chewing gum for intestinal function recovery after...
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Review ArticleChewing Gum for Intestinal Function Recovery after ColorectalCancer Surgery: A Systematic Review and Meta-Analysis
Binbin Mei,1 Wenting Wang,1 Feifei Cui,2 Zunjia Wen,3 and Meifen Shen4
1Department of Neurosurgery, The First Affiliated Hospital of Soochow University & School of Nursing Soochow University,Suzhou 215006, China2Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Suzhou 215006, China3Nanjing Children’s Hospital, Nanjing 210000, China4Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
Correspondence should be addressed to Meifen Shen; [email protected]
Received 18 June 2017; Revised 21 August 2017; Accepted 6 September 2017; Published 8 October 2017
Academic Editor: Per Hellström
Copyright © 2017 Binbin Mei et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background. This meta-analysis was performed to assess the efficacy and safety of chewing gum in intestinal function recovery aftercolorectal cancer surgery. Methods. A systematic search was conducted in PubMed, Embase, Science Direct, and Cochrane libraryfor relevant randomized controlled trials (RCTs) published until April 2017. Summary risk ratios or weighted mean differenceswith 95% confidence intervals were used for continuous and dichotomous outcomes, respectively. Results. 17 RCTs with a totalnumber of 1845 patients were included. Gum chewing following colorectal cancer surgery significantly reduced the time to firstpassage of flatus (WMD −0.55; 95% CI −0.94 to −0.16; P = 0 006), first bowel movement (WMD −0.60; 95% CI −0.87 to −0.33;P < 0 0001), start feeding (WMD −1.32; 95% CI −2.18 to −0.46; P = 0 003), and the length of postoperative hospital stay(WMD −0.88; 95% CI −1.59 to −0.17; P = 0 01), but no obvious differences were found in postoperative nausea, vomiting,abdominal distention, pneumonia, and mortality, which were consistent with the findings of intention to treat analysis.Conclusions. Chewing gum could accelerate the recovery of intestinal function after colorectal cancer surgery. However, itconfers no advantage in postoperative clinical complications. Further large-scale and high-quality RCTs should be conductedto confirm these results.
1. Introduction
Colorectal cancer is one of the most common tumors, whichis associated with multiple risk factors and accounts forapproximately 10% of cancer-related mortality in westerncountries [1, 2]. With increased colorectal cancer incidence,the number of colorectal cancer surgery has also elevateddramatically. Laparoscopic or open colorectal resections, asthe main surgical approach for colorectal cancer, may alsoresult in many serious complications like postoperative ileus,nausea, and vomiting, which could lead to significant post-operative morbidity and a prolonged length of hospital stayand place a significant financial burden on health care facil-ities [3, 4]. Therefore, targeting the recovery of intestinal
function after colorectal cancer surgery may contribute topromote rehabilitation for the patient. Now, it is widelyaccepted that early postoperative feeding is beneficial todecrease the postoperative ileus and shorten the length ofhospital stay, and there is significant interest in identifyingthe measures to stimulate gut function, rather than simplywaiting for it to return spontaneously [5–7].
Gum chewing (GC), a kind of sham feeding alternative toearly feeding, which is expected to stimulate the cephalic-vagal reflex to increase hormone secretion and then enhanceintestinal motility [8], may produce a positive effect on post-operative ileus by reducing postoperative inflammation [9].However, the underlying mechanisms behind the effects ofgum chewing works remain elusive and the results of clinical
HindawiGastroenterology Research and PracticeVolume 2017, Article ID 3087904, 13 pageshttps://doi.org/10.1155/2017/3087904
studies to date are inconclusive, and thus chewing gum hasnot yet been incorporated into the related guidelines orstandard pathways for postoperative nursing [10, 11].
Previous meta-analyses [7, 12–14] have suggested thatpatients who had gum chewing after surgery might recoverintestinal function earlier; however, the sample sizes of therandomized controlled trials (RCTs) included in theseanalyses were small and an increasing body of relevantresearch recently have been reported, making it worthreconsidering the evidence on this issue. The aims of thisstudy, therefore, were to review the current evidence onthe influence of gum chewing in intestinal function andreassess the efficacy of chewing gum in intestinal functionrecovery after colorectal surgery.
2. Methods
2.1. Search Strategy. A general literature search was con-ducted in PubMed, Embase, Science Direct, and Cochranelibrary (until April 2017), using the following search terms:“gum-chewing,” “chewing-gum,” “sham-feeding,” “bowel,”“colonic,” “rectal,” “resection,” or “surgery.” We combinedthese terms in accordance with the instructions of the data-base. Reference lists and bibliographies from included studiesand relevant reviews were used to find additional articles toreview. The search was limited to articles written in English,but there was no restriction on publication year.
2.2. Study Selection. Two reviewers independently reviewedtitles and abstracts to distinguish potentially relevant studies,and articles for more extensive review were selected using thefollowing criteria. Inclusion criteria were as follows: (1) RCTdesign; (2) study subjects were those who had undergonecolorectal cancer surgery; (3) the study made a comparisonbetween gum chewing and standard nursing care postcolorectal surgery; and (4) the study contained explicit out-come data. Exclusion criteria were as follows: (1) reviews,systematic reviews, meta-analysis, editorials, case studies,and nonhuman studies; (2) studies not focusing on the effectof chewing gum on colorectal cancer surgery; and (3) studieswith no accessible outcome data.
