Clinicopathologic Characteristics and Prognoses for Multicentric Occurrence and Intrahepatic Metastasis in Synchronous Multinodular Hepatocellular Carcinoma Patients


Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and theoutcomes for patients are still poor. It is important to determine the original type of synchronous multinodularHCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosisafter treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentricoccurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC).
Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The controlgroup comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumoremboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study groupwere categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were usedto determine the important clinicopathologic characteristics in the two groups.
Results: In the study group, 20cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM.Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg),cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus andthe histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis andportal vein and/or microvascular tumor thrombus were independent factors differentiating between IM andMO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IMsubjects (25.7±4.8 months vs. 8.9±3.1 months, p=0.017). Similarly, the overall survival time of the MO subjectswas longer (31.6±5.3 months vs. 15.4±3.4 months, p=0.024). The multivariate analysis further demonstrated thatthe original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survivaltime. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictorsof overall survival time.
Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portalvein and/or microvascular tumor embolus and histological grade of the primary nodule are important factorsfor differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.