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Background: Fine-needle aspiration cytology (FNAC) is very accurate in detecting papillary thyroid carcinomas (PTCs). According to the Bethesda system for reporting thyroid cytopathology, the risk for malignancy is 97-99% when FNAC is used to diagnose PTC; the malignancy risk is 60-75% when FNAC results in suspected PTCs. The presence of hyalinizing trabecular tumor (HTT) of the thyroid can cause misdiagnosis because its cytological features mimic PTCs. However, the use of frozen section analysis can assist in the recognition of unique architecture features of HTT, and thus may help prevent the undertaking of an unnecessarily aggressive operation. Methods: We retrospectively reviewed all patients diagnosed with HTT by permanent histopathology from February 2009 to October 2013. After acquired agreement of the patients, we analyzed all data and reviewed another nine cases of HTT reported in the English-language medical literature to examine the efficacy of frozen section. Results: There were six patients included in our research (5 women and 1 man), with an average age of 48.8 years. Using frozen section, four patients were diagnosed with HTT and two patients were misinterpreted as PTC. Consequently, four patients had lobectomy and two patients had total thyroidectomy, with no surgical complications. Of the nine cases of HTT reviewed from the English literature, the use of frozen section showed three HTT cases, three PTC cases, two medullary thyroid carcinoma cases, and one deferral case. Overall, the use of frozen section as a diagnostic method prevented additional surgical resection in eight patients (53%). Conclusion: Frozen section can sometimes but not always be used to diagnose HTT. When HTT is diagnosed by its trabecular pattern through the use of frozen section, it may prevent total thyroidectomy.

Insulin resistance (IR) is the core for type 2 diabetes and metabolic syndrome. The homeostasis assessment model is a straightforward and practical tool for quantifying insulin resistance (HOMA-IR). Multiple adaptive regression spline (MARS) is a machine learning method used in many research fields but has yet to be applied to estimating HOMA-IR. This study uses MARS to build an equation to estimate HOMA-IR in pre-menopausal Chinese women based on a sample of 4,071 healthy women aged 20-50 with no major diseases and no medication use for blood pressure, blood glucose or blood lipids. Thirty variables were applied to build the HOMA-IR model, including demographic, laboratory, and lifestyle factors. MARS results in smaller prediction errors than traditional multiple linear regression (MLR) methods, and is thus more accurate. The model was established based on key impact factors including waist-hip ratio (WHR), C reactive protein (CRP), uric acid (UA), total bilirubin (TBIL), leukocyte (WBC), serum glutamic oxaloacetic transaminase (GOT), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), serum glutamic pyruvic transaminase (GPT), and triglycerides (TG). The equation is as following:HOMA-IR = 6.634 - 1.448MAX(0, 0.833 - WHR) + 10.152MAX(0, WHR - 0.833) - 1.351MAX(0, 0.7 - CRP) - 0.449MAX(0, CRP - 0.7) + 1.062MAX(0, UA - 8.5) + +1.047(MAX(0, 0.83 - TBIL) + 0.681MAX(0, WBC - 11.53) - 0.071MAX(0, 11.53 - WBC) + 0.043MAX(0, 24 - GOT) - 0.017MAX(0, GOT - 24) + 0.021MAX(0, 59 - HDL) - 0.005MAX(0, HDL - 59) - 0.013MAX(0, 141 - SBP) - 0.033MAX(0, 100 - GPT) + 0.013MAX(0, GPT - 100) - 0.004MAX(303 - TG)Results indicate that MARS is a more precise tool than fasting plasma insulin (FPI) levels, and could be used in the daily practice, and further longitudinal studies are warranted.

Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium-glucose co-transporter-2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real-time quantitative RT-PCR (qRT-PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib-treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28-day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib-induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT-dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib-treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib-promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib-stimulated proinflammatory signaling (TNF-α/IL-1β/IL-6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib-promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding., (© 2024 Wiley Periodicals LLC.)

