Intrahepatic cholangiocarcinoma (iCCA) has been a contraindication for liver transplantation due to frequent recurrence and poor survival. We sought to determine the true proportion of transplantation-eligible iCCA patients and their outcomes without transplantation. Data from patients evaluated for iCCA at two academic medical centers between 2008 and 2018 were analyzed retrospectively. Overall survival was determined for patients categorized as eligible for liver transplantation based on six criteria: unresectability, no extrahepatic disease, stable disease after chemotherapy, functional status (maximum age, 72 years), no major comorbidity, and no involvement of major vasculature. Of 1407 iCCA patients with sufficient data, 327 (23%) had advanced liver-confined disease. Most (n = 180 [55%]) progressed or died before 6 months of therapy. Others were ineligible owing to resection after pretreatment (n = 47), poor performance status (n = 8), advanced age (n = 32), comorbidity (n = 19), or extensive extrahepatic vascular involvement (n = 2). Only 39 patients (12% of 327; 2.8% of 1,407; 95% confidence interval [CI] 2-3.8%) met eligibility, with more than half (n = 22 [56%]) treated with hepatic arterial infusion pump chemotherapy. Their median survival from diagnosis was 39 months (95% CI 28-62 months); 3-year survival from estimated eligibility was 46% (95% CI 32-65%). Patients who meet stringent eligibility criteria for liver transplantation constitute approximately 3% of patients with iCCA. The observed survival exceeds benchmarks established for systematic therapy alone and is likely attributable to favorable tumor biology and hepatic artery infusion chemotherapy.

Lenvatinib stands out as a first-line therapy for individuals with advanced hepatocellular carcinoma (HCC). Concurrently, hepatic arterial infusion chemotherapy comprising oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) has emerged as a potential option for those with advanced HCC. It is necessary to investigate the efficacy and safety of lenvatinib plus FOLFOX-HAIC (lenvaHAIC) for advanced HCC in real-world situations. In this retrospective analysis, 127 consecutive patients underwent lenvaHAIC, while 184 patients received lenvatinib alone as first-line treatment at six Chinese academic centers between January 2019 and June 2022. Following 1:1 propensity score matching, we established paired cohorts (113 patients in each group) for evaluating survival. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety profiles were compared between the two groups. The lenvaHAIC group exhibited significantly prolonged median PFS and OS than the lenvatinib group (PFS: 12.3 vs. 6.2months; OS: 25.6 vs. 12.3months; P < .001 for each). In the propensity score-matched cohorts (113 pairs), both PFS and OS were notably extended in the lenvaHAIC group compared with those in the lenvatinib group (P < .001). Multivariate analysis identified lenvaHAIC treatment as an independent factor for improved PFS (hazard ratio [HR] 0.45; P < .001) and OS (HR 0.38; P < .001). Grade 3-4 adverse events, including nausea, vomiting, diarrhea, thrombocytopenia, and neutropenia, were more prevalent in the lenvaHAIC group. In this real-world study, lenvaHAIC, compared with lenvatinib monotherapy, was associated with significantly prolonged PFS and OS and a higher ORR, while demonstrating a manageable safety profile in patients with advanced HCC.

Biliary Abnormality on Imaging During Lenvatinib Plus Hepatic Arterial Infusion Chemotherapy With Cisplatin for Hepatocellular Carcinoma: A Pilot Descriptive Study.

Postoperative comfort management for patients with hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy remains unstandardized, with fragmented evidence limiting clinical practice. To establish China's first evidence-based framework for postoperative physiologic comfort management in patients with hepatocellular carcinoma undergoing hepatic arterial infusion chemotherapy, a systematic evidence synthesis, guided by the 6S Pyramid, was conducted. Sixteen databases, including PubMed®, Cochrane Library, and CNKI, were searched from inception to July 2024. Literature was systematically retrieved, appraised, and synthesized. Two researchers independently assessed study quality using AGREE II (Appraisal of Guidelines for Research and Evaluation) and JBI tools. Evidence extraction followed hierarchical principles, with conflicts resolved through panel arbitration. 14 studies were included, yielding 13 recommendations across the following six domains: patient education, nausea and vomiting control, gastrointestinal recovery, pain management, urinary retention, and early mobilization. The proposed postoperative physiologic comfort management framework enables standardized nursing protocols across hospital settings, prioritizes patient-centered outcomes, and establishes measurable comfort metrics. Nurses can implement structured preoperative education and functional training while adopting stratified symptom management for patients undergoing hepatic arterial infusion chemotherapy.

