Simultaneous Treatment of 5-Aminosalicylic Acid and Treadmill Exercise More Effectively Improves Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 µL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC.

Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

The Risk of Endoscopy-Related Bleeding in Patients with Liver Cirrhosis: A Retrospective Study.

Background and Objectives: The risk of bleeding after endoscopic procedures in patients with liver cirrhosis remains unclear because of secondary blood coagulation disorders. In this study, we used various indices to evaluate the risk of bleeding in patients with cirrhosis. Materials and Methods: Patients with liver cirrhosis aged ≥18 years who underwent endoscopic interventions at Kyung Hee University Hospital at Gangdong between February 2007 and September 2021 were included. Clinical information, including demographic data, laboratory results, the presence of cirrhosis complications, and the degree of fibrosis, was checked and evaluated based on medical records. Results: A total of 101 patients with cirrhosis were analyzed. A total of 16 of the 101 patients (15.8%) experienced bleeding after the endoscopic procedure. One patient (0.99%) presented with spurting, while the others presented with mild oozing. All patients underwent hemostatic procedures using hemoclips. The presence of a varix significantly increased post-endoscopic bleeding (p = 0.03). Patients with FIB > 3.25 showed a statistically significant bleeding tendency (p = 0.00). Conclusions: There was no significant difference in bleeding risk according to the platelet count, prothrombin time, Child−Pugh score, and model for end-stage liver disease (MELD). Considering the degree of liver fibrosis and the invasiveness of the planned procedure, most endoscopic procedures can be performed safely but should be further evaluated in a cohort with a larger sample size.

Artificial intelligence-based measurement outperforms current methods for colorectal polyp size measurement.

OBJECTIVES: An accurate polyp size estimation during colonoscopy is crucial to determine the surveillance interval and predict the risk of malignant progression. However, there is a high degree of subjectivity in estimating polyp size among endoscopists in clinical practice. We aimed to assess the efficacy of a novel method that uses artificial intelligence (AI) to measure the size of colon polyps and compare it with current approaches. METHODS: Using the W-Net model for vessel segmentation and based on retinal image datasets (DRIVE, STARE, CHASE-DB, and HRF) and colonoscopy images, we developed the bifurcation-to-bifurcation (BtoB) distance measuring method and applied it to endoscopic images. Measurements were compared with those obtained by eight endoscopists (four expert and four trainees). Diagnostic ability and reliability were evaluated using Lin's concordance correlation coefficients (CCCs) and Bland-Altman analyses. RESULTS: For both experts and trainees, visually estimated sizes of the same polyp were significantly inconsistent depending on the camera view used (P < 0.001). Bland-Altman analyses showed that there was a trend toward underestimation of the sizes of the polyps in both groups, especially for polyps larger than 10 mm. The new technique was highly accurate and reliable in measuring the size of colon polyp (CCC, 0.961; confidence interval 0.926-0.979), clearly outperforming the visual estimation and open biopsy forceps methods. CONCLUSION: The new AI measurement method improved the accuracy and reliability of polyp size measurements in colonoscopy images. Incorporating AI might be particularly important to improve the efficiency of trainees at estimating polyp size during colonoscopy.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

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.

Probiotics Ameliorate Stool Consistency in Patients with Chronic Constipation: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND/AIMS: The efficacy of probiotics for improving clinical symptoms, altering the fecal microbiota, and regulating serum immune cytokine levels was investigated in patients with irritable bowel syndrome-constipation (IBS-C) or functional constipation (FC). METHODS: A randomized, double-blind, placebo-controlled trial was conducted at Kyung Hee University Hospital between October 2016 and February 2017. Consecutive 18-75-year-old patients with diagnosis of IBS-C or FC (based on Rome IV criteria) consumed probiotics (3.0 × 108 CFU/g Streptococcus thermophilus MG510 and 1.0 × 108 CFU/g Lactobacillus plantarum LRCC5193) or a placebo daily for 4 weeks (weeks 1-4) and were followed up for a 4-week washout period without intervention (weeks 5-8). The primary outcomes of the study were Bristol Stool Form Scale and Complete Spontaneous Bowel Movements (CSBM). Efficacy was assessed by per protocol. RESULTS: Stool consistency measured by the Bristol Stool Form Scale was significantly better in the probiotic group (n = 88) than in the placebo group (n = 83) at 4 and 8 weeks (3.7 ± 1.1 vs. 3.1 ± 1.1 at 8 weeks, P = 0.002). No significant difference was found in CSBM. The quality of life was significantly better in the probiotic group than in the placebo group at 4 weeks (P = 0.044) and 8 weeks (P = 0.049). The relative abundance of L. plantarum among the fecal microbiomes was significantly greater in the probiotic group than in the placebo group at 4 weeks (P = 0.029). However, the levels of other microbiomes and of serum cytokines (IL-10/IL-12 ratio and TNF-α) did not differ significantly between the two groups. CONCLUSIONS: Probiotics significantly ameliorated stool consistency in patients with chronic constipation. In addition, the beneficial effect of L. plantarum on stool consistency remained after the probiotic supplementation was discontinued. The mechanism whereby probiotics benefit patients with chronic constipation should be clarified in further studies.

