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Journal of Hepatology Mar 2022There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and... (Review)
Review
There have been major advances in the armamentarium for hepatocellular carcinoma (HCC) since the last official update of the Barcelona Clinic Liver Cancer prognosis and treatment strategy published in 2018. Whilst there have been advances in all areas, we will focus on those that have led to a change in strategy and we will discuss why, despite being encouraging, data for select interventions are still too immature for them to be incorporated into an evidence-based model for clinicians and researchers. Finally, we describe the critical insight and expert knowledge that are required to make clinical decisions for individual patients, considering all of the parameters that must be considered to deliver personalised clinical management.
Topics: Carcinoma, Hepatocellular; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Prognosis; Severity of Illness Index
PubMed: 34801630
DOI: 10.1016/j.jhep.2021.11.018 -
World Journal of Gastroenterology Feb 2023Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative... (Review)
Review
Hepatocellular carcinoma (HCC) is the most frequent liver neoplasm, and its incidence rates are constantly increasing. Despite the availability of potentially curative treatments (liver transplantation, surgical resection, thermal ablation), long-term outcomes are affected by a high recurrence rate (up to 70% of cases 5 years after treatment). HCC recurrence within 2 years of treatment is defined as "early" and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden. A recurrence that occurs after 2 years of treatment is defined as "late" and is related to de novo HCC, independent of the primary neoplasm. Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence. Different pathogenesis corresponds to different predictors of the risk of early or late recurrence. An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance. Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens. This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Prognosis; Neoplasm Recurrence, Local; Hepatectomy; Risk Factors; Retrospective Studies
PubMed: 36925456
DOI: 10.3748/wjg.v29.i8.1243 -
Signal Transduction and Targeted Therapy Aug 2020The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). Sorafenib has been the mainstay of... (Review)
Review
The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). Sorafenib has been the mainstay of treatment for a decade and newer modalities were ineffective and did not confer any increased therapeutic benefit until the introduction of lenvatinib which was approved based on its non-inferiority to sorafenib. The subsequent success of regorafenib in HCC patients who progress on sorafenib treatment heralded a new era of second-line treatment and was quickly followed by ramucirumab, cabozantinib, and the most influential, immune checkpoint inhibitors (ICIs). Over the same period combination therapies, including anti-angiogenesis agents with ICIs, dual ICIs and targeted agents in conjunction with surgery or other loco-regional therapies, have been extensively investigated and have shown promise and provided the basis for exciting clinical trials. Work continues to develop additional novel therapeutic agents which could potentially augment the presently available options and understand the underlying mechanisms responsible for drug resistance, with the goal of improving the survival of patients with HCC.
Topics: Carcinoma, Hepatocellular; Drug Delivery Systems; Drug Resistance, Neoplasm; Humans; Immune Checkpoint Inhibitors; Liver Neoplasms; Phenylurea Compounds; Pyridines; Sorafenib
PubMed: 32782275
DOI: 10.1038/s41392-020-00264-x -
Bioscience Trends Jul 2021Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and cirrhosis is a risk factor for HCC. Resection is indicated for those unilobar tumors... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and cirrhosis is a risk factor for HCC. Resection is indicated for those unilobar tumors without vascular invasion and metastases in the liver and preserved liver function. Small HCC (< 2 cm) without microvascular invasion is associated with a 5-year recurrence rate as high as 50% to 60%, whereas liver transplantation is indicated for those within the Milan criteria (solitary tumor ≤ 5 cm or two or three nodules ≤ 3 cm) who have decompensated cirrhosis. The 1-, 3-, and 5-year survival rates of living donor liver transplantation for HCC are 85%, 75%, and 70%, respectively. This review summarizes the scientific evidence supporting the clinical practice recommendations for patients with HCC, and it discusses surgical treatment of HCC.
