Out of 1549 articles initially identified by the search, 70 were selected for a full text review (Fig. 1). Fifty-five articles were excluded for the following reasons: forty-two articles did not describe the criteria for elective surgery nor did they report separately on the results of acute and elective surgery. Six studies included less than 25 elective patients [9,10,11,12,13,14]. Four studies reported on two identical or overlapping cohorts [15,16,17,18] and were, therefore, combined for the purpose of our analysis. One study described staged management [19], and three other studies did not report on this review’s primary outcome [20,21,22]. One study was a conference abstract. Finally, fifteen studies (10 retrospective cohort studies [16, 17, 23,24,25,26,27,28,29,30] and five prospective cohort studies [31,32,33,34,35]) were included, comprising a total of 1380 patients who had undergone elective ECF/EAF surgery. Included studies were published between 2004 and 2016. Table 1 presents the characteristics and outcomes of the included studies.

Fig. 1 Flowchart of the systematic review Full size image

Table 1 Study characteristics and outcome Full size table

Baseline characteristics of included studies

The mean or median age varied between 48 [26] and 61 [28] years. Studies were comparable for the included percentage of small bowel fistulas, being more than 65% in each study. Other fistulas included were colonic fistulas, and four studies [24,25,26, 34] included gastric fistulas (less than 6% of the fistulas). The etiologies of the fistulas were comparable in most studies, with more than 75% of the patients having fistulas as a result of complicated abdominal surgery. Only one study showed a lower percentage (50%) of postoperative fistulas [27]. The percentage of patients with inflammatory bowel disease (IBD) varied between 10% [25] and 50% [23]. Most studies included both simple and complex fistulas such as EAF, and low as well as high-output fistulas. Wainstein [30] focused on patients with EAF only, and the study of Martinez [34] included 84% EAF. Connoly et al. [31] included fistulas within the open abdomen. Two other studies [28, 33] focused on ECF takedown and simultaneous large complex hernia repair. It is likely that these studies included more complex fistulas than the other studies, but this was difficult to determine. Not all studies reported on all outcome parameters, and therefore, the number of studies included in each meta-analysis varied.

Quality of the studies included

All the studies included were scored using MINORS, and the scores ranged from 6 to 14 points (maximum possible score is 14, Table 1). No studies were excluded after scoring.

Outcomes

ECF recurrence

Recurrence rates ranged from 5 to 38% (Table 1). In four studies, recurrence was defined as 30-day recurrence [25, 26, 28, 33], in two studies as 3-month recurrence [23, 27], and in one study as 6-month recurrence [32]. Eight other studies defined recurrence as recurrence at any point of time during follow-up (Table 1). The weighted pooled ECF recurrence rate was 19% (95% CI 15–24), I 2 76% (Fig. 2). Figure 3 shows the median time to surgery and the minimum of the range (left y-axis) and the percentage of recurrent ECF (right y-axis). Lower recurrence rates were found in studies with a longer median time and/or, at the minimum of the range, a longer time interval to surgery. Lynch et al. [23] found an overall recurrence rate of 21%. A subgroup analysis of those patients who had undergone surgery within 3 months showed a recurrence rate of 28% (10 of 36) compared to a recurrence rate of 15% (7 of 114) in patients who had their operation after more than 3 months (P = .088). In a univariate analysis, Martinez [34] found that fistula surgery within 20 weeks was positively associated with mortality (P = 0.03). However, they did not find an association with fistula recurrence (P = 0.55). Brenner et al. [24] found that a waiting time of 36 weeks or longer was a significant risk factor for fistula recurrence. Patients who had undergone surgery after 36 weeks found a recurrence rate of 36%, compared to 12% in patients who had waited less than 36 weeks (P = .003). However, no statistical correction for confounding variables such as (co)morbidity was performed and these patients may have had significant morbidities delaying their surgery.

Fig. 2 Weighted pooled ECF recurrence rates Full size image

Fig. 3 Median and range in time to surgery and ECF recurrence Full size image

Mortality

Short-term mortality rates were described in all studies except in two [23, 34]. Mortality rates ranged from 0 to 7% (Table 2). The overall weighted pooled mortality was 3% (95% CI 2–5), I 2 0% (Fig. 4). The highest mortality rate (7%) was reported by the study with the shortest median waiting period to definitive surgery (median 72 days, range 4–270 days) among the included studies [16]. All other studies reported mortality rates of 5% or less. Lynch et al. [23] reported a 3-month mortality rate of 3%. Martinez [34] reported a mortality rate of 20%, but this was mortality at any point during follow-up and the total follow-up time was not recorded.

