Side-to-side versus end-to-side ileocolic anastomosis in right-sided colectomies: A cohort control study.

Aims: The three main types of anastomotic configurations following colorectal resection are Side-to-Side Anastomosis (S-S), End-to-Side Anastomosis (E-S) and End-to-End Anastomosis (E-E). This study aims to present results from a local cohort supplemented by a systematic review with meta-analysis of existing literature to compare the post-operative outcomes between E-S and S-S.
Methods: A cohort study of patients who underwent right colectomy with E-S or S-S anastomosis, was conducted at the National University Hospital Singapore. Electronic databases Embase and Medline were systematically searched from inception to 21 August 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Studies were included if they compared post-operative outcomes between E-S and S-S.
Results: In the cohort study, 40 underwent E-S and 154 underwent S-S. Both post-operative ileus (12.5% vs. 29.2%, P = 0.041) and length of hospital stay (9.35 days vs. 14.04 days, P = 0.024) favoured E-S, but anastomotic bleed favoured S-S (15.0% vs. 3.2%, P = 0.004). Five studies were included in the meta-analysis with 860 E-S and 1126 S-S patients. Similarly, post-operative ileus (odds ratio [OR] =0.302; 95% confidence interval [CI]: 0.122-0.747; P = 0.010) and length of hospital stay (mean differences = ‒1.54 days; CI: ‒3.00 to ‒0.076 days; P = 0.039) favoured E-S. Additional sensitivity analysis including only stapled anastomosis showed a lower rate of anastomotic leak in E-S patients (OR = 0.185; 95% CI: 0.054-0.627; P = 0.007). Conclusions: This is the first systematic review to show that the E-S technique produces superior post-operative outcomes after right colectomy compared to S-S. However, the choice of anastomosis was largely surgeon dependent, but surgeon factors were not reported.

INTRODUCTION

Following bowel resection, anastomosis is performed to ensure bowel continuity.[1] There are three main anastomotic techniques which can be performed after right colectomy, namely the Side-to-Side Anastomosis (S-S), End-to-Side Anastomosis (E-S) and End-to-End Anastomosis (E-E). Even though the anastomotic technique potentially affects post-operative outcomes, there is currently no gold standard for right colectomy,[2] and the choice of anastomosis is largely dependent on the surgeons’ preference.[23] In addition, colonic anastomosis could be handsewn or stapled, with substantial evidence favouring the latter as the safer option.[45] With stapled anastomosis regarded as the safer option, it is therefore widely adopted in current practice.[1]

The S-S technique involves connecting the sides of two bowels and sewing or stapling close the ends of the bowel,[6] either in an anti-peristaltic or isoperistaltic fashion, for which both methods have presented similar results in terms of performance and safety.[7] Contrastingly, the E-S technique involves sewing or stapling the end of the ileum through an opening made at the side of the colon.[6] However, there are conflicting evidence on the safety of either technique. In a Cochrane meta-analysis published, the stapled S-S was reported to have a lower incidence of anastomotic leakage,[5] and has since widely accepted as the standard approach for right colectomy, especially in the case of colon cancer.[3] However, E-S has its utility in joining bowel segments when there is a size mismatch with existing evidence supporting its superior post-operative outcomes.[89] Most recently, preliminary results from a randomised controlled trial (RCT) by Kim et al.[10] suggested that E-S and S-S have similar post-operative outcomes in cancer patients and, neither was superior. Hence, this study aims to present results from our local cohort supplemented with a meta-analysis of the existing literature to investigate the post-operative outcomes of E-S and S-S.

