Introduction

Surgical lateral internal sphincterotomy (LIS) has been widely accepted as the treatment of choice for chronic anal fissures (CAF), and it is effective in more than 90% of cases [1, 2]. The fundamental drawback of this surgery is potential gas, mucus, or occasionally stool incontinence, which is permanent in 8%–30% of patients [3, 4]. Therapies that induce a reversible reduction in anal sphincter pressure, as a major pathophysiologic factor for CAF, have been used to achieve fissure healing without permanent damage to the continence mechanism. Intrasphincteric injection of botulinum toxin (BT) is one of those therapies [5–12], and it has been found to be a reliable and effective new option in the treatment of uncomplicated CAF. This method was described initially by Jost and Schimrigk [13]. Furthermore, BT was more effective than topical nitrate, which constitutes another common therapeutic option [8].

The aim of the present prospective trial was to compare effectiveness and morbidity of chemical sphincterotomy with botulinum toxin injection versus surgical lateral internal sphincterotomy for treatment of uncomplicated chronic anal fissure.

Methods

Patients and study design

This trial included consecutive adult patients with symptomatic chronic anal fissure in which conservative treatment had failed. Full clinical assessment was done, including complete history and general, abdominal, and local anal examination. Digital anal examination and anuscopy were performed in each case to confirm the diagnosis. The diagnosis of chronic anal fissure was based on evidence of a circumscribed ulcer at the anal canal, with indurations at the edges and exposure of the horizontal fibers of the internal anal sphincter at its floor.

Criteria for exclusion from the study were anal fissure that had been operated on before, complicated fissure with cicatricial deformation, large sentinel pile, associated hemorrhoids, suspected inflammatory bowel disease, or malignancy.

Fully informed written consent was obtained from each patient prior to entry into the trial. The study was approved by the Ethical Committee of Theodore Bilharz Research Institute (TBRI).

Patients who entered the trial were randomized into two groups: group 1 underwent a conservative lateral internal sphincterotomy (LIS group) and group 2 underwent intrasphincteric botulinum toxin injection (BT group); depending on whether the patient’s registration number was odd or even, respectively.

Lateral internal sphincterotomy

The procedures were performed with the patient under general anesthesia and in the lithotomy position. Lateral internal sphincterotomy was performed by the subcutaneous method. The internal sphincter was cut under direct visualization up to the height of the fissure apex or just below it. We removed “small sentinel piles” or hypertrophied papillae in patients undergoing sphincterotomy as a routine.

Botulinum toxin injection

Botulinum toxin injection was done as an outpatient procedure under local anesthesia (Xylocaine jell 5%). We used a 100 U vial of lyophilized botulinum toxin type A (Botox, Allergan, Westport, Co. Mayo, Ireland) stored at −8°C. The day of injection it was diluted with saline to 40 U/ml, and 10 U was injected into the internal anal sphincter on both sides of the fissure (total dose 20 U and volume 0.5 ml) by the so-called insulin 1 ml syringe with a short, thin needle (10 mm, gauge 26).

Postoperative follow-up

Postoperative stool softener and Sitz baths were advised for all patients for three weeks to avoid constipation and reduce pain, bleeding, and infection. After the patient was discharged from the hospital, postoperative follow-up involved a visit to the doctor every three weeks. The follow-up period of 18 weeks was chosen because complete recovery from postoperative pain and soiling takes about 8–12 weeks. At each follow-up visit pain, healing of fissure, and continence scores were the outcomes assessed. Assessment of fissure healing was done by asking about any pain with defecation and by visual inspection. Healing was defined as complete re-epithelialization of fissure and absence of pain. The continence severity was assessed according the validated Cleveland Clinic Scoring System because it is practical and easy to use and interpret. It involves giving points for each mode of anal incontinence, whether gas (1–3), liquid stool (4–6), solid stool (7–9), or the requirement of wearing a pad (1–3) according frequency (occasionally, >1/week or daily), respectively. The Cleveland Clinic incontinence score is the sum of those points: 0 = perfect continence, 1–7 = good continence, 8–14 = moderate incontinence; 15–20 = severe incontinence; and 21 = completely incontinent [14].

The treatment was considered successful if complete healing of the CAF occurred within 9 weeks after treatment. Unhealed fissures were considered as treatment failures. Recurrent fissures were defined by relapse of fissure symptoms and loss of epithelialization, with exposure of the horizontal fibers of the internal anal sphincter at its floor at a later follow-up examination, following a complete healing. All data were documented and analyzed.

