4-Hexylresorcinol induced angiogenesis potential in human endothelial cells / 대한악안면성형재건외과학회지

Background@#4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. @*Methods@#As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. @*Results@#Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. @*Conclusion@#Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

Development of a standardized mucositis and osteoradionecrosis animal model using external radiation

Objectives@#Although the side effects of radiation therapy vary from mucositis to osteomyelitis depending on the dose of radiation therapy, to date, an experimental animal model has not yet been proposed. The aim of this study was to develop an animal model for assessing complications of irradiated bone, especially to quantify the dose of radiation needed to develop a rat model. @*Materials and Methods@#Sixteen Sprague-Dawley rats aged seven weeks with a mean weight of 267.59 g were used. Atraumatic extraction of a right mandibular first molar was performed. At one week after the extraction, the rats were randomized into four groups and received a single dose of external radiation administered to the right lower jaw at a level of 14, 16, 18, or 20 Gy, respectively. Clinical alopecia with body weight changes were compared and bony volumetric analysis with micro-computed tomography (CT), histologic analysis with H&E were performed. @*Results@#The progression of the skin alopecia was different depending on the irradiation dose. Micro-CT parameters including bone volume, bone volume/tissue volume, bone mineral density, and trabecular spaces, showed no significant differences. The progression of osteoradionecrosis (ORN) along with that of inflammation, fibrosis, and bone resorption, was found with increased osteoclast or fibrosis in the radiated group. As the radiation dose increases, osteoclast numbers begin to decrease and osteoclast tends to increase. Osteoclasts respond more sensitively to the radiation dose, and osteoblasts are degraded at doses above 18 Gy. @*Conclusion@#A standardized animal model clinically comparable to ORN of the jaw is a valuable tool that can be used to examine the pathophysiology of the disease and trial any potential treatment modalities. We present a methodology for the use of an experimental rat model that incorporates a guideline regarding radiation dose.

4-Hexylresorcinol induced angiogenesis potential in human endothelial cells / 대한악안면성형재건외과학회지

Background@#4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. @*Methods@#As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. @*Results@#Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. @*Conclusion@#Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

Chronic non-bacterial osteomyelitis in the jaw

Chronic recurrent multifocal osteomyelitis (CRMO) is one of the most severe form of chronic non-bacterial osteomyelitis (CNO), which could result in bone and related tissue damage. This autoinflammatory bone disorder (ABD) is very difficult for its clinical diagnosis because of no diagnostic criteria or biomarkers. CRMO in the jaw must be suspected in the differential diagnosis of chronic and recurrent bone pain in the jaw, and a bone biopsy should be considered in chronic and relapsing bone pain with swelling that is unresponsive to treatment. The early diagnosis of CRMO in the jaw will prevent unnecessary and prolonged antibiotic usage or unnecessary surgical intervention. The updated researches for the identification of genetic and molecular alterations in CNO/CRMO should be studied more for its correct pathophysiological causes and proper treatment guidelines. Although our trial consisted of reporting items from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), there are very few articles of randomized controlled trials. This article was summarized based on the author's diverse clinical experiences. This paper reviews the clinical presentation of CNO/CRMO with its own pathogenesis, epidemiology, recent research studies, and general medications. Treatment and monitoring of the jaw are essential for the clear diagnosis and management of CNO/CRMO patients in the field of dentistry and maxillofacial surgery.

Chronic non-bacterial osteomyelitis in the jaw

Chronic recurrent multifocal osteomyelitis (CRMO) is one of the most severe form of chronic non-bacterial osteomyelitis (CNO), which could result in bone and related tissue damage. This autoinflammatory bone disorder (ABD) is very difficult for its clinical diagnosis because of no diagnostic criteria or biomarkers. CRMO in the jaw must be suspected in the differential diagnosis of chronic and recurrent bone pain in the jaw, and a bone biopsy should be considered in chronic and relapsing bone pain with swelling that is unresponsive to treatment. The early diagnosis of CRMO in the jaw will prevent unnecessary and prolonged antibiotic usage or unnecessary surgical intervention. The updated researches for the identification of genetic and molecular alterations in CNO/CRMO should be studied more for its correct pathophysiological causes and proper treatment guidelines. Although our trial consisted of reporting items from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), there are very few articles of randomized controlled trials. This article was summarized based on the author's diverse clinical experiences. This paper reviews the clinical presentation of CNO/CRMO with its own pathogenesis, epidemiology, recent research studies, and general medications. Treatment and monitoring of the jaw are essential for the clear diagnosis and management of CNO/CRMO patients in the field of dentistry and maxillofacial surgery.

