Safety and efficacy analysis of hepatic artery infusion chemotherapy combined with immune targeted therapy for single CNLC Ⅰb hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the safety and efficacy of FOLFOX (5-fluorouracil + calcium folinate + oxaliplatin) hepatic arterial infusion chemotherapy (FOLFOX-HAIC) combined with immune and targeted therapy as triple combination therapy for patients with single China Liver Cancer Staging (CNLC) Ⅰb hepatocellular carcinoma.Methods:A total of 20 patients with single CNLC Ⅰb hepatocellular carcinoma who received FOLFOX-HAIC combined with immune and targeted therapy as triple combination therapy in the First Affiliated Hospital of Guangxi Medical University from October 2021 to August 2022 were included. The clinical data of all patients was retrospectively analyzed. There were 18 males and 2 females, with the age of (55.1±9.9) years. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Modified Response Evaluation Criteria in Solid Tumors (mRECIST) were used to evaluate the efficacy of FOLFOX-HAIC combined with immune and targeted therapy, and the clinical safety of triple combination therapy was evaluated by common terminology criteria for adverse events 4.0.Results:According to RECIST 1.1, objective response rate of 20 patients was 70.0% (14/20) and disease control rate was 100.0% (20/20) after 2 cycles of treatment (one cycle of FOLFOX-HAIC plus programmed death-1 antibody). According to mRECIST, objective response rate was 90.0% (18/20) and the disease control rate was 100.0% (20/20) after 2 cycles of treatment. Following the treatment, 12 patients (60.0%) received liver tumor resection, and all of them achieved R 0 resection, 2 patients (10.0%) received radiotherapy, 3 patients (15.0%) stopped drug treatment for surgery, 2 patients (10.0%) refused surgery, and 1 patient (5.0%) died of multiple organ failure caused by immune hepatitis. According to pathological results, 3 patients (25.0%, 3/12) achieved pathological complete response, and 4 patients (33.3%, 4/12) achieved major pathological response. In the safety evaluation, the overall incidence of adverse events was 100.0% (20/20). Seven patients (35.0%) had grade 3 adverse events and 1 patient (5.0%) died of multiple organ failure due to immune hepatitis (grade 5). Grade 1-3 adverse events could be relieved after symptomatic treatment. Conclusion:The triple combination therapy of FOLFOX-HAIC combined with immune and targeted therapy is safe and has high objective response rate and disease control rate, which could be a new strategy for the neoadjuvant treatment of hepatocellular carcinoma.

Advances in neoadjuvant therapy for hepatocellular carcinoma / 中华消化外科杂志

In recent years, the rapid development of systematic therapy and local therapy, represented by targeted therapy, immunotherapy and vascular interventional therapy, has signifi-cantly improved the therapeutic effects of advanced hepatocellular carcinoma (HCC), and also greatly promoted the development of neoadjuvant therapy of HCC. The main purpose of neoadjuvant therapy is to decrease the size of tumor and the difficulty of surgery, and to reduce the postoperative recurrence rate. But meanwhile it also brings potential risks such as tumor progression and loss of surgical opportunity. At present, most experts recommend that patients with Ⅱb stage and Ⅲa stage HCC according to China Liver Cancer staging system are the preferred target population for neoadjuvant therapy. However, due to the lack of high-quality medical evidence, it is recommended to be cautiously carried out after multidisciplinary discussion. Moreover, it is suggested that neoadjuvant therapy with rapid onset of effect, less and mild side effects, high objective response rate and low probability of disease progression should be carried out. The author expects that neoadjuvant therapy can further improve the prognosis of HCC, and provide more options for clinical practice.

Clinical efficacy of hepatic arterial infusion chemotherapy combined with immune plus targe-ted therapy for lung metastasis of advanced hepatocellular carcinoma / 中华消化外科杂志

Hepatocellular carcinoma (HCC) is one of the most common tumors of primary hepatic carcinoma, and one of the major causes of cancer related deaths worldwide. HCC has high incidence and mortality, with limited treatment. The prevention and treatment of HCC faces great challenges. At present, interventional therapy combined with immune plus targeted therapy has a synergistic effect and a significant effect in prolonging the survival time of patients and controlling tumors, which brings a brand-new therapeutic hope to patients with advanced HCC. The authors report a case of advanced HCC with lung metastasis who underwent hepatic arterial infusion chemotherapy combined with immune plus targeted therapy, with a result of good clinical effect on tumor controlling in a short time.

