 1.8% (0-16%); ascites, 8.3% (0-52%); upper gastrointestinal bleeding; 3% (0-22%); and hepatic or splenic abscess, 1.3% (0-2.5%). Treatment-related mortality was 2.4% (0-9.5%), mainly due to acute liver failure. Our meta-analysis of nine randomized controlled trials (RCTs) confirmed that TACE improves survival; but a meta-analysis of TACE versus TAE alone (3 RCTs, 412 patients) demonstrated no survival difference. No chemotherapeutic agent appears better than any other. There is no evidence for benefit with lipiodol. Gelatin sponge is the most used embolic agent, but PVA particles may be better. TAE appears as effective as TACE. New strategies to reduce the risk of post-TACE complications are required.

Adenovirus Vector-Mediated Gene Transfer Using Degradable Starch Microspheres for Hepatocellular Carcinoma in Rats

When gene therapy is performed for malignant tumors, gene transfer efficiency and selectivity are extremely important. The delivery of anticancer agents and embolic agents through tumor feeding artery is known as transarterial embolization. We speculated that genes might be efficiently and selectively transferred to hepatocellular carcinomas (HCCs) by degradable starch microspheres (DSM) as the embolic agent, which could be trapped within the tumor and release a gene vector. Therefore, we studied the use of DSM for adenovirus vector-mediated gene transfer to HCC in vivo. HCC was induced in rats with diethylnitrosamine and phenobarbital, after which either AxCALacZ and DSM or AxCALacZ alone was injected through the hepatic artery. Histological examination revealed that beta-galactosidase expression was greater (P < 0.001), and more selective (P < 0.001) in tumors after injection of AxCALacZ and DSM, than after injection of the vector alone. Injection of DSM together with an adenovirus vector through the hepatic artery can result in efficient and cancer-selective transfer of genes to HCC.

Transarterial Chemoembolization With Degradable Starch Microspheres, Irinotecan, and Mitomycin-C in Patients With Liver Metastases

Degradable starch microspheres (DSMs) provide transient occlusion of small arteries and are thought to improve the therapeutic effect of anticancer drugs. Irinotecan (CPT-11) is one of the most effective anticancer agents. We herein report cases with liver metastases treated with transarterial chemoembolization with DSM, CPT-11, and mitomycin-C (DSM-CPT therapy). Five patients underwent DSM-CPT therapy for liver metastases that originated from colorectal cancer for four and gastric cancer for one. They all lack indication for surgery. They were all male with an age range of 42-78 years (mean, 55.2 years). Three of them had pretreatment histories with 5-fluorouracil or related agents, and four of them had combined systemic or local chemotherapy at the period. Required doses for stasis of whole blood flow of hepatic artery of DSMs were used with CPT-11 and mitomycin-C. After one to six injections, four patients had a partial response and the disease progressed in one patient with gastric cancer origin. Two of the partial response patients underwent surgery after 2 months of the partial response period. Carcinoembryonic antigen and CA19-9 levels in partial response patients decreased to 16.1% and 19.3% of the level before treatment, respectively. DSM-CPT therapy can be a potential therapy for liver metastases.

Liver microcirculation after hepatic artery embolization with degradable starch microspheresin vivo

To observe the dynamic changes of liver microcirculation in vivo after arterial embolization with degradable starch microspheres (DSM). DSM were injected into the proper hepatic artery through a silastic tube inserted retrogradely in gastroduodenal artery (GDA) of SD rats. Fluorescent microscopy was used to evaluate the dynamic changes of blood flow through the terminal portal venules (TPVs), sinusoids and terminal hepatic venules (THVs). The movements of DSM debris were also recorded. Six hours after injection of DSM, percentages of THVs with completely stagnant blood flow were recorded. Two phases of blood flow change were recorded. In phase one: after intra-arterial injection of DSM, slow or stagnant blood flow was immediately recorded in TPVs, sinusoids and THVs. This change was reversible, and blood flow resumed completely. In phase two: after phase one, blood flow in TPVs changed again and three patterns of blood flow were recorded. Six hours after DSM injection, 36.9% +/- 9.2% of THVs were found with completely stagnant blood flow. DSM can stop the microcirculatory blood flow in some areas of liver parenchyma. Liver parenchyma supplied by arteries with larger A-P shunt is considered at a higher risk of total microcirculatory blood stagnation after injection of DSM through hepatic artery.

