Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Long-Term Clinical Effects of Carotid Intraplaque Neovascularization in Patients with Coronary Artery Disease.

OBJECTIVE: To investigate the predictive value of intraplaque neovascularization (IPN) for cardiovascular outcomes. MATERIALS AND METHODS: We evaluated 217 patients with coronary artery disease (CAD) (158 men; mean age, 68 ± 10 years) with a maximal carotid plaque thickness ≥ 1.5 mm for the presence of IPN using contrast-enhanced ultrasonography. We compared patients with (n = 116) and without (n = 101) IPN during the follow-up period and investigated the predictors of major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, coronary artery revascularization, and transient ischemic accident/stroke. RESULTS: During the mean follow-up period of 995 ± 610 days, the MACE rate was 6% (13/217). Patients with IPN had a higher maximal thickness than those without IPN (2.86 ± 1.01 vs. 2.61 ± 0.84 mm, p = 0.046). Common carotid artery-peak systolic velocity, left ventricular mass index (LVMI), and ventricular-vascular coupling index were significantly correlated with MACE. However, on multivariate Cox regression analysis, increased LVMI was independently related to MACE (p < 0.05). The presence of IPN could not predict MACE. CONCLUSION: The presence of IPN was related to a higher plaque thickness but could not predict cardiovascular outcomes better than conventional clinical factors in patients with CAD.

Current Anticoagulant Usage Patterns and Determinants in Korean Patients with Nonvalvular Atrial Fibrillation.

PURPOSE: Stroke prevention in patients with atrial fibrillation (AF) is influenced by many factors. Using a contemporary registry, we evaluated variables associated with the use of warfarin or direct oral anticoagulants (OACs). MATERIALS AND METHODS: In the prospective multicenter CODE-AF registry, 10529 patients with AF were evaluated. Multivariate analyses were performed to identify variables associated with the use of anticoagulants. RESULTS: The mean age of the patients was 66.9±14.4 years, and 64.9% were men. The mean CHA2DS2-VASc and HAS-BLED scores were 2.6±1.7 and 1.8±1.1, respectively. In patients with high stroke risk (CHA2DS2-VASc ≥2), OACs were used in 83.2%, including direct OAC in 68.8%. The most important factors for non-OAC treatment were end-stage renal disease [odds ratio (OR) 0.27; 95% confidence interval (CI): 0.19-0.40], myocardial infarct (OR 0.53; 95% CI: 0.40-0.72), and major bleeding (OR 0.57; 95% CI: 0.39-0.84). Female sex (OR 1.40; 95% CI: 1.21-1.61), cancer (OR 1.78; 95% CI: 1.38-2.29), and smoking (OR 1.60; 95% CI: 1.15-2.24) were factors favoring direct OAC use over warfarin. Among patients receiving OACs, the rate of combined antiplatelet agents was 7.8%. However, 73.6% of patients did not have any indication for a combination of antiplatelet agents. CONCLUSION: Renal disease and history of valvular heart disease were associated with warfarin use, while cancer and smoking status were associated with direct OAC use in high stroke risk patients. The combination of antiplatelet agents with OAC was prescribed in 73.6% of patients without definite indications recommended by guidelines.

Reduced Coronary Flow Reserve Is Associated with Impaired Ventricular-vascular Interaction in Patients with Obstructive Sleep Apnea.

