Liver Carcinoma Research Articles

Zorlayıcı ve Nadir Bir Vaka: Karaciğerin Mukoepidermoid Karsinomu

Mucoepidermoid carcinoma is the most common malignant tumor of the salivary gland. It rarely occurs in other organs. Less than 20 cases of mucoepidermoid carcinoma of liver have been reported in the literature.
 
 A 70-year-old woman with a liver mass is reported in this case report. After liver segmentectomy operation, the specimen was examined microscopically, a tumor consisting of epidermoid, mucinous, and intermediate cells was observed. It was interpreted as mucoepidermoid carcinoma. As no other focus was detected from comprehensive scanning of the patient, it was diagnosed as primary mucoepidermoid carcinoma of liver. Due to mimicking other tumors such as adenosquamous carcinoma and squamous cell carcinoma; cautious examination and differential diagnosis are important.

Diagnostic dilemma in a patient with history of medullary thyroid carcinoma and abnormal serum liver enzymes; a case report with six years follow up

BackgroundMedullary thyroid carcinoma (MTC) is a neuroendocrine tumor that originates from parafollicular C-cells. Calcitonin (Ctn) and carcinoembryonic antigen (CEA) are useful biomarkers for monitoring MTC cases.Case presentationHere, we describe a 48-year-old woman, who presented in 2014 with bilateral thyroid nodules. Report of fine needle aspiration was suspicious for MTC; initial laboratory evaluation showed serum Ctn level of 1567 pg/mL. After excluding type 2 multiple endocrine neoplasia syndrome clinically, total thyroidectomy and neck lymph node dissection were performed. The final histopathological diagnosis was right lobe MTC with neither vascular invasion nor lymph node involvement. On regular follow-up visits, Ctn and CEA levels have been undetectable, and repeated cervical ultrasonographic exams were unremarkable from 2014 to 2021. As liver enzymes became elevated in 2016, the patient was further evaluated by a gastroenterologist. Abdominopelvic ultrasonography revealed a coarse echo pattern of the liver parenchyma with normal bile ducts. A liver fibroscan showed a low fibrosis score (7kPa). The patient was recommended to use ursodeoxycholic acid. According to the progressive rise of liver enzymes with a cholestatic pattern in October 2020, a liver biopsy was performed that showed tiny nests of neuroendocrine-like cells with a background of primary biliary cholangitis (PBC). Immunohistochemical stainings were positive for chromogranin A (CgA), and synaptophysin and negative for Ctn, CEA, and thyroglobulin. Further imaging investigations did not reveal any site of a neuroendocrine tumor in the body. Considering normal physical exam, imaging findings, as well as normal serum levels of Ctn, CEA, CgA, and procalcitonin, the patient was managed as a PBC.ConclusionIn follow-up of a patient with MTC, we reported progressively increased liver enzymes with a cholestatic pattern. Liver biopsy revealed nests of neuroendocrine-like cells with a background of PBC, the findings that might suggest acquiring neuroendocrine phenotype by proliferating cholangiocytes.

