Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

BACKGROUND AND AIMS: A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. APPROACH AND RESULTS: Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28 y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). CONCLUSIONS: In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Efficacy of Transarterial Chemoembolization (TACE) for Early-Stage Hepatocellular Carcinoma.

Backgound and Objectives: The treatments of choice for patients with early-stage hepatocellular carcinoma (HCC) are surgical resection, local ablation therapy, and liver transplantation; however, transarterial chemoembolization (TACE) is commonly performed due to variations among patients and liver diseases. This study aimed to assess the efficacy of TACE in patients with early-stage HCC. Materials and Methods: A retrospective analysis was performed of all TACE procedures performed at Kyung Hee University Hospital at Gangdong over a 15-year period (July 2006 to November 2021). The study included a total of 97 eligible patients with early-stage HCC ≤ 5 cm initially treated with TACE. The mean participant age was 63.47 ± 11.02 years; 69 were men (71.1%). The number of Child-Pugh class A patients was the highest (74 patients [76.3%]), followed by Child-Pugh class B (19 patients [19.6%]) and Child-Pugh class C (4 patients [4.12%]). Results: A complete response was achieved in 84 (86.6%) patients after the first TACE procedure, with 1-, 2-, and 3-year survival rates of 91.8%, 87.3%, and 75.4%, respectively. In the multivariate analysis, the patients with a low initial alpha-fetoprotein (AFP) ≤ 20 ng/mL (p = 0.02) and a complete response after the first TACE (p = 0.03) were associated with favorable overall survival. Conclusions: TACE can be used to treat patients with early-stage HCC who are unsuitable for ablation or surgery. If patients are well selected, TACE may be an alternative treatment for patients with low AFP levels who respond well to the initial TACE procedure.

Endoscopic resection of early gastric cancer.

Endoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without metastases. Existing endoscopic mucosal resection (EMR) is easy to perform, has few complications, and can be applied when the lesion size is small. However, en bloc and complete resection rates vary depending on the size and severity of the lesion. EMR using the cap-mounted panendoscopic method and EMR after circumferential preamputation of the lesion are useful in the treatment of EGC. However, completely oversized lesions (≥2 cm) and lesions associated with ulcers or submucosal fibrosis are more likely to fail resection. Endoscopic submucosal dissection has been widely used to resect tumors larger than 2 cm in diameter and has a higher acceptable complication rate and en bloc and complete resection rates than EMR. ER for EGC is superior to surgical resection in terms of improving patient quality of life. Additionally, compared to surgery, emergency rooms have a lower rate of treatment-related complications, shorter hospital stays, and lower costs. Accordingly, the indications for ER are expanding in the field of therapeutic endoscopy. Long-term outcomes regarding recurrence are excellent in both absolute and extended criteria for ER in EGC. Close surveillance should be performed after ER to detect early metachronous gastric cancer and precancerous lesions that can be treated with ER. Follow-up gastroscopy and abdominopelvic computed tomography scans every 6 to 12 months are recommended for patients who undergo curative ER for EGC on absolute or extended criteria.

Personalized Antiviral Drug Selection in Patients With Chronic Hepatitis B Using a Machine Learning Model: A Multinational Study.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) for the prevention of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B; however, it has distinct long-term renal and bone toxicities. This study aimed to develop and validate a machine learning model (designated as Prediction of Liver cancer using Artificial intelligence-driven model for Network-antiviral Selection for hepatitis B [PLAN-S]) to predict an individualized risk of HCC during ETV or TDF therapy. METHODS: This multinational study included 13,970 patients with chronic hepatitis B. The derivation (n = 6,790), Korean validation (n = 4,543), and Hong Kong-Taiwan validation cohorts (n = 2,637) were established. Patients were classified as the TDF-superior group when a PLAN-S-predicted HCC risk under ETV treatment is greater than under TDF treatment, and the others were defined as the TDF-nonsuperior group. RESULTS: The PLAN-S model was derived using 8 variables and generated a c-index between 0.67 and 0.78 for each cohort. The TDF-superior group included a higher proportion of male patients and patients with cirrhosis than the TDF-nonsuperior group. In the derivation, Korean validation, and Hong Kong-Taiwan validation cohorts, 65.3%, 63.5%, and 76.4% of patients were classified as the TDF-superior group, respectively. In the TDF-superior group of each cohort, TDF was associated with a significantly lower risk of HCC than ETV (hazard ratio = 0.60-0.73, all P < 0.05). In the TDF-nonsuperior group, however, there was no significant difference between the 2 drugs (hazard ratio = 1.16-1.29, all P > 0.1). DISCUSSION: Considering the individual HCC risk predicted by PLAN-S and the potential TDF-related toxicities, TDF and ETV treatment may be recommended for the TDF-superior and TDF-nonsuperior groups, respectively.

