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Hepatitis B virus infection, diabetes mellitus, and their synergism for cholangiocarcinoma development: A casecontrol study in Korea

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World Journal of Gastroenterology 2015年第2期21卷 502-510页

作者： Ban Seok Lee Eun-Cheol park seung woo park Chung Mo Nam Jaehoon Roh Department of Medicine Graduate SchoolYonsei University College of MedicineSeoul 120-752South Korea Digestive Disease Center and Department of Internal Medicine Cheju Halla General HospitalJeju 690-766South Korea Department of Preventive Medicine Yonsei University College of MedicineSeoul 120-752South Korea Institute of Health Services Research Yonsei University College of MedicineSeoul 120-752South Korea Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoul 120-752South Korea

AIM: To identify possible risk factors and their synergism for cholangiocarcinoma ***: A hospital-based, case-control study in which we included 276 cholangiocarcinoma patients [193 extrahepatic cholangiocarcinoma(ECC) and 83 intrahepatic cholangiocarcinoma(ICC)], diagnosed at a training hospital in Korea between 2007 and 2013, and 552 healthy controls matched 2:1 for age, sex, and date of diagnosis. Risk factors for cholangiocarcinoma and possible synergism between those factors were evaluated using conditional logistic regression and synergism index, ***:There was an association between cholangiocarcinoma and hepatitis B virus(HBV) infection, diabetes mellitus(DM), cholecystolithiasis, choledocholithiasis, and hepatolithiasis, with the adjusted odds ratios(AORs) of 4.1, 2.6, 1.7, 12.4, and 39.9, respectively. Synergistic interaction on the additive model was investigated between HBV infection and DM(AOR = 12.2; 95%CI: 1.9-80.1). In the subgroup analyses, cholecystolithiasis, choledocholithiasis, hepatolithiasis, and DM were significant risk factors for ECC(AOR = 2.0, 18.1, 14.9, and 2.0, respectively), whereas choledocholithiasis, hepatolithiasis, HBV infection, and DM were risk factors for ICC(AOR = 8.6, 157.4, 5.3 and 4.9, respectively). Synergistic interaction was also observed between HBV infection and DM(OR = 22.7; 95%CI: 2.4-214.1). However, there was no synergistic interaction between other significant risk factors for ***: In this Korean study, HBV infection and DM were found to exert independent and synergistic effects on the risk for cholangiocarcinoma, including ICC. Exploring the underlying mechanismsfor such synergy may lead to the development of cholangiocarcinoma prevention strategies in high-risk individuals.

关键词： Cholangiocarcinoma Risk factor Hepatitis Synergism

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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

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Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang Hee seung Lee Moon Jae Chung Jeong Youp park seungmin Bang seung woo park Si Young Song Division of Gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer

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World Journal of Gastrointestinal Oncology 2018年第11期10卷 421-430页

作者： Huapyong Kang Jung Hyun Jo Hee seung Lee Moon Jae Chung seungmin Bang seung woo park Si Young Song Jeong Youp park Division of Gastroenterology Department of Internal Medicine Yonsei University College of Medicine

AIM To directly compare the efficacy and toxicity of standarddose FOLFIRINOX(sFOLFIRINOX) and modified-dose FOLFIRINOX(mFOLFIRINOX, 75% of standard-dose) for pancreatic *** One hundred and thirty pancreatic cancer patients who received sFOLFIRINOX(n = 88) or mFOLFIRINOX(n = 42) as their first-line chemotherapy from January 2013 to July 2017 were retrospectively reviewed. For efficacy analysis, the objective response rate(ORR),disease control rate(DCR), progression-free survival(PFS), and overall survival(OS) were evaluated and compared using Pearson's chi-square test, Kaplan-Meier plot and log-rank test. The adverse events(AEs) were evaluated, and severe(≥ grade 3) AEs rates of the two groups were compared for toxicity *** The mFOLFIRINOX group included more female patients(30.7% vs 57.1%; P = 0.004) and older patients [age(median), 57 vs 63.5; P = 0.018] than the sFOLFIRINOX group. In the efficacy analysis, the ORR and DCR were not significantly different between the two groups(ORR: 39.8% vs 35.7%; P = 0.656; DCR: 80.7% vs 83.3%; P = 0.716). The median PFS and OS were also not different between the groups(PFS: 8.7 mo vs 8.1 mo, P = 0.272; OS: 13.9 mo vs 13.7 mo, P = 0.476). In the safety analysis with severe AEs, the rates of neutropenia(83.0% vs 66.7%; P = 0.044), anorexia(48.9% vs 28.6%; P = 0.029) and diarrhea(13.6% vs 0.0%; P = 0.009) were markedly lower in the mFOLFIRINOX *** m FOLFIRINOX showed comparable efficacy but better safety compared to sFOLFIRINOX. If clinically necessary, initiating FOLFIRINOX with 75% of the standard-dose can alleviate toxicity concerns without compromising efficacy.

