Incidence of Prolonged Postoperative Ileus after Colorectal Surgery: a systematic review

and meta-analysis

A.M. Wolthuis1, MD, G. Bislenghi1, MD, S. Fieuws2, PhD, A. de Buck van Overstraeten1,

MD, G. Boeckxstaens3, MD, PhD, A. D’Hoore1, MD, PhD

1Department of Abdominal Surgery, University Hospital Leuven, Belgium

2KU Leuven- University of Leuven & Universiteit Hasselt, Interuniversity Center for

Biostatistics and Statistical Bioinformatics, Leuven, Belgium

3KU Leuven- Translational Research Center for GastroIntestinal Disorders (TARGID),

University Hospital Leuven, Belgium

Corresponding author:

A.M. Wolthuis, MD

University Hospital Gasthuisberg Leuven, Department of Abdominal Surgery

Herestraat 49

3000 Leuven

Belgium

Tel. +32 16 34 42 65

Fax. +32 16 34 48 32

E-mail: albert.wolthuis@uzleuven.be

There are no conflicts of interest.

Word count: 1922

Abstract

Aim:

Prolonged postoperative ileus (PPOI) after colorectal surgery remains a leading cause for

delayed postoperative recovery and prolonged hospital stay. Its exact incidence is unknown.

The aim of this systematic review is to investigate the incidence of PPOI in relation to the

definition used.

Method:

Medline, Embase, and the Cochrane Database of Systematic Reviews (up to July 2014) were

searched. Two authors independently reviewed citations using predefined inclusion and

exclusion criteria.

Results:

The search strategy yielded 3,233 citations; 54 were eligible, comprising 18,983 patients.

Twenty-six studies were prospective (17 of these being randomized controlled trials (RCTs))

and 28 were retrospective. Meta-analysis revealed an incidence of PPOI of 10.3 per cent (95

per cent confidence interval (CI) 8.4 to 12.5) and 10.2 per cent (CI: 5.6 to 17.8) for non-RCTs

and RCTs, respectively. Significant heterogeneity was observed for both non-RCTs and for

RCTs. Used definition of PPOI, type of surgery and access (laparoscopic, open), and duration

of surgery lead to significant variability of reported PPOI between studies. A lower PPOI

incidence occurs after laparoscopic colonic resection.

Conclusion:

The reported incidence of PPOI after colorectal resection is about 10%, with a large

variability between studies. A uniform definition of PPOI is needed to allow meaningful inter-

study comparisons and to evaluate strategies to prevent PPOI.

What does this study add to the literature?

This is the first systematic review and meta-analysis on incidence of prolonged postoperative

ileus (PPOI) after colorectal surgery. It shows that PPOI incidence depends on the definition

used. Heterogeneity between studies is explained by the differences in definition of PPOI. It is

a useful study to allow future inter-study comparisons.

Introduction

Prolonged postoperative ileus (PPOI) after colorectal surgery remains a leading cause of

delayed postoperative recovery, failure of enhanced recovery protocols, and prolonged

hospital stay. It is characterized by the presence of nausea and vomiting, inability to tolerate

oral diet, abdominal distension and delayed passage of flatus and stool. Insertion of a

nasogastric tube (NG tube) may be necessary. PPOI hampers patients’ recovery, increases

postoperative morbidity and therefore leads to longer length of hospital stay[1-4]. There is an

ongoing debate on how to define PPOI and as a consequence on its exact occurrence.

Incidences ranging from 3% to 32% have been reported and a variety of definitions are in

use[5-8]. These definitions either relate to the interval between time of surgery and time of

bowel function recovery or relate to the duration patients have an NG tube to avoid vomiting.

These issues have to be carefully considered when assessing and comparing future studies.

Although previous attempts have been made to define POI, this review aims to reflect on the

need for clarity of the definition of prolonged POI in relation to its incidence after colorectal

surgery. Defining PPOI and assessing its incidence is crucial prior to evaluating strategies to

prevent and treat PPOI or reduce the severity of PPOI. Assuming this, we hypothesized that

incidence of PPOI after colorectal surgery depends on the definition used. The aim of this

systematic review and meta-analysis was to investigate this hypothesis.

Method

Search strategy

A systematic search was performed in the electronic databases of Medline (through PubMed),

EMBASE, and the Cochrane Library up to July 2014. Boolean AND/OR operators were used

to combine keywords and MeSH search terms. The following search criteria were used:

keywords (colorectal OR surgery) AND [(postoperative OR postsurgical) AND (ileus OR

prolonged ileus)] and MeSH terms [(ileus) OR (intestinal  pseudo-obstruction) AND

colorectal surgery] mapping to preferred terminology and allowing explosion search.

Reference lists of retrieved articles were hand-searched for additional publications. There was

no language restriction. The systematic review was conducted in compliance with PRISMA

guidelines[9].

