Purpose To evaluate regeneration after liver venous embolization in healthy and cirrhotic swine and to assess computed tomography (CT) radiomics for predicting these markers. Materials and Methods Twenty-two pigs with healthy (n = 11) or cirrhotic (n = 11) livers underwent portal vein embolization (PVE) with microspheres and coils, n-butyl cyanoacrylate, combined PVE and hepatic vein embolization (PVE + HVE), or sham control. Four weeks after intervention, future liver remnant (FLR) tissue was analyzed for angiogenesis, proliferation, and epithelial integrity using vascular endothelial growth factor (VEGF), angiopoietin-1, Ki-67, and cytokeratin 8/18/19 immunofluorescence and for apoptosis in the embolized lobe using caspase 3. Spearman correlations were computed between biomarker expression and relative FLR hypertrophy. Biomarkers were dichotomized into high versus low groups based on group-specific means. Logistic regression (LR) and random forest (RF) models were trained on baseline CT radiomics using repeated fivefold cross-validation (100 iterations) to predict biomarker expression. Model performance was assessed by mean area under the curve (AUC), with 95% CIs estimated from the 2.5th and 97.5th percentiles across runs. Results All animals completed the study. PVE + HVE resulted in significantly higher expression of VEGF, Ki-67, angiopoietin-1, and caspase 3 than sham controls in both liver conditions (all P < .05). Angiogenesis was greater after PVE + HVE than after PVE in healthy (P < .01) and cirrhotic (P < .001) livers. Ki-67 showed the highest predictive performance (RF AUC, 0.84; LR AUC, 0.81). Conclusions Liver venous embolization induces distinct regenerative responses in healthy and cirrhotic swine. Baseline CT radiomics demonstrated moderate discriminative performance for predicting regenerative biomarkers.

PURPOSE:To evaluate the impact of neoadjuvant systemic PD-1 immune checkpoint inhibition on the local immune response in residual tumors following partial cryoablation in a TIB-75 murine hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS:Forty-eight BALB/c mice (6-12 weeks) were orthotopically implanted with TIB-75 cells to induce a single lesion of HCC. Mice were randomized into 4 treatment groups: (a) control, (b) anti-PD-1, (c) partial cryoablation, and (d) anti-PD-1 and partial cryoablation. Anti-PD-1 was administered on Days 7, 9, and 11 after inoculation, followed by partial cryoablation on Day 13 and tumor harvest on Day 18. The presence of T cell subsets (CD3+, CD4+, and CD8+), tumor-associated macrophages (CD68+ and CD206+), PD-1, and PD-L1 were assessed by histopathological analysis of immunohistochemistry. The percentage of positively stained cells within the tumor was determined using QuPath. RESULTS:Mice treated with anti-PD-1 (n = 12) had greater infiltration of CD3+, CD4+, and CD8+ T cells into residual tumors than control (CD3+: median, 22.4% vs 5.5% [P < .001]; CD4+: median, 19.8% vs 5.1% [P < .001]; CD8+: median, 8.2% vs 3.1% [P = .007]). Partial cryoablation alone (n = 12) increased CD206+ M2-like macrophages (median, 36.6% vs 14.7%; P = .03). Partial cryoablation combined with neoadjuvant anti-PD-1 (n = 12) showed significantly higher infiltration of CD3+ T cells (median, 14.3% vs 4.5%; P = .048) than partial cryoablation alone (n = 12) and significantly lower PD-1 expression than anti-PD-1 alone (median, 2.9% vs 7.3%; P = .004). CONCLUSIONS:In a mouse model of HCC, neoadjuvant PD-1 immune checkpoint inhibition can modulate the immunosuppressive tumor microenvironment observed after cryoablation. This highlights the potential of a combination therapy to treat both early- and advanced-stage HCCs.

