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© 2017 EDIZIONI MINERVA MEDICA Minerva Medica 2017 August;108(4):324-33

Online version at http://www.minervamedica.it DOI: 10.23736/S0026-4806.17.04788-7

ORIGINAL ARTICLE

Comparison of hepatectomy with or without hepatic

inflow occlusion in patients with hepatocellular
carcinoma: a single-center experience
Jing-Hang JIANG  1, 2, Kai-Xiu WANG  3, Ji-Ye ZHU  4, Pei-Pei YANG  2, Zhe GUO  5,
Song-Lin MA 2, Yang LÜ  2, Bang-De XIANG  1 *, Jian-Hong ZHONG  1, Le-Qun LI  1

1Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangxi Medical University, Nanning,

China; 2Department of General Surgery, Second People’s Hospital of Jingmen, Jingmen, China; 3Department of
Obstetrics and Gynecology, Second People’s Hospital of Jingmen, Jingmen, China; 4Department of Hepatobiliary
Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China; 5Department of Thyroid and
Breast Surgery, Wuhan Central Hospital, Wuhan, China
*Corresponding author: Bang-De Xiang, Department of Hepatobiliary Surgery, Affiliated Cancer Hospital of Guangxi Medical Uni-
versity, 71 Hedi Road, Nanning, 530021 Guangxi, China. E-mail: 474522490@qq.com

A B S T RAC T
BACKGROUND: The negative effects of hepatic inflow occlusion (HIO) on postoperative liver function of patients with
hepatocellular carcinoma (HCC) after liver resection have been reported. Nevertheless, whether or not HIO could influ-
ence the long-term outcomes remains unclear.
METHODS: A total of 396 patients were included in this study and divided into without occlusion (WO) group (N.=112)
and HIO group (N.=284). Aiming to minimize influence of selection bias and confounding variables, we used propensity
score matching (PSM) of a 0.2 caliper to balance baseline variables. Overall survival (OS) and disease-free survival
(DFS) were compared by the Kaplan-Meier method. Independent prognostic factors for OS and DFS were identified by
Cox proportional hazards regression model.
RESULTS: PSM were used to generate 101 pairs of patients. After PSM, OS was not significantly different between WO
and HIO group (1-year: 86.1% vs. 83.2%; 3-year: 61.4% vs. 61.4%; 5-year: 45.5% vs. 39.6%; P = 0.626). Similar results
of DFS were obtained between WO and HIO group (1-year: 54.5% vs. 53.5%; 3-year: 30.5% vs. 28.7%; 5-year: 14.2%
vs. 14.9%; P=0.873). WO and HIO groups did not differ in 30-day, 90-day mortality and rate of postoperative complica-
tions (all P>0.05).
CONCLUSIONS: Our data indicates that HIO might not negatively affect the OS and DFS of HCC patients undergoing
liver resection and is likely to be a safe and viable option for intraoperative blood loss control.
(Cite this article as: Jiang JH, Wang KX, Zhu JY, Yang PP, Guo Z, Ma SL, et al. Comparison of hepatectomy with or without
hepatic inflow occlusion in patients with hepatocellular carcinoma: a single-center experience. Minerva Med 2017;108:324-
33. DOI: 10.23736/S0026-4806.17.04788-7)
Key words: Hepatocellular carcinoma - Hepatic insufficiency - Mortality - Disease-free survival - Hepatectomy.
or other proprietary information of the Publisher.

H epatocellular carcinoma (HCC) is the fifth

most common malignancy and the second
leading cause of cancer-related death in the
world, and can be therefore considered a major
public health issue.1 Attempting to improve the
survival of patients with HCC, a wide range
of therapeutic approaches, such as hepatic re-
section, liver transplantation and transarterial
chemoembolization, have been applied and
hepatic resection has been proved to be a nor-
mative and effective therapeutic strategy for
patients with HCC.2-6 Although liver resection
undoubtedly provides survival benefits, such
a life-threatening risk as severe blood loss

