Liver Metastases Research Articles

Pseudomyogenic Hemangioendothelioma: A Case Report of a Rare Tumor with Unusual Presentation

Abstract Introduction/Objective Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare neoplasm recently categorized by the World Health Organization (WHO) as an intermediate-grade vascular soft tissue tumor affecting young adults. While most documented cases exhibit local aggressiveness, we present a case with unusual presentation characterized by multiple pelvic and femoral lytic bone lesions associated with documented liver metastases. Methods/Case Report A mid-forties female presented with progressive left hip pain persisting for 2 weeks. Radiological assessments showed multiple lytic lesions in the left superior pubic ramus, right iliac wing, and left greater trochanter with associated pathologic fractures and soft tissue involvement. Additionally, multiple indeterminate hepatic and splenic hypodensities were noted. Histologic examination of the bone and liver biopsies revealed a neoplasm composed of spindled and epithelioid cells with hyperchromatic nuclei and eosinophilic cytoplasm. The neoplastic cells are arranged haphazardly and in short fascicles within a fibromyxoid stroma or sinusoidal spaces (in the liver) associated with scattered acute and chronic inflammation. Frequent mitoses are noted; however, no necrosis was identified. Tumor cells were positive for CD31, ERG, FOSB with equivocal staining for pankeratin and CK8/18. The top differential consideration was epithelioid hemangioendothelioma (EHE); however, sarcoma fusion next-generation sequencing panel exhibited features of a vascular neoplasm with WWTR1-FOSB, favoring PHE. Results (if a Case Study enter NA) NA Conclusion Pseudomyogenic hemangioendothelioma is a rare tumor that is prone for local recurrence and usually affect young adults (mean age: 30 years). Metastases are uncommon. To the best of our knowledge, we report a case of PHE with unusual presentation of early metastases to liver and possibly the spleen and highlights the complexity of PHE diagnosis.

Impact of contrast-enhanced CT in the dosimetry of SBRT for liver metastases treated with MR-Linac

BackgroundTo investigate the impact of using contrast-enhanced computed tomography (CHCT) in the dosimetry of stereotactic body radiation therapy (SBRT) for liver metastases treated with MR-Linac.MethodsA retrospective study was conducted on 21 liver cancer patients treated with SBRT (50 Gy in 5 fractions) using a 1.5 Tesla Unity MR-Linac. The clinical treatment plans optimised on plain computed tomography (pCT) were used as reference. The electronic density (ED) of regions of interest (ROIs) including the liver, duodenum, esophagus, spinal cord, heart, ribs, and lungs, from pCT and CHCT, was analysed. The average ED of each ROI from CHCT was used to generate synthetic CT (sCT) images by assigning the average ED value from the CHCT to the pCT. Clinical plans were recalculated on sCT images. Dosimetric comparisons between the original treatment plan (TPpCT) and the sCT plan (TPsCT) were performed using dose-volume histogram (DVH) parameters, and gamma analysis.ResultsSignificant ED differences (p < 0.05) were observed in the liver, great vessels, heart, lungs, and spinal cord between CHCT and pCT, with the lungs showing the largest differences (average deviation of 11.73% and 12.15% for the left and right lung, respectively). The target volume covered by the prescribed dose (VDpre), and the dose received by 2% and 98% of the volume (D2%, and D98%, respectively) showed statistical differences (p < 0.05), while the gradient index (GI) and the conformity index (CI) did not. Average deviations in target volume dosimetric parameters were below 1.02%, with a maximum deviation of 5.57% for. For the organs at risk (OARs), significant differences (p < 0.05) were observed for D0.35cc and D1.2cc of the spinal cord, D10cc for the stomach, D0.5cc for the heart, and D30% for the liver-GTV, with mean deviations lower than 1.83% for all the above OARs. Gamma analysis using 2%-2 mm criteria yielded a median value of 95.64% (range 82.22–99.65%) for the target volume and 99.40% (range 58–100%) for the OARs.ConclusionThe findings suggest that the use of CHCT in the SBRT workflow for liver metastases may result in minor target volume overdosage, indicating its potential for adoption in clinical settings. However, its use should be further explored in a broader context and tied to personalized treatment approaches.

Systemic Immunological Changes After Yttrium-90 Radioembolization: A Pilot Prospective Observational Study-Clinical Insights.