METHODS

Retrospective cohort study

A retrospective data collection of patients who underwent right colectomy was performed at a tertiary hospital in Singapore, National University Hospital, from January 2016 to December 2019. Patient information including, but not limited to age, gender, stage of cancer, type of anastomosis and post-operative outcomes (anastomotic bleed, anastomotic leak, wound infection, ileus, length of hospital stay and 30-day post-operative mortality) were extracted and analysed in two respective groups (E-S vs. S-S). Anastomotic bleed being defined as those that experience post-operative intraluminal bleeding, presenting as a persistent melena.[11] Ileus is defined as the absence of passage of flatus or the presence of vomiting beyond postoperative day 3. Anastomotic leak is defined as a defect in the integrity of surgical connection between two hollow viscera, resulting in communication between the intraluminal and extraluminal compartments.[12] In our cohort, E-S anastomosis was performed with a 29-mm circular stapler (CDH29A) and S-S anastomosis with a 100 mm linear stapler, with extracorporeal anastomosis and 2 Stapler lines were being used for both methods. Statistical analysis was performed on stata 16.1 using the Students t-test for continuous outcomes, whereas the Chi-square and Fisher's exact tests were used for categorical/binary outcomes.

Meta-analysis

Search strategy and selection criteria

The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used in the synthesis of this review.[13] An electronic database search of Medline and Embase was performed on 21 August 2020 using keywords synonymous with ‘Anastomosis’ and; Colectomy.’ An example of the search strategy can be found in the Supplementary Material 1. Articles were included if they compared between E-S and S-S predominately in right-sided colorectal cancer surgery. However but case reports, cohort studies and RCTs were included in this review, reviews and commentaries were excluded., studies with no mention of right colectomy or did not compare between the anastomotic configurations were excluded. Observational, Sieving and Data Extraction

Article selection was performed by two authors, based on the pre-determined inclusion criterion, and any discrepancies were resolved based on the consensus with a third author. The blinded pair then independently extracted data regarding post-operative outcomes including the rate of anastomotic bleed, anastomotic leak, wound infection, post-operative ileus, length of hospital stays and mortality. When the mean and standard deviation data were unavailable, conversions of data were performed using the existing methods.[1415]

Statistical analysis and quality assessment

Meta-analysis was performed in this study using odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Regardless of heterogeneity as indicated by I and Cochran's Q test, random-effects models were applied. Analyses were carried out using RevMan 5.3. The Newcastle-Ottowa Scale (NOS)[16] and Jadad Scale were used to assess the quality of the included articles,[17] with NOS evaluating the nonrandomised cohort studies and the Jadad scale evaluating the RCTs, significance was considered at P ≤ 0.05.

RESULTS

A total of 194 patients were identified in this observational study. This comprises 40 E-S and 154 S-S patients. The mean age of the participants was 68.1 years old and 67.4 years old in the E-S and S-S groups, respectively. In the E-S and S-S groups, 82.5% and 90.3% of the patients had malignant etiologies, respectively. Laparoscopic surgery was more commonly associated with E-S patients (n = 28, 70%) than with S-S patients (n = 87, 56.5%) but was not significant (P = 0.121). Table 1 presents the summary of patients’ characteristics included in the study.

