Cabozantinib in Japanese patients with advanced hepatocellular carcinoma: Final results of a multicenter phase II study.

AIM: Cabozantinib showed a favorable benefit-risk profile in Japanese patients with advanced hepatocellular carcinoma (HCC) in an open-label, phase II study (NCT03586973). This analysis presents cumulative data to final database lock. METHODS: Patients with previously treated, advanced HCC received cabozantinib 60 mg/day. Progression-free survival (PFS) and tumor response rates in prior-sorafenib and sorafenib-naïve cohorts were assessed by independent radiology committee (IRC) and an investigator. Liver function was evaluated by albumin-bilirubin (ALBI) score. RESULTS: Median cabozantinib exposure was 5.6 months. In the prior-sorafenib cohort (n = 20), median PFS was 7.4 months per IRC assessment and 5.6 months per investigator assessment. In the sorafenib-naïve cohort (n = 14), median PFS was 3.6 and 4.4 months per IRC and investigator assessment, respectively. Six-month PFS rate per IRC and investigator assessment in the prior-sorafenib cohort was 59.8% and 49.5%, respectively, and in the sorafenib-naïve cohort was 16.7% and 35.7%, respectively. Disease control rate by both IRC and investigator assessment was 85.0% in the prior-sorafenib cohort and 64.3% in the sorafenib-naïve cohort. Median overall survival (Kaplan-Meier estimate) was 19.3 and 9.9 months in the prior-sorafenib and sorafenib-naïve cohort, respectively. Mean ALBI score remained relatively constant in patients able to continue treatment. The most frequent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, hypertension, and decreased appetite. No new safety concerns were identified. CONCLUSIONS: Cabozantinib showed efficacy and a manageable safety profile in Japanese patients with advanced HCC.

Final efficacy and safety results and biomarker analysis of a phase 2 study of cabozantinib in Japanese patients with advanced renal cell carcinoma.

BACKGROUND: Cabozantinib was established as the standard of care for the treatment of patients with renal cell carcinoma (RCC) whose disease had progressed after vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in the global randomized trial METEOR. A phase 2 study was conducted to bridge the findings in METEOR to Japanese patients. Here, we report a biomarker analysis and update the efficacy and safety results of cabozantinib treatment. METHODS: Japanese patients with RCC who received at least one prior VEGFR-TKI were enrolled and received cabozantinib 60 mg orally once daily. The primary endpoint was objective response rate. Secondary endpoints included progression-free survival, overall survival, and safety. Exploratory analyses included the relationship between plasma protein hepatocyte growth factor (HGF) levels and treatment responses. RESULTS: In total, 35 patients were enrolled. The median treatment duration was 58.3 (range 5.1-131.4) weeks. The objective response rate was 25.7% (90% confidence interval [CI] 14.1-40.6). Kaplan-Meier estimate of median progression-free survival was 11.1 months (95% CI 7.4-18.4). The estimated progression-free survival proportion was 73.1% (95% CI 54.6-85.0) at 6 months. Median overall survival was not reached. Adverse events were consistent with those in METEOR and the safety profile was acceptable. Nonresponders to cabozantinib showed relatively higher HGF levels than responders at baseline. CONCLUSIONS: Updated analyses demonstrate the long-term efficacy and safety of cabozantinib in Japanese patients with advanced RCC after at least one VEGFR-TKI therapy. Responders tended to show lower baseline HGF levels ClinicalTrials.gov Identifier: NCT03339219.

Cabozantinib in advanced renal cell carcinoma: A phase II, open-label, single-arm study of Japanese patients.

OBJECTIVES: To evaluate the efficacy and safety of cabozantinib, through a bridging study to METEOR, in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy. METHODS: This phase II, open-label, single-arm study (ClinicalTrials.gov registration number: NCT03339219) included adult Japanese patients with advanced renal cell carcinoma and measurable disease who had received one or more tyrosine kinase inhibitors. Patients received cabozantinib 60 mg orally once daily while there was clinical benefit, or until unacceptable toxicity or disease progression. The primary end-point was objective response rate per Response Evaluation Criteria in Solid Tumors Version 1.1. Secondary end-points included clinical benefit rate (complete or partial response, or ≥8-week stable disease), progression-free survival, overall survival and safety. RESULTS: Of the 35 patients enrolled, 68.6%, 22.9% and 8.6% had previously received one, two and three prior tyrosine kinase inhibitors, respectively. The median duration of cabozantinib exposure was 27.0 weeks (range 5.1-43.0 weeks). The objective response rate was 20.0% (90% confidence interval 9.8-34.3%), and the clinical benefit rate was 85.7% (95% confidence interval 69.7-95.2%). The 6-month estimated progression-free survival was 72.3% (95% confidence interval 53.3-84.6%); the median progression-free survival and overall survival were not reached. All patients reported adverse events, which were manageable by supportive treatment or dose modification; two patients (5.7%) discontinued therapy due to adverse events. CONCLUSIONS: The results showed that findings from METEOR can be extrapolated, and that cabozantinib 60 mg/day is a viable treatment option in Japanese patients with advanced renal cell carcinoma who had progressed after prior tyrosine kinase inhibitor therapy.