关键词： Dose modification Adverse event Pancreatic cancer Adenocarcinoma FOLFIRINOX Chemotherapy

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FOLFIRINOX vs gemcitabine/nab-paclitaxel for treatment of metastatic pancreatic cancer: Single-center cohort study

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World Journal of Gastrointestinal Oncology 2020年第2期12卷 182-194页

作者： In Rae Cho Huapyong Kang Jung Hyun Jo Hee seung Lee Moon Jae Chung Jeong Youp park seung woo park Si Young Song Chansik An Mi-Suk park seungmin Bang Department of Internal Medicine International Saint Mary’s HospitalCatholic Kwandong University College of MedicineIncheon 22711South Korea Department of Medicine Yonsei University Graduate School50-1 Yonsei-roSeoul 03722South Korea Division of Gastroenterology Department of Internal MedicineYonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea Department of Radiology Yonsei University College of Medicine50-1 Yonsei-roSeoul 03722South Korea

BACKGROUND FOLFIRINOX and gemcitabine plus nab-paclitaxel(Gem+nabPTX)were recently introduced for metastatic pancreatic cancer ***,studies that compared these two regimens and studies in Asian populations are *** To compare the treatment outcomes of FOLFIRINOX and Gem+nabPTX regimen for metastatic pancreatic cancer treatment in Korean *** Patients with metastatic or recurrent pancreatic cancer treated with FOLFIRINOX(n=86)or Gem+nabPTX(n=81)as the first-line since January 2015 were identified using the Severance Hospital Pancreatic Cancer Cohort *** efficacy,treatment-related adverse events and economic aspects were *** Patients in the FOLFIRINOX group were significantly younger(54 vs 65 years;P<0.001)and had better performance statuses at *** median overall survival(10.7 vs 12.1 mo;P=0.157),progression-free survival(8.0 vs 8.4 mo;P=0.134),and objective response rates(33.7%vs 46.9%;P=0.067)were not significantly different when compared with Gem+nabPTX ***≥3 neutropenia and gastrointestinal adverse events were more common in the FOLFIRINOX *** drug costs of both regimens were *** Treatment efficacy and economic burdens were comparable between the two ***,the details of adverse event were ***+nabPTX regimen might be considered preferentially in certain conditions.

关键词： Pancreatic cancer Chemotherapy FOLFIRINOX Gemcitabine Nabpaclitaxel Survival

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Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma

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World Journal of Gastroenterology 2017年第18期23卷 3301-3308页

作者： Jang Han Jung Hyun Jik Lee Hee seung Lee Jung Hyun Jo In Rae Cho Moon Jae Chung Jeong Youp park seung woo park Si Young Song seungmin Bang Division of Gastroenterology Department of Internal Medicine Hallym University Dongtan Sacred Heart Hospital Division of Gastroenterology Department of Internal Medicine and Yonsei Institute of Gastroenterology Yonsei University College of Medicine

To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA).METHODSWe retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative *** median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01).CONCLUSIONNACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.

关键词： Klatskin tumor Locally advanced Survival rate Neoadjuvant therapy Chemoradiotherapy

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Role of oxygen free radicals in patients with acute pancreatitis

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World Journal of Gastroenterology 2003年第10期9卷 2266-2269页

作者： Byung Kyu park Jae Bock Chung Jin Heon Lee Jeong Hun Suh seung woo park Si Young Song Hyeyoung Kim Kyung Hwan Kim Jin Kyung Kang Department of Internal Medicine Institute of GastroenterologyCollege of MedicineYonsei UniversitySeoulKorea Department of Pharmacology College of MedicineYonsei UniversitySeoulKorea Departmentof Internal Medicine Institute of GastroenterologyCollege of MedicineYonsei UniversitySeoulKorea

AIM:The generation of oxygen free radicals has been implicated in the pathogenesis of experimental pancreatitis. The aim of this study was to determine the role of oxygen free radicals in patients with acute pancreatitis. METHODS:The plasma levels of C-reactive protein(CRP), lipid peroxide(LPO),myeloperoxidase(MPO)and superoxide dismutase(SOD)were measured in 13 patients with acute pancreatitis and 14 healthy volunteers. RESULTS:Among the patients with acute pancreatitis,there were higher plasma levels of LPO and MPO and lower SOD activity in patients with severe pancreatitis than in those with mild ***,there was no significant difference in the serum marker of oxidative stress no matter what the etiology *** LPO level was especially correlated with the concentration of serum CRP and CT severity index. CONCLUSION:The oxygen free radicals may be closely associated with inflammatory process and the severity of acute ***,the concentration of plasma LPO is a meaningful index for determining the severity of the disease.

