Therapy of Acute Anal Fissure
Acute anal fissures heal spontaneously in the majority of cases. In a randomized study conducted in 1986, 87% of acute anal fissures healed with bran and sitz baths, 60% with the application of lidocaine, and 82.4% with hydrocortisone ointment [1]. A prospective cohort study showed that treatment with nifedipine ointment over 8 weeks led to healing in 85.2% of fissures [2]. Nitrates can also be successfully used to treat acute fissures, although the evidence is less compared to locally applied nifedipine preparations [3, 4]. Jensen et al. studied patients after healing of a first anal fissure through conservative measures. In the placebo group, 68% experienced a fissure recurrence within 18 months. The group taking 15 g of bran per day for a year had a recurrence rate of only 16% [5].
Conservative Treatment of Chronic Anal Fissure
In contrast to acute fissures, the chronic form heals significantly less often under conservative measures. In their prospective study, Emile et al. showed a negative relationship between the duration of fissure symptoms and their healing rate [6]. About 50% of chronic anal fissures can heal under conservative treatment [7, 8, 9]. It is undisputed that surgical interventions have a better healing rate, faster symptom relief, and a reduced recurrence rate [7, 9].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
It is recommended that all patients with chronic anal fissure be offered a conservative therapy trial (nitrates, calcium channel blockers, botulinum toxin) over a period of 6 weeks before surgical therapy is performed. Surgical therapy can be performed as first-line therapy if the patient wishes or if there are additional fistulas and/or pronounced secondary morphological changes.
Calcium Channel Antagonists (CCA)
Calcium channel blockers reduce calcium ion influx into smooth muscle cells, leading to reduced contractility and thus vasodilation and reduction of sphincter tone. In the meta-analysis published by Nelson et al. in 2012, CCA and nitrates had the same healing rate, but CCA treatment resulted in significantly fewer side effects [9].
Nifedipine can be administered for fissure treatment both orally and topically. The healing rate of topical therapy was determined by comparative RCTs to be equivalent or even better [10, 11, 12]. Topical CCA were associated with a significantly lower rate of unhealed fissures compared to oral CCA in a meta-analysis of four randomized studies [13]. In a meta-analysis, headaches were the most common side effect (oral CCA 37.5%, topical application 16%, placebo 8.4%) [8]. Rare side effects included allergic reactions, sweating, and edema [10, 11, 12].
To date, CCA have not been officially approved for use in anal fissure therapy in Germany (off-label therapy). Topical formulations frequently used are nifedipine 0.2% or diltiazem 2%.
Evidence-based recommendation according to the German S3 guideline, as of 2021:
For chronic anal fissures, the first-line drug therapy should consist of topically applied calcium antagonists. They are as effective as nitrates but have fewer systemic side effects. An alternative treatment option is the use of oral calcium antagonists. Topical application should be preferred due to the more favorable ratio of effect to side effect.
Nitrates
Through the release of nitric oxide, nitrates such as glyceryl trinitrate (GTN) cause relaxation of smooth muscle cells and thus lower sphincter tone [14]. Healing rates under GTN were significant in a meta-analysis but only slightly higher than those of a placebo (48.9% versus 35.5%) [9]. In 50% of cases of healed chronic fissures, a recurrence developed.
CCA and nitrates showed no significant difference in healing rate. However, side effects occurred more frequently under nitrates, especially headaches. In an update of the meta-analysis by Nelson et al. 2017, the rate of headaches due to GTN in all studies was 30% [8]. These results were confirmed in a systematic review and meta-analysis of seven RCTs comparing CCA and nitrates by Sajid et al. [15]. In the literature, headaches are often described as a reason for non-compliance and therapy discontinuation.
Several RCTs examined the dose-dependent effect of GTN (0.05 to 0.4%) and found no difference. The healing rate was also independent of the application site (topical or intra-anal) [9].
In a prospective randomized study, Galliardi et al. investigated the optimal therapy duration of GTN and compared two patient groups with a therapy duration of 40 and 80 days. The optimal treatment duration was 6 weeks. No further improvement in symptoms was expected thereafter [16].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
With similarly high healing rates compared to calcium antagonists, nitrates can be used to treat chronic anal fissures. The downside is frequent side effects, primarily headaches.
Botulinum Toxin A
Botulinum toxin A is a protein that acts as a muscle relaxant by inhibiting the transmission of excitation from nerve to muscle cell. In this way, it reduces the resting tone of the internal anal sphincter muscle after local injection [17].
In a meta-analysis by Ebinger et al., the healing rate of botulinum toxin was 62.6% compared to 93.1% in patients after lateral internal sphincterotomy (LIS) and 58.6% in patients with conservative therapy (CCA, nitrates, placebo) [7]. Healing rates in the 16 meta-analysis studies ranged from 25% to 96% [18, 19]. Compared to botulinum toxin, LIS had a significantly higher risk of fecal incontinence.
A meta-analysis of six RCTs comparing botulinum toxin with nitrates found no significant difference in the frequency of unhealed fissures or recurrences [20]. Botulinum toxin led to a higher rate of transient incontinence but with fewer overall side effects, particularly fewer headaches.
Several meta-analyses compared the outcomes after botulinum toxin and LIS and all showed a significantly higher healing rate for LIS, but also a higher incontinence rate compared to treatment with botulinum toxin [21, 22, 23].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
In meta-analyses, the healing rates of botulinum toxin were slightly but significantly higher compared to GTN and CCA. It can therefore be offered to affected patients as a second-line therapy in case of resistance to calcium antagonists, as an alternative to surgical intervention.
