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.

Hepatic artery infusion with raltitrexed or 5-fluorouracil for colorectal cancer liver metastasis

AIM To evaluate the efficiency and safety of hepatic artery infusion chemotherapy(HAIC) using raltitrexed or 5-fluorouracil for colorectal cancer(CRC) liver metastasis(CRCLM).METHODS A retrospective analysis of patients with unresectable CRCLM who failed systemic chemotherapy and were subsequently treated with HAIC at our institute from May 2013 to April 2015 was performed. A total of 24 patients were treated with 5-fluorouracil, and 18 patients were treated with raltitrexed. RESULTS The median survival time(MST) from diagnosis of CRC was 40.8 mo in the oxaliplatin plus raltitrexed(TOMOX) arm and 33.5 mo in the oxaliplatin plus 5-fluorouracil(FOLFOX) arm(P = 0.802). MST from first HAIC was 20.6 mo in the TOMOX arm and 15.4 mo in the FOLFOX arm(P = 0.734). Median progression-free survival(PFS) from first HAIC was 4.9 mo and 6.6 mo, respectively, in the TOMOX arm and FOLFOX arm(P= 0.215). Leukopenia(P = 0.026) was more common in the FOLFOX arm, and hepatic disorder(P = 0.039) was more common in the TOMOX arm. There were no treatment-related deaths in the TOMOX arm and one treatment-related death in the FOLFOX arm. Analysis of prognostic factors indicated that response to HAIC was a significant factor related to survival.CONCLUSION No significant difference in survival was observed between the TOMOX and FOLFOX arms. HAIC treatment with either TOMOX or FOLFOX was demonstrated as an efficient and safe alternative choice.

Hepatic artery infusion of antisense oligodeoxynucleotide and lipiodol mixture transfect liver cancer in rats

AIM: To study the distribution and stability of antisense oligodeoxynucleotide (ASODN) in Walker-256 cells and their distribution in liver, lung and kidney tissues after being infused alone or mixed with lipiodol via hepatic artery in a rat liver tumor model.METHODS: 5'-Isothiocyananate (FITC)-labeled vascular endothelial growth factor (VEGF) ASODN was added into Walker-256 cell culture media. Its distribution in cells was observed by fluorescence microscope at different time points. Walker-256 carcinosarcoma was transplanted into Wistar rat liver to establish a liver cancer model. 5'-FITC-labeled VEGF ASODN mixed with (mixed group, n = 6) or without (TAI group, n = 6)ultra-fluid lipiodol was administrated via hepatic artery.Frozen samples of liver, lung and kidney tissue were taken from rats after 1, 3 and 6 d, respectively. The distribution of ASODN was observed under fluorescent microscope.RESULTS: ASODN could enter cytoplasm within 2 h and nuclei within 6 h. Accumulation of ASODN reached the peak point in nuclei at 12 h, and then disappeared gradually. No fluorescence could be seen in cells at 48 h. In vivo experiment, on d 1 and 3 the fluorescence staining in liver was stronger in mixed group than in TAI group and more fluorescence could be detected in lung and kidney in TAI group than in mixed group. On d 6, no fluorescence could be detected in TAI group, but faint fluorescence could be seen in mixed group. ASODN could be seen in cancer cells and normal hepatic cells. In mixed group, ASODN was mainly distributed in liver tumor tissues.CONCLUSION: ASODN can transfect Walker-256 cells.ASODN mixed with lipiodol infusion via hepatic artery can be used in the treatment of HCC.

