The Effect of Acellular Dermal Matrix on the Success of Primary Palatoplasty With Intravelar Veloplasty


 BackgroundAcellular Dermal Matrix graft is usually used to repair fistulas following a cleft palate and has had positive results. But its use for primary palatoplasty has been less studied. Our aim was to compare the usefulness of using Acellular Dermal Matrix transplantation for primary palatoplasty with intravelar veloplasty in contrast to its lack of useMaterials and methodsA total of 72 children (6 months to 6 years old) with cleft palate were included in the study. The case-control prospective observations were conducted. A group underwent primary palatoplasty with intravelar veloplasty using Acellular Dermal Matrix and the control group had the same surgery without using Acellular Dermal Matrix. Patients were monitored for fistula formation, post-operative infection, and ulcers.ResultsNo post-surgical infection and wound opening was seen in any group. In the recipients of Acellular Dermal Matrix and control group three and six fistula was reported in which patients had soft and hard palate involvement and the cleft with length greater than 15 mm.ConclusionsConsidering the double incidence of fistulas in the control group compared to the ADM recipient, it seems that the use of ADM can be effective in reducing the incidence of fistulas. Since fistula is one of the complications of primary palatoplasty surgery and leads to secondary surgeries, the use of ADM can be helpful.

complications of primary palatoplasty surgery and leads to secondary surgeries, the use of ADM can be helpful.

Background
The surgical procedure used to correct or repair a palate in a person with cleft palate is called palatoplasty (1). The primary goal is to close the cavities between mouth and nose so that patients could have natural speaking (2), ingestion, respiration, and development of structures in their mouth (2,3).
Palatoplasty could be used for any degree of cleft palate. This surgical procedure is usually operated on infants with the ages between 6 to 12 months as the most suitable ones (4). Following the closure of the palate layers, an intravelar veloplasty is performed to correct and change the position of the palatal muscles (5). Because of the improvements in palate performance, the patient's complaint about the complications decreases (6, 7). If palate reconstruction is successful, the velopharyngeal area closes completely and the patient obtains the proper speech capability (6). Although it has not yet been fully scienti cally proven, it seems that palatoplasty may reduce the chance of patients with cleft palate to have middle ear in ammation and develop deafness (2). Various techniques including local mucoperiosteal ap, V-Y two-layer repair, superior lip mucosal or myomucosal ap, buccal myomucosal ap, superiorly based facial artery myomucosal ap, tongue ap, free ap, free cartilage graft, Distraction Osteogenesis, Acellular Dermal Matrix have been reported for cleft palate (8-10).
Fistula, infection and bleeding are the complications reported after cleft palate repair (11). The criteria for the successful palatoplasty is the absence of oronasal stula formation (12). Factors leading to the occurrence of stula include the width of the cleft, the technique used in the surgery, the inappropriate repair of the cleft, the inappropriate selection of the suture region and thus the pressure on the area, age and gender of the patient during surgery (13). After primary palatoplasty, the primary palatal stula formation with the probability of 0 to 67% and recurrence of about 25-100% were reported. If the cleft palate is closed with the epidermal mucus aps, the probability of recurrence of forming stula is higher (14).
Medical researchers have proposed various methods to reduce stula formation including the use of buccal aps (14), bone grafting (15), buccal myomucosal ap (16) Buccal fat pad ap (17), buccal mucosal ap (18), and high growth factor (PRGF) plasma (19). Acellular Dermal Matrix is widely used in multiple plastic surgeries (20). Acellular matrices have different usages including their potential role in the regeneration of organs or tissues. The ability to mimic the physiological conditions in the microscopic environment of the recipient tissue is one of the advantages of using these matrices (21). Once ADM is used in transplantation, it acts as a scaffold for the implantation of the recipient's cells and facilitator of subsequent adhesions and angiogenesis. These natural scaffolds are used in the manufacture of arti cial limbs and tissue repair and could be considered a solution to one of the biggest medical challenges from organ failure to plastic surgeries (22). Acellular Dermal matrix (ADM) is derived from the dermis, which is soft tissue. During the process of decellularization, the skin extracellular matrix structure is retained. This skin graft does not lead to immune response stimulation due to its lack of cells; therefore, patients do not require to receive high doses of immune system suppressors. As a result, they are used in initial closure of wide openings in soft and hard tissues such as cleft palate and lip (23).
In recent years, Acellular Dermal Matrix has been used to repair the cleft palate stula (24); however, use of this tool for primary palatoplasty has been less studied. In addition, in few previous studies generalized results have not been reported due to small sample size. Therefore, there is a need for further studies (25). The present study was designed to investigate the usage and effect of alloderm in the early stages of palatoplasty. The result help in improving the quality of life of patients with Cleft pallet.

