Comparison of efficacy of simo decoction and acupuncture or chewing gum alone on postoperative ileus in colorectal cancer resection: A randomized trial

Abstract

To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for 5 consecutive days. Patients treated with SMD and acupuncture experienced significantly shorter hospital stay, shorter time to first flatus and shorter time to defecation than patients in the other groups (all P < 0.05). Incidence of grade I and II complications was also significantly lower in patients treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no intervention in terms of hospital stay, incidence of complications, and time to first bowel motion, flatus, and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum does not appear to affect recovery of bowel function or hospital stay, though it may benefit patients who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).

Full text

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Scientific RepoRts | 7:37826 | DOI: 10.1038/srep37826
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Comparison of ecacy of simo
decoction and acupuncture
or chewing gum alone on
postoperative ileus in colorectal
cancer resection: a randomized trial
Yang Yang*, Hong-Qun Zuo*, Zhao Li*, Yu-Zhou Qin, Xian-Wei Mo, Ming-Wei Huang, Hao Lai,
Liu-Cheng Wu & Jian-Si Chen
To compared the ability of chewing gum or simo decoction (SMD) and acupuncture to reduce incidence
of postoperative ileus (POI) after colorectal cancer resection, patients with colorectal cancer undergoing
open or laparoscopic resection were randomized to receive SMD and acupuncture (n = 196), chewing
gum alone (n = 197) or no intervention (n = 197) starting on postoperative day 1 and continuing for
5 consecutive days. Patients treated with SMD and acupuncture experienced signicantly shorter
hospital stay, shorter time to rst atus and shorter time to defecation than patients in the other
groups (all P < 0.05). Incidence of grade I and II complications was also signicantly lower in patients
treated with SMD and acupuncture. Patients who chewed gum were similar to those who received no
intervention in terms of hospital stay, incidence of complications, and time to rst bowel motion, atus,
and defecation (all P > 0.05). The combination of SMD and acupuncture may reduce the incidence of POI
and shorten hospital stay for patients with colorectal cancer after resection. In contrast, chewing gum
does not appear to aect recovery of bowel function or hospital stay, though it may benet patients
who undergo open resection. (Clinicaltrials.gov registration number: NCT02813278).
Colorectal cancer resection is one of the most frequent types of abdominal surgery. ough most patients under-
going colorectal resection recover bowel movements within a week, some suer prolonged intestinal paralysis or
postoperative ileus (POI), reducing comfort, increasing morbidity and mortality, and extending hospitalization,
all of which increase healthcare costs1–3. is highlights the importance of preventing POI2–4.
Over the past two decades, many treatments and approaches have been reported for managing POI, including
uid restriction, early enteral nutrition, and nonsteroidal anti-inammatory drugs5,6. Randomized controlled
trials (RCTs) and systematic reviews have concluded that two traditional Chinese approaches are eective either
alone or together for accelerating the recovery of gastrointestinal function aer several types of surgery: oral
simo decoction (SMD) and acupuncture at the tsusanli acupoint5,7–9. Chewing gum has emerged as a popular
method for reducing the incidence of POI, but its ecacy is controversial. While some systematic reviews and
meta-analyses indicate that it can lead to signicantly better postoperative bowel function4,10–16 and several o-
cial guidelines recommend it for preventing POI17–20, three recent RCTs failed to demonstrate an eect of chewing
gum on the recovery of bowel function aer colorectal resection21–23.
Since nearly all previous RCTs of SMD, acupuncture or chewing gum have examined small cohorts, we wished
to perform a parallel comparison with a large sample in order to gain more reliable insights into ecacy and
safety. In addition, the ecacy of acupuncture alone on the recovery of bowel function was not well dened7. And
the ecacy of combination of SMD and acupuncture was superior to chewing gum alone5. erefore we con-
ducted this RCT comparing the combination of SMD and acupuncture, chewing gum alone, and no intervention
for aecting POI incidence, length of hospital stay, and complications following colorectal resection.
