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Contents lists available at ScienceDirect

Surgery
journal homepage: www.elsevier.com/locate/surg

Quality of life after single-incision laparoscopic cholecystectomy: A

randomized, clinical trial
Eitaro Ito, MD a,∗, Akihiro Takai, PhD a, Yoshinori Imai, PhD b, Hiromi Otani, PhD c,
Yoshihiro Onishi, PhD d, Yosuke Yamamoto, PhD e, Kohei Ogawa, PhD a, Taiji Tohyama, PhD a,
Shunichi Fukuhara, DMSc e, Yasutsugu Takada, PhD a
a
Department of Hepato-Biliary-Pancreatic and Breast Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan
b
Department of Gastrointestinal Surgery, Uwajima City Hospital, Uwajima, Ehime, Japan
c
Department of Gastrointestinal Surgery, Ehime Prefectural Central Hospital, Matsuyama, Ehime, Japan
d
Institute for Health Outcomes & Process Evaluation Research (iHope International), Nakagyo-ku, Kyoto, Japan
e
Department of Healthcare Epidemiology, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan

a r t i c l e i n f o a b s t r a c t

Article history: Background: Controversy continues as to whether single-incision laparoscopic cholecystectomy, with the
Accepted 8 August 2018 somewhat larger incision at the umbilicus, may lead to a worse postoperative quality of life and more
Available online xxx
pain compared with the more classic 4-port laparoscopic cholecystectomy. The aim of this study was to
compare single-incision and 4-port laparoscopic cholecystectomy from the perspective of quality of life.
Methods: This study was a multicenter, parallel-group, open-label, randomized clinical trial. A total of 120
patients who were scheduled to undergo elective cholecystectomy were randomly assigned 1:1 into the
single-incision laparoscopic cholecystectomy or the 4-port laparoscopic cholecystectomy group and then
assessed continuously for 2 weeks during the postoperative period. The primary outcome was quality
of life, defined as the time to resume normal daily activities. Postoperative pain was also assessed. To
explore the heterogeneity of treatment effects, we assessed the interactions of sex, age, and working
status on recovery time.
Results: A total of 58 patients in the single-incision group and 53 in the 4-port group (n = 111, 47 male,
mean age 57 years) were analyzed. The mean time to resume daily activities was 10.2 days and 8.8 days,
respectively, for single-incision and 4-port laparoscopic cholecystectomy (95% confidence interval –0.4
to 3.2, P = .12). Similarly, the time to relief from postoperative pain did not differ significantly between
the groups. Statistically insignificant but qualitative interactions were noted; in the subgroups of women,
full-time workers, and patients younger than 60 years, recovery tended to be slower after single-incision
laparoscopic cholecystectomy.
Conclusion: Postoperative quality of life did not differ substantially between single-incision laparoscopic
cholecystectomy and 4-port laparoscopic cholecystectomy. Patients younger than 60 years, women, and
full-time workers tended to have a somewhat slower recovery after single-incision laparoscopic cholecys-
tectomy.
© 2018 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY-NC-ND license.
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

Introduction single-incision laparoscopic cholecystectomy (SILC) has been pro-

The classic 4-port laparoscopic cholecystectomy (4PLC) has
been the gold standard in the treatment of benign gallbladder
diseases such as symptomatic cholecystolithiasis.1 More recently,
∗
Corresponding author: Department of Surgery, Hepato-Biliary-Pancreatic
Surgery and Breast Surgery, Ehime University Graduate School of Medicine,
Shitsukawa, Toon City, Ehime 791-0295, Japan.
E-mail address: hmnsj175@m.ehime-u.ac.jp (E. Ito).
posed as an improvement in minimally invasive cholecystectomy.2
This new technique allows the procedure to be performed using a
special access device to simultaneously insert instruments and the
laparoscope through just 1 small incision. With the scar largely
concealed in the concave aspect of the umbilicus, SILC offers a
virtually invisible scar to patients. This technique, along with
the expectation of less pain and quicker recovery, has gained
some acceptance and currently accounts for 16% of laparoscopic
cholecystectomies performed in Japan.3 In contrast, SILC requires

