Clinical efficacy of FOLFOX-HAIC combined with lenvatinib and PD-1 inhibitor in the treatment of inter-mediate and advanced Hepatocellular Carcinoma / 实用医学杂志

Objective To investigate the clinical efficacy and safety of nivolumab(PD-1 inhibitor)in combination with lenvatinib and FOLFOX regimen[5-fluorouracil(5-FU),oxaliplatin(L-OHP),and calcium folinate(LV)]in the treatment of intermediate and advanced hepatocellular carcinoma(HCC)via hepatic arterial infusion chemotherapy(HAIC).Methods A total of 160 patients with intermediate and advanced HCC admitted to the Second Affiliated Hospital of Guilin Medical University from January 2021 to January 2023 were randomly divided into the control group and the observation group,with 80 patients in each group,using a random number table.The control group received once-daily oral lenvatinib and intravenous carrizumab infusions for 12 weeks as part of transcatheter arterial chemoembolization(TACE)therapy.The observation group was administered with FOLFOX regimen via HAIC chemotherapy,plus intravenous infusion of carrizumab for 12 weeks and once-daily oral lenvatinib.All the patients were followed up regularly.The clinical efficacy was evaluated using the mRECIST criteria.The objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and incidence of adverse reactions were compared between the two groups.Results There were no significant differences in the objective response rate and incidence of adverse reactions between the groups.The disease control rate,overall survival,and progression-free survival in the observation group were significantly higher than those in the control group(P<0.05).Conclusions The FOLFOX-HAIC regimen in combination with nivolumab and lenvatinib is safe and effective for the treatment of intermediate and advanced HCC,without adverse reactions.It can prolong the overall survival and progression-free survival,and improve the patient's quality of life.

Status and progress of chemical drug therapy in hepatocellular carcinoma / 中华消化外科杂志

With the application of FOLFOX regimen (oxaliplatin, fluorouracil, and leucovorin) in hepatic arterial perfusion (HAIC), chemotherapy has shown a higher value in the comprehensive treatment of hepatocellular carcinoma. Especially in the era of integration of targeted therapy and immunotherapy, the FOLFOX-HAIC, combined with immunotherapy and targeted therapy, further improves antitumor effect. The FOLFOX systemic chemotherapy combined with immunotherapy and targeted therapy scheme explored by the authors has achieved similar effects to triple therapy. Advanced hepatocellular carcinoma exhibits systemic disease characteristics, and systemic chemotherapy combined with targeted and immunotherapy has achieved higher disease control rates in the initial exploration. The mechanism may be that systemic chemotherapy changes the overall immune micro-environment of tumors, transforming the immune microenvironment from immunosuppressive to immune supportive, thereby better enhancing the efficacy of immunotherapy. The optimal regimen of systemic chemotherapy in comprehensive treatment may be obtained from the phase 3 study and basic studies in the future, which will be more efficient, safe and economical in the treatment of advanced hepatocellular carcinoma.

Treatment progress of pains caused by transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy in hepatocellular carcinoma / 局解手术学杂志

Conversion therapy such as transcatheter arterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)is the main treatment method to transform unresectable advanced liver cancer into resectable liver cancer,which can not only effectively increase the survival rate of patients,but also provide patients with the opportunity of liver transplantation.However,pain is a major complication of TACE and HAIC in the treatment of liver cancer,and the incidence of abdominal pain after TACE is from 19.3%to 71.2%,and nearly 64.6%of patients have different degrees of pain during HAIC,which seriously affects the quality of life of patients and shortens their survival time.At present,the mechanism of pains caused by TACE and HAIC is not clear,and it may be related to local liver tissue swelling after embolic agents block the tumor blood supply artery,increased pressure in the liver tissue envelope or traction of the mass capsule,chemical stimulation of the hepatic artery by embolic agents and antineoplastic drugs,thrombosis adjacent to the normal organs,and visceral pain sensitization caused by intestinal ischemia.There are two main intervention measures for pain,one of which is lidocaine,opioids,non-steroidal anti-inflammatory drugs and glucocorticoids,and the other is wrist and ankle acupuncture and traditional Chinese medicine decoction,but their treatment effects are uneven.This article summarizes the status and treatment of pain caused by TACE and HAIC therapies for liver cancer,in order to provide reference for its clinical treatment.

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.

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.

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.