Hepatic Arterial Infusion Chemotherapy Review.

ObjectiveTo retrospective analysis the efficacy and safety of Transarterial Chemoembolization (TACE) combined with Hepatic Arterial Infusion Chemotherapy (Ralox-HAIC, Oxaliplatin + Raltitrexed) and systemic therapy in patients with unresectable Hepatocellular Carcinoma (uHCC).MethodsClinical data of patients with uHCC who received TACE combined with Ralox-HAIC followed by sequential systemic therapy at our hospital between January 2023 and December 2024 were analyzed. The primary endpoint was Objective Response Rate (ORR). Secondary endpoints included Progression-Free Survival (PFS), Overall Survival (OS) and treatment safety.ResultsA total of thirty-six patients with complete data were included. Efficacy evaluation showed: Complete Response (CR) in 6 cases (16.67%), Partial Response (PR) in 22 cases (61.11%), Stable Disease (SD) in 5 cases (13.89%), and Progressive Disease (PD) in 2 cases (5.56%). The ORR was 77.78%, and the Disease Control Rate (DCR) was 91.67%. The median PFS was 12.0 months, and the median OS was 19.0months. The one-year and two-year survival rates were 89% and 38%, respectively. No Grade 4 treatment-related adverse events or treatment-related deaths occurred.ConclusionTACE combined with Ralox-HAIC and systemic therapy demonstrated a high ORR and DCR with manageable safety in uHCC, warranting further prospective studies for validation.

Surgical Considerations for Primary Liver Neoplasms.

Background:Beyond surgical intervention, hepatocellular carcinoma is mainly treated with 3 main approaches: transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) as local treatment, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs). Up to now, clinical experts have not reached a consistent consensus on how to reasonably select combination therapy. Therefore, we performed this research to contrast the clinical outcomes of local treatment plus ICIs and TKIs (Local-ICIs-TKIs) with ICIs and TKIs, aiming to offer a practical reference basis for clinical practice.Methods:We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases on the computer, covering literature from their establishment to August 1st, 2025, for (Local-ICIs-TKIs) compared to ICIs and TKIs Clinical Investigation. The primary outcome indicators were treatment-related adverse events, median overall survival, median progression-free survival, objective response rate, and disease control rate. All statistical analyses were conducted using Stata 17 statistical software in this study.Results:We screened 15 relevant pieces of literature, including 3208 patients. Compared with the ICIs-TKIs group, the Local-ICIs-TKIs treatment enhanced the pooled disease control rate (relative risk = 1.27; 95% confidence interval [CI]: 1.21–1.33) and objective response rate (relative risk = 1.87; 95% CI: 1.71–2.05). The combination therapy individually prolonged the median progression-free survival (hazard ratio = 0.59; 95% CI: 0.47–0.71) and median overall survival (hazard ratio = 0.48; 95% CI: 0.40–0.56). TACE and HAIC significantly elevated the risks of abdominal pain, anorexia, nausea, appetite loss, leukopenia, and liver injury. HAIC exhibited a higher incidence of abdominal pain, whereas TACE was more likely to lead to severe liver injury. The majority of adverse events were mild to moderate, and both interventions demonstrated favorable safety.Conclusion:In comparison to the foundation of ICIs-TKIs systemic therapy, the addition of TACE or HAIC treatment exhibits good tolerability and can further yield superior clinical responses and prolong survival time for hepatocellular carcinoma patients.

Resectability redefined: Lessons from quadruple therapy in HCC.