Department of Gastrointestinal Surgery, Aliated Tumor Hospital of Guangxi Medical University, Nanning, PR China.
*These authors contributed equally to this work. Correspondence and requests for materials should be addressed to
Y.-Z.Q. (email: qinyuzhou00@126.com) or J.-S.C. (email: yangyango123456@163.com).
Received: 25 July 2016
accepted: 02 November 2016
Published: 19 January 2017
OPEN

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Methods
e protocol for this trial was designed in accordance with the Declaration of Helsinki and the ethical princi-
ples of the International Conference on Harmonization-Good Clinical Practice. e trial protocol was approved
by the Medical Ethics Committee of the Aliated Tumor Hospital of Guangxi Medical University. All study
participants provided written informed consent. Data were collected, analyzed and reported according to the
Consolidated Standards of Reporting Trials (CONSORT) statement24. e trial is retrospectively registered (June
23, 2016) at Clinicaltrials.gov (NCT02813278).
Patients. Participants were recruited between March 2014 and April 2016 from the two Departments of
Gastrointestinal Surgery at the Aliated Tumor Hospital of Guangxi Medical University (Nanning, China).
Patients older than 18 years scheduled for primary colorectal cancer resection, whether laparoscopic or open,
were asked to participate. Diagnosis of colorectal cancer was conrmed by histopathological examination of sur-
gical samples. Patients were ineligible if they were younger than 18 years or underwent emergency surgery, had a
history of exploratory laparotomy or laparoscopic surgery, had ulcerative colitis or Crohn disease, had a history of
abdominal radiation, were pregnant or lactating, were allergic to mint or SMD, required postoperative intensive
care for more than 24 h, or were otherwise deemed unsuitable for the study, such as if they had psychological or
social conditions that might interfere with their participation.
Randomization. e trial protocol was explained to all enrolled participants before randomization. Aer
written informed consent was obtained, research sta used TenAlea soware (http://nl.tenalea.net) to allocate
participants randomly on a 1:1:1 basis to the three arms: SMD combined with acupuncture, chewing gum or no
intervention. Randomization was performed the day before colorectal cancer resection. And then, sequentially
numbered, opaque sealed envelopes were used. Randomization was stratied by department and, within each
department, by resection type (laparoscopy or laparotomy) and disease type (colon or rectal cancer). Patients
were informed that the ecacy of SMD, acupuncture, or chewing gum to promote recovery of bowel function
aer colorectal resection was unknown, and that none of these measures was expected to cause obvious side
eects.
Blinding. Given the dierent characteristics of SMD, acupuncture, and chewing gum, no blinding was applied
to participants or doctors. Nevertheless, the nursing sta and statistician were blinded to treatment allocation
throughout data collection and analysis.
Interventions. All colorectal resections were performed by senior surgeons (length of services ≥ 10 years)
using general anesthesia, who consistently applied the same evidence-based, standardized protocols for perioper-
ative management and postoperative care25–27. e nasogastric drainage tube was removed on the rst postopera-
tive morning. en the medical team administered the appropriate interventions to each of the three randomized
groups. Interventions were recorded in patient records. Nursing sta dispensed SMD and chewing gum to par-
ticipants every day.
Participants allocated to the SMD + acupuncture group were treated as described5. ey were asked to take
oral SMD decoction (10 mL/dose; Hansen, Yiyang, Hunan, China) three times per day beginning on the rst day
aer colorectal resection. ey also received bilateral injections of vitamin B1 (50 mg × 2) at the tsusanli acu-
point once per day. is intervention was performed for 5 consecutive days or until atus. Participants allocated
to the chewing gum group were instructed to chew commercially available sugar-free gum (Extra & Reg, Wm.