关键词： Oxidative Stress Severity of Illness Index Acute Disease Adult Aged Female Humans Lipid Peroxides Male Middle Aged Pancreatitis Peroxidase Predictive Value of Tests Prognosis Reactive Oxygen Species Superoxide Dismutase

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Incidence of coronary artery disease before valvular surgery in isolated severe aortic stenosis

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Chinese Medical Journal 2014年第22期127卷 3963-3969页

作者： Eun Jeong Cho Sung-Ji park Sung-A Chang Dong Seop Jeong Sang-Chol Lee seung woo park Pyo Won park Division of Cardiology Department of Internal MedicineCardiovascular Imaging Center Cardiac and Vascular Center Samsung Medical CenterSungkyunkwan University School of Medicine Seoul Korea Department of Thorax Surgery Samsung Medical CenterSungkyunkwan University School of Medicine Seoul Korea

Background Angina pectoris has been recognized as one of the principal symptoms of aortic valve stenosis （AS）,even in patients without significant coronary artery disease （CAD）.However,the incidence of angina pectoris and related CAD in such patients is *** is continuing debate as to whether coronary angiography is necessary before aortic valve replacement （AVR） in patients with severe *** purpose of this study was to evaluate the incidence and predictors of CAD in patients with severe AS in a Korean *** Data from all consecutive patients with severe AS undergoing AVR at a major tertiary cardiac and vascular center in Korea were entered in a prospective registry beginning in *** and echocardiographic follow-up data were recorded into the database *** CAD was defined as one or more major coronary arteries having an estimated narrowing of ≥70％ and left main coronary arteries having an estimated narrowing of ≥50％ on coronary *** excluded patients with multiple valve disease,significant aortic regurgitation,or prior CAD or valve *** Totally 574 patients with severe AS （mean age,（65.9±9.6） years） were enrolled in this *** CAD was found in 61 patients （10.6％）.Factors associated with increased likelihood of CAD were age,hypertension,diabetes mellitus,chronic renal failure,carotid disease,and aorta *** Logistic regression analysis,the independent predictor of the presence of CAD was age （P=0.011）.The incidence of CAD increased significantly at 69.2 years of *** two risk factors for cardiovascular disease was the most useful cutoff to predict whether a patient was going to have significant *** There was a low incidence of significant CAD in a population of Korean patients with severe ***,coronary angiography before AVR will be considered in patients with multiple risk factors for cardiovascular disease or in patients more than 69 years of

关键词： severe aortic stenosis coronary artery disease aortic valve replacement

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What is the real practice of exercise echocardiographic testing in asymptomatic patients with severe aortic stenosis？

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Chinese Medical Journal 2013年第24期126卷 4649-4654页

作者： Eun Jeong Cho Sung-Ji park Jung-Eun Song Seol-Hwa Kim Yung-Joo Lee Ji-Hye Gakt Sung-A Chang Sang-Chol Lee seung woo park Division of Cardiology Department of Internal MedicineCardiovascular Imaging Center Cardiac and Vascular CenterSamsung Medical Center Sungkyunkwan University School ofMedicine Seoul Republic of Korea

Background Although exercise testing has been suggested to help predict clinical outcome, limited data are available to guide how exercise Doppler echocardiography （ECG） can be used clinically in asymptomatic patients with aortic stenosis （AS）. The aim of this study was to assess the clinical value of exercise echocardiographic testing in asymptomatic patients with severe AS. Methods Symptom-limited treadmill exercise testing using the modified Bruce protocol was performed in 31 asymptomatic patients （mean age （62＋11） years） with severe AS （aortic valve area 〈1 cm2, peak aortic velocity （AV Vmax）〉4 m/sec, or a mean transaortic pressure gradient （AV mean PG）〉40 mmHg （1 mmHg=0.133 kPa）） with normal left ventricular （LV） systolic function （LV ejection fraction （EF）〉50%）. Clinical symptoms, vital signs, ECG, and Doppler hemodynamics were obtained during and/or immediately after exercise. Results Aortic valve replacement （AVR） was performed in 18 patients during follow-up. The patients who had AVR exhibited higher baseline AV mean PG （51 （35-84） vs. 44 （25.2-57.0） mmHg; P=0.031）. There were no significant differences between the AVR group and non-AVR group including exercise duration （7.47 （2.32-11.59） vs. 7.25 （4.06- 10.52） minutes, P=0.917）, exercise capacity （10.1 （4.6-12.8） vs. 10.1 （7.0-12.8） metabolic equivalents, P=0.675）, and an increment in AV mean PG by exercise （18.5 （3.2-48.0） vs. 12.6 （4.4-32.1） mmHg, P=0.366）. Univariate regression analysis revealed that independent determinant of AVR was the baseline AV mean PG （P=-0.031）. Conclusions Although additional value of exercise ECG was demonstrated, baseline transaortic mean pressure gradient is the major determinant of AVR. Further large-scale prospective studies are required to determine whether surgery should be recommended in the presence of an abnormal exercise ECG in asymptomatic severe AS.

