Malignant Liver Tumors Research Articles

Machine Learning Combined with Radiomics Facilitating the Personal Treatment of Malignant Liver Tumors.

In the realm of managing malignant liver tumors, the convergence of radiomics and machine learning has redefined the landscape of medical practice. The field of radiomics employs advanced algorithms to extract thousands of quantitative features (including intensity, texture, and structure) from medical images. Machine learning, including its subset deep learning, aids in the comprehensive analysis and integration of these features from diverse image sources. This potent synergy enables the prediction of responses of malignant liver tumors to various treatments and outcomes. In this comprehensive review, we examine the evolution of the field of radiomics and its procedural framework. Furthermore, the applications of radiomics combined with machine learning in the context of personalized treatment for malignant liver tumors are outlined in aspects of surgical therapy and non-surgical treatments such as ablation, transarterial chemoembolization, radiotherapy, and systemic therapies. Finally, we discuss the current challenges in the amalgamation of radiomics and machine learning in the study of malignant liver tumors and explore future opportunities.

Diagnostic Accuracy of Conventional Ultrasound (US) Compared to Contrast Enhanced Ultrasound (CEUS) for Diagnosing Liver Tumours: A Systematic Review and Meta -analysis

The accurate diagnosis of liver tumours is essential for effective treatment. This study is aimed at comparing the diagnostic accuracy of conventional ultrasound (US) and contrast enhanced ultrasound (CEUS) for detecting and characterizing liver tumours. There is still an unsolved problem regarding differentiation of benign and malignant liver tumours. Thus, an evaluation of the overall sensitivity and specificity of conventional US and CEUS for diagnosing benign and malignant liver tumours is presented in this systematic literature review and meta-analysis. This study followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). A search of relevant databases including Scopus, PubMed, and Cochrane Library was conducted from inception to March 31, 2023 using specific keywords. Among the studies included, diagnostic performance was assessed and data was extracted. Average weighted was carried out to calculate the pooled estimates of overall sensitivity and specificity as well as 95% confidence interval (95% CI) by using Wilson score interval of the sensitivity and specificity of the studies. The selected studies were evaluated for reliability using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2). A total of 11 studies involving 1605 patients were included in the study, with publication years ranging from 2022 to 2004. A comparison of conventional US and CEUS showed that CEUS demonstrated high diagnostic accuracy for diagnosing liver tumours. Based on the pooled estimation of diagnostic accuracy (95% CI), liver tumour diagnosis for differentiation of benign and malignant tumours (CEUS: sensitivity: 0.89 [0.87-0.90], specificity: 0.80 [0.78-0.82] and conventional US: sensitivity: 0.51 [0.49-0.53], specificity: 0.44 [0.42-0.53]). It is clear from this study that CEUS has a significant role to play in clinical practice. These results indicate its value in detecting and diagnosing liver tumours, resulting in better outcomes for patients

Patlak Reconstruction Using Dynamic 18 F-FDG PET Imaging for Evaluation of Malignant Liver Tumors : A Comparison of HCC, ICC, and Metastatic Liver Tumors.

The aim of this study was to explore the different patterns of dynamic whole-body (D-WB) FDG PET/CT parameters among liver malignancy types as potential diagnostic clues and investigate the association between static and dynamic PET/CT parameters for each tumor histology. Seventy-one patients with intrahepatic cholangiocarcinoma (ICC), metastatic liver tumor (MLT), or hepatocellular carcinoma (HCC) who underwent D-WB and static dual-time-point FDG PET/CT were enrolled. We obtained Pearson correlation coefficients between the metabolic rate of FDG (MR FDG ; mg/min/ 100ml) or distribution volume of free FDG (DV FDG , %) and static PET/CT parameters. We compared MR FDG and DV FDG values by tumor type and performed receiver operating characteristic analyses for MR FDG and static images. A total of 12 ICC, 116 MLT, and 36 HCC lesions were analyzed. MR FDG and DV FDG showed excellent correlation with early (SUV e ) and delayed SUV max (SUV d ) ( r = 0.71~0.97), but DV FDG in the HCC lesions did not ( r = 0.62 and 0.69 for SUV e and SUV d , respectively) ( P < 0.001 for all). HCC lesions showed significantly lower MR FDG (2.43 ± 1.98) and DV FDG (139.95 ± 62.58) than ICC (5.02 ± 3.56, 207.06 ± 97.13) and MLT lesions (4.51 ± 2.47, 180.13 ± 75.58) ( P < 0.01 for all). The optimal MR FDG could differentiate HCC from ICC and MLT with areas under the curve of 0.84 and 0.80, respectively. Metastatic liver tumor lesions showed the widest distribution of MR FDG and DV FDG values but with no significant difference among most primary sites. MR FDG was strongly correlated with SUV max in the 3 malignancies and showed utility for differentiating HCC from ICC and MLT. Each tumor type has a different glucose metabolism, and D-WB FDG PET/CT imaging has the potential to visualize those differences.

