삼중음성유방암에서 PD-L1 과발현과 면역관문억제제 효과의 연관성

학위논문(석사) -- 서울대학교대학원 : 의과대학 협동과정 종양생물학전공, 2024. 2. 한원식.Recently, there has been substantial progress in immunotherapy, with a specific focus on immune checkpoints, such as programmed death ligand 1(PD-L1). These advances have potential for enhancing anti-tumor immunity and addressing the limitations in cancer treatment by targeting immune checkpoints that tumor cells exploit to evade immune surveillance. However, a notable limitation exists; the relationship between the expression of PD-L1 and anti-PD-L1 effects is unclear and comprehensive knowledge of the efficacy of PD-L1 immunotherapy remains incomplete. A key challenge is to understand the effect of anti-PD-L1 based on PD-L1 levels, and the genes and pathways that contribute to its efficacy. In orthotopic syngeneic tumor models, PD-L1 upregulation was not associated with elevated tumorigenesis and enhancement of anti-PD-L1 effect. At the cellular level, PD-L1 overexpression increased the migration, invasion, and proliferation rates. Notably, the treatment of anti-PD-L1 also resulted in an increase, rather than a reduction, in proliferation rates. At the tumor microenvironment level, CD4+ T cell infiltration was increased in tumors treated with PD-L1 inhibitors, regardless of PD-L1 expression levels. However, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses based on bulk RNA sequencing revealed differences between tumors that responded to treatment and those that did not. Th1, Th2, and Th17 differentiation of immature CD4+ T cells, as well as T cell receptor signaling, were upregulated in control tumors that responded to PD-L1 inhibitors. Conversely, these pathways were downregulated in PD-L1 overexpressed tumors that do not respond to PD-L1 inhibitors. In conclusion, this study consistently reveals an inverse correlation between PD-L1 expression and efficacy of anti-PD-L1 immunotherapy, indicating a potential intrinsic resistance linked to high PD-L1 levels. It also highlights a potential connection between the efficacy of PD-L1 inhibitors and CD4+ T cell differentiation pathways, T cell receptor signaling. Furthermore, the findings suggest a possibility that the importance of differentiation and activation of CD4+ T cells over simple infiltration in the context of PD-L1 immunotherapy, and the functional properties of these cells play an important role in influencing treatment outcomes.최근에는 PD-L1과 같은 면역 체크포인트에 초점을 맞춘 면역 요법이 크게 발전하고 있다. 이러한 발전은 종양 세포가 면역 감시를 회피하기 위해 이용하는 면역 체크포인트를 표적으로 삼아 항종양 면역을 강화하고 암 치료의 한계를 해결할 수 있는 잠재력을 가지고 있다. 그러나 PD-L1의 발현과 항 PD-L1 효과 사이의 관계가 불분명하고 PD-L1 면역치료의 효능에 대한 이해가 불완전하다는 한계가 존재한다. 핵심 과제는 PD-L1 발현에 따른 PD-L1 억제제의 효과와 그 효능에 기여하는 유전자 및 경로를 이해하는 것이다. 동종 종양 모델에서 PD-L1 상향 조절은 종양 형성을 촉진했지만 PD-L1 억제제의 효과는 향상시키지 않았다. 세포 수준에서도 확인한 결과, PD-L1 과발현은 이동, 침입 및 증식 속도를 증가시켰다. 특히, PD-L1 억제제를 처리하면 증식 속도가 감소하는 것이 아니라 오히려 증가하는 것으로 나타났다. 종양 미세 환경 수준에서는 PD-L1 발현 수준과 관계없이 PD-L1 억제제를 투여한 종양에서 CD4+ T 세포 침윤이 증가했다. 그러나 대량 RNA 시퀀싱에 기반한 GO 및 KEGG 경로 분석 결과, PD-L1 억제제에 치료효과를 보였던 대조군 종양에서 미성숙 CD4+ T 세포의 Th1, Th2, Th17 분화와 T 세포 수용체 신호가 상향 조절된 것으로 나타났다. 반대로, 이러한 경로는 PD-L1 억제제에 반응하지 않는 PD-L1 과발현 종양에서는 하향 조절되었다. 결론적으로, 이 연구는 PD-L1 발현 증가와 PD-L1 면역치료의 효과 사이의 반비례 관계를 밝혀냈으며, 이는 높은 PD-L1 수치와 관련된 내재적 내성 가능성을 시사한다. 뿐만 아니라 CD4+ T 세포의 분화 경로 및 T 세포 수용체 신호가 반대의 패턴을 보임을 확인하였다. 이를 통해 PD-L1 면역 치료의 맥락에서 단순 침윤보다 CD4+ T 세포의 분화 및 활성화가 중요하며, 이러한 세포의 기능적 특성이 치료 결과에 영향을 미치는 데 중요한 역할을 할 수 있다는 가능성을 시사한다.Abstract ⅰ Table of Contents ⅳ List of Tables ⅴ List of Figures ⅵ Ⅰ. Introduction 1 Ⅱ. Materials and Methods 4 Ⅲ. Results 16 Ⅳ. Discussion 43 Ⅴ. Conclusion 52 Ⅵ. References 53 Abstract in Korean 62석

