Performance of the EDACS-ADP incorporating high-sensitivity troponin assay:Do components of major adverse cardiac events matter?

BACKGROUND:The accelerated diagnostic protocol(ADP)using the Emergency Department Assessment of Chest pain Score(EDACS-ADP),a tool to identify patients at low risk of a major adverse cardiac event(MACE)among patients presenting with chest pain to the emergency department,was developed using a contemporary troponin assay.This study was performed to validate and compare the performance of the EDACS-ADP incorporating high-sensitivity cardiac troponin I between patients who had a 30-day MACE with and without unstable angina(MACE I and II,respectively).METHODS:A single-center prospective observational study of adult patients presenting with chest pain suggestive of acute coronary syndrome was performed.The performance of EDACS-ADP in predicting MACE was assessed by calculating the sensitivity and negative predictive value.RESULTS:Of the 1,304 patients prospectively enrolled,399(30.6%;95%confidence interval[95%CI]:27.7%–33.8%)were considered low-risk using the EDACS-ADP.Among them,the rates of MACE I and II were 1.3%(5/399)and 1.0%(4/399),respectively.The EDACS-ADP showed sensitivities and negative predictive values of 98.8%(95%CI:97.2%–99.6%)and 98.7%(95%CI:97.0%–99.5%)for MACE I and 98.7%(95%CI:96.8%–99.7%)and 99.0%(95%CI:97.4%–99.6%)for MACE II,respectively.CONCLUSION:EDACS-ADP could help identify patients as safe for early discharge.However,when unstable angina was added to the outcome,the 30-day MACE rate among the designated lowrisk patients remained above the level acceptable for early discharge without further evaluation.

Comparison of macular changes according to the etiology of optic neuritis:a cross-sectional study

AIM:To compare the macular structure including foveal thickness among patients with optic neuritis(ON)according to the etiology and to investigate the possible correlation between structural and visual outcomes METHODS:In this retrospective cross-sectional study,the clinical data of patients with aquaporin-4 immunoglobulin G-related ON(AQP4 group,40 eyes),myelin oligodendrocyte glycoprotein IgG-related ON(MOG group,31 eyes),and multiple sclerosis-related ON(MS group,24 eyes)were obtained.The retinal thickness of the foveal,parafoveal and perifoveal regions were measured.Visual acuity(VA),visual field index and mean deviation were measured as visual outcomes.RESULTS:The AQP4 group showed a significantly thinner fovea(226.4±13.4μm)relative to the MOG(236.8±14.0μm,P=0.015)and MS(238.9±14.3μm,P=0.007)groups.The thickness in the parafoveal area also was thinner in the AQP4 group,though the difference in perifoveal retinal thickness was not significant.Foveal thickness was correlated with VA in the AQP4 group(coefficientρ=-0.418,P=0.014),but not in the MOG and MS groups(P=0.218 and P=0.138,respectively).There was no significant correlation between foveal thickness and visual field test in all three groups.CONCLUSION:The significant thinning in the fovea and parafoveal areas in the AQP4 group compared to the MOG and MS groups are found.Additionally,macular changes in AQP4-ON show a significant correlation with VA.The results provide the possibility that retinal structural damage could reflect functional damage in AQP4-ON,distinct from MOGON and MS-ON.

Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several countries.AIM To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.METHODS This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies.Colonoscopy-related complications by age group were also determined.RESULTS The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age group.During the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age.Since 2009,the increase has been rapid,showing a pattern similar to the increase in colonoscopies.The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007.The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.CONCLUSION The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed.As the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

Comparison of totally laparoscopic total gastrectomy using an endoscopic linear stapler with laparoscopic-assisted total gastrectomy using a circular stapler in patients with gastric cancer: a single-center experience

