Search Results (280)

Background: Ischemic cholangiopathy (IC) is an under-recognized complication after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Our goal was to estimate the incidence, timing, clinical presentation, and management of IC after drug-eluting bead TACE. Methods: Single-center retrospective cohort of consecutive drug-eluting bead TACE procedures (1 January 2020–31 December 2023) with imaging follow-up to 31 December 2024 was conducted. IC was defined radiologically as bile duct dilatation without mechanical obstruction, biloma formation, biliary strictures, or ischemic cholecystitis occurring after TACE. The primary outcome was the incidence of IC. Secondary outcomes included clinical presentation, need for hospitalization, and management. Results: Among 106 patients, 14 developed IC (13.2%). Imaging abnormalities were detected a mean of 3.1 months after TACE. Six patients (42.9%) were asymptomatic. Among symptomatic patients, the most common manifestations were abdominal pain (n = 6) and fever (n = 4). Five patients required hospitalization, including 2 with infected bilomas requiring antibiotics and/or drainage. Subsequent HCC therapy was feasible in most cases; no deaths were directly attributed to IC. Conclusions: IC after TACE is not rare and is frequently asymptomatic, often detected incidentally on routine CT follow-up. Systematic biochemical monitoring and selective MRCP could improve detection, particularly when TACE sessions are closely spaced. Full article

Transarterial chemoembolization (TACE) is the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC), yet nearly half of treated patients fail to achieve durable benefit, and reliable biomarkers enabling early therapeutic stratification are still lacking. Treatment response is typically assessed by imaging one month after TACE and at three-month intervals, potentially delaying timely access to alternative therapies in non-responding patients. Circulating microRNAs (miRNAs) represent promising biomarkers due to their stability in body fluids and ease of detection. Here, we evaluated circulating miR-22 as an early predictor of TACE non-responder status and as a mechanistically relevant therapeutic target. Circulating miR-22 levels were measured by microarray and quantitative RT–PCR in three independent cohorts of early-to-intermediate-stage HCC patients undergoing TACE. Circulating miR-22 increased significantly in non-responders as early as 48 h after treatment, and fold changes consistently predicted treatment failure across two independent validation cohorts. Mechanistically, we identified the G2/M checkpoint kinase WEE1 as a direct functional target of miR-22. Modulation of the miR-22/WEE1 axis affected cell-cycle progression, proliferation, apoptosis, and DNA damage response in HCC cell lines and xenograft models. Under hypoxia-mimicking conditions combined with doxorubicin exposure, pharmacological inhibition of WEE1 induced mitotic catastrophe in highly proliferative miR-22-silenced cells. Collectively, these findings identify early post-TACE elevation of circulating miR-22 as a biomarker of non-response and highlight the miR-22/WEE1 axis as a potential target for precision treatment strategies in HCC. Full article

Hepatocellular carcinoma (HCC) remains a major contributor to global cancer mortality, with many patients presenting beyond the bounds of upfront curative therapy (resection/transplant). Locoregional therapies, particularly transarterial chemoembolization (TACE), transarterial embolization (TAE), and transarterial radioembolization (TARE), therefore play an essential role in bridging and downstaging strategies designed to enable curative intent in otherwise ineligible patients. Bridging therapy aims to maintain transplant eligibility and reduce waitlist dropout, whereas downstaging seeks to reduce tumor burden to meet accepted criteria for resection or transplantation. This review synthesizes current evidence on TACE, TAE, and TARE for bridging to resection and transplantation, as well as for downstaging to surgical eligibility, drawing from systematic reviews and cohort studies in the recent literature. We examine modality-specific outcomes, contextualized by tumor biology, liver function, and treatment selection criteria. Comparative effectiveness and the need for standardized outcome measures will be highlighted, reflecting heterogeneity in study endpoints and patient populations. Finally, future directions in personalized locoregional therapy, integration with systemic therapies, and refined conversion strategies will be discussed, with emphasis on the need for consensus in defining treatment success. By integrating evolving clinical evidence with practical application, this review will help clarify the expanding role of locoregional therapies in enabling curative-intent strategies for HCC. Full article