Study selection

There were no limits to the type of studies: randomized controlled trials, systematic reviews

and meta-analyses, controlled clinical trials, comparative, prospective, and retrospective

studies were considered. Inclusion criteria included all publications concerning postoperative

ileus as a primary or secondary endpoint following colorectal surgery. Papers relating to PPOI

as one of several outcomes when examining unrelated interventions were also included. Only

studies on prolonged postoperative ileus were included. The main prerequisite for inclusion

was that the definition used for PPOI was clearly mentioned in the study. This definition

could either be based on clinical or radiological findings at a certain point of time

postoperatively, or on therapeutic measures, such as reinsertion of the NG tube. If a preset

definition of PPOI was not reported, the study was excluded. Other exclusion criteria were

studies concerning only bowel ‘motility’ (no link to PPOI), and ileus occurring after surgery

other than colorectal surgery. Conference abstracts and case reports were also excluded. Two

independent reviewers selected the studies to be included in the meta-analysis. Of the initially

identified publications, titles and abstracts were screened to exclude non-related articles. Of

the remaining publications, the full text was read to determine whether they were eligible for

inclusion. Discordance in study inclusion between the two reviewers was resolved through

discussion and consultation with an expert specialist.

Data extraction and quality assessment

Relevant data of the included studies were extracted with a standard fill-out form and entered

into an Excel-database. Recorded variables included definition of PPOI referring to clinical,

radiological, therapeutic criteria used to assess the onset of PPOI, time point in days at which

this definition became applicable, incidence of PPOI, numbers of patients enrolled, type of

surgery, type of access (laparoscopic, open), diagnosis, type of study, year of publication,

gender, age, blood loss, body mass index, and duration of surgery. The quality of included

studies was assessed with the Jadad-scale for randomized controlled trials (RCTs) and with

the Newcastle-Ottawa Score (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp)

for non-RCTs [10-12]. The Jadad scale is a scale-scoring tool that was developed in 1996 and

it is composed of five total points: two points that are related to randomization, two points that

are related to blinding and one point that is related to dropouts. The Newcastle-Ottawa Score

evaluates patient selection, comparability of study groups and outcome assessment. A

maximum of 9 stars can be obtained.

Statistical analysis

A random-effects meta-analysis using the approach of DerSimonian and Laird was used to

combine the estimates of PPOI incidence from various studies (non-RCTs and RCTs)[13].

The analysis was performed on log-transformed odds. Observed ileus rate per center was

plotted versus the number of patients in funnel plots with 99% prediction limits around

overall ileus incidence to illustrate whether the observed between-study variability exceeded

the pure sampling variability. These limits indicated the range wherein 99% of the observed

ileus incidences were expected, if the studies had been drawn from a population with the same

ileus incidence. The larger the study was, the smaller the range. Prediction limits were

constructed based on the binomial distribution with a continuity correction[14]. Heterogeneity

was quantified by the I² statistic, which is the percentage of total variation in study estimates

that is due to heterogeneity[15] and tested by Cochran’s X²-test. Random-effects meta-

regression was used to evaluate if PPOI incidence depended on study and/or patient

characteristics, or put differently, if the observed heterogeneity could be (partially) explained

by these characteristics[16]. This was done for each characteristic separately. Tukey-Kramer

adjustments for multiple testing were used for pairwise comparisons in the meta-regression.

The number of estimates used in the meta-regression varied, depending on (1) availability of

the information in the original article and (2) whether or not the characteristic could vary

within a study. The percentage variability explained by each characteristic was reported,

based on the decrease of between-estimate variance parameters. Note that in settings where

the reported number of patients with ileus equals zero, a value 0.5 was added to numerator

and denominator to obtain values for the estimate (the log-transformed odds) and its variance.

P-values smaller than 0.05 were considered significant. No corrections for multiple testing

were performed. Therefore, a single p-value should be interpreted carefully. All analyses were

performed using SAS software, version 9.2 of the SAS System for Windows.

Results

The predefined search strategy returned 3,233 non-duplicated references (Fig. 1). Publication

titles and abstracts were screened and 117 publications were retrieved for full-text review.

Subsequently, 63 articles were excluded. In total, 54 publications were included with a total

number of 18,983 patients. Seventeen studies were RCTs[17-33], 4 were case-controlled

studies[34-37], 9 were prospective studies[5, 38-45], and 24 were retrospective studies[46-

69]. The methodological quality of the included studies is shown in Table 1 and 2.

In studies with multiple arms, all reported incidences and study characteristics were included

in the meta-analysis. Five different definitions were used for PPOI. According to these

different definitions, different incidences of PPOI were observed (Table 3). Overall, PPOI

was observed in 10.4% of patients in non-RCTs and in 9.1% in RCTs. Many studies fall

outside the 99% prediction limits, visualizing this presence of between-study variability (Fig.