Table 1

Summary of patients’ characteristics in retrospective cohort study

Characteristics	E-S (n=40)	S-S (n=154)	P
Age (years)	68.1 (13.1)	67.4 (12.4)	0.756
BMI (kg/m2)	24.1 (4.70)	23.4 (4.67)	0.433
Gender
Male	23 (57.5%)	74 (48%)	0.287
Female	17 (42.5%)	80 (52%)
Race
Chinese	31 (77.5%)	119 (77.3%)	0.412
Malay	4 (10%)	7 (4.55%)
Indian	0	6 (3.90%)
Others	5 (12.5%)	22 (14.3%)
Lifestyle
Smoking	4 (10%)	23 (14.9%)	0.608
Alcohol	0	10 (6.49%)	0.126
Nature of tumour
Benign	7 (17.5%)	15 (9.73%)	0.431
Stage of tumour
1	2 (5%)	15 (9.73%)	0.573
2	15 (37.5%)	58 (37.7%)
3	14 (35%)	51 (33.1%)
4	2 (5%)	15 (9.73%)
Comorbidities
Diabetes mellitus	12 (30%)	53 (34.4%)	0.708
Hypertension	22 (55%)	93 (60.4%)	0.590
Hyperlipidaemia	21 (52.5%)	79 (51.3%)	1.00
Type of surgery
Open	12 (30%)	67 (43.5%)	0.121
Laparoscopy	28 (70%)	87 (56.5%)
Conversion to open	2 (5%)	9 (5.8%)	0.837
Elective	32 (80%)	124 (80.5%)	0.941
Emergency	8 (20%)	30 (19.5%)
Additional treatments
Adjuvant treatment	14 (35%)	56 (36.4%)	0.181
Neoadjuvant chemotherapy	0	4 (2.60%)	0.586
Anatomical measurements
Tumour length	4.59 (2.62)	4.81 (2.40)	0.627
Proximal margin	17.1 (13.1)	13.9 (11.8)	0.147
Distal margin	9.1 (3.53)	10.1 (5.99)	0.334

Values are given as n (%) or mean (SD). SD: Standard deviation, S-S: Side-to-side anastomosis, E-S: End-to-side anastomosis

Postoperatively, the outcomes were similar between both groups apart from anastomotic bleed, ileus and length of hospital stay. Anastomotic bleeding was more commonly associated with E-S than S-S (15.0% vs. 3.2%, P = 0.004), whereas ileus was less commonly associated with E-S compared to S-S (12.5% vs. 29.2%, P = 0.041). The length of hospital stay was significantly shorter in E-S compared to S-S patients (9.35 days vs. 14.04 days, P = 0.024). No significant differences were observed for anastomotic leak (2.50% vs. 8.44%, P = 0.308), wound infection (7.50% vs. 8.44%, P = 1.00) and mortality (5.00% vs. 7.14%, P = 1.00). Details of the E-S and S-S outcomes can be found in Table 2.

Table 2

Summary of end-to-side anastomosis and side-to-side anastomosis outcomes in retrospective cohort study

Outcome	E-S (n=40; 20.6%)	S-S (n=154; 79.4%)	P
Anastomotic leak	1 (2.50%)	13 (8.44%)	0.308
Anastomotic bleed	6 (15.0%)	5 (3.2%)	0.004*
Wound infection	3 (7.50%)	13 (8.44%)	1.00
Hospital stay (days)	9.35 (5.19)	14.04 (12.73)	0.024*
Ileus	5 (12.5%)	45 (29.2%)	0.041*
30 days mortality	2 (5.00%)	11 (7.14%)	1.00
Clavien-Dindo
0	11 (27.5%)	34 (22.1%)	0.602
1	14 (35%)	71 (46.1%)
2	12 (30%)	31 (20.1%)
3	2 (5%)	10 (6.50%)
4	1 (2.5)	5 (3.25%)
5	0	3 (1.95%)

*Significance where P≤0.05. Values are given as n (%) or mean (SD). SD: Standard deviation, S-S: Side-to-side anastomosis, E-S: End-to-side anastomosis

Meta-Analysis

The search strategy yielded a total of 30 studies, 20 were excluded based on the study titles and abstracts. Ten articles were derived for full-text review, of which five articles were subsequently included in the meta-analysis [Figure 1]. All articles included involved surgery performed on the right colon. The included articles originated from five different countries: two in Korea,[810] one in France,[18] Italy[9] and Spain.[19] Of the five studies, 1 was a prospective cohort study,[8] 2 were retrospective cohort studies[919] and the remaining 2 were RCTs.[1018] In total, taking into account the retrospective cohort study, 1986 patients underwent right colectomy, of which 860 underwent E-S while 1126 underwent S-S. Stapled anastomoses were performed in 598 and 664 patients in E-S and S-S, respectively. Colorectal cancer accounted for the majority cause of the operations (85.4%–100%). A summary of the included articles can be found in Supplementary Table 1.

