Annals of Surgical Oncology

, Volume 20, Issue 4, pp 1223–1229

Microvascular Invasion Does Not Predict Long-Term Survival in Hepatocellular Carcinoma up to 2 cm: Reappraisal of the Staging System for Solitary Tumors

  • Junichi Shindoh
  • Andreas Andreou
  • Thomas A. Aloia
  • Giuseppe Zimmitti
  • Gregory Y. Lauwers
  • Alexis Laurent
  • David M. Nagorney
  • Jacques Belghiti
  • Daniel Cherqui
  • Ronnie Tung-Ping Poon
  • Norihiro Kokudo
  • Jean-Nicolas Vauthey
Hepatobiliary Tumors



Excellent long-term outcomes have been reported recently for patients with small (≤2 cm) hepatocellular carcinoma (HCC). However, the significance of microvascular invasion (MVI) in small HCC remains unclear. The purpose of this study was to determine the impact of MVI in small HCC up to 2 cm.


In 1,109 patients with solitary HCC from six major international hepatobiliary centers, the impact of MVI on long-term survival in patients with small HCC (≤2 cm) and patients with tumors larger than 2 cm was analyzed.


In patients with small HCC, long-term survival was not affected by MVI (p = 0.8), whereas in patients with larger HCC, significantly worse survival was observed in patients with MVI (p < 0.0001). In multivariate analysis, MVI (hazard ratio [HR] 1.59; 95 % confidence interval (CI) 1.27–1.99; p < 0.001), elevated alpha-fetoprotein (HR 1.41; 95 % CI 1.11–1.8; p = 0.005), and higher histologic grade (HR 1.29; 95 % CI 1.01–1.64; p = 0.04) were significant predictors of worse survival in patients with HCC larger than 2 cm but were not correlated with long-term survival in small HCC. When the cohort was divided into three groups—HCC ≤2, >2 cm without MVI, and HCC >2 cm with MVI—significant between-group survival difference was observed (p < 0.0001).


Small HCC is associated with an excellent prognosis that is not affected by the presence of MVI. The discriminatory power of the 7th edition of the AJCC classification for solitary HCC could be further improved by subdividing tumors according to size (≤2 vs. >2 cm).


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Copyright information

© Society of Surgical Oncology 2012

Authors and Affiliations

  • Junichi Shindoh
    • 1
  • Andreas Andreou
    • 1
  • Thomas A. Aloia
    • 1
  • Giuseppe Zimmitti
    • 1
  • Gregory Y. Lauwers
    • 2
  • Alexis Laurent
    • 3
  • David M. Nagorney
    • 4
  • Jacques Belghiti
    • 5
  • Daniel Cherqui
    • 3
  • Ronnie Tung-Ping Poon
    • 6
  • Norihiro Kokudo
    • 7
  • Jean-Nicolas Vauthey
    • 1
  1. 1.International Cooperative Study Group on Hepatocellular Carcinoma, Department of Surgical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of PathologyMassachusetts General HospitalBostonUSA
  3. 3.Department of Digestive and Hepatobiliary Surgery and Liver TransplantationHôpital Henri MondorCréteilFrance
  4. 4.Department of Gastroenterologic and General SurgeryMayo ClinicRochesterUSA
  5. 5.Department of Hepato-pancreato-biliary and Transplantation SurgeryBeaujon Hospital, Assistance Publique Hôpitaux de ParisClichyFrance
  6. 6.Department of Surgery, Queen Mary HospitalThe University of Hong KongHong KongChina
  7. 7.Hepato-biliary-pancreatic Surgery Division, Department of SurgeryUniversity of TokyoTokyoJapan

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