Background and Objectives: Obstructive sleep apnea (OSA) is associated with cardiac and arterial damage and adverse cardiovascular outcomes. We aimed to determine whether coronary flow reserve (CFR), which represents microvascular dysfunction, might be associated with the ventricular-vascular coupling index (VVI), which represents the afterload-adjusted contractility in patients with OSA. Methods: We enrolled 281 patients (257 males; mean age, 43±11 years) with newly diagnosed OSA. Transthoracic echocardiography was performed, and adenosine-associated CFR was measured in the left anterior descending coronary artery. We evaluated the differences between the patients with normal CFR ≥2.5 and reduced CFR <2.5. VVI was calculated using the effective arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees) as follows: 10×Ea/Ees. Results: The normal CFR group (n=214) showed increased Ees (7.28±2.31 vs. 8.14±2.33 mmHg/mL, p=0.016) and preserved VVI (3.17±1.53 vs. 2.78±1.20, p=0.044) compared with the reduced CFR group (n=67). There were no differences in LV dimension, LV ejection fraction, left atrial-volume index, E/e', left atrial strain and LV global longitudinal strain between the 2 groups (all p>0.05). CFR was significantly correlated to Ees (r=0.139; p=0.023) and VVI (r=-0.137; p=0.025). Conclusions: Reduced CFR is associated with decreased Ees and impaired VVI in OSA patients. It suggests the necessity of more intensive observation in OSA patients with reduced CFR to improve cardiovascular outcomes.

A prospective survey of the persistence of warfarin or NOAC in nonvalvular atrial fibrillation: a COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF).

BACKGROUND/AIMS: Efforts to reduce stroke in patients with atrial fibrillation (AF) have focused on increasing physician adherence to oral anticoagulant (OAC) guidelines; however, the high early discontinuation rate of vitamin K antagonists (VKAs) is a limitation. Although non-VKA OACs (NOACs) are more convenient to administer than warfarin, their lack of monitoring may predispose patients to nonpersistence. We compared the persistence of NOAC and VKA treatment for AF in real-world practice. METHODS: In a prospective observational registry (COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation [CODE-AF] registry), 7,013 patients with nonvalvular AF (mean age 67.2 ± 10.9 years, women 36.4%) were consecutively enrolled between June 2016 and June 2017 from 10 tertiary hospitals in Korea. This study included 3,381 patients who started OAC 30 days before enrollment (maintenance group) and 572 patients who newly started OAC (new-starter group). The persistence rate of OAC was evaluated. RESULTS: In the maintenance group, persistence to OAC declined during 6 months, to 88.3% for VKA and 95.5% for NOAC (p < 0.0001). However, the persistence rate was not different among NOACs. In the new-starter group, persistence to OAC declined during 6 months, to 78.9% for VKA and 92.1% for NOAC (p < 0.0001). The persistence rate was lower for rivaroxaban (83.7%) than apixaban (94.6%) and edoxaban (94.1%, p < 0.001). In the new-starter group, diabetes, valve disease, and cancer were related to nonpersistence of OAC. CONCLUSION: Nonpersistence was significantly lower with NOAC than VKA in both the maintenance and new-starter groups. In only the new-starter group, apixaban or edoxaban showed higher persistence rates than rivaroxaban.

The Electrical Isolation of the Left Atrial Posterior Wall in Catheter Ablation of Persistent Atrial Fibrillation.

OBJECTIVES: This study explored whether complete electrical isolation of the left atrial (LA) posterior wall improves the rhythm outcome of catheter ablation of persistent atrial fibrillation (AF). BACKGROUND: Although the STAR AF2 (Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II) proved no additional benefit of empirical extra-pulmonary vein (PV) LA ablation, the long-term recurrence rate after circumferential PV isolation (CPVI) alone remains high. METHODS: We randomly assigned 217 patients with persistent AF (83.1% men, age 58.7 ± 10.8 years, 73.3% long-standing persistent AF) to ablation with CPVI alone (CPVI group) or CPVI with a POsterior wall Box Isolation (POBI group). The endpoint of the POBI group was the elimination of the posterior atrial potentials by roof and posterior inferior lines and touch-up focal ablation. RESULTS: After a mean follow-up of 16.2 ± 8.8 months, the clinical recurrence rate did not significantly differ between the 2 groups (23.8% vs. 26.5%; p = 0.779) in the CPVI and POBI groups. The recurrence rate for atrial tachycardias (16.0% vs. 11.1%; p = 0.913) and cardioversion rates (6.7% vs. 13.7%; p = 0.093) to control clinical recurrences also did not significantly differ between the 2 groups. At the final follow-up, sinus rhythm was maintained without antiarrhythmic drug in 50.5% and 55.9% in the CPVI and POBI groups, respectively (p = 0.522). No significant difference was found in the major complication rates between the 2 groups, but the total ablation time was significantly longer in the POBI group (4,289 ± 1,837 s vs. 5,365 ± 2,358 s; p < 0.001). CONCLUSIONS: In patients with persistent AF, an empirical complete POBI did not improve the rhythm outcome of catheter ablation or influence the type of recurrent atrial arrhythmia. (Comparison of Circumferential Pulmonary Vein Isolation Alone Versus Linear Ablation in Addition to Circumferential Pulmonary Vein Isolation for Catheter Ablation in Persistent Atrial Fibrillation: Prospective Randomized Controlled Trial; NCT02721121).