Background/Objectives: Transarterial chemoembolization (TACE) is included in international guidelines for the treatment of hepatocellular carcinoma (HCC), but it is still not a standardized intervention in terms of vector and chemotherapy. This study aims to report on clinical and radiological outcomes of degradable starch microspheres TACE (DSM-TACE) with idarubicin and compare with DSM-TACE with an epirubicin protocol after a single session. Methods: This is a single-center retrospective study analyzing cirrhotic patients affected by HCC in early or intermediate stages. Primary objectives were to assess the safety and efficacy of a single DSM-TACE with 10 mg idarubicin in terms of adverse event (AE) occurrences evaluated via the CTCAE 5.0 system and mRECIST criteria with computed tomography (CT) at 3 months. The secondary purpose was to compare the procedural outcomes with those from patients treated with DSM-TACE with 50 mg epirubicin. Results: Thirty-seven patients were included, 19 treated with idarubicin (IDA group) and 18 with epirubicin (EPI group); demographic data and lesion characteristics were comparable. No major AE (grade ≥ 3) occurred overall. In the IDA group, the minor AE incidence was 52.7%: one patient presented with mild ascites, eight developed hyperbilirubinemia and one leucopenia. At the 3-month CT follow-up, mRECIST criteria reported an overall response rate (ORR) of 63.2% and a disease control rate (DCR) of 84.2%. No statistically significant differences were appreciable comparing both AE occurrence and mRECIST findings with the EPI group (50% minor AE, 77.8% ORR, 88.9% DCR). Conclusions: In this sample of cirrhotic patients with HCC, DSM-TACE with 10 mg idarubicin was safe and effective comparable to DSM-TACE with 50 mg epirubicin. Full article

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality in the world. Although there is an armamentarium of therapeutic options available for HCC therapy, current treatment modalities still face challenges, such as limited effectiveness and resistance to therapy due to inherent intratumoral heterogeneity. Hence, the development of novel therapeutics is an unmet need. Microalgae possess the ability to provide naturally derived compounds that are attractive for biomedical applications. The multifunctional nature of microalgae, with its unique combination of anticancer metabolites, oxygen-generating capability, and photosensitizing activity, make them a versatile platform for developing next-generation cancer therapeutics. In light of the above, this succinct narrative review highlights the potential biomedical applications of microalgae in cancer therapy, with a focus on HCC. Preclinical studies have shown the significant potential of microalgae as naturally occurring sources of chemopreventive and anticancer agents against HCC. Future directions include the use of biotechnology to enhance the production of microalgal-derived bioactive compounds and the formulation of biocompatible and biodegradable drug–microalgae embolic agents with prolonged release of anticancer drugs, thereby giving rise to synergistic antitumor effects, and their application for the delivery of immune checkpoint inhibitors for immunotherapy in HCC. Overall, microalgae hold considerable promise for advancing innovative therapeutic strategies against HCC. Full article

Background: Transarterial chemoembolization (TACE) is an established image-guided, minimally invasive therapy for unresectable hepatocellular carcinoma (HCC). However, post-embolization hypoxia often triggers compensatory angiogenesis and an immunosuppressive microenvironment, limiting long-term efficacy. We hypothesized that the immediate image-guided hepatic arterial infusion (HAI) of a PD-1 inhibitor following TACE could synergistically enhance local tumor control. Methods: In this retrospective, propensity-score-matched study, 226 patients with unresectable HCC (January 2021–June 2024) were analyzed. After 1:1 matching, 84 pairs were included: Study Group (TACE + HAI-nivolumab) and Control Group (TACE alone). Nivolumab (3 mg/kg) was infused via the hepatic artery under fluoroscopic guidance immediately after embolization. Primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included objective response rate (ORR) by mRECIST and changes in serum angiogenesis/immune biomarkers. Results: The Study Group demonstrated significantly longer median OS (16.2 vs. 12.8 months; HR 0.62, 95% CI: 0.44–0.88, p = 0.007) and median PFS (9.8 vs. 6.5 months; p < 0.001). ORR was higher with combination therapy (58.3% vs. 36.9%, p = 0.006). Mechanistically, HAI-nivolumab suppressed the post-TACE surge in VEGF and Ang-2 (p < 0.001) and increased the peripheral CD4+/CD8+ T-cell ratio. Grade 3/4 adverse events were comparable between groups (14.3% vs. 10.7%, p = 0.485). Conclusions: The image-guided combination of TACE with immediate HAI of nivolumab is associated with improved survival and tumor response in unresectable HCC. This strategy may counteract the adverse post-embolization microenvironment by simultaneously inhibiting angiogenesis and reactivating local immunity, representing an advanced image-guided combination therapy with strong translational relevance. Full article

Hepatocellular carcinoma remains one of the most common and lethal cancers worldwide, and many patients are diagnosed at stages where curative therapy is not possible. Recent progress in systemic therapies and refinements in locoregional treatment have shifted how clinicians approach this disease. As evidence has accumulated from trials such as KEYNOTE-937, IMbrave050, and CheckMate 9DX, it has become clear that pairing immunotherapy with ablation or transarterial interventions can deepen and extend treatment responses compared with using either approach alone. This review summarizes the current landscape of these combination strategies, explains the biological and clinical principles that support their use, and highlights ongoing trials that aim to clarify optimal sequencing and patient selection. It also considers future directions for integrating locoregional and systemic therapies to expand curative opportunities and improve long-term outcomes for a broader range of patients. Full article

