Rottlerin-Liposome Inhibits the Endocytosis of Feline Coronavirus Infection.

Rottlerin (R) is a natural extract from Mallotus philippensis with antiviral properties. Feline infectious peritonitis (FIP) is a fatal disease caused by feline coronavirus (FCoV) that is characterized by systemic granulomatous inflammation and high mortality. We investigated the antiviral effect of liposome-loaded R, i.e., rottlerin-liposome (RL), against FCoV. We demonstrated that RL inhibited FCoV replication in a dose-dependent manner, not only in the early endocytosis stage but also in the late stage of replication. RL resolved the low solubility issue of rottlerin and improved its inhibition efficacy at the cellular level. Based on these findings, we suggest that RL is worth further investigation as a potential treatment for FCoV.

Zwitterionic Inhaler with Synergistic Therapeutics for Reprogramming of M2 Macrophage to Pro-Inflammatory Phenotype.

Myriad lung diseases are life threatening and macrophages play a key role in both physiological and pathological processes. Macrophages have each pro-/anti-inflammatory phenotype, and each lung disease can be aggravated by over-polarized macrophage. Therefore, development of a method capable of mediating the macrophage phenotype is one of the solutions for lung disease treatment. For mediating the phenotype of macrophages, the pulmonary delivery system (PDS) is widely used due to its advantages, such as high efficiency and accessibility of the lungs. However, it has a low drug delivery efficiency ironically because of the perfect lung defense system consisting of the mucus layer and airway macrophages. In this study, zwitterion-functionalized poly(lactide-co-glycolide) (PLGA) inhalable microparticles (ZwPG) are synthesized to increase the efficiency of the PDS. The thin layer of zwitterions formed on PLGA surface has high nebulizing stability and show high anti-mucus adhesion and evasion of macrophages. As a reprogramming agent for macrophages, ZwPG containing dexamethasone (Dex) and pirfenidone (Pir) are treated to over-polarized M2 macrophages. As a result, a synergistic effect of Dex/Pir induces reprogramming of M2 macrophage to pro-inflammatory phenotypes.

Association between Prehospital Visits and Poor Health Outcomes in Korean Acute Stroke Patients: A National Health Insurance Claims Data Study.

This study aimed to determine whether prehospital visits to other medical institutions before admission are associated with prolonged hospital stay, readmission, or mortality rates in acute stroke patients. Using the claims data from the Korean Health Insurance Service, a cross-sectional study was conducted on 58,418 newly diagnosed stroke patients aged ≥ 20 years from 1 January 2019 to 31 December 2019. Extended hospital stay (≥7 days; median value) following initial admission, readmission within 180 days after discharge, and all-cause mortality within 30 days were measured as health outcomes using multiple logistic regression analysis after adjusting for age, sex, income, residential area, and medical history. Stroke patients with a prehospital visit (10,992 patients, 18.8%) had a higher risk of long hospitalization (odds ratio = 1.06; 95% confidence interval = 1.02-1.10), readmission (1.19; 1.14-1.25), and mortality (1.23; 1.13-1.33) compared with patients without a prehospital visit. Female patients and those under 65 years of age had increased unfavorable outcomes (p < 0.05). Prehospital visits were associated with unfavorable health outcomes.

Oncogenic signaling pathways and hallmarks of cancer in Korean patients with acral melanoma.

Acral melanoma (AM), a rare subtype of cutaneous melanoma, shows higher incidence in Asians, including Koreans, than in Caucasians. However, the genetic modification associated with AM in Koreans is not well known and has not been comprehensively investigated in terms of oncogenic signaling, and hallmarks of cancer. We performed whole-exome and RNA sequencing for Korean patients with AM and acquired the genetic alterations and gene expression profiles. KIT alterations (previously known to be recurrent alterations in AM) and CDK4/CCND1 copy number amplifications were identified in the patients. Genetic and transcriptomic alterations in patients with AM were functionally converge to the hallmarks of cancer and oncogenic pathways, including 'proliferative signal persistence', 'apoptotic resistance', and 'activation of invasion and metastasis', despite the heterogeneous somatic mutation profiles of Korean patients with AM. This study may provide a molecular understanding for therapeutic strategy for AM.

Molecular characterization of dysplasia-initiated colorectal cancer with assessing matched tumor and dysplasia samples.