Aberrant growth of the anterior cranial base relevant to severe midface hypoplasia of Apert syndrome / 대한악안면성형재건외과학회지

BACKGROUND: A 9-year-old male showed severe defects in midface structures, which resulted in maxillary hypoplasia, ocular hypertelorism, relative mandibular prognathism, and syndactyly. He had been diagnosed as having Apert syndrome and received a surgery of frontal calvaria distraction osteotomy to treat the steep forehead at 6 months old, and a surgery of digital separation to treat severe syndactyly of both hands at 6 years old. Nevertheless, he still showed a turribrachycephalic cranial profile with proptosis, a horizontal groove above supraorbital ridge, and a short nose with bulbous tip. METHODS: Fundamental aberrant growth may be associated with the cranial base structure in radiological observation. RESULTS: The Apert syndrome patient had a shorter and thinner nasal septum in panthomogram, PA view, and Waters’ view; shorter zygomatico-maxillary width (83.5 mm) in Waters’ view; shorter length between the sella and nasion (63.7 mm) on cephalogram; and bigger zygomatic axis angle of the cranial base (118.2°) in basal cranial view than a normal 9-year-old male (94.8 mm, 72.5 mm, 98.1°, respectively). On the other hand, the Apert syndrome patient showed interdigitating calcification of coronal suture similar to that of a normal 30-year-old male in a skull PA view. CONCLUSION: Taken together, the Apert syndrome patient, 9 years old, showed retarded growth of the anterior cranial base affecting severe midface hypoplasia, which resulted in a hypoplastic nasal septum axis, retruded zygomatic axes, and retarded growth of the maxilla and palate even after frontal calvaria distraction osteotomy 8 years ago. Therefore, it was suggested that the severe midface hypoplasia and dysostotic facial profile of the present Apert syndrome case are closely relevant to the aberrant growth of the anterior cranial base supporting the whole oro-facial and forebrain development.

Proper management of suspicious actinic cheilitis / 대한악안면성형재건외과학회지

BACKGROUND@#Actinic cheilitis (AC) is a variant of actinic keratosis which is known to be a premalignant condition that could develop into squamous cell carcinoma (SCC). Epimyoepithelial carcinoma (EC) is a very rare salivary gland (SG) neoplasm that has classical biphasic histologic findings of small tubules and glandular lumina surrounded by clear myoepithelial cells.CASE PRESENTATION: We report a very rare case of AC occurring on the lower lip of a 70-year-old woman, which is developing to the EC later.@*CONCLUSIONS@#Diverse appearances of AC include edematous reddish in the acute stage and grey-whitish or dried hyperkeratotic wrinkled lesions in the chronic stage for several months or even years. Accurate treatment of AC in its initial stage could be recommended to avoid further malignant transformation; proper management of clinically suspicious AC is suggested.

Changes in oncogenic protein levels in peri-implant oral malignancy: a case report / 대한악안면성형재건외과학회지

BACKGROUND@#Oral squamous cell carcinoma (OSCC) constitutes a group of tumors that exhibit heterogeneous biology, histopathology, and clinical behaviors.CASE PRESENTATION: A 73-year-old male had a whitish leukoplakia-like lesion around inflamed peri-implant area (#42, #43, and #44), and this lesion had transformed to OSCC within 3 years. He underwent mass resection, selective neck dissection, and reconstructive surgery. To detect any carcinogenesis progression, we examined the removed tumor tissue as well as the patient's preoperative and postoperative sera to identify causative oncogenic proteins using immunoprecipitation high-performance liquid chromatography (IP-HPLC).@*CONCLUSIONS@#The protein expression levels of p53, E-cadherin, β-catenin, MMP-10, HER2, NRAS, Met, HER2, and ERb were significantly lower in the serum collected on postoperative day 10 than in the preoperative serum, and if these proteins are consistently not elevated in the serum 3 months after surgery compared with the preoperative serum, these proteins can be potential oncogenic proteins. However, we also found that the serum extracted 3 months after the operation had elevated levels of oncogenic proteins compared with that of the preoperative and 10-day postoperative serum indicating the possibility of tumor recurrence. At postoperative follow-up period, ipsilateral neck metastasis and second primary lesion were found and additional surgery was performed to the patient. IP-HPLC using the patient's serum shows the possibility of oncogenic protein detection. However, follow-up IP-HPLC data is needed to find out patient-specific prognostic factors.