Research progress of vascular interventional therapy in the conversion therapy of hepato-cellular carcinoma / 中华消化外科杂志

Primary liver cancer is the fourth most common malignancy and the second most common cause of cancer death in China, which poses a serious threat to the life and health of the Chinese people. Hepatocellular carcinoma (HCC) represents more than 90% of the pathology of primary liver cancer, among them around 60% of patients are at the intermediate-advanced stage when diagnosed. Therefore, increasing the rate of resection via conversion therapies is particularly important to improve the prognosis of these patients. Vascular interventional therapies represented by transarterial chemoembolization and hepatic arterial infusion chemotherapy are important treatment methods for HCC patients in intermediate-advanced stage, showing good rates of tumor response and surgical conversion. Combined with research data at home and abroad, the authors analyze research progress of vascular interventional therapy in the conversion therapy of HCC, review the history and the strategies of conversion therapies based on vascular interventional therapy in this article.

Hepatic Arterial Infusion Chemotherapy in the Era of Precise Medicine / 中山大学学报(医学科学版)

@# Hepatocellular carcinoma（HCC）is the most common malignant liver tumor in the world. Hepatectomy， liver transplantation and ablation may be the potential radical treatments for early liver cancer patients. At present，most of the patients with HCC in China are in the late stage of the disease，mainly requiring systematic treatment. Sorafenib and Lenvatinib are internationally recognized as first-line therapy for advanced HCC. In Asia，hepatic arterial infusion chemotherapy（HAIC）is used as a first-line regimen for the treatment of advanced HCC. In HAIC，antineoplastic drugs are directly injected into the blood supply vessels of liver tumors，obtaining high reaction rate and obvious survival advan⁃ tages，and reducing the systemic toxicity and side effects of chemotherapy drugs. However，HAIC is not yet widely used worldwide due to the lack of accurate evidence from randomized controlled clinical trials（RCT）targeting global populations. In this paper，we will systematically review the current research status of HAIC and its dominant population. More⁃ over，we speculate that HAIC will be the standard therapy for advanced HCC or combined with tyrosine kinase inhibitor （TKI）and / or immunotherapy to prolong these patients′ life in the near future.

Clinical significance of microvascular invasion in the comprehensive diagnosis and treatment of hepatocellular carcinoma / 中华消化外科杂志

Microvascular invasion (MVI) is one of the invasive characteristics of hepatocellular carcinoma (HCC) and also an independent risk factor for intrahepatic and distant metastasis of hepatocellular carcinoma.The occurrence of MVI in patients with hepatocellular carcinoma is universal and can occur in different stages of hepatocellular carcinoma,which is the result of the joint action of multiple factors,including tumor diameter,tumor morphology,tumor pathological grading,and hepatitis B virus activity and replication.For patients with preoperative assessment of MVI risk factors,reasonable surgical plans should be made according to the basic conditions of patients.Non-anatomic hepatectomy is performed to expand the resection scope as far as possible (at least ＞ 1 cm),and anatomic hepatectomy is performed with complete Laennec cystectomy along the Glisson system.Pathological examination is the gold standard of MVI diagnosis,and standardized diagnosis can improve the detection rate of MVI.MVI is mainly related to early postoperative recurrence of hepatocellular carcinoma (within 1 year).For patients with positive MVI after HCC resection,selective combination with transcatheter arterial chemoembolization,radiotherapy and molecular targeted drugs can reduce tumor recurrence and prolong the survival time of patients with liver cancer without recurrence.Therefore,MVI has important clinical significance for the comprehensive diagnosis and treatment of hepatocellular carcinoma.