https://doi.org/10.1016/j.surg.2018.08.004
0039-6060/© 2018 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license.
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
JID: YMSY
ARTICLE IN PRESS
2 E. Ito et al. / Surgery 000 (2018) 1–7
some specific skills to ensure triangulation under the interfer-
ence between instruments, which leads to a somewhat increased
workload on surgeons and prolonged operative time.4
After the introduction of this new technique, more than a dozen
randomized clinical trials were conducted to compare SILC with
4PLC.5-20 These trials were designed to focus on cosmesis, pain,
or quality of life (QOL), with patient-reported outcomes to eval-
uate subjectively the degree of patient suffering. In particular, QOL
is drawing attention as a key measure to understand how pa-
tients evaluate their physical, mental, or social health status.21
So far, several studies have consistently reported greater cosmetic
satisfaction with SILC over 4PLC.7-10 In contrast, controversy per-
sists regarding pain; some studies have reported that SILC has
an advantage regarding pain because of the decreased number of
ports,5,7,10,16 whereas other studies have reported that an unfavor-
able pain profile resulted from the larger umbilical incision re-
quired for SILC.8,14 Similarly, it remains poorly understood whether
SILC contributes to a substantive improvement in QOL.22-24 Not
much literature is available on QOL after SILC, and, furthermore,
published results seem to lack agreement and reproducibility.
The aim of this study was to compare QOL between the SILC
and conventional 4PLC by continuous QOL assessment in the post-
operative period. Based on our clinical experience, patients who
undergo SILC seem to have increased postoperative pain. Thus we
hypothesized that SILC delays the resumption of normal daily ac-
tivities compared with 4PLC.
Methods
Study design
This was a multicenter, 2-arm parallel group, open-label, ran-
domized clinical trial involving 3 investigational sites in Japan.
This study was approved by the Ethics Committee of Ehime Uni-
versity Hospital (approval number: 1304001) and by the other
sites. The study team was organized by members from Ehime
University, Kyoto University, and NPO iHOPE International. Be-
fore trial commencement, the protocol was registered in the Uni-
versity Hospital Medical Information Network Clinical Trial Reg-
istry (registration number: UMIN0 0 0 010583 http://www.umin.ac.
jp/english/). Written informed consent was obtained from all par-
ticipants. This study was conducted in accordance with the Decla-
ration of Helsinki, and this report is based on the CONSORT (Con-
solidated Standards of Reporting Trials) statement (http://www.
consort-statement.org).
Participants
Participants were recruited at 3 teaching hospitals, where both
SILC and 4PLC procedures were performed as routine medical care:
Ehime University Hospital, Uwajima City Hospital, and Ehime Pre-
fectural Central Hospital.
Patients were eligible if they were 20 years or older and were
scheduled to undergo elective laparoscopic cholecystectomy for
symptomatic cholelithiasis, gallbladder polyp, or adenomyomato-
sis. Exclusion criteria were history of acute cholecystitis, severe
cirrhosis, suspected cases of gallbladder cancer, when other op-
erations were combined with cholecystectomy, body mass index
greater than 35 kg/m2 , pregnancy, and mental disorder or demen-
tia.
Randomization
After obtaining written consent, the surgeon sent the regis-
tration form via fax to the coordinating center (Clinical Research
Support Center of Ehime University Hospital) by the day before
Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
[m5G;October 9, 2018;20:28]
the operation. Then a dynamically allocated, 1:1 random sequence
stratified by institution, sex, age (<70 years or not), and working
status (yes or no, including domestic duties) was computer gen-
erated in the coordinating center. The patient allocation was sent
back to the surgeon via fax, and the surgeon informed patients of
the assigned procedure before the operation.
Surgical procedures
All laparoscopic cholecystectomies were performed in the same
way as routine practice by members in the study sites ranging
from specialist to resident, including those having performed fewer
than 5 SILCs. Bile ducts were evaluated with preoperative magnetic
resonance cholangiopancreatography. Perioperative management in
both groups was the same using the clinical pathway of each site.
Prophylactic cefazolin 1.0 g was administered intravenously within
30 minutes before skin incision and postoperatively on that day.
SILC procedure
A 25-mm incision was made in the umbilicus. After a small-size
wound protector was installed through the incision, an access de-