To prospectively investigate levels of circulating cytokines, changes in frequencies of various immune cell subsets and expression of proliferation and checkpoint molecules on T cells in the peripheral blood after yttrium-90 radioembolization (TARE) of colorectal cancer liver metastases (CLM). We prospectively collected, isolated, and froze peripheral blood mononuclear cells (PBMC) and plasma samples from 15 patients immediately before, immediately after, 3 and 6 weeks post-TARE of CLM. Plasma samples were assessed for various cytokines using a multiplex immunoassay platform. PBMC samples were analyzed in a monocyte/dendritic cell (DC)/B cell flow panel and a T cell activation/exhaustion flow phenotyping panel. We compared the levels at the respective time points using Wilcoxon signed rank test. IFN-g significantly decreased immediately after (mean 1.62 vs. 3.02 at baseline, p = 0.04) and increased at 6weeks compared to the immediately post-TARE nadir (mean 9.42 vs. 1.62, p = 0.04). IL-10 decreased at 3weeks (mean 0.36 vs. 1.75, p = 0.025) post-TARE compared to baseline. Increased CD3+T cells (mean 78.24 vs. 60.8, p = 0.002) and decreased CTLA-4+CD4+T cells (mean 2.58 vs. 4.41, p = 0.033) were observed at 3weeks compared to baseline. Increased Ki-67+ proliferating CD8+T cells at 3 and 6weeks (mean 7.28 and 9.06, respectively, vs. 3.93 at baseline, p = 0.02 and 0.03) were recorded. A shift toward a favorable antitumoral cytokinic and immune cells response was observed after TARE. Significant changes were in specialized immune cells subsets playing important roles in the activation of the immune system. These results support trials combining TARE with immunotherapy for patients with CLM.

Liver metastases in high-grade neuroendocrine neoplasms: A comparative study of hepatic tumor volume and biochemical findings in NET G3 versus NEC.

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high-grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow-up. Alkaline phosphatase (AP), gamma-GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02-1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43-0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver-directed therapies.

Prognostic significance of malignant pleural effusions in patients with advanced luminal B breast cancer

BackgroundThough the survival of breast cancer (BC) patients with malignant pleural effusion (MPE) has been studied, this has not been specifically studied in the luminal B subtype. Therefore, this study investigated the characteristics and survival of luminal B-BC patients presenting with MPE.MethodsWe retrospectively analyzed 141 patients diagnosed with postoperative advanced Luminal B breast cancer, including 54 cases with MPE and 87 cases without MPE at the Tianjin Cancer Hospital from January 2012 to January 2015. We assessed the clinical characteristics between the groups.ResultsThe mean age of all patients was 47 years, with no significant difference between the two groups. Altogether, 29 (33%), 24 (28%), 28 (32%), 45 (52%), and 10 (11%) patients had lung, liver, bone, lymph node, and chest wall metastases, respectively. In addition. The difference in overall survival between the two groups was not significant (P>0.05). However, cox regression analysis showed that only the tumor clinical stage at initial diagnosis was related to short overall survival. Further, we conducted a subgroup analysis and found that the higher the clinical stage at initial diagnosis in age < 50 years patients, the shorter the overall survival, while age > 50 years patients was not. (P < 0.05).ConclusionsThere was no difference in the overall survival between luminal B-BC patients with MPE and those without. Clinical stages at initial diagnosis were an independent prognostic factor for age < 50 years luminal B BC with MPE overall survival. Our results may help clinicians make positive decisions regarding personalized treatment of luminal B-BC with MPE.

M6A-modified circXPO1 accelerates colorectal cancer progression via interaction with FMRP to promote WWC2 mRNA decay