The main outcomes we collected for data analysisincluded (1) the time to first passage of flatus (days); (2) thetime to first defecation (days); (3) the time to first bowelmovement (days); (4) the time to start feeding (days); (5)postoperative ileus (POI); (6) postoperative clinical compli-cations such as nausea, vomiting, abdominal distension,and pneumonia; (7) the length of postoperative hospital stay(days); and (8) mortality.
2.3. Quality Assessment. The methodological quality andrisk of bias of included studies were assessed using theCochrane Collaboration’s “risk of bias” tool, which addressesthe seven specific domains: random sequence generation,allocation concealment, blinding of participants and person-nel, blinding of outcome assessment, incomplete outcomedata, selective reporting, and other sources of bias. Eachdomain in the tool is achieved by assigning a judgement of“low risk” of bias, “high risk” of bias, or “unclear risk” of bias
(Cochrane Handbook for Systematic Reviews of Interven-tion. Part 2: 8.5) [15].
2.4. Data Extraction. Two reviewers independently extractedthe following data information: first author, publication year,study design, participants, population, methods of gumchewing, other concurrent interventions, main outcomes,and finding. Disagreements were resolved by discussion or,when necessary, adjudicated by a third reviewer.
2.5. Statistical Analysis. Review Manager 5.3 software wasused for statistical analyses. We calculated risk ratio (RR)and weighted mean difference (WMD) to present the dichot-omous and continuous data, respectively, and 95% confidenceinterval (CI)was included for all estimates. “Intention to treat”analysis was also conducted. P < 0 05 indicated statistical sig-nificance. Heterogeneity was tested by applying a chi-squared(χ2) test and I-squared (I2) statistic test. A fixed-effect modelwas adopted when P value of χ2 test> 0.10 and I2≤ 50%, anda random-effect model was adopted otherwise.
3. Results
3.1. Literature Search. Using the search strategy, 295 poten-tially relevant references were identified. Of these, 278 articleswere excluded due to duplicates or their failure to fulfilpredefined inclusion criteria. So finally, we formally included17 trials with 1845 patients in the main analyses of thisreview [16–32] (Figure 1).
3.2. Study Characteristics. The characteristics of 17 includedstudies are presented in Table 1. The included studies com-prised a total of 1845 patients who had received surgicaltreatment for colorectal cancer. Of these, 918 followed agum chewing intervention, and 927 received standard post-operative care. For most studies, gum chewing started fromthe first day post operation, and the frequency varied fromthree to four times per day. Although a lot of researchconfirmed the benefits of chewing gum, the outcomes for theefficacy of gum chewing in each study were still controversial.
3.3. Methodological Quality and Risk of Bias. Figure 2(a)describes all of the bias classifications for the included RCTs,with the summary of qualitative methodological qualityaccording to the bias classification (“low risk,” “unclear risk,”and “highrisk”)whichwaspresented inFigure2(b).Concisely,although all includedRCTsmentioned randomization in theirresearch, only nine studies [17, 19, 20, 24, 25, 27, 29, 31, 32]reported correct method of random sequence generationwhich marked as low risk of selection bias, and only six RCTs[17, 20, 24, 25, 27, 31] described adequate allocation con-cealments, which serves as a strategy to prevent againstascertainment bias and scored as low risk of bias. In gen-eral, sequentially numbered, opaque, sealed envelopes areassigned to each participant to prevent selective bias. Ade-quate blinding of personnel, participants, and outcomeassessment is necessary to prevent against performanceand detection bias; however, only one study [25] explicitlydescribed how to maintain patient blinding in all includedresearch, and six RCTs [17, 24, 25, 27, 29, 31] had mentioned
2 Gastroenterology Research and Practice
the blinding design for assessing the outcomes. Verifica-tion on selective reporting of outcomes is necessarybecause it may help to evaluate the integrity of outcomereporting and protect against bias, yet the majority ofthe included studies [16, 18–23, 25–29, 31, 32] did notprovide sufficient information to assess whether an impor-tant risk of bias exists; thus, we judged the risk of otherpotential sources of bias as unclear. Most of the includedstudies appear to be free of other sources of bias exceptfor two studies [26, 32], so we judged the risk of bias as lowrisk for these trials.
3.4. Publication Bias Analysis. A funnel plot is a simplescatter plot of the intervention effect estimates from indi-vidual studies against some measure of each study’s sizeor precision which is used for indication of publicationbias [15]. Ten or more studies are needed to enable a fun-nel plot to give significant evidence of bias, and in thisstudy, we performed a funnel plot analysis on the timeto first passage of flatus and the length of postoperativehospital stay. Based on Figures 3(a) and 3(b), we foundthat the funnel plots were symmetrical, and no significantpublication bias was found.
3.5. Main Analysis. The effect of gum chewing on multipleparameters of colorectal function following surgery reportedin the included studies was assessed. The RRs or WMDs foreach study were presented in Figures 4–14.
3.5.1. The Time to First Passage of Flatus. All studiesreported the time to the first passage of flatus, yet sevenstudies [17, 18, 20, 22, 24, 29, 31] failed to provide accurate
and necessary data for further analysis. As shown inFigure 4, we found that gum chewing probably shorten thetime to first passage of flatus (WMD −0.55; 95% CI −0.94to −0.16; P = 0 006) with a clear statistical heterogeneityacross the trials (I2 = 78%).
3.5.2. The Time to First Defecation. Four studies reported thetime to first defecation after colorectal surgery under gumchewing intervention or standard nursing. We found noevidence of a statistically significant difference regardingthe time to first defecation between the gum chewinggroup and control group (WMD −0.96; 95% CI −2.74 to0.83; P = 0 29) (Figure 5), with a clear statistical heteroge-neity between trials (I2 = 88%).