2 and 3). The random-effects estimate for the incidence of PPOI was 10.3% (95% CI: 8.4%-

12.5%) and 10.2% (95% CI: 5.6%-17.8%) for non-RCTs and RCTs, respectively. Significant

heterogeneity was observed for non-RCTs (I2=93%, Q=499, df=36, P<0.0001) and for RCTs

(I2=96%, Q=395, df=16, P<0.0001), respectively. Criteria for reinsertion of the NG tube were

reported in 4 out of 20 non-RCTs and in 5 out of 13 RCTs (Table 4). Vomiting was the most

important clinical sign to reinsert an NG tube, and some studies also included frequency

(number of episodes) and/or amount (in cc) to determine whether or not reinsertion was

necessary.

Non-RCTs

Access used to perform colorectal resection explains the variability between studies for 21%

(P=0.005). Incidence of PPOI after laparoscopic procedures is lower compared to that after

open procedures or after a combination of laparoscopic and open colorectal resections: 7.4%

versus 12.4% (P=0.065) versus 17.7% (P=0.007), respectively. Type of study, definition of

PPOI, diagnosis, age, gender, BMI, duration of surgery, and blood loss did not significantly

explain variability between reported PPOI estimates.

RCTs

A large part (71%) of heterogeneity in PPOI estimates obtained from RCTs is explained by

the difference in the definition of PPOI used. As a result, analyzing 13 RCTs reporting the

same definition of ‘reinsertion of the NG tube’, evidence for between-study variability

disappears (I2=13%, Q=13.7, df=12, P=0.32). Moreover, type of surgery (rectum, segmental

colectomy, or both) and mean duration of surgery also significantly explained variability

between estimates of PPOI incidence. Incidence of PPOI was 6.6% (95% CI: 3.9-10.9%) for

segmental colectomy, 14.2% (95% CI: 7.2-26%) for procedures involving colon or rectum

resections, and 30.9% (95% CI: 12.7-57.8%) for rectal resections (39% explained

heterogeneity, P=0.008). A lower incidence of PPOI after laparoscopic resections was

observed. Incidence of PPOI was 6.4% (95% CI: 3.5-11.5%) after laparoscopic resection, and

10% (95% CI: 6.2-15.8%) after open colorectal resection. Duration of surgery significantly

affected incidence of PPOI (48% explained heterogeneity, P=0.004). Longer operating time

was associated with a higher PPOI-rate (the odds ratio for a difference of 10 minutes equals

2.19). Diagnosis, age, gender, BMI, and blood loss were not significantly related with PPOI.

Discussion

The principal finding of this meta-analysis is that the overall incidence of PPOI after

colorectal surgery is around 10%. This incidence varies and is evidently related to the

definition used. This is an important finding in assessing and comparing future study

outcomes. Moreover, when therapeutic or prophylactic measures are developed, the

magnitude of this postoperative problem should be known. It is necessary to be aware of the

incidence of postoperative complications in order to appreciate the need and result of new

strategies to prevent or shorten PPOI. Standardized and universally accepted endpoints should

be used for evaluating therapeutic interventions[70].

A predefined time interval of bowel function absence or so-called gut dysmotility

differentiates normal postoperative recovery and PPOI. However, the exact point in time

when normal POI changes to PPOI is still subject of discussion. Therefore, it remains difficult

to exactly define and assess PPOI after colorectal surgery due to the lack of an objective

endpoint. In literature, absence of bowel function on postoperative day 3 to 7 has been

proposed to define the interval between normal and PPOI[71-74]. Absence of bowel function

usually involves one or more of the following criteria: nausea or vomiting, inability to tolerate

oral diet over the last 24h, absence of flatus over the last 24h, abdominal distention, and

radiologic confirmation[73]. In 2006, different types of POI (primary, secondary, recurrent,

prolonged) were defined through consensus, and PPOI was defined as absence of bowel

function after the 3rd postoperative day for laparoscopic surgery and after the 5th postoperative

day for open abdominal surgery, respectively[74]. This review showed the use of 5 different

definitions to define PPOI. In 4 of these, a preset interval between surgery and recovery of

bowel function was used. The high statistical heterogeneity between studies with regard to

PPOI incidence could be the result of non-uniform definitions used to detect PPOI. Indeed,

we found that in a subset of studies where the same definition was used, heterogeneity

disappeared. Therefore, the authors propose ‘reinsertion of the NG tube’ as the most relevant

definition of PPOI after colorectal surgery, because this is a straightforward therapeutic act

postoperatively, and can be recorded in prospective trials. Moreover, in the era of fast-track

surgery, omission of an NG tube after colorectal resection is considered standard of care. It

has been shown that routine postoperative nasogastric placement is unnecessary and has been

associated with a higher risk of pneumonia, fever, and delayed return of gastrointestinal

function[75, 76].

