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Shota Ueda,1 Shinichi Hori,2 Atsushi Hori,2 Kazuhiro Makitani,2 Ke Wan,3 Tetsuo Sonomura1 1Department of Radiology, Wakayama Medical University, Wakayama, Japan; 2Department of Radiology, Institute for Image Guided Therapy, Izumisano City, Osaka, Japan; 3Clinical Study Support Center, Wakayama Medical University Hospital, Wakayama, JapanCorrespondence: Shota Ueda, Department of Radiology, Wakayama Medical University, 811-1, Kimiidera, Wakayama, Japan, Tel/Fax +81-73-441-0605, Email uedaaa@wakayama-med.ac.jpPurpose: To evaluate the efficacy and safety of chemoembolization with drug-eluting microspheres (DEM-TACE) combined with intra-arterial infusion of bevacizumab in patients with unresectable hepatocellular carcinoma (uHCC) and to identify possible prognostic factors.Patients and Methods: Between November 2014 and December 2020, 34 patients underwent DEM-TACE combined with intra-arterial infusion of bevacizumab for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) beyond the Up-to-seven criteria or BCLC stage C HCC. Patients with extrahepatic metastasis or inferior vena cava invasion were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were safety (assessed using Common Terminology Criteria for Adverse Events v5.0), the response rate at 1 month, and the identification of prognostic factors. The median OS was calculated using the Kaplan–Meier method. The response rate was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Prognostic factors were investigated by univariate and multivariable analysis using the Cox proportional hazards model.Results: The median OS was 13 months. BCLC stage and presence of portal vein invasion were not significantly associated with OS. There were no grade ≥ 3 adverse events. The Child–Pugh class did not decline after treatment in 31 of 34 patients. The overall response rate was 14.2% and the disease control rate was 100%. Significant prognostic factors were alcoholic liver disease, Child–Pugh score of ≥ 8, and microsphere size of 50– 100 μm.Conclusion: DEM-TACE combined with intra-arterial infusion of bevacizumab is safe and effective, and it could be a treatment option for unresectable HCCs.Keywords: bevacizumab, hepatocellular carcinoma, microspheres, transarterial chemoembolization

Intrahepatic cholangiocarcinoma is hardly diagnosed in early stages as the symptoms are non-specific. Due to an advanced stages at the time of first diagnosis, the therapeutic options for patients with unresectable cholangiocarcinoma are mostly limited to systemic chemotherapy or radiotherapy, but good local control or preferable prognostic effects are hardly obtained. The transarterial chemoembolization had not been a standard of care because of hepatic functional damages caused by lipiodol and gelatin sponge. A newly developed spherical embolic material causes limited hepatic damages might be an option for these patients. It makes it possible to repeat the procedure in a short period. Eventually, better prognosis can be expected using a spherical embolic material. We report a case of a 15 cm locally advanced intrahepatic cholangiocarcinoma treated by chemoembolization using a drug-eluting spherical embolic material and achieved good local tumor control without liver damage. The patient survived longer than 4 years without additional or concomitant treatments.

In recent years, transcatheter arterial embolization (TAE) using imipenem/cilastatin (IPM/CS) has attracted attention as a treatment for relieving osteoarthritis (OA) pain. However, IPM/CS is not approved by Japanese medical insurance for use as an embolic material. Therefore, it is necessary to develop new embolic materials for TAE to relieve OA pain. The purpose of this study was to develop a swine model of knee arthritis and embolize abnormal neovessels (ANs) using two different embolic materials. We compared the embolic effects and tissue damage in knees.Knee arthritis was induced by intra-articular injection of papain into 12 knees in six female swine. The swine were divided into two groups of three swine each (six knees per group) for embolization of ANs in the knees with either IPM/CS or soluble gelatin sponge particles (SGSs). Three days after embolization, we compared the embolic effects using angiography and the tissue damage histopathologically.ANs were observed in all 12 knees at 42 days after papain injection. The ANs disappeared and the patent arteries were recanalized 3 days after TAE in all 12 knees. Histopathological evaluation revealed synovitis changes, such as synovial thickening and inflammatory cell infiltration, in all 12 knees. There was no evidence of skin or muscle necrosis in either group. The appearance of ANs, recanalization of the parent arteries, and histopathological outcomes were not significantly different between the two groups.SGSs were as safe as IPM/CS for TAE of ANs in this swine model of knee arthritis.