2018 Korean Guideline of Atrial Fibrillation Management.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population. The Korean Heart Rhythm Society organized a Korean AF Management Guideline Committee and analyzed all available studies regarding the management of AF, including studies on Korean patients. This guideline is based on recent data of the Korean population and the recent guidelines of the European Society of Cardiology, European Association for Cardio-Thoracic Surgery, American Heart Association, and Asia Pacific Heart Rhythm Society. Expert consensus or guidelines for the optimal management of Korean patients with AF were achieved after a systematic review with intensive discussion. This article provides general principles for appropriate risk stratification and selection of anticoagulation therapy in Korean patients with AF. This guideline deals with optimal stroke prevention, screening, rate and rhythm control, risk factor management, and integrated management of AF.

Clinical characteristics and prevalence of adrenal insufficiency in hemodynamically stable patients with cirrhosis.

It is well known that adrenal insufficiency is common in septic shock or hemodynamically unstable patients. But, there is as yet no sufficient clinically significant data about the exact prevalence or differences in the cause of cirrhosis with adrenal insufficiency. To investigate adrenal insufficiency prevalence in hemodynamically stable patients with cirrhosis and determine differences based on cirrhosis severity or etiology.From July 2011 to December 2012, 69 hemodynamically stable patients with cirrhosis without infection admitted at Hallym University Medical Center were enrolled. Adrenal insufficiency was defined as a peak cortisol level < 18 µg/dL, 30 or 60 minutes after 250 µg Synacthen injection.The study included 55 male patients (79.7%), and the mean age was 57.9 ±â€Š12.9 years. Cirrhosis etiology was alcohol consumption, HBV, HCV, both viral and alcohol related, and cryptogenic in 49, 15, 7, 11, 9 patients, respectively. Adrenal insufficiency occurred in 24 patients (34.8%). No differences were found in age, sex, mean arterial pressure, heart rate, HDL, cirrhosis etiology, degree of alcohol consumption, encephalopathy, variceal bleeding history, or hepatocellular carcinoma between patients with or without adrenal insufficiency. Serum albumin level was lower (P < .05), and INR was higher (P < .05) in patients with than in those without adrenal insufficiency. However, multivariate analysis revealed no independent adrenal insufficiency predictor. Significant negative correlations were found between Child-Pugh score and peak cortisol levels (γ=-0.365, P = .008).Adrenal insufficiency was frequent even in hemodynamically stable patients with cirrhosis and tended to be associated with only liver disease severity, being unrelated to cirrhosis etiology.

Evidence from a familial case suggests maternal inheritance of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an idiopathic autoimmune liver disease characterized by chronic cholestasis and destruction of the intrahepatic bile ducts. Similar to other autoimmune diseases, the pathogenesis of PBC is considered to be a complex etiologic phenomenon involving the interaction of genetic and environmental factors. Although a number of common variants associated with PBC have been reported from genome-wide association studies, a precise genetic mechanism underlying PBC has yet to be identified. Here, we describe a family with four sisters who were diagnosed with PBC. After the diagnosis of the index patient who was in an advanced stage of PBC, one sister presented with acute hepatitis, and two sisters were subsequently diagnosed with PBC. Notably, one half-sister with a different mother exhibited no evidence of PBC following clinical investigation. Our report suggests the possibility of a maternal inheritance of PBC susceptibility. Moreover, judging from the high-penetrance of the disease observed in this family, we inferred that a pathogenic genetic variant might be the cause of PBC development. We describe a family that exhibited diverse clinical presentations of PBC that included asymptomatic stages with mildly increased liver enzyme levels and symptomatic stages with acute hepatitis or advanced liver fibrosis. Additional studies are needed to investigate the role of genetic factors in the pathogenesis of this rare autoimmune disease.

