REVIEW ARTICLE ANZJSurg.com
Meta-analysis of handsewn versus stapled reversal of loop ileostomy Georgios A. Markides,* Imeshi U. Wijetunga,* Steve R. Brown† and Suhail Anwar* *Department of Colorectal Surgery, Calderdale and Huddersfield NHS Trust, Huddersfield, UK and †Department of General Surgery, Northern General Hospital, Sheffield, UK
Key words handsewn anastomosis, ileostomy, reversal, stapled anastomosis. Correspondence Mr Suhail Anwar, Calderdale and Huddersfield NHS Trust, Huddersfield Royal Infirmary, Lindley, Huddersfield HD3 3EA, UK. Email: [email protected] G. A. Markides MSc, MRCS; I. U. Wijetunga MBChB, MRCS; S. R. Brown MD, BMedSci, FRCS; S. Anwar MPhil, FRCS. Accepted for publication 17 April 2014. doi: 10.1111/ans.12684
Abstract Background: The morbidity associated with closure of loop ileostomy (LI) may be attributed to the various surgical techniques employed for the closure. The purpose of this review was to review the hand-sutured (HS) versus the stapled anastomosis (SA) techniques, used in the reversal of LI. Methods: The MEDLINE, PubMed, CINHAL, Cochrane library and Web of Knowledge databases were searched for randomized controlled trials (RCTs) and casecontrol trials (CCTs), evaluating HS and SA in reversal of LI. Data extraction with risk of bias assessment was followed by subgroup and pooled data meta-analysis where applicable per outcome. Results: Four RCTs (HS: 321, SA: 328) and 10 CCTs (HS: 2808, SA: 1044) were identified, with a total of 4508 patients. Regardless of subgroup analysis, no difference was seen between the two techniques with regard to anastomotic leaks (P = 0.24, odds ratio (OR): 1.37, 95% confidence interval (CI): 0.81–2.29) or re-operation. The stapled group showed a significantly lower rate of conservatively managed small bowel obstruction (SBO)/ ileus at 30 days (P < 0.001, OR: 2.27, 95% CI: 1.59–2.96) (P < 0.001) and SBO during combined short- and long-term follow-up (P < 0.001). The SA also showed significant shorter operative time (P = 0.02; WMD 11.52 min), time to first bowel opening (P < 0.001; WMD 0.52 days) and length of hospital stay (P = 0.03; WMD 0.70 days). Conclusion: The stapled technique offers an advantage in terms of lower postoperative subacute SBO rates, a faster operative technique and shorter hospitalization times. These perceived benefits make it potentially superior to HS for the reversal of LI.
Introduction During the 2011–2012 period alone, approximately 5000 patients underwent reversal of a loop ileostomy in England.1 This large number probably relates to the increase in the number of sphincter preserving operations with low colorectal or coloanal anastomoses after rectal cancer resection, and the concomitant use of temporary defunctioning loop ileostomies to protect the anastomosis.2–4 Often the ileostomy is reversed some time later after confirmation of an intact anastomosis. The technique used to perform the reversal of the loop ileostomy varies between two different approaches.5–8 Once the stoma is released via a circumferential skin incision, the enterotomy can either be closed with hand-suturing, or stapling can be used to form a side-to-side anastomosis with cross stapling to remove the excess ends. © 2014 Royal Australasian College of Surgeons
Although perceived to be a minor procedure, reversal of a loop ileostomy may be fraught with complications. These include bowel obstruction at the site of the anastomosis or an anastomotic leak (AL)9,10 which may lead to re-operation and even mortality. Proponents of the stapling technique advocate that the stapler allows a larger diameter anastomosis which is particularly important as the distal defunctioned limb lumen is often narrow following a period of inactivity. Consequently, the risk of bowel obstruction is reduced. Although a stapled technique costs more, this may be counterbalanced by shorter operating times, and a reduction in the length of hospital stay in this group.11 A meta-analysis of two randomized controlled trials (RCTs) and four case-control trials (CCTs) in 2008 compared the two techniques of hand-suturing against stapling.11 However, a poor methodological quality and the relatively small patient numbers meant a lack of ANZ J Surg •• (2014) ••–••
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sufficient statistical power. A trend towards reduced obstructive complications was shown with the stapling technique. There was also a trend towards reduced operating times but both failed to reach any statistical significance. A recent meta-analysis of four RCTs indicated that the stapled group had a shorter operating time and lower risk of post-operative small bowel obstruction (SBO).12 The primary outcome of this review was AL; with its calculated risks of occurrence between 8 and 14 per 1000 procedures, results of no difference between the two techniques carry the potential for a significant type II error.13 This was mainly due to the inadequate number of patients included in this review (645 patients). We have tried to overcome this problem by including both RCTs and CCTs in our study albeit with a rigorous selection criteria and validity assessment.
Materials and methods Search and selection strategy Electronic database searches of the Cochrane Library’s Controlled Trials Registry and Database of Systematic Reviews, MEDLINE (Ovid) (1950–May 2013), PubMed, CINHAL, Web of Knowledge and SCOPUS were performed, without any additional search limits. Medical subject headings (MeSH) and free text terms were used and adapted accordingly to individual databases combined with the Boolean database features ‘AND’ and ‘OR’: Ileostomy (MeSH) Anastomosis (MeSH) ‘ileostomy reversal’, ‘ileostomy closure’, ‘defunctioning ileostomy’, ‘loop ileostomy’, ‘surgical stapling’, ‘linear stapler’, ‘TLC 75’, ‘GI auto suture’, ‘handsewn’ and ‘suture technique’ (free text)
Markides et al.
assumptions regarding the original data variance. In addition, subgroup data analysis of RCTs, higher quality CCTs based on risk of bias, and all studies together were performed for each outcome. The Mantel–Haenszel statistical method was used to analyse dichotomous variables such as ALs and bowel obstructions providing ORs and 95% CIs. The difference between the two techniques was considered statistically significant if the 95% CI did not include the value 1. Weighted mean difference (WMD) was used to analyse continuous variables such as length of hospital stay, and difference between the two techniques was considered to be significant if the 95% CI for WMD did not include the value 0. Fixed-effects and random-effects analysis models were employed depending on heterogeneity between studies (increased heterogeneity especially in smaller studies and poorer quality of bigger studies favoured the random-effects model). Statistical heterogeneity was also assessed using the χ2 (statistically significant if P < 0.10) and I2 ( 18, elective procedure, previous low anterior resection Exclusion: expected lack of compliance, preoperative residual anastomotic leak from primary surgery, participation in another intervention trial Inclusion: integrity of colorectal anastomosis, previous rectal cancer excision Exclusion: signs of cancer progression Inclusion: consecutive patients requiring loop ileostomy reversal
74 + 27Res
20
136
28 + 34Res
1278
66
149 + 26Res
466 + 163Res
129
149 + 70Res
30
70
56
HS (n)
Inclusion and exclusion criteria
9
20
152
47
226
25
22
315
96
132
31
71
63
163
ST (n)
E-E, excision of ends or folding with double-layer suture
E-E, folding with single-layer extramucosal suture
E-E, excision of ends and single- or double-interrupted serosubmucosal layer suture E-E, excision of ends or folding with single-layer suture E-E, folding with single-layer interrupted suture
E-E single-layer continuous suture
E-E, excision of ends or folding with double-layer suture E-E, excision of ends or folding with double-layer suture
E-E, excision of ends and seromuscular suture
E-E, excision of ends and single seromuscular layer continuous
E-E, excision of ends and single layer interrupted or continuous E-E, excision of ends and single layer interrupted
E-E, excision of ends and double layer interrupted
E-E , continuous two-layer transmural and extramural oversewing
HS technique
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling and crotch stitch
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
Excision of ends and S-S stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling, overstitching of cross-stapled line and crotch stitch
S-S stapling, overstitching of cross-stapled line
SP technique
HS Med: 64 months (15–118) ST Med: 30 (11–16) HS Med: 15 months (9–21) Med: 36 months (ST) NR
19 months ± 5
NR
NR
Med: 34 months (1.9–64.2)
30 days
30 days
30 days
30 days
NR
30 days
12 months (tel)
Follow-up
CCT, case-control trial; CS, case series; E-E, end to end; HS, handsewn; IAAP, ileoanal anastomotic pouch; LI, loop ileostomy; NR, not reported; P, prospective; R, retrospective; RCT, randomized controlled trial; Res, with resection; SGA, subgroup analysis; SP, stapled; S-S, side to side. Data reporting: mean ± standard deviation; Med: median (range).
