Diazo-Transfer Reaction of Nonactivated Ketones with 2-Azido-1,3-bis(2,6-diisopropylphenyl)imidazolium Hexafluorophosphate (IPrAP).

The diazo-transfer reaction of nonactivated ketone under mild reaction conditions was developed. Various nonactivated ketones such as aryl methyl ketones, sec-alkyl methyl ketones, and cyclic ketones were transformed into their corresponding α-diazoketones in one step by treating 2-azido-1,3-bis(2,6-diisopropylphenyl)imidazolium hexafluorophosphate (IPrAP) in the presence of iPr2NH in ethylene glycol. In the reaction of IPrAP with prim-alkyl methyl ketone and prim-alkyl aryl ketones, migratory amidation proceeded under the reaction conditions to afford the corresponding amides.

Safety, tolerability, and pharmacokinetics of half-life extended SARS-CoV-2-neutralizing monoclonal antibodies AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults.

INTRODUCTION: The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults. METHODS: In this randomized, double-blind, placebo-controlled, phase 1 study, AZD7442 was administered intramuscularly (300 or 600 mg) or intravenously (300 or 1000 mg) to healthy Japanese adults. Primary endpoints were safety, tolerability, and pharmacokinetics. Anti-drug antibodies and neutralizing antibody activities were secondary endpoints. RESULTS: A total of 40 participants were randomized to receive AZD7442 (n = 30) or placebo (n = 10). Adverse events (AEs) occurred in 12 (40%) and 3 (30%) participants, respectively; there were no deaths, serious AEs, or AEs leading to study withdrawal. Tixagevimab and cilgavimab had mean half-lives of 82.1-95.9 and 77.9-92.0 days, respectively, which were generally similar regardless of administration route. SARS-CoV-2-neutralizing antibody titers were >4-fold higher than baseline levels from Day 8 to Day 211 in participants receiving AZD7442. CONCLUSIONS: AZD7442 was well tolerated in healthy Japanese adults, with predictable pharmacokinetics and an extended half-life, consistent with previous studies. CLINICALTRIALS: gov, NCT04896541.

Cancer Awareness and Understanding of Students in Japan: What Do Students Having Close Relatives with Cancer Think About the Disease?

Students have become more familiar with cancer because of media, such as television or the Internet, reporting on celebrity cancer cases. Moreover, with Japan's increasing age and cancer rates, the number of students whose parents/relatives develop cancer is likely to increase. This study examined cancer awareness and understanding among students aged 10 to 16 or more. A cross-sectional nationwide survey was conducted using a self-administered questionnaire. Cancer awareness and cancer understanding were assessed using a self-administered questionnaire. We collected a total of 9139 questionnaires and excluded those with missing data. Thus, we analyzed the responses of 8701 students: 2135, 2902, and 3664 from elementary, junior, and high school, respectively. Data were analyzed using a multivariable model adjusted for gender and grade. Approximately 30% of respondents had parents/relatives with cancer. In addition, there was a significant association between having parents/relatives with cancer and cancer awareness; however, students having parents/relatives with cancer had more negative awareness (i.e., "I think cancer is scary," "I think I will get cancer in the future," and "I think cancer is preventable"). Furthermore, there was a significant association between cancer understanding and awareness. These findings suggest that cancer education could have a desirable effect on students whose parents/relatives have cancer. Further, cancer education offers benefits to students who are naive about cancer and ill prepared to cope when a family member discloses a cancer diagnosis.

A Cross-sectional Investigation of Cancer-Screening Intentions, Sources of Information, and Understanding of Cancer in Japanese Adolescents.