Differential diagnosis of periapical cyst using collagen birefringence pattern of the cyst wall

OBJECTIVES: Periapical lesions, including periapical cyst (PC), periapical granuloma (PG), and periapical abscess (PA), are frequently affected by chemical/physical damage during root canal treatment or severe bacterial infection, and thus, the differential diagnosis of periapical lesions may be difficult due to the presence of severe inflammatory reaction. The aim of this study was to make differential diagnosis among PC, PG, and PA under polarizing microscope. MATERIALS AND METHODS: The collagen birefringence patterns of 319 cases of PC (n = 122), PG (n = 158), and PA (n = 39) obtained using a polarizing microscope were compared. In addition, 6 cases of periodontal fibroma (PF) were used as positive controls. RESULTS: Collagen birefringence was condensed with a thick, linear band-like pattern in PC, but was short and irregularly scattered in PG, and scarce or absent in PA. PF showed intense collagen birefringence with a short, palisading pattern but no continuous band-like pattern. The linear band-like birefringence in PC was ascribed to pre-existing expansile tensile stress of the cyst wall. CONCLUSIONS: In this study all PCs (n = 122) were distinguishable from PGs and PAs by their characteristic birefringence, despite the absence of lining epithelium (n = 20). Therefore, the authors suggest that the presence of linear band-like collagen birefringence of the cyst wall aids the diagnostic differentiation of PC from PG and PA.

Bimaxillary orthognathic surgery and condylectomy for mandibular condyle osteochondroma: a case report / 대한악안면성형재건외과학회지

Osteochondroma is rarely reported in the maxillofacial region; however, it is prevalent in the mandibular condyle. This slowly growing tumor may lead to malocclusion and facial asymmetry. A 39-year-old woman complained of gradual development of anterior and posterior unilateral crossbite, which resulted in facial asymmetry. A radiological study disclosed a large tumor mass on the top of the left mandibular condyle. This bony tumor was surgically removed through condylectomy and the remaining condyle head was secured. Subsequently, bimaxillary orthognathic surgery was performed to correct facial asymmetry and malocclusion. Pathological diagnosis was osteochondroma; immunohistochemistry showed that the tumor exhibited a conspicuous expression of BMP-4 and BMP-2 but rarely expression of PCNA. There was no recurrence at least for 1 year after the operation. Patient's functional and esthetic rehabilitation was uneventful.

Tongue Growth during Prenatal Development in Korean Fetuses and Embryos

BACKGROUND: Prenatal tongue development may affect oral-craniofacial structures, but this muscular organ has rarely been investigated. METHODS: In order to document the physiology of prenatal tongue growth, we histologically examined the facial and cranial base structures of 56 embryos and 106 fetuses. RESULTS: In Streeter's stages 13-14 (fertilization age [FA], 28 to 32 days), the tongue protruded into the stomodeal cavity from the retrohyoid space to the cartilaginous mesenchyme of the primitive cranial base, and in Streeter's stage 15 (FA, 33 to 36 days), the tongue rapidly swelled and compressed the cranial base to initiate spheno-occipital synchondrosis and continued to swell laterally to occupy most of the stomodeal cavity in Streeter's stage 16-17 (FA, 37 to 43 days). In Streeter's stage 18-20 (FA, 44 to 51 days), the tongue was vertically positioned and filled the posterior nasopharyngeal space. As the growth of the mandible and maxilla advanced, the tongue was pulled down and protruded anteriorly to form the linguomandibular complex. Angulation between the anterior cranial base (ACB) and the posterior cranial base (PCB) was formed by the emerging tongue at FA 4 weeks and became constant at approximately 124degrees-126degrees from FA 6 weeks until birth, which was consistent with angulations measured on adult cephalograms. CONCLUSIONS: The early clockwise growth of the ACB to the maxillary plane became harmonious with the counter-clockwise growth of the PCB to the tongue axis during the early prenatal period. These observations suggest that human embryonic tongue growth affects ACB and PCB angulation, stimulates maxillary growth, and induces mandibular movement to achieve the essential functions of oral and maxillofacial structures.

