Innovations in chronic anal fissure treatment: A systematic review

Table 1 Studies comparing healing and recurrence rates of different pharmacological therapies

S/N	Ref.	Study details	Healing	Remarks
1	Lund et al[17] 1997 Double armed, prospective, randomized	0.2% GTN vs placebo 80 patients	GTN-68% healing rate within 8 wk Placebo-8% healing rate Recurrences-7.9% in GTN group. Treated successfully with additional 6 wk of GTN
2	Kennedy et al[18] 1999 Double arm, prospective, randomized, placebo-controlled	0.2% GTN vs placebo 43 patients	GTN group-46% healing rate Placebo group-16% healing rate	Statistically significant
3	Altomare et al[19] 2000 Double arm, prospective, randomized	0.2% GTN vs placebo 132 patients	GTN-49.2% healing rate Placebo-51.7% healing rate Recurrence-19% in GTN group	Failed to establish superiority of GTN over placebo
4	Scholefield et al[20] 2003 Four armed, prospective, randomized	0.1% GTN vs 0.2% GTN vs 0.4% GTN vs placebo 200 patients	Intention-to-treat analysis: Placebo-37.5% healing rate 0.1% GTN-46.9% healing rate 0.2% GTN-40.4% healing rate 0.4% GTN-54.1% healing rate	High placebo healing rates noted-possibly due to inclusion of acute fissures Lowest healing rate with 0.2% GTN likely due to anomaly due to small sample size
5	Kocher et al[23] 2002 Double arm, prospective, randomized	0.2% GTN vs 2% Diltiazem cream 61 patients	GTN-25/29 (86.2%) patients improved or healed Diltiazem-24/31 (77.4%) patients healed or improved
6	Knight et al[27] 2001 Single arm, prospective, non-randomized	2% Diltiazem cream for chronic anal fissures 71 patients	59/66 (89.4%) patients healed within 16 wk 7/59 (11.8%) patients on follow-up developed recurrences
7	Carapeti et al[25] 2002 Two separate pilot studies	2% Diltiazem cream vs 0.1% bethanechol gel 30 patients	Diltiazem-67% healing rate Bethanechol-60% healing rate
8	Jonas et al[26] 2002 Single arm, prospective, non-randomized	Topical 2% Diltiazem for fissures failing GTN therapy 39 patients	49% healing rate
9	Maria et al[21] 1998 Double arm, prospective, randomized	Botulinum toxin 20 units vs saline 30 patients	Botulinum toxin-11/15 (73.3%) patients healed at 2 mo. Remaining 4 patients (26.7%) healed after additional 25 units Saline-2/12 patients healed at 2 mo No recurrences in the botulinum group
10	Lindsey et al[24] 2003 Single arm, prospective, non-randomized	Botulinum toxin 20 units injection for non-healing anal fissures after initial 8 wk of 0.2% GTN 40 patients	43% complete healing 12% unhealed with symptom resolution 18% unhealed with symptom improvement 27% unhealed with no symptom improvement 27% underwent eventual surgery
11	Brisinda et al[22] 1999 Dual arm, prospective randomized, non-controlled	Botulinum toxin 20 units injection vs 0.2% GTN for 8 wk Failure to heal after 8 wk-treatment offered from the other arm 50 patients	Botulinum toxin–96% healed fissures after 2 mo 0.2% GTN-60% healed fissures after 2 mo	Statistically significant
12	Jones et al[28] 2006 Dual arm, prospective randomized, non-controlled	Botulinum toxin 25 units injection and 0.2% GTN vs Botulinum toxin 25 units alone 30 patients	Botulinum toxin and GTN-47% complete healing at 8 wk Botulinum toxin alone-27% complete healing Botulinum toxin and GTN-27% treatment failure by 6 mo Botulinum toxin alone-47% treatment failure by 6 mo	Not statistically significant Not statistically significant
13	Garrido et al[8] 2007 Single arm, prospective, non-randomized	Gonyautoxin 100 units injection 23 patients	18/23 patients-healed in 7 d 3/23-healed in 12 d 2/23 patients-healed in 14 d

GTN: Glyceryl trinitrate.

