Comparison of topical glyceryl trinitrate ointment and oral nifedipine in the treatment of chronic anal fissure

This study was designed to compare the effect of topical glyceryl trinitrate (GTN) and oral nifedipine treatments on maximal anal resting pressure (MARP) and subsequently to assess their effectiveness in healing of chronic anal fissure (CAF). Patients were allocated randomly to receive either oral nifedipine retard (10 patients) 20 mg twice daily or instructed to apply glyceryl trinitrate (0.2 percent) ointment (10 patients) into the lower half of the anal canal twice daily. They were reviewed and assessed at the first visit and every fortnight for measurement of MARP, pain scores, blood pressure, pulse rate, healing of the fissure and adverse effects. Treatment were continued until healing had occurred or for up to 8 weeks. MARP values before and after application of the GTN ointment was 113.2 cm H2O and 72.5 cm H2O respectively (P < 0.001). Nifedipine caused a reduction in mean MARP from 105.2 to 74.0 cm H2O (P < 0.001). Linear analogue pain scores were significantly reduced after 2 weeks treatment with GTN and nifedipine (P < 0.001) and continued throughout the treatment period. At the end of the study; 7 of the 10 patients in the GTN group were deemed to be healed (5) or improved (2), compared with 6 of the 10 patients in the nifedipine group (5 healed, 1 improved). Headaches occurred in 3 patients in the GTN group, compared with one patient in the nifedipine group. There was no significant difference between GTN and nifedipine in terms of reduction in MARP and pain score, healing of the fissure and incidence of early recurrence and side effects of treatments. We conclude that GTN ointment and oral nifedipine are equally effective in the treatment of chronic anal fissure.     

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.     

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.     

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 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.     

Topical 0.2% glyceryl trinitrate ointment for anal fissures: long-term efficacy in routine clinical practice

Objective Randomized controlled trials have reported fissure healing rates of 60–70% using topical 0.2% GTN ointment, but the effectiveness of this therapy in routine clinical practice, particularly in the long term, is uncertain. This study aimed to evaluate the efficacy of topical GTN for anal fissures in an outpatient setting. Patients and methods A case note review and postal questionnaire survey were undertaken for patients with a diagnosis of anal fissure dispensed 0.2% GTN ointment from one hospital pharmacy over a two year period (June 1996–May 1998). Results Ninety‐three patients (53 male) applied 0.2% GTN ointment twice daily to the anoderm for anal fissure. They were reviewed on average 8 (2–16), weeks later, by which time 57 (61%) fissures had healed, 33 persisted and 3 patients were lost to follow up. Seventy‐two patients (41male), median age 42 (22–83) years, returned completed questionnaires (77% response rate). Forty‐nine (68%) had healed with GTN, but 25 had recurrent symptoms after a median of 6 (1–18) months. Sixteen of those patients reporting symptomatic recurrence were prescribed further GTN for a recurrent fissure: 14 (88%) healed, but 2 persisted, and had surgery. In the other nine patients symptoms resolved spontaneously. Thirty‐five (49%) experienced headaches, 3 (4%) discontinuing treatment as a result. The median follow up was 25 (13–36) months. Conclusion 0.2% GTN heals 60% of fissures in the outpatient setting but half the patients develop headaches. Up to one third of healed fissures may recur within 18 months but the majority respond to further GTN. Only 4% of patients initially healed with GTN later require sphincterotomy for recurrences.     

Quality of life assessment in patients with chronic anal fissure after lateral internal sphincterotomy

BACKGROUND: The aim of this study was to compare quality of life of patients with chronic anal fissure before and after open lateral internal sphincterotomy. METHODS: A prospective study was undertaken of 108 consecutive patients with a history of chronic anal fissure who underwent lateral internal sphincterotomy. Quality of life was measured before and 6 months after operation with the Short-Form 36 (SF-36) Health Survey. RESULTS: Quality of life improved significantly in six of the eight scales of the SF-36 questionnaire: physical functioning, role physical, bodily pain, energy, social functioning and mental health. There were no significant differences between the 70 patients who had no change in continence after operation and the 38 patients with continence disturbances after sphincterotomy. However, there were significant improvements in four scales in patients without changes in continence compared with improvements in only two scales in those with continence disturbances. CONCLUSION: Patients with chronic anal fissure showed an improvement in quality of life 6 months after internal lateral sphincterotomy. Patients with postoperative continence disturbances showed improvement in fewer scales of the SF-36 questionnaire than those without changes in continence.     

