Clinical Nutrition xxx (2016) 1e12

Contents lists available at ScienceDirect

Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Meta-analyses

Optimal postoperative nutrition support for patients with

gastrointestinal malignancy: A systematic review and meta-analysis
Xia Yan, Fu-xiang Zhou*, Tian Lan, hui Xu, xiao-xi Yang, Cong-hua Xie, Jing Dai,
Zhen-ming Fu, Yan Gao, Lu-lu Chen
Zhongnan Hospital of Wuhan University, Department of Oncology, Wuhan University, Wuhan, 430071, China

a r t i c l e i n f o s u m m a r y

Article history: Objective: To improve clinical outcomes, parenteral nutrition, standard enteral nutrition and immuno-
Received 10 December 2015 enhanced nutrition are widely used in the gastrointestinal tumor patients undergoing surgery, but the
Accepted 15 June 2016 optimal management of postoperative nutrition support remains uncertain.
Methods: We systematically searched the PUBMED, EMBASE and CNKI to identify latent studies which
Keywords: the effects of standard EN compared with PN or IEN on gastrointestinal tumor patients until the end of
Parenteral nutrition
November, 2015. The quality of included trials was assessed according to the handbook for Cochrane
Enteral nutrition
reviewer. Statistical analysis was carried out by RevMan5.1 software.
Immune
Gastrointestinal cancer
Results: 30 randomized controlled trials containing 3854 patients were contained in our meta-analysis,
Surgery the results indicated that postoperative SEN could absolutely reduce the incidence of postoperative in-
Meta-analysis fectious (P < 0.00001) and non-infectious complications (P 0.0003), together with its positive effect on
the length of hospital stay (P < 0.00001). Additionally, enteral nutrition enhanced with immune stim-
ulation was conrmed to be better, with a signicant difference between groups in terms of total in-
fectious (P < 0.00001) and non-infectious complications (P 0.04), and IEN could also signicantly
shorten the length of hospital stay (P < 0.00001).
Conclusion: Early use of Enteral nutrition in digestive tumor patients after surgery could signicantly
reduce the postoperative complications and shorten the length of hospital stay, IEN should be the
optimal management, while the use of parenteral nutrition should be restrict to few patients with severe
intolerance to enteral nutrition.
2016 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction
Patients received elective gastrointestinal operations due to
malignant tumor are at high risk of developing postoperative in-
fectious, such as wound infection (WI), respiratory tract infection
(RTI) etc [1], some evidence suggests that malnutrition is the most
important factor [2e4]. Therefore, nutrition management is
essential for patients received elective gastrointestinal operations.
Energy needed for the body could be covered either by enteral
nutrition (EN) or parenteral nutrition (PN). Several studies have
reached the same conclusion that enteral route was better for some
patients, some other studies even found that application of PN in
patients did more harm than good [8,10e27]. Therefore, EN is
recommended in patients requiring nutrition support based on
* Corresponding author.
E-mail address: fxzhouwhu@gmail.com (F.-x. Zhou).
ESPEN guidelines, but there are still some centers prefer PN than EN
[6,7].
As one of postoperative management, nutrition support was not
only needed for pure energy supplement, but also for restoring
immune function. Thus, immunonutrition was put forward, which
aimed to relieve immune and inammatory responses induced by
surgery via the use of essential immune elements, like arginine,
glutamine, omega-3-fatty acids, and nucleotides [5]. Several trials
in patients undergoing general surgery indicated that early EN with
immune modulating formula could decrease postoperative com-
plications in both undernourished and well-nourished patients
[28e38,41] Therefore, immunonutrition highly recommended by
ESPEN guideline in patients undergoing major cancer surgery [8].
However, as Federico Bozzetti mentioned [3], clinical practice
guidelines (CPGs), which aimed to offer recommendations based on
good research, have made little progress to modulate its situation

http://dx.doi.org/10.1016/j.clnu.2016.06.011
0261-5614/ 2016 The Author(s). Published by Elsevier Ltd. 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 in press as: Yan X, et al., Optimal postoperative nutrition support for patients with gastrointestinal malignancy: A
systematic review and meta-analysis, Clinical Nutrition (2016), http://dx.doi.org/10.1016/j.clnu.2016.06.011
2 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12

Table 1
Search terms (PICO strategy) used for search strategy.

