ORIGINAL PAPER

Long-term outcomes after curative resection for patientswith macroscopically solitary hepatocellular carcinomawithout macrovascular invasion and an analysis of prognosticfactors

Shu-Hong Li • Wei Wei • Rong-Ping Guo •

Ming Shi • Zhi-Xing Guo • Zhi-Yuan Chen •

Cheng-Zuo Xiao • Mu-Yan Cai • Lie Zheng

Received: 25 June 2013 / Accepted: 9 August 2013 / Published online: 22 August 2013

� Springer Science+Business Media New York 2013

Abstract The long-term outcome and prognostic factors

after curative in patients with single hepatocellular carci-

noma (HCC) without macrovascular invasion are still

unclear. The objective of this study is to evaluate the effect

of curative resection on survival and analyze the prognostic

clinicopathologic factors, especially the presence of micro-

vascular invasion (MVI), in these patients. Two hundred and

sixty consecutive patients with single HCC without macro-

vascular invasion who underwent curative resection from

December 2004 to December 2007 were retrospectively

reviewed in this study. Survival rates were calculated by

using the Kaplan–Meier method. Univariate and multivari-

ate analyses of 14 clinicopathologic factors were performed

to determine the significant prognostic factors. No patient

died within 1 month after the operation. The 1-, 3-, and

5-year overall survival rates after curative resection were

96.54, 83.46, and 74.01 %, respectively. Multivariate anal-

ysis revealed that only the presence of MVI was an

independent negative prognostic factor affecting overall

survival. The 1-, 3-, and 5-year disease-free survival rates

were 79.62, 62.69, and 56.01 %, respectively. The presence

of MVI was the only independent unfavorable prognostic

factor for disease-free survival. According to our analysis,

patients with single HCC without macrovascular invasion

after curative resection can be expected to have considerable

long-term survival. The presence of MVI was an indepen-

dent negative prognostic factor for both overall survival and

disease-free survival. To improve the prognosis, these

patients should be followed up more carefully and might be

good candidates for adjuvant therapy.

Keywords Hepatocellular carcinoma �Hepatectomy � Prognostic factor � Survival �Tumor recurrence � Microvascular invasion

Shu-Hong Li and Wei Wei contributed to the manuscript equally.

S.-H. Li � W. Wei � R.-P. Guo (&) � M. Shi � Z.-Y. Chen �C.-Z. Xiao

Department of Hepatobiliary Oncology, Cancer Center,

Sun Yat-sen University, 651 Dongfeng Road East,

Guangzhou 510060, People’s Republic of China

e-mail: guorp@sysucc.org.cn

S.-H. Li � W. Wei � R.-P. Guo � M. Shi � Z.-X. Guo �Z.-Y. Chen � C.-Z. Xiao � M.-Y. Cai � L. Zheng

State Key Laboratory of Oncology in South China,

Cancer Center, Sun Yat-sen University, 651 Dongfeng Road

East, Guangzhou 510060, People’s Republic of China

Z.-X. Guo

Department of Ultrasound, Cancer Center, Sun Yat-sen

University, 651 Dongfeng Road East, Guangzhou 510060,

People’s Republic of China

C.-Z. Xiao

Department of General Surgery, Shenzhen Shajing Affiliated

Hospital of Guangzhou Medical University, 3 Shajing

Town Street, Shengzheng 518104, People’s Republic of China

M.-Y. Cai

Department of Pathology, Cancer Center, Sun Yat-sen

University, 651 Dongfeng Road East, Guangzhou 510060,

People’s Republic of China

L. Zheng

Department of Medical Imaging and Interventional Radiology,

Cancer Center, Sun Yat-sen University, 651 Dongfeng Road

East, Guangzhou 510060, People’s Republic of China

123

Med Oncol (2013) 30:696

DOI 10.1007/s12032-013-0696-3

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common

malignancy worldwide [1]. Although it is common in Asia

and Africa, the incidence of HCC has increased rapidly in

the USA [2]. Because of technical improvements in hepatic

resection and earlier diagnosis, the overall and disease-free

survival rates after resection of HCC have improved sig-

nificantly in recent decades [3]. However, long-term sur-

vival remains unsatisfactory because of a high incidence of

recurrence. Even after curative resection, the postoperative

recurrence rate remains high, and most recurrences tend to

occur in remnant liver.