The pharmacodynamics of low and standard doses of ticagrelor in patients with end stage renal disease on hemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) respond poorly to clopidogrel. We assessed the utility of low-dose ticagrelor in ESRD patients on maintenance HD. METHODS: In this single-center, prospective, randomized pharmacodynamic study, 52 ESRD patients on HD were prescribed clopidogrel (300mg loading dose [LD], then 75mg daily), standard-dose ticagrelor (180mg LD, then 90mg twice daily), or low-dose ticagrelor (90mg LD, then 90mg daily) for 14days. Platelet function was evaluated before and after therapy via light transmittance aggregometry and the VerifyNow™ P2Y12 assay. RESULTS: The adenosine diphosphate (ADP)-induced maximal extent of platelet aggregation differed significantly between the low-dose ticagrelor and clopidogrel groups (ANCOVA, p=0.04 after stimulation with 5µmol/L ADP; p<0.01 after stimulation with 20µmol/L ADP). Inhibition of platelet aggregation increased significantly in the order of clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor, as revealed by adjusted intergroup comparison analysis (ANCOVA, p=0.04 after stimulation with 5µmol/L ADP; p=0.005 after stimulation with 20µmol/L ADP). The rates of onset of the antiplatelet effect curves from 0 to 5h after administration of the LDs were greater in the standard- and low-dose ticagrelor groups than in the clopidogrel group. Significant sequential reductions in P2Y12 reaction units were noted, in the following order: clopidogrel, low-dose ticagrelor, and standard-dose ticagrelor (ANCOVA, p<0.001). No bleeding occurred in the low-dose ticagrelor group. CONCLUSIONS: Low-dose ticagrelor afforded greater platelet inhibition than did clopidogrel in ESRD patients on HD.

Close look at the experiences of patients enrolled in a clinical trial of acupuncture treatment for atrial fibrillation in Korea: a qualitative study nested within a randomised controlled trial.

OBJECTIVE: To explore the experiences of patients with atrial fibrillation (AF) in the context of a prospective, two-parallel-armed, participant-blinded and assessor-blinded sham-controlled randomised trial. DESIGN: A nested qualitative study within an ongoing randomised controlled trial to explore acupuncture's antiarrhythmic effects on drug refractory acupuncture in persistent atrial fibrillation (AF) (ACU-AF trial). PARTICIPANTS: Participants were recruited using purposeful sampling and a maximum variation strategy with regard to treatment allocation (treatment or control) and protocol completion (completion or non-completion). SETTING: This was a single-centre in-depth interview qualitative study conducted at a tertiary-level university hospital in Seoul, Republic of Korea. RESULTS: Data saturation was reached after 8 participants. Thematic analysis identified that most patients were not aware of their condition until medical check-up; physician referral was the main reason for trial participation, and patients had high expectations regardless of previous acupuncture experiences. Patients tended to depend on their physicians' opinions because they felt helpless of their condition. No one questioned their assigned treatment groups and generally believed acupuncture treatment was different for cardiovascular diseases. A few patients expressed disappointment in the strict and rigid protocols, in which most practitioners refrained from explaining their acupuncture procedures. CONCLUSIONS: For cardiovascular patients their physician's advice was one of the biggest reasons for enrolling in the acupuncture trial therefore relying on standard recruitment methods may not be effective. Fortunately both real and sham acupuncture groups in our sample were receiving treatment as intended, but in the future, designing a more pragmatic trial (better reflecting clinical settings, expanding the inclusion criteria and using more treatment points) will allow researchers to better explore the comprehensive effects of acupuncture. The findings of this study will allow researchers to improve the currently ongoing ACU-AF trial and to further help interpretation of main trial outcomes once the trial is completed. TRIAL REGISTRATION NUMBER: NCT02110537.

