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Liver Resection Is Justified in Patients with BCLC Intermediate Stage Hepatocellular Carcinoma without Microvascular Invasion

  • Han Wang
  • You-Wen Qian
  • Meng-Chao Wu
  • Wen-Ming CongEmail author
Original Article
  • 36 Downloads

Abstract

Background

Large, multinodular (> 3 nodules and/or > 3 cm) hepatocellular carcinoma (HCC) is not an indication for liver resection based on the Barcelona Clinic Liver Cancer (BCLC) staging classification. We hypothesize that microvascular invasion (MVI) is a strong indication for surgery in these patients.

Methods

Between December 2009 and December 2010, a retrospective cohort of the patients with BCLC intermediate stage HCC undergoing surgical resection at Eastern Hepatobiliary Surgery Hospital was analyzed. Propensity score matching (PSM) was conducted to balance the patients with regard to their baseline characteristics. Survival analysis was performed according to the Kaplan–Meier method. Logistic regression was conducted to identify the predictors of MVI. Risk factors were evaluated using the Cox proportional hazards model.

Results

Among 323 patients, the MVI-negative group (26.0%) had a more favorable prognosis than did the MVI-positive group (5-year recurrence-free survival: 25.2% vs. 7.8%; 5-year overall survival: 49.5% vs. 24.0%). Similar results were identified after PSM. Compared with MVI-negative patients, MVI-positive patients experienced more early recurrence (< 2 years, P = 0.006), multinodular recurrence (P = 0.004), and extrahepatic recurrence (P = 0.026). Total bilirubin levels > 17.1 μmol/L, alpha fetal protein levels > 400 ng/mL, the presence of > 2 nodules, and the lack of a capsule were independent predictors of MVI.

Conclusions

In BCLC intermediate stage HCC, MVI predicted an adverse recurrence pattern and poor prognosis and has the potential to be used as a reference index when deciding whether to operate. Factors predictive of MVI could assist in choosing preoperative treatment and postoperative surveillance.

Keywords

Hepatocellular carcinoma Barcelona clinic liver cancer Intermediate stage Microvascular invasion Propensity score matching 

Abbreviations

HCC

Hepatocellular carcinoma

BCLC

Barcelona Clinic Liver Cancer

MVI

Microvascular invasion

PSM

Propensity score matching

AASLD

American Association for the Study of Liver Diseases

EASL

European Association for the Study of the Liver

MHCC

Multiple nodular HCC

TACE

Transarterial chemoembolization

IM

Intrahepatic metastasis

MO

Multicentric occurrence

ECOG

Eastern Cooperative Oncology Group

AFP

Alpha fetal protein

RFS

Recurrence-free survival

OS

Overall survival

TBIL

Total bilirubin

ALB

Albumin

RBC

Red blood cell

HR

Hazard ratio

CI

Confidence interval

OR

Odds ratio

Notes

Acknowledgments

We thank Hua Yu and Zhen-Ying Cao (Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Shanghai) for their advice regarding the pathological techniques used in this study.

Authors’ contributions

Conception: Wen-Ming Cong; study design: Wen-Ming Cong, Han Wang; administrative support: Meng-Chao Wu; data collection and acquisition: Han Wang, You-Wen Qian; data analysis: Han Wang; manuscript preparation: Han Wang, You-Wen Qian, Wen-Ming Cong; critical revision: Wen-Ming Cong; final approval of manuscript: all authors.

Funding

We received funding from the National Natural Science Foundation of China (Grant No. 81472278 and No. 8150101732), the Funds for Creative Research Groups of the National Natural Science Foundation of China (Grant No. 81521091), and the Scientific Research Foundation of the Shanghai Municipal Commission of Health and Family Planning (Grant No. 20154Y0140) for this study.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

11605_2019_4251_Fig4_ESM.png (230 kb)
Supplementary Fig. 1

Cumulative overall survival after the first recurrence in patients with and without microvascular invasion (PNG 230 kb)

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High resolution image (TIF 1210 kb)
11605_2019_4251_Fig5_ESM.png (293 kb)
Supplementary Fig. 2

Cumulative early recurrence-free survival (2A) and late recurrence-free survival (2B) in patients with and without microvascular invasion (PNG 293 kb)

11605_2019_4251_MOESM2_ESM.tif (1.5 mb)
High resolution image (TIF 1504 kb)
11605_2019_4251_Fig6_ESM.png (494 kb)
Supplementary Fig. 3

Cumulative recurrence-free survival (3A) and overall survival (3B) in patients with different degrees of risk for microvascular invasion (PNG 493 kb)

11605_2019_4251_MOESM3_ESM.tif (1.6 mb)
High resolution image (TIF 1616 kb)

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Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  1. 1.Department of PathologyEastern Hepatobiliary Surgery Hospital, The Second Military Medical UniversityShanghaiChina
  2. 2.Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer, The Second Military Medical University, Ministry of EducationShanghaiChina
  3. 3.Shanghai Key Laboratory of Hepatobiliary Tumor Biology, Eastern Hepatobiliary Surgery HospitalShanghaiChina
  4. 4.Department of Hepatic SurgeryEastern Hepatobiliary Surgery Hospital, The Second Military Medical UniversityShanghaiChina

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