Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial

Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial Mohammed Esmail Al-Sabahi, Omer Mohammed Jamali, Mostafa Ibrahim Shindy, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2007675/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Reconstruction of mandibular defects following ablative surgery remains a challenge even for experienced surgeons. Virtual planning and guided surgery, including computer-aided design/computer-aided manufacturing (CAD/CAM), afford optimized ways by which to plan complex surgery. This study aimed to evaluate and compare aesthetic outcome and surgical efficiency of free fibular flap (FFF) with and without CAD/CAM customized osteotomy guide (COG) for reconstruction of onco-surgical mandibular defects. Methods Twenty-two patients indicated for segmental mandibulectomy were randomly assigned to either CAD/CAM with COG group or that without COG- Model based reconstruction (MB group) at a 1:1 ratio. Aesthetic outcomes were evaluated by means of morphometric assessment and comparison for each differential area (DAr) and angle (DAn) in the affected side to the contralateral side of the mandible using computerized digital imaging analysis (CDIA) based on the post-operative 3D CT-scan. Subjective evaluation was performed using the Visual Analogue Scale (VAS) and Patient’s Satisfaction Score (PSS). Surgical efficiency was a secondary outcome and evaluated as total operative time and ischemia time. Results The mean sagittal DAr was significantly lower in the COG group (277.28 ± 127.05 vs 398.67 ± 139.10 mm 2 , P = 0.045). Although there was an improvement in the axial DAr (147.61 ± 55.42 vs 183.68 ± 72.85 mm 2 ), the difference was not statistically significant ( P = 0.206). The mean differences (Δ) in both sagittal and coronal DAn were significantly lower in the COG group than in the MB group (6.11 ± 3.46 and 1.77 ± 1.12° vs 9.53 ± 4.17 and 3.44 ± 2.34°), respectively. There were no statistically significant differences in the axial DAn between the two groups ( P = 0.386). The PSS was significantly higher in the COG group, reflecting better aesthetic satisfaction than in the MB group ( P = 0.041). The total operation and ischemia time were significantly shorter in favor of the COG group with a mean of (562.91 ± 51.22, 97.55 ± 16.80 min vs 663.55 ± 53.43, 172.45 ± 21.87 min), respectively. Conclusion The CAD/CAM with COG is more reliable and highly valuable in enhancing aesthetic outcomes and surgical efficiency of mandibular reconstruction by FFF compared to that without COG (MB reconstruction). Trial registration: This trial was registered at ClinicalTrials.gov. Registration number: NCT03757273. Registration date: 28/11/2018. Aesthetic reconstruction CAD/CAM Customized osteotomy/cutting guide Free fibula flap Head and neck cancer Mandibular defects Model-based reconstruction Virtual planning. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Background Maxillofacial defects resulting from surgical resection of neoplasms can be associated with devastating functional and aesthetic deficits. Taking into consideration the mandible's importance as a major determinant in facial aesthetics and function; disruption of mandibular integrity following onco-surgical resection can create extensive composite defects, leading to functional and aesthetic impairments [ 1 – 3 ]. Facial deformities affecting the lower facial contour can have major consequences. Therefore, the reconstruction process should be highly considered to limit further repercussions and thus avoid concurrent impairments [ 4 ]. Reconstruction of such mandibulectomy defects continues to be extremely demanding and challenging for reconstructive surgeons intending both functional and aesthetic restoration with the least surgical morbidity [ 1 ]. Various options and modalities for reconstruction have been reported. Currently, the microvascular fibular flap has been established as the gold standard for optimal onco-mandibular defects reconstruction [ 5 ]. The main goals of mandibular reconstruction are to obtain a structural replacement with restoration of facial symmetry and functions. The face is an individual's interface with society, and the aesthetic result should be the best possible. Therefore, re-establishing the form of the lower third of the face is extremely important for facial aesthetics, as the mandible forms its’ bony foundation [ 6 – 9 ]. Before the advent of computer-assisted surgery (CAS), the traditional/conventional method was based on a freehand approach for segmental osteotomies. Conforming flap to defect was a complex and crucial task that involved a tedious learning curve, and results varied greatly between surgeons according to experience and technical skills. In recent years, Virtual surgical planning (VSP) including, Computer-Aided Design and Manufacturing (CAD-CAM), has significantly revolutionized and changed the way of bony reconstruction [ 10 , 11 ]. Aesthetic outcomes are one of the main goals of mandibular reconstruction. However, standard criteria for measuring these outcomes are currently insufficient [ 12 ]. Earlier forms of evaluation were based on pantomography to evaluate mandibular symmetry [ 5 , 13 , 14 ]. Current methods of evaluation are based on 3D imaging analysis. Nevertheless, standardization regarding the evaluation process is still a concern. In the literature, most studies have focused on the accuracy of the transfer from pre-operative planning to post-operative implementation, with few making a comparison between the VSP cases and a control group [ 11 ]. Furthermore, all of those comparative studies have used conventional technique as a control group or still consider accuracy rather than symmetry, thus aesthetics. There are currently no published randomized clinical studies that have compared the aesthetic outcome of the FFF using VSP with that of the MB technique. Therefore, the aim of this study was to evaluate and compare the aesthetic outcomes and surgical efficiency of mandibular reconstruction using FFF with CAD/CAM COG to that without COG (MB reconstruction) after mandibulectomy in patients with mandibular tumors. PATIENTS AND METHODS Study Setting This study was conducted in the National Cancer Institute (NCI) and Faculty of Dentistry, Cairo University, Egypt, from November 2018 to December 2021. A total of 22 patients with primary mandibular tumors and indicated for segmental resection were recruited for randomization, regardless of age, sex, and ethnicity. Patients with poor oncological prognosis, poor performance status, or those with relative or absolute vascular contraindications for FFF were excluded. Patients indicated for double free-flap reconstruction or those who just required marginal resection were also excluded from this study. Patients were evaluated preoperatively by clinical history, physical examination, CT scans for the craniofacial skeleton and lower extremities (bilateral fibula angiographic CT scan), and biopsy from the primary lesion. This study was approved by the Research Ethical Committee at the Faculty of Dentistry, Cairo University (identifier 24/12/18) and was conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from all patients. The trial was registered at ClinicalTrials.gov with identifier NCT03757273. Registration date: 28/11/2018. The 2010 CONSORT statement and guidelines for reporting parallel-group randomized trials were applied in the reporting of this study. Trial Design This was a prospective, randomized, parallel, controlled clinical study. The participants were screened by two investigators (M.E.A. and M.H.Z.). The randomization sequence was created on www.randomization.com with a 1:1 allocation using random block sizes of 2 and 4. Allocation concealment was implemented with sequentially numbered, opaque sealed envelopes (SNOSE). After preoperative evaluation, the envelope with the previously generated sequence was opened by a clinician not involved in the study, and the patient was randomly assigned to one of two groups, Group I comprised 11 patients whose mandibular reconstruction was performed using FFF with the COG technique (COG group). Group II comprised 11 patients whose mandibular reconstruction was performed using FFF with the MB technique (MB group). Treatment VSP and Design of Guiding Templates The acquired CT images with fin cuts (< 1 mm) in DICOM format were imported into the Synthes ProPlan CMF TM software, V. 3.0 (Materialise ® NV, Technologielaan 15, 3001 Leuven, Belgium. https://www.materialise.com/en/medical/software/proplan-cmf) to be processed and transformed for the creation of three-dimensional (3D) virtual models of the craniofacial skeleton and the bony fibula (Figure 1A). In the interactive surgical planning, the process of virtual mandibular resection and fibular osteotomies were clearly mapped, this was fulfilled via the designer-surgeon communication and work to confirm the osteotomy lines together. Virtual mandibulectomy was performed according to the pre-determined plan and mapped resection osteotomies that were planned in accordance with the principles of radical tumour resection and confirmed in the inter-team communication sessions (Figure 1B). Once the extent of the defect had been clearly defined, the virtual reconstruction phase had begun. For the study (COG) group, the 3D virtual models were clearly reviewed and used to map the segments’ size, number, and shape of fibular bone cuts. Next, the patient’s 3D-reconstructed fibula was precisely superimposed on the mandibular defect. Fibular osteotomies were then virtually validated to recreate and renovate the native mandibular contour through a trial-and-error process, which was accomplished if the outer contour of the mandible was preserved. Otherwise, if destroyed by the tumor, a mirroring based-image was used to form the ideal mandibular contour by replicating the corresponding contralateral anatomy (Figure 1C & D). After that, a 3D-model of the virtually reconstructed mandible with fibular bone was created for the COG group. While, for the MB group, just a mirroring-based 3D-model of the mandible was created with the resection margins marked over the model. The virtually approved resection/reconstruction data were accordingly used to design and fabricate surgical cutting/osteotomy guides for both planned tumour resection and fibular osteotomies (Figure 2A, B). Surgical Phase and post-operative data collection The surgical procedures were performed by two surgical teams working simultaneously, one in charge of cervicofacial resection and the other for harvesting the flap. The extent of surgery and thus the approach to access the resection block were determined based on each patient’s case specifications. After neck dissection (where indicated) and access to the mandible were obtained, the surgical field was exposed and the tumour was surgically approached and explored. The customized 3D mandibular guiding templates for tumor resection were then applied and secured by monocortical screws in the predesignated virtually planned position. The osteotomies to resect the tumor were adopted either using a surgical saw or by Lindemann bur. Following the complete tumor resection and ensuring that radicality obtained, the recipient’s surgical bed was clear and ready for reconstruction procedures. The vascularized FFF was concurrently prepared by the second surgical team in charge of flap harvesting. In all patients, the FFF harvests were performed using the lateral approach. The procedure for cutting, conformation, and fixation of the flap varies between the two groups. In the COG group, the fibula was fully prepared and contoured at the donor site prior to vascular pedicle clamping according to the pre-operative planning using the COG. Before the execution of fibular osteotomies, the osteotomy guiding templates were temporarily adapted on the fibula to validate and confirm its accurate position. Once the correct position and orientation of the guide were affirmed, it was then secured accurately to the fibula using monocortical screws. In-situ, fibular osteotomies were then executed using a Lindemann bur inserted through the cutting slots where deperiostation had been performed. On completion of the guided fibular osteotomies, the cutting guides were removed along with the fixation screws from the fibula. Proceeding in situ, the fibular segments were then aligned/reassembled together and secured to the pre-bent reconstruction plate that was moulded on the 3D prefabricated mandibular model. Thereafter, the neo-mandible construct was confirmed and kept ready for microvascular transfer to the defect (Figure 3). Once the recipient site had been ready, the vascular pedicle was detached. In the MB group, the same procedures for surgical resection and reconstruction were adopted, except that no customized cutting/osteotomy guides have been used neither for the mandibular resection nor for the fibula osteotomies. Only a 3D guiding template (model) for the mandible was virtually designed by mirroring the contralateral intact side and acquired to assist in plate conformation and accurate positioning. In this group, the fibula was fully prepared and contoured (construct) after the vascular pedicle had been detached. Once the FFF had been harvested, it was brought to the back table to perform the osteotomies without using osteotomy guides and depending on the surgeon’s experience and skills guided by the 3D-model of the mandible to confirm adequate contouring (Figure 4) . The flap construct was then transferred to the defect area, and reconstruction was achieved by securing the osseous construct with the plate to the native mandibular segments at its virtually pre-planned ideal position. Thereafter, the microvascular anastomoses were established. All patients in both groups received conventional free flap post-operative care and medications. During the routine follow-up visit in the 3 rd month after the operation, a CT scan was performed to obtain the post-operative data for evaluation. Outcomes The primary endpoint to be assessed was aesthetic outcome within 3 months of surgery. The post-operative aesthetic evaluation was performed objectively by the acquisition of a high-resolution craniofacial CT-scan to be used in outcome estimation by CDIA. The resultant measurements for each parameter were then rigorously calculated, summarized, and compared as a differential area (DAr) in square millimeters (sq. mm/mm 2 ) and as differential angles (DAn) in degrees. Differential area (DAr) measurements: The post-operative CT-scan images in the DICOM format were imported into Synthes ProPlan CMF TM software and processed for the production of 3D virtual models of the craniofacial skeleton. The contralateral native side of the mandible was simply mirrored and superimposed on the affected side with the transparency