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.

Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases

Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.

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.

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.

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.

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.

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.

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma

AIM： To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein （PGP） and p53 protein in advanced hepatocellular carcinoma （HCC）. METHODS： The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug （epirubicin hydrochloride; anthracycline group）, and the remaining 21 were treated with a non-anthracycline drug （mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group）. The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS： Before the start of the treatment, PGPpositive rate was 90.2% （strongly-positive, 36.6%） and p53 protein-positive rate was 34.1% （strongly-positive, 19.5%）. In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression （P= 0.005）, and their prognoses were poor （P= 0.001）. in the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients （P= 0.012）, irrespective of the survival outcome. CONCLUSION： The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

AIM:To investigate the efficacy of hepatic arterial infusion chemotherapy(HAIC) using floxuridine(FUDR) in patients with advanced hepatocellular carcinoma(HCC) confined to the liver.METHODS:Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at ourhospital between March 2005 and May 2008.Among the 34 patients,9 patients were classified as Child class C,and 18 patients had portal vein tumor thrombus(PVTT).One course of chemotherapy consisted of continuous infusion of FUDR(0.3 mg/kg during day 1-14) and dexamethasone(10 mg on day 1,4,7 and 11),and this treatment was repeated every 28 d.RESULTS:Two patients(5.9%) displayed a complete response,and 12 patients(35.3%) had a partial response.The tumor control rate was 61.8%.The median overall survival times were 15.3 mo,12.4 mo and 4.3 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0392).The progression-free survival was 12.9 mo,7.7 mo and 2.6 mo for the patients who were classified as Child class A,Child class B and Child class C,respectively(P = 0.0443).The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT.In addition to hepatic reserve capacity and PVTT,the extent of HCC was an independent factor in determining a poor prognosis.The most common adverse reactions to HAIC were mucositis,diarrhea and peptic ulcer disease,but most of these complications were improved by medical treatment and/or a delay of HAIC.CONCLUSION:The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities,even in patients with advanced cirrhosis.

Transarterial chemoembolization with hepatic arterial infusion chemotherapy plus S-1 for hepatocellular carcinoma

BACKGROUND Transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)have shown promising local benefits for advanced hepatocellular carcinoma(HCC).S-1,a composite preparation of a 5-fluorouracil prodrug,has proven to be a convenient oral chemotherapeutic agent with definite efficacy against advanced HCC.AIM To evaluate the efficacy and safety of TACE followed by HAIC with or without oral S-1 for treating advanced HCC.METHODS In this single-center,open-label,prospective,randomized controlled trial,117 participants with advanced HCC were randomized to receive TACE followed by oxaliplatin-based HAIC either with(TACE/HAIC+S-1,n=56)or without(TACE/HAIC,n=61)oral S-1 between December 2013 and September 2017.Two participants were excluded from final analysis for withdrawing consent.The primary endpoint was progression-free survival(PFS)and secondary endpoints included overall survival(OS),objective response rate,disease control rate and safety.RESULTS In total,115 participants(100 males and 15 females;mean age,57.7 years±11.9)were analyzed.The median PFS and OS were 5.0 mo(0.4–58.6 mo)(95%confidence interval(CI):3.82 to 6.18)vs 4.4 mo(1.1–54.4 mo)(95%CI:2.54 to 6.26;P=0.585)and 8.4 mo(0.4–58.6 mo)(95%CI:6.88 to 9.92)vs 8.3 mo(1.4–54.4 m)(95%CI:5.71 to 10.96;P=0.985)in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.The objective response rate and disease control rate were 30.9%vs 18.4%and 72.7%vs 56.7%in the TACE/HAIC+S-1 and TACE/HAIC groups,respectively.Grade 3/4 adverse events had a similar frequency in both treatment groups.CONCLUSION No improvements in tumor response rates,PFS or OS were observed with the addition of S-1 to TACE/HAIC in advanced HCC.Both treatment regimens had a similar safety profile.

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.

Transcatheter arterial infusion chemotherapy and embolization for primary lacrimal sac squamous cell carcinoma: A case report

BACKGROUND Although tumors of the lacrimal sac are rare,they represent a potentially lifethreatening situation that can easily be overlooked since patients present with features consistent with chronic dacryocystitis.Lacrimal sac squamous cell carcinoma is the most common lacrimal sac malignancy,but no definitive treatment is currently available.CASE SUMMARY We describe a 34-year-old unmarried male who presented with a red and swollen right lower eyelid,which gradually developed into a mass of the lower eyelid that obstructed vision in his right eye.He was treated with transcatheter arterial infusion chemotherapy and interventional embolization based on the tumor characteristics,and we also administered intensity-modulated radiotherapy and targeted therapy after tumor shrinkage.The tumor treatment demonstrated good efficacy,and the patient’s condition was stable after 10 mo of follow-up.CONCLUSION To our knowledge,this is the first report of lacrimal sac squamous cell carcinoma treated with transcatheter arterial infusion chemotherapy and interventional embolization,which might expand clinical treatment options for lacrimal sac carcinoma.

PERIPANCREATIC ARTERIAL LIGATION COMBINED WITH ARTERIAL INFUSION REGIONAL CHEMOTHERAPY FOR TREATING PATIENTS WITH ADVANCED PANCREATIC CARCINOMA

Objective To find out a new treatment method for advanced pancreatic carcinoma. Methods Twenty nine patients with advanced pancreatic carcinoma and liver metastases were randomly divided into 2 groups.Group A ( n =11) underwent bilio enterostomy and/or gastro enterostomy combined with systemic chemotherapy after operation;Group B( n =18) underwent bilio enterostomy and/or gastro enterostomy combined with peripancreatic arterial ligation and arterial infusion regional chemotherapy.The alleviation of clinical symptom,the change of carcinoma volume by BUS and CT scan,survival period and serum CEA were observed in two groups. Results The symptoms were alleviated apparently in most cases in Group B;BUS and CT scan showed that the tumor volume decreased apparently in Group B;The response rate was 67.7% in Group B,and 18.2% in Group A,respectively( 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,respectively( P <0.01),there was significant difference between the two groups.The decrease of serum CEA was 54% in Group A and 60% in Group B,but the difference was not significant( P >0.05). Conclusion Peripancreatic arterial ligation combined with arterial infusion regional chmotherapy is believed to be effective against both pancreatic carcinoma and liver metastases,and it can alleviate the clinical symptoms,postpone the growth speed of tumor,and prolong the survival period.

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.

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.