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: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Background/Aims: The safety of direct oral anticoagulants (DOACs) compared with warfarin in patients with both nonvalvular atrial fibrillation (AF) and clinically confirmed liver cirrhosis (LC) has not been well studied. We compared the risk of a major bleeding event between DOAC and warfarin treatments in this patient population. Methods: A total of 238 cirrhotic patients with AF were retrospectively analyzed. The major bleeding event risk was compared between DOAC- and warfarin-treated groups. The median follow-up duration was 5.6 years. Results: Among the 238 study patients with LC and AF, 128 (53.8%) received DOACs and 110 (46.2%) received warfarin. The mean patient age was 68.8 years, and 78.2% were men. A major bleeding event occurred in 10 and 20 patients in the DOAC and warfarin groups, respectively, most commonly caused by gastrointestinal bleeding (70.0%). The cumulative risk of major bleeding did not differ between the groups by log-rank test (p = 0.12). This finding did not change when using 60 propensity score-matched pairs. A multivariable Cox regression model indicated that the concomitant use of antiplatelet agents (adjusted hazard ratio [aHR], 2.06; 95% confidence interval [CI], 1.00 to 4.30; p = 0.048) and presence of esophageal or gastric varices confirmed by endoscopic examination (aHR, 2.31; 95% CI, 1.03 to 5.17; p = 0.04) were associated with major bleeding in the entire cohort. Conclusions A major bleeding event risk is not increased by DOAC compared with warfarin treatment. Antiplatelet agent use and varices are independently associated with a higher risk of major bleeding during anticoagulation.

Background/Aims: The care cascade for hepatitis C virus (HCV) infection is impeded by multiple barriers, including suboptimal anti-HCV testing, link to care, and diagnosis. We explored the changes in the care cascade of HCV for the past 20 years and its current status in a large cohort from a tertiary referral center. Methods: We analyzed 1,144,468 patients who had anti-HCV testing between January 2001 and June 2020. Metrics related to the care cascade of HCV infection and the long-term prognosis of patients were explored. Results: The seroprevalence of anti-HCV positivity was 1.8%, with a recent decreasing trend.In all, 69.9% of anti-HCV positive patients performed HCV RNA testing, with a 65.7% positivity. Patients who did not have HCV RNA testing were older and more likely to have a non-hepatocellular carcinoma malignancy, normal alanine aminotransferase level, and good liver function. Linkage times for HCV RNA testing from the anti-HCV positivity and for antiviral treatment from HCV diagnosis decreased, notably after 2015, when highly efficacious oral antiviral treatment was introduced to Korea. The average treatment uptake rate was 35.4%, which increased to 38.9% after 2015. Of the 5,302 patients analyzed for long-term prognosis, the annual incidences of hepatocellular carcinoma were 1.02 or 2.14 per 100 person-years in patients with or without a sustained virological response, respectively. Conclusions The care cascade of HCV infection has been suboptimal for the past 20 years, despite the recent changes. More effort should be made to increase HCV RNA testing and treatment uptake.

Background/Aims: The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival. Methods: Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017. Results: The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients. Conclusions The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

PURPOSE: A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status. MATERIALS AND METHODS: The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases. RESULTS: A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis. CONCLUSION: This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.
Adult ; Cohort Studies ; Diagnosis ; Drug Therapy ; Epidemiology ; Humans ; Incidence ; Korea ; National Health Programs ; Sarcoma ; Survival Rate

BACKGROUND/AIMS: α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk. METHODS: A total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months. RESULTS: The proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P < 0.001 and P = 0.015). However, no significant association was found between the αSYN pathology in the stomach and colon mucosa and constipation, as well as other GI symptoms including dyspepsia symptoms and abdominal discomfort or pain, regardless of the presence or absence of clinical PD (P > 0.05). No incident PD cases were diagnosed during study period. CONCLUSIONS: Our present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.
Biopsy ; Brain ; Colon ; Constipation ; Dyspepsia ; Enteric Nervous System ; Follow-Up Studies ; Gastrointestinal Tract ; Humans ; Mucous Membrane ; Parkinson Disease ; Pathology ; Stomach

