Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a pivotal enzyme in the Toll-like receptor (TLR)/MYD88 dependent signaling pathway, which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL). Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of lymphoma. Moreover, proviral integration site for Moloney murine leukemia virus 1 (PIM1) functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib resistance. We developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in vivo. In rheumatoid arthritis mouse models, treatment with KIC-0101 significantly ameliorated cartilage damage and inflammation. KIC-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in ABC-DLBCLs. In addition, KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 kinase. Our results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

Objective: To compare the clinical and radiological features of various etiologies of chronic diffuse lacrimal gland enlargement. Materials and Methods: We retrospectively reviewed 91 consecutive patients who underwent surgical biopsy for chronic diffuse lacrimal gland enlargement and were diagnosed with non-specific dacryoadenitis (DA) (n = 42), immunoglobulin G4-related dacryoadenitis (IgG4-RD) (n = 33), and lymphoma (n = 16). Data on patient demographics, clinical presentation, and CT imaging findings (n = 73) and MRI (n = 43) were collected. The following radiologic features of lacrimal gland enlargement were evaluated: size, unilaterality, wedge sign, angle with the orbital wall, heterogeneity, signal intensity, degree of enhancement, patterns of dynamic contrast-enhanced, and apparent diffusion coefficient value. Radiological features outside the lacrimal glands, such as extra-lacrimal orbital involvement and extra-orbital head and neck involvement, were also evaluated. The clinical and radiological findings were compared among the three diseases. Results: Compared to the DA and IgG4-RD groups, the lymphoma group was significantly older (mean 59.9 vs. 46.0 and 49.4 years, respectively; p = 0.001) and had a higher frequency of unilateral involvement (62.5% vs. 31.0% and 15.2%, respectively;p = 0.004). Compared to the IgG4-RD and lymphoma groups, the DA group had significantly smaller lacrimal glands (2.3 vs. 2.8 and 3.3 cm, respectively; p < 0.001) and a lower proportion of cases with a wedge sign (54.8% vs. 84.8% and 87.5%, respectively; p = 0.005). The IgG4-RD group showed more frequent involvement of the extra-orbital head and neck structures, including the infraorbital nerve (36.4%), paranasal sinus (72.7%), and salivary gland (58.6%) compared to the DA and lymphoma groups (4.8%–28.6%) (all p < 0.005). Conclusion Patient age, unilaterality, lacrimal gland size, wedge sign, and extra-orbital head and neck involvement differed significantly different between lymphoma, DA, and IgG4-RD. Our results will be useful for the differential diagnosis and proper management of chronic lacrimal gland enlargement.

Background/Aims: While switching strategies of P2Y12 receptor inhibitors (RIs) have sometimes been used in acute myocardial infarction (AMI) patients, the current status of in-hospital P2Y12RI switching remains unknown. Methods: Overall, 8,476 AMI patients who underwent successful revascularization from Korea Acute Myocardial Infarction Registry-National Institute of Health (KAMIR-NIH) were divided according to in-hospital P2Y12RI strategies, and net adverse cardiovascular events (NACEs), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), stroke, or thrombolysis in myocardial infarction (TIMI) major bleeding during hospitalization were compared. Results: Patients with in-hospital P2Y12RI switching accounted for 16.5%, of which 867 patients were switched from clopidogrel to potent P2Y12RI (C-P) and 532 patients from potent P2Y12RI to clopidogrel (P-C). There were no differences in NACEs among the unchanged clopidogrel, the unchanged potent P2Y12RIs, and the P2Y12RI switching groups. However, compared to the unchanged clopidogrel group, the C-P group had a higher incidence of non-fatal MI, and the P-C group had a higher incidence of TIMI major bleeding. In clinical events of in-hospital P2Y12RI switching, 90.9% of non-fatal MI occurred during pre-switching clopidogrel administration, 60.7% of TIMI major bleeding was related to pre-switching P2Y12RIs, and 71.4% of TIMI major bleeding was related to potent P2Y12RIs. Only 21.6% of the P2Y12RI switching group switched to P2Y12RIs after a loading dose (LD); however, there were no differences in clinical events between patients with and without LD. Conclusions In-hospital P2Y12RI switching occurred occasionally, but had relatively similar clinical outcomes compared to unchanged P2Y12RIs in Korean AMI patients. Non-fatal MI and bleeding appeared to be mainly related to pre-switching P2Y12RIs.

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI). METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months. RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924). CONCLUSIONS Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.