function applied. A digital (virtual) reference in form of a measured bar was then placed and endorsed for real-size transfer and calibration during DAr measurements in sq. mm. In the axial view, a virtual axial cut was made in the contralateral mandible that was superimposed on the reconstructed side in order to clearly identify and measure the contour differences at the level of the fibula (Figure 5 A- E) . The resultant mirrored-based superimpositions in both sagittal and axial planes, including the endorsed digital reference, were captured and saved as two-dimensional (2D) images. The obtained 2D-images were imported directly to ImageJ software V. 1.53k (Wayne Rasband and contributors, National Institutes of Health, USA). The DAr was then traced and delineated using the Polygon selection tool and analyzed using the measure function tool after calibration by set scale function based on the digital reference placed previously, this was easily accomplished when modulated in ROI Manager (Figure 6A, B) . Differential Angle (DAn) measurements: Angular measurements based on the 3D-CT imaging were used to evaluate the morphologic restoration and degrees of asymmetry after reconstruction. Morphometric comparisons were made between the affected and the contralateral side of the reconstructed mandible by calculating differences in angular parameters (Figure 7 A- C) . Results were recorded as DAn (mean difference) in degrees, which are important for the facial profile. The greater the difference, the greater the surgical impact on mandible morphology. Symmetry was also assessed by calculating the ratio of the reconstructed to the contralateral side for the different angles. The closer the ratio to 1, the better the symmetry or the less the surgical impact on symmetry. Subjective evaluation: All patients were independently assessed and screened clinically by two evaluators (the oncologic surgeon and maxillofacial professional). The esthetic outcome seen in the patients was then scored and indicated as a grade for each patient using a Visual Analogue Scale (VAS), which ranges from 0 to 10, where one near 0 represented a poor outcome and one near 10 represented an excellent esthetic outcome. Subjective aesthetic evaluation has been carried out also using patients’ perceptions of the aesthetic outcome measured as Patient’s satisfaction Score (PSS), in which the patients had expressed their attitude and degree of satisfaction or dissatisfaction . In order to assess the patient’s satisfaction, a standard size mirror (size A5) was given to the subjects for assessment. Then the patients were instructed to score or put a mark on the scale that best reflected their satisfaction with the aesthetic result. The scored results were expressed in numbers from zero (worst aesthetic) to 10 (best aesthetic). Operation time evaluation (secondary outcome) Regarding the surgical efficiency, total operation time and ischemia time were assessed as secondary endpoints. Total operation time was the duration from the moment of surgical incision to the end of wound closure, which included the time for tumor resection, flap harvesting, and reconstruction. Since our study included both benign and malignant tumor cases, the neck dissection time was not included in the total operative time. The ischemic time was the time between the flap’s pedicle detachment and re-anastomosis. The entire surgical procedure was timed and recorded as a final value on a timing sheet in minutes (min) and summarized as a mean. Statistical methods: Based on a previous study by Azuma et al. in 2014 [13], the clinical important difference in DAn between the two groups was expected to be 6̊, with a standard deviation (SD) of the control group was ±4.38̊. Considering a significance level of 5.0% and statistical power of 80.0%, 9 patients per group would be necessary (18 totals). Taking into account possible losses to follow-up, this number was increased to a sample size of 11 patients per group (22 totals, 20% more than the calculated) for losses compensation. The sample size was calculated using PS program. Data analysis was conducted using IBM SPSS advanced statistics, version 24 (SPSS Inc., Chicago, IL). Summary statistics were presented with either the mean ± standard deviation or the median (range) for numerical data and with counts and percentages for categorical data. Kolmogorov-Smirnov test and Shapiro-Wilk test were used to explore the data for normality. The Student’s t-test was used to compare the normally distributed numeric variables of aesthetic outcomes and operation times, while comparisons for non-normally distributed numerical variables were done by Mann-Whitney test. Comparisons between categorical variables were performed using the chi-square test. A P -value less than or equal to 0.05 ( P ≤ 0.05) was considered statistically significant. All tests were two-tailed. Results Patients’ clinicodemographic data Of 64 patients screened for eligibility, 42 were ineligible. Twenty-two patients were randomized in equal numbers to the two study groups ( n = 11 patients/group). Figure (8 ) shows the consort flow chart of the study. Comparison of the two groups yielded the following results Table (1) . The mean age in the COG group was 41 ± 18.5 years (range, 10- 63 years) versus 47.81± 13.6 years (range, 29- 63 years) in the MB group. Based on Brown’s classification of mandibular defects, in the COG group, 5 (45.4 %) patients had CL II, 2 (18.2 %) patients had CL IIc, 3 (27.3 %) patients had CL III, and 1 (9.1 %) had CL IV. While in the MB group, 5 (45.4 %) patients had CL II, 1 (9.1 %) patient had CL IIc, 2 (18.2 %) patients had CL III, 2 (18.2 %) patients had CL IV, and 1 (9.1 %) had CL IVc. The mean mandibular defects’ length was 8.5 ± 2.56 cm in the COG group versus 9.42 ± 4.65 cm in the MB group. Table (1) shows the clinicodemographic data and tumor characteristics of all patients. Table (1): Clinicodemographic characteristics of both groups of patients enrolled in this study Variable COG group (N= 11) MB group (N= 11) p- value Count % Count % Gender Male 7 63.60 6 54.50 Female 4 36.40 5 45.50 Age ( yr) (Mean ± SD) 41 ±18.54 47.81 ±13.75 .339 Indication / diagnosis Benign 3 27.30 3 27.30 Malignant 8 72.70 8 72.70 Site L t Mandible 7 63.60 6 54.50 R t Mandible 2 18.20 3 27.30 B i Mandible 2 18.20 2 18.20 Mandibular Defect Length (cm) (Mean ±SD) 8.50 ±2.56 9.42 ±4.65 .575 Classification II 5 45.40 5 45.40 IIc 2 18.20 1 09.10 III 3 27.30 2 18.20 IV 1 09.10 2 18.20 IVc 0 0.0 1 09.10 Flap harvest side L t leg 6 54.50 7 63.60 R t leg 5 45.50 4 36.40 Abbreviations: Bi, bilateral, CAD/CAM, CL, classification, COG, customized osteotomy guide, F, female, F. fibula flap, Lt, left, M, male, MB, model-based, N, number, Pt, patient, Rt, right, SD, standard deviation, Yr, year. Aesthetic Outcomes: Differential Area (DAr): Quantitively, the CDIA revealed that patients in the COG group showed improved aesthetic outcome (contour symmetry) regarding the sagittal DAr with a mean of (277.28 ± 127.05 mm 2 ) compared to (398.67 ± 139.10 mm 2 ) in the MB group. The difference in the sagittal DAr was statistically significant ( P = 0.045). Although the axial DAr was better in the COG group than in the MB group, there was no statistically significant difference between the two groups ( P = 0.206) Table (2) . Table (2): Comparison of differential area (Sagittal and Axial DAr, mean ± SD) according to group Differential area (DAr) COG group MB group P- value Mean (mm 2 ) ± SD Mean (mm 2 ) ± SD Sagittal DAr 277.28 ± 127.05 398.67 ± 139.10 0.045* Axial DAr 147.61 ± 55.42 183.68 ± 72.85 0.206 Abbreviations: COG, customized osteotomy guide, DAr , differential area, MB, model-based, mm 2 , square millimeter, SD, standard deviation, * Significant P-value. Differential Angle (DAn): The mean difference (Δ) and thus deviation for the sagittal and coronal DAn were significantly lower in the COG group than in the MB group (6.11 ± 3.46 and 1.77 ± 1.12° vs 9.53 ± 4.17 and 3.44 ± 2.34°, P < 0.05), respectively. While in the axial DAn, there was no statistically significant difference between the two groups ( P = 0.386). Although these results indicate that the mandibular contour symmetry was improved, and even that better symmetry results have been found regarding the sagittal, coronal, and axial mandibular angles in favor of the COG group. However, there were no statistically significant differences in the symmetry for sagittal, coronal, and axial angles between the two groups ( P > 0.05) Table (3) Table (3): Comparison of the mean difference (Sagittal, Coronal and Axial DAn) and symmetry according to group. Differential and symmetry angle (affected /contralateral side) COG group MB group P -value Mean (°) ± SD Mean (°) ± SD Sagittal DAn (Δ) 6.11 ± 3.46 9.53 ± 4.17 0.049* Symmetry angle 1.09 ± 0.13 1.15 ± 0.19 0.389 Coronal DAn (Δ) 1.77 ± 1.12 3.44 ± 2.34 0.046* Symmetry angle 1.00 ± 0.03 1.03 ± 0.05 0.083 Axial DAn (Δ) 2.60 ± 0.74 2.93 ± 0.97 0.386 Symmetry angle 1.05 ± 0.10 1.11 ± 0.09 0.185 Abbreviations: COG, customized osteotomy guide, DAn , differential angle, MB, model-based, Δ, mean difference, (°) , degrees, * Significant P -value. Subjective evaluation of aesthetic outcome by VAS and PSS: The mean assessment score of the aesthetic outcome in VAS was higher in the COG group than in the MB group (8.18 ± 0.75 vs 7.64 ± 0.84), respectively. However, there were no statistically significant differences between the two groups ( P = 0.12). On the other hand, the mean PSS was better in the COG group than in the MB group (8.14 ± 0.67 vs 7.45 ± 0.79), with statistically significant differences reflecting enhanced aesthetic outcome and better satisfaction ( P = 0.041) Table (4) . Table (4): Comparison of Visual analogue scale (VAS) and Patient’s satisfaction score (PSS) according to group Subjective evaluation COG group MB group P- value Mean (score 1- 10) ± SD Mean (score 1- 10) ± SD VAS 8.18 ± 0.75 7.64 ± 0.84 0.124 PSS 8.14 ± 0.67 7.45 ± 0.79 0.041* Abbreviations: COG, customized osteotomy guide, MB, model-based, PSS, patient satisfaction score, VAS, visual analogue scale. Secondary outcome (operation and ischemic time): In the COG group, the total operation time ranged from 467 to 645 minutes (562.91 ± 51.22 min, mean ± SD) compared to 571- 728 minutes (663.55 ± 53.43 min, mean ± SD) in the MB group, there were statistically significant differences between the two groups ( P = 0.0002). The mean ischemia time was 97.55 ± 16.80 minutes in the COG group, compared to 172.45 ± 21.87 minutes in the MB group. The difference in the ischemia time was statistically significant ( P = 0.000) Table (5) . Table (5): Comparison of total operation time and ischemia time according to group (in minutes) COG group MB group P- value Mean (min) ± SD Mean (min) ± SD Total operation time 562.91 ± 51.22 663.55 ± 53.43 0.0002* Ischemia time 97.55 ± 16.80 172.45 ± 21.87 0.0000* Abbreviations: COG, customized osteotomy guide, MB, model-based, Min, minutes. Discussion The mandible is an anatomically intricate structure, making ideal renovation and reconstruction extremely challenging. Suboptimal reconstruction may result in poor oral function as well as aesthetic deformities. Over the years, the microvascular fibular flap has been established as the workhorse for onco-mandibular reconstruction [5, 15]. However, the greatest challenge that remains is how to most accurately shape vascularized bone flaps so that facial symmetry, as well as function, are best restored and minimize the operative time of such complex surgeries [10]. Conventional techniques, either freehand or MB-approached, depend mainly on the surgeons’ experience and lack effective quantitative strategies [10, 16-19]. The advent of VSP, including CAD-CAM, has overcome the dilemma and changed the way of bony reconstruction in the past few years [5, 20, 21]. This randomized controlled trial aimed to evaluate and compare the aesthetic outcome and surgical efficiency of FFF with and without CAD/CAM COG for reconstruction of mandibular defects. In the present study, DAr in both sagittal and axial planes has been introduced as a new criterion for the evaluation of aesthetic outcome. DAn (Sagittal, Coronal, and Axial) has been a part of objective evaluation as well. On the other hand, a subjective dual assessment of the aesthetic outcome has been performed using VAS and PSS. These intended-to analysis parameters are particularly important for facial aesthetics because the maintenance of the mandibular-arch diameter and angles’ amplitude are fundamentally crucial to fully imitate the native mandible and achieve facial symmetry [22]. Our study shows a significant improvement in mandibular contour symmetry regarding the sagittal DAr and thus a better aesthetic outcome in the COG group compared to the MB reconstruction group ( P = 0.045). Likewise, the mean difference between the affected and the contralateral side and thus deviation was significantly lower in terms of the sagittal and coronal mandibular angle (DAn) in the COG group compared to the MB group ( P < 0.05), suggesting better overall symmetry and, notably, enhanced condyle sitting using cutting guides. These findings are all the more interesting for the current practice and imperatively adherent to the crucial goal of reconstruction. Earlier forms of evaluation were based on pantomography to evaluate mandibular symmetry [5, 13, 14]. Although image standardization was performed according to the authors. However, concerns regarding under- or over-estimation are unfortunately still present, possibly because the radiograph is a uni-directional image. Current methods of evaluation are based on 3D-imaging analysis. Nevertheless, standardization regarding the evaluation process is still a concern. In this study, standardization of the evaluation process was addressed and seems to be mostly in line with the Jove-published protocol by van Baar et al. [23] in terms of imaging, machine and setting parameters, defects classification, using image-based 3D medical software, natural head position, and axis orientation. However, some steps were not exactly adherent to the Jove- published protocol, as our evaluation is based mainly on comparing the reconstructed mandible to the contralateral native mandible postoperatively. Thus far, few data have been reported concerning the reconstruction quality in terms of restoration of the native morphology and preserving symmetry. Almost all studies have compared the reconstructed mandible to virtual planning rather than to the contralateral native mandible, which could overestimate the undoubted benefits of virtual planning [11]. In this study, morphological evaluation was achieved by comparing the superimposed virtual images of the reconstructed side to the contralateral native side of the mandible using 3D-CDIA on a post-operative CT-scan for the selected parameters. Given that symmetry