Wrigley Jr., Shanghai, China) three times daily starting on the rst postoperative morning. ey were instructed
to chew the piece of gum for at least 10 min. is intervention was performed for 5 consecutive days or until
atus. Participants in the control group were asked not to undertake any postoperative intervention that might
inuence recovery of bowel function, including SMD, acupuncture, chewing gum, or adjuvant drugs.
Acceptability and compliance. Acceptability of SMD + acupuncture and chewing gum was assessed by
briey interviewing participants in these two treatment arms at least 1 full day aer resection. ey were asked
how they felt about the intervention and whether they had any problems or diculties receiving it. Compliance
was assessed by asking participants to record how many SMD doses they took or how long they chewed each
piece of gum. Participants in the empty control group were asked at the time of discharge whether they had taken
oral SMD or chewed gum during their hospital stay. Participants who discontinued the study or received the
incorrect intervention were recorded. All analyses were performed on an intention-to-treat basis.
Outcome measures. Primary outcomes of this study were time to rst bowel motion, time to rst atus
and time to defecation, which were obtained from participant questionnaires lled out once daily with assistance
from nursing sta who were educated to keep the group allocation secret on days 1–5 aer resection. Time to
rst bowel motion means passage of regular rst bowel sounds more than two sounds in every minute rst heard
on postoperative day5,28. Secondary endpoints were length of hospital stay, hospital mortality, and postoperative
clinical complications such as vomiting, fever, pneumonia, wound infection, and bleeding. Secondary outcomes
were assessed by the medical team. Length of hospital stay was calculated as the number of days from the date of
colorectal resection to the date of discharge, transfer or death. Criteria for hospital discharge included stable vital
signs with no fever, ability to tolerate solid food without nausea or vomiting aer defecation, control of postoper-
ative pain, absence of other obvious postoperative complications, and ability to function at home independently
or with the home care provided. ose with comorbidity (such as diabetes millitus) will be transfer to another
department. Extent of nausea and abdominal pain was reported by participants using a visual analogue scale29
once daily on days 1–5 aer resection. Postoperative complications were classied and graded according to the
Clavien–Dindo classication30. Numbers of participants who experienced adverse events were recorded.

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Power calculation and sample size. At the beginning of the study, we did not notice the importance of
power calculation for the sample size. Approximately 500 resections for primary colorectal cancer are performed
each year in both Departments of Gastrointestinal Surgery at our hospital. To ensure an adequately large sample,
we recruited consecutive participants with primary colorectal cancer over two years.
Based on data in the literature, it was assumed that chewing gum could reduce the time to rst atus by 16 h28.
To achieve a power of 0.8, the sample size for this study was targeted as 42 in each arm. erefore, the nial sam-
ple size (n = 590) was larger enough.
Statistical analysis. Data for continuous variables were reported using mean (SD) for normally distributed
data or median (range) for skewed data. Data for categorical variables were expressed as number (percentage).
Intergroup dierences were assessed for signicance using Student’s t test for normally distributed continuous
variables or the Mann-Whitney U test for skewed continuous variables. Intergroup dierences in categorical data
were assessed using the χ
2 test or Fisher’s exact tests (2-tailed), as appropriate. Length of hospital stay was cal-
culated using Kaplan-Meier analysis and compared between groups using the log-rank test. Data were analyzed
using SPSS 19.0 (IBM, USA), with the threshold of signicance dened as a two-tailed P < 0.05.
Subgroup analysis based on open or laparoscopic resection was performed in order to compare the ecacy of
SMD + acupuncture or chewing gum for each type of surgery. In this analysis, patients who underwent laparo-
scopic surgery that was converted to open surgery were classied as having undergone open resection. Patients
who underwent laparoscopically assisted surgery were classied as having undergone laparoscopic surgery.