PURPOSE: Ulcerative colitis (UC) is known to have an association with the increased risk of colorectal cancer (CRC), and UC-associated CRC does not follow the typical progress pattern of adenoma-carcinoma. The aim of this study is to investigate molecular characteristics of UC-associated CRC and further our understanding of the association between UC and CRC. METHODS: From 5 patients with UC-associated CRC, matched normal, dysplasia, and tumor specimens were obtained from formalin-fixed paraffin-embedded (FFPE) samples for analysis. Genomic DNA was extracted and whole exome sequencing was conducted to identify somatic variations in dysplasia and tumor samples. Statistical analysis was performed to identify somatic variations with significantly higher frequencies in dysplasia-initiated tumors, and their relevant functions were investigated. RESULTS: Total of 104 tumor mutation genes were identified with higher mutation frequencies in dysplasia-initiated tumors. Four of the 5 dysplasia-initiated tumors (80.0%) have TP53 mutations with frequent stop-gain mutations that were originated from matched dysplasia. APC and KRAS are known to be frequently mutated in general CRC, while none of the 5 patients have APC or KRAS mutation in their dysplasia and tumor samples. Glycoproteins including mucins were also frequently mutated in dysplasia-initiated tumors. CONCLUSION: UC-associated CRC tumors have distinct mutational characteristics compared to typical adenoma-carcinoma tumors and may have different cancer-driving molecular mechanisms that are initiated from earlier dysplasia status.

Determining the etiology of small bowel obstruction in patients without intraabdominal operative history: a retrospective study.

PURPOSE: Most of the causes of small bowel obstruction (SBO) in patients without a history of abdominal surgery are unclear at initial assessment. This study was conducted to identify the etiology and clinical characteristics of SBO in virgin abdomens and discuss the proper management. METHODS: A retrospective review involving operative cases of SBO from a single institute, which had no history of abdominal surgery, was conducted between January 2010 and December 2020. Clinical information, including radiological, operative, and pathologic findings, was investigated to determine the etiology of SBO. RESULTS: A total of 55 patients were included in this study, with a median age of 57 years and male sex (63.6%) constituting the majority. The most frequently reported symptoms were abdominal pain and nausea or vomiting. Neoplasm as an underlying cause accounted for 34.5% of the cases, of which 25.5% were malignant cases. In patients aged ≥60 years (n=23), small bowel neoplasms were the underlying cause in 12 (52.2%), of whom 9 (39.1%) were malignant cases. Adhesions and Crohn disease were more frequent in patients aged <60 years. Coherence between preoperative computed tomography scans and intraoperative findings was found in 63.6% of the cases. CONCLUSION: There were various causes of surgical cases of SBO in virgin abdomens. In older patients, hidden malignancy should be considered as a possible cause of SBO in a virgin abdomen. Patients with symptoms of recurrent bowel obstruction who have no history of prior abdominal surgery require thorough medical history and close follow-up.

Unraveling the Structured Solvation Shell of Zwitterion Nanoparticles for Controlled Release of Nitric Oxide.

Zwitterions have been attracting emerging attention as an anti-fouling polymer. However, the relationship between structured solvation shells and controlled drug release induced by deceleration of water molecule's translational and vibrational motions of zwitterions is an uncharted territory. Herein, sulfobetaine zwitterion nanoparticles (ZWNPs) were designed as a stable nitric oxide (NO)-delivering carrier. The condensed water structure of the solvation shell at its isoelectric point (PI) and the loose structure of water under different pH conditions were investigated through rheological and thermodynamical analyses. The ZWNPs showed a sustained-release profile at the PI, which presented a structured solvation barrier. On the other hand, NO-loaded ZWNPs showed different release profiles with the burst release at pH 5.5. Notably, an increased cell proliferation rate and a decreased antibacterial effect were observed at the same concentration depending on solvation shell's characteristics.

Fast Healthcare Interoperability Resources (FHIR)-Based Quality Information Exchange for Clinical Next-Generation Sequencing Genomic Testing: Implementation Study.