Figure 1

Preferred reporting items for systematic reviews and meta-analysis flow diagram of included articles

Supplementary Table 1

Summary of included studies

Author	Year	Study design	Outcomes of interest (as reported by each study, or based on analysis of results)	Number of patients	Age (mean±SD)	Cancer (%)	Summary of inclusion criteria	Percentage of stapled	Quality assessment
Kracht et al.	1992	RCT	Anastomotic Leak: E-S: 12; S-S: 3 30 days mortality: E-S: 6; S-S: 2	E-S: 173; S-S: 106	E-S: 70.4±12.7; S-S: 68.0±14.0	100	Right hemicolectomy for right colon adenocarcinoma, both curative and palliative intent	E-S: 0; S-S: 100	3*
Golda et al.	2013	RNR	Anastomotic bleed: E-S: 5; S-S: 0	E-S: 174; S-S: 176	E-S: 68.2±10.4; S-S: 64.8±15.9	85.4	All patients who underwent elective right colectomy with anastomosis at the University Hospital of Bellvitge between 1 January 2006 and 31 December 2011	E-S: 100; S-S: 33.5	8
Puleo et al.	2013	RNR	Anastomotic leak: E-S: 6; S-S: 28 Anastomotic bleed: E-S: 1; S-S: 1 Wound infection: E-S: 2; S-S: 1 30-day mortality: E-S: 0; S-S: 2	E-S: 365; S-S: 579	-	100	Right hemicolectomy for both benign and malignant conditions from 2002 to 2007	E-S: 75.6; S-S: 40.4	7
Lee et al.	2016	PNR	Anastomotic leak: E-S: 0; S-S: 0 Anastomotic bleed: E-S: 0; S-S: 2 Wound infection: E-S: 1; S-S: 3 Post-operative ileus: E-S: 1; S-S: 6 Length of hospital stay: Mean (SD) E-S: 6 (1.53); S-S: 7.33 (2.3)	E-S: 43; S-S: 46	E-S: 62.5±12.3; S-S: 66.9±8.80	100	Elective laparoscopic right hemicolectomy and qualifies for the enhanced recovery programme	E-S: 100; S-S: 100	8
Kim et al.	2020	RCT	Length of hospital stay: Mean (SD) E-S: 5.67 (1.52); 6 (1.52)	E-S: 65; S-S: 65	-	100	Laparoscopic right hemicolectomy for colon cancer between September 2016 and August 2019	-	2*

*The study design of Kracht et al. and Kim et al. are graded using the Jadad Scale. RNR: Retrospective non-randomised study, PNR: Prospective non-randomised study, RCT: Randomised controlled trial, SD: Standard deviation, S-S: Side-to-side anastomosis, E-S: End-to-side anastomosis, NOS: Newcastle–Ottawa scale

Similar to the results in the retrospective cohort, E-S resulted in a significantly lower rate of post-operative ileus than S-S [OR = 0.302; 95% confidence interval (CI): 0.122–0.747; P = 0.010, Figure 2].[20] However, no significant differences were observed in the other complications such as anastomotic bleed [OR = 2.77; CI: 0.641–11.9; P = 0.173, Figure 3], anastomotic leak [OR = 0.646; CI: 0.149–2.80; P = 0.560; [Figure 4] and wound infection (OR = 0.921; 95% CI: 0.330–2.57; P = 0.876). Length of hospital stay was also found to be significantly shorter in the E-S when compared to S-S (MD = ‒1.54 days; CI: ‒3.00 to ‒0.076 days; P = 0.039), whereas the mortality rate was comparable between both groups (OR = 0.952; CI: 0.333–2.72; P = 0.927).