Results
Patient characteristics. From 1 February 2014 to 28 February 2016, 904 patients with primary colorectal
cancer were assessed for eligibility. Of these, 143 were excluded because they did not meet the inclusion criteria,
132 declined to participate or withdrew consent, 32 did not have sucient time to provide consent before surgery,
5 were unwilling to receive acupuncture and 2 were unwilling to receive chewing gum. e remaining 590 partic-
ipants were randomly assigned to receive SMD + acupuncture (n = 196), chewing gum (n = 197), or no interven-
tion (n = 197). Aer randomization, 17 patients were withdrawn from the study by investigators before treatment
began because they did not undergo colorectal resection, they underwent emergency surgery, or they remained
in the intensive care unit longer than 24 h and so could not begin the study intervention in parallel with the other
patients. Another 8 patients were excluded aer randomization because they were diagnosed with benign tumors
based on postoperative pathology. ese 25 patients were excluded from the nal analysis. In contrast, patients
who experienced protocol violations during the study were retained in the nal analysis; these violations were
failure to receive the planned intervention of SMD + acupuncture or chewing gum (n = 5), administration of the
incorrect intervention (n = 15), or patient choice to discontinue the intervention (n = 9). In the end, the nal
analysis involved 565 patients: 186 in the SMD + acupuncture arm, 190 in the chewing gum arm, and 189 in the
no-treatment control arm (Fig.1). Most patients said that they did not have any problems or diculties to chew
the gum (97.3%) or drink SMD and received acupuncture (97.8%).
Participant characteristics and baseline measures are shown in Table1. Overall, there were slightly more
patients with colon cancer than with rectal cancer, and more than half underwent laparoscopic resection. e
three arms were comparable across all demographic and clinical measures. Follow-up on the last participant was
28 May 2016.
Abdominal pain and nausea. The SMD + acupuncture arm showed significantly lower abdominal
pain and nausea scores than the two other arms on day 3 aer resection (all P < 0.05). e chewing gum and
no-intervention arms showed similar scores (Table2). e three arms showed similar scores on days 4 and 5 (data
not shown).
POI. Participants in the three arms showed similar time to rst bowel motion (all P > 0.05). In contrast, time to
rst atus and time to rst defecation were signicantly shorter in the SMD + acupuncture arm than in the other
two arms (all P < 0.05). All three outcomes tended to be shorter in the chewing gum arm than the no-treatment
arm, but these dierences did not achieve signicance (all P > 0.05; Table2).
Within the subgroup of participants who underwent open resection, all three time intervals were signicantly
shorter in the two intervention arms than in the no-intervention arm (all P < 0.05), and all three intervals tended
to be shorter in the SMD + acupuncture arm than in the chewing gum arm (all P > 0.05; Table3). Within the
subgroup of participants who underwent laparoscopic resection, the three time intervals varied among the three
patient arms similarly to how they varied across the entire patient arms (data not shown).
Length of hospital stay. Hospital stay lasted a mean of 8.9 d (SD 1.9, median 9.0) for patients receiving
SMD + acupuncture, 10.5 d (SD 2.5, median 10.4) for patients receiving chewing gum, and 10.9 d (SD 2.4, median
10.5) for no-intervention controls (Table2). Kaplan-Meier analysis showed that length of stay was signicantly
shorter for the SMD + acupuncture group than for the other two groups (all P < 0.05). Length of hospital stay was
similar between the chewing gum and no-intervention groups (P = 0.318).
Within the subgroup of participants who underwent open resection, the hospital stay lasted a mean of 9.1 d
(SD 2.1, median 9.6) for patients receiving SMD + acupuncture, 10.4 d (SD 2.9, median 10.1) for patients receiv-
ing chewing gum, and 11.1 d (SD 3.3, median 11.3) for no-intervention controls (Table3). Kaplan-Meier analysis
showed that length of stay was signicantly shorter for either of the two interventions than for no intervention (all
P < 0.05). Results for the subgroup of participants who underwent laparoscopic resection were similar to those
observed across the entire study population (data not shown).

