Full text of DOI:10.1007/s005950050612

Surg Today (2000) 30:403–409
Original Articles
Significant Changes in the Serum Levels of IL-6, h-HGF, and Type IV
Collagen 7S During the Perioperative Period of a Hepatectomy:
Relevance to SIRS
Koji Namekata, Shigeru Takamori, Kuniaki Kojima, Tomoe Beppu, and Shunji Futagawa
Second Department of Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Abstract: We analyzed the changes in the serum levels of
both interleukin-6 (IL-6), human hepatocyte growth factor (h-
HGF), and type IV collagen 7S (7S) during the perioperative
period of a hepatectomy and evaluated their relationship
with systemic inflammatory response syndrome (SIRS). The
study subjects consisted of 40 patients who underwent a
hepatectomy. In 14 out of 40 patients, postoperative SIRS(؉)
was observed. Between the SIRS(؉) and SIRS(؊) cases,
there were significant differences in the preoperative values
of prothrombin time, hepaplastin test, cholinesterase, and
maneuvers. In the field of gastrointestinal surgery, most
of the cases with SIRS symptoms immediately after
surgery and a number of humoral factors, especially
proinflammatory cytokines, have been considered to be
of great importance. Proinflammatory cytokines are
known to play an important role in the progression from
SIRS and a septic condition to multiple organ dysfunc-
tion syndrome (MODS).2,3 The most common underly-
ing complications in hepatectomy cases include liver
dysfunction due to the basal disease of chronic hepatitis
and liver cirrhosis. Such conditions may readily lead to
postoperative liver failure and MODS. However, the
exact pathophysiological mechanism involved in the
onset of multiple organ failure after a hepatectomy has
yet to be elucidated. In response to such cytokines, the
liver produces both acute phase proteins and various
cytokines.4 In several reports, interleukin-6 (IL-6) and
human hepatocyte growth factor (h-HGF) have been
measured during the perioperative period of a hepatec-
tomy and found to be significant indicators of surgical
stress.5,6 In addition, the level of type IV collagen 7S,
which is a marker for liver fibrosis, has been known to
have significant predictive value for postoperative com-
plications in hepatectomy cases with underlying liver
dysfunction.7 We measured the serum levels of IL-6, h-
HGF, and 7S over the postoperative course, and studied
their relationship to the liver function tests and SIRS.
Consequently, we attempted to determine whether or
not the IL-6, h-HGF, and 7S levels measured during the
perioperative period are significant predictive factors
for complications.
indocyanine green retention at 15min (P
with the SIRS(؊) cases, the IL-6, h-HGF, and 7S of the
SIRS(؉) cases fluctuated in a higher range and remained
< 0.01). Compared
significantly higher after postoperative day 1 (P
< 0.05). Eight
out of 14 SIRS(؉) patients had postoperative complications.
In the 8 SIRS(؉) patients with postoperative complications
and in the 4 patients in which the SIRS(؉) state lasted 3 days
or longer, the 7S levels were significantly higher during the
perioperative period (P
< 0.05). In the SIRS(؉) cases, the
postoperative levels of IL-6 and h-HGF, as well as pre- and
postoperative levels of 7S, were elevated. We therefore con-
sider these levels to be risk factors for complications during
the perioperative period of a hepatectomy.
Key Words: interleukin-6, human hepatocyte growth factor,
type IV collagen 7S, systemic inflammatory response
syndrome
Introduction
In recent years, the concept of systemic inflammatory
response syndrome (SIRS)1 has been commonly applied
to specific clinical symptoms, including fever, tachy-
cardia, and leukocytosis, caused by various invasive
Materials and Methods
The study subjects included 40 patients, who underwent
a hepatectomy from 1994 to 1997 (average age of 58.1
and a male to female ratio of 7:1) at the Second Depart-
ment of Surgery, Juntendo University Hospital, and
Reprint requests to: K. Namekata
(Received for publication on Dec. 14, 1998; accepted on Nov.
