Search Results (129)

Hepatocellular carcinoma (HCC) is a global health threat, and gut microbiota play a pivotal role in its pathogenesis through the gut–liver axis. However, the literature contains divergent or opposing findings: key microbial metabolites, such as secondary bile acids and indole derivatives, exhibit potent pro- and anti-tumorigenic activities across different studies, hindering a unified understanding of their veritable roles. To resolve this ambiguity, this review proposes a unifying “context dependency” framework. We posit that the functions of gut microbiota and their metabolites are not fixed but are dynamically determined by the host’s physiological and pathological “context,” defined here as the integrated dynamic background shaped by local metabolite concentrations, host immune status, specific receptor expression, and tumor microenvironment (TME) features. This framework is systematically substantiated through an analysis of the dichotomous effects of major microbial metabolites, including bile acids (BAs), short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), and indole derivatives. We further elucidate that the key “contextual factors” governing these functional outcomes include the TME, host immune status, metabolite concentration gradients, and the activation patterns of specific signaling pathways (e.g., farnesoid X receptor/takeda G protein-coupled receptor 5, aryl hydrocarbon receptor). This novel framework not only provides a theoretical foundation for integrating existing paradoxical findings but also paves the way for the future development of context-specific precision diagnostic biomarkers and targeted microbial intervention therapies for HCC. Full article

Transarterial radioembolization (TARE) is an established therapy for primary and secondary hepatic malignancies. Outcomes depend heavily on dosimetry, which has evolved from empirical and body-surface-area methods to partition and voxel-based approaches. This review summarizes current evidence for advanced (personalized) dosimetry across tumor types, highlights emerging dose–response concepts, and outlines practical barriers and implementation strategies. A narrative review of peer-reviewed clinical studies and trials evaluating dosimetry in TARE, with emphasis on hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), metastatic colorectal cancer (mCRC), neuroendocrine tumor (NET), and breast cancer liver metastases, was performed with comparison of single-compartment medical internal radiation dosimetry method (MIRD), partition (multicompartment) methods, and voxel-based dosimetry methodologies. Personalized dosimetry improves outcomes in multiple tumor types. A randomized trial in HCC showed superior overall survival with partition-based dosing versus MIRD. In selective HCC treatments, voxel-derived metrics (e.g., D95) correlate with complete pathologic necrosis, suggesting benefit beyond mean dose targets. For iCCA, data associate higher tumor doses with better radiologic response, progression-free survival, and downstaging. In mCRC, voxel-based and threshold analyses link specific tumor and margin doses with metabolic/radiographic response and survival. Smaller series in NET and breast cancer indicate dose–response relationships using advanced dosimetry. Evidence supports broader adoption of advanced dosimetry in TARE. Emerging strategies that ensure adequate coverage of the “coldest” tumor regions and thoughtful particle-load planning may further optimize results. Standardized protocols, prospective validation, and scalable workflows are needed to accelerate implementation. Full article

Background and Objectives: Robot-assisted procedures represent a significant advancement in minimally invasive liver resection techniques. Nonetheless, the introduction of a novel surgical technique in a new environment necessitates meticulous planning and a gradual, stepwise approach. This study describes the adoption of a robotic surgical platform for liver resection at a high-volume tertiary care center. Materials and Methods: We retrospectively analyzed data that had been prospectively collected from fifty robot-assisted liver resections. Descriptive statistics, including frequencies, percentages, means/medians, and standard deviations, were employed for description and summary. Results: The median operative duration was 166 min (range: 85–400 min), with an average intraoperative blood loss of 200 mL (range: 50–1000 milliliters). Intraoperative or postoperative blood transfusion was required in 8% of patients. Conversion to open resection was necessary in one patient (2%). The mean duration of hospitalization was 5 days (range: 3–20 days), with a 30-day readmission rate of 6% and no mortality within 90 days. Postoperative complications classified as Clavien-Dindo grade 3 or higher were observed in five patients (10%). The mean tumor size varied according to pathology: 58.5 mm (range: 30–120 mm) in the hepatocellular carcinoma group; 27.4 mm (range: 10–32 mm) in the secondary malignancy group; and 42.6 mm (range: 24–60 mm) in the intrahepatic cholangiocarcinoma group. The median number of lymph nodes harvested during lymphadenectomy (IHHCA/GBCA) was 5.4, ranging from 1 to 11. The R0 resection rate for malignant tumors was 88.2% (of 30/34). Conclusions: This study validates the safe integration of robot-assisted surgery into liver disease treatment, supported by our initial experience. Despite its technical advantages, robotic-assisted liver surgery remains complex and demanding. Structured robotic training within established programs, meticulous patient selection, and a stepwise implementation approach are critical during the early phases to optimize the outcomes. Full article

