Original Articles : The usefulness of contrast-enhanced ultrasonography in the early detection of hepatocellular carcinoma viability after transarterial chemoembolization: pilot study

( Youn Zoo Cho ),( So Yeon Park ),( Eun Hee Choi ),( Soon Koo Baik ),( Sang Ok Kwon ),( Young Ju Kim ),( Seung Hwan Cha ),( Moon Young Kim ) 대한간학회 2015 Clinical and Molecular Hepatology(대한간학회지) Vol.21 No.2

Background/Aims: The therapeutic effect of transarterial chemoembolization (TACE) against hepatocellular carcinoma (HCC) is usually assessed using multidetector computed tomography (MDCT). However, dense lipiodol depositions can mask the enhancement of viable HCC tissue in MDCT. Contrast-enhanced ultrasonography (CEUS) could be effective in detecting small areas of viability and patency in vessels. We investigated whether arterial enhancement in CEUS after treatment with TACE can be used to detect HCC viability earlier than when using MDCT. Methods: Twelve patients received CEUS, MDCT, and gadoxetic-acid-enhanced dynamic magnetic resonance imaging (MRI) at baseline and 4 and 12 weeks after TACE. The definition of viable HCC was defined as MRI positivity after 4 or 12 weeks. Results: Eight of the 12 patients showed MRI positivity at 4 or 12 weeks. All patients with positive CEUS findings at 4 weeks (n=8) showed MRI positivity and residual viable HCC at 4 or 12 weeks. Five of the eight patients with positive CEUS findings at 4 weeks had negative results on the 4-week MDCT scan. Four (50%) of these eight patients did not have MRI positivity at 4 weeks and were ultimately confirmed as having residual HCC tissue at the 12-week MRI. Kappa statistics revealed nearperfect agreement between CEUS and MRI (κ=1.00) and substantial agreement between MDCT and MRI (κ=0.67). Conclusions: In the assessment of the response to TACE, CEUS at 4 weeks showed excellent results for detecting residual viable HCC, which suggests that CEUS can be used as an early additive diagnosis tool when deciding early additional treatment with TACE. (Clin Mol Hepatol 2015;21:165-174)

LC : Effect of Mesenchymal Stem Cell on Hepatic Fibrosis in Thioacetamide-Induced Cirrhotic Rat Model

( Boo Sung Kim ),( Youn Zoo Cho ),( Soon Koo Baik ),( Moon Young Kim ),( Won Ki Hong ),( Hye Won Hwang ),( Jin Hyung Lee ),( Myeong Hun Chae ),( Seung Yong Shin ),( Jung Min Kim ),( Mee Yon Cho ),( Sa 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis and no effective therapy except liver transplantation is currently available for decompensated cirrhosis. However, some practical limitations in liver transplantation lead us to a need for new therapeutic paradigm in this field. Recent reports have shown that the mesenchymal stem cells (MSCs) have the plasticity to differentiate into some kinds of tissue cells and improve organ function. Hence, we investigated the effect of direct inoculation of human bone marrow derived MSCs (BM-MSCs) in thioacetamide (TAA)-induced cirrhosis in a rat model. Methods: Adult Sprague-Dawley rats were allocated into three groups (each group, n = 15) as follows: G1, shame; G2, TAAcontrol; G3, TAA+BM-MSC. To induce cirrhosis, 200mg/kg TAA injection was done twice a week for 12weeks in G2 and G3. 2×106 cells of amplified human BM-MSCs were injected directly into the right liver lobe twice, at weeks 6 and 8 in G3. At 12 weeks, the effect of BM-MSCs on cirrhosis was analyzed histomorphologically using Laennec scores. α-Smooth muscle actin(α-SMA) expression by immunohistochemical staining, relative expression of collagen type 1, and transforming growth factor β (TGF-β) were also evaluated by real-time reverse transcriptase- polymerase chain reaction. Results: Laennec scores were 0, 5.4±0.7 and 3.7±1.06 in G1, G2 and G3, respectively. Histologically, BM-MSCs injected group (G3) showed significant suppression of hepatic fibrosis compared with TAA-control group (G2)(P<0.001). Expressions of α-SMA(%) were significantly lower in G3 than in G2 (3.08±1.26 vs. 7.00±4.12, P<0.05). Also, the relative expression of collagen type 1 and TGF-β1 in RT-PCR were 0.64±0.24, 2.06±0.51, 1.32±0.31 and 0.62±0.28, 5.89±3.05, 2.22±1.41 in G1, G2 and G3, respectively P<0.005). Conclusions: Our results showed that BM-MSCs could attenuate liver fibrosis in rats with TAA-induced cirrhosis, raising the possibility for clinical use of BM-MSCs in the treatment of cirrhosis.