Design and centres
Study
Table 1 Summary of studies investigating handsewn versus stapled reversal of loop ileostomy
Review of reversal of ileostomy techniques 3
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Markides et al.
Table 2 Overall risk of bias assessment Reference
Selection bias risk
Loffler et al.19 Shelygin et al.20 Hasegawa et al.17 Hull et al.18 Gustavsson et al.25 Balik et al.22 Luglio et al.28 D’Haeninck et al.23 Horisberger et al.26 Wong et al.29 Garcia-Botello et al.24 Kraemer et al.27 Bain et al.21 Feinberg et al.5
R
AC
B
+ + − −
+/− +/− − − − − − − − − − − − −
− + − −
Performance bias risk
Attrition bias risk
Selective reporting
Detection bias risk
Threads to external validity
Overall risk of bias
Level of evidence
− + + + − + − − − − − − − −
+ + + + + + + + + + + + + +
+ +/− + − + + + + + + + + + +
− − + − − − − − − − − − − −
+/− − − − − − − − − − − − − −
− − − − − − − − − − − − − −
2b 2b 2b 2b 3b 3b 3b 4 3b 4 4 4 4 4
(−), high risk; (+), low risk; AC, allocation concealment; B, blinding; R, randomization.
Hand-suturing Stapling Study or Subgroup Events Total Events Total Weight 4.1.1 Randomized controlled trials Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
2 0 0 3
70 30 56 165 321
0 0 0 5
71 31 63 163 328
1.9%
Odds Ratio M-H, Fixed, 95% CI Year 5.22 [0.25, 110.69] Not estimable Not estimable 0.59 [0.14, 2.49] 0.99 [0.30, 3.28]
1996 2000 2010 2012
8.5% 6.7% 10.1% 14.0% 79.0%
0.16 [0.01, 1.98] Not estimable 2.25 [0.20, 25.14] 0.94 [0.24, 3.72] 1.96 [0.46, 8.40] Not estimable 1.90 [0.36, 9.98] 0.62 [0.07, 5.54] 2.53 [0.55, 11.61] 1.42 [0.36, 5.59] 1.46 [0.82, 2.61]
1987 1996 2000 2005 2005 2010 2011 2011 2011 2012
1372 100.0%
1.37 [0.81, 2.29]
19.1% 21.0%
Odds Ratio M-H, Fixed, 95% CI
Fig. 1. Anastomotic leaks.
5 Total events 5 Heterogeneity: Chi² = 1.65, df = 1 (P = 0.20); I² = 39% Test for overall effect: Z = 0.01 (P = 0.99) 4.1.2 Case-control trials Feinberg et al 1987 Bain et al 1996 Kraemer et al 2000 Garcia-Botello et al 2005 Wong et al 2005 Horisberger et al 2010 Balik et al 2011 DHaeninck et al 2011 Luglio et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
2 0 2 5 22 0 5 5 10 7
101 20 136 62 1278 66 129 175 629 219 2815
1 0 1 4 2 0 2 1 2 3
9 20 152 47 226 25 96 22 315 132 1044
7.0% 3.6% 16.2% 12.9%
Total events 58 16 Heterogeneity: Chi² = 4.82, df = 7 (P = 0.68); I² = 0% Test for overall effect: Z = 1.29 (P = 0.20) Total (95% CI)
3136
63 Total events 21 Heterogeneity: Chi² = 6.81, df = 9 (P = 0.66); I² = 0% Test for overall effect: Z = 1.18 (P = 0.24) Test for subgroup differences: Chi² = 0.33, df = 1 (P = 0.57), I² = 0%
reversal techniques were very well described and comparable in all studies including the CCTs, minimizing heterogeneity in regard to the actual interventions tested. Meta-analysis was performed in three subgroups (for the main outcome measures), all the RCTs together, the RCTs plus highquality CCTs, and RCTs plus CCTs together. In only one outcome, the ‘post-operative bleeding’, there was a difference between the statistical results analysed among subgroups. Statistical heterogeneity was negligible in all outcome comparisons apart from the ‘operating time’, and thus the random-effects model was employed in that case. Funnel plots did not reveal any evidence of publication bias among studies.
Complications Anastomotic leaks (Fig. 1) There was no statistically significant difference between the two groups in regard to the incidence of ALs (RCTs: P = 0.51, all studies:
0.01 0.1 1 10 100 Favours suturing Favours stapling
P = 0.15), with an overall AL rate of 1.9% (84/4508). Fifty per cent of these cases required a re-operation. Small bowel obstruction (Fig. 2) A consistent definition of SBO was lacking in majority of the studies. Most of the studies defined any prolonged (more than 5 days) inability to have oral intake with nausea and/or vomiting, potentially requiring a nasogastric tube placement, as SBO. The majority of these cases though were subsequently treated and settled with conservative measures, and only a minority needed surgical intervention. In addition, six studies18–20,22,25,28 report on this outcome at 30 days post-operatively, with one23 reporting on ileus at 30 days. The rest of the studies either do not provide this information or combine it in a longer follow-up. Five different types of subgroup analyses were thus performed for this outcome. The first included all patients reported by studies as suffering from SBO, the second included all patients with SBO requiring re-operation, and the third © 2014 Royal Australasian College of Surgeons
Review of reversal of ileostomy techniques
Fig. 2. Reported small bowel obstruction at 30 days (a) and during combined short- and long-term follow-up (b).
5
(a)
Hand-suturing Stapling Total Events Total Weight Study or Subgroup Events 4.3.1 Randomized controlled trials Hasegawa et al 2000 Hull et al 1996 Loffler et al 2012 Shelygin et al 2010 Subtotal (95% CI)
10 2 24 2
70 30 165 56 321
2 1 17 1
Odds Ratio M-H, Fixed, 95% CI
71 31 163 63 328
2.8% 1.5% 24.1% 1.5% 30.0%
5.75 [1.21, 27.28] 2.14 [0.18, 24.96] 1.46 [0.75, 2.84] 2.30 [0.20, 26.03] 1.94 [1.11, 3.40]
96 132 315 543
10.7% 17.4% 42.0% 70.0%
0.99 [0.33, 2.96] 2.24 [1.07, 4.71] 2.60 [1.62, 4.17] 2.27 [1.57, 3.29]
871 100.0%
2.17 [1.59, 2.96]
Odds Ratio M-H, Fixed, 95% CI
21 38 Total events Heterogeneity: Chi² = 2.60, df = 3 (P = 0.46); I² = 0% Test for overall effect: Z = 2.31 (P = 0.02) 4.3.2 Case-control trials Balik et al 2011 Gustavsson et al 2012 Luglio et al 2011 Subtotal (95% CI)
8 34 107
129 219 629 977
6 10 23
39 Total events 149 Heterogeneity: Chi² = 2.53, df = 2 (P = 0.28); I² = 21% Test for overall effect: Z = 4.33 (P < 0.0001) Total (95% CI)
1298
60 Total events 187 Heterogeneity: Chi² = 5.42, df = 6 (P = 0.49); I² = 0% Test for overall effect: Z = 4.91 (P < 0.00001) Test for subgroup differences: Chi² = 0.21, df = 1 (P = 0.65), I² = 0%
(b)
Hand-suturing Stapling Study or Subgroup Events Total Events Total Weight 4.5.1 Randomized controlled trials Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
2 10 2 24
30 70 56 165 321
1 2 1 17
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
Odds Ratio M-H, Fixed, 95% CI Year
31 71 63 163 328
1.0% 1.8% 1.0% 15.4% 19.2%
2.14 [0.18, 24.96] 5.75 [1.21, 27.28] 2.30 [0.20, 26.03] 1.46 [0.75, 2.84] 1.94 [1.11, 3.40]
1996 2000 2010 2012
9 20 226 47 25 315 22 96 132 892
0.8% 3.2% 20.1% 3.5% 3.6% 26.9% 4.9% 6.8% 11.1% 80.8%
3.67 [0.20, 66.12] 1.33 [0.30, 5.93] 1.27 [0.68, 2.37] 0.49 [0.08, 3.05] 2.16 [0.57, 8.21] 2.60 [1.62, 4.17] 1.01 [0.28, 3.66] 0.99 [0.33, 2.96] 2.24 [1.07, 4.71] 1.84 [1.38, 2.46]
1987 1996 2005 2005 2010 2011 2011 2011 2012
1220 100.0%
1.86 [1.44, 2.40]
Odds Ratio M-H, Fixed, 95% CI
Total events 38 21 Heterogeneity: Chi² = 2.60, df = 3 (P = 0.46); I² = 0% Test for overall effect: Z = 2.31 (P = 0.02) 4.5.2 Case-control trials Feinberg et al 1987 Bain et al 1996 Wong et al 2005 Garcia-Botello et al 2005 Horisberger et al 2010 Luglio et al 2011 DHaeninck et al 2011 Balik et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
16 5 85 2 15 107 24 8 34
101 20 1278 62 66 629 175 129 219 2679
0 4 12 3 3 23 3 6 10
Total events 296 64 Heterogeneity: Chi² = 8.23, df = 8 (P = 0.41); I² = 3% Test for overall effect: Z = 4.13 (P < 0.0001) Total (95% CI)
3000