Recent advancements have elucidated the multifaceted roles of the Schlafen (SLFN) family, including SLFN5, SLFN11, SLFN12, SLFN13, and SLFN14, which are implicated in immunological responses. However, little is known about the roles of this gene family in relation to malignancy development. The current study aimed to explore the diagnostic and prognostic potential of Schlafen family genes in colorectal adenocarcinoma (COAD) through bioinformatics analysis. Leveraging advanced bioinformatics tools of bulk RNA-sequencing and single-cell sequencing, we conducted in-depth analyses of gene expressions, functional enrichment, and survival patterns of patients with colorectal cancer compared to normal tissue. Among Schlafen family genes, the transcription levels of SLFN5 in COAD tissues were significantly elevated and correlated with poor survival outcomes. Furthermore, SLFN5 regulated the immune response via Janus kinase (JAK)/signal transduction and activator of transcription (STAT)/interferon (IFN)-alpha/beta signaling. These chemokines in inflammation are associated with diabetes and metabolism, suggesting their involvement in altered cellular energetics for COAD progress. In addition, an immune cell deconvolution analysis indicated a correlation between SLFN5 expression and immune-related cell populations, such as regulatory T cells (Tregs). These findings highlighted the potential clinical significance of SLFN5 in COAD and provided insights into its involvement in the tumor microenvironment and immune regulation. Meanwhile, the drug discovery data of SFLN5 with potential targeted small molecules suggested its therapeutic potential for COAD. Collectively, the current research demonstrated that SFLN5 play crucial roles in tumor development and serve as a prospective biomarker for COAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The burden of asymptomatic left ventricular dysfunction (LVD) is greater than that of heart failure; however, a cost-effective tool for asymptomatic LVD screening has not been well validated. We aimed to prospectively validate an artificial intelligence (AI)-enabled electrocardiography (ECG) algorithm for asymptomatic LVD detection and evaluate its cost-effectiveness for opportunistic screening., Methods: In this prospective observational study, patients undergoing ECG at outpatient clinics or health check-ups were enrolled in 2 hospitals in Taiwan. Patients were stratified into LVD (left ventricular ejection fraction ≤ 40%) risk groups according to a previously developed ECG algorithm. The performance of AI-ECG was used to conduct a cost-effectiveness analysis of LVD screening compared with no screening. Incremental cost-effectiveness ratio (ICER) and sensitivity analyses were used to examine the cost-effectiveness and robustness of the results., Results: Among the 29,137 patients, the algorithm demonstrated areas under the receiver operating characteristic curves of 0.984 and 0.945 for detecting LVD within 28 days in the 2 hospital cohorts. For patients not initially scheduled for ECG, the algorithm predicted future echocardiograms (high-risk, 46.2%; medium-risk, 31.4%; low-risk, 14.6%) and LVD (high-risk, 26.2%; medium-risk, 3.4%; low-risk, 0.1%) at 12 months. Opportunistic screening with AI-ECG could result in a negative ICER of -$7,439 for patients aged 65 years, with consistent cost-savings across age groups and particularly in men. Approximately 91.5% of the cases were found to be cost-effective at the willingness-to-pay threshold of $30,000 in the probabilistic analysis., Conclusions: The use of AI-ECG for asymptomatic LVD risk stratification is promising, and opportunistic screening in outpatient clinics has the potential to reduce costs., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The identification of risk factors for future prediabetes in young men remains largely unexamined. This study enrolled 6247 young ethnic Chinese men with normal fasting plasma glucose at the baseline (FPG base ), and used machine learning (Mach-L) methods to predict prediabetes after 5.8 years. The study seeks to achieve the following: 1. Evaluate whether Mach-L outperformed traditional multiple linear regression (MLR). 2. Identify the most important risk factors. The baseline data included demographic, biochemistry, and lifestyle information. Two models were built, where Model 1 included all variables and Model 2 excluded FPG base, since it had the most profound effect on prediction. Random forest, stochastic gradient boosting, eXtreme gradient boosting, and elastic net were used, and the model performance was compared using different error metrics. All the Mach-L errors were smaller than those for MLR, thus Mach-L provided the most accurate results. In descending order of importance, the key factors for Model 1 were FPG base , body fat (BF), creatinine (Cr), thyroid stimulating hormone (TSH), WBC, and age, while those for Model 2 were BF, white blood cell, age, TSH, TG, and LDL-C. We concluded that FPG base was the most important factor to predict future prediabetes. However, after removing FPG base , WBC, TSH, BF, HDL-C, and age were the key factors after 5.8 years.

Purpose: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC)., Method: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups., Results: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922)., Conclusions: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Splenectomy has previously been found to increase the risk of cancer development, including lung, non-melanoma skin cancer, leukemia, lymphoma, Hodgkin's lymphoma, and ovarian cancer. The risk of cancer development in liver transplantation (LT) with simultaneous splenectomy remains unclear., Aim: To compare hepatocellular carcinoma (HCC) recurrence and de novo malignancy between patients undergoing LT with and without simultaneous splenectomy., Methods: We retrospectively analyzed the outcomes of 120 patients with HCC within the University of California San Francisco criteria who received LT with ( n = 35) and without ( n = 85) simultaneous splenectomy in the Tri-Service General Hospital. Univariate and multivariate Cox regression analyses for cancer-free survival and mortality were established. The comparison of the group survival status and group cancer-free status was done by generating Kaplan-Meier survival curves and log-rank tests., Results: The splenectomy group had more hepatitis C virus infection, lower platelet count, higher -fetoprotein level, and longer operating time. Splenectomy and age were both positive independent factors for prediction of cancer development [hazard ratio (HR): 2.560 and 1.057, respectively, P < 0.05]. Splenectomy and hypertension were positive independent factors for prediction of mortality. (HR: 2.791 and 2.813 respectively, P < 0.05). The splenectomy group had a significantly worse cancer-free survival (CFS) and overall survival (OS) curve compared to the non-splenectomy group (5-year CFS rates: 53.4% vs 76.5%, P = 0.003; 5-year OS rate: 68.1 vs 89.3, P = 0.002)., Conclusion: Our study suggests that simultaneous splenectomy should be avoided as much as possible in HCC patients who have undergone LT., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The COVID-19 outbreak has not only changed the lifestyles of people globally but has also resulted in other challenges, such as the requirement of self-isolation and distance learning. Moreover, people are unable to venture out to exercise, leading to reduced movement, and therefore, the demand for exercise at home has increased., Objective: We intended to investigate the relationships between a Nintendo Ring Fit Adventure (RFA) intervention and improvements in running time, cardiac force index (CFI), sleep quality (Chinese version of the Pittsburgh Sleep Quality Index score), and mood disorders (5-item Brief Symptom Rating Scale score)., Methods: This was a randomized prospective study and included 80 students who were required to complete a 1600-meter outdoor run before and after the intervention, the completion times of which were recorded in seconds. They were also required to fill out a lifestyle questionnaire. During the study, 40 participants (16 males and 24 females, with an average age of 23.75 years) were assigned to the RFA group and were required to exercise for 30 minutes 3 times per week (in the adventure mode) over 4 weeks. The exercise intensity was set according to the instructions given by the virtual coach during the first game. The remaining 40 participants (30 males and 10 females, with an average age of 22.65 years) were assigned to the control group and maintained their regular habits during the study period., Results: The study was completed by 80 participants aged 20 to 36 years (mean 23.20, SD 2.96 years). The results showed that the running time in the RFA group was significantly reduced. After 4 weeks of physical training, it took females in the RFA group 19.79 seconds (P=.03) and males 22.56 seconds (P=.03) less than the baseline to complete the 1600-meter run. In contrast, there were no significant differences in the performance of the control group in the run before and after the fourth week of intervention. In terms of mood disorders, the average score of the RFA group increased from 1.81 to 3.31 for males (difference=1.50, P=.04) and from 3.17 to 4.54 for females (difference=1.38, P=.06). In addition, no significant differences between the RFA and control groups were observed for the CFI peak acceleration (CFIPA)&#95;walk, CFIPA&#95;run, or sleep quality., Conclusions: RFA could either maintain or improve an individual's physical fitness, thereby providing a good solution for people involved in distance learning or those who have not exercised for an extended period., Trial Registration: ClinicalTrials.gov NCT05227040; https://clinicaltrials.gov/ct2/show/NCT05227040., (©Yi-Syuan Wu, Wei-Yun Wang, Ta-Chien Chan, Yu-Lung Chiu, Hung-Che Lin, Yu-Tien Chang, Hao-Yi Wu, Tzu-Chi Liu, Yu-Cheng Chuang, Jonan Wu, Wen-Yen Chang, Chien-An Sun, Meng-Chiung Lin, Vincent S Tseng, Je-Ming Hu, Yuan-Kuei Li, Po-Jen Hsiao, Chao-Wen Chen, Hao-Yun Kao, Chia-Cheng Lee, Chung-Bao Hsieh, Chih-Hung Wang, Chi-Ming Chu. Originally published in JMIR Serious Games (https://games.jmir.org), 22.03.2022.)

