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PloS One 2024Ultrasound-guided biopsy of focal liver lesions (FLL) is a well-established procedure with crucial impact on therapeutic decisions. The safety and accuracy depend on...
PURPOSE
Ultrasound-guided biopsy of focal liver lesions (FLL) is a well-established procedure with crucial impact on therapeutic decisions. The safety and accuracy depend on needle type, tumour location and comorbidities. Modern oncological concepts often require large tumour specimens which may increase the procedural risk.
MATERIALS AND METHODS
We retrospectively collected data from consecutively scheduled ultrasound-guided FLL biopsies performed in an interdisciplinary ultrasound unit at a university hospital from 2015-2020. We analysed complication rates, diagnostic accuracy, and patient outcome in a one-year period.
RESULTS
Of 426 scheduled interventions, 339 were included: 322 primary biopsies (40% female, median age 65 years, median BMI 25.4 kg/m2) and 17 rebiopsies in cases with undetermined diagnosis. Indications comprised 309 (96%) cases with suspected malignant lesions. Important comorbidities were type 2 diabetes (n = 107, 33%) and cirrhosis (n = 64, 20%). A conclusive histopathological diagnosis was achieved in 270 (84%) cases with a weak association with lesion size (OR 1.12 per cm, 95%CI 0.99-1.27). Greater BMI (OR 0.60 per 10 BMI points, 95%CI 0.34-1.05) showed a trend towards an insufficient diagnosis. Relevant complications occurred in 8 (2.5%) cases (2 major; 1 life-threatening). Multiple passes showed a trend towards adverse events (OR 2.32 for > 1 pass, 95%CI 0.99-5.42). 93 (29%) patients died during a median follow-up of 171 days.
CONCLUSION
Ultrasound-guided FLL biopsy is an efficient and safe diagnostic measure. The limitations of the procedure and its associated risks should be considered in patients with advanced malignancies.
Topics: Humans; Female; Male; Aged; Image-Guided Biopsy; Middle Aged; Retrospective Studies; Liver Neoplasms; Liver; Ultrasonography, Interventional; Adult
PubMed: 38776359
DOI: 10.1371/journal.pone.0304026 -
JCI Insight May 2024Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage....
Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive. We used an autochthonous SCLC mouse model and matched samples from patients with primary and metastatic SCLC to investigate the molecular characteristics of tumor metastasis. We demonstrate that tumor cell invasion and liver metastasis in SCLC are triggered by an Angiopoietin-2 (ANG-2)/Integrin β-1-dependent pathway in tumor cells, mediated by focal adhesion kinase/Src kinase signaling. Strikingly, CRISPR-Cas9 KO of Integrin β-1 or blocking Integrin β-1 signaling by an anti-ANG-2 treatment abrogates liver metastasis formation in vivo. Interestingly, analysis of a unique collection of matched samples from patients with primary and metastatic SCLC confirmed a strong increase of Integrin β-1 in liver metastasis in comparison with the primary tumor. We further show that ANG-2 blockade combined with PD-1-targeted by anti-PD-1 treatment displays synergistic treatment effects in SCLC. Together, our data demonstrate a fundamental role of ANG-2/Integrin β-1 signaling in SCLC cells for tumor cell invasion and liver metastasis and provide a potentially new effective treatment strategy for patients with SCLC.
Topics: Animals; Angiopoietin-2; Small Cell Lung Carcinoma; Mice; Lung Neoplasms; Humans; Signal Transduction; Integrin beta1; Liver Neoplasms; Cell Line, Tumor; Neoplasm Invasiveness; Neoplasm Metastasis
PubMed: 38775153
DOI: 10.1172/jci.insight.166402 -
Frontiers in Immunology 2024Despite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low...
AIM
Despite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets.
METHOD
Utilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and experimental studies conducted on key targets.
RESULTS
Building on the research by Kamber RA et al., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells.
CONCLUSION
We have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Prognosis; RNA-Seq; Immunotherapy; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Single-Cell Analysis; Phagocytosis; Tumor Microenvironment; Gene Expression Profiling; Male; Claudins; Female; Single-Cell Gene Expression Analysis
PubMed: 38774870
DOI: 10.3389/fimmu.2024.1397541 -
Transplant International : Official... 2024Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT...
