Efficacy and safety of targeted therapy plus immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX) for unresectable hepatocarcinoma

BACKGROUND The advent of cutting-edge systemic therapies has driven advances in the treatment of hepatocellular carcinoma(HCC),and therapeutic strategies with multiple modes of delivery have been shown to be more efficacious than mono-therapy.However,the mechanisms underlying this innovative treatment modality have not been elucidated.AIM To evaluate the clinical efficacy of targeted therapy plus immunotherapy combined with hepatic arterial infusion chemotherapy(HAIC)of FOLFOX in patients with unresectable HCC.METHODS We enrolled 53 patients with unresectable HCC who received a combination of targeted therapy,immunotherapy,and HAIC of FOLFOX between December 2020 and June 2021 and assessed the efficacy and safety of the treatment regimen.RESULTS The objective response rate was 60.4%(32/53),complete response was 24.5%(13/53),partial response was 35.9%(19/53),and stable disease was 39.6%(21/53).The median duration of response and median progression-free survival were 9.1 and 13.9 months,respectively.The surgical conversion rate was 34.0%(18/53),and 1-year overall survival was 83.0%without critical complicating diseases or adverse events(AEs).CONCLUSION The regimen of HAIC of FOLFOX,targeted therapy,and immunotherapy was curative for patients with unresectable HCC,with no serious AEs and a high rate of surgical conversion.

Camrelizumab,apatinib and hepatic artery infusion chemotherapy combined with microwave ablation for advanced hepatocellular carcinoma

BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.

Analysis of the Effects of Preoperative Hepatic Artery Chemoembolization and Quality Nursing Intervention on the Perioperative Safety and Short-term Prognosis of Liver Transplantation in Patients with Hepatocellular Carcinoma

Objective: To investigate the effects of preoperative hepatic artery chemoembolization (TACE) and quality nursing interventions on the perioperative safety and short-term prognosis in patients with hepatocellular carcinoma undergoing liver transplantation. Methods: The study period spanned from January 2021 to December 2023, and 125 patients with hepatocellular carcinoma admitted to our hospital were selected, all of whom underwent liver transplantation. They were randomly divided into an observation group (n = 63) and a control group (n = 62). The patients in the control group did not undergo TACE before the operation, and the patients in the observation group underwent TACE and quality nursing intervention before the operation. The operation time, intraoperative blood loss, length of hospitalization, liver- free period, complication rate, short-term prognosis, and liver function indexes between the two groups were compared. Results: There was no significant difference in operation time, intraoperative blood loss, and length of hospitalization between the two groups (P < 0.05). The liver-free period of patients in the observation group was longer than that of the control group (P < 0.05). The two groups had no significant difference in the incidence of biliary complications, vascular complications, and postoperative infections (P > 0.05). The rate of immune reactive complications in the observation group was lower than that of the control group (P < 0.05). There was no significant difference in the perioperative mortality rate, 1-year postoperative survival rate, and 2-year postoperative survival rate (P > 0.05). The two groups had no significant difference in postoperative liver function indexes (P > 0.05). Conclusion: Preoperative TACE and high-quality nursing intervention in patients with hepatocellular carcinoma had no adverse effect on the perioperative safety and short-term prognosis, prolonged the liver-free time, and reduced the incidence of immune-reactive complications.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma

Hepatic artery infusion chemotherapy(HAIC)has good clinical efficacy in the treatment of advanced hepatocellular carcinoma(HCC);however,its efficacy varies.This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications.As of October 25,2023,51 articles have been retrieved based on keyword predictions and HAIC.Sixteen eligible articles were selected for inclusion in this study.Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing,gene testing,and imaging testing.The above indicators and their combined forms showed excellent predictive effects in retrospective studies.This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC,analyzed each marker's ability to predict HAIC efficacy,and provided a reference for the clinical application of the prediction system.