324 Minerva Medica August 2017

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HEPATIC INFLOW OCCLUSION IN HCC PATIENTS JIANG
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during hepatectomy should not be neglected.
Massive hemorrhage plus blood transfusion
could increase postoperative mortality of he-
patic resection, a broad range of strategies of
vascular occlusion have been used to control
blood flow, reduce blood loss, and avoid peri-
operative allogenic blood transfusion.7-10
Two of the most widely used techniques of
vascular occlusion are Pringle maneuver and
hemi-hepatic vascular occlusion. For the Prin-
gle maneuver, it was firstly described in 1908
and could transiently control the hepatic in-
flow by clamping hepatoduodenal ligament.8
This technique effectively reduces the intraop-
erative blood loss but inevitably results in liver
perfusion deficiency and then ischemia-reper-
fusion (I/R) injury, which may subsequently
cause liver impairment and dysfunction.10-12
In terms of hemi-hepatic vascular occlusion, it
merely blocks the blood flow of right or left
hemi-liver where the tumor locates and thus
avoids the influence of vascular occlusion on
contralateral hemi-liver.13 However, hemi-he-
patic vascular occlusion could not completely
prevent I/R damage in remnant liver, espe-
cially for patients undergoing segment resec-
tion or non-anatomic resection.13 Additionally,
HCC often occurs in the liver with cirrhosis
caused by persist infection of hepatitis B virus
or hepatitis C virus, which significantly de-
creases the tolerance of the ischemia.14 There-
fore, both Pringle maneuver and hemi-hepatic
vascular occlusion are likely to cause I/R in-
jury to the remnant liver and may affect HCC
patients’ postoperative liver function and long-
term survival.
Previous researches have reported that he-
patic inflow occlusion (HIO) exerts an influ-
ence on the postoperative liver function, but
the effects of HIO on long-term survival re-
mains unclear.9, 12, 15 Therefore, we performed
this retrospective study to investigated wheth-
or other proprietary information of the Publisher.
er HIO could affect long-term survival of HCC
patients.
Materials and methods
This study was approved by the ethics com-
mittee of the Affiliated Cancer Hospital of
Vol. 108 - No. 4 Minerva Medica 325
Guangxi Medical University, and performed
in compliance with principles of the Helsinki
Declaration. Written informed consent was ob-
tained from all patients.
Patients
This retrospective study was conducted
based on medical records of 396 patients di-
agnosed with HCC and treated with curative
hepatectomy who had been admitted between
January 2004 and December 2009 at the Af-
filiated Cancer Hospital of Guangxi Medical
University, in Nanning, China. The inclusion
criteria were: 1) postoperative histopathol-
ogy confirmed as HCC; 2)  no more than 3
tumor nodules; 3) no invasion of the portal
vein, hepatic vein, common hepatic duct and
inferior vena cava; 4) pre-surgical imaging
did not show intra- or extra-hepatic metasta-
sis or satellite nodules; 5) the resection mar-
gin were negative; 6) post-surgical imaging
displayed no residual tumor or portal tumor
thromboses; 7) no previous treatments for
HCC; 8) tumor location was not beyond liver
segment 3.
Treatment
All patients were treated with curative re-
section carried out by the same experienced
surgeons able to independently perform stan-
dard anatomical resection. Surgical techniques
and perioperative management were as previ-
ously described.16 The included patients were
divided into the without occlusion (WO) group
and HIO group. The mode of vascular occlu-
sion using to control the portal blood flow was
decided by the hepatic surgeons. In the HIO
group, Pringle maneuver or hemi-hepatic vas-
cular inflow occlusion was applied to control
the per-operative blood loss. For Pringle ma-
neuver, the entire hepatoduodenal ligament
was encircled and tightened with an elastic
tourniquet. Intermittent vascular occlusion was
performed less than 20 minutes each time with
an unclamp interval of 5 minutes. The hemi-
hepatic vascular inflow occlusion technique
was conducted as previously described.15
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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JIANG HEPATIC INFLOW OCCLUSION IN HCC PATIENTS
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Follow-up and treatment for recurrence
After surgery, all the patients had been fol-
lowed at the first month, every 3 months in
the first year, and thereafter twice a year. All
evaluations comprised physical examination,
liver function tests, measurement of serum al-
pha fetal protein (AFP) and abdominal ultra-
sonography combining with computed tomog-
raphy (CT) or magnetic resonance imaging
(MRI). Patients were diagnosed as recurrence
and/or distant metastasis according to the cri-
teria made by the European Association for
the Study of the Liver.17 The endpoint for fol-
low-up was set at 5 years after initial curative
hepatectomy. The overall survival (OS) and
disease-free survival (DFS) were defined as
