Use of Chewing Gum in Reducing Postoperative Ileus After Elective Colorectal Resection: A Systematic Review

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1 Use of Chewing Gum in Reducing Postoperative Ileus After Elective Colorectal Resection: A Systematic Review Miranda K. Y. Chan, M.B.B.S., F.R.A.C.S., 1 Wai Lun Law, M.S., F.R.C.S.(Edinb.) 2 1 Department of Surgery, Caritas Medical Centre, Hong Kong SAR, China 2 Department of Surgery, Queen Mary Hospital, University of Hong Kong Medical Centre, Hong Kong SAR, China Presented at the 20th World Congress of International Society for Digestive Surgery, Rome, Italy, November 29 to December 2, Correspondence to: Miranda K. Y. Chan, M.B.B.S., F.R.A.C.S., Department of Surgery, Caritas Medical Centre, 111, Wing Hong Street, Shum Shui Po, Kowloon, Hong Kong SAR, China, mirchan@hotmail.com Dis Colon Rectum 2007; 50: DOI: /s * The American Society of Colon and Rectal Surgeons Published online: 21 August 2007 PURPOSE: Published studies comparing the addition of chewing gum to standardized postoperative care to shorten postoperative ileus showed controversial results. This study was designed to conduct a systematic review of all relevant trials on chewing gum to reduce postoperative ileus after colorectal resection. METHODS: All published trials that compared the additional use of gum chewing with standard postoperative management were identified from Ovid MEDLINE, EMBASE, CINAHL, and All Evidence-Based Medicine Reviews between January 1991 and January The clinical outcomes were extracted and meta-analysis was performed by Forest plot review. RESULTS: Five randomized, controlled trials with 158 (94 males) patients with mean age of 61.9 years were included. Seventy-eight patients received an addition of gum chewing and 80 had standard postoperative care for colorectal resection. Operating time (P=0.78) and blood loss (P=0.48) were similar. All patients tolerated the gum without any side-effects. With combined standard postoperative care and gum chewing, the patients passed flatus 24.3 percent earlier (weighted mean difference, j20.8 hours; P=0.0006) and had bowel movement 32.7 percent earlier (weighted mean difference, j33.3 hours; P=0.0002). They were discharged 17.6 percent earlier than those having ordinary postoperative treatment (weighted mean difference, j2.4 days; P< ). The gum-chewing group was associated with similar overall postoperative complication rate (odds ratio, 0.45; P=0.05) with individual complication showing a trend favoring gum chewing, although they were not of statistical significance. Readmission (odds ratio, 0.36; P=0.24) and reoperation rates (odds ratio, 1.36; P=0.83) of the two groups were similar. CONCLUSIONS: The use of gum chewing in the postoperative period is a safe method to stimulate bowel motility and reduce ileus after colorectal surgery. [Key words: Chewing gum; Postoperative ileus; Motility; Colorectal resection] P ostoperative ileus occurs after all abdominal operations and often is one of the limiting factors that prevents early hospital discharge. 1 The duration of ileus is related to the anatomic location of the operation and the time for restoration of motility is longest after colorectal surgery. 2 4 This delay in recovery from surgery results in prolonged hospitalization, impairs nutritional intake, and tremendously increases health care costs. The annual cost of postoperative ileus in the United States alone was estimated to be $7.5 billion per year, not including the expense of loss of work. 5,6 The etiology of postoperative ileus is multifactorial. Many strategies have been investigated in efforts to alleviate postoperative ileus and its clinical consequences. Laparoscopic colorectal resection has been reported to be associated with a shorter 2149

2 2150 CHAN AND LAW Dis Colon Rectum, December 2007 duration of ileus. 7,8 Many pharmaceutical agents have been used to combat against ileus but only limited clinical efficacy was obtained Early water intake and postoperative feeding have been used to stimulate the gastrointestinal tract However, a high rate of intolerance and significant potential complications were reported. 15 Sham feeding was demonstrated to be one of the methods to increase bowel motility. 18,19 It caused both vagal stimulation and hormonal release, either one or both could modulate the bowel motility. Gum chewing, as an alternative to sham feeding, 20 provides the benefits of gastrointestinal stimulation without the complications associated with feeding. The use of gum chewing to reduce ileus had been studied in a few randomized, controlled trials only and the results were conflicting. The present study was designed to conduct a systematic review of all available evidence on chewing gum to reduce postoperative ileus after colorectal resection. METHODS Search Strategy for Identification of Studies All the original clinical studies comparing the standard postoperative management against an addition of gum chewing after colorectal resection were considered. A literature search through the Ovid MEDLINE, EMBASE, CINAHL, and All EBM Reviews (Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, and Database of Abstracts of Reviews of Effects) and their corresponding electronic-links to the related articles was performed up to January The search items used were as follows: gum*, gum chewing, chewing gum, sham*, feeding, ileus, colectomy, prospective. A manual review of the reference lists of all retrieved articles, reviews, and abstracts from meetings was performed to identify additional relevant trials for potential inclusion. These were limited to published English literature and human studies. Inclusion and