Pilot study of the Korean national breast implant registry: Experiences and lessons learned.

BACKGROUND: To improve the safety and early detection of unexpected breast implant-related complications, the Korean Breast Implant Registry (K-BIR) was launched in 2020 in cooperation with the Korean Society of Plastic and Reconstructive Surgeons and the Korean Ministry of Food and Drug Safety, and a pilot study was conducted. OBJECTIVE: This article provides an overview of our pilot study and experiences of the K-BIR. METHODS: The dataset to be used in the pilot form of K-BIR was constructed by holding online surveys and meetings focusing on the global breast device registry's minimum dataset. A pilot study was implemented from April 1, 2020, to July 31, 2020, with six university teaching hospitals and four private clinics. RESULTS: During the pilot study period, 325 patients, 451 procedures, and 366 implants were entered into the K-BIR. The most common procedure registered was augmentation mammaplasty (30%) for cosmetic indications, followed by direct-to-implant breast reconstruction (27%). Smooth silicone implant was the most common type (73%) of implant used. A feedback survey after the pilot study included questions about the registration rate compared with an actual procedure, entry time, reasons for difficulty in entry, and additional data needed. CONCLUSIONS: The continuous maintenance and development of K-BIR will require an effective dataset, a strengthened legal system for an opt-out registry and personal data protection, various incentives for increasing participation rates, and an electronic platform that patients, manufacturers, and clinicians can easily access. K-BIR has the potential to provide quality assurance and outcomes for research and post-market surveillance systems for breast implants as well as methods for enhancing patient safety.

Effects of BMP-2 on the osteogenic differentiation of bone marrow stem cells in fibrous dysplasia.

OBJECTIVES: The purpose of this study was to evaluate the effects of BMP-2 on bone-grafting procedures for the treatment of fibrous dysplasia based on in vitro and in vivo experiments. SUBJECTS AND METHODS: Proliferation of stem cells was determined by colony-forming assay, CCK-8 assay and BrdU staining. OCT4 and NANOG expression was analysed by flow cytometry and immunocytochemistry. Osteogenic differentiation was assessed by measuring ALP activity, Alizarin red S staining and in vivo transplantation. Gene expression of the osteogenic markers, osteocalcin and type 1 collagen, was determined by RT-PCR. RESULTS: FD-BMSCs showed few calcium deposits and low ALP activity. Bone formation by transplanted FD-BMSCs was also suppressed relative to that of normal BMSCs. However, BMP-2 treatment enhanced osteogenic differentiation of FD-BMSCs mixed with normal BMSCs in vitro and in vivo. Overall, BMP-2 treatment promoted osteogenic differentiation of FD-BMSCs mixed with normal BMSCs. CONCLUSIONS: In patients with FD, stem cells in affected bone are influenced by the mutation, resulting in weak bone formation with the proliferation of immature osteogenic cells. Current treatment of FD involves surgical removal of excess bulk lesions, which can cause facial disfigurement. Our results suggest that BMP-2 application is a good adjunctive modality to the surgical treatment of patients with FD.

Fate of mandibular canals displaced by enlarged cystic lesions: does the inferior alveolar neurovascular bundle relocate to its original position?

Our aim was to identify the positional changes of the inferior alveolar neurovascular bundle and evaluate the relocation of the displaced mandibular canal after enucleation of a cyst. Seventy patients (72 sites) who had had cysts enucleated were divided into three groups based on the degree of encroachment of the cystic lesion into the mandibular canal and whether a bone graft had been inserted after the cyst had been enucleated. The mean (range) of patients' ages was 45 (18-75) years, and there were 29 male and 41 female patients. Group A comprised cysts with encroachment on the mandibular canal that were enucleated without a bone graft; Group B consisted of cysts with no encroachment of the mandibular canal, but were enucleated without a bone graft; and Group C comprised cysts with encroachment of the mandibular canal that were enucleated with a bone graft. The displacement of the mandibular canal was identified from analysis of computed tomographic (CT) images. Changes in the position of the mandibular canal were measured on panoramic radiographs. The mandibular canal was repositioned superiorly by a mean (SD) of 2.4 (1.65)mm after enucleation of the cyst, which was significant in Group A (p<0.001), but not in Groups B and C. These results indicate that the displaced inferior alveolar neurovascular bundles that were not surrounded by bony canal tended to relocate towards a supposedly normal position, and after enucleation of the cyst the mandibular canal was remodelled in this new location. This tendency to relocate was blocked by bone grafting. Bone grafts are therefore recommended in cases where enough bony height is required for future insertion of implants.