3.5.3. The Time to First Bowel Movement. Six studies reportedthe time to first bowel movement; we found that gumchewing shorten the time to first bowel movement com-pared with the control group (WMD −0.60; 95% CI −0.87to −0.33; P < 0 0001) (Figure 6), with a moderate statisticalheterogeneity across the studies (I2 = 41%).
3.5.4. Time to Start Feeding. Only two studies reported thetime to start feeding; the meta-analysis showed a statisticallysignificant reduction in the time to start feeding for thegum chewing group (WMD −1.32; 95% CI −2.18 to −0.46;P = 0 003) (Figure 7), with no evidence of heterogeneityacross the trials (P value of the homogeneity test = 0.79;I2 = 0%).
3.5.5. Postoperative Ileus (POI). No significant difference wasobserved between the gum chewing group and control group
279 of records identi�edthrough database searching
16 of additional records identi�edthrough other sources
(Reference lists and bibliographies)
96 of records a�er duplicatesremoved
199 of recordsscreened
157 of recordsexcluded
42 of full-text articlesassessed for eligibility
25 of full-text articlesexcluded with reasons
17 of studies included inqualitative synthesis
17 of studies included inquantitative synthesis(meta-analysis)
Figure 1: Study flow diagram.
3Gastroenterology Research and Practice
Table1:The
characteristicsof
includ
edstud
ies.
Autho
r(year)
Patient
popu
lation
Num
berof
patients
(GC/N
GC)
GCintervention
Outcomes
Results
Asao2002
[16]
Electivelaparoscop
iccolectom
yfor
colorectalcancer
19(10/9)
Patientschew
edgum
threetimes
aday
from
thefirstpo
stop
erativeAM
untilthe
daythey
beganoralintake.
①②⑤⑦
Gum
chew
ingaids
earlyrecovery
from
postop
erativeileus
andisan
inexpensive
andph
ysiologicmetho
dforstim
ulating
bowelmotility.
Atkinson2016
[17]
Electivecolorectalresection
402(199/203)
Patientschew
edgum
forat
least10
min,
four
times
adayfor5consecutivedays
(orun
tild
ischarge,iflessthan
5days)
from
thefirstpo
stop
erativemorning.
①③⑥⑦⑧⑩⑪
Chewinggum
didno
talterthereturn
ofbowelfunction
orLO
Safter
colorectalresection.
Fernandez2016
[18]
Electivecolorectalsurgery
64(32/32)
Chewinggum
withinthefirst24
hafter
surgery,for15
minutes
everyfour
hours
througho
uttheirho
spitalstay,w
ithsix
restingho
ursat
night.
①⑤⑥⑦⑧
The
useof
chew
inggum
aftercolorectal
surgerywas
associated
withless
postop
erative
ileus
andvomiting,andwithan
increased
passageof
flatus
withinthefirst48
hours
aftersurgery.
Forrester2014
[19]
Opencolonresection
oralaparoscop
icsigm
oidcolectom
y31
(13/18)
Gum
chew
ingbeganon
themorning
ofthefirstpo
stop
erativedayor
after
removalof
thenasogastrictube,and
the
times
ofgum
chew
ingcorrespo
nded
with
routinemedicationadministrationtimes.
①③④⑦⑨
Postoperative
gum
chew
ingwas
notmore
effective
than
standard
postop
erativecare
orattention-controlinterventionin
redu
cing
thedu
ration
ofpo
stop
erativeileus
symptom
s,length
ofstay,orcomplications
amon
gpatientsfollowingop
enlaparoscop
icsigm
oidcolectom
y.
Heijkant2015
[20]
Electivecolorectalsurgery
120(58/62)
Patientsstartedchew
inggum
3hbefore
andaftersurgery.The
frequencyand
duration
ofgum
chew
ingwere
notstandardized.
①②⑤⑦⑧⑫
Gum
chew
ingisasafeandsimpletreatm
ent
toredu
cePOIandisassociated
witha
redu
ctionin
system
icinflam
matorymarkers
andcomplications.
Hirayam
a2006
[21]
Electiveop
ensurgery
forcolorectalcancer
24(10/14)
Patientschew
edgum
threetimes
daily
for30
minutes
everytime.
①②⑥
Gum
-chewingprovides
asimpleandeffective
metho
dto
improvethepo
stop
erativestate
ofpatients.
Hwang2013
[22]
Laparoscop
iccolorectal
cancer
surgery
132(65/67)
Patientsstartedto
chew
gum
onthefirst
postop
erativeday,3times
aday,
approxim
ately10–20minutes
atatime,
untiln
ormalfeedingwas
resumed.
①⑦
Gum
chew
ingisan
easy
andcost-effective
metho
dto
redu
cethelength
ofthe
postop
erativeho
spitalstay
forlaparoscop
iccolorectalcancer
surgery.
Kob
ayashi
2015
[23]
Left-sided
resectionfor
colorectalcancer
43(21/22)
Patientschew
edgum
threetimes
daily
for≥5
minutes
(morning,n
oon,
and
evening)
untilthe
firstdayof
regularoral
dietaryintake.
①③⑦⑬
Gum
chew
ingchangedtheserum
levelsof
des-acylghrelin
andgastrin,
butwewere
unableto
demon
stratean
effecton
the
recovery
ofbowelfunction
.