Cerebral metastasis of Hepatoblastoma: a case report and literature review

BackgroundHepatoblastoma (HB) is the most frequent malignant liver tumor in infants and young children. While it is rare, the brain seems to be the most habitual site of non-pulmonary metastasis.Case presentationIn this report, we present the case of a 13-month-old girl followed for metastatic hepatoblastoma in the lung. She was brought to the emergency department with tonic–clonic seizure, and a brain CT scan revealed a single intra-parenchymal metastasis.ConclusionsIn children with a history of hepatoblastoma, the development of neurologic symptoms should prompt cerebral imaging, to exclude the presence of cerebral metastases.

The expression of VEGF and cyclin D1/EGFR in common primary liver carcinomas in Egypt: an immunohistochemical study.

The most common types of primary malignant liver tumours are hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Treatment options for patients who are inoperable/advanced, or recurring are challenging. Cyclin D1, epidermal growth factor (EGFR) and vascular endothelial growth factor (VEGR) are common carcinogenic proteins that have potential therapeutic targets in various cancers. They have been implicated in the development of HCC and CCA. In this study, we aimed to evaluate the oncogenic function expression of cyclin D1, EGFR and VEGF in HCC and CCA of Egyptian patients. This could help to validate their therapeutic potential. Tumour cases were selected from 82 cases of primary liver carcinomas, with 58 cases being from HCC and 24 cases from CCA compared to 51 non-tumour adjacent liver cases and 18 from normal liver tissue. The immunohistochemical study of cyclin D1, EGFR and VEGR was conducted. Cyclin D1, EGFR and VEGF are overexpressed in HCC and CCA as compared to the control group (p < 0.001). Cyclin D1 was related to well-differentiated grade and early pathologic stage in HCC (p = 0.016 and p = 0.042, respectively). The well-differentiated grade showed significantly higher VEGF levels (p = 0.04). In the CCA group, however, EGFR was strongly related to high tumour size (p = 0.047). EGFR and VEGF were overexpressed in HCC raised in the non-cirrhotic liver compared to those developed in post-hepatitic liver cirrhosis (p = 0.003 and p = 0.014). Cyclin D1, EGFR and VEGF shared significant overexpression in HCC and CCA. EGFR and VEGF may play an oncogenic function in the development of HCC in non-cirrhotic liver. Furthermore, cyclin D1 and VEGF may play a good prognostic function in HCC, but EGFR may play a bad prognostic role in CCA.