Clinical study of interventional preoperative bronchial artery infusion chemotherapy combined with surgical resection for advanced non-small cell lung cancer

Objective： How to improve the postoperative 5-year survival rate for lung cancer and to give more patients a chance of surgery have become research hotspots. The aim of this research is to evaluate the clinical and pathohistological responses and effects of preoperative bronchial artery infusion （BAI） chemotherapy in patients with locally advanced （stage Ⅲ） non-small cell lung cancer （NSCLC）. Methods： A total of 92 patients with locally advanced NSCLC were randomly divided into two groups. BAI group received BAI chemotherapy for 2 cycles before surgical resection. Surgery group received operation only. The complete resection rate and clinical response were compared between the two groups. Results： In the BAI group, the clinical response rate and the pathohistological response rate were 68.3% and 51.3%, respectively. The complete resection rate in the BAI group was 89.7%, which was significantly higher than that in the surgery group （72.5%） （P 〈 0.05）. The 1- and 2-year survival rate was 100.0% and 80.6% in the BAI group, and 94.1% and 60.0% in the surgery group. Conclusion： BAI neoadjuvant chemotherapy is safe and effective, which has a good clinical and pathohistological response. It might increase the complete resection rate of the tumor and improve the long term survival rate of stage Ⅲ NSCLC patients.

The effects on surgery and preoperative patients with non-small cell lung cancer by preoperative bronchial artery infusion chemotherapy

Objective： To study the efficiency, safety and feasibility of preoperative bronchial artery infusion （BAI） chemotherapy on operation in patients with locally advanced （stage Ⅲ） non-small cell lung cancer （NSCLC）. Methods： 92 cases with locally advanced NSCLC patients were randomly divided into two groups： （1） BAI chemotherapy group： 39 cases were received BAI chemotherapy for 2 courses and followed surgery; （2） surgery alone group： 51 cases were treated by operation alone. The complete resection rate and preoperative complications were compared between these two groups. Results： In BAI chemotherapy group, the rate of clinical efficiency was 68.3% with slight toxicity. In BAI chemotherapy group the surgery complete resection rate was 89.7%, which was significantly higher than that in surgery alone group （72.5%, P 〈 0.05）. No significant differences of blood loss, operative complications and mortality were observed between these two groups. Conclusion： BAI neoadjuvant chemotherapy was safe and effective, which can increase the complete resection rate of the tumor and did not increase the operative complications and mortality.

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.

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.

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.

Selective Internal Iliac Artery Oxaliplatin Infusion： Another Facultative Treatment to Unremitting Hematuria in Stage T4 Bladder Carcinoma

OBJECTIVE To observe and evaluate the value of utilizing selective internal iliac artery infusion and selective internal iliac artery embolization for the treatment of unremitting gross hematuria of stage T4 bladder carcinoma. METHODS Fifty-eight stage T4 bladder carcinoma patients were selected. The patients were grouped to the TAI group and the TAE group. The main symptom of hemorrhage was gross hematuria. None of the patients in our study could receive trunk embolization. The infusion plan was oxaliplatin （100 mg/m2） and epirubicin （EPI 50mg/m2）. Embolization was done with coils or strips of gelatin sponge. The duration of gross hematuria was observed. Routine urinalysis and routine blood examination were performed. EORTC QLQ-C30 was used to evaluate the quality of life before and after treatment. RESULTS Gross hematuria and hematuria by light microscope in all patients were reviewed. Resolution time of gross hematuria in the TAI group was 6.7 ± 1.8 days and that in the TAE group was 3.5 ± 0.7 days. The changes in routine urianlysis, routine blood examination and EORTC QLQ-C30 are shown in Figs.l-3. Gross hematuria disappeared in both groups within 7 days after treatment, but the time for the gross hematuria to resolve in the TAE group was much less than that in TAI group （t = 2.51, P 〈 0.01）, and there were no significant differences in the 7th and 21st day between the 2 groups. On the 90th day, the number of erythrocytes in the urine was near 30, close to gross hematuria. The EORTC QLQ-C30 scores decreased after interventional therapy in both groups, which means that quality of life was increased, but there were no significant differences between the 2 groups. CONCLUSION Selective internal iliac artery infusion and selective internal iliac artery embolization are safe, and, in our study, therapeutic efficacy was satisfactory in treating unremitting gross hematuria of stage T4 bladder carcinoma in patients who could not receive trunk embolization. TAE can stop gross hematuria in the short term, but it can be used just once and the long-term therapeutic effect is not satisfactory. TAI had a therapeutic effect similar to TAE, but for a shorter duration, and TAI can be performed multiple times. TAI is one of the facultative treatments for treating gross hematuria of stage T4 bladder carcinoma.