Lim
2013
[24]
Colorectalresection
157(77/80)
Chewinggum
for15
minutes
4times
aday(8AM,12PM,4PM,and
8PM).
①③⑥⑦⑧
Chewinggum
issafe,but
does
nothasten
thereturn
ofgastrointestinalfunction
inpatientswho
receiveaccelerated
postop
erativefeeding.
4 Gastroenterology Research and Practice
Table1:Con
tinu
ed.
Autho
r(year)
Patient
popu
lation
Num
berof
patients
(GC/N
GC)
GCintervention
Outcomes
Results
Matros2006
[25]
Electivepartialcolectomy
forcolorectalcancer
43(22/21)
Chewinggum
for45
minutes
threetimes
daily
at9AM,4
PM,and
8PM.
①③⑦
Gum
chew
ing,althou
ghsafe,d
oesno
tredu
cedu
ration
ofpo
stcolectom
yileus.
McC
ormick2005
[26]
Electivecolonresection
88(53/35)
Gum
chew
ing4times
adayfor15
min.
①③⑦
Chewinggum
inthepo
stop
erativeperiod
may
bean
inexpensiveintervention
tofacilitaterecovery
anddecrease
hospitalcost.
Quah2006
[27]
Opensurgery
forleft-sided
colorectalcancer
38(19/19)
The
patientschew
edgum
forat
least5min,
threetimes
daily
from
thefirstpo
stop
erative
morning
untilthe
intake
ofasolid
dietorally.
①②⑦⑧⑭
The
addition
ofgum
chew
ingto
astandardized
postop
erativeregimen
didno
tredu
cetheperiod
ofpo
stop
erativeileus
orshortenlength
ofstay
followingop
ensurgery
forleft-sided
colorectalcancer.
Schu
ster
2006
[28]
Electiveop
ensigm
oidresections
34(17/17)
Chewinggum
3times
daily
for1ho
ureach
timeun
tild
ischarge.
①③⑦⑨
Gum
chew
ingspeeds
recovery
afterelective
open
sigm
oidresectionby
stim
ulating
bowelmotility.
Shum
2016
[29]
Laparoscop
iccolorectal
resection
82(41/41)
Chewinggum
threetimes
daily
for30
min
each
timefrom
day1un
tild
ischarge.
①③⑦⑨
Chewinggum
isasimpleintervention
that
speeds
intestinaltransitin
patientsmanaged
witharecovery
programmeafterlaparoscop
iccolorectalresection
Top
cu2016
[30]
Plann
edop
encolorectalsurgery
60(30/30)
Patientschew
edgum
threetimes
adayafter
mealsforaperiod
of15
min
from
thefirstm
orning
aftertheop
erationun
tilthe
timeof
theirdischarge.
①②④⑦
Chewinggum
isasimpleintervention
for
redu
cing
postop
erativeileus
after
colorectalsurgery.
Yang2017
[31]
Openor
laparoscopic
resection
394(197/197)
Chewinggum
threetimes
daily
forat
least
10min,startingon
postop
erativeday1and
continuing
for5consecutivedays
orun
tilfl
atus.
①③⑥⑦⑧
Chewinggum
does
notappear
toaffect
recovery
ofbowelfunction
orho
spitalstay,
thou
ghitmay
benefitpatientswho
undergo
open
resection.
Zaghiyan2013
[32]
Major
colorectalsurgery
114(54/60)
Chewinggum
for45
minutes,3
times
daily
onpo
stop
erativedays
1to
7.①③⑥⑦
There
does
notappear
tobe
anybenefitto
sugaredchew
inggum
incomparison
withno
gum
inpatientsun
dergoing
major
colorectalsurgery
Note:①
thetimeto
firstp
assage
offlatus;②
thetimeto
firstd
efecation;③
thetimeto
firstb
owelmovem
ent;④
timeto
startfeeding;⑤
postop
erativeileus
(POI);⑥
clinicalcomplications
such
asnausea,vom
iting,
abdo
minaldistension
,pain,pn
eumon
ia,w
ound
infection,bleeding,and
others;⑦
thelength
ofpo
stop
erativeho
spitalstay;⑧
mortality;⑨
timetofirsth
unger;⑩
firstd
ayofauscultatedbowelsoun
ds;⑪
solid
food
consum
ptionandtolerance;⑫
localand
system
icinflam
mationandgastricem
ptying;⑬
gutho
rmon
es;⑭
toleranceandsatisfaction
ofgum
chew
ing.
5Gastroenterology Research and Practice
in the incidence of POI (RR 0.29; 95% CI 0.08 to 1.11;P = 0 07) (Figure 8), with no statistical heterogeneity betweentrials (P = 0 97; I2 = 0%).
3.5.6. Postoperative Nausea. There was no significant dif-ference between the groups in the incidence of postoper-ative nausea (RR 0.97; 95% CI 0.82 to 1.15; P = 0 74)
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of outcome assessment (detection bias)
Blinding of participants and personnel (performance bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias
Low risk of biasUnclear risk of biasHigh risk of bias
0 25
(%)
50 75 100
(a) Risk of bias graph
Random sequence generation (selection bias)
Allocation concealment (selection bias)
Blinding of outcome assessment (detection bias)
Blinding of participants and personnel (performance bias)
Incomplete outcome data (attrition bias)
Selective reporting (reporting bias)
Other bias
Asa
o 20
02
Atki
nson
201
6
Fern
201
6
Forr
este
r 201
4
Hei
jkan
t 201
5
Hira
yam
a 200
6
Hw
ang
2013
Koba
yash
i 201
5
Lim
201
3
Mat
ros 2
006
McC
orm
ick
2005
Qua
h 20
06
Schu
ster 2
006
Shum
201
6
Topc
u 20
16
Yang
201
7
Zagh
iyan
201
3
+?