The purpose of this study was to describe the cancer-screening intention, sources of cancer information, and cancer understanding among Japanese adolescents. A cross-sectional nationwide survey involving a self-administered questionnaire was conducted. Response rates of the target schools were 46.4 % (n = 103) for junior high schools and 55.8 % (n = 116) for high schools. From these, we analyzed the data of 2960 junior high school students (1520 males, 1440 females) and 3703 high school students (1546 males, 2157 females) to examine the association between cancer-screening intention and sources of cancer-related information and understanding. A significant association between cancer-screening intention and sources of cancer information and cancer understanding was observed. The screening intention group identified more sources of cancer information than the no-screening intention group did. Understanding about cancer was reported by a higher proportion of students in the screening intention group compared with the no-screening intention group. Recognition that healthy people must take part in cancer screening was significantly associated with screening intention in both junior high (odds ratio (OR), 1.859; 95 % confidence interval (CI), 1.582-2.185; P < 0.001) and high school (OR, 2.485; 95 % CI, 2.139-2.887; P < 0.001) students. Health education at school was indicated by a high proportion of students as a source of cancer-related information, although the association was not significant. The present survey indicated that those in of our sample who intended to undergo future cancer screening (67.8 %) had more sources of information and understanding regarding cancer. Thus, schools should enrich health education curricula with more information and understanding about cancer to promote cancer-screening intention among Japanese adolescents.

Effects of DPP-4 inhibitor linagliptin and GLP-1 receptor agonist liraglutide on physiological response to hypoglycaemia in Japanese subjects with type 2 diabetes: A randomized, open-label, 2-arm parallel comparative, exploratory trial.

Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce the risk of hypoglycaemia, possibly through augmentation of glucose-dependent insulinotropic polypeptide (GIP) action, but not that of glucagon-like peptide-1 (GLP-1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP-4 inhibitor linagliptin on glucagon and other counter-regulatory hormone responses to hypoglycaemia were evaluated and compared with those of the GLP-1 receptor agonist liraglutide in a multi-centre, randomized, open-label, 2-arm parallel comparative, exploratory trial. Three-step hypoglycaemic clamp glucose tests preceded by meal tolerance tests were performed before and after 2-week treatment with the drugs. Glucagon levels were increased during the hypoglycaemic clamp test at 2.5 mmol/L. This increase was similar in the linagliptin and liraglutide groups, both before and after the 2-week treatment. Changes in other counter-regulatory hormones (ie, growth hormone, cortisol, epinephrine and norepinephrine) were also similar between the groups, but were suppressed substantially after 2-week treatment compared to baseline. In conclusion, we confirmed that the glucagon response to hypoglycaemia was not affected by linagliptin or liraglutide treatment in Japanese individuals with T2D.

[Anesthetic Management of a Patient with von Recklinghausen Disease after Surgeries for Thoracic and Spinal Neurofibroma].

Von Recklinghausen disease is an autosomal domi- nant neurocutaneous disorder, characterized by cuta- neous neurofibromas, accompanied by café-au-lait spots. We report a case of a 51-year-old man with von Recklinghausen disease who had been operated on for thoracic and spinal neurofibroma. Exploratory thoracotomy was performed under general anesthesia combined with epidural anesthesia. After tracheal intubation with spiral tube, one lung ventilation was performed using blocker tube. General anesthesia was maintained by inhalation of oxygen, air, and desflurane and the continuous infusion of remifentanil. The opera- tive course was uneventful. The patient emerged from general anesthesia smoothly, and was extubated safely. There was no neurological abnormality after operation. Preoperative evaluation of airway status and neuro- logical findings are essential in the anesthetic management of the patient with von Recklinghausen disease. This case suggests that we must take the complication into account for anesthetic management and select the appropriate anesthetic method by routine preoperative estimation. It is of great importance that anesthesiologists evaluate the airway status and neurological find- ings of patients with von Recklinghausen disease.

Cancer understanding among Japanese students based on a nationwide survey.