Materials And Methods
This research is a case-control, prospective observational study. The participants were the patients who were referred to the Cleft palate clinic of Isfahan University of Medical Sciences. After being examined by the experts, they were registered for the primary palatoplasty. Inclusion criteria were having ages between 6 months to 6 years old and cleft palate Veau classes II to IV. Exclusion criteria were parents' unwillingness to give consent, diagnosis of a craniofacial syndrome, a disorder such as Ehlers Danlosus Syndrome and Pseudoxanthoma elasticum which are characterized with wound healing defect, and the Veau class I cleft palate.
All children referred to Alzahra University Hospital in Isfahan who had inclusion criteria were divided into two groups: primary palatoplasty with ADM and other primary palatoplasty procedures.
Ethical considerations of this study were the willingness of patients to participate in the study. Patients were assured that if they did not want to participate in the study, no changes will be made in their treatment plan. Written consent was obtained from patients' parents. The consent allowed us to use the information recorded in the medical documents if necessary. Patients were assured that only de-identi ed information will be published. Patient information was recorded in a checklist containing patient characteristics, type of surgery, type of cleft, presence or absence of stula, infection, hemorrhage and hematoma. The results were analyzed using SPSS version 16 and Chi-square statistical test.

Palatoplasty Method
All surgical procedures were performed under general anesthesia through the general tracheal tube with topical injection of lidocaine 1% with 1:100,000 epinephrine as well as the dose of rst-generation cephalosporin for prophylaxis (cefalotin 50 / kg in children and 1 g / IV in adults). Then, the location of the cleft palate in the oral mucosa on the bone surface of the palate was separated from nasal part by the surgeon. In the next step, the palate mucoperiostoneal ap covered the cleft ap and about 2 to 3 mm of it, and was prepared as a pocket for Acellular Dermal Matrix. Then the alloderm was used which was usually a thin piece with a thickness of 0.33-0.76 mm ( Figure 1). The alloderm was placed around the cleft palate and below the surface of the mucoperiosteum ap was sutured with vicryl or monocyral 4.0.
For 36 patients in the study group alloderm, and for 36 patients in the control group the same method without alloderm was used. Patients were followed up 6 months after their recharge from hospital. The width of the cleft palate was de ned using the Veau classi cation.
Recommended care after primary palatoplasty were oral antibiotic therapy, using chlorhexidine mouthwash for one week and a diet containing drinks and soft foods for three weeks after the palatoplasty.

Results
A total of 72 patients with cleft palate were referred to Alzahra University Hospital for primary palatoplasty in 2017. Patients were 32 girls and 40 boys (16 girls and 20 boys in each group) 6 months to 6 years old (patients' age in control group ranged from 6 months to 3 years and in ADM recipient group 6 months to 6 years). Other information such as cleft palate size, type, and duration of hospitalization is available in Table 1 none of the patients were excluded from the study. Patients were monitored for 6 months following the primary palatoplasty. They were examined for stula formation, postoperative infections and wound dehiscence ( Table 2). As shown in Table 2, the relative frequency of lack of stula is reported more than the occurrence of stula in each group. In patients treated with Acellular Dermal Matrix, only in three cases (8.3%) and in control group six (16%) stula formation was observed. there was no cases of infection in the surgical site in both study groups. No cases of wound dehiscence have been reported in all groups

