Systematic review

doi:10.1111/j.1463-1318.2008.01483.x

Surgical management of anal stulae: a systematic review

A. I. Malik and R. L. Nelson
Colorectal Unit, Department of Surgery, Northern General Hospital, Shefeld, UK Received 10 September 2007; accepted 12 September 2007

Abstract
Objective The anal stula has been a common surgical ailment reported since the time of Hippocrates but little systematic evidence exists on its management. We aimed to systematically review the available studies relating to the surgical management of anal stulas. Method Studies were identied from PubMED, EMBASE, Cochrane Controlled Trials Register, ClinicalTrials.Gov and Current Controlled Trials. All uncontrolled, nonrandomized, retrospective studies, duplications or those unrelated to the surgical management of anal stulas were excluded. Results The search strategy revealed 443 trials. After exclusions 21 randomized controlled trials remained evaluating: stulotomy vs stulectomy (n = 2), seton treatment (n = 3), marsupialization (n = 2), glue therapy (n = 3), anal aps (n = 3), radiosurgical approaches (n = 2), incision (n = 1). drainage stulotomy stulectomy at time of abscess (n = 5) and intra-operative anal retractors Two meta-analyses evaluating incision and alone vs incision + stulotomy were obtained.

Conclusion Marsupialization after stulotomy reduces bleeding and allows for faster healing. Results from small trials suggest ap repair may be no worse than stulotomy in terms of healing rates but this requires conrmation. Flap repair combined with brin glue treatment of stulae may increase failure rates. Radiofrequency stulotomy produces less pain on the rst postoperative day and may allow for speedier healing. Major gaps remain in our understanding of anal stula surgery. Keywords Systematic review, stula-in-ano, seton, stulotomy, stulectomy, perianal abscess, glue therapy, ap repair

Background and aims

Anal stulae have been known as a common surgical ailment for over two and a half millennia. One of the earliest papers written by Hippocrates in 400 BC described stulotomy as well as his use of a cutting seton made of horse hair wrapped with lint threads [1]. Current management remains dependent on surgeon preference between options like stulotomy, stulectomy and (loose or cutting) seton insertion. Recently, newer sphinctersaving approaches utilizing aps, brin glue and plugs of various types have emerged especially for dealing with complex (high or trans-sphincteric) anal stulae. The rst meta-analysis was by Nelson who suggested that recurrence was less likely if stulotomy was performed at the same time as incision of a perianal abscess [2]. A more detailed meta-analysis by Quah et al. looked at the same area [3]. They analysed data from ve studies

again looking specically at the role of stulotomy at the time of perianal abscess drainage. We feel pooling of data from these analyses is open to question for reasons explained in this article. To date there is no other systematic evidence available evaluating global treatment for anal stulae. We reviewed all available randomized controlled studies relating to the surgical management of anal stulae.

Method
Study search and selection

Correspondence to: Prof. R Nelson, Department of Surgery, Northern General Hospital, Herries Road, Shefeld S5 7AU, UK. E-mail: rick.nelson@sth.nhs.uk

English and non-English randomized controlled trials (RCTs) relating to the surgical management of anal stulae were identied from PubMED, EMBASE, Cochrane Controlled Trials Register, ClinicalTrials.Gov and Current Controlled Trials. A high sensitivity, low specicity approach was utilized in order to reduce chances of missing relevant studies. For example the search terms used for PUBMED were (anal OR anus OR anorectal OR in-ano) AND (stul*) AND (randomized OR randomized

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A. I. Malik & R. L. Nelson

Surgical management of anal stulae

OR trial OR control*) with similar but slightly altered terminology for compatibility with the other databases. Selected articles and reviews were scanned for further citations. To minimize publication bias a hand-search of colorectal conference proceedings (ACPGBI and ASCRS) for the previous 5 years was performed to detect any unpublished studies with negative results. All uncontrolled, nonrandomized, retrospective studies, duplications, those unrelated to the surgical management of anal stulae or studies purely recruiting Crohns patients were excluded.
Quality assessment