Age-adapted Variation in Screening Interval of Fecal Immunochemical Test May Improve its Participation and Colonoscopy Acceptance.

GOALS: We determined appropriate intervals for administering the fecal immunochemical test (FIT) and performance outcomes in an Asian national colorectal cancer (CRC) screening program. BACKGROUND: The optimal interval for FIT in CRC screening is unclear, especially in Asian populations. STUDY: Between January 2009 and December 2015, 13,480 individuals aged 50 years or older with an initial negative FIT result underwent 2 rounds of FIT screening at intervals of 1 (annual group, 5333), 2 (biennial group, 7363), or 3 years (triennial group, 784). Positive rates of FIT, colonoscopy acceptance, colonoscopy findings, and detection rates for CRC and advanced neoplasia were compared according to FIT intervals. RESULTS: The overall positivity rate of FIT in the second screening round was significantly higher in men and in older subjects than in the entire sample. Younger subjects were less likely to undergo annual FIT (36.0% vs. 46.4%, P<0.001). The colonoscopy acceptance rate was decreased in the biennial and triennial groups compared with an annual group among younger subjects (odds ratio, 0.56; 95% confidence interval, 0.33-0.95 for the biennial group vs. odds ratio, 0.19; 95% confidence interval, 0.03-1.37 for the triennial group). Detection rates for CRC and advanced neoplasia in the second round were significantly higher and accompanied by increased FIT screening intervals in older, but not younger subjects. CONCLUSIONS: Age-adapted variation in FIT screening intervals, such as annual screening for elderly subjects and biennial screening for younger subject, may improve FIT participation and colonoscopy acceptance.

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.

Successful Endoscopic Hemostasis Is a Protective Factor for Rebleeding and Mortality in Patients with Nonvariceal Upper Gastrointestinal Bleeding.

BACKGROUND: Rebleeding and mortality rates remain high in patients with nonvariceal upper gastrointestinal bleeding. AIM: To identify clinical and endoscopic risk factors for rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding. METHODS: This study was performed in patients with nonvariceal upper gastrointestinal bleeding who underwent upper endoscopic procedures between July 2006 and February 2013. Clinical and endoscopic characteristics were compared among patients with and without rebleeding and mortality. Logistic regression analysis was performed to determine independent risk factors for rebleeding and mortality. RESULTS: After excluding 64 patients, data for 689 patients with nonvariceal upper gastrointestinal bleeding were analyzed. Peptic ulcer (62.6 %) was by far the most common source of bleeding. Endoscopic intervention was performed within 24 h in 99.0 % of patients, and successful endoscopic hemostasis was possible in 80.7 % of patients. The 30-day rebleeding rate was 13.1 % (n = 93). Unsuccessful endoscopic hemostasis was found to be the only independent risk factor for rebleeding (odds ratio 79.6; 95 % confidence interval 37.8-167.6; p = 0.000). The overall 30-day mortality rate was 3.2 % (n = 23). Unsuccessful endoscopic hemostasis (odds ratio 4.9; 95 % confidence interval 1.7-13.9; p = 0.003) was also associated with increased 30-day mortality in patients with nonvariceal upper gastrointestinal bleeding. CONCLUSIONS: Successful endoscopic hemostasis is an independent protective factor for both rebleeding and mortality in patients with nonvariceal upper gastrointestinal bleeding.

The Clinical Outcomes of Lower Gastrointestinal Bleeding Are Not Better than Those of Upper Gastrointestinal Bleeding.