Exclusion Criteria Type of studies. Studies were included if they were prospective, clinical trials comparing the additional use of gum chewing and the standard postoperative management after colorectal resection during the period from January 1991 to January If the trial did not provide information on the inclusion and exclusion criteria, patient selection and allocation, study design, outcome, and measurement methods, it would be excluded. All case series, case reports, and studies reported in abstract form without presenting the outcome variables were not included for analysis. Type of participants. The target population was patients who underwent colorectal resection laparoscopic or open surgery for benign or malignant colorectal diseases. Patients with metastatic disease, history of inflammatory bowel disease, previous abdominal radiation, allergy to mint, dentures, concomitant small bowel resection, more than one concomitant bowel anastomosis, defunctioning ileostomy, or placement of nasogastric tube beyond first day postoperative morning, were ineligible. Those patients who required elective postoperative mechanical ventilation or planned intensive care also were excluded from the study. Type of interventions. The intervention under investigation was gum chewing during the postoperative period after colorectal resection. The patient in the gum-chewing group was given gum each day. The quantity, frequency, and duration of the chewing of gum should be clearly stated. The intervention for comparison was standardized postoperative care management, including the analgesics regimen, guidelines on removal of nasogastric tubes, physiotherapy, mobilization and ambulation plan, and postoperative feeding protocol. Placebo might be used. Outcomes of interest. The outcome measures were extracted from all relevant articles on the efficacy and safety of the intervention. The operative data were recorded, including the requirement for extensive adhesiolysis, duration of operation, intraoperative complications, and blood loss. The efficacy end points included the time to first feeling of hunger, time to pass flatus, time to first bowel opening, duration of hospital stay, rate of readmission, and reoperation. The overall complication rate, the individual postoperative complications (leakage, intraabdominal abscess, hemorrhage, wound dehiscence, wound infection, ileus, and medical complications), and the mortality rate were used to assess the safety of the intervention. Other data on the inclusion/exclusion criteria, nature of studies, method of randomization or stratification, blinding of assessment, operative data, and perioperative care also were noted. Articles were included if they provided information on at least one outcome parameter as listed. Data from duplicate studies was analyzed once only, as appropriately, from the most updated one.

3 Vol. 50, No. 12 CHEWING GUM REDUCING POSTOPERATIVE ILEUS 2151 Review Methodology The quality of the randomized, clinical trials and comparative studies were evaluated with Jadad score and Newcastle Ottawa assessment scale respectively. All eligible studies were methodologically evaluated and appraised, and assessed according to the inclusion and exclusion criteria by two independent reviewers. The adequacy of concealment of patient_s allocation, blinding of assessment, compliance to the management protocol, and withdrawal from the trial, also were assessed. The results and data extraction was undertaken according to standardized proforma. All these were processed by two independent reviewers and agreement on whether to include the study or discrepancies on data extraction was resolved by discussion. For particular outcome measures that were evaluated, if the data were not specifically reported, they were regarded as missing and no assumption was made from the missing data. Statistical Analysis In analyzing the results of the clinical trials, the dichotomous data were tested by computing the odds of the treatment group reporting an outcome variable relative to that of the control group (odds ratio, OR) by Mantel-Haenszel method with correction. The continuous variable presented in means and standard deviations were used to derive a weighted mean difference (WMD). The effect measures were pooled with random-effects model and heterogeneity of results was tested by evaluating the interstudy variability. P<0.05 was considered to indicate statistical significance. The meta-analysis was represented by Forest plot with the 95 percent confidence interval (CI) represented by a horizontal line and the confidence interval for totals represented by a diamond (0). Statistical analysis was performed with the software RevMan 4.2 from Cochrane Collaboration \. 21 The reports of metaanalysis followed the Quality of Reporting of Metaanalysis (QUOROM) guideline. The presence of publication bias was assessed by Funnel plot analysis. RESULTS Until January 2007, there were five published, randomized, controlled clinical trials that compared the additional use of gum chewing and the standard postoperative management after colorectal resection. No other relevant, nonrandomized, comparative studies on gum chewing were identified. Quality of Trials Three of five studies had Jadad score of three or more classifying as good randomized, clinical trials Most of the funnel plot analysis with regard to the outcomes variables did not show good symmetrical distribution. All five studies had documented the inclusion criteria, whereas exclusion criteria were stated in only two of them. 24,25 Two trials failed to provide any information on the randomization process. 