Although the present study shows important insight into the relation between definition of

PPOI and postoperative incidence after colorectal surgery, there also are some weaknesses to

be addressed. The major limitation of this meta-analysis is the limited availability of high-

quality prospective studies: 28 out of 54 studies included were retrospective studies. As such,

the quality of the data, especially on the occurrence of PPOI as a postoperative complication,

cannot be assured.

The above-mentioned data should lead to prospective studies evaluating risk factors for PPOI

and strategies for prevention. This frequent postoperative problem results in considerable

patient suffering, and leads to a significant financial burden for the healthcare system[77].

References

1. Delaney CP, Senagore AJ, Viscusi ER et al. Postoperative upper and lower

gastrointestinal recovery and gastrointestinal morbidity in patients undergoing bowel

resection: pooled analysis of placebo data from 3 randomized controlled trials. Am J

Surg 2006; 191: 315-9.

2. Luckey A, Livingston E, Tache Y. Mechanisms and treatment of postoperative ileus.

Arch Surg 2003; 138: 206-14.

3. Mattei P, Rombeau JL. Review of the pathophysiology and management of

postoperative ileus. World J Surg 2006; 30: 1382-91.

4. Baig MK, Wexner SD. Postoperative ileus: a review. Dis Colon Rectum 2004; 47:

516-26.

5. Franko J, O'Connell BG, Mehall JR et al. The influence of prior abdominal operations

on conversion and complication rates in laparoscopic colorectal surgery. JSLS 2006;

10: 169-75.

6. Petros JG, Realica R, Ahmad S, Rimm EB, Robillard RJ. Patient-controlled analgesia

and prolonged ileus after uncomplicated colectomy. Am J Surg 1995; 170: 371-4.

7. Pikarsky AJ, Saida Y, Yamaguchi T et al. Is obesity a high-risk factor for laparoscopic

colorectal surgery? Surg Endosc 2002; 16: 855-8.

8. Raue W, Haase O, Junghans T, Scharfenberg M, Muller JM, Schwenk W. "Fast-track"

multimodal rehabilitation program improves outcome after laparoscopic

sigmoidectomy: A controlled prospective evaluation. Surg Endosc 2004; 18: 1463-8.

9. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for

systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6:

e1000097.

10. Jadad AR, Moore RA, Carroll D et al. Assessing the quality of reports of randomized

clinical trials: is blinding necessary? Controlled Clin Trials 1996; 17: 1-12.

11. Wells GA SB, O'Connell D, Peterson J, Welch V, Losos M. The Newcastle-Ottawa

Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses.

Assessed on March 3rd 2015.

12. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the

quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 2010; 25: 603-5.

13. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clin Ttrials 1986;

7: 177-88.

14. Spiegelhalter DJ. Funnel plots for comparing institutional performance. Statistics in

Med 2005; 24: 1185-202.

15. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in

Med 2002; 21: 1539-58.

16. van Houwelingen HC, Arends LR, Stijnen T. Advanced methods in meta-analysis:

multivariate approach and meta-regression. Statistics in Med 2002; 21: 589-624.

17. Boelens PG, Heesakkers FFBM, Luyer MDP et al. Reduction of postoperative ileus

by early enteral nutrition in patients undergoing major rectal surgery: Prospective,

randomized, controlled trial. Ann Surg 2014; 259: 649-55.

18. Deng G, Wong WD, Guillem J et al. A phase II, randomized, controlled trial of

acupuncture for reduction of postcolectomy ileus. Ann Surg Oncol 2013; 20: 1164-9.

19. El Nakeeb A, Fikry A, El Metwally T et al. Early oral feeding in patients undergoing

elective colonic anastomosis. Int J Surg 2009; 7: 206-9.

20. Meng ZQ, Garcia MK, Chiang JS et al. Electro-acupuncture to prevent prolonged

postoperative ileus: A randomized clinical trial. World J Gastroenterol 2010; 16: 104-

11.

21. Ng SS, Leung WW, Wong CY, Lee JF. Electroacupuncture for postoperative ileus

after laparoscopic colorectal surgery: An interim analysis of a randomized sham-

controlled study. Gastroenterol 2010; 138: S869.

22. Ortiz H, Armendariz P, Yarnoz C. Is early postoperative feeding feasible in elective

colon and rectal surgery? Int J Colorectal Dis 1996; 11: 119-21.

23. Schwenk W, Bohm B, Haase O, Junghans T, Muller JM. Laparoscopic versus

conventional colorectal resection: A prospective randomised study of postoperative

ileus and early postoperative feeding. Langenbeck's Arch Surg 1998; 383: 49-55.

24. 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: 333-7.