Hepatocellular carcinoma risk in patients with chronic hepatitis B receiving tenofovir- vs. entecavir-based regimens: Individual patient data meta-analysis.

BACKGROUND & AIMS: The comparative risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) receiving tenofovir disoproxil fumarate (TDF) vs. entecavir (ETV) remains controversial. In this individual patient data (IPD) meta-analysis, we aimed to compare HCC risk between the two drugs and identify subgroups who may benefit more from one treatment than the other. METHODS: Published meta-analyses, electronic databases and congress proceedings were searched to identify eligible studies through January 2021. We compared HCC risk between the two drugs using a multivariable Cox proportional hazards model with anonymised IPD from treatment-naïve patients with CHB receiving TDF or ETV for ≥1 year. Treatment effect consistency was explored in propensity score matching (PSM), weighting (PSW) and subgroup analyses for age, sex, hepatitis B e-antigen (HBeAg) positivity, cirrhosis and diabetes status. RESULTS: We included 11 studies from Korea, Taiwan and Hong Kong involving 42,939 patients receiving TDF (n = 6,979) or ETV (n = 35,960) monotherapy. Patients receiving TDF had significantly lower HCC risk (adjusted hazard ratio [HR] 0.77; 95% CI 0.61-0.98; p = 0.03). Lower HCC risk with TDF was consistently observed in PSM (HR 0.73; 95% CI 0.59-0.88; p <0.01) and PSW (HR 0.83; 95% CI 0.67-1.03; p = 0.10) analyses and in all subgroups, with statistical significance in the ≥50 years of age (HR 0.76; 95% CI 0.58-1.00; p <0.05), male (HR 0.74; 95% CI 0.58-0.96; p = 0.02), HBeAg-positive (HR 0.69; 95% CI 0.49-0.97; p = 0.03) and non-diabetic (HR 0.79; 95% CI 0.63-1.00; p <0.05) subgroups. CONCLUSION: TDF was associated with significantly lower HCC risk than ETV in patients with CHB, particularly those with HBeAg positivity. Longer follow-up may be needed to better define incidence differences between the treatments in various subgroups. IMPACT AND IMPLICATIONS: Previous aggregate data meta-analyses have reported inconsistent conclusions on the relative effectiveness of tenofovir disoproxil fumarate and entecavir in reducing hepatocellular carcinoma risk in patients with chronic hepatitis B (CHB). This individual patient data meta-analysis on 11 studies involving 42,939 patients from Korea, Taiwan and Hong Kong suggested that tenofovir disoproxil fumarate-treated patients have a significantly lower hepatocellular carcinoma risk than entecavir-treated patients, which was observed in all subgroups of clinical interest and by different analytical methodologies. These findings should be taken into account by healthcare providers when determining the optimal course of treatment for patients with CHB and may be considered in ensuring that treatment guidelines for CHB remain pertinent.

Postresection Period-Specific Hazard of Recurrence as a Framework for Surveillance Strategy in Patients with Hepatocellular Carcinoma: A Multicenter Outcome Study.