PICO' criteria Descriptions and search terms used for each criteria

Patients Patients with gastrointestinal cancer after surgery (esophageal or Esophagus or gastrointestinal OR gastric OR intestinal or Pancreatic or
colorectal) AND (cancer OR tumor OR neoplasms or carcinoma) AND (operation OR operated OR postoperative OR gastrectomy OR
pancreatectomy OR pancreaticojejunostomy)
Intervention EN or PN or IEN (enteral nutrition OR parenteral nutrition OR articial feeding OR nutritional support OR immune or immunol)
Comparisons Comparison between SEN and TPN or IEN and SEN (randomized controlled trial)
Outcomes Morbidity (infectious complication OR non-infectious complication OR respiratory infection, OR urinary infection OR wound
infection OR abscess OR anastomotic leakage OR delayed gastric emptying OR hemorrhage), length of hospital stay (length of
hospital stay OR hospitalization OR time in hospital), mortality (mortality OR death OR dead)

that most of recommendations were base on low-grade research
evidence (Grade A, 15.8%; Grade B, 28.2%; and Grade C, 56.0%).
Therefore, proceeding from the current situation mentioned
above, we conducted a meta-analysis of randomized controlled
trials (RCTs) to systematically review the effect of TPN, SEN and IEN
in patients undergoing gastrointestinal surgery, and to explore the
most favorable nutrition therapy for gastrointestinal tumor pa-
tients undergoing surgery, and attempt to provide higher-grade
evidence to CPGs recommendations.
inception of each database to October 31, 2105, and the search was
carried out using the combination of search terms shown in Table 1.
Additionally, the search was carried out following the PICO
strategy, and was restricted to studies with a main body in English or
Chinese, but free to sample size. The selection began with review of
titles and abstracts, but if it was not sufcient to make judgments,
the full-texts followed. At the same time references of the identied
studies were also manually searched to locate the probable related
studies. All searches were conducted by two independent in-
vestigators, and conicts were all resolved by discussing.

2. Materials and methods 2.2. Inclusion and exclusion criteria

2.1. Search strategy
We carried out this systematic review and meta-analysis in
accordance with Preferred Reporting Items for Systematic Review
and Meta-analysis (PRISMA) statement and Cochrane Handbook for
Systematic Reviews of Intervention [39]. The electronic databases
PubMed, Embase, CNKI were searched for eligible studies from the
The eligibility criteria for this study were as follows: 1 study
designed as randomized controlled trial (RCTs); 2 patients
received surgery were pathologically diagnosed as gastrointes-
tinal cancer (including esophagus, gastric, pancreas, and colo-
rectal). 3 RCTs aimed at comparing the clinical outcomes between
PN and EN or between IEN and SEN. 4 the nutritional support was
postoperative.

Fig. 1. Flow chart of study selection.

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Table 2
Basic characteristics of each study included in the meta-analysis of PN and EN.

Study ID Year Country Number Age Nutrition status Approaches NS duration Primary tumor site Outcomes
(PN/EN) (PN/EN) (mal/good) (PN/EN) (day) (PN/EN)