60 months for those who survived more than
5 years.
According to the patients’ liver function,
performance status, tumor size and number,
following treatments were applied to the pa-
tients with recurrence or metastasis: reopera-
tion, transarterial chemoembolization (TACE),
radiofrequency ablation (RFA), percutaneous
ethanol injection (PEI), radiation therapy, or
sorafenib therapy.
Propensity score matching
Given that patients in this study were not
randomly treated with HIO, there might be
baseline differences between groups, which
diminish the reliability of the results.18 To min-
imize influences of selection bias and potential
confounding characteristics, propensity score
matching (PSM) was used to balance treat-
ment choice-related variables, thereby simu-
lating random allocation.19 Logistic regression
model, on which the estimation of propensity
scores were based, were used the following
baseline characteristics as covariates: gender,
or other proprietary information of the Publisher.
age, body mass index (BMI), status of hepa-
titis B virus (HBV), family history of HCC,
total bilirubin (TBIL), albumin (ALB), alanine
aminotransferase (ALT), aspartate amino-
transferase (AST), prothrombin (PT), platelet
count (PLT), levels of AFP, tumor size, tumor
number, presence of liver cirrhosis, antiviral
326 Minerva Medica August 2017
therapies, type of resection (anatomic or non-
anatomic), surgical margins, blood loss, blood
transfusion, tumor capsule, tumor location, liv-
er function Child-Pugh class, Barcelona Clinic
Liver Cancer (BCLC) classification. One-to-
one matching was performed using a 0.2 cali-
per.20 A total of 101 pairs of score-matched pa-
tients were used in subsequent analyses.
Statistical analysis
All analyses were performed with statisti-
cal software SPSS v. 19.0 (IBM, USA). The
Shapiro-Wilk test was used to test the normal-
ity. The differences between the continuous
data were compared using the t-test and Mann-
Whitney U-test where appropriate. Chi-square
was used to compare categorical classification
data. Curves of DFS and OS were plotted by
the Kaplan-Meier method and compared by
the log-rank test. Multivariate Cox proportion-
al hazard regression was performed to assess
the ability of clinicopathological variables to
predict OS and DFS for variables significant
in univariate analysis. All the statistical tests
were two-sided. If less than 0.05, P value was
considered statistically significant.
Results
The baseline characteristics of all included
patients with HCC were presented in Table I. Be-
fore PSM, the baseline clinicopathological char-
acteristics of WO and HIO group did not differ
in gender, age, BMI, HBV infection, family his-
tory of HCC, TBIL, ALB, ALT, AST, PT, PLT,
levels of AFP, tumor number, presence of liver
cirrhosis, antiviral therapies, type of resection
(anatomic or non-anatomic), surgical margins,
blood loss, blood transfusion, tumor capsule (all
P>0.05). However, tumor size (P=0.001), tumor
location (P=0.001), liver function (P=0.002),
BCLC stage (P=0.001) were significantly dif-
ferent between WO and HIO group.
Overall survival
At the end of follow-up, median follow-up
was 64.6 months (range: 1 to 120 months) for
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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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Table I.—Baseline clinical characteristics of HCC patients treated with curative resection.
Before PSM After PSM
Variable WO group HIO group WO group HIO group
P value P value
(N.=112) (N.=284) (N.=101) (N.=101)
Gender
Male 96 120 0.741 88 91 0.506
Female 16 18 13 10
Age, yr 46.5±12.1 48.5±11.4 0.107 46.8±12.0 48.3±11.1 0.377
BMI, kg/m2 21.2±2.0 21.0±1.8 0.904 21.3±2.0 21.2±1.9 0.953
HBsAg
Positive 98 247 0.888 87 87 1.000
Negative 14 37 14 14
Family history of HCC
Yes 24 51 0.427 21 20 0.861
No 88 233 80 81
Total bilirubin, mol/L 14.0±6.9 14.1±6.6 0.935 14.1±7.1 14.0±6.1 0.892
Albumin, g/L 39.2±4.2 40.0±4.4 0.124 39.5±4.2 39.6±4.4 0.948
ALT, U/L 41 (30-55) 38 (26-54) 0.234 40 (30-53) 37 (27-58) 0.750
AST, U/L 41 (33-55) 41 (31-60) 0.890 40 (31-53) 39 (32-58) 0.985
Prothrombin time, s 13.2±1.9 13.0±1.9 0.306 13.2±1.9 13.9±2.4 0.869
Platelet count, ×109/L 187.7±90.1 175.5±72.3 0.202 184.3±88.6 177.5±70.9 0.545
AFP, ng/mL
<400 73 190 0.744 65 67 0.767
≥400 39 94 36 34
Tumor size, cm 5.5±2.7 6.6±3.2 0.001 5.6±2.7 5.7±2.8 0.798
N. tumors
1 100 239 0.190 89 91 0.651
2-3 12 45 12 10
Liver cirrhosis
Positive 78 181 0.265 70 73 0.643
Negative 34 103 31 28
Antiviral therapies
Yes 98 247 0.888 87 87 1.000
No 14 37 14 14
Resection
Anatomic 54 117 0.204 48 44 0.572
Non-anatomic 58 167 53 57
Surgical margins, cm
≥1 86 193 0.083 76 79 0.617
<1 26 91 25 22
Blood loss, mL 300 (200-500) 300 (200-600) 0.199 300 (200-500) 300 (200-500) 0.923
Blood transfusion
Yes 29 89 0.286 26 28 0.751
No 83 195 75 73
Tumor capsule
Complete 54 137 0.996 51 60 0.203
Incomplete 58 147 50 41
Tumor location 0.001 0.609
Segment 1 51 86 43 42
Segment 2 54 142 51 48
Segment 3 7 56 7 11
Child-Pugh class
or other proprietary information of the Publisher.