and thus aesthetics is the imperative goal rather than accuracy, that has been vastly reported. Results, either in the form of a mean difference or symmetry ratio, can indicate and estimate the aesthetic outcome. In the relevant literature, several studies have addressed the valuable use of VSP for mandibular reconstruction. Weitz et al. [5] found significantly smaller differences between the pre- and post-operative angle of the mandible in the virtual group compared to conventionally treated cases, 4.5° versus 11.5°, which is a measure that strongly influences the aesthetic outcomes and consistent proportions of the lower third of the face. Similar to Jacek and Azuma [13, 14] , Weitz et al. used pantomographic analysis, and hence only used one angle to compare results. Zhang et al. [24] when studying outcomes between computer-aided group vs freehand reconstruction, compared the VSP to the post-operative mandible alone. Even though their results show improved angle deviation in favor of the CAD group, the impact on aesthetic estimation may be limited since post-operative comparison with the contralateral native mandible was not done. Ren et al. [10] mentioned that the mean differences between the pre-operative and post-operative gonial angles were significantly smaller in the computer-assisted group compared with the conventional group ( P = 0.007). Similarly, Yu et al. [25] found that the variation between the reconstructed and contralateral mandibular angles was significantly different, favoring CAD-based over the conventional group ( P = 0.001). Similar to the present study, Bartier et al. [11] in a retrospective study provided interesting results in favor of cutting guides. The mean difference between pre- and post-operative values of the coronal mandibular angles was significantly lower in the virtual planning group than in the traditional freehand group. Likewise, he found equivalent results in both techniques regarding post-operative symmetry for the coronal and axial mandibular angles but was significantly better regarding the sagittal angle in the 3D group. In general, the results of the present study are mostly in line with those of the Bartier study. Variations could be attributed to that conventional technique was used as a comparative control group in the Bartier study versus a 3D MB group in the present study, which could minimize the difference. However, it is difficult to directly compare the results of the present study with the aforementioned studies as all were compared to conventional reconstruction as a control, and most were performed retrospectively with the variations in the methodologies and parameters included in the evaluation, and thus potentially underrepresents the actual relevancy to the current imperative goals. Additionally, there is either a lack or an unclarified method for standardization in most of the studies. De Maesschalck et al. [26] found equivalent results in both techniques regarding the mean difference and post-operative mandible symmetry in terms of sagittal and axial angles between the groups. Similarly, Stirling Craig et al. [27] found similar results in both techniques regarding post-operative body-symphyseal angle on axial view and thus mandible symmetry. Generally, the findings of these studies are contradictory to the present study and other reports regarding the efficiency of VSP, particularly cutting guides in improving aesthetic outcomes. In terms of subjective aesthetic assessment (SAA), findings of the present study have shown comparable results in both groups regarding VAS scores (8.18 versus 7.64), respectively. However, the PSS was significantly better scored (8.14) in the COG group compared to (7.45) in the MB group. In contrast to the present study, Bouchet et al. [28] reported that aesthetic satisfaction by PSS was higher in the conventional group (a score of ≥7 was reported by 85% (11/13) patients in the conventional group vs. 58% (7/12) patients in the CAD/CAM group. Given that satisfaction with the aesthetic result is vastly subjective and strictly related to patients’ expectations, the results can surprisingly vary. Regarding surgical efficiency, Chang et al. [29] found that VSP significantly decreased operation and ischemia times compared to the MB group. Much the same findings have been presented by Toto et al., in 2015 [30]. This was also observed in several other studies that compared VSP with conventional technique [1, 10, 24, 31, 32]. The present study showed that the mean total operation time and ischemia time were significantly shorter in the COG group compared to the MB group, which is consistent with those studies. In contrast to the present study, Yu et al. [25] and Bartier et al. [11], even though they used conventional technique as a control, they found that the mean operative time did not significantly differ between the groups, which is contradictory to our findings. This could be because of many parameters either directly related or unrelated to the use of cutting guides and their impact on surgery time. Although the surgical efficiency of VSP has been vastly investigated. However, our results have resolved the conflict that resurfaced in some reports. To the best of our knowledge, this study is the first randomized controlled clinical trial (RCT) investigating the aesthetic outcomes of FFF for reconstruction of the onco-mandibular defects by using the VSP and cutting guides versus that of Model-based reconstruction. Conclusion The results of the present study indicated that the CAD/CAM with COG enhanced the aesthetic outcome in patients undergoing mandibular reconstruction using FFF compared to that without COG (MB reconstruction). It also has been shown to significantly enhance the surgical efficiency by minimizing total operative time and ischemia time. The limitation of this study is the relatively small sample size and the need to use a second-party software for DAr evaluation. Our measurements considered underlying hard bony tissue, further studies are required to analyze their impact on overlying structures. Abbreviations CAD/CAM: Computer-aided design and Computer-aided manufacturing, CAS: Computer-assisted surgery, CDIA: Computerized Digital Imaging Analysis, COG: Customized osteotomy guide, CT: Computed tomography, DAr: Differential area, DAn: Differential angle, DICOM: Digital Imaging and Communications in Medicine, FFF: Free fibular flap, MB: Model based, NCI: National Cancer Institute, Min: Minutes, PSS: Patient’s Satisfaction Score, SAA: Subjective aesthetic assessment, SNOSE: Sequentially numbered, opaque sealed envelopes, Sq. mm/mm 2 : Square millimeters, VAS: visual analogue scale, VSP: Virtual surgical planning, Vs: Versus, 3D: Three-dimensional, Δ: Mean difference, °: Degree. Declarations Ethical approval and consent to participate Ethical review and approval for This study was committed by the Research Ethics Committee of the Faculty of Dentistry, Cairo University (identifier 24/12/18). The patients/participants provided their written informed consent to participate in this study and for any potentially identifiable images or data included in this article. Consent for publication Not applicable Data Availability Statement The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study is totally self-funded and wasn’t supported by any grants. Authors’ contributions Conception: M.E.A., M.I.S., and A.A.A. Design of the work: M.E.A., B.G.M., and M.I.S. Virtual planning and surgical work: M.E.A. and M.H.Z. Data collection, Assembly and Formal analysis: M.E.A., M.I.S., and O.M.J. Supervision and Visualization: M.I.S., M.H.Z., and A.A.A. Drafted the manuscript and Data curation: M.E.A. Critical revision of the manuscript: M.E.A., O.M.J., and M.H.Z. Final approval: All authors. Acknowledgments Our acknowledgment extends to all staff members of the Head and Neck Unit at NCI, and Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Cairo University for their cooperation in completing this study and their provision of equipment and services. Our acknowledgment also extends to Dr. Mohamed Ghorab, Assistant lecturer of Oral and Maxillofacial Surgery, Cairo University for his valuable aid in the CAD/CAM workflow. References Succo G, Berrone M, Battiston B, Tos P, Goia F, Appendino P, et al. Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning. Eur Arch Otorhinolaryngol. 2015,272(6):1491-501. Lonie S, Herle P, Paddle A, Pradhan N, Birch T, Shayan R. Mandibular reconstruction: meta-analysis of iliac- versus fibula-free flaps. ANZ J Surg. 2016,86(5):337-42. Hoffmann J, Horn D. 34 - Reconstruction of the Mandible. In: Brennan PA, Schliephake H, Ghali GE, Cascarini L, editors. Maxillofacial Surgery (Third Edition): Churchill Livingstone, 2017. p. 497-506. Batstone MD. Reconstruction of major defects of the jaws. Aust Dent J. 2018,63 Suppl 1:S108-s13. Weitz J, Bauer FJ, Hapfelmeier A, Rohleder NH, Wolff KD, Kesting MR. Accuracy of mandibular reconstruction by three-dimensional guided vascularised fibular free flap after segmental mandibulectomy. Br J Oral Maxillofac Surg. 2016,54(5):506-10. Bak M, Jacobson AS, Buchbinder D, Urken ML. Contemporary reconstruction of the mandible. Oral Oncol. 2010,46(2):71-6. Pai D, Wodeyar A. Evolution of Mandibular Defects Reconstruction Procedures: From Older Principles to Newer Techniques and Technology. Acta Scientific Dental Sciences. 2019,3(5):08-18. Paré A, Bossard A, Laure B, Weiss P, Gauthier O, Corre P. Reconstruction of segmental mandibular defects: Current procedures and perspectives. Laryngoscope Investig Otolaryngol. 2019,4(6):587-96. Ali MN, Anwar RB, Banik R, Hasan S, Arefin MRU, Uddin MW. Mandibular reconstruction: a review. Update Dent Coll J 2019,9(2):50-4. Ren W, Gao L, Li S, Chen C, Li F, Wang Q, et al. Virtual Planning and 3D printing modeling for mandibular reconstruction with fibula free flap. Med Oral Patol Oral Cir Bucal. 2018,23(3):e359-e66. Bartier S, Mazzaschi O, Benichou L, Sauvaget E. Computer-assisted versus traditional technique in fibular free-flap mandibular reconstruction: A CT symmetry study. Eur Ann Otorhinolaryngol Head Neck Dis. 2021,138(1):23-7. Ueda N, Imai Y, Yamakawa N, Yagyuu T, Tamaki S, Nakashima C, et al. Assessment of facial symmetry by three-dimensional stereophotogrammetry after mandibular reconstruction: A comparison with subjective assessment. J Stomatol Oral Maxillofac Surg. 2021,122(1):56-61. Azuma M, Yanagawa T, Ishibashi-Kanno N, Uchida F, Ito T, Yamagata K, et al. Mandibular reconstruction using plates prebent to fit rapid prototyping 3-dimensional printing models ameliorates contour deformity. Head Face Med. 2014,10:45. Jacek B, Maciej P, Tomasz P, Agata B, Wiesław K, Radosław W, et al. 3D printed models in mandibular reconstruction with bony free flaps. J Mater Sci Mater Med. 2018,29(3):23. Patel A, Harrison P, Cheng A, Bray B, Bell RB. Fibular Reconstruction of the Maxilla and Mandible with Immediate Implant-Supported Prosthetic Rehabilitation: Jaw in a Day. Oral Maxillofac Surg Clin North Am. 2019,31(3):369-86. Wang YY, Zhang HQ, Fan S, Zhang DM, Huang ZQ, Chen WL, et al. Mandibular reconstruction with the vascularized fibula flap: comparison of virtual planning surgery and conventional surgery. Int J Oral Maxillofac Surg. 2016,45(11):1400-5. Han HH, Kim HY, Lee JY. The Pros and Cons of Computer-Aided Surgery for Segmental Mandibular Reconstruction after Oncological Surgery. Arch Craniofac Surg. 2017,18(3):149-54. Monsalve-Iglesias F, Rico ÁM-S, Fraile-Ruiz L. Virtual surgical planning in fibula flap mandibular reconstruction. Front Oral Maxillofac Med. 2020,2(12):1-8. Zavattero E, Bolzoni A, Dell'Aversana G, Santagata M, Massarelli O, Ferri A, et al. Accuracy of Fibula Reconstruction Using Patient-Specific Cad/Cam Plates: A Multicenter Study on 47 Patients. Laryngoscope. 2021,131(7):E2169-e75. Foley BD, Thayer WP, Honeybrook A, McKenna S, Press S. Mandibular reconstruction using computer-aided design and computer-aided manufacturing: an analysis of surgical results. J Oral Maxillofac Surg. 2013,71(2):e111-9. Oh JH. Recent advances in the reconstruction of cranio-maxillofacial defects using computer-aided design/computer-aided manufacturing. Maxillofac Plast Reconstr Surg. 2018,40(1):2. Tarsitano A, Ciocca L, Scotti R, Marchetti C. Morphological results of customized microvascular mandibular reconstruction: A comparative study. J Craniomaxillofac Surg. 2016,44(6):697-702. van Baar GJC, Liberton NPTJ, Winters HAH, Leeuwrik L, Forouzanfar T, Leusink FKJ. A Postoperative Evaluation Guideline for Computer-Assisted Reconstruction of the Mandible. J Vis Exp. 2020(155):e60363. Zhang L, Liu Z, Li B, Yu H, Shen SG, Wang X. Evaluation of computer-assisted mandibular reconstruction with vascularized fibular flap compared to conventional surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016,121(2):139-48. Yu Y, Zhang WB, Liu XJ, Guo CB, Yu GY, Peng X. Three-Dimensional Accuracy of Virtual Planning and Surgical Navigation for Mandibular Reconstruction With Free Fibula Flap. J Oral Maxillofac Surg. 2016,74(7):1503 e1- e10. De Maesschalck T, Courvoisier DS, Scolozzi P. Computer-assisted versus traditional freehand technique in fibular free flap mandibular reconstruction: a morphological comparative study. Eur Arch Otorhinolaryngol. 2017,274(1):517-26. Stirling Craig E, Yuhasz M, Shah A, Blumberg J, Salomon J, Lowlicht R, et al. Simulated surgery and cutting guides enhance spatial positioning in free fibular mandibular reconstruction. Microsurgery. 2015,35(1):29-33. Bouchet B, Raoul G, Julieron B, Wojcik T. Functional and morphologic outcomes of CAD/CAM-assisted versus conventional microvascular fibular free flap reconstruction of the mandible: A retrospective study of 25 cases. J Stomatol Oral Maxillofac Surg. 2018,119(6):455-60. Chang EI, Jenkins MP, Patel SA, Topham NS. Long-Term Operative Outcomes of Preoperative Computed Tomography-Guided Virtual Surgical Planning for Osteocutaneous Free Flap Mandible Reconstruction. Plast Reconstr Surg. 2016,137(2):619-23. Toto JM, Chang EI, Agag R, Devarajan K, Patel SA, Topham NS. Improved operative efficiency of free fibula flap mandible reconstruction with patient-specific, computer-guided preoperative planning. Head Neck. 2015,37(11):1660-4. Avraham T, Franco P, Brecht LE, Ceradini DJ, Saadeh PB, Hirsch DL, et al. Functional outcomes of virtually planned free fibula flap reconstruction of the mandible. Plast Reconstr Surg. 2014,134(4):628e-34e. Bao T, He J, Yu C, Zhao W, Lin Y, Wang H, et al. Utilization of a pre-bent plate-positioning surgical guide system in precise mandibular reconstruction with a free fibula flap. Oral Oncol. 