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Meta-Analysis
. 2012 Feb 15;2012(2):CD003431.
doi: 10.1002/14651858.CD003431.pub3.

Non surgical therapy for anal fissure

Richard L Nelson  1 , Kathryn Thomas, Jenna Morgan, Abigail Jones
Affiliations
Meta-Analysis

Non surgical therapy for anal fissure

Richard L Nelson et al. Cochrane Database Syst Rev. .

Abstract

Background: Because of the disability associated with surgery for anal fissure and the risk of incontinence, medical alternatives for surgery have been sought. Most recently, pharmacologic methods that relax the anal smooth muscle, to accomplish reversibly what occurs in surgery, have been used to obtain fissure healing.

Objectives: To assess the efficacy and morbidity of various medical therapies for anal fissure.

Search methods: Search terms include "anal fissure randomized". Timing from 1966 to August 2010. Further details of the search below.

Selection criteria: Studies in which participants were randomized to a non-surgical therapy for anal fissure. Comparison groups may include an operative procedure, an alternate medical therapy or placebo. Chronic fissure, acute fissure and fissure in children are included in the review. Atypical fissures associated with inflammatory bowel disease or cancer or anal infection are excluded.

Data collection and analysis: Data were abstracted from published reports and meeting abstracts, assessing method of randomization, blinding, "intention to treat" and drop-outs, therapies, supportive measures (applied to both groups), dosing and frequency and cross-overs. Dichotomous outcome measures included Non-healing of the fissure (a combination of persistence and recurrence), and Adverse events (including incontinence, headache, infection, anaphylaxis). Continuous outcome measures included measures of pain relief and anorectal manometry.

Main results: In this update 23 studies including 1236 participants is added to the 54 studies and 3904 participants in the 2008 publication, however 2 studies were from the last version reclassified as un included, so the final number of participants is 5031.49 different comparisons of the ability of medical therapies to heal anal fissure have been reported in 75 RCTs. Seventeen agents were used (nitroglycerin ointment (GTN), isosorbide mono & dinitrate, Botulinum toxin (Botox), diltiazem, nifedipine (Calcium channel blockers or CCBs), hydrocortisone, lignocaine, bran, minoxidil, indoramin, clove oil, L-arginine, sitz baths, sildenafil, "healer cream" and placebo) as well as Sitz baths, anal dilators and surgical sphincterotomy. GTN was found to be marginally but significantly better than placebo in healing anal fissure (48.9% vs. 35.5%, p < 0.0009), but late recurrence of fissure was common, in the range of 50% of those initially cured. Botox and CCBs were equivalent to GTN in efficacy with fewer adverse events. No medical therapy came close to the efficacy of surgical sphincterotomy, though none of the medical therapies in these RCTs were associated with the risk of incontinence.

Authors' conclusions: Medical therapy for chronic anal fissure, currently consisting of topical glyceryl trinitrate, botulinum toxin injection or the topical calcium channel blockers nifedipine or diltiazem in acute and chronic fissure and fissure in children may be applied with a chance of cure that is marginally better than placebo. For chronic fissure in adults all medical therapies are far less effective than surgery. A few of the newer agents investigated show promise based only upon single studies (clove oil, sildenifil and a "healer cream") but lack comparison to more established medications.

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Conflict of interest statement