Peripancreatic artery ligation and artery infusion chemotherapy for advanced pancreatic carcinoma

Objective To develop a new treatment for advanced pancreatic carcinoma. Methods Twenty-nine patients with advanced pancreatic carcinoma (12 patients with liver metastasis at the same time) were randomly divided into two groups. In group A (n=11), patients underwent bilio-enterostomy and/or gastro-enterostomy combined with systemic chemotherapy after surgery. In group B (n=18), patients underwent bilio-enterostomy and/or gastro-enterostomy combined with peripancreatic arterial ligation and arterial infusion regional chemotherapy. Twenty-four patients were followed up for 3-18 months. The palliation of clinical symptoms, changes in carcinoma size by B ultrasound (BUS) and CT scan, survival period and serum carcinoembryonic antigen (CEA) were observed and compared between the two groups. Results Symptoms were alleviated in most patients in group B, and BUS and CT scan showed that tumor volume decreased in group B. The response rate was 66.7% in group B and 18.2% in group A (P<0.01). The mean survival period was 4.8±0.6 months in group A and 12.5±1.2 months in group B (P<0.01); there were significant differences between the two groups. The decrease in serum CEA was 54% in group A and 60% in group B; the difference was not significant (P>0.05). Conclusion Peripancreatic arterial ligation combined with arterial infusion regional chemotherapy is effective against both pancreatic carcinoma and with liver metastases. It can alleviate clinical symptoms, postpone the growth rate of tumor and prolong the survival period.

Retrograde embolization technique of the right gastric artery during the implantation of port-catheter system for hepatic arterial infusion chemotherapy

Objective:This study aimed to introduce and evaluate a new embolization technique for the right gastric artery(RGA) during percutaneous implantation of a port-catheter system for hepatic arterial infusion chemotherapy(HAIC).Methods:From January 2013 to January 2017,159 patients with unresectable advanced liver cancer underwent percutaneous implantation of a port-catheter system.In 86 of these patients(56 men;aged 28-88 years;mean:60.6±12.0 years),in whom the RGA was obvious on arteriography,embolization of RGA was attempted using microcoils to protect the gastric mucosa during HAIC.In the first phase(first three years),antegrade embolization of the RGA using a 2.7 Fr microcatheter was performed in 55 patients.In the second phase(next two years),embolization of the RGA was attempted by combining antegrade embolization and retrograde embolization through the left gastric artery(LGA) in 31 patients.The success rates and the incidence of acute gastroduodenal mucosal toxicity(AGMT) in these two groups were compared.Results:The total success rate of the RGA embolization was 70.9%.The success rate was 83.9% in 31 patients who underwent combined antegrade and retrograde embolization,which was significantly higher than that of antegrade embolization alone(63.6%) performed in 55 patients(p=0.047).No complications related to embolization of RGA were documented.The incidence of AGMT was 29.1%(16/55) in patients in the first phase,which was significantly higher than that in the patients in the second phase(9.7%,3/31)(p=0.037).Conclusion: A combination of retrograde embolization via LGA could increase the success rates of RGA embolization and reduce the incidence of AGMT after HAIC.

Tumor-feeding artery diameter reduction is associated with improved short-term effect of hepatic arterial infusion chemotherapy plus lenvatinib treatment