25. Stewart BT, Woods RJ, Collopy BT, Fink RJ, Mackay JR, Keck JO. Early feeding

after elective open colorectal resections: A prospective randomized trial. ANZ J Surg

1998; 68: 125-8.

26. Taqi A, Hong X, Mistraletti G, Stein B, Charlebois P, Carli F. Thoracic epidural

analgesia facilitates the restoration of bowel function and dietary intake in patients

undergoing laparoscopic colon resection using a traditional, nonaccelerated,

perioperative care program. Surg Endosc 2007; 21: 247-52.

27. Vlug MS, Wind J, Hollmann MW et al. Laparoscopy in combination with fast track

multimodal management is the best perioperative strategy in patients undergoing

colonic surgery: A randomized clinical trial (LAFA-study). Ann Surg 2011; 254: 868-

75.

28. Zaghiyan K, Felder S, Ovsepyan G et al. A prospective randomized controlled trial of

sugared chewing gum on gastrointestinal recovery after major colorectal surgery in

patients managed with early enteral feeding. Dis Colon Rectum 2013; 56: 328-35.

29. Kang SB, Park JW, Jeong SY et al. Open versus laparoscopic surgery for mid or low

rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): Short-term

outcomes of an open-label randomised controlled trial. Lancet Oncol 2010; 11: 637-

45.

30. Hewett PJ, Allardyce RA, Bagshaw PF et al. Short-term outcomes of the Australasian

randomized clinical study comparing laparoscopic and conventional open surgical

treatments for colon cancer: the ALCCaS trial. Ann Surg 2008; 248: 728-38.

31. Ortiz H, Armendariz P, Yarnoz C. Early postoperative feeding after elective colorectal

surgery is not a benefit unique to laparoscopy-assisted procedures. Int J Colorectal

Dis 1996; 11: 246-9.

32. Targarona EM, Gracia E, Garriga J et al. Prospective randomized trial comparing

conventional laparoscopic colectomy with hand-assisted laparoscopic colectomy:

applicability, immediate clinical outcome, inflammatory response, and cost. Surg

Endosc 2002; 16: 234-9.

33. Veldkamp R, Kuhry E, Hop WC et al. Laparoscopic surgery versus open surgery for

colon cancer: short-term outcomes of a randomised trial. Lancet Oncol 2005; 6: 477-

84.

34. Kim HJ, Choi GS, Park JS, Park SY. Comparison of intracorporeal single-stapled and

double-stapled anastomosis in laparoscopic low anterior resection for rectal cancer: A

case-control study. Int J Colorectal Dis 2013; 28: 149-56.

35. Shabbir A, Roslani AC, Wong KS, Tsang CBS, Wong HB, Cheong WK. Is

laparoscopic colectomy as cost beneficial as open colectomy? ANZ J Surg 2009; 79:

265-70.

36. Zargar-Shoshtari K, Connolly AB, Israel LH, Hill AG. Fast-track surgery may reduce

complications following major colonic surgery. Dis Colon Rectum 2008; 51: 1633-40.

37. Senagore AJ, Madbouly KM, Fazio VW, Duepree HJ, Brady KM, Delaney CP.

Advantages of laparoscopic colectomy in older patients. Arch Surg 2003; 138: 252-6.

38. Abodeely A, Schechter S, Klipfel A, Vrees M, Lagares-Garcia J. Does Alvimopan

enhance return of bowel function in laparoscopic right colectomy? Am Surg 2011; 77:

1460-2.

39. Chen HH, Wexner SD, Iroatulam AJN et al. Laparoscopic colectomy compares

favorably with colectomy by laparotomy for reduction of postoperative ileus. Dis

Colon Rectum 2000; 43: 61-5.

40. Delaney CP, Marcello PW, Sonoda T, Wise P, Bauer J, Techner L. Gastrointestinal

recovery after laparoscopic colectomy: Results of a prospective, observational,

multicenter study. Surg Endosc 2010; 24: 653-61.

41. Joo JS, Amarnath L, Wexner SD. Is laparoscopic resection of colorectal polyps

beneficial? Surg Endosc 1998; 12: 1341-4.

42. Kahokehr A, Sammour T, Zargar-Shoshtari K, Srinivasa S, Hill AG. Recovery After

Open and Laparoscopic Right Hemicolectomy: A Comparison. J Surg Research 2010;

162: 11-6.

43. Raue W, Paolucci V, Asperger W, Albrecht R, Buchler MW, Schwenk W.

Laparoscopic sigmoid resection for diverticular disease has no advantages over open

approach: Midterm results of a randomized controlled trial. Langenbeck's Arch Surg

2011; 396: 973-80.

44. Zargar-Shoshtari K, Paddison JS, Booth RJ, Hill AG. A Prospective Study on the

Influence of a Fast-Track Program on Postoperative Fatigue and Functional Recovery

After Major Colonic Surgery. J Surg Research 2009; 154: 330-5.