22,26 The other trials used computer-generated code in sealed envelops, 24 computer-generated random numbers, 25 or sequential randomized card pull design. 23 No trial used central randomization scheme for the allocation of patients. Blinding of assessors to the intervention and the outcome was documented to be enforced in three trials One study also mentioned blinding of surgeons to the arms of the intervention. 25 In one of the trials, there were three arms of regimens comparing standardized care, gum chewing, and placebo. 25 Matros et al. 25 used the acupressure wrist bracelet as the placebo so that the patients were unaware of which regimen constituted treatment or placebo. Characteristics of Trials The five trials included a total of 158 patients, of whom 78 had an adjunct of gum chewing in standardized care regimen and 80 received standardized postoperative management only. The sample size of the trials varied from 19 to ,25 The demographic characteristics were clearly listed in all trials with a slight male preponderance (male/female ratio=94/64) and the mean age was similar (gumchewing group 62.4 vs. control group 62.5). The baseline characteristics and patient demographics were comparable. No drop-outs were reported in any of the five trials All trials investigated the outcomes after elective colorectal resection. One study 22 was about laparoscopic surgery and the others were about open procedures. Three trials 22,24,26 assessed the outcomes of surgery for colorectal cancer, whereas the other two studies 23,25 looked into both benign and malignant colorectal diseases. The protocol for gum chewing was clearly stated in all trials All used commercially available sugarless gum with the ingredients clearly stated in two of them. 25,26 The frequency of gum chewing was three times per day and was the same in all trials. The patients started chewing gum on

4 2152 CHAN AND LAW Dis Colon Rectum, December 2007 the first postoperative day until first passage of flatus 22,25,26 or bowel motion. 23,24 All patients tolerated gum chewing well without any side-effects. In one of the studies, 24 three patients did not chew gum during the postoperative period because two of them had reoperation within first postoperative 24 hours and one patient had poor-fitting dentures. The preoperative care was documented in one trial and consisted of bowel preparation, preoperative dietary preparation, prophylactic antibiotics, and preventive measures for thromboembolism. 24 Standardized postoperative care program included feeding regimen, postoperative analgesia, chest physiotherapy, and mobilization plan. Three trials had a clear description of the protocol for resumption of oral feeding. 22,24,25 The patients in all trials received epidural anesthesia during the early postoperative days. Concomitant use of subcutaneous local anesthetics and patient-controlled analgesia with morphine, 23 or addition of paracetamol, opioid, or nonsteroidal anti-inflammatory drugs after cessation of epidural analgesia were used in two of the trials. 23,24 Three studies stated the postoperative physiotherapy and mobilization plan for the patients after colorectal surgery Efficacy The operative data were similar (operating time: OR, 2.27, P=0.78; intraoperative blood loss: OR, 10.45, P=0.48). Three trials mentioned the details of previous surgery and one of them 23 reported on the extent of adhesiolysis during the operation. These were comparable between the gum chewing and the control groups. As shown by the five trials, the addition of gum chewing to standardized postoperative care was associated with significantly earlier return of bowel function than simple postoperative management (Figs. 1 and 2; P<0.05) The patients passed flatus 24.3 percent earlier (WMD, j20.8 hours; P=0.0006) and had bowel movement 32.7 percent earlier (WMD, j33.3 hours; P=0.0002). Of the four clinical trials reporting on hospital stay, three trials had data appropriate for a metaanalysis (Fig. 3). The hospital stay was significantly shorter with the adjunct gum chewing compared with standardized postoperative care (WMD, j2.4 days; P< ). The patients were discharged 17.6 percent earlier than those having conventional postoperative treatment. The test for heterogeneity showed no significant difference (P=0.73), although the study by Asao et al. 22 reported particularly long length of stay in both gum-chewing (mean 13.5 days) and control (14.5 days) groups. Reanalysis with exclusion of Asao_s study did not change the improvement in hospital stay by gum chewing (test of overall effect, P< ; test of heterogeneity, P=0.66). Safety All five clinical trials reported the incidences of postoperative complications The overall complication rates did not differ significantly between the gum-chewing and control groups, but there was a trend favoring the addition of gum chewing to the standardized postoperative care (16.7 percent for gumchewing group vs percent for control group; OR, 0.45; P=0.05; Fig. 4). The incidence of postoperative ileus was reduced but not to a significant extent (OR, 0.36; P=0.24). 22,23,25 The severity of the ileus was not adequately elaborated in the studies. The meta-analysis on other individual complications did favor gum chewing but the difference was again not significant (Table 1). Four and three of the studies reported the readmission and reoperation rate, respectively, for patients receiving chewing gum and standardized postoperative care after colorectal resection. There was no significant difference between the two groups Figure 1. Time to pass flatus (hr). Additional use of chewing gum vs. standardized postoperative management. SD = standard deviation; WMD = weighted mean difference; CI = confidence interval.