Figure 2

Illustration of side-to-side versus end-to-side, adapted from Zurbuchen et al.[20]

Figure 3

Forest plot for post-operative ileus

Figure 4

Forest plot for anastomotic bleed

Sensitivity analysis was performed for patients who received only stapled anastomoses in both E-S and S-S groups [Table 3]. After excluding hand-sewn patients, E-S results in a significantly lower rate of anastomotic leak [OR = 0.185; 95% CI: 0.054–0.627; P = 0.007, Figure 5]. Rate of post-operative ileus (OR = 0.30; CI: 0.12–0.75; P = 0.010) and length of hospital stay (OR = ‒1.54; CI: ‒3.00 to ‒0.076; P = 0.040) remained significantly lower and shorter in E-S patients. There was still no observable difference in the rates of anastomotic bleed (OR = 2.00; CI: 0.462–8.65; P = 0.35, [Figure 4]) and wound infection (OR = 0.87, CI: 0.30–2.53, P = 0.80). A summary of the results can be found in Table 3.

Table 3

Comparative and sensitivity analysis of end-to-side anastomosis and side-to-side anastomosis

Outcome	Comparative analysis of E-S versus S-S			Sensitivity analysis of E-S versus S-S
	Sample size	Effect size (95% CI)	P	Sample size	Effect size (95% CI)	P
Anastomotic leak	E-S: 621; S-S: 885	0.646 (0.149-2.80)	0.560	E-S: 319; S-S: 280	0.185 (0.054-0.627)	0.007*
Anastomotic bleed	E-S: 622; S-S: 955	2.77 (0.641-11.9)	0.173	E-S: 493; S-S: 339	2.00 (0.462-8.65)	0.35
Wound infection	E-S: 448; S-S: 779	0.921 (0.330-2.57)	0.876	E-S: 319; S-S: 280	0.87 (0.30-2.53)	0.80
Hospital stay (days)	E-S: 148 ;S-S: 265	-1.54 (-3.00--0.076)	0.039*	E-S: 108 ;S-S: 111	-1.54 (-3.00–-0.0764)	0.04*
Ileus	E-S: 83; S-S: 200	0.302 (0.122-0.747)	0.010*	E-S: 43; S-S: 46	0.30 (0.12-0.75)	0.01*
Mortality	E-S: 578; S-S: 839	0.952 (0.333-2.72)	0.927	-	-	-

*Significance where P≤0.05. CI: Confidence interval, S-S: Side-to-side anastomosis, E-S: End-to-side anastomosis

Figure 5

Forest plot for anastomotic leak before and after sensitivity analysis

DISCUSSION

In current clinical practice, the anastomotic technique following right colectomy remains widely varied.[1] Studies comparing E-S and S-S presented conflicting results,[38] and preliminary evidence from a recent randomised controlled trial (RCT) by Kim et al.[10] also showed that E-S and S-S resulted in similar outcomes. While post-operative outcomes can potentially be analysed to determine the optimal technique, the outcomes are usually confounded by factors such as the presence of adjuvant therapy, post-operative medications, patient's diabetic and nutritional status,[21] leading to the lack of a clearly superior anastomotic approach.

In this retrospective cohort study, post-operative complications such as the rate of anastomotic leak, wound infection and mortality were found to be comparable across E-S and S-S. Similar to previous studies,[810] the length of hospital stay was observed to be shorter in E-S than S-S and this was also reaffirmed in our meta-analysis comparing E-S and S-S. Lee et al.[8] suggested that the lower rate of post-operative ileus could be attributed to the isoperistaltic direction achieved by E-S anastomosis at the ileocolic junction,[22] which resembles the natural configuration, thus possibly allowing for an earlier recovery and shorter hospital stay. Isoperistaltic anastomosis allows for the coordination between the circular and longitudinal muscles, which might result in less damage to the muscular structure and earlier recovery of normal bowel function.[23] Contrastingly, all the S-S procedures were performed in the anti-peristaltic direction which do not support the early recovery of normal bowel function.[23]