Background/Objectives: This review and meta-analysis assessed whether combining transarterial chemoembolization (TACE) with iodine-125 brachytherapy (I-125 brachytherapy) offers greater efficacy and safety than TACE alone in treating hepatocellular carcinoma (HCC). Methods: PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science were searched for articles published between 1 January 2010 and 30 November 2023. Eligible studies compared TACE with and without I-125 brachytherapy from randomized controlled trials (RCTs) and non-randomized comparative studies published in English. The primary outcome was overall survival (OS) at 1, 2, and 3 years. The secondary outcomes included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. ROB-2 and ROBINS-I tools were used to assess study quality. Results: Eighteen studies (n = 1872 patients) were included. All 18 studies originated from China, with the majority being retrospective cohorts (n = 16), one non-randomized prospective study, and one RCT. Compared with TACE alone, TACE + I-125 brachytherapy significantly improved OS at 1 year (OR = 3.64, 95% CI: 2.92–4.55), 2 years (OR = 3.93, 95% CI: 2.29–6.77), and 3 years (OR = 4.12, 95% CI: 2.24–7.56). The tumor response rates, including the ORR and DCR, were also significantly higher in the combination group. Subgroup analysis revealed that the survival benefit was maintained in studies without systemic chemotherapy (OR = 3.68, 95% CI: 2.89–4.70) and in studies with systemic chemotherapy (OR = 4.13, 95% CI: 1.69–10.09). Although larger effect estimates were observed with low-dose I-125 brachytherapy (<80 Gy; OR = 8.55, 95% CI: 4.32–16.92) compared to high-dose (≥100 Gy; OR = 2.87, 95% CI: 2.05–4.00), this finding is hypothesis-generating rather than conclusive and should be interpreted cautiously as it is based on only three studies. Adverse event rates were comparable between groups. GRADE assessment indicated low to very low certainty for all outcomes, primarily due to the retrospective nature of most included studies. Conclusions: TACE combined with I-125 brachytherapy was associated with improved survival and tumor response without a statistically significant increase in adverse events. High-quality, multicenter RCTs are warranted to confirm these results. Full article

Background: The role of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) management has evolved over recent years. Although it appears that the overall number of procedures is declining, international guidelines now endorse TACE beyond the Barcelona Clinic Liver Cancer (BCLC) intermediate stage, and multiple TACE platforms allow patient-tailored treatments. In this context, degradable starch microspheres TACE (DSM-TACE) may be valuable when the goal is to preserve liver function and spare healthy parenchyma. This study reports multicenter retrospective Italian data to assess the efficacy and safety of DSM-TACE with EmboCept^® in patients with early-to advanced-stage HCC, and to evaluate whether procedural selectivity (superselective vs. lobar) influences outcomes. Methods: This retrospective multicenter study included 201 patients initially; after applying exclusion criteria, 187 patients (334 HCC nodules) treated across eight centers (2014–2024) were analyzed. Treatment indications were discussed in multidisciplinary tumor boards in all centers. Superselective DSM-TACE was performed in 48 patients (66 nodules, 19.8%), while 139 patients (268 nodules, 80.2%) underwent a lobar approach. Repeated sessions were performed on demand and recorded for lobar treatments. Tumor response was assessed using mRECIST criteria at 1, 3–6, 6–9, and 9–12 months; adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE). efficacy and safety outcomes were compared according to the DSM-TACE approach. Results: In terms of safety, analysis confirmed the overall good tolerability of DSM-TACE, with no grade ≥ 3 adverse events and no major complications or procedure-related deaths. No significant differences were observed in post-embolization syndrome (PES) rates between groups. With regard to efficacy, for the entire cohort, the overall response rate (ORR) was 70% at 1 month, 31.6% at 3–6 months, 20.5% at 6–9 months, and 13.5% at 9–12 months, while the disease control rate (DCR) was 91.4% at 1 month, 69% at 3–6 months, 38.6% at 6–9 months, and 27% at 9–12 months. At intermediate follow-up, superselective DSM-TACE achieved higher ORR than lobar treatment at 3–6 months (53.8% vs. 26.4%; p = 0.009) and 6–9 months (43.8% vs. 15.3%; p = 0.009). Per-nodule analysis confirmed this advantage at 3–6 months (ORR = 66.7% vs. 31.3%; p = 0.0008). Conclusions: DSM-TACE with EmboCept^® provides favorable tumor control and a good safety profile in routine clinical practice. A superselective approach is associated with improved response at intermediate follow-up compared with lobar strategy, supporting DSM-TACE as a flexible therapeutic option for localized HCC. Full article