Current hepatocellular carcinoma (HCC) surveillance guidelines rely on manually defined LI-RADS (Liver Imaging Reporting and Data System) features rather than imaging data analysis. This study evaluates the feasibility of machine-learning (ML)-based image analysis frameworks to identify and localize hepatic parenchyma at elevated risk for HCC. In this retrospective study, cirrhotic patients with HCC diagnosis undergoing MRI between 2008 and 2023 were included. The analysis included negative screening MRI preceding a positive screening MRI confirming a LR-5 lesion within 18 months. Volume-of-interest (VOI) annotations of ‘non-malignant’ and ‘malignant’ liver tissue on the screening MRI were manually or automatically placed, mapped from future HCC lesion on positive screening MRI. Radiomics were extracted from these VOIs using PyRadiomics. Logistic regression (LR), random forest (RF), and eXtreme Gradient Boosting (XGB) models were trained and validated across four manual/automatic annotation combinations. Exploratory voxel-level heatmaps were generated to visualize high-risk HCC areas. Model performance was summarized using median values and 95

BACKGROUND AND OBJECTIVE:Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with rising global incidence; most patients present with unresectable disease, and intrahepatic recurrence is common after curative-intent surgery. Locoregional therapies (LRTs), including future liver remnant (FLR) augmentation, percutaneous ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), hepatic arterial infusion chemotherapy (HAIC), and stereotactic body radiotherapy (SBRT), are increasingly applied across the disease continuum. This narrative review focuses primarily on unresectable iCCA, while also addressing surgical-adjunct and downstaging roles, and aims to clarify how each modality is best integrated within modern multimodal management. METHODS:We performed a focused literature search of PubMed/MEDLINE for English-language publications from January 2000 through March 2026, combining population terms ("cholangiocarcinoma", "intrahepatic cholangiocarcinoma", "iCCA", "biliary tract cancer") with intervention terms covering the principal locoregional modalities. Supplementary targeted searches were performed for context on epidemiology, systemic and targeted therapy, biology, imaging, and current guidelines. Randomized trials, prospective cohort studies, large multicenter retrospective series, systematic reviews, and current clinical practice guidelines were prioritized. KEY CONTENT AND FINDINGS:FLR augmentation with portal vein embolization or liver venous deprivation expands the pool of surgical candidates but requires careful interval management to limit disease progression. Thermal ablation can yield outcomes comparable to repeat resection in selected patients with small recurrent or solitary lesions; SBRT offers a non-invasive option for centrally located or perihilar tumors not amenable to ablation. TACE and TARE achieve comparable survival in selected patients, with TARE often preferred for infiltrative, unilobar, or portal-vein-compromised disease. The strongest prospective evidence for LRT integration with first-line systemic chemotherapy comes from the MISPHEC trial of concomitant Y-90 SIRT plus gemcitabine/cisplatin, the PUMP-2 trial of hepatic arterial infusion pump floxuridine plus systemic gemcitabine/cisplatin, and pooled comparative analyses. Emerging retrospective data suggest a survival benefit when LRT is added to first-line chemoimmunotherapy, but prospective confirmation is awaited. CONCLUSIONS:LRTs have evolved from salvage interventions to integral components of multidisciplinary iCCA care. Stage-stratified, biology-informed selection and integration with modern systemic backbones offer the most promising path forward. Prospective, modality-stratified trials with standardized endpoints are needed to translate promising signals into evidence-based practice.

PURPOSE:To evaluate the effectiveness of combined portal vein embolization (PVE) and hepatic vein embolization (HVE) compared with that of PVE alone in cirrhotic and noncirrhotic swine. MATERIALS AND METHODS:Sixteen Yorkshire pigs were included in this study. In the cirrhotic group (n = 8) and noncirrhotic group (n = 8), subjects underwent embolization according to established protocols. Computed tomography (CT) scans were acquired before and at 2- and 4-week intervals following the embolization. Liver volumes were segmented in the portal venous phase. Student t test with a significance level at P < .05 was used. RESULTS:Across all swine, the future liver remnant (FLR) was significantly larger after PVE + HVE than after PVE at 2 weeks (24.12% [95% CI, 15.36%-32.88%] vs 12.75% [95% CI, 7.43%-18.07%]; P = .021) and 4 weeks (23.23% [95% CI, 15.79%-33.47%] vs 15.08% [95% CI, 9.98%-20.87%]; P = .043) after embolization. In the cirrhotic group, the FLR increase was greater following PVE + HVE than after PVE at 2 weeks (20.85% [95% CI, 14.40%-27.30%] vs 8.66% [95% CI, 6.47%-10.86%]; P = .0089) and 4 weeks (19.27% [95% CI, 17.87%-20.67%] vs 13.33% [95% CI, 9.23%-13.33%]; P = .0003) after embolization. CONCLUSIONS:PVE + HVE resulted in greater FLR hypertrophy than PVE alone, indicating that cirrhotic livers may benefit from the addition of HVE.

