Does PRP therapy affect wound epithelialization time after excision of chronic anal fissure? Results of a randomized trial (NCT07268261)

OBJECTIVE: to evaluate the efficacy of PRP therapy following excision of chronic anal fissure (CAF) combined with pharmacological relaxation of the internal anal sphincter using 40 units of botulinum toxin type A (BTA).

PATIENTS AND METHODS: single-center prospective randomized controlled trial (NCT07268261) was held between September 2023 and November 2025comparing outcomes of fissure excision (FE) combined with 40 units of BTA plus platelet-rich plasma injection (FE + BTA + PRP — study group) versus FE with BTA alone (FE + BTA — control group).142 patients were randomized during this period: 70 in FE + BTA + PRP group and 72 in FE + BTA group. 125 patients were included in the final analysis after applying exclusion criteria: 60 in the study group and 65 in the control group. During preoperative and postoperative period patients underwent control examinations, pain intensity assessment using the visual analog scale (VAS), profilometry, and evaluation of transient fecal incontinence using the Wexner scale. The primary end point was the rate of wound epithelialization at 60 days post-surgery.

RESULTS: on the 60^th days, wound healing rates were comparable between both groups: 43/60 (71.7%; 95% confidence interval [CI]: 58.6–82.5) in the FE + BTA + PRP group versus 47/65 (72.3%; 95% CI: 59.8–82.7) in the FE + BTA group (p = 0.936). However, on the 15th days, no patients had epithelialized wounds; on the 30th days, wound healing occurred in 11/60 (18.3%) patients in the FE + BTA + PRP group versus none in the FE + BTA group (p = 0.0003); on the 45th days — in 18/60 (30.0%) versus 3/65 (4.6%) patients respectively (p = 0.0001). No postoperative complications developed in any patient. Transient fecal incontinence on the 30th days was observed in 12/60 (20.0%) patients in the studied group and 10/65 (15.4%) in the control group (p = 0.498); on the 60th days — in 5/60 (8.3%) and 2/64 (3.1%) patients, respectively (p = 0.262). Pain intensity during the day and during defecation in the postoperative period was comparable between two groups throughout the observation period, except of day 10 (during defecation, p = 0.049) and day 12 (during the day, p = 0.036; during defecation, p = 0.035), with lower scores in the control group; by day 60, pain was successfully relieved in almost all patients in both groups. According to profilometry data on the 30th days internal anal sphincter (IAS) spasm persisted in 15/48 (31.3%) patients in the study group and 10/51 (19.6%) in the control group (p = 0.183); on the 60th days — in 15/45 (33.3%) and 11/49 (22.4%) patients, respectively (p = 0.239). No statistically significant differences were achieved in favor of the study group regarding the number of days of temporary disability — 15 (11; 22) days in the FE + BTA + PRP group versus 20 (13; 27) in the FE + BTA group (p = 0.079). Female gender was identified as a factor significantly increasing the odds of absence of epithelialization on the 30th days in univariate logistic regression analysis (odds ratio [OR] = 3.95; 95% CI: 1.09–14.37; p = 0.037). On the 45th days, in addition to gender (OR = 3.29; 95% CI: 1.26–8.61; p = 0.015), significant factors were: treatment method in favor of the FE + BTA + PRP group (OR = 0.11; 95% CI: 0.03–0.41; p = 0.0009); age (OR = 1.07; 95% CI: 1.01–1.13; p = 0.015); and presence of constipation (OR = 5.14; 95% CI: 1.43–18.53; p = 0.013). On the 60th days, only female gender was statistically significantly associated with non-healing wound (OR = 3.22; 95% CI: 1.22–6.66; p = 0.019). No factors influencing the presence of transient fecal incontinence were identified.

CONCLUSION: the use of platelet-rich plasma combined with BTA injection and FE in the treatment of CAF does not increase the rate of postoperative wound epithelialization at 2 months after surgery; however, it offers an advantage by increasing the rate of epithelialization at 30 and 45 days. At the same time this method does not affect the incidence of postoperative complications, pain intensity, functional treatment outcomes, or social and occupational rehabilitation of patients.