Chronic maxillary sinusitis caused by root canal overfilling of Calcipex II

This is a case report of chronic maxillary sinusitis caused by root canal overfilling of Calcipex II (Techno-Dent). A 60 year-old male complained of dull pain in the right maxillary molar area after complicated endodontic treatment using Calcipex II paste and was finally diagnosed with a chronic maxillary sinusitis through a clinical and radiological observation. In the biopsy examination, the periapical granuloma contained a lot of dark and translucent Calcipex II granules which were not stained with hematoxylin and eosin. They were usually engulfed by macrophages but rarely resorbed, resulting in scattering and migrating into antral mucosa. Most of the Calcipex II granules were also accumulated in the cytoplasms of secretory columnar epithelial cells, and small amount of Calcipex II granules were gradually secreted into sinus lumen by exocytosis. However, chronic granulomatous inflammation occurred without the additional recruitment of polymorphonuclear leukocytes (PMNs) and lymphocytes, and many macrophages which engulfed the Calcipex II granules were finally destroyed in the processes of cellular apoptosis. It is presumed that Calcipex II granules are likely to have a causative role to induce the granulomatous foreign body inflammation in the periapical region, and subsequently to exacerbate the chronic maxillary sinusitis in this study.

Current Concepts and Occurrence of Epithelial Odontogenic Tumors: II. Calcifying Epithelial Odontogenic Tumor Versus Ghost Cell Odontogenic Tumors Derived from Calcifying Odontogenic Cyst

Calcifying epithelial odontogenic tumors (CEOTs) and ghost cell odontogenic tumors (GCOTs) are characteristic odontogenic origin epithelial tumors which produce calcifying materials from transformed epithelial tumor cells. CEOT is a benign odontogenic tumor composed of polygonal epithelial tumor cells that show retrogressive calcific changes, amyloid-like deposition, and clear cytoplasm. Differentially, GCOTs are a group of transient tumors characterized by ghost cell presence, which comprise calcifying cystic odontogenic tumor (CCOT), dentinogenic ghost cell tumor (DGCT), and ghost cell odontogenic carcinoma (GCOC), all derived from calcifying odontogenic cysts (COCs). There is considerable confusion about COCs and GCOTs terminology, but these lesions can be classified as COCs or GCOTs, based on their cystic or tumorous natures, respectively. GCOTs include ameloblastomatous tumors derived from dominant odontogenic cysts classified as CCOTs, ghost cell-rich tumors producing dentinoid materials as DGCTs, and the GCOT malignant counterpart, GCOCs. Many authors have reported CEOTs and GCOTs variably express keratins, beta-catenin, BCL-2, BSP, RANKL, OPG, Notch1, Jagged1, TGF-beta, SMADs, and other proteins. However, these heterogeneous lesions should be differentially diagnosed to allow for accurate tumor progression and prognosis prediction.

Different Protein Expressions between Peripheral Ameloblastoma and Oral Basal Cell Carcinoma Occurred at the Same Mandibular Molar Area