The integration of artificial intelligence (AI) into medicine, oncology, and radiology represents a marked shift in the diagnosis, prognostication, and management of hepatocellular carcinoma (HCC), a malignancy with high global incidence and poor prognosis. This review examines the application of AI, including machine learning (ML) and deep learning (DL), across the spectrum of HCC care. As AI advances, new convolutional neural networks (CNNs) and other models are enhancing diagnostic accuracy, reducing interpretation times, and improving the characterization of liver lesions across major imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Beyond diagnosis, the transformative role of AI in prognostication is also improving, where AI can now noninvasively predict critical factors such as microvascular invasion, genetic mutation status, tumor recurrence, and treatment response. Furthermore, AI has shown promise in facilitating patient-specific treatment planning by stratifying patients for interventions such as transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT). The review also addresses the emerging fields of pathomics and the use of AI in positron emission tomography (PET), while critically evaluating the cost-effectiveness of these technologies. Despite its promise, the widespread clinical adoption of AI faces challenges, including limited generalizability, maintaining patient privacy, ethical considerations, and the need for robust prospective validation. Ultimately, this review illustrates that the future of HCC management lies in a collaborative, hybrid-intelligence model, where AI-driven insights augment clinical expertise to optimize diagnostic pathways, personalize therapy, and improve patient outcomes. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer mortality worldwide. Because HCC usually arises in cirrhotic livers, prognosis is shaped by the dual threats of tumor progression and hepatic decompensation, requiring treatment decisions that balance anticancer efficacy with preservation of liver function, portal hypertension control, and quality of life. In recent years, management has shifted from a predominantly locoregional approach to an integrated continuum that spans curative resection, ablation, and transplantation; refined transarterial and radiotherapy techniques; and modern systemic therapy dominated by immunotherapy-based combinations. These advances have improved response rates, enabled downstaging and conversion in selected patients, and expanded opportunities for sequential and multimodal treatment. However, challenges persist, including therapeutic decision-making in patients with Child–Pugh B liver function, lack of robust predictive biomarkers, and resistance after initial response. Emerging tools—liquid biopsy, radiomics, AI-assisted imaging, and microbiome modulation—may support future precision strategies and optimized treatment allocation. In this review, we summarize current evidence guiding staging and therapy selection, outline practical considerations across curative, locoregional, and systemic modalities, and discuss evolving biomarkers and next-generation immunotherapy as key steps toward more personalized, durable, and equitable global HCC care. Full article

Objectives: To compare the therapeutic efficacy and safety of balloon-assisted transarterial chemoembolization (B-TACE) versus conventional TACE (C-TACE) in hepatocellular carcinoma (HCC) and to evaluate the potential predictive value of intraoperative balloon-occluded arterial stump pressure (Boasp). Methods: In this prospective, single-centre, randomized controlled study, 60 patients with hepatocellular carcinoma were allocated to either the B-TACE group (n = 30) or the C-TACE group (n = 30). One patient in the B-TACE group was lost to follow-up after allocation. The primary analyses were conducted according to the intention-to-treat (ITT) principle, including all randomized patients, with conservative handling of missing data. Sensitivity analyses were performed to assess the robustness of the results. Tumor response and survival outcomes were evaluated using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Cox proportional hazards regression models. Intraoperative balloon-occluded arterial stump pressure (BOASP) was measured as an exploratory parameter to quantify embolization adequacy. Adverse events (AEs) were systematically assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Results: TACE achieved a higher 3-month ORR (63.3% vs. 10.0%, p < 0.001) and 6-month disease control rates (80.0% vs. 36.7%, p < 0.001), with PFS (HR = 0.30, 95% CI 0.148–0.608) and procedures within 6 months (1 vs. 3, p < 0.001). The 6-month surgical conversion rate was higher (34.5% vs. 6.7%, p = 0.009). Changes in Boasp correlated with efficacy (AUC = 0.825, p = 0.0398). Severe infections were lower in B-TACE (17.2% vs. 76.7%, p < 0.001). Conclusions: B-TACE offers superior efficacy, survival, and surgical conversion versus C-TACE with favorable safety. Boasp provides a quantitative biomarker for predicting treatment response. Full article