The incidence of lower gastrointestinal bleeding (LGIB) is increasing; however, predictors of outcomes for patients with LGIB are not as well defined as those for patients with upper gastrointestinal bleeding (UGIB). The aim of this study was to identify the clinical outcomes and the predictors of poor outcomes for patients with LGIB, compared to outcomes for patients with UGIB. We identified patients with LGIB or UGIB who underwent endoscopic procedures between July 2006 and February 2013. Propensity score matching was used to improve comparability between LGIB and UGIB groups. The clinical outcomes and predictors of 30-day rebleeding and mortality rate were analyzed between the two groups. In total, 601 patients with UGIB (n = 500) or LGIB (n = 101) were included in the study, and 202 patients with UGIB and 101 patients with LGIB were analyzed after 2:1 propensity score matching. The 30-day rebleeding and mortality rates were 9.9% and 4.5% for the UGIB group, and 16.8% and 5.0% for LGIB group, respectively. After logistic regression analysis, the Rockall score (P = 0.013) and C-reactive protein (CRP; P = 0.047) levels were significant predictors of 30-day mortality in patients with LGIB; however, we could not identify any predictors of rebleeding in patients with LGIB. The clinical outcomes for patients with LGIB are not better than clinical outcomes for patients with UGIB. The clinical Rockall score and serum CRP levels may be used to predict 30-day mortality in patients with LGIB.

Predictive Factors for Endoscopic Visibility and Strategies for Pre-endoscopic Prokinetics Use in Patients with Upper Gastrointestinal Bleeding.

BACKGROUND: Although current guideline recommends selective use of pre-endoscopic prokinetics to increase diagnostic yield in upper gastrointestinal bleeding (UGIB) patients, no data to guide the use of these drugs are available. AIMS: We aimed to investigate predictive factors for endoscopic visibility and develop simple and useful strategies for pre-endoscopic prokinetics use in UGIB patients. METHODS: A total of 220 consecutive patients who underwent upper endoscopy for suspicious UGIB were enrolled. Patients were randomly allocated to either a training or a validation set at a 2:1 ratio. Significant parameters on univariate analysis were subsequently tested by a classification and regression tree (CART) analysis. RESULTS: Time to endoscopy and nasogastric aspirate findings were independently related to endoscopic visibility. The CART analysis generated algorithms proposed sequential use of time to endoscopy (≤5.2 vs. >5.2 h) and nasogastric aspirate findings (red blood or coffee rounds vs. clear aspirate) for predicting endoscopic visibility. Prediction of unacceptable visibility in the validation set produced sensitivity, specificity, positive predictive value, and negative predictive value of 75.8, 67.5, 65.8, and 77.1 %, respectively. Accurate prediction for visibility was identified in 52 of 73 patients (71.2 %). CONCLUSIONS: Time to endoscopy and nasogastric aspirate findings were independently related to endoscopic visibility in patients with UGIB. A decision-tree model incorporating these two variables may be useful for selecting UGIB patients who benefit from pre-endoscopic prokinetics use.

A Multicenter Survey of Percutaneous Endoscopic Gastrostomy in 2019 at Korean Medical Institutions.

Background/Aims: : This study aimed to review the indications, methods, cooperation, complications, and outcomes of percutaneous endoscopic gastrostomy (PEG). Methods: : Questionnaires were sent to 200 hospitals, of which 62 returned their questionnaires, with a response rate of approximately 30%. Descriptive statistics were calculated to analyze the responses to the questionnaires. Results: : In 2019, a total of 1,052 PEGs were performed in 1,017 patients at 62 hospitals. The main group who underwent PEG was older adult patients with brain disease, particularly stroke. Nutritional supply was an important purpose of the PEG procedure. "The pull method" was the most commonly used for initial PEG insertion. The complications related to PEG were mostly mild, with leakage being the most common. Patients who underwent PEG procedures were primarily educated regarding the post-procedure management and complications related to PEG. Preoperative meetings were skipped at >50% of the institutions. Regarding the cooperation between the nutrition support team (NST) and the physician performing PEG, few endoscopists answered that they cooperated with NST before and after PEG. Moreover, the rate of NST certification obtained by physicians performing PEG and the frequency of attendance at NST-related conferences were relatively low. Conclusions: : This study shows a similar trend to that found in the previous PEG guidelines. However, it covers new aspects, including team-based work for PEG procedure, nutrition support, and education for patients and guardians. Therefore, each medical institution needs to select an appropriate method considering the medical environment and doctor's abilities.