Efficacy of hepatic arterial infusion chemotherapy and its combination strategies for advanced hepatocellular carcinoma:A network meta-analysis

BACKGROUND With the rapid progress of systematic therapy for hepatocellular carcinoma(HCC),therapeutic strategies combining hepatic arterial infusion chemotherapy(HAIC)with systematic therapy arised increasing concentrations.However,there have been no systematic review comparing HAIC and its combination strategies in the first-line treatment for advanced HCC.AIM To investigate the efficacy and safety of HAIC and its combination therapies for advanced HCC.METHODS A network meta-analysis was performed by including 9 randomized controlled trails and 35 cohort studies to carry out our study.The outcomes of interest comprised overall survival(OS),progression-free survival(PFS),tumor response and adverse events.Hazard ratios(HR)and odds ratios(OR)with a 95% confidence interval(CI)were calculated and agents were ranked based on their ranking probability.RESULTS HAIC outperformed Sorafenib(HR=0.55,95%CI:0.42-0.72;HR=0.51,95%CI:0.33-0.78;OR=2.86,95%CI:1.37-5.98;OR=5.45,95%CI:3.57-8.30;OR=7.15,95%CI:4.06-12.58;OR=2.89,95%CI:1.99-4.19;OR=0.48,95%CI:0.25-0.92,respectively)and transarterial chemoembolization(TACE)(HR=0.50,95%CI:0.33-0.75;HR=0.62,95%CI:0.39-0.98;OR=3.08,95%CI:1.36-6.98;OR=2.07,95%CI:1.54-2.80;OR=3.16,95%CI:1.71-5.85;OR=2.67,95%CI:1.59-4.50;OR=0.16,95%CI:0.05-0.54,respectively)in terms of efficacy and safety.HAIC+lenvatinib+ablation,HAIC+ablation,HAIC+anti-programmed cell death 1(PD-1),and HAIC+radiotherapy had the higher likelihood of providing better OS and PFS outcomes compared to HAIC alone.HAIC+TACE+S-1,HAIC+lenvatinib,HAIC+PD-1,HAIC+TACE,and HAIC+sorafenib had the higher likelihood of providing better partial response and objective response rate outcomes compared to HAIC.HAIC+PD-1,HAIC+TACE+S-1 and HAIC+TACE had the higher likelihood of providing better complete response and disease control rate outcomes compared to HAIC alone.CONCLUSION HAIC proved more effective and safer than sorafenib and TACE.Furthermore,combined with other interventions,HAIC showed improved efficacy over HAIC monotherapy according to the treatment ranking analysis.

Prediction of hepatic artery occlusion after liver transplantation by ultrasound characteristics and clinical risk factors

BACKGROUND Hepatic artery occlusion(HAO)after liver transplantation(LT)is a devastating complication,resulting in early graft loss and reduced overall survival.Ultra-sound is an established assessment method for HAO in patients following LT,especially those with complex hepatic artery reconstruction.METHODS We retrospectively analyzed the ultrasound characteristics and the clinic risk factors associated with HAO in 400 adult LT patients who were enrolled and treated at the Third People's Hospital of Shenzhen between November 2016 and July 2022.Fourteen patients diagnosed with acute HAO(A-HAO)by surgery and fifteen diagnosed with chronic HAO(C-HAO)were included.A control group of 33 patients without HAO complications during the same period were randomly selected using a random number table.All patients underwent an ultrasono-graphy examination.Parameters including resistance index(RI),peak systolic velocity(PSV),and portal vein velocity(PVV)were compared across the groups.Additionally,basic clinical data were collected for all patients,including gender,age,primary diagnosis,D-dimer concentration,total operation time,cold ischemia time,hot ischemia time,intraoperative blood loss and transfusion,intraoperative urine volume,infusion,model for end-stage liver disease(MELD)score,and whether complex hepatic artery reconstructions were performed.Furthermore,risk factors influencing HAO formation after LT were analyzed.RESULTS Compared to the non-HAO group,PVV and RI were higher in the A-HAO group,while PSV was lower.Conversely,both PSV and RI were lower in the C-HAO group compared to the non-HAO group.The proportion of patients undergoing complex hepatic artery reconstructions and the gamma-glutamyltransferase(GGT)level before occlusion were significantly higher in the A-HAO group compared to the non-HAO group.However,there were no distinct differences between the two groups in D-dimer,MELD score,pre-occlusion alanine transaminase and aspartate transaminase levels,or intraoperative conditions.CONCLUSION Ultrasound features of the hepatic artery before occlusion are significantly associated with postoperative HAO development.Additionally,complex hepatic artery reconstructions,defined as revascularization of the graft requiring additional anastomosis between donor hepatic arteries,constitute a risk factor for A-HAO.Besides,abnormal pre-occlusion GGT elevation is an important biochemical indicator.Therefore,ultrasound examination serves as an important tool for screening HAO,especially in patients with the identified risk factors.