5 Vol. 50, No. 12 CHEWING GUM REDUCING POSTOPERATIVE ILEUS 2153 Figure 2. Time to first opening of bowel (hr). Additional use of chewing gum vs. standardized postoperative management. SD = standard deviation; WMD = weighted mean difference; CI = confidence interval. in the requirement for readmission (OR, 0.36; P=0.24; Fig. 5) or reoperation (OR, 1.36; P=0.83; Fig. 6) secondary to complications. One death from postoperative hemorrhage was reported in the gumchewing group in the study by Quah et al. 24 However, the meta-analysis showed that the mortality rates in the gum chewing and the control group were similar (OR, 3.16; P=0.49). DISCUSSION This is a systematic review of five randomized, controlled, clinical trials for 158 patients comparing additional use of gum chewing and standardized postoperative care regimen in the reduction of postoperative ileus after colorectal surgery. This meta-analysis showed that gum chewing, together with standardized postoperative care, after elective colorectal resection had significant advantages in stimulating bowel function and enhancing recovery during the postoperative period. All studies had a small sample size with less than 50 patients in each trial; however, more than half of the studies scored as good quality. The trials had adequate descriptions of inclusion and exclusion criteria, methods of randomization, definition of outcome parameters studied, and statistics used. The patient selection and accrual were not sufficiently described in some studies, but the types of operation, the standardized postoperative feeding regimen, epidural anesthesia protocol, and mobilization protocol were well described. These studies had associated methodologic limitations. There was absence of blinding to the patient and inadequate blinding of the surgeons. The effect of bias might have to be taken into consideration. Blinding of the patients is desirable but difficult to achieve and is not practicable. Most trials did not incorporate the placebo arm, whereas Matros et al. 25 used wrist bracelet as the placebo. Thus, the outcomes could be assessed in a blinded manner and the patient would be unaware of which was the active therapy. A more objective assessment could be obtained by documenting the postoperative events by an independent assessor. This was particularly important for the end point assessment, such as passage of flatus and discharge time. There was heterogeneity among the studies, of which some studied open colectomy, whereas one trial was for laparoscopic procedure. The magnitude of ileus might be greater after laparotomy and the improvement could be easier to measure. It is difficult to postulate that there is a fundamental difference in ileus after laparoscopic operation than in open surgery to explain the positive finding after laparoscopy. Moreover, the hospital stay reported by Asao et al. 22 was markedly longer than other studies 7 about laparoscopic procedures. The author attributed it to the private health Figure 3. Hospital stay (days). Additional use of chewing gum vs. standardized postoperative management. SD = standard deviation; WMD = weighted mean difference; CI = confidence interval.