Efficacy and safety of trelagliptin in combination with insulin therapy in Japanese patients with type 2 diabetes: Results from a randomized, Phase IV study.

We aimed to explore the efficacy and safety of once-weekly trelagliptin 100 mg as an add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control. Patients with haemoglobin A1c (HbA1c) 7.5% to 10.0% who were receiving 8 to 40 units of insulin per day were randomized to receive, with insulin, trelagliptin 100 mg (A/A, n = 116) or placebo (P/A, n = 124) for a 12-week double-blind (DB) phase, after which all received trelagliptin for a 40-week open-label phase. Primary endpoints were HbA1c change from baseline to the end of the DB phase and adverse events (AEs). HbA1c significantly decreased in the A/A group vs the P/A group at the end of the DB phase (least square mean difference, -0.63% [95% CI, -0.83 to -0.44]: P < .0001). The frequency of treatment-emergent AEs during the DB phase was 44.0% in the A/A group and 47.6% in the P/A group. No patient experienced severe hypoglycaemia during trelagliptin treatment. Once-weekly trelagliptin 100 mg therapy with insulin demonstrated a significant reduction in HbA1c. Long-term treatment was well-tolerated, with no clinically significant hypoglycaemia, suggesting that trelagliptin with insulin is a meaningful treatment option in this patient population.

Unilateral mandibular condylar osteochondroma treated with ipsilateral condylectomy and contralateral ramus osteotomy.

We successfully treated a 32-year-old woman who had facial asymmetry and unilateral mandibular condylar osteochondroma using ipsilateral mandibular condylectomy and contralateral ramus osteotomy. Mirror image analysis with a noncontact 3-dimensional image scanner showed that the soft tissue on the deviated side was protruded more than 5.50 mm compared with the nondeviated side. The patient was diagnosed as having facial asymmetry with a skeletal Class III jaw-base relationship caused by unilateral mandibular condylar osteochondroma. After 18 months of preoperative orthodontic treatment, an ipsilateral condylectomy and a contralateral sagittal split ramus osteotomy were performed. As the result of postoperative orthodontic treatment for 20 months, an ideal occlusion with a Class I molar relationship and an adequate interincisal relationship was achieved. Facial asymmetry and mandibular protrusion were dramatically improved, and the total differences between the deviated and nondeviated sides were decreased to less than 1.11 mm. The acceptable occlusion and the symmetric face were maintained throughout the 1-year retention period. Our results indicated stability after condylectomy without condylar reconstruction in a patient with unilateral condylar osteochondroma.

Long-term stability of maxillary group distalization with interradicular miniscrews in a patient with a Class II Division 2 malocclusion.

We successfully treated a Class II Division 2 patient with maxillary group distalization using interradicular miniscrews. A woman, aged 28 years 11 months, had a convex profile and an excessive overjet caused by a skeletal Class II jaw-base relationship. After leveling and alignment, titanium miniscrews were obliquely implanted between the maxillary second premolar and first molar. To distalize the maxillary dentition, nickel-titanium closing coil springs with a 2-N load were placed between the screws and the hooks on the archwire. After 28 months of active orthodontic treatment, a proper facial profile and an acceptable occlusion were achieved with a 4-mm distalization of the maxillary dentition. The resultant occlusion was stable throughout a 5-year retention period. Interradicular miniscrews were useful to distalize the maxillary dentition for correcting a Class II malocclusion. This new strategy, group distalization with miniscrews, can make the treatment simpler with greater predictability.

Histomorphometric analysis of overloading on palatal tooth movement into the maxillary sinus.