Background: Patients with advanced gastric cancer (AGC) with peritoneal carcinomatosis (PC) usually have poor outcomes and high mortality risk, even with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study analyzed the prognostic factors of AGC with PC and evaluated laparoscopic HIPEC (LHIPEC) plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) as a conversion surgery for AGC patients with PC with a poor initial prognosis. Patient and Methods . We retrospectively evaluated 127 patients with AGC and PC from January 1, 2012, to March 1, 2020. After the exclusion of 32 ineligible patients, the conversion group comprised 34 patients who underwent LHIPEC + NIPS as a conversion surgery followed by CRS plus HIPEC. The CRS + HIPEC group included 15 patients who underwent CRS with HIPEC alone. Additionally, the C/T group comprised 23 patients who received systemic chemotherapy, and the palliative group comprised 23 patients who received only conservative therapy or palliative gastrectomy., Results: The conversion group demonstrated a significantly better mean overall survival compared to the CRS + HIPEC, C/T, and palliative groups ( p < 0.001). Patients in the conversion group who underwent LHIPEC + NIPS had significantly decreased peritoneal cancer index (PCI) scores ( p < 0.001) and ascites ( p =0.003). Malignant ascites amount also significantly decreased after treatment in the LHIPEC + NIPS group ( p < 0.001)., Conclusions: LHIPEC + NIPS can significantly improve the overall survival, the PCI score, and malignant ascites amount in peritoneal cytology-positive gastric cancer with PC, and an initially high PCI score. Therefore, it may be a feasible conversion strategy for AGC patients with PC., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this study., (Copyright © 2021 Ting-Ying Lee et al.)

Aims: Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC., Main Methods: The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay., Key Findings: Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = -0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells., Significance: The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to compare the outcomes of infection between liver transplant patients with and without simultaneous splenectomy., Methods: We retrospectively analyzed the records of 211 patients who underwent liver transplantation in the Tri-Service General Hospital from 2012 to 2017. The frequency of blood cultures obtained after liver transplantation; incidence of bacteremia, pathogens, and complications; and overall survival rates were compared between the groups., Results: One hundred thirty-three of 211 patients underwent liver transplantation without simultaneous splenectomy. There were no significant differences in the frequency of blood cultures obtained after liver transplantation (non-splenectomy group and splenectomy group: 63% and 62%, respectively); incidences of bacteremia after liver transplantation (21% and 21%, respectively), repeat bacteremia (39% and 35%, respectively), cytomegalovirus infection (4% and 3%, respectively), herpes infection (6% and 7%, respectively), and fungal infection (3% and 3%, respectively); and overall survival rate between the two groups. However, there was a significant difference in infection-related deaths between the groups. Simultaneous splenectomy and episodes of antibody-related rejection were significant risk factors associated with infection-related death in multivariate analyses., Conclusion: Although simultaneous splenectomy does not increase the incidence of infection, simultaneous splenectomy definitely carries risks of infection-related mortality in liver transplantation., (© 2021. The Society for Surgery of the Alimentary Tract.)