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Background: Image-guided tumor ablation is the first-line therapy for early-stage hepatocellular carcinoma (HCC), with ongoing investigations into its combination with immunotherapies. Matrix metalloproteinase (MMP) inhibition demonstrates immunomodulatory potential and reduces HCC tumor growth when combined with ablative treatment. Purpose: To evaluate the effect of incomplete cryoablation with or without MMP inhibition on the local immune response in residual tumors in a murine HCC model. Materials and Methods: Sixty 8- to 10-week-old female BALB/c mice underwent HCC induction with use of orthotopic implantation of syngeneic Tib-75 cells. After 7 days, mice with a single lesion were randomized into treatment groups: (a) no treatment, (b) MMP inhibitor, (c) incomplete cryoablation, and (d) incomplete cryoablation and MMP inhibitor. Macrophage and T-cell subsets were assessed in tissue samples with use of immunohistochemistry and immunofluorescence (cell averages calculated using five 1-mu m2 fields of view [FOVs]). C -X -C motif chemokine receptor type 3 (CXCR3)- and interferon gamma (IFN gamma)- positive T cells were assessed using flow cytometry. Groups were compared using unpaired Student t tests, one-way analysis of variance with Tukey correction, and the Kruskal-Wallis test with Dunn correction. Results: Mice treated with incomplete cryoablation (n = 6) showed greater infiltration of CD206+ tumor-associated macrophages (mean, 1.52 cells per FOV vs 0.64 cells per FOV; P = .03) and MMP9-expressing cells (mean, 0.89 cells per FOV vs 0.11 cells per FOV; P = .03) compared with untreated controls (n = 6). Incomplete cryoablation with MMP inhibition (n = 6) versus without (n = 6) led to greater CD8+ T-cell (mean, 15.8% vs 8.29%; P = .04), CXCR3+CD8+ T-cell (mean, 11.64% vs 8.47%; P = .004), and IFN gamma+CD8+ T-cell infiltration (mean, 11.58% vs 5.18%; P = .02). Conclusion: In a mouse model of HCC, incomplete cryoablation and systemic MMP inhibition showed increased cytotoxic CD8+ T-cell infiltration into the residual tumor compared with either treatment alone.

Aims To establish and define a new, not previously reported hepatocellular carcinoma (HCC) variant, termed fibronodular HCC (FN-HCC). Methods We retrospectively reviewed 290 HCC cases and identified 29 FN-HCC and 24 scirrhous HCC (SCHCC). Clinical, pathological and radiological features of FN-HCC were reviewed and compared with 30 conventional HCCs (CV-HCC) and SC-HCC. Results FN-HCCs were more likely to arise in non-advanced fibrotic livers with lower advanced Barcelona Clinic Liver Cancer (BCLC) stage, had lower rates of progression and longer time to progression and were more likely to be surgically resected compared with CV-HCCs and SC-HCCs. Imaging analysis of FN-HCCs demonstrated higher rates of non-peripheral washout and a new distinct pattern of enhancement which is characterised by the presence of multiple rounded nodules within a lesion embedded in fibrotic-appearing parenchyma. Conclusions FN-HCC may represent a specific variant of HCC with distinct pathological, radiological and clinical features with potential ramifications for outcome.