A Case of Horizontal Partial Laryngectomy for Laryngeal Trauma

Laryngeal trauma is rare compared to other head and neck traumas, but it occurs, it can be life threatening. As for treatment, a laryngeal fracture that involves displacement of cartilage or extensive injury requires appropriate surgical treatments. For severe laryngeal fractures, conservative management is usually preferred with placing a stent to prevent laryngeal stenosis. But the downside of placing stents in the larynx includes the risk of granulation and infection. In this report, the authors describe a 35-year-old patient, who was diagnosed with blunt laryngeal trauma and treated by Horizontal partial laryngectomy. The patient's post-operative breathing and voice were fair, and airway stenosis did not occur afterwards.ope

성남시 자원순환가게re100을 중심으로

학위논문(석사) -- 서울대학교대학원 : 환경대학원 환경조경학과, 2023. 2. 김세훈.As more than half of the world's population lives in cities, most environmental problems such as greenhouse gas emissions, waste, and energy are occurring in cities. In particular, Korea's high population density, urban consumption culture, economic development, aging, and redevelopment are the main causes of the absolute increase in the amount of waste, and the importance of waste treatment innovation is emerging. Following this trend, Seongnam City introduced the Resource Circulation Platform, a resource circulation project to increase the value of resources and promote active civic participation, and the Resource Circulation Store re100, which was introduced in 2020, has spread to 17 branches in three years, creating a voluntary resource circulation culture in the region. The "resource circulation store re100" is a resident-participating oil price compensation project in the private, government, and corporate cooperation system. The project has sustainable characteristics such as high value-added resources, post-processing attempts in generation support, and participation of various members of the city, and has the potential to maximize waste treatment efficiency in the future. This study attempted to analyze the successful settlement factors of the project by dividing it into physical factors, economic and social factors, and environmental and cultural factors. The research method consisted of business network analysis using internal data and interviews and empirical analysis through field research and in-depth interviews. The field survey consisted of three branches of resource circulation store re100, one local government official, five resource circulation activists, two environmental civic groups, one affiliated company (Lotte Chemical) official, and one affiliated agency official. Chapter 3 analyzes the model and system of the project and describes the differentiation from the existing waste system and the associated institution. Chapter 4 attempted to analyze the difference between the resource circulation store re100 as a resident participation project based on the operation network of the resource circulation store re100 analyzed in Chapter 3 in terms of physical, economic, environmental, and cultural aspects. The conclusions of each aspect are as follows. First, Seongnam Resource Circulation Store re100 is a regional customized project that reflects urban characteristics