백서 하악 골수염에서 감압술 효과

학위논문 (석사) -- 서울대학교 대학원 : 치의학대학원 치의과학과, 2021. 2. 김성민.연구의 배경 및 목적 턱의 골수염 (Osteomyelitis, OM) 은 대개 만성적인 치성 감염이나 턱뼈를 파괴하는 여러 가지 다른 이유로 인해 발생한다. 포도상구균(Staphylococcus aureus, S. aureus) 과 같은 미생물은 중요한 병원균이다. 악안면 낭포종에 드레인을 이용한 감압술은 신뢰할 수 있는 치료방법으로 낭포종 내벽에 배농을 위한 최소한의 배관을 뚫어 낭포종의 크기의 줄이고, 낭포종의 내압을 줄임으로써 주변으로부터 점진적인 뼈 성장을 가능하게 한다. 이 연구의 목적은 하악 골수염 백서 동물 모델에서 감압술의 효과에 대해서 알아보는 것이다. 연구방법 평균 몸무게 230.13±13.87의 8주 된 수컷 Sprague-Dawley 백서 14마리를 실험에 사용하였다. 하악에 직경 4 mm의 결손부를 만들어 1x107 CFU/ml 농도의 포도상구균 20ul를 결손부에 주입하여 골수염을 유발하였다. 백서는 치료방법에 따라 대조군은 치료하지 않은 그룹을 대조군 1 (control, C1), 소파술을 시행한 그룹을 대조군 2 (control, C2) 로 설정하였고, 실험군은 소파술, 드레인을 이용한 감압술을 시행한 그룹을 실험군 1 (experimental 1, E1), 소파술, 드레인을 이용한 감압술과 드레인을 통해 생리식염수로 세척을 시행한 그룹을 실험군 2 (experimental 2, E2) 로 설정하였다. 치료 후 4주에 백서를 희생하여 마이크로 단층촬영 (micro-CT), 헤마톡실린-에오신 (hematoxylin and eosin, H&E) 과 Masson’s trichrome 염색을 사용한 조직학적 분석을 시행하였고, 염증 관련 항체 IL-6와 TNF-α, 신생 혈관 관련 항체 VEGF-A와 TGF-β1, 골 형성 관련 항체 OPN와 ALP 항체를 사용해 면역화학적 분석을 시행하였다. 연구결과 백서 하악골 골수염 모델에서 포도상구균에 의해 골수염이 유발된 것을 임상과 실험적 결과로 확인하였다. 마이크로 단층촬영 (micro-CT) 에서 골 치유에 대한 대부분의 매개변수는 대조군 1 (C1) 과 대조군 2 (C2) 그룹에서 현저히 낮았다. 특히 실험군 2 (E2) 에서 대조군 1 (C1) 과 대조군 2 (C2) 에서 볼 수 있는 것 보다 골량 (bone volume) 과 골밀도 (bone mineral density, BMD) 가 크게 향상되었고, bone volume/volume of interest 가 유의미하게 높았다 (p < 0.05). 조직학적 분석에서 실험군 1 (E1) 과 실험군 2 (E2) 에서 결손부위에 발견되는 골세포 (osteocyte) 의 수가 현저히 많은 것으로 두드러진 골 치유를 보였다 (p < 0.05). 면역화학적 염색에서 실험군 2 (E2) 는 대조군 1 (C1) 에 비해 IL-6의 표현이 가장 약했고, TNF-α의 표현은 다른 그룹과 비교하여 실험군 1 (E1) 에서 강하게 착색되었다. VEGF-A의 표현은 실험군 2 (E2) 에 비해 대조군 1 (C1) 에서 가장 높았고, TGF-β1, ALP, OPN 표현은 실험군 1 (E1) 에서 현저하게 높았으며, 대조군 1 (C1) 에서는 다른 그룹과 비교했을 때 TGF-β1, ALP, OPN 표현이 없었다. 결론 마이크로 단층촬영 (micro-CT), 헤마톡실린-에오신 (hematoxylin and eosin, H&E)과 Masson`s trichrome 염색을 사용한 조직학적 분석 및 면역화학적 분석은 골수염 백서 모델에서 드레인을 이용한 감압술이 기존의 수술적 치료에 비해 이상적인 골 치유 결과를 보였음을 확인하였다. 이러한 결과를 바탕으로 임상의는 악안면 골수염 치료를 위해 배농 (drainage) 과 세척 (irrigation) 을 동반한 감압술을 사용하는 것을 권장할 수 있을 것으로 사료된다.Introduction Osteomyelitis (OM) of the jaw is usually caused by odontogenic infection or by a variety of other reasons which result in jaw bone destruction. Microorganisms such as Staphylococcus aureus (S. aureus) are known to be significant pathogens at the pathogenesis of OM. Decompression using a drain is a reliable technique, which releases the intraluminal pressure causing reduction of cyst and allows gradual bone regeneration from the periphery. The aim of this study was to analyze the effectiveness of decompression in an OM rat mandible model. Materials and methods A 4 mm diameter defect was made on the mandibles of 14 male Sprague-Dawley rats (8 weeks old with weight of 230.13+/-13.87 g) and 20 μl of 1x107 CFU/ml S. aureus was inoculated. Two weeks later, the animals were randomly divided into non-treatment control (C1), curettage only control (C2), curettage and decompression using drain (E1), and curettage and decompression using drain with normal saline irrigation (E2) groups. After four weeks, the animals were assessed with micro-computed tomography (micro-CT), histology stained with hematoxylin and eosin (H&E) and Masson's trichrome (MT), and immunohistochemistry (IHC) stained with inflammation-related IL-6 and TNF-α, angiogenesis-related VEGF-A and TGF-β1, and osteogenesis-related OPN and ALP antibodies, followed by statistical analysis. Results S. aureus infected osteomyelitis model was successfully created in a rat mandible. Most parameters showed significantly lower bone healing in the C1 and C2 groups in micro-CT analysis. Especially in the E2 group, bone mineral density with bone volume was significantly enhanced compared to that seen in the C1 or C2 groups, and bone volume/volume of interest parameter was significantly higher (p < 0.05) in the E2 group. In the histological analysis, the E1 and E2 groups showed the most prominent bone healing with a significantly high number of osteocytes found in the defect area (p < 0.05). In IHC staining, the E2 group had the weakest expression of IL-6 compared to that of the C1 group. The TNF-α antibody was stained strongly in the E1 group compared to that of other groups. The expression of VEGF-A was the highest in the C1 group compared to the E2 group. The TGF-β1, ALP, and OPN expressions were markedly high in the E1 group, while the C1 group had no TGF-β1, ALP, and OPN expression compared to that of the other groups. Conclusion The micro-CT, H&E, and MT stained histological analysis, and IHC analyses showed that decompression drains exhibited superior bone healing results compared with that of conventional surgical treatment alone in an OM rat mandible model. Based on these results, it is recommended that clinicians use decompression with drainage and irrigation to treat jaw OM.Contents I. Introduction 01 II. Materials and Methods 04 II.1. Establishment of an S. aureus-infected jaw 04 osteomyelitis model in rat II.2. Grouping and experimental design 07 II.3. The analysis of bone healing with micro-CT 08 II.4. The histological and immunohistochemical 09 analysis of OM healing II.5. Statistical analyses of micro-CT and histological 10 data of bone healing III. Results 11 III.1. Establishment of an S. aureus-infected jaw 11 osteomyelitis model in rat III.2. Clinical evaluation with blood test 11 III.3. Micro-CT results of bone healing 12 III.4. Histological and immunohistochemical results of OM healing 13 IV. Discussion 15 V. Conclusion 20 References 21 Tables 25 Figures and Figure legends 29 Abstract in Korean 47Maste

