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      Management of hepatocellular carcinoma: An update

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          Abstract

          Since the publication of the American Association for the Study of Liver Diseases (AASLD) practice guidelines on the management of hepatocellular carcinoma (HCC) in 2005, new information has emerged that requires that the guidelines be updated. The full version of the new guidelines is available on the AASLD Web site at http://www.aasld.org/practiceguidelines/Documents/Bookmarked&percnt;20Practice%20Guidelines/HCCUpdate2010.pdf. Here, we briefly describe only new or changed recommendations. Surveillance and Diagnosis In the previous guideline, groups were specified for which surveillance was likely to be cost-effective because the hepatocellular carcinoma (HCC) incidence was high enough. New data on defining HCC risk have emerged for hepatitis B virus,1,2 hepatitis C virus,3 and autoimmune hepatitis.4 Surveillance is deemed cost-effective if the expected HCC risk exceeds 1.5% per year in patients with hepatitis C and 0.2% per year in patients with hepatitis B. Analysis of recent studies show that alpha-fetoprotein determination lacks adequate sensitivity and specificity for effective surveillance (and for diagnosis).5,6 Thus, surveillance has to be based on ultrasound examination. The recommended screening interval is 6 months. Diagnosis of HCC should be based on imaging techniques and/or biopsy.The 2005 diagnostic algorithm has been validated and the diagnostic accuracy of a single dynamic technique showing intense arterial uptake followed by “washout” of contrast in the venous-delayed phases has been demonstrated.7-9 Contrast-enhanced US may offer false positive HCC diagnosis in patients with cholangiocarcinoma and thus, has been dropped from the diagnostic techniques. The diagnostic algorithm is shown in Fig. 1. The application of dynamic imaging criteria should be applied only to patients with cirrhosis of any etiology and to patients with chronic hepatitis B who may not have fully developed cirrhosis or have regressed cirrhosis. Interpretation of biopsies and distinction between high-grade dysplatic nodules and HCC is challenging. Expert pathology diagnosis is reinforced by staining for glypican 3, heat shock protein 70, and glutamine synthetase, because positivity for two of these three stains confirms HCC.10 Fig. 1 Diagnostic algorithm for suspected HCC. CT, computed tomography; MDCT, multidetector CT; MRI, magnetic resonance imaging; US, ultrasound. Staging and Treatment of HCC The BCLC staging system (Fig. 2)11 has come to be widely accepted in clinical practice and is also being used for many clinical trials of new drugs to treat HCC. Therefore, it has become the de facto staging system that is used. Fig. 2 The BCLC staging system for HCC. M, metastasis classification; N, node classification; PS, performance status; RFA, radiofrequency ablation; TACE, transarterial chemoembolization. The recommendations for liver transplantation have not changed. No new data have emerged that can be used to define a new limit for expanding the patient selection criteria. The usefulness of portal pressure measurement to predict the outcome of patients and define optimal candidates for resection has been validated in Japan.12 Thus, resection should remain the first option for patients who have the optimal profile, as defined by the BCLC staging system. Although resection can be performed in some of these patients with advanced liver disease, the mortality is higher and they might be better served by liver transplantation or ablation. A cohort study of radiofrequency ablation demonstrated that complete ablation of lesions smaller than 2 cm is possible in more than 90% of cases, with a local recurrence rate of less than 1%.13 These data should be confirmed by other groups before positioning ablation as the first-line approach for very early HCC. The recommendations regarding patient selection and method of administration of chemoembolization are unchanged. Radioembolization, i.e., the intra-arterial injection of yttrium-90 bound to glass beads or to resin, has been shown to induce tumor necrosis, but there are no data comparing its efficacy to transarterial chemoembolization or to sorafenib treatment for those with portal vein invasion. However, for patients who have either failed transarterial chemoembolization or who present with more advanced HCC, new data indicates the efficacy of sorafenib (a multikinase inhibitor with activity against Raf-1, B-Raf, vascular endothelial growth factor receptor 2, platelet-derived growth factor receptor, c-Kit receptors, among other kinases) in prolonging life.14,15 Sorafenib induces a clinically relevant improvement in time to progression and in survival The magnitude of the improvement in survival compares with other established molecular targeted therapies for other advanced cancers, and the associated toxicity is easily managed without treatment-related mortality. The most frequent adverse events were diarrhea (sorafenib versus placebo: 11% versus 2%) and hand–foot skin reaction (sorafenib versus placebo: 8% versus <1%), fatigue, and weight loss. Sorafenib is now considered first-line treatment in patients with HCC who can no longer be treated with potentially more effective therapies. In summary, in the past decade HCC has gone from being an almost universal death sentence to a cancer that can be prevented, detected at an early stage, and effectively treated. Physicians caring for patients at risk need to provide high-quality screening, proper management of screen-detected lesions, and provision of therapy that is most appropriate for the stage of disease.