11, 1999)

404
K. Namekata et al.: Cytokine Changes in Hepatectomy Patients
preoperatively did not demonstrate SIRS. Among
these 40 patients, 26 had hepatocellular carcinoma, 9
metastatic liver tumor, 2 cholangiocellular carcinoma,
and 1 each of combined hepatocellular and cholangio-
carcinoma, bile duct cystadenocarcinoma, and liver he-
mangioma. In 22 patients (55%) there was histological
evidence of liver cirrhosis as a background factor. The
mean operating time was 276min, the mean blood loss
was 1201ml, and the mean weight of the resected liver
was 308g. Ten patients underwent a partial resection, 10
a subsegmental resection, 11 a unisegmental resection,
and 9 a bisegmental resection. The SIRS(ϩ) cases were
defined as those in which the SIRS diagnostic criteria
(Table 1) were fulfilled on the second day after the
operation.1 Sepsis was defined as a SIRS accompanying
infection.1 Postoperative complications were included
only when medical or interventional treatment was
given.
The serum levels of IL-6, h-HGF, and 7S were mea-
sured during the perioperative period of a hepatectomy,
and were analyzed separately in the SIRS(ϩ) and
SIRS(Ϫ) groups. In addition, the relationship between
the changes in the liver function tests before and after a
hepatectomy was comparatively analyzed.
For each case, peripheral venous blood samples were
obtained before the operation, immediately after the
operation (0), and on postoperative days (POD) 1, 3, 5,
and 7. The separated serum was preserved at Ϫ80°C for
measurement of IL-6, h-HGF, and 7S. The IL-6 was
measured by CLEIA (Fuji-Revio, Tokyo, Japan), the h-
HGF by the ELISA kit (Ohtsuka-Assay Laboratories,
Tokushima, Japan) and the 7S by the RIA kit (Japan
DPC, Tokyo, Japan).
liver function tests were also determined. The results
are presented as the mean Ϯ standard error. A P value
of less than 0.05 was considered to be statistically
significant.
Results
SIRS and Changes in the Serum IL-6, h-HGF,
and 7S Levels
The changes in the serum levels of IL-6, h-HGF, and 7S
of the SIRS(ϩ) group were compared with those of the
SIRS(Ϫ) group. The mean IL-6 level in the SIRS(ϩ)
group was 4.5 Ϯ 0.6pg/ml before the operation, 136
Ϯ 23pg/ml on POD 0, 145 Ϯ 41pg/ml on POD 1, 70 Ϯ
15pg/ml on POD 3, 30 Ϯ 5pg/ml on POD 5, and 36 Ϯ
7pg/ml on POD 7. The IL-6 level peaked on POD 1.
The postoperative values were significantly higher
than the corresponding values for the IL-6 levels in
the SIRS(Ϫ) group (P Ͻ 0.05). Furthermore, in the
SIRS(Ϫ) group, the IL-6 levels peaked on POD 0, and
gradually decreased thereafter. The h-HGF levels in the
SIRS(ϩ) group were 0.34 Ϯ 0.03ng/ml before the op-
eration, 0.45 Ϯ 0.05ng/ml on POD 0, 0.59 Ϯ 0.08ng/ml
on POD 1, 0.55 Ϯ 0.06ng/ml on POD 3, 0.47 Ϯ 0.06ng/
ml on POD 5, and 0.46 Ϯ 0.04ng/ml on POD 7. The h-
HGF level peaked on POD 1. The h-HGF levels were
significantly higher on POD 1, 3, and 7 in the SIRS(ϩ)
than in the SIRS(Ϫ) group (P Ͻ 0.05). In the SIRS(Ϫ)
group, the levels peaked on POD 1, and gradually de-
creased thereafter. The 7S level in the SIRS(ϩ) group
was 6.6 Ϯ 0.4ng/ml before the operation, 6.4 Ϯ 0.5ng/ml
on POD 0, 8.9 Ϯ 0.6ng/ml on POD 1, 8.9 Ϯ 0.4ng/ml on
POD 3, 7.4 Ϯ 0.7ng/ml on POD 5, and 7.2 Ϯ 0.6ng/ml
on POD 7. The levels peaked on POD 1 and 3. The 7S
levels on POD 1, 3, and 7 were significantly higher in the
SIRS(ϩ) than those in the SIRS(Ϫ) group (P Ͻ 0.05).
In addition, in the SIRS(Ϫ) group, the levels peaked
on POD 3, and then gradually decreased thereafter
(Fig. 1).
Statistical Analyses
Statistical analyses of the results were made using the
Mann-Whitney U-test. Differences in proportions
were compared using a ø2 test or Fisher’s Exact test.