INTRODUCTION: Our objective was to evaluate the effect of overloading on the palatal movement of the maxillary molar. METHODS: The maxillary first molars of male C57Bl/6 mice were moved palatally with loads of 10 or 30 g for 14 days, and the amount of tooth movement was longitudinally measured on microcomputed tomography images. Bone remodeling around the molar root with the 30-g load was evaluated at days 3, 5, 7, and 14 after the start of tooth movement using histomorphometry and immunodetection of bone-restricted interferon inducible transmembrane-like protein, a novel marker of active bone formation. RESULTS: In the 10-g load group, the amount of tooth movement increased dramatically between days 5 and 7 and increased gradually thereafter. Tooth movement at days 5 and 7 was significantly lower in the 30-g-load group than in the 10-g load group; however, the total tooth movement at 14 days was similar in the 2 groups. An orthodontic load of 30 g stimulated bone formation on the sinus wall, but bone resorption on the periodontal ligament side was delayed because of hyalinization, which means that strong force application did not accelerate tooth movement. Moreover, some root resorption was induced by the excessive force. CONCLUSIONS: Root penetration into the sinus and bone height reduction do not occur because new bone formation on the maxillary sinus is induced before bone resorption on the periodontal side, even though an excessive orthodontic force is applied. However, an excessive force can induce root resorption.

Torque ratio as a predictable factor on primary stability of orthodontic miniscrew implants.

OBJECTIVE: To evaluate the torque ratio (TR) as a predictable factor on primary stability of orthodontic miniscrews. DESIGN: Fifty-eight orthodontic patients (17 men, 41 women; mean age, 21.9 years) with a total of 112 titanium miniscrews of 3 different diameters were subjected. Maximum insertion torque (MIT) and maximum removal torque (MRT) were measured by a digital torque checker at the screw placement. Four weeks after the placement, the stable screw was recorded as a success. Multiple logistic regression analysis was performed to estimate the influence of each clinical variable on success. RESULTS: Success rates were 82.1% to 89.5%, and there were no significant differences in the 3 types of miniscrews. MIT and MRT showed a positive correlation but did not affect the success rates of miniscrews directly. On the contrary, TR was significantly higher in the success group than in the failure group. In multiple regression analysis, age, TR, and screw proximity had a significant influence on the miniscrew success. CONCLUSIONS: TR might be related with the miniscrew success rates, and it can be used as a predictable factor on primary stability of orthodontic miniscrew implants. Miniscrew implants should be replaced if MRT is significantly lower than MIT at placement surgery.

Long-term stability of implant-anchored orthodontics in an adult patient with a Class II Division 2 malocclusion and a unilateral molar scissors-bite.

This article reports the successful treatment using miniscrew anchorage of an adult patient with a severe deep overbite and a unilateral scissors-bite. A 23-year-old woman had chief complaints of maxillary incisal crowding and difficulty chewing. She was diagnosed with a severe Class II Division 2 malocclusion with anterior crowding and a unilateral scissors-bite caused by buccal elongation of the maxillary left second molar. The maxillary first premolars were extracted, and 3 miniscrews were implanted as skeletal anchorage to resolve the functional and esthetic problems. The total active treatment period was 41 months. As a result of the implant-anchored orthodontic treatment, both the patient's facial profile and occlusion significantly improved. The asymmetric movements of the incisor paths and bilateral condyles during lateral excursions disappeared. The satisfactory facial profile and resultant occlusion were maintained throughout a 49-month retention period. The patient was satisfied with the treatment results.

Interdisciplinary treatment of a nonsyndromic oligodontia patient with implant-anchored orthodontics.

We successfully treated a nonsyndromic oligodontia patient with implant-anchored orthodontics and prosthetic restorations. A woman, age 18 years 11 months, had a straight profile and a skeletal Class I jaw-base relationship but had spaced arches because of 7 congenitally missing teeth. After leveling and alignment of the dentition, a titanium miniscrew was temporarily placed at the distal alveolus of the mandibular right first premolar, and the posterior teeth were mesialized to reduce the restorative spaces. After determination of the incisor positions, 3 dental implants were respectively inserted at the sites of the maxillary canines and the mandibular left lateral incisor with guided bone regeneration procedures. Then, screw-retained temporary prostheses were delivered after subepithelial connective tissue grafting and used for molar mesialization as absolute anchorage. After 36 months of active orthodontic treatment, an acceptable occlusion was achieved, both functionally and esthetically, with the 3 dental implants. The maxillary and mandibular molars were mesialized, but the changes of incisor position were minimal. As a result, a proper facial profile was maintained, and an attractive smile was achieved. The resultant occlusion was stable throughout a 3-year retention period. In conclusion, interdisciplinary treatment combined with orthodontics, implant surgery, and prosthodontics was useful for a nonsyndromic oligodontia patient. Especially, the new strategy-implant-anchored orthodontics-can facilitate the treatment more simply with greater predictability.

