Purpose: To develop and validate a decision aid to help make individualized estimates of tumor recurrence for patients with resected combined hepatocellular cholangiocarcinoma (CHC).
Patients and methods: Risk factors of recurrence were identified in the derivation cohort of 208 patients who underwent liver resection between 1995 and 2014 at Zhongshan Hospital to develop a prediction score. The model was subsequently validated in an external cohort of 101 CHC patients using the C concordance statistic and net reclassification index (NRI).
Results: On multivariate analysis, five independent predictors associated with tumor recurrence were identified, including sex, γ-glutamyl transferase, macrovascular invasion, hilar lymphoid metastasis and adjuvant transcatheter arterial chemoembolization. The prediction score was constructed using these 5 variables, with scores ranging from 0 to 5. A patient with a score of 0 had a predicted 1- and 5-year recurrence risk of 11.1% and 22.2%, respectively. In the validation cohort, the NRIs of prediction score vs American Joint Committee on Cancer 7th, TNM staging system at 1-year and 5-year were 0.185 (95% CI, 0.090–0.279, P<0.001) and 0.425 (95% CI, 0.044–0.806, P=0.03), respectively.
Conclusion: Our developed and validated prediction score might be a simple and reliable method in postoperative CHC patients and help clinicians identify candidates who may benefit from future adjuvant therapies.

Keywords: combined hepatocellular cholangiocarcinoma, recurrence prediction, prognosis, liver resection


Combined hepatocellular cholangiocarcinoma (CHC) is a rare liver malignancy, accounting for 0.4~14.2% of all primary liver cancers.1 It is comprised of dual histologic features: hepatocellular and biliary epithelial differentiation. Since the first report of Allen and Lisa in 1949,2 there have been an increasing number of clinical studies describing both the demographic and clinical features of CHC.3–5Due to the limitations of small study populations in previous reports, the demographic, clinical characteristics, and prognostic factors are far from clearly understood.6

Over the past decades, many staging systems have been developed to guide the prognosis and treatment of patients with hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC), including the Barcelona Clinic Liver Cancer,7 Hong Kong Liver Cancer,8 American Joint Committee on Cancer (AJCC) 7th edition,9 Nathan10 and Liver Cancer Study Group of Japan staging systems,11 but none for CHC patients. Previously, we established a novel risk prediction model that could be applied to facilitate the diagnosis of CHC patients in contrast to HCC or ICC patients.12 Further, we observed that surgical resection could provide the same outcome between elderly and younger patients.13Though CHCs share similar clinical and pathological characteristics (mean age, positive viral hepatitis and solitary tumors) with HCC patients, the features of CHC are genetically closer to that of ICC.5,14Considering the vastly different mechanisms of carcinogenesis and biological behavior, the current cancer classification for HCC or ICC may not be suitable for CHC patients. Thus, developing an accurate recurrence prediction model would make a contribution to treatment for CHC patients postoperatively.

In the present study, our aim was to establish a prognostic estimation of CHCs after resection (PECAR) score predicting recurrence on the basis of the clinicopathological data from Zhongshan Hospital and validate with an external cohort from Mengchao Hepatobiliary Hospital in China.

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