Stigmasterol: Remodeling gut microbiota and suppressing tumor growth through Treg and CD8+ T cells in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC), the most primary malignant liver tumor and is ranked as the fifth most common malignancy worldwide. Despite various therapeutic approaches being used in clinical practice, the overall effectiveness remains insufficient. Stigmasterol, a compound known for its anti-tumor properties and ability to induce apoptosis in tumor cells, has been found to influenced the composition of the intestinal microbiota. However, the mechanism through which stigmasterol influences the intestinal microbial-host crosstalk in HCC remains elusive. PurposeThis study was to investigate whether stigmasterol can remodel gut microbiota, and suppress tumor volume by regulating Treg and IFN-γ+ CD8+ cell in the host with HCC. MethodStigmasterol (at dosages of 0, 50, 100, or 200 mg/kg) was orally administered to Balb/c mice with subcutaneous tumor once every 2 days for 3 weeks. ResultsWe first found that tumors volume in the group treated with 100 mg/kg stigmasterol were significantly decreased compared with those in the control group (P < 0.05), which exhibited a similar effect as the sorafenib treatment in mice with HCC. This resulted in a significant upregulation of Caspase3, Bax, and P53 expressions, as well as a decrease in Cyclin D1 expression, ultimately leading to a reduction in tumor volume. Additionally, stigmasterol can alter the α and β diversity of the intestinal flora and significantly increase the abundance of Lactobacillus_johnsonii, Lactobacillus_murinus, and Lactobacillus_reuteri (P<0.05), which can lead to a decrease in the ratio of regulatory T cells (Tregs) to CD8+ T cells in the intestinal tract and tumor tissue, and consequently enhance immune response in the tumor microenvironment (TME) in the host with HCC. ConclusionIn this study, we initially utilized different dosages of stigmasterol to intervene in mice with HCC and confirmed its inhibitory effects on tumor growth in vivo, and discovered that stigmasterol affected Lactobacillus johnsonii, Lactobacillus murinus, and Lactobacillus reuteri, resulting in an increased proportion of IFN-γ+ CD8+ T cells and Treg cells in both the intestinal mucosa and tumor tissues, and ultimately leading to increased levels of apoptotic proteins and the subsequent death of tumor cells, which shed light on the effect of stigmasterol on host intestinal tissue and intratumoral immune cells by reshaping the intestinal microbiota, and provide a theoretical foundation for the potential clinical application of stigmasterol in the treatment of HCC.

Update on the Pathology of Pediatric Liver Tumors: A Pictorial Review

Liver tumors in children are uncommon and show remarkable morphologic heterogeneity. Pediatric tumors may arise from either the epithelial or mesenchymal component of the liver and rarely may also show both lines of differentiation. Both benign and malignant liver tumors have been reported in children. The most common pediatric liver tumors by age are benign hepatic infantile hemangiomas in neonates and infants, malignant hepatoblastoma in infants and toddlers, and malignant hepatocellular carcinoma in teenagers. Here, we provide an up-to-date review of pediatric liver tumors. We discuss the clinical presentation, imaging findings, pathology, and relevant molecular features that can help in the correct identification of these tumors, which is important in managing these children.

Application of cryogenic technologies in complicated cases of surgical treatment of colorectal cancer liver metastases. Case report

Surgical resection is a standard treatment strategy for both primary and secondary malignant liver neoplasms. Liver transplantation is considered the most effective treatment method for colorectal cancer liver metastasis. Palliative debulking liver resection is one of the optimal alternative procedures for patients ineligible for a liver transplant, as it improves overall survival. Resectability rates depend on the functional efficiency of the remaining portion of the liver, which can be improved by increasing the future liver remnant. The application of cryogenic technologies for the ablation of a residual tumour invading the intraparenchymal segments of the major hepatic vessel may have advantages in cases where it is impossible to expand the scope of the surgical intervention due to the insufficiency of the future liver remnant and/or the presence of severe concomitant pathology.&#x0D; Objective — to present a case report of cryogenic technology application in complicated cases of surgical treatment of patients with colorectal cancer liver metastases.&#x0D; Case report. The case report presents an experience of cryoablation of the metastasis tissue with invasion into the intraparenchymal portal branch of Sg III, which was revealed during the I stage of the split in situ/ligation of the portal vein (ALPPS) liver resection. Cryoablation was performed by the application method with a single cryocycle and spontaneous thawing. Device — Cryo‑Pulse (Ukraine). Cryoagent — liquid nitrogen (T ‑180...‑196°С). Exposure time was 3 min. The specific complications associated with cryoablation were not observed.&#x0D; Conclusions. The application of cryogenic technologies for combined debulking surgical treatment of malignant focal liver lesions may be a safe treatment option in cases of residual tumour invasion into portal vein branches. The study is still ongoing.