Drug-drug interactions between azoles and calcineurin inhibitors can cause issues for organ transplant specialists. Clinical practice guidelines for the treatment of solid-organ transplant recipients with invasive aspergillosis infection are lacking. Here, we present a patient who developed pulmonary aspergillosis after liver transplant. The patient had prolonged treatment with echinocandin that was not effective. A drug-drug interaction between azoles and tacrolimus caused issues for the clinical physician. We adjusted the doses, and the patient was successfully treated. A reduction in the tacrolimus dose, intensive monitoring of associated parameters, and elimination of risk exposures are important for a favorable outcome.

Background: Laparoscopic surgery is the main trend method in a variety of surgical fields. Post-operative shoulder pain remains a bothersome issue although many surgical techniques have been applied to minimize it. A simple novel approach to reduce shoulder pain without adverse effects during and after laparoscopic surgery is desired., Methods: This prospective randomized controlled study was conducted to enroll a total of 140 patients to evaluate the efficacy of low flow rate (1 L/min) for induction followed by high flow rate (10 L/min) for maintaining 12 mmHg pneumoperitoneum (group A, n = 70) during laparoscopic cholecystectomy (LC), compared to the continuous high flow rate group (group B, n = 70) in postoperative shoulder pain and other clinical features. The 10-visual analog scale (VAS) was applied for the severity of shoulder pain and scores were obtained at 1, 6, 12, 24, and 48 h after LC., Results: There was no obvious difference in baseline characteristics as well as operative time, occurrence of bradycardia, or hospital stay between groups. The incidence of shoulder pain was not significantly different (group A 45.7% vs group B 48.6%, p = 0.866). However, the patients in group A with shoulder pain reported significantly less pain scores (p < 0.001) at 12 and 24 h after surgery, compared with those in group B., Conclusions: Applying the strategy of low flow rate to induce pneumoperitoneum followed by high flow rate to maintain the pressure provides advantages to reduce the severity of shoulder pain for patients who underwent LC and then experienced shoulder pain.

Anemia defined as reduced hemoglobin levels of red blood cells may carry less oxygen to skeletal muscle and impair physical performance. Previous studies have shown that exercise intolerance was related to moderate or severe anemia, however, the relationship to mild anemia was unknown. We investigated the cross-sectional association of mild anemia defined as a hemoglobin level of 10.0-13.9 g/dL with physical fitness in 3,666 military young males in Taiwan in 2014. Aerobic fitness was evaluated by 3000-meter run test, and anaerobic fitness was evaluated by 2-minute sit-ups and 2-minute push-ups, respectively. Multiple logistic regressions for the best 10% and the worst 10% performers were used to determine the relationship. There were 343 mild anemic males in whom 47.8% were microcytic anemia and 3,323 non-anemic males for the analysis. The multiple logistic regression shows that as compared with non-anemic males, mild anemic males were more likely to be the worst 10% performers in the 3000-meter run test (odds ratios (OR) and 95% confidence intervals: 1.47, 1.01-2.14) after adjusting for age, service specialty, body mass index, waist size, mean blood pressure, unhealthy behaviors, lipid profiles, and exercise frequency. On the contrary, mild anemic males had higher possibility to be the best 10% performers in the 2-minute push-ups test (OR: 1.48, 1.08-2.04). However, there was no association between mild anemia and 2-minute sit-ups. Our findings suggest that unspecified mild anemia might be associated with lower cardiorespiratory fitness but not with anaerobic fitness in physically active military males.

BACKGROUND Patients with massive ascites (MA) after liver transplantation (LT, defined here as daily ascitic drainage more than 1000 ml per day for more than 7 days after liver transplantation) are at increased risks of infection, hypoalbuminemia, graft loss, and even mortality. The aim of this retrospective cohort study was to investigate the effects of somatostatin on patients with MA after LT. MATERIAL AND METHODS Twenty-eight patients with liver cirrhosis or hepatocellular carcinoma who underwent LT complicated by MA postoperatively were included. Ten participants were receiving somatostatin therapy. The postoperative course and adverse drug effects were investigated. Daily postoperative ascitic drainage and urine output were also recorded and compared to those in the non-somatostatin group. RESULTS The somatostatin group had significantly less ascites drainage after LT compared to the non-somatostatin group (p=0.002). Urine output was significantly increased after somatostatin administration (p<0.001). No serious adverse effects influencing graft function or fatal complications occurred after somatostatin therapy. CONCLUSIONS Somatostatin treatment is beneficial for the management of MA after liver transplantation.

