UNASSIGNED: Individualized treatment of colorectal cancer liver metastases (CRLM) remains challenging due to differences in the severity of metastatic disease and tumour biology. Exploring specific prognostic risk subgroups is urgently needed. The current study aimed to investigate the prognostic value of chromosomal instability (CIN) in patients with initially resectable CRLM and the predictive value of CIN for the efficacy of bevacizumab.
UNASSIGNED: Ninety-one consecutive patients with initially resectable CRLM who underwent curative liver resection from 2006 to 2018 at Sun Yat-sen University Cancer Center were selected for analysis. CIN was evaluated by automated digital imaging systems. Immunohistochemistry (IHC) was performed to detect interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA) and CD31 expression in paraffin-embedded specimens. Recurrence-free survival (RFS) and overall survival (OS) were analysed using the Kaplan-Meier method and Cox regression models.
UNASSIGNED: Patients with high chromosomal instability (CIN-H) had a worse 3-year RFS rate (HR, 1.953; 95% CI, 1.001-3.810; p = 0.049) and a worse 3-year OS rate (HR, 2.449; 95% CI, 1.150-5.213; p = 0.016) than those with low chromosomal instability (CIN-L). CIN-H was identified as an independent prognostic factor for RFS (HR, 2.569; 95% CI, 1.078-6.121; p = 0.033) and OS (HR, 3.852; 95% CI, 1.173-12.645; p = 0.026) in the multivariate analysis. The protein levels of IL-6, VEGFA and CD31 were upregulated in patients in the CIN-H group compared to those in the CIN-L group in both primary tumour and liver metastases tissues. Among them, 22 patients with recurrent tumours were treated with first-line bevacizumab treatment and based on the clinical response assessment, disease control rates were adversely associated with chromosomal instability (p = 0.043).
UNASSIGNED: Our study showed that high chromosomal instability is a negative prognostic factor for patients with initially resectable CRLM after liver resection. CIN may have positive correlations with angiogenesis through expression of IL-6-VEGFA axis and be used as a potential predictor of efficacy of bevacizumab.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor in women. Between 20 % and 30 % of patients develop metastases from BC, 50 % of them in the liver. The mean survival rate reported in patients with liver metastases from BC (LMBC) ranges from 3 to 29 months. The role of surgery in LMBC is not clearly defined. The objective of the present study was to determine the long-term survival and disease-free survival of patients undergoing surgery for LMBC and to identify the patients who most likely benefit from surgery.
METHODS: This retrospective multicenter cohort study included all consecutive patients undergoing LMBC surgery at the participating European centers from January 1, 2010, to December 31, 2015. The ClinicalTrials.gov ID is NCT04817813.
RESULTS: A hundred women (mean age 52.6 years) undergoing LMBC surgery were included. Five-year disease-free survival was 29 %, and 5-year overall survival was 60 %. Median survival after BC surgery was 12.4 years, and after LMBC surgery, 7 years. Patients with ECOG 1, ASA score I-II, metachronous LMBC, positive hormone receptors, and who had received neoadjuvant and adjuvant hormone treatment obtained the best overall and disease-free survival results.
CONCLUSIONS: In cases of correct patient selection and as part of a comprehensive onco-surgical strategy, surgery for LMBC improves overall long-term survival. In our series, certain factors were linked to better disease-free and overall survival; consideration of these factors could improve the selection of the best candidates for LMBC surgery.
RESULTS:
UNASSIGNED: NCT04817813.