The impact of liver abscess formation on prognosis of patients with malignant liver tumors after transarterial chemoembolization.

Liver abscess is a rare and serious complication after transarterial chemoembolization (TACE) for liver cancer; however, its impact on the prognosis is unclear. This retrospective study examined the outcomes of patients with liver abscess formation following TACE for malignant liver tumors to elucidate the impact of liver abscess formation on the prognosis of thesepatients. From January 2017 to January 2022, 1,387 patients with malignant tumors underwent 3,341 sessions of TACE at our hospital. Clinical characteristics of patients at baseline and follow-up were examined, including treatment and outcome of liver abscess, tumor response to the TACE leading to liver abscess, and overall survival time. Of 1,387 patients, 15 (1.1%) patients with liver abscess complications after TACE resulted in a total of 16 (0.5%) cases of liver abscess after 3,341 TACE sessions (including one patient with two events). After antibiotic or percutaneous catheter drainage (PCD) treatment, all the infections associated with liver abscesses were controlled. In the PCD group, eight patients died before drainage tube removal, one retained the drainage tube until the end of follow-up, and five underwent drainage tube removal; the mean drainage tube removal time was 149.17 ± 134.19 days. The efficacy of TACE leading to liver abscess was evaluated as partial response (18.75%), stable disease (37.5%), and progressive disease (43.75%). Eleven patients died during the follow-up period owing to causes unrelated to infections caused by liver abscesses. The survival rates at 3 months, 6 months, 1 year, and 5 years were 86.7%, 50.9%, 25.5%, and 17%,respectively. Patients with liver abscess formation following TACE for malignant liver tumors experienced prolonged drainage tube removal time after PCD; while this condition did not directly cause death, it indirectly contributed to a poor prognosis in these patients.

Prognostic related gene index for predicting survival and immunotherapeutic effect of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. It is an aggressive disease with high mortality rate. In this study, we investigated a new prognosis-related gene index (PRGI) that can predict the survival and efficacy of immunotherapy in patients with HCC. RNA-seq data and clinical data of HCC samples were obtained from the cancer genome atlas and ICGC databases. Prognosis-related genes were obtained using log-rank tests and univariate Cox proportional hazards regression. Univariate and multivariate analyses were performed on the overall survival rate of patients with prognosis-related genes and multiple clinicopathological factors, and a nomogram was constructed. A PRGI was then constructed based on least absolute shrinkage and selection operator or multivariate Cox Iterative Regression. The possible correlation between PRGI and immune cell infiltration or immunotherapy efficacy was discussed. Eight genes were identified to construct the PRGI. PRGI can predict the infiltration of immune cells into the tumor microenvironment of HCC and the response to immunotherapy. PRGI can accurately predict the survival rate of patients with HCC, reflect the immune microenvironment, and predict the efficacy of immunotherapy.

Clinical application of two dimensional shear wave elastography with a propagation map in evaluating liver fibrosis in patients with liver tumors.