A Case of Complete Response with Biliary Stenosis after Hepatic Arterial Injection and Stereotactic Body Radiotherapy to Hepatoecllular Carcinoma with Portal Vein Thrombosis

Curative treatment of hepatocellular carcinoma (HCC) with portal vein invasion is difficult to achieve, and the prognosis is dismal. Combining external beam radiotherapy (EBRT) with hepatic arterial infusion chemotherapy (HAIC) has shown favorable local therapeutic effects for patients with HCC exhibiting portal vein invasion. Stereotactic body radiotherapy (SBRT) is a recently developed EBRT modality that shows excellent tumor control. The combination of SBRT and HAIC for HCC with portal vein invasion has not been well-studied. We report a patient with HCC and portal vein invasion who achieved 15 months of survival with complete response status after combination SBRT and HAIC. The patient later experienced grade 3 biliary stricture and died of liver abscesses of unknown etiologies that subsequently appeared.

Can metronomic chemotherapy be an alternative to sorafenib in advanced hepatocellular carcinoma?

No abstract available.

Treatments Other than Sorafenib for Patients with Advanced Hepatocellular Carcinoma

Sorafenib is the standard treatment for advanced hepatocellular carcinoma according to the Barcelona Clinic Liver Cancer staging system. However, because of its unsatisfactory efficacy, adverse effects, and high cost, the use of sorafenib is limited, and other treatment modalities are required. Recent studies reported that treatment modalities other than sorafenib, such as hepatic arterial infusion chemotherapy and transarterial radioembolization, showed comparable or better response rates and survival rates than sorafenib. In this review, treatment modalities that could be used as alternatives to sorafenib will be discussed.

A Study of Variant Hepatic Arterial Anatomy and Its Relevance in Current Surgical Practice.

Background: With increase in the number of laparoscopic procedures, oncologic surgical interventions and organ transplant cases, anatomy and variations of hepatic arterial systemhave become increasingly important. Variations in these vessels may predispose the patients to inadvertent injury during open surgical procedures or percutaneous interventions. Aims: The present study is intended to contribute to the pre-existing data regarding the variations in the branching pattern of hepatic artery and throw light on their clinical implications. Methods: Extrahepatic branching pattern of hepatic arteries were studied in 40 embalmed cadavers of both sexes by dissection method. Results: Classical text book pattern of hepatic arterial anatomy was seen in 30(75%) cases and ten (25%) cases showed the presence of aberrant hepatic arteries. 12 aberrant hepatic arteries were seen in these ten cases, eight (20%) cases with single aberrant hepatic artery and two (5%) with combination of aberrant right and left hepatics. Aberrant right hepatic arteries were seen in four (10%) cases and all of them were replaced right hepatics arising directly from celiac trunk. Aberrant left hepatic arteries were seen in eight (20%) cases, of which six (15%) were accessory, two (5%) were replaced and all of them arose from the left gastric artery. Conclusion: Because of high incidence of variations in branching pattern of hepatic artery it is very important to have a thorough knowledge of these variants and identify them so as to prevent iatrogenic injuries and increase rate of success of the surgical and interventional procedures in hepatobiliary region.

Efficacy and safety of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma as first-line therapy

BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and cisplatin for intractable advanced hepatocellular carcinoma (HCC) may have survival benefits. We aimed to determine the efficacy and safety of HAIC for advanced HCC as first-line therapy. METHODS: A total of 54 patients who received only HAIC with 5-fluorouracil (750 mg/m2 on days 1-4) and cisplatin (25 mg/m2 on days 1-4) for advanced HCC from Jan. 2009 to Dec. 2011 were selected. According to Child-Pugh class, the overall survival (OS), progression-free survival (PFS), and adverse events after HAIC were investigated retrospectively. RESULTS: Median OS and PFS between the Child-Pugh A group (n=24) and the Child-Pugh B/C group (n=30) were 8.7 (95% confidence interval [CI]: 4.7-12.7) vs. 3.7 months (95% CI: 2.0-5.3), and 7.1 (95% CI: 3.8-10.4) vs. 3.6 months (95% CI: 2.0-5.2), respectively. Although median OS and PFS were not statistically significant between the two groups (P=0.079, P=0.196), the Child-Pugh class B/C tended to influence poor OS. Serious adverse events > or = grade 3 occurred frequently in both groups (83.3 vs. 96.7%, P=0.159). Responders (22.2%, complete or partial response) significantly differed in median OS, compared to non-responders (13.1 vs. 4.4 months, P=0.019). Achievement of complete or partial response was an independent prognostic factor of OS (hazard ratio: 0.4, 95% CI: 0.2-0.8, P=0.011). CONCLUSIONS: Achievement of response after HAIC provide a survival benefit in patients with advanced HCC, but HAIC should be administered cautiously in patients with Child-Pugh class B/C, because of a relatively low survival and high incidence of serious adverse events.

