Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.

Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of hepatocellular carcinoma (HCC). Its primary mechanism of action involves inhibiting signal pathways such as vascular endothelial growth factor receptors (VEGFR) and fibroblast growth factor receptors (FGFR), thereby reducing tumor cell proliferation and angiogenesis and affecting the tumor's immune microenvironment. In the treatment of liver cancer, although lenvatinib monotherapy has shown good clinical effect, the problem of drug resistance is becoming more and more serious.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Incidence of hepatobiliary malignancies in primary sclerosing cholangitis: systematic review and meta-analysis.

Background And Aims: Primary sclerosing cholangitis (PSC) is a known risk factor for hepatobiliary malignancies. We conducted a systematic review and meta-analysis of published studies to determine the incidence and risk factors for hepatobiliary malignancies in people with PSC.

Methods: Pubmed and Embase databases were searched from inception to April 10, 2024 for cohort studies reporting data on the incidence of cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), or gallbladder cancer (GBC) in PSC.

Pathological roles of lncRNA HOTAIR in liver cancer: An updated review.

Liver cancer ranks as the sixth most prevalent form of cancer and stands as the fourth leading cause of cancer-related fatalities on a global scale. The two primary types of liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). While ICC originates from the bile ducts, HCC develops from hepatocytes, which are the primary functional cells of the liver.

A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma.

Background: At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors.

Final results of a multicenter prospective study of stereotactic body radiotherapy for previously untreated solitary primary hepatocellular carcinoma (the STRSPH study): Stereotactic body radiotherapy for newly diagnosed single primary liver cancer.

Aim: To report final results of a prospective study of stereotactic body radiotherapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC).

Methods: This prospective, single-arm, multicenter phase II trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival (OS) rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in five fractions.

Synergistic Anticancer Strategy Targeting ECM Stiffness: Integration of Matrix Softening and Mechanical Signal Transduction Blockade in Primary Liver Cancers.

The development of primary liver cancer (hepatocellular carcinoma [HCC] and intrahepatic cholangiocarcinoma [ICC]) is linked to its physical microenvironment, particularly extracellular matrix (ECM) stiffness. Potential anticancer strategies targeting ECM stiffness include prevention/reversal of the stiffening process and disruption of the response of cancer cells to mechanical signals from ECM. However, each strategy has limitations.

Global, regional, and national temporal trends in incidence and mortality for liver cancer due to hepatitis B, 1990-2021: a decomposition and age-period-cohort analysis for the Global Burden of Disease Study 2021.

Objective: This study comprehensively assessed the burden of liver cancer due to hepatitis B (LCHB) from 1990 to 2021, analyzing temporal trends in disease burden and associations with age, period and birth cohort.

Methods: Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) of LCHB from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021. Joinpoint regression analysis estimated long-term trends.

Exosomal miR-6126 as a novel therapeutic target for overcoming resistance of anti-cancer effect in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) stands as the sixth most prevalent cancer globally, presenting a substantial health challenge, particularly due to late-stage diagnoses that limit treatment effectiveness. Sorafenib, a multi-kinase inhibitor, is the primary chemotherapeutic agent for advanced HCC, but it only extends survival by 2-3 months. However, drug resistance remains a major clinical challenge, necessitating the exploration of new molecular mechanisms, including the role of microRNAs (miRNAs) in sorafenib resistance.

The role of inflammasomes in hepatocellular carcinoma: Mechanisms and therapeutic insights.

Hepatocellular carcinoma is among the most frequent forms of primary liver cancer and develops within a context of chronic inflammation, frequently associated with a multitude of risk factors, including viral infections, metabolic dysfunction-associated fatty liver disease, metabolic dysfunction-associated steatohepatitis and liver fibrosis. The tumor microenvironment is crucial for the progression of HCC, as immune cells, tumor-associated fibroblasts and hepatic stellate cells interact to promote chronic inflammation and tumor spread. Inflammasomes, the multiprotein complexes that launch the innate immune response, emerge as important mediators in the pathogenesis of HCC.

Stereotactic Body Radiotherapy vs Sorafenib Alone in Hepatocellular Carcinoma: The NRG Oncology/RTOG 1112 Phase 3 Randomized Clinical Trial.

Importance: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

Objective: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

Design, Setting, And Participants: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion.

Value of HCC surveillance in a landscape of emerging surveillance options: Perspectives of a multi-stakeholder modified delphi panel.

Hepatocellular carcinoma (HCC) surveillance is recommended by liver professional societies but lacks broad acceptance by several primary care and cancer societies due to limitations in the existing data. We convened a diverse multidisciplinary group of cancer screening experts to evaluate current and future paradigms of HCC prevention and early detection using a rigorous Delphi panel approach. The experts had high agreement on twenty-one statements about primary prevention, HCC surveillance benefits, HCC surveillance harms, and the evaluation of emerging surveillance modalities.

HEPATECTOMIES: INDICATIONS AND RESULTS FROM A REFERENCE HOSPITAL IN THE BRAZILIAN AMAZON.

Background: Hepatectomy is historically associated with higher morbidity and mortality, related to intraoperative blood loss and biliary fistulas. Technological advances and improvements in surgical and anesthetic techniques have led to greater safety in performing these surgeries.

Aims: The aim of this study was to analyze morbidity and mortality in patients undergoing hepatectomy.

Gallium-68 Labeled Positron Emission Computed Tomography Tracer Targeting Glypican-3 with High Contrast for Hepatocellular Carcinoma Imaging.