Background: Glypican-3 (GPC3) is overexpressed in most hepatocellular carcinoma (HCC) tissues but is absent in normal adult liver. We evaluated whether tumor GPC3 expression is associated with clinical outcomes in patients with advanced HCC treated with atezolizumab–bevacizumab (AB). Methods: We conducted a single-center retrospective cohort study of 139 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received AB between January 2022 and August 2025. Tumor GPC3 expression was assessed by immunohistochemistry. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: Baseline characteristics were largely balanced between GPC3-positive (n = 87) and GPC3-negative (n = 52) groups. Median OS was significantly shorter in patients with GPC3-positive tumors than in those with GPC3-negative tumors (p = 0.006). In multivariable analysis, GPC3 positivity remained independently associated with higher mortality (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.05–3.00; p = 0.033), along with Child–Pugh class B. PFS did not differ significantly between the groups (p = 0.712). ORR was lower in GPC3-positive tumors than in GPC3-negative tumors (approximately 17–18% vs. ~32%; p = 0.023). Membranous GPC3 localization was associated with inferior OS compared with cytoplasmic or absent expression (p = 0.025). Conclusions: Tumor GPC3 expression was associated with decreased OS and lower ORR among AB-treated patients with advanced HCC, suggesting potential clinical relevance and may help in risk stratification. Full article

Background/Objectives: Over the past few years, high-dose radioembolization (≥150 Gy) has become widely adopted for the treatment of primary liver cancer, while evidence for its application in hepatic metastases is still limited. The aim of this study was to evaluate the safety and efficacy of high-dose transarterial radioembolization (TARE) in patients with hepatic metastases using resin Yttrium-90 (⁹⁰Y) microspheres. Methods: In this retrospective analysis, patients who were treated with high-dose TARE for hepatic metastases with ⁹⁰Y resin microspheres between May 2019 and April 2025 were included. The primary outcomes were treatment efficacy and toxicity assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Treatment efficacy was evaluated based on radiological response according to Response Evaluation Criteria in Solid Tumors version 1.1, time to progression and overall survival (OS). Secondary outcomes included ⁹⁰Y PET/CT post-treatment voxel-based local deposition model dosimetry and its relations to response. Results: A total of 15 patients were included, with hepatic metastases originating from colorectal cancer (n = 11, 73.3%), neuroendocrine tumor (n = 3, 20%) and breast cancer (n = 1, 6.7%). Seven patients (47.7%) had undergone one or multiple prior loco(regional) liver treatments and 13 (86.7%) patients had prior systemic therapy. The median mean tumor absorbed dose was 160.7 Gy (IQR 127.6–245.0 Gy), and the median normal liver parenchyma dose was 40.3 Gy (IQR 21.7–52.3 Gy). Disease control was achieved in all patients, with partial response in 10 patients (66.7%) and stable disease in 5 patients (33.3%) after 3 months. The median OS was 26.5 months (95% CI 24.5 months to no estimate). Two patients (13.3%) experienced grade 3 laboratory toxicity. No grade 4 or 5 toxicities were observed. Conclusions: High-dose TARE with ⁹⁰Y resin microspheres resulted in a high disease control rate and demonstrated a favorable safety profile, even in this heavily pretreated cohort. Full article

