To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following ...institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones' volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm
, 19.22 ± 5.77 cm
, and 8.80 ± 3.33 cm
for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.
Hemostasis is a complex physiological process based on the balance between pro-coagulant and anticoagulant systems to avoid pathological bleeding or thrombosis. The changes in standard coagulation ...tests in liver disease were assumed to reflect an acquired bleeding disorder, and cirrhotic patients were considered naturally anticoagulated. In the light of the new evidence, the theory of rebalanced hemostasis replaced the old concept. According to this model, the hemostatic alteration leads to a unique balance between pro-coagulant, anticoagulant, and fibrinolytic systems. But the balance is fragile and may prone to bleeding or thrombosis depending on various risk factors. The standard coagulation tests INR (international normalized ratio), platelet count and fibrinogen only explore parts of the hemostasis, not offering an entire image of the process. Rotational thromboelastometry (ROTEM) and thromboelastography (TEG) are both point of care viscoelastic tests (VET) that provide real-time and dynamic information about the entire hemostasis process, including clot initiation (thrombin generation), clot kinetics, clot strength, and clot stability (lysis). Despite prolonged PT/INR (international normalized ratio of prothrombin time) and low platelet counts, VET is within the normal range in many patients with both acute and chronic liver disease. However, bleeding remains the dominant clinical issue in patients with liver diseases, especially when invasive interventions are required. VET has been shown to asses more appropriately the risk of bleeding than conventional laboratory tests, leading to decrial use of blood products transfusion. Inappropriate clotting is common but often subtle and may be challenging to predict even with the help of VET. Although VET has shown its benefit, more studies are needed to establish cut-off values for TEG and ROTEM in these populations and standardization of transfusion guidelines before invasive interventions in cirrhotic patients/orthotopic liver transplantation.
Two 3-oxo-Δ
fetal bile acids, 3-oxachola-4,6-dien-24-oic acid (1) and 7α-hydroxy-3-oxochol-4-en-24-oic acid (2), occur normally in the human fetus but remain elevated in neonates and children with ...severe cholestatic liver disease due to an autosomal recessive inborn error of metabolism affecting Δ
-3-oxo-steroid 5β-reductase (AKR1D1). Relatively little is known about 1 and 2 in adult patients with liver disease. The chemical synthesis of 1 and 2 is therefore described and their quantitation in plasma by ultrarapid chromatography-triple quadrupole mass spectrometry. Plasma concentrations of 1 and 2 were investigated in 25 adult patients with varying degrees of liver cirrhosis with and without hepatocellular carcinoma (HCC). Highly statistically significant correlations (P < 0.0001) were found between severity of liver cirrhosis, determined by the Child-Pugh and MELD scores, with plasma 1 and 2 concentrations, both alone and combined. The presence of HCC did not influence these correlations. Plasma cholic, chenodeoxycholic, deoxycholic, lithocholic or ursodeoxycholic acids, free and as their glycine or taurine conjugates, did not correlate with Child-Pugh or MELD score when corrected for multiple comparisons. These findings demonstrate that plasma levels of fetal bile acids 3-oxachola-4,6-dien-24-oic acid and 7α-hydroxy-3-oxochol-4-en-24-oic acid and likely deteriorating AKR1D1 activity indicate the severity of liver cirrhosis measured by the Child-Pugh and MELD scores.
Aims: To report on the long-term impact of tumor and non-tumor related parameters on local recurrence, distant recurrence and survival in patients with naïve or recurrent type hepatocellular ...carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods: We performed 240 RFA sessions on 133 patients with 156 HCC nodules developed on a background of liver cirrhosis and analyzed the outcomes.Results: Contrast-enhanced ultrasound performed one month after RFA showed complete ablation in 119 out of 133 (89.65%) patients. With a median follow-up of 46 months, 3-, 5- and 7-year survival rates were 61.7%, 35.7%, and 22.6%, respectively. Previous ethanol injection and histological grade were significantly related to local tumor progression. Child-Pugh class, incomplete ablation, histological grade, previous ethanol injection, alpha-fetoprotein level before the treatment, and local recurrence were all significantly related to distant recurrence. Multivariate analysis demonstrated that age, Child-Pugh class, distant recurrence and multiple incomplete ablations were significantly related to survival.Conclusion: Radiofrequency ablation could be locally curative for HCC, resulting in a survival longer than 7 years. Previous ethanol injection and incomplete ablations were strongly associated with poor outcomes.
Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins ...one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin’s type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.
Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially ...curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (
= 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.
The field of hepatocellular carcinoma (HCC) has faced significant change on multiple levels in the past few years. The increasing emphasis on the various HCC phenotypes and the emergence of novel, ...specific therapies have slowly paved the way for a personalized approach to primary liver cancer. In this light, the role of percutaneous liver biopsy of focal lesions has shifted from a purely confirmatory method to a technique capable of providing an in-depth characterization of any nodule. Cancer subtype, gene expression, the mutational profile, and tissue biomarkers might soon become widely available through biopsy. However, indications, expectations, and techniques might suffer changes as the aim of the biopsy evolves from providing minimal proof of the disease to high-quality specimens for extensive analysis. Consequently, a revamped position of tissue biopsy is expected in HCC, following the reign of non-invasive imaging-only diagnosis. Moreover, given the advances in techniques that have recently reached the spotlight, such as liquid biopsy, concomitant use of all the available methods might gather just enough data to improve therapy selection and, ultimately, outcomes. The current review aims to discuss the changing role of liver biopsy and provide an evidence-based rationale for its use in the era of precision medicine in HCC.
Background
Biliary cancer, comprising cholangio‐ and gallbladder carcinomas, is associated with high mortality due to asymptomatic disease onset and resulting late diagnosis. Currently, no robust ...diagnostic biomarker is clinically available. Therefore, we explored the feasibility of extracellular vesicles (EVs) as a liquid biopsy tool for biliary cancer screening and hepatobiliary cancer differentiation.
Methods
Serum EVs of biliary cancer, hepatocellular carcinoma, colorectal cancer and non‐small cell lung cancer patients, as well as from healthy individuals, were isolated by sequential two‐step centrifugation and presence of indicated EVs was evaluated by fluorescence activated cell sorting (FACS) analysis.
Results
Two directly tumour‐related antigen combinations (AnnV+CD44v6+ and AnnV+CD44v6+CD133+) and two combinations related to progenitor cells from the tumour microenvironment (AnnV+CD133+gp38+ and AnnV+EpCAM+ CD133+gp38+) were associated with good diagnostic performances that could potentially be used for clinical assessment of biliary cancer and differentiation from other cancer entities. With 91% sensitivity and 69% specificity AnnV+CD44v6+ EVs showed the most promising results for differentiating biliary cancers from HCC. Moreover using a combined approach of EV levels of the four populations with serum AFP values, we obtained a perfect separation of biliary cancer and HCC with sensitivity, specificity, positive and negative predictive value all reaching 100% respectively.
Conclusions
EV phenotyping, especially if combined with serum AFP, represents a minimally invasive, accurate liquid biopsy tool that could improve cancer screening and differential diagnosis of hepatobiliary malignancies.
The use of contrast-enhanced ultrasonography (CEUS) has recently become synonymous with high-standard ultrasonography (US). From expanding the reach of US diagnostics to improving the precision of ...various invasive procedures, CEUS is rapidly becoming a standard in numerous niches. However, proficiency in CEUS comes with a cost, both from a learning curve and material standpoint, and as every growing field, lacks firm evidence and standardization. Therefore, in the current paper, we aim to provide an evidence-based review of available methods and to discuss the advantages and pitfalls of CEUS in interventional procedures, trying to provide strong evidence whenever available, or at least an educated expert opinion if data are lacking.
Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians ...in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, among others. In this regard, the "HCC circulome", defined as the pool of circulating molecules in the bloodstream derived from the primary tumor, represents an appealing target, the so called liquid biopsy. Such molecules encompass circulating tumor proteins, circulating tumor cells (CTCs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), and circulating tumor nucleic acids, namely circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA). In this article, we summarize recent findings highlighting the promising role of liquid biopsies as novel potential biomarkers in HCC, emphasizing on its clinical performance.
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