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: Smoking cessation intervention is one of the key components of successful lung cancer screening program. We investigated the effectiveness and related factors of smoking cessation services provided to the participants in a population-based lung cancer screening trial. Materials and Methods: The Korean Lung Cancer Screening Project (K-LUCAS) is a nationwide, multi-center lung cancer screening trial that evaluates the feasibility of implementing population-based lung cancer screening. All 5,144 current smokers who participated in the K-LUCAS received a mandatory smoking cessation counseling. Changes in smoking status were followed up using a telephone survey in 6 months after lung cancer screening participation. The lung cancer screening’s impact on smoking cessation is analyzed by variations in the smoking cessation interventions provided in screening units. Results: Among 4,136 survey responders, participant’s motivation to quit smoking increased by 9.4% on average after lung cancer screening. After 6 months from the initial screening, 24.3% of participants stopped smoking, and 10.6% of participants had not smoked continuously for at least 6 months after screening. Over 80% of quitters stated that participation in lung cancer screening motivated them to quit smoking. Low-cost public smoking cessation program combined with lung cancer screening increased the abstinence rates. The smokers were three times more likely to quit smoking when the smoking cessation counseling was provided simultaneously with low-dose computed tomography screening results than when provided separately. Conclusion A mandatory smoking cessation intervention integrated with screening result counselling by a physician after participation in lung cancer screening could be effective for increasing smoking cessation attempts.

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.

Purpose: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. Materials and Methods: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. Results: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07–1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61–8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). Conclusion Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.

Background: Swallowing of foreign bodies (FBs) is the most common indication of therapeutic endoscopy in children. Endoscopic removal may be necessary depending on the type of FB, age of the child, and location of the FB. We attempted to analyze the characteristics of each device used for the endoscopic removal of FBs in children. Methods: Medical records of the patient’s age, sex, weight, type, location, size, shape, type of device used for endoscopic removal, and endoscopic time were retrospectively collected. Results: A total of 424 FB removal procedures were analyzed. The average age of the patients at the time of FB removal was 4.1 ± 3.7 years. Coins were the most common FBs (192, 45.3%). The most common locations of the FBs were the esophagus (45.7%) and the stomach (48.3%), respectively. For a total of 371 cases, forceps were used in 96 cases (25.9%) for esophageal FBs and in 25 cases for gastric FBs (6.7%), while nets were used in 250 cases (67.4%) for gastric FBs retrieval; the average durations of the procedures were 7.2 ± 7.4 minutes, 8.5 ± 7.2 minutes, and 5.7 ± 7.3 minutes, respectively (P = 0.003). The procedure time was significantly shorter, in the group of patients with low body weights, when nets were used than when forceps were used to remove gastric FBs (P = 0.001). Conclusion The endoscopic procedure duration, in low-weight children, was shorter when retrieval nets were used than that with forceps.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. Results: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. Conclusion Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Background: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. Results: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. Conclusions This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Purpose: Effectiveness and safety of clofarabine (one of the treatment mainstays in pediatric patients with relapsed/refractory acute lymphoblastic leukemia [ALL]) was assessed in Korean pediatric patients with ALL to facilitate conditional coverage with evidence development. Materials and Methods: In this multicenter, prospective, observational study, patients receiving clofarabine as mono/combination therapy were followed up every 4-6 weeks for 6 months or until hematopoietic stem cell transplantation (HSCT). Response rates, survival outcomes, and adverse events were assessed. Results: Sixty patients (2-26 years old; 65% B-cell ALL, received prior ≥ 2 regimen, 68.3% refractory to previous regimen) were enrolled and treated with at least one dose of clofarabine; of whom 26 (43.3%) completed 6 months of follow-up after the last dose of clofarabine. Fifty-eight patients (96.7%) received clofarabine combination therapy. Overall remission rate (complete remission [CR] or CR without platelet recovery [CRp]) was 45.0% (27/60; 95% confidence interval [CI], 32.4 to 57.6) and the overall response rate (CR, CRp, or partial remission [PR]) was 46.7% (28/60; 95% CI, 34.0 to 59.3), with 11 (18.3%), 16 (26.7%), and one (1.7%) patients achieving CR, CRp, and PR, respectively. The median time to remission was 5.1 weeks (95% CI, 4.7 to 6.1). Median duration of remission was 16.6 weeks (range, 2.0 to 167.6 weeks). Sixteen patients (26.7%) proceeded to HSCT. There were 24 deaths; 14 due to treatment-emergent adverse events. Conclusion Remission with clofarabine was observed in approximately half of the study patients who had overall expected safety profile; however, there was no favorable long-term survival outcome in this study.

Extensor muscle strengthening exercises with counterforce braces (EX) is a conventional conservative treatment for lateral epicondylitis (LE) of the elbow. In addition, polydeoxyribonucleotide (PDRN) or extracorporeal shockwave therapy (ESWT) has been recently used for LE. Methods: Sixty-three patients with chronic LE participated in this study and randomly allocated in three groups (G1: EX, G2: EX+PDRN injection, and G3: EX+ESWT). All of the three groups were taught to perform EX at the first out-patient department (OPD) visit. Group 2 was injected with 3 mL PDRN (5.625 mg/3 mL), while group 3 received ESWT at the first OPD visit. Visual analog scale pain score, Mayo elbow performance score (MEPS), and ultrasonographic examination were checked before, 6 weeks, and 12 weeks after the treatments. Results: Overall functional scores and ultrasonographic findings in all three groups improved after treatment. The mean MEPS in group 2 improved more than groups 1 and 3 at 6 weeks (G1, 56.9>62.4; G2, 54.3>65.0; G3, 55.7>62.6), and more than group 1 at 12 weeks (G1, 56.9>67.9; G2, 54.3>73.6). The mean common extensor tendon depth (CETD) on ultrasonography in group 2 increased more than groups 1 and 3 at 6 and 12 weeks (6 weeks: G1, 0.385>0.386; G2, 0.332>0.392; G3, 0.334>0.357; 12 weeks: G1, 0.385>0.409; G2, 0.332>0.438; G3, 0.334>0.405 [cm]). Conclusions: PDRN injections combined with EX exhibited a greater improvement in mean MEPS and mean CETD compared to EX only or EX combined with ESWT for LE within the 12 weeks follow-up.