Reynolds JV 1997 England 34/33 67 (25e86) 27/7 Central venous catheter POD 1-7 Esophagus 19/23 RTI, Ab, DGE, Al, Hemo,
Mortality
69 (51e81) 27/6 Nasojejunal feeding tube POD 1-7 Stomach 7/7
Pancreas 8/3
Sand J 1997 Finland 16/13 63 (46e82) Not given Introvenous Not given Stomach 16/13 RTI, UTI, WI, Ab, AL, Hemo
57 (48e72) Nasojejunal feeding tube Not given
Gianotti L 1997 Italy 86/87 63.8 12.1 Not given Introvenous POD 1-7 Stomach 39/40 RTI, UTI, WI, Ab, AE, LOH,
Mortality
64.5 13.4 Nasojejunal feeding tube POD 1-7 Pancreas 47/47
Bozzetti F 2001 Italy 158/159 64.1 9$8 Mal Central venous catheter POD 9.6 4.3 Stomach/oesophagus RTI, UTI, WI, Ab, DGE, Al,
76/83 Hemo, LOH, Mortality
64.8 10$8 Nasojejunal feeding tube POD 8.4 2.5 Hepatobiliary 8/10
Colon/rectum 43/36
Pancreas 31/30
Braga M 2001 Italy 131/126 62.9 12.4 48/83 Not given POD 13.4 4.9 Esophagus 10/16 RTI, UTI, WI, Ab, DGE, Al,
64.1 13.1 43/83 Nasojejunal feeding tube POD 12.8 5.5 Stomach 62/59 Hemo, AE, LOH, Mortality
Pancreas 59/51
Aiko S 2001 Japan 11/13 69.3 Not given Central venous catheter Not given Esophagus 11/13 RTI, WI, AL, LOH
65.6 Jejunostomy Not given
Page RD 2002 Liverpool 20/20 65.6 8.8 Not given Introvenous POD 1-6 Esophagus 20/20 RTI, WI, LOH
69.1 7.5 Nasojejunal feeding tube POD 1-6
Wu PR 2006 China 53/53 Not given Not given Introvenous POD 1-7 Esophagus 53/53 RTI, AL
Not given Nasojejunal feeding tube POD 1-7
Barlow R 2011 UK 57/64 63 Not given Introvenous POD 12.4 Esophagus 54 RTI, UTI, WI, DGE, Al, Hemo,
64.5 Nasojejunal feeding tube Not given Stomach 38 LOH, Mortality
Pancreas 29
Liu C 2011 China 30/30 60.5 11.9 Well Central venous catheter POD 1-7 Pancreas 60 RTI, WI, Ab, DGE, AL, Hemo,
59.7 11.2 Nasojejunal feeding tube >POD 6 LOH, Mortality
Feng HQ 2012 China 15/20 60.9 8.0 Not given Central venous catheter Not given Esophagus 15/20 BM
61.1 7.7 Nasojejunal feeding tube Not given
Ghafouri A 2012 Iran 30/30 57.26 5.4 54/6 Introvenous POD 1-5 Gastrointestinal WI, AL, LOH
54.00 4.5 Nasojejunal feeding tube POD 1-5 30/30
Park Js 2012 Korean 20/18 61.3 13.2 Well Central venous catheter POD 6.7 4.4 Pancreas 20/18 WI, DGE, AL, Hemo, LOH
62.7 10.3 Nasojejunal feeding tube POD 5.7 2.7
Boelens P 2013 Holland 62/61 65.0 1.2 Well Central venous catheter POD 1-5 Rectum 62/61 RTI, UTI, WI, Ab, AL
64.0 1.4 (*weight loss < 10%) Nasojejunal feeding tube POD 1-5
Yu G 2013 China 46/50 67.5 (65e78) Not given Central venous catheter POD 1-7 Esophagus AE, LOH
68.9 (65e79) Nasojejunal feeding tube POD 1-7 Stomach
Xiao Bo-Y 2014 China 56/64 63.05 16.2 Mal Central venous catheter POD 1-7 Esophagus 56/64 RTI, WI, AE, LOH
65.06 13.03 (SGA assessment) Nasojejunal feeding tube POD 1-7
Zhao G 2014 China 30/30 53.2 8.4 Well (BMI  15) Central venous catheter POD 1-7 Esophagus 30/30 RTI, WI, AL, AE, LOH
54.2 7.3 Nasojejunal feeding tube POD 1-7
Li B 2015 China 200/200 60.8 5.9 Not given Not given POD 1-7 Stomach 200/200 AE, LOH
56.0 7.6 Nasojejunal feeding tube POD 1-7

PN parenteral nutrition, EN enteral nutrition, NS duration nutrition support duration, RTI: Respiratory tract infection, UTI Urinary tract infection, WI wound
infection, Ab intra-abdominal abscess, DGE delayed gastric emptying, Al anastomotic leakage, BM rst time of bowel movement (day), AE rst time of anal exhaust
(day), Hemo postoperative hemorrhage, LOH length of hospitalization, POD postoperative day.
* indicates supplement contents which used to elaborate more details.