6 2154 CHAN AND LAW Dis Colon Rectum, December 2007 Figure 4. Overall complication rate. Additional use of chewing gum vs. standardized postoperative management. n/n = number of events relative to total number of patients in chewing gum or no chewing gum groups; OR = odds ratio; CI = confidence interval. insurance not covering the expenditure for hospitalization of less than seven days in the Japanese medical system. 27 This interstudy variation also could relate to the differences in surgical techniques and expertise as far as laparoscopic resection was concerned. However, reanalysis still favored shortening of hospital stay by chewing gum with exclusion of the Japanese trial and statistical tests confirmed no significantly difference in heterogeneity. While interpreting the results of the meta-analysis, it was important to consider issues, such as quality of included studies, heterogeneity of results of trials, and existence of publication bias. In our review, three of five studies were of good quality and the heterogeneity of studies was insignificant. However, funnel plot analysis showed that there was concern about publication and related bias. Inclusion of a small number of primary studies in our review also tended to produce funnel plot asymmetry because a small-sized study would have wider distribution of results than studies of larger size as a result of higher degree of random variation. Therefore, more large-scale, randomized, clinical trials of good quality was warranted. As inferred from the meta-analysis, gum chewing with standardized postoperative care after elective colorectal resection was beneficial in enhancing recovery from ileus in postoperative period. The most significant advantages of gum chewing were stimulating bowel function and earlier discharge from hospital, without compromising safety, requirement for readmission, and reoperation. Gum chewing was associated with a lower incidence of postoperative complications. The trend of less postoperative morbidities also was in favor of use of Table 1. Comparison of Morbidities with the Additional Use of Chewing Gum and Standardized Postoperative Management Additional Use of Chewing Gum Standardized Postoperative Management 95 Percent Confidence Interval No. of No. of No. of No. of Odds Complications Events Patients Events Patients Ratio P Value Overall complications Hemorrhage Anastomotic Not Not Not leak estimable estimable estimable Intra-abdominal abscess Ileus Wound dehiscence Wound infection Medical complication

7 Vol. 50, No. 12 CHEWING GUM REDUCING POSTOPERATIVE ILEUS 2155 Figure 5. Readmission rate. Additional use of chewing gum vs. standardized postoperative management. n/n = number of events relative to total number of patients in chewing gum or no chewing gum groups; OR = odds ratio; CI = confidence interval. chewing gum with standardized postoperative management, although the difference was not statistically significant. None of these clinical trials has reported any fatal complications. The mortality in the gumchewing group was similar to that of the control group. The data on the efficacy and safety profile of gum chewing were homogeneous, further enhancing the reliability of the analysis. However, the number of patients in all studies was small and statistical significance was marginal (P=0.05). More randomized, controlled trials with a large sample size are required to comment on the reduction of postoperative complications. Postoperative ileus is self-limiting and recovery begins in the small bowel, then the stomach, and finally the colon. Factors accounting for the ileus are multifactorial. 28,29 It can be from physical factors, such as manipulation of bowel 30 or peritoneal irritation, 31 during the operation, neural factors by postoperative sympathetic hyperactivity, and humoral factors, including increased circulating catecholamines, vasoactive intestinal peptides, substance P 32,33 and suppressed gastrin, neurotensin, and pancreatic polypeptide. 34 Various studies have been conducted to investigate the approach to reduce postoperative ileus. The most recently studied pharmacologic agent, Alvimopan, was a peripheral active selective opioid antagonist acting predominantly on mu-receptor. It blocked the opioid-induced inhibitory effects of the gastrointestinal transit without affecting the centrally mediated analgesic effects of opioid. 35 Time to bowel recovery and hospital discharge was significantly reduced in patients treated with Alvimopan. 36 Data from other studies demonstrated that early oral feeding after elective colorectal surgery was safe and well tolerated Fast-track rehabilitation program reduced the time to defecation, hospital stay, and morbidity However, there was controversy on its use in elderly and high-risk patients after surgery. 41 One might formulate that gum chewing could be used as a transition protocol in the rehabilitation program. With effective epidural anesthesia, early enteral feeding and mobilization reduce the duration of ileus and shorten the postoperative stay at the same time preserving the cardiopulmonary function. Gum chewing provided comparable result of enhanced recovery from postoperative ileus as early feeding did. The mechanism is believed to act on cephalic-vagal stimulation of digestion and on the increase in promotility neural and humoral factors 44 Figure 6. Reoperation rate. Additional use of chewing gum vs. standardized postoperative management. n/n = number of events relative to total number of patients in chewing gum or no chewing gum groups; OR = odds ratio; CI = confidence interval.