45. Mohn AC, Bernardshaw SV, Ristesund SM, Hovde Hansen PE, Rokke O. Enhanced

recovery after colorectal surgery. Results from a prospective observational two-centre

study. Scand J Surg 2009; 98: 155-9.

46. Asgeirsson T, El-Badawi K, Mahmood A et al. Post-operative ileus; It costs more than

you expect. Dis Colon Rectum 2009; 52: 806.

47. Chapuis PH, Bokey L, Keshava A et al. Risk factors for prolonged ileus after resection

of colorectal cancer: An observational study of 2400 consecutive patients. Ann Surg

2013; 257: 909-15.

48. Franklin Jr ME, Dorman JP, Jacobs M, Plasencia G. Is laparoscopic surgery applicable

to complicated colonic diverticular disease? Surg Endosc 1997; 11: 1021-5.

49. Harbaugh CM, Al-Holou SN, Bander TS et al. A statewide, community-based

assessment of alvimopane's effect on surgical outcomes. Ann Surg 2013; 257: 427-32.

50. Hellan M, Anderson C, Pigazzi A. Extracorporeal versus intracorporeal anastomosis

for laparoscopic right hemicolectomy. JSLS 2009; 13: 312-7.

51. Itawi EA, Savoie LM, Hanna AJ, Apostolides GY. Alvimopan addition to a standard

perioperative recovery pathway. JSLS 2011; 15: 492-8.

52. Kolozsvari NO, Capretti G, Kaneva P et al. Impact of an enhanced recovery program

on short-term outcomes after scheduled laparoscopic colon resection. Surg Endosc

2013; 27: 133-8.

53. Kronberg U, Kiran RP, Soliman MSM et al. A characterization of factors determining

postoperative ileus after laparoscopic colectomy enables the generation of a novel

predictive score. Ann Surg 2011; 253: 78-81.

54. Kuruba R, Fayard N, Snyder D. Epidural analgesia and laparoscopic technique do not

reduce incidence of prolonged ileus in elective colon resections. Am J Surg 2012; 204:

613-8.

55. Longo WE, Virgo KS, Johnson FE et al. Outcome after proctectomy for rectal cancer

in Department of Veterans Affairs Hospitals: A report from the National Surgical

Quality Improvement Program. Ann Surg 1998; 228: 64-70.

56. Manceau G, d'Annunzio E, Karoui M et al. Elective subtotal colectomy with

ileosigmoid anastomosis for colon cancer preserves bowel function and quality of life.

Colorectal Dis 2013; 15: 1078-85.

57. Millan M, Biondo S, Fraccalvieri D, Frago R, Golda T, Kreisler E. Risk factors for

prolonged postoperative ileus after colorectal cancer surgery. World J Surg 2012; 36:

179-85.

58. Park JS, Kang SB, Kim DW, Lee KH, Kim YH. Laparoscopic versus open resection

without splenic flexure mobilization for the treatment of rectum and sigmoid cancer:

A study from a single institution that selectively used splenic flexure mobilization.

Surg Endosc 2009; 19: 62-8.

59. Pelloni A. Colorectal surgery in patients over 80 years old. Hepatogastroenterol 2012;

59: 120-3.

60. Poon JTC, Fan JKM, Lo OSH, Law WL. Enhanced recovery program in laparoscopic

colectomy for cancer. Int J Colorectal Dis 2011; 26: 71-7.

61. Reshef A, Gurland B, Zutshi M, Kiran RP, Hull T. Colectomy with ileorectal

anastomosis has a worse 30-day outcome when performed for colonic inertia than for

a neoplastic indication. Colorectal Dis 2013; 15: 481-6.

62. Tong DK, Law WL. Laparoscopic versus open right hemicolectomy for carcinoma of

the colon. JSLS 2007; 11: 76-80.

63. Vather R, Bissett IP. Risk factors for the development of prolonged post-operative

ileus following elective colorectal surgery. Int J Colorectal Dis 2013; 28: 1385-91.

64. Watanabe K, Funayama Y, Fukushima K, Shibata C, Takahashi KI, Sasaki I. Hand-

assisted laparoscopic vs. open subtotal colectomy for severe ulcerative colitis. Dis

Colon Rectum 2009; 52: 640-5.

65. Zmora O, Hashavia E, Munz Y et al. Laparoscopic colectomy is associated with

decreased postoperative gastrointestinal dysfunction. Surg Endosc 2009; 23: 87-9.

66. Zmora O, Lebedyev A, Hoffman A et al. Laparoscopic colectomy without mechanical

bowel preparation. Int J Colorectal Dis 2006; 21: 683-7.