The tumor number [4–7] and macrovascular invasion

[4, 7] are poor predictive factors after resection in HCC

patients. The latest TNM classification for HCC from

UICC/AJCC also emphasizes that the number of nodes and

vascular invasion are the crucial factors for classification

and prognosis of HCC [8]. Although several previous

studies have reported the outcomes and prognostic factors

after hepatectomy in patients with single HCC [7, 9, 10],

they were performed in patients who had confounding

factors, such as noncurative resection [7, 9] and macro-

vascular invasion [7, 9, 10]. So far, no study has focused on

patients with single HCC without macrovascular invasion,

and the long-term outcome and prognostic factors of these

patients remain unknown.

Tumor vessel invasion can be divided into macroscopic

and microscopic or only microscopic. Macroscopic vessel

invasion is an important prognostic factor after surgical

resection of HCC [4, 7]. Although several studies have

suggested that the presence of MVI is an independent

factor predictive of poor survival after resection of HCC

[11–14], the prognostic significance of MVI after curative

resection of patients with solitary HCC without macro-

vascular invasion is still unclear.

We retrospectively reviewed 260 patients with single

HCC without macrovascular invasion. The purpose of this

study was to evaluate the prognostic value of clinical and

histopathologic variables, especially MVI, after curative

resection.

Materials and methods

Patients

From December 2004 to December 2007, 491 consecutive

patients with macroscopically single HCC underwent

hepatectomy in the Hepatobiliary Department of the Sun

Yat-sen University Cancer Center. The diagnosis of HCC

was confirmed by histopathologic examination. Patient

inclusion criteria for this study were as follows: (1)

macroscopically single HCC; (2) no evidence of macro-

vascular invasion as evaluated by two independent, expe-

rienced imaging physicians who examined the preoperative

imaging and resected specimens; (3) underwent curative

hepatic resection; (4) received no previous therapy. Cura-

tive resection of single HCC without macrovascular inva-

sion was performed as described. First, the tumor was

resected. Second, negative surgical margins were con-

firmed by histologic examination. Third, the absence of

extrahepatic metastasis was confirmed. Fourth, the absence

of a residual tumor was confirmed by dynamic contrast-

enhanced computerized tomography (CT) or ultrasonog-

raphy 3–5 weeks postsurgery. Of these 491 patients, 293

patients met these criteria. Thirty-three of the 293 patients

were excluded from the study because detailed records

regarding survival and/or cancer recurrence were not

available, and the remaining 260 patients were enrolled in

this study.

Clinicopathologic variables

We obtained the following clinicopathologic information

from chart review: gender, age, ALT, AST, albumin, total

bilirubin, prothrombin time, hepatitis B serology, HCV-Ab,

cirrhosis, AFP, tumor size, tumor capsule, Edmondson–

Steiner grade, microvascular invasion, resection margin,

blood loss, blood transfusion, and hepatectomy procedure.

Tumor size was based on the largest diameter of the tumor

specimen. The width of the surgical margin was measured

as the smallest distance from the tumor edge to the resec-

tion line.

The histologic grade (I–IV) was determined by using the

criteria of Edmondson and Steiner and was based on the

areas showing the highest grade. Microvascular invasion

was defined as the presence of clusters of cancer cells

floating in the vascular space lined by endothelial cells on

histopathologic examination of the resected specimens.

The presence of MVI was assessed by two independent

pathologists.

Patient follow-up

After discharge, ultrasonography or contrast-enhanced

dynamic CT was performed monthly in the first

2–3 months after surgery, then every 2–3 months in the

first year, and every 3–6 months thereafter. When tumor

recurrence or metastasis was suspected, further investiga-

tions, including magnetic resonance imaging (MRI),

hepatic angiography, and biopsies, were performed. Tele-

phone calls were performed when necessary. The follow-

up data were regularly updated in the database for each

patient. Follow-up data were obtained from the patient’s

database for this study. Follow-up ended on September 1,

Page 2 of 8 Med Oncol (2013) 30:696

123

2012 or the date of the patient’s death. By the end of fol-

low-up, none of the 260 patients were lost. The median

follow-up of the 260 patients was 60.90 months (range

5.40–93.87 months).

Statistical analysis

Overall survival (OS) was measured from the date of

hepatectomy to death or the most recent follow-up time.

