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( Keungmo Yang ),( Pil Soo Sung ),( Young Kyoung You ),( Dong Goo Kim ),( Jung Suk Oh ),( Ho Jong Chun ),( Seawon Hwang ),( Jeong Won Jang ),( Si Hyun Bae ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: We aimed to confirm the prognostic significance of a pathological response (PR) achieved with preoperative transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) preceding liver resection (LR) or liver transplantation (LT). Methods: Between 2005 and 2016, 124 patients underwent preoperative TACE before LR, and 166 underwent preoperative TACE before LT. PR was defined as the mean percentage of necrotic tumor area within each tumor. A complete PR (CPR) was defined as the absence of viable tumor in the surgical specimens. Results: A total of 34 (27%) and 38 (23%) patients had CPR before LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR than in those without CPR after LR (87% vs. 63%, P=0.005) and LT (91% vs. 75%, P=0.021). The 5-year recurrence-free survival (RFS) rates were also significantly higher in patients with CPR (71% vs. 38% after LR, P=0.001 and 97% vs. 75% after LT, P=0.008). Among patients with complete radiological remission, those with CPR had better prognosis than those without CPR. Subgroup analyses showed that PR ≥ 90% predicted OS and RFS in patients with a single resected tumor. On multivariate analyses, PR ≥ 90% remained an independent predictor of better OS and RFS in both groups. Independent factors associated with CPR were a preoperative alpha-fetoprotein level < 100 ng/mL and a single tumor. Conclusions: Overall, CPR or nearly CPR improves long-term survival after LR and LT, independent of other pathological and clinical variables.
S-408 Graves`` Disease Coexisting with Idiopathic Hypoparathyroidism
( Keungmo Yang ),( Young Wook Cho ),( Kyeong Pyo Lee ),( Woo Jung Kim ),( Tae Seo Sohn ),( Hyun Shik Son ),( Hannah Seok ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1
Graves’ disease and hypoparathyroidism are very difficult to be correlated because of different pathogenetic characters. We report the first case of Graves’ disease coexisting with idiopathic hypoparathyroidism on adult in Korea. A 60-year-old woman was admitted with sudden loss of consciousness and seizure. She had been diagnosed with Graves’ disease a year ago and taken carbimazole. Laboratory findings were as follows: calcium 4.4 mg/dL; phosphorus 6.3 mg/dL; magnesium 1.6 mg/dL; TSH 0.19 mIU/L; free T4 1.4 ng/dL; intact PTH 3.6 pg/mL; 1.25 (OH)2 vitamin D3 18.8 pg/mL; 25 (OH) vitamin D total 12.6 ng/mL. The brain CT showed bilateral and symmetrical calcifications in the basal ganglia and the brain MRI didn’t have other lesions. The ECG showed QT interval prolongation and the EEG was normal. Our final diagnosis was Graves’ disease coexisting with idiopathic hypoparathyroidism and we conclude that seizure was happened by hypocalcemia. Hypoparathyroidism was probably idiopathic since she doesn’t have the history of surgeries or radiative therapies. Also there was no evidence of immunodeficiency disease or congenital disease which can induce hypocalcemia. Primary hypopararthyroidism is usually occurred by immune-mediated destruction of the parathyroid glands and sometimes coexisted with other diseases to be considered as a part of autoimmune polyendocrine syndrome (APS). We didn’t get the results to screen other diseases in APS. Considering the general symptoms and past medical history, the possibility to accompany these diseases is unlikely.
