Is Gum Chewing Useful for Ileus After Elective Colorectal Surgery? A Systematic Review and Meta-Analysis of Randomized Clinical Trials

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1 J Gastrointest Surg (200) 13: DOI.07/s ORIGINAL ARTICLE Is Gum Chewing Useful for Ileus After Elective Colorectal Surgery? A Systematic Review and Meta-Analysis of Randomized Clinical Trials Wenceslao Vásquez & Adrián V. Hernández & Jose Luis Garcia-Sabrido Received: 20 August 2008 / Accepted: 12 November 2008 / Published online: 3 December 2008 # 2008 The Society for Surgery of the Alimentary Tract Abstract Background The evaluation of the usefulness of gum chewing for postoperative ileus has given inconclusive results. We evaluated the efficacy of gum chewing in the treatment of ileus after elective colorectal surgery. Materials and Methods We performed a meta-analysis of randomized clinical trials comparing the effect of gum chewing+ standard treatment vs. standard treatment on ileus after colorectal surgery. MEDLINE, EMBASE, the Cochrane Controlled Trial Register, and the Cochrane Database of Systematic Reviews were searched until August Primary outcomes were time to first flatus, time to first passage of feces, and length of hospital stay. The mean difference (MD) in hours was calculated with the random effects model to assess the effect of gum chewing on the outcomes. Results Six trials including 4 patients were analyzed. Time to first flatus was significantly reduced with gum chewing+ standard treatment compared to standard treatment alone (MD 14 h, 5% confidence interval [5%CI] 23.5 to 4.6). Time to first passage of feces was significantly reduced (MD 25 h, 5%CI 42.3 to 7.7), but the length of hospital stay was only marginally reduced (MD 26.2 h, 5%CI 57.5 to 5.2) with gum chewing. Conclusion In patients with ileus after colonic surgery, gum chewing in addition to standard treatment significantly reduces the time to first flatus and the time to first passage of feces when compared to standard treatment alone. There is also a trend to reduce the length of hospital stay. Gum chewing should be added to the standard treatment of these patients. Keywords Gum chewing. Ileus. Colorectal surgery. Randomized clinical trials. Meta-analysis Introduction Postoperative ileus is a major health care problem and an important cause of prolonged hospital stay. 1 3 It is known W. Vásquez (*) : J. L. Garcia-Sabrido Department of Surgery, Hospital Universitario Gregorio Marañón, Dr. Esquerdo 46, Madrid, Spain tumi0@yahoo.com A. V. Hernández Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, 500 Euclid Avenue, Cleveland, OH 445, USA that the most prolonged ileus occurs in colonic surgery, especially when this is open. 1 5 Normal bowel motility depends on several physiologic mechanisms, which include the autonomous nervous system, gastrointestinal hormones, and inflammatory mediators. 4,5 The surgical procedure and the use of some drugs may alter some of these mechanisms. 1 5 Multimodal approaches to treat postoperative ileus in colorectal surgery include early feeding, avoidance of unnecessary use of nasogastric tube, thoracic epidural analgesia, unspecific pharmacologic agents such as water-soluble contrast (gastrografin), 6 specific agents such as alvimopan, a selective μ receptor opioid antagonist, and lately, gum chewing. 1 7 Gum chewing is a form of sham feeding which stimulates the cephalic phase of digestion. This produces the release of neurohormonal mediators and the increase of gastrointestinal motility and glandular secretion (salivary, gastric, biliopancreatic). These events may clinically translate into a faster recovery of gas and feces transit, as well as

2 650 J Gastrointest Surg (200) 13: a better tolerance to oral ingestion and a shortening of the length of hospital stay. 1,4,5 Recently, several randomized clinical trials with limited number of patients reported contradictory clinical outcomes of gum chewing in the management of postoperative colonic ileus Lately, Chan and Law 14 and Purkayastha et al. 15 published nearly identical meta-analyses of five of these trials, including 158 patients, and concluded that gum chewing reduces postoperative ileus after colorectal surgery. We performed an updated systematic review and a metaanalysis of randomized clinical trials that investigated the effects of gum chewing on ileus after elective colonic surgery. Materials and Methods Identification of Trials We searched MEDLINE (January 66 through August 1, 2008), EMBASE (74 through August 1, 2008), the Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews (Cochrane Library, Issue 1, 2008) for randomized trials dealing with gum chewing for ileus after colorectal surgery. All searches used the key words colon or colonic surgery, ileus, and gum chewing in conjunction with each of the following words: postoperative, postsurgery, postsurgical, randomised controlled trials, and randomised clinical trials. We reviewed the bibliographies of relevant studies (trials and nontrials) to search for additional eligible randomized trials. We also searched for abstracts of randomized trials from conference proceedings available in major