BackgroundRecent evidence has demonstrated the vital roles of circular RNAs (circRNAs) in the progression of colorectal cancer (CRC); however, their functions and mechanisms in CRC need to be further explored. This study aimed to uncover the biological function of circXPO1 in CRC progression.MethodsCircXPO1 was identified by Sanger sequencing, RNase R, and actinomycin D treatment assays. Colony formation, scratch, transwell assays, and mouse xenograft models were adopted to evaluate CRC cell growth and metastasis in vitro and in vivo. Subcellular expression of circXPO1 was detected by FISH and nuclear-cytoplasmic separation assays. Molecular mechanisms were investigated by MeRIP, RIP, and RNA pull-down assays. Target molecular expression was detected by RT-qPCR, Western blotting and immunohistochemical staining.ResultscircXPO1 was up-regulated in CRC tissues and cells, which indicated a poor prognosis of CRC patients. circXPO1 deficiency delayed the growth, EMT, and metastasis of CRC cells. Mechanistical experiments indicated that down-regulation of ALKBH5 enhanced IGF2BP2-mediated m6A modification of circXPO1 to increase circXPO1 expression. Furthermore, circXPO1 interacted with FMRP to reduce the mRNA stability of WWC2, which consequently resulted in Hippo-YAP pathway activation. Rescue experiments suggested that WWC2 overexpression abrogated circXPO1-mediated malignant capacities of CRC cells. The in vivo growth and liver metastasis of CRC cells were restrained by circXPO1 depletion or WWC2 overexpression.Conclusionsm6A-modified circXPO1 by ALKBH5/IGF2BP2 axis destabilized WWC2 via interaction with FMRP to activate Hippo-YAP pathway, thereby facilitating CRC growth and metastasis. Targeting circXPO1 might be a potential therapeutic strategy for CRC.

Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma.

Uveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, which are CLPP activators, which inhibit OXPHOS indirectly and have demonstrated safety in patients. We assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201 and ONC212) on the growth, survival, signaling and metabolism of UM cell lines in vitro, and for therapeutic efficacy in vivo in UM liver metastasis models. CLPP expression was detected in primary and mUM patient samples. ONC201 and 212 decreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis in human UM cell lines in vitro. ONC212 inhibited OXPHOS, increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survival in vivo in two UM liver metastasis models. Imipridones are a promising strategy for further testing and development in mUM.

Epidemio-Clinical, Anatomopathological, Computed Tomography Aspects from Breast Cancer to Imaging and Medical Oncology Departments at Chu – Mother-Child “Luxembourg”

Introduction: Cancer results from an anarchic proliferation of abnormal cells of the mammary gland and is the most common cancer in women in developed countries with 50,000 new cases in 2008. Objectives: The aim of our work was to describe the sociodemographic characteristics of patients, to determine the different sites and the frequency of metastases; and to describe the CT and histological aspects in the diagnosis of extension, therapy and assessment. Methods: Our study was retrospective descriptive over a period of 12 months from January 2020 to December 2020 in the radiology and medical oncology department of CHUME Luxembourg. It concerned all patients with histologically confirmed cancer who had undergone a scan before, during treatment or during therapeutic monitoring. The examinations were carried out with a HITACHI SUPRIA 16 BARRETTES CT scanner installed in 2015. Results: During the period of our study, the frequency of breast cancer was 10.7% (130 cases) out of 1204 scans carried out with a female predominance of 98%, an average age of 52 years and extremes of 12 to 90 years. The main metastases were: pulmonary (59%), followed by lymph node metastases (66%), bone (51%), liver (29%) and brain (2%). The association of pulmonary, lymph node, liver and bone metastasis represented 27% of the most frequent associations. As for the histological aspect, non-specific invasive carcinoma grade II SBR and TNM was the most frequent.

Identification of novel diagnostic biomarkers associated with liver metastasis in colon adenocarcinoma by machine learning

BackgroundLiver metastasis is one of the primary causes of poor prognosis in colon adenocarcinoma (COAD) patients, but there are few studies on its biomarkers.MethodsThe Cancer Genome Atlas (TCGA)-COAD, GSE41258, and GSE49355 datasets were acquired from the public database. Differentially expressed genes (DEGs) between liver metastasis and primary tumor samples in COAD were identified by limma, and functional enrichment analysis were performed. MuTect2 and maftools were used to measure somatic mutation rates, while ADTEx was used to measure copy number variations (CNVs). The intersection of three machine learning methods, support vector machine (SVM), Random Forest, and least absolute shrinkage and selection operator (LASSO), is utilized to screen biomarkers, and their diagnostic performance is subsequently validated. The correlation between biomarkers and immune cells infiltration was analyzed by Spearman method.Results47 DEGs between liver metastasis and primary tumor samples in COAD were obtained, which were mainly enriched in the complement and coagulation, extracellular matrix (ECM), and peptidase regulator activity, etc. 38 out of 47 DEGs had mutations and exhibited a high frequency of CNV amplification or deletion. Furthermore, 3 biomarkers (MMP3, MAB21L2, and COLEC11) were screened, which showed good diagnostic performance. The proportion of multiple immune cells, such as B cells naive, T cells CD4 naive, Monocytes, and Dendritic cells resting, was higher in liver metastasis samples than that in primary tumor samples. Meanwhile, MMP3, MAB21L2, and COLEC11 exhibited an outstanding correlation with immune cells infiltration.ConclusionIn short, 3 biomarkers with good diagnostic efficacy were identified, providing a new perspective of therapeutic targets for liver metastasis in COAD.