BACKGROUND: Next-generation sequencing (NGS) technology has been rapidly adopted in clinical practice, with the scope extended to early diagnosis, disease classification, and treatment planning. As the number of requests for NGS genomic testing increases, substantial efforts have been made to deliver the testing results clearly and unambiguously. For the legitimacy of clinical NGS genomic testing, quality information from the process of producing genomic data should be included within the results. However, most reports provide insufficient quality information to confirm the reliability of genomic testing owing to the complexity of the NGS process. OBJECTIVE: The goal of this study was to develop a Fast Healthcare Interoperability Resources (FHIR)-based web app, NGS Quality Reporting (NGS-QR), to report and manage the quality of the information obtained from clinical NGS genomic tests. METHODS: We defined data elements for the exchange of quality information from clinical NGS genomic tests, and profiled a FHIR genomic resource to enable information exchange in a standardized format. We then developed the FHIR-based web app and FHIR server to exchange quality information, along with statistical analysis tools implemented with the R Shiny server. RESULTS: Approximately 1000 experimental data entries collected from the targeted sequencing pipeline CancerSCAN designed by Samsung Medical Center were used to validate implementation of the NGS-QR app using real-world data. The user can share the quality information of NGS genomic testing and verify the quality status of individual samples in the overall distribution. CONCLUSIONS: This study successfully demonstrated how quality information of clinical NGS genomic testing can be exchanged in a standardized format. As the demand for NGS genomic testing in clinical settings increases and genomic data accumulate, quality information can be used as reference material to improve the quality of testing. This app could also motivate laboratories to perform diagnostic tests to provide high-quality genomic data.

Mutational Characterization of Colorectal Cancer from Korean Patients with Targeted Sequencing.

Purpose: Effective treatment of colorectal cancer could benefit from understanding molecular characteristics including mutation profiles of important genes. This study aimed to explore the molecular characteristics of colorectal cancer based on next generation sequencing. Methods: The mutational characteristics by targeted next generation sequencing in 172 colorectal tumor samples from Korean patients were evaluated to explore their associations with clinical features. Targeted sequencing of 375 genes was performed with an average target-depth of 800X. Results: TP53 and APC showed higher mutation frequencies from the left-sided tumors, while CTNNB1 were more frequent from the right-sided tumors. The tumor suppressor NOTCH1 and the DNA strand break repair gene PALB2 were more frequently mutated in early onset tumors. KRAS and PTEN mutations were more frequent from patients with advanced cancers by cancer antigen markers. TP53 and BRAF mutations were more frequent from patients of T3 and T4 stages, where their variant allele fractions were generally higher in T4 tumors, implying that advanced tumors have higher fraction of cancer cells with TP53 and BRAF mutations. Mutational profiles of these patients were also assessed with other clinical features. Comparison of mutational characteristics with the Caucasian subjects from independent data showed that the identified mutational characteristics are largely Korean-specific except for a few key colorectal cancer genes. Conclusion: Next generation sequencing-based targeted sequencing can provide valuable information on molecular characterization of colorectal cancer patients, and its clinically relevant information can provide benefits to better understand colorectal cancer.

Identifying metastasis-initiating miRNA-target regulations of colorectal cancer from expressional changes in primary tumors.

Colorectal cancer (CRC) is prevalent with high mortality, with liver metastasis contributing as a major factor that worsens the survival of patients. The roles of miRNAs in CRC have been elucidated, subsequent to recent studies that suggest the involvement of miRNAs in cancer biology. In this study, we compare the miRNA and gene expression profiles of primary tumors between two groups of patients (with and without liver metastasis) to identify the metastasis-initiating microRNA-target gene regulations. Analysis from 33 patients with metastasis and 14 patients without metastasis revealed that 17 miRNAs and their 198 predicted target genes are differentially expressed, where the target genes showed association with cancer progression and metastasis with statistical significance. In order to evaluate the clinical implications of the findings, we classified CRC patients of independent data into two groups based on the identified miRNA-target regulations, where one group was closer to primary tumors with metastasis than the other group. The comparison of survival showed statistically significant difference, thereby implying the roles of the identified miRNA-target regulations in cancer progression and metastasis. The identification of metastasis-initiating miRNA-target regulations in this study will lead to better understanding of the roles of miRNAs in CRC progression.

Comparison of Epidural Pressure Decrease Pattern According to Different Lumbar Epidural Approaches.

