Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial.

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Pathologic findings in patients who underwent robot-assisted radical prostatectomy following active surveillance: a prospective study in a single center.

AIM: Active surveillance is the recommended treatment of option for men with very low-risk prostate cancer. In this study, the clinicopathological results of patients who were initially treated with active surveillance and subsequently underwent robot-assisted radical prostatectomy during follow-up are described. METHODS: A prospective cohort of 106 men enrolled in active surveillance was reviewed. Pathologic specimens for patients who ultimately underwent robot-assisted radical prostatectomy for progression or personal preference were analyzed. RESULTS: After exclusion of 14 patients who were lost to follow-up or with incomplete data collection, 92 men were included in the present analyses. Median follow-up was 27.6 months (range 3.3 to 193.1). Twenty-nine patients underwent robot-assisted radical prostatectomy. Progression occurred in 32 patients (34.8%), of which 23 men elected to undergo surgery. Robot-assisted radical prostatectomy was performed in 6 additional patients who chose definitive intervention due to anxiety. Pathologic analyses revealed organ-confined disease in 24 patients (82.8%), and Gleason score was ≥ 7 in nine (31%). Fourteen (48.3%) specimens were identified as having an advanced disease (Gleason score ≥ 7 and/or T3). In comparison to the patients with low-risk disease post-operatively (Gleason score <7 and T2), patients with advanced disease had significantly higher PSA density level and lower prostate volume. CONCLUSION: In this prospective active surveillance cohort, the progression rate was 34.8% over the follow-up period of 27.6 months. In specimens of patients who underwent robot-assisted radical prostatectomy, 48.3% displayed advanced pathologic features. Therefore we recommend that patients considering active surveillance should be counseled on risk of advanced disease as a possible hazard.

Oncologic outcomes of laparoscopic nephroureterectomy for pT3 upper urinary tract urothelial carcinoma.

AIM: We present the oncologic outcomes of laparoscopic nephroureterectomy management of pT3 upper urinary tract urothelial carcinoma. METHODS: Between October 2003 and January 2011, 50 patients with pT3 upper urinary tract urothelial carcinoma which had pathologically confirmed underwent laparoscopic nephroureterectomy at our institution. Demographic data, perioperative results, pathological findings and oncologic outcomes were reviewed and analyzed retrospectively. RESULTS: There were 36 patients (72%) of high grade lesion and 14 patients (28%) of low grade lesion. Lymphovascular invasion was observed in 16 patients (32%) and the surgical margin was positive in one patient. N stage was pN0 in 16 (32%), pN1 in 3 (6%), pN2 in 1 (2%) and pN3 in 1 (2%). The 5-year overall survival rate was 52.6% and the 5-year cancer-specific survival rate was 65.3%. Overall recurrence developed in 23 patients. There were 10 patients (20%) of urothelial recurrence which were all occurred in the bladder at the mean period of 13.6 months, and 7 patients of them were invasive bladder cancer. There were 16 patients (32%) of non-urothelial recurrence developed at the mean period of 9.69 months. On multivariate analyses lymphadenopathy and lymph node involvement of cancer (N+) were identified as independent predictive factors for the cancer-specific survival, and concomitant bladder tumor, grade and lymphovascular invasion were identified as independent predictive factors for the overall recurrence free survival. CONCLUSION: Laparoscopic nephroureterectomy in patients with high stage upper urinary tract urothelial carcinoma appear comparable to those of open surgery in the regard of oncologic outcomes.

Orthodontic correction of anterior open bite using skeletal anchorage: systematic review and meta-analysis.

The purpose of this study was to investigate the scientific evidence on the short- and long-term effects of orthodontic correction of anterior open bite (AOB) using skeletal anchorage (SA). Clinical studies on the use of SA for AOB in patients with permanent dentition, or at least 12 years of age, were searched. Short- and long-term (≥2 years) outcomes were collected. Mean differences were calculated from pooled data. Twenty-four eligible articles with a total of 362 subjects were selected for inclusion in the meta-analysis. There was a significant increase in overbite (3.88 mm, P < 0.001) and maxillary molar intrusion (-2.15 mm, P < 0.001). The mandible showed counterclockwise rotation with anterosuperior chin movement (all P < 0.001). Long term, the decrease in overbite was 19.9% and decrease in molar intrusion was 22.9%. The decrease in the mandibular projection was 14.6% for ANB (A-point-nasion-B-point angle) and 46.2% for mandibular anteroposterior position. The overall risk of bias in the included studies was rated as moderate to high, and publication bias existed for several key variables. SA for maxillary molar intrusion effectively improved dental and skeletal outcomes, but there was a long-term decrease in overbite and maxillary molar position. The variable data quality, heterogeneity, and publication bias in investigated outcomes are limitations in interpreting the findings.

