내시경적 절제술로 치료된 바터팽대부의 동시 발현된 신경절세포부신경절종과 이소성 췌장 1예

강균은 ( Gyoun-eun Kang ),김현수 ( Hyunsoo Kim ),이재광 ( Jae Kwang Lee ),김동현 ( Dong Hyun Kim ),정비나 ( Bi-na Jeong ),장지훈 ( Ji-hun Jang ),여상명 ( Sang-myung Yeo ),손경락 ( Kyung-rak Sohn ) 대한췌담도학회 2016 대한췌담도학회지 Vol.21 No.4

저자들은 상복부 불편감으로 발견된 바터팽대부 점막하종양의 진단과 치료를 위해 시행한 내시경적 절제술상 신경절세포 부신경절종과 이소성 췌장이 동시 발현된 증례를 경험하여 문헌고찰과 함께 보고하는 바이다. Gangliocytic paraganglioma is an uncommon tumor of digestive system that is usually found in the second portion of duodenum. It is generally considered benign tumor, although few reports of local recurrences and regional lymph node metastases have been made. Gangliocytic paraganglioma is characterized by its histologic pattern including ganglion cells, spindle cells and epithelioid cells. Heterotopic pancreas, also known as ectopic pancreas, is a pancreatic tissue appeared outside of its normal location lacking anatomic or vascular connection with the pancreas. In duodenum, it is a relatively unusual lesion that may be found incidentally during surgery or endoscopy. We present a case of 39-year-old woman with gangliocytic paraganglioma combined with heterotopic pancreas in the ampulla of Vater successfully treated by endoscopic resection.

The Diagnostic Efficacy of M2BPGi for Liver Fibrosis in HCC and NAFLD Patients

( Se Young Jang ),( Won Young Tak ),( Soo Young Park ),( Young-oh Kweon ),( Yu Rim Lee ),( Bina Jeong ),( Sangkyung Seo ),( Gyoun-eun Kang ),( Gyeonghwa Kim ),( Keun Hur ),( Heon Tak Ha ),( Jae Min Ch 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Mac-2 binding protein glycan isomer (M2BPGi) is recently identified as a useful non-invasive biomarker for the diagnosis of liver fibrosis. This study aimed to evaluate the diagnostic efficacy of serum M2BPGi for liver fibrosis in hepatocellular carcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD) patients. Methods: M2BPGi levels were analyzed in serum samples collected from biopsy-proven HCC (n=135) and NAFLD (n=113) patients. Fibrosis was graded histopathologically in non-tumorous portion of HCC and NAFLD. Serum M2BPGi levels were determined with an automated immunoassay analyzer. Spearman’s correlation and Kruskal-Wallis test were used to evaluate the correlation and comparison among groups. Diagnostic efficacy for fibrosis was evaluated by the area under the receiver operating characteristic curve (AUC). Results: Median levels (range) of M2BPGi in HCC and NAFLD patients were 1.21 (0.12-14.33) cut-off index (COI) and 0.59 (0.13-5.90) COI, respectively. In HCC patients, fibrosis stages were 0 (n=22), 1 (n=10), 2 (n=11), 3 (n=16), and 4 (n=76). The M2BPGi levels showed a significant positive correlation (r= 0.436, P<0.001) with fibrosis grade in HCC patients and yielded the lower AUC value, 0.787 (P< 0.001) than transient elastography (TE), AUC value, 0.806 (P=0.030) to predict advanced fibrosis (F >2). In NAFLD patients, fibrosis stages were 0 (n=22), 1 (n=34), 2 (n=28), 3 (n=19), and 4 (n=10). The M2BPGi levels showed a significant positive correlation (r=0.578, P<0.001) with fibrosis grade in NAFLD patients and yielded the higher AUC value, 0.824(P< 0.001) than TE, AUC value, 0.637(P=0.035) to predict advanced fibrosis (F >2). Conclusions: Serum M2BPGi can be a useful non-invasive biomarker for predicting fibrosis in HCC and especially in NAFLD patients.