This study aimed to evaluate the diagnostic performance of two-dimensional shear wave elastography (2D-SWE) with a propagation map in evaluating the degree of hepatic fibrosis in patients with liver tumors before resection. From January 2020 to April 2021, 128 patients with liver tumors were prospectively enrolled, including 20 benign liver tumors and 108 malignant liver tumors. 2D-SWE with a propagation map technology was used to measure the stiffness of liver parenchyma 2 cm away from the tumor. The median value of five measurements was used in this study. The stage of hepatic fibrosis was graded in accordance with Scheuer standard. Spearman correlation was used to analyze the correlation between liver fibrosis stage and the liver stiffness. Univariate and multivariate linear regression analyses were used to determine significant affecting factors for liver stiffness value. The diagnostic performance of 2D-SWE with a propagation map in predicting fibrosis stage was evaluated by receiver operating characteristic curve analysis. The median liver stiffness value in patients with benign liver tumors was lower than that in patients with malignant liver tumors (6.0 kPa vs. 9.4 kPa, p < 0.05). The median liver stiffness values in patients with primary liver cancer were higher than that in patients with benign liver tumors and other types of malignant liver tumors (9.6 kPa vs. 6.0 kPa, p < 0.05). The liver stiffness measured by 2D-SWE was highly correlated with the fibrosis stage confirmed by postoperative pathology (r = 0.834, p < 0.05). For the liver stiffness value, PLT,TB,ALB and fibrosis stage are significantly associated with liver stiffness. The median liver stiffness values in stages S0-S4 of fibrosis were 6.0, 7.2, 8.0, 9.4, and 12.6 kPa, respectively. The areas under the ROC curve of S≥1, S≥2, S≥3, and S = 4 as predicted by SWE were 0.932, 0.945, 0.945, and 0.916, respectively. According to the Youden index, the optimal critical values for predicting fibrosis S≥1, S≥2, S≥3, and S = 4 were 6.8 (sensitivity of 89.69% and specificity of 93.55%), 7.5 (sensitivity of 87.50 % and specificity of 95.00 %), 8.3 (sensitivity of 87.14 % and specificity of 87.93 %) and 9.8 (sensitivity of 79.55 % and specificity of 86.90 %) kPa. 2D-SWE with a propagation map could noninvasively and accurately predict the staging of liver fibrosis in patients with liver tumors before resection.

Application of transradial and transfemoral accesses during hepatic artery chemoembolization in the treatment of patients with malignant liver neoplasms

Introduction Malignant neoplasms of the liver are one of the most common pathologies in oncology. Chemoembolization of the hepatic artery is currently widely used in the treatment of unresectable liver tumors. Transradial vascular access is actively used in interventional cardiology due to fewer local vascular complications. At the same time, until recently, chemoembolization of the hepatic artery was more often performed via transfemoral vascular access.The aim of the work is a comparative analysis of the results of transradial and transfemoral vascular accesses for the purpose of hepatic artery chemoembolization.Material and methods The data of 69 patients who underwent 212 hepatic artery chemoembolization procedures for malignant neoplasms in the liver were analyzed. The group of transradial access included 107 (50.5 %) interventions, the group of transfemoral access – 105 (49.5 %). The groups were comparable in terms of the main initial clinical and anamnestic data.Results Chemoembolization of the hepatic artery was successfully performed in 98.1 % in the transradial access group and 99 % in the transfemoral access group (p = 1.0). The total duration of intervention, time spent on catheterization of the target artery and radiation exposure were significantly shorter in the transradial access group than in the opposite group. The incidence of local vascular complications was not significantly different between the groups: 11 (10.3 %) and 12 (11.4 %) cases, respectively (p = 0.79). According to the results of patient interviews, the use of transradial access was accompanied by significantly less discomfort associated with the procedure.Discussion Traditionally, embolization of peripheral arteries is performed via transfemoral access, and the total incidence of local vascular complications (large subcutaneous hematomas, false aneurysms, arterovenous fistulas, etc.) is relatively high. According to the results of studies, it is possible to reduce the incidence of local vascular complications without increasing the cost of the procedure by performing the same interventions using transradial access.Conclusion Transradial vascular access has a number of significant advantages over transfemoral access, and therefore can be recommended as a priority for performing hepatic artery chemoembolization.

Circulating microRNA Panels for Detection of Liver Cancers and Liver-Metastasizing Primary Cancers.

Malignant liver tumors, including primary malignant liver tumors and liver metastases, are among the most frequent malignancies worldwide. The disease carries a poor prognosis and poor overall survival, particularly in cases involving liver metastases. Consequently, the early detection and precise differentiation of malignant liver tumors are of paramount importance for making informed decisions regarding patient treatment. Significant research efforts are currently directed towards the development of diagnostic tools for different types of cancer using minimally invasive techniques. A prominent area of focus within this research is the evaluation of circulating microRNA, for which dysregulated expression is well documented in different cancers. Combining microRNAs in panels using serum or plasma samples derived from blood holds great promise for better sensitivity and specificity for detection of certain types of cancer.

MiR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma.