Objective: To evaluate the safety, diagnostic yield, and ablation efficacy of a single-session workflow combining stereotactic percutaneous core-needle biopsy (CNB) immediately followed by microwave ablation (MWA) for liver tumors. Methods: We retrospectively reviewed consecutive patients (December 2021–May 2025) who underwent stereotactic CNB followed by MWA in the same procedure. Primary endpoints were primary technique efficacy (PTE) and complications. Secondary endpoints were 6-month local tumor progression (LTP) and diagnostic yield. Six-month LTP was summarized using a Kaplan–Meier (KM) point estimate with Greenwood 95% CIs. Results: Thirty-three patients underwent single-session biopsy and ablation (33 biopsied; 41 lesions ablated). PTE was 95.1% (39/41); two residual tumors were successfully re-ablated. Six-month LTP was 3.6% (patient level; KM 95% CI 0.0–10.5%) and 2.8% (lesion level; KM 95% CI 0.0–8.2%). There was one major complication (3%, post-ablation abscess) and no minor complications. Adequate tissue was obtained in all biopsies; a definitive diagnosis was established in 88% (29/33): malignancy in 73% (24/33) and benignity in 15% (5/33); 12% (4/33) were nondiagnostic. In the hepatocellular carcinoma (HCC)-suspected subgroup (LI-RADS LR-3 to LR-5; n = 24), all LR-5 lesions were HCC (11/11). Among LR-4 lesions (n = 7), histology showed HCC in 1/7 (14%) and cholangiocarcinoma in 2/7 (29%); 4/7 (57%) were benign or nondiagnostic. Among LR-3 lesions (n = 6), 2/6 (33%) were HCC and 4/6 (67%) were benign or nondiagnostic. In the metastasis-suspected subgroup (n = 9), malignancy was confirmed in 8/9 (89%); 1/9 (11%) was nondiagnostic. Conclusions: Single-session stereotactic CNB followed by MWA is feasible and safe, yields diagnostically useful tissue, and achieves high ablation efficacy. Full article

Background: Conventional CT- or US-guided radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) often limits repeat contrast-enhanced imaging and provides suboptimal intraprocedural conspicuity, which can hinder precise targeting and margin assessment. Purpose: To describe a single-center angiography-assisted cone–beam CT (angio-CBCT) RFA workflow and report early outcomes versus an institutional conventional CT-guided cohort. Materials and Methods: In this IRB-approved single-center retrospective study, consecutive patients underwent angio-CBCT-guided RFA for HCC (n = 14). Selective intra-arterial injections (≈20–40 mL iodinated contrast per CBCT) through a 5-Fr catheter permitted multiple intraprocedural CBCT acquisitions for targeting, verification, and endpoint assessment under general anesthesia. Primary outcomes were technical success, early local recurrence, and complications (CTCAE v6.0). For a secondary imaging analysis, within-patient change in lesion conspicuity (ΔHU = HU_tumor − HU_liver) from preprocedural contrast-enhanced CT to intraprocedural imaging was compared in available cases (angio-CBCT n = 12; conventional CT n = 13). Descriptive statistics were used. Results: Angio-CBCT RFA achieved technical success in 14/14 (100%) procedures; early local recurrence was 0/14 (0.0%); and one complication occurred (1/14, 7.1%; Grade 3). Intraprocedural refinements included immediate re-ablation in 3/14 (21.4%) and electrode repositioning in 2/14 (14.3%), with on-table detection of an additional lesion in 1/14 (7.1%). In the institutional conventional cohort, technical success was 19/20 (95.0%), early local recurrence 2/20 (10.0%), and complications 0/20 (0%). Lesion conspicuity improved with angio-CBCT (median ΔHU 290.1 HU, n = 12) but not with conventional CT (−10.5 HU, n = 13). Conclusions: Angio-CBCT-guided RFA for HCC is feasible and safe and enables repeatable, low-volume contrast-enhanced intraprocedural imaging that supports precise targeting, verification, and timely refinements. Early outcomes and markedly improved lesion conspicuity suggest potential advantages over conventional CT-guided workflows and warrant prospective validation in larger cohorts. Full article