Triple combination therapy consisting of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab has shown encouraging clinical efficacy in patients with advanced hepatocellular carcinoma (HCC). However, robust prognostic models to predict treatment outcomes remain lacking. A total of 83 patients with unresectable HCC receiving HAIC combined with lenvatinib and tislelizumab were enrolled to develop a prognostic prediction model, which was subsequently validated in an independent cohort of 26 patients. Underlying mechanisms were investigated using targeted exome sequencing and RNA sequencing. We assessed the cumulative impact of gene mutations and identified three signaling pathways associated with progression-free survival (PFS), namely the Hedgehog, ErbB, and focal adhesion pathways, in patients undergoing triple combination therapy. An integrated prognostic model incorporating these PFS-related pathways and key clinical risk factors-aspartate aminotransferase, Child-Pugh class, and presence of metastasis-was established and validated. Mechanistic analyses demonstrated enrichment of angiogenesis- and hypoxia-related signatures, along with increased immune cell infiltration in responders, providing a biological basis for the observed therapeutic efficacy. This integrated prognostic model, combining pathway-level genomic alterations with clinical risk factors, enables reliable prediction of treatment outcomes in patients with unresectable HCC receiving HAIC, lenvatinib, and tislelizumab. It may serve as a valuable tool for guiding personalized therapeutic decision-making.

Background:Gastric cancer (GC) is the fifth most common cancer and the fourth leading cause of cancer-related mortality worldwide. The liver is the primary metastatic site, and the prognosis of gastric cancer with liver metastasis (GCLM) remains poor. While transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used for liver cancer, their roles in GCLM remain underexplored.Objectives:This study aimed to evaluate the efficacy and safety of drug-eluting bead TACE (DEB-TACE) combined with HAIC in patients with unresectable GCLM.Design:This was a retrospective, single-center cohort study.Methods:We retrospectively analyzed 62 patients with GCLM treated at Peking University Cancer Hospital between July 2018 and June 2023. Patients underwent 135 sessions using either HepaSphere beads plus HAIC-FOLFOX (HEPA-HAIC, n = 33) or DC bead plus HAIC-FOLFOX (DCB-HAIC, n = 29). The primary endpoint was median overall survival (mOS); secondary endpoints included median hepatic progression-free survival (mhPFS), median progression-free survival (mPFS), tumor response, and safety.Results:Among the patients (53 male, 9 female), 75.8% had intestinal-type cancer. Over 95% underwent prior treatments. The mOS was 10.7 months in both groups. The HEPA-HAIC cohort achieved longer mhPFS (8.6 vs 7.6 months) and mPFS (5.7 vs 4.4 months), though not statistically significant. Objective response rate and disease control rate were similar (30.3%/75.8% vs 31.0%/75.9%). Propensity score matching confirmed these findings. Univariate Cox regression suggested primary tumor location and carcinoembryonic antigen were prognostic for hPFS and OS, respectively. No treatment-related deaths occurred. Common adverse events (AEs) were transaminase elevation and pain. Nausea, vomiting, and severe pain were significantly less frequent with HEPA-HAIC (5.6% vs 31.7%, p = 0.001; 4.2% vs 31.7%, p < 0.001; 8.3% vs 22.2%, p = 0.01).Conclusion:DEB-TACE plus HAIC was feasible and demonstrated intrahepatic disease control with acceptable tolerability in unresectable GCLM; HEPA-HAIC showed a favorable safety profile.