Treatment of Hepatocellular Carcinoma with Portal Vein Thrombosis by Sorafenib Combined with Hepatic Arterial Infusion Chemotherapy

Treatment with sorafenib prolongs both the median survival and time to progression by nearly 3 months in patients with advanced hepatocellular carcinoma. Although the effects of combining sorafenib therapy with other anticancer treatment modalities have not been clarified, combination treatment is strongly expected to be beneficial. We report the case of a 50-year-old man who exhibited a partial response and portal vein thrombosis (PVT) revascularization after sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). He exhibited a decrease in tumor size and PVT after 2 months of sorafenib monotherapy. However, no additional response was seen during the subsequent 2 months. To achieve a better tumor response, we combined HAIC with sorafenib. Daily cisplatin (7 mg/m2 on days 1-5) and 5-fluorouracil (170 mg/m2 on days 1-5) were infused repeatedly every 4 weeks, and the sorafenib prescription was modified. After four cycles of combined therapy, both the tumor size and PVT were much improved and exhibited partial response.

Which treatment modality should we choose for advanced hepatocellular carcinoma? / 대한간학회지

No abstract available.

A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial chemoembolization using doxorubicin for intractable, advanced hepatocellular carcinoma / 대한간학회지

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC. METHODS: The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks. RESULTS: Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group. CONCLUSIONS: High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.

A Case of Hepatocellular Carcinoma with Pulmonary Metastases Treated Successfully with a Combination of Repeated Hepatic Arterial Infusion Epirubicin and Cisplatin Chemotherapy and Systemic Low-Dose Infusion of 5-Fluorouracil

We report a case of hepatocellular carcinoma (HCC) with pulmonary metastases treated with repeated hepatic arterial infusion chemotherapy (HAIC) comprising epirubicin and cisplatin, and systemic infusion of 5-fluorouracil (a modified EC/F protocol), which led to complete remission. A 49-year-old man with compensated liver cirrhosis experienced intrahepatic recurrence of HCC with extensive lung metastases. The modified EC/F therapeutic protocol, which was applied at the tenth cycle every 4-5 weeks, resulted in disappearance of the pulmonary metastases and normalization of serum alpha-fetoprotein levels. A single small HCC lesion was found in the left lobe of the liver 13 months after the final chemotherapy session. HAIC with the same regimen was conducted again, followed by percutaneous intratumoral chemoinjection therapy with 5-fluorouracil and interferon-gamma. Thereafter, there was no evidence of recurrence in either the liver or the lung, as evidenced by image analysis and expression of tumor markers. The disease-free intervals for the liver and lung were 41 and 54 months, respectively.

Preventive effect of hepatic arterial infusion (DDS) against post-operative recurrence of hepato-cellular carcinoma / 中国癌症杂志

Purpose:To explore the preventive effect of hepatic arterial infusion (DDS) against recurrence of hepato- cellular carcinoma (HCC) after radical resection.Methods:From Jan,1996 to May,1998,287 patients of HCC after radical resection were randomly divided into four groups:intra-hepatic arterial infusion(97),intra-portal vein(80),intra-hepatic artery and portal vein (60),control (50).All patients received chemotherapy for two years and observed for postoperative recurrence of HCC.Results:The postoperative recurrence rate of HCC with intra-hepatic arterial infusion was significantly lower than that of intra-portal vein (P0.05).The 1～、2～ and 3～year survival rate of intra-hepatic arterial infusion was significantly higher than any of the other groups.Conclusions:Intra-hepatic arterial infusion (DDS) through gastro-duodenal artery can effectively pro- long the postoperative survival and decrease the post-operative recurrence rate of HCC.The preventive method of DDS through gastro-duodenal artery was safer and effective.