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor.

The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells' biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. In summary, our findings revealed resting NK cells exhibited a clinical relevance with CCLM, which may be exploited for novel strategies to improve therapeutic outcomes for patients with CCLM.

Resting natural killer cells promote the progress of colon cancer liver metastasis by elevating tumor-derived stem cell factor

The abundance and biological contribution of natural killer (NK) cells in cancer are controversial. Here, we aim to uncover clinical relevance and cellular roles of NK cells in colon cancer liver metastasis (CCLM). Here, we integrated single-cell RNA-sequencing, spatial transcriptomics (ST), and bulk RNA-sequencing datasets to investigate NK cells’ biological properties and functions in the microenvironment of primary and liver metastatic tumors. Results were validated through an in vitro co-culture experiment based on bioinformatics analysis. Useing single-cell RNA-sequencing and ST, we mapped the immune cellular landscape of colon cancer and well-matched liver metastatic cancer. We discovered that GZMK+ resting NK cells increased significantly in tumor tissues and were enriched in the tumor regions of both diseases. After combining bulk RNA and clinical data, we observed that these NK cell subsets contributed to a worse prognosis. Meanwhile, KIR2DL4+ activated NK cells exhibited the opposite position and relevance. Pseudotime cell trajectory analysis revealed the evolution of activated to resting NK cells. In vitro experiments further confirmed that tumor-cell-co-cultured NK cells exhibited a decidual-like status, as evidenced by remarkable increasing CD9 expression. Functional experiments finally revealed that NK cells exhibited tumor-activating characteristics by promoting the dissociation of SCF (stem cell factor) on the tumor cells membrane depending on cell-to-cell interaction, as the supernatant of the co-culture system enhanced tumor progression. In summary, our findings revealed resting NK cells exhibited a clinical relevance with CCLM, which may be exploited for novel strategies to improve therapeutic outcomes for patients with CCLM.

Prognostic Prediction and Immune Microenvironment Characterization in Uveal Melanoma: A Novel Mitochondrial Metabolism-Related Gene Signature.

Uveal Melanoma (UM), a highly aggressive and metastatic intraocular cancer with a strong propensity for liver metastasis, presents limited therapeutic alternatives and unfavorable survival outcomes. Despite its low incidence, the underlying mechanisms of UM pathogenesis and the precise role of mitochondrial metabolism in UM remain inadequately understood. Utilizing Cox proportional hazards regression analysis was used to assess prognostic relevance, and consensus clustering was employed for molecular subtyping. A risk signature was constructed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. We further conducted comparative analyses on clinicopathological characteristics, somatic mutation profiles, drug sensitivity, gene expression patterns, and tumor microenvironment features across different molecular subtypes. Moreover, a nomogram was developed and evaluated. Among 1234 mitochondria metabolism-related genes (MMRGs), 343 were identified as significantly associated with the prognosis of UM. These prognosis-associated MMRGs facilitated the classification of UM into two distinct molecular subtypes, which displayed notable differences in prognosis and pathological staging. Furthermore, an index termed the MMRGs-derived index (MMI) was derived from eight MMRGs, serving as a quantitative measure for poor prognosis risk in UM. MMI demonstrated significant associations with clinicopathological characteristics, somatic mutations, drug responsiveness, and the tumor microenvironment, where higher MMI levels corresponded to worse prognosis, advanced pathological stages, and increased immune cell infiltration. The nomogram built upon MMI provided a potential tool for clinical prognosis assessment in UM patients. This study demonstrated the potential value of MMRGs in predicting prognosis and molecular stratification within UM; however, additional clinical and basic research is warranted to validate their applicability and elucidate the related mechanisms.

Comparing Open, Laparoscopic and Robotic Liver Resection for Metastatic Colorectal Cancer-A Systematic Review and Network Meta-Analysis.

