Efficacy of combined bland embolization and chemoembolization for huge (≥10 cm) hepatocellular carcinoma.

INTRODUCTION: To assess the efficacy of combined therapy involving bland transarterial embolization using gelatin sponge particles (bland GS-TAE) followed by transarterial chemoembolization using lipiodol mixed with anticancer agents and GS particles (Lip-TACE) to reduce the adverse events and increase the therapeutic effect of Lip-TACE in the treatment of huge (≥10 cm) hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Twenty-one consecutive patients with huge HCCs (≥10 cm in diameter) were enrolled in this study. First, bland GS-TAE was performed to reduce the tumor volume, and then Lip-TACE was performed to control the remaining tumor at intervals of around three weeks. Tumor response, survival, and adverse events of this combined therapy were assessed. RESULTS: The tumor response was assessed three months after combined TACE, with complete response in 38.1% and partial response in 57.1% of cases. Severe adverse events were seen in two patients, acute cholecystitis and tumor rupture. The median survival time was 2.7 years, and the one-, two-, three-, and five-year overall survival rates were 76.2%, 66.7%, 42.9%, and 25.0%, respectively. CONCLUSION: Combined therapy involving bland GS-TAE followed by Lip-TACE can be performed safety and may improve survival in patients with huge HCCs.

Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy after unification of the blood supply in an animal model.

PURPOSE: The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) with temporary unification of the pancreatic blood supply for advanced pancreatic cancer in an animal model. MATERIALS AND METHODS: Nine pigs were divided into three groups of three pigs each. 5-FU (20 mg/kg) was infused via jugular vein (group I), celiac artery (group II), and celiac artery with balloon occlusion of the superior mesenteric artery (SMA; group III). At 0, 10, 30, and 60 minutes after drug infusion, the concentrations of 5-FU were measured in plasma and tissues including the liver, pancreatic head, pancreatic uncinate process, and duodenum. Areas under the concentration-time curve (AUCs) were calculated and statistically compared. RESULTS: The temporary unification of the pancreatic blood supply by converting from dual blood supply through the celiac artery and SMA into a single celiac arterial supply was confirmed by dye injection. Mean AUCs in the pancreas head and liver were significantly higher for groups II and III compared with group I (P < .05). In contrast, there were no significant differences in plasma 5-FU concentrations between groups. In addition, the AUC in the pancreatic uncinate process was significantly higher for group III compared with groups I and II (P < .05). CONCLUSIONS: Pancreatic arterial infusion chemotherapy allows efficient regional drug delivery into the pancreas and liver. Importantly, the unification of the pancreatic blood supply may be required to induce maximum efficacy of arterial infusion chemotherapy for the tumor in the pancreatic uncinate process.

[Locally advanced pancreatic cancer successfully treated by arterial infusion chemotherapy combined with stereotactic radiotherapy--a case report].

We report a 60-year-old female with locally advanced pancreatic cancer successfully treated with stereotactic radiotherapy after arterial chemoinfusion. Using the indwelling catheter-port system with the unification of the pancreatic blood supply, we initially conducted an arterial infusion of weekly high-dose 5-FU (1,000 mg/m2/qw) combined with systemic gemcitabine (1,000 mg/m2/qw). As a result, the tumor was remarkably decreased. However, a part of the tumor where the drug had not been distributed remained in no reduction. Therefore, we added the stereotactic radiotherapy (50 Gy) targeted on the limited residual tumor and combined with concurrent systemic gemcitabine (1,000 mg/m2/qw). The residual tumors have been controlled well without distant metastases, and the patient is alive today 36 months after our initial treatment.

A novel interventional radiology technique for arterial infusion chemotherapy against advanced pancreatic cancer.

OBJECTIVE: Arterial infusion chemotherapy for unresectable pancreatic cancer may be an attractive strategy. We are currently developing a new interventional radiology technique to unify the pancreatic blood supply for chemoinfusion. In this article, we evaluated the feasibility, therapeutic potential, and limitations of this technique. MATERIALS AND METHODS: Twenty-eight patients with advanced pancreatic cancer were retrospectively reviewed. After the superior mesenteric artery was embolized, the drug distribution to the tumor was evaluated by a unified CT angiography system. RESULTS: In all patients, tumors had dual arterial blood supplies from both the celiac and superior mesenteric arteries. Unification of pancreatic blood supply was successful in 14 patients (50%). The whole pancreatic tumor was exclusively supplied by the celiac artery in these patients. In the remaining 14 patients, a part of the tumor was still supplied by the superior mesenteric artery even after embolization. In most failed cases, the tumor had invaded to the root of the small-bowel mesentery or transverse mesocolon. By contrast, unification of the pancreatic blood supply could be achieved in cases invading to the stomach and duodenum. The whole liver was also successfully supplied by arterial infusion from the celiac artery after embolization. CONCLUSION: Our novel technique for arterial infusion chemotherapy is simple, feasible, and well tolerated. Furthermore, arterial chemoinfusion may be a breakthrough in selected patients with unresectable pancreatic cancer.

