Ia call

TACE was performed based on the following steps. A catheter was inserted into the feeding artery. There we monitored a densely stained tumor using angiography. An epirubicin‐lipiodol suspension (a mixture of 5 mL of lipiodol and 5 mL of a contrast medium containing 50 mg of epirubicin) was injected until the blood flow in the target artery stagnated according to the tumor size. The hepatic artery was embolized with porous gelatin particles from the feeding artery based on the tumor size and vascular diameter.
In the TACE+TAI group, a catheter was placed in proper hepatic artery. The cisplatin fine powder formulation (IA‐call; Nippon Kayaku, Tokyo, Japan) was solubilized in saline, at a concentration of 100 mg/70 mL, immediately prior to use. Cisplatin was administered for the whole liver from the proper hepatic artery with a total dose of 65 mg/m². TACE with epirubicin was subsequently performed as mentioned above.

LEN was administered until the progression of disease (PD) or the discontinuation due to AEs. TACE was added on demand according to the condition of the tumor. LEN was re-administered at the discretion of each attending physician while monitoring the patient’s physical condition and liver function. In conventional TACE (cTACE), an emulsion containing iodized oil (Lipiodol; Guerbet, Tokyo, Japan) and miriplatin (60–120 mg; Miripla^®; Sumitomo Dainippon Pharma, Osaka, Japan), cisplatin (50–100 mg; IAcall^®; Nippon Kayaku, Tokyo, Japan), or Epirubicin (20–50 mg; Epirubicin^®; Nippon Kayaku, Tokyo, Japan) were injected selectively or segmentally until high-grade stasis was reached, followed by embolization with absorbable gelatin sponge particles (Gelpart^®; Nippon Kayaku, Tokyo, Japan). The study also included cases in which drug-eluting beaded TACE (DEB-TACE) was used instead of cTACE at the facility’s discretion. DEB-TACE was performed using DC Beads^® (Biocompatibles UK, Surrey, UK) impregnated with Epirubicin (50 mg).

TACE and/or TAI were performed according to the clinical practice guidelines for HCC of the Japan Society of Hepatology [22 ]. Briefly, TACE or TAI is recommended for patients with multiple tumors and Child–Pugh class A or B hepatic impairment severity. The TAI procedure consists of the injection of cisplatin (IA-call®; Nippon Kayaku Co., Ltd., Tokyo, Japan), MIRIPLAtin (MIRIPLA®; Dainippon Sumitomo Pharma Co., Ltd., Osaka, Japan), or an emulsion of epirubicin (Farmorubicin®; Pfizer Japan Inc., Tokyo, Japan) in lipiodol into hepatic arteries, including tumor-nourishing arteries. TACE includes subsequent embolization of the feeding arteries with gelatin sponge particles (Gelpart®; Nihonkayaku, Tokyo, Japan) following the TAI procedure. TAI without embolization was implemented when multiple tumors were extensively distributed bilaterally in the lobes of the liver, the arterial anatomy precluded a super-selective injection, or there were significant arteriovenous fistulas or tumor thrombi in the main trunk of the portal vein.

To prepare the cisplatin solution, we added 70 mL of saline solution warmed to 50 °C to a vial containing 100 mg of fine-powder cisplatin (IA Call; Nippon Kayaku). The solution containing 65 mg/mm² of cisplatin was manually infused for 20 min through a microcatheter that was nonselectively placed in the proper hepatic artery to enable complete exposure of all tumors to the drug. If necessary, the drug was separately injected from the right or left hepatic artery to account for anatomical variations.
Following cisplatin infusion, all hepatic arteries were embolized with 100–300 μm trisacryl gelatin microspheres (Embosphere; Nippon Kayaku). However, microsphere injections into the cystic, left gastric, and right gastric arteries were avoided. Completion of the therapy was defined as the disappearance of all tumor enhancements on postembolization digital subtraction angiography of the proper hepatic artery. In cases of vascular lakes and arteriovenous shunts, porous gelatin particles (Gelpart; Nippon Kayaku) were used. Lipiodol (Guerbet, France) was not used. To prevent renal damage, 1000 and 1500 mL of electrolytes were administered over a period of 4 h before and 6 h after the procedure, respectively. Antiemetic agents, including a 5-HT3 antagonist and steroids, were prophylactically administered to reduce nausea and vomiting.