2017,75:133-9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 13 Oct, 2022 Reviews received at journal 12 Oct, 2022 Reviewers agreed at journal 28 Sep, 2022 Reviewers agreed at journal 18 Sep, 2022 Reviewers invited by journal 15 Sep, 2022 Editor assigned by journal 15 Sep, 2022 Editor invited by journal 15 Sep, 2022 Submission checks completed at journal 15 Sep, 2022 First submitted to journal 28 Aug, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2007675","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":136900647,"identity":"be733c27-0cc6-44e5-b283-22139789e140","order_by":0,"name":"Mohammed Esmail 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University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ayman","middleName":"Abdel-Wahab","lastName":"Amin","suffix":""},{"id":136900652,"identity":"1b3f6795-ef63-40df-8245-bea7653d6f8c","order_by":5,"name":"Mohamed Hamdallah Zedan","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Hamdallah","lastName":"Zedan","suffix":""}],"badges":[],"createdAt":"2022-08-28 21:29:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-2007675/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-2007675/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":26853264,"identity":"3e6f9a8f-785c-4fb8-8c5b-a05003fd26aa","added_by":"auto","created_at":"2022-09-22 21:58:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":456592,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e 3D virtual models of the craniofacial skeleton, \u003cstrong\u003e(B)\u003c/strong\u003e Virtual planned mandibular resection in frontal views, \u003cstrong\u003e(C)\u003c/strong\u003e 3D virtual models of the bony fibula and mandible with planned fibular osteotomies, \u003cstrong\u003e(D)\u003c/strong\u003e 3D reconstructed fibula was superimposed on the mandibular defect in lateral view.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/33c738ddd4b17bd8bb65a02c.png"},{"id":26853265,"identity":"80c53100-bd7d-4c5c-8576-5dd4c68d875d","added_by":"auto","created_at":"2022-09-22 21:58:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":529928,"visible":true,"origin":"","legend":"\u003cp\u003e(A) 3D designs of mandibular and fibular cutting guides, (B) Virtual reconstructed mandibular models.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/d96eff4cd1836c78bc99777f.png"},{"id":26853126,"identity":"1b9fd5bf-3670-4cad-937e-dba6b91d8dd0","added_by":"auto","created_at":"2022-09-22 21:53:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1073708,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Cutting guides and Model of the reconstructed mandible for another case\u003cstrong\u003e, (B) \u003c/strong\u003eCutting guide was fixed on the fibula\u003cstrong\u003e, (C) \u003c/strong\u003eOsteotomies performed and fibular segments assembled into the neomandible before clamping the pedicle.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/24b2daba0661e350fb3412a7.png"},{"id":26853128,"identity":"a2a459b6-62b0-46f9-a74c-59c89bd97222","added_by":"auto","created_at":"2022-09-22 21:53:34","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":864328,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Harvested fibula,\u003cstrong\u003e \u003c/strong\u003eblue arrow showed the FFF Pedicle detached, \u003cstrong\u003e(B)\u003c/strong\u003e 3D mandibular model, and \u003cstrong\u003e(C)\u003c/strong\u003e The fibular construct prepared on the back table.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/54a1546686f1189610d145cc.png"},{"id":26853123,"identity":"8c671ef6-69f0-46bc-b74a-db91c6d06820","added_by":"auto","created_at":"2022-09-22 21:53:34","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":447575,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Post-operative 3D virtual models of the maxillofacial skeleton, (B) The contralateral side of the mandible was simply mirrored and superimposed on affected side with transparency function applied, (C)Lateral view, (D) Virtual osteotomy in axial plane to reveal axial DAr, (E) Axial view.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/8f9637edf70fec2cbd6c0f68.png"},{"id":26853267,"identity":"2cf8a9d5-0ac6-4d1f-8d2e-18cd64c89801","added_by":"auto","created_at":"2022-09-22 21:58:34","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":321981,"visible":true,"origin":"","legend":"\u003cp\u003eDifferential area measurements performed using ImageJ software in both (A) Sagittal, and (B) Axial view.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/b206742b59774083694a0ccf.png"},{"id":26853333,"identity":"b87e374c-537b-4db5-a393-dd3181266f9d","added_by":"auto","created_at":"2022-09-22 22:03:34","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":570802,"visible":true,"origin":"","legend":"\u003cp\u003eDifferential Angles measurements performed using ProPlan CMF software for (A) Sagittal, (B) Coronal, and (C) Axial angles. NOTE: Sagittal angle is formed by the plane passing through the gonion (Go) and parasymphysis (ParaSym) and the plane passing through the Go and condylion (Co)\u003cstrong\u003e,\u003c/strong\u003eCoronal angle is formed by the line passing through the two condyles parallel to Frankfort horizontal plan and the ascending ramus\u003cstrong\u003e,\u003c/strong\u003e Axial angle is formed by the plane passing through the Go and ParaSym and the midsagittal plane.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/0df4717c46f94682cacdcc12.png"},{"id":26853124,"identity":"847ca7c7-877d-47e8-8f05-47c53876e865","added_by":"auto","created_at":"2022-09-22 21:53:34","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":150023,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram showing phases of the RCT.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/f156a430a7d81f42c6d6a846.png"},{"id":26853334,"identity":"6e27b5eb-bc52-44c3-a346-68f461d91665","added_by":"auto","created_at":"2022-09-22 22:03:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3696924,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-2007675/v1/5868690c-afe3-4bbc-b323-25cc4c344c2c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial","fulltext":[{"header":"Background","content":"\u003cp\u003eMaxillofacial defects resulting from surgical resection of neoplasms can be associated with devastating functional and aesthetic deficits. Taking into consideration the mandible's importance as a major determinant in facial aesthetics and function; disruption of mandibular integrity following onco-surgical resection can create extensive composite defects, leading to functional and aesthetic impairments [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFacial deformities affecting the lower facial contour can have major consequences. Therefore, the reconstruction process should be highly considered to limit further repercussions and thus avoid concurrent impairments [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Reconstruction of such mandibulectomy defects continues to be extremely demanding and challenging for reconstructive surgeons intending both functional and aesthetic restoration with the least surgical morbidity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVarious options and modalities for reconstruction have been reported. Currently, the microvascular fibular flap has been established as the gold standard for optimal onco-mandibular defects reconstruction [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The main goals of mandibular reconstruction are to obtain a structural replacement with restoration of facial symmetry and functions. The face is an individual's interface with society, and the aesthetic result should be the best possible. Therefore, re-establishing the form of the lower third of the face is extremely important for facial aesthetics, as the mandible forms its\u0026rsquo; bony foundation [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Before the advent of computer-assisted surgery (CAS), the traditional/conventional method was based on a freehand approach for segmental osteotomies. Conforming flap to defect was a complex and crucial task that involved a tedious learning curve, and results varied greatly between surgeons according to experience and technical skills. In recent years, Virtual surgical planning (VSP) including, Computer-Aided Design and Manufacturing (CAD-CAM), has significantly revolutionized and changed the way of bony reconstruction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAesthetic outcomes are one of the main goals of mandibular reconstruction. However, standard criteria for measuring these outcomes are currently insufficient [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Earlier forms of evaluation were based on pantomography to evaluate mandibular symmetry [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Current methods of evaluation are based on 3D imaging analysis. Nevertheless, standardization regarding the evaluation process is still a concern. In the literature, most studies have focused on the accuracy of the transfer from pre-operative planning to post-operative implementation, with few making a comparison between the VSP cases and a control group [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFurthermore, all of those comparative studies have used conventional technique as a control group or still consider accuracy rather than symmetry, thus aesthetics. There are currently no published randomized clinical studies that have compared the aesthetic outcome of the FFF using VSP with that of the MB technique. Therefore, the aim of this study was to evaluate and compare the aesthetic outcomes and surgical efficiency of mandibular reconstruction using FFF with CAD/CAM COG to that without COG (MB reconstruction) after mandibulectomy in patients with mandibular tumors.\u003c/p\u003e "},{"header":"PATIENTS AND METHODS","content":"\u003ch2\u003eStudy Setting \u003c/h2\u003e\n\u003cp\u003eThis study was conducted in the National Cancer Institute (NCI) and Faculty of Dentistry, Cairo University, Egypt, from November 2018 to December 2021. A total of 22 patients with primary mandibular tumors and indicated for segmental resection were recruited for randomization, regardless of age, sex, and ethnicity. Patients with poor oncological prognosis, poor performance status, or those with relative or absolute vascular contraindications for FFF were excluded. Patients indicated for double free-flap reconstruction or those who just required marginal resection were also excluded from this study. Patients were evaluated preoperatively by clinical history, physical examination, CT scans for the craniofacial skeleton and lower extremities (bilateral fibula angiographic CT scan), and biopsy from the primary lesion. This study was approved by the Research Ethical Committee at the Faculty of Dentistry, Cairo University (identifier 24/12/18) and was conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from all patients. The trial was registered at ClinicalTrials.gov with identifier NCT03757273. Registration date: 28/11/2018. The 2010 CONSORT statement and guidelines for reporting parallel-group randomized trials were applied in the reporting of this study.\u003c/p\u003e\n\n\u003ch2\u003eTrial Design\u003c/h2\u003e\n\u003cp\u003eThis was a prospective, randomized, parallel, controlled clinical study. The participants were screened by two investigators (M.E.A. and M.H.Z.). The randomization sequence was created on www.randomization.com with a 1:1 allocation using random block sizes of 2 and 4. Allocation concealment was implemented with sequentially numbered, opaque sealed envelopes (SNOSE). After preoperative evaluation, the envelope with the previously generated sequence was opened by a clinician not involved in the study, and the patient was randomly assigned to one of two groups, Group I comprised 11 patients whose mandibular reconstruction was performed using FFF with the COG technique (COG group). Group II comprised 11 patients whose mandibular reconstruction was performed using FFF with the MB technique (MB group). \u003c/p\u003e\n\n\u003ch2\u003eTreatment\u003c/h2\u003e\n\u003ch2\u003eVSP and Design of Guiding Templates\u003c/h2\u003e\n\u003cp\u003eThe acquired CT images with fin cuts (\u0026lt; 1 mm) in DICOM format were imported into the Synthes ProPlan CMF\u003csup\u003eTM\u003c/sup\u003e software, V. 3.0 (Materialise\u003csup\u003e\u0026reg;\u003c/sup\u003e NV, Technologielaan 15, 3001 Leuven, Belgium. https://www.materialise.com/en/medical/software/proplan-cmf) to be processed and transformed for the creation of three-dimensional (3D) virtual models of the craniofacial skeleton and the bony fibula (Figure 1A). In the interactive surgical planning, the process of virtual mandibular resection and fibular osteotomies were clearly mapped, this was fulfilled via the designer-surgeon communication and work to confirm the osteotomy lines together.\u003c/p\u003e\n\u003cp\u003eVirtual mandibulectomy was performed according to the pre-determined plan and mapped resection osteotomies that were planned in accordance with the principles of radical tumour resection and confirmed in the inter-team communication sessions (Figure 1B). Once the extent of the defect had been clearly defined, the virtual reconstruction phase had begun. For the study (COG) group, the 3D virtual models were clearly reviewed and used to map the segments\u0026rsquo; size, number, and shape of fibular bone cuts. Next, the patient\u0026rsquo;s 3D-reconstructed fibula was precisely superimposed on the mandibular defect. Fibular osteotomies were then virtually validated to recreate and renovate the native mandibular contour through a trial-and-error process, which was accomplished if the outer contour of the mandible was preserved. Otherwise, if destroyed by the tumor, a mirroring based-image was used to form the ideal mandibular contour by replicating the corresponding contralateral anatomy (Figure 1C \u0026amp; D). After that, a 3D-model of the virtually reconstructed mandible with fibular bone was created for the COG group. While, for the MB group, just a mirroring-based 3D-model of the mandible was created with the resection margins marked over the model. The virtually approved resection/reconstruction data were accordingly used to design and fabricate surgical cutting/osteotomy guides for both planned tumour resection and fibular osteotomies (Figure 2A, B). \u003c/p\u003e\n\n\u003ch2\u003eSurgical Phase and post-operative data collection\u003c/h2\u003e\n\u003cp\u003eThe surgical procedures were performed by two surgical teams working simultaneously, one in charge of cervicofacial resection and the other for harvesting the flap. The extent of surgery and thus the approach to access the resection block were determined based on each patient\u0026rsquo;s case specifications. After neck dissection (where indicated) and access to the mandible were obtained, the surgical field was exposed and the tumour was surgically approached and explored. The customized 3D mandibular guiding templates for tumor resection were then applied and secured by monocortical screws in the predesignated virtually planned position. The osteotomies to resect the tumor were adopted either using a surgical saw or by Lindemann bur. Following the complete tumor resection and ensuring that radicality obtained, the recipient\u0026rsquo;s surgical bed was clear and ready for reconstruction procedures. The vascularized FFF was concurrently prepared by the second surgical team in charge of flap harvesting. In all patients, the FFF harvests were performed using the lateral approach. The procedure for cutting, conformation, and fixation of the flap varies between the two groups. In the COG group, the fibula was fully prepared and contoured at the donor site prior to vascular pedicle clamping according to the pre-operative planning using the COG. Before the execution of fibular osteotomies, the osteotomy guiding templates were temporarily adapted on the fibula to validate and confirm its accurate position. Once the correct position and orientation of the guide were affirmed, it was then secured accurately to the fibula using monocortical screws. In-situ, fibular osteotomies were then executed using a Lindemann bur inserted through the cutting slots where deperiostation had been performed. On completion of the guided fibular osteotomies, the cutting guides were removed along with the fixation screws from the fibula. Proceeding in situ, the fibular segments were then aligned/reassembled together and secured to the pre-bent reconstruction plate that was moulded on the 3D prefabricated mandibular model. Thereafter, the neo-mandible construct was confirmed and kept ready for microvascular transfer to the defect (Figure 3). Once the recipient site had been ready, the vascular pedicle was detached.