Effect of decompression on cystic lesions of the mandible: 3-dimensional volumetric analysis.

Decompression is effective in reducing both the size of cystic lesions on jaws and the associated morbidity of resection. However, quantitative measurement of reduced volume after decompression among different cystic diseases has not been fully investigated. We have retrospectively investigated the difference in reduction in volume among keratocystic odontogenic tumours (n=17), unicystic ameloblastomas (n=10), and dentigerous cysts (n=10) of the posterior mandible using 3-dimensional computed tomography (CT). Various other influential factors such as age, sex, the presence of impacted teeth, and the number of drains were also recorded. There was no significant difference in the speed of shrinkage among the 3 groups, but there was a significant correlation (p<0.01) between the initial detected volume of the lesion and the absolute speed of shrinkage in each type of cyst. Initial volume was also significantly associated (p<0.01) with reduction of total volume in each type of cyst. Age may correlate negatively with the rate of reduction in dentigerous cysts, which means that the older the patient is, the less the reduction. Treatment seemed to last longer as the speed of shrinkage lessened in the keratocystic tumours and dentigerous cysts (p<0.05) as multiple regression has shown. The relative speed of shrinkage of unicystic ameloblastomas seemed to be slower when an impacted tooth was involved in the lesion (p=0.019). However, the sample size was too small to make any definite statistical statement. These results suggest that the rate of reduction of volume was related to the original size of the lesion. Despite the need for a second operation and longer duration of treatment compared with excision alone, decompression is a valuable way of reducing the size of large cystic lesions, with low morbidity and recurrence rate. There was no difference in the rate of reduction according to the underlying histopathological picture.

Responses of periodontal ligament stem cells on various titanium surfaces.

OBJECTIVE: Periodontal ligament has been reported to have adult stem cells (PDLSCs) which are responsible to regenerate the alveolar bone tissue after tooth is removed from its socket. Also PDLSCs may be the stem cells responsible for the osseointegration of titanium implants after installing the implant immediately in the fresh extracted socket. Here we tested cellular responses of PDLSCs on the various titanium surfaces to verify this notion. MATERIALS AND METHODS: Titanium disc were prepared for the different surface textures; smooth machined, blasted with 75 and 125 µm Al(2) O(3) particles, and anodized. PDLSCs were cultured on these titanium discs and tested their proliferation and gene expressions of osteocalcin, osteopontin, type I collagen, and GAPDH. RESULTS: Proliferation of PDLSCs was higher on the rough surface blasted with 75 µm Al(2) O(3) particles. Osteocalcin expression was increased on the Al(2) O(3) particle treated-surface regardless of its particle size. Type I collagen expression was generally decreased with time in 6 days culture. CONCLUSIONS: In this experiment, it was shown that cultured PDLSCs proliferate in higher rate on the rough surface especially at the 75 µm Al(2) O(3) particle treated surface than other surfaces. Also, osteocalcin was highly expressed on the rough surfaces treated with 75 µm and 125 µm Al(2) O(3) particles.

SHED repair critical-size calvarial defects in mice.

OBJECTIVE: Stem cells from human exfoliated deciduous teeth (SHED) are a population of highly proliferative postnatal stem cells capable of differentiating into odontoblasts, adipocytes, neural cells, and osteo-inductive cells. To examine whether SHED-mediated bone regeneration can be utilized for therapeutic purposes, we used SHED to repair critical-size calvarial defects in immunocompromised mice. MATERIALS AND METHODS: We generated calvarial defects and transplanted SHED with hydroxyapatite/tricalcium phosphate as a carrier into the defect areas. RESULTS: SHED were able to repair the defects with substantial bone formation. Interestingly, SHED-mediated osteogenesis failed to recruit hematopoietic marrow elements that are commonly seen in bone marrow mesenchymal stem cell-generated bone. Furthermore, SHED were found to co-express mesenchymal stem cell marker, CC9/MUC18/CD146, with an array of growth factor receptors such as transforming growth factor beta receptor I and II, fibroblast growth factor receptor I and III, and vascular endothelial growth factor receptor I, implying their comprehensive differentiation potential. CONCLUSIONS: Our data indicate that SHED, derived from neural crest cells, may select unique mechanisms to exert osteogenesis. SHED might be a suitable resource for orofacial bone regeneration.

