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      Pattern of distant extrahepatic metastases in primary liver cancer: a SEER based study

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          Abstract

          Background and Aims: Primary liver cancer remains still the common cause of cancer-related deaths globally and the prognosis for patients with extrahepatic metastasis is poor. The aim of our study was to assess extrahepatic metastatic pattern of different histological subtypes and evaluate prognostic effects of extrahepatic metastasis in patients with advanced disease.

          Methods: Based on the Surveillance, Epidemiology and End Results (SEER) database, eligible patients diagnosed with primary liver cancer was identified between 2010 to 2012. We adopted Chi-square test to compared metastasis distribution among different histological types. We compared survival difference of patients with different extrahepatic metastasises by Kaplan-Meier analysis. Cox proportional hazard models were performed to identify other prognostic factors of overall survival.

          Results: We finally identified 8677 patients who were diagnosed with primary liver cancer from 2010 to 2012 and 1775 patients were in distant metastasis stages. Intrahepatic cholangiocarcinoma was more invasive and had a higher percentage of metastasis compared with hepatocellular carcinoma. Lung was the most common metastasis and brain was the least common site for both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Extrahepatic metastasis could consider as an independent prognostic factor for patients with liver cancer. Patients with brain metastasis had the worst prognosis, compared with other metastasis in overall survival (OS) and cancer-specific survival (CSS) analysis.

          Conclusions: Different histological subtypes of liver cancer had different metastasis patterns. There were profound differences in risk of mortality among distant extrahepatic metastatic sites. Results from our studies would provide some information for follow-up strategies and future studies.

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          Emerging trends in hepatocellular carcinoma incidence and mortality.

          The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence-based (IB) mortality in HCC from 1973 to 2011. Secular trends in age-adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality.
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            Extrahepatic metastases of hepatocellular carcinoma.

            To determine the relative frequency, incidence, and locations of metastases of hepatocellular carcinoma (HCC), correlate extrahepatic metastatic disease with intrahepatic tumor staging, and determine the computed tomographic (CT) manifestations of HCC metastases. CT findings in 403 consecutive patients with HCC at our institution since 1992 were reviewed retrospectively. One hundred forty-eight patients with extrahepatic metastatic HCC were identified, and the locations, sizes, and attenuation and enhancement characteristics of the lesions were recorded. A majority (128 [86%] of 148) of patients with extrahepatic HCC foci had either intrahepatic stage IVA tumor (112 [76%] patients) or an intrahepatic stage III tumor (16 [11%] patients) at the occurrence of metastases. The most frequent site of the first detectable metastasis was the lung (58 [39%] patients). Tabulation of all extrahepatic metastatic sites showed the most common to be the lung in 81 (55%) patients, the abdominal lymph nodes in 60 (41%) patients, and the bone in 41 (28%) patients. The lung, abdominal lymph nodes, and bone are the most common sites of extrahepatic metastatic HCC. Most extrahepatic HCC occurs in patients with advanced intrahepatic tumor stage (stage IVA). Incidental extrahepatic lesions at CT in patients with stage I or II intrahepatic HCC are unlikely to represent metastatic HCC.
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              Clinical features of hepatocellular carcinoma with extrahepatic metastases.

              There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC. The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed. Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1-59 months) and 24.9%, respectively. Patients with Child-Pugh grade B and C (P = 0.0018) and patients with positive serum alpha-fetoprotein (P = 0.011) had significantly poor prognosis. Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method. (c) 2005 Blackwell Publishing Asia Pty Ltd.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2017
                21 July 2017
                : 8
                : 12
                : 2312-2318
                Affiliations
                [1 ]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
                [2 ]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China
                [3 ]Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University Medical School, Hangzhou 310016, China
                Author notes
                ✉ Corresponding author: State Key Laboratory for Diagnosis and Treatment of Infectious Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, P. R. China. Tel.: +86-571-8723-6458; Fax: +86-571-8723-6459; E-mail: ljli@ 123456zju.edu.cn .

                *Authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interests exist.

                Article
                jcav08p2312
                10.7150/jca.19056
                5560150
                28819435
                34a3735f-193d-4a74-9c28-a3c09926f3ab
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 4 January 2017
                : 2 May 2017
                Categories
                Research Paper

                Oncology & Radiotherapy
                neoplasm metastasis,liver neoplasms,seer program,survival analysis
                Oncology & Radiotherapy
                neoplasm metastasis, liver neoplasms, seer program, survival analysis

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