Search Results (437)

Immune checkpoint inhibitor (ICI)-based combinations have become central systemic treatment options for advanced hepatocellular carcinoma (HCC) and are now being integrated into selected intermediate-stage settings. As tumor responses have improved, some patients who were not initially candidates for curative-intent treatment may later become candidates for resection, ablation, or liver transplantation. However, radiographic response alone does not define curative-intent candidacy, and no shared framework currently guides how post-immunotherapy response should be translated into a treatment decision. Terminology also differs regionally: Asian literature frames a resection-anchored paradigm, whereas Western practice uses transplant-anchored downstaging. This narrative review proposes a multidisciplinary framework for immunotherapy-based conversion to curative-intent treatment in HCC. We first clarify the lexicon of conversion, downstaging, bridging, neoadjuvant therapy, post-ICI transplantation, and drug-free or treatment-free status. We then summarize conversion-relevant evidence across key clinical decision settings, including transarterial chemoembolization (TACE)-unsuitable intermediate-stage disease, portal vein tumor thrombus or macrovascular invasion, borderline-resectable or locally advanced disease, and transplant downstaging or bridging. The central framework defines curative-intent transition through the intersection of three domains: technical suitability, oncologic suitability, and physiologic or liver-reserve suitability. Biomarkers, imaging response, tumor-marker kinetics, liver function, and treatment-related toxicity are discussed as inputs into candidacy rather than as response measures alone. Finally, we propose a multidisciplinary workflow and highlight lessons from pancreatic cancer, biliary tract cancer, and colorectal liver metastases. As an expert-opinion-based framework, this approach should structure multidisciplinary discussion rather than serve as validated selection criteria; harmonized terminology, prospective conversion registries, and conversion-specific endpoints are needed for prospective validation. Full article

Complete resection with microscopically negative (R0, or no tumor cells within 1 mm of resection surface) margins has long been considered the cornerstone of curative-intent hepatectomy for colorectal liver metastases (CRLM). R1 resection is defined as the presence of tumor cells at or within 1 mm of the inked margin. A growing body of contemporary evidence, however, shows that the traditional binary R0/R1 framework obscures biologically meaningful subcategories of positive margin. An R1 parenchymal (R1p) margin on the transected liver surface carries a distinctly adverse prognosis, whereas an R1 vascular (R1v) margin (created by intentional detachment of tumor from the adventitia of a major intrahepatic vessel along Laennec’s capsule) yields oncologic outcomes that are, in essence, equivalent to R0: modern series report five-year overall survival rates of 34–45% after R1v, comparable to matched R0 cohorts. This insight has radical implication, enabling parenchyma-preserving hepatectomy (PPH) for patients who would otherwise require major hepatectomy (i.e., trisectionectomy) for multifocal and centrally located tumors, as well as allowing patients who would otherwise be considered unresectable to undergo curative intent resection. Careful patient selection, taking into consideration anatomic variation, use of intraoperative ultrasound guidance, response to systemic therapy, and molecular tumor profiling is essential for the safe application of R1v PPH. This review synthesizes the evidence supporting the R1p/R1v distinction, places it within the broader evolution of margin paradigms in CRLM, and outlines the clinical, anatomical, and biological criteria that should guide its judicious use in the current era of precision hepatobiliary surgery. Full article