Table 2 Significant risk factors influencing recurrence and mortality extracted from included studies Full size table

Fig. 4 Weighted pooled short-term mortality rates Full size image

Morbidity

There was a wide variation in the methods of reporting morbidity in the 15 studies. As listed in Table 1, morbidity was reported in only 10 of the 15 studies. Different classification systems were used, and therefore, pooling of morbidity data for meta-analysis was not possible. Six studies observed overall morbidity varying between 72 and 88% [16, 25, 27, 28, 30, 31]. One study reported a postoperative complication rate of 36% (scored according to the Clavien–Dindo classification Grade III or IV) [29]. Four studies reported on the occurrence of surgical site infections (SSIs) as described by the Center for Disease Control and Prevention [25, 28, 31, 33]. These ranged from 21% to 65%. Krpata et al. [34] found the highest percentage of SSIs, 65%; 19% of patients required an additional surgical intervention; and 19% required interventional radiology. Other studies reported less than 40% SSIs (range 21–38%). In one of these studies [31], 5% of the patients needed radiological drainage and in another study [32] 3% needed surgical re-interventions. More detailed information about the need for interventions for SSI was not provided. One study [23] did not report on morbidity but described a 6% reoperation rate after surgery.

Hernia recurrence rate

Only three studies reported hernia recurrences rates [28, 31, 33]. The weighted pooled recurrence rate was 31% (95% CI 24.0–39.0) (Fig. 5). All studies involved large abdominal wall defects with simultaneous ECF takedown. Information on removal of infected mesh was not reported.

Fig. 5 Weighted pooled hernia recurrence rates Full size image

Krpata et al. [33] used a non-cross-linked biologic mesh in 97% of the cases. In 11%, a bridging mesh was required. They had a hernia recurrence rate of 32%, at a mean follow-up of 20 months. Connoly et al. [31] used either suture repair, suture repair with inlay prosthetic mesh, or prosthetic mesh alone and found an overall hernia recurrence rate of 29% (follow-up median 29 months). Slater et al. [28] found a hernia recurrence rate of 36% (mean follow-up of 63 months), using a component separation technique in 87% (34 of 39) of the patients, with a lightweight polypropylene mesh as reinforcement in 35% (12 of 34) of them. In that study, 10% of the patients had a bridging repair.

Fistula closure rate

Twelve studies reported a total fistula closure rate that varied between 80 and 97% [16, 17, 24,25,26,27, 29, 30, 32,33,34,35]. Some of the patients needed up to three reoperations to achieve fistula closure; some patients died after recurrent fistulas; and others were left with a fistula because the risk of a reoperation was deemed too high.

Enteral autonomy

Only four studies reported on patients regaining enteral autonomy. Datta [32] reported that of 12 patients receiving PN before definitive surgery, none remained dependent after surgery. In another study [27], in which 52% of the patients required preoperative PN, all but two could discontinue PN. In two other studies [25, 29], with 80 and 100% of the patients requiring PN preoperatively, respectively, 86 and 79% of the patients were able to discontinue PN postoperatively.

Risk factors for recurrence and mortality

Many of the studies performed analyses to define risk factors for ECF recurrence, mortality, morbidity, hernia recurrence, or other factors negatively associated with healing. As ECF recurrence was the primary outcome of the present review, and mortality was also regarded as an important other outcome, risk factors that were found to be statistically significant for recurrence and mortality in one or more of the included articles have been summarized. Eight studies performed a specific analysis for risk factors for recurrence and mortality. For this review, these factors were divided into preoperative, operative, and postoperative risk factors and are summarized in Table 2.

Some of the risk factors are generally related to poor outcomes, such as postoperative complications or comorbidity. Other risk factors such as surgical technique are of more interest as they can be amended by the surgeon. Lynch et al. [25] found a fistula recurrence rate of 36% in those patients who underwent oversewing or wedge repair of an ECF, in contrast to a 17% recurrence in those patients who had undergone complete resection of the affected bowel segment. Brenner et al. [27] also found a fistula recurrence percentage of 22% for oversewing or wedge repair and 11% for complete segment resection. Although this effect on short-term fistula recurrence was not significant, it did have a significant effect on 1-year mortality (P = .003). Two studies showed that a stapled anastomosis was associated with a less favorable outcome [27, 28]. Brenner et al. [27] found a stapled anastomosis to be independently associated with ECF recurrence, and Owen et al. [28] found a significant negative effect of a stapled anastomosis during fistula surgery on 1-year mortality.