Familial coaggregation of MASLD with hepatocellular carcinoma and adverse liver outcomes: Nationwide multigenerational cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly NAFLD) is the fastest growing cause of hepatocellular carcinoma (HCC) worldwide. However, whether family members of individuals with MASLD also share an increased risk of developing HCC is unknown. This nationwide multigenerational cohort study involved family members of all Swedish adults diagnosed with biopsy-proven MASLD (1969-2017), and matched general population comparators. Using the Swedish Multi-generation Register, we identified 38,018 first-degree relatives (FDRs: parents, siblings, offspring) and 9,381 spouses of patients with MASLD, as well as 197,303 comparator FDRs and 47,572 comparator spouses. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) for HCC, major adverse liver outcomes (cirrhosis, decompensated liver disease or liver transplantation), liver-related mortality, extrahepatic cancer, and non-liver-related mortality. Over a median of 17.6 years, the rate of the primary outcome HCC was higher in MASLD FDRs vs. comparator FDRs (13 vs. 8/100,000 person-years [PY]; aHR 1.80, 95% CI 1.36-2.37). The HCC risk was further increased in FDRs of individuals with liver fibrosis/cirrhosis (aHR 2.14, 95% CI 1.07-4.27; PHeterogeneity= 0.03). MASLD FDRs also had higher rates of major adverse liver outcomes (73 vs. 51/100,000 PY; aHR 1.52, 95% CI 1.36-1.69) and liver-related mortality (20 vs. 11/100,000 PY; aHR 2.14, 95% CI 1.67-2.74). MASLD FDRs with any concomitant chronic liver condition experienced accelerated progression of liver disease (aHR 1.47, 95% CI 1.29-1.67). MASLD spouses were at higher risks of major adverse liver outcomes (86 vs. 74/100,000 PY; aHR 1.23, 95% CI 1.01-1.51) and liver-related mortality (25 vs. 19/100,000 PY; aHR 1.93, 95% CI 1.15-3.23), but not of HCC (aHR 1.43, 95% CI 0.87-2.35). There is distinct familial clustering of adverse liver-related outcomes in families of individuals with biopsy-proven MASLD, with higher relative risks of HCC, progressive liver disease, and liver-related mortality, but absolute risks are low. Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly termed NAFLD) clusters in families with high genetic susceptibility and shared environmental risk factors, but the risks of developing hepatocellular carcinoma and other major liver-related outcomes in family members of individuals with MASLD are largely unknown. This large nationwide multigenerational cohort study involving family members (first-degree relatives and spouses) of individuals with biopsy-proven MASLD and of matched general population comparators found slightly increased risks of hepatocellular carcinoma in first-degree relatives, and of developing cirrhosis and liver-related mortality in all family members of individuals with biopsy-proven MASLD. The findings of this study provide large-scale evidence to inform clinical practice guidelines for recommendations on the early identification of individuals at higher risk of liver-related morbidity and mortality.

Extended lifespan and improved genome stability in HepaRG-derived cell lines through reprogramming by high-density stress

The characteristics and fate of cancer cells partly depend on their environmental stiffness, i.e., the local mechanical cues they face. HepaRG progenitors are liver carcinoma cells exhibiting transdifferentiation properties; however, the underlying mechanisms remain unknown. To evaluate the impact of external physical forces mimicking the tumor microenvironment, we seeded them at very high density for 20 h, keeping the cells round and unanchored to the substrate. Applied without corticoids, spatial confinement due to very high density induced reprogramming of HepaRG cells into stable replicative stem-like cells after replating at normal density. Redifferentiation of these stem-like cells into cells very similar to the original HepaRG cells was then achieved using the same stress but in the presence of corticoids. This demonstrates that the cells retained the memory required to run the complete hepatic differentiation program, after bypassing the Hayflick limit twice. We show that physical stress improved chromosome quality and genomic stability, through greater efficiency of DNA repair and restoration of telomerase activity, thus enabling cells to escape progression to a more aggressive cancer state. We also show the primary importance of high-density seeding, possibly triggering compressive stress, in these processes, rather than that of cell roundness or intracellular tensional signals. The HepaRG-derived lines established here considerably extend the lifespan and availability of this surrogate cell system for mature human hepatocytes. External physical stress is a promising way to create a variety of cell lines, and it paves the way for the development of strategies to improve cancer prognosis.

Giant mitochondria in human liver disease.

This thematic review aims to provide an overview of the current state of knowledge about the occurrence of giant mitochondria or megamitochondria in liver parenchymal cells. Their presence and accumulation are considered to be a major pathological hallmark of the health and fate of liver parenchymal cells that leads to overall tissue deterioration and eventually results in organ failure. The first description on giant mitochondria dates back to the 1960s, coinciding with the availability of the first generation of electron microscopes in clinical diagnostic laboratories. Detailed accounts on their ultrastructure have mostly been described in patients suffering from alcoholic liver disease, chronic hepatitis, hepatocellular carcinoma and non-alcoholic fatty liver disease. Interestingly, from this extensive literature survey, it became apparent that giant mitochondria or megamitochondria present themselves with or without highly organised crystal-like intramitochondrial inclusions. The origin, formation and potential role of giant mitochondria remain to-date largely unanswered. Likewise, the biochemical composition of the well-organised crystal-like inclusions and their possible impact on mitochondrial function is unclear. Herein, concepts about the possible mechanism of their formation and three-dimensional architecture will be approached. We will furthermore discuss their importance in diagnostics, including future research outlooks and potential therapeutic interventions to cure liver disease where giant mitochondria are implemented.