ATLAS trial of adjuvant axitinib in patients with renal cell carcinoma: subgroup analyses with focus on axitinib dosing and racial groups.

BACKGROUND: The ATLAS trial, investigating adjuvant axitinib versus placebo in renal cell carcinoma (RCC), was stopped for futility at a preplanned interim analysis. We report subgroup outcome analyses by ethnicity, time on treatment, dose modification and toxicity. PATIENTS AND METHODS: Patient demographics, baseline characteristics, treatment duration and exposure and safety were analysed for Asian versus non-Asian patients treated with axitinib versus placebo. Disease-free survival (DFS) was analysed by ethnicity, treatment duration (≥1 versus <1 year), dose modification and adverse event (AE) grade. RESULTS: No DFS benefit was observed for Asian {hazard ratio (HR) 0.883 [95% confidence interval (CI) 0.638-1.220]} or non-Asian [HR 0.828 (95% CI 0.490-1.400)] patients treated with axitinib or placebo. Fewer Asian versus non-Asian patients were in the highest-risk group in axitinib (51.9% versus 72.3%) or placebo (51.5% versus 66.0%) arm. Highest-risk patients in both subgroups had no DFS benefit with either treatment. More axitinib-treated Asian versus non-Asian patients had dose reductions due to AEs (58.8% versus 46.0%; P = 0.028). Asian patients experienced more nasopharyngitis but less fatigue or asthenia than non-Asians. Among Asian patients, proteinuria, hypothyroidism, nasopharyngitis, and hypertension were more common in Japanese patients than Korean patients and more common in Korean patients than Chinese patients. Patients receiving axitinib >1 year versus ≤1 year did not have different DFS: HR 0.572 (95% CI 0.247-1.327); P = 0.1874. Compared with patients on stable axitinib dose, DFS was longer in patients with dose reduction [HR 0.458 (95% CI 0.305-0.687); P = 0.0001], whereas DFS was not different in those with dose escalation [HR 1.936 (95% CI 0.937-3.997); P = 0.0685]. DFS was not different in patients experiencing grade ≥2 versus <2 AEs within 6 months of initiating axitinib: HR 0.885 (95% CI 0.419-1.869); P = 0.7488. CONCLUSIONS: Asian versus non-Asian subgroup analysis revealed differences in AE experience and drug exposure. There were no DFS differences based on ethnicity or treatment duration, but axitinib dose reduction led to longer DFS.

Influence of mandibular setback surgery on three-dimensional pharyngeal airway changes.

The aim of this study was to investigate the factors influencing three-dimensional changes in pharyngeal airway space after mandibular setback surgery. Airway changes in 48 skeletal class III patients who had undergone mandibular setback surgery alone (n=25, group 1) or with maxillary surgery (n=23, group 2) were analyzed. Linear parameters, cross-sectional area, and volumes of the pharyngeal airway were evaluated before (T0), immediately after (T1), and 1year after surgery (T2) by cone beam computed tomography. Although the reduced airway volume and cross-sectional area recovered slightly in the long term after surgery, the total pharyngeal airway volume (TPV) was significantly reduced compared to baseline, by 15% in group 1 and 12% in group 2. Regression analysis showed that maxillary posterior impaction in two-jaw surgery had a protective effect on preserving TPV. A change in body mass index from T0 to T2 was an important predictor of decreased TPV in one-jaw surgery patients. Maxillary posterior impaction can be a reliable option for compensating the pharyngeal airway reduction after mandibular setback surgery. Postoperative weight gain can increase the risk of postoperative pharyngeal airway reduction. Therefore, these factors need to be considered before and after mandibular setback surgery.

Association of C-509T and T869C polymorphisms of transforming growth factor-beta1 gene with chronic allograft nephropathy and graft survival in Korean renal transplant recipients.