Internal anal sphincter function following lateral internal sphincterotomy for anal fissure: a long-term manometric study

BACKGROUND: Anal fissure is a common and painful disorder. Its relation to hypertonic anal sphincter is controversial. The most common surgical treatment of chronic anal fissure is lateral internal sphincterotomy. OBJECTIVE: The aim of this study was to evaluate long-term manometric results of sphincter healing following lateral internal sphincterotomy. PATIENTS AND METHODS: Between 2000 and 2003, 50 patients with anal fissure were included in this study and underwent sphincterotomy; 12 healthy patients served as controls. All patients with anal fissure underwent manometric evaluation using a 6-channel perfusion catheter. All patients were examined 1 month before surgery and 1, 3, 6, and 12 months following surgery. The control group had 3 manometric evaluations 6 months apart. RESULTS: The mean basal resting pressure before surgery was 138 +/- 28 mm Hg. One month after surgery, the pressure dropped to 86 +/- 15 mm Hg (P < 0.0001) and gradually rose to a plateau at 12 months (110 +/- 18 mm Hg, P < 0.0001). At 12 months, the manometric pressure was significantly lower than the baseline (P < 0.0001). However, manometric measurements in the fissure group were still significantly higher than in the control group (110 +/- 18 versus 73 +/- 4.8 mm Hg, P < 0.0001). All patients were free of symptoms at the 12-month follow-up. CONCLUSION: Lateral internal sphincterotomy caused a significant decline in the resting anal pressure. During the first year following surgery, the tone of the internal anal sphincter gradually increased, indicating recovery, but still remained significantly lower than before surgery. However, postoperative resting pressures were higher than those in the control, and no patient suffered any permanent problems with incontinence, so this decrease may not be clinically significant.     

Open lateral sphincterotomy is still the best treatment for chronic anal fissure

Chronic anal fissure is the main cause of anal pain and is very common. Many treatment modalities have been tried-none is ideal. Recently, topical nitric oxide releasing agents and botulin toxin injections have been used, trying to replace surgery. No long-term experience is available. Personal experience with 2,108 open, ambulatory, lateral sphincterotomy with follow-up of 4-20 years is presented.     

Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure

INTRODUCTION: Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects. METHODS: A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent. RESULTS: Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31). DISCUSSION: DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.     

Treatment of anal fissure with glyceryl trinitrate in patients referred for surgical management

Background : A number of recent studies indicate that anal fissure may be treated by applying glyceryl trinitrate (GTN) ointment. The present study aims to determine the effectiveness and patient acceptability of GTN treatment for patients referred to a consultant surgeon. Methods : A prospective study of 65 consecutive patients referred to one surgeon (ALP) over a 12‐month period was undertaken. All patients were offered 0.2% GTN ointment to be applied intra‐anally four times daily for 4 weeks. Informed consent was obtained and review planned for 4 weeks. Results : Fourteen patients declined treatment and nine of the 14 (64%) subsequently underwent lateral sphincterotomy. Twelve of the 51 patients (18.5%) who accepted treatment could not complete it due to headache or persisting severe anal pain. Thirty‐nine of the 51 patients (77%) were able to complete 4 weeks of treatment. Twenty‐two of the 39 reported an improvement in symptoms. A total of 22 patients (43%) who started GTN treatment subsequently underwent lateral sphincterotomy. Conclusions : Evidence from the present study suggests that GTN ointment has a place in the management of referred patients with severe and/or chronic anal fissure, but sphincterotomy remains an important treatment option for the majority.     