Biochemical composition and bioactivity of the crude extract of Sargassum dentifolium (Turner) C. Agardh, of Western Coast of the Red Sea, Hurghada, Egypt

This study evaluated the biochemical composition and bioactivity of the crude extract of Sargassum dentifolium on the western coast of the Red Sea, Hurghada, Egypt. The biomass contained approximately 25.80% of total carbohydrates, and 8.40% of total protein, while lipids constitute about 2% of the total dry weight which is consistent with the low lipid content typically found in seaweeds. S. dentifolium also produces volatile and non-volatile compounds as part of its metabolic processes. The most abundant volatile compound identified was phytol, which has various industrial and pharmaceutical applications. Saturated fatty acids (SFAs) were the most frequently detected non-volatile compounds, with palmitic acid being the most common. The total phenolic content was 50.6 mg g−1 (5.06%), and the total flavonoid content was 33.9 mg g−1 (3.39%) of the total dry-weight extract. S. dentifolium extract demonstrated significant antioxidant activity, with radical scavenging properties and phenolic content that may contribute to its antioxidant efficacy. It also showed cytotoxic activity against cancer cells, particularly human hepatocellular liver carcinoma (HepG2) and human colon carcinoma (HCT-116) cells, indicating their potential as a source of anti-cancer agents. However, the extract exhibited moderate to weak antiviral activity and limited antimicrobial activity against specific microorganisms. This research could contribute to the development of new functional macroalgae-based food or nutraceutical products with potential health benefits.

Cirrhosis of the liver

Cirrhosis of the liver is a life-threatening chronic liver disease, accompanied by an irreversible replacement of the parenchymal tissue of the liver with fibrous connective tissue, or stroma. In economically developed countries, cirrhosis is one of the six main causes of death in patients aged 35 to 60, accounting for 14-30 cases per 100,000 population. Every year, 40 million people worldwide die from viral cirrhosis of the liver and hepatocellular carcinoma, which develops against the background of carriage of the hepatitis B virus. In the CIS countries, cirrhosis occurs in 1% of the population. Diagnosing advanced cirrhosis is not as difficult as treating it. However, in order to select the most effective treatment regimen, it is necessary to carefully study all aspects in the liver disorders. This approach to the prevention and treatment of liver cirrhosis is based on research protocols and therapeutic programs recognized in European countries using new and safe drugs.

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

Pathology of Hepatocellular Carcinoma and Tumor-Bearing Liver Tissue in Association with hTERT Promoter Mutation.

The hTERT promoter mutation represents a common and early event in hepatocarcinogenesis, but its linkage to the morphological status of the underlying liver tissue is poorly understood. We analyzed the connection between the histopathological changes in tumor-bearing liver tissue and the occurrence of the hTERT promoter mutation in hepatocellular carcinoma (HCC), correlated with clinical data. The study cohort comprised 160 histologically confirmed HCC in patients with or without cirrhosis that were investigated for the hTERT promoter mutation. We evaluated the frequency of the hTERT promoter mutation in patients with HCC with or without cirrhosis and correlated it with potential clinical and histopathological drivers. In particular, we examined tumor-bearing noncirrhotic liver tissue regarding inflammation; the modified histological activity index (mHAI), fibrosis, and steatosis; and its correlation with the frequency of the hTERT promoter mutation in HCC. We evaluated overall survival with multivariate Cox regression. Furthermore, we compared hTERT antibody immunohistochemistry and molecular hTERT promoter mutation analysis of both HCC and background liver tissue. The hTERT promoter mutation was especially related to HCC in cirrhotic compared with noncirrhotic liver (p < 0.001) and independently of cirrhosis in patients ≥ 60 years (p = 0.005). Furthermore, the hTERT promoter mutation was associated with cirrhosis caused by alcohol toxicity and hepatitis C virus infection. In noncirrhotic liver tissue, the frequency of hTERT-promoter-mutated HCC increased with the degree of inflammation and fibrosis. Nevertheless, 25% of the hTERT-promoter-mutated HCC developed in normal liver tissue without HCC risk factors. Multivariate Cox regression analysis did not reveal an influence of the hTERT promoter mutation in HCC on overall survival at 3, 5, and 16 years. Immunohistochemical analysis with the hTERT antibodies LS-B95 and 2D8 in hTERT-promoter-mutated HCC and hTERT-wildtype HCC showed a mildly stronger immunoreaction compared with the tumor-bearing liver tissue (LS-B95: p < 0.01, 2D8: p < 0.01). Our study reveals a connection between pathological changes in tumor-bearing liver tissue and the hTERT promoter mutation in most HCC, even in noncirrhotic liver tissue. Immunohistochemical hTERT antibodies do not discriminate between hTERT-promoter-mutated and wildtype HCC.