Total events 334 85 Heterogeneity: Chi² = 10.83, df = 12 (P = 0.54); I² = 0% Test for overall effect: Z = 4.72 (P < 0.00001) Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.87), I² = 0%
group included the reported SBOs that settled with conservative management, that is, potentially the subacute SBO or ileus at 30 days. The first two analyses were performed twice, once including studies reporting only 30-day outcomes and the second time including all studies together. A statistically significant lower rate of reported SBO, both at 30 days (RCTs: P = 0.02, all studies: P < 0.001) and during combined short- and long-term follow-up (RCTs: P = 0.02, all studies: P < 0.001), was seen in the stapled group. Similar results were seen for the 30-day conservatively managed SBO outcome (RCTs: P = 0.03, all studies: P < 0.001). The overall short- and long-term incidence rate of reported SBO was 11.4% and 9.9%, respectively. There was no significant difference between the two groups in regard to the number of SBOs requiring re-operation at 30 days (RCTs: P = 0.96, all studies: P = 0.63) or during combined shortand long-term follow-up (RCTs: P = 0.80, all studies: P = 0.47). The rate of re-operation for SBO was 1.6% within 30 days and © 2014 Royal Australasian College of Surgeons
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
1.8% during combined short- and long-term follow-up in all studies. The use of a two-layer closure compared to one-layer loop ileostomy closure in the handsewn group could have potentially narrowed the lumen, further creating a bias against this group in terms of subacute SBO. This hypothesis was tested by stratifying the studies accordingly and was rejected as the same benefit was still found in favour of the stapled group regardless of the use of a oneor two-layer handsewn closure. Re-operations (Fig. 3) Re-operation rates between the two groups were similar (RCTs: P = 0.84, all studies: P = 0.663) with a reported rate of 4.3% (111/2607). The two main complications leading to re-operation were SBO, accounting for at least 50% of cases, and ALs, accounting for at least 25% of cases. Other causes included volvulus, bleeding, iatrogenic enterotomies and fistulas.
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Markides et al.
Hand-suturing Stapling Total Events Total Weight Events Study or Subgroup 4.7.1 Randomized controlled trials 1 1 1 7
30 70 56 165 321
2 3 0 4
Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
Odds Ratio M-H, Fixed, 95% CI Year
31 71 63 163 328
2.1% 2.2% 3.2% 15.9% 23.5%
2.14 [0.18, 24.96] 3.13 [0.32, 30.88] 0.37 [0.01, 9.24] 0.55 [0.16, 1.93] 0.91 [0.37, 2.23]
1996 2000 2010 2012
9 20 25 315 22 96 132 619
2.0% 3.9% 1.6% 32.5% 15.0% 5.1% 16.2% 76.5%
0.68 [0.03, 14.07] 1.59 [0.24, 10.70] 1.17 [0.05, 29.62] 1.19 [0.58, 2.44] 0.42 [0.13, 1.41] 1.90 [0.36, 9.98] 1.43 [0.54, 3.83] 1.14 [0.71, 1.83]
1987 1996 2010 2011 2011 2011 2012
947 100.0%
1.09 [0.72, 1.65]
Odds Ratio M-H, Fixed, 95% CI
Fig. 3. Re-operations.
10 9 Total events Heterogeneity: Chi² = 2.50, df = 3 (P = 0.47); I² = 0% Test for overall effect: Z = 0.20 (P = 0.84) 4.7.2 Case-control trials 101 20 66 629 175 129 219 1339
3 3 1 26 15 5 14
Feinberg et al 1987 Bain et al 1996 Horisberger et al 2010 Luglio et al 2011 DHaeninck et al 2011 Balik et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
0 2 0 11 4 2 6
25 67 Total events Heterogeneity: Chi² = 3.43, df = 6 (P = 0.75); I² = 0% Test for overall effect: Z = 0.56 (P = 0.57) 1660
Total (95% CI)
35 76 Total events Heterogeneity: Chi² = 6.09, df = 10 (P = 0.81); I² = 0% Test for overall effect: Z = 0.41 (P = 0.68) Test for subgroup differences: Chi² = 0.19, df = 1 (P = 0.66), I² = 0%
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
Hand-suturing Stapling Study or Subgroup Mean SD Total Mean SD Total Weight 4.11.1 Randomized controlled trials
Mean Difference IV, Random, 95% CI Year
Loffler et al 2012 Subtotal (95% CI)
91.5
43.7
165 165
76.5 29.3
163 163
32.0% 32.0%
15.00 [6.96, 23.04] 2012 15.00 [6.96, 23.04]
15 37
25 315 340
31.1% 36.8% 68.0%
18.00 [9.40, 26.60] 2010 3.00 [-1.87, 7.87] 2011 10.06 [-4.61, 24.74]
Mean Difference IV, Random, 95% CI
Fig. 4. Operating time.
Heterogeneity: Not applicable Test for overall effect: Z = 3.66 (P = 0.0003) 4.11.2 Case-control trials Horisberger et al 2010 Luglio et al 2011 Subtotal (95% CI)
102 99
26 34
66 629 695
84 96
Heterogeneity: Tau² = 99.79; Chi² = 8.85, df = 1 (P = 0.003); I² = 89% Test for overall effect: Z = 1.34 (P = 0.18) Total (95% CI)
860
503 100.0%
11.52 [1.46, 21.57]
Heterogeneity: Tau² = 65.32; Chi² = 12.09, df = 2 (P = 0.002); I² = 83% Test for overall effect: Z = 2.24 (P = 0.02) Test for subgroup differences: Chi² = 0.33, df = 1 (P = 0.56), I² = 0%
Operating time (Fig. 4) Mean and SD of operating times, time to first bowel movement and length of hospital stay outcomes were only reported in three studies.19,26,28 Meta-analysis of these studies revealed a significantly shorter operating time for the stapled group (P = 0.02, WMD: 11.52, 95% CI: 1.46–21.57 min) but with statistically high heterogeneity, I2: 83%. The three additional RCTs17,18,20 and two of the CCTs23,27 (not included in the forest plot) reporting on this outcome also individually found a statistically significant shorter operating time in the stapled group. Only one study21 undertaken in 1996 with a group sample of 20 patients failed to show any difference in operating time between the two groups. Length of hospital stay (Fig. 5) Patients undergoing a stapled ileostomy reversal were found to have a shorter length of hospital stay compared to the handsewn group (P = 0.003, WMD: 0.70, 95% CI: 0.24–1.17 days). Two remaining RCTs (not included in the forest plot) reporting on this outcome showed a nearly statistically significant difference, P = 0.0720 and P = 0.09,17 with three additional CCTs22,25,27 confirming the same finding. Only two of the CCTs21,29 found no difference between the two groups of patients.
-100 -50 0 50 100 Favours [suturing] Favours [stapling]
Discussion A defunctioning loop ileostomy is fashioned to protect a more distal bowel anastomosis, especially when the risk of AL is considered to be high.30 It has been shown that in patients with a loop ileostomy, the impact of an AL is lower, especially after an anastomosis has been created below the peritoneal reflection or close to the anal canal.31,32 An AL is a dreaded complication which can result in sepsis with peritonitis and re-operation, and contribute to higher morbidity and mortality. Two previous reviews and meta-analyses failed to show any significant difference between loop ileostomy techniques, in relation to this outcome.11,12 The findings from this study appear to concur with these findings; no significant difference was seen for the risk of AL either between RCTs or pooled analysis of all studies. The overall 30-day mortality in this group of 4508 patients of approximately 0.1% is low and appears to be in keeping with the literature.10 Definition of SBO has been inconsistent on these studies. Nevertheless, regardless of how SBO is defined and whether only RCTs, high-quality CCTs or all studies together are considered, it appears that there is a significantly lower rate of conservatively managed © 2014 Royal Australasian College of Surgeons
Review of reversal of ileostomy techniques
Fig. 5. Length of hospital stay.