Introduction: In spite of the high frequency of recurrence of hepatocellular carcinoma (HCC) after resection, little evidence exists to directly help to plan a reasonable schedule for the frequency and intensity of postoperative surveillance for recurrence. Methods: 1,918 consecutive patients with Child-Turcott-Pugh class A who had T1- or T2-staged HCCs detected by active surveillance and underwent curative resection for their tumors at 3 teaching hospitals in Korea, followed by recurrence screening at 6-monthly or shorter intervals. To set an evidence-based timetable for postoperative surveillance, we investigated the annual hazard rate of recurrence through postoperative year 10 in patients undergoing hepatectomy for HCC, and the clinical and morphological phenotypes associated with early versus late recurrence. Results: The estimated hazard rate for recurrence peaked during year 0-1 (21.7%), with a subsequent gradual decrease through 5 years, followed by stabilization at <7.0% until year 10, except in the case of cirrhotics, who had a rate of 10.5% during year 4-5. Multivariate time-to-recurrence analysis by recurrence period revealed that serum alpha-fetoprotein ≥200 ng/mL, larger size of tumor, tumor multiplicity, microvascular invasion, capsular invasion, and higher METAVIR fibrosis stage were significantly related to disease recurrence within 5 years after resection, while cirrhosis (METAVIR F4) alone was related to disease recurrence beyond 5 years (Ps < 0.05). Post-relapse overall survival was better in the latter group (p = 0.033). Conclusions: Our chronological and morphological insights into recurrence after resection of primary HCCs may help implement an optimal intensity of surveillance for recurrence.

Real-World Single-Center Comparison of the Safety and Efficacy of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide in Patients with Chronic Hepatitis B.

INTRODUCTION: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting. METHODS: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled. RESULTS: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0-74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894). CONCLUSIONS: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Development of a Novel Prognostic Model for Predicting Lymph Node Metastasis in Early Colorectal Cancer: Analysis Based on the Surveillance, Epidemiology, and End Results Database.

BACKGROUND: Identification of a simplified prediction model for lymph node metastasis (LNM) for patients with early colorectal cancer (CRC) is urgently needed to determine treatment and follow-up strategies. Therefore, in this study, we aimed to develop an accurate predictive model for LNM in early CRC. METHODS: We analyzed data from the 2004-2016 Surveillance Epidemiology and End Results database to develop and validate prediction models for LNM. Seven models, namely, logistic regression, XGBoost, k-nearest neighbors, classification and regression trees model, support vector machines, neural network, and random forest (RF) models, were used. RESULTS: A total of 26,733 patients with a diagnosis of early CRC (T1) were analyzed. The models included 8 independent prognostic variables; age at diagnosis, sex, race, primary site, histologic type, tumor grade, and, tumor size. LNM was significantly more frequent in patients with larger tumors, women, younger patients, and patients with more poorly differentiated tumor. The RF model showed the best predictive performance in comparison to the other method, achieving an accuracy of 96.0%, a sensitivity of 99.7%, a specificity of 92.9%, and an area under the curve of 0.991. Tumor size is the most important features in predicting LNM in early CRC. CONCLUSION: We established a simplified reproducible predictive model for LNM in early CRC that could be used to guide treatment decisions. These findings warrant further confirmation in large prospective clinical trials.

Real-world single-center experience with direct-acting antivirals for improvement of the liver fibrosis after chronic hepatitis C treatment.

BACKGROUND: Recently, new direct-acting antivirals (DAAs) are known to eradicate chronic hepatitis C (CHC) virus infection and prevent the progression of liver fibrosis. Liver fibrosis may predispose to liver cirrhosis or hepatocellular carcinoma. We investigated the effect of DAAs on liver fibrosis using non-invasive methods, and evaluated the correlations of these methods. METHODS: We retrospectively analyzed 68 patients with CHC who were treated with DAAs and reached sustained virologic response at 12 weeks post-treatment from January 2016 to October 2018. The degree of liver fibrosis was assessed using serum biomarkers, such as AST-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. Liver stiffness was assessed using two-dimensional shear-wave elastography (2 D-SWE). The pre- and post-treatment serum biomarker levels and SWE findings were evaluated and compared. RESULTS: A total of 68 patients with CHC were enrolled. The median age was 58 years (52.3-73 years) and 37 patients (54.4%) were female. After treatment, the median APRI was decreased from 0.701 to 0.328 (P < 0.0001), and the median FIB-4 was decreased from 2.355 to 1.860 (P < 0.0001). The median kPa in 2 D-SWE significantly reduced from 6.85 to 5.66 (P = 0.013). APRI and FIB-4 were significantly correlated pre- and post-treatment; however, the correlation between the serum biomarkers and 2 D-SWE was partially significant. CONCLUSION: The serum fibrosis biomarkers and liver stiffness on 2 D-SWE were shown to be improved after the treatment with DAAs. Further research including larger number of patients is needed to compare the efficacy of each evaluating method.

Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice.

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 µL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

Novel candidate drugs in anti-tumor necrosis factor refractory Crohn's diseases: in silico study for drug repositioning.

Biologicals like anti-tumor necrosis factor (TNF) therapy for Crohn's disease (CD) are safe and effective but there is a significant rate of primary and secondary nonresponse in the patients. In this study, we applied a computational approach to discover novel drug therapies for anti-TNF refractory CD in silico. We use a transcriptome dataset (GSE100833) for the anti-TNF refractory CD patients from NCBI GEO. After co-expression analysis, we specifically investigated the extent of protein-protein interactions among genes in clusters based on a protein-protein interaction database, STRING. Pathway analysis was performed using the clEnrich function based on KEGG gene sets. Co-expressed genes in cluster 1, 2, 3, 4, up or down-regulated genes and all differentially expressed genes are highly connected. Among them, cluster 1, which is highly enriched for chemokine signaling, also showed enrichment for cytokine-cytokine receptor interaction and identifies several drugs including cyclosporin with known efficacy in CD. Vorinostat, histone deacetylase inhibitors, and piperlongumine, which is known to have inhibitory effect on activity of NF-κB, were also identified. Some alkaloids were also selected as potential therapeutic drugs. These finding suggest that they might serve as a novel therapeutic option for anti-TNF refractory CD and support the use of public molecular data and computational approaches to discover novel therapeutic options for CD.

Multidisciplinary and Multisociety Practice Guideline on Reprocessing Flexible Gastrointestinal Endoscopes and Endoscopic Accessories.

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

The current capacity and quality of colonoscopy in Korea.

BACKGROUND/AIMS: Little is known for the capacity and quality of colonoscopy, and adherence to colonoscopy surveillance guidelines in Korea. This study aimed to investigate the present and potential colonoscopic capacity, colonoscopic quality, and adherence to colonoscopy surveillance guidelines in Korea. METHODS: We surveyed representative endoscopists of 72 endoscopy units from June to August 2015, using a 36-item questionnaire regarding colonoscopic capacity, quality, and adherence to colonoscopy surveillance guidelines of each hospitals. RESULTS: Among the 62 respondents who answered the questionnaire, 51 respondents were analyzed after exclusion of 11 incomplete answers. Only 1 of 3 of endoscopy units can afford to perform additional colonoscopies in addition to current practice, and the potential maximum number of colonoscopies per week was only 42. The quality of colonoscopy was variable as reporting of quality indicators of colonoscopy were considerably variable (29.4%-94.1%) between endoscopy units. Furthermore, there are substantial gaps in the adherence to colonoscopy surveillance guidelines, as concordance rate for guideline recommendation was less than 50% in most scenarios. CONCLUSIONS: The potential capacity and quality of colonoscopy in Korea was suboptimal. Considering suboptimal reporting of colonoscopic quality indicators and low adherence rate for colonoscopy surveillance guidelines, quality improvement of colonoscopy should be underlined in Korea.

Gastrointestinal endoscopy satisfaction questionnaire is a valid tool to measure patient satisfaction in Asian country.

Patient satisfaction is a key quality indicator of gastrointestinal endoscopy (GIE). The gastrointestinal endoscopy satisfaction questionnaire (GESQ) was recently developed to assess patient satisfaction undergoing GIE in Europe; however, it was not validated in Asian countries. We aimed to translate and validate the GESQ in Korea and identify predictors for patient satisfaction during GIE.Translation of the original GESQ was performed according to accepted linguistic validation guidelines. Between March 2016 and July 2016, 350 consecutive patients were asked to complete a GESQ after GIE at Kyung Hee University Hospital. Total sum of scores was transformed from 0 to 100 by the formula: (Score-lowest possible/Score range) × 100.Exploratory and confirmatory factor analyses for construct validation reconfirmed that 4 factors were extracted from the Korean GESQ. Internal consistency reliability was acceptable with an overall Cronbach α score of 0.87. Female and nonsmoker were associated with less satisfaction with GIE (P = .021 and .006, respectively). Other factors, including age, alcohol, education or economic level, sedative endoscopy, gastroscopy with or without colonoscopy, experience of previous endoscopy, and additional examinations such as biopsy, were not associated with patient satisfaction during GIE.The Korean version of the GESQ was a valid and acceptable tool to measure satisfaction in patients who had undergone a GIE in Korea. Patient satisfaction measurement could contribute to systematic improvement of qualified GIE.