and exists in various physical forms. In the case of the old city center, it can be seen that the complexly intertwined urban problems are solved through resource circulation living labs. Residents continue to explore ideas to create a physical space that can solve the problem of illegal waste disposal and odor in the old city, aging urban landscape and empty houses, aging and women's career breaks, and economic stagnation in the city. In the case of a new city, it can be seen that a physical form is created in consideration of the living patterns of urban users. For example, the resource circulation store re100 is often located around large discount stores, administrative welfare centers, dong offices, and schools where continuous consumption takes place. In addition, the shape of the resource circulation store re100 in the new city has a more flexible shape than the old city center. In the case of re100, an in-school resource circulation store where members of the school mainly participate, it is operated flexibly during the period excluding the vacation period. Attempts to make differences in physical forms based on urban characteristics and user characteristics by base show that Seongnam Resource Circulation Store re100 has settled as a sustainable business. Second, Seongnam Resource Circulation Store re100 is differentiated in that it creates social and economic value in terms of the waste management industry, which is difficult to make high value-added. The operating system, which fosters resource circulation activists for Seongnam-si citizens to create jobs and allows local currency refunds to residents participating in the resource circulation store re100, is an attempt to solve various problems in the city. Through interviews and field surveys, there are two reasons why the creation of social and economic value through resource circulation projects could continue, not just one-off. The first factor is the intervention of the public and private sectors to select citizens with clear environmental motives and foster activists through appropriate education and experiential activities. Seongnam City and Seongnam Environmental Movement Association included the link between climate crisis, carbon neutrality, and resource circulation in the curriculum to enhance understanding of resource circulation projects and to raise interest through lectures inviting resource circulation cases. In addition, after the education, through the connection with environmental companies, they were allowed to participate in the waste treatment process by directly completing volunteer activities. The process of fostering resource circulation activists with this detailed system raised the capabilities of residents who originally had high environmental awareness and potential and promoted responsibility. The second factor is efforts to solve the waste problem by linking other types of urban problems such as digital alienation due to aging and stagnation of local commercial districts. Resource circulation store re100 is also a business that attempts to introduce and link new technologies, where data-based oil price compensation is made. However, the fact that it is helping the age group unfamiliar with digital transformation through resource circulation