‒‒
+?
?
+?
‒+
+?
+
??
??
++
+
++
‒+
+?
+
??
??
+?
+
??
??
+?
?
??
??
+?
+
+?
??
+?
+
??
??
+?
+
??
??
+?
+
??
??
+?
+
??
??
+?
+
++
?+
+?
+
++
++
+?
+
++
‒+
+?
+
++
‒+
++
+
++
‒‒
+?
+
(b) Risk of bias summary
Figure 2: Methodological quality and risk of the included studies.
0
0
0.5
1
‒1 1
1.5
2‒2 2
MD
SE (MD)
(a) Funnel plot for the time to first passage of flatus
0
0
1
2
‒2 2
3
4
5‒4 4
MD
SE (MD)
(b) Funnel plot for the length of postoperative hospital stay
Figure 3
6 Gastroenterology Research and Practice
0‒1 1‒2 2
Favours [GC] Favours [NGC]
Study or subgroup Mean SD Total Mean SDNGC
Total Weight Mean differenceIV, random, 95% CI
Mean differenceIV, random, 95% CI
GC
Asao 2002Forrester 2014Hirayama 2006Kobayashi 2015Matros 2006McCormick 2005Quah 2006Schuster 2006Topcu 2016Zaghiyan 2013
Total (95% CI) 249 244 100.0% ‒0.55 [‒0.94, ‒0.16]
2.12.992.312.212.752.552.1
2.732.132.03
0.53.270.630.080.921.05
10.620.821.39
10131021225319173054
3.23.423.752.04
32.62.7
3.343.361.96
0.92.180.751.081.181.45
10.8
1.081.23
9171422213519173060
9.8%2.9%
10.8%11.6%10.1%10.7%10.1%11.4%11.3%11.3%
‒1.10 [‒1.76, ‒0.44]‒0.43 [‒2.49, 1.63]‒0.44 [‒1.99, ‒0.89]0.17 [‒0.28, 0.89]‒0.25 [‒0.88, 0.38]‒0.05 [‒0.61, 0.51]‒0.60 [‒1.24, 0.04]‒0.61 [‒1.09, ‒0.13]‒1.23 [‒1.72, ‒0.74]0.07 [‒0.41, 0.89]
Test for overall effect: Heterogeneity:
Z =2.75 (P = 0.006)�휏2=0.29; �휒2=40.01, df =9 (P < 0.00001); I2 = 78%
Figure 4: Forest plot for the time to first passage of flatus.
0‒2 2‒4 4
Favours [GC] Favours [NGC]
Study or subgroup Mean SD Total Mean SDNGC
Total Weight Mean differenceIV, random, 95% CI
Mean differenceIV, random, 95% CI
GC
Asao 2002Hirayama 2006Quah 2006Topcu 2016
‒2.70 [‒4.29, ‒1.11]‒2.15 [‒3.73, ‒0.57]‒0.70 [‒1.65, 0.25]1.38 [0.39, 2.37]
Total (95% CI)
Test for overall effect: Z = 1.05 (P = 0.29)Heterogeneity: �휏2 = 2.88; �휒2 = 25.56, df = 3 (P < 0.00001); I2 = 88%
69 72 100.0% ‒0.96 [‒2.74, ‒0.16]
3.13.523.2
5.77
1.11.581.5
1.84
10101930
5.85.673.9
4.39
2.22.371.5
2.06
9141930
23.4%23.5%26.6%26.5%
Figure 5: Forest plot for the time to first defecation.
1.88 [‒1.23, 4.99]‒0.62 [‒1.61, ‒0.37]‒0.28 [‒1.11, 0.55]‒0.50 [‒1.03, 0.03]‒1.10 [‒1.59, ‒0.03]‒0.26 [‒0.84, 0.32]
Total (95% CI)
Test for overall effect: Z = 4.31 (P < 0.0001)Heterogeneity: �휒2 = 8.53, df = 5 (P = 0.13); I2 = 41%
176 170 100.0% ‒0.60 [‒0.87, ‒0.33]
0.8%7.6%
10.9%26.7%31.4%22.6%
Forrester 2014Kobayashi 2015Matros 2006McCormick 2005Schuster 2006Zaghiyan 2013
Study or subgroup Mean SD Total Mean SDNGC
Total Weight Mean differenceIV, fixed, 95% CI
Mean differenceIV, fixed, 95% CI
GC
0‒2 2‒4 4
Favours [GC] Favours [NGC]
5.213.923.583.1
2.632.37
4.621.831.251.050.231.56
92122531754
152221351760
3.334.543.863.6
3.732.63
1.521.461.5
1.351
1.57
Figure 6: Forest plot for the time to first bowel movement.
‒2.04 [‒7.29, 3.21]‒1.30 [‒2.17, ‒0.43]
Total (95% CI)
Test for overall effect: Z = 3.00 (P = 0.003)Heterogeneity: �휒2 = 0.07, df = 1 (P = 0.79); I2 = 0%
40 40 100.0% ‒1.32 [‒2.18, ‒0.46]
2.7%97.3%Topcu 2016
Forrester 2014
0‒5 5‒10 10
Favours [GC] Favours [NGC]
4.153.07
3.911.53
1030
1030
6.194.37
7.511.9
Study or subgroup Mean SD Total Mean SDNGC
Total Weight Mean differenceIV, fixed, 95% CI
Mean differenceIV, fixed, 95% CI
GC
Figure 7: Forest plot for the time to start feeding.