고빌리루빈혈증과 담도 침범을 동반한 간세포암에 대한 경동맥화학 리피오돌색전술의 안전성과 예후 인자
양경모 ( Keungmo Yang ),성필수 ( Pil Soo Sung ),오정석 ( Jung Suk Oh ),천호종 ( Ho Jong Chun ),장정원 ( Jeong Won Jang ),배시현 ( Si Hyun Bae ),최종영 ( Jong Young Choi ),윤승규 ( Seung Kew Yoon ) 대한간암학회 2018 대한간암학회지 Vol.18 No.2
Background/Aims: The treatments and outcomes of hepatocellular carcinoma (HCC) with bile duct invasion are not well known. We aimed to confirm the safety of transarterial chemolipiodolization (TACL) and identify prognostic factors for patients with bile duct invasion treated with TACL. Methods: Fifty patients with central bile duct invasion treated with TACL between 2005 and 2017 were enrolled. Patients were divided into three groups: hyperbilirubinemia (total bilirubin ≥2.5 mg/dL) with pre-TACL biliary drainage, hyperbilirubinemia without biliary drainage, and without hyperbilirubinemia. Tumor response to TACL, survival outcomes, length of hospitalization, adverse events using Common Terminology Criteria for Adverse Events (CTCAE), and factors affecting overall survival were compared. Results: TACL-induced changes of mean CTCAE grades for albumin, alanine aminotransferase, creatinine, prothrombin time, and platelet were not significantly different among patients with or without initial hyperbilirubinemia. Serum bilirubin level was not significantly changed after TACL in all the three groups. Overall survival was not significantly different among the three groups (P=0.097). On multivariate analysis, alpha-fetoprotein <400 ng/dL (hazard ratio [HR]=0.477, P=0.048) and highest total bilirubin level of <2.5 mg/dL within one month after TACL (HR=0.335, P=0.004) were significantly associated with longer survival. Conclusions: TACL was a safe treatment for HCC patients with central bile duct invasion, irrespective of the presence of initial hyperbilirubinemia. (J Liver Cancer 2018;18:121-129)
( Pil Soo Sung ),( Keungmo Yang ),( Si Hyun Bae ),( Jung Suk Oh ),( Ho Jong Chun ),( Jeong Won Jang ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1
Aims: There are limited studies on the impact of intrahepatic tumor control on patient survival in advanced hepatocellular carcinoma (HCC). The purpose of this study is to confirm survival benefits of reduced intrahepatic tumor burden by hepatic arterial infusion chemotherapy (HAIC) in advanced HCC patients. Methods: Between January 2012 and December 2017, a total of 138 consecutive patients with advanced HCC treated with HAIC were enrolled. Thirty-six patients (26.1%) had extrahepatic metastasis when HAIC was started. Survival outcomes and tumor response rate (both intrahepatic and extrahepatic) after HAIC were analyzed. Multivariate analysis was performed to estimate clinical factors associated with survival outcomes. Results: Most of the patients (86.2%) included in the study were on Barcelona Clinic Liver Cancer stage C. The presence of extrahepatic metastasis at the start of HAIC had no significant effect on overall survival (P=0.17). The intrahepatic objective response rate (ORR) (complete response + partial response) of all the enrolled patients to HAIC was 17.4%. The intrahepatic OR was 13.8% for patients with extrahepatic metastasis, and 18.6% for patients without extrahepatic metastasis. Patients with intrahepatic OR by HAIC showed significantly better survival outcomes than those without OR did, irrespective of the initial distant metastases. On multivariate analysis, the achievement of intrahepatic OR by HAIC and Child-Pugh classification at the time of first response evaluation were two independent Conclusions: HAIC-induced intrahepatic tumor reduction prolongs patient survival irrespective of the status of distant metastasis. Our study demonstrates that it is critical to reduce intrahepatic tumor burden in advanced HCC even when patients have initial extrahepatic metastasis.
Young-Ri Shim,Hee-Hoon Kim,Keungmo Yang,Tom Ryu,Kyurae Kim,Sung Eun Choi,Minjeong Kim,Chae-Rin Woo,Young-Sun Lee,Won-Il Jeong 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Liver is challenged by diverse detrimental substances through multiple metabolic processes, but it is less prone to inflammation. In chronic alcohol consumption, although the migration of monocytes from bone marrow (BM) into liver is increased, alcoholic hepatitis rarely occurs. Thus, we investigated the sub-population of liver macrophages showing anti-inflammatory roles through single-cell RNA sequencing (scRNA-Seq) after chronic EtOH-feeding. Interestingly, in scRNA-seq and flow cytometry analyses of hepatic macrophages, the phenotype of Ly6Clow (anti-inflammatory) cells was dramatically altered by ethanol intake. In particular, they were highly expressed interleukin-1 type II receptor (IL-1R2), a decoy receptor of IL-1β. Intriguingly, IL-1R2+ Ly6Clow macrophages showed decreased CX3CR1 expression, which was confirmed not only in the liver, but also BM and blood, suggesting monocytes from BM affected by ethanol might migrate into the liver. We found that the Leptin Receptor+ mesenchymal stromal cells (LepR+ MSCs), which were located around blood vessels expressing CX3CL1 to hold CX3CR1+ macrophages, could express alcohol dehydrogenase to metabolize ethanol in BM. Ethanol metabolism in LepR+ MSCs was induced both production of chemokines (CXCL9 and 10) and the excretion of glutamate via cystine-glutamate anti-porter xCT to recruit and activate the CXCR3+ BM NK cells to produce interferon-γ in a metabotropic glutamate receptor 5 (mGluR5)-dependent manner. Indeed, IFN-γ production was significantly decreased in EtOH-fed mice when we depleted mGluR5 in NK cells. In turn, NK cell-derived IFN-γ down-regulated CX3CR1 expression in BM Ly6Clow monocytes, consequently induced egress of Ly6Clow monocytes into the blood and migration into the liver to suppress alcoholic inflammation. In conclusion, glutamate of LepR+ MSCs imposed egress license on anti-inflammatory IL-1R2+ Ly6Clow monocytes through NK cell-derived IFN-γ-mediated suppression of CX3CR1, suggesting a potential therapeutic inter-organ crosstalk between BM and liver in alcoholic liver disease.
