Dataset Information

New insights into the pathophysiology and clinical care of rare primary liver cancers.

ABSTRACT: Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (DNAJB1-PRKCA and CAMTA1-WWTR1 fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which remains challenging even in an expert centre because of the low incidences of these liver cancers. Resection, when feasible, is the cornerstone of treatment, together with liver transplantation for hepatic haemangioendothelioma. The role of locoregional therapies and systemic treatments remains poorly studied. In this review, we aim to describe the recent advances in terms of diagnosis and clinical management of these rare primary liver cancers.

SUBMITTER: Gigante E

PROVIDER: S-EPMC7653076 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New insights into the pathophysiology and clinical care of rare primary liver cancers.

Gigante Elia E Paradis Valérie V Ronot Maxime M Cauchy François F Soubrane Olivier O Ganne-Carrié Nathalie N Nault Jean-Charles JC

JHEP reports : innovation in hepatology 20200824 1

Hepatocholangiocarcinoma, fibrolamellar carcinoma, hepatic haemangioendothelioma and hepatic angiosarcoma represent less than 5% of primary liver cancers. Fibrolamellar carcinoma and hepatic haemangioendothelioma are driven by unique somatic genetic alterations (<i>DNAJB1-PRKCA</i> and <i>CAMTA1-WWTR1</i> fusions, respectively), while the pathogenesis of hepatocholangiocarcinoma remains more complex, as suggested by its histological diversity. Histology is the gold standard for diagnosis, which ...[more]

PMID: 33205035

Similar Datasets

Project description:Background: Rare cancers occur with an incidence of no more than six cases per 100,000 people according to the definition used by the Surveillance of Rare Cancers in Europe project. For a variety of reasons (low prevalence, cytotoxicity), it is challenging to perform the necessary clinical studies to investigate the safety and efficacy of investigational medicines against such rare malignancies, reformulating even at the earliest stages of the drug development process. This article investigates the differences between phase I rare cancer trials performed in commercial (companies) and non-commercial settings (academic hospitals). Materials and Methods: The differences were explored through the conduct of semi-structured interviews with three different stakeholder groups: representatives from academia (n = 7), representatives from companies (n = 4) and representatives from patient organizations (n = 4). All the interviews were transcribed verbatim and analyzed in NVivo using the framework method. Results: According to the interviewees, the academic and commercial stakeholders collaborate in the majority of phase I rare cancer trials. In general, the commercial partner finances the trial, whereas academia is responsible for the execution of the study procedures. The average cost of undertaking these trials is difficult to estimate because it depends on what is specifically requested during the trial. The 3 + 3 study design remains the most widely used design and the use of expansion cohorts is controversial. With regard to the regulatory aspects of phase I rare cancer trials, it was expressed that a good regulatory framework facilitates the conduct of these studies, but that increased regulation and oversight also has drawbacks, e.g., differences in standards between different ethics committees, over interpretation of the rules, insufficient availability of qualified personnel and higher workloads. The patient organization representatives claimed that patients experience no differences in terms of accommodation, compensation and paperwork between the academic and commercial settings or the degree of follow-up. They also believed that the direct input of patients can bring added value to such studies not only with regard to the recruitment process and the feasibility of the study but also the legibility of the informed consent forms. Conclusion: The growing need for first-in-man trials in rare malignancies needs to be highlighted, as difficult as they are to undertake and to co-develop, not only because rare cancer patients deserve an appropriate treatment, but also because these medicines represent the future of cancer therapy in the precision medicine era. Cooperation of commercial and academic sites are needed. Patient organizations need to be educated to take part in this process.

Project description:Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

Project description:Cirrhotic cardiomyopathy (CCM) is defined as systolic or diastolic dysfunction in the absence of prior heart disease or another identifiable cause in patients with cirrhosis, in whom it is an important determinant of outcome. Its underlying pathogenic/pathophysiological mechanisms are rooted in two distinct pathways: 1) factors associated with portal hypertension, hyperdynamic circulation, gut bacterial/endotoxin translocation and the resultant inflammatory phenotype; 2) hepatocellular insufficiency with altered synthesis or metabolism of substances such as proteins, lipids, carbohydrates, bile acids and hormones. Different criteria have been proposed to diagnose CCM; the first in 2005 by the World Congress of Gastroenterology, and more recently in 2019 by the Cirrhotic Cardiomyopathy Consortium. These criteria mainly utilised echocardiographic evaluation, with the latter refining the evaluation of diastolic function and integrating global longitudinal strain into the evaluation of systolic function, an important addition since the haemodynamic changes that occur in advanced cirrhosis may lead to overestimation of systolic function by left ventricular ejection fraction. Advances in cardiac imaging, such as cardiac magnetic resonance imaging and the incorporation of an exercise challenge, may help further refine the diagnosis of CCM. Over recent years, CCM has been shown to contribute to increased mortality and morbidity after major interventions, such as liver transplantation and transjugular intrahepatic portosystemic shunt insertion, and to play a pathophysiologic role in the genesis of hepatorenal syndrome. In this review, we discuss the pathogenesis/pathophysiology of CCM, its clinical implications, and the role of cardiac imaging modalities including MRI. We also compare diagnostic criteria and review the potential diagnostic role of electrocardiographic QT prolongation. At present, no definitive medical therapy exists, but some promising potential treatment strategies for CCM are reviewed.

Dataset Information

New insights into the pathophysiology and clinical care of rare primary liver cancers.

Publications

New insights into the pathophysiology and clinical care of rare primary liver cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets