Randomized clinical trial comparing botulinum toxin injections with 0.2 per cent nitroglycerin ointment for chronic anal fissure

BACKGROUND: In recent years treatment of chronic anal fissure has shifted from surgical to medical. This study compared the ability of two non-surgical treatments-botulinum toxin injections and nitroglycerin ointment-to induce healing in patients with idiopathic anal fissure. METHODS: One hundred adults were assigned randomly to receive treatment with either type A botulinum toxin (30 units Botox or 90 units Dysport) injected into the internal anal sphincter or 0.2 per cent nitroglycerin ointment applied three times daily for 8 weeks. RESULTS: After 2 months, the fissures were healed in 46 (92 per cent) of 50 patients in the botulinum toxin group and in 35 (70 per cent) of 50 in the nitroglycerin group (P=0.009). Three patients in the botulinum toxin group and 17 in the nitroglycerin group reported adverse effects (P<0.001). Those treated with botulinum toxin had mild incontinence to flatus that lasted 3 weeks after treatment but disappeared spontaneously, whereas nitroglycerin treatment was associated with transient, moderate-to-severe headaches. Nineteen patients who did not have a response to the assigned treatment crossed over to the other therapy. CONCLUSION: Although treatment with either topical nitroglycerin or botulinum toxin is effective as an alternative to surgery for patients with chronic anal fissure, botulinum toxin is the more effective option.     

Surgical versus chemical (botulinum toxin) sphincterotomy for chronic anal fissure: long-term results of a prospective randomized clinical and manometric study

BACKGROUND: The aim of this prospective randomized trial was to compare the effectiveness and morbidity of surgical versus chemical sphincterotomy in the treatment of chronic anal fissure after a 3-year follow-up. METHODS: Eighty patients with chronic anal fissure were treated by whether open lateral internal sphincterotomy (group 1) or chemical sphincterotomy with 25 U botulinum toxin injected into the internal sphincter (group 2). Clinical and manometric results were analyzed. RESULTS: Overall healing was 92.5% in the open sphincterotomy group and 45% in the toxin botulinum group (P<.001). There is a group of patients with clinical (duration of disease >12 months and presence of a sentinel pile before treatment) and manometric factors (persistently elevated mean resting pressure, % of time presence of slow waves, and number of patients or the time presence ultra slow waves after treatment) associated with a higher recurrence of anal fissure. The final percentage of incontinence was 5% in the open sphincterotomy group and 0% in the botulinum toxin group (P>.05). CONCLUSION: We recommend surgical sphincterotomy as the first therapeutic approach in patients with clinical and manometric factors of recurrence. We prefer the use of botulinum toxin in patients older than 50 years or with risk factors for incontinence, despite the higher rate of recurrence, since it avoids the greater risk of incontinence in the surgical group.     

Treatment of chronic anal fissure using closed internal and lateral sphincterotomy

When the conservative treatment of the chronic anal fissure (nitrates, topical calcium channel blockers, topical nifedipine, lignocaine and cortisone compounds) proves to be inefficient, the surgery may be opted for. From among all surgical procedures (anal dilation, fissure excision, anal advancement flap) we have opted for closed internal and lateral sphincterotomy. During the period of 1990-2002, there have been performed by just one surgeon 47 sphincterotomies (15 men-32 women), average age 49 (23-76). Results: There has not been any case of anal incontinence for gases or faeces, precocious or late; 1 para anal hematoma (2.12%) solved through puncture; 2 anal abscesses (4.25%), solved through incision and tegmen drainage. Control in 6 month's time and 1 year time: normal quality of life, without any subjective complaints; painless rectal touch, healing of the fissure, extensible anal sphincter, normal continence. The sphincterotomy was followed by the disappearance of the cleft syndrome with all patients. Although the literature contains citations of transitory and minimum incontinence in 2-4% of the cases, we have not noticed in any; no recurrences have been registered; morbidity is acceptable. The future will decide if, between sphincterotomy and the injection with the botulinum toxin, the latter one is to be preferred.     

Botulinum toxin injection versus lateral internal sphincterotomy for the treatment of chronic anal fissure: randomized prospective controlled trial

Purpose

Lateral internal sphincterotomy has been the gold standard treatment for chronic anal fissure, but it still carries the risk of permanent damage of the anal sphincter, which has led to the implementation of alternative treatment like botulinum toxin injection. The aim of this randomized prospective controlled trial was to compare the efficacy and morbidity of botulinum toxin injection and lateral internal sphincterotomy in the treatment of chronic anal fissure.

Methods

Fifty consecutive adults with chronic anal fissure were randomly treated with either lateral internal sphincterotomy or botulinum toxin (BT) injection with 50 U BT into the internal sphincter. The complications, healing and recurrence rate, and incontinence score were assessed 2, 3, 6, 12 months after the procedure.

Results

Inspection at the 2-month visit revealed complete healing of the fissure in 11 (44?%) of the patients in the BT group and 22 (88?%) of the patients in the lateral internal sphincterotomy (LIS) group (p?=?0.001). At the 3-month visit, there was no significant difference between the two groups in healing. The overall recurrence rate after 6 months in the BT group was higher than in the LIS group (p?<?0.05). In the 3-month follow-up, the LIS group had a higher rate of anal incontinence compared to the BT group (p?<?0.05). The final percentage of incontinence was 4?% in the LIS group (p?>?0.05).

Conclusions

The treatment of chronic anal fissure must be individualized depending on the different clinical profiles of patients. Botulinum toxin injection has a higher recurrence rate than LIS, and LIS provides rapid and permanent recovery. However, LIS carries a higher risk of anal incontinence in patients.     

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.     

Injections of botulinum A toxin for the treatment of anal fissures.

OBJECTIVE: To find out how injections of botulinum A toxin influence the healing of anal fissures. DESIGN: Retrospective study. SETTING: Medical University of Lodz, Poland. SUBJECTS: 13 patients (6 women, 7 men), mean age 49 (range 31-78), treated with injections of botulinum A toxin 50 units on either side of the anal fissure into the internal anal sphincter from May to December 1999. MAIN OUTCOME MEASURES: Complications and relapse. RESULTS: Seven fissures had healed by one month and four by two months. Two remained unhealed but asymptomatic. There was no incontinence of flatus or faeces after three months of treatment. Resting anal pressure was significantly lower in 10 of 13 patients compared with before treatment (p < 0.05). One fissure relapsed after 4 months and this patient had a successful anal stretch. CONCLUSION: Injection of botulinum A toxin gives good results in the treatment of anal fissures.     

Botulinum toxin injections in the internal anal sphincter for the treatment of chronic anal fissure: long-term results after two different dosage regimens.

OBJECTIVE: To investigate the effects of two different dosage regimens of botulinum toxin to induce healing in patients with idiopathic anal fissure. SUMMARY BACKGROUND DATA: Chronic anal fissure is maintained by contraction of the internal anal sphincter. Sphincterotomy, which is successful in 85% to 95% of patients, permanently weakens the sphincter and therefore might be associated with anal deformity and incontinence. METHODS: Fifty-seven consecutive outpatients were evaluated. Type A botulinum toxin was injected into the internal anal sphincter. RESULTS: Patients were divided into two treatment groups based on the number of botulinum toxin units injected. Patients in the first group were treated with 15 units and retreated with 20 units. Patients in the second group were treated with 20 units and retreated with 25 units. Two months after treatment, 10 patients in the first group and 23 patients in the second group had a healing scar. Symptomatic improvement was observed in 13 patients in the first group and in 24 patients in the second group. Statistical analysis showed that resting anal pressure varied from baseline values as a function of treatment; in contrast, the treatment had no effect on maximum voluntary pressure. Long-term healing was achieved in 13 patients in the first group and in all patients in the second group who underwent a complete treatment. CONCLUSIONS: Botulinum toxin is safe and effective in the treatment of anal fissure. It is less expensive and easier to perform than surgical treatment. No adverse effects resulted from injections of the toxin. The higher dosage is effective in producing long-term healing without complications.     

Chronic anal fissure: 1994 and a decade later--are we doing better?