Original Article : Effects of candesartan and propranolol combination therapy versus propranolol monotherapy in reducing portal hypertension

( Jae Hyun Kim ),( Jung Min Kim ),( Youn Zoo Cho ),( Ji Hoon Na ),( Hyun Sik Kim ),( Hyoun A Kim ),( Hye Won Kang ),( Soon Koo Baik ),( Sang Ok Kwon ),( Seung Hwan Cha ),( Young Ju Kim ),( Moon Young 대한간학회 2014 Clinical and Molecular Hepatology(대한간학회지) Vol.20 No.4

Background/Aims: Angiotensin receptor blockers (ARBs) inhibit activated hepatic stellate cell contraction and are thought to reduce the dynamic portion of intrahepatic resistance. This study compared the effects of combined treatment using the ARB candesartan and propranolol versus propranolol monotherapy on portal pressure in patients with cirrhosis in a prospective, randomized controlled trial. Methods: Between January 2008 and July 2009, 53 cirrhotic patients with clinically significant portal hypertension were randomized to receive either candesartan and propranolol combination therapy (26 patients) or propranolol monotherapy (27 patients). Before and 3 months after the administration of the planned medication, the hepatic venous pressure gradient (HVPG) was assessed in both groups. The dose of propranolol was subsequently increased from 20 mg bid until the target heart rate was reached, and the candesartan dose was fixed at 8 mg qd. The primary endpoint was the HVPG response rate; patients with an HVPG reduction of >20% of the baseline value or to <12 mmHg were defined as responders. Results: The mean portal pressure declined significantly in both groups, from 16 mmHg (range, 12.28 mmHg) to 13.5 mmHg (range, 6.20 mmHg) in the combination group (P<0.05), and from 17 mmHg (range, 12.27 mmHg) to 14 mmHg (range, 7.25 mmHg) in the propranolol monotherapy group (P<0.05). However, the medication-induced pressure reduction did not differ significantly between the two groups [3.5 mmHg (range, -3.11 mmHg) vs. 3 mmHg (range, -8.10 mmHg), P=0.674]. The response rate (55.6% vs. 61.5%, P=0.435) and the reductions in mean blood pressure or heart rate also did not differ significantly between the combination and monotherapy groups. Conclusions: The addition of candesartan (an ARB) to propranolol confers no benefit relative to classical propranolol monotherapy for the treatment of portal hypertension, and is thus not recommended. (Clin Mol Hepatol 2014;20:376-383)

Plenary Session l : Hepatic Vein Arrival Times Using a Microbubble Contrast Ultrasonography can Predict Disease Severity Non-invasively in Patients with Alcoholic Liver Disease

( Won Ki Hong ),( Moon Young Kim ),( Soon Koo Baik ),( Youn Zoo Cho ),( Hye Won Hwang ),( Jin Hyung Lee ),( Myeong Hun Chae ),( Seung Yong Shin ),( Jung Min Kim ),( Mee Yon Cho ),( Sang Ok Kwon ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: A reliable non-invasive assessment of the severity is essential in the management of chronic liver disease. The hepatic vein arrival time (HVAT) as assessed by microbubble contrast-enhanced ultrasonography (CEUS) has been known to show good correlation with histological grade in HCV related liver disease. However, little has been known about the relationship with alcoholic liver disease. We investigated the utility of HVAT in prediction of histological grade of alcohol related chronic liver disease. Methods: One-hundred twenty seven patients with biopsy proven alcohol related chronic liver disease were studied prospectively. Histological grades were estimated by METAVIR fibrosis scoring system (F0-F4). After an overnight fast, a bolus of contrast agent (SonoVue) was injected into an antecubital vein and signals were recorded from the right or middle hepatic veins for analysis. HVATs were calculated as the time from injection to a sustained rise in Doppler signal 10% above baseline. Results: Mean HVAT from F0 to F4 cirrhosis showed a significant progressive shortening of 26.1±5.5 (F0, 7), 20.3±1.4 (F1, 9), 17.4±0.6 (F2, 12), 15.1±1.4 (F3, 34) and 12.7±1.8 (F4, 65) seconds, respectively (P<0.001). The area under the receiver operating characteristic curve (AUROC) was 0.924 for F4 cirrhosis and the sensitivity, specificity for F4 cirrhosis for an HVAT cutoff value of 14.8 sec were 87.7%, 82.3%, respectively. In addition, HVAT also showed significant correlation with Child- Pugh`s score (P<0.001, r2=0.406), the presence of large esophageal varices (P=0.002), ascites (P<0.001) and the history of esophageal variceal hemorrhage (P=0.036). Conclusions: HVAT using a microbubble CEUS could be effective noninvasive method in assessment of the histological severity and disease severity in alcohol related chronic liver disease.

