Glyceryl trinitrate (GTN) and isosorbide dinitrate (ISDN) are the NO donors used to treat anal fissure. These are administered topically to the anal skin with the aims of relaxing the IAS and increasing local blood flow. GTN has been applied at two different concentrations: 0.2 % and 0.4 %. ISDN needs to be administered five times a day to achieve the same amount of nitrate that GTN provides with only two applications a day (although in published studies GTN is applied at a 1 % concentration three times a day) [8]. This is why ISDN is not routinely used in practice. GTN at a concentration of 0.4 % has been marketed in Europe. The topical application of GTN is associated with transient headache in 27–50 % of patients [8]. These may occur during the first 2 or 3 weeks of treatment and last between 10 and 30 min. The headaches usually respond to standard treatment with pain killers, but 10–20 % of patients abandon GTN treatment because of the headaches [6]. The pain caused by the anal fissure begins to improve between the fifth and seventh days, but the treatment must be maintained for minimum of 8 weeks to increase the chances of a cure. A meta-analysis of 75 studies showed that GTN has a better rate of healing of anal fissure than placebo (48.6 % vs. 37 %; P = 0.004) [8].

The figures published on recurrence are diverse and range between 17 % and 67 % [9–13]. A significant proportion of patients with long-term recurrence can be treated again with topical GTN or other topical medications, and surgery is not always necessary. In fact, the number of surgeries for anal fissure has decreased in recent years to between 60 % and 72 %.

Patients with a risk of hypotension and those taking sildenafil (Viagra) or another type of phosphodiesterase type 5 (tadalafil [Cialis], vardenafil [Levitra]) inhibitors should be treated with medications different from GTN because of such risk.

Calcium channel antagonists such as nifedipine and diltiazem have been shown to relax the IAS and decrease resting pressure in the anal canal [14]. These drugs have been administered both orally and topically. Oral forms increase the risk of dizziness and episodes of significant hypotension in up to 5 % of patients and are not more effective than topical forms [15, 16]. Calcium channel antagonists are generally used as the first-line treatment or in patients resistant to treatment with GTN.

There is no commercial preparation available in Europe, so calcium channel antagonists must be compounded (custom-made) and prescribed as formulations: either diltiazem 2 % or nifedipine 0.2–0.5 %. Prescriptions are generally associated with lidocaine (a local anaesthetic) to help with the pain caused by the anal fissure. Their effectiveness is difficult to assess based on the literature because of the small number of publications and their short follow-up, but studies comparing nifedipine and diltiazem with GTN show that calcium channel antagonists are at least as effective as GTN (50–65 %), with a similar incidence of recurrence and fewer adverse effects (flushing, headache) [18, 19]. Headache occur in only 0–25 % of patients, that is, half of the prevalence when compared with GTN (33–50 %) [17].

A systematic review of studies comparing diltiazem and GTN included 481 patients. It concluded that their effectiveness and relapse rates are comparable, but the diltiazem group showed fewer adverse effects (Risk ratio (RR) = 0.48; 95 % CI = 0.27–0.86; P < 0.01) [20].

ISDN has also been compared to surgery; in a large study involving 207 patients with chronic anal fissures, success at 6 months was 77 % (ISDN) and 97 % (surgery). Recurrence at 12 months occurred in 4.8 % (ISDN) and 1 % (surgery). De novo fecal incontinence was diagnosed in 6 patients (3 %) of those treated with surgery and in none of the patients treated with ISDN [21].

There are several commercial presentations of BT. Those used in the treatment of anal fissure are botulinum toxin type A (Botox; 50 or 100 IU/vial), incobotulinumtoxinA (Xeomin; 50 and 100 IU/vial), and abobotulinumtoxinA (Dysport; 500 IU/vial). When Disport is used it should be remembered that dosing is on a ratio of approximately 1 to 3, meaning that 50 IU of Botox or Xeomin have the same effect as 150 IU of Disport [22]. Correct administration of BT is followed by local muscle relaxation that lasts around 2 to 4 months.

BT has been injected in different ways—unilateral or multilateral, at the base of the fissure or at one or both sides of the fissure, at the IAS, in the external anal sphincter, or both—and at different doses: from 5 to 50 IU (most commonly 50 IU) in single or multiple applications. This large variation in administration makes interpreting the results described so far difficult.

The first published results on the effectiveness of BT described a success rate over 80 % [22], but subsequent studies have shown that healing is accomplished in around 50 % of patients when follow-up is longer than 12 months [3, 23].