Combination therapy with polydeoxyribonucleotide and proton pump inhibitor enhances therapeutic effectiveness for gastric ulcer in rats.

AIMS: The main action of proton pump inhibitors (PPIs) is to inhibit gastric acid secretion, and PPIs are widely used to treat gastric ulcer (GU). However, if the action of promoting gastric mucosal regeneration is added, the effectiveness of GU treatment can be enhanced. Thus, in order to improve the therapeutic effect on GU, we tried to develop combination therapy promoting regeneration in injured tissue besides suppressing gastric acid secretion. MAIN METHODS: Polydeoxyribonucleotide (PDRN) was selected to evaluate tissue regeneration, and pantoprazole was chosen as one of the PPIs. GU was induced by oral administration of indomethacin once a day for 7 days. Rats in drug-administered groups were intraperitoneally injected with 100 µL normal saline, containing each drug at the indicated concentration, once a day for 14 days after inducing GU. KEY FINDINGS: PDRN and PPI combination therapy potently improved tissue regeneration and inhibited production of pro-inflammatory cytokines. PDRN treatment with or without PPI increased the concentration of cyclic adenosine-3,5'-monophosphate (cAMP) and the ratio of phosphorylated cAMP response element-binding protein (p-CREB) to cAMP response element-binding protein (CREB). PDRN treatment with or without PPI also increased the expressions of vascular endothelial growth factor (VEGF) and adenosine A2A receptor. SIGNIFICANCE: PDRN and PPI combination therapy showed more potent therapeutic effect on GU compared to the PDRN monotherapy or PPI monotherapy. The excellent therapeutic effect of PDRN and PPI combination therapy on GU appeared by promoting regeneration of damaged tissue as well as inhibiting gastric acid secretion.

Quality Metrics of a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program in Korea.

BACKGROUND/AIMS: Knowledge regarding the quality metrics of fecal immunochemical test (FIT)-based colorectal cancer screening programs is limited. The aim of this study was to investigate the performance and quality metrics of a FIT-based screening program. METHODS: In our screening program, asymptomatic subjects aged ≥50 years underwent an annual FIT, and subjects with positive FIT results underwent a subsequent colonoscopy. The performance of the FIT and colonoscopy was analyzed in individuals with a positive FIT who completed the program between 2009 and 2015 at a university hospital. RESULTS: Among the 51,439 screened participants, 75.1% completed the FIT. The positive rate was 1.1%, and the colonoscopy completion rate in these patients was 68.6%. The positive predictive values of cancer and advanced neoplasia were 5.5% and 19.1%, respectively. The adenoma detection rate in the patients who underwent colonoscopy after a positive FIT was 48.2% (60.0% for men and 33.6% for women). The group with the highest tertile quantitative FIT level showed a significantly higher detection rate of advanced neoplasia than the group with the lowest tertile (odds ratio, 2.6; 95% confidence interval, 1.4 to 5.1; p＜0.001). CONCLUSIONS: The quality metrics used in the United States and Europe may be directly introduced to other countries, including Korea. However, the optimal quality metrics should be established in each country.

Evaluation of scoring systems without endoscopic findings for predicting outcomes in patients with upper gastrointestinal bleeding.