Topics: Carcinoma, Hepatocellular; Disease-Free Survival; Evidence-Based Medicine; Hepatectomy; Humans; Liver Neoplasms; Liver Transplantation; Medical Oncology; Neoplasm Recurrence, Local; Neoplasm Staging; Practice Guidelines as Topic; Risk Factors; Survival Rate
PubMed: 33746184
DOI: 10.5582/bst.2021.01094 -
Cells Jun 2020Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. Thus, there is a constant search for improvement in screening, diagnosis, and treatment strategies to improve the prognosis of this malignancy. The identification of useful biomarkers for surveillance and early HCC diagnosis is still deficient, with available serum biomarkers showing low sensitivity and heterogeneous specificity despite different cut-off points, even when assessed longitudinally, or with a combination of serum biomarkers. In contrast, HCC biomarkers used for prognostic (when associated with clinical outcomes) or predictive purposes (when associated with treatment response) may have an increased clinical role in the near future. Furthermore, some serum biomarkers are already implicated as a treatment selection tool, whether to provide access to certain therapies or to assess clinical benefit after treatment. In the present review we will discuss the clinical utility and foreseen future of HCC biomarkers implicated in surveillance, diagnosis, prognosis, and post-treatment assessment.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Genomics; Humans; Liver Neoplasms; Neoplasm Staging; Prognosis; Treatment Outcome
PubMed: 32492896
DOI: 10.3390/cells9061370 -
Bioscience Trends Jul 2021The preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of... (Review)
Review
The preferred treatment for hepatocellular carcinoma (HCC) is surgery, which is the only way to achieve long-term survival and even a cure. However, the vast majority of patients with liver cancer in China are already in the middle to advanced stage of the disease and no longer have the opportunity to undergo surgery. The goal of conversion therapy is to transform unresectable advanced liver cancer or potentially resectable liver cancer into resectable cancer, so it has become a topic of interest in the treatment of advanced liver cancer. Common modalities of conversion therapy are: local treatment (TACE, TARE, or HAIC), systemic treatment (targeted therapy alone or combined with immunotherapy), and a therapeutic alliance (TACE combined with radiation therapy, TACE combined with targeted therapy, HAIC combined with targeted therapy, or HAIC combined with targeted therapy and immunotherapy). The plan for maintenance treatment after conversion therapy is determined based on the outcome of conversion therapy to obtain the best survival benefit for patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; China; Hepatectomy; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Survival Rate; Treatment Outcome
PubMed: 34039818
DOI: 10.5582/bst.2021.01091 -
World Journal of Gastroenterology Apr 2022Hepatocellular adenoma (HCA) is a benign hepatocellular neoplasm, commonly occurs in young women with a history of oral contraceptive use. Complications including...
Hepatocellular adenoma (HCA) is a benign hepatocellular neoplasm, commonly occurs in young women with a history of oral contraceptive use. Complications including hemorrhage and malignant transformation necessitate the need for a thorough understanding of the underlying molecular signatures in this entity. Recent molecular studies have significantly expanded our knowledge of HCAs. The well-developed phenotype-genotype classification system improves clinical management through identifying "high risk" subtype of HCAs. In this article, we attempt to provide updated information on clinical, pathologic and molecular features of each subtype of HCAs.
Topics: Adenoma, Liver Cell; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Female; Hemorrhage; Humans; Liver Neoplasms
PubMed: 35582672
DOI: 10.3748/wjg.v28.i14.1384 -
Signal Transduction and Targeted Therapy Jun 2020Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular... (Review)
Review
Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.
Topics: Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Drug Resistance, Neoplasm; Humans; Liver Neoplasms; Sorafenib; Tumor Microenvironment
PubMed: 32532960
DOI: 10.1038/s41392-020-0187-x -
Future Oncology (London, England) Apr 2021For a decade, sorafenib remained the only approved first-line treatment and standard of care for advanced hepatocellular carcinoma. The treatment landscape has been... (Review)
Review
For a decade, sorafenib remained the only approved first-line treatment and standard of care for advanced hepatocellular carcinoma. The treatment landscape has been evolving rapidly over the past 2 years with the approval of additional first-and second-line systemic treatments, most of which are targeted therapies. The expected approval of immunotherapies constitutes a paradigm shift: for the first time in years, a checkpoint inhibitor in combination with a VEGF antibody recently outperformed sorafenib with regards to efficacy. The wider availability of systemic therapies increases the chance for longer overall survival but raises new questions concerning the role of local options, treatment choice and sequential treatment. Following an expert discussion at the German Cancer Congress 2020 in Berlin, this article aims to summarize the current evidence on and experience of treatment choice and sequence in first- and second-line therapy.
Topics: Carcinoma, Hepatocellular; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Liver Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Treatment Outcome
PubMed: 33307782
DOI: 10.2217/fon-2020-0758 -
EBioMedicine Jan 2020In most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate... (Review)
Review
In most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate transition in response to sorafenib or other targeted drugs in the presence or absence of genetic mutations. Therefore, understanding the major characteristics of drug-resistant cells state helps to discover new treatments that overcome drug resistance. To note, little is known about the metabolic or microenvironmental aspects of the certain tumor cell states beyond the genome. This review mainly focuses on the underlying mechanisms of acquired sorafenib resistance based on CSCs and EMT models, which explain tumor heterogeneity and have been considered the major cause of secondary sorafenib resistance. In particular, it discusses how the tumor microenvironment and tumor metabolism regulate cell stemness, mesenchymal state, and sorafenib resistance through epigenetic regulations, and provides reliable targets that might have synergetic effect with sorafenib.
Topics: Carcinoma, Hepatocellular; Drug Resistance, Neoplasm; Epigenesis, Genetic; Humans; Liver Neoplasms; Sorafenib; Tumor Microenvironment
PubMed: 31918403
DOI: 10.1016/j.ebiom.2019.102610