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Complications. Most complications were grade I or II and included wound pain, abdominal distension,
fever, and nausea/vomiting. e rate of complications was signicantly higher in the no-intervention group than
in the other two groups (P < 0.001; Table4). More serious complications requiring pharmacological or other
interventions included anastomotic leakage (n = 21), anastomotic bleeding (15), bowel obstruction (18), wound
infection (15), pneumonia (8), and death (3) (Table5). Incidence of serious complications was similar among the
three arms, although the rate of bowel obstruction was marginally higher in the no-intervention arm (9 of 189,
4.8%) than in the SMD + acupuncture (3 of 186, 1.6%) or chewing gum arms (6 of 190, 3.2%). All these serious
complications were classied as unrelated or likely to be unrelated to the interventions.
Discussion
A substantial proportion of patients suers transient impairment of gastrointestinal motility known as POI aer
abdominal surgery31. Since POI increases healthcare costs and resource utilization32, investigators have explored
various strategies to reduce its incidence, but none is cost-eective33. Our results based on a relatively large sam-
ple suggest that the combination of SMD and acupuncture signicantly enhances bowel function recovery and
shortens hospital stay in patients with colorectal cancer aer open or laparoscopic resection. Chewing gum may
also reduce incidence of POI and aect hospital stay of patients aer open resection. However, chewing gum did
not signicantly enhance bowel function or shorten hospital stay among the entire study population or within the
subgroup of those who underwent laparoscopic resection.
e mechanism of POI is complex, characterized mainly by intestinal inammatory inltration34–36. In tra-
ditional Chinese medicine, SMD and acupuncture at the tsusanli acupoint have long been used to reduce risk of
POI and manage various functional gastrointestinal disorders8–9,37. e tsusanli acupoint is located on the stom-
ach meridian, and acupuncture there is thought to regulate the intestines. Concurrent administration of vitamin
B1 at acupoints is thought to intensify and prolong acupoint stimulation. ese considerations may help explain
why SMD + acupuncture with concurrent vitamin B1 therapy promoted bowel function to a greater extent than
chewing gum or no intervention in our study.
Our results are consistent with randomized trials demonstrating positive eects of SMD and acupuncture
on their own or in combination for reducing POI incidence. ese benets have been demonstrated for patients
following hepatic resection5, gastrectomy38, and other surgeries8–9. We extend the literature by showing, for the
rst time in colorectal cancer resection, the clinical ecacy of SMD + tsusanli acupoint injection + vitamin B1.
At the same time, we did not observe enhancement of bowel function in the entire chewing gum group or in the
Figure 1. CONSORT diagram for the study. SMD + acupun, simo decoction with acupuncture. *Number
of participants who received the allocated intervention. †Withdrawn by investigators before treatment began,
because they did not undergo colorectal resection (n = 8), underwent emergency surgery (2), or remained in
the intensive care unit for more than 24 h and so could not receive SMD or chewing gum (7). ‡Postoperative
pathology revealed benign tumors (n = 8).

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subgroup of those who underwent laparoscopic resection. is is inconsistent with most randomized trials and
meta-analyses on this question4,10–15. Nevertheless, consistent with this previous work4,10–15, we did nd clinical
benet for chewing gum in the subgroup of those who underwent open resection. Since each treatment arm in the
present study was larger than in most previous studies, and since we performed a three-way parallel comparison,
our results constitute strong evidence that the combination SMD + acupuncture is likely to provide substantially
greater clinical benet than chewing gum to a larger proportion of patients with colorectal cancer aer resection.
e rate of postoperative complications in our study was signicantly lower in the two intervention arms, and
most complications were grade I or II (Table4). e rate of serious complications was comparable among the
three arms (Table5), and none of the complications was attributed to the study interventions. Only two of 565
patients in the entire population (0.35%) died within 90 days aer surgery, and none of the deaths was attributed
to the intervention (chewing gum). ese ndings are consistent with similar reports showing the safety of SMD,
acupuncture and chewing gum aer surgery1–2,5,21–23. We conclude that SMD, acupuncture, and chewing gum
do not signicantly aect risk of incidence or type of complications. Moreover, most patients found SMD + acu-
puncture or chewing gum acceptable and they adhered to the treatment: only 29 of 590 patients (4.9%) received
incorrect interventions or discontinued intervention (Fig.1).
