HCC : Histologic Differentiation Predicts the Survival of Patients with Hepatic Resection for Hepatocellular Carcinoma

( Woong Cheul Lee ),( Jae Young Jang ),( Jin Nyoung Kim ),( Soung Won Jeong ),( Eui Ju Park ),( Byoung Moo Lee ),( Yun Nah Lee ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang Woo Cha ),( Young Seok Kim ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: In resection for hepatocellular carcinoma (HCC), patient selection depends on morphological features and liver function. In patients with HCC, we performed a clinico- pathological analysis of risk factors that affected survival after liver resection. Methods: Sixty seven patients with liver resection for HCC were enrolled and data were collected retrospectively. Variables were age, gender, etiology, preoperative alpha-fetoprotein (AFP) levels, Child-Pugh and MELD scores, modified UICC stage, portal vein tumor invasion, and histological differentiation. Results: Sixty seven patients were evaluated and 6 patients were excluded (Three patients with combined hepatocellularcholangiocarcinoma, two patients because of early postoperative death without HCC recurrence and one patient accidental death without HCC recurrence). The mean age of the patients was 57.4±10.5 years. The mean follow-up time was 51.2±34.8 months. The cumulative 1-, 3-, 5-, and 7-year survival rates were 91.3%, 64.5%, 45.0%, and 45.0%, respectively. The 1-, 3-, 5-, and 7-year disease-free survival rates were 80.4%, 50.5%, 12.9%, and 12.9%, respectively. Multivariate analysis showed that modified UICC stage (P=0.005), portal vein tumor invasion (P=0.024) and poor histological differentiation (P=0.012) were independent factors for survival and tumor recurrence. Conclusions: Although morphological stage and liver function are important factors of liver resection, for proper patient selection in liver resection for HCC, prognostic criteria related to tumor histology (especially histological differentiation) should be considered. Poor histological differentiation is indicators of poor prognosis after liver resection for HCC.

HCV, Acute, LT : The Clinico-Pathological Features of Drug Induced Liver Injury

( Woong Cheul Lee ),( Jae Young Jang ),( Jin Nyoung Kim ),( Soung Won Jeong ),( Eui Ju Park ),( Byoung Moo Lee ),( Yun Nah Lee ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang Woo Cha ),( Young Seok Kim ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Drug-induced liver injury (DILI) has recently increased and is one of major cause of acute hepatitis. We investigated the clinico-pathological findings in patients with DILI whom liver biopsy was conducted. Methods: A retrospective analysis was performed using medical records of sixty five cases of DILI that were selected based on a modified RUCAM (Roussel Uclaf Causality Assessment Method) score of 7 or above. Results: The incidence was higher in women (n=41) than men (n=24). The age (mean±SD) of the patients was 48.2±13.1 years. The major causes of the DILI included the use of herbal medications (43.2%), prescription medications (21.6%) and traditional therapeutic preparations and dietary supplements (35%). At the time of admission, various symptoms (anorexia and abdominal discomfort (46.2%), jaundice and itching (40%), myalgia and fatigue (32.3%), fever and chill (16.9%), headache and dizziness (6.2%)) were presented. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, alkaline phosphatase (ALP) and γ-glutamyl transpeptidase peak levels were 650.1±685.2 IU/L, 855.7±780.9 IU/ 10±9.5 mg/dL, 371±454 IU/L and 247.9±227.2 IU/L, respectively. The mean modified RUCAM score of the patients was 8.01±0.75. The types of liver injury according to R ratio ([ALT/ UNL]/[ALP/UNL]) were hepatocellular type (67.7%), mixed type (10.8%) and cholestatic type (21.5%). The main pathologic findings were zone 3 necrosis and swelling (53.8%), increased eosinophilic infiltration (43.1%) and bridging necrosis (21.5%). Herbal medications and traditional therapeutic preparations were associated with hepatocellular type`s liver injury compared to prescription medications (P<0.002). All patients were recovered without complication. Conclusions: The clinico-pathologic findings of DILI were diverse. Zone 3 necrosis and swelling was most common pathologic feature. The type of liver injury with herbal medications and traditional therapeutic preparations revealed hepatocellular type.

