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.

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy. Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data. Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival. Conclusion While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.

There are limited data on outcomes after implantation of everolimus-eluting stents (EES) in East Asian patients with small vessel coronary lesions. A total of 1,600 patients treated with XIENCE EES (Abbott Vascular, CA, USA) were divided into the small vessel group treated with one ≤2.5 mm stent (n=119) and the non-small vessel group treated with one ≥2.75 mm stent (n=933). The primary end point was a patient-oriented composite outcome (POCO), a composite of all-cause death, myocardial infarction (MI), and any repeat revascularization at 12 months. The key secondary end point was a device-oriented composite outcome (DOCO), a composite of cardiovascular death, target-vessel MI, and target lesion revascularization at 12 months. The small vessel group was more often female, hypertensive, less likely to present with ST-elevation MI, and more often treated for the left circumflex artery, whereas the non-small vessel group more often had type B2/C lesions, underwent intravascular ultrasound, and received unfractionated heparin. In the propensity matched cohort, the mean stent diameter was 2.5±0.0 mm and 3.1±0.4 mm in the small and non-small vessel groups, respectively. Propensity-adjusted POCO at 12 months was 6.0% in the small vessel group and 4.3% in the non-small vessel group (p=0.558). There was no significant difference in DOCO at 12 months (small vessel group: 4.3% and non-small vessel group: 1.7%, p=0.270).Outcomes of XIENCE EES for small vessel disease were comparable to those for non-small vessel disease at 12-month clinical follow-up in real-world Korean patients.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Unexpected conversion to thoracotomy during planned video-assisted thoracoscopic surgery (VATS) can lead to poor outcomes and comparatively high morbidity. This study was conducted to assess preoperative risk factors associated with unexpected thoracotomy conversion and to develop a risk scoring model for preoperative use, aimed at identifying patients with an elevated risk of conversion. Methods: A retrospective analysis was conducted of 1,506 patients who underwent surgical resection for non-small cell lung cancer. To evaluate the risk factors, univariate analysis and logistic regression were performed. A risk scoring model was established to predict unexpected thoracotomy conversion during VATS of the lung, based on preoperative factors. To validate the model, an additional cohort of 878 patients was analyzed. Results: Among the potentially significant clinical variables, male sex, previous ipsilateral lung surgery, preoperative detection of calcified lymph nodes, and clinical T stage were identified as independent risk factors for unplanned conversion to thoracotomy. A 6-point risk scoring model was developed to predict conversion based on the assessed risk, with patients categorized into 4 groups. The results indicated an area under the receiver operating characteristic curve of 0.747, with a sensitivity of 80.5%, specificity of 56.4%, positive predictive value of 1.8%, and negative predictive value of 91.0%. When applied to the validation cohort, the model exhibited good predictive accuracy. Conclusion We successfully developed and validated a risk scoring model for preoperative use that can predict the likelihood of unplanned conversion to thoracotomy during VATS of the lung.

Background and Objectives: Inherited arrhythmia (IA) is a more common cause of sudden cardiac death in Asian population, but little is known about the genetic background of Asian IA probands. We aimed to investigate the clinical characteristics and analyze the genetic underpinnings of IA in a Korean cohort. Methods: This study was conducted in a multicenter cohort of the Korean IA Registry from 2014 to 2017. Genetic testing was performed using a next-generation sequencing panel including 174 causative genes of cardiovascular disease. Results: Among the 265 IA probands, idiopathic ventricular fibrillation (IVF) and Brugada Syndrome (BrS) was the most prevalent diseases (96 and 95 cases respectively), followed by long QT syndrome (LQTS, n=54). Two-hundred-sixteen probands underwent genetic testing, and 69 probands (31.9%) were detected with genetic variant, with yield of pathogenic or likely pathogenic variant as 6.4%. Left ventricular ejection fraction was significantly lower in genotype positive probands (54.7±11.3 vs. 59.3±9.2%, p=0.005). IVF probands showed highest yield of positive genotype (54.0%), followed by LQTS (23.8%), and BrS (19.5%). Conclusions There were significant differences in clinical characteristics and genetic yields among BrS, LQTS, and IVF. Genetic testing did not provide better yield for BrS and LQTS. On the other hand, in IVF, genetic testing using multiple gene panel might enable the molecular diagnosis of concealed genotype, which may alter future clinical diagnosis and management strategies.