Osteoporosis is associated with the risk of colorectal adenoma in women.

BACKGROUND: Recently, it was reported that postmenopausal women with lower bone mineral density have an increased risk of colorectal cancer. An association between lower bone mineral density and colorectal cancer suggests that colorectal adenoma, which is a precursor of colorectal cancer, may also be associated with lower bone mineral density. OBJECTIVE: The aim of this study was to determine the association between colorectal adenoma and osteoporosis. DESIGN AND PATIENTS: We conducted a retrospective cross-sectional study between January 2007 and May 2011. Women older than 50 years of age who underwent dual-energy x-ray absorptiometry for bone mineral density and screening colonoscopy at Gangdong Kyung Hee University Hospital in Korea during a routine health checkup were eligible for this study. We performed multivariate analysis adjusted for age, family history of colorectal cancer, alcohol consumption, current smoking, regular aspirin use, exercise, menopause, and postmenopausal hormone use to identify independent predictors for the presence of colorectal adenoma. MAIN OUTCOME MEASURES: The primary outcome measured was the prevalence of colorectal adenoma according to the bone mineral density level. RESULTS: A total of 992 women older than 50 years were assigned to an osteoporosis group (n = 231) or a control group (n = 231) after menopause matching. In univariate analysis, the proportion of colorectal adenoma was significantly higher in the osteoporosis group than in the control group (29.9% vs 20.8%, p = 0.025). Furthermore, osteoporosis (OR = 1.592, 95% CI = 1.004-2.524, p = 0.048) was found to be an independent risk factor for the presence of colorectal adenoma. CONCLUSIONS: Osteoporosis is associated with an increased risk of colorectal adenoma in women older than 50 years.

Association between HLA-G 14-bp insertion/deletion polymorphism and hepatocellular carcinoma in Korean patients with chronic hepatitis B viral infection.

BACKGROUND/AIMS: The aim of this study was to determine whether the major HLA-G gene was associated with hepatocellular carcinoma (HCC). Abnormal HLA-G expression is present in various diseases, such as renal cell carcinoma, asthma and classical Hodgkin's lymphoma. METHODOLOGY: To investigate the possible association with susceptibility to HCC, 181 chronic hepatitis patients and 180 HCC patients were enrolled in this study. The HLA-G 14-bp insertion/deletion polymorphism is located in the 3' untranslated region of the HLA-G gene and was analyzed using polymerase chain reaction. For analysis of genetic data, SNPStats and SPSS 18.0 were used. Logistic regression models were performed to determine the odds ratio, 95% confidence interval, and p value. RESULTS: Allele and genotype frequencies of the HLA-G 14-bp insertion/deletion polymorphism in the hepatitis group had a similar pattern, as compared to those in the HCC group. Furthermore, no differences were observed between patients with and without liver cirrhosis. CONCLUSIONS: These results suggest that the HLA-G 14-bp insertion/deletion polymorphism may not be associated with HCC susceptibility and liver cirrhosis development in the Korean population.

Polymorphisms of interferon gamma gene and risk of hepatocellular carcinoma in korean patients with chronic hepatitis B viral infection.

BACKGROUNDS/AIMS: Increasing evidence supports the contribution of the pro-/anti-inflammatory cytokine balance and genetic factors to hepatocellular carcinoma (HCC). Here, we investigated whether genetic interferon gamma polymorphisms were associated with HCC in Korean patients with chronic hepatitis B. METHODOLOGY: We genotyped a single nucleotide polymorphism (SNP, rs2430561, +874A/T) and a microsatellite (rs3138557, (CA)n repeat), located in the first intron of the interferon gamma gene, by direct sequencing and the gene scan method. A population-based case-control study of HCC was conducted and included 170 patients with chronic hepatitis and HCC, and 171 with chronic hepatitis B patients without hepatocellular carcinoma in a Korean population. RESULTS: Genotype and allele distributions of the interferon gamma gene SNP were associated with HCC. The frequencies of the AA genotype and the A allele were significantly increased in hepatocellular carcinoma subjects (p<0.05). Combined analysis using the genotype of rs2430561 and the number of microsatellites revealed that the frequencies of AT-CA12 and TT-CA12 increased significantly in hepatocellular carcinoma subjects (p<0.0001). CONCLUSIONS: Our results suggest that the interferon gamma gene may be a susceptibility gene and a risk factor for HCC in the Korean population.