For assessment of study quality, individual study quality assessment was made focussing on the presence or otherwise of randomization, concealed allocation of participants, blinded outcome assessment if feasible, and description extent of follow-up attrition rates. For some studies where clinical issues affecting randomization were considered important, e.g. preoperative vs intra-operative randomization, inclusion of high vs low stulae and patients with Crohns disease, this was also taken into account.
Data retrieval and analysis

stulectomy stulotomy (n = 2), cutting seton vs internal anal sphincter (IAS) preserving seton with mucosal ap (n = 1), incision and drainage of perianal abscessstula vs incision with stulotomy stulectomy at time of abscess incision (n = 5), stulotomy stulectomy alone vs stulotomy stulectomy with marsupialization (n = 2), anodermal island ap vs stulotomy or loose seton insertion (n = 1), advancement ap vs stulotomy with sphincter reconstruction (n = 1), endoanal advancement ap vs endoanal ap with antibiotic impregnated sponge (n = 1), brin glue vs stulotomy or loose seton insertion (n = 1), brin glue with either intra-adhesive antibiotic or surgical closure of primary opening or both (n = 1), advancement ap vs advancement ap with brin glue obliteration of stula tract (n = 1), radiofrequency stulotomy vs conventional stulotomy stulectomy (n = 2) and Parks vs Scott retractors during stula surgery (n = 1). Both meta-analyses looked at incision and drainage alone vs incision + stulotomy for perianal abscess-stula [2,3].
Quality of included trials

From each study the participants (stula type, randomized, treated, followed up, dropouts) overall and per group were assessed. We also extracted information on outcomes and adverse events from each study. This included but was not limited to rates of patient satisfaction, postoperative pain and bleeding, stula healing, stula recurrence, perianal abscess, repeat surgery for stula or abscess and incontinence. Analysis was performed on an intention to treat basis. Patients without end-points were not assumed to be treatment failures. For analysis of outcomes in the radiofrequency stula studies, relative risks (RR), their condence intervals and the chi-squared test for heterogeneity were calculated. The calculations were performed utilizing the RevMan version 4.2 software (http:// www.cc-ims.net/RevMan) courtesy of the Cochrane Collaboration.

Only four studies mentioned the randomization method utilized [47]. In the Gupta study, the operation theatre nurse picked a sealed envelope after the patient arrived in theatre [4]. Zbar et al. used random numbers [5] and Perez et al. used computer generated randomization [6], but it was unclear if these numbers were concealed from the investigators prior to participant randomization and hence could have been open to selection bias. The fourth study utilized a research secretary to create randomization sequences in blocks of four which were unknown to the surgeons or patients and kept in sealed envelopes [7]. We found 13 of 21 studies reported the use of sealed envelopes to conceal allocation of participants after random numbers had been generated [4,718]. Only one study by Hebjorn et al. [19] had blinded assessors during postoperative follow-up. Losses to follow-up were mentioned by nine of 21 trials [611,1820]. Five studies had average follow-up beyond a year ranging from 13 to 42 months [4,6,13,17,20]. Eight RCTs had average follow-up of 1 year [5,7,8,11,12,16,19,21] and the remaining eight trials had less than 1 year follow-up [9,10,14,15,18,2224].
Fistulotomy vs stulectomy

Results
Description of studies

The search strategy revealed 443 trials and two meta-analyses. After the exclusions described above 21 randomized controlled trials remained evaluating: stulotomy vs stulectomy (n = 2), chemical seton vs

To date only two RCTs have looked at stulotomy vs stulectomy (Table 1). An RCT from Mexico demonstrated signicantly larger IAS and external anal sphincter (EAS) defects on endoanal ultrasound in 40 patients randomized to stulectomy compared with stulotomy

2008 The Authors. Journal Compilation 2008 The Association of Coloproctology of Great Britain and Ireland. Colorectal Disease, 10, 420430

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Table 1 Fistulotomy versus stulectomy (n = 2). Study, Year Kronborg, 1985 [21] Participants Simple stulae n 47 Interventions Fistulotomy vs stulectomy Outcome Healing time: 34 days vs 41 days (P < 0.02) Repeat surgery: 3 26 vs 2 21 (ns) Recurrence: 3 24 vs 2 21 (ns) Incontinence: 1 24 vs 3 21 (ns) Defect size on ultrasound at 6 weeks: Internal anal sphincter: 8.5 mm vs 9.08 mm (ns) Internal and external sphincter: 9.25 vs 11.38 (P < 0.05) Follow-up 12 months

Belmonte Montes, 1999 [22]

Simple stulae

40

Fistulotomy vs stulectomy

6 weeks

n, study sample size.

[22]. Whether the larger defect size with stulectomy translated into meaningful differences in clinical outcome could not be ascertained as there are neither follow-up data published nor were they obtainable from the authors. The one study which has looked further is by Kronborg and was published over two decades ago. He demonstrated shorter healing times (34 days vs 41 days) with stulotomy compared to stulectomy (P < 0.02) in 47 randomized patients [21]. No signicant differences in repeat surgery, recurrence or incontinence rates were shown.
Setons for the treatment of anal stulae

Setons, in use for over two millennia by mankind, consist of passing a suture through the stula tract and tied tightly as a cutting seton to perform a slow stulotomy over weeks. Alternatively a loose seton may be placed which is thought to control infection and attendant symptoms, and also may eventually cut out producing a cure. Astoundingly to date there are only four RCTs with randomization which have evaluated this technique and none have looked at the clinically important question of how plain cutting setons compare with gold-standard stulotomy in terms of recurrence and incontinence rates [3,7,9,15]. Two studies have looked at chemical (Ayurvedic) setons when compared with stulectomy [8] or stulotomy [9] (summarized in Table 2). This is essentially an ancient Indian cutting seton technique where linen threads are coated with layers of latex and plant extracts producing a strongly alkaline outer layer which cuts through tissues chemically at a rate of 1 cm every 6 days. The large multicenter Indian study by Shukla (n = 503) showed longer healing with chemical setons compared to stulectomy but a lower recurrence rate (4% vs 11%) [3]. Losses to follow-up at 1 year were signicant (59%) and

could have affected the ndings if those who received stulectomy and healed completely were less likely to return for follow-up when compared with those having chemical setons. The 2001 Ho paper (n = 108) compared chemical setons to stulotomy in low anal stulae. He found no difference in healing times, complications or functional outcome. There was more pain in the seton group during the rst 24 days postop but this became insignicant by day 7 [9]. Zbar (n = 34) on the other hand, compared conventional cutting setons vs internal anal sphincter preserving cutting seton in high trans-sphincteric stulae [5]. The latter procedure consisted of closure of the internal stula opening by a short mucosal ap, an IAS repair and rerouting of the cutting seton through the intersphincteric portion for EAS cutting. While improvements in resting anal manometry were demonstrated, these were not statistically signicant and there were no differences in postoperative Pescatori incontinence scores, recurrence or healing times at 12 months. The only other RCT evidence relates to the use of loose setons in patients with complex stulae as compared with brin glue treatment in the Lindsey study [10] and is described further on in this article.
Fistulotomy with incision of perianal abscess-stula

The perianal abscess contributes signicantly to emergency surgical workload and the large number of studies in this area reects ease of patient recruitment. We identied ve studies summarized in Table 3 (n = 408) exploring incision and drainage alone of perianal abscessstula vs incision combined with stula surgery [11 13,19,20]. The Tang study randomized patients after an internal opening was demonstrated in theatre prior to incision of the abscess [11]. Hebjorn et al. performed incision of the

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Table 2 RCTs evaluating seton in stula surgery (n = 3). n Interventions Chemical seton vs stulectomy or stulotomy 12 months Healing time: 8 vs 4 weeks (median) Healing at 12 weeks: 180 265 vs 210 237 (P < 0.01) Recurrence: 6 155 vs 16 142 (P = 0.03) Incontinence (atus liquid): 8 160 vs 13 144 (ns) 2 months Outcome Follow-up Notes 15% vs 14% had high stulae in either group. 205 502 lost to follow-up Crohns included; Perianal cellulitis excluded High stulas excluded 502

Study, Year

Participants

A. I. Malik & R. L. Nelson

Shukla, 1991 [8]

Uncomplicated anal stulae

Ho, 2001 [9]

Consecutive intersphincteric or transsphincteric stula patients 34 Internal anal sphincter preserving seton with mucosal ap vs conventional cutting seton 12 months

108

Chemical seton vs stulotomy

Zbar, 2003 [5]

High transsphincteric stulae

Pain score Day 2: 5 vs 3 (P < 0.02) Pain score Day 7: 2 vs 2 (ns) Healing time: 54 days vs 45 days (ns) Repeat surgery: 2 45 vs 1 54 (ns) Incontinence to atus liquid: 3 43 vs 2 52 (ns) Healing time: 14 weeks vs 12 weeks (ns) Recurrence: 2 18 vs 1 16 (ns) Incontinence: 1 18 vs 2 16 (ns)

Crohns patients excluded

N, study sample size

Table 3 Studies comparing stula surgery at time of Incision of perianal abscess (n = 5). Recurrence further surgery Minor incontinence Follow-up 12 months 42.5 months 12 months 15.5 months 12 months Notes

Study, Year

Hebjorn, 1987 [19]

41

Schouten, 1991 [20]

70

Patients randomized next day after I&D and stulotomy performed on 3rd postoperative day 32 36 randomized to stulectomy found to have stula

Tang, 1996 [11]

45

Ho YH, 1997 [13]

52

Sealed envelope randomization in theatre after internal opening was demonstrated 21 24 in stula surgery arm found to have stula 83 100 in stula surgery arm found to have stula

2008 The Authors. Journal Compilation 2008 The Association of Coloproctology of Great Britain and Ireland. Colorectal Disease, 10, 420430

Oliver, 2003 [12]

200

I&D I&D I&D I&D I&D I&D I&D I&D I&D I&D

alone, 3 18 (17%) + F, 2 20 (10%) alone, 13 34 (41%) + F, 1 36 (3%) alone, 3 21 (14%) + F, 0 24 (0%) alone, 8 28 (29 %) + F, 1 24 (0%) alone, 29 100 (29%) + F, 5 100 (5%) I&D I&D I&D I&D I&D I&D I&D I&D I&D I&D

alone, 0 18 (0%) + F, 8 20 (10%)* alone, 6 28 (21.4%) + F, 13 33 (39.4%) alone, 1 21(4%) + F, 0 24 (0%) alone, 0 28 (0%) + F, 0 24 (0%) alone, 0 100 (0%) + F, 6 100 (6%)

Surgical management of anal stulae

n, study sample size; I&D, incision and drainage; I&D + F, incision and drainage with stula surgery. *Includes six patients with atus incontinence and two with soiling. Includes four patients with recurrence who subsequently had stulectomy. Fistula surgery patients underwent incision, drainage and stulectomy with primary partial internal sphincterectomy.

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abscess and then patients were randomized on the 1st postoperative day for stula surgery on the 3rd postoperative day (i.e. on same admission) [19]. The other three studies randomized patients preoperatively but large numbers (8388%) were found to have an anal stula in the stula surgery arm. As the incidence of stula in follow-up after drainage of perianal abscess ranges from 26% to 37% [2] this raises questions about the majority of stulae found in these studies, i.e., The majority of the patients allocated to stula surgery were not destined to have stulas and thus had unnecessary sphincter division.
Marsupialization after stulotomy

Marsupialization after anal stula surgery is postulated to leave less raw unepithelialized tissue in the stulotomy (or stulectomy) wound thereby resulting in less postoperative blood loss and faster wound healing. Two RCTs have evaluated this area (Table 4). Ho (1998) (n = 103) randomized patients to laying open alone vs laying open + marsupialization and demonstrated faster healing times (6 weeks vs 10 weeks, P < 0.001) in favour of marsupialization [15]. Pescatori randomized 46 stula patients to stulotomy vs stulotomy + marsupialization. He showed less bleeding and quicker reduction in postoperative wound size with marsupialization [14]. While data from the two studies cannot be pooled because of differences between the participants and outcome measures, taken together the two studies provide good evidence that marsupialization is benecial after stulotomy.
Table 4 Marsupialization at time of stulotomy stulectomy (n = 2).

Flap repair of anal stulae

Flap repair of anal stulae has garnered much attention recently as a sphincter-preserving approach for dealing with high or complex stulae where conventional surgery (e.g. stulotomy) may produce high incontinence rates. We identied three RCTs summarized in Table 5, two comparing anal ap repair with stulotomy [6,23] and one evaluating the effect of an antibiotic impregnated sponge on ap healing rates [7]. Additionally the Zbar paper mentioned earlier compared traditional cutting seton vs an internal anal sphincter-preserving seton with closure of the internal opening by a short mucosal ap [5]. Ho KS [23] compared conventional treatment mainly stulotomy with anodermal island ap repair of high trans-sphincteric stulae (n = 20). There were no demographic differences between the two groups in terms of age (conventional treatment mean age 40.1 years; island ap 42.5 years) or in terms of gender (all males). Two patients in the conventional therapy arm underwent loose seton insertion rather than stulotomy.

