title: Clinicopathologic characteristics and prognoses for multicentric occurrence and intrahepatic metastasis in synchronous multinodular hepatocellular carcinoma patients.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment.
  
  
  OBJECTIVE
  To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (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 control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups.
  
  
  RESULTS
  In the study group, 20 cases 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 and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects (25.7 ∓ 4.8 months vs. 8.9 ∓ 3.1 months, p=0.017). Similarly, the overall survival time of the MO subjects was longer (31.6 ∓ 5.3 months vs. 15.4 ∓ 3.4 months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time.
  
  
  CONCLUSIONS
  HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.
authors.affiliation: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Shi-Lai
authors.initials: SL
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Su
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Kai-Yin
authors.initials: KY
authors.lastname: Xiao
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Shang
authors.forename: Bang-Hao
authors.initials: BH
authors.lastname: Xu
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Su
authors.forename: Xin-Ping
authors.initials: XP
authors.lastname: Ye
authors.forename: Ning
authors.initials: N
authors.lastname: Peng
authors.forename: Quan-Lin
authors.initials: QL
authors.lastname: Qin
authors.forename: De-Feng
authors.initials: DF
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Le-Qun
authors.initials: LQ
authors.lastname: Li
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics / Q000556:secondary*; D004272:DNA, Mitochondrial; D018572:Disease-Free Survival; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology*; D008297:Male; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009378:Neoplasms, Multiple Primary / Q000097:blood / Q000235:genetics / Q000473:pathology*; D011169:Portal Vein / Q000473:pathology; D017422:Sequence Analysis, DNA; D013997:Time Factors; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D006513:Hepatitis B e Antigens