Percutaneous microwave ablation and transcatheter arterial chemoembolization for serum tumor markers and prognostics of middle-late primary hepatic carcinoma

BACKGROUND Primary hepatic carcinoma(PHC)has an insidious onset and is usually diagnosed in the middle and late stages.Although transcatheter arterial chemoembolization(TACE)is the preferred option for treating middle-and advanced-stage PHC,it has limited efficacy in killing tumor cells and poor long-term efficacy.TACE plus percutaneous microwave coagulation therapy(PMCT)is more effective than interventional therapy alone and can improve survival time.However,there are few reports on the effects of TACE and PMCT on serum marker levels and the prognosis of patients with advanced PHC.AIM To investigate the effect of PMCT+TACE on serum tumor markers and the prognosis of middle-late PHC.METHODS This retrospective study included 150 patients with middle-late PHC admitted to Zhongshan People’s Hospital between March 2018 and February 2021.Patients were divided into a single group(treated with TACE,n=75)and a combined group(treated with TACE+PMCT,n=75).Before and after treatment,the clinical efficacy and serum tumor marker levels[carbohydrate antigen 19-9(CA19-9),alpha-fetoprotein(AFP),and carcinoembryonic antigen(CEA)]of both groups were observed.The 1-year survival rates and prognostic factors of the two groups were analyzed.RESULTS The combined group had 21 and 35 cases of complete remission(CR)and partial remission(PR),respectively.The single group had 13 and 25 cases of CR and PR,decreased,with the decrease in the combined group being more significant(P<0.05).The 1-year survival rate of the combined group(80.00%)was higher than that of the single group(60.00%)(P<0.05).The average survival time within 1 year in the combined group was 299.38±61.13 d,longer than that in the single group(214.41±72.97 d,P<0.05).COX analysis revealed that tumor diameter,tumor number,and the treatment method were prognostic factors for patients with middle-late PHC(P<0.05).CONCLUSION TACE+PMCT is effective in treating patients with mid-late PHC.It reduces the levels of tumor markers,prolongs survival,and improves prognosis.

Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma:a prospective non.randomized study

Background: Transarterial chemoembolization(TACE) is recommended as the standard care for unresectable hepatocellular carcinoma(HCC) at Barcelona Clinic Liver Cancer(BCLC) stage A-B. However, the efficacy of TACE on large(> 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy(HAIC)might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX(mFOLFOX) regimen and those ofTACE in patients with massive unresectable HCC.Methods: A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen(oxaliplatin, 85 mg/m^2 intra-arterial infusion; leucovorin,400 mg/m^2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m^2 continuous infusion)every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression(TTP), and safety were assessed.Results: A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group(52.6% vs. 9.8%, P < 0.001;83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months(hazard radio[HR] = 2.35,95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection(10 vs. 3,P = 0.033). The proportions of grade 3-4 adverse events(AE) and serious adverse events(SAE) were lower in the HAIC group than in the TACE group(grade 3-4 AEs: 13 vs. 27, P = 0.007;SAEs: 6 vs. 15,p = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent(10 vs. 2,P = 0.026).Conclusions: HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.

Hepatic blood inflow occlusion without hemihepatic artery control in treatment of hepatocellular carcinoma

AIM:To investigate the clinical significance of hepatic blood inflow occlusion without hemihepatic artery control (BIOwHAC) in the treatment of hepatocellular carcinoma (HCC).METHODS:Fifty-nine patients with HCC were divided into 3 groups based on the technique used for achieving hepatic vascular occlusion:group 1,vascular occlusion was achieved by the Pringle maneuver (n=20);group 2,by hemihepatic vascular occlusion (HVO) (n=20);and group 3,by BIOwHAC (n=19).We compared the procedures among the three groups in term of operation time,intraoperative bleeding,postoperative liver function,postoperative complications,and length of hospital stay.RESULTS:There were no statistically significant differences (P > 0.05) in age,sex,pathological diagnosis,preoperative Child's disease grade,hepatic function,and tumor size among the three groups.No intraoperative complications or deaths occurrred,and there were no significant intergroup differences (P > 0.05) in intraoperative bleeding,hepatic function change 3 and 7 d after operation,the incidence of complications,and length of hospital stay.BIOwHAC and Pringle maneuver required a significantly shorter operation time than HVO;the difference in the serum alanine aminotransferase or aspartate aminotransferase levels before and 1 d after operation was more significant in the BIOwHAC and HVO groups than in the Pringle maneuver group (P < 0.05).CONCLUSION:BIOwHAC is convenient and safe;this technique causes slight hepatic ischemia-reperfusion injury similar to HVO.