103

Uncomplicated interor trans-sphincteric stulae included. High, recurrent and horse-shoe stulae included

Participants

46

Fistulotomy vs stulotomy with marsupialization Fistulotomy stulectomy vs stulotomy stulectomy with marsupialization n, study sample size. Ho, 1998 [15] Pescatori 2006 [14]

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Study, Year

Interventions

Healing time: 10 weeks vs 6 weeks (P < 0.001) Minor incontinence: 6 52 vs 1 51 (ns) Recurrence: 2 52 vs 1 51 (ns) Pain scores at 12 h: 3.4 vs 3.5 (ns) Bleeding: 11 24 vs 8 22 (P < 0.05) Wound size: 543 mm2 vs 217 mm2 (P < 0.01) Repeat surgery: 3 24 vs 3 22 (ns) Minor Incontinence: 2 24 vs 2 22 (ns)

Outcome

10 months

Follow-up

9 weeks

High, recurrent, horse-shoe or extrasphincteric stulae or those with multiple openings excluded Intersphincteric or supercial stulae excluded

Notes

A. I. Malik & R. L. Nelson

Surgical management of anal stulae

Healing: 9 10 vs 9 10 (ns) Incontinence scores (mean): 1.3 vs 1.3 (ns) Recurrence: 0 10 vs 0 10 Quality of Life score (mean): 123 vs 124 (ns)

Healing time: 3.4 weeks vs 4.6 weeks (ns) Incontinence: 8 27 vs 9 28 (ns) Recurrence: 2 20 vs 2 20 (ns)

Overall healing: 47 83 patients (57%) Healing at 1 year: 21 41 vs 26 42 (ns)

No signicant differences in pain scores, incontinence, or quality of life was found, with 9 10 patients healed in each group at 4-month follow-up. The authors concluded that dermal ap is a satisfactory treatment for high stulas. Nevertheless the short follow-up and small numbers make it difcult to draw rm conclusions. A somewhat larger RCT was performed by Perez [6] who randomized 60 patients with complex stulas to either rectal advancement ap (AF, n = 30) or stulotomy with sphincter reconstruction (FSR, n = 30). The groups were equally balanced in terms of age, male:female ratio and anatomy of the stula. Forty-four patients had high trans-sphincteric (22 27 in AF and 22 28 in FSR groups) and 11 had supra-sphincteric stulas (5 27 in AF and 6 28 in FSR groups). There were no signicant differences in recurrence rates between the two groups (2 30 in each group) and similarly there were no signicant differences in continence after a mean follow-up of 36 months (see Table 5).
Do submucosal antibiotics aid ap repair?

Notes

Follow-up

36 months

4 months

12 months

No patients had TB, IBD or malignancy on histology of stula tract curettage Conventional therapy arm: 8 10 had stulotomy and 2 10 had loose seton insertion Patients with previous anorectal surgery, acute anal sepsis, recurrent or IBD-associated stulae were excluded Those with multiple internal stula openings or Crohns disease or ongoing perioperative antibiotic usage were excluded

Table 5 Flap repair for anal stulae (n = 3).

High transsphincteric stulae conrmed on preoperative ultrasound

Intersphincteric or higher anal stulae

Complex stulae

Gustafsson looked at healing rates after insertion of a bovine collagen sponge impregnated with gentamicin sulphate beneath an endoanal advancement ap (n = 42 treatment, n = 41 controls) [7]. The authors theorized that a proportion of ap failures might be due to local ap infection and thus be prevented. Those with intersphincteric or high anal stulae were enroled but Crohns stulae or those with multiple internal openings were excluded. There were no signicant differences in age, sex-ratio, stula type or history of previous stula surgery between the groups. The 12.5 cm2 sponge released antibiotic for upto 72 h and dissolved over the subsequent 17 weeks. At 1-year follow-up, 57% patients overall had healed but there was no signicant difference in the primary healing rate between the two groups (26 42 of gentamicin-collagen patients vs 21 41 of ap alone patients) (Table 5). The overall healing rate in this study ts in well with other series where recurrence rates of 3140% are reported [2527].
Fibrin glue in stula surgery

Outcome

20

60

Participants

83

Endoanal advancement ap alone vs endoanal advancement ap with antibiotic impregnated sponge

Anodermal island ap repair vs conventional treatment

Advancement ap vs stulotomy with sphincter reconstruction

Interventions

Fibrin glue obliteration of the stula tract has been the subject of considerable interest as a possible option in patients with high transsphincteric or suprasphincteric stulae where most surgeons remain wary of performing a conventional stulotomy on account of the perceived risk of serious incontinence. Administration consists of injecting thrombin and brinogen from a two-chambered syringe into the stula tract. This occurs via a single

Gustafsson, 2006 [7]

2008 The Authors. Journal Compilation 2008 The Association of Coloproctology of Great Britain and Ireland. Colorectal Disease, 10, 420430

n, study sample size.

Ho KS, 2005 [23]

Perez, 2006 [6]

Study, Year

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A. I. Malik & R. L. Nelson

Table 6 Glue therapy for anal stulae (n = 3).