7
Stapling Hand-suturing SD Total Mean SD Total Weight Mean Study or Subgroup 4.13.1 Randomized controlled trials Loffler et al 2012 Subtotal (95% CI)
8.5
4.9
Mean Difference IV, Random, 95% CI Year
165 165
8.3 7.9
163 163
10.7% 10.7%
0.20 [-1.22, 1.62] 2012 0.20 [-1.22, 1.62]
66 629 695
7 2.7 4.7 3.5
25 315 340
11.3% 78.0% 89.3%
1.20 [-0.18, 2.58] 2010 0.70 [0.17, 1.23] 2011 0.76 [0.27, 1.26]
Mean Difference IV, Random, 95% CI
Heterogeneity: Not applicable Test for overall effect: Z = 0.28 (P = 0.78) 4.13.2 Case-control trials Horisberger et al 2010 Luglio et al 2011 Subtotal (95% CI)
8.2 5.4
3.7 4.6
Heterogeneity: Tau² = 0.00; Chi² = 0.44, df = 1 (P = 0.51); I² = 0% Test for overall effect: Z = 3.03 (P = 0.002) Total (95% CI)
860
503 100.0%
Heterogeneity: Tau² = 0.00; Chi² = 0.97, df = 2 (P = 0.61); I² = 0% Test for overall effect: Z = 2.96 (P = 0.003) Test for subgroup differences: Chi² = 0.54, df = 1 (P = 0.46), I² = 0%
SBO in the stapling group in the 30-day post-operative period. The lower rate of subacute SBO in the stapled group is potentially in keeping with the theory behind the formation of a wider anastomosis in this group compared to hand-suturing. Interestingly, when a more major complication such as the rate of re-operation secondary to SBO is considered, there is no difference between the two techniques either at 30 days or in the combined follow-up periods. Unfortunately, the cause of obstruction in this group of studies was scarcely reported. Studies that did report on the causation of operated SBO mostly reported adhesional causes.21 There was no effect on the results when the two studies21,28 reporting on the inclusion of mostly patients with inflammatory bowel disease (IBD) as their primary pathology were excluded from the calculations. Over this period of time when most of these studies were conducted, attitudes towards early nutrition, mobilization and discharge have changed especially with the use of enhanced recovery programme (ERP).33–35 Lengths of stay (LOS) after loop ileostomy reversal varied between studies from mean stay of 4.7–10 days, with no reported discharge criteria. The overall tendency was for a shorter LOS in the stapled group, confirmed by the meta-analysis of three of the studies (P = 0.003) conducted in the last 3 years. This finding is in accordance with the reduced rates of subacute SBO/ileus and earlier bowel movement found in the stapled group may confer an additional cost benefit. However in the setting of the ERP, the goal posts might shift and the shorter LOS in the stapled group might not have as big an impact as suggested by this review. All studies included in this review recruited patients undergoing loop ileostomy reversal for patients who had previously undergone surgery for malignancy, IBD or ileoanal pouch restoration. This has created potential clinical heterogeneity among studies, even though the reversal procedures were very well standardized within and among studies minimizing the degree of heterogeneity in regard to the actual interventions performed. A further feature of heterogeneity is the lack of a standardized perioperative care pathway. The included RCTs were also only powered to report on their primary outcomes, which are all different between studies. The secondary outcomes remained relatively poorly defined and underpowered. In view of the potential of clinical heterogeneity reported in this review, both a fixed-effects and a random-effects model were used with no difference between the two models in regard to outcome results. A cost-effectiveness analysis between the two techniques has not been conducted as part of this review. It could be argued that whether © 2014 Royal Australasian College of Surgeons
0.70 [0.24, 1.17] -100 -50 0 50 100 Favours [suturing] Favours [stapling]
the cost of stapler can be justified by the reduction in the LOS and reduction in the risk of SBO, which in turn increase the LOS. This perhaps can be the subject of another review with built-in costeffectiveness parameters. In conclusion, there appears to be no difference between handsewn and stapled techniques in the reversal of loop ileostomy with regard to short- and medium-term outcomes such as 30-day mortality (level 2 evidence), ALs (level 2 evidence), re-operations (level 2 evidence), post-operative bleeding (level 2 evidence) and 30-day wound infections (level 2 evidence). There is though a significant difference in favour of the stapled technique in terms of subacute SBO (level 2 evidence), operation time (level 2 evidence), time to first bowel motion (level 2 evidence) and length of hospital stay (level 2 evidence). On the basis of the level of evidence found in this review and meta-analysis, a Grade B recommendation (Oxford CEBM) can be made supporting the stapled technique as the preferred choice over handsewn anastomosis for the reversal of a loop ileostomy.
References 1. Hospital Episode Statistics. Main procedures and interventions 2011–12. 2012. 2. Habr-Gama A, Perez RO, Kiss DR et al. Preoperative chemoradiation therapy for low rectal cancer. Impact on down staging and sphincter saving operations. Hepatogastroenterology 2004; 51: 1703–7. 3. Matthiessen P, Hallbook O, Rutegard J et al. Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomised multicenter trial. Ann. Surg. 2007; 246: 207–14. 4. Ulrich AB, Seiler C, Rahbari N et al. Diverting stoma after low anterior resection: more arguments in favour. Dis. Colon Rectum 2009; 52: 412–8. 5. Feinberg SM, McLeod RS, Cohen Z. Complications of loop ileostomy. Am. J. Surg. 1987; 153: 102–6. 6. Shirley F, Kodner IJ, Fry RD. Loop ileostomy: techniques and indications. Dis. Colon Rectum 1984; 27: 382–6. 7. Turnbull RBJ, Weakley FL. Atlas of intestinal stomas. St Lewis: Mosby, 1968; 32–9. 8. Kestenberg A, Becker JM. A new technique of loop ileostomy closure after endorectal ileoanal anastomosis. Surgery 1985; 98: 109–11. 9. Kaidar-Person O, Person P, Wexner SD. Complications of construction and closure of temporary loop ileostomy. J. Am. Coll. Surg. 2005; 201: 759–73. 10. Chow A, Tilney HS, Paraskeva P et al. The morbidity surrounding reversal of defunctioning ileostomies: a systematic review of
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48 studies including 6107 cases. Int. J. Colorectal Dis. 2009; 24: 711– 23. Leung TTW, MacLean AR, Buie WD, Dixon E. Comparison of stapled versus handsewn loop ileostomy closure: a meta-analysis. J. Gastrointest. Surg. 2008; 12: 939–44. Sajid MS, Craciunas L, Baig MK, Sains P. Systematic review and meta-analysis of published, randomised, controlled trials comparing suture anastomosis to stapled anastomosis for ileostomy closure. Tech. Coloproctol. 2013; 17: 631–9. Neyman J, Pearson ES. The Testing of Statistical Hypotheses in Relation to Probabilities a Riori. Cambridge: Cambridge University Press, 1967. Critical Appraisal Skills Programme UK. Randomised control trials. [Cited 6 Jun 2014.] Available from URL: http://www.casp-uk.net/ #!casp-tools-checklists/c18f8 Critical Appraisal Skills Programme UK. Case-control studies. [Cited 6 Jun 2014.] Available from URL: http://www.casp-uk.net/#!casp-tools -checklists/c18f8 The Cochrane Collaboration. Cochrane handbook for systematic reviews of interventions. [Cited 6 Jun 2014.] Available from URL: http:// www.cochrane.org/handbook Hasegawa H, Radley S, Morton DG, Keighley MRB. Stapled versus sutured closure of loop ileostomy. A randomised controlled trial. Ann. Surg. 2000; 231: 202–4. Hull TL, Kobe I, Fazio VW. Comparison of handsewn with stapled loop ileostomy closures. Dis. Colon Rectum 1996; 39: 1086–9. Loffler T, Rossion I, Brucker T et al. Hand Suture Versus Stapling for closure of Loop ileostomy (HASTA Trial). Ann. Surg. 2012; 256: 828– 36. Shelygin YA, Chernyshov SV, Rybakov EG. Stapled ileostomy closure results in reduction of postoperative morbidity. Tech. Coloproctol. 2010; 14: 19–23. Bain IM, Patel R, Keighley MRB. Comparison of sutured and stapled closure of loop ileostomy after restorative proctocolectomy. Ann. R. Coll. Surg. Engl. 1996; 78: 55–6. Balik E, Eren T, Bugra D et al. Revisiting stapled and handsewn loop ileostomy closures: a large retrospective study. Clinics 2011; 66: 1935– 41.