Trials did not meet the inclusion criteria were excluded, moreover
patients identied with secondary or unresectable neoplasm, studies
lacking of essential information or indicators of interest, or
with duplicate data, would be also excluded, studies originally pub-
lished in language other than English or Chinese were also the same.
following items: randomization sequence generation, allocation
concealment, blinding, incomplete outcome data, selective report-
ing and other biases, each domain was rated as high-risk or low-risk,
if there were enough information to state what was done, otherwise,
unclear risk was applied for studies without sufcient details.

2.3. Data extraction 2.5. Missing data

Essential information and continuous or dichotomous data for
special outcomes of each eligible article were extracted by two
independent investigators (X.Y and T.L), using the Table prede-
signed which included following items: study ID, year of publica-
tion, country, sample size, age of participants, duration of nutrition
support, approach of nutrition, primary tumor site and outcomes-
analyzed. Disagreements were resolved by consensus.
2.4. Quality assessments
Two authors independently assessed the quality of selected
studies using the Cochrane collaboration tool, which included
Connections with corresponding authors were made for
necessary information of missing data, as well as other relevant
information needed for analysis.
2.6. Statistical analysis
Meta-analysis was performed by Cochrane Collaboration's
Revman Manager 5.1 software. P value < 0.05 was considered sta-
tistically signicant. The intervention effect was expressed with
risk ratios (RRs) for dichotomous outcomes and mean differences
(MDs) for continuous outcome measures, with their condence
intervals of 95% (CI 95%). Heterogeneity, which represents the

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Table 3
Basic characteristics of each study included in the meta-analysis of IEN and SEN.

Study ID Year Country Number Age (IEN/SEN) Nutrition status Approaches (IEN/ Immuno-elements NS duration Primary tumor Outcomes
(IEN/SEN) (mal/good) SEN) (day) site