Colorectal cancer frequently metastasizes to the liver, and a substantial proportion of patients present with unresectable colorectal liver metastases (CRLM), which are associated with limited survival. While systemic chemotherapy remains a central component of management, advances in liver-directed therapies and transplantation have significantly expanded therapeutic possibilities in selected patients. This review provides a comprehensive and up-to-date overview of current management strategies for unresectable CRLM, with a focus on systemic chemotherapy, intra-arterial therapies, and liver transplantation. Systemic chemotherapy plays a central role, either as conversion therapy aimed at achieving secondary resectability or as palliative treatment to prolong survival and maintain quality of life. The integration of targeted agents and molecular profiling has enabled increasingly personalized therapeutic strategies. Liver-directed therapies, including hepatic arterial infusion chemotherapy, transarterial chemoembolization, and radioembolization, provide effective local disease control and may facilitate downstaging in selected patients. In parallel, liver transplantation has re-emerged as a promising option for highly selected patients with liver-only disease, demonstrating encouraging long-term survival in recent prospective studies. However, optimal patient selection, timing, and sequencing of these modalities remain key challenges. The management of unresectable CRLM is evolving toward a multidisciplinary and individualized approach that integrates systemic, locoregional, and transplant-based strategies. In selected patients, this paradigm shift may translate into meaningful survival benefit, although further prospective studies are required to refine indications and optimize treatment sequencing. Full article

Background: Early recurrence following curative-intent hepatectomy for colorectal liver metastases (CRLMs) remains a significant clinical challenge. This study investigates risk factors for recurrence within 6 and 12 months and evaluates the impact of salvage surgery on long-term survival. Methods: We conducted a retrospective cohort study of 109 patients who underwent liver resection for CRLMs between 2013 and 2024. The primary outcome was the identification of predictors for early recurrence using Cox proportional-hazards models. The secondary outcomes focused on overall survival (OS) stratified by the timing of recurrence and subsequent treatment. Results: High tumor burden (>4 metastases) was an independent predictor of recurrence at both 6 months (HR 3.526; p = 0.008) and 12 months (HR 3.115; p = 0.004). Intraoperative blood loss >1000 mL was significantly associated with 6-month recurrence (HR 3.356; p = 0.004) and 12-month recurrence (HR 2.171; p = 0.041). For the 12-month window, independent predictors included AJCC T3/T4 stage (HR 6.513; p = 0.011) and RAS mutation (HR 2.740; p = 0.006). Notably, patients with early recurrence who underwent salvage re-hepatectomy achieved 5-year OS rates that did not statistically differ from those without recurrence (p = 0.907 for <6 months; p = 0.433 for <12 months); however, these subgroup analyses are highly underpowered. Conclusions: High tumor burden (>4 metastases), RAS mutations, significant blood loss (>1000 mL), and primary tumor T3/T4 identify patients at high risk for early recurrence. While aggressive salvage re-hepatectomy is associated with prolonged survival in select patients, the non-significant p-values in our small salvage cohorts cannot be interpreted as evidence of survival equivalence. The observed survival benefits in the salvage cohort are heavily confounded by inherent selection biases, and therefore, the true extent of this ‘rescue’ effect must be interpreted with extreme caution and validated in larger, adequately powered multicenter studies. Full article

Background: Accurate preoperative prediction of length of hospital stay (LOS) after surgery for colorectal liver metastases (CRLMs) could improve patient counselling and resource planning, yet reliable risk tools are lacking. We aimed to develop an interpretable machine learning model predicting LOS following first-time liver-directed surgery for CRLMs. Methods: In this multicenter cohort study, we included patients who underwent first-time liver resection, ablation, or a combination for CRLMs at three Danish hepatobiliary centers between 2016 and 2023. Preoperative features from two national registries were used to train Elastic Net, Random Forest, HistGradientBoosting, and Explainable Boosting Machine (EBM) algorithms. Hyperparameters were optimized using five-fold cross-validation. Performance was evaluated on a 20% hold-out test sample using mean absolute error (MAE) with bootstrapped 95% confidence intervals (CIs). Results: Among 915 patients, median LOS was 4.0 days (interquartile range (IQR) 3.0–6.0). All four algorithms achieved comparable prediction error (MAE 3.0–3.1 days). The EBM (MAE 3.1 days, 95% CI 2.6–4.3) algorithm was selected for its inherent interpretability. Surgical approach was the strongest predictor, where percutaneous and laparoscopic approaches were associated with reductions of 1.9 and 1.2 days, respectively. Tumor burden, including number of lesions and largest lesion diameter, showed progressive non-linear associations with longer stays. Nonetheless, overall explained variance was low (R² ≤ 0.10), and calibration showed systematic underestimation of stays beyond five days. Conclusions: An inherently interpretable machine learning model matched the predictive performance of opaque algorithms for LOS after CRLM surgery, although overall predictive accuracy was modest and longer stays were underestimated. Explainability analysis identified surgical approach and tumor burden as the most influential predictors. External validation in healthcare systems with different discharge practices is warranted. Full article