Human Hertwig's epithelial root sheath cells play crucial roles in cementum formation.

UNLABELLED: Hertwig's epithelial root sheath (HERS) cells are a unique population of epithelial cells in the periodontal ligament compartment. To date, their functional role has not been fully elucidated. Our hypothesis was that HERS cells may be involved in regulating differentiation of periodontal ligament stem cells (PDLSCs) and forming cementum in vivo. In this study, we found that HERS cells may be capable of promoting PDLSC differentiation and undergoing epithelial-mesenchymal transition in vitro. Immunohistochemical staining, Western blot analysis, a transwell co-culture system, and in vivo transplantation were used to characterize the interplay between HERS cells and PDLSCs, as well as the epithelial-mesenchymal transition (EMT) of HERS cells. TGFbeta1 was capable of inducing the epithelial-mesenchymal transition of HERS cells through activating the PI3K/AKT pathway. Furthermore, HERS cells were able to form cementum-like tissue when transplanted into immunocompromised mice. ABBREVIATIONS: bone marrow mesenchymal stem cell, BMMSC; bone sialoprotein, BSP; hydroxyapatite/tricalcium phosphate, HA/TCP; Hertwig's epithelial root sheath, HERS; osteocalcin, OCN; periodontal ligament, PDL; periodontal ligament stem cell, PDLSC; phosphatidylinositol 3-kinase, PI3K.

Long-term follow up on recurrence of 305 ameloblastoma cases.

The aim of this study was to determine the appropriate treatment for ameloblastoma by considering the factors associated with recurrence, and to make a quantitative prediction of the risk factors for recurrence. Data on age and gender distribution, location of the tumour, histopathological findings, treatment method, and whether or not patients had a preoperative biopsy confirmation report were collected in 305 cases (239 patients; M: 139, F: 100) of ameloblastoma diagnosed and treated in 1985-2002. After initial statistical evaluation (chi(2)-test and Fisher's exact test), logistic regression analysis was performed to check relative significance and predict recurrence. The disease-free survival function curves of the patients with or without recurrence were obtained by the Kaplan-Meier method and compared using univariate regression analysis. The correlation between recurrence and the treatment method or histopathological type was significant. The differences between the 'conservative' and 'resection with bone margin' and between the 'conservative' and 'segmental resection or maxillectomy' groups in terms of disease-free survival were highly significant. The difference between the 'resection with bone margin' and 'segmental resection or maxillectomy' groups was not significant. A resection with safety margin is the best method to treat most proven ameloblastomas, and conservative treatment is reasonable for patients in their first decade or with unicystic or plexiform ameloblastoma.

Recovery of stem cells from cryopreserved periodontal ligament.

Human post-natal stem cells possess a great potential to be utilized in stem-cell-mediated clinical therapies and tissue engineering. It is not known whether cryopreserved human tissues contain functional post-natal stem cells. In this study, we utilized human periodontal ligament to test the hypothesis that cryopreserved human periodontal ligament contains retrievable post-natal stem cells. These cryopreserved periodontal ligament stem cells maintained normal periodontal ligament stem cell characteristics, including expression of the mesenchymal stem cell surface molecule STRO-1, single-colony-strain generation, multipotential differentiation, cementum/periodontal-ligament-like tissue regeneration, and a normal diploid karyotype. Collectively, this study provides valuable evidence demonstrating a practical approach to the preservation of solid-frozen human tissues for subsequent post-natal stem cell isolation and tissue regeneration. The present study demonstrates that human post-natal stem cells can be recovered from cryopreserved human periodontal ligament, thereby providing a practical clinical approach for the utilization of frozen tissues for stem cell isolation.

The efficacy of mesenchymal stem cells to regenerate and repair dental structures.