OBJECTIVE: The objective of this study was to determine cancer understanding among Japanese primary and secondary school students. METHODS: The study design was a cross-sectional nationwide survey using a self-administered questionnaire. The prefecture with the lowest student population was set to 1, and that with the highest student population was set to 18 for elementary schools and 19 for junior high and high schools based on the ratio of the student population. In this way, 213 elementary schools, 222 junior high schools, and 208 high schools were selected from all 47 prefectures in Japan, and questionnaires were sent to each school. The questionnaire listed the names of 15 cancers and asked respondents to choose one answer from three: "Never heard of," "Heard of/Don't understand," or "Heard of/Understand." RESULTS: Response rates for schools were 44.1 % (n = 94) for elementary schools, 46.4 % (n = 103) for junior high schools, and 55.8 % (n = 116) for high schools. A total of 8,876 questionnaires were used for the analysis. Our survey suggests that the most commonly understood types of cancer differed by grade, with lung cancer the most commonly understood in elementary school, leukemia in junior high schools, and breast cancer in high schools. Girls tended to demonstrate greater cancer understanding than boys, with particularly large differences by gender in rates of understanding of breast and uterine cancer at each assessed grade level. CONCLUSIONS: Here, we examined Japanese primary and secondary school students. Marked differences in cancer recognition by grade and gender suggest that educational efforts are needed at various grade levels and gender-specific cancer education. Further, more than 50 % of students at any school level were not familiar with most cancers. It suggests that cancer education is deficient.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. METHODS: This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 µg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. RESULTS: There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. CONCLUSIONS: A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. TRIAL REGISTRATION: NCT number: NCT04354480; Clinical Registry number: CR108768.

Retrospective analysis of severe neutropenia in patients receiving concomitant administration of docetaxel and clarithromycin.

BACKGROUND: Neutropenia is one of the most important dose-limiting toxicities of docetaxel. Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Clarithromycin, a potent inhibitor of CYP3A4, is occasionally used in combination with docetaxel. The aim of this study was to evaluate whether the risk of severe neutropenia induced by docetaxel was increased by concomitant administration of clarithromycin. METHODS: Patients with advanced lung cancer receiving docetaxel were identified from an electronic medical record system and divided into 2 groups: concomitant administration of clarithromycin and no concomitant administration of clarithromycin. The proportion of patients experiencing grade 4 neutropenia between the 2 groups was compared. Potential risk factors associated with grade 4 neutropenia were also examined using univariate and multivariate logistic regression analyses. RESULTS: One hundred and fifty-eight patients were analysed. Grade 4 neutropenia was more frequently detected in the patients receiving clarithromycin than in those not receiving the drug (63.2 vs. 35.3%; p = 0.025). Multivariate analysis showed that co-administration of clarithromycin [odds ratio (OR) 4.98; p = 0.004], pre-treatment absolute neutrophil count (OR 2.62; p = 0.011) and female gender (OR 2.75; p = 0.029) resulted in an increase in the incidence of grade 4 neutropenia. CONCLUSIONS: This study shows that concomitant administration of clarithromycin potentiated docetaxel-induced myelosuppression.

Pharmacokinetics and Bioequivalence of Mirogabalin Orally Disintegrating Tablets and Conventional Tablets in Healthy Japanese Participants.

This single-center, randomized, open-label, single-dose, 2-group, 2-stage crossover trial evaluated the bioequivalence of 15 mg of mirogabalin as orally disintegrating tablets (ODTs) with conventional mirogabalin tablets in healthy Japanese men. The trial involved two studies: in Study 1, the ODT formulation was taken without water, and in Study 2, the ODT formulation was taken with water. The conventional tablet was taken with water in both studies. We investigated the pharmacokinetic parameters and bioequivalence of the 2 formulations, including the maximum plasma concentration and the area under the plasma concentration-time curve up to the last quantifiable time. The plasma concentrations of mirogabalin were determined by a validated liquid chromatography with tandem mass spectrometry method. A total of 72 participants were enrolled and completed the trial. The geometric least-squares mean ratios of maximum plasma concentration of the ODT formulation to the conventional formulation were within the prespecified bioequivalence range of 0.80-1.25 (Study 1, 0.995; Study 2, 1.009), as was the area under the plasma concentration-time curve up to the last quantifiable time (Study 1, 1.023; Study 2, 1.035). No serious adverse events were observed. In conclusion, mirogabalin 15-mg ODTs, either with or without water, were bioequivalent to conventional 15-mg tablets.