Decompressive effects of draining tube on suppurative and sclerosing osteomyelitis in the jaw

Background Osteomyelitis (OM) in the jaw is an inflammatory disease of osseous tissue that begins in the medullary space and progressively expands to the cortical portion of the bone, the Haversian system, the periosteum and the overlying soft tissue. Despite advances in dental and medical care, OM persists and is of important concern in modern medicine. Active negative pressure is known to prevent post-operative hematoma; decrease the number of bacterial pathogens, accumulation of toxins, and necrotic tissue; and promote osteogenesis and angiogenesis with the use of a draining tube such as the Jackson-Pratt (JP) or Hemovac. The purpose of this study was to assess the effectiveness of decompression for the treatment of OM in the jaw. Methods This retrospective study included a total of 130 patients, 55 patients with sclerosing OM and 75 patients with suppurative OM were included. The radiographic bone densities expressed as a grayscale values (GSVs), were measured using an easy digitalized panoramic analysis (EDPA) method, processed on the conditional inference tree, generated by the R program® 3.2.3 with a probability of 96.8%. Rectangle annotation analysis of INFINITT PACS® (INFINITT Healthcare, Seoul, Korea) of 50 mm2 was determined as the region of interest (ROI). Students t-test and ANOVA were used to determine significance (p < 0.05). Results Significant changes was observed between radiographic bone density in the sclerosing type with drain and without drain at the six-month and one-year follow-up (p < 0.05). Significant difference was demonstrated between the suppurative OM with drain and without drain groups at the one-year follow-up (p < 0.05). Conclusion The OM groups with drain exhibited more enhanced bone density compared to the groups without drain at the six-month and one-year follow-ups. The drain insertion for decompression is effective for the management of sclerosing and suppurative OM. It is recommended to implement it for the management of OM.This study was supported by grant no 03–2019-0043 from the SNUDH Research Fund and by Basic Science Research Program of NRF funded by the Ministry of Education (2017R1D1A1B04029339)

