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      Modified staging classification for intrahepatic cholangiocarcinoma based on the sixth and seventh editions of the AJCC/UICC TNM staging systems

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          Abstract

          Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems.

          We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan–Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging.

          Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696–0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P < .001), and the AJCC 6th edition staging system (0.712, P = .033). Moreover, in the stratified data, the differences between the stages identified using the modified AJCC staging classification were significant, especially among patients over 60 years in age, white patients and patients who underwent surgery.

          These findings suggest that the modified AJCC staging classification may be applicable to the staging of ICC and can be adopted in clinical practice.

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          Most cited references 23

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          Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment.

          To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.
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            Epidemiology of cholangiocarcinoma.

            Cholangiocarcinoma (CCA) is a cancer arising from the intra- or extrahepatic bile ducts and mainly characterized by its late diagnosis and fatal outcome. CCA is the second most common primary liver tumour and accounts for approximately 10-15% of all hepatobiliary malignancies. The development of CCA is linked to a wide spectrum of conditions causing biliary inflammation, cholestasis and inflammation of the liver. The geographic diversity of risk factors is reflected in considerable differences in incidence worldwide. Although data are not consistent, incidence seems to be rising in the Western World. Given the limited opportunities of treating advanced CCA, surveillance has been suggested as a strategy for detection of early disease in the high-risk group of patients with primary sclerosing cholangitis (PSC). In this review we present an updated overview of the epidemiology of CCA. We also highlight the risk of CCA in PSC with special focus on surveillance strategies.
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              Impact of classification of hilar cholangiocarcinomas (Klatskin tumors) on the incidence of intra- and extrahepatic cholangiocarcinoma in the United States.

              Cholangiocarcinomas are topographically categorized as intrahepatic or extrahepatic by the International Classification of Diseases for Oncology (ICD-O). Although hilar cholangiocarcinomas (Klatskin tumors) are extrahepatic cholangiocarcinomas, the second edition of the ICD-O (ICD-O-2) assigned them a histology code 8162/3, Klatskin, which was cross-referenced to intrahepatic cholangiocarcinoma. Recent studies in the United States that included this code (8162/3, Klatskin) with intrahepatic cholangiocarcinoma reported an increasing incidence of intrahepatic cholangiocarcinoma and a decreasing incidence of extrahepatic cholangiocarcinoma. To investigate the impact of this misclassification on site-specific cholangiocarcinoma incidence rates, we calculated annual percent changes (APCs) with data from the Surveillance, Epidemiology, and End Results (SEER) program using a Poisson regression model that was age-adjusted to the year 2000 U.S. population. All statistical tests were two-sided. During 1992-2000, when SEER used ICD-O-2, 1710 intrahepatic cholangiocarcinomas, 1371 extrahepatic cholangiocarcinomas, and 269 hilar cholangiocarcinomas identified by code 8162/3, Klatskin were diagnosed. Ninety-one percent (246 of 269) of the hilar cholangiocarcinomas were incorrectly coded as intrahepatic cholangiocarcinomas, resulting in an overestimation of intrahepatic cholangiocarcinoma incidence by 13% and underestimation of extrahepatic cholangiocarcinomas incidence by 15%. However, even after the exclusion of tumors that were coded to the histology code 8162/3, Klatskin, age-adjusted annual intrahepatic cholangiocarcinoma incidence increased during this period (APC = 4%, 95% confidence interval = 2% to 6%, P<.001).
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                August 2017
                25 August 2017
                : 96
                : 34
                Affiliations
                [a ]Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital
                [b ]Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian, People's Republic of China.
                Author notes
                []Correspondence: Yan-Ling Chen, Fujian Medical University Union Hospital, Fuzhou, Fujian, People's Republic of China (e-mail: drchenyl@ 123456126.com ).
                Article
                MD-D-17-02984 07891
                10.1097/MD.0000000000007891
                5572027
                28834905
                Copyright © 2017 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

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                Research Article
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