Kenler AS 1996 USA 17/18 62.8 2.7 Not given Jejunostomy tube N-3 fatty acids POD 1-7 Not given RTI, UTI, WI, AB,
Mortality
64.4 3.4 POD 1-7
Gianotti L 1997 Italy 87/87/86 62.7 14.3 Not given Nasojejunal tube/ Arginine, Omega-3 POD 1-7 Stomach 41/40/ RTI, UTI, WI, Ab, AE,
jejunostomy fatty acids and 39 LOH, Mortality
[RNA]
64.5 13.4 POD 1-7 Pancreas 46/47/
47
Senkal M 1997 Germany 77/77 65.1 1.5 Not given Jejunostomy tube Arginine, Omega-3 Not given Esophagus 13/ RTI, UTI, WI, Ab, AL,
fatty acids and 16 LOH, Mortality
[RNA]
66.3 1.8 Stomach 41/38
Pancreas 15/16
Others 8/7
Ferreras N 2005 Spain 30/30 66.7 8.3 5/25 Not given Arginine, Omega-3 POD 1-7 Not given RTI, UTI, WI, AB,
fatty acids and LOH, Mortality
[RNA]
69.2 13.8 8/22 POD 1-7
Lobo DN 2006 UK 54/54 65.7 1.4 4/50 Jejunostomy tube Glutamine, Not given Esophagus 36/ RTI, WI, AB, AL,
Arginine 28 Hemo, LOH,
Mortality
66.6 1.4 5/49 Stomach 11/18
Pancreas 7/8
Aiko S 2008 Japan 15/14 60 2 Not given Jejunostomy tube Arginine, Omega-3 POD 1-7 Esophagus 15/ WI, RTI, AL, LOH
fatty acids and 14
[RNA] (*w-6 to w-3
ratio of 3.0)
64 2 w-6 to w-3 ratio of POD 1-7
0.8
Klek s* 2008 Poland 92/91 62.1 10.9 Good (*Karnofsky Nasojejunal feeding Not given POD Stomach 58/56 RTI, UTI, WI, Ab, AL,
>80/(ECOG) grade tube 8.6 1.4 LOH, Mortality
0 or 1)
65.7 1.4 POD Pancreas 34/35
8.4 1.2
KleK S 2010 Poland 152/153 60.2 12.4 Mal (*BMI < 18/ Jejunostomy tube Glutamine, POD 1-7 Stomach 109/ RTI, UTI, WI, AB, AL,
weight loss > 10%) Arginine 102 Hemo, LOH,
Mortality
61.5 11.8 POD 1-7 Pancreas 43/51
Liu JZ 2011 China 53/53 57.6 9.7 Mal (SGA B/C) Nasojejunal/ Omega-3 fatty acids POD 1-7 Stomach 22/21
jejunostomy tube and [RNA]
55.4 11 POD 1-7 Colon 15/17 RTI, WI, Ab, AL, LOH
Rectum 16/15
Liu H 2012 China 28/24 57.3 7.1 Not given Nasojejunal tube Glutamine, POD 1-7 Stomach 28/24 RTI, WI, AL, AE, LOH
Arginine
58.4 6.3
Marano L 2013 Italy 54/54 66.6 (55e78) 33/61 Jejunostomy tube Arginine, Omega-3 POD 1-7 Stomach 54/55 RTI, UTI, WI, AL,
fatty acids and LOH, Mortality
[RNA]
65.1 (49e83) 30/54 POD 1-7
Zhao H 2013 China 37/36 59 (42e73) Mal (*weight Nasojejunal tube Arginine POD 1-7 Stomach 37/36 RTI, WI, AE, LOH
loss  10%)
57 (45e74) POD 1-7

* indicates supplement contents which used to elaborate more details.

differences among studies, was assessed using the Q-test and sta-
tistical value I2. If I2 50%, the studies was thought to be homo-
geneity, and the xed-effects model was used for secondary
analysis. Otherwise, we used the random-effects model. If included
studies have signicant heterogeneity we would only describe their
characteristics, if required we will carry out the sensitivity analysis
to test the stability of our study.
2.7. Publication bias
Funnel plots were constructed to assess the potential bias of
publication, furthermore Begg rank correlation test and egger-test
would be proceeded if required.
3. Results
3.1. Eligible studies
A total of 420 studies was reviewed, of these studies, 369 studies
were excluded because of obvious irrelevance to our topic by
reviewing the titles and abstracts. We identied 51 potential
studies for further evaluation, nally, 30 studies met our inclusion
criteria for this meta-analysis. Among them, 18 studies were
distributed to the group of the comparison between SEN and TPN
[10e27], 12 studies were allocated in the SEN with IEN [13,28e38],
1 studies met the conditions at the same time [13]. Detailed search
steps were described using the PRISNA 2009 ow diagram [39]
(Fig. 1).

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 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12 5

Fig. 2. Risk of bias summary of PN and EN.

Fig. 3. Risk of bias summary of IEN and SEN.

Table 4
Summary of ndings.

Outcomes Studies num Num of participants Relative effect (95% CI) Heterogeneity (I2) p-Value