Colorectal liver metastases (CRLM) can be surgically managed through open resections (OLR), laparoscopic resections (LLR), or robotic liver resections (RLR). However, there is ongoing uncertainty regarding the safety and effectiveness of minimally invasive approaches like LLR and RLR. This study aims to clarify these issues by conducting a network meta-analysis (NMA) to compare outcomes across OLR, LLR and RLR for patients with CRLM. Following the PRISMA-NMA guidelines, the meta-analysis included 13 studies with a combined total of 6582 patients. Of these, 50.6% underwent LLR, 45.3% underwent OLR, and 4.1% underwent RLR. The analysis found no significant differences in R0 resection rates between LLR (odds ratio [OR] 1.03, 95% confidence interval [CI]: 0.84-1.26) and RLR (OR 1.57, 95% CI: 0.98-2.51) when compared to OLR. Additionally, there were no significant differences in disease-free survival (DFS) and overall survival (OS) at 1, 3, and 5 years. Despite these findings, both LLR and RLR were associated with reduced postoperative complication rates (RLR: OR 0.52, 95% CI: 0.32-0.86; LLR: OR 0.50, 95% CI: 0.37-0.68). However, patients undergoing LLR were more likely to require conversion to open surgery compared to those undergoing RLR (OR: 12.46, 95% CI: 2.64-58.67). Furthermore, RLR was associated with a reduced need for blood transfusions (OR: 0.13, 95% CI: 0.05-0.32), and LLR resulted in shorter hospital stays (mean difference: -6.66 days, 95% CI: -11.6 to -1.88 days). This study demonstrates the oncological safety of LLR and RLR approaches for CRLM relative to OLR, with enhanced perioperative outcomes anticipated following minimally invasive resections of CRLM.

Exosomal miR-106a-5p from highly metastatic colorectal cancer cells drives liver metastasis by inducing macrophage M2 polarization in the tumor microenvironment

BackgroundThe tumor microenvironment (TME) is a dynamic system orchestrated by intricate cell-to-cell crosstalk. Specifically, macrophages within the TME play a crucial role in driving tumor progression. Exosomes are key mediators of communication between tumor cells and the TME. However, the mechanisms underlying exosome-driven crosstalk between tumor cells and macrophages during colorectal cancer (CRC) progression remain incompletely elucidated.MethodsSingle-cell RNA sequencing were analyzed using the Seurat package. Exosomes were isolated using ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blot. miRNAs differentially expressed in exosomes were analyzed using the limma package. CD206 expression in CRC tissues, exosomes tracing, and exosomal miR-106a-5p transport were observed through immunofluorescence. Macrophage polarization was assessed via qRT-PCR, ELISA, and flow cytometry. The interactions between miR-106a-5p, hnRNPA1, and SOCS6 were evaluated using miRNA pull-down, RIP, and dual-luciferase reporter assays. Transwell assays and liver metastasis model explored the role of exosomal miR-106a-5p-induced M2 macrophages in promoting CRC liver metastasis.ResultThe proportion of M2 macrophages is increased in CRC with liver metastasis compared to those without. Highly metastatic CRC cells release exosomes enriched with miR-106a-5p, which promote macrophages M2 polarization by suppressing SOCS6 and activating JAK2/STAT3 pathway. These M2 macrophages reciprocally enhance CRC liver metastasis. hnRNPA1 regulate the transport of miR-106a-5p into exosomes. Clinically, elevated miR-106a-5p in plasma exosomes correlated with liver metastasis and poor prognosis.ConclusionCRC-derived exosomal miR-106a-5p plays a critical role in promoting liver metastasis and is a potential biomarker for the prevention and treatment of CRC liver metastasis.

Surgical microwave ablation of 397 neuroendocrine liver metastases: a retrospective cohort analysis of 16 years of experience.