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          Most cited references 12

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          Current strategy for staging and treatment: the BCLC update and future prospects.

          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.
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            Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

            If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC
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              Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: Prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma.

              This study prospectively evaluates the accuracy of contrast-enhanced ultrasound (CEUS) and dynamic magnetic resonance imaging (MRI) for the diagnosis of nodules 20 mm or smaller detected during ultrasound (US) surveillance. We included 89 patients with cirrhosis [median age, 65 years; male 53, hepatitis C virus 68, Child-Pugh A 80] without prior hepatocellular carcinoma (HCC) in whom US detected a small solitary nodule (mean diameter, 14 mm). Hepatic MRI, CEUS, and fine-needle biopsy (gold standard) (FNB) were performed at baseline. Non-HCC cases were followed (median 23 months) by CEUS/3 months and MRI/6 months. FNB was repeated up to 3 times and on detection of change in aspect/size. Intense arterial contrast uptake followed by washout in the delayed/venous phase was registered as conclusive for HCC. Final diagnoses were: HCC (n = 60), cholangiocarcinoma (n = 1), and benign lesions (regenerative/dysplastic nodule, hemangioma, focal nodular hyperplasia) (n = 28). Sex, cirrhosis cause, liver function, and alpha-fetoprotein (AFP) levels were similar between HCC and non-HCC groups. HCC patients were older and their nodules significantly larger (P < 0.0001). First biopsy was positive in 42 of 60 HCC patients. Sensitivity, specificity, and positive and negative predictive values of conclusive profile were 61.7%, 96.6%, 97.4%, and 54.9%, for MRI, 51.7%, 93.1%, 93.9%, and 50.9%, for CEUS. Values for coincidental conclusive findings in both techniques were 33.3%, 100%, 100%, and 42%. Thus, diagnosis of HCC 20 mm or smaller can be established without a positive biopsy if both CEUS and MRI are conclusive. However, sensitivity of these noninvasive criteria is 33% and, as occurs with biopsy, absence of a conclusive pattern does not rule out malignancy. These results validate the American Association for the Study of Liver Disease (AASLD) guidelines.
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                Author and article information

                Journal
                Hepatology
                hep
                Hepatology (Baltimore, Md.)
                Wiley Subscription Services, Inc., A Wiley Company
                0270-9139
                1527-3350
                March 2011
                : 53
                : 3
                : 1020-1022
                Affiliations
                [1 ]Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain
                [2 ]University of Toronto and University Health Network Toronto, Canada
                Author notes
                Address reprint requests to: Jordi Bruix, M.D., Hospital Clinic, University of Barcelona, IDIPAPS, CIBERehd, c/Villarroel 170, Barcelona 08036, Catalonia, Spain. E-mail: bruix@ 123456ub.edu ; fax: (34) 93-227-9803.

                Potential conflict of interest: Dr. Bruix advises, consults for, serves on the speaker's bureau of, and received grants from Bayer. Dr. Bruix consults for Biocompatibles, GlaxoSmithKline, Kowa, Novartis, and Arqule. Dr. Bruix also advises and consults for Bristol-Myers Squibb. Dr. Sherman serves on the speakers' bureau of Bayer

                Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

                Article
                10.1002/hep.24199
                3084991
                21374666
                Copyright © 2011 American Association for the Study of Liver Diseases

                Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.

                Categories
                AASLD Practice Guideline

                Gastroenterology & Hepatology

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