UNASSIGNED: Treatment of metastatic colorectal cancer (mCRC) includes resection of liver metastases (LM), however, no validated biomarker identifies patients most likely to benefit from this procedure. This meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC (i.e., RAS, BRAF, SMAD4, PIK3CA) as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM resection.
UNASSIGNED: A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM, stratified according to RAS, BRAF, PIK3CA, and SMAD4 mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were combined. The search was conducted in numerous databases, including MEDLINE (PubMed), Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO host), and WHO Global Index Medicus, through March 18th, 2022. Meta-analyses, editorials, letters to the editor, case reports, studies on other primary cancers, studies with primary metastatic sites other than the liver, studies lacking specific oncological outcome variables or genetic data, non-English language studies, and studies omitting residual disease data from liver metastasectomy were excluded. The remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically presented.
UNASSIGNED: RAS mutation status was negatively associated with overall survival (OS) (HR, 1.68; 95% CI, 1.54-1.84) and recurrence free survival (RFS) (HR, 1.46; 95% CI, 1.33-1.61). A negative association was also found for BRAF regarding OS (HR, 2.64; 95% CI, 2.15-3.24) and RFS (HR, 1.89; 95% CI, 1.32-2.73) and SMAD4 regarding OS (HR, 1.93; 95% CI, 1.56-2.38) and RFS (HR, 1.95; 95% CI, 1.31-2.91). For PIK3CA only three studies were eligible and no significant association with either OS or RFS could be highlighted.
UNASSIGNED: RAS, BRAF, and SMAD4 are negatively associated with OS and RFS in patients undergoing curative liver metastasectomy from colorectal cancer. No conclusion can be drawn for PIK3CA due to the limited literature availability. These data support the integration of RAS, BRAF, and SMAD4 mutational status in the surgical decision-making for colorectal liver metastasis. Nevertheless, we have to consider several limitations, the major ones being the pooling of results from studies that evaluated patient outcomes as either disease-free survival (DFS) or RFS; the inclusion of patients with minimal residual disease and unconsidered potential confounding factors, such as variability in resectability definitions, chemotherapy use, and a potential interaction between biological markers and pre- and post-resection pharmacological treatments.

Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs.

BACKGROUND: Genetic And Morphological Evaluation (GAME) score is the newest prognostic model for patient with colorectal liver metastases (CRLMs). Pathological and radiological responses to neoadjuvant chemotherapy (NAC) are key factors for prognostic stratification of these patients. The present study aims to evaluate the GAME-score\'s ability to predict pathological and radiologic responses to NAC.
METHODS: CRLM patients who underwent liver resection after NAC from January 2010 to December 2021 were categorized by GAME scores: low risk (LR, 0-1), moderate risk (MR, 2-3), and high risk (HR, ≥4). Correlations between groups and radiological/pathological features were analyzed. Poor pathological response was defined as Tumor Regression Grade 4-5.
RESULTS: Of 1054 liver resections for CRLMs, 448 were included. GAME scores were LR: 80 (18 %), MR: 228 (51 %), and HR: 140 (31 %). In this cohort, HR-GAME scores were associated with lower pathological response (LR: 67.1 %, MR: 74.9 %, HR: 82.6 %; p = 0.010). Radiologic progression occurred in 10 % of HR patients, significantly more than in LR (3.8 %) and MR (3.5 %) groups (p = 0.011). Multivariable analysis for independent predictors of pathological response confirmed HR-GAME (RR 1.843, p=0.025) along with age higher than 70 years (RR 2.111, p=0.022) and irinotecan-based NAC (RR 3.066, p < 0.001). For radiological progression disease after NAC, the HR-GAME score (RR 2.77, p=0.016) was the only independent predictor. HR-GAME scores were also associated with higher rates of mucinous differentiation (p = 0.021), satellitosis (p = 0.001), vascular invasion (p = 0.011), and perineural invasion (p = 0.010).
CONCLUSIONS: GAME score category should be considered into planning of therapeutic strategy of patients with CRLMs.

The discontinuous peripheral enhancement is a pattern of enhancement usually attributed to typical cavernous hemangioma, that is the most common benign solid lesion of the liver. The discontinuous peripheral enhancement, however, may be encountered in many other benign and malignant focal liver lesions as an atypical presentation or evolution, and hemangiomas with discontinuous peripheral hyperenhancement on hepatic arterial phase may not always have the typical post-contrast pattern on portal venous and delayed phases. Therefore, abdominal radiologists may be challenged in their practice by lesions with discontinuous peripheral enhancement. This pictorial essay aims to review the spectrum of benign and malignant focal liver lesions that may show discontinuous peripheral enhancement. A particular point of interest is the diagnostic tree pathway that may guide the radiologists in the differential diagnosis.