67. Gu J, Stocchi L, Remzi FH, Kiran RP. Total abdominal colectomy for severe

ulcerative colitis: does the laparoscopic approach really have benefit? Surg Endosc

2014; 28: 617-25.

68. Reshef A, Alves-Ferreira P, Zutshi M, Hull T, Gurland B. Colectomy for slow transit

constipation: effective for patients with coexistent obstructed defecation. Int J

Colorectal Dis 2013; 28: 841-7.

69. Singh A, Muthukumarasamy G, Pawa N, Riaz AA, Hendricks JB, Motson RW.

Laparoscopic colorectal cancer surgery in obese patients. Colorectal Dis 2011; 13:

878-83.

70. Vather R, O'Grady G, Bissett IP, Dinning PG. Postoperative ileus: mechanisms and

future directions for research. Clin Exp Pharmacol Physiol 2014; 41: 358-70.

71. Artinyan A, Nunoo-Mensah JW, Balasubramaniam S et al. Prolonged postoperative

ileus - Definition, risk factors, and predictors after surgery. World J Surg 2008; 32:

1495-500.

72. Livingston EH, Passaro EP, Jr. Postoperative ileus. Dig Dis Sci 1990; 35: 121-32.

73. Vather R, Trivedi S, Bissett I. Defining postoperative ileus: results of a systematic

review and global survey. J Gastrointest Surg 2013; 17: 962-72.

74. Delaney CP, Kehlet H, Senagore A et al. Clinical Consensus Update® in General

Surgery, postoperative ileus: profiles, risk factors, and definitions-a framework for

optimizing surgical outcomes in patients undergoing major abdominal and colorectal

surgery. Clinical Consensus Update in General Surgery [Consensus statement]. 2006.

75. Cheatham ML, Chapman WC, Key SP, Sawyers JL. A meta-analysis of selective

versus routine nasogastric decompression after elective laparotomy. Ann Surg 1995;

221: 469-76; discussion 76-8.

76. Nelson R, Edwards S, Tse B. Prophylactic nasogastric decompression after abdominal

surgery. Cochrane Database Syst Rev 2007: CD004929.

77. Goldstein JL, Matuszewski KA, Delaney CP et al. Inpatient economic burden of

postoperative ileus associated with abdominal surgery in the United States. P and T

2007; 32: 82-90.

Legends to the figures

Figure 1. Prisma flow diagram of the systematic literature review.

Figure 2. Funnel plot of non-RCTs. The horizontal line refers to the crude incidence of PPOI

(10.4%), and the dashed lines refer to the 99% prediction limits.

Figure 3. Funnel plot of RCTs. The horizontal line refers to the crude incidence of PPOI

(9.1%), and the dashed lines refer to the 99% prediction limits.

Table 1. Methodological quality of included non-RCTs according to the Newcastle-Ottawa

Scale.

Author, year Type of study

Number of study arms

Definition of PPOI NOS

Franklin, 1997 Retrospective 2 Absence of bowel function on POD 7 4Joo, 1998 Prospective 2 Reinsertion of NG tube 5Longo, 1998 Retrospective 1 Absence of bowel function on POD 5 5Chen, 2000 Prospective 2 Reinsertion of NG tube 7Senagore, 2003 Case-control 4 Absence of bowel function on POD 5 6Franko, 2006 Prospective 1 Absence of bowel function on POD 3 5Zmora, 2006 Retrospective 2 Reinsertion of NG tube 7Tong, 2007 Retrospective 2 Reinsertion of NG tube 7Zargar-Shoshtari, 2008 Case-control 2 Reinsertion of NG tube 7Asgeirsson, 2009 Retrospective 3 Reinsertion of NG tube 8Hellan, 2009 Retrospective 2 Reinsertion of NG tube 6Mohn, 2009 Prospective 2 Reinsertion of NG tube 7Park, 2009 Retrospective 2 Reinsertion of NG tube 4Shabbir, 2009 Case-control 2 Absence of bowel function on POD 3 5Watanabe, 2009 Retrospective 2 Reinsertion of NG tube 4Zargar-Shoshtari, 2009 Prospective 2 Reinsertion of NG tube 6Zmora, 2009 Retrospective 2 Reinsertion of NG tube 5Delaney, 2010 Prospective 1 Absence of bowel function on POD 5 5Kahokehr, 2010 Prospective 2 Reinsertion of NG tube 6Singh, 2010 Retrospective 1 Reinsertion of NG tube 5Abodeely, 2011 Prospective 2 Reinsertion of NG tube 8Itawi, 2011 Retrospective 2 Absence of bowel function on POD 3 7Kronberg, 2011 Retrospective 1 Absence of bowel function on POD 5

OR Reinsertion of NG tube7

Poon, 2011 Retrospective 2 Absence of bowel function on POD 5 7Raue, 2011 Prospective 2 Reinsertion of NG tube 6Kuruba, 2012 Retrospective 3 Absence of bowel function on POD 5