Do antibiotics help in brin glue therapy?

The second RCT is by Singer who randomized 75 patients to either brin sealant admixed with antibiotic (cefoxitin) or sealant with closure of the internal stula opening or sealant with both [16]. The initial healing rates were 21%, 40% and 31% respectively (P = 0.34). As in the Lindsey study patients were offered re-treatment; this was with a single application of brin sealant alone

Fibrin sealant with either intra-adhesive antibiotic or surgical closure of the primary opening or both Transsphincteric stulae

Complex stulae

Participants

Simple stulae

cannula inserted through the external stula opening allowing the two components to mix together during delivery to form the brin. The cannula tip is initially inserted upto the internal stula opening. Once a blob of brin glue is seen protruding from there, the cannula is slowly withdrawn while the glue is injected steadily. There were three RCTs identied evaluating the effects of brin glue in anal stula surgery which are summarized in Table 6. Only the Lindsey study asked the most relevant question which is how does brin glue compare with existing conventional therapy [10]. The other two studied the additive effects of brin glue on ap repair [17] and admixed with a cephalosporin antibiotic [16]. Lindsey et al. [10] randomized 13 simple and 29 complex stula patients to either one or two applications of brin glue or conventional methods with nal followup at 3 months post-treatment. There was differing conventional treatment for the simple and complex stula patients and in fact the two groups were analysed separately by the authors. Those with simple stulae were treated by stulotomy alone and complex stula patients were given loose setons followed by ap repair in selected cases. Lindsey found that brin glue healed 50% (three of six) and stulotomy healed 100% (seven of seven) of low stulas (P < 0.06). There were no differences in continence scores, anal pressures or pain scores between the two groups. While return to work was quicker with glue treatment, satisfaction scores were higher in the stulotomy group. Of the 29 patients with complex stulae, glue healed 46% (six of 13) patients with one treatment and an additional three patients after a re-glue thus achieving 69% cumulative healing. Only 13% (two of 16) were cured by conventional methods which was loose seton insertion for all 16 complex stula patients in this arm. Two of the six Crohns patients were randomized to glue therapy, with four given conventional therapy i.e. loose seton insertion. Unsurprisingly the results of conventional treatment of complex stulae were not too impressive. There were no differences in incontinence scores or anal pressures but understandably satisfaction was higher with glue therapy with its higher healing rate.

12 months

13

29

75

58

Fibrin glue vs loose seton insertion and 2nd line ap repair Fibrin sealant + antibiotic vs sealant + closure of internal stula opening vs sealant + antibiotic + closure of internal stula opening Advancement ap alone vs advancement ap with brin glue obliteration of the stula tract n, study sample size Singer, 2005 [16] Ellis, 2006 [17]

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Lindsey, 2002 [10]

Study, Year

Fibrin glue vs stulotomy

Interventions

Recurrence: 6 30 vs 13 28 (P < 0.05)

Healing: 3 6 vs 7 7 (P = 0.06) Incontinence: 0 7 vs 0 6 (ns) Return to work: 1.8 days vs 5.8 days Satisfaction score (mean): 4.5 vs 8.7 Healing: 9 13 vs 2 16 (P = 0.003) Incontinence: 0 13 vs 3 16 (ns) Satisfaction score (mean): 8.3 vs 7.8 Healing: 21% vs 40% vs 31% (ns) Healing after 2nd treatment: 25% vs 44% vs 35% (ns) Incontinence: Nil in any of the groups

Outcome

22 months

Follow-up

3 months

3 months

Two Crohns patients were in the glue therapy arm vs 4 in the loose seton group Suprasphincteric stulae and stulae associated with HIV, Crohns and an anastomotic leak included Crohns, radiation-induced and obstetric stulae excluded

Notes

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Surgical management of anal stulae

which only 18 of 52 failed patients agreed to undergo. The nal healing rates at 1 year were 25%, 44% and 35% respectively but this did not reach statistical signicance (P = 0.37). Longer-term eventual recurrence rates may have been even higher than those published. Of note, this study included patients with additional risk factors like Crohns disease (n = 3), HIV (n = 3), penicillin allergy (n = 3) and anastomotic leak as stula aetiology (n = 1). These patients uniformly failed treatment. An important question which the study did not answer is how effective is brin glue treatment alone compared to the addition of antibiotic or internal opening closure.
Can brin glue aid ap repair?

18 months

Follow-up

Table 7 Radiofrequency compared to conventional stula surgery (n = 2).