AIM To evaluate the safety and efficacy of totally laparoscopic total gastrectomy(TLTG) with esophagojejunostomy using a linear stapler compared with laparoscopic-assisted total gastrectomy(LATG) using a circular stapler in gastric cancer patients.METHODS We retrospectively reviewed 687 patients who underwent laparoscopic total gastrectomy for gastric cancer at a single institution from August 2008 to August 2014. The patients were divided into two groups according to the type of operation: 421 patients underwent TLTG and 266 underwent LATG. Clinicopathologic characteristics and surgical outcomes in the two groups were compared and analyzed.RESULTS The TLTG group had higher mean ages at the time of operation(57.78 ± 11.20 years and 55.69 ± 11.96 years,P = 0.020) and more histories of abdominal surgery(20.2% and 12.4%,P = 0.008) compared with the LATG group. Surgical outcomes such as intraoperative and postoperative transfusions,combined operations,pain scores and administration of analgesics,and complications were similar between the two groups. However,compared with the LATG group,the TLTG group required a shorter operation time(149 min vs 170 min,P < 0.001),had lower postoperative hematocrit change(3.49% vs 4.04%,P = 0.002),less intraoperative events(3.1% vs 10.2%,P < 0.001),less intraoperative anastomosis events(2.4% vs 7.1%,P = 0.003),faster postoperative recovery such as median time to first flatus(3.30 d vs 3.60 d,P < 0.001),faster median commencement of soft diet(4.30 d vs 4.60 d,P < 0.001) and shorter length of postoperative hospital stay(6.75 d vs 7.02 d,P = 0.005). CONCLUSION The intracorporeal method for reconstruction of esophagojejunostomy using a linear stapler may be considered a feasible procedure comparing with extracorporeal anastomosis using circular stapler because TLTG is simpler and more straightforward than LATG. Therefore,TLTG can be recommended as an appropriate procedure for gastric cancer.

Prevalence of clonorchiasis in patients with gastrointestinal disease: A Korean nationwide multicenter survey

AIM： To investigate prevalence of C/onorchis sinensis in patients with gastrointestinal symptoms, and the relation of the infection to hepatobiliary diseases in 26 hospitals in Korea. METHODS： Consecutive patients who had been admitted to the Division of Gastroenterology with gastrointestinal symptoms were enrolled from March to April 2005. Of those who had been diagnosed with clonorchiasis, epidemiology and correlation between infection and hepatobiliary diseases were surveyed by questionnaire. RESULTS： Of 3080 patients with gastrointestinal diseases, 396 （12.9%） had clonorchiasis and 1140 patients （37.2%） had a history of eating raw freshwater fish. Of those with a history of raw freshwater fish ingestion, 238 （20.9%） patients had clonorchiasis. Cholangiocarcinoma was more prevalent in C. sinensis-infected patients than nonnfected patients [34/396 （8.6%） vs 145/2684 （5.4%）, P = 0.015]. Cholangiocarcinoma and clonorchiasis showed statistically significant positive cross-relation （P = 0.008）. Choledocholithiasis, cholecystolithiasis, cholangitis, hepatocellular carcinoma, and biliary pancreatitis did not correlate with clonorchiasis. CONCLUSION： Infection rate of clonorchiasis was still high in patients with gastrointestinal diseases in Korea, and has not decreased very much during the last two decades. Cholangiocarcinoma was related to clonorchiasis, which suggested an etiological role for the parasite.

Liver transplantation for combined hepatocellular carcinoma and cholangiocarcinoma:A multicenter study