关键词： aortic stenosis exercise echocardiography asymptomatic, aortic valve replacement

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Placement of a fully covered self-expandable metal stent in a young patient with chronic pancreatitis

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World Journal of Gastrointestinal Endoscopy 2010年第11期2卷 375-378页

作者： Kyong Joo Lee Kwang Joon Kim Dong Ho Shin Joo Won Chung Jeong Youp park seungmin Bang seung woo park Si Young Song Division of Gastroenterology Department of Internal MedicineYonsei Institute of GastroenterologyYonsei University College of MedicineSeoul 120-752South Korea Brain Korea 21 Project for Medical Science Division of Gastroenterology Department of Internal Medicine Severance Biomedical Science Institute Yonsei University College of MedicineSeoulKorea

Plastic stent insertion is a treatment option for pancreatic duct stricture with chronic ***, recurrent stricture is a limitation after removing the plastic ***-expandable metal stents have long diameters and patency.A metal stent has become an established management option for pancreatic duct stricture caused by malignancy but its use in benign stricture is still *** introduce a young patient who had chronic pancreatitis and underwent several plastic stent insertions due to recurrent pancreatic duct *** symptoms improved after using a fully covered self-expandable metal covered stent and there was no recurrence found at follow-up at the outpatient department.

关键词： Chronic Pancreatitis Pancreatic duct stricture Fully covered self-expandable metal covered stent Young patient

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Comprehensive molecular characterization to predict immunotherapy response in advanced biliary tract cancer:a phase II trial of pembrolizumab

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Oncology Research 2025年第1期33卷 57-65页

作者： RYUL KIM JOO KYUNG park MINSUK KWON MINAE AN JUNG YONG HONG JOON OH park SUNG HEE LIM seung TAE KIM Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Division of Gastroenterology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulKorea Department of Hematology-Oncology Ajou University School of MedicineSuwon-siGyeonggi-doKorea Samsung Advanced Institute of Health Science and Technology Sungkyunkwan University School of MedicineSeoulKorea

Background:Immune checkpoint inhibitors(ICIs)are effective in a subset of patients with metastatic solid ***,the patients who would benefit most from ICIs in biliary tract cancer(BTC)are still *** and methods:We molecularly characterized tissues and blood from 32 patients with metastatic BTC treated with the ICI pembrolizumab as second-line ***:All patients had microsatellite stable(MSS)type *** of the 32 patients achieved partial response(PR),with an objective response rate(ORR)of 9.4%(95%confidence interval[CI],2.0–25.2)and nine showed stable disease(SD),exhibiting a disease control rate(DCR)of 37.5%(95%CI,21.1–56.3).For the 31 patients who had access to PD-1 ligand 1(PD-L1)combined positive score(CPS)testing(cut-off value≥1%),the ORR was not different between those who had PD-L1-positive(PD-L1+;1/11,9.1%)and PDL1-(2/20,10.0%)tumors(p=1.000).The tumor mutational burden(TMB)of PD-L1+BTC was comparable to that of PD-L1-BTC(p=0.630).TMB and any exonic somatic mutations were also not predictive of pembrolizumab *** analysis of blood and tumor samples demonstrated a relatively high natural killer(NK)cell proportion in the peripheral blood before pembrolizumab treatment in patients who achieved tumor ***,the tumors of these patients presented high enrichment scores for NK cells,antitumor cytokines,and Th1 signatures,and a low enrichment score for cancer-associated ***:This study shows the molecular characteristics associated with the efficacy of pembrolizumab in BTC of the MSS type.

关键词： Pembrolizumab Whole-exome sequencing Whole-transcriptome sequencing Biliary tract cancer

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