Introduction

The aim of anal fistula treatment is to drain the infection, eradicate the fistula tract, prevent recurrences, and preserve continence. Simple anal fistulas such as intersphincteric fistulas and low transsphincteric fistulas that involve < 30% of the sphincter are easily treated by fistulotomy or fistulectomy [1]. However, the management of complex cryptoglandular fistulas remains challenging and controversial [1].

Complex anal fistula cases have been managed with a cutting seton to minimise faecal incontinence and recurrence [2]. However, the use of a cutting seton reportedly results in faecal incontinence in 12% of cases [3]. In an attempt to preserve faecal continence, various sphincter-preserving procedures have been proposed, including video-assisted anal fistula treatment, ligation of the intersphincteric fistula tract, and fistula laser closure; the success rates of these procedures reportedly range from 57 to 96% [4, 5]. Currently, the standard surgical treatment for complex anal fistulas is the rectal advancement flap (RAF), with a success rate of approximately 80% [6].

To increase the rate of healing and reduce the risk of faecal incontinence after treatment of complex anal fistulas, clinicians have applied biomaterials such as fibrin glue, anal fistula plugs, and stem cells [7,8,9]. One recently introduced minimally invasive treatment for anal fistulas is the injection of a saline suspension of porcine, acellular, cross-linked, dermal collagen paste (Permacol™ paste (PP); Medtronic, Mansfield, MA, USA) [10,11,12]. The collagen matrix is injected into the appropriately prepared fistula tract to promote cell migration of fibroblasts and muscle cells, and integration with the surrounding tissues, which promotes healing [11].

The aim of the present study was to compare the RAF and PP in the treatment of complex cryptoglandular anal fistulas in terms of healing rate, faecal continence, and patient satisfaction.

Materials and methods

This was a retrospective analysis of the electronic medical records on all patients treated for complex cryptoglandular anal fistulas with RAF or PP by a single colorectal surgery unit (“S. Maria dei Battuti” Hospital, Conegliano, Treviso, Italy) between September 1, 2013 and January 31, 2016.

Eligibility

Patients affected by primary and recurrent complex cryptoglandular anal fistulas, defined according to the American Society of Colon and Rectal Surgeons guidelines [1], who underwent RAF or PP procedures were included. The inclusion criteria were (1) transsphincteric fistula (tract crossing more than 30% of the external anal sphincter); (2) suprasphincteric fistula, (3) extrasphincteric fistula, or (4) horseshoe fistula. Exclusion criteria were Crohn’s disease, intersphincteric or low transsphincteric fistulas (involving < 30% of the sphincter complex), ano- or rectovaginal fistulas, rectourethral fistulas, faecal incontinence (Continence Grading Scale (CGS) > 9) [13, 14], prior rectal anastomosis, or prior pelvic radiotherapy. Therefore, after application of the exclusion criteria, 31 RAF patients and 21 PP patients were included in the present study.

Preoperative evaluation

The preoperative evaluation included clinical and proctologic examinations. During the clinical examination, the following variables were recorded: age, sex, and details regarding fistula surgery (i.e. aetiology of the fistula, number of previous repairs, and seton placement). The proctologic examination was carried out according to the American Society of Colon and Rectal Surgeons guidelines [1]. The severity of faecal incontinence was evaluated using the continence grading scale (CGS) [13]. We defined continence disorders (CGS ≤ 4) as the inadvertent escape of flatus or partial soiling of undergarments with liquid stool.

All patients received endoanal ultrasonography to assess fistula tracks according to the Parks classification [15]. The site of the internal opening was defined according to the criteria of Cho et al. [16] and categorised as being above, at, or below the dentate line (in relation to the presumed location of the dentate line at the middle third of the anal canal). The site of the internal opening was also characterised as being located at the 1- to 12-o’clock position. Other parameters evaluated were the tract length, presence of secondary tracts, horseshoe extension, degree of surrounding soft tissue changes, and associated sphincteric lesions.

MRI was performed in patients with recurrent fistulas, and in those in whom endoanal ultrasonography could not adequately assess the fistula tracks. All patients underwent preoperative anorectal manometry to assess sphincter function.

Surgical technique

All procedures were performed using general anaesthesia or locoregional anaesthesia. A single dose of antibiotics (cefotaxime 2 g and metronidazole 500 mg) was administered at the time of induction of anaesthesia.