vice (EZ ACCESS, HAKKO, Nagano, Japan) or a surgical glove (glove
technique)25 with 3 5-mm trocars was attached to the wound pro-
tector. Additionally, a 3-mm or smaller instrument was inserted
in the right epigastrium to retract the fundus of the gallbladder.
The operator performed cholecystectomy in the standard fashion
for conventional 4PLC.
4PLC procedure
A 15-mm incision was made in the umbilicus. A 12-mm trocar
was inserted by an open method, and 3 5-mm trocars were placed
in the right upper quadrant.
After operation, analgesics were administered intravenously
(flurbiprofen 50 mg, a nonsteroidal anti-inflammatory agent) as
necessary during the fasting period and then orally (loxoprofen 60
mg, also an oral nonsteroidal anti-inflammatory agent) for 3 days
or more if necessary. No opioids were administered throughout the
study. Discharge from the hospital was on the second to fifth post-
operative day.
Outcomes
The primary outcome was the time to resume normal daily ac-
tivities (work or other daily activities) postoperatively. This out-
come was selected as the most relevant one to assess the QOL of
patients who underwent laparoscopic cholecystectomy. Difficulties
in daily activities were measured by the Role Physical subscale (RP)
of the 36-Item Short Form Health Survey (SF-36),26,27 which asks
patients 4 questions concerning problems with work or other ac-
tivities as a result of physical health. Patients answered the ques-
tions once the day before operation and every day from postop-
erative day 1 (the first day postoperatively) to the first outpatient
visit (typically days 14–20). The time to resume normal daily activ-
ities was defined as the number of days postoperatively when the
RP score first returned to the preoperative level or the norm-based
scoring 50 (standardized value of a general population in Japan,
mean = 50, SD = 10), whichever came first after discharge.
The secondary outcomes were the following: time to relief of
postoperative pain, time to resume working, operative time, bleed-
ing, duration of hospital stay, inflammatory responses, and clinical
complications. Postoperative pain was assessed by the following 3
instruments: the Bodily Pain subscale of the SF-36, a numeric rat-
ing scale of 0 to 10, and a modified Surgical Pain Scale28 including
degrees at rest, with daily activities, with hard work/exercise, and
contrasted with what had been expected.
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E. Ito et al. / Surgery 000 (2018) 1–7
Data collection
To collect reports from participants, a health diary that com-
prised a series of questions including RP, pain, and working sta-
tus was used. It took approximately 5 minutes to complete the
questionnaire per day. Each participant was asked to complete the
questionnaire once before and every day postoperatively until the
first outpatient visit after discharge. Demographic data, operative
findings, and complications were recorded in each patient data
sheet by the surgeons. These data were sent to the coordinating
center and entered in a computer file by coordinators.
Sample size
The time course of the change in QOL was unknown for the
early recovery phase after laparoscopic cholecystectomy. A pilot
survey was therefore performed to estimate the time to recovery
of RP, which was found to be 12 days with a standard deviation of
3.3 to 4.8 days. Assuming a clinically relevant difference between
SILC and 4PLC of 2 days, 50 patients per group were required to
detect this difference with a 2-sided α error of .05 and a power of
0.8. Considering dropouts, the sample size was determined to be
60 per group.
Statistical methods
Data were analyzed according to the principle of intention to
treat (ITT). Numeric data are summarized by means and standard
deviation. Categorical data are presented as raw counts. The size of
treatment effects (difference between 2 groups) on the time to re-
covery is expressed as an absolute difference in days and the 95%
confidence interval (95% CI). For patients who did not reach com-
plete recovery during the observation period (ie, were censored),
the time to recovery was replaced by the day of last observation.
The t test and Fisher exact test (or χ 2 test if appropriate) were
used for numeric and categorical data, respectively.
For the primary outcome, in addition to the previously stated
outcomes, differences between groups were identified by Kaplan-
Meier curves, and sensitivity analyses29 were performed to ascer-
tain the robustness of ITT results with a per-protocol set analysis
and excluding censored patients.
To explore the heterogeneity of treatment effects on resum-
ing normal daily activities and postoperative pain, interactions30 of