Transcriptomics-based analysis of sex-differentiated mechanisms of hepatotoxicity in zebrafish after long-term exposure to bisphenol AF

Bisphenol AF (BPAF) is an emerging endocrine-disrupting chemical (EDC) prevalent in the environment as one of the main substitutes for bisphenol A. Sex-specific effects of EDCs have been commonly reported and closely linked to sexually dimorphic patterns of hormone metabolism and related gene expression during different exposure windows, but our understanding of these mechanisms is still limited. Here, following 28-day exposure of adult zebrafish to an environmentally relevant concentration of BPAF at 10 μg/L, the global transcriptional networks applying RNA sequencing (RNA-seq) and Ingenuity Pathway Analysis (IPA) were respectively investigated in the male and female fish liver, connecting the sex-dependent toxicity of the long-term exposure of BPAF to molecular responses. As a result, more differentially expressed genes (DEGs) were detected in males (811) than in females (195), and spermatogenesis was the most enriched Gene Ontology (GO) functional classification in males, while circadian regulation of gene expression was the most enriched GO term in females. The expression levels of selected DEGs were routinely verified using qRT-PCR, which showed consistent alterations with the transcriptional changes in RNA-seq data. The causal network analysis by IPA suggested that the adverse outcomes of BPAF in males including liver damage, apoptosis, inflammation of organ, and liver carcinoma, associated with the regulation of several key DEGs detected in RNA-seq, could be linked to the activation of upstream regulatory molecules ifnα, yap1, and ptger2; while, the inhibition of upstream regulators hif1α, ifng, and igf1, leading to the down-regulated expression of several key DEGs, might be involved in BPAF’s effects in females. Furthermore, BPAF exposure altered hepatic histological structure and inhibited antioxidant capability in both male and female livers. Overall, this study revealed different regulation networks involved in the sex-dependent effects of BPAF on the fish liver, and these detected DEGs upon BPAF exposure might be used as potential biomarkers for further assessing sex-specific hepatotoxicity following environmental EDC exposure.