Safety, reactogenicity, and immunogenicity of Ad26.COV2.S: Results of a phase 1, randomized, double-blind, placebo-controlled COVID-19 vaccine trial in Japan.

BACKGROUND: This study evaluated safety, reactogenicity, and immunogenicity of a 2-month homologous booster regimen of Ad26.COV2.S in Japanese adults. METHODS: In this multicenter, placebo-controlled, Phase 1 trial, adults (Cohort 1, aged 20-55 years, N = 125; Cohort 2, aged ≥ 65 years, N = 125) were randomized 2:2:1 to receive Ad26.COV2.S 5 × 1010 viral particles (vp), Ad26.COV2.S 1 × 1011 vp, or placebo, followed by a homologous booster 56 days later. Safety, reactogenicity, and immunogenicity were assessed. RESULTS: Two hundred participants received Ad26.COV2.S and 50 received placebo. The most frequent solicited local adverse event (AE) was vaccination-site pain, and the most frequent solicited systemic AEs were fatigue, myalgia, and headache. After primary vaccination, neutralizing and binding antibody levels increased through Day 57 (post-prime) in both cohorts. Fourteen days after boosting (Day 71), neutralizing antibody geometric mean titers (GMTs) had almost reached their peak value in Cohort 1 (5 × 1010 vp: GMT = 1049; 1 × 1011 vp: GMT = 1470) and peaked in Cohort 2 (504; 651); at Day 85, GMTs had declined minimally in Cohort 2. For both cohorts, binding antibody levels peaked at Day 71 with minimal decline at Day 85. CONCLUSION: A single dose and homologous Ad26.COV2.S booster increased antibody responses with an acceptable safety profile in Japanese adults (ClinicalTrials.gov Identifier: NCT04509947).

DS-5670a, a novel mRNA-encapsulated lipid nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2: Results from a phase 2 clinical study.

BACKGROUND: DS-5670a is a vaccine candidate for coronavirus disease 2019 (COVID-19) harnessing a novel modality composed of messenger ribonucleic acid (mRNA) encoding the receptor-binding domain (RBD) from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encapsulated in lipid nanoparticles. Here, we report the safety, immunogenicity, and pharmacokinetic profile of DS-5670a from a phase 2 clinical trial in healthy adults who were immunologically naïve to SARS-CoV-2. METHODS: The study consisted of an open-label, uncontrolled, dose-escalation part and a double-blind, randomized, uncontrolled, 2-arm, parallel-group part. A total of 80 Japanese participants were assigned to receive intramuscular DS-5670a, containing either 30 or 60 µg of mRNA, as two injections administered 4 weeks apart. Safety was assessed by characterization of treatment-emergent adverse events (TEAEs). Immunogenicity was assessed by neutralization titers against SARS-CoV-2, anti-RBD immunoglobulin (Ig)G levels, and SARS-CoV-2 spike-specific T cell responses. Plasma pharmacokinetic parameters of DS-5670a were also evaluated. RESULTS: Most solicited TEAEs were mild or moderate with both the 30 and 60 µg mRNA doses. Four participants (10 %) in the 60 µg mRNA group developed severe redness at the injection site, but all cases resolved without treatment. There were no serious TEAEs and no TEAEs leading to discontinuation. Humoral immune responses in both dose groups were greater than those observed in human convalescent serum; the 60 µg mRNA dose produced better responses. Neutralization titers were found to be correlated with anti-RBD IgG levels (specifically IgG1). DS-5670a elicited antigen-specific T helper 1-polarized cellular immune responses. CONCLUSIONS: The novel mRNA-based vaccine candidate DS-5670a provided favorable immune responses against SARS-CoV-2 with a clinically acceptable safety profile. Confirmatory trials are currently ongoing to evaluate the safety and immunogenicity of DS-5670a as the primary vaccine and to assess the immunogenicity when administered as a heterologous or homologous booster. TRIAL REGISTRY: https://jrct.niph.go.jp/latest-detail/jRCT2071210086.