7Gastroenterology Research and Practice
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Asao 2002Fern 2016
02
17
82
1032
932
0.30 [0.01, 6.62]0.29 [0.06, 1.27]
18.3%81.7%
Total (95% CI)
Test for overall effect: Z = 1.81 (P = 0.07)Heterogeneity: �휒2 = 0.00, df = 1 (P = 0.97); I2 = 0%
42 41 100.0% 0.29 [0.08, 1.11]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
Figure 8: Forest plot for postoperative ileus.
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Fern 2016Hirayama 2006Lim 2013
60
64
321077
321480
112
62
0.55 [0.23, 1.30]0.27 [0.01, 5.13]1.07 [0.92, 1.25]
14.9%2.9%
82.3%
7570Total (95% CI)
Test for overall effect: Z = 0.33 (P = 0.74)Heterogeneity: �휒2 = 4.00, df = 2 (P = 0.14); I2 = 50%
119 126 100.0% 0.97 [0.82, 1.15]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
Figure 9: Forest plot for postoperative nausea.
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, random, 95% CIRisk ratio
M-H, random, 95% CIGC
Events
Fern 2016Lim 2013
236
835
4338
3277
3280
0.25 [0.06, 1.09]1.07 [0.76, 1.51]
38.1%61.9%
Total (95% CI)
Test for overall effect: Z = 0.67 (P = 0.50)Heterogeneity: �휏2 = 0.82; �휒2 = 3.78, df = 1 (P = 0.05); I2 = 74%
109 112 100.0% 0.61 [0.15, 2.55]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
Figure 10: Forest plot for postoperative vomiting.
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Fern 2016Lim 2013
454
758
6558
3277
3280
0.57 [0.19, 1.76]0.29 [0.79, 1.18]
11.0%89.0%
Total (95% CI)
Test for overall effect: Z = 0.75 (P = 0.45)Heterogeneity: �휒2 = 0.90, df = 1 (P = 0.34); I2 = 0%
109 112 100.0% 0.92 [0.75, 1.13]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
Figure 11: Forest plot for postoperative abdominal distention.
8 Gastroenterology Research and Practice
(Figure 9), with a moderate statistical heterogeneity acrossthe trials (I2 = 50%).
3.5.7. Postoperative Vomiting. There was no significant differ-ence between the groups in the incidence of postoperativevomiting (RR 0.61; 95% CI 0.15 to 2.55; P = 0 50)
(Figure 10), with a clear statistical heterogeneity betweentrials (I2 = 74%).
3.5.8. Postoperative Abdominal Distension. There was nosignificant difference between the groups in the incidence ofpostoperative abdominal distension (RR 0.92; 95% CI 0.75
Risk ratioM-H, fixed, 95% CI
10.1 100.01 100
Favours [experimental] Favours [control]
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIGC
Events
Fern 2016Yang 2017
33
24
66
32190
32189
1.50 [0.27, 8.38]0.75 [0.17, 3.29]
33.3%66.7%
Total (95% CI)
Test for overall effect: Z = 0.01 (P = 1.00)Heterogeneity: �휒2 = 0.36, df = 1 (P = 0.55); I2 = 0%
222 221 100.0% 1.00 [0.33, 3.02]Total events
Figure 12: Forest plot for postoperative pneumonia.
Study or subgroup Mean SD Total Mean SDNGC
Total WeightMean difference
IV, random, 95% CIMean difference
IV, random, 95% CIGC
Asao 2002Fern 2016Forrester 2014Heijkant 2015Kobayashi 2015Matros 2006McCormick 2005Quah 2006Schuster 2016
Yang 2017Topcu 2016
Zaghiyan 2013 4.7 0.7 54 4.5 19 60 14.6% 0.20 [‒0.32, 0.72]
Total (95% CI)
Test for overall effect: Z = 2.43 (P = 0.01)Heterogeneity: �휏2 = 0.83; �휒2 = 75.34, df = 11 (P < 0.00001); I2 = 85%
519 514 100.0% ‒0.88 [‒1.59, ‒0.17]
13.57.5
6.319.5
19.84.924.89.44.3
7.6310.5
35.1
5.474.9
12.60.421.32.5
0.431.472.5
10321358212253191730
190
14.59
6.2614
16.44.735.3
11.16.8
9.4710.9
6.15.7
5.8314.516.90.271.957.3
1.382.672.4
9321862222135191730
189
2.2%4.9%2.6%2.8%0.6%
15.6%13.5%3.3%
13.7%11.5%14.7%
‒1.00 [‒5.40, 3.40]‒1.50 [‒4.15, 1.15]0.05 [‒3.96, 4.06]
‒4.50 [‒8.32, ‒0.68]3.40 [‒5.48, 12.18]0.19 [‒0.02, 0.40]‒0.50 [‒1.23, 0.23]‒1.70 [‒5.17, 1.77]‒2.50 [‒3.19, ‒1.81]‒1.84 [‒2.93, ‒0.75]‒0.40 [‒0.89, 0.09]
0‒2 2‒4 4
Favours [GC] Favours [NGC]
Figure 13: Forest plot for the length postoperative hospital stay.