Arterial infusion of 5-fluorouracil combined with concurrent radiotherapy for unresectable pancreatic cancer: results from a pilot study.

OBJECTIVE: Systemic chemotherapy and chemoradiotherapy, the standard treatments, do not satisfactorily improve the poor prognosis of unresectable pancreatic cancer. The authors administered arterial infusion of 5-fluorouracil (5-FU) combined with concurrent radiation therapy to enhance the antitumor effect of chemotherapy. The purpose of this study was to examine the efficacy and safety of this combined therapy. MATERIALS AND METHODS: One or two catheters were placed into the pancreas-supplying arteries angiographically. To obtain adequate drug distribution, the positions of the catheters were determined in accordance with the results of CT during arterial injection of contrast material. A dose of 333 mg/m2/d of 5-FU was continuously infused for 5 days a week for 5 weeks, with concurrent radiation therapy (50 Gy at 2.0 Gy per fraction). Twenty patients with unresectable pancreatic cancer were enrolled in this study. RESULTS: Of the 20 patients, 19 (95%) completed the scheduled course of this combined therapy. Fourteen patients showed a partial response (response rate, 70%). Serum cancer antigen 19-9 (CA 19-9) levels were reduced by more than 50% in 16 of 18 patients (80%). The 1-year and 3-year survival rates were 40% and 17%, respectively, with a median survival time of 11.0 months. Grade 3 or worse nonhematologic toxicity was observed in 11 patients (55%), but there were no life-threatening toxicities or complications. CONCLUSION: Arterial infusion of 5-FU combined with concurrent radiation therapy is tolerable and can produce a high response rate with encouraging survival duration for unresectable pancreatic cancer.

Long-term outcome of transcatheter subsegmental and segmental arterial chemoemobolization using lipiodol for hepatocellular carcinoma.

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.

Experimental study of poly-L-lactic acid biodegradable stents in normal canine bile ducts.

PURPOSE: This study was designed to clarify the advantages of biodegradable stents in terms of mucosal reaction and biodegradation after placement. We designed a biodegradable stent and assessed stent degradation and changes in the normal bile ducts of dogs. METHODS: The biodegradable stent is a balloon-expandable Z stent consisting of poly-L-lactic acid (PLLA) with a diameter of 6 mm and a length of 15 mm. We assessed four groups of three beagle dogs each at 1, 3, 6, and 9 months of follow-up. After evaluating stent migration by radiography and stent and bile duct patency by cholangiography, the dogs were sacrificed to remove the bile duct together with the stent. The bile duct lumen was examined macroscopically and histologically, and the stent degradation was examined macroscopically and by scanning electron microscopy (SEM). RESULTS: Bile duct obstruction was absent and none of the stents migrated. Macroscopic evaluation showed moderate endothelial proliferation in the bile ducts at the implant sites at 3 and 6 months and a slight change at 9 months. Slight mononuclear cell infiltration was histologically identified at all time points and epithelial hyperplasia that was moderate at 3 months was reduced to slight at 6 and 9 months. Stent degradation was macroscopically evident in all animals at 9 months and was proven by SEM in two dogs at 6 months and in all of them at 9 months. CONCLUSIONS: Our results suggest that PLLA bioabsorbable stents seems to be useful for implantation in the biliary system with further investigation.

Hepatic arterial infusion chemotherapy combined with venous embolization in a patient with hepatic metastases with an arteriovenous shunt.

We describe herein a patient who had hepatic metastases with an arteriovenous shunt and was treated by hepatic arterial infusion chemotherapy. The arteriovenous shunt was diagnosed by (99m)Tc-macroaggregated albumin scintigraphy and hepatic venous embolization was performed to reduce shunt flow.

Transarterial chemoembolization using cisplatin powder in a rabbit model of liver cancer.