BACKGROUND AND OBJECTIVES: There is a paucity of data regarding the benefit of clopidogrel monotherapy after dual antiplatelet therapy (DAPT) in patients treated with drug-eluting stents (DES). This study compared outcome between clopidogrel versus aspirin as monotherapy after DES for acute myocardial infarction (MI).METHODS: From Korea Acute Myocardial Infarction Registry-National Institute of Health database, 1,819 patients treated with DES who were switched to monotherapy with clopidogrel (n=534) or aspirin (n=1,285) after uneventful 12-month DAPT were analyzed. The primary endpoint was net adverse clinical events (NACE), defined as a composite of death from any cause, MI, repeat percutaneous coronary intervention (PCI), stent thrombosis, ischemic stroke, or major bleeding during the period from 12 to 24 months.RESULTS: After adjustment using inverse probability of treatment weighting, patients who received clopidogrel, compared with those treated with aspirin, had a similar incidence of NACE (0.7% and 0.7%; hazard ratio, 1.06; 95% confidence interval, 0.31–3.60; p=0.923). The 2 groups had similar rates of death from any cause (0.1% in each group, p=0.789), MI (0.3% and 0.1%, respectively; p=0.226), repeat PCI (0.1% and 0.3%, respectively; p=0.548), stent thrombosis (0.1% and 0%, respectively; p=0.121), major bleeding (0.2% in each group, p=0.974), and major adverse cardiovascular and cerebrovascular events (0.5% in each group, p=0.924).CONCLUSIONS: Monotherapy with clopidogrel, compared to aspirin, after DAPT showed similar clinical outcomes in patients with acute MI treated with DES.
Aspirin ; Drug-Eluting Stents ; Hemorrhage ; Humans ; Incidence ; Korea ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; Stents ; Stroke ; Thrombosis

BACKGROUND: Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM. METHODS: Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used. RESULTS: The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change. CONCLUSION This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

BACKGROUND/AIMS: Colorectal cancer incidence among patients aged ≤50 years is increasing. This study aimed to develop and validate an advanced colorectal neoplasm (ACRN) screening model for young adults aged <50 years in Korea. METHODS: This retrospective cross-sectional study included 59,575 consecutive asymptomatic Koreans who underwent screening colonoscopy between 2003 and 2012 at a single comprehensive health care center. Young Adult Colorectal Screening (YCS) score was developed as an optimized risk stratification model for ACRN using multivariate analysis and was internally validated. The predictive power and diagnostic performance of YCS score was compared with those of Asia-Pacific Colorectal Screening (APCS) and Korean Colorectal Screening (KCS) scores. RESULTS: 41,702 and 17,873 subjects were randomly allocated into the derivation and validation cohorts, respectively, by examination year. ACRN prevalence was 0.9% in both cohorts. YCS score comprised sex, age, alcohol, smoking, obesity, glucose metabolism abnormality, and family history of CRC, with score ranges of 0 to 10. In the validation cohort, ACRN prevalence was 0.6% in the low-risk tier (score, 0–4), 1.5% in the moderate-risk tier (score, 5–7), and 3.4% in the high-risk tier (score, 8–10). ACRN risk increased 2.5-fold (95% confidence interval [CI], 1.8–3.4) in the moderate-risk tier and 5.8-fold (95% CI, 3.4–9.8) in the high-risk tier compared with the low-risk tier. YCS score identified better balanced accuracy (53.9%) than APCS (51.5%) and KCS (50.7%) scores and had relatively good discriminative power (area under the curve=0.660). CONCLUSIONS: YCS score based on clinical and laboratory risk factors was clinically effective and beneficial for predicting ACRN risk and targeting screening colonoscopy in adults aged <50 years.
Adult ; Cohort Studies ; Colonoscopy ; Colorectal Neoplasms ; Comprehensive Health Care ; Cross-Sectional Studies ; Early Detection of Cancer ; Glucose ; Humans ; Incidence ; Korea ; Mass Screening ; Metabolism ; Multivariate Analysis ; Obesity ; Prevalence ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Smoke ; Smoking ; Young Adult

OBJECTIVE: Data on the intensity of statin therapy for patients with acute myocardial infarction (MI) and very low baseline low-density lipoprotein (LDL) cholesterol level are lacking. We sought to assess the impact of statin intensity in patients with acute MI and LDL cholesterol <70 mg/dL. METHODS: A total of 1,086 patients with acute MI and baseline LDL cholesterol <70 mg/dL from the Korea Acute Myocardial Infarction Registry-National Institute of Health database were divided into less intensive statin (expected LDL reduction <40%, n=302) and more intensive statin (expected LDL reduction ≥40%, n=784) groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, MI, revascularization occurring at least 30 days after admission, and stroke, at 12 months. RESULTS: After 1:2 propensity matching, differences were not observed between less intensive (n=302) and more intensive statin (n=604) groups in incidence of cardiac death (0.3% vs. 0.3%) and hemorrhagic stroke (0.3% vs. 0.5%, p=0.727) at 12 months. Compared with the less intensive statin group, the more intensive statin group showed lower target-vessel revascularization (4.6% vs. 1.8%, p=0.027) and MACCE (11.6% vs. 7.0%, p=0.021). Major bleeding was not different between less intensive and more intensive statin groups (1.0% vs. 2.6%, p=0.118). CONCLUSION: More intensive statin therapy was associated with significantly lower major adverse cardiovascular events in patients with acute MI and very low LDL cholesterol compared with less intensive statin therapy.
Cholesterol ; Cholesterol, LDL ; Death ; Hemorrhage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Korea ; Lipoproteins ; Myocardial Infarction ; Stroke