18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG

PurposeThe radiopharmaceutical [18F]AlF-NOTA-FAPI-04 presents a promising alternative to 68 Ga-FAPI owing to its relatively longer half-life. This study aimed to evaluate the clinical usefulness of [18F]AlF-NOTA-FAPI-04 PET/CT for the diagnosis of primary and metastatic lesions in various types of gastrointestinal system cancers, compared with 18F-FDG PET/CT.MethodsPatients diagnosed with gastrointestinal system malignancies were prospectively enrolled. All patients underwent both 18F-FDG and 18F-FAPI-04 PET/CT scans within one week, with 44 (73.3%) for cancer staging and 16 (26.7%) for tumor restaging. Diagnostic efficacy of the primary tumor, as well as the presence and number of lymph nodes and distant metastases, were assessed. Tumor uptake was quantified by the maximum standard uptake value (SUVmax).ResultsFor detection of primary tumor, the diagnostic sensitivity of 18F-FDG PET/CT was 72.7%, while it was 97.7% for 18F-FAPI-04 PET/CT. Based on per-lymph node analysis, the sensitivity, specificity, and accuracy of 18F-FAPI-04 PET/CT in diagnosing metastatic lymph nodes were 91.89%, 92.00%, and 91.96%, respectively. These values were notably higher than those 18F-FDG PET/CT (79.72%, 81.33% and 80.80%, respectively). The 18F-FAPI-04 PET/CT surpassed 18F-FDG PET/CT in detecting suspected metastases in the brain (7 vs. 3), liver (39 vs. 20), bone (79 vs. 51), lung (11 vs. 4), and peritoneal carcinoma (48 vs. 22). Based on per-patient analysis, differential diagnostic accuracies (18F-FAPI-04 vs. 18F-FDG PET/CT) were observed in all patients (91.7% vs. 76.7%), the initial staging group (90.9% vs. 79.5%), and the re-staging group (93.8% vs. 68.7%). Additionally, 18F-FAPI-04 PET/CT revised final diagnosis in 31.7% of patients, contrasting with 18F-FDG PET/CT, and prompted changes in clinical management for 21.7% of the patients.Conclusion18F-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in delineating the primary gastrointestinal tumors and detecting suspected metastatic lesions due to a higher target-to-background ratio (TBR). Moreover, 18F-FAPI-04 PET/CT could provide valuable guidance for tumor staging, thereby having a potential impact on patient management.

Increased age, bilirubin, international normalized ratio, and creatinine score to triglyceride ratio are associated with alcohol-associated primary liver carcinoma: a single-centered retrospective study

BackgroundThis study analyzed the clinical features and biomarkers of alcohol-associated liver disease (ALD) to investigate the diagnostic value of age, bilirubin, international normalized ratio (INR), and creatinine (ABIC) score to triglyceride (TG) ratio (ABIC/TG) in ALD-associated primary liver carcinoma (PLC).Materials and methodsData were collected from 410 participants with ALD, and the epidemiological and clinical records of 266 participants were analyzed. Participants were divided into ALD-without-PLC and ALD-associated-PLC groups. Relationships between clinical characteristics, biomarkers and ALD-associated PLC were estimated. Serum lipid levels and liver function were compared between ALD patients without PLC and patients with ALD-associated PLC. Scoring systems were calculated to investigate ALD severity. The robustness of the relationship was analyzed by the receiver operating characteristic (ROC) curve.ResultsAge and dyslipidemia were more strongly associated with ALD-associated PLC than with ALD-without PLC, with AORs of 2.39 and 0.25, respectively, with P less than 0.05. Drinking time and average daily intake, ABIC score, and ABIC/TG ratio were significantly higher in the ALD-associated-PLC group than in the ALD-without-PLC group. The AUC for the ABIC/TG ratio predicting the incidence of PLC was 0.80 (P < 0.01), which was higher than that of the ABIC and TG scores alone; additionally, the specificity and Youden index for the ABIC/TG ratio were also higher, and the cutoff value was 6.99.ConclusionsIn ALD patients, age, drinking time, and average daily intake were risk factors for PLC. Drinking time, average daily intake, TG and ABIC score have diagnostic value for ALD-associated PLC. The ABIC/TG ratio had a higher AUC value and Youden index than the ABIC score and TG level.

Spectroscopic imaging to assess biochemical alterations in liver carcinoma cells exposed to transition metals

Despite the invaluable role of transition metals in every living organism, it should be remembered that failure to maintain the proper balance and exceed the appropriate dose may have the opposite effect. In the era of such a popular and propagated need for supplementation in the media, one should bear in mind the harmful effects that may become the result of improper and excessive intake of transition metals.This article establishes the feasibility of Raman (RS) and Fourier-transform infrared (FT-IR) spectroscopic imaging at the single-cell level to investigate the cellular response to various transition metals. These two non-destructive and perfectly complementary methods allow for in-depth monitoring of changes taking place within the cell under the influence of the agent used. HepG2 liver carcinoma cells were exposed to chromium, iron, cobalt, molybdenum, and nickel at 1 and 2 mM concentrations.Spectroscopic results were further supported by biological evaluation of selected caspases concentration. The caspase- 3, 6, 8, 9, and 12 concentrations were determined with the use of the enzyme-linked immunosorbent assay (ELISA) method. This study shows the induction of apoptosis in the intrinsic pathway by all studied transition metals. Cellular metabolism alterations are induced by mitochondrial metabolism changes and endoplasmic reticulum (ER) metabolism variations. Moreover, nickel induces not only the intrinsic pathway of apoptosis but also the extrinsic pathway of this process.