The purpose of this study was to investigate the pharmacological advantages of transarterial chemoembolization (TACE) with cisplatin powder for hypervascular hepatic tumors in animal experiments. VX2 tumors were transplanted to the livers of nine rabbits. Cisplatin (1 mg/kg) was infused into the proper hepatic artery. In the cisplatin-HAI group, cisplatin solution was infused. In the cisplatin-GS-TACE group, after infusion of cisplatin solution, gelatin sponge particles were used for embolization. In the cisplatin-Lp-TACE group, after infusion of a cisplatin powder and lipiodol (10 mg/ml) suspension, gelatin sponge particles were used for embolization. Before and after administration, platinum concentrations in plasma were measured. Using liver specimens that were excised 60 min after infusion, platinum concentrations in tumorous and nontumorous liver tissues were measured. The mean platinum concentration in tumorous tissue was 0.88 microg/ml for the cisplatin-HAI group, 1.23 microg/ml for the cisplatin-GS-TACE group, and 12.65 microg/ml for the cisplatin-Lp-TACE group. The platinum concentration for the cisplatin-Lp-TACE group was significantly higher than that for the cisplatin-HAI group (p = 0.004) and the cisplatin-GS-TAE group (p = 0.004). The mean platinum concentration in nontumorous liver tissue was 0.98 microg/ml for the cisplatin-HAI group, 1.13 microg/ml for the cisplatin-GS-TACE group, and 1.09 microg/ml for the cisplatin-Lp-TACE group; no significant differences were seen. At both 5 and 10 min after infusion, the platinum concentrations for the cisplatin-Lp-TACE group were lower than those for the other two groups. The present results suggest that TACE using cisplatin powder/lipiodol suspension and gelatin sponge for hypervascular hepatic tumors has a number of pharmacological advantages.

Sclerotherapy for simple cysts with use of ethanolamine oleate: preliminary experience.

We evaluated the efficacy of ethanolamine oleate (EO) as a sclerosing agent for a symptomatic hepatic or renal cyst. Seven patients with symptomatic hepatic (n = 3) or renal cysts (n = 4) were treated by sclerotherapy with EO. The cyst size in the greater diameter ranged from 6 to 13 cm. The cyst was punctured under ultrasound guidance, and after all of the cyst's content was aspirated, an iodized contrast agent was injected to check the absence of communication between the cyst and biliary tree, urinary tract, or vessels. Then, the solution of ethanolamine oleate-iopamidol mixture (EOI) of 10% of the volume of the cyst's content was injected via catheter. After 30 min, the injected EOI was aspirated completely before catheter removal. A follow-up computed tomography scan was performed at 1 and 3 months after treatment. The volume of the cyst and its reduction rate was calculated. In addition, symptoms and complications were assessed. The volume of the cyst ranged from 64 to 636 ml (mean: 328 ml) before treatment. Three months after treatment, it ranged from 2 to 50 ml (mean: 15ml) and the reduction rate of the cyst's volume was more than 90% on average. Symptoms caused by the cyst disappeared in all cases and no major complication was encountered. Although two patients had a low-grade fever after sclerotherapy, it was easily controlled. It is suggested that the sclerotherapy with EO might be a safe, effective, well-tolerated treatment for symptomatic hepatic or renal cysts.

Catheter position for adequate intra-arterial chemotherapy for advanced pancreatic cancer: evaluation with CT during arterial injection of contrast material.

PURPOSE: To identify the drug infusion vessel for use in obtaining the best drug distribution in arterial infusion chemotherapy for advanced pancreatic cancer. MATERIALS AND METHODS: In 16 cases of advanced pancreatic cancer (pancreatic head, n = 12; pancreatic body and/or tail, n = 4), computed tomography during arterial injection of contrast material was performed at the time of angiography. The sites of catheter placement were celiac artery, superior mesenteric artery, and their branches, such as gastroduodenal artery, inferior pancreatico-duodenal artery, or dorsal pancreatic artery. RESULTS: In the cases of pancreatic head cancer, all except one with hepatomesenteric vascular variation were supplied by the celiac artery and superior mesenteric artery (dual supply). In the cases of pancreatic body and/or tail cancer, two were supplied by celiac artery alone and two showed dual supply. In the cases of pancreatic head cancer, when the areas supplied by the main trunk were compared with those supplied by its branches, three of nine cases on the celiac artery side and four cases on the superior mesenteric artery side showed that the areas were not consistent, with a partial defect observed in the areas supplied by branches of the superior mesenteric artery. In the cases of pancreatic body and/or tail cancer, on both sides, one of two cases was not consistent. CONCLUSIONS: To achieve optimal drug distribution in arterial infusion chemotherapy for advanced pancreatic cancer, drug infusion via both the celiac artery and superior mesenteric artery is required in the majority of cases. In many cases, optimal drug distribution is not attainable with drug infusion via a branch; therefore, drug infusion should be administered via the main trunk.