\u003c/p\u003e\n\u003cp\u003eIn the MB group, the same procedures for surgical resection and reconstruction were adopted, except that no customized cutting/osteotomy guides have been used neither for the mandibular resection nor for the fibula osteotomies. Only a 3D guiding template (model) for the mandible was virtually designed by mirroring the contralateral intact side and acquired to assist in plate conformation and accurate positioning. In this group, the fibula was fully prepared and contoured (construct) after the vascular pedicle had been detached. Once the FFF had been harvested, it was brought to the back table to perform the osteotomies without using osteotomy guides and depending on the surgeon\u0026rsquo;s experience and skills guided by the 3D-model of the mandible to confirm adequate contouring \u003cstrong\u003e(Figure 4)\u003c/strong\u003e. \u003c/p\u003e\n\u003cp\u003eThe flap construct was then transferred to the defect area, and reconstruction was achieved by securing the osseous construct with the plate to the native mandibular segments at its virtually pre-planned ideal position. Thereafter, the microvascular anastomoses were established. All patients in both groups received conventional free flap post-operative care and medications. During the routine follow-up visit in the 3\u003csup\u003erd\u003c/sup\u003e month after the operation, a CT scan was performed to obtain the post-operative data for evaluation.\u003c/p\u003e\n\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003cp\u003eThe primary endpoint to be assessed was aesthetic outcome within 3 months of surgery. The post-operative aesthetic evaluation was performed objectively by the acquisition of a high-resolution craniofacial CT-scan to be used in outcome estimation by CDIA. The resultant measurements for each parameter were then rigorously calculated, summarized, and compared as a differential area (DAr) in square millimeters (sq. mm/mm\u003csup\u003e2\u003c/sup\u003e) and as differential angles (DAn) in degrees. \u003c/p\u003e\n\n\u003ch2\u003eDifferential area (DAr) measurements:\u003c/h2\u003e\n\u003cp\u003eThe post-operative CT-scan images in the DICOM format were imported into Synthes ProPlan CMF\u003csup\u003eTM\u003c/sup\u003e software and processed for the production of 3D virtual models of the craniofacial skeleton. The contralateral native side of the mandible was simply mirrored and superimposed on the affected side with the transparency function applied. A digital (virtual) reference in form of a measured bar was then placed and endorsed for real-size transfer and calibration during DAr measurements in sq. mm. In the axial view, a virtual axial cut was made in the contralateral mandible that was superimposed on the reconstructed side in order to clearly identify and measure the contour differences at the level of the fibula \u003cstrong\u003e(Figure 5 A- E)\u003c/strong\u003e. The resultant mirrored-based superimpositions in both sagittal and axial planes, including the endorsed digital reference, were captured and saved as two-dimensional (2D) images.\u003c/p\u003e\n\u003cp\u003eThe obtained 2D-images were imported directly to ImageJ software V. 1.53k (Wayne Rasband and contributors, National Institutes of Health, USA). The DAr was then traced and delineated using the Polygon selection tool and analyzed using the measure function tool after calibration by set scale function based on the digital reference placed previously, this was easily accomplished when modulated in ROI Manager \u003cstrong\u003e(Figure 6A, B)\u003c/strong\u003e. \u003c/p\u003e\n\u003ch3\u003eDifferential Angle (DAn) measurements:\u003c/h3\u003e\n\u003cp\u003eAngular measurements based on the 3D-CT imaging were used to evaluate the morphologic restoration and degrees of asymmetry after reconstruction. Morphometric comparisons were made between the affected and the contralateral side of the reconstructed mandible by calculating differences in angular parameters \u003cstrong\u003e(Figure 7 A- C)\u003c/strong\u003e. Results were recorded as DAn (mean difference) in degrees, which are important for the facial profile. The greater the difference, the greater the surgical impact on mandible morphology. Symmetry was also assessed by calculating the ratio of the reconstructed to the contralateral side for the different angles. The closer the ratio to 1, the better the symmetry or the less the surgical impact on symmetry.\u003c/p\u003e\n\n\u003ch3\u003eSubjective evaluation:\u003c/h3\u003e\n\u003cp\u003eAll patients were independently assessed and screened clinically by two evaluators (the oncologic surgeon and maxillofacial professional). The esthetic outcome seen in the patients was then scored and indicated as a grade for each patient using a Visual Analogue Scale (VAS), which ranges from 0 to 10, where one near 0 represented a poor outcome and one near 10 represented an excellent esthetic outcome. \u003c/p\u003e\n\u003cp\u003eSubjective aesthetic evaluation has been carried out also using patients\u0026rsquo; perceptions of the aesthetic outcome measured as Patient\u0026rsquo;s satisfaction Score (PSS), in which the patients had expressed their attitude and degree of satisfaction or dissatisfaction\u003cstrong\u003e. \u003c/strong\u003eIn order to assess the patient\u0026rsquo;s satisfaction, a standard size mirror (size A5) was given to the subjects for assessment. Then the patients were instructed to score or put a mark on the scale that best reflected their satisfaction with the aesthetic result. The scored results were expressed in numbers from zero (worst aesthetic) to 10 (best aesthetic).\u003c/p\u003e\n\n\u003ch2\u003eOperation time evaluation (secondary outcome)\u003c/h2\u003e\n\u003cp\u003eRegarding the surgical efficiency, total operation time and ischemia time were assessed as secondary endpoints. Total operation time was the duration from the moment of surgical incision to the end of wound closure, which included the time for tumor resection, flap harvesting, and reconstruction. Since our study included both benign and malignant tumor cases, the neck dissection time was not included in the total operative time. The ischemic time was the time between the flap\u0026rsquo;s pedicle detachment and re-anastomosis. The entire surgical procedure was timed and recorded as a final value on a timing sheet in minutes (min) and summarized as a mean.\u003c/p\u003e\n\n\u003ch2\u003eStatistical methods:\u003c/h2\u003e\n\u003cp\u003eBased on a previous study by Azuma et al. in 2014 [13], the clinical important difference in DAn between the two groups was expected to be 6̊, with a standard deviation (SD) of the control group was \u0026plusmn;4.38̊. Considering a significance level of 5.0% and statistical power of 80.0%, 9 patients per group would be necessary (18 totals). Taking into account possible losses to follow-up, this number was increased to a sample size of 11 patients per group (22 totals, 20% more than the calculated) for losses compensation. The sample size was calculated using PS program.\u003c/p\u003e\n\u003cp\u003eData analysis was conducted using IBM SPSS advanced statistics, version 24 (SPSS Inc., Chicago, IL). Summary statistics were presented with either the mean \u0026plusmn; standard deviation or the median (range) for numerical data and with counts and percentages for categorical data. Kolmogorov-Smirnov test and Shapiro-Wilk test were used to explore the data for normality. The Student\u0026rsquo;s t-test was used to compare the normally distributed numeric variables of aesthetic outcomes and operation times, while comparisons for non-normally distributed numerical variables were done by Mann-Whitney test. Comparisons between categorical variables were performed using the chi-square test. A \u003cem\u003eP\u003c/em\u003e-value less than or equal to 0.05 (\u003cem\u003eP \u003c/em\u003e\u0026le; 0.05) was considered statistically significant. All tests were two-tailed.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003ePatients\u0026rsquo; clinicodemographic data\u003c/h2\u003e\n\u003cp\u003eOf 64 patients screened for eligibility, 42 were ineligible. Twenty-two patients were randomized in equal numbers to the two study groups (\u003cem\u003en\u0026nbsp;\u003c/em\u003e= 11 patients/group). \u003cstrong\u003eFigure (8\u003c/strong\u003e) shows the consort flow chart of the study. Comparison of the two groups yielded the following results \u003cstrong\u003eTable (1)\u003c/strong\u003e. The mean age in the COG group was 41 \u0026plusmn; 18.5 years (range, 10- 63 years) versus 47.81\u0026plusmn; 13.6 years (range, 29- 63 years) in the MB group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBased on Brown\u0026rsquo;s classification of mandibular defects, in the COG group, 5 (45.4 %) patients had CL II, 2 (18.2 %) patients had CL IIc, 3 (27.3 %) patients had CL III, and 1 (9.1 %) had CL IV. While in the MB group, 5 (45.4 %) patients had CL II, 1 (9.1 %) patient had CL IIc, 2 (18.2 %) patients had CL III, 2 (18.2 %) patients had CL IV, and 1 (9.1 %) had CL IVc. The mean mandibular defects\u0026rsquo; length was 8.5 \u0026plusmn; 2.56 cm in the COG group versus 9.42 \u0026plusmn; 4.65 cm in the MB group. \u003cstrong\u003eTable (1)\u003c/strong\u003e shows the clinicodemographic data and tumor characteristics of all patients. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (1):\u0026nbsp;\u003c/strong\u003eClinicodemographic characteristics of both groups of patients enrolled in this study\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 15.969%;\" valign=\"top\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 26.6851%;\" width=\"19.937694704049843%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOG group (N= 11)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 9.3503%;\" width=\"20.093457943925234%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMB group (N= 11)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"25.33783783783784%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCount\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"17.905405405405407%\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"25.675675675675677%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCount\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"17.905405405405407%\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.682242990654206%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e63.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.838006230529595%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e54.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e36.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e45.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (\u003c/strong\u003e\u003cstrong\u003eyr) (Mean \u0026plusmn; SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.682242990654206%\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e\u0026plusmn;18.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.838006230529595%\"\u003e\n \u003cp\u003e47.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e\u0026plusmn;13.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e.339\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication / diagnosis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBenign\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.682242990654206%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e27.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.838006230529595%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e27.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMalignant\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e72.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e72.70\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"3\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSite\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003eL\u003csub\u003et\u003c/sub\u003e Mandible\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.682242990654206%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e63.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.838006230529595%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e54.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csub\u003et\u003c/sub\u003e Mandible\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e27.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003csub\u003ei\u003c/sub\u003e Mandible\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 8.7199%;\" width=\"5.616224648985959%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMandibular Defect\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2842%;\" width=\"20.2808112324493%\"\u003e\n \u003cp\u003e\u003cstrong\u003eLength\u003csub\u003e(cm)\u003c/sub\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(Mean \u0026plusmn;SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.132605304212168%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.700468018720748%\"\u003e\n \u003cp\u003e8.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.268330733229329%\"\u003e\n \u003cp\u003e\u0026plusmn;2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.856474258970358%\"\u003e\n \u003cp\u003e9.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.268330733229329%\"\u003e\n \u003cp\u003e\u0026plusmn;4.