Aim: The study was conducted in order to examine the sex-specific association of serum uric acid (SUA) levels with elevated serum alanine aminotransferase (ALT) in a Taiwanese military cohort., Methods: We made a cross-sectional examination of the sex-specific relationship using 6728 men and 766 women, aged 18-50 years from a large military cohort in Taiwan. SUA levels within the reference range (<7.0 mg/dL for men and <5.7 mg/dL for women respectively) were divided into quartiles and SUA levels greater than the upper reference limits were defined as hyperuricemia. Elevated ALT levels were defined as ≥40 U/L. Multivariate logistic regression analysis was performed to determine the association between each SUA category and elevated ALT levels in men and women, respectively., Results: The prevalence of hyperuricemia and elevated ALT in men were 18.7% and 12.7%, respectively, and in women were 3.3% and 2.1%, respectively. As compared with the lowest SUA quartile, hyperuricemia was associated with elevated ALT in men (odds ratios (OR): 1.62, 95% confidence intervals (CI): 1.19-2.20) after controlling for age, service specialty, body mass index, metabolic syndrome components, current cigarette smoking, alcohol intake status, and weekly exercise times, but the associations for the other SUA quartiles were null. By contrast, the associations of hyperuricemia (OR: 0.81, 95% CI: 0.10-6.64) and the other SUA quartiles with elevated ALT were null in women., Conclusion: Our findings suggest that the relationship between each SUA level and elevated ALT may differ by sex among military young adults. The mechanism for the sex difference requires further investigations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Splitting deceased donor livers and creating 3 grafts from a whole liver may be feasible and shorten the waiting time for organ donation in patients with high mortality rates. We hypothesized that it might be reasonable to procure 3 grafts for donation from one deceased donor liver by splitting the liver into left (segment II, III, IV), right anterior (segment V, VIII), and right posterior lobes (segment VI, VII) for liver transplantation according to the portal system trifurcated variations. We designed the right anterior branch with the main portal trunk and middle hepatic artery to become inflow of right anterior lobe, the left portal vein and left hepatic artery to become the inflow of left lobe and right posterior branch, and right hepatic artery to become the inflow of right posterior lobe. We retrospectively reviewed the volumetric computed tomography and magnetic resonance cholangiopancreatography of 153 liver donors. The hepatic and portal veins, hepatic artery, and biliary system were reorganized and classified. The volumetric proportions of the liver grafts were measured. Trifurcation of the portal vein variation was found in approximately 13.7% of portal systemic variations. The left lobe accounted for 29.18% of the total liver volume, the right anterior lobe, 35.22%, and the right posterior lobe, 35.6%. We validated this principle by dissecting the explanted liver and identified the triple grafts' weights, percentages, vessels, and biliary ducts system. The splitting of deceased donor livers into 3 split liver grafts for use in liver transplantation surgery can be clinically useful., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Routine use of intraoperative neuromonitoring (IONM) in thyroid cancer surgery is controversial. We aimed to investigate whether it improves the completeness of thyroidectomy and ensures safety. This retrospective study included 380 thyroid cancer patients who underwent thyroidectomy, by one surgeon, between July 2006 and November 2015. Patients were grouped according to the surgeon's adaptation of IONM, as follows: none (period 1; n = 92), early (period 2; n = 141), and late (period 3; n = 147). The operative time and rates of vocal cord palsy were determined. Surgical completeness was assessed by technetium-99m imaging of the thyroid remnant and serum thyroglobulin measurement before ablation. The rate of recurrent laryngeal nerve (RLN) palsy showed a decreasing trend over time. No permanent RLN palsies occurred in nerves not invaded by tumor after routine IONM was introduced. Technetium-99m uptake (periods 1-3, 0.62 vs 0.32 vs 0.20; P < 0.01) and thyroglobulin levels (periods 1 and 2, 37.93 vs 8.98 ng/mL, respectively; P = 0.034; period 3, 9.10 ng/mL) progressively decreased. The mean thyroglobulin level dropped significantly after introduction of routine IONM. We conclude that routine IONM during thyroid cancer surgery improves surgical completeness and might prevent permanent RLN palsy over time.

Introduction: Betel nut chewing may cause obesity, neurohormonal activation and inflammation, possibly impairing exercise performances., Methods: We examined the cross-sectional association in 4388 military male adults aged 18-50 years from the cardiorespiratory fitness in armed forces study in Taiwan between 2013 and 2014. The status of betel nut chewing was classified as current and former/never based on each participant's response to a questionnaire. Physical fitness was evaluated by three basic exercise tests including 3000 m running, 2 min sit-ups and 2 min push-ups. Multiple logistic regression for the best 10% and the worst 10% performers in each exercise, and linear regression were used to determine the relationship., Results: There were 564 current chewers and 3824 non-current chewers for the analysis. The linear regression shows that current betel nut chewing was positively correlated with 3000 m running duration (r=0.37, p=0.042) after adjusting for age, service specialty, body mass index, exercise frequency and alcohol intake. In addition, the logistic regression shows that as compared with non-current chewers, current chewers had lower odds of being the top 10% performers in 2 min push-ups and higher odds of being the bottom 10% performers in 2 min sit-ups (ORs and 95% CIs: 0.71 (0.50 to 0.99) and 1.32 (1.00 to 1.75), respectively). However, the associations between betel nut chewing and physical fitness were all insignificant after further adjusting for current smoking., Conclusions: Our findings suggest that the impairment of physical fitness associated with betel nut chewing of military young men might be mainly mediated or moderated by the coexisted cigarette smoking., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In contrast to the feasibility of hepatectomy for resectable large hepatocellular carcinoma (HCC, >5 cm) in the younger patients, the concerns of benefits for the elderly patients remain in practice. This study aimed to evaluate the long-term outcomes and safety after hepatectomy in elderly patients with resectable large HCC compared with younger patients., Methods: Between 2003 and 2014, a total of 2211 HCC patients were reviewed using a prospective database and 257 patients with resectable large HCC undergoing hepatectomy were included: 79 elderly patients with age ≥70 years and 178 younger patients with age <70 years. The last follow-up was assessed in December 2017. The complications, long-term outcomes and risk factors of disease-free and overall survival were analysed., Results: The 1-, 3-, 5- and 7-year overall survival rates in the elderly and younger groups were 76%, 55%, 48%, and 42% and 79%, 57%, 51%, and 49%, respectively (P = 0.319). The 1-, 3-, 5-, and 7-year disease-free survival rates in the elderly and younger groups were 60%, 40%, 38%, and 27% and 54%, 36%, 32%, and 32%, respectively (P = 0.633). The analysis of post-operative outcomes of interest, including hospital stay and hospital death and hepatectomy-related complications in both groups revealed no significant difference. Serum albumin and AJCC TNM stage were independent risk factors for survival. Serum alpha-fetoprotein, tumour number and AJCC TNM stage predicted HCC recurrence., Conclusions: Our results suggested that hepatectomy can achieve comparable long-term outcomes in the selected younger and elderly patients with resectable large HCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Antibody-mediated rejection after liver transplant, especially when the donor is not a direct relative; it is associated with additional inconvenience for patients. We encountered a case in which antibody-mediated rejection because of de novo donor specific antibodies against donor human leukocyte antigen developed 6 months after ABO-compatible living-donor liver transplant and was treated with retransplant. A 38-year-old man with hepatitis B virus-related hepatocellular carcinoma underwent living-donor liver transplant with a graft from his wife. Six months later, he experienced fatigue and jaundice. Liver biopsy revealed C4d deposits, and histologic examination showed an antibody-mediated rejection pattern. We re-evaluated recipient-donor human leukocyte antigen matching and tested the patient's blood for antihuman leukocyte antigen donor-specific antibodies against donor human leukocyte antigen. De novo auto-antibodies against human leukocyte antigen-DQ6 were identified by Luminex single antigen beads.Because exhausting all treatment options, a rescue second living-donor liver transplant was planned with the patient's stepdaughter as the donor. Pretransplant human leukocyte antigen matching was performed, and the patient was discharged without event. Two months later, hyperbilirubinemia was noted, and a residual common bile duct from the first donor with chronic fibrosis and stricture was strongly suspected. Redo hepaticojejunostomy was successfully performed, with no problems during 1-years' follow-up. Thus, liver retransplant could be a rescue treatment for antibody-mediated rejection complicated with hepatic failure.