Substrate distortion contributes to the catalysis of orotidine 5'-monophosphate decarboxylase.

Orotidine 5'-monophosphate decarboxylase (ODCase) accelerates the decarboxylation of orotidine 5'-monophosphate (OMP) to uridine 5'-monophosphate (UMP) by 17 orders of magnitude. Eight new crystal structures with ligand analogues combined with computational analyses of the enzyme's short-lived intermediates and the intrinsic electronic energies to distort the substrate and other ligands improve our understanding of the still controversially discussed reaction mechanism. In their respective complexes, 6-methyl-UMP displays significant distortion of its methyl substituent bond, 6-amino-UMP shows the competition between the K72 and C6 substituents for a position close to D70, and the methyl and ethyl esters of OMP both induce rotation of the carboxylate group substituent out of the plane of the pyrimidine ring. Molecular dynamics and quantum mechanics/molecular mechanics computations of the enzyme-substrate complex also show the bond between the carboxylate group and the pyrimidine ring to be distorted, with the distortion contributing a 10-15% decrease of the ΔΔG(⧧) value. These results are consistent with ODCase using both substrate distortion and transition-state stabilization, primarily exerted by K72, in its catalysis of the OMP decarboxylation reaction.

Relationship between orthodontic expertise and perception of need for orthodontic treatment for mandibular protrusion in Japan.

The aims of this study were to investigate how the Peer Assessment Rating (PAR index) predicts the perceived need for orthodontic treatment of mandibular protrusion in Japanese subjects, and to elucidate whether the perceived need for treatment was affected by the raters' orthodontic expertise. The subjects were 110 dental students and 32 orthodontists. We showed them casts of 10 untreated mandibular protrusion cases and gave them a questionnaire in which they had to describe their perceptions of the orthodontic treatment needs using a 10-point visual analog scale (VAS). The PAR index was used for cast evaluation. The PAR index scores showed significant correlations with the VAS scores. In casts with a low PAR score, there were no differences in the VAS scores between orthodontists and students. In casts with a PAR score greater than 23, the orthodontists perceived a significantly greater treatment need than did the students;for scores of 22, 28, and 29, students who had received orthodontic treatment themselves were more likely to perceive the treatment need. The PAR index is a good clinical predictor for assessing the perceived treatment needs for mandibular protrusion. Perception of the need for orthodontic treatment for mandibular protrusion depended on the degree of orthodontic expertise in Japanese subjects.

Mechanical stress induces bone formation in the maxillary sinus in a short-term mouse model.

OBJECTIVES: Clinicians occasionally face the challenge of moving a tooth through the maxillary sinus. The objective of this study was to evaluate tissue remodeling during tooth movement into the maxillary sinus, more specifically as regards to bone formation. MATERIALS AND METHODS: The maxillary first molar of 20 male mice was moved toward the palatal side by a nickel-titanium super elastic wire for 1 to 14 days, and the bone remodeling around the root was evaluated using histomorphometry and immunodetection of bone-restricted Ifitm-like (Bril) protein, a novel marker of active bone formation. RESULTS: When mechanical stress was applied to the tooth, the periodontal ligament on the palatal side was immediately compressed to approximately half of its original width by the tipping movement of the tooth. At the same time, osteoblasts deposited new bone on the wall of the maxillary sinus prior to bone resorption by osteoclasts on the periodontal side, as evidenced by the high level of expression of Bril at this site. As a result of these sequential processes, bone on the sinus side maintained a consistent thickness during the entire observation period. No root resorption was observed. CONCLUSIONS: Bone formation on the surface of the maxillary sinus was evoked by mechanotransduction of mechanical stress applied to a tooth over a 2-week period, and was induced ahead of bone resorption on the periodontal ligament side. CLINICAL RELEVANCE: Mechanical stress can be exploited to induce bone formation in the maxillary sinus so that teeth can be moved into the sinus without losing bone or causing root damage.