Applications of Dynamic Contrast-Enhanced Ultrasound in Differential Diagnosis of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma in Non-cirrhotic Liver.

The aim of the work described here was to investigate the value of dynamic contrast enhanced ultrasound (DCE-US) and quantitative analysis in pre-operative differential diagnosis of intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) in non-cirrhotic liver. In this retrospective study, patients with histopathologically proven ICC and HCC lesions in non-cirrhotic liver were included. All patients underwent contrast-enhanced ultrasound (CEUS) examinations with an Acuson Sequoia unit (Siemens Healthineers, Mountain View, CA, USA) unit or LOGIQ E20 (GE Healthcare, Milwaukee, WI, USA) within 1 wk before surgery. SonoVue (Bracco, Milan, Italy) was used as the contrast agent. B-mode ultrasound (BMUS) features and CEUS enhancement patterns were analyzed. DCE-US analysis was performed by VueBox software (Bracco). Two regions of interest (ROIs) were set in the center of the focal liver lesions and their surrounding liver parenchyma. Time-intensity curves (TICs) were generated, and quantitative perfusion parameters were obtained and compared between the ICC and HCC groups using the Student t-test or Mann-Whitney U-test. From November 2020 to February 2022, patients with histopathologically confirmed ICC (n=30) and HCC (n=24) lesions in non-cirrhotic liver were included. During the arterial phase (AP) of CEUS, ICC lesions exhibited heterogeneous hyperenhancement (13/30, 43.3%), heterogeneous hypo-enhancement (2/30, 6.7 %) and rim-like hyperenhancement (15/30, 50.0%), whereas all HCC lesions exhibited heterogeneous hyperenhancement (24/24, 100.0%) (p < 0.05). Subsequently, most of the ICC lesions exhibited AP wash-out (83.3%, 25/30), whereas a few cases exhibited wash-out in the portal venous phase (PVP) (15.7%, 5/30). In contrast, HCC lesions exhibited AP wash-out (41.7%, 10/24), PVP wash-out (41.7%, 10/24) and a small part of late phase wash-out (16.7%, 4/24) (p < 0.05). Compared with those of HCC lesions, TICs of ICCs revealed earlier and lower enhancement during the AP, faster decline during the PVP and reduced area under the curve. The combined area under the receiver operating characteristic curve (AUROC) of all significant parameters was 0.946, with 86.7% sensitivity, 95.8% specificity and 90.7% accuracy in differential diagnosis between ICC and HCC lesions in non-cirrhotic liver, which improved the diagnostic efficacy of CEUS (58.3% sensitivity, 90.0% specificity and 75.9% accuracy). ICC and HCC lesions in non-cirrhotic liver might exhibit some overlap of CEUS features in diagnosis. DCE-US with quantitative analysis would be helpful in pre-operative differential diagnosis.

Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease.

Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.

Synthesis of Pyrazole, Pyridine, and Pyrimidine Derivatives Incorporating Glucaminoid Moiety and Their Antioxidant, Antitumor Activities and Docking Study