Hepatoblastoma (HB) is a malignant liver tumor predominantly found in children and tumor metastasis is one of the main causes of poor prognosis in affected patients. The precise molecular mechanisms responsible for HB metastasis remain incompletely understood. However, there is evidence suggesting a connection between the dysregulation of microRNAs (miRNAs) and the progression of tumor metastasis in HB. The study utilized weighted gene co-expression network analysis (WGCNA) to analyze a miRNA microarray dataset of HB. The expression of miR-181b-5p in HB tissues and cells was detected using quantitative real-time PCR. The impact of miR-181b-5p on the metastatic capacity of HB was evaluated through scratch and Transwell assays. The effects of exogenously expressing miR-181b on the metastatic phenotypes of HB cells were evaluated in vivo. Furthermore, a luciferase reporter assay was performed to validate a potential target of miR-181b-5p in HB. We found that miR-181b-5p was highly expressed in HB tissues and HB cell lines. Overexpression of miR-181b enhanced scratch healing, cell migration, and invasion abilities in vitro, as well as enhancing HB lung metastasis potential in vivo. Dual-luciferase reporter assays showed that Suppressor Of Cytokine Signaling 2 (SOCS2) was a direct target of miR-181b. The overexpression of miR-181b resulted in the suppression of SOCS2 expression, subsequently activating the epithelial-mesenchymal transition and JAK2/STAT5 signaling pathways. The rescue experiment showed that SOCS2 overexpression attenuated the effects of miR-181b on HB cells. Our study showed that miR-181b promotes HB metastasis by targeting SOCS2 and may be a potential therapeutic target for HB.

Efficiency of Transarterial Chemoembolization with Drug-Eluting Microspheres in the Treatment of Metastatic and Primary Liver Tumors

Background: Transarterial chemoembolization (TACE) is coming into use in the treatment of liver tumors, with drug-eluting microspheres as one of the technique variations. However, at the moment there are no systematic studies that would answer the questions: what is the role of the method in the treatment regimen for patients with primary and metastatic liver tumor and at what stage should it be used? Aim: to evaluate the effectiveness of transarterial chemoembolization with drug-eluting microspheres for the treatment of metastatic and primary malignant liver tumors at different stages of the disease. Methods: We performed а retrospective observational uncontrolled study of 65 patients with liver metastases (Group 1), and 10 patients with primary malignant liver tumors (Group 2), who underwent 102 operations of transarterial chemoembolization with drug-eluting microspheres. To plan transarterial chemoembolization and evaluate its effectiveness, computed tomography and magnetic resonance imaging were used every 89 weeks during the treatment. Results: After two transarterial chemoembolization controls, Group 1 included 51 responders (79%) and 14 non-responders (21%). Among the responders by the 16th week there was a decrease in the volume of the tumor mass in the liver from 12.4 [4.7; 24.6] to 5.2 cm3 [2; 15.5] for colorectal cancer, from 26 [18; 35] to 19 cm3 [13; 25] for neuroendocrine cancer, from 12 [4; 20] to 4 cm3 [0.6; 9] for adenocarcinomas of different localizations. There was no progression in Group 2, while, by week 16, there was a decrease in the tumor volume from 142 [51; 206] to 68 cm3 [23; 185] for hepatocellular carcinoma, from 465 [330; 600] to 187 cm3 [137;237] for intrahepatic cholangiocarcinoma. With repeated transarterial chemoembolization, a decrease in the volume of the tumor mass was also noted, while the time without progression decreased from 303 [170; 369] to 180 [105; 225] days in Group 1, from 266 [200; 367] to 120 [62; 215] days in Group 2. Conclusions: Transarterial chemoembolization with drug-eluting microspheres is an effective treatment for primary and metastatic liver tumors. It should be considered as a palliative therapy, which allows achieving a good antitumor response at different stages of cancer.

The Carcinogenic Potential of Bisphenol A in the Liver Based on Transcriptomic Studies.