1. Anal fissure. Clinical guidelines. Moscow; 2024. URL: https://cr.minzdrav.gov.ru/preview-cr/172_3. (In Russ.).

2. Trzpis M, Klaase JM, Koop RH, et al. Fissurectomy combined with botulinum toxin A: a review of short- and long-term efficacy of this treatment strategy for chronic anal fissure; a consecutive proposal of a treatment algorithm for chronic anal fissure. Coloproctology. 2020; 42:400-408. doi:10.1007/s00053-020-00480-7.

3. Lindsey I, Cunningham C, Jones OM, et al. Fissurectomy-botulinum toxin: a novel sphincter-sparing procedure for medically resistant chronic anal fissure. Dis Colon Rectum. 2004;47(11):1947-52. doi: 10.1007/s10350-004-0693-x.

4. Goloktionov N.A., Titov A.Yu., Ponomarenko A.A., et al. Early outcomes of chronic anal fissure treatment using the lateral internal sphincterotomy method without excision (randomized trial NCT05117697). Koloproktologia. 2023;22(3):50-61. (in Russ.). doi:10.33878/2073-7556-2023-22-3-50-61.

5. Khryukin R.Yu., Zharkov E.E., Goloktionov N.A., et al. Treatment of chronic anal fissure using botulinum toxin type A at a dose of 40 U compared with lateral subcutaneous sphincterotomy (NCT03855046). Koloproctologia. 2022;21(1):60–70. (In Russ.). doi:10.33878/2073-7556-2022-21-1-60-70.

6. Sagidova K.I., Ignatenko M.A., Zharkov E.E., et al. Results of chronic anal fissure treatment with botulinum toxin type A at a dose (dosage) of 80 units without its incision (single-center prospective randomized controlled trial NCT05598164). Koloproktologia. 2025;24(3):35-47. (In Russ.). https://doi.org/10.33878/2073-7556-2025-24-3-35-47.

7. Solovyev D. The use of Platelet-rich-plasma in the treatment of patients with chronic anal fissure. Budapest Proctology Meeting: How We Do It? November 24—26, 2016. Budapest: Hungary. 2016;13. Ac cessed November 2016. Available at: www.proctologybpmeeting.hu; www.convention.hu.

8. Yilmaz G, Tanrikulu Y. Short-term Results of Platelet-Rich Plasma in the Treatment of Chronic Anal Fissure: Randomized Controlled Clinical Study. Dis Colon Rectum. 2021;64(6):714–723. doi: 10.1097/DCR.0000000000001903. PMID: 33399410.

9. Krylov N.N., Lyatifova L.V. Autoplasmotherapy in coloproctology. Pirogov Russian Journal of Surgery. 2017; (7):61 64. (In Russ.). https://doi.org/10.17116/hirurgia2017761-64.

10. Leitner GC, Gruber R, Neumüller J, et al. Platelet content and growth factor release in platelet-rich plasma: A comparison of four different systems.Vox Sang. 2006;91(2):135-9. doi: 10.1111/j.1423-0410.2006.00815.x

11. Belik B.M., Kovalev A.N. The use of autologous platelet-rich plasma in the complex treatment of anal fissure combined with anal sphincter spasm in non-hospital settings. Koloproktologia. 2022;21(1):50-59. (In Russ.). https://doi.org/10.33878/2073-7556-2022-21-1-50-58

12. GuninAG, Petrov VV, Golubtzova NN, et al. Age-related changes in angiogenesis in human dermis. Experimental Gerontology. 2014;55:143-151, ISSN 0531-5565, https://doi.org/10.1016/j.exger.2014.04.010.

13. Lecce L, Lam YT, Lindsay LA, et al. Aging impairs VEGF-mediated, androgen-dependent regulation of angiogenesis. Mol Endocrinol. 2014 Sep;28(9):1487-501. doi: 10.1210/me.2013-1405. Epub 2014 Jul 24. PMID: 25058601; PMCID: PMC4154238.

14. Hoch M, Eberle AN, Peterli R, et al. LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-α in human adipocytes. Cytokine. 2008;41(1):29–37.

15. Bordakov P., Gain Yu. Tissue Engineering in Complex Treatment of Chronic Anal Fissures Using Minimally Invasive Technologies. Hematology. Transfusiology. Eastern Europe. 2019; 5(4):437-449. (In Russ.).