Effect of topical glyceryl trinitrate on anodermal blood flow in patients with chronic anal fissures

Introduction : Recent studies have highlighted the role of increased internal anal sphincter pressure and decreased anodermal blood flow in the pathogenesis of chronic anal fissures. The duration of the effect of topical 0.2% glyceryl trinitrate (GTN) ointment on anodermal blood flow in fissure and normal areas was investigated in patients with chronic anal fissures. Methods : Six patients with chronic anal fissures in the posterior midline participated in the study. Blood flow measurements were performed on the anoderm using laser Doppler flowmetry before and immediately after the topical application of 0.2% GTN ointment and subsequent readings were taken at 5, 15, 30, 45 and 60 min in all four quadrants. Results : The mean anodermal blood flow in the fissure region is significantly lower than the mean blood flow of the rest of the anoderm before 0.2% GTN ointment is applied (228.7 ± 61.8 flux units vs 439.3 ± 25.5 flux units, respectively; P < 0.05). Immediately after the application of local 0.2% GTN ointment there is a significant increase in anodermal blood flow over the anal fissure region (457.8 ± 56.5 flux units; P < 0.05) compared to the rest of the anoderm (457.4 ± 30.8 flux units). This increase is most marked at 5 min post‐GTN ointment application in the fissure area (474.6 ± 41.1 flux units) and the blood flow in the fissure region is consistently above the rest of the anoderm for most of the 60 min. Conclusion : There is clearly reduced blood flow to the chronic anal fissure region compared to the rest of the anoderm. Topical application of glyceryl trinitrate ointment seems to significantly improve the blood flow to the fissured area in the first hour. This may therefore help in the healing of chronic anal fissures.     

Closed lateral subcutaneous sphincterotomy under local anaesthesia in the treatment of chronic anal fissure.

We studied 65 consecutive ambulatory patients with chronic anal fissure that were treated by sphincterotomy under local anaesthesia. The patients were allowed to leave the clinic immediately after the operation. Healing rate was determined three to four months postoperatively by clinical examination and proctoscopy. Fifty-seven patients (88%) were free of symptoms and the fissure was healed. Eight unhealed patients were subjected to a repeated procedure under local anaesthesia, leaving two unhealed patients, that were operated with open sphincterotomy under general anaesthesia. We conclude that local anaesthesia can be recommended for the closed lateral subcutaneous sphincterotomy in ambulatory treatment of chronic anal fissure.     

Efficacy and safety of Propionibacterium extract gel versus glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized controlled trial

Aim

Chronic anal fissure (CAF) is an extremely frequent finding in clinical practice. Several topical agents have been proposed for its treatment with the common goal of increasing anodermal blood flow to promote healing. The aim of this study was to compare the efficacy and safety of a Propionibacterium extract gel (PeG) and 0.4% glyceryl trinitrate ointment (GTN) in patients with CAF.

Method

Patients were randomly allocated to a PeG or GTN group and medication was administered every 12 h for 40 days. The primary outcome was the success rate, as measured by a decrease in the REALISE scoring system for anal fissure at 10, 20 and 40 days after initiating either treatment. The secondary outcomes recorded at the same time points were healing rate, visual analogue scales for itching and burning, rate of complications and adverse events, patient quality of life and satisfaction, and cost analysis.

Results

A total of 120 patients were enrolled, and 96 patients (PeG, n = 53; GTN, n = 43) completed the primary outcomes. A significant decrease over time in the REALISE score was observed in both groups. Adverse events occurred more frequently in the GTN group than in the PeG group, peaking at visit 1 [37 (63.8%) vs. 2 (3.4%), respectively], with headache being the most prevalent. The between-treatment cumulative average costs per patient were significantly higher for GTN than that for PeG at each follow-up visit. There were no other significant differences between the two groups for any of the other outcomes.

Conclusion

While there was no difference in healing rates between the two treatments, PeG was more cost-effective and associated with fewer adverse events.