Construction of nursing quality evaluation index system of bronchial arterial infusion chemotherapy for lung cancer / 中国实用护理杂志

Objective:To construct the nursing quality evaluation index system of bronchial arterial infusion chemotherapy for lung cancer, and to provide theoretical basis for nursing quality evaluation of patients undergoing bronchial arterial infusion chemotherapy.Methods:Based on the structure-process-result three-dimensional quality theory, relevant literature and clinical practice were retrieved to construct the index item pool of the nursing quality evaluation index system of bronchial arterial infusion chemotherapy for lung cancer, and the index items were determined by expert interviews. Finally, the index and its weight were determined by Delphi method and analytic hierarchy process.Results:The positive coefficients of the two rounds of expert letter consultation were 100%, the expert authority coefficients were 0.862, and the expert coordination coefficients were 0.141-0.250 ( P<0.05). The At finally, the nursing quality evaluation index system of bronchial arterial infusion chemotherapy for lung cancer included 3 first-level indexes, 10 second-level indexes and 47 third-level indexes. Conclusions:The nursing quality evaluation index system of bronchial arterial infusion chemotherapy for lung cancer is scientific and practical, which provides a scientific basis for evaluating the nursing quality of patients undergoing bronchial arterial chemotherapy for lung cancer.

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.

A rare case of cerebral hemorrhage associated with intra-arterial infusion chemotherapy for advanced sphenoid sinus cancer

Central nervous damage related to intra-arterial infusion chemotherapy (IAC) for head and neck cancer reported to date are cerebral infarction, transient ischemic attack, and neuropathy. There have been no reports of cerebral hemorrhage as an IAC-related complication for head and neck cancer. Authors report a case that underwent intra-arterial infusion chemoradiotherapy for advanced sphenoid sinus cancer which extended to the left cavernous sinus and cranium, subsequently suffered cerebral hemorrhage thought to have been caused by IAC. Treatment should be performed with greater caution when the head and neck cancer involves the cavernous sinus or cranium, as in the present case

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.

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.

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.

Clinical observation of somatostatin combined with transcatheter arterial infusion chemotherapy in the treatment of malignant intestinal obstruction / 中国生化药物杂志

Objective To observe the effect of somatostatin combined with transcatheter arterial infusion chemotherapy in the treatment of malignant intestinal obstruction.Methods 60 patients with malignant intestinal obstruction were enrolled in our hospital from January 2013 to June 2015.The rats were randomly divided into 4 groups: the conventional group(n=15),the growth inhibition group(n=15),the low dose intra-arterial infusion chemotherapy group(n=15)and somatostatin plus low-dose intra-arterial infusion chemotherapy group(n=15).The clinical symptom remission time,duration of clinical symptom remission and survival time were compared between the four groups.Results The study showed that somatostatin group of gastrointestinal decompression and symptom remission time were significantly better than the conventional group.Especially the symptom remission time is significantly faster than the conventional group and chemotherapy group(P< 0.05); the duration of chemotherapy group and somatostatin+artery perfusion chemotherapy group in survival time and relieve symptoms,were significantly better than the conventional group and somatostatin group(P< 0.05).Conclusion Somatostatin is beneficial to reduce the amount of gastrointestinal decompression in the treatment of malignant intestinal obstruction.Celiac artery infusion chemotherapy can help to improve the maintenance time and prolong the survival time of patients with malignant obstruction.The combination of somatostatin and celiac artery infusion chemotherapy is beneficial to relieve the symptoms and prolong the time interval,and improve the survival time of patients.

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.

Transcatheter arterial infusion chemotherapy increases expression level of miR‑142‑5p in stage III colorectal cancer.

OBJECTIVE: To investigate the expression level of miR-142-5p and its potential target gene endothelial PAS domain protein 1(EPAS1) in Stage III colorectal cancer during Transcatheter arterial infusion chemotherapy (TAI). MATERIALS AND METHODS: Illumina high-throughput sequencing was used to obtain miRNA expression profiles of paired tumor and adjacent normal tissues from one patient received TAI 1 week before the operation and another patient directly underwent an operation. The expression levels of miR-142-5p was measured with both high-throughput sequencing and quantitative real time-polymerase chain reaction. RESULTS: The expression levels of miR-142-5p, were significantly reduced in tumor tissues of stage III CRC, then significantly increased in tumor tissues receiving TAI and higher than tumor tissues without TAI. The apoptosis rate of HT-29 colon cancer cells was mildly increased after transfection with pre-miR-142. miR-142-5p could bind directly to the 3´untranslated region of endothelial PAS domain protein 1 and reduce its expression. CONCLUSIONS: miR-142-5p is a potential tumor suppressor in CRC and is upregulated in tumor tissues after TAI, suggesting its potential clinical values for testing the functionality of TAI and predicting the progress of CRC.

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.

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.

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

No abstract available.