Statistical analysis

Statistical analysis was performed with the aid of the SPSS computer program (version 6.0 for Windows; SPSS Inc., Chicago, IL). Continuous variables are expressed as number and percentage of patients or the mean ± standard deviation. Statistical significance of fissure healing etc. in the two groups was calculated with the χ2 test and a 95% confidence interval. Statistical significance was defined as p < 0.05. Comparison of the proportions of cases having a negative outcome in the two groups, relative to demographic data, fissure duration, and associated problems was performed by the z-statistic program, which calculates the relative risk with confidence interval 95% (= 95% CI) and two-tailed p value. If p is less than 0.05, it can be concluded that the proportions are significantly different in the two groups, and there is an increased risk in one group compared to the other.

Results

A total of 80 patients were enrolled in the study. Their mean age was 33.8 ± 1.33 years (range: 19–54 years); 52 were women and 28 were men. The mean duration of symptoms was 7.6 ± 2.1 months (range: 3–18 months). The main symptom was anal pain in all cases; it was followed in frequency by bleeding after defecation (73 cases); constipation (63 cases), and pruritus ani (53 cases). The site of the anal fissure was posterior midline in all cases. There were accompanying anterior midline fissure in 19 cases. The two groups were almost similar, and selection bias has been ruled out as the mean age, male/female ratio, mean duration of the fissure symptoms, and mean of the number of cases with associated anterior fissures and/or fissure base fibrosis were found nonsignificant statistically (Table 1).

Table 1 Fissure non-healing, post-treatment anal incontinence, and fissure relapse following botulinum injection and surgical sphincterotomy
Full size table

The single complication occurring after botulinum toxin injection was ecchymosis at the point of injection, which occurred in eight patients. Early complications after lateral internal sphincterotomy were bleeding in five patients and urinary retention in three patients.

Inspection at the sixth week after treatment revealed a healing scar in 22 patients (55 %) in the BT group and 32 patients (80 %) in the LIS group. Fissure healing at the ninth week was found in another three cases in the BT group and another four cases in the LIS group. At the end of follow-up; overall healing was found in 36 (90%) of the LIS patients and 25 (62.5%) of the BT patients (Fig. 1). There was a statistically significantly higher rate of healing in the LIS group than in the BT group (p = 0.0086 and 95% CI = 7.38–45.69%). The risk of fissure non-healing in BT group was significantly higher for fissure duration >12 months (two-tailed p value = 0.0001 and 95% CI = −1.3335, −0.4443), associated anterior fissure (two-tailed p value = 0.0142 and 95% CI = 0.0869, 0.7798) and fissure base fibrosis (two-tailed p value = 0.0086 and 95% CI = 0.1239, 0.8510) (Table 1). Relative risk of non-healed fissure in the LIS group was fissure duration >12 months (two-tailed p value = 0.0135 and 95% CI = 0.0687, 0.5980) and fissure base fibrosis (two-tailed p value = 0.0149, 95% CI = 0.0520, 0.4814) (Table 1). The patients with BT injection whose fissures were not healed underwent LIS at 2 months after BT treatment. The other patients had asymptomatic fissures and refused surgical treatment.

Fig. 1
figure 1

Comparison of botulinum injection versus anal sphincterotomy in the treatment of chronic anal fissure regarding healing, incidence of postoperative anal incontinence and fissure relapse

Full size image

In the 18th week of follow-up, postoperative moderate anal incontinence (Cleveland Clinic Scoring System [8–14]) was found in six of the patients (15%) in the sphincterotomy group. None of those patients suffered anal incontinence following treatment with Botox (0%) (Fig. 1). The LIS procedure was associated with a high rate of anal incontinence as compared to Botox (p = 0.0338 and 95% CI = −1.64–27.53%). Relative risk of the postoperative occurrence of anal incontinence after LIS was age >50 years (two-tailed p value = 0.0022 and 95% CI = −1.1850, −0.2611) (Table 1). At the end of the eighteenth week of follow-up three of the six patients who suffered postoperative anal incontinence in the LIS group had improved symptoms with a good continence score. Anal incontinence completely disappeared in one patient and it was persistent in two others. Thus, persistent incontinence in the sphincterotomy group was found in only 5% of patients at the end of follow-up.

The number of patients with recurrence of the fissure by re-evaluation for symptoms and anal examination was as follows: two patients at the 15th week and three patients at the 18th week of the follow-up period in the sphincterotomy group, for an overall recurrence in five patients (12.5%). The number of patients with recurrence of the fissure at follow-up in the botulinum toxin group was as follows: three patients at the 9th week, four more patients at the 12th week, four patients at the 15th week, and five patients at the 18th week. Thus, overall, recurrence was found in 16 patients (40%) (Fig. 1). The recurrence rate in the botulinum toxin group was significantly higher than in the sphincterotomy group (p = 0.0111 and 95% CI = 6.68–46.13%). Relative risk of fissure relapse in the BT group was fissure duration >12 months (two-tailed p value = 0.0000 and 95% CI = −1.4496, −0.5504) and fissure base fibrosis (two-tailed p value = 0.0011 and 95% CI = 0.2499, 1.0001). The relative risk of fissure relapse in the LIS group was associated anterior fissure (two-tailed p value = 0.0149 and 95% CI = 0.0520, 0.4814) and fissure base fibrosis (two-tailed p value = 0.0014 and 95% CI = 0.1536, 0.6429) (Table 1). Ten of the patients with recurrent fissure (62.5%) on anal examination were asymptomatic, and their previous pain disappeared. No treatment was prescribed for them.