none

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Funnel plot of comparison: 1 GTN versus Placebo, outcome: 1.1 NON ‐ Healing of fissure (persistence or recurrence).
4
4
Funnel plot of comparison: 16 Any Surgery vs any Medical Therapy, outcome: 16.1 NON ‐ Healing (persistence or recurrence).
1.1
1.1. Analysis
Comparison 1 GTN versus Placebo, Outcome 1 NON ‐ Healing of fissure (persistence or recurrence).
1.2
1.2. Analysis
Comparison 1 GTN versus Placebo, Outcome 2 Headache.
2.1
2.1. Analysis
Comparison 2 GTN or IDN versus sphincterotomy, Outcome 1 NON ‐ Healing of Fissure (persistence or recurrence_.
2.2
2.2. Analysis
Comparison 2 GTN or IDN versus sphincterotomy, Outcome 2 Minor Incontinence.
2.3
2.3. Analysis
Comparison 2 GTN or IDN versus sphincterotomy, Outcome 3 Headache.
3.1
3.1. Analysis
Comparison 3 GTN or IDN versus Botox, Outcome 1 NON ‐ Healing.
3.2
3.2. Analysis
Comparison 3 GTN or IDN versus Botox, Outcome 2 Headache.
3.3
3.3. Analysis
Comparison 3 GTN or IDN versus Botox, Outcome 3 Minor Incontinence.
4.1
4.1. Analysis
Comparison 4 GTN versus Calcium Channel Blocker, Outcome 1 NON ‐ Healing.
4.2
4.2. Analysis
Comparison 4 GTN versus Calcium Channel Blocker, Outcome 2 Adverse Events.
4.3
4.3. Analysis
Comparison 4 GTN versus Calcium Channel Blocker, Outcome 3 Headache.
5.1
5.1. Analysis
Comparison 5 GTN versus Patch GTN, Outcome 1 NON ‐ Healing.
5.2
5.2. Analysis
Comparison 5 GTN versus Patch GTN, Outcome 2 Headache.
6.1
6.1. Analysis
Comparison 6 Dilator & Normal Care versus Normal Care Alone for acute and chronic fissure, Outcome 1 NON ‐ Healing in acute and ?chronic? fissure.
7.1
7.1. Analysis
Comparison 7 Botox versus Placebo (or Lignocaine (Colak)), Outcome 1 Non‐healing of Fissure.
7.2
7.2. Analysis
Comparison 7 Botox versus Placebo (or Lignocaine (Colak)), Outcome 2 Adverse Events.
8.1
8.1. Analysis
Comparison 8 Botox versus sphincterotomy, Outcome 1 NON ‐ Healing of the fissure.
8.2
8.2. Analysis
Comparison 8 Botox versus sphincterotomy, Outcome 2 Minor Incontinence.
9.1
9.1. Analysis
Comparison 9 Botox dose levels: High versus Higher, Outcome 1 NON ‐ Healing.
10.1
10.1. Analysis
Comparison 10 Topical CCB (0.3% topical Nifedipine) versus Hydrocortisone (both got Lignocaine), Outcome 1 NON ‐ Healing (persistence and recurrence).
11.1
11.1. Analysis
Comparison 11 Diltiazem Oral versus Topical, Outcome 1 NON ‐ Healing (persistence & recurrence).
11.3
11.3. Analysis
Comparison 11 Diltiazem Oral versus Topical, Outcome 3 Adverse Events.
12.1
12.1. Analysis
Comparison 12 GTN vs. Placebo in children, Outcome 1 NON ‐ Healing.
13.1
13.1. Analysis
Comparison 13 GTN vs placebo in adults, Outcome 1 NON ‐ Healing.
14.1
14.1. Analysis
Comparison 14 GTN vs. Lignocaine, Outcome 1 NON ‐ Healing.
14.2
14.2. Analysis
Comparison 14 GTN vs. Lignocaine, Outcome 2 Adverse Events.
15.1
15.1. Analysis
Comparison 15 CCB (Topical Nifedipine) vs. lignocaine + HC gel, Outcome 1 NON ‐ Healing.
16.1
16.1. Analysis
Comparison 16 Any Surgery vs any Medical Therapy, Outcome 1 NON ‐ Healing (persistence or recurrence).
17.1
17.1. Analysis
Comparison 17 Lignocaine ointment vs. placebo in children, Outcome 1 NON ‐ Healing.
18.1
18.1. Analysis
Comparison 18 bran vs placebo, Outcome 1 Acute Fissure Recurrence; a prophylaxis study.
19.1
19.1. Analysis
Comparison 19 lignocaine vs bran, Outcome 1 NON ‐ Healing.
20.1
20.1. Analysis
Comparison 20 lignocaine vs hydrocortisone, Outcome 1 NON ‐ Healing.
21.1
21.1. Analysis
Comparison 21 bran vs hydrocortisone, Outcome 1 NON ‐ Healing.
22.1
22.1. Analysis
Comparison 22 Sensitivity analyses, Outcome 1 Sensitivity analysis: Excluding GTN/Placebo RCTs with very low placebo response rates (<10%): NON‐healing.
22.2
22.2. Analysis
Comparison 22 Sensitivity analyses, Outcome 2 Excluding RCT in Children with very low Placebo response rate: NON‐healing.