23. D’Haeninck A, Wolthuis AM, Penninckx F et al. Morbidity after closure of a defunctioning loop ileostomy. Acta Chir. Belg. 2011; 111: 136–41. 24. Garcia-Botello SA, Garcia-Armengol J, Garcia-Granero E et al. A prospective audit of the compilations of loop ileostomy construction and takedown. Dig. Surg. 2004; 21: 440–6. 25. Gustavsson K, Gunnarsson U, Jestin P. Postoperative complications after closure of a diverting ileostoma-differences according to closure technique. Int. J. Colorectal Dis. 2012; 27: 55–8. 26. Horisberger K, Beldi G, Candinans D. Loop ileostomy closure: comparison of cost effectiveness between suture and stapler. World J. Surg. 2010; 34: 2867–71. 27. Kraemer M, Seow-Choen F, Ho YH, Eu KW. A comparison of sutured and stapled closure of diverting loop ileostomies. Tech. Coloproctol. 2000; 4: 89–92. 28. Luglio G, Pendlimari R, Holubar SD et al. Loop ileostomy reversal after colon and rectal surgery. A single institutional 5-year experience in 944 patients. Arch. Surg. 2011; 146: 1191–6. 29. Wong K-S, Remzi FH, Gorgun E et al. Loop ileostomy closure after restorative proctocolectomy: outcome in 1504 patients. Dis. Colon Rectum 2005; 48: 243–50. 30. Rullier E, Laurent C, Garellon JL et al. Risk factors for anastomotic leakage after resection of rectal cancer. Br. J. Surg. 1998; 85: 355–8. 31. Huser N, Michalski CW, Erkan M et al. Systematic review and metaanalysis of the role of defunctioning stoma in low rectal cancer surgery. Ann. Surg. 2008; 248: 52–60. 32. Montedori A, Cirocchi R, Farinella E et al. Covering ileo- or colostomy in anterior resection for rectal carcinoma. Cochrane Database Syst. Rev. 2010; (5): CD006878. 33. Kalady MF, Fields RC, Klein S et al. Loop ileostomy closure at an ambulatory surgical facility: a safe and cost-effective alternative to routine hospitalization. Dis. Colon Rectum 2003; 46: 486–90. 34. Joh Y-G, Lindestmo R-O, Stulberg J et al. Standardised postoperative pathway: accelerating recovery after ileostomy closure. Dis. Colon Rectum 2008; 51: 1786–9. 35. Basse L, Jacobsen DH, Billesbolle P, Henrik K. Colostomy closure after Hartman’s procedure with fast-track rehabilitation. Dis. Colon Rectum 2002; 45: 1661–4.
© 2014 Royal Australasian College of Surgeons
Meta-analysis of handsewn versus stapled reversal of loop ileostomy Georgios A. Markides,* Imeshi U. Wijetunga,* Steve R. Brown† and Suhail Anwar* *Department of Colorectal Surgery, Calderdale and Huddersfield NHS Trust, Huddersfield, UK and †Department of General Surgery, Northern General Hospital, Sheffield, UK
Key words handsewn anastomosis, ileostomy, reversal, stapled anastomosis. Correspondence Mr Suhail Anwar, Calderdale and Huddersfield NHS Trust, Huddersfield Royal Infirmary, Lindley, Huddersfield HD3 3EA, UK. Email: [email protected] G. A. Markides MSc, MRCS; I. U. Wijetunga MBChB, MRCS; S. R. Brown MD, BMedSci, FRCS; S. Anwar MPhil, FRCS. Accepted for publication 17 April 2014. doi: 10.1111/ans.12684
Abstract Background: The morbidity associated with closure of loop ileostomy (LI) may be attributed to the various surgical techniques employed for the closure. The purpose of this review was to review the hand-sutured (HS) versus the stapled anastomosis (SA) techniques, used in the reversal of LI. Methods: The MEDLINE, PubMed, CINHAL, Cochrane library and Web of Knowledge databases were searched for randomized controlled trials (RCTs) and casecontrol trials (CCTs), evaluating HS and SA in reversal of LI. Data extraction with risk of bias assessment was followed by subgroup and pooled data meta-analysis where applicable per outcome. Results: Four RCTs (HS: 321, SA: 328) and 10 CCTs (HS: 2808, SA: 1044) were identified, with a total of 4508 patients. Regardless of subgroup analysis, no difference was seen between the two techniques with regard to anastomotic leaks (P = 0.24, odds ratio (OR): 1.37, 95% confidence interval (CI): 0.81–2.29) or re-operation. The stapled group showed a significantly lower rate of conservatively managed small bowel obstruction (SBO)/ ileus at 30 days (P < 0.001, OR: 2.27, 95% CI: 1.59–2.96) (P < 0.001) and SBO during combined short- and long-term follow-up (P < 0.001). The SA also showed significant shorter operative time (P = 0.02; WMD 11.52 min), time to first bowel opening (P < 0.001; WMD 0.52 days) and length of hospital stay (P = 0.03; WMD 0.70 days). Conclusion: The stapled technique offers an advantage in terms of lower postoperative subacute SBO rates, a faster operative technique and shorter hospitalization times. These perceived benefits make it potentially superior to HS for the reversal of LI.
Introduction During the 2011–2012 period alone, approximately 5000 patients underwent reversal of a loop ileostomy in England.1 This large number probably relates to the increase in the number of sphincter preserving operations with low colorectal or coloanal anastomoses after rectal cancer resection, and the concomitant use of temporary defunctioning loop ileostomies to protect the anastomosis.2–4 Often the ileostomy is reversed some time later after confirmation of an intact anastomosis. The technique used to perform the reversal of the loop ileostomy varies between two different approaches.5–8 Once the stoma is released via a circumferential skin incision, the enterotomy can either be closed with hand-suturing, or stapling can be used to form a side-to-side anastomosis with cross stapling to remove the excess ends. © 2014 Royal Australasian College of Surgeons
Although perceived to be a minor procedure, reversal of a loop ileostomy may be fraught with complications. These include bowel obstruction at the site of the anastomosis or an anastomotic leak (AL)9,10 which may lead to re-operation and even mortality. Proponents of the stapling technique advocate that the stapler allows a larger diameter anastomosis which is particularly important as the distal defunctioned limb lumen is often narrow following a period of inactivity. Consequently, the risk of bowel obstruction is reduced. Although a stapled technique costs more, this may be counterbalanced by shorter operating times, and a reduction in the length of hospital stay in this group.11 A meta-analysis of two randomized controlled trials (RCTs) and four case-control trials (CCTs) in 2008 compared the two techniques of hand-suturing against stapling.11 However, a poor methodological quality and the relatively small patient numbers meant a lack of ANZ J Surg •• (2014) ••–••
2
sufficient statistical power. A trend towards reduced obstructive complications was shown with the stapling technique. There was also a trend towards reduced operating times but both failed to reach any statistical significance. A recent meta-analysis of four RCTs indicated that the stapled group had a shorter operating time and lower risk of post-operative small bowel obstruction (SBO).12 The primary outcome of this review was AL; with its calculated risks of occurrence between 8 and 14 per 1000 procedures, results of no difference between the two techniques carry the potential for a significant type II error.13 This was mainly due to the inadequate number of patients included in this review (645 patients). We have tried to overcome this problem by including both RCTs and CCTs in our study albeit with a rigorous selection criteria and validity assessment.