All patients underwent a two-stage procedure. The first stage was the same for all patients, whereas the second stage differed between the two groups. In the first stage, a draining silicon seton was placed in the fistula tract. Patients were discharged home within 6–8 h postprocedure. The seton remained in situ until the fistula tract had completely drained, in order to obtain a non-suppurating tract without any residual abscess. During the second stage, the RAF was done in the RAF group, while the PP injection was performed in the PP group. All procedures were performed by the same experienced proctologic surgeon.

Rectal advancement flap group

The RAF was done according to the following technique [17]. The loose seton was removed, and the fistula tract was excised up to the external anal sphincter. The crypt-bearing tissue around the internal opening of the fistula was excised. The internal and external openings were sutured with interrupted sutures using 3/0 Vicryl (Ethicon Endo-Surgery, Cincinnati, OH, USA). A trapezoidal flap comprising mucosa, submucosa, and a few muscular fibres of the internal anal sphincter was raised immediately above the internal opening and mobilised by approximately 4–6 cm. The flap was advanced distally, without tension, 1 cm below the dentate line, and sutured with interrupted sutures using 3/0 Vicryl (Ethicon Endo-Surgery, Cincinnati, OH, USA). The external wound was left open for drainage.

Permacol™ paste group

The seton was removed, and the fistula tract was accurately debrided with a brush and flushed with sterile saline solution. The internal opening was excised, including the crypt-bearing tissue. The internal opening was then closed with one or two sutures using 2/0 Vicryl (Ethicon Endo-Surgery, Cincinnati, OH, USA). A flexible cannula sheath was then inserted into the external opening of the fistula, and PP was injected to fill the tract completely. In patients with a horseshoe anal fistula, the Permacol™ paste was injected through each of the external orifices. The external wound was partially closed with interrupted sutures using 3/0 Vicryl (Ethicon Endo-Surgery, Cincinnati, OH, USA) to prevent early leakage of the biomaterial.

Postoperative follow-up

The patients were discharged within the first 24 h postoperatively with a prescription for stool softeners for 4 weeks. All patients received scheduled follow-up clinical and proctologic examinations at the outpatient clinic at postoperative 1, 2, and 4 weeks, and 3, 6, 12, and 24 months.

Healing was defined as the complete reepithelisation of the external opening, closure of the internal opening, and clinical absence of any drainage through the external or internal opening at 6 months postoperatively. Operative failure was defined as persistence of symptoms within 6 months of intervention, whereas it was considered recurrent if it was completely healed at any point followed by redischarge. In cases of operative failure or recurrence, the patients were admitted for further surgical treatment. All patients underwent anorectal manometry at 3 months after the second stage of surgery.

At each follow-up visit, the degree of pain was evaluated on a numeric rating scale where 1 indicated no pain, and 10 indicated the worst pain imaginable.

At 2 years postoperatively, patients completed a questionnaire comprising the following questions concerning patient satisfaction with the surgical outcome: (1) ‘How well did the surgery relieve the symptoms related to anal fistula?’, (2) ‘Would you have this operation again?’, and (3) ‘Would you recommend this operation to another?’ The answers were recorded using a 10-point rating scale ranging from 1 (dissatisfied) to 10 (very satisfied). The satisfaction scores were grouped into four categories: “very satisfied” (score 8–10), “satisfied” (score 5–7), “poorly satisfied” (score 3–4), and “dissatisfied” (score 1–2).

Statistical analysis

Data were analysed using IBM SPSS Statistics for Mac OS, version 22.0 (IBM Corp., Armonk, NY, USA). The results were reported as the mean ± standard deviation, median (range), and number of patients (percentage). Continuous data were analysed using the Mann–Whitney U test (Wilcoxon Rank Sum test). Differences between categorical data were evaluated using the Fisher’s exact test or the Pearson’s chi-squared test, as appropriate. The Kaplan–Meier method was used to generate survival curves. The Log-Rank test (Mantel Cox) was applied to compare the differences between the two curves. Comparisons between preoperative and follow-up data were carried out using the Wilcoxon test for continuous data for two related samples, and the test of marginal homogeneity for non-dichotomous categorical data. Mixed-model ANOVA for repeated measures was used to estimate the effect of treatment, time, and the treatment-by-time interaction on each outcome variable, adjusted for the baseline value of that outcome variable. The treatment-by-time interaction allowed the treatment effect to vary (i.e. increase or decrease) over time. In this analysis, no structure was imposed on the (co)variances of the residual error term. Baseline-adjusted mean levels and differences between the treatment groups and their standard errors and confidence intervals were estimated. A p value of less than 0.05 was considered statistically significant.