22.3
22.3. Analysis
Comparison 22 Sensitivity analyses, Outcome 3 Excluding RCT in Adults with very low Placebo response rate: NON‐healing.
22.4
22.4. Analysis
Comparison 22 Sensitivity analyses, Outcome 4 Excluding RCT with very low Placebo response rate: NON‐healing; Lignocaine.
22.5
22.5. Analysis
Comparison 22 Sensitivity analyses, Outcome 5 Excluding study with < 10% non healing.
22.6
22.6. Analysis
Comparison 22 Sensitivity analyses, Outcome 6 Excluding Mishra to investigate heterogeneity, Comparison 16; Medicine vs. Surgery.
22.7
22.7. Analysis
Comparison 22 Sensitivity analyses, Outcome 7 Three Largest GTN/Placebo Studies.
23.1
23.1. Analysis
Comparison 23 Botox versus Botox Dysport, Outcome 1 Non‐healing of fissure.
24.1
24.1. Analysis
Comparison 24 CCB versus LIS, Outcome 1 Non‐Healing of the Fissure.
24.2
24.2. Analysis
Comparison 24 CCB versus LIS, Outcome 2 Incontinence.
24.3
24.3. Analysis
Comparison 24 CCB versus LIS, Outcome 3 Headache.
25.1
25.1. Analysis
Comparison 25 Minoxidil versus Lidocaine, Outcome 1 Non‐healing of the fissure.
26.1
26.1. Analysis
Comparison 26 Indoramine versus placebo, Outcome 1 Non‐healing of the fissure.
26.2
26.2. Analysis
Comparison 26 Indoramine versus placebo, Outcome 2 Headache.
27.1
27.1. Analysis
Comparison 27 GTN Dose Comparisons, Outcome 1 Non‐healing of the fissure.
28.1
28.1. Analysis
Comparison 28 Calcium Channel blocker (oral Nifedipine) versus Botox, Outcome 1 Non healing of the fissure.
29.1
29.1. Analysis
Comparison 29 Long Term Follow‐up (> 1 year) ; Any Operation vs. Any Medical Therapy, Outcome 1 Non‐healing of the fissure.
30.1
30.1. Analysis
Comparison 30 GTN vs. Patient Self Dilation (vs. both), Outcome 1 Non Healing.
30.2
30.2. Analysis
Comparison 30 GTN vs. Patient Self Dilation (vs. both), Outcome 2 Headache.
31.1
31.1. Analysis
Comparison 31 Lignocaine vs Clove Oil, Outcome 1 NON ‐ Healing.
32.1
32.1. Analysis
Comparison 32 L‐Arginine vs Surgery, Outcome 1 NON ‐ Healing.
32.2
32.2. Analysis
Comparison 32 L‐Arginine vs Surgery, Outcome 2 Headache.
33.1
33.1. Analysis
Comparison 33 Sitz Baths vs Control, Outcome 1 NON ‐ Healing.
34.1
34.1. Analysis
Comparison 34 Sildenafil versus Placebo, Outcome 1 NON ‐ Healing.
35.1
35.1. Analysis
Comparison 35 Nitroglycerine Topical vs Intra‐anal injection, Outcome 1 NON ‐ Healing.
35.2
35.2. Analysis
Comparison 35 Nitroglycerine Topical vs Intra‐anal injection, Outcome 2 Headache.
36.1
36.1. Analysis
Comparison 36 diltiazem vs. no treatment, Outcome 1 NON ‐ Healing.
37.1
37.1. Analysis
Comparison 37 GTN vs ISMN, Outcome 1 NON ‐ Healing.
37.2
37.2. Analysis
Comparison 37 GTN vs ISMN, Outcome 2 Headache.
38.1
38.1. Analysis
Comparison 38 ISMN vs Placebo, Outcome 1 NON ‐ Healing.
38.2
38.2. Analysis
Comparison 38 ISMN vs Placebo, Outcome 2 Headache.
39.1
39.1. Analysis
Comparison 39 "Healer cream" vs Lignocaine, Outcome 1 NON ‐ healing.
39.2
39.2. Analysis
Comparison 39 "Healer cream" vs Lignocaine, Outcome 2 Headache.
40.1
40.1. Analysis
Comparison 40 "Healer Cream" vs GTN, Outcome 1 NON ‐ Healing.
40.2
40.2. Analysis
Comparison 40 "Healer Cream" vs GTN, Outcome 2 Headache.
41.1
41.1. Analysis
Comparison 41 Lignocaine + Botox vs Lignocaine + GTN, Outcome 1 NON ‐ Healing.
41.2
41.2. Analysis
Comparison 41 Lignocaine + Botox vs Lignocaine + GTN, Outcome 2 Headache.
42.1
42.1. Analysis
Comparison 42 Botox vs Botox + GTN, Outcome 1 NON ‐ Healing.
42.2
42.2. Analysis
Comparison 42 Botox vs Botox + GTN, Outcome 2 Minor incontinence.
43.1
43.1. Analysis
Comparison 43 GTN vs GTN + cryothermal dilators, Outcome 1 NON ‐ Healing.
43.2
43.2. Analysis
Comparison 43 GTN vs GTN + cryothermal dilators, Outcome 2 Headache.
44.1
44.1. Analysis
Comparison 44 Botox injection site location, Outcome 1 Non healing of the fissure.
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References