Background: Precise intraoperative localisation of small colorectal tumours during laparoscopic surgery remains challenging due to absent tactile feedback and subserosal tumour location. Current standard methods, particularly India ink tattooing, demonstrate 15–30% failure rates for lesions less than 10 mm, leading to prolonged operative times, incomplete resections, and re-operations. Multiple emerging technologies promise improved localisation, yet comparative evidence remains fragmented. Objective: To map and characterise the current landscape of intraoperative marking and identification technologies for small colorectal tumour localisation during laparoscopic surgery, with emphasis on radiofrequency-based methods and alternative approaches, and to identify evidence gaps guiding future research. Methods: Following PRISMA-ScR guidelines, we systematically searched PubMed, Web of Science, and Scopus databases from January 2000 through December 2025 for studies evaluating tumour localisation technologies in colorectal cancer surgery, including primary tumour localisation during laparoscopic colectomy and localisation of colorectal liver metastases during hepatic surgery, or transferable anatomical applications with documented translational potential to colorectal surgery. Two independent reviewers screened all records, with discrepancies resolved through discussion and a third senior reviewer consulted for unresolved disagreements; data were extracted on technical performance, safety, feasibility, cost-effectiveness, usability, innovation potential, and evidence quality. Results: We included 89 studies comprising 18 colorectal-specific articles and 71 transferable/GI-adjacent studies. Detection success rates ranged from 71% to 100% across modalities. Near-infrared fluorescence with indocyanine green demonstrated the strongest clinical evidence with 75–100% detection across eight colorectal studies encompassing 2134 procedures and seamless workflow integration. Radiofrequency identification systems achieved 91.9–99% detection in feasibility studies with promising tissue penetration of 15–35 mm but limited colorectal validation. Electromagnetic navigation excelled in rigid organs with 85–98% success but showed degraded performance in mobile bowel at 71–75%. Critical evidence gaps included absent head-to-head comparative trials, non-standardised outcome metrics limiting cross-study comparability, and limited long-term safety data with only 14 studies providing follow-up exceeding six months. Conclusions: ICG fluorescence represents the most clinically mature technology identified, representing a priority candidate for colorectal-specific validation in challenging localisation scenarios. RFID systems demonstrate promising characteristics justifying prioritised research investment through adequately powered comparative trials. Future research must emphasise consortium-based comparative effectiveness studies, standardised outcome metrics, and integration with robotic and AI-assisted surgical platforms to accelerate clinical translation. Full article

Background: Non-colorectal cancer liver metastases (NCRLMs) represent a therapeutically challenging condition with poorly defined locoregional treatment options. This study evaluates the safety, oncological efficacy, and survival outcomes of microwave ablation (MWA) for NCRLMs in a large single-centre series. Methods: Retrospective analysis of patients undergoing MWA for NCRLM between January 2010 and December 2024 at a high-volume hepatobiliary centre. Endpoints were safety, efficacy, textbook outcome (TO) achievement, and overall survival (OS). Results: A total of 138 patients underwent 172 MWA procedures across eight primary tumour categories via a video-assisted (n = 110, 64%) or percutaneous (n = 62, 36%) approach. Major complications (Clavien–Dindo ≥ 3) occurred in 1.8% of procedures, with a median hospital stay of 2 days and a 90-day mortality of 1.7%. The median follow-up was 24.9 (10.3, 55.8) months. Complete response (CR) was achieved in 77% of procedures and TO in 54%, with incomplete response as the main driver of TO failure. The 5-year OS varied by histology, from 100% (GIST) and 80.0% (GEP-NET) to 44.7% (breast) and 0% (pancreatic adenocarcinoma). The video-assisted ablation was associated with superior OS compared to the percutaneous one (5-year OS 54.4% vs. 26.0%, p = 0.00025). In the multivariable analysis, the percutaneous approach (HR 2.44), ECOG PS ≥ 2 (HR 6.06) and a higher tumour burden score (HR 1.09) independently predicted worse OS, whereas the histological group was not independently associated with OS. Repeat MWA was the most frequent treatment for first hepatic recurrence, and 50% of patients reached no evidence of disease (NED) at last follow-up. Conclusions: MWA is a safe and repeatable locoregional treatment for NCRLMs, with outcomes shaped by tumour biology, disease burden, patient fitness and procedural approach. The high rate of liver-dominant recurrence treated with repeat MWA, combined with a final NED rate of 50%, supports MWA as a platform for iterative locoregional disease control in selected patients. Full article