Disease-free survival (DFS) was measured from the date of

hepatic resection to the date of the first diagnosis of tumor

recurrence or the most recent follow-up time. Survival rates

were calculated by using the Kaplan–Meier method. Sur-

vival rates were compared by the log-rank test for uni-

variate analysis. All of the variables that were significant in

univariate analysis were then entered into a Cox propor-

tional hazards model for multivariate analysis by using

stepwise selection to identify independent variables corre-

lated with disease-free survival and overall survival. Sta-

tistical analysis was performed by using SPSS 16.0 for

Windows. p values \ 0.05 were considered statistically

significant.

Results

Clinicopathologic characteristics

There were 35 women and 225 men. The median age was

49 years (range 15–76, mean 49.15 ± 11.68). All 260

patients in this study were stage I according to the 7th

NCCN TNM classification for HCC. Table 1 summarizes

the clinicopathologic characteristics of the 260 patients

with single HCC without macrovascular invasion.

Predictors of overall survival

No patients died within 1 month after the operation. The

1-, 3-, and 5-year overall survival rates for this series of

patients were 96.54, 83.46, and 74.01 %, respectively

(Fig. 1).

The results of univariate analysis for survival rate after

curative resection of single HCC without macrovascular

invasion are summarized in Table 1. According to univariate

analysis, the presence of microvascular invasion (p = 0.015)

was a significant prognostic factor associated with poor

prognosis (Fig. 2), while resection margin C 1 cm, tumor

size [ 5 cm, and AFP elevation were not significant

(Table 1). The overall survival rate tended to be higher in

patients who underwent curative resection with resection

margin C 1 cm (77.46 % at 5 years) than in those who with

resection margin \ 1 cm (66.94 % at 5 years), although this

difference did not reach statistical significance (p = 0.0504).

To further evaluate the relationship between tumor size, AFP

level and overall survival in patients with single HCC without

macrovascular invasion, we divided these patients into

groups according to the different cutoff values and compared

overall survival rates between these groups. We defined 3

groups according to tumor size: group I (n = 158), tumor

size B 5 cm; group II (n = 115), tumor size between 5 and

10 cm; group III (n = 47), tumor size [ 10 cm. We found no

difference in overall survival between these three groups

(p = 0.202). We defined low-AFP, intermediate-AFP, and

high-AFP groups by using 100, 400, and 1000 ng/ml as cutoff

values, respectively. We found that AFP level was not asso-

ciated with survival in this population (low AFP: p = 0.784;

intermediate AFP: p = 0.796; high AFP: p = 0.157).

The results of a multivariate analysis model including

microvascular invasion and resection margin indicated that

only microvascular invasion was a significant predictive

factor of survival after curative resection for single HCC

without macrovascular invasion (Table 2). The overall

survival rates at 1, 3, and 5 years for patients with and

without MVI were 88.46, 71.15, 63.30 and 98.56, 86.54,

76.70 %, respectively (Table 1).

Predictors of disease-free survival

During follow-up, 122 patients were diagnosed as having

HCC recurrence, and 138 patients had no evidence of

recurrence. The overall recurrence rate was 46.92 %. At

the date of the first diagnosis of tumor recurrence, 105

patients had developed intrahepatic recurrence only, 15

patients had developed extrahepatic recurrence only, and 2

patients had developed both intrahepatic and extrahepatic

recurrence. The disease-free survival rates for this series of

patients at 1, 3, and 5 years were 79.62, 62.69, and

56.01 %, respectively (Fig. 3).

Univariate analysis identified two significant prognostic

factors for disease-free survival: gender (p = 0.031) and

microvascular invasion (p = 0.031) (Figs. 4, 5). The

cumulative disease-free survival rate tended to be higher in

patients who underwent curative resection with resection

margin C 1 cm (59.68 % at 5 years) than in those with

resection margin \ 1 cm (48.51 % at 5 years), although this

difference did not reach statistical significance (p = 0.090).

Multivariate analysis including microvascular invasion,

gender, and resection margin indicated that only microvas-

cular invasion was a significant predictor of disease-free

survival for this series of patients (Fig. 4). The disease-free

survival rates at 1, 3, and 5 years for patients with and

without MVI were 65.38, 51.92, 45.93 and 83.17, 65.38,

58.53 %, respectively (Table 1).