Table 2 Studies comparing complication rates of different pharmacological therapies

S/N	Ref.	Study details	Results
1	Lund et al[17] 1997 Double armed, prospective, randomized	0.2% GTN vs placebo 80 patients	Headaches-56.4% (GTN) vs 17.9% (placebo)
2	Altomare et al[19] 2000 Double arm, prospective, randomized	0.2% GTN vs placebo 132 patients	Headaches-33.8% (GTN) vs 7.8% (placebo)
3	Scholefield et al[20] 2003 Four armed, prospective, randomized	0.1% GTN vs 0.2% GTN vs 0.4% GTN vs placebo 200 patients	Headaches-31% (treatment group) vs 12.5% (placebo group) Severe headaches-19.6% (0.4% GTN) vs 5.9% (0.2% GTN) vs 2% (0.1% GTN) vs 4.2% (placebo)
4	Knight et al[27] 2001 Single arm, prospective, non-randomized	2% Diltiazem cream for chronic anal fissures 71 patients	Complications: 1 (headache) and 1 (allergic dermatitis)
5	Jonas et al[26] 2002 Single arm, prospective, non-randomized	Topical 2% diltiazem for fissures failing GTN therapy 39 patients	Perineal itchiness-10% (no drop-out from treatment)
6	Maria et al[21] 1998 Double arm, prospective, randomized	Botulinum toxin 20 units vs saline 30 patients	No significant complications noted in the botulinum toxin group
7	Lindsey et al[24] 2003 Single arm, prospective, non-randomized	Botulinum toxin 20 units injection for non-healing anal fissures after initial 8 wk of 0.2% GTN 40 patients	18% minor incontinence-resolved
8	Brisinda et al[22] 1999 Dual arm, prospective randomized, non-randomized	Botulinum toxin 20 units injection vs 0.2% GTN for 8 wk Failure to heal after 8 wk-treatment offered from the other arm 50 patients	Headaches – 20% in GTN arm No bleeding complications in Botulinum arm
9	Jones et al[28] 2006 Dual arm, prospective randomized, non-randomized	Botulinum toxin 25 units injection and 0.2% GTN vs Botulinum toxin 25 units alone 30 patients	Botulinum toxin and GTN-33% transient incontinence rate Botulinum toxin alone-13% transient incontinence rate
10	Garrido et al[8] 2007 Single arm, prospective, non-randomized	Gonyautoxin 100 units injection 23 patients	No flatus or fecal incontinence

GTN: Glyceryl trinitrate.