LC : Renal Function Predicts 14 Days Mortality in Cirrhotic Patient with Spontaneous Bacterial Peritonitis; Multicenter Retrospective Study

( Woong Cheul Lee ),( Jae Young Jang ),( Young Don Kim ),( Yun Nah Lee ),( Young Sin Cho ),( Jin Nyoung Kim ),( Eui Ju Park ),( Byoung Moo Lee ),( Soung Won Jeong ),( Sae Hwan Lee ),( Sang Gyune Kim ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Spontaneous bacterial peritonitis (SBP) is one of severe complications in liver cirrhosis. Early detection of high-risk patients is essential for prognostic improvement. We investigate the predictive factors related with 14 days mortality in patient with SBP. Methods: We conducted a retrospective study of two hundred seventy five SBP patients admitted in four tertiary referral hospitals between August 2002 and February 2013. We collect patients` laboratory and radiologic data from medical record. We calculated Child-Turcotte-Pugh score (CTP), Model for End- Stage Liver Disease-Na (MELD-Na) score using the laboratory data at the time of SBP occurrence. Results: The mean age of the patients was 56.9 years (213 male, 62 female). The cause of liver cirrhosis was hepatitis B (44%), alcohol (41.8%) and hepatitis C (6.9%). Mean score of MELD-Na and CTP score were 27.44 and 10.67, respectively. The patients who die from SBP within 14 days were 17.8% (n=49). The statistically significant factor of multivariate analysis were baseline MELD-Na (P=0.002) and GFR (P=0.034). Two hundred thirty three patients who could follow-up were analyzed. Baseline MELD-Na (P=0.027) and maximal creatinine level during the follow-up (P=0.02) were significantly associated with 14 days mortality. The prognostic accuracy of baseline MELD-Na, initial GFR and maximal creatinine during the follow-up were 75.6%, 74.0% and 78.0%, respectively (P<0.001). The cut-off values were 27 (baseline MELD-Na), 35.9 mL/min (initial GFR) and 2 mg/dL (maximal creatinine), respectively (P<0.001). Conclusions: Renal function was important predictive factor of 14 days mortality in cirrhotic patients with SBP. The patients with SBP and renal insufficiency should be treated more intensively.

Endoscopic Treatment of Various Gastrointestibal Tract Defects with an Over-the-Scope Clip: Case Series from a Tertiary Referral Hospital

Woong Cheul Lee,Weon Jin Ko,Jun-Hyung Cho,Tae Hee Lee,Seong Ran Jeon,Hyun Gun Kim,Joo Young Cho 대한소화기내시경학회 2014 Clinical Endoscopy Vol.47 No.2

Recently, increasingly invasive therapeutic endoscopic procedures and more complex gastrointestinal surgeries such as endoscopic mucosalresection, endoscopic submucosal dissection, and novel laparoscopic approaches have resulted in endoscopists being confrontedmore frequently with perforations, fistulas, and anastomotic leakages, for which nonsurgical closure is desired. In this article, we presentour experiences with the use of over-the-scope clip (OTSC) for natural orifice transluminal endoscopic surgery (NOTES) closure, preventionof perforation, anastomotic leakages, and fistula closures. The OTSC is a valuable device for closing intestinal perforations and fistulas,for NOTES closure, and for the prevention of perforation after the excision of a tumor from the proper muscle layer. Furthermore, itseems to be quite safe to perform, even by endoscopists with little experience of the technique.

White Esophageal Mucosa and Black Gastric Mucosa: Upper Gastrointestinal Injury Due to Hydrochloric Acid Ingestion

Woong Cheul Lee,이태희,Jun-Hyung Cho 대한소화기내시경학회 2014 Clinical Endoscopy Vol.47 No.1

Poster Session : PS 0937 ; Liver : Predictors of the Complete Virologic Response in Naive Chronic Hepatitis B Patients with Entecavir Therapy