However, the rate of anastomotic bleed was significantly higher in E-S than S-S in the retrospective cohort study and this corresponded with the retrospective study by Golda et al.,[19] but was not significantly different when results were pulled in the meta-analysis. The circular stapler used in E-S anastomosis has a resultant taller stapler height than the linear stapler used in S-S anastomosis which is the fundamental reason why there is an increased chance of anastomotic bleed.[24] Moreover, the linear stapler is stapled at a constant pressure while the force of the circular stapler depends on the user, and it is evident that the pressure employed may not always be suitable for the tissue thickness.[12] This observation was corroborated by Golda et al. and Noguchi et al. which showed a higher rate of lower gastrointestinal tract bleeding when a circular stapler was employed for the E-S procedure was compared against the linear stapler used for S-S.[1925]

The difference observed in our centre compared to other centre could be due to the lack of routine reinforcing suturing for stapled anastomosis in our center when compared to other centers. Though not explicitly mentioned in all papers quoted in our review, the use of reinforcing sutures remains a debatable practice in many centres worldwide. Despite the overall increased in bleeding, almost all cases of post-operative bleeding stopped spontaneously, without the need for further intervention. Individuals with the anastomotic leak, on the other hand, were managed in the Intensive Care Unit or resolved through a reoperation, depending as to whether they were classified as Clavien Dindo 3 and 4, respectively.

Sensitivity analysis was performed to include only stapled anastomosis in E-S and S-S anastomosis and revealed that stapled E-S resulted in a significantly lower rate of the anastomotic leak while the rate of anastomotic bleed remained insignificant. Colonic anastomotic leak, though rare in ileocolic anastomosis (1%–3%),[26] is often associated with increased mortality, length of hospital stay, health-care cost and decreased long-term survival.[27] Stapled anastomosis has been shown to reduce the rate of anastomotic leak,[45] hence the modality of anastomosis (handsewn or stapled) is a confounder. When removed in the sensitivity analysis, a significantly reduced rate of anastomotic leak in E-S was observed. Stapled E-S anastomosis differs from stapled S-S in 2 fundamental principles (a) E-S anastomosis is done at a distance from the resection margin unlike that of S-S. This brings the anastomosis further away from the watershed area, thereby decreasing the likelihood of poor blood supply (b) E-S anastomosis is fashioned with 2 non-overlapping staple lines whereas the conventional stapled S-S anastomosis results in an overlapping cross-staple line at the T-junction. The T-junction formed is the site at the highest risk of ischemia and is also the usual site of anastomotic leak. Since stapled E-S anastomosis could potentially reduce the rate of anastomotic leak, it explains the lack of significant reduction when handsewn E-S and S-S were included in the initial analysis.

Limitations

However, there were several limitations in this study. First, the choice of anastomosis (E-S or S-S) was largely surgeon dependent; however, surgeon factors were not reported in the included studies. Second, potential confounding factors such as variation in patients’ characteristics (e.g., diabetes mellitus and health status), or surgical techniques (e.g., adoption of reinforcing sutures) across the different centre were not always reported and thus could not be controlled for. Third, there could be differences in the definitions of post-operative complications across the various centre which can result in heterogeneity. While post-operative ileus was defined as the absence of passage of flatus or presence of vomiting beyond post-operative day 3 in the retrospective cohort, the included study Lee et al.,[8] defined postoperative ileus as the patient's intolerance of oral feeding. Moreover, the detection of anastomotic leak was not reported to be based on clinical or radiological findings. Finally, the analysis was based on a relatively small sample size which reduces the interpretability of the findings.

CONCLUSIONS

In all, this is the first systematic review to show that E-S is superior to S-S based on our centre's cohort which concurs with the meta-analysis of the available evidence. E-S anastomosis when compared to S-S anastomosis resulted in a decreased rate of postoperative ileus and decreased length of hospital stay. The meta-analysis of stapled-only procedures shows that E-S results had a lower rate of anastomotic leak than S-S. However, further evidence will be required from well-designed RCTs to clearly establish the superiority of E-S for right colectomy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.