Differential DNA Methylation as a Potential Biomarker for Stratification of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

( Yu Rim Lee ),( Eunhye Lee ),( Se Young Jang ),( Won Young Tak ),( Young Oh Kweon ),( Bina Jung ),( Gyoun Eun Kang ),( Sang Kyung Seo ),( Jung Gil Park ),( Hye Won Lee ),( Young Seok Han ),( Jae Min 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Non-alcoholic fatty liver disease (NAFLD) can progress to advanced liver disease, but only in a minority of patients. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has been shown to distinguish patients in terms of fibrosis severity in NAFLD. However, a study of methylation of PPARγ gene promoter in human with a sufficient number of patients is still scarce. We therefore determined the prognostic significance of DNA methylation of PPARγ gene promoter in patients with NAFLD. Methods: This study enrolled 54 biopsy proven NAFLD patients and 18 healthy controls who attended Kyungpook National University Hospital, Republic of Korea between March 2015 and October 2016. We extracted genomic DNA from liver tissue of enrolled patients. Bisulfite modification of genomic DNA was performed and PPARγ methylation level was confirmed with pyrosequencing. Results: The average of 4CpG methylation of PPARγ promoter had significantly lower in the NAFLD group (15.03% DNA methylation) when compared to the healthy controls (19.55%) (P=0.001). Quantitative DNA methylation of PPARγ stratified patients into mild (Kleiner 0-2) and severe (Kleiner 3-4) fibrosis (14.21% vs 17.87%, P=0.007). Moreover, hypermethylation at the PPARγ promoter of liver was also associated with higher age, the presence of DM, NAFLD fibrosis score, the degree of steatosis and fibrosis (P=0.015, 0.024, 0.012, 0.027, 0.009, respectively). However, they were not associated with presence and degree of inflammation, ballooning, NAFLD activity score, the presence of NASH, and other liver function test. Patients with advanced fibrosis exhibited significantly higher NAFLD fibrosis score, FIB-4, and PPARγ DNA methylation (all P<0.05) and showed borderline significance with transient elastography (P=0.084). These markers, including NAFLD fibrosis score, FIB- 4, and PPARγ DNA methylation, had an area under the receiver operating curve (AUROC) of 0.855, 0.778, 0.75, respectively for predicting advanced fibrosis. PPARγ mRNA was also related to the fibrosis and steatosis severity (P<0.05). This showed negative regulation with DNA methylation level (P=0.001). Conclusions: DNA methylation level of PPARγ may be useful in NAFLD patients for stratification and prediction of progressive liver fibrosis, which is a very important factor of NAFLD patients that is currently impossible to predict. It may be possible to generate an algorithm that can predict more precisely which patients are likely to progress on to a severe fibrosis in patients with NAFLD using DNA methylation and other markers related to liver fibrosis.

Hypomethylation of Long Interspersed Nuclear Element-1 (LINE-1) Leads to Activation of CD133 and ST18 in Hepatocellular Carcinoma

( Yu Rim Lee ),( Kyunghwa Kim ),( Se Young Jang ),( Won Young Tak ),( Young Oh Kweon ),( Bina Jung ),( Gyoun Eun Kang ),( Sang Kyung Seo ),( Jung Gil Park ),( Hye Won Lee ),( Young Seok Han ),( Jae Mi 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Long interspersed nuclear element-1 (LINE-1) hypomethylation, representing global DNA methylation level, is associated with prognosis via activation of oncogenic functions of genes. This experiment was performed to evaluate prognostic implication of LINE-1 methylation in patients with hepatocellular carcinoma (HCC) and the possible mechanisms related to oncogene activation. Methods: Ninety-six HCC patients between October 2014 and September 2015 at Kyungpook National University Hospital, Daegu, South Korea were enrolled for this prospective study. Quantitative pyrosequencing was performed to quantify the methylation level of for CpG sites in the LINE-1 promotor. The expression of CD133 and ST18 were measured by immunohistochemistry and their correlation with LINE-1 methylation levels were analyzed. Results: LINE-1 was significantly hypomethylated in tumor tissues compared with nontumor tissues (64.0 ±11.6% vs. 75.6 ±4.0%, respectively, P<0.0001). In this study population, LINE-1 hypomethylation group had a large proportion of female gender, smaller tumor size, and nonexistence of ascites (P< 0.05). Contrary to previous reports, LINE-1 hypomethylation was not an independent risk factor for overall survival and disease progression (all P >0.05). A total of 81 (84.4%) patients had demethylation of LINE-1 (ΔMI<0), and 15 (15.6%) patients had hypermethylation of LINE-1 (ΔMI≥0). HCC with demethylation of LINE-1 (ΔMI<0) had higher CD 133 expression than HCC with hypermethylation of LINE-1 (ΔMI≥0) (P=0.011). Moreover, when patients divided into two groups based on the mean value of tumor line-1 methylation, ST18 showed borderline significance in distinguishing the LINE-1 hypomethylation group than the other (P=0.053). Conclusions: LINE-1 demethylation is associated with expression of CD133 and ST18 in Hepatocellular carcinoma. In this study, LINE-1 hypomethylation was not related to overall survival and disease progression, this is probably due to the enrollment of HCC patients with various tumor stages and liver function.