Surgical Therapy of Chronic Anal Fissure
Fissurectomy
In fissurectomy according to Gabriel, the fissure and inflamed-scarred tissue are excised at the mucosal level, and a perianal drainage triangle is also created [24]. There are hardly any studies on fissurectomy without additional measures such as a flap or botulinum toxin.
A meta-analysis showed that sphincterotomy had a significantly higher healing rate compared to fissurectomy and that there was no significant difference in incontinence rate [25, 26]. In another meta-analysis, fissurectomy was combined with the advancement flap. The healing rate after fissurectomy and advancement flap was 79.8%, compared to 93.1% with LIS. Compared to LIS, the incontinence rate was 4.9% [7].
In 2003, a prospective randomized study was published comparing fissurectomy with LIS. After three months, a healing rate of 73% was found in the fissurectomy group and 80% in the LIS group among the 60 patients included. The postoperative incontinence rate for LIS was 20% and for fissurectomy 11% [27].
A case-control study with a follow-up of five years showed a recurrence rate of 11.6%. In patients who were continent before fissurectomy, the median Vaizey score for incontinence (0 to 24) was 0.8, while it was 0.4 in the control group [28]. In another RCT, 3.3% of patients experienced urinary retention after fissurectomy, and infections or abscesses and postoperative bleeding were not detected [29].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Compared to all conservative treatment options, fissurectomy has a higher healing rate, but lower than that of lateral internal sphincterotomy. Fissurectomy should be considered as primary therapy in surgical interventions because the incontinence rate is lower.
Fissurectomy Combined with Botulinum Toxin
The combination of fissurectomy with botulinum toxin injection could have additional benefits, as both measures target the pathogenic factors of the fissure, namely sphincter hypertonia and fibrotic-inflammatory ulceration. There are no randomized controlled studies on this combination therapy to date.
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Botulinum toxin can be applied for sphincter relaxation during a surgical procedure such as fissurectomy or an advancement flap.
Anal Advancement Flap
Various techniques of the advancement flap have been described in the literature, where the fissurectomy wound is covered with either anal mucosa or perianal skin (e.g., V-Y flap, dermal flap).
A meta-analysis conducted in 2018 compared the anal advancement flap with lateral sphincterotomy. In the analysis, the anal advancement flap was associated with a significantly lower incontinence rate compared to sphincterotomy. There were no differences in unhealed fissures and wound complications [30]. In a prospective study of 52 "flap patients," all fissurectomy wounds healed, and no incontinence occurred. Early postoperative flap dehiscences delayed healing in 5.9% of patients, and 5.7% of patients developed fissures at another site over time [31].
A prospective, multicenter study reported the results in 257 patients treated with fissurectomy including flap coverage. In all patients, the condition healed after an average duration of 7.5 weeks. In a questionnaire conducted one year postoperatively, 79% of patients participated. None of the patients developed a fissure recurrence, and 7% reported newly developed incontinence [32].
Hancke et al. published a retrospective comparative study in 2010 between open LIS and fissurectomy with dermal flap. In a long-term follow-up (78.5 months after LIS and 88.4 months after dermal flap), 10 out of 30 patients in the LIS group and 1 patient out of 29 patients in the dermal flap group suffered from incontinence. No reoperations were required in either group due to recurrences [33].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
The advancement flap can be performed to complement fissurectomy as first-line surgical therapy or as second-line therapy after unsuccessful conventional fissurectomy.
Lateral Internal Sphincterotomy (LIS)
"Of all surgical options, LIS is the treatment of choice for chronic anal fissures," states the current US guideline, recommending LIS as the gold standard among surgical procedures due to its high healing rates [34]. There is disagreement in the literature about the frequency of postoperative incontinence after LIS, with individual RCTs and several meta-analyses showing inconsistent results [7, 8, 35].
In 2003, Hancke et al. published the first prospective randomized study comparing LIS with the fissurectomy commonly used in Germany [33]. After three months, a healing rate of 73% was found in the fissurectomy group and 80% in the LIS group among the 60 patients included. The postoperative incontinence rate for LIS was 20% and for fissurectomy 11%. The authors concluded that LIS should no longer be performed in the future. Hasse et al. published figures from a cohort study with 209 out of 523 patients who underwent lateral sphincterotomy for chronic anal fissure between 1986 and 1997 [36]. The cohort study had a median follow-up of 124 months. The healing rate was 94.7%. 14.8% of patients developed incontinence in the twelfth week after surgery. This number increased over time to 21%, with 60% of incontinence being severe. Both studies led to LIS being banned from the repertoire of surgical fissure treatment in Germany.
A meta-analysis of 22 randomized, prospective, and retrospective studies from 2013 with a follow-up period between 24 and 124 months confirmed the high incontinence rate after LIS at 14% [37]. In another meta-analysis of RCTs, the authors found no significant difference in incontinence rate between the various surgical procedures [35].
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Lateral internal sphincterotomy has the highest healing rates in RCTs and meta-analyses, but also significantly higher incontinence rates than after fissurectomy, with the literature being inconsistent. For this reason, LIS should not be used as first-line therapy. In individual cases, LIS can be discussed with the patient after all other therapy options have been exhausted. LIS should be performed cautiously in postpartum women, patients with reduced sphincter tone, or previous anal surgeries to avoid postoperative incontinence.
Anal Dilation
Manual anal dilation under anesthesia according to Lord has the highest risk of postoperative incontinence of all procedures in the literature, as well as a lower healing rate than LIS. According to a meta-analysis from 2017, more than 18% of patients were affected by postoperative incontinence. In accordance with other guidelines, dilation should no longer be used [7, 35, 38, 34].