Simple regression analyses were performed to assess
the correlations of the serum levels of IL-6, h-HGF, and
7S, and the correlations of these cytokine levels and
Relationship Between SIRS and the Maximum IL-6,
h-HGF, and 7S Levels
Table 1. Criteria for SIRS
The maximum postoperative levels of IL-6, h-HGF, and
7S in the SIRS(ϩ) group were compared with those in
the SIRS(Ϫ) group. The maximum IL-6 level was 223 Ϯ
32pg/ml in the SIRS(ϩ) group, which was significantly
higher than the level of 95 Ϯ 10pg/ml observed in the
SIRS(Ϫ) group (P Ͻ 0.01). The maximum levels of h-
HGF and 7S in the SIRS(ϩ) group were 0.7 Ϯ 0.08ng/
ml and 9.7 Ϯ 0.6ng/ml, respectively, which were also
significantly higher than those in the SIRS(Ϫ) group (P
Ͻ 0.05) (Fig. 2).
SIRS to a variety of severe clinical insults. The response is
manifested by two or more of the following conditions:
1. Temperature
2. Heart rate
Ͼ38°C or Ͻ36°C
Ͼ90 beats/min
3. Respiratory rate
Ͼ20 breaths/min or PaCO2 Ͻ 32 torr
(4.3kPa)
4. WBC count
Ͼ12000 cells/mm3, Ͻ4000 cells/mm3
or Ͼ10% immature (bands) forms
SIRS, systemic inflammatory response syndrome; WBC, white blood
cell

K. Namekata et al.: Cytokine Changes in Hepatectomy Patients
405
Fig. 1. Changes in the serum interleukin-6 (IL-6), human
hepatocyte growth factor (h-HGF), and type IV collagen 7S
(7S) levels after a hepatectomy with and without systemic
inflammatory response syndrome (SIRS). Compared with the
SIRS(Ϫ) cases (circles, n ϭ 26), the IL-6, h-HGF, and 7S
levels of the SIRS(ϩ) cases (squares, n ϭ 14) showed a greater
range of fluctuation and a significantly higher than after POD
1 (*P Ͻ 0.05)
Fig. 2. Maximum serum IL-6, h-
HGF, and 7S levels after a hepatec-
tomy with and without SIRS. The
postoperative maximum serum IL-6,
h-HGF, and 7S levels of SIRS(ϩ)
cases were significantly higher than
those of SIRS(Ϫ) cases
Table 2. Correlations between the maximum postoperative
serum IL-6, h-HGF, and 7S levels and liver function tests (PT,
HPT, ChE)
Preoperative and Intraoperative Parameters in
SIRS Cases
Postoperatively, 14 patients developed SIRS(ϩ) and 26
continued to demonstrate SIRS(Ϫ). The preoperative
and intraoperative background data for the two groups
are shown in Table 3. There were no significant differ-
ences between the two groups in terms of age, sex ratio,
intraoperative blood loss, operating time, and the
weight of resected liver. The preoperative liver function
tests, and serum levels of PT, HPT, and ChE, were
significantly lower in the SIRS(ϩ) group than in the
SIRS(Ϫ) group (P Ͻ 0.01). The value of indocyanine
green dye retention rate at 15min after the injection
of 0.5mg/kg (ICG-R15) was significantly higher in the
SIRS(ϩ) group than in the SIRS(Ϫ) group (P Ͻ 0.01)
(Table 3).
PT (%)
HPT (%)
ChE (IU/l)
IL-6
h-HGF
7S
r ϭ Ϫ0.55
P Ͻ 0.01
r ϭ Ϫ0.4
P Ͻ 0.05
r ϭ Ϫ0.38
P Ͻ 0.05
r ϭ Ϫ0.42
P Ͻ 0.01
r ϭ Ϫ0.41
P Ͻ 0.01
r ϭ Ϫ0.41
P Ͻ 0.01
r ϭ Ϫ0.58
P Ͻ 0.01
r ϭ Ϫ0.64
P Ͻ 0.01
r ϭ Ϫ0.45
P Ͻ 0.01
IL-6, interleukin-6; h-HGF, human hepatocyte growth factor; 7S, type
IV collagen 7S; PT, activated prothrombin time; HPT, activated
hepaplastin test; ChE, cholinesterase
Analyses of the Postoperative Maximum Levels of
IL-6, h-HGF, and 7S and Liver Function Tests
The maximum postoperative IL-6 level negatively
correlated with the serum level at activated prothrom-
bin time (PT) (r ϭ Ϫ0.55, P Ͻ 0.01) and the serum
level in the activated hepaplastin test (HPT) (r ϭ Ϫ0.4,
P Ͻ 0.05). The maximum levels of h-HGF and 7S
also showed a negative correlation with the serum
levels of PT, HPT, and cholinesterase (ChE) (Table
2).