BACKGROUND Patients with combined hepatocellular carcinoma and cholangiocarcinoma(cHCC-CC)are not traditionally considered eligible for liver transplantation(LT)AIM To compare outcomes between living donor LT(LDLT)patients with hepatocellular carcinoma(HCC)and LT patients with cHCC-CC and to identify risk factors for tumor recurrence and death after LT in cHCC-CC patients.METHODS Data for pathologically diagnosed cHCC-CC patients(n=111)who underwent LT from 2000 to 2018 were collected for a nine-center retrospective review.Patients(n=141)who received LDLT for HCC at Samsung Medical Center from January 2013 to March 2017 were selected as the control group.Seventy patients in two groups,respectively,were selected by 1:1 matching.RESULTS Cumulative disease-free survival(DFS)and overall survival(OS)in the cHCC-CC group were significantly worse than in the HCC group both before and after matching.Extrahepatic recurrence incidence in the cHCC-CC group was higher than that in the HCC group(75.5%vs 33.3%,P<0.001).Multivariate analysis demonstrated that the cHCC-CC group had significantly higher rates of tumor recurrence and death compared to the HCC group.In cHCC-CC subgroup analysis,frequency of locoregional therapies>3,tumor size>3 cm,and lymph node metastasis were predisposing factors for tumor recurrence in multivariate analysis.Only a maximum tumor size>3 cm was a predisposing factor for death.CONCLUSION The poor prognosis of patients diagnosed with cHCC-CC after LT can be predicted based on the explanted liver.Frequent regular surveillance for cHCC-CC patients should be required for early detection of tumor recurrence.

Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review

The natural history of hepatocellular carcinoma(HCC)with portal vein tumor thrombosis(PVTT)is dismal(approximately 2-4 mo),and PVTT is reportedly found in 10%-40%of HCC patients at diagnosis.According to the Barcelona Clinic Liver Cancer(BCLC)Staging System(which is the most widely adopted HCC management guideline),sorafenib is the standard of care for advanced HCC(i.e.,BCLC stage C)and the presence of PVTT is included in this category.However,sorafenib treatment only marginally prolongs patient survival and,notably,its therapeutic efficacy is reduced in patients with PVTT.In this context,there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options.To date,many studies on transarterial chemoembolization,3-dimensional conformal radiotherapy,hepatic arterial chemotherapy,and transarterial radioembolization report better overall survival than sorafenib therapy alone,but their outcomes need to be verified in future prospective,randomized controlled studies in order to be incorporated into current treatment guidelines.Additionally,combination strategies have been applied to treat HCC patients with PVTT,with the hope that the possible synergistic actions among different treatment modalities would provide promising results.This narrative review describes the current status of the management options for HCC with PVTT,with a focus on overall survival.

Clinical significance of MET gene amplification in metastatic or locally advanced gastric cancer treated with first-line fluoropyrimidine and platinum combination chemotherapy

Objective: To investigate the clinical significance of MET gene amplification in patients with gastric cancer in the palliative setting.Methods: MET amplification was assessed using fluorescence in situ hybridization(FISH) in 50 patients and quantitative polymerase chain reaction(qPCR) in 326 patients;259 patients treated with first-line fluoropyrimidine and platinum were included for survival analysis.Results: The results of FISH and qPCR indicated that the c-MET/CEP7 ratio was correlated with gene copy number. The optimal cutoff value for the copy number using qPCR to detect MET gene amplification with FISH was 5(κ=0.778, P<0.001). Twenty-one out of 326 patients(6.4%) were identified as MET amplification with a copy number of >5 detected by qPCR. MET-amplified gastric cancer was associated with an Eastern Cooperative Oncology Group(ECOG) performance status(PS) score of ≥2(33.3% vs. 10.5% P=0.007), peritoneal metastasis(76.2% vs. 46.2%, P=0.008), and elevated bilirubin levels(28.6% vs. 7.3%, P=0.006). The median overall survival(OS) and progression-free survival(PFS) were 11.9 and 5.6 months, respectively. MET-amplified gastric cancer was not associated with survival outcomes [hazard ratio(HR)=0.68, 95% confidence interval(95% CI): 0.35-1.32,P=0.254 for PFS;HR=0.68, 95% CI: 0.35-1.32, P=0.251 for OS].Conclusions: qPCR can be used to detect MET gene amplification. MET amplification was not a predictor of poor prognosis in patients with metastatic or unresectable gastric cancer.