Intraoperative ultrasonography during radiofrequency ablation for hepatic carcinoma

Objective： To explore the feasibility and efficiency of intraoperative ultrasonography （IOUS） in the cool-tip ra- diofrequency ablation （RFA） of hepatic carcinoma. Methods： Thirty-one patients of hepatic carcinoma were enrolled in this study. In the process of open-surgical cool-tip radiofrequency ablations, IOUS was applied to assess the hepatic lesions, guide and monitor the process of RFA in real-time. Results： Under the guidance of intraoperative ultrasonography, the open surgical RFA in all patients proceed smoothly. Seven additional hepatic lesions were found that were not detected in preoperative imaging. A false positive focal lesion reported by preoperative MRI was accurately ruled out by IOUS. Conclusion： Intraoperative ultrasonography is superior to ordinary imaging techniques in finding missed lesions, avoiding complications such as injuries of bile ducts and vessels. Monitoring the real-time RFA process thereby obviously optimizing the treatment of hepatic carcinoma.

Experimental Study of the Effect of the Bax Gene on Human Hepatocellular Carcinoma and Therapy via Hepatic Artery Delivery

OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the Bax gene transferred to the human hepatocellular carcinoma QGY7703 cell line was examined. In addition the Bax gene was transferred in vivo in mice via the caudal vein or hepatic artery to investigate the differences in target organ and non-target organ transfection. RESULTS 1）The Bax gene mediated by a binary adenoviral vector system induced apoptosis in the human hepatic carcinoma QFY7703 cell line. The cell apoptotic rate in the experimental group （Bax） was 50.2±6.9% but only 32.1 ± 9.7% in the Ad/CMV-p53 group, showing that the Bax-apoptotic rate was significantly higher than the control group. 2） LacZ expression was higher in the target organ （liver） when given through the hepatic artery than through the tail vein. In contrast, LacZ expression in the nontarget organs was higher if given through the tail vein compared to the hepatic artery. CONCLUSION Superselective hepatic artery delivery with Bax gene therapy is safe, specific, effective and has low toxicity. This study provided the basis for Bax-gene therapy via the hepatic artery in vivo.

Differentiation of intrahepatic cholangiocarcinoma from hepatocellular carcinoma in high-risk patients: a predictive model using contrast-enhanced ultrasound

AIM To develop a contrast-enhanced ultrasound(CEUS)predictive model for distinguishing intrahepatic cholangiocarcinoma(ICC) from hepatocellular carcinoma(HCC) in high-risk patients.METHODS This retrospective study consisted of 88 consecutive high-risk patients with ICC and 88 high-risk patients with HCC selected by propensity score matching between May 2004 and July 2016. Patients were assigned to two groups, namely, a training set and validation set, at a 1:1 ratio. A CEUS score for diagnosing ICC was generated based on significant CEUS features. Then, a nomogram based on the CEUS score was developed, integrating the clinical data. The performance of the nomogram was then validated and compared with that of the LR-M of the CEUS Liver Imaging Reporting and Data System(LI-RADS).RESULTS The most useful CEUS features for ICC were as follows: rim enhancement(64.5%), early washout(91.9%), intratumoral vein(58.1%), obscure boundary of intratumoral non-enhanced area(64.5%), and marked washout(61.3%, all P < 0.05). In the validation set, the area under the curve(AUC) of the CEUS score(AUC = 0.953) for differentiation between ICC and HCC was improved compared to the LI-RADS(AUC = 0.742)(P < 0.001). When clinical data were added, the CEUS score nomogram was superior to the LI-RADS nomogram(AUC: 0.973 vs 0.916, P = 0.036, Net Reclassification Improvement: 0.077, Integrated Discrimination Index: 0.152). Subgroup analysis demonstrated that the CEUS score model was notably improved compared to the LIRADS in tumors smaller than 5.0 cm(P < 0.05) but not improved in tumors smaller than 3.0 cm(P > 0.05).CONCLUSION The CEUS predictive model for differentiation between ICC and HCC in high-risk patients had improved discrimination and clinical usefulness compared to the CEUS LIRADS.