Similarly to our results for the primary endpoints of bowel function recovery, we found that across the entire
study population, SMD + acupuncture signicantly shortened hospital stay by 2.0 d (8.9 vs. 10.9), while chewing
gum reduced it by an insignicant 0.4 d (10.5 vs. 10.9). However, chewing gum did signicantly shorten hospital
stay in the subgroup of patients who underwent open resection. ese results have several possible explanations.
One is that SMD + acupuncture stimulates gastrointestinal motility more strongly than chewing gum, thereby
Var i a b l e
Simo decoction + acupuncture
(n = 186)
Chewing gum
(n = 190)
No intervention
(n = 189)
Age, yr*53.7 (15.1) 53.3 (14.9) 54.1 (16.2)
Sex†
Male 103 (55.4) 106 (55.8) 102 (54.0)
Female 83 (44.6) 84 (44.2) 87 (46.0)
Educational background†
None or primary school 95 (51.1) 94 (49.5) 98 (51.9)
Secondary school 70 (37.6) 71 (37.4) 72 (38.1)
University degree or above 21 (11.3) 24 (12.6) 19 (10.0)
Body mass index, kg/m2,‡ 23.4 (18.6–29.3) 23.3 (16.5–29.9) 23.5 (17.1–30.1)
Type 2 diabetes mellitus†31 (16.7) 32 (16.8) 29 (15.3)
Smoking status†
Current smoker 30 (16.1) 32 (16.8) 35 (18.5)
Former smoker 31 (16.7) 25 (13.2) 23 (12.2)
Never smoked 125 (67.2) 133 (70.0) 131 (69.3)
ASA tness grade†
I 45 (24.2) 43 (22.6) 43 (22.8)
II 120 (64.5) 124 (65.3) 125 (66.1)
III 21 (11.3) 23 (12.1) 21 (11.1)
Indication for resection†
Colon cancer 103 (55.4) 108 (56.8) 108 (57.1)
Rectal cancer 83 (44.6) 82 (43.2) 81 (42.9)
Type of surgery†
Laparoscopic 21 (11.3) 19 (10.0) 19 (10.1)
Laparoscopically assisted 118 (63.4) 117 (61.6) 119 (63.0)
Open 40 (21.5) 44 (23.2) 43 (22.8)
Laparoscopic converted to open 7 (3.8) 10 (5.3) 8 (4.2)
Primary procedure†
Total colectomy 10 (5.4) 10 (5.3) 9 (4.8)
Le-sided colectomy 36 (19.4) 34 (17.9) 32 (16.9)
Right-sided colectomy 48 (25.8) 55 (28.9) 56 (29.6)
Rectal resection 83 (44.6) 82 (43.2) 81 (42.9)
Other§9 (4.8) 9 (4.8) 11 (5.8)
Surgical time, min‡141 (60–305) 145 (66—265) 142 (62–271)
Opioid analgesia use†62 (33.3) 63 (33.2) 57 (30.2)
Table 1. Clinicopathological data of patients with colorectal cancer treated by resection (all types)
followed by simo decoction + acupuncture, chewing gum or no intervention. ASA, American Society of
Anesthesiologists. *Values are mean (s.d.). †Values in parentheses are percentages. ‡Values are median (range).
§Includes partial resection and small bowel resection.