Carbohydrate antigen 19-9 (CA19-9) is widely used as a tumor marker in gastrointestinal malignancies; however, its clinical significance in patients undergoing resection for colorectal liver metastases (CRLM) remains unclear. This review summarizes current evidence regarding the prognostic value of CA19-9 in CRLM, with particular emphasis on its role compared with carcinoembryonic antigen (CEA) and its integration into modern prognostic models. Across multiple cohort studies, elevated preoperative CA19-9 levels have consistently been associated with worse recurrence-free and overall survival after hepatectomy. In several multivariable analyses, CA19-9 emerged as a significant prognostic factor whereas CEA did not. CA19-9 has also been incorporated into several prognostic scoring systems and nomograms, including the JSHBPS nomogram (Beppu score) and the Imai nomogram, highlighting its value as a surrogate marker of potentially unfavorable tumor biology. Reported cutoff values vary widely across studies, ranging from near-normal levels (34–37 U/mL) to higher thresholds (100–200 U/mL), and the optimal cutoff remains uncertain. In addition to its role as a categorical risk factor, dynamic changes in CA19-9 during preoperative chemotherapy may provide additional prognostic information. Routine assessment of CA19-9 together with CEA at CRLM diagnosis and during perioperative management may improve risk stratification and guide personalized multidisciplinary treatment strategies. Full article

Lung cancer is a leading cause of death worldwide and is often accompanied by declines in musculoskeletal health (i.e., cachexia). Despite affecting a majority of lung cancer patients, cachexia remains understudied and currently has no cure. We have previously demonstrated that liver metastases (LMs) exacerbate cachexia in murine models of colorectal cancer, and, while the liver represents a common site of metastases and is associated with poor prognosis in patients with lung cancer, whether LMs heighten musculoskeletal wasting in mice bearing lung cancer is unknown. Here, we aimed to characterize the impact of LMs on musculoskeletal health in a mouse model of lung cancer cachexia. C57BL/6J male mice were injected with LLC tumor cells either subcutaneously or intrasplenically (LMs) to mimic hepatic metastases (n = 6–9/group). Upon sacrifice, skeletal muscle, bone, and plasma were collected for morphological and molecular analyses. Consistently, compared to healthy controls, metastatic tumor hosts displayed greater reductions in muscle weights (~17%), in line with decreased muscle torque (~23%) and reduced muscle cross-sectional area (~10%). On a molecular level, skeletal muscle from mice bearing LMs had elevated levels of pStat3, Murf1, and Atrogin-1, suggesting enhanced protein catabolism. Similar to skeletal muscle, metastatic tumor hosts displayed greater losses in trabecular bone and increased skeletal fragility. Plasma proteomics identified 211 and 131 differentially expressed proteins in metastatic hosts compared to control animals and subcutaneous LLC hosts, respectively. Top regulated pathways in mice bearing LMs included neutrophil degranulation, BAG2 signaling, and cachexia signaling. Overall, our findings demonstrate that LMs are accompanied by accelerated musculoskeletal wasting and weakness in a mouse model of lung cancer cachexia. This work highlights the need for animal models that mimic advanced cancer, thus providing a better understanding of the mechanisms that mediate cachexia. Full article