Chemoocclusion vs chemoperfusion for treatment of advanced hepatocellular carcinoma: A randomised trial

AimsTransarterial chemoembolization (TACE) can be associated with considerable toxicity and treatment-associated mortality. Transient transarterial chemoocclusion (TACO) using degradable starch microspheres (DSM) has been proposed as a potentially safer alternative while maintaining anti-tumour efficiency. In a randomised phase II trial TACO was compared to transarterial chemoperfusion without DSM (TACP). MethodsSeventy-four patients with advanced HCC were randomised to two treatment arms: (i) TACO (600–1200mg DSM) and (ii) TACP. In both arms regional chemotherapy consisted of cisplatin (100mg/m2) and doxorubicin (60mg/m2). Both arms were corresponding in terms of age, gender, liver performance state, and tumour-stage. A maximum of six treatment cycles was applied in monthly intervals. Follow-up was performed in terms of tumour response, time to progression, survival and quality of life. ResultsTumour response rates did not differ significantly between the two treatment arms, however, there was a tendency towards higher response rates in the TACO arm (TACO vs TACP): partial response: 26 vs 9%, stable disease: 41 vs 55%, progressive disease: 33 vs 36%. Time to tumour progression (32 vs 27 weeks), and overall survival (60 vs 69 weeks) were not significantly different. Grade 4 adverse events were rare in both arms and treatment-associated mortality was not observed. In addition, there was no significant difference in terms of quality of life under therapy (EORTC). ConclusionTACO with DSM did not improve response or survival significantly compared to TACP in advanced non-resectable HCC.

Changes in vascularity of liver tumours after hepatic arterial embolization with degradable starch microspheres.

The role of vascularity as a prognostic factor was investigated in 35 patients undergoing arterial chemotherapy for liver tumours. Compared with parenchyma, tumour vascularity was classified as hot (18 cases), cold (12 cases), and mixed (12 cases) using 99mTc-macroaggregated albumin (MAA) hepatic arterial scans. The proportion of patients showing complete and partial responses to treatment was higher in the hot group (56 per cent) than in the combined cold and mixed group (12 per cent). In 15 cases (six hot, six cold and three mixed lesions), additional MAA scans were performed immediately after arterial embolization with degradable starch microspheres (DSMs). Either complete or partial reversal of tumour vascularity was observed after DSM-embolization in five and seven cases respectively, two and two of them respectively showing native cold lesions. As tumour vascularity appears to be a prominent prognostic factor, DSM-embolization should improve the efficacy of treatment by improving liver extraction of drugs and causing flow redistribution towards hypovascular areas.

Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases

Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy.

Treatment of patients with irresectable liver metastases from colorectal cancer by chemo-occlusion with degradable starch microspheres.

Chemo-occlusion of the liver increases the tumour concentration of drugs. Thirty-nine patients with colorectal liver metastases received a monthly bolus administration of mitomycin C (10 mg/m2 on day 1) plus a continuous infusion of 5-fluorouracil (500 mg/m2 daily from days 1 to 5). Drugs were given via both portal (one-third of the dose) and arterial (two-thirds) routes to control large and small metastases. Arterially administered mitomycin C was mixed with individualized doses of degradable starch microspheres. In 16 patients treatment was not started or was interrupted early because of arterial or portal catheter problems. In 23 patients who received two or more cycles of treatment the mean(s.d.) microsphere dose was 835(399) mg. Toxicity was mild, consisting mainly of pain. Five complete and five partial responses were seen, and six patients had stable disease. The median time to progression and length of survival were 6 and 16 months respectively. The relatively high rates of complete and overall response in hypovascular tumours (six of 12 lesions) may support the rationale of chemo-occlusion.

Liver Metastases in Rats: Chemoembolization Combined with Interstitial Laser Ablation for Treatment

To assess the effect of transcatheter arterial chemoembolization (TACE) combined with laser-induced thermotherapy (LITT) for treatment of liver metastases in an animal model. All experiments were approved by the German government and the institutional animal research review board. After subcapsular liver implantation of colorectal cancer cells in 30 WAG rats (on day 0), the animals were randomly assigned to three interventional treatment groups. In the 10 rats in group A, TACE was performed: Fourteen days after cancer cell implantation and within 20 minutes after laparotomy and retrograde placement of a microcatheter into the gastroduodenal artery, these rats were injected with mitomycin (0.1 mg), iodized oil (0.1 mL), and degradable starch microspheres (5.0 mg). In the 10 rats in group B, LITT was performed: Also on day 14, the tumors in these animals were exposed to Nd:YAG laser light of 1064 nm at 2 W for 5 minutes. In the 10 rats in group C, combined treatment was administered: TACE was performed on day 14, and LITT was performed on day 21. Tumor volumes were measured before (on day 13) and after (on day 28) treatment with magnetic resonance (MR) imaging, and the mean tumor growth ratio (day 13 tumor volume divided by day 28 tumor volume) was calculated. The mean tumor volumes measured before and after the treatments were, respectively, 0.11 and 0.60 cm(3) in group A, 0.11 and 0.68 cm(3) in group B, and 0.11 and 0.35 cm(3) in group C. The mean tumor growth ratio was 5.42 in group A, 6.14 in group B, and 3.15 in group C. According to Bonferroni test results, compared with the rats in groups A and B (controls), the group C rats had significantly inhibited tumor growth (P < .01 for both comparisons). Use of combined TACE-LITT treatment, compared with the use of TACE or LITT alone, significantly inhibits tumor growth.