Use of Autologous Platelet-Rich Plasma in Complete Cleft Palate Repair

Transcription

1 The Laryngoscope VC 2016 The American Laryngological, Rhinological and Otological Society, Inc. Use of Autologous Platelet-Rich Plasma in Complete Cleft Palate Repair Mohammad Waheed El-Anwar, MD; Ahmed Abdel Fattah Nofal, MD; Mohamed Khalifa, MD; Amal Saeed Quriba, MD Objectives/Hypothesis: Evaluate the effect of topical application of autologous platelet-rich plasma (PRP) in primary repair of complete cleft palate and then compare the result with another group of patients using the same surgical technique, without application of PRP with regard to the incidence of oronasal fistula, velopharyngeal closure, and grade of nasality. Study Design: Case control study. Methods: This study was carried on 44 children with complete cleft palate with age range from 12 to 23 months. The children were divided into two age- and gender-matched groups: All children were subjected to the same technique of V-Y pushback repair of the complete cleft palate. In group A (22 children), the PRP prepared from the patient was topically applied between the nasal and oral mucosa layer during palatoplasty, whereas in group B (22 children) the PRP was not applied. Results: All cases were recovered smoothly without problems. In group A, no oronasal fistula was reported, whereas in group B three patients (13.6%) had postoperative fistulae and two patients (9.1%) needed revision palatoplasty. At 6 months postoperative assessment, group A (with PRP application) showed significantly better grade of nasality (P ) and better endoscopic velopharyngeal closure (P ) than group B. Conclusion: Usage of autologous PRP in complete cleft palate repair is simple; effective; can decrease the incidence of oronasal fistula; and also significantly improves the grade of nasality and velopharyngeal closure, which decreases the need of further surgical intervention in cleft palate patients. Key Words: Platelet-rich plasma, cleft palate, oronasal fistula, velopharyngeal incompetence. Level of Evidence: 3b. Laryngoscope, 126: , 2016 INTRODUCTION Cleft lip and/or cleft palate are the most common congenital anomalies in the oral and maxillofacial region. The overall incidence of orofacial clefting is about one in 700 live births, and the incidence of isolated cleft palate is approximately 0.5 per 1,000 live births. 1 The principal concern in cleft palate repair is closure of the physical defect, with the best velopharyngeal (VP) function and perfect speech, without affecting the maxillofacial growth or hearing. 1,2 Velopharyngeal insufficiency and oronasal fistula represent the most common complication after cleft palate repair. 3,4 Even in experienced hands, the incidence of oronasal fistula is 10% to 20%. 3 Although fistula could occur at any site of the palate, it is common among the junction of From the Audiology Unit, Otorhinolaryngology Head and Neck Surgery Department (A.S.Q.), the Otorhinolaryngology Head and Neck Surgery Department (M.W.E A., A.A.F.N.), and the Surgery Department (M.K.), Faculty of Medicine, Zagazig University, Zagazig, Egypt Editor s Note: This Manuscript was accepted for publication December 15, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Ahmad Abdel Fattah Nofal, MD, Otorhinolaryngology, Head and Neck Surgery Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. E mail: nofal_9999@hotmail.com DOI: /lary the hard and soft palate posteriorly or at the premaxillary maxillary junction anteriorly. 3,5 Persistent VP incompetence following cleft palate repair that require surgery has been reported as a rate of up to 30%. 6 8 A variety of factors lead to the development of such complications, such as the type of surgical repair employed, extent of clefting, timing of the repair, and expertise of the surgeon. 9 Platelet-rich plasma (PRP) is a simple and minimally invasive way to get a high concentration of autologous growth factors (GFs), which can be easily and safely applied directly into the surgical field. 10 The PRP was used in repair defects caused by dental extraction 11 or tumor resection, 12 as well as for alveoloplasty in dental and maxillofacial surgery. It was also used in other surgical procedures such as acromioplasty, 13 arthroscopy, 14 rhytidectomy with fat grafts, 15 skin wounds, 16 and infiltration due to ankle ligament injury. 17 Accelerated healing, decreased risk of infection, less postoperative discomfort, and faster recovery were reported in all these applications. The aim of this study was to evaluate the effect of topical use of autologous PRP during primary complete cleft palate repair and then compare the result with another group of patients using the same surgical repair technique, without PRP application with regard to the incidence of oronasal fistula, velopharyngeal closure, and grade of nasality.