Effect of Coffee Added to a Polyethylene glycol plus Ascorbic acid Solution for Bowel Preparation prior to Colonoscopy.

BACKGROUND AND AIMS: Conventional bowel cleansers for colonoscopy have an unpleasant taste and a large volume of solution must be ingested. Coffee increases bowel motility and has an intense flavor. The addition of coffee to a polyethylene glycol+ascorbic acid solution reduces the volume of the solution to be consumed without reducing efficacy, improves the taste of the solution and enhances patient comfort. METHODS: Outpatients with clinical indication or people who wanted screening for cancer were considered eligible. Control group (PEGAS group) consumed a 1-L solution of polyethylene glycol+ascorbic acid twice. Study group (COF group) consumed 750 mL of coffee+polyethylene glycol+ascorbic acid twice. Bowel cleansing was rated using the Aronchick, Ottawa scale, polyp detection rate and colonoscopic insertion time. Tolerability, acceptability, preference, and adverse events were investigated by questionnaires. RESULTS: The COF group had non-inferiority in efficacy (non-inferiority margin, -15%; lower limit of 95% confidence interval for difference between success rates, -4.7% and -8.4% from both scales, respectively). Polyp detection rates were 0.48 and 0.60, respectively (P=0.067). Colonoscopic insertion times were 323.6+/-166.8 s and 330.7+/-243.6 s, respectively (P=0.831). Significant improvement was observed with respect to ease of drinking (P=0.012), taste (P=0.026) and preference (P=0.046) in the COF group. Adverse events occurred in 52.4% and 60.4% in the two groups, respectively (P = 0.251). CONCLUSION: The addition of coffee to polyethylene glycol+ascorbic acid solution reduces the required volume for bowel preparation without reduced efficacy and enhances patient comfort in coffee-drinkers.

Changes in the Practice of Coronary Revascularization between 2006 and 2010 in the Republic of Korea.

PURPOSE: Evidence suggests that technological innovations and reimbursement schemes of the National Health Insurance Service may have impacted the management of coronary artery disease. Thus, we investigated changes in the practice patterns of coronary revascularization. MATERIALS AND METHODS: Revascularization and in-hospital mortality among Koreans ≥20 years old were identified from medical claims filed between 2006 and 2010. The age- and sex-standardized procedure rate per 100,000 person-years was calculated directly from the distribution of the 2008 Korean population. RESULTS: The coronary revascularization rate increased from 116.1 (95% confidence interval, 114.9-117.2) in 2006 to 131.0 (129.9-132.1) in 2010. Compared to the rate ratios in 2006, the rate ratios for percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in 2010 were 1.16 (1.15-1.17) and 0.80 (0.76-0.84), respectively. Among patients who received PCI, the percentage with drug-eluting stents increased from 89.1% in 2006 to 93.0% in 2010. In-hospital mortality rates from PCI significantly increased during the study period (p=0.03), whereas those from CABG significantly decreased (p=0.01). The in-hospital mortality rates for PCI and CABG were higher in elderly and female patients and at the lowest-volume hospitals. CONCLUSION: The annual volume of coronary revascularization continuously increased between 2006 and 2010 in Korea, although this trend differed according to procedure type. A high percentage of drug-eluting stent procedures and a high rate of in-hospital mortality at low-volume hospitals were noted.

Endoscopic submucosal dissection for early gastric cancer with undifferentiated-type histology: A meta-analysis.