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Atkinson 2016Heijkant 2015Lim 2013
Yang 2017Quah 2006
32
2
01
199587719
190
203628019
189
01100
7.14 [0.37, 137.34]2.14 [0.20, 22.95]0.35 [0.01, 8.37]
3.00 [0.013, 69.31]4.97 [0.24, 102.91]
12.6%24.6%37.4%12.7%12.7%
28Total (95% CI)
Test for overall effect: Z = 1.60 (P = 0.11)Heterogeneity: �휒2 = 2.20, df = 4 (P = 0.70); I2 = 0%
543 553 100.0% 2.57 [0.81, 8.15]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
Figure 14: Forest plot for mortality.
9Gastroenterology Research and Practice
to 1.13; P = 0 45) (Figure 11), with no statistical heterogene-ity between trials (P = 0 34; I2 = 0%).
3.5.9. Postoperative Pneumonia.No significant difference wasobserved between the gum chewing group and control groupin the incidence of postoperative pneumonia (RR 1.00; 95%CI 0.33 to 3.02; P = 1 00) (Figure 12), with no statisticalheterogeneity between trials (P = 0 55; I2 = 0%).
3.5.10. The Length of Postoperative Hospital Stay. Twelvestudies reported the length of postoperative hospital stayafter colorectal surgery under gum chewing intervention orstandard nursing. The meta-analysis showed a statisticallysignificant reduction in the length of postoperative hospitalstay for the gum chewing group (WMD −0.88; 95% CI −1.59to −0.17; P = 0 01) (Figure 13), with a clear statistical hetero-geneity across the studies (I2 = 85%).
3.5.11. Mortality. There was no significant difference betweenthe groups in the incidence of mortality (RR 2.57; 95% CI0.81 to 8.15; P = 0 11) (Figure 14), with no evidence ofheterogeneity across the trials (P = 0 70; I2 = 0%).
3.6. Intention to Treat Analysis. In the included studies, tenstudies reported the individual withdrawal after randomiza-tion. In order to provide unbiased assessments of treatmentefficacy, intention to treat analysis was conducted. Theresult showed that no obvious differences were found inpostoperative nausea, vomiting, abdominal distention, andmortality between the gum chewing group and control group(P > 0 05), which was consistent with the aforementionedfindings (Figure 15).
4. Discussion
The results of our meta-analysis have authenticated thatchewing gum after colorectal cancer surgery is helpful forthe recovery of the patient, which was associated with thereduction of the time to first passage of flatus, first bowelmovement, start feeding, and the length of postoperativehospital stay. However, no difference was observed in theincidence of postoperative nausea, vomiting, abdominal dis-tension, pneumonia, and mortality. In the included studies,most of them described the inclusion and exclusion criteriafor disease, age, and informed consent, yet only one study[19] mentioned that patients were excluded if they had aller-gies to chewing gum, and just one research [17] presented theacceptability and compliance of chewing gum, which mayresult in a risk of selection bias. Additionally, ten studiesreported the individual withdrawal after randomization.Remarkably, the main reasons for the patient’s withdrawalfrom the study or not included in the analyses were thatpatients did not receive chewing gum and inability to chewgum. In order to provide unbiased assessments of treatmentefficacy, intention to treat analysis was also conducted inour study. Similarly, we found that there were no obviousdifferences in postoperative nausea, vomiting, abdominaldistention, and mortality between two arms. Complexand various influencing factors of long-term outcome andfewer data were incorporated regarding the outcome of
postoperative complications that may account for the phe-nomenon. In our study, we only included the colorectalsurgery but not the whole abdominal surgery (cesareansection, and others) with the following consideration. Onthe one hand, not all abdominal surgery actually relate tothe gastrointestinal tract, and the process of intestinal func-tion recovery may be different following different surgery.Chewing gum acts as sham feeding which, therefore, maypromote the recovery of gastrointestinal function throughvarious ways. On the other hand, colorectal surgery changesand affects the integrity of the intestinal tract. The recovery ofintestinal function may mainly depend on the process ofintestinal tract itself, and chewing gum may provide limitedeffects on reducing some complications, which just couldexplain our findings.
How gum chewing works remains unclear. The possiblepresupposition is that gum chewing mimics the mechanismof food intake, which may significantly stimulate motility inthe stomach, duodenum, and rectum [33]; promote gastric,pancreatic, and duodenal secretion [34, 35]; and enhancethe release of neuropeptides [33]. The proposed physiologicmechanism is that gum chewing activates the cephalic-vagalaxis, which stimulates intestinal myoelectric activity to offsetthe activation of gastrointestinal opioid receptors [36]. Inaddition, gum chewing may also stimulate the saliva secre-tion, resulting in the production of nitrous oxide in sufficientquantities to combat the pathogens in the mouth and gut[37]. Furthermore, gum chewing may offer a better optionto regulate a potential risk which is associated with earlypostoperative enteral or oral feeding.