PURPOSE: Transforming growth factor-beta1 (TGF-beta1) has been associated with the promotion of renal allograft interstitial fibrosis and thereby chronic allograft nephropathy (CAN). The literature on TGF-beta1 polymorphisms and their importance in graft survival and CAN is not conclusive. METHODS: TGF-beta1 gene polymorphisms (C-509T and T869C) were examined in a group of 207 Korean renal transplant recipients using real-time polymerase chain reaction assays. The CAN group (n = 18) was defined by a typical biopsy confirming CAN or chronic calcineurin inhibitor nephrotoxicity. The rest of the patients were classified into the No CAN group (n = 189). RESULTS: No significant differences were observed in the genotype distributions of both C-509T and T869 polymorphisms between the two groups. Allele frequencies and age-, sex-, HLA mismatch-adjusted odds ratio of each genotype as assessed by logistic regression analysis were also not significantly different between the two groups. Linkage disequilibrium coefficients between polymorphisms indicated that investigated polymorphisms of TGF-beta1 (D' = 0.98) were in tight linkage. However, there were no significant differences in the frequencies of the reconstructed haplotypes between the two groups. Kaplan-Meier method and log-rank tests did not indicate any statistically significant effects of TGF-beta1 gene polymorphisms on graft survival. CONCLUSION: TGF-beta1 gene polymorphisms (C-509T, T869C) are not significantly associated with an increased risk of development of CAN and graft survival in Korean renal transplant recipients.

Three-dimensional analysis of mandibular condyle position in patients with deviated mandibular prognathism.

The purpose of this study was to evaluate the bilateral difference in condyle position in patients with deviated mandibular prognathism. Patients with asymmetrical (n=28) and symmetrical mandibular prognathism (n=23) were compared using the three-dimensional (3D) reformatted image from cone beam computed tomography. Significant positional differences in the condyle and subcondyle region (sigmoid notch) were found between the deviated and contralateral sides in the group with asymmetrical mandibular prognathism, but not in the control group. The lateral condyle was more laterally and inferiorly positioned on the contralateral side than on the deviated side (P<0.05). The sigmoid notch was more laterally, superiorly, and posteriorly positioned on the deviated side (P<0.01). Interestingly, condyle width and height on the deviated side was narrower and shorter than on the contralateral side and in the control group. Menton deviation was closely correlated with the bilateral difference in condyle height and 3D position of the sigmoid notch (P<0.01). The degree of asymmetry was more highly correlated with condyle height than with the spatial orientation of the condyle head. The results demonstrated that mandibular prognathism with asymmetry is associated with bilateral differences in 3D morphology and orientation of the condyle. Therefore, clinicians should consider these variations during surgical planning.

Histopathological and scanning electron microscopy findings of retrieved porous polyethylene implants.

Porous polyethylene (PPE) implants are biocompatible alloplastic materials commonly used for facial augmentation. However, the effect of sub-periosteal PPE application on the surrounding tissues has not been analyzed clearly. This report documents the case of a 22-year-old woman who underwent peri-alar augmentation with PPE to improve midface retrusion. Although no infection or inflammation occurred at the surgical site, the patient requested removal of the PPE implant for aesthetic reasons alone at 1 year after the surgery. The removed implant was subjected to histological and morphological evaluation using conventional histological staining and scanning electron microscopy (SEM). Histopathological staining revealed bone ingrowth into the pores of the implant near the boundary with the host bone. Little evidence of a foreign body reaction was observed. SEM revealed densely arranged collagen fibres and osteoblastic cells in the pores. Moreover, the outer surface of the PPE implant in contact with the periosteum showed fibrous tissue ingrowth, leading to tissue adhesion. These findings confirm bone ingrowth into the PPE pore structure in humans.

A comparison of craniofacial morphology in patients with and without facial asymmetry--a three-dimensional analysis with computed tomography.

