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
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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
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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)