Background/Objectives: Advanced hepatocellular carcinoma (HCC) presents limited treatment options; however, immunotherapy demonstrates encouraging outcomes and acceptable adverse reactions in advanced HCC. This study evaluates the efficacy and safety of combining serplulimab, the bevacizumab biosimilar HLX04, and hepatic arterial infusion chemotherapy (HAIC) as a first-line therapy. Methods: This prospective, observational, single-center phase II trial enrolled untreated HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C. All patients received serplulimab (4.5 mg/kg) and HLX04 (15.0 mg/kg) every 3 weeks, followed by the HAIC-FOLFOX regimen. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), and safety. Results: A total of 32 patients were enrolled. The best outcomes showed an ORR of 53.1%, including 17 partial responses (PR, 53.1%) and 12 stable diseases (SD, 37.5%), resulting in a DCR of 90.6%. Subgroup analysis showed a higher ORR in patients with a single lesion and those receiving ≥3 treatment cycles, with an ORR of 60.7% in the latter group. Additionally, five patients underwent successful hepatectomy after ≥3 treatment cycles, with postoperative pathology confirming extensive tumor necrosis. Kaplan–Meier analysis estimated PFS rates of 89.9% (95% CI: 79.5–100.0%) at 6 months and 70.8% (95% CI: 54.2–92.4%) at 12 months. No deaths related to adverse events (AEs) occurred; four (12.5%) patients experienced grade IV AEs and twelve (37.5%) patients experienced grade III AEs. Conclusions: Serplulimab, HLX04, and HAIC combined as a first-line treatment for advanced HCC have demonstrated promising efficacy, particularly in patients completing ≥3 cycles, with an acceptable safety profile. Further investigation in larger trials is required. Full article

Background: Hemangiomatosis is a rare condition characterized by the presence of multiple benign vascular tumors that may affect various organs, including the skin, liver, and spleen. Complications are closely linked to the location and size of the lesions. Case Presentation: We describe a rare presentation of infantile hemangiomatosis with widespread cutaneous and oral mucosal lesions, further complicated by splenic and hepatic involvement and secondary cholestasis. The initial progression was unfavorable, with an increase in both the number and size of the lesions. Cardiologic evaluation identified minor valvular insufficiencies, but no secondary cardiac failure. Treatment with propranolol and prednisone was initiated, with a slow favorable evolution. There were no new hemangiomas developed, and those on the face and limbs decreased in size, some disappearing entirely. Hepatic and splenic hemangiomas regressed more slowly, but their reduction and the improvement of cholestasis were progressive. Due to significant iatrogenic Cushing’s syndrome, prednisone was gradually tapered. Transient subclinical hypothyroidism occurred during treatment, resolving spontaneously. Conclusions: The present case illustrates the rarity and complexity of multifocal infantile haemangiomatosis and highlights the importance of early diagnosis, comprehensive organ evaluation, and tailored multidisciplinary management. It clearly demonstrates that prompt intervention and careful therapy adjustment can lead to favorable outcomes even in the setting of extensive visceral involvement. Full article

Background: Liver cancer, either primary or metastatic, is a leading cause of cancer-related deaths and in many cases is presented in stages requiring major hepatectomy. Adequate future liver remnant (FLR) volume is essential before any major hepatectomy. Portal vein embolization (PVE) has long been the standard technique for preoperative liver hypertrophy, but liver venous deprivation (LVD) has emerged as a novel method, potentially offering faster and superior results. The aim of this study is to compare FLR hypertrophy outcomes between LVD and PVE in patients undergoing major hepatectomy for liver malignancy. Methods: A systematic literature search was conducted across PubMed, Cochrane library, and clinicaltrials.gov for studies assessing FLR volume changes after LVD or PVE in patients with primary or secondary liver tumors undergoing liver resection. Data extraction was performed independently by two reviewers. The study protocol was registered in PROSPERO and was prepared according to the PRISMA guidelines. Results: Twelve retrospective cohort studies were included in this systematic review. Liver venous deprivation consistently demonstrated superior FLR hypertrophy, with a faster and higher percentage increase compared to PVE. Time to resection was also shorter in the LVD groups in most studies. Safety outcomes were comparable, with no consistent difference in post-procedural complications or mortality. Conclusions: Liver venous deprivation may potentially be a safe and effective alternative to PVE, offering more robust and rapid FLR hypertrophy with similar morbidity and mortality rates. While current evidence supports its superiority in selected patients, future validation with larger prospective clinical trials is essential before it can be adopted as standard management of patients with insufficient FLR volume. Full article