원 저 : ST절 상승 급성 심근경색증 환자에서 혈전흡인술에 따른 신호평균화 심전도 비교

이준영 ( Jun Young Lee ),최원석 ( Won Suk Choi ),정병천 ( Byung Chun Jung ),이봉렬 ( Bong Ryeol Lee ),강현재 ( Hyun Jae Kang ),김재희 ( Jae Hee Kim ),강균은 ( Gyoun Eun Kang ) 대한내과학회 2016 대한내과학회지 Vol.90 No.1

목적: ST절 상승 급성 심근경색에서 경피적 관상동맥중 재술이 표준 치료로 시행된다. 혈전흡인술이 혈전 찌거기(thrombus burden)를 줄임으로써 ST절 상승 급성 심근경색증 환자의 심실부정맥 발생을 줄일 수 있을지에 대한 여러 연구가 진행되어 왔다. 이 연구는 ST절 상승 급성 심근경색증 환자에서 전통적인 경피적 관상동맥중재술 그룹과 비교할 때 혈전흡인술을 시행한 그룹에서 심근의 전기학적 불안정성을 향상 시킬 수 있는가를 SAECG 분석을 통해 밝히고자 하였다. 방법: 연구 대상은 ST절 상승 급성 심근경색증에서 경피적관상동맥중재술을 시행한 170명을 대상으로 하였다. 환자는 두 군으로 나누어서 80명은 전통적인 경피적 관상동맥중재술만 시행하였고 90명은 경피적 관상동맥중재술 시행 전 혈전흡인술을 시행하였다. SAECG는 시술 후 5 ± 2일 날 시행하였다. 시술 후 심전도상 atrial fibrillation, bundle branch block, hemiblock, intraventricular conduction defect가 있는 군은 SAECG분석에서 제외하였다. 결과: 급성 심근경색증 환자에서 양 군 간 기본 특성상에는 특별한 차이가 없었다. SAECG 분석에서 QRSD (ms)의 경우미시행군에서 4 ms 길게 나왔고, RMS40의 경우 5 μV 높게 측정되었고, LAS40의 경우 시행군에서 3 μV 높게 측정되었다. 이는 통계적 유의성을 보여주지는 못하였지만, SAECG양성소견을 비교하였을 때 QRSD가 114 ms 이상, RMS40이 20 μV 이하인 경우는 혈전흡인술군에서 모두 적게 나왔으며 (19 [23.7%] vs. 8 [8.8%], p = 0.011, and 16 [20%] vs. 8 [8.8%],p = 0.047). LAS40가 38 ms 이상으로 나온 경우도 혈전흡인 술군에서 적었다(18 [22.5%] vs. 8 [8.8%], p = 0.018). 결론: STEMI 환자에서 혈전흡인술은 SAECG 상에서 심실부정맥 발생과 관련된 임상지표들을 향상시키는 결과를 보여주었다. 앞으로 이에 대한 장기적인 임상연구 결과가 추가적으로 필요하다. Background/Aims: Percutaneous coronary intervention (PCI) is the standard method of treating ST-segment elevation myocardial infarction (STEMI). There is continuing uncertainty as to whether reducing the thrombus burden through catheter aspiration improves the arrhythmogenic structure of the myocardium in STEMI. We compared the changes in electrical instability after thrombus aspiration-assisted primary PCI using conventional primary PCI. Methods: The study population included 170 consecutive patients with STEMI who underwent primary PCI. The patients were divided into 80 patients who underwent primary PCI only and 90 patients who underwent thrombus aspiration before PCI. The signal- averaged ECG (SAECG) was obtained 5 ± 2 days after the intervention. Results: There were no significant differences between the groups in terms of sex, age, cardiovascular risk factors, or time from the onset of symptoms to treatment. The duration of the low amplitude signals less than 40 μV (LAS40), duration of the QRS complex (QRSD), and root mean square voltage of the terminal 40 ms of the QRS complex (RMS40) did not differ between the thrombus aspiration and no thrombus aspiration groups. The incidences of QRSD > 114 ms and RMS40 < 20 μV were significantly lower in the thrombus aspiration group than the no thrombus aspiration group (19 vs. 8, p = 0.011 and 16 vs. 8, p = 0.047, respectively), while the incidence of LAS > 38 ms was significantly higher in the non-thrombus aspiration group (18 vs. 8, p = 0.018). Conclusions: Among random patients with STEMI, thrombus aspiration improved all of the parameters of SAECG, which is related to ventricular arrhythmogenesis, although the long-term clinical outcomes need to be assessed. (Korean J Med 2016;90:26-31)