activists made it possible to use it smoothly. In addition, the difference is that it contributes to revitalizing the local economy as well as the economic benefits that residents get by compensating oil prices in local currency. Third, the resource circulation store re100 effectively delivers the environmental effects generated from the project to residents through linked organizations and allows eco-friendly culture to be transplanted through linked projects and programs. The difference in the aspect of forming an eco-friendly culture of the resource circulation store re100 can be explained in two ways, and each can be divided into disclosure of environmental impact information of the project and discovery of linked projects. First of all, the environmental effects generated through the project are converted into low carbon dioxide reduction and tree planting effects to facilitate residents' understanding. In addition, information and current status necessary to form an environmental culture are shared through websites and SNS. In addition, there is a difference in the method of cultural diffusion through the post-processing system and institutional linkage. The post-processing system, which is linked to the resource circulation store re100, has a priority goal in promoting environmental and cultural awareness, and in the operation of branches, linkage with religious institutions has contributed to revitalizing the project. Through the interview, it was confirmed that environmental and cultural citizenship can be enhanced in that indirect learning is being conducted to see and follow the project even if the resource circulation store does not use the re100 branch. This study revealed the operating system of Korea's first resident-participating resource circulation platform in the form of private, government, and corporate collaboration, and discovered physical, economic, social, and environmental and cultural factors that could have established the project as a successful model. Since this study suggests a way to link various technologies to the waste industry that is difficult to add value, it can contribute to the establishment of a smart waste treatment system in future cities. In addition, it is expected that resource circulation can be implemented and applied in various urban forms in the future through the new type of waste treatment model covered in this study.전 세계적으로 인구 절반 이상이 도시에 거주함에 따라 온실가스 배출, 폐기물, 에너지 등 환경문제의 대부분이 도시에서 발생하고 있다. 특히, 한국의 높은 인구 밀도, 도시의 소비문화, 경제발전, 고령화, 재개발은 폐기물의 양이 절대적으로 증가하게 만드는 주된 원인이 되고 있으며 이에 따라 폐기물 처리 혁신의 중요성이 대두되고 있다. 이러한 흐름에 따라 성남시에서는 자원의 고부가가치화와 능동적 시민참여를 도모하기 위한 자원순환 사업인 '자원순환플랫폼'을 도입했고, 그 중 2020년부터 도입된 '자원순환가게 re100'은 3년 만에 17개 지점으로 확산되며 지역 내 자발적 자원순환 문화가 생성되는 성과를 보이고 있다. '자원순환가게re100(recycling100)'은 민·관·기업 협업 체계의 주민참여형 유가보상형 사업이다. 해당 사업은 자원의 고부가가치화, 발생지원에서의 후처리 시도, 도시의 다양한 구성원의 참여 등의 지속가능한 특성을 가지고 있고, 기업 연계를 통한 스마트기술을 접목하려는 시도를 하고 있어 향후 폐기물 처리 효율성 극대화의 잠재성을 지니고 있다. 본 연구에서는 해당 사업의 성공적 정착 요인을 물리적 요인, 경제·사회적 요인, 환경·문화적 요인으로 구분하여 분석하고자 하였다. 연구 방법은 크게 내부자료와 인터뷰를 활용한 사업 네트워크 분석과 현장조사·심층인터뷰를 통한 실증 분석으로 이루어졌으며, 현장조사는 자원순환가게re100 지점 중 가장 원활한 참여가 이루어지는 3개 지점, 인터뷰는 지자체 공무원 1명, 자원순환활동가 5명, 환경시민단체 2명, 연계기업(롯데케미칼) 관계자 1명, 연계기관 관계자 1명으로 이루어졌다. 