References to studies included in this review

Ahmad 2007 {published data only}
    1. Ahmad J, Andrabi S.I.H, Rathore M.A. Comparison of topical glyceryl trinitrate with lignocaine ointment for treatment of anal fissure: A randomised controlled trial.. International Journal of Surgery 2007;5(6):429‐432. - PubMed
Altomare 2000 {published data only}
    1. Altomare DF, Rinaldi M, Milito G, Arcana F, et al. Glyceryl trinitrate for chronic anal fissure ‐ ‐ healing or headache? results of a multicenter, randomized, placebo‐controlled double blind trial.. Dis Colon & Rectum 2000;43(2):174‐179. [MEDLINE: ] - PubMed
Antropoli 1999 {published data only}
    1. Antripoli C, Perrotti P, Rubino M, Martino A, et al. Nifedipine for local use in conservative treatment of anal fissures: preliminary results of a multicenter study. Dis Colon & Rectum 1999;42(8):1011‐1015. [MEDLINE: ] - PubMed
Arroyo 2005 {published data only}
    1. Arroyo A, Perez F, Serrano P, Candela F, Lacueva J, Calpena R. Surgical versus chemical (botulinum toxin) sphincterotomy for chronic anal fissure: long‐term results of a prospective randomized clinical and manometric study. Am J Surg 2005;189:429‐34. - PubMed
Bacher 1997 {published data only}
    1. Bacher H, Mischinger HJ, Werkgartner G, Cerwenka H, et al. Local nitroglycerin for treatment of anal fissures: an alternative to lateral sphincterotomy?. Dis Colon & Rectum 1997;40(7):840‐845. [MEDLINE: ] - PubMed
Bailey 2002 {published data only}
    1. Bailey HR, Beck DE, Billingham RP, Binderow SR, et al. A study to determine the nitroglycerin ointment dose and dosing interval that best promote the healing of chronic anal fssures. Dis. Colon & Rectum 2002;45(9):1192‐1199. - PubMed
Bielecki 2003 {published data only}
    1. Bielecki K, Kolodziejczak M. A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure. Colorectal Disease 2003;5:256‐7. - PubMed
Boschetto 2004 {published data only}
    1. Boschetto S, Giovannone M, Tosoni M, Barberani F. Hydropneumatic anal dilation in conservative treatment of Chronic anal fissure: Clinical outcomes and randomized comparison with topical nitroglycerin. Tech Coloproctology 2004;8(2):89‐92. - PubMed
Brisinda 1999 {published data only}
    1. Brisinda G, Maria G, Bentivoglio AR, Cassetta E. Gui D, Albanese A. A comparison of injections of botulinum toxin and topical nitroglycerin ointment for the treatment of chronic anal fissure. New Eng J Med 1999;341(2):65‐69. - PubMed
Brisinda 2002 {published data only}
    1. Brisinda G, Maria G, Sganga G, Bentivoglio AR, et al. Effectiveness of higher doses of botulinum toxin to induce healing in patient with chronic anal fissures. Surgery 2002;131(2):179‐184. - PubMed
Brisinda 2004 {published data only}
    1. Brisinda G, Albanese A, Cadeddu F, Bentivoglio AR, Mabisonbi A, Maringa G, Maria G. Botulinum neurotoxin to treat anal fissure: Results of a randomized Botox vs Disport controlled trial. Alimentary Pharm and Therapeutics 2004;19(6):695‐701. - PubMed
Brisinda 2007 {published data only}
    1. Brisinda, G, Cadeddu, F, Brandara, F, Marniga, G, Maria. G. Randomized clinical trial comparing botulinum toxin injections with 0.2 per cent nitroglycerin ointment for chronic anal fissure. British Journal of Surgery 2007;94(2):162‐7. - PubMed
Carapeti 1999 {published data only}
    1. Carapeti EA, Kamm MA, McDonald PJ, Chadwick, et al. Randomised controlled trial shows that glyceral trinitrate heals anal fissures, higher doses are not more effective and there is a high recurrence rate. Gut 1999;44:727‐730. - PMC - PubMed
Chaudhuri 2001 {published data only}
    1. Chaudhuri S, Pal AK, Acharya A, Dey A, et al. Treatment of chronic anal fissure with topical glyceral trinitrate: a double blind, placebo controlled trial. Indian J Gastroent 2001;20(3):101‐102. - PubMed
Colak 2002 {published data only}
    1. Colak T, Ipek T, Kanik A, Aydin S. A randomized trial of botulinum toxin vs lidocaine pomade for chronic anal fissure. Acta Gastro. Enterologica Belgica 2002;65(4):187‐90. - PubMed
Colak 2003 {published data only}
    1. Colak T, Ipek T, Urkaya N, Kanik A, Dirlik M. A randomized study comparing systemic transdermal treatment and local application of glyceryl trinitrate in the management of chronic anal fissure. European J of Surgery, Suppl. 2003;168(588):18‐22. - PubMed
deNardi 2006 {published data only}
    1. deNardi P, Ortolano E, Radaelli G, Staudacher C. Comparison of glycerine trinitrate and botulinum toxin‐A for the treatment of chronic anal fissure: Long term results. Dis. Colon & Rectum 2006;49(4):427‐32. - PubMed
di Visconte 2006 {published data only}
    1. Visconte MS, Bella R, Munegato G. Randomised prospective trial comparing 0.25% glycerine trinitrate ointment and anal cryothermal dilators with 0.25% glycerine trinitrate ointment alone and with anal cryothermal dilators alone in the treatment of chronic anal fissure: a two year follow up.. Dis Colon & Rectum 2006;49(12):1822. - PubMed