surgery journals in the last years. Only data accessible in peer-reviewed journals were included, and we were not masked with regard to authors or journal. Inclusion and Exclusion Criteria Inclusion criteria were: prospective, parallel group, phase III clinical trials with random assignment to either gum chewing±standard treatment or standard treatment/placebo, patients with postoperative ileus after colonic or colorectal cancer or other type of colorectal disease (e.g., diverticulitis), and patients with elective open or laparoscopyassisted surgery, which included right hemicolectomy, transverse colectomy, left hemicolectomy, sigmoidectomy, anterior resection, and/or abdominoperianal resection. We included main clinical trial reports or trial abstracts with complete information, written in the English language, and with patients older than 15 years. Trials with time to first flatus as primary outcome were included. Other outcomes were time to first passage of feces and/or length of hospital stay. There was no restriction about the number of patients included or the treatment duration. We excluded nonrandomized studies, surgery other than colonic, and other types of treatment or interventions other than gum chewing. Data Extraction One author (WV) screened the titles and abstracts to exclude nonhuman studies, retrieved potentially relevant manuscripts for detailed evaluation, and selected publications compliant with the inclusion and exclusion criteria. Jointly with another author (AVH), both researchers reassessed the inclusion and exclusion criteria. Clinical trial quality was evaluated with respect to four strictly predefined criteria: allocation concealment, blinding, intention to treat analysis, and completeness of follow-up ( Each of these criteria was judged as good or unknown. Differences in judgement of the criteria were resolved by discussion until a consensus was reached. We were not masked to authors or journals, and some bias may have been introduced. If all the necessary data to perform a meta-analysis (e.g., standard deviations of outcomes) were not specified within the articles, authors were contacted. The primary author of the study was contacted and asked for the additional data. We only needed to contact one lead author and he provided the requested information. Statistical Analysis Primary outcomes of the study were time to first flatus, time to first passage of feces and length of hospital stay. The mean difference (MD) and its 5% confidence interval (5%CI) were calculated as a measure of effect size because outcome measurements in all trials were made in the same scale (i.e., hours). MD is the simple mean difference between the mean time to first flatus with gum chewing±standard treatment and the mean time to first flatus with standard treatment/placebo. MD was calculated using the inverse variance method and the random effects model, which was described by DerSimonian and Laird. The data were analyzed using the Cochrane Review Manager 5 software. To test heterogeneity across trials, we used the chi-square test with a p value <0.1 required to determine significant statistical heterogeneity. To test the overall effect of gum chewing on the time of flatus, we used the conventional Z test. To assess the risk of publication bias, we built a funnel plot by graphically showing the relation between effect size and statistical weight for each trial. A symmetric and funnel-shaped plot supports the lack of significant publication bias, whereas a strongly asymmetric plot suggests the underlying presence of publication bias. Publication bias, if not recognized and

3 J Gastrointest Surg (200) 13: acknowledged, can lead to meta-analyses with biased and overly optimistic findings and should thus be actively investigated and appraise. Using time to first flatus as outcome, subgroup analyses per type of colorectal disease (cancer vs. cancer+nonmalignant disease) and type of elective surgery (open vs. laparoscopic) were also performed. Subgroup analyses were exploratory in nature and underpowered to detect true subgroup effects. Results Potentially relevant abstracts retrieved and screened (n=5) Articles retrieved for detailed information (n=) Articles suitable for meta-analysis (n=6) The initial search identified 5 potential studies on gum chewing and colon surgery (Fig. 1). Hand searching of retrieved articles yielded no additional clinical trials. Included Studies Abstracts excluded because of failure to deal with ileus after colon surgery (n=40) Articles excluded because of failure to meet inclusión criteria (n=13) Figure 1 Identification of randomized clinical trials available for analysis. The systematic review revealed six randomized clinical trials (Table 1), 8 13 involving 4 patients, published between 2002 and Four trials showed a significant reduction in the time to first flatus. 