Background: Neuroendocrine neoplasms are frequently diagnosed after the detection of liver metastases, often when the primary tumor remains occult. Accurate non-invasive differentiation of neuroendocrine liver metastases (NELMs) from other focal hepatic lesions is therefore crucial. This study aimed to characterize the magnetic resonance imaging (MRI) features of NELMs using hepatocyte-specific contrast agents and to identify a potential radiologic “signature” that may suggest a neuroendocrine origin. Methods: This retrospective study included three cohorts: patients with histologically confirmed NELMs (n = 51; 146 lesions), patients with colorectal cancer liver metastases (n = 18; 46 lesions), and patients with benign hepatic hemangiomas (n = 28; 51 lesions). All subjects underwent standardized liver MRI with Gd-EOB-DTPA. Lesions were evaluated for size, diffusion-weighted imaging characteristics, apparent diffusion coefficient values, arterial-phase enhancement, T2-weighted signal, hepatobiliary-phase appearance, and hemorrhagic components. Statistical analyses included univariate and multivariate testing and receiver operating characteristic curve analysis. Results: NELMs commonly demonstrated arterial hyperenhancement, diffusion restriction, and variable T2 and hepatobiliary-phase signal heterogeneity. Compared with colorectal metastases and hemangiomas, NELMs showed distinctive patterns, particularly higher rates of hepatobiliary-phase heterogeneity and arterial enhancement. Lesion size, ADC metrics, T2 heterogeneity, and hemorrhage were significant discriminators. Conclusions: Hepatocyte-specific MRI enables identification of characteristic imaging features of NELMs. An integrated assessment of morphologic, diffusion, and hepatobiliary-phase findings may facilitate early recognition of neuroendocrine metastases, even when the primary tumor is unknown, improving diagnostic confidence and clinical management. Full article

Background: Hepatic malignancies are a major global health burden, with rising incidence, high mortality, and frequent diagnosis at advanced or unresectable stages. Although surgical resection, locoregional therapies, and systemic treatments have improved outcomes, many patients remain ineligible for curative strategies because of tumor burden, anatomical constraints, or liver dysfunction. Liver transplantation (LT) has therefore evolved from a treatment limited to selected hepatocellular carcinoma (HCC) cases within strict morphological criteria to a broader oncologic option guided by tumor biology and treatment response. This review provides an updated overview of the expanding role of LT in hepatic malignancies and the transition toward precision transplant oncology. Methods: We conducted a narrative review of current evidence on LT in HCC, cholangiocarcinoma (CCA), and colorectal liver metastases (CRLM), focusing on candidate selection, neoadjuvant strategies, molecular profiling, immunological aspects, and future perspectives. Results: In HCC, expanded criteria and bridging/downstaging strategies, including immunotherapy, have increased transplant eligibility, although concerns remain regarding rejection risk and post-transplant management. In CCA, especially perihilar disease, standardized neoadjuvant protocols followed by LT have achieved encouraging long-term survival in highly selected patients, whereas intrahepatic CCA remains investigational within prospective biomarker-driven studies. In CRLM, once considered an absolute contraindication, recent evidence supports LT in selected patients with liver-confined and biologically favorable disease, emphasizing the importance of tumor kinetics, molecular features, and response to systemic therapy. Conclusions: Integration of molecular oncology, immunology, and advanced therapies is redefining LT indications for hepatic malignancies. Future progress will depend on biomarker-driven selection, precision medicine, and multidisciplinary decision-making to optimize outcomes while addressing ethical challenges in organ allocation. Full article