The association of metabolic syndrome (MetS) components with elevated serum alanine aminotransferase (ALT) levels, a marker of hepatic injury, may differ between men and women. However, the sex-specific association in a military young population which has a low prevalence of MetS was unclear. We conducted a cross-sectional examination in 6738 men and 766 women, aged 18-50 years, from the cardiorespiratory fitness study in armed forces (CHIEF) in eastern Taiwan. The components of MetS were defined according to the updated International Diabetes Federation (IDF) ethnic criteria for Asians. Elevated ALT levels were defined as ≥40 U/L for both sexes and ≥30 U/L for women alternatively. Multivariate logistic regression analysis was performed to determine the sex-specific association between MetS components and elevated ALT. The prevalence of MetS and elevated ALT in men were 11.9% and 12.7% respectively, and in women were 3.5%, and 3.8% respectively. In men, high-density lipoprotein < 40 mg/dL, blood pressures ≥ 130/85 mmHg, serum triglycerides ≥ 150 mg/dL, and waist size ≥ 90 cm were associated with elevated ALT (odds ratios (OR) and 95% confidence intervals: 1.59 (1.34-1.90), 1.40 (1.19-1.65), 2.00 (1.68-2.39), and 1.68 (1.38-2.04); all p < 0.001); whereas in women, only fasting plasma glucose ≥ 100 mg/dL was associated with elevated ALT ≥ 40 U/L (OR: 7.59 (2.35-24.51), p = 0.001) and ALT ≥ 30 U/L (2.67 (0.89-7.95), p = 0.08). Our findings suggest that the relationship between metabolic abnormalities and elevated ALT may differ by sex, possibly due to the MetS more prevalent in young adult men than in women., Competing Interests: The authors declare no conflict of interest.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis.

Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). HCV core protein is considered as a positive regulator of telomerase activity. In this study, we focused on the deregulated microRNA-138 (miR-138) in HCV-associated HCC. Differential expression of miR-138 was determined by TaqMan quantitative real-time PCR. The target gene of miR-138 was verified by luciferase reporter assay, quantitative real-time PCR, and Western blotting. Moreover, three assays based on telomerase activity, cell proliferation, and senescence-associated β-galactosidase activity were performed. The correlation analysis revealed a significantly negative correlation between miR-138 and telomerase reverse transcriptase (TERT) mRNA expression in HCC. Further, we showed that mature HCV core protein of 173 amino acids, but not full-length form of 191 amino acids, suppressed miR-138 expression. TERT was verified as a direct target of miR-138 in HCC cells. Furthermore, TERT-targeting miR-138 supplementation can prevent HCV core protein from repressing HCC cell replicative senescence. Collectively, HCV core protein can enhance TERT protein expression through downregulating TERT-targeting miR-138 expression, which in turn inhibits HCC cell replicative senescence. This study may further help our understanding on the pathogenic mechanisms of HCV core protein in HCV-associated HCC development. KEY MESSAGE: miR-138 is downregulated in HCV-associated HCC. Mature HCV core protein plays a pathogenic role in suppressing miR-138 expression. Telomerase reverse transcriptase represents a direct target of miR-138 in HCC cells. miR-138 promotes HCC cell senescence, suggesting potential for HCC treatment.