AIM: To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) with undifferentiated-type histology. METHODS: A systematic literature review was conducted using the core databases. Complete resection, curative resection, en bloc resection, recurrence and adverse event rate were extracted and analyzed. A random effect model was applied. The methodological quality of the enrolled studies was assessed using the Newcastle-Ottawa Scale. Publication bias was evaluated using a funnel plot, the trim and fill method, Egger's test, and a rank correlation test. RESULTS: Fourteen retrospective studies between 2009 and 2014 were identified (972 EGC lesions with undifferentiated-type histology). The total en bloc and complete resection rates were estimated as 92.1% (95%CI: 87.4%-95.2%) and 77.5% (95%CI: 69.3%-84%), respectively. The total curative resection rate was 61.4% (95%CI: 44.5%-75.9%). The overall recurrence rate was 7.6% (95%CI: 3.4%-16%). Limited to histologically diagnosed expanded-criteria lesions, the en bloc and complete resection rates were 91.2% and 85.6%, respectively. The curative resection rate was 79.8%. CONCLUSION: In this analysis, ESD is a technically feasible treatment modality for EGC with undifferentiated-type histology. Long-term studies are needed to confirm these therapeutic outcomes.

Platelet reactivity after receiving clopidogrel compared with ticagrelor in patients with kidney failure treated with hemodialysis: a randomized crossover study.

BACKGROUND: Patients with kidney failure treated with maintenance hemodialysis (HD) are poor responders to clopidogrel. More beneficial platelet-inhibiting strategies in HD patients therefore are required. STUDY DESIGN: Single-center, prospective, randomized, crossover study. SETTING & PARTICIPANTS: 25 HD patients in Seoul, Korea. INTERVENTION: Patients were randomly assigned to receive clopidogrel (300mg loading, 75mg once daily for maintenance dose) or ticagrelor (180mg loading, 90mg twice daily for maintenance dose) for 14 days, and after a 14-day washout period, crossover treatment for another 14 days. All patients received aspirin (100mg/d). OUTCOMES & MEASUREMENTS: Platelet function was evaluated predosing and at 1, 5, and 48 hours and 14 days after the first loading dose. During the offset phase, platelet function was assessed at 1 hour and 2, 4, and 14 days after the last dose by light transmittance aggregometry and the VerifyNow P2Y12 assay, and patients were genotyped for the CYP2C19*2 allele. Maximal extent of aggregation, inhibition of platelet aggregation (IPA), P2Y12 reaction units (PRUs), and percentage of inhibition were evaluated. We performed per-protocol analysis, excluding patients who did not complete the protocol. RESULTS: 9 patients did not complete the protocol (7 patients due to adverse events; 2, nonadherence). Higher IPA occurred with ticagrelor than with clopidogrel at 1, 5, and 48 hours and 14 days after loading. By 5 hours after loading, a greater proportion of patients in the ticagrelor group than in the clopidogrel group achieved IPA>50% (75% vs 12%, respectively; P<0.05) and IPA>70% (44% vs 0%, respectively; P<0.05). Rates (slope) of onset and offset of the antiplatelet effect were faster in patients receiving ticagrelor than for those receiving clopidogrel (P<0.05). Regardless of CYP2C19*2 allele, the ticagrelor group had significantly lower PRUs at all times than the clopidogrel group. LIMITATIONS: Single-center study with a small number of patients, not a double-blind study, and not intention-to-treat analysis. CONCLUSIONS: Ticagrelor may result in more rapid and greater platelet inhibition than clopidogrel in patients with kidney failure receiving HD.

A phase II study of capecitabine and oral leucovorin as a third-line chemotherapy in patients with metastatic colorectal cancer.