BACKGROUND: Debate exists regarding whether the use of topical agents and Botox injections are as efficacious as sphincterotomy for the treatment of chronic anal fissure. METHODS: A retrospective review was performed to assess changes in management and outcomes of chronic anal fissure care in a community based colorectal practice between the individual years 1994 and 2003. RESULTS: Forty-seven patients in 1994 underwent lateral partial internal sphincterotomy and had a 100% healing rate. Thirty-nine patients were treated in 2003, with 32 undergoing Botox injection and 7 undergoing sphincterotomy initially. Of the Botox patients, 35% had recurrence, and 7 subsequently required sphincterotomy. Ultimate healing rates in 2003 were 97%. Time to heal was markedly prolonged in 2003 compared with 1994. Complication rates were similar, and there was no lifestyle-altering incontinence. CONCLUSIONS: Our review documents a significant change in the community approach to chronic fissure management. The addition of multiple treatment modalities prolongs time to healing from initial evaluation, but they allowed 72% of patients to avoid the need for permanent sphincter division while maintaining ultimate rates of healing.     

The Treatment of Chronic Anal Fissure with Botulinum Toxin

Background /Aims: The aim of this study was to evaluate the effectiveness of botulinum toxin for the treatment of uncomplicated dorsal chronic idiopathic anal fissure.

Material and Methods: Forty-five patients who reported post defecatory anal pain since two months or more were given a total of 20U botulinum toxin in the anal sphincter apparatus on both sides as well as below the anal fissure. Results: Thirty-seven patients received a second session of 25U botulinum toxin injection. Thirty-five patients (78%) presented completely healed anal fissure, while ten needed lateral internal sphincterotomy. All patients were followed up for 8-36 months. Two patients relapsed.

Conclusion: Local injection of botulinum toxin is a new and safe treatment; however, two sessions of injections are necessary to be effective and long-term follow-up to assess the recurrence rate of fissure is needed to evaluate further this method of treatment. Partial internal lateral sphincterotomy is no more the treatment of choice for chronic anal fissure.     

Changing patterns of treatment for chronic anal fissure.

To assess changing patterns of treatment for chronic anal fissure, a retrospective analysis of treatment for chronic anal fissure within one hospital between January 1990 and December 1996 was undertaken. A total of 221 patients received treatment for a chronic anal fissure in this period, of whom 209 had a surgical procedure. Manual dilatation of the anus was performed in 21 patients (10%) and has not been performed since 1995. Lateral internal sphincterotomy was performed in 183 patients (88%) and continues to be the mainstay of treatment. Five female patients (2%) were identified as having a sphincter defect by anal manometry combined with endoanal ultrasound and were treated by an anal advancement flap. From 1996 onwards, 15 patients (7%) were treated by topical glyceryl trinitrate (GTN) paste as the first line of treatment. Of these patients, nine have experienced healing of their fissure, and three have had relief of pain without healing of the fissure. Three have gone on to have a lateral internal sphincterotomy. Lateral internal sphincterotomy remains the primary form of treatment for chronic anal fissure. GTN cream has increasingly been offered as preliminary treatment over the last 12 months. Perioperative use of endoanal ultrasound allowed identification of patients who may be at high risk of postoperative incontinence from a sphincterotomy. An anal advancement flap has been used as an alternative surgical approach for these patients.     

Treatment of chronic anal fissure

Current treatment of chronic anal fissure continues to be based on conventional conservative measures in a high percentage of cases. What is known as chemical sphincterotomy aims to achieve a temporary decrease of anal pressures that allows fissures to heal. There are various alternatives such as nitroglycerine or diltiazem ointment and botulinum toxin injections. However, because of collateral effects and recurrences in the medium term, the definitive role of these treatments remains to be elucidated. Nevertheless, chemical sphincterotomy should be the first option in patients with a high risk of incontinence. "Open" or "closed" lateral internal sphincterotomy performed in the ambulatory setting with local anesthesia can currently be considered the ideal treatment of chronic anal fissure refractory to conservative measures so long as the patient is informed about the risk of minor incontinence. This procedure provides rapid and permanent recovery in more than 95% of patients. There is evidence demonstrating that the incontinence rate is related to the extent of the lateral internal sphincterotomy and consequently the extent of this procedure should be reduced to the length of the fissure.     