Local complications occur in less than 5 % of patients and include local hematoma or infection at the site of administration. General complications are toxin allergy or temporary incontinence (0–13 %), all of which are not frequent but dose dependent.

A meta-analysis including more than 270 patients demonstrated the superiority of surgery when compared with BT (RR = 1.31; 95 % CI = 1.50–1.57), a greater absolute benefit from surgery (23 %), and a higher recurrence with the toxin (RR = 5.83; 95 % CI = 2.96–11.49). Surgery was associated with increased rates of fecal incontinence (RR = 0.08; 95 % CI = 0.01–0.59) [24]. The benefits of BT treatment are ease of application, even in a doctor’s office. The main disadvantage is the high cost.

Comparative results of BT against a combined treatment of GTN and BT in patients who did not respond to ISDN did not show the superiority of the combination. Although the association had a better cure rate after 6 weeks of treatment (66 % vs. 20 %), this superiority was not found at the 8th (73 % vs. 73 %) or at the 12th week of treatment (60 % vs. 66 %) [25].

NO donors have also been compared with BT in several studies. A recent study with a small number of patients compared BT (Dysport 60 IU) with ISDN. Toxin cure rates were higher and adverse effects were fewer than those observed with ISDN, although recurrence rates were high in both groups (50 % and 28 %, respectively) [26]. GTN and BT have also been compared in several studies. A meta-analysis of these studies concluded that the two treatments are equally effective, but incontinence after treatment is more common in patients treated with BT. BT is a more invasive treatment and also has a higher cost—these are reasons why many groups consider BT as a second-line treatment, for use in cases where topical treatment has not been effective [8].

Diltiazem was compared with BT in a randomized study with 143 patients. The two treatments were equally effective in the treatment of chronic anal fissure: a healing rate of 43 % was found for both treatments and a significant reduction in pain occurred in 78 % (diltiazem) and 82 % (BT) [27].

There are two different techniques described for a sphincterotomy: posterior and lateral, depending on the sectioned part of the internal sphincter. Posterior sphincterotomy, although used in the past, is not recommended today because it produces a keyhole deformity in the anus that is related to postoperative soiling. It is only performed in patients with a posterior anal fissure associated with intersphincteric abscess.

Lateral sphincterotomy is more effective than medical management; a greater than 90 % chance of cure and the patient satisfaction rate support this conclusion. It can be done under local anesthesia and is mostly performed as a same-day surgical procedure.

Sphincterotomy can be performed using an open or a closed technique. When both techniques were compared, no significative differences were found, although the open technique is related to superior healing rates but increased flatus incontinence [6].

Lateral sphincterotomy is more easily performed with the help of an anal retractor to correctly identify the intersphincteric groove. An incision is made at this level in the lateral quadrant of the anus (3 o’clock for right-handed or 9 o’clock for left-handed surgeons). The incision can be either circumferential or radial; there are no differences among the short- and long-term results when both have been compared [28]. Dissection of the internal sphincter from the anal mucosa and the external sphincter is followed by a partial section of the internal sphincter. No differences in healing or complications have been found when comparing suturing versus no suturing of the skin (Figs. 5.3, 5.4, 5.5, 5.6, and 5.7).

With respect to the internal sphincter section, limiting it to less than half the length of the sphincter does not increase the recurrence rate and diminishes postoperative fecal incontinence, although some groups recommend a more economical length of division at less than 25 % of its length, which in women corresponds to less than 1 cm [29].

When performing a lateral sphincterotomy, a tear produced while dissecting the anal sphincter from the anal mucosa is best solved by opening the entire involved mucosa, as in a lay-open technique, to avoid creating a postoperative fistula.

Fissurectomy includes excision of the fibrotic edge of the fissure, curettage of its base, and excision of the sentinel pile and⁄or anal papilla, if present. Some groups consider it to be a more conservative treatment for anal fissure. It can be combined with the application of BT [30] in an effort to improve the results, which are poorer when fissurectomy is done alone [31]. Published healing rates when combined with BT are between 70 % [32] and 90 % [30], and de novo incontinence is usually temporal and minimal (occurring in <5 % of patients), or even absent in some other series [33].

Another novel procedure has recently been introduced in the surgical armamentarium for anal fissure: fissurotomy. It consists of unroofing the fissure, which significantly widens the distal anal canal, rendering internal sphincterotomy unnecessary [34]. Results have been promising, with less than a 2 % recurrence rate and no change in continence status. More studies and longer follow-up are needed to support these findings, which could also be influenced by the amount of anal dilatation involved in the procedure.