Sex inequities in liver transplantation (LT) have been documented in several, mostly US-based, studies. Our aim was to describe sex-related differences in access to LT in a system with short waiting times. All adult patients registered in the RETH-Spanish Liver Transplant Registry (2000-2022) for LT were included. Baseline demographics, presence of hepatocellular carcinoma, cause and severity of liver disease, time on the waiting list (WL), access to transplantation, and reasons for removal from the WL were assessed. 14,385 patients were analysed (77% men, 56.2 ± 8.7 years). Model for end-stage liver disease (MELD) score was reported for 5,475 patients (mean value: 16.6 ± 5.7). Women were less likely to receive a transplant than men (OR 0.78, 95% CI 0.63, 0.97) with a trend to a higher risk of exclusion for deterioration (HR 1.17, 95% CI 0.99, 1.38), despite similar disease severity. Women waited longer on the WL (198.6 ± 338.9 vs. 173.3 ± 285.5 days, < 0.001). Recently, women's risk of dropout has reduced, concomitantly with shorter WL times. Even in countries with short waiting times, women are disadvantaged in LT. Policies directed at optimizing the whole LT network should be encouraged to guarantee a fair and equal access of all patients to this life saving resource.
Topics: Humans; Female; Liver Transplantation; Middle Aged; Registries; Male; Waiting Lists; Health Services Accessibility; Aged; Spain; End Stage Liver Disease; Healthcare Disparities; Sex Factors; Adult; United States; Severity of Illness Index; Carcinoma, Hepatocellular; Liver Neoplasms
PubMed: 38773987
DOI: 10.3389/ti.2024.12732 -
Technology in Cancer Research &... 2024This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and... (Comparative Study)
Comparative Study
This is a retrospective study aimed at comparing the clinical efficacy and safety between drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) and conventional TACE (C-TACE) in the treatment of unresectable hepatocellular carcinoma. From July 2019 to April 2021, we enrolled 282 patients with unresectable hepatocellular carcinoma who were admitted to our hospital, of which 179 and 103 were in the DEB-TACE and C-TACE groups, respectively. General information was collected, and treatment effects were evaluated following the modified Response Evaluation Criteria in Solid Tumors. To compare the indexes of liver and kidney function, routine blood and coagulation were collected before treatment, and 1 day, 1 month, 3 months, and 6 months postoperatively. Postoperative adverse reactions (ie, fever, nausea, vomiting, anorexia, abdominal pain) were recorded to evaluate the safety of treatment. The two groups' progression-free survival and overall survival were also calculated to assess the treatment effect. Preoperatively, the bilirubin, transaminase, and absolute neutrophil values between the two groups were not statistically significant ( > .05). At 1 month postoperatively, the absolute neutrophil values were significantly higher in the DEB-TACE group than those in the C-TACE group ( < .05). At 3 months postoperatively, AST, total bilirubin, and direct bilirubin levels were significantly elevated in the DEB-TACE group ( < .05), compared with the C-TACE group. However, at 6 months postoperatively, total and direct bilirubin levels in the C-TACE group were higher than those in the DEB-TACE group, showing a statistically significant difference ( < .05). For patients undergoing DEB-TACE, the survival risk was lower compared to those undergoing C-TACE. The survival risk of patients undergoing DEB-TACE was lower than that of C-TACE within 20 months postoperatively. The survival risk of patients undergoing DEB-TACE was lower than that of patients undergoing C-TACE. DEB-TACE may be superior to C-TACE in terms of safety and efficacy in the treatment of unresectable hepatocellular carcinoma.
Topics: Humans; Carcinoma, Hepatocellular; Male; Liver Neoplasms; Female; Chemoembolization, Therapeutic; Retrospective Studies; Middle Aged; Treatment Outcome; Aged; Adult
PubMed: 38773767
DOI: 10.1177/15330338241250315 -
Journal of Translational Medicine May 2024Hepatocellular carcinoma (HCC) causes significant cancer mortality worldwide. Cancer organoids can serve as useful disease models by high costs, complexity, and...