Prevention and treatment of hepatic artery thrombosis after liver transplantation

BACKGROUND: Hepatic artery thrombosis (HAT) which is a serious complication after orthotopic liver transplanta- tion (OLT) remains a significant cause of graft loss. The purpose of this study was to sum up our experiences in the prevention, diagnosis and management of HAT after liver transplantation. METHODS: From April 1993 to September 2003, a total of 198 patients underwent OLT at our hospital. The hepatic artery was anastomosed using 7/0 prolane with running continuous suture in 96 patients (group 1) and with inter- rupted suture in 102 (group 2). Ultrasonography was per- formed every day in two weeks after operation and selec- tively afterwards. RESULTS: HAT occurred in 6 patients (6.3%, 6/96) of group 1, and in 1 (1%, 1/102) of group 2 (x2=4.027, P= 0.045). Six patients received emergency thrombectomy, and 1 conservative therapy but died from tumor recurrence eventually. Biliary complication developed in 3 patients af- ter thrombectomy of whom 2 died of liver failure and one waited for retransplantation. In the other 3 patients after thrombectomy, 1 died of renal failure, and 2 survived. The mortality of patients with HAT was 57.1% (4/7). CONCLUSIONS: The technique of hepatic arterial anasto- mosis is the key factor for the prevention of HAT. Routine ultrasonography is very important in early detection of HAT after OLT. Biliary complication is a severe outcome secondary to HAT.

Ultrasound-guided fine needle biopsy of intra- hepatic nodules and low elevation of AFP in early diagnosis of hepatocellular carcinoma

BACKGROUND: With the progress in early clinical treat- ment of hepatocellular carcinoma (HCC), early detection and diagnosis of HCC have been increasingly pressing. Combined alpha-fetoprotein ( AFP) determination and ul- trasonography has become the main method for the detec- tion of small HCC; but the relationship between low eleva- tion of AFP and pathologic findings of small HCC has not been well defined. The aim of this study was to assess the value of ultrasound-guided fine needle biopsy of intrahe- patic nodules and low elevation of serum AFP in the early diagnosis of HCC. METHODS; Fifty-nine patients with serum AFP exceeding 20 ng/ml and intrahepatic nodules varying from 0.8 cm to 5.0 cm in diameter who had been detected by ultrasonogra- phy underwent ultrasound-guided percutaneous fine needle biopsy, and cytological staining and histological sectioning were performed at the same time. RESULTS: Among the 59 patients, 11 patients (18.6%) showed AFP level above 400 ng/ml, 5 (8. 5%) from 200 ng/ml to 400 ng/ml, 18 (30. 5%) from 50 ng/ml to 200 ng/ml and 25 (42. 4% ) from 20 ng/ml to 50 ng/ml. Fol- low-up demonstrated that 53 patients (89.8%) had a pro- gressive increase of AFP level. In 58 patients (98.3%) cancer cells were found by cytological staining and/or his- tological sectioning. CONCLUSIONS: In those patients with slightly increased or continuously positive AFP, hepatic carcinoma should be highly suspected when AFP increases gradually and intrahe- patic nodules are detected by ultrasonography in follow-up. Once intrahepatic carcinoma nodules are suspected, ultra- sound-guided fine needle biopsy should be performed as early as possible for early diagnosis and treatment.

Treatment strategies for advanced hepatocellular carcinoma:Sorafenib vs hepatic arterial infusion chemotherapy

Sorafenib is used worldwide as a first-line standardsystemic agent for advanced hepatocellular carcinoma(HCC) on the basis of the results of two large-scale Phase Ⅲ trials. Conversely,hepatic arterial infusion chemotherapy(HAIC) is one of the most recommended treatments in Japan. Although there have been no randomized controlled trials comparing sorafenib with HAIC,several retrospective analyses have shown no significant differences in survival between the two therapies. Outcomes are favorable for HCC patients exhibiting macroscopic vascular invasion when treated with HAIC rather than sorafenib,whereas in HCC patients exhibiting extrahepatic spread or resistance to transcatheter arterial chemoembolization,good outcomes are achieved by treatment with sorafenib rather than HAIC. Additionally,sorafenib is generally used to treat patients with Child-Pugh A,while HAIC is indicated for those with either Child-Pugh A or B. Based on these findings,we reviewed treatment strategies for advanced HCC. We propose that sorafenib might be used as a first-line treatment for advanced HCC patients without macroscopic vascular invasion or Child-Pugh A,while HAIC is recommended for those with macroscopic vascular invasion or Child-Pugh A or B. Additional research is required to determine the best second-line treatment for HAIC non-responders with Child-Pugh B through future clinical trials.