A 99 274 0.002 96 94 0.552

B 13 10 5 7
BCLC stage
A 60 100 0.001 54 52 0.778
B 52 184 47 49
Values are reported as mean±SD or as median (interquartile range).
PSM: propensity score matching; WO: without occlusion; HIO: hepatic inflow occlusion; BMI: Body Mass Index; HCC: hepatocellular
carcinoma; ALT: alanine aminotransferase; AST: aspartate aminotransferase; AFP: alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer
Staging System.

Vol. 108 - No. 4 Minerva Medica 327

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the WO group and 56.8 months (range, 1 to
121 months) for the HIO group. 62 out of 112
(55.4%) patients in WO group and 159 out of
284 patients (56.0%) in HIO group died. The
overall cumulative 1-, 3-, and 5-year survival
rates were 83.0%, 58.9%, 43.8% (WO group)
and 78.2%, 51.1%, 34.9% (HIO group), re-
spectively (P=0.122; Figure 1).
Univariate analysis showed that serum
WO group, all patients
HIO group, all patients
WO group, matched patients
HIO group, matched patients
Overall survival (%)
AST level ≥70  U/L (P<0.001), serum AFP
level ≥400  ng/mL (P=0.014), antiviral thera-
pies (P=0.019), tumor capsule (P<0.001), and
BCLC B stage (P=0.001) were correlated with
mortality (Table II). Multivariate Cox regres-
sion further confirmed that serum AST level
≥70  U/L (hazard ratio [HR] 1.628; 95%  CI:
1.204-2.201; P=0.002), antiviral therapies
(HR=1.640; 95% CI: 1.069-2.516; P=0.024),
tumor capsule (incomplete vs. complete)
(HR=1.767; 95% CI: 1.366-2.284; P<0.001)
and BCLC B stage (HR=1.379; 95% CI: 1.061-
1.792; P=0.016) were independent prognostic
predictors.

Disease-free survival analysis

P=0.122
P=0.626
Follow-up (months)
Figure 1.—Cumulative overall survival curves for patients
treated with or without hepatic inflow occlusion during cura-
tive resection. The curves are plotted based on all patients
(P=0.122) and on PSM patients (P=0.626).
In all patients before PSM, DFS was slightly
higher in WO group than in HIO group (1-year:
53.6% vs. 49.6%; 3-year: 29.3% vs. 25.0%;
5-year: 13.7% vs. 12.0%; P=0.295; Figure 2).
Univariate analysis demonstrated that se-
rum AST level ≥70  U/L (P<0.001), antiviral
therapies (P=0.004), blood loss ≥1000  mL
(P=0.002), blood transfusion (P=0.016), tumor
capsule (P=0.029), BCLC B stage (P=0.004)
and tumor size ≥5  cm (P=0.015) were asso-
ciated with higher incidence of tumor recur-
rence (Table III). As shown in Table IV, multi-

Table II.—Univariate analysis of prognostic factors for overall survival.