Original Article : The usefulness of non-invasive liver stiffness measurements in predicting clinically significant portal hypertension in cirrhotic patients: Korean data

( Won Ki Hong ),( Moon Young Kim ),( Soon Koo Baik ),( Seung Yong Shin ),( Jung Min Kim ),( Yong Seok Kang ),( Yoo Li Lim ),( Young Ju Kim ),( Youn Zoo Cho ),( Hye Won Hwang ),( Jin Hyung Lee ),( Myeo 대한간학회 2013 Clinical and Molecular Hepatology(대한간학회지) Vol.19 No.4

Background/Aims: Liver stiffness measurement (LSM) has been proposed as a non-invasive method for estimating the severity of fibrosis and the complications of cirrhosis. Measurement of the hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence of portal hypertension, but its invasiveness limits its clinical application. In this study we evaluated the relationship between LSM and HVPG, and the predictive value of LSM for clinically significant portal hypertension (CSPH) and severe portal hypertension in cirrhosis. Methods: LSM was performed with transient elastography in 59 consecutive cirrhotic patients who underwent hemodynamic HVPG investigations. CSPH and severe portal hypertension were defined as HVPG ≥10 and ≥12 mmHg, respectively. Linear regression analysis was performed to evaluate the relationship between LSM and HVPG. Diagnostic values were analyzed based on receiver operating characteristic (ROC) curves. Results: A strong positive correlation between LSM and HVPG was observed in the overall population (r2=0.496, P<0.0001). The area under the ROC curve (AUROC) for the prediction of CSPH (HVPG ≥10 mmHg) was 0.851, and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for an LSM cutoff value of 21.95 kPa were 82.5%, 73.7%, 86.8%, and 66.7%, respectively. The AUROC at prediction of severe portal hypertension (HVPG ≥12 mmHg) was 0.877, and the sensitivity, specificity, PPV, and NPV at LSM cutoff value of 24.25 kPa were 82.9%, 70.8%, 80.6%, and 73.9%, respectively. Conclusions: LSM exhibited a significant correlation with HVPG in patients with cirrhosis. LSM could be a non-invasive method for predicting CSPH and severe portal hypertension in Korean patients with liver cirrhosis.

Clinical Research Article : Postoperative renal function in patients is unaltered after robotic-assisted radical prostatectomy

( Jae Hyun Ahn ),( Choon Hak Lim ),( Hye In Chung ),( Seong Uk Choi ),( Seung Zoo Youn ),( Hae Ja Lim ) 대한마취과학회 2011 Korean Journal of Anesthesiology Vol.60 No.3

Background: Pneumoperitoneum with an intra-abdominal pressure (IAP) of 14 mmHg is known to decrease renal function. Robotic-assisted radical prostatectomy (RARP) requires an IAP of more than 15 mmHg for operation. Therefore, we retrospectively investigated whether patients who underwent RARP experienced renal insuffi ciency during the postoperative period (at postoperative days 7 and 30). Methods: One hundred patients who underwent RARP were enrolled in this study. Preoperative serum blood urea nitrogen (BUN) and serum creatinine (Cr) levels were measured. Creatinine clearance (CrCl) was calculated using the Cockcroft and Gault formula. CrCl was calculated at 1 day before surgery (baseline), 2 hr postoperatively, and at 1, 3, 7, and 30 days postoperatively (POD 1, POD 3, POP 7, and POD 30). Patients were assigned to abnormal CrCl (n = 52) or normal CrCl groups (n = 48) on the basis of these measurements. Results: Significant inter-group differences in BUN, Cr, and CrCl were observed at all postoperative time points. BUN and Cr decreased significantly at postoperative 2 hr and POD 1, 3, and 7 versus baseline in both groups, whereas CrCl increased significantly at postoperative 2 hr and POD 1, 3, and 7 versus baseline in both groups. However, BUN, Cr, and CrCl were similar at POD 30 and preoperatively in the two groups. Conclusions: RAPR, which requires an IAP of 15-20 mmHg for more than 4 hr, does not induce renal dysfunction during the postoperative period, and even in those patients with an abnormal CrCl. (Korean J Anesthesiol 2011; 60: 192-197)

Carbonylation of Bromo(Bromomethyl)Benzenes to Alkyl Carboalkoxyphenylacetates Catalyzed by Cobalt Carbonyl

Shim, Sang-Chul,Doh, Chil-Hoon,Lee, Dong-Yub,Youn, Young-Zoo,Lee, Seung-Yub,Chae, Shin-Ae,Oh, Dae-Hee,Oh, Hun-Seung Korean Chemical Society 1992 Bulletin of the Korean Chemical Society Vol.13 No.1

A synthetic method for bis-carbonylation of bromo(bromomethyl)benzenes was described. Alkyl carboalkoxyphenylacetates were easily prepared by the carbonylation of benzylic and arylic bromide moieties in bromo(bromomethyl)benzenes with alcohols in the presence of $K_2CO_3,\;CH_3I$, and a catalytic amount of cobalt carbonyl under the atmospheric pressure of carbon monoxide at room temperature in good to excellent yields. The base played a decisive role in the selectivity of product and $K_2CO_3$ was the best one among bases used.