The retrospective cohort study for survival rate in patients with advanced hepatocellular carcinoma receiving radiotherapy or palliative care

은혁수,김민정,김혜진,고광훈,문희석,이엄석,김석현,이헌영,이병석 대한간학회 2011 Clinical and Molecular Hepatology(대한간학회지) Vol.17 No.3

Background/Aims: This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC). Methods: From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients'Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in survival between the two groups was done to investigate the efficacy of RT. Results: Under the analysis in survival, the mean survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein,transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients. In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha fetoprotein was an independent predictors of worse overall survival rate in patients. Conclusions: We found that the survival of patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good option for in patients with advanced HCC.

Cons: Statin (HMG-CoA reductase inhibitors) for portal hypertension

은혁수 ( Hyuk Soo Eun ) 대한간학회 2017 간학회 싱글토픽 심포지움 Vol.2017 No.2

Over the past 30 years, statins have been widely used for dyslipidemia. In addition to lipid-lowering roles, statins have pleiotropic effects on various diseases. Recently, the use of statins in patients with portal hypertension have been actively investigated, and situation in which statins may aggravate the disease will be discussed. In addition, we will discuss the possible side effects of statins in patients with underlying chronic liver disease or liver cirrhosis. In case of chronic liver injury, hedgehog signaling pathway is activated by various hedgehog ligands secreted by injured cells and the portal hypertension is exacerbated. Here, when portal hypertension is accompanied by liver cirrhosis, statin effectively reduces portal hypertension by inhibiting its molecular target. However, if there was no cirrhosis, but only portal hypertension is existed, it is reported that portal hypertension is aggravated when statin used. Therefore, statin use should be done selectively through sufficient consideration of the underlying disease of the patients. Moreover, the use of statins may lead to hepatotoxicity, drug-induced liver injury, and myopathies, especially in patients with chronic liver disease or cirrhosis in base.

비알코올성 지방간의 새로운 치료 표적: 염증성 대식세포의 Nicotinamide Adenine Dinucleotide Phosphate Oxidase 2와 Reactive Oxygen Species