Table 3 Studies comparing healing rates of different surgical therapies

S/N	Ref.	Study details	Results	Remarks
1	Garcea et al[30] 2002 Single arm, retrospective, non-randomized	Conservative lateral sphincterotomy for chronic anal fissures 65 patients	97% healing rate	98% of patients had prior failure of healing with GTN Maximum of 5 mm of internal sphincter divided
2	Tocchi et al[31] 2004 Single arm, prospective, non-randomized	Lateral subcutaneous internal sphincterotomy for non-responders to 0.2% GTN 164 patients	100% healing rate within 6 wk
3	Liratzopoulos et al[32] 2006 Single arm, prospective, non-randomized	Lateral subcutaneous sphincterotomy for chronic anal fissures 246 patients	Overall healing rate-97.5% at 3 mo
4	Wiley et al[33] 2004 Dual arm, prospective, randomized	Open vs closed lateral sphincterotomy 79 patients	Open technique-95% healing rates Closed technique-97% healing rates	Closed technique: Blind division of internal sphincter guided by finger Open technique: Division under direct vision
5	Jensen et al[34] 1984 Double arm, prospective, randomized	Lateral sphincterotomy vs simple anal dilatation	Sphincterotomy-100% healing rate Anal dilatation-96.4% Recurrences-3.3% (sphincterotomy) vs 28.6% (anal dilatation)
6	Renzi et al[13] 2007 Double arm, prospective, randomized	Pneumatic balloon dilatation vs lateral sphincterotomy 53 patients	Balloon dilatation-83.3% healing rate Sphincterotomy-92%	Balloon dilated to 20 PSI and maintained for 6 min Division of half of internal sphincter
7	Richard et al[35] 2000 Double arm, prospective, randomized	Internal sphincterotomy vs 0.25% GTN 90 patients	Internal sphincterotomy-92.1% healing rate at 6 wk GTN-27.2% healing rate at 6 wk 5.5% of GTN group had an eventual sphincterotomy Recurrences-0 (sphincterotomy) vs 5/44 (11.4%) (GTN)
8	Evans et al[36] 2001 Dual arm, prospective, randomized	0.2% GTN vs lateral sphincterotomy for chronic anal fissures 65 patients	Sphincterotomy-97% healing rate after 8 wk GTN-60.6% healing rate after 8 wk 12/13 (92%) of patients not healed by GTN healed after sphincterotomy Recurrence-50% (GTN) vs 15.4% (sphincterotomy) 11/13 (85%) of GTN failures not compliant with treatment-7/13 (54%) (lack of effect) and 4/13 (31%) (headaches)
9	Brown et al[37] 2007 Double arm, prospective, randomized, multi-centric	2% GTN vs lateral internal sphincterotomy at 6 yr post-treatment 82 patients	GTN-11/27 (40.7%) patients had recurrence Sphincterotomy-no recurrence Patient satisfaction-100% (sphincterotomy) vs 56% (GTN)	60% of GTN patients underwent subsequent sphincterotomy
10	Menteş et al[29] 2003 Double arm, prospective, randomized	Botulinum toxin 0.3 units/kg vs internal sphincterotomy 111 patients	Sphincterotomy healing rates-82% (1 mo)-98% (2 mo)-94% (6 mo)-94% ( 12 mo) Botulinum toxin healing rates-62.3% (1 mo)-73.8% (2 mo)-86.9% (6 mo, with a second injection given at end of 2nd month for non-healers)-75.4% (12 mo, with 7 patients having recurrences)
11	Schiano di Visconte et al[14] 2009 Double arm, prospective, randomized	0.25% GTN and anal cryothermal dilators BD vs 0.4% GTN 60 patients	Dilators and 0.25% GTN-86.6% healing rate 0.4% GTN-73.3% healing rate Recurrence after 1 year-3.3% (GTN and dilators) vs 13.3% (GTN only)	Dilators soaked for 15 min in 40 degrees water
12	Yucel et al[15] 2009 Double arm, prospective, randomized	Controlled intermittent anal dilatation (CIAD) vs lateral sphincterotomy 40 patients	Dilatation-90% healing rate at 2 mo Sphincterotomy-85% healing rate at 2 mo	Adjustable anal speculum dilated to 4.8 cm followed by relaxation for 15 times over 5 min
13	Singh et al[9] 2005 Single arm, prospective, non-randomised	Rotational flap for treatment of chronic anal fissures 21 patients	Complete healing in 17/21 (81.0%) patients
14	Giordano et al[10] 2009 Single arm, prospective, non-randomised	Cutaneous advancement flap anoplasty for chronic anal fissures 51 patients	98% healing rate No recurrences at median 6 mo follow-up 3/51 developed new fissures at new locations
15	Pelta et al[11] 2007 Double arm, prospective, randomized	Subcutaneous fissurotomy for chronic anal fissures 109 patients	98.2% healing rate	Opening up of subcutaneous tract beneath fissure and excision of sentinel tag
16	Soll et al[12] 2004 Single arm, prospective, non-randomized	Fissurectomy and botulinum toxin 20-25 units for chronic anal fissures not responsive to medical therapy 31 patients	93% healing rate by 16 wk with 7% having symptomatic relief despite non-healing fissures
17	Gupta[16] 2008 Single arm, prospective, non-randomized	Closed anal sphincter manipulation (sphincterolysis) for chronic anal fissures 312 patients	96.5% healing rate within 8 wk No recurrence	Finger fracture of internal sphincter fibres over left lateral side without breaching anal mucosa
18	Tan et al[7] 2009 Single arm, prospective, non-randomized	Effect of posterior perineal support on chronic anal fissure healing	Moderate (or more) improvement in: Pain-50% (2 wk) and 97.5% (3 mo) Bleeding-46.9% (2 wk) and 65.6% (3 mo) Constipation-40.6% (2 wk) and 84.4% (3 mo) Need for laxatives-15.6% (2 wk) and 40.6% (3 mo) Abdominal discomfort-31.3% (2 wk) and 68.8% (3 mo) Decrease in pain score from 5 (before treatment) to 0 (after 3 mo)

GTN: Glyceryl trinitrate.