( Pil Soo Sung ),( Si Hyun Bae ),( Keungmo Yang ),( Ie Ryung Yoo ),( Seawon Hwang ),( Jeong Won Jang ),( Jong Young Choi ),( Seung Kew Yoon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Sorafenib, an oral multikinase inhibitor, remains the only standard treatment offered for patients with Barcelona Clinic Liver Cancer (BCLC) -C stage hepatocellular carcinoma (HCC). <sup>18</sup>F-fluorodexoyglucose positron emission tomography (<sup>18</sup>F-FDG PET) has been used to assess glucose metabolic activity of various types of tumors. The aim of this study is to evaluate the performance of <sup>18</sup>F-FDG PET for predicting the response to sorafenib treatment. Methods: We formed a retrospective cohort comprising patients treated with sorafenib for at least 30 days and undergone <sup>18</sup>F-FDG PET/CT scan within 1 month before treatment. Thirty-five HCC patients fulfilling these criteria were included, who began sorafenib treatment between May 2009 and December 2015 at Seoul St. Mary’s hospital. For statistical analyses, the standardized uptake value (SUV) of the most hypermetabolic lesion was measured and assigned as the SUVmax value for each patient. Results: Among total patients enrolled, two patients obtained partial remission, and 11 patients showed stable disease after first response evaluation during sorafenib treatment. Patients with SUVmax ≥ 6 (n = 17) had median overall survival (OS) of 3.7 months after sorafenib treatment, whereas patients with SUVmax < 6 (n = 18) had median of 12.2 months (P < 0.001). For progression-free survival (PFS), patients with SUVmax ≥ 6 had PFS of 1.9 months, whereas patients with SUVmax < 6 had median of 4.7 months (P = 0.023). SUVmax ≥ 6 (HR = 32.901, P < 0.001), high MELD score (MELD > 9) (HR = 6.629, P = 0.015), and poor performance state demonstrated by ECOG score (ECOG = 2) (HR = 6.607, P = 0.018) were poor prognostic factors for OS by multivariate analysis. For progression-free survival (PFS), patients with SUVmax ≥ 6 had PFS of 1.9 months, whereas patients with SUVmax < 6 had median of 4.7 months (P = 0.023). Regarding PFS, SUVmax ≥ 6 (HR = 3.160, P =0.023) was the only poor prognostic factor by multivariate analysis. Conclusions: Overall, our data clearly demonstrate that tumor metabolic activity assessed by 18F-FDG PET/CT is an independent prognostic factor in patients BCLC-C stage HCC after sorafenib treatment.
( Pil Soo Sung ),( Eun Byul Lee ),( Dong Jun Park ),( Keungmo Yang ),( Jeong Won Jang ),( Si Hyun Bae ),( Seung Kew Yoon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Standard care of chronic hepatitis C virus (HCV) infection has been shifted from IFN-α-based therapies to directly acting antiviral agents (DAAs), which demonstrate excellent efficacy and tolerability in real-life practice. However, there is increasing concern regarding hepatitis B virus (HBV) reactivation during DAA therapy with current or past HBV infections. HCV is known to replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. Moreover, it is well known that the gene expression profile of PBMC mirrors that in liver. In this study, we explored the dynamic gene expression profiles of PBMCs collected from HCV- infected patients undergoing DAA therapy. Methods: We formed a cohort comprising 23 patients treated with DAAs (18 patients with daclatasvir plus asunaprevir, 5 patients with sofosbuvir plus ribavirin). Six different interferon-stimulated genes (ISGs) selected from our previous study (Sung et al, PNAS, 2015) were measured quantitatively in PBMCs before (on the DAA start day) and after therapy (on the DAA end day) and correlated with therapy outcome as well as with clinical data. Results: We identified a significant decrease of ISGs expression during treatment in PBMCs of HCV-infected patients (Figure 1). Among the ISGs examined, the expression of CXCL10, which plays an important role in T-cell recruitment to peripheral inflammatory sites, markedly decreased after DAA treatment. Since all patients in the cohort achieved rapid virological response (RVR), and sustained virological response after 12 weeks (SVR12), we could not determine significant gene expression differences by treatment outcome during therapy. Gene expression of a representative ISG, IFI44, in PBMCs did not correlate with baseline viral load (Figure 2). Furthermore, whereas viral load and PBMC ISG expression both declined on-treatment, the magnitude of gene expression changes and viral kinetic decline were not significantly correlated in a group analysis. Conclusions: Pretreatment activation of the type I IFN response, as reflected by ISGs transcripts upregulation, is rapidly normalized after DAA treatment. Our study suggests that decreased antiviral ISGs expression by the clearance of HCV may be one of the factors that cause HBV reactivation during DAA therapy.