은혁수 ( Hyuk Soo Eun ) 대한소화기학회 2018 대한소화기학회지 Vol.72 No.4

비알코올성 지방간 발생의 여러 원인들 중에서 염증세포들에서의 활성산소종(reactive oxygen species)의 발생은 지방간 질환과 인슐린 저항성의 주요 원인들 중 하나이다. 이들 활성산소는 대부분이 간으로 침윤된 대식세포로부터 유래되는데 특히 니코틴아미드 아데닌 디뉴클레오티드인산염 산화효소(nicotinamide adenine dinucleotide phosphate oxidase, NOX)에 의하여 주로 발현된다. 그중에서도 간내 염증세포 내에서 NOX를 매개로 활성산소가 발생할 수 있음은 잘 알려졌으나 어떤 세포에서 주로 활성산소가 발생하는지와 어떠한 기전으로 NOX2가 지방간병증과 인슐린 저항성에 기여하는지에 관한 자세한 내용은 알려지지 않았다. 본 연구에서는 NOX2를 발현하는 대표적인 간내 염증세포들로서 호중구, 간내 거주 쿠퍼세포, 간으로 이행한 대식세포 등 여러 세포 유형들 중에서, 주로 간으로 이행된 대식세포에서 NOX2를 매개로 활성산소를 생산하고 있다는 사실을 밝혀내었다. 이 같은 내용은 사람과 마우스의 간내 면역세포들을 분리하여 활성산소를 측정할 수 있는 방법인 2,7-Dichlorodihydrofluorescein acetate (DCFDA)를 이용하여 사람에서는 CD68^highCD14^low 쿠퍼세포가 아닌 CD68^lowCD14^high 대식세포에서 주로 활성산소를 발현하며, 마우스에서는 CD11b⁺F4/80^high 쿠퍼세포가 아닌 CD11b⁺F4/80^low대식세포에서 대부분의 활성산소를 발생시키고 있음을 증명하였다. 한편, lipopolysaccharide (LPS)-toll-like receptor 4(TLR4) 복합체의 내포 작용(endocytosis) 과정과 유사하게, 마우스 대식세포와 사람 단핵구에서 팔미트산(palmitate)은 다이나민(dynamin)을 매개로 팔미트산염의 내포 작용이 이루어진다. 서로 다른 지질 리간드들과 TLR4-myeloid dif-ferentiation factor 2 (MD2) 복합체와의 상호 작용을 크기 배제 크로마토그래피(size-exclusion chromatography)와 에스디에스 페이지(SDS-PAGE) 방법을 이용하여 분석한 결과, TLR4-MD2와 이합체(dimeric)로 결합하는 LPS와는 다르게 팔미트산은 상기 수용체와 단량체(monomeric) 형태로 나타남을 확인하였다. 또한, 정상 마우스와 비교하였을 때 TLR4 결여 마우스, NOX2 결여 마우스의 대식세포에서는 팔미트산 처리 시에 활성산소의 발생이 현저히 감소하지만, Myd88/Toll/Interleukin-1 receptor-domain-containing adapter-inducing interferon-β (TRIF) 결여 마우스의 대식세포에서는 활성산소의 발생이 전혀 감소하지 않는 결과를 보였다. 종합하면, 대식세포의 주 염증 매개체인 LPS가 TLR4-MD2복합체와 이합체의 형태로 결합되어 Myd88 혹은 TRIF 의존적으로 염증성 신호 전달을 하는 것과 다르게, 장관에서 흡수되거나 지방조직으로부터 용해된 혈중 유리지방산(free fatty acid)의 일종인 팔미트산의 경우 TLR4-MD2 복합체와 결합 후 단량체의 형태로 내포 작용이 이루어지며, Myd88과 TRIF 비의존적으로 특이적 활성산소가 발생함을 본 연구에서 보여주었다. 결론적으로 본 연구는 비알코올성 지방간 질환 발생시 이행성 대식세포들에서 팔미트산과 결합하는 TLR4의 내포 작용을 억제할 경우 활성산소의 발생을 감소시킬 수 있음을 증명한 첫 연구이다.

Tumor stage prediction study of hepatocellular carcinoma using Alginate-graphene oxide hybrids

조현철,은혁수,이태희,고연오,이규감,최희권,김하늘,최정현,박현성,손채연,부지윤 대한내과학회 2022 대한내과학회 추계학술대회 Vol.2022 No.2

대장전이로 재발한 경계성 난소암종 1례

김민정,은혁수,김혜진,김규섭,김설영,문희석,정현용 대한노인병학회 2011 Annals of geriatric medicine and research Vol.15 No.3

This report describes the case of a patient who had previously undergone surgery for resection of bilateral ovarian tumors and after 5 years presented with colonic metastasis. A 70-year-old woman visited the hospital for a clinical survey due to severe anemia. In 2007, the patient was diagnosed with cancer(papillary serous adenocarcinoma) in both ova- ries. The patient had undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by postoperative adjuvant chemotherapy. After treatment, the patient was stable during follow-up. After 5 years, she underwent incidental colonoscopic examination because of severe anemia. The colonoscopic findings revealed an elevated irregular lesion in the descending colon. Colonic metastasis from the papillary serous adenocarcinoma of the ovary was confir- med by immunohistochemical staining during the pathological diagnosis.