Before PSM After PSM
Variable 1-yr 3-yr 5-yr 1-yr 3-yr 5-yr
N. P value N. P value
OS, % OS, % OS, % OS, % OS, % OS, %
AST (U/L) <0.001 0.134
≥70 74 58.1 35.1 23.0 35 71.4 51.4 34.3
<70 322 84.5 57.5 40.7 167 87.4 63.5 44.3
AFP (ng/mL) 0.014 0.036
≥400 133 73.7 45.1 30.1 70 78.6 51.4 34.3
<400 263 82.5 57.4 41.1 132 87.9 66.7 46.9
Antiviral therapies 0.019 0.010
Yes 345 82.4 64.7 52.9 174 92.9 82.1 64.1
or other proprietary information of the Publisher.

No 51 79.1 51.6 35.1 28 83.3 58.0 39.1

Tumor capsule <0.001 0.004
Incomplete 205 75.1 40.5 26.8 91 82.4 49.5 33.0
Complete 191 84.3 67.0 48.7 111 86.5 71.2 50.4
BCLC 0.001 0.054
B 236 72.5 46.6 32.2 96 77.1 55.2 36.5
A 160 90.0 63.1 45.0 106 91.5 67.0 48.1
PSM: propensity score matching; OS: overall survival; AST: aspartate aminotransferase; AFP: alpha-fetoprotein; BCLC: Barcelona Clinic
Liver Cancer Staging System.

328 Minerva Medica August 2017

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means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
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WO group, all patients 1.110-1.901; P=0.007), antiviral therapies

HIO group, all patients
WO group, matched patients
(HR=1.687; 95% CI: 1.181-2.409; P=0.004)
HIO group, matched patients and BCLC B stage (HR=1.280; 95% CI:
1.023-1.603; P=0.031).
Disease-free survival (%)

Characteristics of patients after PSM

P=0.295
P=0.873
Follow-up (months)
Figure 2.—Disease-free survival curves for patients treat-
ed with or without hepatic inflow occlusion during cura-
tive resection. The curves are plotted based on all patients
(P=0.295) and on PSM patients (P= 0.873).
variate regression identified three independent
prognostic factors for tumor recurrence: se-
rum AST level ≥70 U/L (HR=1.453; 95% CI:
In order to eliminate all significant differ-
ences in measured variables, PSM was used to
generate 101 pairs of matched patients. Table I
showed no significant differences in baseline
variables between groups after PSM, confirm-
ing the effectiveness of the matching proce-
dure.
Overall survival of patients after PSM
After PSM, the median follow-up period
was 63.5 months (range: 3 to 112 months)
for the patients in WO group and 64.5
months (range: 2 to 121 months) for the pa-
tients in HIO group. A total of 56 (55.4%)
patients in WO group died, compared with

Table III.—Univariate analysis of prognostic factors for disease-free survival.

Before PSM After PSM
Variable 1-yr 3-yr 5-yr 1-yr 3-yr 5-yr
N. P value N. P value
DFS, % DFS, % DFS, % DFS, % DFS, % DFS, %
AST (U/L) <0.001 0.359
≥70 74 33.8 14.9 5.4 35 42.9 25.7 11.4
<70 322 54.7 28.8 14.1 167 56.3 30.4 15.2
Antiviral therapies 0.004 0.001
Yes 345 54.9 37.3 31.4 174 67.9 46.4 42.9
No 51 50.1 24.6 9.7 28 51.7 26.9 9.9
Blood loss (mL) 0.002
≥1000 38 31.6 13.2 2.6 4 50.0 25.0 0.770
<1000 358 52.8 27.6 13.5 198 54 29.7 14.8
Blood transfusion 0.016 0.440
Yes 118 45.8 17.8 5.9 54 57.4 16.7 11.1
No 278 52.9 29.8 15.3 148 52.7 34.4 15.8
Tumor capsule 0.029 0.678
Incomplete 205 45.4 21.8 10.4 91 50.5 27.3 14.8
Complete 191 56.5 30.9 14.7 111 56.8 31.5 14.4
BCLC 0.004 0.106
or other proprietary information of the Publisher.