Materials and methods Search and selection strategy Electronic database searches of the Cochrane Library’s Controlled Trials Registry and Database of Systematic Reviews, MEDLINE (Ovid) (1950–May 2013), PubMed, CINHAL, Web of Knowledge and SCOPUS were performed, without any additional search limits. Medical subject headings (MeSH) and free text terms were used and adapted accordingly to individual databases combined with the Boolean database features ‘AND’ and ‘OR’: Ileostomy (MeSH) Anastomosis (MeSH) ‘ileostomy reversal’, ‘ileostomy closure’, ‘defunctioning ileostomy’, ‘loop ileostomy’, ‘surgical stapling’, ‘linear stapler’, ‘TLC 75’, ‘GI auto suture’, ‘handsewn’ and ‘suture technique’ (free text)
Markides et al.
assumptions regarding the original data variance. In addition, subgroup data analysis of RCTs, higher quality CCTs based on risk of bias, and all studies together were performed for each outcome. The Mantel–Haenszel statistical method was used to analyse dichotomous variables such as ALs and bowel obstructions providing ORs and 95% CIs. The difference between the two techniques was considered statistically significant if the 95% CI did not include the value 1. Weighted mean difference (WMD) was used to analyse continuous variables such as length of hospital stay, and difference between the two techniques was considered to be significant if the 95% CI for WMD did not include the value 0. Fixed-effects and random-effects analysis models were employed depending on heterogeneity between studies (increased heterogeneity especially in smaller studies and poorer quality of bigger studies favoured the random-effects model). Statistical heterogeneity was also assessed using the χ2 (statistically significant if P < 0.10) and I2 ( 18, elective procedure, previous low anterior resection Exclusion: expected lack of compliance, preoperative residual anastomotic leak from primary surgery, participation in another intervention trial Inclusion: integrity of colorectal anastomosis, previous rectal cancer excision Exclusion: signs of cancer progression Inclusion: consecutive patients requiring loop ileostomy reversal
74 + 27Res
20
136
28 + 34Res
1278
66
149 + 26Res
466 + 163Res
129
149 + 70Res
30
70
56
HS (n)
Inclusion and exclusion criteria
9
20
152
47
226
25
22
315
96
132
31
71
63
163
ST (n)
E-E, excision of ends or folding with double-layer suture
E-E, folding with single-layer extramucosal suture
E-E, excision of ends and single- or double-interrupted serosubmucosal layer suture E-E, excision of ends or folding with single-layer suture E-E, folding with single-layer interrupted suture
E-E single-layer continuous suture
E-E, excision of ends or folding with double-layer suture E-E, excision of ends or folding with double-layer suture
E-E, excision of ends and seromuscular suture
E-E, excision of ends and single seromuscular layer continuous
E-E, excision of ends and single layer interrupted or continuous E-E, excision of ends and single layer interrupted
E-E, excision of ends and double layer interrupted
E-E , continuous two-layer transmural and extramural oversewing
HS technique
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling and crotch stitch
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
Excision of ends and S-S stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling and cross stapling
S-S stapling, overstitching of cross-stapled line and crotch stitch
S-S stapling, overstitching of cross-stapled line
SP technique
HS Med: 64 months (15–118) ST Med: 30 (11–16) HS Med: 15 months (9–21) Med: 36 months (ST) NR
19 months ± 5
NR
NR
Med: 34 months (1.9–64.2)
30 days
30 days
30 days
30 days
NR
30 days
12 months (tel)
Follow-up
CCT, case-control trial; CS, case series; E-E, end to end; HS, handsewn; IAAP, ileoanal anastomotic pouch; LI, loop ileostomy; NR, not reported; P, prospective; R, retrospective; RCT, randomized controlled trial; Res, with resection; SGA, subgroup analysis; SP, stapled; S-S, side to side. Data reporting: mean ± standard deviation; Med: median (range).
Design and centres
Study
Table 1 Summary of studies investigating handsewn versus stapled reversal of loop ileostomy
Review of reversal of ileostomy techniques 3
4
Markides et al.
Table 2 Overall risk of bias assessment Reference
Selection bias risk
Loffler et al.19 Shelygin et al.20 Hasegawa et al.17 Hull et al.18 Gustavsson et al.25 Balik et al.22 Luglio et al.28 D’Haeninck et al.23 Horisberger et al.26 Wong et al.29 Garcia-Botello et al.24 Kraemer et al.27 Bain et al.21 Feinberg et al.5
R
AC
B
+ + − −
+/− +/− − − − − − − − − − − − −
− + − −
Performance bias risk
Attrition bias risk
Selective reporting
Detection bias risk
Threads to external validity
Overall risk of bias
Level of evidence
− + + + − + − − − − − − − −
+ + + + + + + + + + + + + +
+ +/− + − + + + + + + + + + +
− − + − − − − − − − − − − −
+/− − − − − − − − − − − − − −
− − − − − − − − − − − − − −
2b 2b 2b 2b 3b 3b 3b 4 3b 4 4 4 4 4
(−), high risk; (+), low risk; AC, allocation concealment; B, blinding; R, randomization.
Hand-suturing Stapling Study or Subgroup Events Total Events Total Weight 4.1.1 Randomized controlled trials Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
2 0 0 3
70 30 56 165 321
0 0 0 5
71 31 63 163 328
1.9%
Odds Ratio M-H, Fixed, 95% CI Year 5.22 [0.25, 110.69] Not estimable Not estimable 0.59 [0.14, 2.49] 0.99 [0.30, 3.28]
1996 2000 2010 2012
8.5% 6.7% 10.1% 14.0% 79.0%
0.16 [0.01, 1.98] Not estimable 2.25 [0.20, 25.14] 0.94 [0.24, 3.72] 1.96 [0.46, 8.40] Not estimable 1.90 [0.36, 9.98] 0.62 [0.07, 5.54] 2.53 [0.55, 11.61] 1.42 [0.36, 5.59] 1.46 [0.82, 2.61]
1987 1996 2000 2005 2005 2010 2011 2011 2011 2012
1372 100.0%
1.37 [0.81, 2.29]
19.1% 21.0%
Odds Ratio M-H, Fixed, 95% CI
Fig. 1. Anastomotic leaks.
5 Total events 5 Heterogeneity: Chi² = 1.65, df = 1 (P = 0.20); I² = 39% Test for overall effect: Z = 0.01 (P = 0.99) 4.1.2 Case-control trials Feinberg et al 1987 Bain et al 1996 Kraemer et al 2000 Garcia-Botello et al 2005 Wong et al 2005 Horisberger et al 2010 Balik et al 2011 DHaeninck et al 2011 Luglio et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
2 0 2 5 22 0 5 5 10 7
101 20 136 62 1278 66 129 175 629 219 2815
1 0 1 4 2 0 2 1 2 3
9 20 152 47 226 25 96 22 315 132 1044
7.0% 3.6% 16.2% 12.9%
Total events 58 16 Heterogeneity: Chi² = 4.82, df = 7 (P = 0.68); I² = 0% Test for overall effect: Z = 1.29 (P = 0.20) Total (95% CI)
3136
63 Total events 21 Heterogeneity: Chi² = 6.81, df = 9 (P = 0.66); I² = 0% Test for overall effect: Z = 1.18 (P = 0.24) Test for subgroup differences: Chi² = 0.33, df = 1 (P = 0.57), I² = 0%
reversal techniques were very well described and comparable in all studies including the CCTs, minimizing heterogeneity in regard to the actual interventions tested. Meta-analysis was performed in three subgroups (for the main outcome measures), all the RCTs together, the RCTs plus highquality CCTs, and RCTs plus CCTs together. In only one outcome, the ‘post-operative bleeding’, there was a difference between the statistical results analysed among subgroups. Statistical heterogeneity was negligible in all outcome comparisons apart from the ‘operating time’, and thus the random-effects model was employed in that case. Funnel plots did not reveal any evidence of publication bias among studies.
Complications Anastomotic leaks (Fig. 1) There was no statistically significant difference between the two groups in regard to the incidence of ALs (RCTs: P = 0.51, all studies:
0.01 0.1 1 10 100 Favours suturing Favours stapling
P = 0.15), with an overall AL rate of 1.9% (84/4508). Fifty per cent of these cases required a re-operation. Small bowel obstruction (Fig. 2) A consistent definition of SBO was lacking in majority of the studies. Most of the studies defined any prolonged (more than 5 days) inability to have oral intake with nausea and/or vomiting, potentially requiring a nasogastric tube placement, as SBO. The majority of these cases though were subsequently treated and settled with conservative measures, and only a minority needed surgical intervention. In addition, six studies18–20,22,25,28 report on this outcome at 30 days post-operatively, with one23 reporting on ileus at 30 days. The rest of the studies either do not provide this information or combine it in a longer follow-up. Five different types of subgroup analyses were thus performed for this outcome. The first included all patients reported by studies as suffering from SBO, the second included all patients with SBO requiring re-operation, and the third © 2014 Royal Australasian College of Surgeons
Review of reversal of ileostomy techniques
Fig. 2. Reported small bowel obstruction at 30 days (a) and during combined short- and long-term follow-up (b).