The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy

Objective The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia. This is thought to improve anal mucosal blood flow and promote healing of the fissure. This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN). Patients and methods Forty‐seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre. Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals. Patients were asked to report side‐effects throughout the study period. Healing of the fissure was assessed after 8 weeks of treatment. Results Forty‐six patients completed treatment; of these, 22 had healed fissures (48%). Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment. Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery. Conclusion This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.     

Advancement flap in the management of chronic anal fissure: a prospective study

Lateral internal sphincterotomy is the surgical treatment of choice of chronic anal fissure after failure of conservative measures. Several randomized trials identified an overall risk of incontinence of 10 % mostly for flatus. Fissurectomy is the most commonly used procedure to preserve the integrity of the anal sphincters. However, a possible complication is keyhole defect that may lead to faecal soiling. In this study, chronic anal fissure (CAF) was treated by fissurectomy and anal advancement flap to preserve the anatomo-functional integrity of sphincters and to reduce healing time and the risk of anal stenosis. In patients with hypertonia, surgical treatment was combined with chemical sphincterotomy by injection of botulinum toxin to enhance tissue perfusion. Forty eight patients with CAF underwent fissurectomy and anal advancement flap. In 22 subjects with hypertonia of the internal anal sphincter, intrasphincter injection of 30 UI of botulinum toxin at the completion of the surgical operation was used. All patients were followed up to 24 months. Since the first defecation, the intensity and duration of pain were significantly reduced. Two patients had urinary retention, five had infections and three had partial breakdowns. No anal stenosis, keyhole deformity or necrosis flap was recorded. At the 24 months follow-up visit, anal incontinence was similar to those detected preoperatively. Only four recurrences were detected at 18 and 20 months. After medical treatment failure, fissurectomy with advancement flap is a valid sphincter-conserving procedure for treatment of anterior or posterior CAF, regardless of hypertonia of the internal anal sphincter.     

Randomized clinical trial comparing oral nifedipine with lateral anal sphincterotomy and tailored sphincterotomy in the treatment of chronic anal fissure

BACKGROUND: The conventional treatment of chronic anal fissure is lateral sphincterotomy (LAS). The alternative options of tailored sphincterotomy (TS) and 'chemical sphincterotomy' using medication such as nifedipine have recently become available. METHODS: A prospective randomized trial was conducted to compare LAS with TS and oral nifedipine. The main endpoints were fissure healing, symptom relief, recurrence and continence. RESULTS: One hundred and thirty-two patients were treated and followed up for 4 months. LAS was significantly more effective than TS in providing pain relief (P = 0.004) and better patient satisfaction (P = 0.020) at 4 weeks. Surgery (LAS and TS) was associated with significantly better fissure healing rates (both P < 0.001 at 16 weeks) and less recurrence (both P = 0.003) than nifedipine. There were substantial problems with compliance in the nifedipine group (17 of 41 patients), related to side-effects and slow healing. There were no differences in continence between the three treatment groups. CONCLUSION: LAS was most effective in providing pain relief and allowing rapid fissure healing, with minimal recurrence and no increased risk of incontinence, in patients with good anal sphincter function.     

Treatment of chronic anal fissure

Chronic anal fissure is a common benign anorectal problem in Western countries that substantially impairs the patient's life. Consequently, a rapid and effective solution is required. We reviewed the various treatments for chronic anal fissure described in the literature, with the aim of establishing a therapeutic protocol. We recommend surgical sphincterotomy (preferably open or closed lateral sphincterotomy) as the first therapeutic approach in patients with chronic anal fissure. However, we prefer the use of chemical sphincterotomy (preferably botulinum toxin) in patients aged more than 50 years old and in those with previous incontinence, risk factors for incontinence (previous anal surgery, multiple vaginal births, diabetes, inflammatory bowel disease, etc.), or without anal hypertonia, despite the higher recurrence rate with medical treatments, since this procedure avoids the greater risk of residual incontinence described in the literature with surgical sphincterotomy in this group of patients.     