8,,,13 In contrast, only two trials showed a significant reduction in the time to first passage of feces, 8, and in the length of hospital stay.,13 Gum was sugar-free in five trials, 8 12 but no reasons were given about this selection. Gum chewing was consistently given three times a day from the first postoperative morning until first passage of flatus or bowel movements starts again. Each chewing lasted between 5 and 60 min.,12 Passage of flatus was used as time to start feeding in all trials. The perioperative standard care of patients included thoracic epidural analgesia, early drinking of water, and early deambulation. Two studies only performed surgery of the left colon and rectum., Asao et al. 8 reported in 2002 a trial evaluating gum chewing in patients with colorectal cancer who underwent laparoscopic surgery. Besides a significant shortening of the time to first flatus by 1 day, they also showed that the time to first passage of feces was significantly reduced by 65 h (74 vs. 13 h). However, they we not able to demonstrate a significant reduction of length of hospital stay. The same group published 4 years later another trial in patients with colorectal cancer who underwent open surgery. The time to first flatus was significantly reduced by h, and the time to first passage of feces was significantly reduced by 52 h (85 vs. 136 h). In 2006, Quah et al. studied patients with cancer of the left colon and rectum. These patients did not benefit from gum chewing: the time to first flatus was about 60 h in both groups and the length of hospital stay was about days in both groups. Interestingly, the group of patients who chewed gum had a better sensation of well-being in comparison to the standard treatment group. Another study dealing with patients who underwent left colonic surgery was published in the same year. However, these inves- Table 1 General Characteristics of Randomized Clinical Trials Included in the Meta-Analysis Author/Year ref. N per arm (gum±standard/ standard placebo) Outcomes Colorectal pathology Type of colorectal surgery Asao/ / Time to flatus, time to feces, Cancer Laparoscopic length of stay Quah/2006 / Time to flatus, time to feces, Cancer Open length of stay Schuster/2006 / Time to flatus, time to first bowel movement, Cancer and nonmalignant Open time to hunger, length of stay conditions Hirayama/2006 / Time to flatus, time to feces Cancer Open Matros/ /21 Time to flatus, time to first bowel movement, Cancer and nonmalignant Open time ready for discharge, length of stay conditions McCormick/ / Time to flatus, time to first bowel Cancer and nonmalignant Open movement, length of stay conditions / Time to flatus, time to first bowel movement, length of stay Cancer and nonmalignant conditions Laparoscopic

4 652 J Gastrointest Surg (200) 13: Hirayama 2006 Matros 2006 Schuster 2006 Gum chewing/standard Standard/Control Difference Difference Weight 14.1% 15.6% 14.6%.4% 13.4% 14.5%.4% [-42., -.45] [-48.58, ] [-21.20,.20] 2.40 [-.40,.20] [-8, 12.08] [-.46, 8.06] [-26.2, -3.31] (5% CI) 132 Heterogeneity: Tau² =.23; Chi² = 15.0, df = 6 (P = 0.01); I² = 62% Test for overall effect: Z = 2.0 (P = 0.004) [-23.45, -4.55] Figure 2 MD and 5%CI of difference in time to first flatus between gum chewing±standard treatment and standard placebo treatment groups. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. McCormick A refers to the open colectomy patients and McCormick B refers to the laparoscopic colectomy patients. tigators also included patients with recidivant diverticulitis. Gum chewing significantly reduced the time to first flatus by 25 h (65 vs. 80 h), the time to first bowel movement by 26 h (63 vs. 8 h), and the length of hospital stay by 60 h (3 vs. 3 h). Matros et al., 12 in 2006, compared three arms in cancer and nonmalignant disease patients: gum chewing+standard treatment, standard treatment, and placebo (acupressure wrist bracelet). There was no significant reduction in the time to first flatus among these three groups (60 vs. 67 vs. h, respectively). The length of hospital stay was not significantly reduced either (5 vs. 2 vs. 8 h, respectively). In a multicenter trial, McCormick et al. 13 compared gum chewing for 15 min QID vs. swallowing of a small amount of water (sips of water) in patients in immediate postoperative care due to elective colorectal surgery. The authors studied patients with both open and laparoscopic surgery. They showed that gum chewing in contrast to control treatment shortened the postoperative ileus period (2.6 vs. 3.3 days, p=0.0047) and hospital stay (4.0 vs. 5.3, p= 0.02) in patients with laparoscopic colectomy, but not in patients with open surgery. Most of the trials were not of good quality. Allocation concealment was good in three trials.,,12 It was not known from three trials whether they performed allocation concealment. 8,,13 Blinding was good in two trials,,12 but the other four did not specify if this was performed or if it was not possible. Intention to treat analysis was used in two trials only.,12 Completeness of follow-up was reported in four trials. 