This study intended to evaluate the morphological characteristics of the cranial base and maxillomandibular structures of facial asymmetry in adult patients, so as to determine whether mandibular asymmetry is a result of primary mandibular deformity or if it is influenced by cranial base deformity. Forty-two adult patients with dentofacial deformity were placed into two groups according to the deviation of the chin: Asymmetry group (n = 24) and Non-asymmetry group (n = 18). They were compared with three-dimensional (3D) CT reformatted images using a 3D visualization and analyzing program. The differences between the two groups, the correlation between the cranial base and maxillomandibular asymmetry were evaluated statistically. The degree of cranial base asymmetry in the Asymmetry group was not statistically different from the Non-asymmetry group. The asymmetric condyle position was found to be associated with skull base characteristics. The 3D position of the condyle and cranial base, however, was not closely related with mandibular asymmetry. The results showed that the cranial measurement variables were not the dominant factors that determined the degree of facial asymmetry. It seems that the mandibular skeletal factors itself, functional or intrinsic asymmetric growth potential, compensate or aggravate the influence of cranial asymmetry during the growth period.

Factors predicting outcomes of penile rehabilitation with udenafil 50 mg following radical prostatectomy.

Udenafil is a selective phosphodiesterase type 5 inhibitor made available in recent years for the treatment of erectile dysfunction. Herein, we evaluated independent predictors of potency recovery in radical prostatectomy (RP) patients who underwent penile rehabilitation with udenafil 50 mg. One hundred and forty-three men who underwent RP were enrolled in a penile rehabilitation program using udenafil 50 mg every other day. The rate of regained potency in the study group was significantly higher compared with the recovery rate seen in patients who were not part of the penile rehabilitation program (41.3% vs 13.0%; P<0.001). On the multivariate Cox analyses, preoperative International Index of Erectile Function-5 scores (hazard ratio (HR), 1.049; P=0.040), alcohol consumption (HR, 2.043; P=0.020) and Gleason biopsy score (HR, 0.368; P=0.024) were independent preoperative predictors for potency recovery. Among post-RP variables, the use of robotic procedures (HR, 2.287; P=0.030) and pathologic stage (HR, 0.506; P=0.038) were significantly associated with potency recovery. This study identified predictive factors for the recovery of potency in patients undergoing penile rehabilitation with udenafil following RP. Our results could provide physicians with useful information for counseling RP patients and selecting optimal candidates for penile rehabilitation.

Soft tissue changes and skeletal stability after modified quadrangular Le Fort I osteotomy.

The purpose of this study was to evaluate the soft tissue changes and skeletal stability of a modification of the Le Fort I osteotomy design - the modified quadrangular Le Fort I osteotomy (MQLI). Patients who had maxillary advancement and mandibular setback surgery for skeletal class III malocclusion with a midface deficiency were included. MQLI patients (n=20) were compared to conventional Le Fort I osteotomy patients (LFI) (n=20) using cephalometric radiographs taken preoperatively (T0), immediately postoperative (T1), and at >6 months postoperative (T2). Soft tissue radiographic changes of the cheek line and perinasal areas, and skeletal movements were analyzed. The basic skeletal characteristics and amount of maxillary and mandibular surgical change were similar in the two groups (group difference, P>0.05). There was no significant difference between the two groups in terms of maxillary and mandibular skeletal stability. The cheek profile angle increased significantly after MQLI by 3.5° (P<0.05), whereas LFI showed a 2.1° increase (P>0.05). Overall, the soft tissue cheek outline moved significantly more anteriorly in MQLI, but the difference to LFI osteotomy did not reach statistical significance. MQLI could be an efficient and stable surgical method to improve maxillary and infraorbital hypoplasia without malar advancement, especially in Asian patients.

Efficacy of rhBMP-2/Hydroxyapatite on Sinus Floor Augmentation: A Multicenter, Randomized Controlled Clinical Trial.

The aim of this randomized single-blinded active-controlled clinical study was to evaluate the early efficacy of low-dose Escherichia coli-derived recombinant human bone morphogenetic protein 2 (rhBMP-2) soaked with hydroxyapatite granules (BMP-2/H) as compared with an inorganic bovine bone xenograft (ABX) in maxillary sinus floor augmentation. In a total of 127 subjects who were enrolled at 6 centers, maxillary sinus floors were augmented with 1 mg/mL of rhBMP-2 (0.5 to 2.0 mg per sinus) and BMP-2/H (0.5 to 2.0 g; n = 65) or with ABX alone (0.5 to 2.0 g; n = 62). Core biopsies were obtained 3 mo after the augmentation surgery and were analyzed histomorphometrically. The mean new bone formation with BMP-2/H and ABX augmentation was 16.10% ± 10.52% and 8.25% ± 9.47%, respectively. The BMP-2/H group was noninferior to the ABX group; the lower limit of the 1-sided 97.5% confidence interval for the difference between the 2 groups was calculated as 4.33%, which was greater than the prespecified noninferiority margin of -3.75%. An additional test with the Wilcoxon rank-sum test with a 2-sided 5% significance level showed that bone formation between the 2 groups was significantly different (P < 0.0001). The soft tissue and residual graft areas showed no significant differences between the groups. With regard to safety, no significant difference between the 2 groups was observed; there was no significant increase in the amount of rhBMP-2 antibody in the serum after BMP-2/H grafting. Our study suggested that low-dose Escherichia coli-derived rhBMP-2 with hydroxyapatite was effective in early stages for enhanced bone formation after maxillary sinus floor augmentation without harmful adverse events (Clinicaltrials.gov NCT01634308).