OBJECTIVES: Identification, characterization, and potential application of mesenchymal stem cells (MSC) derived from human dental tissues. METHODS: Dental pulp and periodontal ligament were obtained from normal human impacted third molars. The tissues were digested in collagenase/dispase to generate single cell suspensions. Cells were cultured in alpha-MEM supplemented with 20% fetal bovine serum, 2 mM l-glutamine, 100 microM l-ascorbate-2-phosphate. Magnetic and fluorescence activated cell sorting were employed to characterize the phenotype of freshly isolated and ex vivo expanded cell populations. The developmental potential of cultured cells was assessed following co-transplantation with hydroxyapetite/tricalcium phosphate (HA/TCP) particles into immunocompromised mice for 8 weeks. RESULTS: MSC were identified in adult human dental pulp (dental pulp stem cells, DPSC), human primary teeth (stem cells from human exfoliated deciduous teeth, SHED), and periodontal ligament (periodontal ligament stem cells, PDLSC) by their capacity to generate clongenic cell clusters in culture. Ex vivo expanded DPSC, SHED, and PDLSC populations expressed a heterogeneous assortment of makers associated with MSC, dentin, bone, smooth muscle, neural tissue, and endothelium. PDLSC were also found to express the tendon specific marker, Scleraxis. Xenogeneic transplants containing HA/TCP with either DPSC or SHED generated donor-derived dentin-pulp-like tissues with distinct odontoblast layers lining the mineralized dentin-matrix. In parallel studies, PDLSC generated cementum-like structures associated with PDL-like connective tissue when transplanted with HA/TCP into immunocompromised mice. CONCLUSION: Collectively, these data revealed the presence of distinct MSC populations associated with dental structures with the potential of stem cells to regenerate living human dental tissues in vivo.

Concomitant reconstruction of mandibular basal and alveolar bone with a free fibular flap.

Repair of long-span mandibular defects with a free fibular flap is now a routine procedure. However, the bone height of the neo-mandible after reconstruction with a fibular flap is about half that of the dentulous mandible. When a fibular graft is placed only at the inferior border of the mandible, the resulting vertical discrepancy between the graft segment and the occlusal plane can adversely affect implant mechanics or denture stability and retention. To overcome these problems, we developed a technique for two-strut type mandibular reconstruction. A vascularized fibular segment is used to reconstruct the inferior basal portion of the neo-mandible, while a non-vascularized residual fibular segment is used to simulate the superior alveolar portion. We used this technique in 22 patients. Graft survival, graft resorption, and the ability to place implants were assessed as compared with those after the conventional one-strut type technique. The fibular segment grafted to the alveolar region was removed in one patient with intraoral wound dehiscence and in two with postoperative infection. All vascularized fibular flaps were successful. The resorption rate was 13.6+/-7.2% for non-vascularized segments and 3.0+/-3.7% for vascularized segments. Dental implants were placed in five of our 22 patients. The crown:fixture length ratio was improved to 1:1.7, as compared with a ratio of 1:1.21 with use of a conventional fibular flap. We conclude that our technique is very easy and safe and provides substantially improved lower-lip and cheek support and implant-prosthetic mechanics than conventional procedures for the repair of long-span mandibular defects.

Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic parameters.

Odontogenic keratocyst (OKC) is of particular interest because of its high recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were reviewed for the age of the patient at diagnosis, sex of the patient, OKC location, and radiographic findings, and 132 patients with OKC were observed to estimate recurrence, which was analyzed for age, sex, location, and several histopathologic findings. OKCs occurred more frequently in men (58.6%) than in women (41.4%), and they occurred in patients within a wide age range, most commonly in patients in the third decade of life (28.9%), followed by those in the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the premolar areas (51.2%) were the most common sites, and the most frequent clinical manifestations at first admission were swelling, pain, or both (82.4% of total cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%), primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and radicular cyst (3.1%). The frequency of recurrence at the follow-up examination was 58.3%. There was no significant difference in the recurrence rate on the basis of the sex of the patient. However, OKCs had a significantly higher recurrence rate in patients in the fifth decade of life than in patients in the other age groups (P = .005).Recurrence rates were significantly dependent on the sites of involvement, and OKCs in the mandibular molar region had significantly higher recurrence rates than those in other sites (P = .001). The histopathologic presence of one or more daughter cysts was significantly related to recurrence (P = .03).

Extra-articular pigmented villonodular synovitis of the temporomandibular joint: case report and review of the literature.

Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder of the synovial tissue, that usually affects the knee, ankle and other major joints. Involvement of the temporomandibular joint is, however, very rare. We describe a new case of recurrent PVNS arising from the temporomandibular joint that was classified as diffuse extra-articular type and was successfully treated surgically. The etiology and clinical features of PVNS are discussed and the previously reported cases in the literature are reviewed.