Peripheral ameloblastoma (PA) in gingiva is rare and often confused with oral basal cell carcinoma (OBCC). The tissues of one case of PA and one case of OBCC with the same mandibular molar area affected were compared via an immunohistochemical examination using 50 antisera. The PA and OBCC showed similar proliferation of basaloid epithelial strands, but toluidine blue staining revealed that the PA had pinkish juxta-epithelial myxoid tissue, whereas the OBCC was infiltrated by many mast cells. Immunohistochemical comparisons showed that the PA was strongly positive for ameloblastin, KL1, p63, carcinoembryonic antigen, focal adhesion kinase, and cathepsin K, and slightly positive for amelogenin, Krox-25, E-cadherin, and PTCH1, whereas the OBCC was not. On the other hand, the OBCC was strongly positive for EpCam, matrix metalloprotease (MMP)-1, alpha1-antitrypsin, cytokeratin-7, p53, survivin, pAKT1, transforming growth factor-beta1, NRAS, TGase-1, and tumor nescrosis factor-alpha, and consistently positive for beta-catenin, MMP-2, cathepsin G, TGase-2, SOS-1, sonic hedgehog, and the beta-defensins-1, -2, -3, while the PA was not. These data suggest that the tumorigeneses of PA and OBCC differ, and that PAs undergo odontogenic differentiation and generate oncogenic signals for infiltrative growth and bone resorption, whereas OBCCs undergo basaloid epidermal differentiation as a result of growth factor/cytokine-related oncogenic signals.

Focal epithelial hyperplasia arising after delivery of metal-ceramic fixed dental prosthesis

Focal epithelial hyperplasia (FEH) is a human papillomavirus (HPV)-induced alteration of the oral mucosa that presents with a clinically distinct appearance. While other HPV-infected lesions such as squamous papilloma, verruca vulgaris, and condyloma acuminatum involve the skin, oral mucosa, and genital mucosa, FEH occurs only in the oral mucosa. The affected oral mucosa exhibits multiple papules and nodules with each papule/nodule being flat-topped or sessile. The affected region resembles the normal color of oral mucosa rather than appearing as a white color since the epithelial surface is not hyperkeratinized. Almost all cases present with multiple sites of occurrence. This rare, benign epithelial proliferation is related to low-risk HPV, especially HPV-13 and -32, and is not transformed into carcinoma. We report a case of FEH that arose on the attached gingiva of an East Asian male adult related to prosthesis without detection of any HPV subtype in HPV DNA chip and sequencing.

Current Concepts and Occurrence of Epithelial Odontogenic Tumors: I. Ameloblastoma and Adenomatoid Odontogenic Tumor

Ameloblastomas and adenomatoid odontogenic tumors (AOTs) are common epithelial tumors of odontogenic origin. Ameloblastomas are clinico-pathologically classified into solid/multicystic, unicystic, desmoplastic, and peripheral types, and also divided into follicular, plexiform, acanthomatous, granular types, etc., based on their histological features. Craniopharyngiomas, derived from the remnants of Rathke's pouch or a misplaced enamel organ, are also comparable to the odontogenic tumors. The malignant transformation of ameloblastomas results in the formation of ameloblastic carcinomas and malignant ameloblastomas depending on cytological dysplasia and metastasis, respectively. AOTs are classified into follicular, extrafollicular, and peripheral types. Ameloblastomas are common, have an aggressive behavior and recurrent course, and are rarely metastatic, while AOTs are hamartomatous benign lesions derived from the complex system of the dental lamina or its remnants. With advances in the elucidation of molecular signaling mechanisms in cells, the cytodifferentiation of epithelial tumor cells in ameloblastomas and AOTs can be identified using different biomarkers. Therefore, it is suggested that comprehensive pathological observation including molecular genetic information can provide a more reliable differential diagnosis for the propagation and prognosis of ameloblastomas and AOTs. This study aimed to review the current concepts of ameloblastomas and AOTs and to discuss their clinico-pathological features relevant to tumorigenesis and prognosis.

Maxillary Sinusitis Caused by Mucormycosis

Prevalence of Human Papillomavirus Infection in the Korean Oral Cancer Patients

Effect of Electron-beam Irradiaton on the Artificial Bone Substitutes Composed of Hydroxyapatite and Tricalcium Phosphate Mixtures with Type I Collagen

The Effect of a Hydroxyapatite and 4-hexylresorcinol Combination Graft on Bone Regeneration in the Rabbit Calvarial Defect Model

0.05) at 8 weeks after grafting. The BMD and BV in the experimental group at 4 weeks after surgery was significantly higher than those in the control group (P<0.05).CONCLUSION: 4-hexylresorcinol and hydroxyapatite combination graft material showed higher initial bone formation than the control, however, there was no difference at 8weeks after operation.