OBJECTIVE: Ablative therapies for primary and secondary liver malignancies are increasingly adopted in current guidelines. Nevertheless, surgical resection remains the gold standard in most curative therapy settings. Extensive studies on mortality and morbidity after ablative treatment of the liver are missing. We investigated complications and mortality after ablative treatment in a large, unselected study cohort.
METHODS: Standardized patient and treatment data in 4374 percutaneous and angiographic ablative procedures of the liver from the DRG-based hospital reimbursement system (diagnosis-related groups) of an academic hospital in Germany were retrospectively evaluated. We analyzed descriptive patient data, length of stay (LOS), pre-existing medical conditions, previous gastrointestinal surgeries, severe complications, and occurrence of death.
RESULTS: Treatment of secondary liver malignancies constituted over two-thirds of all procedures (71%, n = 3053). The mean LOS was 4.1 ± 3.5 days. Severe complications were documented in 1.4% and in-house death in 0.2% of cases, significantly more often after treatment with chemoembolization of primary liver malignancies (p = 0.003; p = 0.0001). Previous partial liver resection, partial bowel resection, and chronic renal failure were independent risk factors for the occurrence of severe complications.
CONCLUSIONS: Severe complications and in-hospital death are rare in the treatment of primary and secondary liver malignancies with percutaneous and angiographic procedures. They are a viable alternative or addition to a surgical approach in treating liver lesions.

Distant metastases and drug resistance account for poor survival of patients with gastrointestinal (GI) malignancies such as gastric cancer, pancreatic cancer, and colorectal cancer. GI cancers most commonly metastasize to the liver, which provides a unique immunosuppressive tumour microenvironment to support the development of a premetastatic niche for tumor cell colonization and metastatic outgrowth. Metastatic tumors often exhibit greater resistance to drugs than primary tumors, posing extra challenges in treatment. The liver metastases and drug resistance of GI cancers are regulated by complex, intertwined, and tumor-dependent cellular and molecular mechanisms that influence tumor cell behavior (e.g. epithelial-to-mesenchymal transition, or EMT), tumor microenvironment (TME) (e.g. the extracellular matrix, cancer-associated fibroblasts, and tumor-infiltrating immune cells), tumor cell-TME interactions (e.g. through cytokines and exosomes), liver microenvironment (e.g. hepatic stellate cells and macrophages), and the route and mechanism of tumor cell dissemination (e.g. circulating tumor cells). This review provides an overview of recent advances in the research on cellular and molecular mechanisms that regulate liver metastases and drug resistance of GI cancers. We also discuss recent advances in the development of mechanism-based therapy for these GI cancers. Targeting these cellular and molecular mechanisms, either alone or in combination, may potentially provide novel approaches to treat metastatic GI malignancies.

BACKGROUND: To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases.
METHODS: A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts.
RESULTS: Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P < 0.001) were independent risk factors for liver metastasis in patients with gastric cancer, and Nomogram was established based on this analysis (C-statistics = 0.911, 95%CI 0.880-0.958), and the C-statistics of the external validation cohorts achieved 0.926. ROC analysis and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic value than single variety.
CONCLUSIONS: By innovatively introducing a new tumor location classification method, systemic inflammatory response indicators such as NLR and PLR, and nutritional index OPNI, the risk factors of gastric cancer liver metastasis were determined and a predictive Nomogram model was established, which can provide clinical prediction for patients with gastric cancer liver metastasis.

Neuroendocrine tumors are an indolent, heterogeneous group of tumors that primarily arise from the gastropancreatic tract and lungs. Most patients present with liver metastases at the time of diagnosis, which cause significant morbidity and mortality due to excess hormone secretion, bile duct obstruction, and liver damage. A small percentage of these patients are eligible for potential cure through surgical resection. However, interventional radiology provides liver-directed therapies, such as percutaneous ablation, transarterial embolization, chemoembolization, and radioembolization, for palliative care and potential bridging to debulking and surgical resection of neuroendocrine liver metastases. This article aims to provide a brief overview of these liver-directed therapies focusing on the pre-, intra-, and postprocedural imaging findings.