B 236 43.6 21.9 9.9 96 45.8 22.7 13.0

A 160 61.2 32.5 16.2 106 61.3 35.8 16.0
Tumor size 0.015 0.043
≥5 238 43.7 21.8 11.3 114 44.7 22.8 13.2
<5 158 61.4 32.8 14.1 48 65.9 38.5 16.3
Resection 0.123 0.027
Non-anatomic 225 53.8 29.2 13.9 110 60.9 35.3 17.6
Anatomic 171 46.8 22.2 10.5 92 45.7 22.8 10.9
PSM: propensity score matching; AST: aspartate aminotransferase; BCLC: Barcelona Clinic Liver Cancer Staging System.

Vol. 108 - No. 4 Minerva Medica 329

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Table IV.—Multivariate analysis of prognostic factors for disease-free survival.

Before PSM After PSM
Variable
HR 95% CI P value HR 95% CI P value
AST (≥70 vs. <70 U/L) 1.453 1.110-1.901 0.007
Antiviral therapies (no vs. yes) 1.687 1.181-2.409 0.004 2.517 1.492-4.247 0.001
Blood loss (≥1000 vs. <1000 mL) 0.773 0.874-1.911 0.198
Blood transfusion (yes vs. no) 1.182 0.912-1.532 0.207
Tumor capsule (incomplete/absent vs. complete) 1.159 0.934-1.439 0.180
BCLC (B vs. A) 1.280 1.023-1.603 0.031
Tumor size (≥5 vs. <5 cm) 1.382 1.006-1.897 0.046
PSM: propensity score matching; AST: aspartate aminotransferase; BCLC: Barcelona Clinic Liver Cancer Staging System; HR: hazard ratio;
CI: confidence interval.

Table III.—Multivariate analysis of prognostic factors for overall survival.

Before PSM After PSM
Variable
HR 95% CI P value HR 95% CI P value
AST (≥70 vs. <70 U/L) 1.628 1.204-2.201 0.002
AFP (≥400 vs. <400 ng/mL) 1.230 0.946-1.600 0.122 1.505 1.037-2.186 0.032
Antiviral therapies (no vs. yes) 1.640 1.069-2.516 0.024 2.437 1.269-4.682 0.007
Tumor capsule (incomplete vs. complete) 1.767 1.366-2.284 <0.001 1.605 1.115-2.31 0.011
BCLC (B vs. A) 1.379 1.061-1.792 0.016
PSM: propensity score matching; AST: aspartate aminotransferase; AFP: alpha-fetoprotein; BCLC: Barcelona Clinic Liver Cancer Staging
System; HR: hazard ratio; CI: confidence interval.

61 (60.4%) patients in HIO group. Curves
of OS of these two groups showed no dif-
ference (1-year: 86.1% vs. 83.2%; 3-year:
61.4% vs. 61.4%; 5-year 45.5% vs. 39.6%;
P=0.626; Figure 1).
In Table  II, univariate analysis identified
serum AFP (P=0.036), antiviral therapies
(P=0.010) and tumor capsule (P=0.004) as
the predictors of increased risk of mortality.
Multivariate Cox regression showed that AFP
(HR=1.505; 95% CI: 1.037-2.186; P=0.032),
antiviral therapies (HR=2.437; 95% CI:
1.269-4.682; P=0.007) and tumor capsule
(HR=1.605, 95% CI: 1.115-2.310, P=0.011)
were independent prognostic factors (Ta-
ble V).
the type of resection (P=0.027) was associated
with decreased DFS (Table IV). The antiviral
therapies (HR=2.517; 95% CI: 1.492-4.247;
P=0.007) and tumor size (HR=1.382; 95% CI:
1.006-1.897; P=0.046) were identified as inde-
pendent prognostic factors for DFS in multi-
variate Cox regression (Table V).
Mortality and morbidity
Our results from all patients and matched
patients showed that 30-day, 90-day mortality
or the complication rate were not significantly
different between the WO and HIO group (all
P>0.05). The details of the two groups were
summarized in Table VI.

