Management of acute anal fissure
The vast majority of acute anal fissure cases heal spontaneously. In a randomized trial undertaken 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] In a prospective cohort study, it was shown that under treatment with nifedipine ointment for 8 weeks fissures healed in 85.2% of cases.[2] While acute fissures may also be successfully treated with nitrates, the evidence is more limited compared with topical nifedipine preparations.[3,4] Jensen et al. studied patients after their initial anal fissure had healed under nonsurgical management. In the placebo group, fissures relapsed in 68% of cases within 18 months. The group taking 15 g of bran per day for more than a year had a recurrence rate of only 16%.[5]
Nonsurgical management of chronic anal fissure
Unlike acute fissure, the chronic variant heals much less often under nonsurgical measures. In their prospective study, Emile et al. demonstrated a negative association between symptom duration and fissure healing rate.[6] About 50% of chronic anal fissures will heal with nonsurgical management.[7,8,9] Undeniably, surgical measures have a better cure rate, faster symptom relief, and a lower 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 course of nonsurgical treatment (nitrates, calcium antagonists, botulinum toxin) for a period of 6 weeks before surgical measures are initiated. Surgical therapy may be performed as first-line therapy if the patient so desires or if additional fistulas and/or marked secondary morphologic changes are present.
Calcium channel blockers (CCB)
Calcium channel blockers reduce calcium ion influx into smooth muscle cells, resulting in reduced contractility, and thereby vasodilation, and reduction of sphincter tone. In the 2012 meta-analysis by Nelson et al, CCBs and nitrates were equal in terms of healing rate, but CCB treatment resulted in significantly fewer adverse effects.[9]
Nifedipine in fissure treatment can be administered orally or topically. Comparative RCTs have demonstrated the healing rate of topical regimens to be equivalent or even better.[10,11,12] A meta-analysis of four randomized trials found topical CCBs to be associated with a significantly lower rate of nonhealing fissures compared with oral CCBs.[13] In a meta-analysis, headache was the most common side effect (oral CCBs 37.5%, topical preparations 16%, placebo 8.4%).[8] Rare side effects included allergic reactions, sweating, and edema.[10,11,12]
To date, Germany has not officially approved CCBs for use in anal fissure management (off-label use). Commonly used topical formulations include nifedipine 0.2% and diltiazem 2%.
Evidence-based recommendation according to the German S3 guideline, as of 2021:
First-line drug regimens in chronic anal fissures should comprise topical calcium channel blockers. They are as effective as nitrates, but cause fewer systemic side effects. Another treatment option is the administration of oral calcium channel blockers. Due to the more favorable effect/adverse-effect profile, topical applications should be preferred.
Nitrates
Nitrates such as gylceryl trinitrate (GTN) release nitric oxide, resulting in smooth muscle cell relaxation and thus lower sphincter tone.[14] In a meta-analysis, healing rates under GTN were significant but only slightly better than with placebo (48.9% vs. 35.5%).[9] Fifty percent of patients with healed chronic fissures developed recurrences.
CCBs and nitrates did not differ significantly in terms of healing rate. However, nitrates were associated with a higher incidence of adverse effects, in particular headache. In an update of the meta-analysis by Nelson et al. 2017, the rate of headache caused by GTN was 30% in all studies.[8] These findings were confirmed in a systematic review and meta-analysis by Sajid et al of seven RCTs comparing CCBs and nitrates.[15] In the literature, headache is frequently reported as a reason for non-compliance and termination of treatment.
Several RCTs examined the dose-dependent effect of GTN (0.05–0.4%) and found no difference. Moreover, the healing rate did not depend on the site of application (topical or intraanal).[9]
In their prospective randomized trial, Galliardi et al. explored the optimal duration of treatment for GTN and compared two groups of patients with treatment durations of 40 and 80 days. Optimum treatment duration was 6 weeks. After that, the symptoms were no longer expected to improve.[16]
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Nitrates can be used to treat chronic anal fissures with healing rates similar to those of calcium channel blockers. The downside includes frequent adverse effects, first and foremost headaches.
Botulinum toxin A
The protein botulinum toxin A inhibits the neuromuscular transmission from the nerve cell to the muscle cell akin to muscle relaxants. After local injection this mechanism reduces the resting tone of the internal anal sphincter muscle.[17]
A meta-analysis by Ebinger et al. found that the healing rate of botulinum toxin was 62.6% compared to 93.1% in patients with lateral internal sphincterotomy (LIS) and 58.6% in patients with nonsurgical management (CCBs, nitrates, placebo).[7] Healing rates in the 16 meta-analysis studies ranged from 25% to 96%.[18,19] However, compared with botulinum toxin, LIS carried a significantly higher risk of fecal incontinence.
A meta-analysis of six RCTs comparing botulinum toxin with nitrates found no significant difference in the incidence of nonhealing fissures or recurrences .[20] Botulinum toxin resulted in a higher rate of transient fecal incontinence but with fewer adverse effects overall, especially less headache.
Several meta-analyses compared outcomes after botulinum toxin and LIS, and all demonstrated a significantly higher healing rate for LIS, but also a higher fecal incontinence rates compared with botulinum toxin management.[21,22,23]
Evidence-based recommendation according to the German S3 guideline, as of 2021:
In meta-analyses, botulinum toxin healing rates were slightly, but significantly, higher compared with GTN and CCBs. Therefore, in case of refractory treatment with calcium channel blockers, patients can be offered botulinum toxin treatment as a second-line therapy and an alternative to surgery.