BACKGROUND Recently,hepatic arterial infusion chemotherapy(HAIC)plus lenvatinib has been frequently used to treat unresectable hepatocellular carcinoma(uHCC)in China.In the clinic,the hepatic arteries of some patients shrink significantly during this treatment,leading to improved short-term efficacy.AIM To investigate the relationship between the shrinkage of hepatic arteries and the short-term effect of HAIC plus lenvatinib treatment.METHODS Sixty-seven participants with uHCC were enrolled in this retrospective study.The patients received HAIC every 3 wk,followed by oral lenvatinib after the first HAIC course.Hepatic artery diameters were measured on CT before treatment and after 1 and 2 mo of treatment.Meanwhile,the changes in tumor capillaries were also examined on pathological specimens before and after 1 mo of treatment.The antitumor response after 1,3,and 6 mo of treatment was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST).The relationship between the changes in vessel diameters and the short-term effect of the combination treatment was evaluated by receiver-operating characteristic and logistic regression analyses.RESULTS The hepatic artery diameters were all significantly decreased after 1 and 2 mo of treatment(P<0.001),but there was no difference in the vessel diameters between 1 and 2 mo(P>0.05).The microvessel density in the tumor lesions decreased significantly after 1 mo of combination treatment(P<0.001).According to mRECIST,46,41,and 24 patients had complete or partial responses after 1,3,and 6 mo of treatment,respectively,whereas 21,21,and 32 patients had a stable or progressive disease at these times,respectively.Shrinkage of the tumor-feeding artery was significantly associated with the tumor response after 1,3,and 6 mo of treatment(P<0.001,P=0.004,and P=0.023,respectively);however,changes in other hepatic arteries were not significantly associated with the tumor response.Furthermore,shrinkage of the tumor-feeding artery was an independent factor for treatment efficacy(P=0.001,P=0.001,and P=0.002 and 1,3,and 6 mo,respectively).CONCLUSION The hepatic arteries shrank rapidly after treatment with HAIC plus lenvatinib,and shrinkage of the tumor-feeding artery diameter was closely related to improved short-term efficacy.

Current research status of transarterial therapies for hepatocellular carcinoma

With continuous advancements in interventional radiology,considerable progress has been made in transarterial therapies for hepatocellular carcinoma(HCC)in recent years,and an increasing number of research papers on transarterial therapies for HCC have been published.In this editorial,we comment on the article by Ma et al published in the recent issue of the World Journal of Gastrointestinal Oncology:“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”.We focus specifically on the current research status and future directions of transarterial therapies.In the future,more studies are needed to determine the optimal transarterial local treatment for HCC.With the emergence of checkpoint immunotherapy modalities,it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

Comparative effectiveness of several adjuvant therapies after hepatectomy for hepatocellular carcinoma patients with microvascular invasion

BACKGROUND For resectable hepatocellular carcinoma(HCC),radical hepatectomy is commonly used as a curative treatment.However,postoperative recurrence significantly diminishes the overall survival(OS)of HCC patients,especially with microva-scular invasion(MVI)as an independent high-risk factor for recurrence.While some studies suggest that postoperative adjuvant therapy may decrease the risk of recurrence following liver resection in HCC patients,the specific role of adju-vant therapies in those with MVI remains unclear.AIM To conduct a network meta-analysis(NMA)to evaluate the efficacy of various adjuvant therapies and determine the optimal adjuvant regimen.METHODS A systematic literature search was conducted on PubMed,EMBASE,and Web of Science until April 6,2023.Studies comparing different adjuvant therapies or comparing adjuvant therapy with hepatectomy alone were included.Hazard ratios(HRs)with 95%confidence intervals were used to combine data on recurrence free survival and OS in both pairwise meta-analyses and NMA.RESULTS Fourteen eligible trials(2268 patients)reporting five different therapies were included.In terms of reducing the risk of recurrence,radiotherapy(RT)[HR=0.34(0.23,0.5);surface under the cumulative ranking curve(SUCRA)=97.7%]was found to be the most effective adjuvant therapy,followed by hepatic artery infusion chemotherapy[HR=0.52(0.35,0.76);SUCRA=65.1%].Regarding OS improvement,RT[HR:0.35(0.2,0.61);SUCRA=93.1%]demonstrated the highest effectiveness,followed by sorafenib[HR=0.48(0.32,0.69);SUCRA=70.9%].INTRODUCTION Hepatocellular carcinoma(HCC)is the sixth most common malignant tumor in the world and ranks third in terms of worldwide malignant tumor mortality rates in 2020[1].Curative treatments for HCC include ablation,radical hepatectomy,and liver transplantation.However,ablation is suitable only for early-stage HCC patients,who represent a small percentage of the overall HCC population.Although liver transplantation serves as the optimal treatment for HCC patients,the scarcity of donor organs restricts the availability of this procedure.Therefore,hepatectomy is the most commonly employed curative treatment for resectable HCC.Unfortunately,the 5-year recurrence rate for patients who undergoing hepatectomy ranges from 50%to 70%[2,3].Recurrence of HCC is associated with several risk factors[4],including single nodule>5 cm,vascular invasion,and multiple nodules.Among these factors,microvascular invasion(MVI)is an independent risk factor for recurrence.MVI is defined as the presence of cancer cells in the lumen of endothelium-lined vessels,typically in the small branches of the portal and hepatic veins of the paracancerous liver tissue,visible only under the microscope[5].Previous studies have shown that among HCC patients who underwent hepatectomy,those with MVI had a higher risk of recurrence and shorter overall survival(OS)than those without MVI[6].Several studies have indicated that adjuvant therapy following curative hepatectomy can prevent recurrence and improve OS in HCC patients with MVI.These postoperative adjuvant therapies include transarterial chemoembolization(TACE)[7],sorafenib[8],hepatic artery infusion chemotherapy(HAIC)[9],and radiotherapy(RT)[10].However,the existing studies mostly compare individual adjuvant therapy with hepatectomy alone.Direct or indirect comparisons between the various adjuvant therapies are lacking.Therefore,we performed the network meta-analysis(NMA)to compare the relative efficacy of each adjuvant therapy to determine the optimal treatment.