Orthodontic occlusal reconstruction after conservative treatment of unicystic ameloblastoma in an adolescent patient: 10-year follow-up.

Conservative treatment of an ameloblastoma often requires an occlusal reconstruction. In this article, we report the successful interdisciplinary treatment of a 14-year-old girl with a unicystic ameloblastoma in the mandible. One year after the marsupialization, enucleation with bone curettage was performed with extraction of the impacted third molar, but the proximal second molar could be maintained. The conservative treatment required long-term use of an obturator, and it caused a total open bite. Additionally, the patient genetically had a Class II malocclusion with severe crowding. Consequently, orthodontic treatment was performed after 4 premolar extractions. There was no recurrence of the ameloblastoma 10 years after the enucleation.

Indirect usage of miniscrew anchorage to intrude overerupted mandibular incisors in a Class II patient with a deep overbite.

Vertical dentoalveolar discrepancies are a common problem in orthodontic patients but are often difficult to treat with traditional mechanics. This case report illustrates the successful treatment of overerupted mandibular incisors via the indirect use of miniscrew anchorage. A woman (age, 22 years 9 months) had chief complaints of maxillary incisor protrusion and crooked teeth. An excessive curve of Spee caused by elongation of the mandibular incisors was also found. The patient was diagnosed with a severe Class II Division 1 malocclusion and a deep overbite. After extraction of the mandibular first premolars and the subsequent leveling phase, the elongated incisors were intruded with a novel method, which involved the combined use of sectional archwires and miniscrews placed in the premolar areas. After the procedure, the mandibular incisors had been intruded by 6.5 mm with no undesirable side effects. The total active treatment period was 42 months. The resultant occlusion and satisfactory facial profile were maintained after 30 months of retention. Our novel intrusion approach shows potential for correcting a deep overbite.

Odontogenic ameloblast-associated and amelotin are novel basal lamina components.

Odontogenic ameloblast-associated (ODAM) and amelotin (AMTN) are secreted by maturation stage ameloblasts and accumulate at the interface with enamel where an atypical basal lamina (BL) is present. This study aimed at determining and quantifying the ultrastructural distribution of ODAM and AMTN at the cell-tooth interface. Ultrathin sections of enamel organs from the early to mid- and late maturation stage of amelogenesis were processed for immunogold labeling with antibodies against ODAM, AMTN or with the lectins wheat germ agglutinin, Helix pomatia agglutinin (HPA) and Ricinus communis I agglutinin. Immunolabeling showed that both ODAM and AMTN localized to the BL. Quantitative analyses indicated that at the beginning of maturation there is a concentration of ODAM on the cell side of the BL while AMTN appears more concentrated on the enamel side. In the late maturation stage, such differential distribution is no longer apparent. All three lectins are bound to the BL. Competitive incubation with native lectins did not affect the binding efficiency of ODAM; however, AMTN binding was significantly reduced after incubation with HPA. In conclusion, ODAM and AMTN are bona fide components of the BL associated with maturation stage ameloblasts and they organize into different subdomains during the early maturation stage. The data also suggest that the BL is a dynamic structure that rearranges its organization as enamel maturation advances. Finally, the abrogation of AMTN antibody labeling by HPA supports the presence of O-linked sugars in the molecule and/or its close association with other O-glycosylated molecules.

Long-term stability of conservative orthodontic treatment in a patient with rheumatoid arthritis and severe condylar resorption.

Rheumatoid arthritis is a chronic inflammatory condition that can result in progressive destruction of the articular surfaces of the joints, including the temporomandibular joint. The purpose of this article is to report the conservative correction of a Class II malocclusion in a woman with rheumatoid arthritis. The patient was 32 years 6 months old at the start of treatment. She had a convex profile and a skeletal Class II jaw-base relationship caused by severe condylar resorption. An anterior open bite of -2.0 mm and an excessive overjet of 10.0 mm were observed. Severe crowding was shown in the mandibular incisors. After 8 months of splint therapy, all first premolars were extracted, and 0.018-in preadjusted edgewise appliances were placed in both arches. Class II elastics were used during space closure. After 41 months of active orthodontic treatment, an acceptable occlusion was achieved, and the facial profile was considerably improved. From the cephalometric evaluations, the mandible was rotated counterclockwise, and the mandibular plane angle was significantly decreased. However, the anteroposterior position of the chin was not changed. The condylar resorption was not changed during and after orthodontic treatment. Conclusively, the proper facial profile was maintained, and the occlusion was stable after a 5-year retention period. Our results suggest the possibility of compromised treatment in a Class II malocclusion with an anterior open bite because of rheumatoid arthritis.