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 3.8872%;\" width=\"12.792511700468019%\"\u003e\n \u003cp\u003e.575\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 16.2842%;\" width=\"21.487603305785125%\"\u003e\n \u003cp\u003e\u003cstrong\u003eClassification\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"16.03305785123967%\"\u003e\n \u003cp\u003e\u003cstrong\u003eII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"12.396694214876034%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.760330578512397%\"\u003e\n \u003cp\u003e45.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"12.561983471074381%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.760330578512397%\"\u003e\n \u003cp\u003e45.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 3.8872%;\" width=\"13.553719008264462%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIIc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e09.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIII\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e27.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e09.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e18.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIVc\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e09.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 25.0041%;\" width=\"26.01246105919003%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFlap harvest side\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"15.109034267912772%\"\u003e\n \u003cp\u003e\u003cstrong\u003eL\u003csub\u003et\u003c/sub\u003e leg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"11.682242990654206%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e54.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"11.838006230529595%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"8.255451713395638%\"\u003e\n \u003cp\u003e63.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 3.8872%;\" width=\"12.77258566978193%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 15.969%;\" width=\"24.681933842239186%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR\u003csub\u003et\u003c/sub\u003e leg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.3387%;\" width=\"19.083969465648856%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11.3464%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e45.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.6226%;\" width=\"19.338422391857506%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4.8327%;\" width=\"13.486005089058525%\"\u003e\n \u003cp\u003e36.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eBi, bilateral, CAD/CAM, CL, classification, COG, customized osteotomy guide, F, female, F. fibula flap, Lt, left, M, male, MB, model-based, N, number, Pt, patient, Rt, right, SD, standard deviation, Yr, year.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ch2\u003eAesthetic Outcomes:\u003c/h2\u003e\n\u003ch3\u003eDifferential Area (DAr):\u003c/h3\u003e\n\u003cp\u003eQuantitively, the CDIA revealed that patients in the COG group showed improved aesthetic outcome (contour symmetry) regarding the sagittal DAr with a mean of (277.28 \u0026plusmn; 127.05 mm\u003csup\u003e2\u003c/sup\u003e) compared to (398.67 \u0026plusmn; 139.10 mm\u003csup\u003e2\u003c/sup\u003e) in the MB group. The difference in the sagittal DAr was statistically significant (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.045). Although the axial DAr was better in the COG group than in the MB group, there was no statistically significant difference between the two groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.206) \u003cstrong\u003eTable (2)\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2):\u003c/strong\u003e Comparison of differential area (Sagittal and Axial DAr, mean \u0026plusmn; SD) according to group\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"24.960998439937597%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifferential area (DAr)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 36.4922%;\" width=\"31.825273010920437%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOG group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 27.5684%;\" width=\"33.385335413416534%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMB group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 12.5566%;\" width=\"9.82839313572543%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 21.4922%;\" width=\"31.26491646778043%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7578%;\" width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.7949%;\" width=\"33.89021479713604%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (mm\u003csup\u003e2\u003c/sup\u003e)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3184%;\" width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSagittal DAr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4922%;\" width=\"20.404984423676012%\"\u003e\n \u003cp\u003e277.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7578%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 127.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.7949%;\" width=\"22.118380062305295%\"\u003e\n \u003cp\u003e398.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3184%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 139.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.5566%;\" width=\"9.813084112149532%\"\u003e\n \u003cp\u003e\u0026nbsp;0.045*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAxial DAr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.4922%;\" width=\"20.404984423676012%\"\u003e\n \u003cp\u003e147.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.7578%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 55.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.7949%;\" width=\"22.118380062305295%\"\u003e\n \u003cp\u003e183.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.3184%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 72.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.5566%;\" width=\"9.813084112149532%\"\u003e\n \u003cp\u003e\u0026nbsp;0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e COG, customized osteotomy guide, DAr\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003edifferential area, MB, model-based,\u0026nbsp;mm\u003csup\u003e2\u003c/sup\u003e, square millimeter, SD, standard deviation, * Significant P-value.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eDifferential Angle (DAn):\u0026nbsp;\u003c/h3\u003e\n\u003cp\u003eThe mean difference (\u0026Delta;) and thus deviation for the sagittal and coronal DAn were significantly lower in the COG group than in the MB group (6.11 \u0026plusmn; 3.46 and 1.77 \u0026plusmn; 1.12\u0026deg; vs 9.53 \u0026plusmn; 4.17 and 3.44 \u0026plusmn; 2.34\u0026deg;, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), respectively. While in the axial DAn, there was no statistically significant difference between the two groups (\u003cem\u003eP\u003c/em\u003e = 0.386). Although these results indicate that the mandibular contour symmetry was improved, and even that better symmetry results have been found regarding the sagittal, coronal, and axial mandibular angles in favor of the COG group. However, there were no statistically significant differences in the symmetry for sagittal, coronal, and axial angles between the two groups (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05) \u003cstrong\u003eTable (3)\u003c/strong\u003e \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u003c/strong\u003eComparison of the mean difference (Sagittal, Coronal and Axial DAn) and symmetry according to group.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" width=\"36.05015673981191%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifferential and symmetry angle \u003csub\u003e(affected /contralateral side)\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25.0469%;\" width=\"27.272727272727273%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOG group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 19.5703%;\" width=\"27.272727272727273%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMB group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 16.5547%;\" width=\"9.404388714733543%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (\u0026deg;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean (\u0026deg;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"25%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"14.263322884012538%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSagittal\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.786833855799372%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDAn\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u0026Delta;)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e6.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 3.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e9.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 4.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"9.404388714733543%\"\u003e\n \u003cp\u003e0.049*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.411334552102378%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymmetry angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn;\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"10.968921389396709%\"\u003e\n \u003cp\u003e0.389\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"14.263322884012538%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCoronal\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.786833855799372%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDAn\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u0026Delta;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 1.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"9.404388714733543%\"\u003e\n \u003cp\u003e0.046*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.411334552102378%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymmetry angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"10.968921389396709%\"\u003e\n \u003cp\u003e0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"14.263322884012538%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAxial\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.786833855799372%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDAn\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(\u0026Delta;)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e2.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e2.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"13.636363636363637%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"9.404388714733543%\"\u003e\n \u003cp\u003e0.386\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.411334552102378%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSymmetry angle\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.5508%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.7969%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10.7051%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e1.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9.1953%;\" width=\"15.904936014625228%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.5547%;\" width=\"10.968921389396709%\"\u003e\n \u003cp\u003e0.185\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eCOG, customized osteotomy guide, DAn\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003edifferential angle, MB, model-based, \u0026Delta;, mean difference, (\u0026deg;)\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003edegrees, * Significant \u003cem\u003eP\u003c/em\u003e-value.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eSubjective evaluation of aesthetic outcome by VAS and PSS:\u0026nbsp;\u003c/h3\u003e\n\u003cp\u003eThe mean assessment score of the aesthetic outcome in VAS was higher in the COG group than in the MB group (8.18 \u0026plusmn; 0.75 vs 7.64 \u0026plusmn; 0.84), respectively. However, there were no statistically significant differences between the two groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.12). On the other hand, the mean PSS was better in the COG group than in the MB group\u0026nbsp;(8.14 \u0026plusmn; 0.67 vs 7.45 \u0026plusmn; 0.79),\u0026nbsp;with statistically significant differences\u0026nbsp;reflecting enhanced aesthetic outcome and better satisfaction\u0026nbsp;(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.041) \u003cstrong\u003eTable (4)\u003c/strong\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (4):\u003c/strong\u003e Comparison of Visual analogue scale (VAS) and Patient\u0026rsquo;s satisfaction score (PSS) according to group\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"24.960998439937597%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubjective evaluation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 26.0176%;\" width=\"31.825273010920437%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOG group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 29.2305%;\" width=\"33.385335413416534%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMB group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 20.0195%;\" width=\"9.82839313572543%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18.3711%;\" width=\"31.26491646778043%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u003csub\u003e(score 1- 10)\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.6426%;\" width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.2969%;\" width=\"33.89021479713604%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u003csub\u003e(score 1- 10)\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3555%;\" width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVAS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3711%;\" width=\"20.404984423676012%\"\u003e\n \u003cp\u003e8.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.6426%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.2969%;\" width=\"22.118380062305295%\"\u003e\n \u003cp\u003e7.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3555%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0195%;\" width=\"9.813084112149532%\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePSS\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18.3711%;\" width=\"20.404984423676012%\"\u003e\n \u003cp\u003e8.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8.6426%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.2969%;\" width=\"22.118380062305295%\"\u003e\n \u003cp\u003e7.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12.3555%;\" width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.0195%;\" width=\"9.813084112149532%\"\u003e\n \u003cp\u003e0.041*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e COG, customized osteotomy guide, MB, model-based, PSS, patient satisfaction score, VAS, visual analogue scale.