PN VS EN
Total infectious com 16 2022 1.80 (1.52, 2.14) 11% <0.00001
Non-infectious com 12 1668 1.68 (1.27, 2.21) 43% 0.0003
RTI 15 1927 1.94 (1.42, 2.64) 0% <0.0001
WI 14 1852 1.56 (1.12, 2.18) 0% 0.008
AL 11 1603 1.85 (1.20, 2.87) 0% 0.006
LOH (day) 10 1519 1.44 (1.10, 1.78) 0% <0.00001
Mortality 10 1552 1.06 (0.54, 2.08) 0% 0.87
IEN VS SEN
Total infectious com 12 1388 0.72 [0.61, 0.84] 37% <0.0001
Non-infectious com 5 859 0.69 [0.48, 0.98] 0% 0.04
RTI 11 1359 0.83 [0.65, 1.06] 0% 0.14
WI 12 1388 0.74 [0.50, 1.09] 0% 0.13
AL 5 859 0.67 [0.43, 1.04] 0% 0.07
LOH (day) 10 1048 1.87 [2.84, 0.91] 81% 0.0001
Mortality 8 1063 0.66 [0.36, 1.24] 0% 0.2

3.2. Study characteristics and assessment of quality
Essential characteristics of 30 RCTs with 3854 patients enrolled
in this study were presented in Tables 2 and 3 and the assessments
of quality followed by Cochrane library handbook were shown in
Figs. 2 and 3.
According to the results presented in Fig. 2, we found that in
the group of the comparison between PN and EN, no trial
was completely free of bias. On the item of Random Sequence
Generation, only one trial did not provide relevant information,
while the rest were all identied to be of low-risk. Potential
selection bias was detected in one trial, while bias of performance
in two. The information were not sufcient when came to
the assessments of detection bias. Almost all the trials were
thought to be of low risk of attrition and reporting bias except
trials by Aiko s [15], which did not state enough details of these
terms. All of the studies included were thought to be free of other
bias.

Please cite this article in press as: Yan X, et al., Optimal postoperative nutrition support for patients with gastrointestinal malignancy: A
systematic review and meta-analysis, Clinical Nutrition (2016), http://dx.doi.org/10.1016/j.clnu.2016.06.011
6 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12

Fig. 4. Meta-analysis on postoperative complications of EN and PN: (A) Total infective complications (B) Total non-infectious complications; (C) RTI; (D) WI; (E) AL; (F) LOH; (G)
Mortality.

Likewise, the result, of the group for comparison between IEN performance and attrition bias, while no sufcient information
and SEN shown in Fig. 3, indicated 3 trials completely free of bias, were provided for assessment of detection bias, and 8 trials were
all the trials were identied to be randomized and free of considered to be of low risk of selection bias.

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Fig. 4. (continued).

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8 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12

Fig. 5. Meta-analysis on postoperative complications of IEN and SEN: (A) Total infective complications (B) Total non-infectious complications; (C) RTI; (D) WI; (E) AL; (F) LOH; (G)
Mortality.

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 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12 9

Fig. 5. (continued).

To sum up, we consider that there are plausible bias among
studies but could hardly effect the outcomes.
3.3. Comparison between postoperative PN and SEN
18 trials, published from 1997 to 2015 with 2556 patients, were
included. 1270 and 1286 patients were randomized to post-
operative PN and early standard EN group respectively [10e27].
Among which, 16 trials with a total of 2022 patients reported
postoperative infectious complications (including RTI, UTI, WI and
Ab), while 12 trials represented the non-infectious complications.
Findings of this comparison were summarized in Table 4.
In this set, the xed-effects meta-analysis showed the EN group
had a signicant lower incidence of postoperative infectious
complications than the PN group (RR, 1.80; 95% CI, 1.52 to 2.14;
p < 0.00001), test for heterogeneity (I2 11%, p 0.33), and the
incidence of non-infectious complications were also reduced in EN
group (RR, 1.65; 95% CI, 1.26 to 2.17; p 0.0003), without evident
heterogeneity (I2 38%, p 0.08), shown in Fig. 4. Furthermore,
the publication bias was not detected in the funnel plot shown in
Fig. 6-A.
The results in Fig. 4 also represented that application of EN for
postoperative nutrition support could also signicantly reduce the
incidence of RTI (RR, 1.94; 95% CI, 1.42 to 2.64; p < 0.0001), the test
of heterogeneity was not signicant (I2 0%, p 0.92). Addi-
tionally, in EN group, the risk of wound infection also reduced
signicantly (RR, 1.56; 95% CI, 1.12 to 2.18; p 0.008), the het-
erogeneity was also not signicant (I2 0%, p 0.91). As for non-
infectious complications, patients in EN group were at low risk of
developing AL (RR, 1.85; 95% CI, 1.20 to 2.87; p 0.006), without
heterogeneity among studies (I2 0%, p 0.52). Moreover, post-
operative administration of EN could also signicantly shorten the
length of hospital stay (MD, 1.44; 95% CI, 1.10 to 1.78; p < 0.00001),
and studies were deemed to be homogeneity (I2 0%, p 0.86).
However, no benet was observed when came to the assessment
of mortality among groups (RR, 1.06; 95% CI, 0.54 to 2.08; p 0.87),
no obvious statistical heterogeneity were identied (I2 0%,
P 0.75).
3.4. Comparison between postoperative IEN and SEN
12 trials including a total of 1388 patients were included in this
comparison group [13,28e38], 696 patients and 692 patients were