Severity of alveolar cleft before palatoplasty affects vertical maxillofacial growth in 6-year-old patients with complete unilateral cleft lip and palate.

INTRODUCTION: In this study, we investigated the association between the severity of alveolar clefts in infants and the succeeding maxillofacial growth in patients affected by complete unilateral cleft lip and palate. METHODS: The subjects were 35 nonsyndromic patients affected by unilateral cleft lip and palate (n = 27) or bilateral cleft lip and palate (n = 8). Plaster models and lateral cephalograms taken at 6 years of age were analyzed and compared with the Japanese norms. In the unilateral cleft lip and palate patients, the relationship between the width of the alveolar cleft before palatoplasty and the skeletal characteristics was also explored. RESULTS: Significant deficiencies of the posterior maxilla and steep palatal planes were noted in both the unilateral and bilateral cleft lip and palate patients. However, they were not clearly observed in the unilateral cleft lip and palate patients born with a small alveolar cleft and were correlated with the severity of alveolar cleft in infancy. Neither cleft type nor the severity of the alveolar cleft was implicated in the maxillary arch form in childhood, but the growth of the alveolar height on the cleft side was less in the unilateral cleft lip and palate patients born with a large alveolar cleft. CONCLUSIONS: The severity of the alveolar cleft before palatoplasty affects the succeeding vertical maxillofacial growth in patients affected by unilateral cleft lip and palate; this suggests the necessity of a different diagnosis and treatment in unilateral cleft lip and palate patients according to the severity of the alveolar cleft in infancy.

Segmental distraction osteogenesis with modified LeFort II osteotomy for a patient with craniosynostosis.

In this article, we report successful orthodontic treatment combined with segmental distraction osteogenesis after a modified LeFort II osteotomy in a patient with craniosynostosis. An 8-year-old boy diagnosed with craniosynostosis had a dished-in face, an anterior crossbite, and a skeletal Class III jaw relationship because of midfacial hypoplasia. At the age of 13 years 6 months, the maxillary second and mandibular first premolars were extracted, and leveling and alignment of both arches was started with preadjusted edgewise appliances. At age 14 years 11 months, the patient had a modified LeFort II osteotomy, and the maxillary segment was advanced 7 mm and fixed to the zygomatic bone. At the same time, segmental distraction osteogenesis was started with a rigid external distraction system, and the nasal segment was advanced for 20 days at a rate of 1.0 mm per day. The total active treatment period was 40 months. As a result of the modified segmental distraction osteogenesis, significant improvement of his severe midfacial hypoplasia was achieved without excessive advancement of the maxillary dentition. Both the facial profile and the occlusion were stable after 1 year of retention. However, the nasal segment relapsed 1.4 mm during the 1.5 years after the segmental distraction osteogenesis. Evaluation of the stability and retention suggests that some overcorrection in midfacial advancement is recommended.

Functional improvements after orthodontic-surgical reconstruction in a patient with multiple maxillofacial fractures.

Patients with multiple craniofacial fractures often suffer from stomatognathic problems after their primary treatment, because administering emergency care is the clinician's highest priority. Therefore, optimal bone repositioning is sometimes difficult because bone fixation is delayed. Moreover, neither an adequate radiographic examination nor an evaluation of primary occlusion is available during the repair of fractured bones. The lack of these assessments can also lead to occlusal dysfunction after bone fixation. As a result, patients with craniofacial fractures often require occlusal reconstruction. This report describes the successful occlusal reconstruction with orthodontic-surgical treatment of a patient with multiple maxillofacial bone fractures. Combined surgery, including an intraoral vertical ramus osteotomy and a mandibular body osteotomy, was performed to reposition the deviated mandible after 3 months of preoperative orthodontic treatment. The total active treatment period was 25 months. After treatment, both the facial asymmetry and the anterior open bite caused by the skeletal disharmony were significantly improved. Additionally, the range of condylar motion, maximum occlusal force, and occlusal contact area during maximum clenching were also increased. These stomatognathic functions were further enhanced by 2 years of retention. Orthodontic-surgical reconstruction appears to improve both facial esthetics and occlusal function in patients with facial asymmetry caused by severe traumatic maxillofacial fractures.