BACKGROUND: During lumbar epidural injection (LEI) using a midline approach, we might encounter failure of identifying the epidural space owing to an equivocal or absent loss of resistance (LOR) sensation. The reason for such absence of LOR sensation has been suggested as paucity of midline ligamentum flavum, paravertebral muscle, and cyst in the interspinous ligament of the lumbar spine. Despite its low specificity, LOR is the most commonly used method to identify the epidural space. OBJECTIVES: The purpose of this study was to analyze lumbar epidural pressure decrease patterns and identify factors contributing to this pressure decrease. STUDY DESIGN: Prospective randomized trial. SETTING: An interventional pain management practice in South Korea. METHODS: This prospective study included 104 patients receiving LEI due to lumbar radiculopathy. A midline or paramedian approach of LEI was determined with randomization. Among various factors, gender, age, body mass index (BMI), and diagnosis were analyzed using a subgroup that included 60 cases of only a paramedian approach. RESULTS: Grades I, II (abrupt decrease), and III (gradual decrease) were found as patterns of epidural pressure decrease. Abrupt pressure decrease was more frequently observed in the paramedian group (P < 0.001). Age, gender, BMI, and diagnosis did not show any significant difference in frequencies between abrupt and gradual pressure decrease. LIMITATIONS: We could not match LOR sensation with epidural pressure decrease shown in the monitor. CONCLUSIONS: This study demonstrates that abrupt pressure decrease occurs more frequently with the paramedian approach. However, age, gender, BMI, or diagnosis did not affect the incidence of epidural pressure decrease. KEY WORDS: Epidural, paramedian, midline, pressure decrease.

The Management of Retained Rectal Foreign Body.

PURPOSE: Because insertion of a foreign body (FB) into the anus is considered a taboo practice, patients with a retained rectal FB may hesitate to obtain medical care, and attending surgeons may lack experience with removing these FBs. We performed this study to evaluate the clinical characteristics of Korean patients with a retained rectal FB and propose management guideline for such cases based on our experience. METHODS: We retrospectively investigated 14 patients between January 2006 and December 2018. We assessed demographic features, mechanism of FB insertion, clinical course between diagnosis and management, and outcomes. RESULTS: All patients were male (mean age, 43 years) and presented with low abdominal pain (n = 2), anal bleeding (n = 2), or concern about a retained rectal FB without symptoms (n = 10). FB insertion was most commonly associated with sexual gratification or anal eroticism (n = 11, 78.6%). All patients underwent general anesthesia for anal sphincter relaxation with the exception of 2 who underwent FB removal in the emergency department. FBs were retrieved transanally using a clamp (n = 2), myoma screw (n = 1), clamp application following abdominal wall compression (n = 2), or laparotomy followed by rectosigmoid colon milking (n = 2). Colotomy and primary repair were performed in four patients, and Hartmann operation was performed in one patient with fecal peritonitis. No morbidity or mortality was reported. All patients refused postextraction anorectal functional and anatomical evaluation and psychological counseling. CONCLUSION: Retained rectal FB is rare; however, colorectal surgeons should be aware of the various methods that can be used for FB retrieval and the therapeutic algorithm applicable in such cases.

Safety and efficacy of peripheral nutrition fluid (MG-TNA®) in patients undergoing surgery for hepatobiliary and pancreatic disease: Results of a phase 4 trial.

BACKGROUNDS/AIMS: Essential nutritional support and nutrition therapy for patients with hepatobiliary and pancreatic diseases undergoing surgery is critical, as it may improve clinical outcome. How to implement rational fluid therapy and nutritional support after surgery and effectively protect organ function is crucial for postoperative recovery. The aim this study was to examine the safety and efficacy of peripheral nutrition fluid (MG-TNA®) in patients undergoing surgery for hepatobiliary and pancreatic disease. METHODS: All adult patients undergoing surgery for hepatobiliary and pancreatic disease received peripheral nutrition fluid (MG-TNA®) on the second postoperative day for 3 days. During administration of parenteral nutrition, patients were closely monitored for adverse effects (primary endpoint). Secondary endpoints included nutritional parameters such as serum prealbumin, transferrin, and creatine kinase (CK) levels. RESULTS: Thirty patients completed the study and were included in the full analysis set. There was no evidence of metabolic complications such as hyperglycemia, azotemia, hypertriglyceridemia, metabolic acidosis and hypokalemia. In addition, there were no adverse effects. There was a significant decrease in serum prealbumin and CK on the third postoperative day (p<0.0001). Although not statistically significant, serum transferrin levels tended to decrease (p=0.0519). CONCLUSIONS: Administration of peripheral nutrition fluid (MG-TNA®) during postoperative period in patients undergoing surgery for hepatobiliary and pancreatic disease proved to be safe with improvement of the nutritional state of the patient.