Hepatocellular carcinoma (HCC) represents the predominant form of primary liver cancer, yet early, precise, and noninvasive detection continues to pose a considerable clinical challenge. Glypican-3 (GPC3), a membrane-bound proteoglycan, is markedly overexpressed in most HCC cases, while exhibiting low expression in normal and hepatitis-affected liver tissues. Given its crucial role in malignant transformation and tumor progression, GPC3 emerges as a compelling target for imaging.

Massive gastrointestinal hemorrhage and iodine-125 seed migration due to hepatogastric fistula: a case report and literature review.

Background: Hepatogastric fistula (HGF) is an uncommon occurrence that can be associated with various medical conditions. The primary causes typically involve peptic ulcer disease, infections (such as pyogenic, amoebic or tuberculosis), or iatrogenic factors (like post transarterial chemoembolization or radiotherapy). Massive gastrointestinal hemorrhage following HGF is extremely rare, with iodine-125 (I) seed migration to the stomach through HGF not previously documented.

Macro-vacuolar steatosis in a cirrhotic liver mimicking metastatic disease.

Multinodular steatosis represents a relatively uncommon manifestation of fatty liver disease (FLD). Co-morbidities such as metabolic syndrome or cirrhosis are often associated. Despite typical features of imaging (ultrasound, CT, and MRI), core biopsy sometimes remains the gold standard for diagnosis.

Adjuvant sorafenib for hepatocellular carcinoma after radiofrequency ablation versus radiofrequency ablation: analysis of its efficacy and safety.

Objectives: For the treatment of early hepatocellular carcinoma, we compared the efficacy and safety of radiofrequency ablation (RFA) alone and radiofrequency ablation combined with sorafenib (RFA+Sor).

Methods: A total of 164 patients with early HCC were included in the study. There were 87 patients who underwent RFA alone, and 77 patients who underwent RFA+Sor treatment.

Synergistic enhancement of low-dose radiation therapy via cuproptosis and metabolic reprogramming for radiosensitization in in situ hepatocellular carcinoma.

Background: Radiotherapy (RT) is a primary clinical approach for cancer treatment, but its efficacy is often hindered by various challenges, especially radiation resistance, which greatly compromises the therapeutic effectiveness of RT. Mitochondria, central to cellular energy metabolism and regulation of cell death, play a critical role in mechanisms of radioresistance. In this context, cuproptosis, a novel copper-induced mitochondria-respiratory-dependent cell death pathway, offers a promising avenue for radiosensitization.

Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

Focal gene amplifications are among the most common cancer-associated mutations but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs) in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures.

Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Recurrent Small Hepatocellular Carcinoma: A Randomized, Open-Label, Controlled Trial.

Purpose: To assess the efficacy and safety of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) in treating recurrent small hepatocellular carcinoma (HCC).

Methods: In this trial, patients with recurrent small HCC (single lesion ≤5 cm) were randomly assigned to receive either SBRT or RFA. The primary end point was local progression-free survival (LPFS), and secondary end points were progression-free survival (PFS), overall survival (OS), local control rate, and safety.

[Primary uterine hepatoid adenocarcinoma: Clinicopathological analysis of 2 cases and literature review].

Primary hepatoid adenocarcinoma (HAC) of the uterus is a particular tumour that bears high similarity to hepatocellular carcinoma histologically, and may easily be misdiagnosed because it is rare if you don' t remember it. In this report, we describe two cases of alpha-fetoprotein (AFP)-producing HAC of the uterus. Case 1 was a 69-year-old postmenopausal woman who was presented to the hospital for a medical examination.

Efficacy and safety of the combination of envafolimab and lenvatinib in unresectable hepatocellular carcinoma: a single-arm, multicentre, exploratory phase II clinical study.

Currently, therapeutic combinations of immune checkpoint inhibitors (ICIs) with anti-angiogenic agents have shown promising outcomes and have the potential to establish a new standard of care. The efficacy and safety of the first-line combination of envafolimab (an ICI) and lenvatinib (an anti-tumor angiogenesis drug) for the treatment of patients with inoperable hepatocellular carcinoma (HCC) have not been demonstrated. Unresectable HCC patients with an Eastern Cooperative Oncology Group (ECOG) physical status score ≤ 1 and a Child-Pugh score ≤ 7 who had not received systemic therapy were included in this single-arm, exploratory, multicentre phase II clinical study.

EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance.

Validation and epidemiologic definition of the novel steatotic liver disease nomenclature in a national United States cohort with cirrhosis.

Background And Aims: Novel steatotic liver disease (SLD) definitions were introduced in 2023. Accurate and meaningful classifications using clinical data are needed to study interventions and outcomes.

Methods: In a national cohort of Veterans with cirrhosis and imaging-confirmed steatosis, seven algorithms differentially emphasizing cardiometabolic risk factors (CMRFs) and alcohol exposure were developed to define alcohol-associated liver disease (ALD), metabolic dysfunction associated SLD (MASLD), and MASLD with increased alcohol intake (MetALD).

Sorafenib combined with tarexib for first-line treatment of unresectable hepatocellular carcinoma and its predictive role and correlation with PD-L1 CTCs.

Background: This study aims to evaluate the safety efficacy of combining the PD-1 antibody Tirelizumab with Sorafenib in the treatment of advanced hepatocellular carcinoma. Additionally we are committed to investigating the relationship between circulating tumor cell (CTC) counts/PD-L1 expression the prognosis of patients with advanced hepatocellular carcinoma.

Methods: This study included 32 patients with unresectable primary liver cancer who received treatment with Tislelizumab in combination with Sorafenib.