5
(a)
Hand-suturing Stapling Total Events Total Weight Study or Subgroup Events 4.3.1 Randomized controlled trials Hasegawa et al 2000 Hull et al 1996 Loffler et al 2012 Shelygin et al 2010 Subtotal (95% CI)
10 2 24 2
70 30 165 56 321
2 1 17 1
Odds Ratio M-H, Fixed, 95% CI
71 31 163 63 328
2.8% 1.5% 24.1% 1.5% 30.0%
5.75 [1.21, 27.28] 2.14 [0.18, 24.96] 1.46 [0.75, 2.84] 2.30 [0.20, 26.03] 1.94 [1.11, 3.40]
96 132 315 543
10.7% 17.4% 42.0% 70.0%
0.99 [0.33, 2.96] 2.24 [1.07, 4.71] 2.60 [1.62, 4.17] 2.27 [1.57, 3.29]
871 100.0%
2.17 [1.59, 2.96]
Odds Ratio M-H, Fixed, 95% CI
21 38 Total events Heterogeneity: Chi² = 2.60, df = 3 (P = 0.46); I² = 0% Test for overall effect: Z = 2.31 (P = 0.02) 4.3.2 Case-control trials Balik et al 2011 Gustavsson et al 2012 Luglio et al 2011 Subtotal (95% CI)
8 34 107
129 219 629 977
6 10 23
39 Total events 149 Heterogeneity: Chi² = 2.53, df = 2 (P = 0.28); I² = 21% Test for overall effect: Z = 4.33 (P < 0.0001) Total (95% CI)
1298
60 Total events 187 Heterogeneity: Chi² = 5.42, df = 6 (P = 0.49); I² = 0% Test for overall effect: Z = 4.91 (P < 0.00001) Test for subgroup differences: Chi² = 0.21, df = 1 (P = 0.65), I² = 0%
(b)
Hand-suturing Stapling Study or Subgroup Events Total Events Total Weight 4.5.1 Randomized controlled trials Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
2 10 2 24
30 70 56 165 321
1 2 1 17
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
Odds Ratio M-H, Fixed, 95% CI Year
31 71 63 163 328
1.0% 1.8% 1.0% 15.4% 19.2%
2.14 [0.18, 24.96] 5.75 [1.21, 27.28] 2.30 [0.20, 26.03] 1.46 [0.75, 2.84] 1.94 [1.11, 3.40]
1996 2000 2010 2012
9 20 226 47 25 315 22 96 132 892
0.8% 3.2% 20.1% 3.5% 3.6% 26.9% 4.9% 6.8% 11.1% 80.8%
3.67 [0.20, 66.12] 1.33 [0.30, 5.93] 1.27 [0.68, 2.37] 0.49 [0.08, 3.05] 2.16 [0.57, 8.21] 2.60 [1.62, 4.17] 1.01 [0.28, 3.66] 0.99 [0.33, 2.96] 2.24 [1.07, 4.71] 1.84 [1.38, 2.46]
1987 1996 2005 2005 2010 2011 2011 2011 2012
1220 100.0%
1.86 [1.44, 2.40]
Odds Ratio M-H, Fixed, 95% CI
Total events 38 21 Heterogeneity: Chi² = 2.60, df = 3 (P = 0.46); I² = 0% Test for overall effect: Z = 2.31 (P = 0.02) 4.5.2 Case-control trials Feinberg et al 1987 Bain et al 1996 Wong et al 2005 Garcia-Botello et al 2005 Horisberger et al 2010 Luglio et al 2011 DHaeninck et al 2011 Balik et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
16 5 85 2 15 107 24 8 34
101 20 1278 62 66 629 175 129 219 2679
0 4 12 3 3 23 3 6 10
Total events 296 64 Heterogeneity: Chi² = 8.23, df = 8 (P = 0.41); I² = 3% Test for overall effect: Z = 4.13 (P < 0.0001) Total (95% CI)
3000
Total events 334 85 Heterogeneity: Chi² = 10.83, df = 12 (P = 0.54); I² = 0% Test for overall effect: Z = 4.72 (P < 0.00001) Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.87), I² = 0%
group included the reported SBOs that settled with conservative management, that is, potentially the subacute SBO or ileus at 30 days. The first two analyses were performed twice, once including studies reporting only 30-day outcomes and the second time including all studies together. A statistically significant lower rate of reported SBO, both at 30 days (RCTs: P = 0.02, all studies: P < 0.001) and during combined short- and long-term follow-up (RCTs: P = 0.02, all studies: P < 0.001), was seen in the stapled group. Similar results were seen for the 30-day conservatively managed SBO outcome (RCTs: P = 0.03, all studies: P < 0.001). The overall short- and long-term incidence rate of reported SBO was 11.4% and 9.9%, respectively. There was no significant difference between the two groups in regard to the number of SBOs requiring re-operation at 30 days (RCTs: P = 0.96, all studies: P = 0.63) or during combined shortand long-term follow-up (RCTs: P = 0.80, all studies: P = 0.47). The rate of re-operation for SBO was 1.6% within 30 days and © 2014 Royal Australasian College of Surgeons
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
1.8% during combined short- and long-term follow-up in all studies. The use of a two-layer closure compared to one-layer loop ileostomy closure in the handsewn group could have potentially narrowed the lumen, further creating a bias against this group in terms of subacute SBO. This hypothesis was tested by stratifying the studies accordingly and was rejected as the same benefit was still found in favour of the stapled group regardless of the use of a oneor two-layer handsewn closure. Re-operations (Fig. 3) Re-operation rates between the two groups were similar (RCTs: P = 0.84, all studies: P = 0.663) with a reported rate of 4.3% (111/2607). The two main complications leading to re-operation were SBO, accounting for at least 50% of cases, and ALs, accounting for at least 25% of cases. Other causes included volvulus, bleeding, iatrogenic enterotomies and fistulas.
6
Markides et al.
Hand-suturing Stapling Total Events Total Weight Events Study or Subgroup 4.7.1 Randomized controlled trials 1 1 1 7
30 70 56 165 321
2 3 0 4
Hull et al 1996 Hasegawa et al 2000 Shelygin et al 2010 Loffler et al 2012 Subtotal (95% CI)
Odds Ratio M-H, Fixed, 95% CI Year
31 71 63 163 328
2.1% 2.2% 3.2% 15.9% 23.5%
2.14 [0.18, 24.96] 3.13 [0.32, 30.88] 0.37 [0.01, 9.24] 0.55 [0.16, 1.93] 0.91 [0.37, 2.23]
1996 2000 2010 2012
9 20 25 315 22 96 132 619
2.0% 3.9% 1.6% 32.5% 15.0% 5.1% 16.2% 76.5%
0.68 [0.03, 14.07] 1.59 [0.24, 10.70] 1.17 [0.05, 29.62] 1.19 [0.58, 2.44] 0.42 [0.13, 1.41] 1.90 [0.36, 9.98] 1.43 [0.54, 3.83] 1.14 [0.71, 1.83]
1987 1996 2010 2011 2011 2011 2012
947 100.0%
1.09 [0.72, 1.65]
Odds Ratio M-H, Fixed, 95% CI
Fig. 3. Re-operations.
10 9 Total events Heterogeneity: Chi² = 2.50, df = 3 (P = 0.47); I² = 0% Test for overall effect: Z = 0.20 (P = 0.84) 4.7.2 Case-control trials 101 20 66 629 175 129 219 1339
3 3 1 26 15 5 14
Feinberg et al 1987 Bain et al 1996 Horisberger et al 2010 Luglio et al 2011 DHaeninck et al 2011 Balik et al 2011 Gustavsson et al 2012 Subtotal (95% CI)
0 2 0 11 4 2 6
25 67 Total events Heterogeneity: Chi² = 3.43, df = 6 (P = 0.75); I² = 0% Test for overall effect: Z = 0.56 (P = 0.57) 1660
Total (95% CI)
35 76 Total events Heterogeneity: Chi² = 6.09, df = 10 (P = 0.81); I² = 0% Test for overall effect: Z = 0.41 (P = 0.68) Test for subgroup differences: Chi² = 0.19, df = 1 (P = 0.66), I² = 0%
0.01 0.1 1 10 100 Favours [suturing] Favours [stapling]
Hand-suturing Stapling Study or Subgroup Mean SD Total Mean SD Total Weight 4.11.1 Randomized controlled trials
Mean Difference IV, Random, 95% CI Year
Loffler et al 2012 Subtotal (95% CI)
91.5
43.7
165 165
76.5 29.3
163 163
32.0% 32.0%
15.00 [6.96, 23.04] 2012 15.00 [6.96, 23.04]
15 37
25 315 340
31.1% 36.8% 68.0%
18.00 [9.40, 26.60] 2010 3.00 [-1.87, 7.87] 2011 10.06 [-4.61, 24.74]
Mean Difference IV, Random, 95% CI
Fig. 4. Operating time.