Discussion

Botulinum toxin injection into the anal sphincter is a therapeutic approach that has been used to treat chronic anal fissure and avoid the risk of permanent injury to the anal sphincter. Chemical denervation produced by the toxin is not permanent and the clinical efficacy lasts for 2–3 months, which corresponds to the time required to reduce the resting pressure of the anal sphincter allowing anal fissure healing and eliminating the need for surgery [15].

The best results in terms of healing in the short term have been (>80%) in the published studies about the use of BT in the treatment of anal fissure [16–18]. However, in studies with longer follow-up, there was a trend to progressive recurrence over time, with lower healing rates than those initially reported and a relapse of anal fissure in 41.5% of patients [19]. This could be related to the temporary reversible effect of the toxin, but a high percentage of the patients with recurrence showed improvement with absence of previous pain and did not require complementary medical or surgical treatment. Clinical factors related to recurrence were longer duration of disease over 12 months, posteriorly localized fissures, and presence of a sentinel pile [10, 12, 19]. The therapeutic success rate of BT was found to be related to both injection site and toxin dose. We injected the BT on each site of the fissure, mainly toward the posterior of the anal sphincter. However it was suggested that anterior injection of BT could better reduce the resting pressure of the anal sphincter, which could be due to the fibrotic base of the fissure. The chemical sphincterotomy alone treats internal sphincter spasm but not chronic fissure fibrosis. The addition of fissurectomy to botulinum toxin injection was suggested to improve the healing rate of resistant fissures over that achieved with botulinum toxin alone [20, 21]. However, whether surgical fissurectomy is performed under general or regional anesthesia, it is, in fact, a more invasive procedure than BT injection, which can be performed under local anesthesia as an outpatient procedure. In addition, the dose of BT is important. We used 20 U in this study. However, it has been suggested that higher doses (up to 50 units) provide a higher success rate (up to 96%), without a significant rise in complications or side effects [22 ].

In the present study the healing rate of 75% in the BT group is similar to that in reported in previous studies [23, 24]. All of our patients had posterior anal fissure and short symptom duration (average: 8 months). These positive predictive factors could be related to the good outcome for our patients treated with BT. Although we found a progressive rate of recurrence during the follow-up period for BT patients, a high percentage of them were asymptomatic. In those with symptomatic recurrence, however, surgical treatment was implemented in view of the high probability of recurrence in the long-term.

Anal incontinence has been a negligible complication of BT treatment. Botulinum toxin is thought to spread to the EAS through the small thickness of the IAS and because of the proximity of EAS to the IAS. Nevertheless, BT does not produce sufficient weakness of the EAS to completely block voluntary control, and the remaining control is enough for incontinence prevention. In this study, we did not try to inject BT specifically into the IAS or EAS. We suggest, like other investigators [24, 25], that BT injection is inferior to LIS in the treatment of CAF. However, within the same follow-up period we found a mild degree of anal incontinence in 15% of the patients treated with partial internal sphincterotomy surgery, compared with 0% in the group treated with the injection of BT (p < 0.001). If anal incontinence is considered a failure of LIS, the advantage of this treatment will be nullified.

A meta-analysis of four prospective randomized controlled trials dealing with surgical sphincterotomy versus chemical sphincterotomy using botulinum toxin which included 279 CAF patients [24, 25]. Authors stated in conclusion that “sphincterotomy surgery has a higher healing rate and a lower recurrence rate than BT treatment” [25]. But “As long as the patient is willing to accept a negligible risk of transient faecal incontinence, surgical sphincterotomy should be the first-line treatment for CAF” [24].

Although, sphincterotomy surgery has a higher healing rate and a lower recurrence rate than BT treatment, BT treatment represents a simple technique that can be performed as an outpatient procedure without anesthesia or incision. Thus it is relatively less invasive and less expensive than surgery, and the complication rate seems negligible. It is an effective alternative for treatment of chronic anal fissure, which continues to be recommended as the first-line treatment. We found that many patients were eager to receive this type of therapy, even after its nature and results were fully explained to them.

Conclusions

Surgical internal sphincterotomy has a higher healing rate and a lower recurrence rate than intrasphincteric injection of botulinum toxin in the treatment of uncomplicated chronic anal fissure. Injection of botulinum toxin, however, is noninvasive and simple technique that avoids the greater risk of incontinence. It could be used as the first therapeutic approach in patients without clinical risk factors of recurrence.