Neuroendocrine tumors (NET) constitute a heterogeneous group of malignancies whose incidence has been on the rise over the past two decades, currently documented at 5.25 per 100,000. Liver metastasis develops in over 60% of NET patients. Even after resection recurrence rates are high, underscoring the importance of parenchymal-sparing interventions. In this study, we conducted 105 surgical microwave ablations and examined outcomes related to survival and local recurrence. Retrospective review of patients who underwent a surgical microwave ablation (MWA) at a single-center, high-volume institution from September 2007 through December 2022 using a prospective database. Primary outcome was overall survival. A total of 105 operations were performed on 94 patients, with 397 tumors undergoing MWA. Median tumor size was 1.3cm (range 0.3-8.0), and the median number of tumors ablated was 2 (range 1-12). Laparoscopic approach was utilized 69.5% of the time. The most common concomitant procedure performed was hepatectomy (33.3%) and cholecystectomy (23.8%). Clavien-Dindo grade III or IV complications occurred in 9 patients (9.6%). Mortality within 30days occurred in 1 patient (1.1%). The rate of incomplete ablation was 0.3% per tumor. Local recurrence occurred in 2.8% of tumors. Median OS was 9.43years [95% CI 4.23-14.63years], with a 5- and 10-year survival probability of 70.2% and 48.2%, respectively. Surgical MWA offers an efficacious, parenchymal-sparing treatment of hepatic metastasis of NET, with low rates of incomplete ablation and local recurrence per tumor.

Identification and Verification of Key Genes in Colorectal Cancer Liver Metastases Through Analysis of Single-Cell Sequencing Data and TCGA Data.

Colorectal cancer (CRC) is highly prevalent worldwide, with more patients experiencing colorectal cancer liver metastases (CRLM). This study aimed to identify key genes in CRLM through single-cell sequencing data reanalysis and experimental validation. The study analyzed single-cell RNA-sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for gene functional enrichment analysis. The Cancer Genome Atlas (TCGA) data enabled bulk-RNA expression and survival prognosis analysis. Real-time polymerase chain reaction (qPCR) detected mRNA expression, whereas Western blot determined protein levels. Cell function experiments assessed SPARC's impact on CRC cell behavior. Cluster analysis showed 23 classes among 17 CRLM samples, representing six cell types. A GO and KEGG analysis identified interleukin-1 beta (IL1B), CD2 molecule (CD2), and C-X-C motif chemokine ligand 8 (CXCL8) as significant prognostic factors in CRC. Secreted protein acidic and cysteine rich (SPARC) was one of the top differentially expressed genes (DEGs) in tissue stem cells, confirmed in primary and metastatic lesions. Metastatic lesions showed higher expression of SPARC and CRC stem cell marker leucine-rich repeat containing G protein-coupled receptor 5 (LGR5), which was significantly correlated positively with LGR5 expression. Knockdown of SPARC reduced CRC cell sphere- and colony-formation, invasion, and migration abilities. Overexpression of SPARC significantly increased the malignancy of CRC cells. Several key genes were identified in the process of CRLM. In CRLM samples and those corresponding to CRC stem cells, SPARC was significantly upregulated. In the therapy of CRLM, SPARC might be a potential target.

New definition of borderline resectable colorectal liver metastasis based on prognostic outcomes.

Although surgical resection is the curative treatment for colorectal liver metastases (CRLM), the efficacy of neoadjuvant chemotherapy (NAC) has been discussed due to recent remarkable advances in chemotherapy. The definition of borderline resectable (BR) is most important, where neoadjuvant chemotherapy should be administered. This study aimed to examine a new definition of BR CRLM based on the results of the treatment outcomes. This study included 127 patients who underwent liver resection for CRLM after exclusion of conversion cases between April 2010 and December 2023. Upfront resection was performed for synchronous and single liver metastasis or metachronous liver metastases. NAC was administered for multiple synchronous liver metastases. In order to find a new definition of BR, we examined the prognostic factors obtained from the treatment outcomes. CA19-9 level > 37.0 was the only prognostic factor in the upfront group [hazard ratio (HR) 2.386, 95% CI, 1.583-4.769; p = 0.049]. in the NAC group, a maximum tumor diameter ˃3 cm (HR 2.248, 95% CI 1.038-4,867, p = 0.040), CA19-9 level > 37.0 (HR 2.239, 95% CI 1.044-4.800, p = 0.038), and a right-sided primary tumor in the colon (HR 2.770, 95% CI 1.284-5.988, p = 0.009) were identified as significant prognostic factors. In cases of CRLM, patients with CA19-9 levels > 37.0, or CA19-9 level with < 37.0 but with a primary tumor in the right colon or a maximum tumor diameter of > 3cm can be defined as BR CRLM and should be treated with NAC.

Metastatic organotropism in small cell lung cancer.