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accelerating bowel function recovery. Such patients more quickly achieve euphagia without vomiting and begin
to ambulate5. At the same time, the lower incidence of grade I and II postoperative complications and bowel
obstruction in the two intervention arms likely contributed to the shorter hospital stay.
is study has at least three strengths. First, the study population of 590 patients, recruited over two years, is
larger than in similar RCTs in the literature. Second, the study population included only patients with colorectal
cancer with no history of abdominal surgery, making it more homogeneous than the populations in previous
trials that included patients with various types of colorectal disease2,22,23 or with a history of abdominal surgery2.
ird, in part because of our large sample, we were able to perform subgroup analysis based on open or laparo-
scopic resection. is allowed us to nuance our nding of no clinical benet to chewing gum across the entire
study population: in fact, chewing gum signicantly improved bowel function recovery and shortened hospital
stay of patients who underwent open resection. It is possible that this surgery-specic eect reects the fact that
laparoscopic resection, although it usually takes longer than open resection, induces less trauma and stress in the
patient. In addition, recovery-enhancing methods are easier to apply aer laparoscopic resection because of less
trauma39,40. us the clinical benet of chewing gum may have been too weak to be observed in the entire study
Var i a b l e
Simo decoction + acupuncture
(n = 186)
Chewing gum
(n = 190)
No intervention
(n = 189) P
Time to rst bowel motion, h 17.1 (8.5–41.2) 18.3 (11.0–42.5) 19.1 (10.5–39.4) 0.247* 0.236† 0.265‡
Time to rst atus, h 46.2 (20.5–72.1) 62.3 (21.4–70.5) 64.1 (24.8–71.3) 0.033* 0.021† 0.613‡
Time to rst defecation, h 75.2 (29.0–241.6) 119.3 (31.5–211.4) 125.8 (34.2–208.7) 0.042* 0.033† 0.165‡
Length of postoperative hospital stay, d 9.0 (5.3–18.1) 10.4 (6.4–24.1) 10.5 (7.4–21.2) < 0.001*< 0.001† 0.113‡
Abdominal pain score on day 3§30 (15–59) 45 (20–79) 49 (23–80) 0.035* 0.027† 0.276‡
Nausea score on day 3§5 (1–50) 9 (2–50) 10 (2–50) 0.039* 0.021† 0.712‡
Table 2. Outcomes for patients with colorectal cancer treated by resection (all types) followed by simo
decoction + acupuncture, chewing gum or no intervention. Values shown are median (range). *Simo
decoction + acupuncture vs. chewing gum. †Simo decoction + acupuncture vs. no intervention. ‡Chewing
gum vs. no intervention. §Visual analogue scale score (in percentage points) on day 3 aer surgery; a score of 0
percent means no pain, 100 percent means severe pain or nausea.
Var i a b l e
Simo decoction + acupuncture
(n = 47)
Chewing gum
(n = 54)
No intervention
(n = 51) P
Time to rst bowel motion, h 17.9 (8.9–41.2) 18.1 (11.6–42.5) 21.1 (11.5–39.4) 0.319* 0.226† 0.391‡
Time to rst atus, h 46.9 (21.2–72.1) 50.3 (22.4–70.5) 66.1 (25.3–71.3) 0.074* 0.017† 0.041‡
Time to rst defecation, h 75.6 (30.1–241.6) 89.4 (31.5–200.0) 127.2 (35.2–208.7) 0.094* 0.018† 0.037‡
Length of postoperative hospital stay, d 9.6 (6.5–18.1) 10.1 (6.4–24.1) 11.3 (8.4–21.2) < 0.001*< 0.001†< 0.001‡
Table 3. Outcomes for patients with colorectal cancer treated by open resection followed by simo
decoction + acupuncture, chewing gum or no intervention. Values shown are median (range). *Simo
decoction + acupuncture vs. chewing gum. †Simo decoction + acupuncture vs. no intervention. ‡Chewing gum
vs. no intervention.