Table 4 Studies comparing complication rates of different surgical therapies

S/N	Ref.	Study details	Results
1	Garcea et al[30] 2002 Single arm, retrospective, non-randomized	Conservative lateral sphincterotomy for chronic anal fissures 65 patients	Flatus or fecal incontinence-3.3%
2	Tocchi et al[31] 2004 Single arm, prospective, non-randomized	Lateral subcutaneous internal sphincterotomy for non-responders to 0.2% GTN 164 patients	Early gas and fecal soilage-9.1% Some degree of incontinence at 3 mo-3% (3/5 patients had pre-op external sphincter damage)
3	Liratzopoulos et al[32] 2006 Single arm, prospective, non-randomized	Lateral subcutaneous sphincterotomy for chronic anal fissures 246 patients	Incidence of new continence at 48 wk-7.02%
4	Wiley et al[33] 2004 Dual arm, prospective, randomized	Open vs closed lateral sphincterotomy 79 patients	Overall incontinence rate-6.8% (no significant difference between the 2 techniques)
5	Elsebae et al[38] 2007 Dual arm, prospective, randomized	Impact of the extent of division of internal anal sphincter on fecal incontinence 108 patients	Up till dentate line-10.86% incontinence rate Up till apex of fissure-2.17% incontinence rate
6	Jensen et al[34] 1984 Double arm, prospective, randomized	Lateral sphincterotomy vs simple anal dilatation	Flatus incontinence-0% (sphincterotomy) vs 28.6% (anal dilatation) Fecal incontinence-0% (sphincterotomy) vs 7.1% (anal dilatation) Fecal soiling of underwear-3.3% (sphincterotomy) vs 39.3% (anal dilatation) All above results statistically significant
7	Renzi et al[13] 2007 Double arm, prospective, randomized	Pneumatic balloon dilatation vs lateral sphincterotomy 53 patients	Fecal incontinence-0% (balloon dilatation) vs 16% (sphincterotomy)
8	Richard et al[35] 2000 Double arm, prospective, randomized	Internal sphincterotomy vs 0.25% GTN 90 patients	Headaches-84% (GTN) No incontinence complications Patient satisfaction-97% (sphincterotomy) vs 61% (GTN)
9	Evans et al[36] 2001 Dual arm, prospective, randomized	0.2% GTN vs lateral sphincterotomy for chronic anal fissures 65 patients	GTN-31% headaches No mention of sphincterotomy complications
10	Brown et al[37] 2007 Double arm, prospective, randomized, multi-centric	2% GTN vs lateral internal sphincterotomy at 6 years post-treatment 82 patients	No difference in fecal incontinence scoring between both groups No difference in symptoms of incontinence-16/24 (66.7%) (sphincterotomy) vs 18/27 (66.7%) (GTN)
11	Menteş et al[29] 2003 Double arm, prospective, randomized	Botulinum toxin 0.3 units/kg vs internal sphincterotomy 111 patients	Incontinence-8/50 (16%) patients (sphincterotomy) had transient flatus incontinence vs 0 (botulinum toxin)
12	Schiano di Visconte et al[14] 2009 Double arm, prospective, randomized	0.25% GTN and anal cryothermal dilators BD vs 0.4% GTN 60 patients	No incontinence reported
13	Yucel et al[15] 2009 Double arm, prospective, randomized	Controlled intermittent anal dilatation (CIAD) vs lateral sphincterotomy 40 patients	No incontinence reported
14	Singh et al[9] 2005 Single arm, prospective, non-randomized	Rotational flap for treatment of chronic anal fissures 21 patients	11.8% flap uptake failure with wound dehiscence No donor site complications No new incontinence complications post-op
15	Giordano et al[10] 2009 Single arm, prospective, non-randomized	Cutaneous advancement flap anoplasty for chronic anal fissures 51 patients	Suture line dehiscence-5.9% No incontinence complications
16	Pelta et al[11] 2007 Double arm, prospective, randomized	Subcutaneous fissurotomy for chronic anal fissures 109 patients	No incontinence complications
17	Soll et al[12] 2004 Single arm, prospective, non-randomized	Fissurectomy and botulinum toxin 20-25 units for chronic anal fissures not responsive to medical therapy 31 patients	7% flatus incontinence rate lasting maximum of 6 wk
18	Gupta[16] 2008 Single arm, prospective, non-randomized	Closed anal sphincter manipulation (sphincterolysis) for chronic anal fissures 312 patients	11/312 patients had incontinence symptoms within first 4 wk Complete continence restored in 97% of patients after 1 mo
19	Tan et al[7] 2009 Single arm, prospective, non-randomized	Effect of posterior perineal support on chronic anal fissure healing	No complications noted

GTN: Glyceryl trinitrate