Preoperative IL-6, h-HGF, and 7S Levels and
Postoperative Complications
The preoperative levels of IL-6, h-HGF, and 7S were
estimated for their predictive relevance to postopera-
tive complications. In the 8 SIRS(ϩ) patients who de-
veloped postoperative complications, the preoperative
levels of IL-6 and h-HGF did not significantly differ

406
K. Namekata et al.: Cytokine Changes in Hepatectomy Patients
Table 3. Background data for cases with and wihout SIRS
SIRS (ϩ)
(n ϭ 14)
SIRS (Ϫ)
(n ϭ 26)
P value
Age
Gender (M/F)
58 Ϯ 2
6:1
58 Ϯ 2
8:1
0.94
0.81
Operative
findings
Blood loss (g)
Operating time (min)
Resected liver weight (g)
1211 Ϯ 198
234 Ϯ 18
227 Ϯ 50
1196 Ϯ 134
285 Ϯ 16
358 Ϯ 64
0.95
0.08
0.16
Preoperative
liver function
tests
PT (%)
81 Ϯ 3
72 Ϯ 5
857 Ϯ 64
0.93 Ϯ 0.1
18.3 Ϯ 3.4
93 Ϯ 2
86 Ϯ 3
1074 Ϯ 51
0.83 Ϯ 0.1
9.8 Ϯ 1.0
Ͻ0.01
Ͻ0.01
Ͻ0.01
0.32
HPT (%)
ChE (IU/l)
T-Bil (mg/dl)
ICG-R15 (%)
Ͻ0.01
Values are expressed as mean Ϯ SE
T-Bil, total bilirubin; ICG-R15, the value of indocyanine green dye retention rate at 15min after
the injection of 0.5mg/kg
Table 4. Postoperative complications and the preoperative serum IL-6, h-HGF, and 7S
levels
(a)
(b)
(c)
(d)
(n ϭ 8)
(n ϭ 32)
P value
(n ϭ 4)
(n ϭ 36)
P value
IL-6
(pg/ml)
5.1 Ϯ 1.0
4.0 Ϯ 0.2
0.23
6.1 Ϯ 1.8
4.0 Ϯ 0.2
0.11
h-HGF 0.34 Ϯ 0.04 0.32 Ϯ 0.01
(ng/ml)
0.94
0.39 Ϯ 0.1 0.32 Ϯ 0.01
8.1 Ϯ 0.7 5.9 Ϯ 0.3
0.57
7S
(ng/ml)
7.2 Ϯ 0.5
5.9 Ϯ 0.2
P Ͻ 0.05
P Ͻ 0.05
Values are expressed as mean Ϯ SE
(a) SIRS (ϩ) and complications (ϩ); (b) all cases other than (a); (c) SIRS (ϩ) for 3 days or longer;
(d) all cases other than (c)
from the control group. The preoperative 7S level, how-
ever, was 7.2 Ϯ 0.5ng/ml, which was significantly higher
than the level of 5.9 Ϯ 0.2ng/ml measured in the
SIRS(Ϫ) group and the cases without postoperative
complications (P Ͻ 0.05). In the 4 patients that demon-
strated SIRS(ϩ) for 3 days or longer, no significant
difference was found in the preoperative levels of IL-6
and h-HGF. However, the preoperative 7S level was
8.1 Ϯ 0.7ng/ml, which was significantly higher than
the level of 5.9 Ϯ 0.3ng/ml measured in other cases
(P Ͻ 0.05) (Table 4).
was 2.3 days, and the period lasted for a day in 5 cases,
2 days in 5 cases, and 3 days or longer in 4 cases. Two
out of 5 patients with SIRS(ϩ) for a day (40%), 2 out
of 5 patients with it for 2 days (40%), and 4 out of 4
patients with it for 3 days or longer (100%) developed
postoperative complications (Table 5).