3장에서는 사업의 모델 및 체계를 분석하며 기존 폐기물 체계와의 차별성과 연계기관에 대해 기술했다. 4장에서는 3장에서 분석한 자원순환가게re100의 운영 네트워크를 기반으로 자원순환가게re100이 주민참여형 사업으로서 어떠한 차별성을 지니고 있는지 물리적, 경제적, 환경·문화적 측면에서 분석하고자 했다. 각 측면의 결론은 다음과 같다. 첫째, 성남 자원순환가게re100은 도시특성을 반영한 지역맞춤형 사업이며, 다양한 물리적 형태로 존재한다. 구도심의 경우에는 복잡하게 얽혀있는 도시의 문제를 자원순환 리빙랩을 통해 복합적으로 해결하고자 함을 알 수 있다. 구도심의 불법 폐기물 적치와 악취 문제, 노후화된 도시 경관과 빈집 문제, 고령화와 여성 경력 단절 문제, 도시의 경제적 침체를 복합적으로 해결할 수 있는 물리적 공간을 만들기 위해 주민이 주체가 되어 지속적으로 아이디어를 발굴한다. 신도시의 경우에는 도시 이용자들의 생활 패턴을 고려하여 물리적 형태를 조성함을 알 수 있다. 이를테면, 지속적 소비가 이루어지는 대형마트, 행정복지센터, 동사무소, 학교 등을 중심으로 자원순환가게re100가 위치하는 경우가 많다. 또한, 신도시 내 자원순환가게re100의 형태는 구도심에 비해 유동적인 형태를 지니고 있다. 학내 구성원들이 주로 참여하는 교내 자원순환가게re100의 경우에는 방학 기간을 제외한 기간을 이용해 유동적으로 운영된다. 도시 특성과 거점 별 이용자 특성을 기반으로 물리적 형태에 차이를 두려는 시도는 성남 자원순환가게re100이 지속가능한 사업으로 정착하게 했음을 알 수 있다. 둘째, 성남 자원순환가게re100은 고부가가치화가 어려운 폐기물 관리 산업 측면에서 사회·경제적 가치를 창출하고 있다는 점에서 차별성이 있다. 성남시 시민을 대상으로 자원순환활동가를 육성하여 일자리를 창출하고, 자원순환가게re100 참여 주민에게 지역 화폐를 통한 환급이 이루어지게 하는 운영 체계는 도시의 다양한 문제를 해결하려는 노력이 보이는 시도이다. 인터뷰와 현장조사를 통해 자원순환사업을 통한 사회·경제적 가치 창출이 일회성에 그치지 않고 지속될 수 있었던 까닭에 대해 두 가지로 정리할 수 있다. 첫 번째 요인은 환경적 동기가 분명한 시민을 선별하여 적절한 교육과 체험 활동을 통해 활동가를 육성하고자 했던 민·관의 개입이다. 성남시와 성남환경운동연합은 기후위기, 탄소중립, 자원순환의 연계성을 교육 과정에 포함하여 자원순환사업의 이해를 높이고 자원순환 사례 초청 강의를 통해 흥미를 높였다. 또한 교육 이후 환경기업과의 연계를 통해 직접 자원순환 봉사활동 이수를 통해 폐기물 처리 과정에 참여하도록 했다. 이러한 세밀한 체계의 자원순환활동가 육성 과정은 본래 높은 환경적 인식과 잠재성을 가지고 있던 주민들의 역량을 높이고 책임감을 증진시켰다. 두 번째 요인은 고령화로 인한 디지털 소외, 동네 상권 침체와 같은 다른 유형의 도시 문제들을 연계해 폐기물 문제를 해결하려는 노력이다. 자원순환가게re100은 데이터 기반 유가보상이 이루어지는, 신기술의 도입과 연계를 시도하는 사업이기도 하다. 그러나 자원순환활동가를 통해 디지털 전환에 익숙하지 않은 연령층의 이용을 돕고 있다는 것이 원활한 이용이 가능하게 했다. 또한 지역화폐로 유가보상을 함으로써 주민들이 얻게 되는 경제적 혜택 뿐 아니라 지역경제 활성화에 기여하고 있다는 점이 차별점이라고 볼 수 있다. 셋째, 자원순환가게re100은 연계 기관을 통해 사업에서 발생한 환경적 효과를 주민에게 효과적으로 전달하며, 연계 사업과 프로그램을 통해 친환경 문화가 이식되도록 한다. 자원순환가게re100의 친환경 문화 형성 측면의 차별성은 두 가지 갈래로 설명할 수 있으며 각각 사업의 환경적 영향 정보 공개와 연계 사업 발굴로 구분할 수 있다. 우선, 사업을 통해 발생한 환경적 효과를 이산화탄소 저감량, 나무를 심는 효과 등으로 환산하여 주민의 이해가 용이하게 한다. 또한, 환경 문화 형성에 필요한 정보와 현황을 웹사이트와 SNS 등을 통해 공유하고 있다. 또한 후처리 체계와 기관 연계를 통한 문화 확산 방식에 차별성이 있다. 롯데케미칼 프로젝트 Loop와 같이 자원순환가게re100과 연계되어 있는 후처리체계는 환경·문화 의식을 증진시키는 데에 우선적 목표를 두고 있으며, 지점 운영에 있어서는 종교기관과의 연계가 사업의 활성화에 기여했다. 인터뷰를 통해 비단 자원순환가게re100 지점을 이용하지 않더라도 사업을 보고 따라 할 수 있는 간접 학습이 이루어지고 있다는 점에서 환경·문화적 시민의식이 증진될 수 있음을 확인할 수 있었다. 본 연구는 국내 최초 민·관·기업 협업 형태의 주민참여형 자원순환플랫폼의 운영 체계를 밝히고, 해당 사업이 성공적 모델로 자리 잡을 수 있었던 물리적 요인, 경제·사회적 요인, 환경·문화적 요인을 발굴했다. 본 연구는 고부가가치화가 어려운 폐기물 산업에 다양한 기술을 연계할 수 있는 방법을 제시하고 있기 때문에, 미래도시 내 스마트 폐기물 처리 시스템 구축에 기여할 수 있다. 또한 본 연구에서 다룬 새로운 형태의 폐기물 처리 모델을 통해 추후 다양한 도시 형태에서 자원순환을 구현 및 적용할 수 있다는 기대를 가지고 있다.1장 서론 1 1절. 연구의 배경 및 목적 1 1. 연구의 배경 1 2. 연구의 목적 4 2절. 연구의 범위 및 방법 5 1. 연구의 범위와 대상 선정 이유 5 2. 연구의 방법 7 3절. 연구의 진행과정 11 2장 문헌고찰 12 1절. 자원순환사회의 정의와 개념 12 1. 탄소중립과 탄소중립도시 12 2. 자원순환 15 3. 자원순환사회 16 2절. 자원순환사회 정책의 흐름과 방향성 19 1. 폐기물 관련 법체계와 추진 경과 19 2. 부문별 정책 추진 경과와 한계점 22 3. 자원순환사회 구현의 방향성 23 3절. 주민참여형 사업 25 1. 주민참여의 개념 25 2. 주민참여의 단계 및 유형 26 4절. 연구의 차별성 29 1. 연구의 차별성 29 3장 성남시 자원순환가게re100의 형성과 운영체계 32 1절. 성남시 자원순환가게re100의 개요 32 1. 자원순환가게re100의 개념 및 도입목적 32 2. 자원순환가게re100 설치 장소 및 형태 32 3. 자원순환가게re100 수집 품목 및 단가 35 4. 자원순환가게re100 주요 경과 및 기관 방문 현황 36 2절. 자원순환가게re100의 운영체계 38 1. 민관기업 협업 38 2. 자원순환가게re100 추진체계 41 1) 오프라인 순환체계 41 2) 온라인/모바일 데이터 관리 43 3. 후처리 체계 45 3절. 소결 48 4장 주민참여형 자원순환사업으로서의 차별성 분석 51 1절. 도시특성과 이용자를 고려한 지역맞춤형 사업 51 2절. 자원순환활동가 육성과 지역경제 활성화 64 3절. 민관 협력 체계를 활용한 친환경 문화 이식 75 4절. 한계 및 지향점 83 5장 결론 88 1절. 연구의 요약 및 시사점 88석