BACKGROUND
Hepatocellular carcinoma (HCC) causes significant cancer mortality worldwide. Cancer organoids can serve as useful disease models by high costs, complexity, and contamination risks from animal-derived products and extracellular matrix (ECM) that limit its applications. On the other hand, synthetic ECM alternatives also have limitations in mimicking native biocomplexity. This study explores the development of a physiologically relevant HCC organoid model using plasma-derived extracellular matrix as a scaffold and nutritive biomatrix with different cellularity components to better mimic the heterogenous HCC microenvironment. Plasma-rich platelet is recognized for its elevated levels of growth factors, which can promote cell proliferation. By employing it as a biomatrix for organoid culture there is a potential to enhance the quality and functionality of organoid models for diverse applications in biomedical research and regenerative medicine and to better replicate the heterogeneous microenvironment of HCC.
METHOD
To generate the liver cancer organoids, HUH-7 hepatoma cells were cultured alone (homogenous model) or with human bone marrow-derived mesenchymal stromal cells and human umbilical vein endothelial cells (heterogeneous model) in plasma-rich platelet extracellular matrix (ECM). The organoids were grown for 14 days and analyzed for cancer properties including cell viability, invasion, stemness, and drug resistance.
RESULTS
HCC organoids were developed comprising HUH-7 hepatoma cells with or without human mesenchymal stromal and endothelial cells in plasma ECM scaffolds. Both homogeneous (HUH-7 only) and heterogeneous (mixed cellularity) organoids displayed viability, cancer hallmarks, and chemoresistance. The heterogeneous organoids showed enhanced invasion potential, cancer stem cell populations, and late-stage HCC genetic signatures versus homogeneous counterparts.
CONCLUSION
The engineered HCC organoids system offers a clinically relevant and cost-effective model to study liver cancer pathogenesis, stromal interactions, and drug resistance. The plasma ECM-based culture technique could enable standardized and reproducible HCC modeling. It could also provide a promising option for organoid culture and scaling up.
Topics: Humans; Organoids; Extracellular Matrix; Liver Neoplasms; Carcinoma, Hepatocellular; Cost-Benefit Analysis; Cell Line, Tumor; Models, Biological; Human Umbilical Vein Endothelial Cells; Animals; Mesenchymal Stem Cells
PubMed: 38773585
DOI: 10.1186/s12967-024-05230-7 -
BMC Cancer May 2024The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains...
The role of adjuvant transcatheter arterial chemoembolization following repeated curative resection/ablation for hepatocellular carcinoma with early recurrence: a propensity score matching analysis.
BACKGROUND
The role of adjuvant transcatheter arterial chemoembolization (TACE) following repeated resection/ablation for recurrent hepatocellular carcinoma (HCC) remains uncertain. The aim of this study was to assess the effectiveness of adjuvant TACE following repeated resection or ablation in patients with early recurrent HCC.
METHODS
Information for patients who underwent repeated surgery or radiofrequency ablation (RFA) for early recurrent HCCs (< 2 years) at our institution from January 2017 to December 2020 were collected. Patients were divided into adjuvant TACE and observation groups according to whether they received adjuvant TACE or not. The recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after propensity score matching (PSM).
RESULTS
Of the 225 patients enrolled, the median time of HCC recurrence was 11 months (IQR, 6-16 months). After repeated surgery or radiofrequency ablation (RFA) for recurrent tumors, 45 patients (20%) received adjuvant TACE while the remaining 180 (80%) didn't. There were no significant differences in RFS (P = 0.325) and OS (P = 0.072) between adjuvant TACE and observation groups before PSM. There were also no significant differences in RFS (P = 0.897) and OS (P = 0.090) between the two groups after PSM. Multivariable analysis suggested that multiple tumors, liver cirrhosis, and RFA were independent risk factors for the re-recurrence of HCC.
CONCLUSION
Adjuvant TACE after repeated resection or ablation for early recurrent HCCs was not associated with a long-term survival benefit in this single-center cohort.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Chemoembolization, Therapeutic; Propensity Score; Male; Female; Neoplasm Recurrence, Local; Middle Aged; Hepatectomy; Aged; Radiofrequency Ablation; Retrospective Studies; Combined Modality Therapy; Treatment Outcome; Chemotherapy, Adjuvant
PubMed: 38773564
DOI: 10.1186/s12885-024-12396-2 -
Journal of Translational Medicine May 2024The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The...
BACKGROUND
The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis.
METHODS
Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1.
RESULTS
UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis.
CONCLUSIONS
UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.