Liver transplant can significantly improve survival in patients with isolated colorectal liver metastases (CRLMs) not amenable to surgical resection. The use of evolving strict selection criteria to identify patients with CRLM best suited for transplant has greatly prolonged disease-free survival and resulted in a post-transplant overall survival similar to that of other established indications for transplant such as advanced cirrhosis or hepatocellular carcinoma. While recurrence of colorectal cancer is still seen in the majority of patients after transplant, lesions are typically slow-growing and treatable without significant mortality. Further profiling of patients’ tumor molecular and biologic activity before transplant can help risk-stratify them for aggressive recurrence. Our current understanding of recurrence after liver transplant for CRLM is based on only a small number of prospective studies but further trials are underway. Novel surgical approaches which could expand the pool of patients eligible for transplant are also being evaluated. We summarize and discuss the current state of the literature describing the patterns, risk factors, and treatment of recurrence after liver transplant for isolated CRLM. Full article

Background/Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity complicate biomarker discovery and clinical management. This study aimed to characterize the spatial metabolomic landscape of CRC and identify progression-associated metabolic alterations and potential metabolic signatures for liver metastasis. Methods: A total of 23 tissue samples were collected from patients with CRC, with and without liver metastasis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to map the spatial metabolite distributions. Region-of-interest analysis guided by histopathology enabled comparative metabolomic profiling across different tissue types. Multivariate statistical analysis, pathway enrichment, and receiver operating characteristic (ROC) curve analyses were performed to identify key metabolic alterations and evaluate potential biomarker performance. Results: Distinct spatial metabolomic profiles were observed across normal mucosa, primary tumors, liver metastases, and normal liver tissues. In primary colorectal tumors, amino acid, purine, and choline metabolism were significantly upregulated, whereas liver metastases were characterized by elevated levels of triglycerides, diglycerides, cholesteryl esters, and acylcarnitines, indicating enhanced lipid synthesis, incomplete fatty acid oxidation, and/or mitochondrial dysfunction. Progression-associated analyses across tissue types revealed consistently increasing trends in glycerides and acylcarnitines, along with heterogeneous alterations in amino acids and phospholipids. Furthermore, 122 differential metabolites were identified between metastatic and non-metastatic CRC, and a four-lipid panel demonstrated strong discriminatory performance. Conclusions: This study provides a spatially resolved characterization of metabolic reprogramming during CRC progression and liver metastasis, highlighting lipid and amino acid metabolism as key features and revealing the metabolic signatures of CRLM. Full article

Purpose: Surgical resection of liver or pulmonary oligometastases (LP-OMD) in colorectal cancer (CRC) has been shown to improve survival. Stereotactic body radiotherapy (SBRT) is a promising alternative for patients with primary lung cancer. However, the efficacy of SBRT for LP-OMD in CRC remains inconclusive, and local control (LC) rates are often unsatisfactory. This prospective study aimed to evaluate the treatment outcomes of dose-escalated and convergent SBRT for patients with LP-OMD from CRC, with the goal of demonstrating its effectiveness as a treatment option for these patients. Methods and materials: This study included 23 CRC patients with LP-OMD who received SBRT between 2017 and 2022. The inclusion criteria were histologically confirmed colorectal adenocarcinoma, one to three oligometastases, and a tumor diameter of 5 cm or less. Patients who were inoperable or declined surgery were included. SBRT was delivered with total doses of 50–60 Gy administered over five fractions, covering the planning target volume surface within the 60% isodose line of the maximum dose. The primary endpoint was the 2-year LC rate, while secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Results: The median follow-up duration was 41.0 months (range: 11.5–77.2). At the time of analysis, five patients had died from CRC, six were alive with disease, and twelve were alive without disease. Only one patient experienced local recurrence of a pulmonary oligometastasis. The 2-year LC, PFS, and OS rates were 95.0% (95% CI: 69.5–99.3), 61.3% (95% CI: 40.0–77.0), and 88.1% (95% CI: 67.6–96.0), respectively. Toxicity was acceptable, with no grade ≥ 3 adverse events. Conclusions: High-central-dose SBRT for LP-OMD from CRC achieved favorable local control with minimal toxicity. These findings should be interpreted cautiously and require validation in larger, multi-institutional studies. Full article