Background: Tracking differential growth of secondary liver metastases is important for early detection of progression but remains challenging due to variable tumor growth rates. We aimed to automate accurate, consistent, and efficient longitudinal monitoring. Methods: We developed an automatic 3D segmentation and tracking algorithm to quantify differential growth, tested on contrast-enhanced MRI follow-ups of patients with neuroendocrine liver metastases (NELMs). The output was integrated into a decision support tool to distinguish between progressive disease, stable disease, and partial/complete response. A user study involving an expert group of seven expert radiologists evaluated its impact. Group comparisons used the Friedman test with post hoc analyses. Results: Our algorithm detected 991 metastases in 30 patients: 13% new, 30% progressive, 18% stable, and 18% regressive; the remainder were either too small to measure (15%) or merged with another metastasis in the follow-up assessment (6%). Diagnostic accuracy improved with additional information on hepatic tumor load and differential growth, albeit not significantly (p = 0.72). The diagnosis time increased (p < 0.001). All radiologists found the method useful and expressed a desire to integrate it in existing diagnostic tools. Conclusions: We automated segmentation and quantification of individual NELMs, enabling comprehensive longitudinal analysis of differential tumor growth with the potential to enhance clinical decision-making. Full article

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with survival outcomes influenced by a range of demographic and pathological factors. While cirrhosis is a well-established risk factor, recent evidence shows that HCC can also develop in patients with only mild to moderate liver fibrosis. However, there is limited understanding of how fibrosis severity interacts with other clinical variables, such as patient age, to affect mortality. This study aims to explore how fibrosis scores relate to both overall and cancer-specific mortality in US HCC patients, with an emphasis on how this relationship may shift across different age groups. Methods: We utilized data from the Surveillance, Epidemiology, and End Results (SEER) database to identify 15,796 adult patients diagnosed with HCC between 2010 and 2021. Baseline demographics, disease characteristics, and treatment variables were examined. Mortality outcomes were evaluated using Cox proportional hazard regression. Variables significant at p < 0.1 in univariate analysis were included in multivariate models to identify independent predictors of mortality (with hazard ratios [HRs] > 1 signifying increased risk). A secondary analysis assessed how age modifies the association between fibrosis score and mortality. Results: The study population was predominantly male (77.2%), with most patients aged 60–79 (59.6%) and presenting with localized disease (61%). A majority had advanced liver fibrosis or cirrhosis (81.7%) and lived in large urban areas (62.9%). Crude comparisons indicated that male sex, older age, single status, advanced tumor stage, lower income, and cirrhosis were linked to worse outcomes. In adjusted models, independent predictors of increased mortality included male sex, older age, unmarried status, and more advanced disease stage. Receipt of surgery or chemotherapy was associated with a lower risk of death. Notably, the influence of fibrosis on mortality was found to be greater in older patients than in their younger counterparts. Conclusions: This analysis identifies key prognostic indicators in HCC and suggests that the relationship between fibrosis and survival is not uniform across age groups. These findings support the need for age-specific clinical management strategies and highlight the potential benefit of early detection and appropriate interventions, even in non-cirrhotic patients. Full article

Liver transplantation (LT) for hepatic malignancies is becoming increasingly common, largely because it offers superior survival relative to other treatment approaches. LT is well-accepted for primary liver cancers such as hepatocellular carcinoma and perihilar cholangiocarcinoma and is being increasingly accepted for intrahepatic cholangiocarcinoma and metastases of colorectal cancer or neuroendocrine tumors to the liver. Over time, indications for transplant oncology have broadened, as has the acceptable disease burden for transplantation, particularly with the advent of new neoadjuvant therapies. Other current frontiers in the field include expanding the donor pool through living donors, extended criteria donors, machine perfusion and increasing access to LT for people from disadvantaged socioeconomic backgrounds. Expanding access to LT can offer renewed hope for long-term survival to patients with primary and secondary liver cancer. Full article

Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article

Background/Objectives: Gypenosides (Gps) are the main active compounds of Gynostemma and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. Methods: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. Results: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of Firmicutes/Bacteroidetes, and elevated Bacteroidia abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12α-hydroxylated to non-12α-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K/AKT pathway and the intestinal BA/FXR/FGF15 axis, suggesting the coordinated regulation of metabolic and gut–liver axis signaling pathways. Conclusions: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut–liver axis. Full article