High-Resolution Contrast-Enhanced 3D-Spoiled Gradient-Recalled Imaging for Evaluation of Intracranial Vertebral Artery and Posterior Inferior Cerebellar Artery in Lateral Medullary Infarction

Purpose : To determine whether high-resolution contrast-enhanced three dimensional imaging with spoiled gradient-recalled sequence (HR-CE 3D-SPGR) plays a meaningful role in the assessment of intracranial vertebral artery (ICVA) and posterior inferior cerebellar artery (PICA) in lateral medullary infarction (LMI). Materials and Methods: Twenty-five patients confirmed with LMI were retrospectively enrolled with approval by the IRB of our institute, and 3T MRI with HR-CE 3D-SPGR and contrast-enhanced magnetic resonance angiography (CE-MRA) were performed. Two radiologists who were blinded to clinical information and other brain MR images including diffusion weighted image independently evaluated arterial lesions in ICVA and PICA. The demographic characteristics, the area of LMI and cerebellar involvement were analyzed and compared between patients with arterial lesion in ICVA only and patients with arterial lesions in both ICVA and PICA on HR-CE 3D-SPGR. Results: Twenty-two of twenty-five LMI patients had arterial lesions in ICVA or PICA on HR-CE 3D SPGR. However twelve arterial lesions in PICA were not shown on CE-MRA. Concurrent cerebellar involvement appeared more in LMI patients with arterial lesion in ICVA and PICA than those with arterial lesion in ICVA alone (p = 0.069). Conclusion: HR-CE 3D-SPGR can help evaluate arterial lesions in ICVA and PICA for LMI patients.ope

Shear-wave elastography for breast masses: local shear wave speed (m/sec) versus Young modulus (kPa)

PURPOSE: To evaluate and compare the performance of shear-wave elastography (SWE) for breast masses using the local shear wave speed (m/sec) vs. Young modulus (kPa). METHODS: A total of 130 breast lesions in 123 women who underwent SWE before ultrasound- guided core needle biopsy or surgical excision were included. With the region-of-interest placed over the stiffest areas of the lesion on SWE, the quantitative mean, maximum, and standard deviation (SD) of the elasticity values were measured in kPa and m/sec for each lesion. The SD was also measured with the region-of-interest including the whole breast lesion (wSD). The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of each elasticity value measured in kPa and m/sec were compared. RESULTS: Of the 130 lesions, 49 (37.7%) were malignant and 81 (62.3%) were benign. The AUCs for the mean, maximum, and SD of the elasticity values using kPa and m/sec did not differ significantly: mean, 0.974 vs. 0.974; maximum, 0.960 vs. 0.976; SD, 0.916 vs. 0.916. However, the AUC for wSD showed a significant difference: 0.964 (kPa) vs. 0.960 (m/sec) (P=0.036). There was no significant difference in the sensitivity and specificity of the mean, maximum, and wSD of the elasticity values. However, the specificity of the SD was significantly different between the two different measurements: 95.1% (kPa) vs. 87.7% (m/sec) (P=0.031). CONCLUSION: The quantitative elasticity values measured in kPa and m/sec on SWE showed good diagnostic performance. The specificity of the SD and AUC of the wSD measured in kPa were significantly higher than those measured in m/sec.ope

Ultrasonographic Features of Medullary Thyroid Carcinoma: Do they Correlate with Pre and PostOperative Calcitonin Levels?