Approval and consent

All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration, last amended at the 64th WMA General Assembly, Fortaleza, Brazil, October 2013, or comparable ethical standards. For this type of study, formal consent by the institutional research committee is not required in Italy. Informed consent was obtained from all individual participants included in this study.

Results

We analysed 31 consecutive patients, 17 male (55%) and 14 female (45%) treated with RAF between October 2013 and November 2014 and 21 consecutive patients, 12 male (57%) and 9 female (43%), treated with PP since Permacol™ collagen paste became available in our Department in November 2014 through January 2016. No patients were lost during follow-up. Three patients in RAF group decline to answer the questionnaire and returned the questionnaire incomplete.

The two groups were comparable in terms of preoperative characteristics. There were no significant differences between the two groups regarding sex, age distribution, type of fistula and location of the internal orifice opening, previous amount of fistula surgery, and episode of recurrence.

The patient demographics and fistula characteristics are listed in Table 1.

Table 1 Preoperative characteristics of both groups
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Patients experienced symptoms of anal fistula for a median of 7 weeks (range 3–12 weeks) in the RAF group, and 8 weeks (range 3–13 weeks) in the PP group (p = 0.933). All 52 patients were treated with a loose seton before the definitive surgery. Seton drainage was done in all patients in both groups for a median duration of 8 weeks (range 4–18 weeks) before the final surgery (p = 0.719). No patient had faecal incontinence (CGS ≥ 5) preoperatively; although one patient (3%) in the RAF group and six (29%) in the PP group experienced continence disorders (p = 0.009). Preoperative anal manometry revealed no differences between the two groups in maximum anal resting pressure (MARP) and maximum squeeze pressure (MSP) (p = 0.507 and p = 0.840, respectively).

Postoperative follow-up

No intraoperative complications were recorded. Operative failure was observed in five (16%) patients within in the RAF group and one (4%) patient within PP group.

In the RAF group, three patients out of the five failures had flap disruption during the first week. Two patients developed a perianal abscess at 4 weeks postoperatively that was immediately drained.

In the PP group, two patients were readmitted with a fever of > 38.5 °C within 1 week postoperatively and discharged after a few days without reintervention; one patient had a perianal hematoma that was successfully managed conservatively. In one patient, the failed surgical procedure required to undergo a second surgery since a postsurgical perianal abscess developed within a week on the same site where paste was installed. Paste was removed and the abscess fully drained.

All patients complained of persistence of the fistula. The patients underwent rectal advancement flap repair (n = 2), mucosal advancement flap repair (n = 1), and ligation of the intersphincteric fistula tract (n = 2) after RAF failure. Fistula closure was achieved in 4 of 5 patients.

One patient underwent an advancement flap procedure after failure of paste injection, which was unsuccessful too.

Out of these, two underwent reoperation for recurrent fistula (cutting seton procedure).

Table 2 summarises the pre- and postoperative characteristics in each group.

Table 2 Assessed parameters before and after the surgical procedures
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Continence grading scale

In the PP group, one of the six patients with a preoperative continence disorder developed faecal incontinence postoperatively, whereas the other 20 patients maintained their initial condition. In the RAF group, the one patient with a preoperative continence disorder developed faecal incontinence postoperatively, along with another four patients without preoperative symptoms. In the RAF group, there was a significant increase in CGS at 3 months postoperatively compared with preoperatively (p = 0.000), which was confirmed for the RAF group in the categorical analysis (p = 0.004). However, these trends in CGS were not significant in the PP group (p = 0.186).

Manometry

At the 3-month postoperative anal manometry, the RAF group had a lower median MARP compared with the PP group (72 (range 44–94) vs. 74 (range 61–89); p = 0.2000). In contrast, the MSP was comparable between the two groups (p = 0.910). Both groups showed a significant decrease in MARP and MSP. There was no significant treatment-by-time interaction for MSP [F (1, 50) = 3.39; p = 0.071]. However, the treatment-by-time interaction for MARP was significant [F (1, 50) = 12.54; p = 0.001], with a greater decrease in mean pressure in the RAF group than in the PP group.