Background: Atrial fibrillation (AF) is a well-known, long-term complication of atrial septal defect (ASD) in adults, even after device closure. Left atrial (LA) strain rate applied to the analysis of chamber function has been demon‑ strated to be an important predictor of LA reverse remodeling. This study aimed to determine the changes in cham‑ ber function after device closure of ASD. Methods: This prospective study enrolled adults with secundum ASD undergoing transcatheter device closure from December 2016 to August 2017. We analyzed the clinical characteristics and LA strain rate before and six months after ASD closure. Results: A total of 11 patients were enrolled. The mean age was 42.6 ± 9.9 years, and six (54.5%) were females. There was no significant change of conventional echocardiographic parameters after ASD closure. The mean global LA res‑ ervoir strain rate before ASD closure was 1.17 ± 0.34 and 0.85 ± 0.30 after ASD closure (p = 0.030). The median global LA conduit strain rate was 0.68 (0.42–1.16) and 0.41 (0.16–0.79) before and after ASD closure (p = 0.213), respectively. The mean global LA contractile strain rate at the six-month follow-up showed significant improvement compared with pre-procedural strain rate (0.33 ± 0.65 vs. − 0.43 ± 0.38, p = 0.006). Conclusions LA functional changes occurred during the six-month follow-up, while LA and right atrial (RA) geo‑ metric changes were not significant. LA reverse remodeling was proved by restoration of LA late diastolic contractile function.

Purpose: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA2DS2-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m2 ), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA2DS2-VASc score 0–1. Materials and Methods: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0–1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated. Results: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA2DS2-VASc score in the stroke risk stratification (C-index=0.618, p=0.015; net reclassification improvement=0.576, p=0.040; integrated differential improvement=0.033, p=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P–Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, p=0.003). Conclusion The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0–1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA2DS2-VASc score 0–1.

Background: Although respiratory tract infection is one of the most important factors triggering acute exacerbation of chronic obstructive pulmonary disease (AE-COPD), limited data are available to suggest an epidemiologic pattern of microbiology in South Korea. Methods: A multicenter observational study was conducted between January 2015 and December 2018 across 28 hospitals in South Korea. Adult patients with moderate-to-severe acute exacerbations of COPD were eligible to participate in the present study. The participants underwent all conventional tests to identify etiology of microbial pathogenesis. The primary outcome was the percentage of different microbiological pathogens causing AE-COPD. A comparative microbiological analysis of the patients with overlapping asthma–COPD (ACO) and pure COPD was performed. Results: We included 1,186 patients with AE-COPD. Patients with pure COPD constituted 87.9% and those with ACO accounted for 12.1%. Nearly half of the patients used an inhaled corticosteroid-containing regimen and one-fifth used systemic corticosteroids. Respiratory pathogens were found in 55.3% of all such patients. Bacteria and viruses were detected in 33% and 33.2%, respectively. Bacterial and viral coinfections were found in 10.9%. The most frequently detected bacteria were Pseudomonas aeruginosa (9.8%), and the most frequently detected virus was influenza A (10.4%). Multiple bacterial infections were more likely to appear in ACO than in pure COPD (8.3% vs. 3.6%, p=0.016). Conclusion Distinct microbiological patterns were identified in patients with moderate-to-severe AE-COPD in South Korea. These findings may improve evidence-based management of patients with AE-COPD and represent the basis for further studies investigating infectious pathogens in patients with COPD.

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.