Endoscopic papillary balloon dilation:Revival of the old technique

Radiologists first described the removal of bile duct stones using balloon dilation in the early 1980s.Recently,there has been renewed interest in endoscopic balloon dilation with a small balloon to avoid the complications of endoscopic sphincterotomy(EST)in young patients undergoing laparoscopic cholecystectomy.However,there is a disparity in using endoscopic balloon papillary dilation(EPBD)between the East and the West,depending on the origin of the studies.In the early 2000s,EST followed by endoscopic balloon dilation with a large balloon was introduced to treat large or difficult biliary stones.Endoscopic balloon dilation with a large balloon has generally been recognized as an effective and safe method,unlike EPBD.However,fatal complications have occurred in patients with endoscopic papillary large balloon dilation(EPLBD).The safety of endoscopic balloon dilation is still a debatable issue.Moreover,guidelines of indications and techniques have not been established in performing endoscopic balloon dilation with a small balloon or a large balloon.In this article,we discuss the issue of conventional and large balloon endoscopic dilation.We also suggest the indications and optimal techniques of EPBD and EPLBD.

Companion diagnostics for the targeted therapy of gastric cancer

Gastric cancer is the fourth most common type ofcancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

Incidence of venous thromboembolism and the role of D-dimer as predictive marker in patients with advanced gastric cancer receiving chemotherapy:A prospective study

To investigated the incidence and risk factors of venous thromboembolism (VTE) in patients with advanced gastric cancer (AGC) receiving chemotherapy. METHODSAll consecutive chemotherapy-naïve patients with AGC who would receive palliative chemotherapy between November 2009 and April 2012 in our hospital were recruited. Their pretreatment clinical and laboratory variables, including D-dimer, were recorded. The frequency of VTE development and survival rates during each chemotherapy cycle and regularly thereafter were assessed. RESULTSA total of 241 patients enrolled between November 2009 and April 2012 were analyzed. During a median follow-up duration of 10.8 mo (95%CI: 9.9-11.7), 27 patients developed VTE and the incidence of VTE was 17.5% (95%CI: 10.5-24.0, 12.0 events/100 person-years). The 6-mo and 1-year cumulative incidences were 7.8% (95%CI: 4.2%-11.4%) and 12.4% (95%CI: 7.3-17.2), respectively. Thirteen (48.1%) patients were symptomatic and the other 14 (51.9%) patients were asymptomatic. In multivariate analysis, pretreatment D-dimer level was the only marginally significant risk factor associated with VTE development (hazard ratio = 1.32; 95%CI: 1.00-1.75, P = 0.051). CONCLUSIONThe incidence of VTE is relatively high in patients with AGC receiving chemotherapy, and pretreatment D-dimer level might be a biomarker for risk stratification of VTE.

Predictors of poor outcomes in patients with wild mushroom-induced acute liver injury

To identify early predictive markers of poor outcomes in patients with acute liver injury from wild mushroom intoxication.METHODSThis observational, retrospective record review involved adults aged ≥ 18 years admitted to emergency department with mushroom intoxication from January 2005 to December 2015. The diagnosis of mushroom intoxication was based on the following: (1) a positive history of recent wild mushroom intake (either raw or cooked); (2) the onset of gastrointestinal symptoms, such as watery diarrhea, vomiting, and/or abdominal pain, after ingestion; and (3) the exclusion of other possible causes of acute liver injury. Acute liver injury was defined by a > 5-fold elevation of liver enzymes or moderate coagulopathy [international normalized ratio (INR) > 2.0]. Clinical and laboratory findings were compared in survivors and non-survivors.RESULTSOf 93 patients with mushroom intoxication, 23, 11 men (47.8%) and 12 women (52.2%), of median age 61 years, developed acute liver injury. The overall in-hospital mortality rate was 43.5% (10/23). Among the laboratory variables, mean serum alkaline phosphatase (73.38 ± 10.89 mg/dL vs 180.40 ± 65.39 mg/dL, P < 0.01), total bilirubin (2.312 ± 1.16 mg/dL vs 7.16 ± 2.94 mg/dL, P < 0.01) concentrations and indirect/direct bilirubin (2.45 ± 1.39 mg/dL vs 0.99 ± 0.45 mg/dL, P < 0.01) ratio as well as prothrombin time (1.88 ± 0.83 mg/dL vs 10.43 ± 4.81 mg/dL, P < 0.01), and activated partial thromboplastin time (aPTT; 32.48 ± 7.64 s vs 72.58 ± 41.29 s, P = 0.01), were significantly higher in non-survivors than in survivors. Logistic regression analysis showed that total bilirubin concentration (OR = 3.58, 95%CI: 1.25-10.22), indirect/direct bilirubin ratio (OR = 0.14, 95%CI: 0.02-0.94) and aPTT (OR = 1.30, 95%CI: 1.04-1.63) were significantly associated with mortality. All patients with total bilirubin > 5 mg/dL or aPTT > 50 s on day 3 died.CONCLUSIONMonitoring of bilirubin concentrations and aPTT may help in predicting clinical outcomes in patients with acute liver injury from wild mushroom intoxication.

