Reductive surgery plus percutaneous isolated hepatic perfusion for multiple advanced hepatocellular carcinoma

Abstract

Objective: To evaluate the efficacy of a novel 2-stage treatment with reductive surgery plus percutaneous isolated hepatic perfusion (PIHP) for multiple hepatocellular carcinoma (HCC), which was previously unresectable.

Summary background data: Surgical resection is the treatment of choice for HCC, but the majority of patients with advanced HCC are not suitable candidates. PIHP is a minimally invasive surgery that allows high-dose regional chemotherapy of the liver, and our phase II studies have shown its profound efficacy for the local control of advanced HCC.

Methods: Twenty-five patients with multiple advanced HCC were enrolled in this prospective study. In the first stage, all patients underwent reductive hepatectomy: major hepatectomy in 13 patients and segmentectomy or less in 12. In 2 patients with subsegmentectomy, the retropancreatic and periportal metastatic lymph nodes were synchronously resected. Regardless of the type of hepatectomy, all patients routinely underwent cholecystectomy, and ligations of the right gastric artery and arterial collaterals of the remnant liver to increase the safety and efficacy of PIHP. In the second stage, PIHP with doxorubicin 60-120 mg/m2/treatment was planned for a period of 1 to 3 months after surgery.

Results: Of 25 enrolled patients, 22 successfully underwent PIHP an average of 1.8 times for the local control of residual liver tumors. In the remaining 3 patients, PIHP was abandoned because 2 had rapid disease progression and 1 had liver failure after surgery. In 22 patients with the 2-stage treatment, 19 (86%) had objective local tumor control (10 complete remissions and 9 partial responses with a median response duration of 16 months). The actuarial survival rate of all 25 patients was 42% at 5 years.

Conclusions: Reductive surgery plus PIHP produced a strong antitumoral effect on multiple advanced HCC, when liver function allows this concentrated treatment approach, and offers long-term survival in a subset of patients who were previously deemed to have unresectable disease.

FIGURE 1. HAG findings of a 34-year-old man with hepatitis B virus-related chronic hepatitis (ICGR15 = 5.1%). The patient underwent extended left lobectomy of the liver at the first stage. The second stage PIHP with 100 mg/m² doxorubicin was performed twice 1 and 2 months after hepatectomy. The serum AFP decreased from the pretreatment level of 64,520 ng/mL to 9 ng/mL 4 months after hepatectomy. However, he died of recurrent disease 16 months after reductive hepatectomy. A, Pretreatment HAG performed via the right hepatic artery, which originated from the superior mesenteric artery. Multiple intrahepatic metastases were noted in the right lobe. B, Pretreatment HAG via the left hepatic artery branching from the celiac axis showing massive type tumors measuring 8.5 cm in the left lobe. C, HAG 5 months after hepatectomy showed a complete clearance of the residual tumors in the remnant liver.

FIGURE 2. HAG and CT scan of a 53-year-old man with hepatitis C virus-related liver cirrhosis (ICGR15 = 16.9%). He underwent extended right lobectomy with portal vein tumor thrombectomy at the first stage. The second-stage PIHP was repeated twice in a period of 1 to 3 months after hepatectomy, using 100 mg/m², and 80 mg/m² doxorubicin, respectively. The serum AFP decreased from the pretreatment level of 20,104 ng/mL to 6 ng/mL 4 months after hepatectomy. He is currently well with no evidence of disease recurrence 14 months after reductive hepatectomy. A, Computed tomography (CT) scan before hepatectomy demonstrated massive type tumors measuring 7.5 cm in the right lobe. Arrows indicate tumor thrombus in the portal vein. B, Contrast-enhancement CT scan before treatment showed disseminated tumors in the left lobe of the liver. C, Pretreatment HAG via the left hepatic artery also demonstrated disseminated tumors in the future remnant liver. D, HAG of the left hepatic artery 8 months after hepatectomy showed the complete clearance of the residual tumors in the remnant liver. E, Contrast enhancement CT scan 9 months after hepatectomy also confirmed the complete clearance of residual hepatic tumors.

FIGURE 3. Survival curves of all 25 patients and 22 patients with hepatectomy and PIHP.

FIGURE 4. Survival curves of all 25 patients according to the tumor type (type 1, distinctive versus type2, multicentric).

FIGURE 5. Survival curves of all 25 patients according to TNM stage (IVA vs. IVB).

FIGURE 6. Survival curves of all 25 patients according to macroscopic portal involvement (VP positive vs. VP negative).