( Yo Han Lee ),( Jae Young Jang ),( Woong Cheul Lee ),( Soung Won Jeong ),( Eui Ju Park ),( Byoung Moo Lee ),( Jin Nyoung Kim ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang Woo Cha ),( Young Seok Kim ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: We assessed baseline and on-treatment variables to determine predictive factors of the complete virologic response in naive chronic hepatitis B patients with entecavir therapy. Methods: A total of 261 naive chronic hepatitis B (CHB) patients treated with entecavir (0.5 mg daily) for at least 12 weeks were enrolled. The complete virologic response was defi ned as the absence of serum HBV-DNA by PCR assay (<20 IU/ml) on 2 consecutive measurement at 48week. Compliance with therapy was assessed whenpatients visit the outpatient clinic and phone calls. The medication adherence was more than 80% of all patients.Results: Finally, 98 patients were treated with entecavir for 96 weeks. And 151 patients were treated with entecavir for 48weeks. The mean follow-up duration was 20 ± 16.5 months. The complete virologic response at 48weeks was 67.5%. The cumulative rates of the virologic response at 12, 24, 48, and 96 weeks were 17.2%, 46.0%, 67.6%, and 71.4%, respectively. An absence of HBeAg and high DNA level at baseline were signifi cant predictors of the complete virologic response at 48 weeks in a univariate analysis (p<0.001, p=0.02). An absence of HBeAg at baseline was signifi cant predictor of the complete virologic response at 48weeks in a multivariate analysis (p<0.001). Also aminotransferase level was signifi cant predictor of the complete virologic response at 48 weeks in HBeAg positive patients (p<0.05). Conclusions: Our data showed a good complete virologic response (67.5%) in naiveCHB patients with entecavir therapy. Additionally, the predictor of the complete virologic response was an absence of HBeAg. Also, aminotransferase level can be used for predictor of the complete virologic response in HBeAg positive patients.

한-인도 CEPA의 무역효과 분석

이순철(Soon-Cheul Lee),이웅(Woong Lee) 한국관세학회 2016 관세학회지 Vol.17 No.2

This study analyzes the effect of Korea-India Comprehensive Economic Partnership Agreement on the trade between Korea and India. To this end, the study investigated the trend and issues of Korea-India CEPA and estimated both trade creation and trade diversion effect of the CEPA with the import of Korea from India, the CEPA preferential tariff rates, and MFN rates of Korea to world during the period of 2010 to 2015 at the level of HS 10. The trend of export and import of Korea to/from India have similarities with those of Korea to/from the world, implying that the CEPA might have insignificant effects on the trade between the two countries. The empirical results show that the trade creation effect of the CEPA to import from India is insignificant but significant only in the case of controlling the market share of the products. Meanwhile, the results show that there is no trade diversion effect of the CEPA. Thus, this study provides the political implementations that in order to increase the effect of the CEPA on the trade, the two countries should increase the trade volume of the comparative advantages products and the specialization strategies for the trade diversion effect for the import of Korea from India.

류마티스 관절염에서 발생한 Cerebral Aspergillosis

이태근 ( Tae Kun Lee ),최재훈 ( Jae Hoon Choi ),최철웅 ( Cheul Woong Choi ),이상용 ( Sang Yong Lee ),이준희 ( Jun Hee Lee ),이정욱 ( Joung Wook Lee ),김상수 ( Sang Soo Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.4

We report a case of aspergillosis of the central nervous system in patient with rheumatoid arthritis (RA). A 46-year-old woman with 20-year history of RA and on treatment with corticosteroid, hydroxychloroquine and methotrexate, was admitted because of drowsiness, dizziness and dysarthria. On admission, physical examination and laboratory data showed, among other findings, disappearance of pupil reflex, positive Babinski and Chaddock reflex. Magnetic resonance imaging (MRI) of brain showed multiple high signal intensity lesion on medulla, pons, midbrain, basal ganglia, internal capsule, thalamus and hypothalmus. Stereotactic brain biopsy was performed and biopsy specimen revealed an invasive Aspergillus.

Graphene oxide induces apoptotic cell death in endothelial cells by activating autophagy via calcium-dependent phosphorylation of c-Jun N-terminal kinases

Lim, Mi-Hee,Jeung, In Cheul,Jeong, Jinyoung,Yoon, Sung-Jin,Lee, Sang-Hyun,Park, Jongjin,Kang, Yu-Seon,Lee, Hansu,Park, Young-Jun,Lee, Hee Gu,Lee, Seon-Jin,Han, Baek Soo,Song, Nam Woong,Lee, Sang Chul Elsevier 2016 Acta Biomaterialia: structure-property-function re Vol.46 No.-