Recent advances in the pharmacotherapy of chronic anal fissure: an update

Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN) ointment (0.2%) has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fissures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.     

Medical and Surgical Treatment of Chronic Anal Fissure: A Prospective Study

The aim of this prospective study was to assess the efficacy of different medical treatments and surgery in the treatment of chronic anal fissure (CAF). From 1/04 to 09/06, 156 patients with typical CAF completed the study. All patients were treated with 0.2% nitroglycerin ointment (GTN) or anal dilators (DIL) for 8 weeks. If no improvement was observed after 8 weeks, patient was assigned to the other treatment or a combination of the two. Persisting symptoms after 12 weeks or recurrence were indications for either botulinum toxin injection into the internal sphincter and fissurectomy or lateral internal sphincterotomy (LIS). During the follow-up (19 ± 8 months), healing rates, symptoms, incontinence scores, and therapy adverse effects were prospectively recorded. Overall healing rates were 65.3 and 96.3% after GTN/DIL or BTX/LIS. Healing rate after GTN or DIL were 39.8 and 46%, respectively. Thirty-six patients (23.1%) responded to further medical therapy. Fifty-four patients (34.6%) underwent BTX or LIS. Healing rate after BTX was 81.8%. LIS group showed a 100% healing rate with no morbidity and postoperative incontinence. In conclusion, although LIS is far more effective than medical treatments, BTX injection/fissurectomy as first line treatment may significantly increase the healing rate while avoiding any risk of incontinence. Presented at the SSAT Annual Meeting, May 2007,Washington, DC, USA.     

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.     

Fissure-in-ano, to divide or not to divide?

Anal fissure is one of the most common and painful proctological pathologies affecting mainly young individuals. The physiopathology in the development of a chronic anal fissure seems to be a combination of internal anal sphincter hypertonia and poor vascularization at the posterior midline. Treatment of acute fissures is conservative with supportive therapy, leading to healing in the majority of the patients. Open or closed lateral internal sphincterotomy is the treatment of choice for chronic anal fissures. In low pressure chronic fissures, sphincterotomy should be avoided and a V-Y island advancement flap may be an alternative procedure. Sphincterotomy can induce anal incontinence, a feared complication of this technique. Recent interest has developed in chemical sphincterotomy with local botulin toxin injections or glyceryl trinitrate application. Long-term follow-up is needed to evaluate these new therapeutic options.     

Topical nitroglycerin versus lateral internal sphincterotomy for chronic anal fissure: prospective, randomized trial

Introduction: Topical nitroglycerin (GTN) is one of the medical treatments of choice in chronic anal fissure. The present prospective, randomized, clinical trial was conducted to study the symptomatic relief, healing, and changes in the maximum anal resting pressure (MARP) in patients with chronic anal fissure comparing topical GTN and lateral sphincterotomy. Methods: Forty consecutive patients with chronic anal fissure were randomized for treatment with either topical GTN or internal sphincterotomy (20 patients in each group). Anal manometry was done before treatment in all patients, and 1 h after application of GTN or sphincterotomy. Patients were followed at 2‐weekly intervals for 6 weeks for symptomatic relief and healing. Results: Both GTN and sphincterotomy brought about a highly significant, but comparable drop in the MARP after treatment (P < 0.0001 in both groups). Sphincterotomy relieved pain much earlier compared to GTN (70% vs 40% at 2 weeks, P = 0.0032); but after 4 weeks of treatment, pain relief in both groups was comparable. Healing in the sphincterotomy group was also earlier than with GTN (55% vs 0% at 2 weeks, P < 0.0001; and 85% vs 30% at 4 weeks, P < 0.0001); but after 6 weeks, healing in both groups was comparable. Sphincterotomy had a significant incidence of minor, short‐term complications; it also required surgical expertise, theatre time, and day‐care beds. Nitroglycerin is safe, with mild and tolerable side‐effects of headache and local burning sensation. Conclusion: Topical GTN should be the initial treatment in chronic anal fissure. Lateral sphincterotomy should be reserved for patients with severe disabling pain (because pain relief is much faster), and for patients not responding to at least 4 weeks of GTN therapy.