8 2156 CHAN AND LAW Dis Colon Rectum, December 2007 that act on different parts of the gastrointestinal tract. 18,19,41,45 Chewing mimics food intake and stimulates the motility of human duodenum, 18 stomach, 19 and rectum. 46 It stimulates the secretion of gastrointestinal hormones, saliva, and pancreatic juices. 19 Gum also gives the patient a sense of well being. 24 The maneuver of chewing, sweet taste, and smell of gum satisfied the patient_s appetite. The gum is inexpensive and well tolerated. Chewing gum in the postoperative period is an easy and safe method to hasten the time to bowel motility and time to resume oral feeding, thus leading to earlier hospital discharge. The follow-up duration of all five trials were short and covered the immediate postoperative period only The duration of ileus might be different for right- or left-sided colectomy. 47 This was not clearly stated in the trials. The sample size in individual studies was small. More studies with larger sample size, longer follow-up duration, and more emphasis on psychologic and economic aspects would more clearly define applicability of gum chewing. Although not statistically significant, there was a tendency toward less complicating postoperative course. This needs to be verified in larger scale, well-designed studies. CONCLUSIONS Postoperative gum chewing is a simple and safe method for stimulating bowel motility and reducing ileus after colorectal surgery. REFERENCES 1. Livingston EH, Passaro EP. Postoperative ileus. Dig Dis Sci 1990;35: Shibata Y, Toyoda S, Nimura Y, Miyati M. Patterns of intestinal motility recovery during the early stage following abdominal surgery: clinical and manometric study. World J Surg 1997;21: Graber JN, Schulte WJ, Condon RE, Cowles VE. Relationship of duration of postoperative ileus to extent and site of operative dissection. Surgery 1982;92: Petros JG, Realica R, Ahmad S, Rimm EB, Robillard RJ. Patient-controlled analgesia and prolonged ileus after uncomplicated colectomy. Am J Surg 1995;170: Kehlet H. Review of postoperative ileus. Am J Surg 2001;182(5A Suppl):3S 10S. 6. Delaney CP. Clinical perspective on postoperative ileus and the effect of opiates. Neurogastroenterol Motil 2004;169(Suppl 2): Tjandra JJ, Chan MK. Systemic review on short-term outcomes of laparoscopic resection for colon and recto-sigmoid cancer. Colorectal Dis 2006;8: Chen HH, Wexner SD, Iroatulam AJ, et al. Laparoscopic colectomy compares favorably with colectomy by laparotomy for reduction of postoperative ileus. Dis Colon Rectum 2000;43: Ferraz AA, Cowles VE, Condon RE, et al. Nonopiod analgesics shorten the duration of postoperative ileus. Am Surg 1995;61: Cheape JD, Wexner SD, James K, Jagelman DG. Does metoclopramide reduce the length of ileus after colorectal surgery? A prospective randomized trial. Dis Colon Rectum 1991;34: Brown TA, McDonald J, Williard W. A prospective, randomized double-blinded, placebo-controlled trial of cisapride after colorectal surgery. Am J Surg 1999;177: Tollesson PO, Cassuto J, Rimback G, Faxen A, Bergman L, Mattsson E. Treatment of postoperative paralytic ileus with cisapride. Scand J Gastroenterol 1991;26: Smith AJ, Nissan A, Lanouette NM, et al. Prokinetic effect of erythromycin after colorectal surgery: randomized, placebo-controlled, double-blind study. Dis Colon Rectum 2000;43: Bonacini M, Quiason S, Reynolds M, Gaddis M, Pemberton B, Smith O. Effect of intravenous erythromycin on postoperative ileus. Am J Gastroenterol 1993;88: Stewart BT, Woods RJ, Collopy BT, et al. Early feeding after elective open colorectal resections: a prospective randomized trial. ANZ J Surg 1998;68: Choi J, O_Connell TX. Safe and effective early postoperative feeding and hospital discharge after open colon resection. Am Surg 1996;62: Carr CS, Ling KD, Boulos P, Singer M. Randomized trial of safety and efficacy of immediate postoperative enteral feeding in patients undergoing gastrointestinal resection. BMJ 1996;312: Soffer EE, Adrian TE. Effect of meal composition and sham feeding on duodenojejunal motility in humans. Dig Dis Sci 1992;37: Stern RM, Crawford HE, Stewart WR, et al. Sham feeding: cephalic-vagal influences on gastric myoelectric activity. Dig Dis Sci 1989;34: Anonymous. By gum, it might be good for you. Recent studies show that gum chewing may speed recovery from bowel surgery. Harv Health Lett 2006;31: Review Manager. RevMan User Guideline Version 4.2 for Windows. Oxford, England: The Cochrane Collaboration, 2002.

