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      Sex differences in disease presentation, treatment and clinical outcomes of patients with hepatocellular carcinoma: a single-centre cohort study

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          Abstract

          Background

          Although sex differences in hepatocellular carcinoma (HCC) risk are well known, it is unclear whether sex differences also exist in clinical presentation and survival outcomes once HCC develops.

          Methods

          We performed a retrospective cohort study of 1886 HCC patients seen in a US medical centre in 1998–2015. Data were obtained by chart review with survival data also by National Death Index search.

          Results

          The cohort consisted of 1449 male and 437 female patients. At diagnosis, men were significantly younger than women (59.9±10.7 vs 64.0±11.6, p<0.0001). Men had significantly higher rates of tobacco (57.7% vs 31.0%, p<0.001) and alcohol use (63.2% vs 35.1%, p<0.001). Women were more likely to be diagnosed by routine screening versus symptomatically or incidentally (65.5% vs 58.2%, p=0.03) and less likely to present with tumours >5 cm (30.2% vs 39.8%, p=0.001). Surgical and non-surgical treatment utilisation was similar for both sexes. Men and women had no significant difference in median survival from the time of diagnosis (median 30.7 (range=24.5–41.3) vs 33.1 (range=27.4–37.3) months, p=0.84). On multivariate analysis, significant predictors for improved survival included younger age, surgical or non-surgical treatment (vs supportive care), diagnosis by screening, tumour within Milan criteria and lower Model for End-Stage Liver Disease score, but not female sex (adjusted HR=1.01, CI 0.82 to 1.24, p=0.94).

          Conclusions

          Although men have much higher risk for HCC development, there were no significant sex differences in disease presentation or survival except for older age and lower tumour burden at diagnosis in women. Female sex was not an independent predictor for survival.

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          Most cited references19

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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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            Hepatocellular Carcinoma – Epidemiological Trends and Risk Factors

            Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide with about 600,000 patients dying from the disease annually. In 70–90%, HCC develops on the background of chronic liver cirrhosis or inflammation. Risk factors and etiologies vary among geographical regions. In regions with a high incidence the majority of cases are related to HBV and HCV hepatitis. In developed countries, in addition to virus-related HCC, high consumption of alcohol as well as non-alcoholic fatty liver disease often in the context of metabolic syndromes are the prevalent causes. Improvement in clinical management of patients with liver cirrhosis and the control of related complications are the key for the rising incidence of HCC. This review gives an overview on epidemiological trends and risk factors and their mechanisms involved in the hepatocarcinogenesis. Knowledge of these factors will help to improve current concepts for prevention, screening and treatment of this disease.
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              Hepatocellular carcinoma confirmation, treatment, and survival in surveillance, epidemiology, and end results registries, 1992-2008.

              Approaches to the diagnosis and management of hepatocellular carcinoma (HCC) are improving survival. In the Surveillance, Epidemiology, and End Results-13 registries, HCC stage, histological confirmation, and first-course surgery were examined. Among 21,390 HCC cases diagnosed with follow-up of vital status during 1998-2008, there were 4,727 (22%) with reported first-course invasive liver surgery, local tumor destruction, or both. The proportion with reported liver surgery or ablation was 39% among localized stage cases and only 4% among distant/unstaged cases. Though 70% of cases had histologically confirmed diagnoses, the proportion with confirmed diagnoses was higher among cases with reported invasive surgery (99%), compared to cases receiving ablation (81%) or no reported therapy (65%). Incidence rates of histologically unconfirmed HCC increased faster than those of confirmed HCC from 1992 to 2008 (8% versus 3% per year). Two encouraging findings were that incidence rates of localized-stage HCC increased faster than rates of regional- and distant-stage HCC combined (8% versus 4% per year), and that incidence rates of reported first-course surgery or tumor destruction increased faster than incidence rates of HCC without such therapy (11% versus 7%). Between 1975-1977 and 1998-2007, 5-year cause-specific HCC survival increased from just 3% to 18%. Survival was 84% among transplant recipients, 53% among cases receiving radiofrequency ablation at early stage, 47% among cases undergoing resection, and 35% among cases receiving local tumor destruction. Asian or Pacific Islander cases had significantly better 5-year survival (23%) than white (18%), Hispanic (15%), or black cases (12%). HCC survival is improving, because more cases are diagnosed and treated at early stages. Additional progress may be possible with continued use of clinical surveillance to follow individuals at risk for HCC, enabling early intervention. Copyright © 2011 American Association for the Study of Liver Diseases.
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                Author and article information

                Journal
                BMJ Open Gastroenterol
                BMJ Open Gastroenterol
                bmjgastro
                bmjgastro
                BMJ Open Gastroenterology
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2054-4774
                2016
                25 July 2016
                : 3
                : 1
                : e000107
                Affiliations
                [1 ]Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University Medical Center , Palo Alto, California, USA
                [2 ]Department of Biology, Washington University , St. Louis, Missouri, USA
                [3 ]Stanford University School of Medicine , Stanford, California, USA
                [4 ]Department of Medicine, Stanford Center for Prevention Research, Stanford University School of Medicine , Stanford, California, USA
                Author notes
                [Correspondence to ] Dr Mindie H Nguyen; mindiehn@ 123456stanford.edu
                Article
                bmjgast-2016-000107
                10.1136/bmjgast-2016-000107
                4964155
                27493763
                1de378c3-9463-4ad1-af7a-2c4b8f5872bf
                Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

                History
                : 12 June 2016
                : 5 July 2016
                Categories
                1506
                Hepatology

                hepatocellular carcinoma,surveillance,screening
                hepatocellular carcinoma, surveillance, screening

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