Combined treatment of hepatocellular carcinoma with partial splenic embolization and transcatheter hepatic arterial chemoembolization

AIM: To prospectively evaluate the effi cacy and safety of partial splenic embolization (PSE) combined with transcatheter hepatic arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC). METHODS: Fifty patients suffering from primary HCC associated with hypersplenism caused by cirrhosis were randomly assigned to 2 groups: group A receiving PSE combined with TACE (n = 26) and group B receiving TACE alone (n = 24). Follow-up examinations included calculation of peripheral blood cells (leukcytes, platelets and red blood cells) and treatment-associated complications. RESULTS: Prior to treatment, there was no signifi cant difference in sex, age, Child-Pugh grade, tumor diameter, mass pathology type and peripheral blood cell counts between the 2 groups. After treatment, leukocyte and platelet counts were significantly higher in group A during the 3-mo follow-up period (P < 0.05), but lower in group B (P < 0.05). Severe complications occurred in 3 patients (11.5%) of group A and in 19 patients (79.2%) of group B (P < 0.05), and there was no significant difference in symptoms of post-embolization syndrome, including abdominal pain, fever, mild nausea and vomiting between the 2 groups (P > 0.05). CONCLUSION: PSE combined with TACE is more effective and safe than TACE alone for patients with HCC associated with hypersplenism caused by cirrhosis.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.

Sorafenib combined with embolization plus hepatic arterial infusion chemotherapy for inoperable hepatocellular carcinoma

BACKGROUND There is little evidence of combining sorafenib with hepatic arterial infusion chemotherapy(HAIC)after transarterial chemoembolization(TACE)for intermediate and advanced hepatocellular carcinoma(HCC).It is important to identify that patients with intermediate and advanced HCC are most likely to benefit from this combination therapy.AIM To investigate the safety and clinical outcomes of sorafenib combined with HAIC with folinic acid,5-fluorouracil(5-FU),and oxaliplatin(FOLFOX)after TACE for intermediate and advanced HCC.METHODS This prospective phase II study enrolled patients with intermediate and advanced HCC who underwent treatment with sorafenib combined with TACEHAIC.All patients initially received the standard 400 mg dose of sorafenib twice daily before TACE-HAIC.Participants at our institute with intermediate and advanced HCC underwent routine TACE.Then,the catheter used for embolization was kept in place in the hepatic artery,and oxaliplatin was intraarterially administered for 6 h,followed by 5-FU for 18 h,and folinic acid was intravenously administered for 2 h.The primary endpoints were safety,as evaluated by the Common Terminology and Criteria for Adverse Events version 4.0,and 12-mo progression-free survival(PFS),as analyzed by the Kaplan-Meier method.As secondary endpoints,the objective response rate(ORR)was evaluated by the modified Response Evaluation Criteria for Solid Tumors,and survival time[overall survival(OS)]was analyzed by the Kaplan-Meier method.RESULTS Sixty-six participants at our institute with intermediate and advanced HCC were enrolled in this prospective study(mean age,53.3±11.7 years).Approximately 56.1%of participants had Barcelona Clinic Liver Cancer(BCLC)stage C disease,and 43.9%had BCLC stage B disease.The ORR was 42.4%.The disease control rate was 87.9%.The grade 3-4 toxicities consisted of thrombocytopenia(4.5%),neutropenia(3.0%),and elevated aspartate aminotransferase(12.2%).Hand-foot skin reaction was also observed(40.9%).The median PFS was 13.1 mo(13.5 mo in the BCLC stage B participants and 9.4 mo in the BCLC stage C participants).The 6-mo,12-mo,and 24-mo PFS rates were 75.0%,54.7%,and 30.0%,respectively.The median OS was 21.8 mo.CONCLUSION Sorafenib combined with HAIC(FOLFOX)after TACE may be a feasible treatment choice for intermediate and advanced HCC because this treatment met the prespecified endpoint of a 6-mo PFS rate exceeding 50%and had good patient tolerance.Prospective randomized controlled trials are needed to confirm the effect of this combination therapy.

Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy(HAIC) for advanced hepatocellular carcinoma(HCC) resistant to transarterial chemoembolization(TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001and 2010 at our hospital.5-fluorouracil(5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010(written in Japanese);one group of patients who did not fulfill the criteria for TACE resistance(group A,n = 23),and another group who fulfilled the criteria for TACE resistance(group B,n = 19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B(response rate:48% vs 16%,P = 0.028,tumor suppression rate:87% vs 53%,P = 0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B(3-,6-,12-,and 24-mo = 83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P = 0.040,and 9.8 mo vs 6.2 mo,P = 0.040).A multivariate analysis(Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival(P = 0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.