Background: The prognosis of advanced liver malignancy with inferior vena cava (IVC) thrombi is poor. Many therapeutic policies are challenging for long-term prognosis. We performed the modified effective technique of transdiaphragmatic intrapericardial IVC isolation for curative resection of IVC tumors and prolonged survival time., Methods: Between 2003 and 2015, 10 patients, sustained liver malignancy with IVC thrombi, underwent surgical intervention. Liver resection with thrombectomy under total hepatic vascular exclusion via the transdiaphragmatic intrapericardial IVC isolation method was performed for these 10 patients. The first 4 patients underwent retrohepatic IVC resection in order to complete resection, and the other 6 patients preserved the retrohepatic IVC. The last 3 patients received preoperative locoregional therapies, and all 10 patients received postoperative adjuvant chemotherapies immediately., Results: All 10 patients underwent gross en bloc tumor resections with thrombectomy with R0 resection. There was no surgical mortality. Shortening of operation time and reduction of both intraoperative blood loss and hospital stay were demonstrated in the last 6 patients with preserving the retrohepatic IVC. However, similar time to recurrence and survival time were noted in the first 7 patients. The last 3 patients, who had received preoperative locoregional therapies, have better disease-free survival time., Conclusion: Simplified surgical procedure combined with preoperative locoregional therapies and rapid postoperative adjuvant treatment may provide a greater advantage for these patients.

Objective(s): Previous studies have shown that preincisional epidural morphine, bupivacaine, and ketamine combined with epidural anesthesia (EA) and general anesthesia (GA) provided pre-emptive analgesia for upper abdominal surgery. Recent studies reported that ultralow-dose naloxone enhanced the antinociceptive effect of morphine in rats. This study investigated the benefits of preincisional and postoperative epidural morphine + ropivacaine + ketamine + naloxone (M + R + K + N) treatment for achieving postoperative pain relief in upper abdominal surgery., Methods: Eighty American Society of Anesthesiology I-II patients scheduled for major upper abdominal surgery were allocated to four groups in a randomized, single-blinded study. All patients received combined GA and EA with a continuous epidural infusion of 2% lidocaine (6-8 mL/h) 30 minutes after pain regimen. After GA induction, in Group I, an epidural pain control regimen (total 10 mL) was administered using 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg; M + R); in Group II, 1% lidocaine 8 (mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg; M + R + K); in Group III, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + naloxone (2 μg; M + R + N); and in Group IV, 1% lidocaine (8 mL) + morphine (2 mg) + ropivacaine (20 mg) + ketamine (20 mg) + naloxone (2 μg; M + R + K + N), respectively. All patients received patient-controlled epidural analgesia (PCEA) with different pain regimens to control subsequent postoperative pain for 3 days following surgery. During the 3-day period following surgery, PCEA consumption (mL), numerical rating scale (NRS) score while cough/moving, and analgesic-related adverse effects were recorded., Results: Total PCEA consumption for the 3-day observation period was 161.5±17.8 mL, 103.2±21.7 mL, 152.4±25.6 mL, and 74.1±16.9 mL for Groups I, II, III, and IV, respectively. (p < 0.05). The cough/moving NRS scores were significantly lower in Group IV patients than Groups I and III patients at 4 hours, 12 hours, and on Days 1 and 2 following surgery except for Group II (p < 0.05)., Conclusion: Preincisional and postoperative epidural M + R + K + N treatment provides an ideal postoperative pain management than preincisional and postoperative epidural M + R, M + R + K, and M + R + N treatments in upper abdominal surgery., (Copyright © 2016. Published by Elsevier B.V.)

Aim: To determine risk factors for early neurologic complications (NCs) after liver transplantation from perspective of recipient, donor, and surgeon., Methods: In all, 295 adult recipients were enrolled consecutively between August 2001 and February 2014 from a single medical center in Taiwan. Any NC in the first 30 d post-liver transplantation, and perioperative variables from multiple perspectives were collected and analyzed. The main outcome was a 30-d NC. Generalized additive models were used to detect the non-linear effect of continuous variables on outcome, and to determine cut-off values for categorizing risk. Risk factors were identified using multiple logistic regression analysis., Results: In all, 288 recipients were included, of whom 142 (49.3%) experienced at least one NC, with encephalopathy being the most common 106 (73%). NCs prolonged hospital stay (35.15 ± 43.80 d vs 20.88 ± 13.58 d, P < 0.001). Liver recipients' age < 29 or ≥ 60 years, body mass index < 21.6 or > 27.6 kg/m(2), Child-Pugh class C, history of preoperative hepatoencephalopathy or mental disorders, day 7 tacrolimus level > 8.9 ng/mL, and postoperative intra-abdominal infection were more likely associated with NCs. Novel risk factors for NCs were donor age < 22 or ≥ 40 years, male-to-male gender matching, graft-recipient weight ratio 0.9%-1.9%, and sequence of transplantation between 31 and 174., Conclusion: NCs post- liver transplantation occurs because of factors related to recipient, donor, and surgeon. Our results provide a basis of risk stratification for surgeon to minimize neurotoxic factors during transplantation.

Population-based evidence of the relative risk of cancer among heart, kidney, and liver transplant recipients from Asia is lacking. The Taiwan National Health Insurance Research Database was used to conduct a population-based cohort study of transplant recipients (n = 5396), comprising 801 heart, 2847 kidney, and 1748 liver transplant recipients between 2001 and 2012. Standardized incidence ratios and Cox regression models were used. Compared with the general population, the risk of cancer increased 3.8-fold after heart transplantation, 4.1-fold after kidney transplantation and 4.6-fold after liver transplantation. Cancer occurrence showed considerable variation according to transplanted organs. The most common cancers in all transplant patients were cancers of the head and neck, liver, bladder, and kidney and non-Hodgkin lymphoma. Male recipients had an increased risk of cancers of the head and neck and liver, and female kidney recipients had a significant risk of bladder and kidney cancer. The adjusted hazard ratio for any cancer in all recipients was higher in liver transplant recipients compared with that in heart transplant recipients (hazard ratio = 1.5, P = .04). Cancer occurrence varied considerably and posttransplant cancer screening should be performed routinely according to transplanted organ and sex.