Experimental Applications of in situ Liver Perfusion Machinery for the Study of Liver Disease

최원묵,은혁수,이영선,김선준,김명호,이준희,심영리,김희훈,김예은,이현승,정원일 한국분자세포생물학회 2019 Molecules and cells Vol.42 No.1

The liver is involved in a wide range of activities in vertebrates and some other animals, including metabolism, protein synthesis, detoxification, and the immune system. Until now, various methods have been devised to study liver diseases; however, each method has its own limitations. In situ liver perfusion machinery, originally developed in rats, has been successfully adapted to mice, enabling the study of liver diseases. Here we describe the protocol, which is a simple but widely applicable method for investigating the liver diseases. The liver is perfused in situ by cannulation of the portal vein and suprahepatic inferior vena cava (IVC), with antegrade closed circuit circulation completed by clamping the infrahepatic IVC. In situ liver perfusion can be utilized to evaluate immune cell migration and function, hemodynamics and related cellular reactions in each type of hepatic cells, and the metabolism of toxic or other compounds by changing the composition of the circulating media. In situ liver perfusion method maintains liver function and cell viability for up to 2 h. This study also describes an optional protocol using densitygradient centrifugation for the separation of different types of hepatic cells, allowing the determination of changes in each cell type. In summary, this method of in situ liver perfusion will be useful for studying liver diseases as a complement to other established methods.

Refractory Hepatic Hydrothorax in Chronic Hepatitis C Controlled by Direct-acting Antivirals

김명희,김덕기,은혁수,류우선,김석현,이병석 대한소화기학회 2020 대한소화기학회지 Vol.75 No.2

Hepatic hydrothorax is a transudative pleural effusion that complicates advanced liver cirrhosis. Patients refractory to medical treatment plus salt restriction and diuretics are considered to have refractory hepatic hydrothorax and may require transjugular intrahepatic portosystemic shunt (TIPS) or liver transplant. Successful antiviral therapy reduces the incidence of some complications of cirrhosis secondary to HCV infection. We report a case of hepatic hydrothorax in a 55-year-old female patient with HCV cirrhosis, which exhibited a spontaneous decrease in pleural effusion after direct antiviral agent (DAA) therapy. In cases of HCV cirrhosis, DAAs are worth administering before treatment by TIPS or liver transplantation.

조기 위암의 내시경적 절제술 후 좁은 안전 마진 발생의 위험인자

박근우,여민경,강선형,이현석,은혁수,문희석,이엄석,김석현,성재규,이병석,정현용 대한내과학회 2022 대한내과학회 추계학술대회 Vol.2022 No.2

The diagnostic value of circulating tumor DNA in hepatitis B virus induced hepatocellular carcinoma: a systematic review and meta-analysis

장영,정승원,장재영,은혁수,이영선,송도선,유수종,이세환,김원,이현웅,김상균,류성호,박수연 대한간암학회 2022 대한간암학회지 Vol.22 No.2

Background/Aim: New biomarkers are urgently needed to aid in the diagnosis of early stage hepatocellular carcinoma (HCC). We performed a meta-analysis on the diagnostic utility of circulating tumor DNA (ctDNA) levels in patients with hepatitis B virus-induced HCC. Methods: We retrieved relevant articles from PubMed, Embase, and the Cochrane Library up to February 8, 2022. Two subgroups were defined; one subset of studies analyzed the ctDNA methylation status, and the other subset combined tumor markers and ctDNA assays. Pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC) were analyzed. Results: Nine articles including 2,161 participants were included. The overall SEN and SPE were 0.705 (95% confidence interval [CI], 0.629-0.771) and 0.833 (95% CI, 0.769-0.882), respectively. The DOR, PLR, and NLR were 11.759 (95% CI, 7.982-17.322), 4.285 (95% CI, 3.098- 5.925), and 0.336 (0.301-0.366), respectively. The ctDNA assay subset exhibited an AUC of 0.835. The AUC of the combined tumor marker and ctDNA assay was 0.848, with an SEN of 0.761 (95% CI, 0.659-0.839) and an SPE of 0.828 (95% CI, 0.692-0.911). Conclusions: Circulating tumor DNA has promising diagnostic potential for HCC. It can serve as an auxiliary tool for HCC screening and detection, especially when combined with tumor markers.

Epidemiologic Characteristics of Hepatitis A Infection

박환희,이주호,이희성,류우선,은혁수,주종석,이엄석,김석현,이병석 대한내과학회 2018 대한내과학회 추계학술대회 Vol.2018 No.1