Med Oncol (2013) 30:696 Page 3 of 8

123

Table 1 Clinicopathologic characteristics of the 320 curatively resected patients with single hepatocellular carcinoma (HCC) without macro-

vascular invasion and univariate analysis of survival after hepatectomy according to clinicopathologic factors

Variables No. of patients (%) Overall survival rate (%) p values

1-year 3-year 5-year

Gender 0.106

Male 225 (86.5) 94.29 71.43 65.71

Female 35 (13.5) 96.89 85.33 75.31

Age (years) 0.447

B 50 142 (54.6) 95.07 83.10 75.18

[ 50 118 (45.4) 98.31 83.90 72.65

ALT(U/L) 0.694

B 40 133 (51.2) 95.49 82.71 76.50

[ 40 127 (48.8) 97.64 84.25 71.45

AST(U/L) 0.258

B 45 188 (72.3) 97.34 84.57 76.42

[ 45 72 (27.7) 94.44 80.56 67.79

Child-Pugh A classification 260 (100.0) 96.54 83.46 74.01 –

Hepatitis B serologya 0.835

Positive 235 (90.4) 96.17 83.40 73.81

Negative 24 (9.2) 100.00 83.33 79.06

HCV-Aba 0.774

Positive 3 (1.2) 100.00 66.67 66.67

Negative 256 (98.5) 96.48 83.60 74.39

Cirrhosis 0.203

Yes 213 (81.9) 96.24 82.16 72.05

No 47 (18.1) 97.87 89.36 82.98

AFP elevationa 0.368

Yes 149 (57.3) 95.30 80.54 71.55

No 110(42.3) 98.18 87.27 77.12

Tumor size (cm) 0.166

B 5 129 (49.6) 98.45 87.60 77.17

[ 5 131 (50.4) 94.66 79.39 70.88

Tumor capsule 0.523

Absent 102 (39.2) 93.14 79.41 71.51

Incomplete 67 (25.8) 98.51 85.07 72.90

Complete 91 (35.0) 98.90 86.81 77.55

Edmondson Steiner grade 0.169

I 31 (11.9) 100.0 96.77 83.75

II 133 (51.2) 97.74 84.21 74.12

III ? IVb 96 (36.9) 93.75 78.13 70.72

Microvascular invasion 0.015

Yes 52 (20.0) 88.46 71.15 63.30

No 208 (80.0) 98.56 86.54 76.70

Hepatectomy procedure

Anatomic resection 174 (66.9) 96.51 81.40 69.50 0.259

Nonanatomic resection 86 (33.1) 96.55 84.48 76.25

Resection margin (cm) 0.050

\ 1 86 (33.1) 97.67 81.40 66.94

C 1 174 (66.9) 95.98 84.48 77.46

Blood loss (ml) 0.346

Page 4 of 8 Med Oncol (2013) 30:696

123

Discussion

Hepatocellular carcinoma has a tendency to invade the

intrahepatic vasculature, such as the portal veins (PVs) and

the hepatic veins (HVs). PV involvement is more common

than HV involvement [15]. In patients with HCC, tumor

vascular invasion can be divided into macroscopic and

microscopic. Macroscopic vascular invasion, such as a

tumor thrombus in the portal vein portal and/or hepatic

vein, has been identified as one of the most important

prognostic factors affecting survival or recurrence after

surgical resection of HCC [16, 17]. The extent of the tumor

thrombus in the portal vein and/or hepatic vein is correlated

with overall survival after treatment with partial hepatec-

tomy [18, 19].

Although some studies have suggested that the presence

of MVI is an independent predictor of poor survival after

resection of HCC, the clinical significance of microvascular

invasion for patients with single HCC without macrovascu-

lar invasion remains unclear. MVI occurrence rates are

between 23 and 29 % in single HCC [12, 20]. Shirabe et al.

[20] investigated 218 HCC patients without any extrahepatic

metastases and vascular invasion detected during preopera-

tive evaluation. Among the 218 patients, 146 patients had

single HCC. They found that 42 of the 146 single HCC

patients had MVI. Cho et al. [12] reported that among 230

Table 1 continued

Variables No. of patients (%) Overall survival rate (%) p values

1-year 3-year 5-year

B 500 224 (86.2) 95.98 84.38 75.27

[ 500 36 (13.8) 100.00 77.78 66.08

Blood transfusion 0.744

Yes 37 (14.2) 95.96 83.86 73.76

No 223 (85.8) 100.00 81.08 75.68

Ligation of the hilus 0.464

Yes 208 (80.0) 96.15 82.21 72.90

No 52 (20.0) 98.08 88.46 78.42

ALT alanine aminotransferase, AST aspartate aminotransferase, HCV-Ab hepatitis C virus antibody, AFP a-fetoproteina Not all data available for all patientsb Only 4 patients with undifferentiated HCC