Discussion
or other proprietary information of the Publisher.

Disease-free survival of patients after PSM

As shown in Figure 2, DFS of WO group
was similar to that of HIO group (1-year:
54.5% vs. 53.5%; 3-year: 30.5% vs. 28.7%;
5-year: 14.2% vs. 14.9%; P=0.873).
Univariate analysis revealed that antiviral
therapies (P=0.001), tumor size (P=0.043) and
HCC is the most prevalent cancer in liver
and causes 745,500 deaths worldwide.1 Despite
implementation of screening for HCC in early
stage, mortality of patients with HCC remains
relatively high and surgical therapies such as
hepatic resection and liver transplantation are

330 Minerva Medica August 2017

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Table VI.—Treatment-related outcomes of WO and HIO patients after curative resection.

Before PSM After PSM
Variable, N. (%) WO group HIO group WO group HIO group
P value P value
(N.=112) (N.=284) (N.=101) (N.=101)
30-day mortality 3 (2.5%) 4 (1.4%) 0.409 2 (2.0%) 1 (1.0%) 0.623
90-day mortality 5 (4.1%) 7 (2.5%) 0.332 3 (3.0%) 2 (2.0%) 0.684
Postoperative complications 20 (17.9%) 47 (16.5%) 0.767 13 (12.9%) 14 (13.9%) 1.000
Abdominal bleeding 2 (3.6%) 3 (1.1%) 0.624 1 (1.0%) 2 (2.0%) 0.623
Abdominal infection 2 (1.8%) 2 (0.7%) 0.318 0 (0%) 0 (0%) 1.000
Bile leakage 3 (4.1%) 8 (2.8%) 1.000 4 (4.0%) 3 (3.0%) 1.000
Wound infection 5 (4.5%) 12 (4.2%) 0.306 2 (2.0%) 3 (3.0%) 0.684
Pulmonary infection 3 (2.5%) 5 (1.8%) 0.692 2 (2.0%) 2 (2.0%) 1.000
Intestinal obstruction 0 (0%) 1 (0.4%) 1.000 0 (0%) 0 (0%) 1.000
Gastrointestinal hemorrhage 0 (0%) 0 (0%) 1.000 0 (0%) 0 (0%) 1.000
Pleural effusion 3 (2.5%) 7 (2.5%) 1.000 3 (3.0%) 3 (3.0%) 1.000
Liver failure 0 (0%) 8 (2.8%) 0.112 0 (0%) 1 (1.0%) 1.000
Hepatic abscess 0 (0%) 0 (0%) 1.000 0 (0%) 0 (0%) 1.000
Delayed wound healing 2 (1.8%) 1 (0.4%) 0.194 1 (1.0%) 0 (0%) 1.000
PSM: propensity score matching.

still the practical options providing better local
control and long-term survival.16, 21 In terms of
hepatectomy, some prognostic factors should
be taken into account during the operation. In-
traoperative blood loss, for instance, is closely
correlated with postoperative complication
and overall survival.7 Due to the application
of occlusion techniques including Pringle ma-
neuver and hemi-hepatic vascular occlusion,
intraoperative hemorrhage has been markedly
reduced and thus so has been done to mortal-
ity of hepatic resection.22 However, the ad-
verse effects of occlusion strategies should not
be neglected. Pringle maneuver is more likely
to cause severe I/R injury to the remnant liver,
which in turn results in impaired postopera-
tive liver function, elevated arterial pressure,
bacteria translocation and endotoxemia.10-12, 23
As to hemi-HIO, it could decrease the amount
of liver parenchyma submitted to reperfusion
damage but still could not totally avoid I/R in-
jury.15, 24 Therefore, both Pringle maneuver and
hemi-hepatic vascular occlusion might lead to
abnormal postoperative liver function but their
or other proprietary information of the Publisher.
ated with poor prognosis but the results of this
RCT has not been reported.26 In the current
study, estimated OS rates were not different
between WO and HIO group of all patients. A
similar result of DFS can be seen in the entire
cohorts. These results indicated that HIO did
not negatively impact OS and DFS of patients
with HCC underwent liver resection, which
is in agreement with results of Huang’s study
showing that intermittent HIO did not adverse-
ly affect either OS or DFS.27
However, findings from retrospective study
are less reliable and provide limited implica-
tions for health care because of selection bias
and potential confounding variables. There
are unbalanced baseline clinicopathological
characteristics in both Huang’s study and our
study.27 In order to minimize the impact of
selection bias and confounding variables, pro-
pensity score matching was conducted in this
study. After PSM, WO and HIO group still did
not differ in OS and DFS. Moreover, multivar-
iate Cox regression showed that the HIO was
not correlated with OS and DFS. Our results