Stability of simultaneous maxillary and mandibular osteotomy for treatment of class III malocclusion: an analysis of three-dimensional cephalograms.

PURPOSE: The current investigation was undertaken to study the three-dimensional (3-D) stability of simultaneous maxillary advancement and mandibular setback using rigid fixation. The study also aimed to analyse the factors involved in postsurgical relapse by evaluation of changes in various parameters. PATIENTS: Twenty-five cases were evaluated of simultaneous Le Fort I maxillary advancement and mandibular setback using rigid fixation. METHODS: Preoperative, immediate and 6-month postoperative skeletal and dental changes were analysed using 3-D cephalograms obtained from biplanar stereoradiography. Maxillary fixation screws were used as landmarks to evaluate postoperative stability. RESULTS: The mean maxillary advancement was 3.7 mm. Relapse in the sagittal, vertical, and transverse planes was not detectable in the maxilla (p > 0.05). However, for an average mandibular setback of 5.7 mm, mean mandibular relapse was 1.1 mm or 19.3% anteriorly (p < 0.05). Surgical or postsurgical skeletal changes in the maxilla had no detectable influence on mandibular relapse (p > 0.05). Vertical alterations of the facial skeleton achieved surgically predicted the mandibular relapse (R2 = 0.27, p < 0.05). CONCLUSION: Maxillary advancement and vertical changes of +/- 2 mm did not influence the postoperative stability of the mandible. Relapse of the mandible seems to be influenced mainly by the amount and direction of the surgical alteration of mandibular position.

The lateral upper arm free flap for intraoral reconstruction.

Twenty-three consecutive patients who were reconstructed with a lateral upper arm free flap (LUFF) were examined especially concerning functional and morphological results at the recipient and donor sites. There were 22 intraoral and one upper oesophageal reconstruction after radical laryngectomy. The LUFF rendered good functional and esthetic results except for one case of complete and one case of incomplete flap necrosis due to vascular insufficiency of the supplying vessel of the neck. There was some sensory deficit of the donor site (n=10), but no radial nerve injury or conspicuous scarring. Recipient site dehiscence occurred in two cases and a temporary orocervical fistula was seen in one case. Oral function was maintained due to the thin and pliable flap. Excellent flap adaptation to the adjacent tissue was obtained in eight cases of complete loss of lingual attached gingiva in the molar region and in four cases of loss of buccal attached gingiva. The success and functional results of LUFF were comparable to the results of 14 cases in which radial forearm free flaps (RFFF) were used. Although the length of the pedicle and the diameter of the vessels in LUFF are smaller than in RFFF, neither pedicle length nor vessel diameter proved to be a problem. Extent of scarring and risk of vascular compromise proved to be less as compared to RFFF. LUFF is, therefore, the flap of choice for intraoral soft tissue reconstruction and it is advised to reserve RFFF for cases in which LUFF fails.

Three-dimensional soft tissue change after paranasal augmentation with porous polyethylene.

The aim of this study was to investigate the effect of porous polyethylene (PPE) in paranasal augmentation on midfacial soft tissue architecture. This retrospective study recruited patients with midface retrusion and mandibular prognathism. Twenty adult patients who had undergone bilateral PPE augmentation (ready-made type, thickness 4.5mm, Medpor) to the piriform aperture and simultaneous mandibular setback surgery were included in this study. The soft tissue morphology and thickness of the midface were evaluated using three-dimensional reformatted images from cone beam computed tomography done before and 6 months after surgery. The soft tissue outline of the midface was augmented 1-4mm. The average increase in soft tissue outline near the peri-alar region was 3.1-3.4mm, which comprised 68-74% of the PPE thickness (P<0.01). The nasolabial angle and columellar inclination were increased significantly (2.2° and 1.4°, respectively; both P<0.05), whereas the nasal tip angle, nasal tip protrusion, columellar length, and bilateral nostril axis angle did not change. The alar base became wider on average by 2.2mm (P<0.01). The results showed that paranasal augmentation with PPE significantly increased the overlying soft tissue outline without influencing the nasal projection and could enhance paranasal aesthetics with minimal morbidity.