Purpose: To correlate ultrasonographic (US) features of medullary thyroid carcinoma (MTC) with pre operative and postoperative calcitonin levels. Materials and Methods: A total of 130 thyroid nodules diagnosed as MTC were evaluated. Two radiologists retrospectively evaluated preoperative US features according to size, shape, margin, echogenicity, type of calcification, and lymph node status. Postoperative clinical and imaging followup (mean duration 31.9 22.5 months) was performed for detection of tumor recurrence. US features, presence of LN metastasis, and tumor recurrence were compared between MTC nodules with and without elevated preoperative calcitonin (>100 pg/mL). Those with normalized and nonnormalized postoperative calcitonin levels groups were also compared. Results: Common US features of MTCs were solid internal content (90.8%), irregular shape (44.6%), circumscribed margin (46.2%), and hypoechogenicity (56.2%). Comparing MTC nodules with and without elevated preoperative calcitonin levels, the size and shape of MTC nodule and lymph node metastasis showed statistical significance (p<0.05). Postoperative calcitonin normalization correlated with US features of tumor size (p0.002), margin (p0.034), shape (p0.001), and presence of calcification (p0.046). Tumor recurrence and LN metastasis were more prevalent in patients without normalization of postoperative calcitonin than in those with normalization (p0.001). Conclusions: Serum calcitonin measurement is helpful for early diagnosis and predicting prognosis. Postoperative calcitonin measurement is also important for postoperative US follow up, especially in cases with larger nodule size, presence of calcification, irregular shape, and irregular margin.ope

Long-Term Outcomes of Acute Low-Tone Hearing Loss

BACKGROUND AND OBJECTIVES: Although acute low-tone hearing loss has been associated with cochlear hydrops or early stage Meniere's disease, its prognosis in the short-term has been reported to be better than sudden hearing loss. However, recurrence of hearing loss and possible progression to Meniere's disease remain important concerns in the clinical setting. This study aims to investigate the long-term audiological outcomes of acute low-tone hearing loss. SUBJECTS AND METHODS: A retrospective review of patients presenting with a first attack of acute low-tone hearing loss was performed. Of the 77 patients, 33 were followed up for more than 3 months. Progression, recovery of hearing loss and recurrence of hearing loss were examined. Also, correlation between long-term outcomes and associated clinical factors were analyzed. RESULTS: Twenty-five patients (75.7%) had complete hearing recovery, five patients (15.1%) had partial recovery, two patients (6.0%) had no recovery, and one patient (3.0%) had progression of hearing loss 1 month after initial treatment. Thirty-three patients were followed up for more than 3 months (mean 22 months, range 3-79 months). Recurrences of acute low-tone hearing loss were observed in five patients (15.2%). All of the recurrences occurred during the first 12 months of follow-up. Long-term prognosis correlated with the initial therapy results (R(2)=0.693). CONCLUSIONS: Recurrences of hearing loss were documented in five patients (15.2%), and all of these cases occurred within one year of the first attack. Audiological outcomes after initial therapy may predict the recurrence of acute low-tone hearing loss.ope

Repeat Diagnoses of Bethesda Category III Thyroid Nodules: What To Do Next?