\u003c/p\u003e\n\u003ch2\u003eSecondary outcome (operation and ischemic time):\u0026nbsp;\u003c/h2\u003e\n\u003cp\u003eIn the COG group, the total operation time ranged from 467 to 645 minutes (562.91 \u0026plusmn; 51.22 min, mean \u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003eSD) compared to 571- 728 minutes (663.55 \u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e53.43 min, mean \u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003eSD) in the MB group, there were statistically significant differences between the two groups (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.0002). The mean ischemia time was 97.55 \u0026plusmn; 16.80 minutes in the COG group, compared to 172.45 \u0026plusmn; 21.87 minutes in the MB group. The difference in the ischemia time was statistically significant (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.000) \u003cstrong\u003eTable (5)\u003c/strong\u003e. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (5):\u003c/strong\u003e Comparison of total operation time and ischemia time according to group (in minutes)\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"24.960998439937597%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"31.825273010920437%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCOG group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" width=\"33.385335413416534%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMB group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"9.82839313572543%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP-\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.26491646778043%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u003csub\u003e(min)\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.89021479713604%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u003csub\u003e(min)\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.422434367541765%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026plusmn;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal operation time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.404984423676012%\"\u003e\n \u003cp\u003e562.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 51.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.118380062305295%\"\u003e\n \u003cp\u003e663.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 53.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.813084112149532%\"\u003e\n \u003cp\u003e0.0002*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.922118380062305%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIschemia time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.404984423676012%\"\u003e\n \u003cp\u003e97.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 16.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.118380062305295%\"\u003e\n \u003cp\u003e172.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.370716510903426%\"\u003e\n \u003cp\u003e\u0026plusmn; 21.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.813084112149532%\"\u003e\n \u003cp\u003e0.0000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e COG, customized osteotomy guide, MB, model-based, Min, minutes.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe mandible is an anatomically intricate structure, making ideal renovation and reconstruction extremely challenging. Suboptimal reconstruction may result in poor oral function as well as aesthetic deformities. Over the years, the microvascular fibular flap has been established as the workhorse for onco-mandibular reconstruction\u0026nbsp;[5, 15]. However, the greatest challenge that remains is how to most accurately shape vascularized bone flaps so that facial symmetry, as well as function, are best restored and minimize the operative time of such complex surgeries\u0026nbsp;[10]. Conventional techniques, either freehand or MB-approached, depend mainly\u0026nbsp;on\u0026nbsp;the surgeons\u0026rsquo; experience and lack effective quantitative strategies\u0026nbsp;[10, 16-19]. The advent of VSP, including CAD-CAM, has overcome the dilemma and changed the way of bony reconstruction in the past few years\u0026nbsp;[5, 20, 21]. This randomized controlled trial aimed to evaluate and compare the aesthetic outcome and surgical efficiency of FFF with and without\u0026nbsp;CAD/CAM\u0026nbsp;COG for reconstruction of mandibular defects.\u003c/p\u003e\n\u003cp\u003eIn the present study, DAr in both sagittal and axial planes has been introduced as a new criterion for the evaluation of aesthetic outcome. DAn (Sagittal, Coronal, and Axial) has been a part of objective evaluation as well. On the other hand, a subjective dual assessment of the aesthetic outcome has been performed using VAS and PSS. These intended-to analysis parameters are particularly important for facial aesthetics because the maintenance of the mandibular-arch\u0026nbsp;diameter\u0026nbsp;and\u0026nbsp;angles\u0026rsquo;\u0026nbsp;amplitude\u0026nbsp;are\u0026nbsp;fundamentally\u0026nbsp;crucial\u0026nbsp;to fully imitate the native mandible and achieve\u0026nbsp;facial symmetry\u0026nbsp;[22].\u003c/p\u003e\n\u003cp\u003eOur study shows a significant improvement in mandibular contour symmetry regarding the sagittal DAr and thus a better aesthetic outcome in the COG group compared to the MB reconstruction group (\u003cem\u003eP\u003c/em\u003e = 0.045). Likewise, the mean difference between the affected and the contralateral side and thus deviation was significantly lower in terms of the sagittal and coronal mandibular angle (DAn) in the COG group compared to the MB group (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05), suggesting better overall symmetry and, notably, enhanced condyle sitting using cutting guides. These findings are all the more interesting for the current practice and imperatively adherent to the crucial goal of reconstruction.\u003c/p\u003e\n\u003cp\u003eEarlier forms of evaluation were based on pantomography to evaluate mandibular symmetry\u0026nbsp;[5, 13, 14]. Although image standardization was performed according to the authors. However, concerns regarding under- or over-estimation are\u0026nbsp;unfortunately still present, possibly because the radiograph is a uni-directional image. Current methods of evaluation are based on 3D-imaging analysis. Nevertheless, standardization regarding the evaluation process is still a concern. In this study, standardization of the evaluation process was addressed and seems to be mostly in line with the Jove-published protocol by van Baar et al.\u0026nbsp;[23]\u0026nbsp;in terms of imaging, machine and setting parameters, defects classification, using image-based 3D medical software, natural head position, and axis orientation. However, some steps were not exactly adherent to the Jove- published protocol, as our evaluation is based mainly on comparing the reconstructed mandible to the contralateral native mandible postoperatively.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThus far,\u0026nbsp;few data have been reported concerning the reconstruction quality in terms of restoration of the native morphology and preserving symmetry. Almost all studies have compared the reconstructed mandible to virtual planning rather than to the contralateral native mandible, which could overestimate the undoubted benefits of virtual planning\u0026nbsp;[11]. In this study, morphological evaluation was achieved by comparing the superimposed virtual images of the reconstructed side to the contralateral native side of the mandible using 3D-CDIA on a\u0026nbsp;post-operative CT-scan for the selected parameters. Given that symmetry\u0026nbsp;and thus aesthetics is the imperative goal rather than accuracy, that has been vastly reported. Results, either in the form of a mean difference or symmetry ratio, can indicate and estimate the aesthetic outcome.\u003c/p\u003e\n\u003cp\u003eIn the relevant literature, several studies have addressed the valuable use of VSP for mandibular reconstruction. Weitz et al.\u0026nbsp;[5]\u0026nbsp;found significantly smaller differences between the pre- and post-operative angle of the mandible in the virtual group compared to conventionally treated cases, 4.5\u0026deg; versus 11.5\u0026deg;, which is a measure that strongly influences the aesthetic outcomes and consistent proportions of the lower third of the face. Similar to Jacek and Azuma\u0026nbsp;[13, 14]\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003eWeitz et al. used pantomographic analysis, and hence only used one angle to compare results. Zhang et al.\u0026nbsp;[24]\u003csup\u003e\u0026nbsp;\u003c/sup\u003ewhen studying outcomes between computer-aided group vs freehand reconstruction, compared the VSP to the post-operative mandible alone. Even though their results show improved angle deviation in favor of the CAD group, the impact on aesthetic estimation may be limited since post-operative comparison with the contralateral native mandible was not done. Ren et al.\u0026nbsp;[10]\u0026nbsp;mentioned that the mean differences between the pre-operative and post-operative gonial angles were significantly smaller in the computer-assisted group compared with the conventional group (\u003cem\u003eP\u003c/em\u003e = 0.007).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSimilarly,\u0026nbsp;Yu et al. [25] found that the variation between the reconstructed and contralateral mandibular angles was significantly different, favoring CAD-based over the conventional group (\u003cem\u003eP\u003c/em\u003e = 0.001). Similar to the present study, Bartier et al.\u0026nbsp;[11]\u0026nbsp;in a retrospective study provided interesting results in favor of cutting guides. The mean difference between\u0026nbsp;pre- and post-operative values of the coronal mandibular angles was significantly lower in the virtual planning group than in the traditional freehand group. Likewise, he found equivalent results in both techniques regarding post-operative symmetry for the coronal and axial mandibular angles but was significantly better regarding the sagittal angle in the 3D group. In general, the results of the present study are mostly in line with those of the Bartier study. Variations could be attributed to that conventional technique was used as a comparative control group in the Bartier study versus a 3D MB group in the present study, which could minimize the difference. However, it is difficult to directly compare the results of the present study with the aforementioned studies as all were compared to conventional reconstruction as a control, and most were performed retrospectively with the variations in the methodologies and parameters included in the evaluation, and thus potentially underrepresents the actual relevancy to the current imperative goals. Additionally, there is either a lack or an\u0026nbsp;unclarified method for standardization in most of the studies.\u003c/p\u003e\n\u003cp\u003eDe Maesschalck et al.\u0026nbsp;[26]\u0026nbsp;found equivalent results in both techniques regarding the mean difference and post-operative mandible symmetry in terms of sagittal and axial angles between the groups. Similarly, Stirling Craig et al.\u0026nbsp;[27]\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efound similar results in both techniques regarding post-operative body-symphyseal angle on axial view and thus mandible symmetry. Generally, the findings of these studies are contradictory to the present study and other reports regarding the efficiency of VSP, particularly cutting guides in improving aesthetic outcomes.\u003c/p\u003e\n\u003cp\u003eIn\u0026nbsp;terms\u0026nbsp;of subjective aesthetic assessment (SAA), findings of the present study have shown comparable results in both groups regarding VAS\u0026nbsp;scores\u0026nbsp;(8.18 versus 7.64), respectively.\u0026nbsp;However,\u0026nbsp;the PSS was significantly better scored (8.14) in the COG group compared to (7.45) in the MB group. In contrast to the present study, Bouchet et al.\u0026nbsp;[28]\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ereported\u0026nbsp;that\u0026nbsp;aesthetic satisfaction by\u0026nbsp;PSS was higher in the conventional group (a score of \u0026ge;7 was reported by 85% (11/13) patients in the conventional group vs. 58% (7/12) patients in the CAD/CAM group.\u0026nbsp;Given\u0026nbsp;that satisfaction with the aesthetic result is vastly subjective and strictly related to patients\u0026rsquo; expectations, the results can surprisingly vary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding surgical efficiency,\u0026nbsp;Chang et al. [29]\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003efound that VSP significantly decreased operation and ischemia times compared to the MB group. Much the same findings have been presented by\u0026nbsp;Toto et al., in 2015 [30].\u0026nbsp;This was also observed in several other studies that compared VSP with conventional technique\u0026nbsp;[1, 10, 24, 31, 32].\u0026nbsp;The present study showed\u0026nbsp;that the mean total operation time and ischemia time were significantly shorter in the COG group compared to the MB group, which is consistent with those studies.\u0026nbsp;In contrast to the present study, Yu et al.\u0026nbsp;[25]\u0026nbsp;and Bartier et al.\u0026nbsp;[11],\u0026nbsp;even though they used conventional technique as a control, they found that the mean operative time did not significantly differ between the groups, which is contradictory to our findings. This could be because of many parameters either directly related or unrelated to the use of cutting guides and their impact on surgery time.\u0026nbsp;Although the surgical efficiency of VSP has been vastly investigated. However, our results have resolved the conflict that resurfaced\u0026nbsp;in some reports.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo the best of our knowledge, this study is the first randomized controlled clinical trial (RCT) investigating the aesthetic outcomes of FFF for reconstruction of the onco-mandibular defects by using the VSP and cutting guides versus that of Model-based reconstruction.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe results of the present study indicated that the CAD/CAM with COG enhanced the aesthetic outcome in patients undergoing mandibular reconstruction using FFF compared to that without COG (MB reconstruction). It also has been shown to significantly enhance the surgical efficiency by minimizing total operative time and ischemia time. The limitation of this study is the relatively small sample size and the need to use a second-party software for DAr evaluation. Our measurements considered underlying hard bony tissue, further studies are required to analyze their impact on overlying structures.