BACKGROUND/AIMS: Portal vein invasion (PVI) is a poor prognostic factor in patients with hepatocellular carcinoma (HCC). We intended to compare the effects of surgical resection and transarterial chemoembolization (TACE) with additional radiation therapy (RT) in HCC patients with PVI. METHODS: The subjects comprised 43 patients who underwent surgical resection for HCC with PVI without previous treatment and another 43 patients who received TACE followed by RT (TACE+RT) as initial treatment who were matched for Child-Pugh class, tumor size, and extent of PVI. Disease progression and death after the treatment were examined, and progression-free survival (PFS) and overall survival (OS) were compared between groups. Predisposing factors affecting OS were analyzed using univariate and multivariate analyses in HCC patients with PVI. RESULTS: The subjects (Age [51, 24-74; median, range], Sex [81/13; male/female], Etiology [78/1/15; hepatitis B virus {HBV}/ hepatitis C virus {HCV}/non-HBV and non-HCV]) were followed for a median of 17 (2-68) months. There were no differences in clinical or tumor characteristics between the resection and TACE+RT groups. The cumulative PFS was not significantly different between groups. The median PFS was 5.6 and 4.0 months in the resection and TACE+RT groups, respectively. However, the cumulative OS was significantly longer in patients treated with resection than in those treated with TACE+RT (P=0.04). The median OS was 26.9 and 14.2 months in the resection and TACE+RT groups, respectively. Univariate and multivariate analyses revealed that surgical resection was an independent predictive factor for better survival outcome. CONCLUSIONS: Surgical resection might be an effective treatment in HCC patients with PVI.
Carcinoma, Hepatocellular* ; Causality ; Disease Progression ; Disease-Free Survival ; Hepacivirus ; Hepatectomy ; Hepatitis B virus ; Humans ; Multivariate Analysis ; Portal Vein*

BACKGROUND/AIMS: Because there is a lack of effective biomarkers, we aimed to discover proteomic candidate markers for hepatocellular carcinoma (HCC) in cirrhotic patients at the highest-risk of HCC, and to validate the markers. METHODS: We collected tumor tissue from 5 cirrhotics with HCC, and from 5 cirrhotics without HCC, who underwent liver resection or transplantation. These tissue samples were analyzed by 2-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and potential markers were validated at the transcriptional and translational levels. We also performed western blot assays using other blood samples from 10 cirrhotics with HCC and 10 without HCC. RESULTS: Among the 66 distinguishable spots on 2-D gel images, we identified 15 proteins overexpressed more than 1.5 fold in terms of volume ratio in the tumors. Ten of the over-expressed proteins were identified by MALDI-TOF MS; of those, only methionine adenosyltransferase 1 (MAT1), a protein specific for liver, and acyl-CoA dehydrogenase were significantly up-regulated in tumors in further immunoblotting analyses (Ps<0.05). There was no between-pair difference in MAT1 mRNA measured by real-time polymerase chain reaction (P=0.96). However, in western blots of serum samples, distinct MAT1 bands were observed in all 10 HCC patients, but in only 2 of the non-HCC patients. CONCLUSIONS: MAT1 is a potential marker for surveillance in cirrhotic patients with and without prior HCC.
Acyl-CoA Dehydrogenase ; Biomarkers ; Blotting, Western ; Carcinoma, Hepatocellular ; Humans ; Immunoblotting ; Liver ; Liver Cirrhosis ; Mass Spectrometry ; Methionine Adenosyltransferase ; Methionine ; Proteomics ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Two-Dimensional Difference Gel Electrophoresis

PURPOSE: Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not. MATERIALS AND METHODS: This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (−) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses. RESULTS: During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (−) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (−) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172–8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (−) group seemed to also have a higher risk of recurrent stroke. CONCLUSION: Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up.
Asymptomatic Diseases ; Coronary Artery Disease/*diagnostic imaging/mortality ; Female ; Follow-Up Studies ; Humans ; Male ; Multidetector Computed Tomography/*utilization ; Propensity Score ; Proportional Hazards Models ; Prospective Studies ; Recurrence ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Stroke/*complications/mortality