title: Hepatocellular carcinoma cases with high levels of c-Raf-1 expression may benefit from postoperative adjuvant sorafenib after hepatic resection even with high risk of recurrence.
abstract: OBJECTIVE
  Liver resection combined with postoperative sorafenib to prevent recurrence remains a controversial approach for cases of hepatocellular carcinoma (HCC), especially cases with a high risk of recurrence. This study aimed to investigate the efficacy and safety of liver resection combined with sorafenib for HCC with a high risk of recurrence.
  
  
  RESULTS
  Most of the cases of HCC were caused by hepatitis B virus (HBV) infection (23 cases, 92%). Most of these tumors (21 cases, 84%) were stage III according to the TNM staging system (12 cases with IIIa, 9 cases with IIIb). In the months after hepatic resection, 19 of the 25 cases (76%) were diagnosed with HCC recurrence or metastasis. Based on the tumor histological biomarker grading system, the group with higher expression levels of c-Raf-1 showed significantly longer overall survival than the group with lower expression of c-Raf-1 (P = 0.012). However, the long-term tumor-free survival advantage disappeared (P = 0.061). Univariate and multivariate analyses indicated that higher expression of c-Raf-1 was significantly associated with better overall survival (hazard ratio [HR]: 1.842; 95% confidence interval [CI]: 1.211-2.542; P = 0.031) and tumor-free survival (HR: 1.319; 95% CI: 1.017-1.543; P = 0.046) in HCC patients who underwent radical hepatic resection.
  
  
  METHODS
  We retrospectively collected 25 HCC cases with a high risk of recurrence who underwent radical liver resection and who took sorafenib postoperatively from Jan 2010 to Dec 2012. Factors that might contribute to tumor recurrence and treatment failure such as clinical factors, tumor features, and molecular biomarkers were included in our analysis.
  
  
  CONCLUSIONS
  HCC patients with a high risk of post-hepatic resection recurrence may benefit from postoperative sorafenib administered as an adjuvant therapy, especially in cases with high levels of c-Raf-1 expression on histological examination.
authors.affiliation: Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China.|Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.|State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Lei
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jinjing
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Hao
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Zhengni
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Third General Surgery, The First Hospital of Handan, Handan, Hebei, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Lixue
authors.initials: L
authors.lastname: Wu
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Lunan
authors.initials: L
authors.lastname: Yan
authors.affiliation: Thyroid and Parathyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Jinqiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Wen
authors.affiliation: Liver Surgery, West China Hospital of Sichuan University, Chengdu, China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Wang
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000188:drug therapy / Q000378:metabolism / Q000601:surgery; D006801:Humans; D008099:Liver / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011184:Postoperative Period; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D012008:Recurrence; D012189:Retrospective Studies; D000077157:Sorafenib
chemical_list: D014408:Biomarkers, Tumor; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D019908:Proto-Oncogene Proteins c-raf
keywords: hepatocellular carcinoma; liver resection; recurrence; risk factors; sorafenib