AbstractThe reaction of N‐(4‐(phenyldiazenyl) phenyl) carbonohydrazonoyl dicyanide (2) with N‐methyl glucamine afforded 3‐amino‐3‐(methyl (2,3,4,5,6‐pentahydroxyhexyl)amino)‐2‐((4‐(phenyldiazenyl)phenyl)diazenyl)acrylonitrile (3). Additionally, compound 2 produced the pyrazole derivatives 4 and 6, respectively, by reactions with hydrazine hydrate and malononitrile. Moreover, when enaminonitrile 3 was treated with malononitrile, N,N‐Dimethylformamide ‐ dimethyl acetal, and thiourea, it generated the glucaminoid derivatives 9, 10, and 13, respectively. In pyridine, compound 19 was obtained when enaminonitrile 3 interacted with the carbon disulfide. While in sodium hydroxide in N,N‐Dimethylformamide, instead of pyridine, it afforded the methyl carbamodithioate 23. Finally, pyrimidinethione derivative 26 was produced when the enaminonitrile 3 and phenyl isothiocyanate interacted. All new compounds were well established by both spectral and elemental analyses. The antitumor activities were evaluated by testing their impact on the viability of four different cell lines: HepG2 (human hepatocellular liver carcinoma), WI‐38 (human lung fibroblast), VERO (African green monkey kidney epithelial), and MCF‐7 (human breast adenocarcinoma). The antitumor study showed that compound 23 has very strong antitumor activity against the HEPG‐2 cell line. The synthesized compounds were analyzed by docking studies that showed good binding scores against the diverse amino acids of the selected proteins B‐Cell Leukemia/Lymphoma‐2 (Bcl‐2). The conducted docking studies were found to be consistent with cytotoxic results.

Comparison of MRI and CT Scan for the Detection of Liver Cancer.

The objective of the paper was to compare the value of CT and MRI in the diagnosis of primary carcinoma of the liver. A retrospective analysis was performed on 132 cases of suspected primary liver carcinoma. CT and MRI diagnosis were performed and pathological results were compared to determine the diagnostic value of the two methods. 96 cases were diagnosed as primary liver carcinoma by pathological examination after operation. The total detection rate of 96 lesions through MRI was 93.75%, while 84.38% through CT (P<0.05). For lesions with a <3 cm diameter, the CT detection rates of lesions in the plain, arterial, portal, and equilibrium phases were 52.94%, 73.53%, 58.82%, and 58.82% respectively. For lesions with a diameter ≥ 3 cm, the CT detection rate was 80.65 %, 93.55%, 85.48%, and 83.87%, respectively (P<0.05). For lesions with <3cm diameter, the MRI detection rates of lesions in the T1WI, T2WI, LAVA arterial phase, LAVA portal phase, and LAVA balance phase were 61.76%, 76.47%, 88.24%, 79.41%, and 52.94%, respectively, and for lesions with ≥3cm diameter, the detection rates of MRI were 77.42%, 87.10%, 91.94%, 90.32%, and 90.32%, respectively, and the detection rate of lesions with ≥3cm diameter in the balance phase of LAVA was higher (P<0.05). Taking pathological results as the gold standard, the sensitivity of diagnosing primary liver carcinoma through CT is 81.25%, specificity is 75.00%, accuracy is 79.55%, the positive predictive value is 89.66%, the negative predictive value is 60.00%, and the values of the same parameters for the MRI are 93.75. %, 86.11%, 91.67%, 94.74%, and 83.78% respectively. Both CT and MRI have diagnostic value for primary liver carcinoma. The comparison showed that MRI has a higher diagnostic value and higher detection rate for small lesions. However, the actual process of diagnosis cannot rely solely on MRI, and a comprehensive combination of diagnosis methods will be effective.

Preoperative planning and intraoperative real-time navigation with indocyanine green fluorescence in robotic liver surgery

PurposeWe aimed at exploring indocyanine green (ICG) fluorescence wide spectrum of applications in hepatobiliary surgery as can result particularly useful in robotic liver resections (RLR) in order to overcome some technical limitations, increasing safety, and efficacy.MethodsWe describe our experience of 76 RLR performed between March 2020 and December 2022 exploring all the possible applications of pre- and intraoperative ICG administration.ResultsHepatocellular carcinoma and colorectal liver metastases were the most common indications for RLR (34.2% and 26.7% of patients, respectively), and 51.3% of cases were complex resections with high IWATE difficulty scores. ICG was administered preoperatively in 61 patients (80.3%), intraoperatively in 42 patients (55.3%) and in both contexts in 25 patients (32.9%), with no observed adverse events. The most frequent ICG goal was to achieve tumor enhancement (59 patients, 77.6%), with a success rate of 94.9% and the detection of 3 additional malignant lesions. ICG facilitated evaluation of the resection margin for residual tumor and perfusion adequacy in 33.9% and 32.9% of cases, respectively, mandating a resection enlargement in 7.9% of patients. ICG fluorescence allowed the identification of the transection plane through negative staining in the 25% of cases. Vascular and biliary structures were visualized in 21.1% and 9.2% of patients, with a success rate of 81.3% and 85.7%, respectively.ConclusionRLR can benefit from the routine integration of ICG fluoresce evaluation according to each individual patient and condition-specific goals and issues, allowing liver functional assessment, anatomical and vascular evaluation, tumor detection, and resection margins assessment.