Recurrences and patient satisfaction

During the follow-up period, after excluding patients with operative failure, fistula recurrence developed in six (19%) patients in the RAF group and nine (43%) in the PP group. In the RAF group, five out of the six recurrences occurred during the first 3 months postoperatively.

All of the patients with a recurrent fistula were symptomatic and underwent reoperation: mucosal advancement flap repair (n = 4) and cutting seton positioning (n = 2). Out of these, three developed recurrence after redo surgery and underwent a new operation and all three were successful.

In the PP group, three patients experienced reopening of the external orifice without drainage; two of these patients developed a recurrence, while one healed. In the PP group, there were three anal abscesses at the paste injection site. One patient experienced PP extrusion at 1 month postoperatively, which evolved into a recurrence. Of these nine patients, three developed recurrence at 6, 12, and 24 months after the surgery, respectively.

The patients were symptomatic and underwent alternative treatments: rectal advancement flap repair (n = 2), mucosal advancement flap repair (n = 4), ligation of the intersphincteric fistula tract (n = 1), and cutting seton positioning (n = 2). Seven patients healed and two procedures were unsuccessful and the patients required redo surgery.

The 2-year disease-free survival was 65% in the RAF group, and 52% in the PP group (p = 0.659).

The Kaplan–Meier estimates in Fig. 1 show a decrease in the percentage of patients with healed fistulas, which after 6 months decreased to 65% in the RAF group and to 66% in PP group; after 12 and 24 months, it remained unchanged (65%) in RAF group. In PP group, it decreased to 57% of patients after 12 months and to 52% after 24 months. At the 2-year follow-up, evaluation of the closure rate demonstrated that successful closure had been achieved in 20 (65%) patients within in the RAF group and 11 (52%) patients within PP group (p = 0.659).

Fig. 1
figure 1

Disease-free survival

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Table 3 summarises the results of the satisfaction questionnaire.

Table 3 Patient satisfaction scores
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The median scores for satisfaction were 5 (range 1–10) in the RAF group, and 7 (range 2–10) in the PP group (p = 0.299). Patients who underwent PP treatment tended to be more satisfied than patients who underwent the RAF treatment, but this difference did not reach statistical significance (p = 0.584). Compared with the PP group, the RAF group were significantly less inclined to have the operation again or to recommend the procedure to others (p = 0.002 and p = 0.005, respectively).

Figure 2 shows patients satisfaction

Fig. 2
figure 2

Patient satisfaction. RAF rectal advancement flap, PP Permacol™ paste

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Discussion

In this study, the recurrence rates in both groups (35% in the RAF group vs 48% in PP group) were not significantly different, at a median follow-up of 24 months.

The current standard surgical option for complex cryptoglandular anal fistulas is RAF, with a success rate ranging from 36.6 to 93% [17, 18].

The long-term effectiveness of preservation of the sphincter muscle function has yet to be clarified. While Schouten et al. reported a 35% incidence of faecal incontinence [19], Mizrahi et al. found that only 9% of patients experienced worsening of anal continence [18]. The different studies have selected heterogeneous populations, and it is difficult to compare the “transanal rectal advancement flap”, which makes it impossible to compare the clinical outcomes between studies (Table 4) [6].

Table 4 Characteristics of previous studies involving rectal advancement flap surgery
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After 2 years of follow-up, the healing rate in RAF group was 65% compared with 52% in the PP group. Our overall healing rates were lower than the results of other studies, which reported healing rates of approximately 76% [19, 20, 22,23,24,25,26,27,28]. The different results reported in the literature suggest that technical factors dependent on the individual surgeon could play a substantial role in the clinical outcome [29]. In our series, 10 patients (32%) in the RAF group needed multiple operations to successfully treat high fistulas. Ozuner et al. reported a high recurrence rate in patients who had undergone previous anal fistula surgery [20].

In the present study, the use of PP seemed to be a promising alternative to the RAF, but the overall success rate of PP was only 57% at 1 year postoperatively. However, in the long-term, PP proved effective in maintaining the results, and our success rate was slightly better than the overall success rate reported in the literature of 54 to 48% [10, 30]. The poor results after PP treatment could be due to the inadequate removal of granulation tissue from the internal wall of the fistula tract, which inhibits fibroblast infiltration, vascular ingrowth, and tissue remodelling [11]. Furthermore, recurrence may result from inadequate drainage of the infection and/or the absence of uniform penetration into the fistula tract and inevitable leakage of PP from the external fistula [12, 30].