9 Vol. 50, No. 12 CHEWING GUM REDUCING POSTOPERATIVE ILEUS Asao T, Kuwano H, Nakamura J, Morinaga N, Hirayama I, Ide M. Gum chewing enhances early recovery from postoperative ileus after laparoscopic colectomy. J Am Coll Surg 2002;195: Schuster R, Grewal N, Greaney GC, Waxman K. Gum chewing reduces ileus after elective open sigmoid colectomy. Arch Surg 2006;141: Quah HM, Samad A, Neathey AJ, Hay DJ, Maw A. Does gum chewing reduce postoperative ileus following open colectomy for left-sided colon and rectal cancer? A prospective randomized controlled trial. Colorect Dis 2006;8: Matros E, Rocha F, Zinner M, et al. Does gum chewing ameliorate postoperative ileus? Results of a prospective, randomized, placebo-controlled trial. J Am Coll Surg 2006;202: Hirayama I, Suzuki M, Ide M, Asao T, Kuwano H. Gumchewing stimulates bowel motility after surgery for colorectal cancer. Hepato-Gastroenterology 2006; 53: Miedema BW. Postoperative ileus after laparoscopic colectomy [letter]. J Am Coll Surg 2003;195: Holte K, Kehlet H. Postoperative ileus: a preventable event. Br J Surg 2000;87: Luckey A, Livingston E, Tache Y. Mechanisms and treatment of postoperative ileus. Arch Surg 2003; 138: Kalff JC, Schraut WH, Simoons RL, Baucer AJ. Surgical manipulation of the gut elicits an intestinal muscularis inflammatory response resulting in postsurgical ileus. Ann Surg 1998;228: Mamel JJ. Gastric emptying disorders. In: Nord HJ, Brady PG, eds. Critical care gastroenterology. New York: Churchill Livingstone, 1982: Deloof S, Croix D, Tramu G. The role of vasoactive intestinal polypeptide in the inhibition of antral and pyloric electrical activity in rabbits. J Auton Nerv Syst 1988;22: Hasler WL. Pharmacotherapy for intestinal motor and sensory disorders. Gastroenterol Clin North Am 2003; 32: Resnick J, Greenwald DA, Brandt LJ. Delayed gastric emptying and postoperative ileus after nongastric abdominal surgery: part 1. Am J Gastroenterol 1997; 92: Delaney CP, Weese JL, Hyman NH, et al. Phase III trial of Alviompan, a novel, peripherally, acting, mu opioid antagonist, for postoperative ileus after major abdominal surgery. Dis Colon Rectum 2004;48: Viscusi ER, Goldstein S, Witkowski T, et al. Alvimopan, a peripherally acting mu-opioid receptor antagonist, compared with placebo in postoperative ileus after major abdominal surgery. Surg Endosc 2006; 20: Hartsell PA, Frazee RC, Harrison JB, Smith RW. Early postoperative feeding after elective colorectal surgery. Arch Surg 1997;132: Di Fronzo LA, Cymerman J, O_Connell TX. Factors affecting early postoperative feeding following elective open colon resection. Arch Surg 1999;134: Bardram L, Funch-Jensen PM, Jensen P, et al. Recovery after laparoscopic colonic surgery with epidural analgesia, and early oral nutrition and mobilization. Lancet 1995;345: Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth 1997;78: Basse L, Hjort Jakobsen D, Billesbolle P, et al. A clinical pathway to accelerate recovery after colonic resection. Ann Surg 2000;232: Basse L, Raskov HH, Hjort Jakobsen D, et al. Accelerated postoperative recovery programme after colonic resection improves physical performance, pulmonary function and body composition. Br J Surg 2002;89: Basse L, Thorbol JE, Lossl K, Kehlet H. Colonic surgery with accelerated rehabilitation or conventional care. Dis Colon Rectum 2004;47: Kellow JE, Delvaux M, Azpiroz F, Camilleri M, Quigley EM, Thompson DG. Principles of applied neurogastroenterology: physiology/motility-sensation. Gut 1999;45(Suppl 2):II Miedema BW. Methods for decreasing postoperative gut dysmotility. Lancet Oncol 2003;4: Jepsen JM, Skoubo K, Elsborg L. Rectosigmoid motility response to sham feeding in irritable bowel syndrome. Evidence of a cephalic phase. Scand J Gastroenterol 1989;24: Roberts JP, Benson MJ, Rogers J, Deeks JJ, Williams NS. Characterization of distal colonic motility in early postoperative period and effect of colonic anastomosis. Dig Dis Sci 1994;39:

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