괴사를 동반한 급성 중증 췌장염에서 경피적 내시경적 괴사 제거술의 성공적인 치험 1예

권문혁 ( Moon Hyuk Kwon ),김현수 ( Hyun Soo Kim ),김태훈 ( Tae Hoon Kim ),권재춘 ( Jae Choon Kwon ),정호진 ( Ho Jin Jung ),박명일 ( Myung Il Park ),김현지 ( Hyun Ji Kim ),강균은 ( Gyoun Eun Kang ) 대한췌담도학회 2013 대한췌담도학회지 Vol.18 No.4

감염성 췌장괴사의 고전적인 치료는 개복 수술이었다. 하지만 개복 수술 후 합병증, 사망률의 유의한 증가가 보고되면서 항생제와 보존적 치료가 일차적 치료로서 우선적으로 선택되고 있다. 보존 치료에 반응이 없는 경우에는 다양한 경로를 통한 배액법 및 괴사제거술 등의 최소 침습시술이 대두되고 있으며, 이러한 최소 침습 시술의 선택은 환자의 임상 양상, 보존적 치료에 대한 치료 반응, 괴사 조직과 위장관의 해부학적 위치 관계에 대한 정확한 평가 및그에 따른 시술 방법의 선택이 이루어져야 한다. 저자들은 급성 감염성 췌장 괴사에서 항생제 등의 보존적 치료와 경피적 배액술을 시행하였으나 치료반응이 없는 환자에서 경피적 내시경적 괴사 제거술을 통한 성공적인 괴사 치료1예를 경험하였기에 보고하는 바이다. Percutaneous endoscopic necrosectomy in acute severe pancreatitis with infected necrosis: a case report. Patients with acute infected necrotizing pancreatitis undergoing surgical management may have high risks of complications and mortality. Thus, as an alternative to surgical management, an endoscopic approach has been introduced. We report a case of successful treatment of acute severe pancreatitis with infected necrosis by percutaneous endoscopic necrosectomy (PEN). A 42-year-old man was hospitalized for acute pancreatitis resulting from biliary sludges. He had some fluid collections around the pancreas with severe epigastric pain. Emergency ERCP with EST was performed, and plastic stents were inserted into the bile duct and pancreatic duct for drainage. Despite using the antibiotics, fever developed with increased fluid collections and necrotic tissues which were found on the follow-up abdominal CT scan. Percutaneous catheter drainage (PCD) was performed, but fever did not go down even though several cha ges of catheter. We then performed the PEN through the opening of PCD. After four sessions of the procedure, much improvement was seen on the follow-up CT scan. With more research and progress, PEN will become a suitable alternative treatment for infected necrotizing pancreatitis.

Prognostic Factors Affecting Treatment Outcomes of Acute Variceal Bleeding in Patients with Hepatocellular Carcinoma : A Single Center Prospective Study

( Yu Rim Lee ),( Soo Young Park ),( Won Young Tak ),( Young Oh Kweon ),( Se Young Jang ),( Jun Sik Yoon ),( Bina Jeong ),( Gyoun Eun Kang ),( Sang Kyung ),( Seo Keun Hur ),( Jung Gil Park ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Because acute variceal bleeding is associated with significant morbidity and mortality in cirrhotic patients, the prediction of prognosis is important. We therefore studied about prognostic factors affecting treatment outcomes of acute variceal bleeding. In addition, factors related acute variceal bleeding in patients with HCC were also determined with particular emphasis. Methods: Endoscopy-proven acute variceal bleeding patients admitted to the Kyungpook National University Hospital between 2007 and 2013 were enrolled in this prospective cohort study. Endoscopic procedures including either endoscopic variceal ligation or sclerotherapy with N-butyl-2-cyanoacrylate were performed for the patients within 24 hours after admission. The prognostic factors were identified by applying the multivariate Cox proportional-hazards regression test using significant variables in univariate analysis. Results: 329 patients were finally included in this study. During the study period (median=15.6 months), 186 patients at a median of 4.3 months were expired. Nineteen patients were expired in 5 days, which accounted for 38.8% of 6-week mortality (n=49). Six-week mortality was related to the MELD score and 5-day treatment failure in multivariate analysis in all patients and HCC subgroup (all P<0.05). When the patients were divided into two groups by MELD score, the risk of 6 week mortality was higher in patients with MELD ≥ 15.5 than in those with MELD < 15.5 (log rank test, P<0.001). We also found that 85% of patients with both MELD score ≥ 15.5 and terminal cancer stage including mUICC stage 4 or BCLC stage D expired within six weeks and 6-week mortality risk is about 10 times higher compared to patients with lower MELD score and earlier stage after adjusting other factors (P<0.05). Conclusions: Follow-up strategy and managements are required for the individual patients, depending on these risk factors. According to our study, overly enthusiastic endoscopic treatment in patients with poor liver function and end-stage HCC may be unnecessary.