Topics: Animals; Humans; Liver Neoplasms; Homeostasis; Prohibitins; Carcinoma, Hepatocellular; Mitochondria; Carcinogenesis; Cell Line, Tumor; Repressor Proteins; Cell Proliferation; Mice; Gene Expression Regulation, Neoplastic; Protein Binding; Apoptosis
PubMed: 38773518
DOI: 10.1186/s12967-024-05208-5 -
BMC Cancer May 2024Hepatocellular carcinoma (HCC) presents a significant threat to individuals and healthcare systems due to its high recurrence rate. Accurate prognostic models are...
BACKGROUND
Hepatocellular carcinoma (HCC) presents a significant threat to individuals and healthcare systems due to its high recurrence rate. Accurate prognostic models are essential for improving patient outcomes. Gamma-glutamyl transpeptidase (GGT) and prealbumin (PA) are biomarkers closely related to HCC. This study aimed to investigate the predictive value of the GGT to PA ratio (GPR) and to construct prognostic nomograms for HCC patients without microvascular invasion.
METHODS
We retrospectively analyzed data from 355 HCC patients who underwent radical hepatectomy at Shengjing Hospital of China Medical University between December 2012 and January 2021. Patients were randomly assigned to a training cohort (n = 267) and a validation cohort (n = 88). The linearity of GPR was assessed using restricted cubic spline (RCS) analysis, and the optimal cut-off value was determined by X-tile. Kaplan-Meier survival curves and log-rank tests were used to investigate the associations between GPR and both progression-free survival (PFS) and overall survival (OS). Cox multivariate regression analysis identified independent risk factors, enabling the construction of nomograms. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the accuracy of the nomograms. Decision curve analysis (DCA) assessed the predictive value of the models.
RESULTS
Patients were categorized into GPR-low and GPR-high groups based on a GPR value of 333.33. Significant differences in PFS and OS were observed between the two groups (both P < 0.001). Cox multivariate analysis identified GPR as an independent risk factor for both PFS (OR = 1.80, 95% CI: 1.24-2.60, P = 0.002) and OS (OR = 1.87, 95% CI: 1.07-3.26, P = 0.029). The nomograms demonstrated good predictive performance, with C-index values of 0.69 for PFS and 0.76 for OS. Time-dependent ROC curves and calibration curves revealed the accuracy of the models in both the training and validation cohorts, with DCA results indicating notable clinical value.
CONCLUSIONS
GPR emerged as an independent risk factor for both OS and PFS in HCC patients without microvascular invasion. The nomograms based on GPR demonstrated relatively robust predictive efficiency for prognosis.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Nomograms; Female; Male; Middle Aged; gamma-Glutamyltransferase; Retrospective Studies; Prognosis; Prealbumin; Biomarkers, Tumor; Hepatectomy; Adult; Aged; ROC Curve; Neoplasm Invasiveness; Kaplan-Meier Estimate; Microvessels; Predictive Value of Tests
PubMed: 38773511
DOI: 10.1186/s12885-024-12387-3 -
BMC Gastroenterology May 2024A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection.
METHODS
Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined.
RESULTS
A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69-0.85) compared to 0.73 (95% CI: 0.65-0.80); specificity of 0.89 (95% CI: 0.81-0.95) compared to 0.86 (95% CI: 0.77-0.91); PLR of 7.4 (95% CI: 3.7-14.9) compared to 5.1 (95% CI: 3.3-8.1); NLR of 0.24 (95% CI: 0.16-0.37) compared to 0.31 (95% CI: 0.24-0.41); DOR of 30.19 (95% CI: 10.68-85.37) compared to 16.34 (95% CI: 9.69-27.56); and AUC of 0.90 (95% CI: 0.87-0.92) compared to 0.85 (95% CI: 0.82-0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82-0.95), 0.94 (95% CI: 0.82-0.98), 14.5 (95% CI: 4.6-45.4), 0.11 (95% CI: 0.06-0.20), 133.34 (95% CI: 29.65-599.61), and 0.96 (95% CI: 0.94-0.98) for the combination of HSPs and AFP.
CONCLUSION
Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.
Topics: alpha-Fetoproteins; Carcinoma, Hepatocellular; Humans; Liver Neoplasms; Biomarkers, Tumor; Sensitivity and Specificity; Heat-Shock Proteins; ROC Curve; Area Under Curve
PubMed: 38773451
DOI: 10.1186/s12876-024-03260-5