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCAD/CAM: Computer-aided design and Computer-aided manufacturing,\u0026nbsp;CAS:\u0026nbsp;Computer-assisted surgery, CDIA: Computerized Digital Imaging Analysis,\u0026nbsp;COG: Customized osteotomy guide,\u0026nbsp;CT: Computed tomography,\u0026nbsp;DAr: Differential area, DAn: Differential angle,\u0026nbsp;DICOM: Digital Imaging and Communications in Medicine,\u0026nbsp;FFF: Free fibular flap, MB: Model based, NCI: National Cancer Institute, Min: Minutes,\u0026nbsp;PSS: Patient\u0026rsquo;s Satisfaction Score, SAA: Subjective aesthetic assessment,\u0026nbsp;SNOSE: Sequentially numbered, opaque sealed envelopes,\u0026nbsp;Sq. mm/mm\u003csup\u003e2\u003c/sup\u003e: Square millimeters, VAS: visual analogue scale, VSP: Virtual surgical planning, Vs: Versus, 3D: Three-dimensional, \u0026Delta;: Mean difference, \u0026deg;: Degree.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e \u003cstrong\u003eand consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical review and approval for This study was committed by the Research Ethics Committee of the Faculty of Dentistry, Cairo University (identifier 24/12/18). The patients/participants provided their written informed consent to participate in this study and for any potentially identifiable images or data included in this article.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\n\u003cp\u003eData Availability Statement\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is totally self-funded and wasn\u0026rsquo;t supported by any grants.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception: M.E.A., M.I.S., and A.A.A. Design of the work: M.E.A., B.G.M., and M.I.S. Virtual planning and surgical work: M.E.A. and M.H.Z. Data collection, Assembly and Formal analysis: M.E.A., M.I.S., and O.M.J. Supervision and Visualization: M.I.S., M.H.Z., and A.A.A. Drafted the manuscript and Data curation: M.E.A. Critical revision of the manuscript: M.E.A., O.M.J., and M.H.Z. Final approval: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur acknowledgment extends to all staff members of the Head and Neck Unit at NCI, and Department of Oral and Maxillofacial Surgery, Faculty of Dentistry Cairo University for their cooperation in completing this study and their provision of equipment and services. Our acknowledgment also extends to Dr. Mohamed Ghorab, Assistant lecturer of Oral and Maxillofacial Surgery, Cairo University for his valuable aid in the CAD/CAM workflow.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSucco G, Berrone M, Battiston B, Tos P, Goia F, Appendino P, et al. Step-by-step surgical technique for mandibular reconstruction with fibular free flap: application of digital technology in virtual surgical planning. Eur Arch Otorhinolaryngol. 2015,272(6):1491-501.\u003c/li\u003e\n\u003cli\u003eLonie S, Herle P, Paddle A, Pradhan N, Birch T, Shayan R. Mandibular reconstruction: meta-analysis of iliac- versus fibula-free flaps. ANZ J Surg. 2016,86(5):337-42.\u003c/li\u003e\n\u003cli\u003eHoffmann J, Horn D. 34 - Reconstruction of the Mandible. In: Brennan PA, Schliephake H, Ghali GE, Cascarini L, editors. Maxillofacial Surgery (Third Edition): Churchill Livingstone, 2017. p. 497-506.\u003c/li\u003e\n\u003cli\u003eBatstone MD. Reconstruction of major defects of the jaws. Aust Dent J. 2018,63 Suppl 1:S108-s13.\u003c/li\u003e\n\u003cli\u003eWeitz J, Bauer FJ, Hapfelmeier A, Rohleder NH, Wolff KD, Kesting MR. Accuracy of mandibular reconstruction by three-dimensional guided vascularised fibular free flap after segmental mandibulectomy. Br J Oral Maxillofac Surg. 2016,54(5):506-10.\u003c/li\u003e\n\u003cli\u003eBak M, Jacobson AS, Buchbinder D, Urken ML. Contemporary reconstruction of the mandible. Oral Oncol. 2010,46(2):71-6.\u003c/li\u003e\n\u003cli\u003ePai D, Wodeyar A. Evolution of Mandibular Defects Reconstruction Procedures: From Older Principles to Newer Techniques and Technology. Acta Scientific Dental Sciences. 2019,3(5):08-18.\u003c/li\u003e\n\u003cli\u003ePar\u0026eacute; A, Bossard A, Laure B, Weiss P, Gauthier O, Corre P. Reconstruction of segmental mandibular defects: Current procedures and perspectives. Laryngoscope Investig Otolaryngol. 2019,4(6):587-96.\u003c/li\u003e\n\u003cli\u003eAli MN, Anwar RB, Banik R, Hasan S, Arefin MRU, Uddin MW. Mandibular reconstruction: a review. Update Dent Coll J 2019,9(2):50-4.\u003c/li\u003e\n\u003cli\u003eRen W, Gao L, Li S, Chen C, Li F, Wang Q, et al. Virtual Planning and 3D printing modeling for mandibular reconstruction with fibula free flap. Med Oral Patol Oral Cir Bucal. 2018,23(3):e359-e66.\u003c/li\u003e\n\u003cli\u003eBartier S, Mazzaschi O, Benichou L, Sauvaget E. Computer-assisted versus traditional technique in fibular free-flap mandibular reconstruction: A CT symmetry study. Eur Ann Otorhinolaryngol Head Neck Dis. 2021,138(1):23-7.\u003c/li\u003e\n\u003cli\u003eUeda N, Imai Y, Yamakawa N, Yagyuu T, Tamaki S, Nakashima C, et al. Assessment of facial symmetry by three-dimensional stereophotogrammetry after mandibular reconstruction: A comparison with subjective assessment. J Stomatol Oral Maxillofac Surg. 2021,122(1):56-61.\u003c/li\u003e\n\u003cli\u003eAzuma M, Yanagawa T, Ishibashi-Kanno N, Uchida F, Ito T, Yamagata K, et al. Mandibular reconstruction using plates prebent to fit rapid prototyping 3-dimensional printing models ameliorates contour deformity. Head Face Med. 2014,10:45.\u003c/li\u003e\n\u003cli\u003eJacek B, Maciej P, Tomasz P, Agata B, Wiesław K, Radosław W, et al. 3D printed models in mandibular reconstruction with bony free flaps. J Mater Sci Mater Med. 2018,29(3):23.\u003c/li\u003e\n\u003cli\u003ePatel A, Harrison P, Cheng A, Bray B, Bell RB. Fibular Reconstruction of the Maxilla and Mandible with Immediate Implant-Supported Prosthetic Rehabilitation: Jaw in a Day. Oral Maxillofac Surg Clin North Am. 2019,31(3):369-86.\u003c/li\u003e\n\u003cli\u003eWang YY, Zhang HQ, Fan S, Zhang DM, Huang ZQ, Chen WL, et al. Mandibular reconstruction with the vascularized fibula flap: comparison of virtual planning surgery and conventional surgery. Int J Oral Maxillofac Surg. 2016,45(11):1400-5.\u003c/li\u003e\n\u003cli\u003eHan HH, Kim HY, Lee JY. The Pros and Cons of Computer-Aided Surgery for Segmental Mandibular Reconstruction after Oncological Surgery. Arch Craniofac Surg. 2017,18(3):149-54.\u003c/li\u003e\n\u003cli\u003eMonsalve-Iglesias F, Rico \u0026Aacute;M-S, Fraile-Ruiz L. Virtual surgical planning in fibula flap mandibular reconstruction. Front Oral Maxillofac Med. 2020,2(12):1-8.\u003c/li\u003e\n\u003cli\u003eZavattero E, Bolzoni A, Dell\u0026apos;Aversana G, Santagata M, Massarelli O, Ferri A, et al. Accuracy of Fibula Reconstruction Using Patient-Specific Cad/Cam Plates: A Multicenter Study on 47 Patients. Laryngoscope. 2021,131(7):E2169-e75.\u003c/li\u003e\n\u003cli\u003eFoley BD, Thayer WP, Honeybrook A, McKenna S, Press S. Mandibular reconstruction using computer-aided design and computer-aided manufacturing: an analysis of surgical results. J Oral Maxillofac Surg. 2013,71(2):e111-9.\u003c/li\u003e\n\u003cli\u003eOh JH. Recent advances in the reconstruction of cranio-maxillofacial defects using computer-aided design/computer-aided manufacturing. Maxillofac Plast Reconstr Surg. 2018,40(1):2.\u003c/li\u003e\n\u003cli\u003eTarsitano A, Ciocca L, Scotti R, Marchetti C. Morphological results of customized microvascular mandibular reconstruction: A comparative study. J Craniomaxillofac Surg. 2016,44(6):697-702.\u003c/li\u003e\n\u003cli\u003evan Baar GJC, Liberton NPTJ, Winters HAH, Leeuwrik L, Forouzanfar T, Leusink FKJ. A Postoperative Evaluation Guideline for Computer-Assisted Reconstruction of the Mandible. J Vis Exp. 2020(155):e60363.\u003c/li\u003e\n\u003cli\u003eZhang L, Liu Z, Li B, Yu H, Shen SG, Wang X. Evaluation of computer-assisted mandibular reconstruction with vascularized fibular flap compared to conventional surgery. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016,121(2):139-48.\u003c/li\u003e\n\u003cli\u003eYu Y, Zhang WB, Liu XJ, Guo CB, Yu GY, Peng X. Three-Dimensional Accuracy of Virtual Planning and Surgical Navigation for Mandibular Reconstruction With Free Fibula Flap. J Oral Maxillofac Surg. 2016,74(7):1503 e1- e10.\u003c/li\u003e\n\u003cli\u003eDe Maesschalck T, Courvoisier DS, Scolozzi P. Computer-assisted versus traditional freehand technique in fibular free flap mandibular reconstruction: a morphological comparative study. Eur Arch Otorhinolaryngol. 2017,274(1):517-26.\u003c/li\u003e\n\u003cli\u003eStirling Craig E, Yuhasz M, Shah A, Blumberg J, Salomon J, Lowlicht R, et al. Simulated surgery and cutting guides enhance spatial positioning in free fibular mandibular reconstruction. Microsurgery. 2015,35(1):29-33.\u003c/li\u003e\n\u003cli\u003eBouchet B, Raoul G, Julieron B, Wojcik T. Functional and morphologic outcomes of CAD/CAM-assisted versus conventional microvascular fibular free flap reconstruction of the mandible: A retrospective study of 25 cases. J Stomatol Oral Maxillofac Surg. 2018,119(6):455-60.\u003c/li\u003e\n\u003cli\u003eChang EI, Jenkins MP, Patel SA, Topham NS. Long-Term Operative Outcomes of Preoperative Computed Tomography-Guided Virtual Surgical Planning for Osteocutaneous Free Flap Mandible Reconstruction. Plast Reconstr Surg. 2016,137(2):619-23.\u003c/li\u003e\n\u003cli\u003eToto JM, Chang EI, Agag R, Devarajan K, Patel SA, Topham NS. Improved operative efficiency of free fibula flap mandible reconstruction with patient-specific, computer-guided preoperative planning. Head Neck. 2015,37(11):1660-4.\u003c/li\u003e\n\u003cli\u003eAvraham T, Franco P, Brecht LE, Ceradini DJ, Saadeh PB, Hirsch DL, et al. Functional outcomes of virtually planned free fibula flap reconstruction of the mandible. Plast Reconstr Surg. 2014,134(4):628e-34e.\u003c/li\u003e\n\u003cli\u003eBao T, He J, Yu C, Zhao W, Lin Y, Wang H, et al. Utilization of a pre-bent plate-positioning surgical guide system in precise mandibular reconstruction with a free fibula flap. Oral Oncol. 2017,75:133-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Aesthetic reconstruction, CAD/CAM, Customized osteotomy/cutting guide, Free fibula flap, Head and neck cancer, Mandibular defects, Model-based reconstruction, Virtual planning.","lastPublishedDoi":"10.21203/rs.3.rs-2007675/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-2007675/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eReconstruction of mandibular defects following ablative surgery remains a challenge even for experienced surgeons. Virtual planning and guided surgery, including computer-aided design/computer-aided manufacturing (CAD/CAM), afford optimized ways by which to plan complex surgery. This study aimed to evaluate and compare aesthetic outcome and surgical efficiency of free fibular flap (FFF) with and without CAD/CAM customized osteotomy guide (COG) for reconstruction of onco-surgical mandibular defects.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eTwenty-two patients indicated for segmental mandibulectomy were randomly assigned to either CAD/CAM with COG group or that without COG- Model based reconstruction (MB group) at a 1:1 ratio. Aesthetic outcomes were evaluated by means of morphometric assessment and comparison for each differential area (DAr) and angle (DAn) in the affected side to the contralateral side of the mandible using computerized digital imaging analysis (CDIA) based on the post-operative 3D CT-scan. Subjective evaluation was performed using the Visual Analogue Scale (VAS) and Patient\u0026rsquo;s Satisfaction Score (PSS). Surgical efficiency was a secondary outcome and evaluated as total operative time and ischemia time.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe mean sagittal DAr was significantly lower in the COG group (277.28\u0026thinsp;\u0026plusmn;\u0026thinsp;127.05 vs 398.67\u0026thinsp;\u0026plusmn;\u0026thinsp;139.10 mm\u003csup\u003e2\u003c/sup\u003e, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045). Although there was an improvement in the axial DAr (147.61\u0026thinsp;\u0026plusmn;\u0026thinsp;55.42 vs 183.68\u0026thinsp;\u0026plusmn;\u0026thinsp;72.85 mm\u003csup\u003e2\u003c/sup\u003e), the difference was not statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.206). The mean differences (Δ) in both sagittal and coronal DAn were significantly lower in the COG group than in the MB group (6.11\u0026thinsp;\u0026plusmn;\u0026thinsp;3.46 and 1.77\u0026thinsp;\u0026plusmn;\u0026thinsp;1.12\u0026deg; vs 9.53\u0026thinsp;\u0026plusmn;\u0026thinsp;4.17 and 3.44\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u0026deg;), respectively. There were no statistically significant differences in the axial DAn between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.386). The PSS was significantly higher in the COG group, reflecting better aesthetic satisfaction than in the MB group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041). The total operation and ischemia time were significantly shorter in favor of the COG group with a mean of (562.91\u0026thinsp;\u0026plusmn;\u0026thinsp;51.22, 97.55\u0026thinsp;\u0026plusmn;\u0026thinsp;16.80 min vs 663.55\u0026thinsp;\u0026plusmn;\u0026thinsp;53.43, 172.45\u0026thinsp;\u0026plusmn;\u0026thinsp;21.87 min), respectively.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe CAD/CAM with COG is more reliable and highly valuable in enhancing aesthetic outcomes and surgical efficiency of mandibular reconstruction by FFF compared to that without COG (MB reconstruction).\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eThis trial was registered at ClinicalTrials.gov. Registration number: NCT03757273. Registration date: 28/11/2018.\u003c/p\u003e","manuscriptTitle":"Aesthetic Reconstruction of Onco-surgical Mandibular Defects Using Free Fibular Flap with and without CAD/CAM Customized Osteotomy Guide: A Randomized Controlled Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-09-22 21:53:32","doi":"10.21203/rs.3.rs-2007675/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-10-13T09:28:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-10-12T15:22:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"343e1e3e-5d4c-4b12-9adf-099b7bbc652a","date":"2022-09-29T02:25:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"abea41eb-21b8-4674-b082-76fe7c1e689b","date":"2022-09-19T02:24:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-09-15T13:47:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-09-15T13:42:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-09-15T10:05:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-09-15T10:04:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2022-08-28T21:23:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2e0b2a2a-ff0f-48a8-bebc-40d2600a36a7","owner":[],"postedDate":"September 22nd, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-11-16T06:29:13+00:00","versionOfRecord":[],"versionCreatedAt":"2022-09-22 21:53:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-2007675","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-2007675","identity":"rs-2007675","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}