Clinical implications of neutrophil-to-lymphocyte ratio and MDSC kinetics in gastric cancer patients treated with ramucirumab plus paclitaxel

Objective: We aimed to investigate the prognostic value of neutrophil-to-lymphocyte ratio(NLR) and myeloidderived suppressor cells(MDSCs) in gastric cancer patients treated with second-line ramucirumab plus paclitaxel.Methods: A total of 116 patients with advanced or metastatic gastric cancer who receive ramucirumab plus paclitaxel were prospectively enrolled. Fresh blood samples were collected before and after treatment, and flow cytometry was performed to assess the proportions of monocytic(m MDSCs) and granulocytic MDSCs(g MDSCs).Results: Median age was 58 years and 71(61.2%) patients were male. A baseline NLR≥2.94 was associated with significantly poorer progression-free survival(PFS) and overall survival(OS) vs. an NLR<2.94(P=0.011 and P=0.002, respectively). In multivariate analysis, an NLR≥2.94 was independently associated with poorer PFS[hazard ratio(HR)=1.58;95% confidence interval(95% CI): 1.01-2.49, P=0.046] and OS(HR=1.77;95% CI:1.04-3.04, P=0.036). While m MDSC counts did not significantly change following two cycles of therapy(P=0.530),g MDSC counts decreased significantly after two treatment cycles(P=0.025) but tended to increase in patients with progressive disease after two treatment cycles(P=0.098). A progressive increase in g MDSC counts(≥44%) was associated with a significantly shorter PFS and OS vs. a g MDSC count increase <44%(P=0.001 and P=0.003,respectively).Conclusions: The baseline NLR may help guide clinical decisions during ramucirumab plus paclitaxel therapy for gastric cancer. Our g MDSC kinetics data warrant further clinical validation and mechanistic investigation.

Efficacy and safety of controlled-release oxycodone/naloxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial

Background: Controlled-release oxycodone/naloxone(OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone(OX-CR) for the control of cancer-related pain in Korean patients.Methods: In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale(NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat(ITT) population were randomized(1:1) to OXNCR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks.The primary efficacy endpoint was the change in NRS pain score from baseline to week4, with non-inferiority margin of-1.5. Secondary endpoints included analgesic rescue medication intake, patientreported change in bowel habits, laxative intake, quality of life(QoL), and safety assessments.Results: Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group(n = 58) and the OX-CR group(n = 59)(-1.586 vs.-1.559,P = 0.948). The lower limit of the one-sided 95% confidence interval(-0.776 to 0.830) for the difference exceeded the non-inferiority margin(P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.Conclusions: OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation.Trial registration ClinicalTrials.gov NCT01313780, registered March 8。

Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson’s disease?

Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson＇s disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups （PBS injection） demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase （dopaminergic neuronal marker） staining and G protein-activated inward rectifier potassium channel 2 （A9 dopaminergic neuronal marker） were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stern cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants （NOACs） and warfarin in Asian octogenarian atrial fibrillation （AF） patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged 〉 80 years with non-valvular AF who had taken either NOACs 048 cases, 50.5%） or warfarin （145 cases, 49.5%） were retrospectively reviewed. The efficacy outcome was the com- posite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years （ 172 patient-years with NOACs and 203 patient-years with warfarin）. Patients on NOACs were slightly older （P = 0.006） and had slightly higher HAS-BLED scores （P = 0.034）. The efficacy of both anticoagulants was high （1.16% for NOACs vs. 2.98% for warfarin per 100 pa- tient-years, P = 0.46）. The safety outcome was relatively high in both NOACs and warfarin groups （8.96% vs. 12.46%, P = 0.29）. The effi- cacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin （0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34）. Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population.

Increased incidence of chemoport-related thrombosis in patients with colorectal cancer receiving bevacizumab: A single-institutional experience

Objective： Chemoport-related thrombosis （CRT） is a serious complication that causes morbidities and interruptsadministration of intravenous cancer therapy. We investigated the incidence and risk of CRT in colorectal cancer（CRC） patients treated with bevacizumab （BEV）.Methods： We retrospectively reviewed 1,534 CRC patients who received chemotherapy with or without BEVusing a chemoport between 2014 and 2016.Results： The participants had a median age of 58 （18-85） years, and 60.3% were male. All participants werestratified into three groups： adjuvant chemotherapy （AC） （n=670）, palliative chemotherapy （PC） without BEV（n=356）, and PC with BEV （n=508）. The median follow-up was 20.19 （interquartile range, 14.07-27.19） months.CRT occurred in 3.8% of all patients; incidence of symptomatic and asymptomatic CRT was 2.9% and 0.9%,respectively. CRT occurred more in patients with BEV （5.7%） than in patients without BEV （2.9%, P=0.008）. Thecumulative incidence of CRT in patients administered PC with BEV was significantly higher than that in thoseadministered AC （P=0.011） and there was a trend toward increased CRY in patients administered PC with BEVcompared with those administered PC without BEV （P=0.044）. Multivariate analysis found that BEV treatment wasthe only variable that was significandy associated with CRT （hazard ratio, 2.06; 95% confidence interval, 1.24-3.43;P=0.006）.Conclusions： BEV treatment was significandy associated with increased incidence of CRT in CRC patients.

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection

BACKGROUND Although the criteria for the indication of endoscopic submucosal dissection(ESD)for undifferentiated early gastric cancer(UD-EGC)have been recently proposed,accumulating reports on the non-negligible rate of lymph node metastasis(LNM)after indicated ESD raise questions on the reliability of the current criteria.AIM To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD.METHODS We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center,a tertiary university hospital in Korea.To identify the risk factors of LNM of UDEGC meeting the expanded criteria for ESD,we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4.We reviewed the clinical,endoscopic,and histologic features of the cases to identify features with a significant difference according to the presence of LNM.Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios(ORs).RESULTS Of the 4780 UD-EGC cases,1240(25.9%)were identified to meet the expanded indication for ESD.Of the 1240 cases,14(1.1%)cases had LNM.Among the various clinical,endoscopic,and histopathological features that were evaluated,mixed histology(tumors consisting of 10%-90%of signet ring cells)had a marginally significant association(P=0.059)with the risk of LNM.Moreover,diffuse blurring of the muscularis mucosae(MM)underneath the tumorous epithelium,a previously unrecognized histologic feature,had a significant association with the absence of LNM(P=0.028).Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM(OR:0.12,95%CI:0.02-0.95;P=0.045).CONCLUSION The risk of LNM is higher than expected when using the current expanded indication for UDEGC.Histological evaluation could provide useful clues for reducing the risk of LNM.