Bisphenol A (BPA) is an environmental toxin widely used in the production of polycarbonate plastics. A correlation exists between BPA tissue contamination and the occurrence of pathological conditions, including cancer. First-passage detoxification of high BPA amounts in the liver promotes hepatotoxicity and morphological alterations of this organ, but there is a lack of knowledge about the molecular mechanisms underlying these phenomena. This prompted us to investigate changes in the liver transcriptomics of 3-month-old female mice exposed to BPA (50 mg/kg) in drinking water for 3 months. Five female mice served as controls. The animals were euthanized, the livers were collected, and RNA was extracted to perform RNA-seq analysis. The multistep transcriptomic bioinformatics revealed 120 differentially expressed genes (DEGs) in the BPA-exposed samples. Gene Ontology (GO) annotations indicated that DEGs have been assigned to many biological processes, including "macromolecule modification" and "protein metabolic process". Several of the revealed DEGs have been linked to the pathogenesis of severe metabolic liver disorders and malignant tumors, in particular hepatocellular carcinoma. Data from this study suggest that BPA has a significant impact on gene expression in the liver, which is predictive of the carcinogenic potential of this compound in this organ.

Recurrent Non-islet Cell Tumor Hypoglycemia Secondary to Hepatocellular Carcinoma: Case Report and Literature Review.

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome caused by tumors other than insulinoma that is primarily due to excessive production of insulin-like growth factor-II (IGF-II). The prevalence of NICTH is likely underestimated because of a lack of clinical recognition. A 41-year-old male with massive malignant liver tumors presented with recurrent severe hypoglycemia, weight loss, and liver cirrhosis. NICTH related to IGF-II produced by hepatocellular carcinoma was diagnosed based on clinical symptoms, biochemical tests, and elevated IGF-II/IGF-I ratio. Initial treatment with intravenous glucose and parenteral nutrition showed limited efficacy. Glucocorticoids and recombinant human growth hormone led to progressive improvement in blood glucose levels. Due to extensive tumor burden and liver failure, surgical resection was not feasible, and the patient ultimately succumbed to refractory hypoglycemia and passed away in two weeks. Early recognition and diagnosis of NICTH are crucial in patients with recurrent hypoglycemia and large tumors. Surgical resection is the preferred treatment option, but supportive care and pharmacological interventions, such as glucocorticoids and growth hormone, can help manage refractory hypoglycemia. Further research is needed to explore novel treatment options, including anti-IGF-I and -IGF-II neutralizing antibodies.

Liver endothelial cells in NAFLD and transition to NASH and HCC.

Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome, which is characterised by obesity, insulin resistance, hypercholesterolemia and hypertension. NAFLD is the most frequent liver disease worldwide and more than 10% of NAFLD patients progress to the inflammatory and fibrotic stage of non-alcoholic steatohepatitis (NASH), which can lead to end-stage liver disease including hepatocellular carcinoma (HCC), the most frequent primary malignant liver tumor. Liver sinusoidal endothelial cells (LSEC) are strategically positioned at the interface between blood and hepatic parenchyma. LSECs are highly specialized cells, characterised by the presence of transcellular pores, called fenestrae, and exhibit anti-inflammatory and anti-fibrotic characteristics under physiological conditions. However, during NAFLD development they undergo capillarisation and acquire a phenotype similar to vascular endothelial cells, actively promoting all pathophysiological aspects of NAFLD, including steatosis, inflammation, and fibrosis. LSEC dysfunction is critical for the progression to NASH and HCC while restoring LSEC homeostasis appears to be a promising approach to prevent NAFLD progression and its complications and even reverse tissue damage. In this review we present current information on the role of LSEC throughout the progressive phases of NAFLD, summarising in vitro and in vivo experimental evidence and data from human studies.

Feeding artery characteristics and enhancement patterns of hepatoblastoma patients treated with transarterial chemoembolization (TACE): Digital subtraction angiography evaluation.