Conventional stulectomy vs radiofrequency stulectomy

Interventions

Radiofrequency stulotomy vs conventional stulectomy stulotomy

200

Radiofrequency surgery as opposed to conventional diathermy is supposed to produce similar cutting of tissues whilst utilizing lower temperatures resulting in less heat damage to the surrounding tissues. Two studies were found evaluating the role of radiofrequency in uncomplicated low anal stulae (Table 7). One single author study used a 4 MHz radiofrequency (RF) device for stulotomy compared to stulectomy of low stulas (n = 100) [4]. It demonstrated less bleeding, lower operative time (22 min vs 37 min), less postoperative pain and improved healing times (47 days

Participants

Posterior submucosal stulae

Low anal stulae

20

Conventional stulotomy vs radiofrequency stulectomy

Ellis et al. randomized 58 patients with trans-sphincteric stulae to advancement ap repair only or ap with brin glue obliteration of the stula tract [17]. Patients with Crohns, obstetric trauma, or radiation exposure were excluded. The proportions of patients in each arm having mucosal advancement aps (60%) and anodermal aps (40%) were similar. The overall recurrence rate was 32.6%. However, this was only 20% (6 30 patients) for advancement ap alone and rose to 46.4% (13 of 28 patients) when the ap was combined with brin glue (P < 0.05). The majority of recurrences in the latter group occurred in those having mucosal advancement ap combined with glue (58.9%, 10 17 patients) as opposed to anodermal ap repair (27%, 3 11 patients) but these subset ndings were not statistically signicant. Although the numbers are small, this study raises the possibility that brin glue as applied by the authors may in fact interfere with anal ap repair and so some of the newer interventions for anal stulae may interact negatively with one another. This might be due to, inter alia, the sealant preventing physical contact between the ap wound edges or by blocking drainage from infected secondary tracts.

Operative time: 37 min vs 22 min (P < 0.001) Intra-operative bleeding: 134 ml vs 47 ml (P = 0.002) Healing time: 64 days vs 47 days (P = 0.01) Recurrence: 3 100 vs 1 100 (P = 0.61) Incontinence to atus: 6 100 vs 2 100 (P = 0.27); Nil at 4 weeks Resumption of usual activities: 11 days vs 7 days (P = 0.012) Postoperative pain (day 1): 4.1 vs 2.8 (P = 0.05) Healing time: 5.9 weeks vs 3.5 weeks Recurrence: 0 11 vs 1 11 (ns) Minor incontinence: 4 11 vs 3 11 (day 5 postop); Nil in either group at nal follow-up n, study sample size. 427 Filigeri, 2004 [18] Gupta, 2003 [4]

2008 The Authors. Journal Compilation 2008 The Association of Coloproctology of Great Britain and Ireland. Colorectal Disease, 10, 420430

Study, Year

Outcome

6 months

Patients with previous anal surgery, multiple stula tracts, nonsubmucosal or anterior stulae, pregnancy, ASA III IV status excluded

High transsphincteric, suprasphincteric, extrasphincteric, IBS-related and horse-shoe stulae excluded

Notes

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vs 64 days) with the RF technique. There were 3 100 recurrences in the conventional group and 1 100 after RF stulotomy (P = 0.01). Filigeri et al. randomized 20 patients to either RF stulectomy or conventional stulotomy [18]. There was signicantly less postoperative pain on day 1 and shorter mean healing times in the RF group compared to controls (3.5 weeks vs 5.9 weeks). The mean operative time was 18.3 min (1526 min) vs 17.9 min (13 21 min). One recurrence occurred in the RF group with none in the conventional arm. Data pooled with the Gupta study revealed nonsignicant benets of RF surgery with respect to minor incontinence (RR = 0.50, CI 0.191.31) and recurrence (RR = 0.71, CI 0.15 3.50).
The Retractor Effect on continence after stula surgery

To date one study, by Zimmerman, has looked at the effect of the Parks vs Scott anal retractors on faecal continence 12 weeks after stula repair (n = 30) [24]. The Parks retractor led to a signicant drop between the pre- and postoperative maximal anal resting pressures (MARP, 76 to 42 mmHg) and a signicant rise in the average Rockwood Faecal Incontinence Severity Index (RFISI, 012) consistent with damage to the internal anal sphincter. There was no signicant change either in the MARP or RFISI with use of the Scott retractor, or in the mean anal squeeze pressure with use of the Scott or Parks retractor.