2 package Epi Info 6 (Centers for Disease Control and Prevention, Atlanta, GA). The patients were assigned to the groups in a randomized and prospective manner. The autologous PRP prepared from the patient was topically applied between the nasal and oral mucosa layer during palatoplasty in group A, whereas in group B PRP was not applied during palatoplasty with the same V-Y pushback technique. All of the patients were subjected to detailed history, routine systemic examination, and comprehensive head and neck examination. Any nasal or upper respiratory tract infections were properly treated preoperatively. Preoperative evaluation by phoniatrician (blind to the groups) was done for all patients. All of the patients in both groups took broad spectrum antibiotic (amoxicillin 1 clavulanic acid) 2 hours preoperatively and continued for 10 days postoperatively. Fig. 1. The platlet-rich plasma after centrifuge of 5 ml of blood. [Color figure can be viewed in the online issue, which is available at MATERIALS AND METHODS This prospective study was conducted in the otolaryngology department and the pediatric unit of the general surgery department in Zagazig University Hospitals in Zagazig, Egypt, in the period from February 2012 to June The study was approved by the institutional review board at Zagazig University Hospitals, and informed written consent was obtained from the parents or relatives of the children. This study was carried on 44 children with complete cleft palate with age range from 12 to 23 months. Syndromic patients, patients with history of previous palatoplasty, or patient with cleft soft palate only were excluded from the study. All patients were subjected to the same surgical technique of V- Y pushback repair by the same surgeons. Patients were assigned into two age- and gender-matched groups, each including 22 children, using a random list generated by statistical Preparation of the Autologous PRP During the operation and under sterile technique, 5 ml of peripheral venous blood was drawn by the anesthetist from the patient with a 16- or 18-gauge butterfly needle or syringe to avoid irritation and damage of the platelets. The collected blood was kept in a 5 ml, plain vacuum tube (without anticoagulant or calcium). The sample was immediately centrifuged using a tabletop centrifuge (Low Speed Centrifuge [800]; Jiangsu Zhengji Instruments, Jiangsu, China) machine for 12 minutes at 3,200 rpm in the operative room temperature. Thus, the blood was separated out into three layers based on density 18 : the bottom layer containing red blood cells; the middle layer containing PRP (about 1.5 ml 3 ) consisting of platelets and white blood cells (WBCs; buffy coat), which could be easily obtained (Fig. 1); and the top layer containing platelet-poor plasma. Application of the Platelet-Rich Plasma The autologous PRP was applied after suturing of the nasal layer of the palatal mucosa. It was applied mainly at the junction of the hard and soft palate (Fig. 2). Next, the oral layer of the palatal mucosa was sutured. Thus, the autologous PRP was secured between the nasal and oral mucosal layer during the palatoplasty procedure. Phoniatric Patient Assessment Every patient in both groups was subjected to the protocol of assessment that is applied in the phoniatric unit of Zagazig Fig. 2. (A) V-Y flap was elevated and the nasal layer of the palate was repaired. (B) Autologous platelet-rich plasma (arrow) was topically applied over the repaired nasal layer of the palatal mucosa (mainly at the junction between the hard and soft palate) before repair of oral mucosa. [Color figure can be viewed in the online issue, which is available at com.] 1525

3 TABLE I. Comparison Between the Two Groups in the Postoperative Fistula. University Hospitals. 