Experimental Study of Hepatic Artery Infusion of Vascular Endothelial Growth Factor Receptor (VEGFR)-2As2O3 Nanospheres for Targeted Therapy of Implanted Hep G2 Liver Cancer in Rats

This study assesses the effect of VEGFR-2/As2O3 invisible nanospheres on treating liver cancer. The following groups were set: Group I: blank control group (hepatic artery perfusion 0.9% saline 0.5 ml), group II: VEGFR-2/As2O3 nanospheres injection via tail vein, group III: hepatic artery perfusion of VEGFR-2/As2O3 nanospheres. The effect of hepatic artery infusion of VEGFR-2/As2O3 nanospheres on cell proliferation, apoptosis and colony forming ability was evaluated by MTT method, flow cytometry and colony formation experiment. Tumor xenotransplantation was established to observe the effect of hepatic artery infusion of VEGFR-2/As2O3 nanospheres on liver cancer. The in vivo and in vitro experiments both confirmed that hepatic artery perfusion of VEGFR-2/As2O3 nanospheres can inhibit the proliferation of liver cancer cells, promote cell apoptosis and inhibit cell migration, thereby enhancing the therapeutic effect. The hepatic artery perfusion of VEGFR-2As2O3 nanospheres may be used as a targeted research and development direction for the treatment of liver cancer, providing a new and efficient targeted drug for the interventionaltreatment of liver cancer.

Meta-Analysis of Postoperative Adjuvant Hepatic Artery Infusion Chemotherapy Versus Surgical Resection Alone for Hepatocellular Carcinoma

BackgroundTo systematically identify the long-term efficacy of postoperative adjuvant hepatic artery infusion chemotherapy (HAIC) for patients with hepatocellular carcinoma (HCC).MethodsPubMed, MedLine, Embase, the Cochrane Library, and Web of Science were searched to collect the eligible studies up to March 31, 2021, that compared the surgical resection (SR) versus SR+HAIC for HCC patients. The endpoints were overall survival (OS) rates and disease-free survival (DFS) rates, and the effect size was determined by hazard ratio (HR) with 95% CI.ResultsA total of 12 studies (two randomized controlled trials (RCTs) and 10 non-RCTs) including 1,333 patients were eligible for this meta-analysis. The pooled results showed that OS and DFS rates in the SR+HAIC group were both better than those in the SR alone group (HR = 0.56, 95% CI = 0.41–0.77, p < 0.001; HR = 0.66, 95% CI = 0.55–0.78, p < 0.001, respectively). Furthermore, the subgroup analysis showed that patients would benefit from SR+HAIC regardless of chemotherapy regimens and courses (all p < 0.05), and patients with microvascular or macrovascular invasion would also benefit more from SR+HAIC in terms of OS and DFS (all p < 0.05).ConclusionPostoperative adjuvant HAIC could improve the long-term prognosis of HCC patients, especially for those with microvascular or macrovascular invasion, regardless of chemotherapy regimens and courses, but it deserves further validation.

Revisiting Hepatic Artery Infusion Chemotherapy in the Treatment of Advanced Hepatocellular Carcinoma

Hepatic artery infusion chemotherapy (HAIC) is a well-established and common treatment for advanced hepatocellular carcinoma (HCC), particularly in East Asia. However, HAIC is not recognized internationally. Although several trials have demonstrated the safety and efficacy of HAIC, evidence corroborating its overall survival (OS) benefits compared with standard treatments is insufficient. Nevertheless, HAIC may provide prominent benefits in selected patients such as patients with portal vein thrombosis or high intrahepatic tumor burden. Moreover, HAIC has been combined with several therapeutic agents and modalities, including interferon-alpha, multikinase inhibitors, radiation therapy, and immunotherapy, to augment its treatment efficacy. Most of these combinations appeared to increase overall response rates compared with HAIC alone, but results regarding OS are inconclusive. Two prospective randomized controlled trials comparing HAIC plus sorafenib with sorafenib alone have reported conflicting results, necessitating further research. As immunotherapy-based combinations became the mainstream treatments for advanced HCC, HAIC plus immunotherapy-based treatments also showed encouraging preliminary results. The trials of HAIC were heterogeneous in terms of patient selection, chemotherapy regimens and doses, HAIC combination agent selections, and HAIC technical protocols. These heterogeneities may contribute to differences in treatment efficacy, thus increasing the difficulty of interpreting trial results. We propose that future trials of HAIC standardize these key factors to reveal the clinical value of HAIC-based treatments for HCC.

Case Report: Hepatic Artery Infusion Chemotherapy After Stage I ALPPS in a Patient With Huge HCC

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can induce rapid hypertrophy of the liver remnant. However, with a background of liver cirrhosis or other chronic liver diseases, patients with a huge hepatocellular carcinoma (HCC) may sometimes face insufficiency of hepatocellular regeneration after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). Herein, we report a 56-year-old male with a vast HCC (13.3 × 8.5 × 13 cm) whose ratio of the future liver remnant (FLR)/standard liver volume (SLV) was 28.7% when the disease was first diagnosed. Inadequate hypertrophy of FLR was shown in postoperative volumetric assessment a month after stage I ALPPS. After multidisciplinary team discussion (MDT), the patient was decided to follow three courses of hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). The last HAIC was performed together with transhepatic arterial embolization (TAE). Finally, ratio of the FLR/SLV increased from 28.7% to 40% during three-month intervals, meeting the requirements of the surgery. Stage II ALPPS, right trisectionectomy, was then successfully performed. There was no recurrence at half years of follow-up. In our case, HAIC seems to be more potent than transcatheter arterial chemoembolization (TACE) in maintaining the hyperplasia of the liver remnant, reducing tumor load, and preventing tumor progression in patients with a large HCC during ALPPS procedure. HAIC, following the first step of ALPPS, a pioneering treatment modality aiming for inadequate hypertrophy of FLR induced by ALPPS, could be an alternative procedure for patients with a vast HCC in clinical practice.