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10 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12
Fig. 6. Assessment of publication bias-Funnel plot: (A) PN and EN; (B) IEN and SEN.
randomized to postoperative IEN group and SEN group prospec-
tively. All of the studies included reported postoperative infectious
complications, and 9 of them contained information of non-
infectious complications. The summary of ndings of this part
was also represented in Table 4.
In this comparison, we evaluated the same indicators, and found
out that postoperative application of IEN in patients with gastro-
intestinal carcinomas could signicantly reduce the incidence of
infectious complications (RR, 0.72; 95% CI, 0.61 to 0.84; p < 0.0001)
as well as non-infectious complications (RR, 0.69; 95% CI, 0.48 to
0.98; p 0.04), with no obvious heterogeneity observed in both
analysis (I2 37%, P 0.10) (I2 0%, P 0.88), shown in Fig. 5. No
evidence of publication bias was observed in the selected funnel
plot in Fig. 6-B.
However, Fig. 5 also represented that patients can not benet
from the application of IEN on the items of RTI (RR, 0.83; 95% CI,
0.65 to 1.06; p 0.14) and WI (RR, 0.74; 95% CI, 0.50 to 1.09;
p 0.13), and test for heterogeneity (I2 0%, P 0.80) (I2 0%,
P 0.95), while similar conclusion was drawn out in the area of AL
(RR, 0.67; 95% CI, 0.43 to 1.04; p 0.07), without heterogeneity
among studies (I2 0%, P 0.89). Moreover, in this set, we also
detected a shorter length of hospitalization in IEN group
(MD, 1.87; 95% CI, 2.84 to 0.91, p 0.0001), unfortunately with
a obvious heterogeneity (I2 81%, P < 0.0001), and similar to the
ndings of comparison between PN and EN, there were no signif-
icance between IEN group and SEN group on the assessment of
mortality (RR, 0.66; 95% CI, 0.36 to 1.24; p 0.20), without het-
erogeneity (I2 0%, P 0.80).
Please cite this article in press as: Yan X, et al., Optimal postoperative nutrition support for patients with gastrointestinal malignancy: A
systematic review and meta-analysis, Clinical Nutrition (2016), http://dx.doi.org/10.1016/j.clnu.2016.06.011
4. Discussion
This systematic review based on 30 randomized controlled tri-
als, containing 3854 patients, is the rst meta-analysis aimed to
evaluate the clinical impact of three different approaches of post-
operative nutrition support in patients with gastrointestinal tumor,
and the results of this meta-analysis revealed a strong link between
the nutritional approaches and the prognosis.
From the results, we found that compared with parenteral
nutrition, enteral nutrition could improve outcomes by reducing
the incidence of postoperative complications including RTI, WI and
AL. Moreover, it could also signicantly shorten the length of
hospital stay. Meanwhile, with further exploration of nutritional
component, a relevant comparison between immuno-enhanced
enteral nutrition and standard enteral nutrition was carried out,
and the result demonstrated that addition of immune elements
could further improved prognosis. We found that although there
were no differences in incidences of RTI, WI and AL among groups
when assessed separately, apparent declines in the overall in-
cidences of both infectious and non infectious complications were
observed. Similar to the nding of PN and EN, no benet was ob-
tained on the item of mortality in this comparison. However the
effect of hospitalization time remains open to question on account
of the obvious heterogeneity.
From the results above, we had reasons to believe that debates
over application of INE/SEN and PN were no longer necessary in
current clinical practice. Patients who could well tolerate the SEN
should be appropriately supported by SEN, and addition of
immuno-elements could further benet patients. However, in pa-
tients who can not tolerate the enteral nutrition or with contrain-
dications to enteral nutrition, PN is obviously an indispensible