19 Speech assessment was done preoperatively, and 3 months and 6 months postoperatively, with speech evaluators who were blind to the technique that was used. Evaluation included subjective as well as objective measures comprising the following levels of assessment: I. Elementary Diagnostic Procedures. A. Patients and parents interview: This included personal data and developmental milestones. B. Auditory perceptual assessment (APA) of the patient s cry or speech: The grade of nasality was evaluated during patient s speech or cry if the language and speech could not be assessed at the time of assessment. The nasality was graded by a 5-point scale (0 5 normal; 4 5 the most severe affection). To overcome individual variation between examiners, three judges (blind to the groups) usually assessed every patient blindly, and the average of the three results was used. C. Examination of the vocal tract: Included visual assessment of lip, teeth, alveolar margin, tongue, hard palate, soft palate, presence or absence of fistula, uvula, movement of palatal muscles, and pharyngeal walls. II. Clinical Diagnostic Aids. A. Documentation (audio recording) of APA: Samples of patient speech or cry were recorded digitally by the computer utilizing a unidirectional microphone in a sound-treated room, which were then assessed by three judges for analysis, providing a score from a 5-point scale (0 5 normal; 4 5 the most severe affection). B. Video nasoendoscopy: With a flexible fiberoptic nasopharyngeal endoscope from (XION GmbH, Berlin, Germany). The velopharyngeal valve movement was recorded while the patient was repeating speech samples that had been recommended by an international working group. 19 Presence of Fistula Presence of fistula Yes 0 (0%) 3 (13.6%) No 22 (100%) 19 (86.4%) n 5 Patients number; X 2 5 Chi-square test. Simple syllables, including both nasal and nonnasal utterances. Both high and low vowels were used. An example would be /ma ma ma/, /pa pa pa/, /ta ta ta/, /ka ka ka/, /mi mi mi/, /pi pi pi/, /ti ti ti/, and /ki ki ki/. Production of at least two sustained fricatives (preferably both voiceless and voiced), such as /sssss/, /fffff/, /zzzzz/, and / vvvvv/. Production of the nasal oral blend in the word /?AmbAr/. Arabic language phrases involving connected speech with varying phonemic contexts: 1. Nasal sentence, for example, (/mama betnajemmanal/) 2. Oral sentence, for example, (/?ali raé jel?abkorah/) 3. Combined oral nasal sentence, for example, (/samiaffostansemsem/) Connected speech: Counting from 1 to 10 in Arabic language to get a varied phonemic sample with nasal to nonnasal transitions and voiced voiceless transitions. Because this study was dealing with young children, 20 of the children could not complete the full protocol, 10 in each group. Thus, assessment was done during crying or simple sounds or words according to the ability of the child. The movement of the velum and lateral pharyngeal walls was traced on the monitor and given a score from 0 to 4 as follows: 0 5 the resting (breathing) position or no movement; 2 5 half the distance to the corresponding wall; 3 5 the velum and lateral pharyngeal wall move more than half the distance in between, but not touching each other or the posterior pharyngeal wall; 4 5 the maximum movement reaching and touching the opposite wall. Pattern of closure of the velopharyngeal valve was specified whether circular, coronal, sagittal, or other. Statistics Results of both groups were compared statistically using SPSS 17.0 (SPSS Inc., Chicago, IL). Chi-square test was used to compare qualitative data. A P value less than 0.05 was considered significant. RESULTS This study included 44 patients with complete cleft palate randomly stratified into two equal groups. Their age ranged from 12 to 23 months. Ten children (45.45%) had repaired cleft lip before (8 unilateral and 2 bilateral) at the age of 3 to 4 months, equally stratified between the two studied groups. According to Veau classification system, all of the patients were in class II at the time of the operation. Group A consisted of 22 children, 13 males (59%) and nine females (41%), with mean age range of months, whereas group B consisted of 22 children, also 13 males and nine females, with mean age range of months. The follow-up period was at least 6 months. The intraoperative bleeding was acceptable in all patients, and all cases recovered smoothly with no recovery problem in both studied groups. In group A (with PRP application), there was no postoperative fistula, infection, suture release, or granulation tissue in the palate. In group B, however, three patients (13.6%) had a postoperative fistula at the area of junction between the hard and soft palate, but comparison between the two groups in the presence of postoperative fistula revealed no significant difference (Chisquare test , P ) (Table I). The results of APA of grade of nasality during speech or crying revealed no significant