8,12 Meta-Analysis Time to first flatus was significantly reduced with gum chewing and standard treatment compared to the standard treatment alone (MD 14 h, 5%CI 23.5 to 4.6; p= 0.001) (Fig. 2). Six trials were suitable for this analysis (n= 4), and they were heterogeneous with respect to this outcome (p=0.01). The time to first passage of feces was significantly reduced with gum chewing and standard treatment compared to the standard treatment alone (MD 25 h, 5%CI 42.3 to 7.7; p=0.01) (Fig. 3). Four trials were used for this analysis (n= 7), 8,,,13 and they were also heterogeneous with respect to this outcome (p=0.05). The length of hospital stay was reduced with gum chewing and standard treatment compared to the standard treatment alone, although the difference was not significant (MD 26.2 h, 5%CI 57.5 to 5.2; p= 0.1) (Fig. 4) with strong evidence of heterogeneity across trials (p<0.0001). Five trials were used for this analysis (n=2). 8,12,13 Hirayama 2006 Gum chewing/standard Standard/Placebo Difference Difference Weight 13.2% 12.3% 25.2% 27.0%.4% [-2.8, ] [-1.82, -.] [-26.62, 12.] -.80 [-34.03, 0.43] -.80 [-3.6, 6.0] (5% CI) 3 Heterogeneity: Tau² = ; Chi² =.51, df = 4 (P = 0.05); I² = 58% Test for overall effect: Z = 2.83 (P = 0.005) [-42.31, -7.66] Figure 3 MD and 5%CI of difference in time to first passage of feces between gum chewing±standard treatment and standard placebo treatment groups. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial.

5 J Gastrointest Surg (200) 13: Matros 2006 Schuster 2006 Gum chewing/standard Standard/Placebo Difference Difference Weight 6.5%.1%.6%.5%.0% 23.3% -.00 [-12.54, 81.54] [-47.65, 5] 7.20 [-13.01, 27.41] [-64., 1.5] [-1.07, 42.47] [-76.4, ] (5% CI) Heterogeneity: Tau² = 27.02; Chi² = 26.70, df = 5 (P < ); I² = 81% Test for overall effect: Z = 1.64 (P = 0.) -26. [-57.51, 5.] Figure 4 MD and 5%CI of difference in length of hospital stay between gum chewing±standard treatment and standard placebo treatment groups. The size of the data markers (squares) is approximately proportional to the statistical weight of each trial. The funnel plot showed no evidence of publication bias for the analysis of the time to first flatus (Fig. 5). No evidence of publication bias was found for the time to first passage of feces or length of hospital stay. Subgroup Analysis Time to first flatus was consistently reduced across different types of colorectal disease, and this reduction was significantly larger in trials which included cancer patients 8,, than in trials which included cancer and nonmalignant disease patients (p=0.01) (Fig. 6). Time to first flatus was also reduced in patients with both open and laparoscopic surgery, but the effect was only significant in the open surgery subgroup (Fig. 7). However, no differences in gum chewing effects were observed between the open and laparoscopic surgery subgroups (p=0.8). Discussion SE(MD) Figure 5 Funnel plot of the six trials included in the meta-analysis. The standard error of MD of each trial was plotted against the MD for time to first flatus (primary outcome for all trials). No skewed distribution was observed, suggesting no publication bias. MD This meta-analysis demonstrates that, in patients who underwent elective colorectal surgery, gum chewing significantly improved postoperative ileus by reducing the time to first flatus by 14 h, the time to first feces by 25 h, and the length of hospital stay by 26 h in comparison with standard treatment. Reductions of the time to first flatus were also observed in subgroups defined by type of colorectal disease and type of surgery. Postoperative ileus is the delay of the resumption of normal gastrointestinal motility after surgical stress. The clinical expression includes the absence of flatus and feces transit, abdominal distension, nausea, and vomiting. Each segment of the digestive tube resumes its motility after surgery at different times. The small intestine has the shortest time of ileus (between 8 and 12 h). The stomach has a longer ileus (between 1 and 2 days), and the colon has the longest time of ileus (between 3 and 5 days). 20 Postoperative ileus is a consequence of the interaction of several factors. Probably the most important factor is the sympathetic hyperstimulation, which inhibits gastrointestinal motility. Some neurohormones of the enteric nervous system such as substance P, vasoactive intestinal peptide, and nitric oxide can also contribute to the duration of ileus. 5,,20 Moreover, surgical aggression may stimulate the inflammatory cascade with liberation of interleukins (IL-6, IL-1b) and chemokines (MCP-1, ICAM-1), which further inhibit gastrointestinal motility.,20 Some drugs may also contribute to postoperative ileus. For instance, anesthetic drugs such as atropine, halothane, and enflurane may have a transitory effect, while opioid analgesics used during surgery and in the postoperative period may have a more prolonged effect After surgery the myoelectric activity of the gastrointestinal tract is disorganized and this is translated into lack of propulsion. The electrical activity of the colon is the last to recover. Colon motility is diminished or absent until approximately the third postoperative day. At the fourth day, the colonic electrical activity consists of disorganized bursts, and later, a coordinated motor response is able to propagate. This allows the passage of flatus, the first indicator of the ileus resolution process. The passage of feces occurs within 1 or 2 days after the first flatus, and it does not necessarily mean the final resolution of the ileus.