BACKGROUND: Risk scoring systems are used to evaluate patients with upper gastrointestinal bleeding (UGIB). We compared Glasgow-Blatchford score (GBS), modified GBS (mGBS), and Pre-endoscopy Rockall score (Pre-E RS) for immediate application without endoscopic findings in predicting the need of interventions and the 30-day mortality in patients with UGIB. METHODS: Patients who visited the emergency room with UGIB from January 2007 to June 2016 were included. GBS, mGBS, and Pre-E RS were obtained for all patients. The area under the receiver-operating characteristic curves (AUC) was used to assess the accuracy of the scoring systems to determine the need for interventions and 30-day mortality. Also, we investigated the potential cutoff scores for predicting 30-day mortality and the need for interventions. RESULTS: In predicting the need for interventions, GBS (AUC = 0.727) and mGBS (AUC = 0.733) outperformed Pre-E RS (AUC = 0.564, P < 0.0001). In predicting 30-day mortality, Pre-E RS (AUC = 0.929) outperformed GBS (AUC = 0.664, P < 0.0001) and mGBS (AUC = 0.652, P < 0.0001). Based on AUC analyses of sensitivities and specificities, the optimal cutoff mGBS and GBS for the need for interventions was 9 (70.71% sensitivity, 89.35% specificity) and 9 (73.57% sensitivity, 82.90% specificity) respectively, and optimal cutoff Pre-E RS for 30-day mortality was 4 (88.0% sensitivity, 97.52% specificity). CONCLUSIONS: GBS and mGBS are considered to be moderately accurate in making an early decision about the need of interventions in patients with UGIB. Pre-E RS is considered to be highly accurate in early detection of patients at high risk for 30-day mortality without endoscopic findings. In addition, we suggested potential cutoff scores to predict the need of interventions for GBS and mGBS, and 30-day mortality for Pre-E RS. Further studies are needed to confirm the clinical applicability of results.

High C-reactive protein level is associated with high-risk adenoma.

BACKGROUND/AIMS: There is substantial evidence supporting a role of inflammation in the pathogenesis of colorectal cancer; however, little is known about the association between serum C-reactive protein (CRP) and the risk of colorectal adenoma. This study was conducted to investigate the association between serum CRP and colorectal adenoma risk. METHODS: A retrospective cross-sectional study was performed on first-time screening colonoscopies in asymptomatic subjects who also had their serum CRP level measured during a routine health check-up between September 2006 and September 2009 in Korea. Serum CRP level was compared between high-risk and low-risk adenoma groups and independent predictors of high-risk adenoma were analyzed using multivariate regression analysis. RESULTS: Among the 3,309 eligible patients, the high-risk adenoma group had higher serum CRP levels than the low-risk adenoma group (P=0.000). In addition, patients with a high-risk adenoma were more frequently included in the high CRP group than in the low CRP group (8.6% vs. 4.0%, P<0.001). The prevalence of high-risk adenoma was 3.5 times higher in the highest quartile of CRP level (P=0.000) compared with that in the lowest quartile. In logistic regression analysis, a higher quartile CRP level was found to be an independent risk factor for high-risk adenoma (odds ratio, 1.8; 95% confidence interval, 1.3-2.5; P=0.000). CONCLUSIONS: High CRP level is associated with high-risk adenoma in both men and women. Our data may support the association between chronic inflammation and colorectal neoplasia, which warrants further investigation.

Prognostic value of KRAS codon 13 gene mutation for overall survival in colorectal cancer: Direct and indirect comparison meta-analysis.

BACKGROUND: The clinical significance of KRAS codon 13 mutation in patients with colorectal cancer (CRC) remains controversial. A systematic review and meta-analysis is necessary for a more precise estimation of the predictive role of KRAS codon 13 mutations in CRC patients. METHODS: We performed a systematic search using the MEDLINE, EMBASE, and Cochrane library databases from January 2000 to November 2016. The prognostic value of KRAS codon 13 mutation for overall survival (OS) was investigated by measuring the hazard ratio (HR) and 95% confidence interval (CI). Data were analyzed with Review Manager Version 5.3 and the Canadian Agency for Drugs and Technologies in Health software. RESULTS: OS in CRC patients with KRAS codon 13 mutation was worse than that in CRC patients with KRAS wild-type (pooled HR = 1.37, 95% CI: 1.03-1.81, P = .03). Subgroup analysis of studies of enrolled CRC patients treated with antiepidermal growth factor receptor (EGFR) therapy showed no significant difference in OS associated with KRAS codon 13 mutation in comparison to KRAS wild-type (pooled HR = 1.57, 95% CI: 0.98-2.51, P = .06). In the indirect comparison, no statistically significant association was observed between codon 12 and 13 mutations for OS in CRC patients (pooled HR = 0.88, 95% CI: 0.65-1.20, P = .43). CONCLUSION: The current meta-analysis suggests that Codon 13 mutation of KRAS gene seems to correlate with the OS of patients with CRC, but has similar OS to those with KRAS wild-type in patients receiving anti-EGFR therapy. No difference was detected in the OS of CRC patients with codon 13 mutation versus codon 12 mutation.