Hepatoblastoma is one of the most common primary malignant liver tumors in children. The incidence of hepatoblastoma has been increasing, reaching 1.2 per million children now. The transarterial chemoembolization (TACE) procedure is one of the most practical and effective treatment options besides surgery. Digital subtraction angiography (DSA) is performed as the first step of the TACE procedure. The aim of this study was to provide information about the feeding arteries and enhancement pattern of the hepatoblastoma that was assessed by DSA before the TACE procedure. A retrospective study was conducted among hepatoblastoma cases that had undergone DSA on the TACE procedure to obtain information on the vascularity of the tumor. A total of 26 hepatoblastoma cases who had DSA examination as a part of their first TACE procedure were included, consisting of 15 boys and 11 girls, aged between 1-15 years. All cases were stage III and IV according to the Pre-Treatment Extent of Tumor (PRETEXT) staging classification. All hepatoblastoma cases had multiple feeding arteries, most of which were branches of the right hepatic artery. The largest diameter of the feeding artery was 1.82 mm, and the smallest was 0.63 mm. Most cases (84.62%) had strong contrast absorption, and spread evenly, either at the edges or in the center of the tumor. DSA is believed to be an accurate procedure to provide a detailed description of the feeding artery; enhancement patterns of hepatoblastoma were influenced by an adequate TACE.

Significance of Radiomics in Predicting Local Control for Patients with Malignant Liver Tumors Treated Using Stereotactic Body Radiotherapy.

We routinely deliver Stereotactic Body Radiotherapy (SBRT) in malignant liver tumors using planning computed tomography (CT) and Magnetic Resonance Images (MRI) to aid target definition. In this study, we extracted radiomic features from the MR images to predict local control (LC) post-SBRT. We retrospectively analyzed patients with either hepatocellular cancers (HCCs) or liver metastases (Mets) treated with SBRT between Aug 2014 and Aug 2020. All patients had CT simulation followed by 1.5 Tesla planning MRI in treatment position. Contrast enhanced T1 VIBE and T2 Haste MR sequences were registered with planning CT for target definition. Radiomic features were extracted from Gross Tumor Volumes (GTV) masked out of 60 seconds post contrast T1 VIBE MR images using the Radiomics calculator tool RaCaT. The output included 480 (408 textural, 50 intensity and 22 morphological) features for each target. Principal Component Analysis of the outputs obtained from all the targets yielded 20 radiomic feature clusters after computational prioritization. These clusters were correlated to LC outcomes at various time points post-SBRT. LC was defined as non-progressive disease. Accuracy of predictions was measured by area under (AUC) receiver operating characteristic curve. Cox regression analysis was done to find univariate and multivariate clinical [HCCs vs. Mets, single vs. multiple lesions, previous local therapy (yes vs. no), GTV volume (≤40 vs. >40 cc)], radiomic and dosimetric predictors (continuous) of LC. In total, 97 patients received SBRT to 122 lesions. The median dose prescribed was 45 Gy (range, 30-50 Gy). Median age was 69 years (interquartile range, IQR 61-73 yrs.). 59 patients had HCCs and 38 had Mets. 24 lesions had prior ablative therapy. 75 patients had one target, and 22 had multiple targets. Median GTV was 43.5 cc (IQR 23.4-78.6 cc). Median follow up was 16.6 months (IQR 9.7-27.2 mths). Median LC was 13.6 months (IQR 8.0-23.5 mths). On univariate analysis, histology (HCCs vs. Mets; Hazard ratio (HR) 2.9, 95% CI 1.4-6.4; p < 0.006), radiomic clusters (p < 0.006) and the max., mean, and min. doses to GTV and Planning Target Volumes correlated with improved LC (all p-values < 0.05). On multivariate analysis, histology (HCCs vs. Mets; HR 4.4, 95% CI 1.6-12.3; p = 0.004), radiomic clusters (p = 0.034) and prescription dose (p = 0.048) were significant covariates. Specifically, the 20 radiomic clusters were predictive of LC, and the accuracy of predictions showed promise with AUC values of 0.74, 0.80, and 0.81 at 12, 24, and 36 months post-SBRT, respectively. AUC values for LC in HCCs vs. Mets at 12, 24, and 36 months were 0.83, 0.77, and 0.70, and 0.66, 0.77, and 0.88, respectively. MR-based radiomics predict LC post-SBRT in patients with malignant liver tumors. Further research focused on independent validation of the model is required to explore its clinical use.