sex, age (<60 years or not), and working status (full-time [5 or
more days per week] worker or not) were assessed using general
linear models, although they were not specified in advance in the
protocol.
All analyses were carried out using SAS 9.4 or JMP 9.0 (SAS In-
stitute, Inc, Cary, NC).
Results
Patients
From May 2013 to October 2015, 392 adult patients under-
went elective laparoscopic cholecystectomy, of whom 123 patients
were enrolled in this study (Fig 1). A total of 63 patients were as-
signed to SILC and 60 to 4PLC. In the SILC group, 1 patient re-
quired the addition of a port and 1 required conversion to 4PLC,
both because of adhesions. One patient in the 4PLC group under-
went the SILC procedure because of the surgeon’s error in confirm-
ing the assignment. No patient in the 4PLC group was converted
to open cholecystectomy. After random allocation, 5 patients with-
drew their consent to change their allocated procedure to the other
one. In 1 patient allocated to 4PLC, the operation was cancelled
because of asthma after induction of anesthesia. During follow-up,
Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
[m5G;October 9, 2018;20:28]
3
the questionnaires of 5 patients were not able to be collected, and
1 patient in the SILC group withdrew from the study because of
dissatisfaction with a staff member. Consequently, a total of 111 pa-
tients were available for ITT analyses: 58 for SILC and 53 for 4PLC.
For per-protocol set analyses, 3 patients who underwent the op-
posite procedure for any reasons were excluded and 108 patients
were available (56 for SILC and 52 for 4PLC).
The characteristics of the patients are shown in Table 1. Their
mean age was 57.4 years (range: 28–79 years), with women ac-
counting for two thirds of the patients. The 2 groups were well
balanced except for working days and hours, which tended to be
less in the SILC group than in the 4PLC group.
Primary outcome
Kaplan-Meier curves indicated the proportions of patients who
resumed normal daily activities in the 2 treatment groups (Fig 2).
These data include censored cases: 11 patients in the SILC group
and 9 in the 4PLC group who did not resume daily activities within
the observation period. The mean time to resume daily activities
was 10.2 ± 4.6 days in the SILC group and 8.8 ± 4.6 days in the
4PLC group (95% CI: –0.4 to 3.2; P = .12; Table 2). The sensitivity
analyses also gave results that were not statistically significant: a
difference of 1.4 days (95% CI: –0.5 to 3.1, P = .15) on the PPS analy-
sis and 1.3 days (95% CI: –0.1 to 2.6, P = .07) by excluding censored
patients.
Secondary outcomes
Table 3 summarizes the results for postoperative pain in the
2 treatment groups. No significant differences were noted in re-
lief from postoperative pain between the SILC group and the 4PLC
group.
Table 4 summarizes other clinical outcomes. The mean oper-
ative time of SILC was similar to that of 4PLC (99 vs 92 min-
utes; P = nonsignificant). Duration of postoperative hospital stay
(4.3 vs 4.2 days) and time to resume working (9.9 vs 9.4 days)
were also similar. As for the postoperative inflammatory response,
that of SILC was similar (white blood cell counts: 8179 vs 7743/μL,
C-reactive protein: 2.5 vs 1.7 mg/dL). Operative complications
(wound infection, incisional hernia, abdominal hematoma, and
choledocholithiasis) did not differ between the groups. One pa-
tient in the SILC group developed an incisional hernia with omen-
tal incarceration on postoperative day 4 and required operative re-
pair. One patient in the SILC group was found to have a perihep-
atic hematoma and was treated conservatively. Two patients in the
4PLC group developed choledocholithiasis and required endoscopic
lithotomy. None of the patients had operative bleeding greater than
50 mL or bile duct injury.
Interactions
The heterogeneity of treatment effects on the primary outcome
is summarized in Fig 3. Statistically nonsignificant but qualitative
interactions were noted; the recovery tended to be slower in the
SILC group than in the 4PLC group in the subgroups of women (a
difference of 2.3 days, 95% CI: –0.3 to 4.9), full-time workers (2.4,
0.5–4.2), and especially patients younger than 60 years (2.1, 0.0–
4.3), whereas there were almost no differences in other subgroups.
Interactions of age and treatment effects on postoperative pain are
shown in Supplementary Fig 1. Again, although not statistically sig-
nificant, relief from pain tended to be slower in the SILC group
than in the 4PLC group in the subgroup of patients younger than
60 years, whereas there were almost no significant differences in
the subgroup of patients aged 60 years or older.
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4 E. Ito et al. / Surgery 000 (2018) 1–7