Adverse reaction to Coartem (artemether/lumefantrine) resulting in oculogyric crisis

Background Artemether/lumefantrine (AL), sold under the brand name Coartem, is the most common artemisinin-based combination therapy for the treatment of malaria. Drug-induced oculogyric crisis is a neurological disorder characterized by frequent upward deviations of the eye. In the literature, no cases of Coartem-induced oculogyric crisis have been reported in Ghana. Case presentation A 19-year-old male patient, who presented fever measuring 37.9 °C, general body pains, and weakness was prescribed with antimalarial therapy artemether/lumefantrine, Coartem®, from a local pharmacy. Just after initiation of treatment, the patient complained of double vision, involuntary upward eye deviation, and inability to close both eyes. The patient was diagnosed with Coartem-induced oculogyric crisis and was treated with the cessation of the causing agent and intramuscular injection of promethazine hydrochloride. Conclusions When a patient exhibits a neurological disorder, such as oculogyric crisis, with normal conscious state and normal vital signs, special attention should be given to obtaining a history of recently administered medications. Clinicians should recognize adverse reactions to drugs based on a thorough patient history and examination. The goal of this report was to present Coartem-induced oculogyric crisis.This research was supported by Basic Science Research Program funded by the Ministry of Education (2017R1D1A1B04029339) and by grant no 03-2019-0043 from the SNUDH Research Fund

Clinical feasibility and benefits of a tapered, sand-blasted, and acid-etched surfaced tissue-level dental implant

Abstract Background It has been 50 years since Brånemark first introduced the concept of osseointegration. Since then, numerous ongoing research, developments, and optimization of implant properties have been conducted. Despite the high survival and success rates of dental implants, failures still occur in a small number of patients that are being rehabilitated by implants. The purpose of this study was to evaluate the survival and success rate of the Stella® implants that incorporate sand-blasted and acid-etched (S&E) surface treatment and tapered body design to confirm their clinical feasibility and benefits after placement. Methods We reviewed 61 partially and fully edentulous patients who underwent a tapered, S&E surfaced tissue-level implant placement between May 2013 and February 2016 in the Department of Oral and Maxillofacial Surgery in the Seoul National University Dental Hospital. Patient characteristics and treatment results were collected, and records of dental implants were analyzed clinically and radiologically. Results A total of 105 implant fixtures were placed in these patients. The mean age at the time of the surgery was 63.7 years with a range of 31 to 88 years. In total, 4.0-mm and 4.5-mm diameter implants were the most frequently used dental implants (40%, 49%) in this study. Implants 8.5 mm in length were predominantly used (60%). Seventy dental implants were placed in the mandible (70%), and only one dental implant was placed in the maxillary anterior region. At the end of the 5-year observation period, the success rate of the Stella® implants was 98.1%. Among the 105 implants placed, 2 were considered to be failures. Summarizing the clinical and radiographic results, the remaining 103 implants were considered successfully integrated. Conclusion The overall success rate was 98.1%. The tapered, S&E surfaced tissue-level implant system exhibited great performance in a variety of clinical situations including failed implant sites that enabled predictable and successful treatment outcomes. The effectives of a tapered design of tissue level, not a parallel design, are shown in this clinical report

Oral Manifestation of Unknown Hematopoietic Malignancy

Burkitt lymphoma is a highly aggressive type of hematopoietic malignancy that is comparatively common in chil dren and young people. It is important that Burkitt lymphoma be diagnosed as early as possible for prompt inter vention due to its rapidly progressive, high-grade malignant nature. Dentists, especially maxillofacial surgeons, can play a life-saving role in patients with such unknown malignancy as the first clinical or radiological manifestation might occur in the oral region.N

Next generation sequencing-based salivary biomarkers in oral squamous cell carcinoma