differences between the two groups before surgery. Although at 3 months postoperative assessment there was a decrease in the grade of nasality in both groups, with slight better results in group A but without significant difference (P ), at 6 months postoperative assessment the difference between the two group became significant in favor of group A (P ) (Table II). In endoscopic overall closure of velopharyngeal valve: In group A at 3 months postoperative assessment, the velopharyngeal closure during speech or cry had competence (grade 4) in 18 patients (81.8%), had mild incompetence (grade 3) in two patients (9.1%), and had moderate incompetence (grade 2) in two patients (9.1%). However, at 6 months postoperative assessment, the two grade 3 patients improved to grade 4, with no changes in the two grade 2 patients (9.1%) of (Table III). 1526

4 TABLE II. Pre and Postoperative Comparison Between Group A and Group B in (APA) of the Grade of Nasality. Grade of Nasality Preoperative 4 5 (22.7%) 6 (27.3%) (50%) 10 (45.5%) 2 2 (9.1%) 2 (9.1%) 1 4 (18.2%) 4 (18.2%) 3 month 4 0 (0%) 0 (0%) Postoperative 3 2 (9.1%) 4 (18.2%) 2 5 (22.7%) 5 (22.7%) 1 6 (27.3%) 9 (40.9%) 0 9 (40.9%) 4 (18.2%) 6 months 4 0 (0%) 1 (4.5%) * Postoperative 3 2 (9.1%) 5 (22.7%) 2 4 (18.2%) 10 (45.5%) 1 5 (22.7%) 4 (18.2%) 0 11 (50%) 2 (9.1%) *Significant. n 5 number of patients; X 2 5 Chi-square test. In group B at 3 months postoperative assessment, the velopharyngeal closure during speech or cry had competence (grade 4) in 12 patients (54.5%), had mild incompetence (grade 3) in four patients (18.2%), and had moderate incompetence (grade 2) in six patients (27.3%). However, at 6 months postoperative assessment, one of the grade 2 patients improved to grade 3, leaving five patients at grade 2 (22.75%). Comparison between the two groups with regard to the results of endoscopic velopharyngeal closure revealed no significant difference preoperatively. At 3 months postoperative assessment, the results were better in group A, but with no significant difference (P ). However, at 6 months postoperative assessment, there were significant differences between the two groups in favor of group A (P ) (Table II). DISCUSSION Oronasal fistula and velopharyngeal insufficiency are the most common complication after palatoplasty. 3 The incidence of palatal fistula formation after primary palatoplasty varies from 13.3%, 19 23%, 20 36%, 21 and up to 76%. 22 The causes of fistula formation after cleft palate repair are related to the type of cleft, type of repair, wound tension, single layer repair, infection, and dead space deep to the mucoperiosteal flap. 23,24 Secondary surgery for velopharyngeal insufficiency is required following cleft palate repair in up to 30%. 6 8 Platelet-rich plasma is a simple and minimally invasive method to obtain a high concentration of autologous growth factors, which accelerates endothelial, epithelial, and epidermal regeneration; stimulates angiogenesis; and fast vascularization of the healing tissue. Moreover, PRP enhances collagen synthesis and soft tissue healing, decreases dermal scarring, and promotes the hemostatic response to injury. Platelet-rich plasma can be easily and safely placed directly into the lesion site. 10,25 It is bactericidal due to its WBCs content. 26,27 Platelet-rich plasma already gave good results of accelerated healing and faster recovery in many studies, with less risk of infection and less postoperative pain ,27,28 Gonzalez-Sanchez and Jimenez-Barragan used autologous bone graft mixed with plasma rich in GFs to close recurrent cleft palate fistulas with a success rate of 90.9%, which was satisfactory compared to other literature with a recurrent rate ranging from 40% to nearly 100%. 29 In the V-Y pushback procedure, the soft palate is retroposed and the palate is lengthened. However, it leaves extensive raw area anteriorly and laterally along the alveolar margin, which is healed by secondary intension that could lead to fibrosis and shortening of the palate with velopharyngeal incompetence, and also could result in alveolar arch deformity and dental malalignment. 