Recently, a significant amount of research focused on thepossible role of chewing gum in the intestinal function recov-ery, yet the evidence from RCTs remains inconclusive; there-upon, several meta-analyses of the efficacy of gum chewingwere published. The meta-analysis by Su’a et al. [12]described the effects of chewing gum on postoperative ileusin adults, showing that chewing gum is beneficial to reducingthe time to flatus and the time to bowel motion, but not thelength of hospital stay or complications. It is noteworthy thatthe included patients in this meta-analysis receiving eithercolorectal surgery or cesarean sections resulted in a heteroge-neous patient group. Another meta-analysis [7] of 10 RCTssuggested that sham feeding following colorectal surgery issafe, leading to the improvement in GI recovery, and is asso-ciated with the reduction in the length of hospital stay, whichis in consistent with our results. Nevertheless, this studyfound that gum chewing conferred no advantage if patientsare placed on a rapid postoperative feeding regime; whileour study revealed that gum chewing might accelerate thetime to first feeding, the difference may be explained by per-forming subgroup analysis on whether the rapid postopera-tive feeding was given to patients, which is just one of thelimitations of our research that the corresponding analysiswas not implemented. An earlier meta-analysis by Nobleet al. [13] identifying nine eligible trials also showed thatchewing sugarless gum following elective intestinal resectionwas associated with improved outcomes, but the efficacy on areduced rate of clinical complications or reduced cost was notconfirmed, which is also in line with our findings. Other
10 Gastroenterology Research and Practice
previous meta-analyses [38–44] that focused on the effectsof gum chewing on the recovery of intestinal functionafter abdominal surgery (e.g., cesarean delivery) also con-firmed the beneficial role of gum chewing after surgery.Currently, several RCTs with moderate or large sample
size investigating the efficacy of chewing gum in patientsundergoing colorectal resection have been published, how-ever, which has not been included for synthesized analysisin the latest meta-analysis by Song et al. [45]. Consequently,we launch this updated meta-analysis to comprehensively
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Fern 2016Hirayama 2006Lim 2013
60
64
321080
321484
112
62
0.55 [0.23, 1.30]0.27 [0.01, 5.13]1.08 [0.92, 1.28]
14.9%2.9%
82.3%
7570Total (95% CI)
Test for overall effect: Z = 0.22 (P = 0.83)Heterogeneity: �휒2 = 3.87, df = 2 (P = 0.14); I2 = 48%
122 130 100.0% 0.98 [0.82, 1.17]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
(a) Forest plot for postoperative nausea
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, random, 95% CIRisk ratio
M-H, random, 95% CIGC
Events
Fern 2016Lim 2013
236
835
4338
3280
3284
0.25 [0.06, 1.09]1.08 [0.76, 1.53]
38.3%61.7%
Total (95% CI)
Test for overall effect: Z = 0.66 (P = 0.51)Heterogeneity: �휏2 = 0.83; �휒2 = 3.81, df = 1 (P = 0.05); I2 = 74%
112 116 100.0% 0.62 [0.15, 2.59]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
(b) Forest plot for postoperative vomiting
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Fern 2016Lim 2013
454
758
6558
3280
3284
0.57 [0.19, 1.76]0.98 [0.79, 1.20]
11.0%89.0%
Total (95% CI)
Test for overall effect: Z = 0.64 (P = 0.52)Heterogeneity: �휒2 = 0.92, df = 1 (P = 0.34); I2 = 0%
112 116 100.0% 0.93 [0.75, 1.16]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
(c) Forest plot for postoperative abdominal distention
Study or subgroup Events TotalNGC
Total WeightRisk ratio
M-H, fixed, 95% CIRisk ratio
M-H, fixed, 95% CIGC
Events
Atkinson 2016Heijkant 2015Lim 2013
Yang 2017Quah 2006
32
2
01
199588019
190
203628419
189
01100
7.14 [0.37, 137.34]2.14 [0.20, 22.95]0.35 [0.01, 8.46]
3.00 [0.013, 69.31]4.97 [0.24, 102.91]
12.6%24.6%37.4%12.7%12.8%
28Total (95% CI)
Test for overall effect: Z = 1.60 (P = 0.11)Heterogeneity: �휒2 = 2.18, df = 4 (P = 0.70); I2 = 0%
546 557 100.0% 2.57 [0.81, 8.18]Total events
10.1 100.01 100
Favours [GC] Favours [NGC]
(d) Forest plot for mortality
Figure 15: Intention to treat analysis.
11Gastroenterology Research and Practice
evaluate the effect and safety of chewing gum for patientsundergoing colorectal resection, which may have moreadvantages in reducing heterogeneity and publication bias.
Several limitations of this study should be addressed.Firstly, owing to the differences in patient population andsurgery approaches involved, this meta-analysis is limitedby the significant heterogeneity of the included studies. Addi-tionally, limited included data subgroup analysis regardingdifferent interventions (e.g., initiation and frequency) ingum chewing was not performed. Besides, there was a lackof blinding in most included studies which may have resultedin significant performance and detection bias. Althoughblinding participants may be difficult in this setting, blindingobservers should be feasible and necessary which is condu-cive to increasing the reliability of the findings. Therefore,to improve the applicability of study results to individualpatients and provide potentially feasible clinical practiceguidelines for postoperative nursing, investigators shouldimprove study design to ensure protocol adherence withminimal loss to selection bias risk and follow-up. Moreover,based on the distribution characteristics of prognostic fea-tures, how to explore potential causes and search for morepowerful evidence still remain to be explored further.
5. Conclusions
This meta-analysis indicates that gum chewing in patientsundergoing colorectal cancer surgery has a beneficial role inintestinal function recovery. However, the limited data sug-gests that it offers no benefit in reducing postoperative clinicalcomplications such as nausea, vomiting, abdominal disten-sion, pneumonia, and mortality. Prospective and blindedRCTs are warranted to further clarify the role of chewinggum in the postoperative care in colorectal cancer patients.
Conflicts of Interest
The authors declare that they have no conflict of interest.
Authors’ Contributions
Binbin Mei and Wenting Wang are co-first authors. FeifeiCui and Zunjia Wen contributed equally to this work.
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