Fig. 1 Survival curve for patients with single hepatocellular carci-

noma (HCC) without macrovascular invasion who underwent curative

resection between 2004 and 2007 (n = 260 patients)

Fig. 2 Overall survival curve for patients with and without micro-

vascular invasion (MVI). The overall survival rate of the MVI(-)

group was significantly better than that of the MVI(?) group

(p = 0.015)

Med Oncol (2013) 30:696 Page 5 of 8

123

HCC patients with single HCC less than 10 cm in diameter,

53 patients had MVI. Our results are similar, as we found that

22.8 % patients with single HCC without macrovascular

invasion had MVI, which suggests that even in early-stage

HCC patients, the MVI rate is relatively high. MVI is often

an independent factor for overall survival [11, 13, 14, 21] and

disease-free survival [12, 13, 21]. In a report of 408 HCC

patients within the Milan criteria who underwent partial

hepatectomy, Fan et al. [14] identified the absence of

microvascular invasion as a favorable predictor for overall

survival. Cho et al. [12] found that the presence of micro-

vascular invasion was a significant prognostic factor for

disease-free survival in both single large HCC ([ 5–10 cm

in diameter) patients and single small HCC (B 5 cm)

patients. Sumie [21] investigated 110 HCC patients without

macroscopic vascular invasion who underwent curative

resection. In their study, MVI was identified as an indepen-

dent risk factor for both recurrence-free survival and disease-

free survival. Similar findings have been reported by other

authors. We also identified the presence of MVI as an inde-

pendent predictor for both poor survival and disease-free

survival after curative resection of HCC. The overall survival

rate and disease-free survival rate were significantly worse

for patients with MVI than those without MVI. These find-

ings indicate that microscopic venous invasion may play an

important role in short-term survival and cancer cell

spreading in HCC patients after curative resection. The

presence of vascular invasion has been considered direct

Table 2 Independent predictors for overall survival identified by

multivariate analysis

Variables Coefficient SE p Hazard

ratio

95 % CI

Microvascular

invasion

0.632 0.265 0.017 1.881 1.119–3.160

Fig. 3 Disease-free survival curve for patients with single hepato-

cellular carcinoma (HCC) without macrovascular invasion who

underwent curative resection between 2004 and 2007 (n = 260

patients)

Fig. 4 Disease-free survival according to gender. The disease-free

survival rate of males was significantly better than that of females

(p = 0.031)

Fig. 5 Disease-free survival according to microvascular invasion

(MVI). The disease-free survival rate of the MVI(-) group was

significantly better than that of the MVI(?) group (p = 0.031)

Page 6 of 8 Med Oncol (2013) 30:696

123

evidence of intrahepatic metastasis. Therefore, it is impor-

tant to detect whether MVI is present in the resected speci-

men of patients with single HCC without macrovascular

invasion because of its importance in predicting both overall

survival and disease-free survival after curative resection.

MVI(?) HCC patients need careful follow-up, and these

patients may be good candidates for adjuvant chemotherapy.

Although some investigators have reported that postopera-

tive TACE could improve the prognosis of HCC patients

with macroscopic portal vein tumor thrombi, its efficacy in

MVI(?) HCC patients is still controversial. So far, no report

has focused on its efficacy in MVI(?) patients with single

HCC without macroscopic vascular invasion. In a future

study, we will further analyze this tissue to improve the

prognosis of these HCC patients (Table 3).

The prognostic significance of resection margin in post-

operative survival and disease-free survival remains contro-

versial in HCC. Some investigators have found that the extent

of the liver resection margin was an independent prognostic

factor for overall survival [22, 23] and disease-free survival

[22–24]. However, other investigators have found that the

extent of liver resection margin did not influence postopera-

tive overall survival [25, 26] or disease-free survival [25–28].

In the present study, we found that the resection margin did

not influence postoperative overall survival or disease-free

survival in patients with single HCC without macrovascular

invasion who underwent curative resection. Although both

the cumulative overall survival rate and disease-free survival

rate tended to be higher in patients who underwent curative

resection with resection margin C 1 cm than those with

resection margin \ 1 cm, this difference did not reach sta-

tistical significance (p = 0.0504; p = 0.090, respectively).