Background: Related to genetic alteration, frequent promoter hypermethylation is also a contributing factor in the development of human cancers. Recently, we discovered numerous novel genes that were aberrantly methylated in hepatocellular carcinoma (HCC) by using Infinium HumanMethylation27 BeadChip array. We utilized a quantitative methylation-specific PCR (Q-MSP) system for the evaluation of PAX6 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent non-tumor tissues. We verified the correlation between the methylation status of PAX6 and clinical characteristics with different viral status., Results: Paired-box 6 promoter methylation was observed in 39.4 %, 15.6 %, and 3.4 % in primary HCCs, adjacent non-tumors, and normal control tissues, respectively. Methylation of the PAX6 promoter region in HCCs significantly increased compared with control tissues. PAX6 was frequently methylated in HCV-positive HCC tissues (61.3 %) and rarely methylated in HBV-positive (22.1 %) and double-negative HCC tissues (33.3 %)., Conclusions: Our data suggests that promoter hypermethylation of PAX6 is a common event in HCCs and the association of PAX6 methylation in clinicopathological features is divergent with different viral status.

Liver resection (LR) and liver transplantation (LT) are curative treatments for early hepatocellular carcinoma (HCC), although their performance remains debated. We compared the survival of patients with HCC conforming to the Milan criteria (MC) after LT and LR and analyzed factors affecting clinical outcomes. Between January 2006 and January 2013, 65 and 184 patients received LT and LR for HCCs fulfilling the MC, respectively. Overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. To investigate effects of liver function and living donor liver transplantation (LDLT) on survival, two subgroup analyses were performed and associations with OS and DFS were examined. We found that OS rates were higher after LT than after LR since 3 years postoperatively. DFS rates were significantly better after LT than after LR. Performance of LR, vascular invasion, and tumor multiplicity were associated with poor DFS, and factors affecting OS included the presence of vascular invasions, liver cirrhosis, and tumor multiplicity. In conclusion, despite of the effects of tumor characteristics on clinical outcomes, LT, including LDLT, should be considered the treatment of choice for patients with HCCs who met the MC. The role of LR is to identify poor prognostic factors through pathological examination.

The correlation between portal vein pressure (PVP) and flow (PVF) has not been established, and there is still lack of consensus about the optimal hemodynamics during liver transplantation (LT). We aimed to establish the correlation between systemic and hepatic hemodynamics during LT by applying the hepatokinetic power hypothesis, based on the law of energy conservation and hydrodynamics.A total of 103 adult liver transplant recipients were enrolled in this study from September 2012 to December 2014. Systemic and hepatic hemodynamics were assessed intraoperatively to calculate the hepatokinetic power status. Severe surgical complications (Clavien-Dindo grade ≥III) were recorded as the main outcome measure, and potential covariates were evaluated including recipient, donor, donor-recipient match, surgery-related factors, conventional hemodynamics, and the intraoperative hepatokinetic power profile.In multivariate analysis, hepatokinetic power gradient >4260 mL mmHg min100 g graft weight (P = 0.001), 2.2 < ratio of hepatokinetic power from the portal vein to the hepatic artery ≤8.7 (P = 0.012), and hepatic resistance of partial grafts ≤0.006 or >0.015 min mmHg mL (P = 0.012) were associated with a higher risk. None of the conventional hemodynamic parameters, such as PVP, PVF, and hepatic venous pressure gradient, entered into this regression model (c-statistic = 0.916) when competing with hepatokinetic power indexes.The hepatokinetic power hypothesis clarifies the correlation of systemic and hepatic hemodynamics in a simple, rational manner. The hepatic resistance, derived from the hepatokinetic power equation, can be quantified and has an effect on the incidence of severe surgical complications. This finding offers a new objective clinical approach to evaluate graft quality during transplantation.

Aim: To examine the methylation levels of interleukin-1 receptor-associated kinase 3 (IRAK3) and GLOXD1 and their potential clinical applications in hepatocellular carcinoma (HCC)., Methods: mRNA expression and promoter methylation of IRAK3 and GLOXD1 in HCC cells were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP), respectively. Using pyrosequencing results, we further established a quantitative MSP (Q-MSP) system for the evaluation of IRAK3 and GLOXD1 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent nontumor tissues. We also calculated Kaplan-Meier survival curves to determine the applications of gene methylation in the prognosis of HCC., Results: IRAK3 and GLOXD1 expression was partially restored in several HCC cell lines after treatment with 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor; 5DAC). A partial decrease in the methylated band was also observed in the HCC cell lines after 5DAC treatment. Using GLOXD1 as an example, we found a significant correlation between the data obtained from the methylation array and from pyrosequencing. The methylation frequency of IRAK3 and GLOXD1 in HCC tissues was 46.9% and 63.8%, respectively. Methylation of IRAK3 was statistically associated with tumor stage. Moreover, HCC patients with IRAK3 methylation had a trend toward poor 3-year disease-free survival (P < 0.05)., Conclusion: IRAK3 and GLOXD1 were frequently methylated in HCC tissues compared to normal controls and nontumor tissues. IRAK3 methylation was associated with tumor stage and poor prognosis of patients. These data suggest that IRAK3 methylation is a novel prognostic marker in HCC.