Polymorphisms of interferon gamma gene and risk of hepatocellular carcinoma in Korean patients with chronic hepatitis B viral infection.

BACKGROUNDS/AIMS: Increasing evidence supports the contribution of the pro-/anti-inflammatory cytokine balance and genetic factors to hepatocellular carcinoma (HCC). Here, we investigated whether genetic interferon gamma polymorphisms were associated with HCC in Korean patients with chronic hepatitis B. METHODOLOGY: We genotyped a single nucleotide polymorphism (SNP, rs2430561, +874A/T) and a microsatellite (rs3138557, (CA) (n) repeat), located in the first intron of the interferon gamma gene, by direct sequencing and the gene scan method. A population-based case-control study of HCC was conducted and included 170 patients with chronic hepatitis and HCC, and 171 with chronic hepatitis B patients without hepatocellular carcinoma in a Korean population. RESULTS: Genotype and allele distributions of the interferon gamma gene SNP were associated with HCC. The frequencies of the AA genotype and the A allele were significantly increased in hepatocellular carcinoma subjects (p < 0.05). Combined analysis using the genotype of rs2430561 and the number of microsatellites revealed that the frequencies of AT-CA12, and TT-CA12 increased significantly in hepatocellular carcinoma subjects (p < 0.0001). CONCLUSIONS: Our results suggest that the interferon gamma gene may be a susceptibility gene and a risk factor for HCC in the Korean population.

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.

A novel animal model for studying pancreatic regeneration by employing photochemical reaction.

PURPOSE: We present photochemical-induced pancreatic necrosis (PIPN) as a novel induction method for studying pancreatic regeneration in an animal model. METHODS: Photosensitive Rose Bengal was injected through the femoral vein in rats, followed by illumination of the surface of the pancreas with a cool halogen light for a period of 20 min. At 3, 6, and 24 h, and 7, 10, 14, and 20 days, experimental animals were sacrificed; all the animals received intravenous injection with 5-bromo-2-deoxyuridine (BrdU) 1 h prior to sacrifice. RESULTS: At 3-6 h of induction of PIPN, pancreatic necrosis was superficially observed in the illuminated field. At 24 h, there was a slight increase in the depth and width of the lesion along with appearance of vascular congestion and thrombosis in the lesion. On days 7-10, the area of illumination was totally replaced by necrotic pancreatic tissue, inflammatory cell infiltrates, and newly appearing cellular components, including mesenchymal and epithelial cells, which formed tubular complexes. On day 14, clusters of tubular complexes intermingled with acinar cells, which were proven as newly formed acinar tissue by BrdU staining. On day 20, all the lesions had returned to a normal state of pancreatic tissue. CONCLUSION: This study demonstrates the potential of PIPN as a valuable method for production of an animal model for studying healing processes or regeneration of pancreatic tissue after injury.

Early use of needle-knife fistulotomy is safe in situations where difficult biliary cannulation is expected.

BACKGROUND AND AIMS: Difficult cannulation is a well known risk for post-ERCP pancreatitis. This study evaluated the outcomes of needle-knife fistulotomy (NKF) used prior to being faced with difficult biliary cannulation. METHODS: Patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of biliary endotherapy between January 2007 and December 2008 were eligible for this study; 218 patients were recruited. Biliary cannulation was performed only by a standard catheter or a pull type papillotome, without wire-guided assistance in all patients. If selective cannulation was not achieved within five cannulation attempts, NKF was performed, and the results were compared with the easy cannulation group that succeeded biliary cannulation within five attempts. RESULTS: Needle-knife fistulotomy (NKF) was performed in 72 (33.0%) of the 218 patients. The total success rate of the ERCP was 98.2% (214/218), and for the NKF group the success rate was 94.4% (68/72). The rate of complications in patients with NKF did not increase compared to patients in the easy cannulation group (P > 0.05): 4.2% (3/72) versus 3.4% (5/146) for acute pancreatitis, 6.9% (5/72) versus 6.8% (10/146) for bleeding, and 1.4% (1/72) versus 0% (0/146) for perforation, respectively. CONCLUSIONS: Our results suggest that the use of NKF for biliary cannulation might be safe and effective. Therefore, in experienced hands, early use of NKF might be recommended.