Fig. 1. The CONSORT flow diagram for this study. ∗ Excluded from per-protocol set analyses. 4PLC, 4-port laparoscopic cholecystectomy; SILC, single-incision laparoscopic
cholecystectomy.

Table 1
Patients’ baseline characteristics.

Total(n = 111) Procedure P

SILC (n = 58) 4PLC (n = 53)

Age (y)∗ 57.4 (12.5) 58.8 (12.9) 55.9 (11.8) .23

Sex (M/F) 47:64 24:34 23:30 .83
BMI (kg/m2 )∗ 24.5 (3.7) 24.8 (3.9) 24.2 (3.5) .35
Disease .63
Cholelithiasis 50 49
Polyp 4 1
Adenomyomatosis 4 3
Working (yes/no)† 85:26 40:18 45:8 .08
Working days per week† 4.0 (2.5) 3.6 (2.6) 4.4 (2.2) .07
Working hours per day† 5.8 (4.0) 5.0 (3.9) 6.7 (3.8) .03
Observation period (days)∗ 16.7 (3.4) 16.8 (2.8) 16.5 (3.9) .56

BMI, body mass index.

∗
Values are means (standard deviation).
†
Working was considered to include domestic duties.

Table 2
Time to resume daily activities in the 2 treatment groups.

Analysis SILC 4PLC Difference P

Mean days (SD) Mean days (SD) (95% CI)

ITT n = 58 n = 53 1.4 (–0.4 to 3.2) .12

10.2 (4.6) 8.8 (4.6)
PPS n = 56 n = 52 1.4 (–0.5 to 3.1) .15
10.3 (4.7) 8.9 (4.7)
Excluding censored patents n = 47 n = 44 1.3 (–0.1 to 2.6) .07
8.8 (3.4) 7.5 (3.0)
Resuming daily activities, return to the preoperative score or to NBS 50 on SF-36 RP.
NBS, Norm-based scoring; PPS, per-protocol set; SD, standard deviation.

Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
JID: YMSY
ARTICLE IN PRESS [m5G;October 9, 2018;20:28]

E. Ito et al. / Surgery 000 (2018) 1–7 5

Table 3
Time for relief from postoperative pain in the 2 treatment groups.

Measure SILC (n = 58) 4PLC (n = 53) Difference P

Mean days (SD) Mean days (SD) (95% CI)

SF-36 BP 5.5 (4.3) 5.1 (3.8) 0.4 (–1.1 to 2.0) .57

NRS 10.7 (5.1) 10.3 (5.6) 0.4 (–1.6 to 2.4) .68
SPS (at rest) 9.0 (5.3) 8.0 (5.7) 1.0 (–1.1 to 3.0) .37
SPS (on daily activity) 10.9 (5.0) 9.6 (5.3) 1.3 (–0.7 to 3.2) .19
SPS (on exercise) 12.1 (5.0) 10.6 (5.4) 1.5 (–0.5 to 3.5) .13
SPS (contrasted with expectation) 9.9 (6.3) 8.2 (5.7) 1.7 (–0.6 to 3.9) .15

BP, Bodily Pain subscale; NRS, numeric rating scale; SD, standard deviation; SPS, Surgical Pain Scale.28

Table 4
Other clinical outcomes.

SILC (n = 58) 4PLC (n = 53)

95% CI 95% CI P

Operative time (min)∗ 99.3 87.3–111.2 91.8 79.3–104.3 0.39

Hospital stay (days)∗ 4.3 3.8–4.7 4.2 3.8–4.7 0.93
Days to resume work∗ 9.9 8.7–11.0 9.4 8.2 to 10.6 0.39
Inflammatory response
Peak WBC (cells/μL)∗ 8,179 7,671–8,687 7,743 7,216–8,270 .24
Peak CRP (mg/dL)∗ 2.5 1.9–3.1 1.7 1.1–2.3 .06
Complications†
Wound infection 1 2 .61
Incisional hernia 1 0 1.00
Abdominal hematoma 1 0 1.00
Choledocholithiasis 0 2 .23

CRP, C-reactive protein; WBC, white blood cells.