effects on long-term survival remain unclear.
The animal experimental researches demon-
strated that I/R of the remnant liver promotes
HCC recurrence and intrahepatic metastasis.25
Furthermore, a randomized controlled trial
(RCT) has been designed to test the hypothesis
that I/R caused by Pringle maneuver is associ-
appear to support the view that HIO is a safe
and viable option for hepatectomy.
Because of the efficiency in reducing blood
loss with little mortality, techniques of HIO,
including Pringle maneuver and hemi-hepatic
vascular occlusion, are widely accepted in
clinical practice.15, 24, 28 Nonetheless, with bet-

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not permitted. It is not permitted to remove, cover, overlay, obscure, block, or change any copyright notices or terms of use which the Publisher may post on the Article. It is not permitted to frame or use framing techniques to enclose any trademark, logo,
means which may allow access to the Article. The use of all or any part of the Article for any Commercial Use is not permitted. The creation of derivative works from the Article is not permitted. The production of reprints for personal or commercial use is
This document is protected by international copyright laws. No additional reproduction is authorized. It is permitted for personal use to download and save only one file and print only one copy of this Article. It is not permitted to make additional copies
JIANG HEPATIC INFLOW OCCLUSION IN HCC PATIENTS
(either sporadically or systematically, either printed or electronic) of the Article for any purpose. It is not permitted to distribute the electronic copy of the article through online internet and/or intranet file sharing systems, electronic mailing or any other
ter understanding of liver anatomy and rapid
development of surgical instrument such as
LigaSure, cavitron ultrasonic surgical aspirator
(CUSA), Biclamp and biolar electrocoagula-
tion, the blood loss of hepatectomy without oc-
clusion are also dramatically reduced.22 In this
study, WO and HIO group seemed not to differ
in amount of bleeding. Furthermore, our results
demonstrated that patients in these two groups
have similar incidence of postoperative com-
plications, which was in agreement with the
results of other study and suggested that hepa-
tectomy with HIO is highly likely to be equally
safe to the one without occlusion.29 Given that
HIO has no negative influence on OS and DFS
of patients with HCC, we should emphasize the
safety and radical removal of tumors over short-
term liver function, especially in the cases that
tumors and large vessels are in close proximity.
Limitations of the study
Although this study provided better un-
derstanding of hepatectomy with and with-
out HIO, it is necessary to point out several
shortcomings of this study. First, the findings
from a retrospective study is less convincing
even after PSM and should be confirmed by
a prospective randomized study. Second, the
sample size is relatively small, especially af-
ter PSM. A study with larger sample size is
urgently needed. Third, the subgroup analyses
such as comparison of WO and HIO group,
etc. are missing because of small sample size.
Conclusions
Our data indicate that HIO might not nega-
tively influence OS and DFS of HCC patients
undergoing the curative resection and is likely
to be a safe and feasible option for blood loss
control in hepatectomy.
or other proprietary information of the Publisher.
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Authors’ contributions.—Jing-Hang Jiang and Kai-Xiu Wang contributed equally to this work.
Funding.—This research was funded by the National Natural Science Foundation of China (grant no. 81260331), National Science
and Technology Major Project of the Ministry of Science and Technology of China (grant no. 2012ZX10002010001009).
Conflicts of interest.—The authors certify that there is no conflict of interest with any financial organization regarding the material
discussed in the manuscript.
Article first published online: February 7, 2017. - Manuscript accepted: January 19, 2017. - Manuscript revised: January 2, 2017. -
Manuscript received: September 12, 2016.
or other proprietary information of the Publisher.

Vol. 108 - No. 4 Minerva Medica 333