Bioequivalence of Esaxerenone Conventional Tablet and Orally Disintegrating Tablet: Two Single-Dose Crossover Studies in Healthy Japanese Men.

We assessed the bioequivalence of a single dose of 5-mg of esaxerenone administered as an orally disintegrating tablet (ODT) with the conventional oral tablet in healthy Japanese men. This single-center, open-label, randomized, two-drug, two-stage crossover, single-dose study was conducted in two parts. In study 1, both formulations were taken with water. In study 2, only the ODT formulation was taken without water. The primary outcome was the evaluation of bioequivalence of the ODT and conventional tablet using the pharmacokinetic (PK) parameters maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve to the last quantifiable time (AUClast ). Plasma concentrations were measured using a validated liquid chromatography/mass spectrometry method and PK parameters were calculated by noncompartmental analysis. The ratios of the geometric least-squares mean (2-sided 90% confidence intervals [90%CIs]) for ODT with (study 1) and without (study 2) water to the conventional tablet were 1.03 (1.00-1.07) and 1.01 (0.96-1.06) for Cmax and 1.03 (1.00-1.07) and 0.96 (0.94-0.98) for AUClast , respectively. The 90%CIs fell within the predefined bioequivalence range of 0.80-1.25. Treatment-emergent adverse events were similar between both formulations. In conclusion, esaxerenone 5-mg ODT taken with or without water was bioequivalent to a single 5-mg conventional oral tablet.

A randomized, single-dose, pharmacokinetic equivalence study comparing MB02 (proposed biosimilar) and reference bevacizumab in healthy Japanese male volunteers.

PURPOSE: MB02 is a biosimilar to bevacizumab that has demonstrated similar physicochemical and functional properties in in vitro studies to the reference bevacizumab (Avastin®). This study aims to assess the pharmacokinetic (PK) similarity of MB02 to the reference bevacizumab in Japanese population. METHODS: This double-blind, randomized, parallel-group, single-dose PK study, was performed in healthy Japanese male volunteers. Subjects were equally randomized (1:1) to receive a single (3 mg/kg) IV dose of MB02 or reference bevacizumab. PK assessments were done up to 70 days post-dose. Non-compartmental parameters were calculated. PK similarity was determined using predefined equivalence range (0.80-1.25) for the area under the serum concentration-time curve from time 0 extrapolated to infinity (AUC0-∞). Immunogenicity samples were taken pre-dose and up to day 70. Safety was assessed throughout the study. RESULTS: In total, 48 subjects (24 in each treatment group) were dosed. Consequently to the observed similar PK profile, the 90% confidence interval for the geometric means ratio for the primary PK endpoint, AUC0-∞, was within the predefined equivalence range (0.981-1.11). Forty-seven treatment-emergent adverse events (TEAEs) were reported in 20 subjects (41.7%) with comparable incidence among MB02 and reference bevacizumab groups (22 and 25, respectively), none of them was severe or serious. Anti-drug antibodies incidence was low and similar between treatment groups. CONCLUSIONS: Pharmacokinetic similarity of MB02 to reference bevacizumab was evidenced in Japanese healthy subjects, with comparable safety and immunogenicity profile between treatments. This study supports the biosimilarity of MB02 to reference bevacizumab in Japanese population. ClinicalTrials.gov identifier: NCT04238650.

Levocetirizine Oral Disintegrating Tablet: A Randomized Open-Label Crossover Bioequivalence Study in Healthy Japanese Volunteers.