Heterogeneity: Not applicable Test for overall effect: Z = 3.66 (P = 0.0003) 4.11.2 Case-control trials Horisberger et al 2010 Luglio et al 2011 Subtotal (95% CI)
102 99
26 34
66 629 695
84 96
Heterogeneity: Tau² = 99.79; Chi² = 8.85, df = 1 (P = 0.003); I² = 89% Test for overall effect: Z = 1.34 (P = 0.18) Total (95% CI)
860
503 100.0%
11.52 [1.46, 21.57]
Heterogeneity: Tau² = 65.32; Chi² = 12.09, df = 2 (P = 0.002); I² = 83% Test for overall effect: Z = 2.24 (P = 0.02) Test for subgroup differences: Chi² = 0.33, df = 1 (P = 0.56), I² = 0%
Operating time (Fig. 4) Mean and SD of operating times, time to first bowel movement and length of hospital stay outcomes were only reported in three studies.19,26,28 Meta-analysis of these studies revealed a significantly shorter operating time for the stapled group (P = 0.02, WMD: 11.52, 95% CI: 1.46–21.57 min) but with statistically high heterogeneity, I2: 83%. The three additional RCTs17,18,20 and two of the CCTs23,27 (not included in the forest plot) reporting on this outcome also individually found a statistically significant shorter operating time in the stapled group. Only one study21 undertaken in 1996 with a group sample of 20 patients failed to show any difference in operating time between the two groups. Length of hospital stay (Fig. 5) Patients undergoing a stapled ileostomy reversal were found to have a shorter length of hospital stay compared to the handsewn group (P = 0.003, WMD: 0.70, 95% CI: 0.24–1.17 days). Two remaining RCTs (not included in the forest plot) reporting on this outcome showed a nearly statistically significant difference, P = 0.0720 and P = 0.09,17 with three additional CCTs22,25,27 confirming the same finding. Only two of the CCTs21,29 found no difference between the two groups of patients.
-100 -50 0 50 100 Favours [suturing] Favours [stapling]
Discussion A defunctioning loop ileostomy is fashioned to protect a more distal bowel anastomosis, especially when the risk of AL is considered to be high.30 It has been shown that in patients with a loop ileostomy, the impact of an AL is lower, especially after an anastomosis has been created below the peritoneal reflection or close to the anal canal.31,32 An AL is a dreaded complication which can result in sepsis with peritonitis and re-operation, and contribute to higher morbidity and mortality. Two previous reviews and meta-analyses failed to show any significant difference between loop ileostomy techniques, in relation to this outcome.11,12 The findings from this study appear to concur with these findings; no significant difference was seen for the risk of AL either between RCTs or pooled analysis of all studies. The overall 30-day mortality in this group of 4508 patients of approximately 0.1% is low and appears to be in keeping with the literature.10 Definition of SBO has been inconsistent on these studies. Nevertheless, regardless of how SBO is defined and whether only RCTs, high-quality CCTs or all studies together are considered, it appears that there is a significantly lower rate of conservatively managed © 2014 Royal Australasian College of Surgeons
Review of reversal of ileostomy techniques
Fig. 5. Length of hospital stay.
7
Stapling Hand-suturing SD Total Mean SD Total Weight Mean Study or Subgroup 4.13.1 Randomized controlled trials Loffler et al 2012 Subtotal (95% CI)
8.5
4.9
Mean Difference IV, Random, 95% CI Year
165 165
8.3 7.9
163 163
10.7% 10.7%
0.20 [-1.22, 1.62] 2012 0.20 [-1.22, 1.62]
66 629 695
7 2.7 4.7 3.5
25 315 340
11.3% 78.0% 89.3%
1.20 [-0.18, 2.58] 2010 0.70 [0.17, 1.23] 2011 0.76 [0.27, 1.26]
Mean Difference IV, Random, 95% CI
Heterogeneity: Not applicable Test for overall effect: Z = 0.28 (P = 0.78) 4.13.2 Case-control trials Horisberger et al 2010 Luglio et al 2011 Subtotal (95% CI)
8.2 5.4
3.7 4.6
Heterogeneity: Tau² = 0.00; Chi² = 0.44, df = 1 (P = 0.51); I² = 0% Test for overall effect: Z = 3.03 (P = 0.002) Total (95% CI)
860
503 100.0%
Heterogeneity: Tau² = 0.00; Chi² = 0.97, df = 2 (P = 0.61); I² = 0% Test for overall effect: Z = 2.96 (P = 0.003) Test for subgroup differences: Chi² = 0.54, df = 1 (P = 0.46), I² = 0%
SBO in the stapling group in the 30-day post-operative period. The lower rate of subacute SBO in the stapled group is potentially in keeping with the theory behind the formation of a wider anastomosis in this group compared to hand-suturing. Interestingly, when a more major complication such as the rate of re-operation secondary to SBO is considered, there is no difference between the two techniques either at 30 days or in the combined follow-up periods. Unfortunately, the cause of obstruction in this group of studies was scarcely reported. Studies that did report on the causation of operated SBO mostly reported adhesional causes.21 There was no effect on the results when the two studies21,28 reporting on the inclusion of mostly patients with inflammatory bowel disease (IBD) as their primary pathology were excluded from the calculations. Over this period of time when most of these studies were conducted, attitudes towards early nutrition, mobilization and discharge have changed especially with the use of enhanced recovery programme (ERP).33–35 Lengths of stay (LOS) after loop ileostomy reversal varied between studies from mean stay of 4.7–10 days, with no reported discharge criteria. The overall tendency was for a shorter LOS in the stapled group, confirmed by the meta-analysis of three of the studies (P = 0.003) conducted in the last 3 years. This finding is in accordance with the reduced rates of subacute SBO/ileus and earlier bowel movement found in the stapled group may confer an additional cost benefit. However in the setting of the ERP, the goal posts might shift and the shorter LOS in the stapled group might not have as big an impact as suggested by this review. All studies included in this review recruited patients undergoing loop ileostomy reversal for patients who had previously undergone surgery for malignancy, IBD or ileoanal pouch restoration. This has created potential clinical heterogeneity among studies, even though the reversal procedures were very well standardized within and among studies minimizing the degree of heterogeneity in regard to the actual interventions performed. A further feature of heterogeneity is the lack of a standardized perioperative care pathway. The included RCTs were also only powered to report on their primary outcomes, which are all different between studies. The secondary outcomes remained relatively poorly defined and underpowered. In view of the potential of clinical heterogeneity reported in this review, both a fixed-effects and a random-effects model were used with no difference between the two models in regard to outcome results. A cost-effectiveness analysis between the two techniques has not been conducted as part of this review. It could be argued that whether © 2014 Royal Australasian College of Surgeons
0.70 [0.24, 1.17] -100 -50 0 50 100 Favours [suturing] Favours [stapling]
the cost of stapler can be justified by the reduction in the LOS and reduction in the risk of SBO, which in turn increase the LOS. This perhaps can be the subject of another review with built-in costeffectiveness parameters. In conclusion, there appears to be no difference between handsewn and stapled techniques in the reversal of loop ileostomy with regard to short- and medium-term outcomes such as 30-day mortality (level 2 evidence), ALs (level 2 evidence), re-operations (level 2 evidence), post-operative bleeding (level 2 evidence) and 30-day wound infections (level 2 evidence). There is though a significant difference in favour of the stapled technique in terms of subacute SBO (level 2 evidence), operation time (level 2 evidence), time to first bowel motion (level 2 evidence) and length of hospital stay (level 2 evidence). On the basis of the level of evidence found in this review and meta-analysis, a Grade B recommendation (Oxford CEBM) can be made supporting the stapled technique as the preferred choice over handsewn anastomosis for the reversal of a loop ileostomy.
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© 2014 Royal Australasian College of Surgeons