Di Visconte 2009 {published data only}
    1. Schiano di Visconte M, Munegato G. Glyceryl trinitrate ointment (0.25%) and anal cryothermal dilators in the treatment of chronic anal fissures.. Journal of Gastrointestinal Surgery. 2009;13(7):1283‐1291. - PubMed
Elwkeel 2007 {published data only}
    1. Elwakeel, H. A, Moneim, H. A, Farid, M, Gohar. A. A. Clove oil cream: a new effective treatment for chronic anal fissure.. Colorectal Disease 2007;9(6):549‐52. - PubMed
Emami 2008 {published data only}
    1. Emami, M. H, Sayedyahossein, S, Aslani. A. Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo‐controlled clinical trial.. Diseases of the Colon and Rectum. 2008;51(7):1079‐83. - PubMed
Eshghi 2007 {published data only}
    1. Eshghi F. The efficacy of L‐arginine gel for treatment of chronic anal fissure compared to surgical sphincterotomy.. Journal of Medical Sciences 2007;7(3):481‐484.
Evans 2001 {published data only}
    1. Evans J, Luck A, Hewett P. Glyceral trinitrate vs. lateral sphincterotomy for chronic anal fissure. Dis. Colon & Rectum 2001;44(1):93‐97. - PubMed
Ezri 2003 {published data only}
    1. Exri T, Susmallian S. Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure. Dis. Colon & Rectum 2003;46(6):805‐8. - PubMed
Festen 2009 {published data only}
    1. Festen S, Gisbertz S.S, Schaagen F, Gerhards M.F. Blinded randomized clinical trial of botulinum toxin versus isosorbide dinitrate ointment for treatment of anal fissure.. BJS 2009;96(12):1393‐1399. - PubMed
Fruehauf 2006 {published data only}
    1. Fruehauf, H, Fried, M, Wegmueller, B, Bauerfeind, P, Thumshirn. M. Efficacy and safety of botulinum toxin a injection compared with topical nitroglycerin ointment for the treatment of chronic anal fissure: a prospective randomized study.. The American Journal of Gastroenterology. 2006;101(9):2107‐12. - PubMed
Gaj 2006 {published data only}
    1. Gaj, F, Trecca, A, Crispino. P. Efficacy of anal dilators in the treatment of acute anal fissure. A controlled clinical trial. Chirurgia Italiana 2006;58(6):761‐5. - PubMed
Gecim 2001 {unpublished data only}
    1. Gecim I. Comparison of glyceryl trinitrate and botulinum toxin A in treatment of chronic anal fissure: a prospective randomized study. Program Abstracts ASCRS San Diego, 2001. 2001.
Gough 1983 {published data only}
    1. Gough MJ, Lewis A. The conservative treatment of fissure in ano. Br J Surg 1983;70(3):175‐176. [MEDLINE: ] - PubMed
Gupta 2006 {published data only}
    1. Gupta P. Randomized, controlled study comparing sitz‐bath and no‐sitz‐bath treatments in patients with acute anal fissures.. ANZ Journal of Surgery. 2006;76(8):718‐721. - PubMed
Ho 2005 {published data only}
    1. Ho KS, Ho YH. Randomized clinical trial comparing oral nifedipine with lateral anal sphincterotomy and tailored sphincterotomy in the treatment of chronic anal fissure. Brit J Surg. 2005;92(4):403‐8. - PubMed
Iswariah 2005 {published data only}
    1. Iswariah H, Stephens J, Reiger N, Rodda D, Hewett P. Randomized prospective controlled trial of lateral internal sphincterotomy versus injections of botulinum toxin for the treatment of idiopathic fissure in ano. ANZ J Surg 2005;75(7):553‐5. - PubMed
Jawaid 2009 {published data only}
    1. Jawaid M, Masood Z, Salim M. Topical diltiazem hydrochloride and glyceryl trinitrate in the treatment of chronic anal fissure.. Journal of the College of Physicians & Surgeons ‐ Pakistan. 2009 Oct;19(10):614‐7. - PubMed
Jensen 1986 {published data only}
    1. Jensen, SL. Treatment of first episodes of acute anal fissure: a prospective randomised study of lignocaine ointment versus hydrocortisone ointment or warm sitz baths plus bran. Br Med J 1986;292(3 May):1167‐1170. - PMC - PubMed
Jensen 1987 {published data only}
    1. Jensen SL. Maintenance therapy with unprocessed bran in the prevention of acute anal fissure recurrence. J Roy. Soc. Med 1987;80(5):296‐298. - PMC - PubMed
Jonas 2001 {published data only}
    1. Jonas M, Neal KR, Abercrombie JF, Scholefield JH. A randomized trial of oral vs. topical diltiazem for chronic anal fissures. Dis. Colon & Rectum 2001;44:1074‐1078. - PubMed
Jones 2006 {published data only}
    1. Jones O.M, Ramalingam T, Merrie A, Cunningham C, George B.D, Mortensen N.J.McC, Lindsey I. Randomized clinical trial of botulinum toxin plus glyceryl trinitrate vs. botulinum toxin alone for medically resistant chronic anal fissure: Overall poor healing rates.. Diseases of the Colon and Rectum 2006;49(10):1574‐1580. - PubMed
Jost1999 {published data only}
    1. Jost WH, Schrank B. Chronic anal fissures treated with botulinum toxin injections: a dose‐finding study with Dysport. Colorectal Dis. 1999;1:26‐8. - PubMed