Background/Objectives: Management of hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) varies between systemic immunotherapy and locoregional approaches. We compared atezolizumab plus bevacizumab (Atezo–Bev) with locoregional therapy in treatment-naïve patients. Methods: We conducted a retrospective cohort study of patients with image- or biopsy-proven HCC and MVI, Child–Pugh A/B, and ECOG 0–1 who received first-line Atezo–Bev or locoregional therapy (transarterial chemoembolization [TACE] with or without external-beam radiotherapy [RT]). Inverse probability of treatment weighting (IPTW) minimized baseline imbalances. Primary outcomes were overall survival (OS) and progression-free survival (PFS). Modified RECIST assessed radiologic response, and major adverse events were classified using Society of Interventional Radiology criteria. Results: We analyzed 475 patients (Atezo–Bev, n = 191; locoregional therapy, n = 284). Baseline characteristics were similar, and IPTW achieved covariate balance. Median OS was 9.3 months with Atezo–Bev and 10.8 months with locoregional therapy; after IPTW, OS remained comparable (hazard ratio [HR] 0.95; 95% CI 0.76–1.19; p = 0.635). Median PFS was 6.0 versus 4.1 months, favoring Atezo–Bev; this persisted after IPTW (HR 0.64; 95% CI 0.52–0.79; p < 0.001). Objective response rates were similar (45% vs. 48%; p = 0.49). Major adverse events occurred in 11% of patients in both groups. Subgroup analyses showed no OS differences and a consistent PFS advantage with Atezo–Bev. Conclusions: In HCC with MVI, first-line Atezo–Bev achieved longer PFS than locoregional therapy, with comparable OS and safety, supporting Atezo–Bev as a valid and effective first-line option for disease control while locoregional modalities remain relevant within multidisciplinary care. Full article

Background: Hepatocellular carcinoma (HCC), the most prevalent primary malignancy of the liver, is commonly treated with transarterial chemoembolization (TACE), a locoregional therapy that combines targeted intra-arterial chemotherapy with selective embolization to induce tumor ischemia and necrosis. However, current methods for monitoring the treatment response—such as the RECIST and mRECIST—often fail to detect early or subtle biological changes, such as tumor necrosis or microstructural remodeling, and therefore may underestimate the therapeutic effects, especially in cases with minimal or delayed tumor shrinkage. Thus, there is a critical need for quantitative imaging strategies that can improve early response assessment and guide more personalized treatment decision-making. The goal of this study was to assess the changes in computed tomography (CT) perfusion parameters and radiomic features in HCC before and after TACE and to evaluate the associations of these parameters/features with the tumor burden. Methods: In this retrospective, single-center study, 32 patients with histologically confirmed HCC underwent CT perfusion and radiomic analysis prior to and following TACE. Multiple quantitative perfusion parameters (arterial flow, perfusion flow, perfusion index) and radiomic features were extracted. Statistical comparisons were performed using the Wilcoxon signed-rank test and Spearman’s correlation. Radiomic feature extraction was performed in strict adherence to the Image Biomarker Standardization Initiative (IBSI) guidelines. Preprocessing steps included voxel resampling (1 × 1 × 1 mm), z-score normalization, and fixed bin-width discretization (bin width = 25). All tumor ROIs were manually segmented in consensus by two experienced radiologists to minimize inter-observer variability. Results: Arterial flow significantly decreased from a median of 56.5 to 47.7 mL/100 mL/min after TACE (p = 0.009), while nonsignificant increases in the perfusion flow (from 101.3 to 107.8 mL/100 mL/min, p = 0.44) and decreases in the perfusion index (from 38.6% to 35.7%, p = 0.25) were also observed. Perfusion flow was strongly and positively correlated with tumor size (ρ = 0.94, p < 0.001). Five radiomic texture feature values—especially those of ShortRunHighGrayLevelEmphasis (Δ = +2.11, p = 0.0001) and LargeAreaHighGrayLevelEmphasis (Δ = +75,706, p = 0.0006)—changed significantly after treatment. These radiomic feature value changes were more pronounced in tumors ≥50 mm in diameter. In addition, we performed a receiver operating characteristic (ROC) analysis of the two most discriminative radiomic features (SRHGLE and LAHGLE). We further developed a multivariable logistic regression model that achieved an AUC of 0.87, supporting the potential of these features as predictive biomarkers. Conclusions: CT perfusion and radiomics offer complementary insights into the treatment response of patients with HCC. While perfusion parameters reflect macroscopic vascular changes and are correlated with tumor burden, radiomic features can indicate microstructural changes after TACE. This combined imaging approach may improve early therapeutic assessment and support precision oncology strategies. Full article