Comparing Pharmacological Potential of Freshwater Microalgae Carotenoids Towards Antioxidant and Anti-proliferative Activity on Liver Cancer (HUH7) Cell Line.

Chemical-based carotenoids have large implications to health as they may cause adverse side effects. Naturally occurring carotenoids mainly from microalgal sources are emerging as excellent substitute to combat cancer diseases. Astaxanthin is the most powerful antioxidant that derived from selected established microalgae with limited yield. Microalgal bioprospecting may provide the high-yielding sources for astaxanthin production. Hence, in the present research, freshwater microalgae Monoraphidium sp. (NCM no. 5585) and Scenedesmus obliquus (NCM no. 5586) were chosen to explore the unique potential of producing astaxanthin. Identification of bioactive metabolites in extracted carotenoid was analyzed through HPLC. Astaxanthin is identified as a major bioactive metabolite in both carotenoid fraction and β carotene only in Scenedesmus obliquus. Antioxidant potential of microalgal carotenoids was obtained by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) assay. The anti-proliferation activity of the extracted carotenoid from Monoraphidium sp. and Scenedesmus obliquus was evaluated against hepatocellular liver carcinoma cell line HUH7 by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Higher astaxanthin in Monoraphidium sp. leads to boosted antioxidant and anti-proliferation activity contrary to Scenedesmus obliquus that possess both astaxanthin and β carotene. Though freshwater microalgae have a huge potential to create beneficial metabolites like carotenoids, they are rarely studied in the pharmaceutical industry. This work was the first to investigate the anti-proliferative activity of Monoraphidium sp. and Scenedesmus obliquus carotenoid fraction on the HUH7 hepatocarcinoma cell line.

Establishment of a Novel Anti-Human CCR6 Monoclonal Antibody C6Mab-19 with the High Binding Affinity in Flow Cytometry.

CC chemokine receptor 6 (CCR6) is a member of the G-protein-coupled receptor family that is highly expressed in B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. CCR6 has been revealed to have important functions in many pathological conditions, such as cancer, intestinal bowel disease, psoriasis, and autoimmune diseases. The only CCR6 chemokine ligand, CC motif chemokine ligand 20 (CCL20), is also involved in pathogenesis by interacting with CCR6. The CCL20/CCR6 axis is drawing attention as an attractive therapeutic target for various diseases. In this study, we developed novel monoclonal antibodies (mAbs) against human CCR6 (hCCR6) using the peptide immunization method, which are applicable to flow cytometry and immunohistochemistry. The established anti-hCCR6 mAb, clone C6Mab-19 (mouse IgG1, kappa), reacted with hCCR6-overexpressed Chinese hamster ovary-K1 (CHO/hCCR6), human liver carcinoma (HepG2), and human differentiated hepatoma (HuH-7) cells in flow cytometry. The dissociation constant (KD) of C6Mab-19 was determined as 3.0 × 10-10 M for CHO/hCCR6, 6.9 × 10-10 M for HepG2, and 1.8 × 10-10 M for HuH-7. Thus, C6Mab-19 could bind to exogenously and endogenously expressed hCCR6 with extremely high affinity. Furthermore, C6Mab-19 could stain formalin-fixed paraffin-embedded lymph node tissues from a patient with non-Hodgkin lymphoma by immunohistochemistry. Therefore, C6Mab-19 is suitable for detecting hCCR6-expressing cells and tissues and could be useful for pathological analysis and diagnosis.