Novel delivery of botulinum toxin for the treatment of anal fissures

OBJECTIVE: Botulinum toxin A (Botox) has been used as a local treatment for anal fissure since 1994. It effects a reversible chemical sphincterotomy without the need for patient compliance. This study examines the feasibility of injecting the treatment using a needle-less system. PATIENTS AND METHODS: The optimal angle for injection was determined in a preclinical study using fresh porcine specimens. Ten patients with chronic anal fissures were then injected with 20 units Botox at the site of the fissure. They underwent assessment with a visual analogue pain scale, incontinence score and anal manometry pre-injection, at 48 h postinjection and at six and 12 weeks postinjection. They were also examined at the initial and final visits. RESULTS: The optimal angle for injection was 60 degrees . All 10 patients (5 male; median age 40.5 years (range 26-68 years)) attended the 48 h follow up visit but only seven attended the six and 12 week visits. Six of seven patients healed their fissures. The remaining three were contacted by telephone at six months post injection and two of three remained asymptomatic without further treatment. In seven patients who underwent full follow up the median pain score pre-injection was 5.5 out of 10 (range 1-10) and this dropped to a median of 1 (range 0-6) at 12 weeks. The median drop in resting pressure was 47 cm H2O or 37% at six weeks. CONCLUSION: No needle injection of Botox is feasible with similar healing rates and reduction of resting pressure to conventional injection techniques.     

Treatment of anal fissures with botulinum toxin

Chronic anal fissure is a common proctological disease. Botulinum toxin (BTX) can be used for temporary chemical denervation. The administration is by intramuscular injections into either the external or the internal anal sphincter muscles. The mode of action, administration techniques and possible complications or adverse effects of BTX therapy are discussed. The healing rate is dependent on the BTX dosage. The short-term healing rate (< or = 6 months) is between 60 and 90 %. In long-term follow-up studies (> 1 year), about 50 % of patients show a complete response. Adverse effects are generally mild but relapses occur more often compared to surgery. Conservative therapies including BTX are currently considered mostly as the first-line treatment. Among the surgical procedures, lateral sphincterotomy is the most effective treatment but shows higher incontinence and general morbidity rates than BTX.     

Real world outcomes of lateral internal sphincterotomy vs botulinum toxin for the management of chronic anal fissures

BackgroundLateral internal sphincterotomy (LIS) remains the gold standard surgical approach for the management of chronic anal fissures (CAF). The procedure however, is complicated by the risk of postoperative incontinence. Intrasphincteric Botulinum Toxin (BT) has gained popularity as an alternative approach, despite being inferior to LIS with regards to cure rates. In the real world, patients at high risk for postoperative incontinence are likely to be offered BT as a preliminary procedure. The aim of this study was to explore the real-world outcomes of LIS and BT for a cohort of CAF patients.Methods251 consecutive patients treated with either BT or LS for CAF by a single surgeon were reviewed. Patients were offered BT as a preliminary procedure if they had risk factors for faecal incontinence, whereas all other patients underwent LIS. Primary outcomes included rates of recurrence and faecal incontinence.ResultsLIS was superior to BT with regards to recurrence rates throughout the mean follow up period of five years (5% vs 15%, p = 0.012). A total of 17 patients experienced a minor degree of flatal incontinence at the 6-week follow up, although there was no difference between LIS and BT (7% vs 6%, p = 1.000). Four LIS patients (2%) continued to experience some minor incontinence to flatus at the 12-month follow up and were managed with biofeedback.ConclusionFor patients with CAF, individualizing the treatment approach according to risk factors for incontinence could mitigate this risk in LIS. High risk patients should be offered BT as a preliminary procedure.     

Effectiveness of higher doses of botulinum toxin to induce healing in patients with chronic anal fissures

BACKGROUND: Botulinum toxin induces healing in patients with idiopathic anal fissures. METHODS: One hundred-fifty patients with posterior anal fissures were treated with botulinum toxin injected in the internal anal sphincter on each side of the anterior midline. Subjects were randomized into 2 treatment groups based on the number of units of botulinum toxin injected. Patients in group I were treated with 20 units of botulinum toxin and, if the fissure persisted, were retreated with 30 units. Patients in group II were treated with 30 units and retreated with 50 units, if the fissure persisted. RESULTS: The 2 groups were comparable in age, gender distribution, duration of symptoms, resting pressure, and maximum voluntary pressure at anorectal manometry. One month after the injection, examinations revealed complete healing in 55 patients (73%) from group I and 65 patients (87%) from group II (P =.04). Five patients from group II reported a mild incontinence of flatus that lasted 2 weeks after the treatment and disappeared spontaneously. The values of the resting anal pressure (P=.3) and the maximum voluntary pressure (P =.2) did not differ between the 2 groups. At 2 months' evaluation, a healing scar was found in 67 patients (89%) from group I and 72 patients (96%) from group II. A relapse of the fissure was observed in 6 patients (8%) from group I who had a healing scar at 1 month, and 2 other patients never healed. A persistent fissure was present in 3 patients from group II who had no other symptoms. CONCLUSIONS: Botulinum toxin injected into the internal anal sphincter is effective in managing anal fissures and avoiding permanent complications. All patients were treated with the active drug and healed after 1 or 2 successive treatments. The results also confirm that higher doses account for a higher success rate, with little increase in complications or side effects, which is probably related to the diffusion of the toxin to the external sphincter.     