Accuracy of maxillary repositioning in two-jaw surgery with conventional articulator model surgery versus virtual model surgery.

The purpose of this study was to compare the accuracy of maxillary repositioning using the recently introduced computerized virtual model surgery (VMS) with conventional articulator model surgery (AMS). Forty-two patients who had undergone bimaxillary surgery were investigated retrospectively in this study. The patients were divided into two groups: conventional AMS (n = 23) and VMS (n = 19) for intermediate splint fabrication in maxillary positioning. Planned surgical movements and actual postsurgical changes of the lateral and frontal cephalometric measurements were compared. Although variations from the planned surgical movements were relatively small, both methods had statistically significant errors in some of the linear measurements. Both groups had a similar range of errors. The overall absolute mean discrepancy between the planned and actual surgical movements for the linear measurements was 1.17 mm (0-3.6 mm) in AMS and 0.95 mm (0-3.2 mm) in VMS. Of the total measurements, measurements reflecting a surgical discrepancy of more than 2 mm or 2° comprised 12.0% of the cases in AMS and 7.9% in VMS. The surgical accuracy of maxillary positioning with VMS was comparable to conventional AMS. Because VMS has the definitive advantage of eliminating the complex laboratory step and shortening the laboratory time, this can be accepted as an alternative to AMS.

Pseudoaneurysm of the facial artery occurred after mandibular sagittal split ramus osteotomy.

INTRODUCTION: Pseudoaneurysms are caused by rupture of arteries with extravasation of blood. The compressed perivascular tissue forms the wall of aneurysmal sac. Pseudoaneurysm directly related with surgical procedure of sagittal split ramus osteotomy (SSRO) was reported quite rarely especially related with facial artery during the vertical osteotomy. CASE REPORT: SSRO was carried out for a 19-year-old male; the patient visited the emergency room with notable swelling 3 weeks after the surgery. We experienced severe intra-oral bleeding with surgical exploration. Angiography revealed a pseudoaneurysm of the right facial artery that might be related with vertical osteotomy over lateral cortex of the mandibular body during orthognathic surgery. This implies that the minor vascular trauma from vertical osteotomy of the mandibular body during the conventional orthognathic surgery might cause later development of pseudoaneurysm.

Craniosynostosis-associated Fgfr2(C342Y) mutant bone marrow stromal cells exhibit cell autonomous abnormalities in osteoblast differentiation and bone formation.

We recently reported that cranial bones of Fgfr2(C342Y/+) craniosynostotic mice are diminished in density when compared to those of wild type mice, and that cranial bone cells isolated from the mutant mice exhibit inhibited late stage osteoblast differentiation. To provide further support for the idea that craniosynostosis-associated Fgfr mutations lead to cell autonomous defects in osteoblast differentiation and mineralized tissue formation, here we tested bone marrow stromal cells isolated from Fgfr2(C342Y/+) mice for their ability to differentiate into osteoblasts. Additionally, to determine if the low bone mass phenotype of Crouzon syndrome includes the appendicular skeleton, long bones were assessed by micro CT. Fgfr2(C342Y/+) cells showed increased osteoblastic gene expression during early osteoblastic differentiation but decreased expression of alkaline phosphatase mRNA and enzyme activity, and decreased mineralization during later stages of differentiation, when cultured under 2D in vitro conditions. Cells isolated from Fgfr2(C342Y/+) mice also formed less bone when allowed to differentiate in a 3D matrix in vivo. Cortical bone parameters were diminished in long bones of Fgfr2(C342Y/+) mice. These results demonstrate that marrow stromal cells of Fgfr2(C342Y/+) mice have an autonomous defect in osteoblast differentiation and bone mineralization, and that the Fgfr2(C342Y) mutation influences both the axial and appendicular skeletons.