Hepatic arterial infusion chemotherapy (HAIC) is a valuable option in patients with liver-dominant metastatic colorectal cancer (mCRC) but remains underutilized due to limited data. We conducted a retrospective study of mCRC patients treated with HAIC in an expert center between 2010 and 2024. Patients were grouped according to treatment setting: intensification (INT; 1st/2nd line) and salvage (SALV; ≥3rd line). Among 213 patients, 99 received INT-HAIC and 114 SALV-HAIC. SALV patients had worse baseline features, including more ECOG ≥2 (16% vs 4%), RAS mutation (55% vs 45%), extra-hepatic disease (45% vs 23%), liver burden >50% (65% vs 40%), and prior IV oxaliplatin progression (41% vs 16%). Oxaliplatin was the main agent used (81% INT, 78% SALV). Objective response and disease control rate were 51%/77% (INT) and 32%/60% (SALV). Median PFS, hepatic PFS and OS were 7.6, 9, and 23 months (INT) and 3.7, 5.7, and 12 months (SALV). Prior IV oxaliplatin progression was associated with poorer outcomes of oxaliplatin-HAIC in the INT-setting. Radical liver treatment followed HAIC in 28% (INT) and 7% (SALV). Grade 3-4 adverse events occurred in 42.7% and catheter complications in 26.7%. Concomitant antiangiogenic therapy was associated with a higher rate of catheter-related complications (44% vs 22%) and remained associated after adjustment for clinical covariates. HAIC demonstrates promising efficacy and manageable toxicity in liver-dominant mCRC when delivered in expert multidisciplinary centers, although careful patient selection and caution with concomitant antiangiogenic therapy are warranted.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy with 5-fluorouracil (5-FU) have been considered; however, it has limited survival benefits because of unbearable toxicity. Hence, a series of 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) prodrugs was designed and synthesized using ProTide technology. By favorable membrane permeability and bypassing enzymatic activation pathway of 5-FU to FdUMP, DL series of ProTide prodrugs circumvented mechanisms of 5-FU resistance and avoided the generation of associated toxic catabolites, resulting in enhanced anti-HCC efficacy and weak toxicity. Antiproliferative activity of compounds was evaluated in both human HCC cell lines and normal hepatocytes. Further anti-HCC activity was assessed in nude mice xenografted human HepG2, HUH7, or histidine triad nucleotide-binding protein 1 (HINT1) knockdown HUH7 cells orthotopically or subcutaneously. Mechanistic studies involving HINT1-silenced cells and co-administration with HINT1 upregulation by taraxasterol were conducted to validate the mode of action. Compound DL-2 effectively inhibited HCC cell growth but exhibited minimal cytotoxicity toward normal hepatocyte cell lines. DL-2 exhibited anticancer activity through bioactivation into FdUMP by hepatic HINT1. Comparatively, DL-2 weakly inhibited the orthotopic xenograft derived from HINT1-silenced human HUH7 cells. Systemic use of DL-2 did not produce significant toxicity in mice. In conclusion, we discovered an orally active and liver-targeted dual prodrug of FdUMP for the treatment of HCC. DL-2 is a promising drug used as a substitute for hepatic arterial infusion chemotherapy regimen.

Transarterial interventions (TAI) for hepatocellular carcinoma (HCC) include transarterial chemoembolization (TACE), transarterial embolization (TAE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy (SIRT). TACE remains the first-line treatment for unresectable HCC. Chinese College of Interventionalists (CCI) previously issued and updated the Chinese Clinical Practice Guidelines of TACE for HCC in 2018, 2021, and 2023, which have played a pivotal role in standardizing TACE procedures in China. In recent years, the application of HAIC and SIRT has become increasingly widespread and standardized in China. With the continuous advancement of TAI techniques, the evolution of therapeutic concepts, and the emergence of high-level evidence, CCI has comprehensively revised and expanded its previous guidelines. The updated Chinese clinical practice guidelines for transarterial interventions of hepatocellular carcinoma (2026 edition) now formally incorporates TACE, HAIC, and SIRT as standard treatment modalities. With the aims to further standardize the use of TAI in the management of HCC, this guideline is developed based on the most current evidence-based medical research, integrates China-specific clinical practices, and incorporates the latest advancements in TAI for HCC. It elaborates on clinical diagnostic criteria and staging, patient indications and contraindications, operational procedures and requirements, perioperative management, common complications management, follow-up and efficacy evaluation, combination therapy, quality control, as well as hot topics and prospects.

This study was designed to provide prospective evidence for the combination of hepatic arterial infusion chemotherapy (HAIC) and toripalimab, which had suggested encouraging antitumor activity and safety in advanced hepatocellular carcinoma (HCC) previously. This single-center, non-comparative, randomized phase II study (NCT04135690) recruited locally advanced HCC participants (1:1) to receive HAIC plus either toripalimab (TorHAIC) or sorafenib (SoraHAIC) per 3 weeks. The primary endpoint was the progression-free survival (PFS) rate at 6 months. Seventy-two participants were randomly assigned to received TorHAIC (n = 36) or SoraHAIC (n = 36). The 6-month PFS rate was 63.9% in the TorHAIC group and 61.1% in the SoraHAIC group. The median OS was 20.9 months in the TorHAIC group and 16.4 months in the SoraHAIC group, while the median PFS was 9.1 and 7.2 months, respectively. There were 12 participants (33.3%) developed grade 3-4 adverse events (AEs) in the TorHAIC group and 16 participants (44.4%) in the SoraHAIC group. Serious AEs were reported in two participants in the TorHAIC group and five participants in the SoraHAIC group. Our study suggested that the TorHAIC regimen had a favorable safety and efficacy profile in locally advanced HCC. However, these findings warrant validation in a phase III trial.