5 In this study, when autologous PRP was topically applied between the repaired nasal and oral mucosal layers during complete cleft palate repair by V-Y pushback technique, no postoperative oronasal fistula was encountered. Usage of the same surgical technique of palatal repair but without use of PRP in the control group showed an oronasal fistula in 13.6% of cases. Although the difference was non significant (P ), this is a highly efficient result with PRP use in comparison to the reported literatures results, even better than the authors result in a previous study without PRP application (13.3%). 19 This is may be due to the high concentrate of autologous GFs that accelerate and promote the healing, WBCs that resist infection, and platelets that improve hemostasis. This may also be due TABLE III. Pre- and Postoperative Comparison Between Group A and Group B in Endoscopic Overall Closure of Velopharyngeal Valve. Grade of Closure Preoperative 4 0 (0%) 0 (0%) (0%) 0 (0%) 2 4 (18.2%) 3 (13.6%) 1 7 (31.8%) 9 (40.9%) 0 11 (50%) 10 (45.5%) 3 month 4 18 (81.8%) 12 (54.5%) postoperative 3 2 (9.1%) 4 (18.2%) 2 2 (9.1%) 6 (27.3%) 1 0 (0%) 0 (0%) 6 months 4 20 (90.9%) 12 (54.5%) * postoperative 3 0 (0%) 5 (22.75%) 2 2 (9.1%) 5 (22.75%) 1 0 (0%) 0 (0%) *Significant. n 5 number of patients; X 2 5 Chi-square test. 1527

5 to filling the dead space between the oral and nasal mucosal layer, which are considered part of the main cause of fistula formation after cleft palate repair. 23,24 Because of the high concentrate of autologous GFs, PRP promotes healing and decreased scarring and fibrosis. Moreover, PRP may promote faster vascularization and induce regeneration. 27 Thus, the grade of nasality and velopharyngeal closure was significantly improved in comparison to group B, in which we used the same surgical technique of palatal repair, but without use of PRP, at 6 months postoperative assessment. This is also better than other studies that did not use PRP: 14% and 15% of the cases needed pharyngeal flap in the study of Marrinan et al., 30 and 13.3% of the cases needed it in the study of Phua and de Chalain. 9 Platelet-rich plasma is safe (from the patient s blood, thus, no fear of infectious diseases transmision); rapid (12 minutes); easy to prepare during surgery (thus its preparation is not a burden on the length of surgery); has a low relative cost (syringe and vacuum tube); does not contain additives (no anticoagulant or any toxic materials); and guards against infection. Along with the main role of autologous PRP GFs in healing, we depended on it to provide protection to the operated site, fill the dead space, and act as a scaffold for regeneration of the mucosa after covering the raw area of the palate anteriorly and laterally along the alveolar margin. The application of autologous PRP between the nasal and mucosal layer during primary repair of complete cleft palate lowered the incidence of oronasal fistula and velopharyngeal incompetence and improved the grade of nasality in the patients in comparison with other patients who used the same surgical technique in the same condition but without use of PRP. Thus, the usage of PRP during palatoplasty may reduce the operative interventions needed for cleft palate repair, which on average reach four surgical procedures per case. As a result, the strengths of the current study are the easy, rapid, and safe preparation and the application of PRP in a prospective randomized study with 100% follow-up. Nevertheless, the sample size needs to be increased. Further studies with greater number of cases are advised. CONCLUSION Usage of autologous PRP in complete cleft palate repair is simple, effective, and improves the grade of nasality and the velopharyngeal closure, which decreases the need for further surgical intervention. It also has potential to decrease the incidence of oronasal fistula, although further investigations are needed. BIBLIOGRAPHY 1. Goodacre T, Swan M C. Cleft lip and palate: current management. Paediatr Child Health 2008;18: Stein S, Dunsche A, Gellrich NC, Harle F, Jonas I. One or two stage palate closure in patients with unilateral cleft lip and palate: comparing cephalometric and occlusal outcomes. Cleft Palate Craniofac J 2007;44: Sadove AM, Eppley BL. Cleft lip and palate, in: Grosfeld JL, O Neill JA, Coran AG, Fonkalsrud EW, Caldamone AA, eds. Pediatric Surgery, 6th ed. Philadelphia, PA: Mosby Elsevier; 2006: Jackson IT. Closure of secondary palatal fistulae with intra oral tissue and bone grafting. Br J Plast Surg 1972;25: Agrawal K. 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