An adequate follow-up duration is essential for the assessment of the cure rate. Mizrahi et al. reported a recurrence rate of 78% within the first year postoperatively, and a recurrence rate of 15.7% after 3 years or more of follow-up [18]. In our series, one patient (4% PP, 1% RAF) in each group developed late recurrence after 1 year of follow-up. According to Soltani et al., studies with a short follow-up should be evaluated with caution [6]. Therefore, the relatively long duration of follow-up in our study could explain the poorer results compared with studies with a shorter follow-up duration.

At 6 months postoperatively, three patients (14%) in the PP group presented with asymptomatic reopening of the external orifice. Endoanal ultrasonography revealed the presence of intersphincteric fistulas. It is likely that these failures occurred due to incomplete filling of the fistula by the PP, thus preventing cellular interaction and void-filling tissue growth [11].

In our series, immediate postoperative disruption of the RAF occurred in three patients (10%). This could be due to ischemia of the flap or to tension. Contrary to the report by Khafagy et al., we did not observe spontaneous closure after RAF disruption [25]. Three patients developed persistence of the fistula. Furthermore, we recorded four anal abscesses at the paste injection site. This may have occurred for technical reasons [10]. It should be noted that we adhered to the guidelines recommended by the manufacturer.

Apart from the healing rate, our end points included continence and patient satisfaction.

Postoperative worsening of faecal continence was found in five patients (16%) in the RAF group, and in one (5%) in the PP group. This may be due to previous surgical treatments, including abscess drainages and previous fistula repair. However, Balciscueta et al. found that all flaps cause some incontinence, which increases with the thickness of the flap [31]. In our series, we included 10 patients (32%) in the RAF group and five (24%) in the PP group who had undergone multiple (more than two) surgical treatments and already had continence disorders. The inclusion of patients with continence disorders affected the rate of faecal incontinence, and explains the incidence of faecal incontinence in the PP group. These patients underwent endoanal ultrasonography that showed partial internal and external sphincter damage. It is difficult to compare the results of various previous studies regarding the state of faecal continence postoperatively [22]; most authors did not use a scoring system, and only mentioned the presence of minor and major continence disturbances [25]. In the present study, we precisely defined continence disorders as a CGS ≤ 4.

Similarly to Garcia-Aguilar et al., our series confirms that patient dissatisfaction is associated with fistula recurrence and anal incontinence [32]. In our study, we found that patients had similar satisfaction results regarding the relief of the symptoms related to anal fistula and this could be explained by the similar recurrence rate between the two groups. On the contrary, the RAF group tended to have a lower rate of satisfaction than the PP group in terms of inclining to have the operation again or to recommend the procedure to others. A greater degree of dissatisfaction was attributed to anal incontinence. Assuming a causal relationship between faecal incontinence and dissatisfaction, a greater degree of dissatisfaction could be prevented by using PP rather than RAF, as PP reduced postoperative faecal incontinence without increasing fistula recurrence.

Our study has several advantages. First, the study included a homogenous population concerning the aetiology and severity of disease. Second, the long follow-up, single-surgeon database, and performance of all procedures by the same experienced proctologic surgeon maximised the certainty of healing and eliminated the technical variability due to different surgeons. Finally, we accurately planned the follow-up period and offered the patients free proctologic examinations in case of new symptoms.

The present study also has some limitations. First, the small number of patients treated limited the strength of our statistical analyses. Second, patients who had received previous surgery for complex anal fistula were included, which may have altered the results in terms of continence and healing rate. Third, the retrospective nature of this study is associated with bias inherent to this study design. Finally, we did not investigate the risk factors for the development of recurrence.

Conclusions

The RAF appeared superior to PP in terms of fistula healing, although this result was not statistically significant. On the contrary, PP has a potential advantage in terms of continence disorders and satisfaction. As the PP injection is minimally invasive and technically easy to install in the fistula tract, it can be considered for use as the initial treatment option for complex cryptoglandular anal fistulas in patients with faecal continence disorders. However, due to the small group size, a definite statement cannot be made. Further studies are needed to evaluate the potential benefits of PP in the treatment of complex cryptoglandular anal fistulas.