Discussion
Various factors have been investigated and analyzed in
association with the development of complications after
surgery. In addition, such factors as age, gender, operat-
ing time, volume of blood loss, the need for transfusion,
and imbalance among the biological defense systems
including the nervous system, endocrine system, and
immune system have all been considered as causes. In
the 1980s, various cytokines were discovered, and as
their functions have been elucidated, increasing atten-
tion has been focused on those which act as mediators,
thus inducing systemic inflammatory responses after
trauma, burn injury, and infection. The concept of
SIRS1 has become well accepted in recent years, and the
Postoperative SIRS(ϩ) Period and Complications
The relationship between the duration of postoperative
SIRS(ϩ) and the development of complications was
investigated. Complications were observed in 8 patients
(20%) and consisted of: renal dysfunction (n ϭ 5); intra-
peritoneal infection (n ϭ 4); pneumonia (n ϭ 2); and
pleural effusion (n ϭ 1). Six of the 14 patients (43%)
with SIRS(ϩ) showed the presence of sepsis. One
SIRS(ϩ) patient with sepsis developed MODS. In 14
SIRS(ϩ) patients, the mean duration of the SIRS state

K. Namekata et al.: Cytokine Changes in Hepatectomy Patients
407
Table 5. Relationship between postoperative complications and SIRS
Duration
of SIRS
Frequency rate
of complications
Complications
1 day
40%
40%
Intraperitioneal infection (1 case),
renal dysfunction (1 case)
(n ϭ 5)
2 days
(n ϭ 5)
Intraperitoneal infection (1 case),
intraperitoneal infection and renal dysfunction
(1 case)
3 days or
longer
(n ϭ 4)
100%
Intraperitoneal infection (1 case),
renal dysfunction and pleural effusion (1 case),
renal dysfunction and pneumonia (2 cases)
Renal dysfunction: serum creatinine level м 1.0mg/dl
state involving proinflammatory cytokines is now
recognized as a step prior to the disease progression
from postoperative complications or sepsis to MODS.2,3
Several reports have indicated the importance of
proinflammatory cytokines in the serum to the patho-
physiology of surgical stress, rejection in organ
transplantation, SIRS, and MODS.2,8–11
and evaluated their predictive worth for complications
after a hepatectomy.
The serum levels of PT, HPT, and ChE, which are
conventional indices of liver parenchymal cell injury
after a hepatectomy, are still considered to be important
and reliable laboratory data. After a hepatectomy, the
serum IL-6, h-HGF, and 7S levels showed negative
correlations with the serum levels of PT, HPT, and ChE
(Table 2), thus suggesting a close association between
the postoperative liver parenchymal cell injury and
the nonparenchymal cell destruction. As a result, the
serum IL-6, h-HGF, and 7S levels may be considered
to be useful markers for estimating the degree of
nonparenchymal cell injury after hepatectomy and
evaluating the hepatic sinusoidal function.
IL-6 is mainly produced by Kupffer and Ito cells in
the hepatic sinusoids, by vascular endothelial cells, and
by fibroblasts.4,12,13 Serum IL-6 is a useful marker for the
early prediction and diagnosis of SIRS and postopera-
tive complications during the perioperative period,14,15
since it promptly reflects the changes in biological re-
sponse of the individual.14–16 h-HGF is produced in the
liver, kidney, and lung. Similarly to IL-6, h-HGF is pro-
duced by endothelial cells, and by Kupffer and Ito cells
of the hepatic sinusoids.17 The serum h-HGF level in-
creased in association with hepatocellular dysfunction,
hepatic necrosis, and systemic inflammation.6,18,19 An el-
evated serum h-HGF level after a hepatectomy usually
represents an unfavorable environment for the restora-
tion of the liver function, and if such a condition per-
sists, it may be necessary to prepare for progression to
hepatic failure.6 Type IV collagen, localized in the Disse
space of the liver, is mainly produced by Ito cells of the
hepatic sinusoids, endothelial cells, and hepatocytes
during the early stage of liver dysfunction, and accumu-
lates as fibrosis and liver impairment progress.20 The 7S
is a fragment located in the N-terminal domain of type
IV collagen21,22 and its measurement in cases compli-
cated by various liver diseases has been reported to be
extremely useful in predicting postoperative complica-
tions.7,23
Ever since the concept of SIRS has been proposed,1
the systemic inflammatory response to infectious
diseases, trauma, burns, and pancreatitis has been
collectively discussed. All the clinical signs listed in
the criteria for diagnosis of SIRS can be explained by
cytokines, and SIRS is thus considered to be a state of
hypercytokinemia.9
Although cytokine measurements are important in
diagnosing SIRS, they play a more important role in
determining whether or not SIRS develops during
the recovery from the surgical stress or is induced by
various complications.15 However, it remains to be elu-
cidated as to exactly when a diagnosis of SIRS in post-
operative cases should be made. In the present study,
we regarded the cases in which the diagnostic criteria
were fulfilled on the second day after surgery to be
SIRS(ϩ), since the circulatory dynamics such as
instabilities in blood pressure and pulse are generally
stabilized by POD 2.