KEDDY: a knowledge-based statistical gene set test method to detect differential functional protein-protein interactions.

MOTIVATION: Identifying differential patterns between conditions is a popular approach to understanding the discrepancy between different biological contexts. Although many statistical tests were proposed for identifying gene sets with differential patterns based on different definitions of differentiality, few methods were suggested to identify gene sets with differential functional protein networks due to computational complexity. RESULTS: We propose a method of Knowledge-based Evaluation of Dependency DifferentialitY (KEDDY), which is a statistical test for differential functional protein networks of a set of genes between two conditions with utilizing known functional protein-protein interaction information. Unlike other approaches focused on differential expressions of individual genes or differentiality of individual interactions, KEDDY compares two conditions by evaluating the probability distributions of functional protein networks based on known functional protein-protein interactions. The method has been evaluated and compared with previous methods through simulation studies, where KEDDY achieves significantly improved performance in accuracy and speed than the previous method that does not use prior knowledge and better performance in identifying gene sets with differential interactions than other methods evaluating changes in gene expressions. Applications to cancer data sets show that KEDDY identifies alternative cancer subtype-related differential gene sets compared to other differential expression-based methods, and the results also provide detailed gene regulatory information that drives the differentiality of the gene sets. AVAILABILITY AND IMPLEMENTATION: The Java implementation of KEDDY is freely available to non-commercial users at https://sites.google.com/site/sjunggsm/keddy. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Clinical significance of post-hepatectomy hepatic failure in patients with liver metastases from colorectal cancer.

BACKGROUNDS/AIMS: This study attempted to identify risk factors for development of post-hepatectomy hepatic failure (PHF) and its effect on long-term survival of patients with liver metastases from colorectal cancer. METHODS: We carried out a retrospective study of 143 patients who had been diagnosed with liver metastases from colorectal cancer and who had undergone hepatectomy between 2003 and 2010. We allocated these patients to PHF and non-PHF groups, using the definition of the International Study Group of Liver Surgery, and compared the clinical factors of the two groups, using Cox regression and Kaplan-Meier analysis to evaluate the differences in overall survival (OS) and recurrence-free survival (RFS) between these groups. RESULTS: The PHF group comprised 19 patients (13.3%); all had Grade A PHF. Independent risk factors for development of PHF were metachronous liver metastases and major hepatectomy. The differences between the PHF and non-PHF groups in OS or RFS were not statistically significant; however, the PHF group tended to have a worse prognosis. Multivariate analysis revealed significant associations between OS and the factors of poor differentiation of the primary colorectal cancer, major hepatectomy, and positive resection margin. CONCLUSIONS: Major hepatectomy is an important risk factor for PHF in patients with liver metastases from colorectal cancer. The pathological characteristics of the primary tumor are more important as predictors than is Grade A PHF.

Clinical Manifestations of Superior Mesenteric Venous Thrombosis in the Era of Computed Tomography.

PURPOSE: Thrombosis of the portal vein, known as pylephlebitis, is a rare and fatal complication caused by intraperitoneal infections. The disease progression of superior mesenteric venous thrombosis (SMVT) is not severe. This study aimed to determine the clinical features, etiology, and prognosis of SMVT. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 41 patients with SMVT from March 2000 to February 2017. We obtained a list of 305 patients through the International Classification of Disease-9 code system and selected 41 patients with SMVT with computed tomography. Data from the medical records included patient demographics, comorbidities, review of system, laboratory results, clinical courses, and treatment modalities. RESULTS: The causes of SMVT were found to be intraperitoneal inflammation in 27 patients (65.9%), malignancy in 7 patients (17.1%), and unknown in 7 patients (17.1%). Among the patients with intraperitoneal inflammation, 14 presented with appendicitis (51.9%), 7 with diverticulitis (25.9%), and 2 with ileus (7.4%). When comparing patients with and without small bowel resection, the differences in symptom duration, bowel enhancement and blood culture were significant (P=0.010, P=0.039, and P=0.028, respectively). CONCLUSION: SMVT, caused by intraperitoneal inflammation, unlike portal vein thrombosis including pylephlebitis, shows mild prognosis. In addition, rapid symptom progression and positive blood culture can be the prognostic factors related to extensive bowel resection. Use of appropriate antibiotics and understanding of disease progression can help improve the outcomes of patients with SMVT.

Fatal Graft-Versus-Host Disease Following Adult-To-Adult Living Donor Liver Transplantation From an HLA Nonhomozygous Donor.