Var i a b l e
Simo decoction + acupuncture
(n = 186)
Chewing gum
(n = 190)
No intervention
(n = 189) P
No complications 86 (46.2) 47 (24.7) 9 (4.8) < 0.001*< 0.001†< 0.001‡
I: deviations from normal
postoperative course 66 (35.5) 94 (49.5) 116 (61.4) 0.006*< 0.001† 0.020‡
II: complications requiring
pharmacological treatment 22 (11.8) 28 (14.7) 44 (23.3) 0.406* 0.004† 0.034‡
IIIa: complications
requiring intervention not
under general anesthesia
7 (3.8) 10 (5.3) 13 (6.9) 0.484* 0.180† 0.510‡
IIIb: complications
requiring intervention
under general anesthesia
5 (2.7) 6 (3.2) 8 (4.2) 0.787* 0.414† 0.579‡
IV: life-threatening
complications 0 (0) 2 (1.1) 0 (0) —
V: death 0 (0) 2 (1.1) 0 (0) —
Table 4. Clavien-Dindo classication of post-resection complications in patients with colorectal
cancer treated by resection (all types) followed by simo decoction + acupuncture, chewing gum,
or no intervention. Values shown are n (%). *Simo decoction + acupuncture vs. chewing gum. †Simo
decoction + acupuncture vs. no intervention. ‡Chewing gum vs. no intervention.

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Scientific RepoRts | 7:37826 | DOI: 10.1038/srep37826
population or in the subgroup of those who underwent the laparoscopic procedure. Whatever the explanation,
our results suggest, for the rst time, that chewing gum may oer clinical benet only to a subset of patients
undergoing surgery. is possibility, which should be veried and extended in future work, is consistent with
studies showing that, with the implementation of fast-track surgery in recent decades, chewing gum can be nei-
ther clearly recommended nor prohibited as a gastrointestinal stimulant21–23.
e present study also has some limitations. One is that length of stay within each arm was calculated over
all patients in each arm, regardless of the type of resection that they underwent, which included open, laparo-
scopic, laparoscopically assisted, and laparoscopic-converted-to-open procedures. is may have confounded the
analysis, though the various types of procedures occurred with similar frequencies among the three study arms.
A second limitation is lack of blinding for patients and doctors, which was judged impractical because of the
nature of the interventions. is limitation is shared with similar trials in the literature21–23, and we attempted to
compensate for potential bias by blinding the nursing sta to assess primary outcomes and statistician to patient
allocation throughout data analysis. A third limitation is that some patients within each arm received opioid anal-
gesia, which may have confounded our analysis5. However, the proportions of patients receiving such analgesia
were similar among the arms.
Despite these limitations, the present study presents some of the strongest evidence to date that SMD + acu-
puncture and chewing gum can be safely administered in a postoperative setting to patients with colorectal can-
cer aer resection, and that SMD + acupuncture signicantly enhances bowel function recovery and shortens
hospital stay, more robustly than chewing gum. Future studies should examine whether SMD + acupuncture or
chewing gum can treat POI aer it has already developed.
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Acknowledgements
e authors thank all the trial participants, without whom this study would not have been possible. e rst
author (Y.Y.) thanks Doctor Zhen-Ling Gong from Harvard University for her kindly help of revision and
suggestion of the manuscript.
Author Contributions
Yang Y. and Chen J.S. conceived and designed the study. Yang Y., Zuo H.Q., Li Z., Qin Y.Z., Mo X.W., Huang
M.W., Lai H., Wu L.C. and Chen J.S. performed the study. Yang Y. and Chen J.S. performed statistical analyses.
Yang Y. and Lai H. draed the manuscript.
Additional Information
Competing nancial interests: e authors declare no competing nancial interests.
How to cite this article: Yang, Y. et al. Comparison of ecacy of simo decoction and acupuncture or chewing
gum alone on postoperative ileus in colorectal cancer resection: a randomized trial. Sci. Rep. 7, 37826; doi:
10.1038/srep37826 (2017).
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