Discussion
The cleft palate is one of the most common craniofacial anomalies which requires a multidisciplinary treatment approach. Physiotherapy, nutrition, orthodontic management, and speech therapy can improve the quality of life of patients with cleft palate. Primary palatoplasty is usually recommended at early ages which ultimately leads to the return of the natural speech production mechanism. In palatoplasty, tensionfree two-layer closure of oral cavities without penetration of water and uids reduces the risk of the oronasal stula. The repair will be effective when less tension is exerted on the oral layers (24). The success criteria of primary palatoplasty are the rate of oronasal stula, Velopharyngeal insu ciency (VPI), and achievement of natural speech. In present study, we achieved the success criteria of the primary palatoplasty with intravelar veloplasty. Because the incidence of infection and wound dehiscence in each group was zero. In addition no stula was reported in 63 of our patients after surgery.
Epidemiological studies of the cleft palate prevalence found that boys more than girls are likely to have this disorder (26). In the present study, stula was observed in ve boys and three girls' patients with a cleft greater than 15 mm. Clark et al. in 2003 reported the use of ADM in primary palatoplasty. In a retrospective study, they investigated patients with a cleft palate greater than 15 mm who were candidates for palatoplasty and were subjected to two-aps intravelar veloplasty using ADM. The result was completely successful in all patients. In two patients ADM was exposed but stula was not formed (27). In our current study, out of 35 patients with a cleft palate greater than 15 mm who received ADM, twenty six had successful treatment.
In recent years, improvements have been made in the management of palatoplasty techniques and the timing to do a surgery leading to a decrease in the incidence of oronasal stulas after primary palatoplasty. One of the studies that investigated the use of ADM in plastic surgeries was the 2012 retrospective case-series study by Aldekhayel et al. stula incidence using ADM was estimated 7.1%. While recurrence of oronasal stula using ADM was reported 11% (28). In our study recurrence of oronasal stula was 8.3%.
When the use of ADM was rst proposed for cleft palate surgery, successful results were observed in a small group of patients. A few years later, Kirschner in an empirical study in 2006 presented the results of using ADM to repair cleft palate stulas. Four other studies assessed the applicability and utility of using ADM to prevent the occurrence of stula in the primary palatoplasty (29).
Helling et al. described 32 surgeries for primary closure of cleft using the Furlow technique. In these surgeries, ADM was placed in junction between hard and soft palate. In 97% of cases the cleft was successfully closed. Only one of the patients had an oronasal stula (30). Our therapeutic research team achieved similar results. The closure success rate was about 92%, and only three ADM recipient who had a cleft more than 15 mm in size and engagement of both soft and hard palate developed stula after six months.
The largest collection of information about the use of ADM in the primary palatoplasty was published by Losee et al. in 2008. In order to close the cleft in these patients, Furlow palatoplasty with ADM and an algorithmic approach that would provide proper stable repair and also close the nasal cavity was used. The size of the cleft was not mentioned in this study; however, the closure of the cleft was achieved in 92.2% of the patients, and in only 4 (7.8%) cases, failure to close the cleft and occurrence of stula was observed. The use of ADM in tenuous repair and the closure of the cleft and nasal defect resulted in satisfactory results (31). Although the evidence presented in this study con rms the results of our study, the differences in the type of palatoplasty technique in these two studies can be controversial.

Recommendations
Although the results of studies are not in favor of ADM, its use is increasing in recent years [35] the type and degree of the initial cleft palate seems to lead to the stula reoccurrence. Since the results of this study showed a signi cant difference in the success of patients' treatment using ADM, it is suggested that further studies will be carried out in the future. In addition, because the incidence of the stula has been observed in patients with a cleft palate greater than 15 mm, this group of patients should be selected for future studies. If a similar type of surgical technique to previous studies is selected, the confounding factors of the study will be less and a better explanation for the results can be provided.

Funding
This research did not receive any speci c grant from funding agencies in the public, commercial, or notfor-pro t sectors.

Availability of Data and Materials
SPSS data of the participant can be requested from the authors. Please write to the corresponding author if you are interested in such data.

Ethics Approval and Consent to Participate
Written informed consent was obtained from the patients in our study. The purpose of this research was completely explained to the patients, and they were assured that their information would be kept con dential by the researcher. Participants below the age of 16 were given written informed consent from parents/legal guardians. The ethical committee approved this research of Isfahan University of Medical Sciences. All procedures performed in studies were following the ethical standards of the Isfahan University of Medical Sciences.

Consent for Publication
Written informed consent was obtained from the patients regarding the publication of this study. For participants below the age 16 years old and written informed consent was given from parents/legal guardians.

Figure 1
Using Acellular Dermal Matrix in palatal repair