6 654 J Gastrointest Surg (200) 13: Cancer trials Hirayama 2006 Subtotal (5% CI) Gum chewing/standard Standard/Placebo Difference Difference Weight Heterogeneity: Tau² = ; Chi² = 7.01, df = 2 (P = 0.03); I² = 71% Test for overall effect: Z = 2.77 (P = 0.006) % 15.6% 14.5% 44.2% [-42., -.45] [-48.58, ] [-.46, 8.06] -.4 [-3., -6.] Cancer + Non-malignant trials Matros 2006 Schuster 2006 Subtotal (5% CI) Heterogeneity: Tau² = 0.00; Chi² = 2.40, df = 3 (P = 0.4); I² = 0% Test for overall effect: Z = 2. (P = 0.03) %.4% 13.4%.4% 55.8% [-21.20,.20] 2.40 [-.40,.20] [-8, 12.08] [-26.2, -3.31] [-., -1.00] (5% CI) 132 Heterogeneity: Tau² =.23; Chi² = 15.0, df = 6 (P = 0.01); I² = 62% Test for overall effect: Z = 2.0 (P = 0.004) Test for subgroup differences: Chi² = 6.48, df = 1 (P = 0.01), I² = 84.6% [-23.45, -4.55] Figure 6 Subgroup analysis of the difference in time to first flatus by type of colorectal disease. The passage of feces depends on the type of surgical procedure, the condition and content of the intestine prior to surgery, dietetic factors, and the usual intestinal frequency of the patient. 5,20,21 Shortening of hospital stay by almost 26 h with gum chewing in comparison to standard care is translated into better well-being of patients, early return to the preoperative functional status, and especially, reduction of hospital costs. 26 To our knowledge, there are no specific studies evaluating the reduction of costs by using gum chewing in patients undergoing colorectal surgery. Additional advantages of gum chewing include stimulation of appetite and sensation of well-being during the postoperative period. Two decades ago, it was described that replication of the cephalic phase of digestion through sham feeding stimulated the electrical, motor, and secretory activities of the gastrointestinal tract through neurohormonal and vagal pathways. In humans, sham feeding produces a significant increase of gastrin and neurotensin release and a partial alteration of the myoelectrical pattern of the gastrointestinal tract during fasting, also known as interdigestive migrating motor complex. Gum chewing is a type of sham feeding and was lately proposed as an activator of these various mechanisms. 27,28 An open colorectal surgery has a more prolonged postoperative ileus than a laparoscopic-assisted colorectal surgery, probably due to a longer visceral manipulation and environmental exposure and higher use of analgesic drugs to control postoperative pain We found that gum chewing especially benefited patients who underwent open surgery. Gum chewing can also extend the benefits of the Gum chewing/standard Standard/Placebo Difference Difference Open surgery trials Hirayama 2006 Matros 2006 Schuster 2006 Subtotal (5% CI) Weight 15.6% 14.6%.4% 14.5%.4%.5% [-48.58, ] [-21.20,.20] 2.40 [-.40,.20] [-.46, 8.06] [-26.2, -3.31] -13. [-25.06, -1.28] Heterogeneity: Tau² = 1.34; Chi² = 12.52, df = 4 (P = 0.01); I² = 68% Test for overall effect: Z = 2. (P = 0.03) Laparoscopic surgery trials Subtotal (5% CI) Heterogeneity: Tau² = 3.07; Chi² = 3.32, df = 1 (P = 0.07); I² = 70% Test for overall effect: Z = 1.46 (P = 0.14) % 13.4% 27.5% [-42., -.45] [-8, 12.08] [-36.5, 5.38] (5% CI) 132 Heterogeneity: Tau² =.23; Chi² = 15.0, df = 6 (P = 0.01); I² = 62% Test for overall effect: Z = 2.0 (P = 0.004) Test for subgroup differences: Chi² = 0.05, df = 1 (P = 0.82), I² = 0% [-23.45, -4.55] Figure 7 Subgroup analysis of the difference in time to first flatus by type of surgery.