Laparoscopic right caudate lobectomy combined with right posterior lobectomy for hepatocellular carcinoma after neoadjuvant therapy (with video).

Multimodal therapeutic efficacy model for predicting early treatment response to TACE-HAIC combined with immune checkpoint inhibitors and tyrosine kinase inhibitors in unresectable hepatocellular carcinoma.

Chemotherapy as a salvage strategy after immunotherapy failure in advanced hepatocellular carcinoma: A case series.

Management of hepatocellular carcinoma (HCC) with main portal vein (MPV) invasion is challenging. We aimed to explore the efficacy and safety of systemic lenvatinib therapy combined with potent locoregional transarterial therapy (e.g., chemoembolisation plus infusion chemotherapy) for the treatment of HCC with MPV invasion. A direct comparison of different therapeutic regimens through a retrospective matched case-control study was conducted to evaluate the survival benefits of lenvatinib monotherapy versus lenvatinib combined with transarterial chemoembolisation (Len-TACE) versus Len-TACE plus hepatic arterial infusion chemotherapy (Len-TACE-HAIC) with oxaliplatin, fluorouracil, and leucovorin. Between January 2022 and December 2024, consecutive patients with HCC and MPV invasion who received lenvatinib, Len-TACE, or Len-TACE-HAIC from multiple centres in South China were enrolled for this analysis. Overall survival (OS), progression-free survival (PFS), and the objective response rate (ORR) were compared across the treatment groups. Adverse events (AEs) related to treatment were also recorded. A total of 169 patients were included in the study: 48 patients received lenvatinib as systemic treatment, 56 received Len-TACE for locoregional and systemic therapy, and 65 received Len-TACE-HAIC for intensified locoregional and systemic treatment. Patients in the Len-TACE-HAIC group achieved a significantly greater ORR (53.8% vs. 28.6% vs. 6.3%, p < 0.001) than those in the Len-TACE group and the Len group did. Consistently, Len-TACE-HAIC resulted in markedly improved PFS (median, 7.0 vs. 5.0 vs. 2.0 months; p < 0.001) and OS (median, 15.0 vs. 10.0 vs. 7.0 months; p < 0.001). The incidence of grade 3-4 AEs was comparable across the three treatment groups. The results demonstrated that lenvatinib combined with potent locoregional therapy, i.e., the Len-TACE-HAIC regimen, provided superior survival benefits with an acceptable safety profile in patients with HCC and MPV invasion.

Background and AimUnresectable hepatocellular carcinoma (u-HCC) is highly heterogeneous, with limited survival expectancy. The aim of this study was to reappraise the efficacy and safety of locoregional hepatic arterial infusion chemotherapy (HAIC)combined with systemic treatment in initially diagnosed u-HCC.MethodsA total of 302 treatment-naive patients with u-HCC who received HAIC and systemic treatment therapy between December 2018 and November 2023 were enrolled. The cumulative progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Factors affecting survival were analyzed via Cox regression analysis.ResultsThe median PFS and OS were 11.5 (95% CI: 8.7–14.3) months and 30.0 (95% CI: 20.7–39.2) months, respectively. The estimated PFS rates were 66.2%, 47.9% and 35.2% at 0.5, 1 and 2 years, respectively, and the estimated OS rates were 68.0%, 52.5% and 41.7% at 1, 2, and 3 years, respectively. Aspartate aminotransferase (AST), alkaline phosphatase (ALP), neutrophil to lymphocyte ratio (NLR), extrahepatic metastasis (EHM), metabolic comorbidity and treatment allocation were identified as factors associated with patient survival. The treatment regimen was well tolerated.ConclusionLocoregional HAIC combined with systemic immune checkpoint inhibitors (ICIs) and targeted therapy represents an effective and safe treatment modality for initially diagnosed u-HCC. Favorable survival outcomes were associated with AST ≤ 56.5 U/L, ALP ≤ 174.5 U/L, NLR ≤ 1.77, absence of extrahepatic metastasis, presence of metabolic comorbidity, and HAIC combined with ICI plus targeted/anti-VEGF therapy. These findings require further validation in external and prospective cohorts.