Katsinelos 2006 {published data only}
    1. Katsinelos P, Papaziogas B, Koutelidakis I, Paroutoglou G, Dimiropoulos S, Souparis A, Atmatzidis K. Topical 0.5% Nifedipine versus Lateral Internal Sphincterotomy for the Treatment of Chronic Anal Fissure. International Journal of Colorectal Disease 2006;21(2):179‐83. - PubMed
Kennedy 1999 {published data only}
    1. Kennedy ML, Sowter S, Nguyen H, Lubowski DZ. Glyceryl trinitrate ointment for the treatment of chronic anal fissure: results of a placebo‐controlled trial and long term follow‐up. Dis. Colon & Rectum 1999;42(8):1000‐1006. [MEDLINE: ] - PubMed
Kenny 2001 {published data only}
    1. Kenny SE, Irvine T, Driver CP, Nunn AT, et al. Double blind randomised controlled trial of topical glyceral trinitrate in anal fissure. Arch Dis Childhood 2001;85:404‐407. - PMC - PubMed
Kocher 2002 {published data only}
    1. Kocher HM, Steward M, Leather AJM, Cullen PT. Randomized clinical trial assessing the side effects of glyceral trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure. Brit. J Surgery 2002;89:413‐417. - PubMed
Libertiny 2002 {published data only}
    1. Libertiny G, Knight JS, Farouk R. Randomised trial of topical 0.2% glyceryl trinitrate and lateral internal sphincterotomy for the treatment of patients with chronic anal fissures: long term follow‐up. Eur J Surg 2002;168(7):418‐421. - PubMed
Lund 1997 {published data only}
    1. Lund JN, Scholefield JH. A randomized, prospective, double‐blind, placebo‐controlled trial of glyceryl trinitrate in treatment of anal fissure. Lancet 1997;349(9044):11‐14. - PubMed
Maan 2004 {published data only}
    1. Maan MS, Mishra R, Thomas S, Hadke N. Randomized double blind trial comparing topical nitroglycerin with xylocaine and Proctosedyl in idiopathic chronic anal fissure. Indian J. Gastroenterology 2004;23(91‐3):91‐3. - PubMed
Maria 1998 {published data only}
    1. Maria G, Cassetta E, Gui D, Brisinda G, et al. A comparison of botulinum toxin and saline for the treatment of chronic anal fissure. New Engl J Med 1998;338:217‐220. - PubMed
Maria 2000 {published data only}
    1. Maria G, Brisinda G, Bentivoglio AR, Cassetta E, Gui D, Albanese A. Influewnce of botulinum toxin site of injections on healing rate in patients with chronic anal fissure. Am J Surgery 2000;179:46‐50. - PubMed
McDonald 1983 {published data only}
    1. MacDonald P, Driscoll AM, Nichollds RJ. The anal dilator in the conservative management of acute anal fissure. Br J Surg 1983;70(1):25‐26. [MEDLINE: ] - PubMed
Mentes 2001 {unpublished data only}
    1. Mentes BB, Irkorucu O, Akin M, Leventoglu S, et al. Botulinum toxin injection compares favorably with lateral internal sphincterotomy in the treatment of chronic anal fissure. Dis. Colon & Rectum 2003;46:232‐237. [PMID 12576897] - PubMed
Mishra 2005 {published data only}
    1. Mishra R, Thomas S, Maan MS, Hadke NS. Topical nitroglycerin versus lateral internal sphincterotomy for chronic anal fissure: prospective randomized trial. ANZ J Surg 2005;75:1032‐5. - PubMed
Moghimi 2006 {published data only}
    1. Moghimi M, Ghodosi I. Topical sildenafil (Viagra) in the treatment of chronic anal fissure: A randomized double blind controlled trial.. International Journal of Pharmacology. 2006;2(6):608‐612.
Mustafa 2006 {published data only}
    1. Mustafa, N. A, Cengiz, S, Türkyilmaz, S, Yücel. Y. Comparison of topical glyceryl trinitrate ointment and oral nifedipine in the treatment of chronic anal fissure.. Acta Chirurgica Belgica. 2006;106(1):55‐8. - PubMed
Muthukumarassamy 2005 {published data only}
    1. Muthukumarassamy R, Robinson SS, Sarath SC, Raveendran R. Treatment of anal fissures using a combination of minoxidil and lignocaine: a randomized, double blind trial. Indian J Gastroenterology 2005;24(4):158‐60. - PubMed
Nasr 2010 {published data only}
    1. Nasr M, Ezzat H, Elsebae M. Botulinum toxin injection versus lateral internal sphincterotomy in the treatment of chronic anal fissure: a randomised controlled trial. World J Surg 2010;34:2730‐2734. - PubMed
Oettle 1997 {published data only}
    1. Oettle GJ. Glyceryl trinitrate vs. sphincterotomy for treatment of chronic fissure in ano: a randomized controlled trial. Dis Colon & Rectum 1997;40(11):1318‐1320. [MEDLINE: ] - PubMed
Oglesby 2001 {unpublished data only}
    1. Oglesby S, Wilson‐Storey D, Munro F. A placebo controlled randomized trial of 0.2% GTN in the treatment of chronic anal fissures in children. Digestive Disease Week‐ USA. 2001.
Parellada 2004 {published data only}
    1. Parellada C. Randomized prospective trial comparing 0.2 percent isosorbide dinitrate ointment with sphincterotomy in treatment of chronic anal fissure: two year follow up. Dis. Colon & Rectum 2004;47(4):437‐43. - PubMed