Surgical management of chronic anal fissure
Fissurectomy
In Gabriel fissurectomy, the fissure and inflamed scar tissue are resected at the mucosal level, and a perianal triangle is also fashioned for drainage.[24] There are hardly any studies on fissurectomy without additional measures such as a flap or botulinum toxin.
A meta-analysis demonstrated that sphincterotomy had a significantly better healing rate compared with fissurectomy and that there was no significant difference in fecal incontinence rates.[25,26] In another meta-analysis, fissurectomy was combined with advancement flap. The healing rate after fissurectomy and advancement flap was 79.8%, compared with 93.1% for LIS. Compared with LIS, the fecal incontinence rate was 4.9%.[7]
In 2003, a prospective randomized trial comparing fissurectomy with LIS was published. For the 60 enrolled patients, the healing rate at three months was 73% in the fissurectomy group and 80% in the LIS group. The postoperative fecal incontinence rate for LIS was 20% and for fissurectomy 11%.[27]
A case-control study with five-year follow-up yielded a recurrence rate of 11.6%. In patients who were continent before fissurectomy, the median Vaizey score for fecal incontinence (0 to 24) was 0.8, whereas in the control group it was 0.4.[28] In another RCT, urinary retention was seen in 3.3% of patients after fissurectomy, while no infections, abscesses or postoperative bleeding were noted.[29]
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Compared to all nonsurgical treatment options, fissurectomy has a higher cure rate, but still lower than lateral internal sphincterotomy. Due to its lower fecal incontinence rate, fissurectomy should be considered the primary procedure among surgical options.
Fissurectomy combined with botulinum toxin
The combination of fissurectomy and botulinum toxin injection might have additional benefits, as both measures attack the pathogenetic factors of the fissure, i.e., sphincteric hypertension and fibrotic-inflammatory ulceration. There have not been any randomized controlled trials of this combination therapy to date.
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Botulinum toxin can be administered for sphincter relaxation during a surgical procedure such as fissurectomy or advancement flap.
Anal advancement flap
Various advancement flap techniques have been reported in the literature, where the fissurectomy wound is covered with either anal mucosa or perianal skin (e.g., VY flap, dermal flap).
A 2018 meta-analysis compared the anal advancement flap with lateral sphincterotomy. In the analysis, the anal advancement flap was associated with a significantly lower fecal incontinence rate compared with sphincterotomy. There were no differences with regard to nonhealing fissures and wound complications.[30] In a prospective study of 52 "flap patients," all fissurectomy wounds healed and there was no fecal incontinence. Early postoperative flap dehiscence delayed healing in 5.9% of patients, while 5.7% of patients developed fissures elsewhere over time.[31]
A prospective, multicenter study reported outcomes in 257 patients treated by fissurectomy including flaps. All patients had healed after a mean period of 7.5 weeks. 79% of patients participated in a questionnaire survey conducted one year following surgery. No patient developed recurrent fissure, but 7% reported new-onset fecal incontinence.[32]
In 2010, Hancke et al. published a retrospective study comparing 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 of 30 patients in the LIS group and one patient of 29 patients in the dermal flap group reported fecal incontinence. No group required reoperation due to recurrence.[33]
Evidence-based recommendation according to the German S3 guideline, as of 2021:
Fissurectomy augmented by advancement can be performed 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 in chronic anal fissures," says the current US guideline, which recommends LIS as the gold standard among surgical procedures because of its high healing rate.[34] The literature is divided on the incidence of postoperative fecal incontinence following LIS, with some RCTs and several meta-analyses yielding inconsistent outcomes in this regard.[7,8,35]
In 2003, Hancke et al. published the first prospective randomized trial comparing LIS with fissurectomy, the latter being the standard procedure in Germany.[33] For the 60 enrolled patients, the healing rate at three months was 73% in the fissurectomy group and 80% in the LIS group. The postoperative fecal incontinence rate for LIS was 20% and for fissurectomy 11%. The authors concluded that LIS should not be performed any more in the future. In 2004, Hasse et al. published figures from a cohort study with 209 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%. The healing rate was 94.7%. 14.8% of patients developed fecal incontinence by week 12 following surgery. This figure increased over time to 21%, with 60% of fecal incontinence being major. Both trials resulted in LIS being banned from surgical fissure management in Germany.
A 2013 meta-analysis of 22 randomized prospective, and retrospective trials with follow-up periods ranging from 24 to 124 months confirmed the high 14% fecal incontinence rate following LIS.[37] In another RCT meta-analysis, the authors found no significant difference in fecal incontinence rates 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 at times also significantly higher fecal incontinence rates than fissurectomy, although the literature remains inconclusive. For this reason, LIS should not be employed as first-line therapy. After all other therapeutic options have been exhausted, LIS may be discussed with the patient in exceptional cases. In order to avoid postoperative fecal incontinence, LIS should be performed sparingly in postpartum patients, in patients with reduced sphincter tone, and patients with prior anal surgery.
Anal dilation
Performed under anesthesia, manual anal dilation according to Lord carries the highest risk of postoperative fecal incontinence of all procedures in the literature, as well as a lower healing rate than LIS. According to a 2017 meta-analysis, postoperative fecal incontinence affected more than 18% of patients. In accordance with other guidelines, dilation should no longer be employed.[7,35,38,34].