Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels

BMC Cancer, Oct 2016

Background Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. Methods We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients’ cancer-specific survival and recurrence-free survival rates. Results High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). Conclusions We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management.

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Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels

Lin et al. BMC Cancer Intrahepatic cholangiocarcinoma prognostic determination using pre- operative serum C-reactive protein levels Zi-Ying Lin 0 1 Zhen-Xing Liang 0 1 Pei-Lin Zhuang 2 Jie-Wei Chen 0 1 Yun Cao 0 1 Li-Xu Yan 3 Jing-Ping Yun 0 1 Dan Xie 0 1 Mu-Yan Cai 0 1 0 Department of Pathology, Sun Yat-sen University Cancer Center , No. 651, Dongfeng Road East, 510060 Guangzhou , China 1 Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine , Guangzhou , China 2 Department of Prosthodontics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou , China 3 Department of Pathology and Laboratory Medicine, Guangdong General Hospital , Guangzhou , China Background: Serum C-reactive protein (CRP), an acute inflammatory response biomarker, has been recognized as an indicator of malignant disease progression. However, the prognostic significance of CRP levels collected before tumor removal in intrahepatic cholangiocarcinoma requires further investigation. Methods: We sampled the CRP levels in 140 patients with intrahepatic cholangiocarcinoma who underwent hepatectomies with regional lymphadenectomies between 2006 and 2013. A retrospective analysis of the clinicopathological data was performed. We focused on the impact of serum CRP on the patients' cancer-specific survival and recurrence-free survival rates. Results: High levels of preoperative serum CRP were significantly associated with well-established clinicopathologic features, including gender, advanced tumor stage, and elevated carcinoembryonic antigen and carbohydrate antigen 19-9 levels (P < 0.05). Univariate analysis demonstrated a significant association between high levels of serum CRP and adverse cancer-specific survival (P = 0.001) and recurrence-free survival (P < 0.001). In patients with stage I/II intrahepatic cholangiocarcinoma, the serum CRP level was a prognostic indicator for cancer-specific survival. In patients with stage I/II or stage III/IV, the serum CRP level was a prognostic indicator for recurrence-free survival (P < 0.05). Additionally, multivariate analysis identified serum CRP level in intrahepatic cholangiocarcinoma as an independent prognostic factor (P < 0.05). Conclusions: We confirmed a significant association of elevated pre-operative CRP levels with poor clinical outcomes for the tested patients with intrahepatic cholangiocarcinoma. Our results indicate that the serum CRP level may represent a useful factor for patient stratification in intrahepatic cholangiocarcinoma management. C-reactive protein; Intrahepatic cholangiocarcinoma; Prognosis - Background Cholangiocarcinoma is a relatively rare neoplasm acquired by humans. Recently, high incidence rates have been reported in Eastern Asia, and especially in Thailand [1]. Based on the location in the body where it develops, cholangiocarcinoma is further classified into intrahepatic, perihilar extrahepatic, or distal extrahepatic. Intrahepatic cholangiocarcinoma (IHCC) originates from the second segment of the bile duct, and is the least common of the cholangiocarcinoma classifications that a person could acquire. It accounts for 8–10 % of total cholangiocarcinoma cases diagnosed [2]. Its etiology is unknown, although various risk factors, including primary sclerosing cholangitis [3], liver fluke infestation [4], hepatolithiasis [5], and hepatitis viruses [6, 7], have been identified. These risk factors all induce a chronic inflammation in the biliary epithelium and partially obstruct the bile duct [8]. These risk factors are considered to be favorable for potential cancer development [8]. IHCC is seemingly incurable, has a rapid © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. progression, and is lethal in most cases, with the 5-years survival rate being less than 5 % for non-resectable cases [9]. Surgical resection offers only a chance to cure IHCC, but the outcomes vary widely across affected patients. Several prognostic factors have been identified for the prediction of IHCC patient survival. These factors include staging [10], para-aortic lymph node status [11], positive node to the total node ratio [12], tumor size, and the presence of multiple tumors [13]. Other novel molecular biomarkers, such as hepatoma-derived growth factor [14], SOX4 [15], loss of FBXW7 expression [16], Homer1 [17], and inactivation of Smad4 [18], se (...truncated)


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Zi-Ying Lin, Zhen-Xing Liang, Pei-Lin Zhuang, Jie-Wei Chen, Yun Cao, Li-Xu Yan, Jing-Ping Yun, Dan Xie, Mu-Yan Cai. Intrahepatic cholangiocarcinoma prognostic determination using pre-operative serum C-reactive protein levels, BMC Cancer, 2016, pp. 792, 16, DOI: 10.1186/s12885-016-2827-7