Discussion
The overall quality of the studies obtained was poor with only 57% of studies describing the method of allocation concealment and demonstrated a trend towards the lower end of the quality spectrum for studies in this eld. Similarly only one study [19] had blinded assessors at postoperative follow-up. Blinded outcome assessment at follow-up may be difcult to achieve in some types of trials e.g. comparing setons to stulotomy stulectomy or with glue treatment compared to stulotomy. However, the lack of blinded follow-up in those studies where this could have been applied remains a source of potential bias. The ndings from the ve RCTs of abscess incision vs incision with stula surgery need cautious interpretation. Only one in three perianal abscesses go on to develop an anal stula [2]. It is intriguing therefore to see a large proportion of patients randomized preoperatively to incision + stula surgery having a stula discovered in three of the trials. It is possible that over-exuberance by the surgeon in searching for a stula may have created

false passages which were then treated as stulae. Other possibilities include the effects of inadequate randomization or investigators not being truly blind to allocation. This means that the Quah et al. meta-analysis may warrant re-evaluation. They concluded there was no conclusive evidence in favour of simple drainage or drainage with a sphincter-cutting procedure. However on pooled analysis of the ve trials they suggested a tendency for reduced stula recurrence (RR 0.17, CI 0.090.32) and higher minor incontinence (RR 2.46, CI 0.758.06) with abscess incision + stula surgery [3]. Further work is needed as these ndings may represent an overestimate of the effect of stula surgery in these patients. The Lindsey paper has boldly attempted to answer the question is glue therapy better than conventional treatment for anal stula?. Their simple stula ndings show the efcacy of gold standard stulotomy in treating anal stulae. While conventional treatment was interpreted as stulotomy for their simple stulas, all the complex stulae in the conventional therapy arm were given loose setons (16 of 16) [10]. While this represents the only RCT where loose setons have actually been tried out as a sole intervention, it may also explain the poor healing rate compared to glue treatment. Of the six Crohns patients in the study, two had glue treatment and four had loose setons and this may have further worsened the results in the conventional treatment arm as Crohns stulae are known to be refractory to conventional therapies. Future studies would do better to compare glue with newer treatments e.g. advancement aps or cutting setons, and either exclude or separately randomize patients with Crohns stulae. The ndings by Zimmerman [24] showing a drop in resting anal pressures and continence scores after use of a Parks retractor are interesting and warrant further attention. We have no knowledge if this Retractor Effect has a role in the ndings of the other 20 RCTs in our review as this information was not available. Bias may have been avoided if equal numbers of patients in each treatment arm were subjected to each type of retractor. However, if more patients in a particular treatment arm were subjected to mainly one sort of retractor or another then this may have confounded some of the results. Lastly a point about the wide variation in persistence and recurrence rates from study to study. Partly this is explained by the differing patient groups assessed by individual trials, i.e. those with low submucosal stulae are likely to fare better than high transsphincteric ones. This may also be explained by the quality issues and effects of surgical technique including retractor type mentioned earlier. Dropouts from treatment or follow-up seem to be a problem for only a minority of trials due to

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the small manageable sample sizes in a majority of studies evaluated the large multi-centre Shukla study being a notable exception. A more important reason is likely the follow-up duration which varies from as little as 6 weeks to 42 months between the trials. The likelihood of picking up recurrent persistent anal stulae should be higher with the longer term follow-ups. We mention these issues as they are relevant for the design of future trials evaluating efcacy of proctological interventions.

Conclusion and future directions

Most studies on anal stula are small and heterogeneous with respect to interventions and patient groups included making it difcult to draw strong inferences. Marsupialization after stulotomy reduces bleeding and allows for faster healing. Chemical setons produce more pain postoperatively but evidence on recurrence and healing rates remains inconclusive. Early results suggest that ap repair of anal stulae may be no worse than stulotomy in terms of healing but this remains to be conclusively shown in repeat trials. At least one study has suggested that anal aps combined with brin glue could increase stula recurrence rates. Radiofrequency stulotomy produces less pain on the rst day postoperatively and may allow for shorter healing times. The role of stulotomy at time of abscess incision remains to be claried denitively. Basic questions remain to be answered. A consensus on stula study methodology is needed dening key stula groups (low, high, trans-sphincteric, intersphincteric) and outcome measures (healing time, incontinence) and to clarify minimum standards for long-term followup to determine true recurrence rates after surgery for anal stula. A good starting point would be comparing stulotomy vs stulectomy vs cutting seton vs ap vs glue in a properly conducted RCT using a standard continence assessment instrument and with uniform timing of continence and recurrence assessment.

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