Advances in Conversion Therapy for Primary Unresectable Hepatocellular Carcinoma

Primary liver cancer is one of the most common malignant tumours in the world, and according to statistics, about half of liver cancers occur in China, which seriously threatens the lives and health of people around the world, especially in China. Hepatocellular carcinoma is the most common type, accounting for about 90 per cent of primary liver cancers. Most patients are asymptomatic in the early stage and fail to pay attention to it. Most of the patients are in the middle or late stage when they are first diagnosed, and only 20% - 30% of them can receive radical hepatectomy. Patients are through the treatment to make the tumour shrinkage and downstaging, to achieve the condition of resectable, that is, the conversion treatment. Conversion therapy has great potential for development and has now become an indispensable treatment for intermediate and advanced hepatocellular carcinoma. However, there are various treatment options for conversion therapy, no uniform guidelines to guide clinical selection, and the overall conversion rate is still low, so it is particularly important to explore appropriate conversion therapy options. This article mainly describes the existing conversion therapies, hoping to provide help and ideas for exploring the best conversion therapies in the future.

Prognostic factors for transarterial chemoembolization combined with sustained oxaliplatin-based hepatic arterial infusion chemotherapy of colorectal cancer liver metastasis

Objective： To investigate the prognostic factors in chemorefractory colorectal cancer liver metastasis（CRCLM）patients treated by transarterial chemoembolization（TACE） and sustained hepatic arterial infusion chemotherapy（HAIC）.Methods： Between 2006 and 2015, 162 patients who underwent 763 TACE and HAIC in total were enrolled in this retrospective study, including 110 males and 52 females, with a median age of 60（range, 26–83） years.Prognostic factors were assessed with Log-rank test, Cox univariate and multivariate analyses.Results： The median survival time（MST） and median progression-free survival（PFS） of the 162 patients from first TACE/HAIC were 15.6 months and 5.5 months respectively. Normal serum carbohydrate antigen 19-9（CA19-9, 〈37 U/m L）（P〈0.001） and carbohydrate antigen 72-4（CA72-4, 〈6.7 U/m L）（P=0.026）, combination with other local treatment（liver radiotherapy or liver radiofrequency ablation）（P=0.034） and response to TACE/HAIC（P〈0.001） were significant factors related to survival after TACE/HAIC in univariate analysis. A multivariate analysis revealed that normal serum CA19-9（P〈0.001）, response to TACE/HAIC（P〈0.001） and combination with other local treatment（P=0.001） were independent factors among them.Conclusions： Our findings indicate that serum CA19-9 〈37 U/m L and response to TACE/HAIC are significant prognostic indicators for this combined treatment, and treated with other local treatment could reach a considerable survival benefit for CRCLM. This could be useful for making decisions regarding the treatment of CRCLM.