The use of a human leukocyte antigen (HLA) homozygous donor to a haploidentical recipient is a well-documented cause of transfusion-associated graft-versus-host disease (GVHD). Several authors have reported that use of a graft from an HLA-homozygous donor with 1-way donor-recipient HLA matching led to an extremely high risk of developing GVHD in LDLT. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a donor who was heterozygous at a single HLA locus. A 53-year-old female underwent LDLT for chronic hepatitis B and recurrent hepatocellular carcinoma. The donor was her 23-year-old son. The HLA phenotype of the donor was not homozygous (A24, -; B54, -; DR4, 9) and revealed one-way donor-dominant HLA matching at two loci with the recipient (A2, 24; B48, 54; DR4, 12). On the fortieth postoperative day, the patient showed erythematous skin lesions. Skin biopsy revealed typical findings of GVHD. Donor-derived chimerism was demonstrated by performing fluorescent in situ hybridization (FISH) using the recipient's skin tissue. As the clinical course deteriorated, etanercept was started in addition to broad-spectrum antibiotics but there was no improvement. As multi-organ failure progressed, the patient succumbed to death on the 54th postoperative day, which was 2 weeks after onset of GVHD. The prevention of GVHD is more important since the results of treatment have been disappointing. We have experienced a fatal case of acute GVHD following adult-to-adult LDLT from a HLA non-homozygous donor. HLA heterozygosity at a single locus does not preclude the possibility of developing GVHD following adult-to-adult LDLT.

In-silico interaction-resolution pathway activity quantification and application to identifying cancer subtypes.

BACKGROUND: Identifying subtypes of complex diseases such as cancer is the very first step toward developing highly customized therapeutics on such diseases, as their origins significantly vary even with similar physiological characteristics. There have been many studies to recognize subtypes of various cancer based on genomic signatures, and most of them rely on approaches based on the signatures or features developed from individual genes. However, the idea of network-driven activities of biological functions has gained a lot of interests, as more evidence is found that biological systems can show highly diverse activity patterns because genes can interact differentially across specific molecular contexts. METHODS: In this study, we proposed an in-silico method to quantify pathway activities with a resolution of genetic interactions for individual samples, and developed a method to compute the discrepancy between samples based on the quantified pathway activities. RESULTS: By using the proposed discrepancy measure between sample pathway activities in clustering melanoma gene expression data, we identified two potential subtypes of melanoma with distinguished pathway activities, where the two groups of patients showed significantly different survival patterns. We also investigated selected pathways with distinguished activity patterns between the two groups, and the result suggests hypotheses on the mechanisms driving the two potential subtypes. CONCLUSIONS: By using the proposed approach of modeling pathway activities with a resolution of genetic interactions, potential novel subtypes of disease were proposed with accompanying hypotheses on subtype-specific genetic interaction information.

Influence of anti-adhesive agent on incidence of bile leakage after liver resection: A prospective cohort study.

BACKGROUND: Anti-adhesive agents are increasingly used to reduce the incidence of postoperative adhesions following abdominal surgery. Bile leakage after liver resection remains a major cause of postoperative morbidity. The aim of this study was to examine the effect of anti-adhesive agent on bile leakage after liver resection. MATERIALS AND METHODS: 77 patients were enrolled to receive an anti-adhesive agent (study group) during liver resection between May 2012 and August 2013. The study group was compared to a match-paired control group. Clinical data were collected including bilirubin concentration in serum and drain fluid and bile leakage rate. In addition, a separate analysis was performed between patients with and without postoperative bile leakage. RESULTS: There was no difference in bile leakage rate or hospital stay between the study group (n = 77) and control group (n = 77). Of the total number of patients (n = 154), there were 29 patients with postoperative bile leak and 125 patients without bile leak. On univariate analysis, patients without history of hepatitis were significantly associated with bile leakage. In addition, liver resection with broader cut surface area was associated with bile leakage. Application of anti-adhesive agent was not associated with bile leakage. On multivariate analysis, resection with broader cut surface area (OR = 2.788, p = 0.026) and patients without history of hepatitis (OR = 5.153, p = 0.039) were significantly associated with bile leakage. CONCLUSIONS: Larger area of cut-surface and patients without history of hepatitis were significant risk factors for bile leakage. The use of anti-adhesive agent was not associated with increased risk of bile leakage.