OR Reinsertion of NG tube8

Millan, 2012 Retrospective 1 Absence of bowel function on POD 5 9Pelloni, 2012 Retrospective 1 Reinsertion of NG tube 6Chapuis, 2013 Retrospective 1 Absence of bowel function on POD 3 9Harbaugh, 2013 Retrospective 3 Absence of bowel function on POD 7 4Kim, 2013 Case-control 2 Reinsertion of NG tube 8

Kolozsvari, 2013 Retrospective 2 Reinsertion of NG tube 7Manceau, 2013 Retrospective 1 Reinsertion of NG tube 4Reshef, 2013 Retrospective 6 Absence of bowel function on POD 5 4Reshef, 2013 Retrospective 2 Absence of bowel function on POD 5 5Vather, 2013 Retrospective 1 Absence of bowel function on POD 3 8Gu, 2014 Retrospective 2 Absence of bowel function on POD 5

OR Reinsertion of NG tube4

NG; Nasogastric, NOS; Newcastle-Ottawa Score, POD; Postoperative day, PPOI; Prolonged postoperative ileus

Table 2. Methodological quality of included RCTs according to the Jadad scale.

Author, year Number of study arms

Definition of PPOI Jadad scale quality assessment

Ortiz, 1996 2 Reinsertion of NG tube 3Ortiz, 1996 2 Reinsertion of NG tube 2Schwenk, 1998 2 Reinsertion of NG tube 1Stewart, 1998 2 Reinsertion of NG tube 3Smith, 2000 2 Reinsertion of NG tube 1Targarona, 2002 2 Reinsertion of NG tube 3Veldkamp, 2005 2 Absence of bowel function on POD 3 3Taqi, 2007 2 Reinsertion of NG tube 1Hewett, 2008 2 Reinsertion of NG tube 3El Nakeeb, 2009 2 Reinsertion of NG tube 1Kang, 2010 2 Reinsertion of NG tube 3Meng, 2010 2 Absence of bowel function on POD 5 2NG, 2010 3 Reinsertion of NG tube 4Vlug, 2011 4 Absence of bowel function on POD 5 3Deng, 2013 2 Reinsertion of NG tube 5Zaghiyan, 2013 2 Reinsertion of NG tube 3Boelens, 2014 2 Absence of bowel function on POD 5

OR Reinsertion of NG tube3

NG; Nasogastric, POD; Postoperative day, POI; Postoperative ileus

Table 3. Incidence of PPOI in relation to definition

Definition Non-RCTs RCTs

Number of studies

Incidence (95%CI)

Number of studies

Incidence (95%CI)

Reinsertion of NG tube 20 9.5 (6.8-13) 13 8.4 (6-11.6)

Absence of bowel function POD 3 5 10.1 (5.4-18) 1 2.3 (0.8-6.8)

Absence of bowel function POD 5 7 11.7 (7.1-18.9) 2 21.7 (11-38.3)

Absence of bowel function POD 7 2 8.1 (2.9-20.6) NA

Absence of bowel function POD 5

OR Reinsertion of NG tube

3 12.6 (5.9-25) 1 61 (33.7-82.7)

NA; Not Available, NG; Nasogastric, POD; Postoperative day, Values are percentages, Values in parentheses are 95% confidence intervals

Table 4. Criteria for NG tube reinsertion from included non-RCTs and RCTs.

Author, year Criteria for NG tube reinsertionNon-RCTsJoo, 1998 Nausea or vomiting of > 200 ccChen, 2000 ≥ 2 episodes of vomiting of > 200 cc without bowel movementZmora, 2006 NRTong, 2007 NRZargar-Shoshtari, 2008 NRAsgeirsson, 2009 NRHellan, 2009 NRMohn, 2009 NRPark, 2009 NRWatanabe, 2009 NRZargar-Shoshtari, 2009 NRZmora, 2009 Abdominal distention or vomiting, based on clinical judgementKahokehr, 2010 NRSingh, 2010 Abdominal distention or vomiting, based on clinical judgementAbodeely, 2011 NRRaue, 2011 NRPelloni, 2012 NRKim, 2013 NRKolozsvari, 2013 NRManceau, 2013 NRRCTsOrtiz, 1996Ortiz, 1996Schwenk, 1998

2 episodes of vomiting2 episodes of vomitingNR

Stewart, 1998 Vomiting of > 100 cc on 2 occasions within 24 hSmith, 2000 Clinical judgementTargarona, 2002 NRTaqi, 2007 NRHewett, 2008 NREl Nakeeb, 2009 2 episodes of vomiting without bowel movementKang, 2010 NRNg, 2010 NRDeng, 2013 NR

Zaghiyan, 2013 NRNG; Nasogastric, NR; Not reported