Title of the proposal

 Efficacy of Platelet rich plasma in reducing the scar width of primary cleft lip repair; a double-blinded randomized control trial

Introduction

Unavoidable visible cheiloplasty scars remain the main topic searched by cleft surgeons¹. Platelet-rich plasma helps to regenerate injured tissues and improve scar appearance, as it is rich in various cytokines and growth factors that promote tissue remodeling, angiogenesis, and healing².

Various studies have reported that PRP acts as an effective therapy for muscle injury, chronic wounds, and atrophic and contractile scars by rejuvenating skin tissue and texture³.

Novelty of our study is that only single study in literature that have prospectively assessed the impact of Platelet-rich plasma on post-surgical cleft lip repair scar till now.

Review of Literature

Cleft lip and palate are the most common congenital conditions affecting the pediatric group5. They affect the child’s appearance, causing psychological and social encumbrance6. Unavoidable visible cheiloplasty scars remain the main topic searched by cleft surgeons. Platelet-rich plasma (PRP) is a concentrate of autologous platelets and plasma that has recently contributed to many fields, such as plastic surgical, orthopaedic, and dental research. Platelet-rich plasma helps to regenerate injured tissues and improve scar appearance, as it is rich in various cytokines and growth factors (GFs) that promote tissue remodelling, angiogenesis, and healing.³

Refahee et al⁴ in did and RCT with sample size of 24 with 12 in each arms to look for the effect of PRP in better scar after cleft lip repair, and found that mean scar width by ultrasound at 6 months was 4.96 + 0.929 and 3.8 + 0.886 mm in the control and study groups, respectively. According to photographic measurements, the scar was significantly narrower at both the first point (0.831 +/- 0.231 mm vs 1.49 +/- 0.442 mm, and the second point (1.015 +/- 0.103 mm vs 2.275 +/- 0.984.

Martinez-Zapata MJ et al⁵ in his systematic review of Autologous platelet-rich plasma for treating chronic wounds, which included 10 RCTs found that the proportion of completely healed chronic wounds was reported in seven RCTs that compared PRP with standard treatment or placebo, with no statistically significant difference between the groups, in diabetic foot ulcers (RR 1.16; 95% CI 0.57 to 2.35), in venous leg ulcers (pooled RR 1.02; 95% CI 0.81 to 1.27; I2=0% ) and in mixed chronic wounds (pooled RR 1.85; 95% CI 0.76 to 4.51; I2=42%). The percentage of wound area healed was reported in two RCTs of mixed chronic wounds, and results were statistically significant in favour of the PRP group (RR 51.78%; 95% CI 32.70 to 70.86; I2= 0%).

In retrospective cohort study by Wen-Hao Zhang et⁶ al found patients of unilateral cleft lip, the upper lip orbicularis oris muscle was scanned using ultrasound in natural closure and pout states. After reconstruction of the unilateral cleft lip, the left and right philtrum columns were still obviously asymmetric, their radian displayed clearly and showed better continuity. So, ultrasound imaging is able to clearly show the hierarchical structure of upper lip orbicularis oris muscle, and will be beneficial in guiding the upper lip repair and reconstruction surgery.

Methodology

Study design: Double-blinded randomized controlled trial with Allocation concealment, operating surgeon and follow up surgeon will be blinded.

Study participants: Patients accepted for randomization with a non-syndromic complete unilateral cleft lip with or without cleft palate and will be planned for repair at 2 to 6 months of age we , excluded syndromic patients, child with very wide cleft lip, children with neuromuscular disorder

We defined our study and control group as, patients with unilateral cleft lip were treated with the modified Millard technique/ Tennison Randal and PRP injection intraoperatively and patients with unilateral cleft lip were treated with the modified Millard technique / Tennison Randal with placebo respectively.

Aim of our study: To compare the efficacy of Platelet rich plasma in Reducing the Scar Width of Primary Cleft Lip Repair with a placebo.

Primary objective: To compare the scar width clinically and with ultrasound in mm in two groups.

Secondary objectives: To evaluate the scar quality based on the Vancouver scar scale, to determine Incidence of Surgical site infection.

We calculated sample size based on the randomized controlled trial carried out by Refahee et al⁴, The mean scar width by ultrasound at 6 months was 4.96+/-0.929 and 3.8 +/- 0.886 mm in the control and study groups respectively. Assuming a true difference in mean scar width 1.16 units, a pooled standard deviation of 0. 90 units, the study would require a sample size of: 13 for each group, to achieve a power of 90% and a level of significance of 5%. Further, assuming a drop-out rate of 20 % from the study, the final sample size comes out to be, 33 with 16 patients in each arm.

Study procedure:

Patients will be prepared as per our institutional protocol. Modified Millard technique or Tennison Randal repair will be performed in a 3-layer closure of the mucosa, muscle, and skin.

In study group PRP will be prepared from 10 mL of the patient’s own blood under completely sterile conditions at the time of surgery. Following muscle closure, approximately 0.25 mL of PRP will be injected on each side along the suture line of the muscle layer and another 0.25 mL of PRP will be injected on each side along the suture line of the dermis layer. Postoperative Period and Follow-Up will be followed as per our institutional protocol.

The width of the scar will be assessed at 6 months postoperatively via ultrasound (7.5-9MHz) and over the skin via photography.

The scar width will be measured at 3 different points with Photoshop (CS5 extended version 12.0; Adobe Systems Inc, San Jose, California) using the ruler as a control reference.

If it can be proved that there is better outcome in terms of scar post-operatively with it may help to modify our institutional practice of cleft lip repair.

References:

1)     Hunt O, Burden D, Hepper P, Johnston C. The psychosocial effects of cleft lip and palate: a systematic review. Eur J Orthodont. 2005;27(3):274-285

2)     McAleer JP, Sharma S, Kaplan EM, Persich G. Use of autologous platelet concentrate in a nonhealing lower extremity wound. Adv Skin Wound Care. 2006;19(7):354-363

3)     Nita A, Orzan O, Filipescu M, Jianu D. Fat graft, laser CO2 and platelet-rich-plasma synergy in scars treatment. J Med Life. 2013;6(4):430

4)     Refahee SM, Aboulhassan MA, Abdel Aziz O, Emara D, Seif El Dein HM, Moussa BG, Abu Sneineh M. Is PRP Effective in Reducing the Scar Width of Primary Cleft Lip Repair? A Randomized Controlled Clinical Study. Cleft Palate Craniofac J. 2020 May;57(5):581-588. doi: 10.1177/1055665619884455. Epub 2019 Oct 30. PMID: 31665898.

5)     Martinez-Zapata MJ, Martí-Carvajal AJ, Solà I, Expósito JA, Bolíbar I, Rodríguez L, Garcia J. Autologous platelet-rich plasma for treating chronic wounds. Cochrane Database Syst Rev. 2012 Oct 17;10:CD006899. doi: 10.1002/14651858.CD006899.pub2. Update in: Cochrane Database Syst Rev. 2016;(5):CD006899. PMID: 23076929

6)     Zhang WH, Chen YY, Liu JJ, Liao XH, Du YC, Gao Y. Application of ultrasound imaging of upper lip orbicularis oris muscle. Int J Clin Exp Med. 2015 Mar 15;8(3):3391-400. PMID: 26064229; PMCID: PMC4443063