∗
Values are means.
†
Fisher exact test.

Fig. 2. Kaplan-Meier curves showing time to resume daily activities after laparo-
scopic cholecystectomy. 4PLC, 4-port laparoscopic cholecystectomy; SILC, single-
incision laparoscopic cholecystectomy.
Fig. 3. Interactions of sex, age, and working status on the time to resume daily
activities. 4PLC, 4-port laparoscopic cholecystectomy; CI, confidence interval; SILC,
single-incision laparoscopic cholecystectomy.

Discussion
In this study the time to resume normal daily activities (QOL)
was not significantly greater in the SILC group than in the 4PLC
group. For subgroups of patients younger than 60 years, women,
and full-time workers, the results suggested that SILC may delay
recovery of QOL compared with 4PLC, but no significant interac-
tions were identified.
This is the first randomized clinical trial conducted in Japan in
which the population included patients who were older and whose
body mass index was low compared with previous studies from
other regions. To the best of our knowledge, the study is the sec-
ond randomized clinical trial designed to assess the QOL as a pri-
mary endpoint of patients undergoing SILC and 4PLC. The present
results are not in line with those of the first study by Abd Ellatif
et al,10 who reported that SILC patients had better QOL (mobil-
ity, self-care, activity, and pain or discomfort on the EuroQoL EQ-
5D) at 1 week postoperatively and an improved pain profile. Six
other published randomized trials explored QOL as a secondary
endpoint6,7,9,11,19,20 ; 3 noted no significant difference between SILC
and 4PLC.6,9,11 Bucher et al7 reported that the SILC group had a
better SF-12 score than the 4PLC group at 1 month postopera-
tively. Lurje et al20 also reported better QOL at 1 year after SILC
in several domains of SF-36 (emotional well-being, physical pain,
physical health, and mental health), whereas Bingener et al,19 us-
ing the Linear Analog Self-Assessment tool, reported that fatigue
was greater in the SILC group at 1 week.
QOL is a broad, multidimensional subjective concept that in-
cludes physical, mental, and social health status, and it can be

Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
JID: YMSY
ARTICLE IN PRESS
6 E. Ito et al. / Surgery 000 (2018) 1–7
elusive, even though its measurement has become common in
medical research today. In addition, there is a lack of standard-
ized methodology, and considerable heterogeneity is found among
studies, including those mentioned earlier. Validated measurement
tools of global QOL such as the SF-36 are available, whereas a
cholecystectomy-specific one is yet to be developed. One poten-
tial problem of using a single global QOL measurement tool is the
low ability to perceive meaningful differences in specific dimen-
sions of QOL.31 Before this study, a pilot survey was performed
to test the SF-36 with 16 patients who underwent laparoscopic
cholecystectomy, including 5 SILCs and 11 4PLCs. Through the re-
sults of the pilot survey and with reference to an earlier study,6 it
was evident that the RP subscale of the SF-36 detected a greater
difference in QOL than the other subscales; patients experienced
difficulty in daily activities or a return to work as a result of la-
paroscopic cholecystectomy. As for the schedule of assessments,
most earlier studies measured outcomes sporadically in the pe-
rioperative period or a long time after the operation. In mini-
mally invasive surgery, however, most patients return to normal
activities quickly. Saad et al11 reported that patients were largely
relieved from pain by day 7 after laparoscopic cholecystectomy.
Therefore in the present study patients were assessed at multiple
time points32 during the perioperative period, and the number of
days to recovery was compared instead of the scores obtained at
certain points.
Our study set out to verify our hypothesis that SILC impedes re-
covery of patients QOL (normal daily activities). A possible expla-
nation for this was our belief that SILC would lead to more pain
at the umbilicus. Although SILC is characterized by fewer access
ports than 4PLC, it requires a somewhat larger incision at the um-
bilicus to place 3 ports, a location with maximum pain sensation
among other port sites in the abdominal wall.11 To date, however,
the amount and importance of postoperative pain of SILC has been
controversial, possibly attributable to disparities in incision size
among studies. Many of the earlier studies limited the operators
to certain experienced surgeons, whereas this study allowed resi-
dents to participate as surgeons. Considering the tradeoff between
incision size at the umbilicus and the interference of instruments
in performing SILC, an adequate incision is required to decrease in-
traoperative stress for surgeons.
The results indicated that SILC tends to impede recovery of QOL
in the subgroups of patients younger than 60 years, women, and
full-time workers. One of the possible causes may be the increased
need for physical activity during convalescence. Various physical
activities in this period contract the rectus abdominis, causing pain
at the umbilicus. Patients younger than 60 years or those per-
forming full-time work restart daily life earlier than other popu-
lation groups, which may have accentuated the intensity of the
pain of SILC. Notably, the present study had some imbalances in
patient characteristics; in the SILC group, the mean age was older,
and the proportion of patients with full-time work was less. Ex-
cept for these imbalances, SILC might have had a worse QOL and
pain than obtained in this study. With respect to a sex difference
in pain perception, several studies reported that women are more
susceptible to pain than men.33 A study of 4,317 patients in var-
ious disease categories reported that women required more anal-
gesics than men after an operation.34 The report also noted that
the sex-related difference disappeared in elderly patients. Although
sex hormones or psychologic factors are thought to affect pain sen-
sitivity, the underlying mechanism of this difference according to
patient sex has not yet been fully determined.35
The operative time for SILC was not statistically significantly
different than that for 4PLC in this study, as reported in previous
studies.22 The technical steps of SILC are basically the same as for
4PLC and not necessarily complicated for surgeons skilled in 4PLC.
Nevertheless, some surgeons have difficulty in the manipulation of
Please cite this article as: E. Ito et al., Quality of life after single-incision laparoscopic cholecystectomy: A randomized, clinical trial,
Surgery (2018), https://doi.org/10.1016/j.surg.2018.08.004
[m5G;October 9, 2018;20:28]
SILC with the instruments because the degrees of freedom are re-
stricted for experienced surgeons.4,36
Our present study has several limitations. First, the participa-
tion rate was low; only 123 of 392 eligible patients (31%) partici-
pated in this study. Therefore this group may have been a poten-
tially nonrepresentative population, which might have led to se-
lection bias. Second, this was an open-label study. The possibility
of the placebo effect and bias in an open-label study cannot be
completely excluded. In theory, patients could have obtained infor-
mation and reconsidered their allocation beforehand; 5 patients in
fact revoked their participation in the study after knowing their al-
location. Third, the subgroup analysis in this study was post hoc. It
involved a multiplicity problem that can lead to false-positive re-
sults and a risk of reporting bias. Therefore the result should be in-
terpreted with caution. To confirm the conclusion in this study, fur-
ther studies with larger sample sizes and subgroup analyses pre-
specified in the protocol would be needed. Fourth, although anal-
gesic use affects patient perception of pain, this study lacked a
strict protocol to monitor administration of analgesics. Fifth, sur-
geon technique differed by years of experience or institutions in
this study. It is possible that, through a learning curve effect, oper-
ating time and the complication rate of the SILC procedure might
differ between the early and late periods.8,12
In conclusion, the time to resume normal daily activities (QOL)
or to be free of pain were not substantially greater after SILC than
after 4PLC. There might be some delay of recovery after SILC in pa-
tients younger than 60 years, women, and full-time workers. These
findings indicate that SILC can be a feasible option in clinical prac-
tice, but 4PLC might be more favorable than SILC specifically for
these subgroups. Further modeling work is required to establish a
more clinically relevant and reproducible QOL assessment for min-
imally invasive surgery.
Disclosures
This study was an investigator-initiated clinical trial, and no fi-
nancial support was received.
Acknowledgments
We wish to thank Dr. Shinsuke Kajiwara and Dr. Kenzo Okada
(Uwajima City Hospital) for patient recruitment.
Supplementary materials
Supplementary material associated with this article can be
found, in the online version, at doi:10.1016/j.psychres.2018.08.040.
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