In this study, we selected IL-6 and h-HGF as param-
eters, since they are relatively easy and reliable to mea-
sure as compared to the other serum cytokines. We also
chose 7S because it is considered to be a useful preop-
erative predictor for postoperative complications. We
next analyzed the correlations among these parameters,
There were no significant differences of the serum IL-
6, h-HGF, and 7S levels, measured before and im-
mediately after surgery, between the SIRS(ϩ) and the
SIRS(Ϫ) groups. However, the serum IL-6, h-HGF, and
7S levels were significantly higher on POD 1 in the

408
K. Namekata et al.: Cytokine Changes in Hepatectomy Patients
SIRS(ϩ) group than in the SIRS(Ϫ) group (Fig. 1).
Therefore, SIRS(ϩ) cases can be predicted by measur-
ing the serum IL-6, h-HGF, and 7S levels on POD 1,
and may thus allow for the early determination of
cases likely to develop postoperative complications and
MODS. In addition, considering the fact that progres-
sion to SIRS(ϩ) is frequent in cases of liver dysfunction
before operation (Table 3), SIRS(ϩ) cases can be pre-
dicted by measuring the preoperative serum levels of
PT, HPT, ChE, and ICG-R15.
The frequency of postoperative complications is con-
sidered to depend on the duration of SIRS, rather than
the number of SIRS-related signs.24 In this study, all 4
patients in whom the SIRS(ϩ) lasted for 3 days or
longer developed postoperative complications. Renal
dysfunction (serum creatinine level м1.0mg/dl) is also
considered to be associated with an increased incidence
of SIRS and postoperative complications, since the
cytokine clearance is reduced.24 In this study, in 5 out of
8 SIRS(ϩ) patients with postoperative complications
the serum creatinine level was elevated to 1.0mg/dl or
higher, thus suggesting that the decrease in cytokine
clearance is related to SIRS. In one patient the SIRS(ϩ)
lasted for 2 days, and was complicated by renal dysfunc-
tion (serum creatinine level of 1.67mg/dl) and sepsis
induced by intraperitoneal methicillin-resistant Staphy-
lococcus aureus infection. A second elevation of the
serum levels of IL-6, h-HGF, and 7S was observed on
POD 3 and the liver dysfunction persisted, thus result-
ing in MODS. The outcome in this case suggested that
the decrease in cytokine clearance was also related to
the severity of SIRS.
serum levels of IL-6, h-HGF, and 7S were regarded to
be SIRS(ϩ). In such patients, intensive management
directed against postoperative complications, septic
SIRS, and MODS is therefore required.
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Utilizing SIRS as one of the warning signs for
determining serious cases is thus considered to be effec-
tive9,15,25 since it may require strict and intensive man-
agement in order to avoid progression to MODS. After
a hepatectomy, the serum peak levels of IL-6, h-HGF,
and 7S were significantly higher in the SIRS(ϩ) cases
(Fig. 2), and were thus found to be a useful marker for
predicting postoperative SIRS(ϩ).
In 8 SIRS(ϩ) patients with postoperative complica-
tions and 4 patients with SIRS(ϩ) lasting for 3 days or
longer, no significant elevation was found in the pre-
operative serum IL-6 and h-HGF levels. However, the
preoperative serum 7S levels in these cases were
significantly higher than in other cases (P Ͻ 0.05) (Table
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In summary, we demonstrated that the measurements
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