Perrotti 2002 {published data only}
    1. Perrotti P, Bove A, Antropoli C, Molino D, et al. Topical nifedipine with lidocaine vs. active control for the treatment of anal fissure. Dis. Colon & Rectum 2002;45(11):1468‐1475. - PubMed
Pitt 2001 {published data only}
    1. Pitt J, Dawson PM, Hallan RI, Boulos PB. A double‐blind randomized placebo controlled trial of oral indoramine to treat chronic anal fissure. Colorectal Dis. 2001;3(3):165‐8. - PubMed
Richard 2000 {published data only}
    1. Richard CS, Gregroire R, Plewes EA, Silverman R, et al. Internal sphincterotomy is superior to topical nitroglycerin in the treatment of chronic anal fissure: results of a randomized controlled trial. Dis Colon & Rectum 2000;43(8):1048‐1057. [MEDLINE: ] - PubMed
Scholefield 2003 {published data only}
    1. Scholefield JH, Bock JU, Marla B, Richter HJ, Athanasiadis S, Prois M, Herold A. A dose finding study with 0.1%, 0.2%, and 0.4% glyceryl trinitrate ointment inpatients with chronic anal fissure. Gut 2003;52:264‐9. - PMC - PubMed
Shrivastava 2007 {published data only}
    1. Shrivastava UK, Jain BK, Kumar P, Saifee Y. A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized clinical trial.. Surgery Today 2007;37(6):482‐5. - PubMed
Siddique 2008 {published data only}
    1. Siddique, M. I, Murshed, K. M, Majid. M. A. Comparative study of lateral internal sphincterotomy versus local 0.2% glyceryl trinitrate ointment for the treatment of chronic anal fissure.. Bangladesh Medical Research Council Bulletin. 2008;34(1):12‐15. - PubMed
Simpson 2003 {published data only}
    1. Simpson J, Lund JN, Thompson RJ, Kapila L, Scholefield JH. The use of glyceryl trinitrate (GTN) in the treatment of chronic anal fissure in children. Medical Science Monitor 2003;9(10):PI123‐6. - PubMed
Siproudhis 2003 {unpublished data only}
    1. Siproudhis L, Sebille V, Pigot F, Hemerey P, Juguet F, Bellissant E. Lack of efficacy of botulinum toxin in chronic anal fissure. Alimentary Pharmacology & Therapeutics 2003;18(5):515‐24. - PubMed
Sonmez 2002 {published data only}
    1. Sonmez K, Demmirogullan B, Ekingen G, Turkyilmaz Z, et al. Randomized Placebo controlled treatment of anal fissure by lidocaine, EMLA and GTN in children. J Ped Surg 2002;37(9):1313‐1316. - PubMed
Suknaic 2008 {published data only}
    1. Suknaic S, Patrlj L, Steresinic M, Skopljanac Macina A, Erdelez L. Surgical or biologic sphincterotomy in the treatment of chronic anal fissure. Acta Medica Croatica. 2008;62(1):73‐80. - PubMed
Tander 1999 {published data only}
    1. Tander B, Guven A, Demirbag S, Ozkan Y, et al. A prospective, randomized, double‐blind, placebo‐controlled trial of glceryl‐trinitrate ointment in the treatment of children with anal fissure. J Pediatr Surg 1999;34(12):1810‐1812. [MEDLINE: ] - PubMed
Tankova 2002 {published data only}
    1. Tankova L, Yoncheva K, Muhtarov M, Kadyan H, Draganov V. Topical mononitrate treatment in patients with anal fissure. Aliment. Pharm & Therapeutics 2002;16(1):101‐3. - PubMed
Tankova 2009 {published data only}
    1. Tankova, L, Yoncheva, K, Kovatchki, D, Doytchinova. I. Topical anal fissure treatment: placebo‐controlled study of mononitrate and trinitrate therapies. International Journal of Colorectal Disease 2009;24(4):461‐4. - PubMed
Torrabadella 2006 {published data only}
    1. Torrabadella, L, Salgado. G. Controlled dose delivery in topical treatment of anal fissure: pilot study of a new paradigm.. Diseases of the Colon and Rectum. 2006;49(6):865‐8. - PubMed
Uluutku 2001 {published data only}
    1. Uluutku H, Akin ML, Erenglu C, Yildiz M, Ukraya N, Celen K. Efficacy of nifedipine, glyceryl trinitrate and botulinum toxin in treatment of chronic anal fissure. Turkish J Surg 2001;17(6):343‐50.
Weinstein 2004 {published data only}
    1. Weinstein D, Halevy A, Negri M, Levy N, Gelertner I, Ziv Y. A prospective randomized double‐blind study on the treatment of anal fissures with nitroglycderin ointment.. Harefuah 2004;143(10):713‐7. [MEDLINE: ] - PubMed
Werre 2001 {published data only}
    1. Werre AJ, Palamba HW, Bilgen EJS, Eggink WF. Isosorbide dinitrate in the treatment of anal fissure: a randomized, prospective double blind placebo controlled trial.. Eur J Surg 2001;167:382‐85. - PubMed
Yakoot 2009 {published data only}
    1. Yakoot M, Salaam M.A. Study of efficacy and safety of a new local cream ("healer") in the treatment of chronic anal fissure. A prospective, randomized, single‐blind, comparative study.. Arquivos De Gastroenterologia. 2009;46(3):179‐182. - PubMed
Zuberi 2000 {published data only}
    1. Zuberi BF, Rajput MR, Abro H, Shaikh SA. A randomized trial of glyceryl trinitrate ointment and nitroglycerin patch in healing of anal fissures. Int J Colorectal Dis 2000;15(4):243‐245. [MEDLINE: ] - PubMed