PURPOSE: This study was conducted to evaluate the efficacy and safety of the combination of capecitabine and oral leucovorin (LV) as a third-line chemotherapy for patients with metastatic colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens. METHOD: Patients who showed disease progression while receiving or within 6 months of discontinuing irinotecan- and oxaliplatin-containing regimens received capecitabine 825 mg/m(2) in combination with oral LV at a fixed dose of 30 mg, twice a day for 2 weeks followed by a 1-week rest. RESULTS: Twenty-five patients were enrolled from July 2011 to June 2014. Three patients achieved PR, and 11 showed SD. The overall response rate was 12 %, and disease control rate was 56 %. With a median follow-up of 6.8 months, the median time to progression was 2.8 months and the median overall survival was 7.1 months. The most common non-hematologic toxicity was hand-foot syndrome (40 %), followed by mucositis (28 %) and diarrhea (12 %). Grade 3 hand-foot syndrome occurred in two patients (8 %), and grade 3 mucositis in one. Hematologic toxicities were mild, and only one patient developed grade 3 thrombocytopenia. CONCLUSION: The combination of capecitabine and oral LV showed a modest activity and tolerable toxicity profile in metastatic CRC patients pretreated with irinotecan- and oxaliplatin-containing regimens. Oral LV seems to be able to reduce the usual dose of capecitabine when the two drugs are combined.

Transenteral bowel preparation for colonoscopy is more comfortable than the traditional method with no inferiority in efficacy.

BACKGROUND: Transenteral (TE) administration of a bowel cleanser prior to colonoscopy avoids the discomfort associated with drinking a large volume of unpalatable cleanser. AIM: To explore patient comfort, preference for future colonoscopy, the efficacy and adverse events associated with TE bowel preparation. METHODS: Bowel preparation is traditionally practised using polyethylene glycol (PEG) + ascorbic acid (ASC), which was the treatment used in the control group (peroral group; PO group). In the study group (TE group), PEG + ASC were administered directly to the third portion of the duodenum through a scope immediately after completing upper gastrointestinal endoscopy. RESULTS: A higher proportion of subjects in the TE group graded their degree of comfort as very or rather comfortable (28.4 % in the PO group, 65.1 % in the TE group; p = 0.000) and had greater preference for future colonoscopy (69.6 % in the PO group, 82.5 % in the TE group; p = 0.030), compared with the PO group. The TE group had non-inferiority in efficacy compared with the PO group (non-inferiority margin -15 %; lower limit of 95 % confidence interval for difference between success rates -6.4 %, when using the Aronchick Scale, and -7.1 % when using the Ottawa Scale). Nausea or vomiting were more prevalent during preparation in the PO group (46.1 vs. 17.5 %; p = 0.000), and dizziness was more common in the TE group (0 vs. 12.6 %; p = 0.000). CONCLUSIONS: TE preparation was found to be more comfortable than the traditional peroral method and not inferior in efficacy. The adverse events rate was acceptable.

Impact of lysophosphatidylcholine on survival and function of UEA-1(+)acLDL (+) endothelial progenitor cells in patients with coronary artery disease.

Lysophosphatidylcholine (LPC) generated from oxidized low-density lipoprotein by lipoprotein-associated phospholipase A2 plays a key role in plaque inflammation and vulnerability. Endothelial progenitor cells (EPCs) can repair injured endothelium and exert anti-inflammatory effects of vulnerable plaque. We study the impact and mechanisms of LPC on UEA-1 and acLDL binding EPCs (UEA-1(+)acLDL(+) EPCs). UEA-1(+)acLDL(+) EPCs from coronary artery disease (CAD) patients were cultured and exposed to LPC at different concentrations and different timepoints. We determined the significant concentration (40 µM). UEA-1(+)acLDL(+) EPCs were preincubated for 30 min with pravastatin (20 µM) with LY249002, a specific inhibitor of the Akt signaling pathway, and exposed for 24 h to LPC 40 µM. The survival, migration, adhesion, and proliferation of UEA-1(+)acLDL(+) EPCs were assessed. To examine the mechanisms of LPC toxicity and pravastatin effects, phosphorylated Akt and endothelial nitric oxide synthase (eNOS) levels and the ratio of Bcl-2/Bax protein expression were assessed. LPC induced apoptosis and impaired migration and adhesion of UEA-1(+)acLDL(+) EPCs significantly. The detrimental effects of LPC were attenuated by pravastatin. However, when UEA-1(+)acLDL(+) EPCs were pretreated with pravastatin and LY249002, a specific inhibitor of the Akt signaling pathway, simultaneously, the beneficial effects of pravastatin were abolished. Furthermore, LPC suppressed Akt and eNOS phosphorylation and increased Bcl-2/Bax expression. The effects of LPC on Akt/eNOS and Bcl-2/Bax activity were reversed by pravastatin. In conclusion, LPC inhibited UEA-1(+)acLDL(+) EPCs survival and impaired its functions, and these were attributable to inhibition of the Akt/eNOS and Bcl-2/Bax pathway. Pravastatin reversed the detrimental action of LPC. These findings suggest that LPC inhibition can be a possible strategy for CAD through EPC revitalization.