Liver transplantation following two conversions in a patient with huge hepatocellular carcinoma and portal vein invasion:A case report

BACKGROUND Surgical resection and liver transplantation(LT)are the most effective curative options for hepatocellular carcinoma(HCC).However,few patients with huge HCC(>10 cm in diameter),especially those with portal vein tumor thrombus(PVTT),can receive these treatments.Selective internal radiation therapy(SIRT)can be used as a conversion therapy for them because it has the dual benefit of shrinking tumors and increasing residual hepatic volume.However,in patients with huge HCC,high lung absorbed dose often prevents them from receiving SIRT.CASE SUMMARY A 35-year-old man was admitted because of emaciation and pain in the hepatic region for about 1 month.The computed tomography scan showed a 20.2 cm×19.8 cm tumor located in the right lobe–left medial lobes with right portal vein and right hepatic vein invasion.After the pathological type of HCC was confirmed by biopsy,two conversions were presented.The first one was drug-eluting bead transarterial chemoembolization plus hepatic arterial infusion chemotherapy and lenvatinib and sintilimab,converted to SIRT,and the second one was sequential SIRT with continued systemic treatment.The tumor size significantly decreased from 20.2 cm×19.8 cm to 16.2 cm×13.8 cm,then sequentially to 7.8 cm×6.8 cm.In the meantime,the ratio of spared volume to total liver volume increased gradually from 34.4%to 55.7%,then to 62.9%.Furthermore,there was visualization of the portal vein,indicating regression of the tumor thrombus.Finally,owing to the new tumor in the left lateral lobe,the patient underwent LT instead of resection without major complications.CONCLUSION Patients with inoperable huge HCC with PVTT could be converted to SIRT first and accept surgery sequentially.

Downstaging strategies for unresectable hepatocellular carcinoma

A significant number of patients with hepatocellular carcinoma(HCC)are usually diagnosed in advanced stages,that leads to inability to achieve cure.Palliative options are focusing on downstaging a locally advanced disease.It is wellsupported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with surgery.Hepatic artery infusion chemotherapy can be a potential downstaging strategy,since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

Continuous regional arterial infusion therapy with gabexate mesilate for severe acute pancreatitis

AIM： To evaluate the efficacy of continuous regional arterial infusion therapy （CRAI） with gabexate mesilate and antibiotics for severe acute pancreatitis （SAP）. METHODS： We conducted a prospective study on patients who developed SAP with or without CRAI. Out of 18 patients fulfilled clinical diagnostic criteria for SAP in Japan, 9 patients underwent CRAI, while 9 patients underwent conventional systemic protease inhibitor and antibiotics therapy （non-CRAI）. CRAI was initiated within 72 h of the onset of pancreatitis. Gabexate mesilate （2400 mg/d） was continuously administered for 3 to 5 d. The clinical outcome including serum inflammation-related parameters were examined. RESULTS- The duration of abdominal pain in the CRAI group was 1.9 =1：0.26 d, whereas that in the non-CRAI group was 4.3 ±0.50. The duration of SIRS in the CRAI group was 2.2 ± 0.22 d, whereas that in the non- CRAI group was 3.2 ± 0.28. Abdominal pain and SIRS disappeared significantly in a short period of time after the initiation of CRAI using gabexate mesilate. The average length of hospitalization significantly differed between the CRAI and non-CRAI groups, 53.3 ± 7.9 d and 87.4± 13.9 d, respectively. During the first two weeks, levels of serum CRP and the IL6/IL10 ratio in the CRAI group tended to have a rapid decrease compared to those in the non-CRAI group. CONCLUSION： The present results suggest that CRAI using gabexate mesilate was effective against SAP.