Selection of potential disease-specific biomarkers from saliva or epithelial tissues through next generation sequencing (NGS)-based protein studies has recently become possible. The early diagnosis of oral squamous cell carcinoma (OSCC) has been difficult, if not impossible, until now due to the lack of an effective OSCC biomarker and efficient molecular validation method. The aim of this study was to summarize the advances in the application of NGS in cancer research and to propose potential proteomic and genomic saliva biomarkers for NGS-based study in OSCC screening and diagnosis programs. We have reviewed four categories including definitions and use of NOS, salivary biomarkers and OSCC, current biomarkers using the NGS-based technique, and potential salivary biomarker candidates in OSCC using NGS.N

A Life-Saving Early Diagnosis of Burkitt Lymphoma: The Role of a Dentist

Burkitt lymphoma (BL) is a subtype of Non-Hodgkin lymphoma, considered one of the fastest growing human tumors. Due to the highly aggressive nature of BL, a prompt diagnosis and aggressive chemotherapeutic treatment are essential. However, the clinical features of BL often can mimic periodontal disease or dentoalveolar abscess. The aim of this study is to present a case of a 31-year-old male patient who was referred to the department of oral and maxillofacial surgery for severe neurosensory disturbance and pain in the lower jaw. He was misdiagnosed with periodontitis and dental abscess at the local clinic. Based on radiographic findings, he was suspected of hematopoietic malignancy. He was referred to the department of hemato-oncology and diagnosed with BL. This case highlights the essential life-saving role of a maxillofacial surgeon in the early diagnosis of a rare malignancy.N

Functional rehabilitation of the maxillary sinus after modified endoscopic sinus surgery for displaced dental implants

Abstract Purpose Dental implants may become displaced into the maxillary sinus due to insufficient primary stability, changes in nasal air pressure, or surrounding bone resorption and should be removed as soon as possible. The aim of this study was to evaluate the efficacy of the modified endoscopic sinus surgery (MESS) approach for removal of displaced dental implants. Methods From September 2010 to November 2021, we studied 15 cases with displaced implants in the maxillary sinus. The patient characteristics, medical history, clinical and imaging results, and post-removal outcomes were retrospectively assessed. Results The symptoms included sinusitis (100%), pain (26.6%), postnasal drip (6.6%), nasal obstruction (26.6%), and oroantral communication (26.6%). Two cases were managed through the crestal approach (13.3%), while two cases were treated with the Caldwell–Luc procedure (13.3%). One case was addressed using functional endoscopic sinus surgery (6.7%), while 10 cases were managed with the MESS approach (66.7%). MESS allows functional rehabilitation of mucociliary clearance by the cilia in the sinus membrane. Implant displacement into the maxillary sinus can be classified as early, late, or delayed displacement. Conclusions MESS is a reliable treatment option that can identify migrated dental implants in any part of the sinus with endoscopic assistance for functional rehabilitation of the maxillary sinus without postoperative sequelae

Identification of biological components for sialolith formation organized in circular multi-layers

Abstract According to the previous studies of sialolithiasis reported so far, this study is aimed to identify the biological components of sialolith, which show different ultrastructures and chemical compositions from other stones, cholelith and urolith. Twenty-two specimens obtained from 20 patients were examined histologically, and analyzed with micro-CT, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), and transmission electron microscopy (TEM). All sialoliths (n = 22) observed in this study showed a central nidus, which was filled with organoid matrix admixed with exosome vesicles, loose calcium apatite crystals, and many bacteria. The micro-CT and SEM observation clearly defined a single or multiple central nidus(es) encircled by highly calcified compact zone. The circular compact zone showed a band-like calcification, about 1–3 mm in thickness, and usually located between the central nidus and the peripheral multilayer zone. But some sialoliths (n = 5) showed severe erosion of compact zone by expanding multilayered zone depending on the level of calcification and inflammation in sialolith. By observing TEM images, many exosome vesicles and degraded cytoplasmic organelles were found in the central nidus, and some epithelial cells were also found in the calcified matrix of peripheral multilayer zone. Particularly, EDS analysis indicated the highest Ca/P ratio in the intermediate compact zone (1.77), and followed by the central nidus area (1.39) and the peripheral multilayer zone (0.87). Taken together, these data suggest that the central nidus containing many inflammatory exosomes and degraded cytoplasmic organelles has a potential to induce a band-like calcification of compact zone, and followed by the additional multilayer deposition of exfoliated salivary epithelial cells as well as salivary materials. Thereby, the calcium apatite-based sialolith is gradually growing in its volume size, and eventually obstructs the salivary flow and provides a site for the bacterial infection