Hepatocellular carcinoma Forner, Alejandro, MD; Llovet, Josep M, MD; Bruix, Jordi, Dr
The Lancet (British edition),
03/2012, Letnik:
379, Številka:
9822
Journal Article
Recenzirano
Summary Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant ...disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50% can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ≤5 cm and up to three nodules ≤3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC)-closely associated with liver cirrhosis and, in fact, the main cause of death in patients with such disease-is now recognized as one of the most-prevalent and lethal ...neoplasms worldwide. Prognosis and allocation of the multiple available treatment options for patients with HCC are influenced not only by tumour stage, but also by the degree of liver-function impairment. Therefore, accurate assessment and classification of disease is important for patient management. According to the Barcelona Clinic Liver Cancer (BCLC) algorithm, intermediate-stage HCC is defined as extensive multifocal disease without vascular invasion in patients with preserved liver function and absence of cancer-related symptoms; in this context, transarterial chemoembolization (TACE) is considered the standard treatment. The use of drug-eluting beads has enabled standardization of this procedure, resulting in higher reproducibility and tolerability of the treatment. Nevertheless, not all patients with intermediate-stage HCC are good candidates for TACE and, for such patients in whom TACE is not appropriate or has failed, other treatments can be considered, including sorafenib. Radioembolization is a promising alternative that deserves further prospective studies. Herein, we review the current approaches used to accurately stratify patients with intermediate-stage HCC and subsequently allocate the most-appropriate treatments. The key developments in therapeutic strategies are also discussed.
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.
Cholangiocarcinoma (CCA) is a heterogeneous group of tumours, derived from cells of the biliary tree, which represent the second most frequent primary liver tumour. According to the most recent ...classifications, CCA can be subdivided into intrahepatic (iCCA) and extrahepatic (eCCA) which include perihilar (pCCA) and distal (dCCA) CCA. CCA are usually identified at advanced stages, when the primary tumour grows enough to produce a large liver mass or when jaundice has developed because of biliary tree obstruction. The ongoing challenges in the identification of risk factors and definition of a specific population at higher risk of developing CCA are the main challenges for the development of screening programs. Therefore, late diagnosis remains an unresolved issue in CCA. Imaging plays an important role in the detection and characterization of CCA, helping with radiological diagnosis, guiding biopsy procedures and allowing staging of the tumour. This review focuses on clinical presentations and diagnosis and staging techniques of CCA.
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently ...accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic ...iCCA, perihilar pCCA, and distal dCCA) in a pan-European cohort.
The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed.
Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. At diagnosis, 42.2% of patients had local disease, 29.4% locally advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival mOS = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 2.13; 95% CI 1.55-2.94; mOS = 23.3 months) compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors.
CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality.
This is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic 2C12, perihilar 2C18, or distal 2C15 affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe.
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•CCA subtypes present different risk factors and tumor features.•CA19-9 shows low sensitivity in early stages but increased sensitivity in advanced disease.•Under surgery, positive margins and lymph node invasion compromise survival.•ECOG-PS, disease status and CA19-9 are independent prognostic factors.
Staging and treatment indication are relevant topics in the management of patients with hepatocellular carcinoma (HCC) and for optimal results, they have to take into account liver function, tumor ...stage, and physical status. For any staging system to be meaningful it has to link staging with treatment indication; this should be based on robust scientific data. Currently, the sole proposal that serves both aims is the Barcelona Clinic Liver Cancer (BCLC) approach. It takes into account the relevant parameters of all important dimensions and divides patients into very early/early, intermediate, advanced, and end-stage. Early-stage HCC patients should be considered for potentially curative options such as resection, ablation, and transplantation. Patients at intermediate stage benefit from chemoembolization, whereas patients at an advanced stage, or who cannot benefit from options of higher priority, have sorafenib as the standard treatment. Finally, patients at end-stage should merely receive palliative care.
Recent advancements have improved the management of patients with liver cancer. Results of studies have informed how to stage and decide the optimal treatment option for each patient with an adequate ...balance between risks and benefits. The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy has been widely endorsed for this purpose. This is not a rigid system: One of the key aspects in the management of patients is the optimal timing for systemic treatment initiation and for declaring tumor progression and/or treatment failure. Some patients at intermediate or even early stage may be considered for systemic therapy as options of higher priority may have failed or may not be feasible. Sorafenib is the sole systemic agent that has shown efficacy in phase 3 trials. Other agents (sunitinib, brivanib, linifanib, everolimus, ramucirumab) have failed in terms of safety and/or survival benefit. Optimal sorafenib administration and adequate adherence of the patients are crucial requirements to obtain the benefits of the drug. Because development of adverse events has been shown to correlate with better outcome, careful dose adjustments should be in place while avoiding unnecessary treatment interruption. Furthermore, recent studies have shown that progression at imaging may not translate in poor prognosis and that treatment beyond progression may be considered if there is no option for a second-line research trial.In this review, the authors examine all of the controversial aspects that affect treatment initiation and maintenance, how response to treatment should be evaluated, and define the needs that are faced by current research.
The genomic era is changing the understanding of cancer, although translation of the vast amount of data available into decision-making algorithms is far from reality. Molecular profiling of ...hepatocellular carcinoma (HCC), the most common cause of death among cirrhotic patients and a fast-growing malignancy in Western countries, is enabling the advancement of novel approaches to disease diagnosis and management. Most HCCs arise on a cirrhotic liver, and predictably, an accurate genomic characterization will allow the identification of procarcinogenic signals amenable to selective targeting by chemopreventive strategies. Molecular diagnosis is currently feasible for small tumors, but it has not yet been formalized by scientific guidelines. Molecular treatment is a reality: Sorafenib confers unprecedented survival benefits in patients at advanced stages. Genomic information from tumor and nontumoral tissue will aid prognosis prediction and facilitate the identification of oncogene addiction loops, providing the opportunity for more personalized medicine.
The most common primary liver tumors are hepatocellular carcinoma and cholangiocarcinoma. They constitute the sixth most common neoplasia and the third cause of cancer-related deaths worldwide. ...Although both tumors may share etiologic factors, diagnosis, prognostic factors, and treatments, they differ substantially in determining distinctive clinical management. In recent years, significant advances have been made in the management of these neoplasms, particularly in advanced stages. In this review, we focus on the most relevant diagnostic, prognostic, and treatment aspects of both, hepatocellular carcinoma and cholangiocarcinoma, underlying their applicability in Latin America.
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