Botulinum toxin A injection in ISDN ointment-resistant chronic anal fissures

BACKGROUND: In the treatment of chronic anal fissures (CAFs), surgical sphincterotomy is more commonly being replaced by chemical sphincterotomy. After the good results of our pilot study including 32 patients, we now describe the effect of botulinum toxin A (BT-A) in a consecutive series of 100 patients with isosorbide dinitrate (ISDN) ointment-resistant CAFs. METHODS: From October 2002 until August 2005, 100 patients (52 males, 48 females) with a median age of 45 (20-79) years were treated with an injection of 40-100 IU BT-A (Dysport, Ipsen, The Netherlands) in the internal anal sphincter. RESULTS: After a median follow-up of 10 (4-38) months, 77 of the 100 CAFs (77%) were cured. 20 patients were given a second injection, 1 a third and 1 a fourth injection. In 11 patients a fissure recurred (14%). In 1 patient (1%) there was temporary incontinence due to flatus. CONCLUSION: With an early response rate of 77% and an overall success rate of 66%, BT-A injections appear to be effective in patients with ISDN ointment-resistant CAFs if initial non-responders are retreated. These results are in concordance with the results of our pilot study. It is a simple technique with little or no side effects, that does not compromise future treatments. Its place in the first-line treatment of CAFs should be investigated further.     

Nonsurgical treatment of chronic anal fissure: nitroglycerin and dilatation versus nifedipine and botulinum toxin.

BACKGROUND: Surgical sphincterotomy for chronic anal fissure can cause fecal incontinence. This has led to the investigation of nonsurgical treatment options that avoid permanent damage to the internal anal sphincter. METHODS: We conducted a retrospective, ongoing chart review with telephone follow-up of 88 patients treated for chronic anal fissure between November 1996 and December 2002. During the first half of the study period, patients were treated with topical nitroglycerin and pneumatic dilatation. With the availability of new therapies in June 1999, subsequent patients received topical nifedipine and botulinum toxin injections (30-100 units). Lateral anal sphincterotomy was reserved for patients who failed medical treatment. RESULTS: In 98% of patients the fissure healed with conservative nonsurgical treatment. The combination of nifedipine and botulinum toxin was superior to nitroglycerin and pneumatic dilatation with respect to both healing (94% v. 71%, p < 0.05) and recurrence rate (2% v. 27%, p < 0.01). There was no statistical difference between the number of dilatations and botulinum toxin injections needed to achieve healing. Three patients who received botulinum toxin reported mild transient flatus incontinence. At an average telephone follow-up of 27 months, 92% of patients reported having no pain or only mild occasional pain with bowel movements. CONCLUSIONS: Chronic anal fissures can be simply and effectively treated medically without the risk of incontinence associated with sphincterotomy. Topical nifedipine and botulinum toxin injections are an excellent combination, associated with a low recurrence rate and minimal side effects.     

Fissurectomy as a treatment for anal fissures in children

INTRODUCTION: Anal fissures, characterised by painful defecation and rectal bleeding, are common in both children and infants. A significant proportion are resistant to simple laxative therapy, and no simple surgical treatment has been described which does not risk compromising sphincteric function. This study reports the initial experience of fissurectomy as a treatment of this condition. PATIENTS AND METHODS: Over a 36 month period, 37 children with an anal fissure were treated by fissurectomy. There were 14 boys and 23 girls, with an age range of 17 weeks to 12 years. Fissurectomy was performed under general anaesthetic, with additional caudal anaesthesia. Stay sutures were used to avoid the need for an anal retractor, thereby preventing stretching of the internal anal sphincter. Of the 37 operations, 36 (97%) were performed as day cases and all children were discharged on laxative therapy. RESULTS: At review, 6 weeks postoperatively, 30 (81%) were asymptomatic. Six (16%) patients were symptomatic; however, 4 of these had failed to comply with the postoperative laxative regimen. One patient failed follow-up. CONCLUSIONS: Fissurectomy is a successful treatment for anal fissures, when combined with postoperative laxative therapy. As dilatation of the internal anal sphincter is not involved, the risk of iatrogenic faecal incontinence is obviated.     