These results imply that resection margin C 1 cm has little

beneficial effect in prolonging both overall survival rate and

disease-free survival rate for patients with single HCC with-

out macrovascular invasion who undergo curative resection.

This observation might have 2 explanations. First, tumor

recurrence could be classified as intrahepatic metastasis and

multicentric occurrence, according to its origin. Multicentric

recurrence could occur anywhere in the liver remnant and

might not be prevented by a wide resection margin. Among

the 15 paired samples from 15 HCC patients who underwent

re-resection, Poon et al. [29] demonstrated that 8 of 9 (89 %)

resected early recurrent (B 1 year) tumors were intrahepatic

metastases, whereas all 6 (100 %) resected late recurrent

([ 1 year) tumors were classified as multicentric occur-

rences. In our study, 57 of the 122 patients with recurrent

HCC developed late intrahepatic recurrence ([ 1 year) that

may have mainly originated from multicentric occurrences.

Second, HCC has a propensity to disseminate by means of

vascular invasion, and intrahepatic metastasis is likely to be

present beyond 1 cm in most patients before operation. Lai

et al. [30] investigated 23 resected liver specimens by serial

sectioning followed by histologic examination, and they

found that 20 of the 23 specimens had either microsatellites or

histologic venous permeation. Among these 20 specimens,

either microsatellites or histologic venous permeation

extended beyond 1 cm from the resection margin in 17

specimens. In their study, 9 specimens had single HCC

without a gross tumor thrombus. Six of the 9 specimens had

either venous permeation or microsatellites, and either

microsatellites or histologic venous permeation was beyond

1 cm from the resection margin in 4 of these 6 specimens.

However, a 2-cm margin improved the potential for a cure in

macroscopically solitary HCC without vascular invasion. Our

previous study showed that micrometastases extended

beyond the 1-cm margin in 28 (24.8 %) patients but beyond

the 2-cm margin in only nine (8.0 %) patients with macro-

scopically solitary tumors without vascular invasion [15].

Thus, a wide resection margin (2 cm) should be recom-

mended for the patient to survive the operation.

Tumor size is not an indicator of poor prognosis in HCC

patients with single tumors after hepatic resection [7, 9, 10].

Yang et al. [9] reported that solitary large HCC patients had

similar overall survival and disease-free survival to small

HCC patients. The latest American Joint Commission on

Cancer (AJCC) staging classification for HCC also classified

single HCC without vascular invasion as T1, irrespective of

its size. The present study is consistent with the previous

studies showing that tumor size did not affect the postoper-

ative outcomes in patients with single HCC. Although AFP

level is the most effective marker for HCC diagnosis and

recurrent surveillance, the prognostic value of AFP has been

controversial. While some studies suggested that AFP was

associated with survival after resection [10, 31], other studies

found that AFP was not a predictor of survival. In the present

study, AFP level did not have prognostic value for overall

survival or disease-free survival.

There are some limitations of this study. First, it was a

retrospective study. Second, we examined only the resected

specimens for MVI. Whether MVI was present in the liver

remnant is not known. Lastly, sampling may have affected

the pathologists’ diagnosis of MVI, and inadequate sam-

pling may have caused false-negative detection.

In conclusion, in patients with single HCC without mac-

rovascular invasion, we found that the presence of MVI was a

poor prognostic factor for both overall survival and disease-

free survival after curative resection. These findings suggest

Table 3 Independent predictors for disease-free survival identified by

multivariate analysis

Variables Coefficient SE p Hazard

ratio

95 % CI

Microvascular

invasion

0.451 0.210 0.032 1.569 1.039–2.370

Med Oncol (2013) 30:696 Page 7 of 8

123

that MVI can be employed to estimate both overall survival

and disease-free survival after curative resection in patients

with single HCC without macrovascular invasion. Patients

with MVI may be good candidates for adjuvant chemotherapy.

Further studies to analyze whether adjuvant chemotherapy can

improve the survival of these patients are necessary.

Acknowledgments We thank Yu Zhang and Yun-Xian Mo for their

contribution to this study. This work was supported by grants from the

National Natural Science Foundation of China (No. 81172037/

H1606) and Guangzhou municipal science and technology project of

China (No.2012J4100078).

Conflict of interest None.

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