Association of visceral obesity and early colorectal neoplasia

AIM:To examine whether visceral adipose tissue(VAT)serves as a risk factor for colorectal adenoma-early colorectal cancer(CRC)sequence.METHODS:A retrospective case-control study was conducted with 153 patients with stageⅠCRC,age/sex-matched 554 patients with colorectal adenoma and557 normal controls.All subjects underwent various laboratory tests,abdominal fat computed tomography(CT),and colonoscopy.VAT was defined as an intraabdominal adipose tissue area measured by CT scan.Adipose tissue area was measured at the level of the umbilicus from CT scan.We used the lowest quartile of VAT and subcutaneous adipose tissue area as a reference group.RESULTS:The body mass index(BMI),total cholesterol,fasting glucose and VAT areas were significantly different among normal,adenoma and CRC groups.The VAT area was 120.6±49.0 cm2in normal controls,130.6±58.4 cm2in adenoma group and 117.6±51.6cm2in CRC group(P=0.002).In univariate analysis,increased BMI was a risk factor for CRC compared to control(P=0.025).However,VAT area was not a risk factor for CRC compared to control.In multivariate analysis that adjusted for smoking,alcohol consumption and subcutaneous adipose tissue area,VAT area was inversely related to CRC,compared to the adenoma(OR=0.53,95%CI:0.31-0.92,highest quartile vs lowest quartile).CONCLUSION:Our study shows that visceral obesity is not a risk factor for early CRC.Visceral obesity might influence the normal-adenoma sequence but not the adenoma-early carcinoma sequence.

Characteristics of fever and response to antipyretic therapy in military personnel with adenovirus-positive community acquired pneumonia

Background:In 2014,an outbreak of adenoviral pneumonia occurred in the Korean military training center.However,there are limited data on the characteristics of the fever and its response to antipyretic therapy in immunocompetent adults with adenovirus-positive community-acquired pneumonia(CAP).Methods:The medical records of the patients who were admitted to the Armed Forces Chuncheon Hospital for the treatment of CAP between January 2014 and December 2016 were retrospectively analyzed.The patients were divided into three groups,namely,the adenovirus-positive(Adv)group,the adenovirus-negative(Non-Adv)group and the unknown pathogen group,according to the results of a polymerase chain reaction(PCR)test and sputum culture used to measure adenovirus and other bacteria or viruses in respiratory specimens.We evaluated and compared the demographics,clinicolaboratory findings and radiological findings upon admission between the two groups.Results:Out of the 251 military personnel with CAP during the study periods,67 were classified into the Adv group,while 134 were classified into the Non-Adv group and 50 were classified into the unknown pathogen group.The patients in the Adv group had a longer duration of fever after admission((3.2±1.6)d vs.(1.9±1.2)d vs.(2.2±1.5)d,P=0.018)and symptom onset((5.8±2.2)d vs.(3.9±2.5)d vs.(3.7±2.0)d,P=0.006)than patients in the Non-Adv and unknown pathogen groups,respectively.The patients in the Adv group had a higher mean temperature at admission(37.8±0.3 vs.37.3±0.3 vs.37.3±0.3,P=0.005),and more patients were observed over 40 and 39 to 40(14.9%vs.2.2%vs.4.0%,35.8%vs.3.7%vs.6.0%,P<0.001)than those in the Non-Adv and unknown pathogen groups,respectively.The Adv group more commonly had no response or exhibited adverse events after antipyretic treatment compared to the Non-Adv group(17.9%vs.1.5%,35.0%vs.4.3%,P<0.001,P=0.05,respectively).In addition,the time from admission to overall clinical stabilization was significantly longer in the patients in the Adv group than in those in the Non-Adv group((4.3±2.8)d vs.(2.9±1.8)d,P=0.034,respectively).Furthermore,no significant difference in the length of hospital stay was observed between the two groups,and no patient died in either group.Conclusions:In this study,Adv-positive CAP in immunocompetent military personnel patients had distinct fever characteristics and responses to antipyretic treatment.