Chronic anal fissures treated with botulinum toxin injections: a dose-finding study with Dysport®

Botox^® injection of the anal sphincter muscle cures chronic uncomplicated anal fissures in up to 80% of patients. This study examines the therapeutic efficacy and side effect profile of the British botulinum product Dysport^®. Fifty patients (29 women) were recruited to participate in this randomized dose-finding study, their mean age being 32.9 years. The low dose group A was treated with a total dose of 20 U injected in two sites each lateral to the fissure, the high dose group B was treated with 40 U. Eighty-two percent of patients were pain-free within a week following the injections. The fissure was healed in 78% of treated patients after 3 months. Three patients relapsed within 6 months. The most common adverse side effect was transient incontinence ( n  = 4). Clinical outcome was not significantly different between the two treatment groups. The low dose can therefore be regarded sufficient for the treatment of anal fissure. Therapeutic efficacy was equivalent to published data on Botox treatment. Both Dysport^® and Botox^® can therefore be used to treat chronic uncomplicated anal fissures. Both Dysport^® and Botox^® therapy are well tolerated, can be performed on an out-patient basis and avoid the risk of permanent faecal incontinence which complicates surgical treatment of anal fissures.     

Modern perspectives in the treatment of chronic anal fissures

INTRODUCTION

Anal fissures are commonly encountered in routine colorectal practice. Developments in the pharmacological understanding of the internal anal sphincter have resulted in more conservative approaches towards treatment. Simple measures are often effective for early fissures. Glyceryl trinitrate is well established as a first-line pharmacological therapy. The roles of diltiazem and botulinum, particularly as rescue therapy, are not well understood. Surgery has a defined role and should not be discounted completely.

METHODS

Data were obtained from Medline publications citing ‘anal fissure’. Manual cross-referencing of salient articles was conducted. We have sought to highlight various controversies in the management of anal fissures.

FINDINGS

Acute fissures may heal spontaneously, although simple conservative measures are sufficient. Idiopathic chronic anal fissures need careful evaluation to decide what therapy is suitable. Pharmacological agents such as glyceryl trinitrate (GTN), diltiazem and botulinum toxin have been subjected to most scrutiny. Though practices in the UK vary, GTN or diltiazem would be suitable as first-line therapy with botulinum toxin used as rescue treatment. Sphincterotomy is indicated for unhealed fissures; fissurectomy has been revisited and advancement flaps have a role in patients in whom sphincter division is not suitable.     

Mechanism of action of botulinum toxin on the internal anal sphincter

BACKGROUND: Botulinum toxin is an effective treatment for anal fissure. Manometric studies support an apparent action of botulinum toxin on the internal anal sphincter (IAS). This aim of this study was to establish the underlying mechanism. METHODS: Porcine IAS strips were suspended in a superfusion organ bath and allowed to equilibrate. Electrical field stimulation (EFS) was applied with parameters that induced nitrergic relaxation followed by noradrenaline-mediated contraction. These responses were compared before and after addition of botulinum toxin. RESULTS: All strips developed myogenic tone, which was slightly increased following the addition of botulinum toxin. EFS-induced nitrergic relaxation was unaffected by toxin treatment. However, EFS-induced contraction was significantly reduced by toxin treatment. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, caused muscle strip contraction, which was blocked by guanethidine, implying the presence of sympathetic ganglia within the IAS. Botulinum toxin significantly attenuated DMPP-induced contraction. CONCLUSION: In the treatment of anal fissure the major effect of botulinum toxin on the IAS is blockade of sympathetic (noradrenaline mediated) neural output. This is probably a postganglionic action, involving a reduction in noradrenaline release at the neuromuscular junction. Botulinum toxin has no significant effect on nitrergic transmission, which is probably not vesicular in nature.     

Botulinum toxin for the treatment of anal fissure

BACKGROUND: The classic treatment for uncomplicated anal fissure is surgical sphincterotomy, i.e. cutting of the internal anal sphincter, thus eliminating spasm of this muscle and breaking the vicious circle of pain, spasm and inflammation. Recently, however, botulinum toxin has become available for the treatment of muscular dystonias, and thus for anal fissure. In the present study, we investigated the effectiveness of treatment with botulinum toxin in 76 patients with uncomplicated anal fissure. MATERIAL AND METHOD: The 76 patients received an injection of 40 U of botulinum toxin on each side of the fissure. Response was monitored 7, 30 and 90 days later. All patients who did not show clear improvement after 30 days received a second dose of 40 U on each side. RESULTS: After 90 days, 51 patients (67%) showed complete recovery, 19 patients (25%) substantial improvement though not complete recovery, and 6 patients (8%) no significant improvement. Transitory gas incontinence was reported by 2 patients (2.6%), and 1 patient presented hemorrhoidal thrombosis. DISCUSSION: Botulinum toxin enables chemical denervation of the internal sphincter, facilitating healing of the anal fissure. Its principal advantages with respect to surgical sphincterotomy are the absence of the general risks of surgery, and reduced incidence of incontinence, which even if it occurs tends to be transitory. The technique does not require hospitalization and is well tolerated. It appears suitable for the initial treatment of uncomplicated anal fissure, reserving surgical treatment for those cases which fail to response adequately.