References to studies excluded from this review

Algaithy 2008 {published data only}
    1. Algaithy Z.K. Botulinum toxin versus surgical sphincterotomy in females with chronic anal fissure.. Saudi Medical Journal 2008;29(9):1260‐63. - PubMed
Bassotti 2000 {published data only}
    1. Bassotti G, Clementi M, Ceccarelli F, Pelli MA. Double blind manometric assessment of two topical glyceral trinitrate formulations in patients with chronic anal fissures. Digest Liver Dis 2000;32:699‐702. - PubMed
Coskun 2000 {published data only}
    1. Coskun A, Ukunkoy A, Akinci OF. The treatment efficacy of medical sphincterotomy with glycerol trinitrate on acute and chronic anal fissures. Ulusal C errhi Dergisi 2000;16(3):176‐181.
Filingeri 2005 {published data only}
    1. Filingeri V, Gravante G. A prospective randomized trial between subcutaneous lateral internal sphincterotomy with radiofrequency bistoury and conventional Parks' operation in the treatment of anal fissure. Eur. Review for Medical and Pharmacolog. Sciences 2005;9(3):175‐8. - PubMed
Jonas 1999 {published data only}
    1. Jonas M, Lobo DN, Gudgeon AM. Lateral internal sphincterotomy is not redundant in the era of glyceryl trinitrate therapy for chronic anal fissure. J R Soc Med 1999;92(4):186‐8. [MEDLINE: ] - PMC - PubMed
Kocher 2001 {published data only}
    1. Kocher HM, Steward M, Leather AJ, Cullen PT. Topical glyceryl trinitrate (GTN ‐ 0.2%) vs topical diltiazem (2%) in the treatment of chronic fissure in ano: a prospective double blind randomized trial.. DDW Abstract CD‐ROM. Alanta: DDW, 2001.
Massoud 2005 {published data only}
    1. Massoud BW, Mehrdad V, Baharak T, Alireza Z. Botulinum toxin injection versus internal anal sphincterotomy for the chronic anal fissure. Ann Saudi Med 2005;25(2):140‐2. - PMC - PubMed
Thornton 2005 {published data only}
    1. Thronton MJ, Kennedy ML, King DW. Manometric effect of topical glyceryl trinitrate and its impact on chronic anal fissure healing. Dis Colon & Rectum 2005;48(6):1207‐12. - PubMed

Additional references

Abcarian 1980
    1. Abcarian H. Surgical correction of chronic anal fissure: results of pateral internal sphincterotomy vs. fissurectomy ‐ midline sphincterotomy.. Dis Colon & Rectum 1980;23:31‐36. - PubMed
Baker 2003
    1. Baker SG, Kramer BS. A perfect correlate does not a surrogate make.. BMC Med Res. Methodol. 2003;3:16. - PMC - PubMed
Garcia‐Aguilar 1996
    1. Garcia‐Aguilar J, Belmonte C, Wong D, Lowry AC, Madoff RD. Open vs Closed sphincterotomy for chronic anal fissure: long term results. Dis Colon & Rectum 1996;39:440‐443. - PubMed
Goligher 1975
    1. Goligher JC. Surgery of the Anus, Rectum & Colon. 3rd Edition. London: Balliere & Tindall, 1975.
Graziano 2001
    1. Graziano A, Svidler Lopez L, Lecinas S, Masciangioloi G, Gualdrini U, Bisisio O. Long term results of topical nitroglycerine in the treatment of shronic anal fissures are disappointing. Techniques in Coloproctology 2001;5(3):143‐7. [MEDLINE: ] - PubMed
Hyman 2004
    1. Hyman N. Incontinence after lateral internal sphincterotomy: a prospective study and quality of life assessment. Dis Colon & Rectum 2004;47:35‐8. - PubMed
Jonas 2002
    1. Jonas M, Lund JN, Scholefield JH. Topical 0.2% glyceryl trinitrate ointment for anal fissure: Long‐term efficacy in routine clinical practice. Colorectal Disease 2002;4(5):317‐20. [MEDLINE: ] - PubMed
Mentes 2006
    1. Mentes BB, Tezcaner T, Yilmaz U, Leventoglu S, Oguz M. Results of lateral internal sphincterotomy for chronic anal fissure with particular reference to quality of life.. Dis Colon & Rectum 2006;49(7):1045‐51. - PubMed
Minguez 2002
    1. Minguez M, Herreros B, Espi A, Garcia‐Granero E, Sanchiz V, Mora F, Lledo S, Benages A. Long‐term follow‐up (42 months) of chronic anal fissure after healing with botulinum toxin. Gastroenterology 2002;123:112‐7. [MEDLINE: ] - PubMed
Nelson 2001
    1. Nelson RL. Outcome of operative procedures for fissure in ano. Cochrane Database of Systematic Reviews 2001, Issue 1. [DOI: 10.1002/14651858.CD002199.pub2] - DOI - PubMed
Nelson 2011
    1. Nelson RL, Chattopadhyay A, Brooks W, Platt I, Paavana T, Earl S. Operative Procedures for fissure in ano. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD002199.pub3] - DOI - PMC - PubMed
Rotholtz 2005
    1. Rotholtz NA, Bun M, Mauri MV, Bosio R, Peczan CE, Mezzadri NA. Long‐term assessment of fecal incontinence after lateral internal sphincterotomy. Tech. Coloproctology 2005;9:115‐8. [MEDLINE: ] - PubMed
Schouten 1994
    1. Schouten WR, Briel HW, Auwerda JJA. Relationship between anal pressure and anodermal blood flow. Dis Colon & Rectum 1994;37:664‐669. - PubMed

References to other published versions of this review

Nelson 2006
    1. Nelson RL. Non‐surgical therapy for anal fissure. Cochrane Database of Systematic Reviews July 30 2006, Issue 4. [DOI: 10.1002/14651858.CD003431.pub2] - DOI

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