approach which may save patients' life.
Our ndings about enteral nutrition give an additional
conrmation to the recommendation of EN in postoperative pa-
tients, it is also an additional evidence to guidelines for patients
with gastrointestinal carcinoma, accompanied by the similar
ndings of previous studies [40]. Moreover, through systemically
reviewing all the RCTs included in our studies, we found that the
hyperglycemia which characterized PN contributed a lot to
our results, therefore more attention should be paid to the con-
trolling of blood glucose in further clinical practice [3,42,43]. In
addition, meta-analysis by Yan zhang in 2012 indicated that
postoperative infectious complications would be reduced either
with preoperative, postoperative or combined preoperative and
postoperative immunonutrition, whereas the decline of non-
infectious complications was not observed with the use of post-
operative IEN [44], which is not in accordance with our ndings,
we consider this could be related to the shortage of RCTs. Addi-
tionally, meta-analysis produced by Emma O in 2014 reached a
similar conclusions [45,46].
With enlarged RCTs included in our systematic review via
extensive literature retrieval, the statistical power and precision
ratio were also increased, thus more accurate estimates of effects
were generated in our study. However, as with all meta-analysis,
there are still some limitations of present study need to be
acknowledged: Firstly, no assessment was performed in terms of
the impact on immunological function and metabolomics due to
lack of data and sample size [47]. Secondly, some included studies
had a poor quality, which induced a prominent heterogeneity in
terms of certain outcome measurements. Thirdly, our retrieval
process only performed in selective databases (Pubmed, EMBASE,
CNKI), and studies in languages rather than English and Chinese
were ineligible for our criteria, so it is possible that additional
relevant studies may have not been identied.
 X. Yan et al. / Clinical Nutrition xxx (2016) 1e12
5. Conclusion
This systematic review and meta-analysis suggest that although
application of enteral nutrition and immuno-enhanced enteral
nutrition could not decrease the incidence of mortality for patients
with gastrointestinal cancer after surgery, but it could signicantly
decrease the morbidity of life-threatening complications, including
respiratory tract infections, wound infections and anastomotic
leakage. Furthermore, patients received gastrointestinal surgery
benet even more from application of enteral nutrition enhanced
with immune stimulants. So the current study favored the early use
of enteral nutrition in gastrointestinal cancer patients after surgery,
and immuno-enhanced enteral nutrition will be the optimal
management for gastrointestinal patients after surgery, while the
use of parenteral nutrition should be restrict to few patients with
severe intolerance to enteral nutrition. Furthermore, trials with
better methodological quality and larger sample sizes are needed to
assess the effects of perioperative immunonutrition, which will
give more details to roles of different immune stimulations played
in patients' nutritional status, and provide more data and evidence
to reinforce our conclusions.
Funding
This work has not received nancial support.
Authorship
Yan Xia performed the database search, Xu hui, Yang xiao-xi, Xie
Cong-hua, Dai Jing, Fu Zhen-ming, Gao Yan, Chen Lu-lu revised the
manuscript. Finally Yan Xia nished the data analysis with the help
of Lan Tian.
Conict of interest
The authors declare no conict of interest.
Acknowledgment
We would like to appreciate the editors and anyone referees for
considering our studies, also thanks very much for the absolute
support I got from Dr. Zhou and anyone relevant.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.clnu.2016.06.011.
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