Levocetirizine is classified as a second-generation antihistamine. Levocetirizine is available for the treatment of allergic disorders such as allergic rhinitis and chronic idiopathic urticaria. This was a single-center, single-dose, open-label, randomized, 2-way crossover study in healthy Japanese male subjects consisting of 2 parts. Part 1 compared the bioavailability of levocetirizine oral disintegrating tablet (ODT) and levocetirizine immediate-release tablet (IRT) taken with water in the fasted state in 24 subjects; all subjects completed this part of the trial. In part 2, the bioavailability of levocetirizine ODT without water was compared with that of levocetirizine IRT with water in the fasted state in 48 subjects; 47 subjects completed this part of the trial. Bioequivalence was demonstrated between levocetirizine IRT 5 mg and ODT 5 mg. The safety profiles were generally similar between levocetirizine ODT and levocetirizine IRT, with no serious adverse events, deaths, or adverse events leading to withdrawal reported during the study.

Point of care testing system via enzymatic method for the rapid, efficient assay of glycated albumin.

The ratio of glycated albumin to albumin concentration in serum is termed the glycated albumin (GA) value. The GA value provides a time-averaged index of the state of glycemic control for the previous 2 weeks. In this study, a dry chemistry system (GA monitor) via an enzymatic method was proposed in order to provide a GA value measurement for point of care testing (POCT). The GA monitor was made from three devices a set of test-tapes, a test-strip and an optical analyzer. A GA test-tape, a ketoamine test-tape and an albumin test-tape were enclosed in the fabricated test-strip. Time-course changes of the optical characteristics were evaluated using the test-strip. It was found that the three test tapes must be enclosed in the test-strip to create a dry chemistry system for small sample volumes (20 microl). A temperature control unit, which could hold the temperature of the GA test-tape at 45 degrees C and at 25 degrees C for the other two types of test-tape was incorporated into the optical analyzer. With the GA test-tape held separately and controlled at 45 degrees C, the analytical time decreased to one-third of the time taken for the three tapes at 25 degrees C. The analytical accuracy of the three types of test-tape showed favorable results, with R2 values of 0.96-0.98 and coefficients of variation (CV) of 2.4-6.8%. Compared with a commercially available liquid chemistry system, the analytical accuracy of the GA monitor exhibited a relatively favorable linearity of R=0.82. According to these results, a new GA value analytical system was realized, in which the GA value could be assayed within five minutes using only 20 microl of blood sample with a disposable test-strip. This system could potentially be used for clinical purposes as test equipment for rapid and efficient POCT.

[A case of hypersensitivity pneumonitis caused by inhalation of Mycobacterium avium from a home bath with a circulating water system].

A 26-year-old man presented with complaints of exertional dyspnea and cough. The patient has already been given corticosteroids at a previous hospital. Chest CT revealed small centrilobular nodules with diffuse ground-glass opacities in both lungs. Lung biopsy specimens at thoracoscopy revealed non-necrotizing granulomas, patchy foci of mononuclear cell infiltration and fibrous thickening of alveolar septa, and Masson's bodies in bronchioles. Sputum culture showed the growth of Mycobacterium avium complex (MAC). Culture of water from the bath tub of his home showed MAC. Administration of antituberculous drugs and corticosteroids, and avoidance of bathing at home resulted in the improvement of his symptoms and CT findings. We believe the case is hypersensitivity pneumonitis to MAC in an immunocompetent patient, simulating hot tub lung. Hypersensitivity pneumonitis caused by MAC is rare in Japan.

[Mandibular anterior alveolar osteotomy and patient with malocculusion and facial deformity after healed mandibular fracture; report of a case].

Recent advances in orthognatic surgery have been remarkable. Among the surgical procedures, sagital ramus osteotomy has been often used for mandibular protrusion. Causes of dentofacial deformities include not only congenital but also acquired ones, which are caused by trauma or resection of tumor in the maxillofacial region. In all cases, functional and psychological disorders would often occur in the patient with these dentofacial deformities. We report a favorable result of anterior alveolar osteotomy of the mandible, which was applied to a patient complaining of malocculusion and facial deformity developed from a healed fracture of the mandible treated at another hospital.