7 J Gastrointest Surg (200) 13: minimally invasive laparoscopic surgery. 8 Moreover, the larger benefit of gum chewing in the subgroup that included patients with colorectal cancer alone can be important, given that these patients usually have a moderate to bad nutritional state and a shorter hospitalization can avoid inhospital complications. 32,33 Our meta-analysis is different than two recently published meta-analyses 14,15 in several ways. Our meta-analysis included six trials with 4 patients, 50% more patients than the other studies (five trials, n=158). We did not restrict the language of the studies; one of the other studies focused on English language studies. 14 The period of our systematic review was until August 2008, longer than the other periods (January and July ). Finally, we focused on randomized controlled trials, not on nonrandomized comparative studies. 14 Multimodal fast-track perioperative care programs in colorectal surgery are oriented to a fast recovery of patients, as well as to a shortened hospital stay. These programs include: adequate patient information about specific procedures, no bowel preparation, no sedative premedication, intake of small quantities of carbohydrate-enriched liquids within 2 h before surgery, epidural thoracic analgesia and short half-life anesthetics, restriction of intravenous perioperative fluids, use of minimally invasive surgery, use of nonopioid systemic analgesic drugs, avoidance of the routine use of drainages or nasogastric tube, early withdrawal of urinary probe, early intake of small quantities of liquid, and early deambulation. All these measures have demonstrated favorable results such as shorter hospitalization, better patient comfort, reduction of in-hospital mortality, and reduction of postoperative costs. 1 3,34 Gum chewing should become part of the multimodal fast-track perioperative care program in colorectal surgery. It is not known whether gum chewing also has a favorable effect in postoperative ileus in abdominopelvic surgery, such as transperitoneal aortic surgery, cesarean section, hysterectomy with abdominal access, 36 and radical cystectomy. 37,38 Our study has some limitations. First, the total number of patients (n=4) included in the meta-analysis was relatively small. However, this meta-analysis is the largest available meta-analysis that adds about 0 patients more than recently published meta-analyses. 14,15 We performed a formal systematic review of all clinical trials published until August 1, 2008 and our analysis did not show evidence of publication bias. Second, we did not have access to original source data (i.e., individual patient data) for any of these clinical trials. Thus, we based the analysis on available data from published studies or directly from authors. Third, clinical trials included in the meta-analysis can be regarded as poorly controlled as far as use of opiates and other analgesics, postoperative feeding, epidural analgesia, fasttrack, or other standard and nonstandard protocols. However, those controls reflected what authors considered their current clinical practice. We expect that a tightly controlled randomized trial will show a smaller clinical effect. Fourth, a meta-analysis may be considered less convincing than a large prospective trial designed to assess the outcome of interest. However, given the lack of an appropriately sized clinical trial evaluating gum chewing for postoperative ileus in colorectal surgery, a well-designed and well-performed meta-analysis is the best option available to answer this clinical question. Conclusion Gum chewing is a cheap, physiological, and secure intervention that significantly improves ileus after elective colorectal surgery. This intervention should be included in the multimodal approach of postoperative colorectal ileus. A tightly controlled, multicenter randomized clinical trial with a substantial number of patients is necessary to confirm the efficacy of gum chewing in patients with elective colorectal surgery. Acknowledgements The authors thank Prof. Edward E. Whang for providing original data from his study. References 1. Wind J, Hofland J, Preckel B et al. Perioperative strategy in colonic surgery, laparoscopy and/or fast track multimodal management versus standard care (LAFA trial). 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