OBJECTIVES: To assess the malignancy rates of thyroid nodules repeatedly classified as Bethesda category III on fine needle aspiration (FNA), and to suggest management guidelines for these lesions. METHODS: This is a retrospective study that included 395 thyroid nodules categorized as Bethesda III undergone either surgery or ultrasound (US) follow-up. There were 67 nodules classified a second time as Bethesda category III on repeat FNA. We compared malignancy rates, clinicopathologic and ultrasonographic characteristics between direct surgery and repeat FNA groups and between the initial and repeat Bethesda category III groups, each. And in the repeat Bethesda III group, clinicopathologic and US variables were compared between benign and malignant nodules. RESULTS: Incidence of concurrent cancer, underlying thyroiditis and positive BRAF mutation were significantly higher in 142 nodules with direct surgery than 243 nodules with repeat FNA (p 0.05). In the repeat Bethesda category III group, solid consistency, irregular/microlobulated margins, nonparallel shape, and number of suspicious findings or "suspicious malignant" US assessments were associated with a high malignancy rate (p < 0.05). On multivariate logistic regression analysis, the factor associated with malignancy in the repeat Bethesda category III group was irregular/microlobulated margin (odds ratio = 15.576; 95% CI, 2.097-115.6804, p = 0.007) with a sensitivity, specificity, positive and negative predictive values, and accuracy of 81.6%, 83.3%, 93.0%, 62.5% and 82.1%, respectively. CONCLUSION: Thyroid nodules with repeated Bethesda category III classification and irregular/microlobulated margins on US are at increased risk of malignancy, and operative management should be considered as opposed to repeat FNA.ope

Associations of the BRAFV600E Mutation with Sonographic Features and Clinicopathologic Characteristics in a Large Population with Conventional Papillary Thyroid Carcinoma

OBJECTIVE: To evaluate the association of the BRAFV600E mutation with sonographic features and clinicopathologic characteristics in a large population with conventional papillary thyroid carcinoma (PTC). METHODS: We retrospectively reviewed the sonographic features, clinicopathologic characteristics, and presence of the BRAFV600E mutation in 688 patients who underwent thyroidectomy for conventional PTC between January and July 2010 at a single institution. The incidence of the BRAFV600E mutation was calculated. The sonographic features and clinicopathologic characteristics were compared between BRAF-positive and BRAF-negative patients. BRAF-positive patients were subdivided into those with papillary thyroid microcarcinoma (the PTMC group) and those with PTC larger than 10 mm (the PTC>10 mm group), and their sonographic features were compared. RESULTS: The BRAFV600E mutation was detected in 69.2% of patients (476 of 688). Sonographic features were not significantly different between BRAF-positive and BRAF-negative PTC, nor between PTMC and PTC>10 mm groups. The BRAFV600E mutation was associated with male sex (P = 0.028), large tumor size, extrathyroidal extension, central and lateral lymph node metastasis, and advanced tumor stage (P<0.0001). CONCLUSION: The BRAFV600E mutation was significantly associated with several poor clinicopathologic characteristics, but was not associated with sonographic features, regardless of tumor size. We recommend that patients with a thyroid nodule with any suspicious sonographic feature undergo preoperative BRAFV600E testing for risk stratification and to guide the initial surgical approach in PTC.ope

다중검출기전산화단층촬영을 이용한 복강경과 개복대부분위절제술 후의 잔류 위내 음식물 정체와 체지방 변화의 비교

Purpose: This study aimed to compare the degree of gastric food stasis and following body fat changes after laparoscopic subtotal gastrectomy (LSTG) versus open subtotal gastrectomy (OSTG). Materials and Methods: For 284 consecutive gastric cancer patients who underwent subtotal gastrectomy (213 LSTG and 71 OSTG), the one-year follow-up CT images were reviewed retrospectively. The characteristics of gastric stasis was divided into 5 degrees (0, no residue; 1, small secretion; 2, poorly-defined amorphous food; 3, well-delineated measurable food; 4, bezoar-like food). The residual food volume was calculated for the patients with degree 3 or 4 gastric stasis. Postoperative visceral, subcutaneous, and total fat changes were measured on CT and were correlated with the residual food volume. Results: The LSTG group showed higher degrees of gastric stasis [degree 3 (LSTG, 15.0%; OSTG, 9.9%), degree 4 (LSTG, 6.5%; OSTG, 2.8%)] (p = 0.072). The mean residual food volume of the LSTG group was larger than that of the OSTG group (13779 cc versus 6295 cc) (p = 0.059). Postoperative abdominal fat change was not significantly different between the 2 groups and was not correlated with the residual food volume. Conclusion: LSTG tends to develop gastric stasis more frequently compared with OSTG, but gastric stasis might hardly affect the postoperative body fat status.ope