<P><B>Abstract</B></P> <P>Despite the rapid expansion of the biomedical applications of graphene oxide (GO), safety issues related to GO, particularly with regard to its effects on vascular endothelial cells (ECs), have been poorly evaluated. To explore possible GO-mediated vasculature cytotoxicity and determine lateral GO size relevance, we constructed four types of GO: micrometer-sized GO (MGO; 1089.9±135.3nm), submicrometer-sized GO (SGO; 390.2±51.4nm), nanometer-sized GO (NGO; 65.5±16.3nm), and graphene quantum dots (GQDs). All types but GQD showed a significant decrease in cellular viability in a dose-dependent manner. Notably, SGO or NGO, but not MGO, potently induced apoptosis while causing no detectable necrosis. Subsequently, SGO or NGO markedly induced autophagy through a process dependent on the c-Jun N-terminal kinase (JNK)-mediated phosphorylation of B-cell lymphoma 2 (Bcl-2), leading to the dissociation of Beclin-1 from the Beclin-1–Bcl-2 complex. Autophagy suppression attenuated the SGO- or NGO-induced apoptotic cell death of ECs, suggesting that SGO- or NGO-induced cytotoxicity is associated with autophagy. Moreover, SGO or NGO significantly induced increased intracellular calcium ion (Ca<SUP>2+</SUP>) levels. Intracellular Ca<SUP>2+</SUP> chelation with BAPTA-AM significantly attenuated microtubule-associated protein 1A/1B-light chain 3-II accumulation and JNK phosphorylation, resulting in reduced autophagy. Furthermore, we found that SGO or NGO induced Ca<SUP>2+</SUP> release from the endoplasmic reticulum through the PLC β3/IP<SUB>3</SUB>/IP<SUB>3</SUB>R signaling axis. These results elucidate the mechanism underlying the size-dependent cytotoxicity of GOs in the vasculature and may facilitate the development of a safer biomedical application of GOs.</P> <P><B>Statement of Significance</B></P> <P>Graphene oxide (GO) have received considerable attention with respect to their utilization in biomedical applications. However, GO-related safety issues concerning human vasculature are very limited. In this manuscript, we report for the first time the differential size-related biological effects of GOs on endothelial cells (ECs). Notably, Subnanometer- and nanometersized GOs induce apoptotic death in ECs via autophagy activation. We propose a molecular mechanism for the GO-induced autophagic cell death through the PLCβ3/IP3/Ca<SUP>2+</SUP>/JNK signaling axis. Our findings could be provide a better understanding of the GO sizedependent cytotoxicity in vasculature and facilitate the future development of safer biomedical applications of GOs.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

HBV : Predictors of the Complete Virologic Response in Na?ve Chronic Hepatitis B Patients Treated with Entecavir

( Jin Nyoung Kim ),( Jae Young Jang ),( Woong Cheul Lee ),( Soung Won Jeong ),( Eui Ju Park ),( Byoung Moo Lee ),( Yun Nah Lee ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Sang Woo Cha ),( Young Seok Kim ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: We assessed baseline and on-treatment variables to determine factors predictive of the complete virologic response in naive chronic hepatitis B patients treated with entecavir. Methods: A total of 261 naive chronic hepatitis B (CHB) patients treated with entecavir (0.5 mg daily) for at least 12 weeks were enrolled. The complete virologic response was defined as the absence of serum HBV-DNA by PCR assay (<20 IU/mL) on 2 consecutive measurement during entecavir treatment. Compliance with therapy was assessed when patients visited the outpatient clinic and phone calls. The medication adherence was more than 80% of all patients. Results: The mean follow-up duration was 20±16.5 months, and 55 patients (56.1%) showed HBeAg positivity. Finally, 98 patients were treated with entecavir for 96 weeks. The median pretreatment levels of serum ALT and HBV DNA were 206±20.53 U/L and 1.50 × 8 log10 IU/mL, respectively. The cumulative rates of the complete virologic response at 12, 24, 48, and 96 weeks were 17.2%, 46.0%, 67.6%, and 71.4%, respectively. An absence of HBeAg and DNA level at baseline were significant predictors of the complete virologic response at 96 weeks in a univariate analysis (P<0.001, P=0.02). An absence of HBeAg at baseline was significant predictor of the complete virologic response at 12 weeks, 24 weeks, 48 weeks, and 96 weeks in a multivariate analysis (P<0.001). Aminotransferase level was significant predictor of the complete virologic response at 12 weeks, 24 weeks, 48 weeks and 96 weeks in HBeAg positive patients (P<0.05). Conclusions: Our data showed a good complete virologic response (71.4%) in naive CHB patients treated with entecavir. Regardless of any period, the predictor of the complete virologic response was an absence of HBeAg. Additionally, aminotransferase level can be used for predictor of the complete virologic response in HBeAg positive patients.