Is annual endoscopic surveillance necessary for the early detection of gastric remnant cancer in Korea? A retrospective multi-center study.

BACKGROUND/AIMS: This study investigated the clinical characteristics, survival outcomes of the patients with gastric remnant cancers (GRC) diagnosed after gastric cancer surgery and the need of annual endoscopic surveillance after gastric resection for early detection of GRC. METHODOLOGY: We reviewed the medical records of 30 patients who underwent endoscopy and diagnosed with GRC between 1999 and 2009. We analyzed the clinical features, tumor characteristics, regular endoscopic surveillance, treatment, and survival outcomes. RESULTS: The median time interval between first operation and diagnosis of GRC was 36 months. Fifteen patients (50%) had GRC at non-anastomotic sites. Seventeen patients (56.7%) underwent annual endoscopic surveillance and nine patients (30%) had no symptom at the time of diagnosis of GRC. GRC were detected earlier in patients with annual endoscopic surveillance than those without surveillance (p=0.0014). The median overall survival (OS) after the diagnosis of GRC for all patients was 35.9 months. The median OS of patients with curative resection including endoscopic resection for early gastric cancer was longer than those without resectability (46.3 vs. 13.6 months, p=0.0026). CONCLUSIONS: These results suggest that annual endoscopic surveillance program after gastric partial resection would be helpful to detect early cancer of remnant stomach for curative resection.

Characteristics of mesenchymal stem cells originating from the bilateral inferior turbinate in humans with nasal septal deviation.

BACKGROUND AND OBJECTIVES: Nasal septal deviation (NSD) is often associated with overgrowth of the unilateral inferior turbinate. In vivo and in vitro studies indicate that human mesenchymal stem cells (MSCs) are able to differentiate into multiple cell types, including osteoblasts. We tested the hypothesis that turbinate size affects human turbinate-derived MSC (hTMSCs) quantity, proliferation, and differentiation into osteogenic lineages, and that hypertrophic turbinates may predispose to NSD on the contralateral side. SUBJECTS AND METHODS: The hypertrophic and contralateral inferior turbinate tissues used in our study were obtained and cultured from the tissue discarded from 10 patients who underwent septoplasty and partial turbinectomy. After isolating the hTMSCs from both turbinates, the cells were enumerated using an automated cell counter. The expression of surface markers for MSCs over four passages was assessed by fluorescent-activated cell sorting analysis (FACS), and cell proliferation was assessed using a cell counting kit (CCK)-8 according to turbinate size. In addition, osteogenic differentiation of hTMSCs was identified using alkaline phosphatase (ALP) and alizarin red S staining, after which osteoblastic gene expression was evaluated. RESULTS: There was no significant difference in the number of hTMSCs. FACS analysis revealed that the hTMSCs were negative for CD14, CD19, CD34, and HLA-DR, and positive for CD29, CD73, and CD90, representing a characteristic MSC phenotype, with no significant difference between the two groups. The cellular proliferation and osteogenic differentiation potential of the hTMSCs were also not significantly different between the two groups. CONCLUSIONS: We conclude that turbinate size does not affect the characterization, proliferation, and osteogenic differentiation potential of hTMSCs in vitro test, and therefore should not affect the clinical decision of whether to use autologous or allogenic hTMSCs. However, more experiments are required to definitively state the relationship of hTMSCs with turbinate size or the process NSD in humans.