Metastasis is the leading cause of cancer-related deaths, yet its regulatory mechanisms are not fully understood. Small-cell lung cancer (SCLC) is the most metastatic form of lung cancer, with most patients presenting with widespread disease, making it an ideal model for studying metastasis. However, the lack of suitable preclinical models has limited such studies. We utilized well-annotated rapid autopsy-derived tumors to develop xenograft models that mimic key features of SCLC, including histopathology, rapid and widespread development of metastasis to the liver, brain, adrenal, bone marrow, and kidneys within weeks, and response to chemotherapy. By integrating in vivo lineage selection with comprehensive transcriptomic and epigenomic analyses, we identified critical cellular programs driving metastatic organotropism to the liver and brain, the most common sites of SCLC metastasis. Our findings reveal the key role of nuclear-cytoskeletal interactions in SCLC liver metastasis. Specifically, the loss of the nuclear envelope protein lamin A/C, encoded by the LMNA gene, increased nuclear deformability and significantly increased the incidence of liver metastasis. Human liver metastases exhibited reduced LMNA expression compared to other metastatic sites, correlating with poorer patient outcomes and increased mortality. This study introduces novel preclinical models for SCLC metastasis and highlights pathways critical for organ-specific metastasis, offering new avenues for the development of targeted therapies to prevent or treat metastatic disease.

Evaluation of the prognostic effectiveness of liver metastasis volume by volumetric measurement in colorectal cancer.

Aim: To evaluate the relationship between liver metastasis volume and survival in colorectal cancer patients using the volumetric measurement method.Methods: 114 colorectal cancer patients with isolated liver metastases were included in the study. Liver tumor volume, total liver volume were calculated from the patients images at the time of diagnosis. Vitrea 7.14 imaging software was used for liver volume analysis and volume analysis of each metastasis.Results: Median overall survival(OS) in the group with tumor volume <42ml3 was 30.98months In the group with tumor volume ≥42ml3, median OS was 16.36months (p: 0.001). In patients who underwent metastasectomy, the median OS in the group with a tumor volume <42ml3 was 52.3months, the median OS in the group with a tumor volume ≥42ml3 was 22.2months. In patients who did not undergo metastasectomy, the median OS in the <42ml3 group was 20.23months, the median OS in the ≥42ml3 group was 15.63months.Conclusion: In our study, we found that liver metastasis volume was prognostic for OS. It is argued that tumor volume measurement by volumetric measurement is a widely used method in the decision for metastasectomy in liver metastatic colorectal cancer patients.

RAS mutant transverse colon cancer with multiple liver metastases achieving long-term disease-free survival with postoperative maintenance therapy with aflibercept + FOLFIRI and four repeated radical resections: a case report

BackgroundManagement of patients with colorectal liver metastases (CRLMs) requires a multidisciplinary approach. For patients with progression of RAS mutant tumors, the choice of angiogenesis inhibitors can be controversial. Here, we report a patient with RAS mutant CRLMs achieving long-term disease-free survival with repeated R0 resections and perioperative treatment, especially aflibercept + FOLFIRI (5-fluorouracil, levofolinate, irinotecan), which may have prevented long-term recurrence.Case presentationThe patient was a 37 year-old woman diagnosed with RAS mutant transverse colon cancer with 19 LMs. As the metastases were limited to the liver, we introduced systemic chemotherapy aiming at conversion surgery. After six cycles of bevacizumab + FOLFOXIRI (5-fluorouracil, levofolinate, oxaliplatin, irinotecan), we performed partial hepatectomy for all LMs, and left hemicolectomy for the primary tumor after another four cycles of bevacizumab + FOLFIRI. Three months after surgery, the patient presented with massive ovarian metastases with carcinomatous ascites. We conducted bilateral oophorectomy, and initiated aflibercept + FOLFIRI therapy considering the possibility of resistance to bevacizumab. The patient was recurrence-free for 2 years during aflibercept + FOLFIRI treatment. After its discontinuation, two distant metastases developed. Both were resectable and the patient achieved recurrence-free survival of 2 years and 3 months after the last operation (6 years since initiation of treatment), without additional chemotherapy.ConclusionsWe believe that multidisciplinary treatment aimed at complete resection could lead to long-term survival even in patients with repeated recurrence of CRLMs. Aflibercept + FOLFIRI could be effective in controlling metastasis of RAS mutant colon cancer even after treatment with bevacizumab.