Oral Sulfate Solution Is as Effective as Polyethylene Glycol with Ascorbic Acid in a Split Method for Bowel Preparation in Patients with Inactive Ulcerative Colitis: A Randomized, Multicenter, and Single-Blind Clinical Trial.

Background/Aims: Low-volume preparations for colonoscopy are gaining attention for their higher acceptability. However, the efficacy and safety of oral sulfate solution (OSS) preparations in patients with ulcerative colitis (UC) has not been well known. Therefore, we aimed to compare OSS and 2-L polyethylene glycol with ascorbic acid (PEG+Asc) for bowel preparation in inactive UC. Methods: A multicenter, randomized, single-blind study was conducted at six tertiary referral hospitals in Korea. Outpatients with UC who had stable disease activity were randomly allocated to the OSS group or the 2-L PEG+Asc group for bowel preparation before colonoscopy. The study outcomes included treatment efficacy, safety, tolerability, and acceptability. Bowel cleansing was assessed using the Boston Bowel Preparation Scale and rated as successful cleansing if the score was ≥6. Patient acceptance and tolerability were assessed using a 4-point ordinal scale. Additionally, disease activity and laboratory data before and after colonoscopy were evaluated to check for safety. Results: The OSS and 2-L PEG+Asc groups included 92 and 93 participants, respectively. No significant between-group difference was noted in successful cleansing (OSS [96.7%] vs 2-L PEG+Asc [97.8%], p=0.64). Moreover, the safety, acceptance, and tolerability were not significantly different (all p>0.05). Furthermore, no significant changes were found in serum electrolytes or disease activity in either group. Conclusions: OSS is effective for colonoscopy cleansing, has acceptable tolerability, and does not affect disease activity; thus, it can be used safely for bowel preparation in patients with inactive UC.

Diagnostic performance of endoscopic ultrasound elastography for differential diagnosis of solid pancreatic lesions: A propensity score-matched analysis.

BACKGROUND: Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method for differential diagnosis of solid pancreatic lesions (SPL). However, the optimal strain ratio (SR) value and diagnostic performance of EUS-EG have not yet been determined in pancreatic neuroendocrine neoplasm (PNEN), mass-forming pancreatitis (MFP), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine the optimal SR value in EUS-EG for differential diagnosis of SPLs. METHODS: Patients who underwent EUS-EG for SPL evaluation between July 2016 and June 2019 were retrospectively investigated. Patients were divided into three groups based on the final diagnosis (PNEN, MFP, or PDAC). Patient demographics, characteristics of SPL, and EUS-EG were compared. RESULTS: The mean (± standard deviation) SR value for each group were 11.85 ± 7.56 (PNEN, n = 10), 11.45 ± 5.97 (MFP, n = 37), and 22.50 ± 13.19 (PDAC, n = 87). Multinomial logistic regression analysis revealed that an increase of SR value was significantly associated with PDAC (PNEN versus PDAC, p = 0.0216; MFP versus PDAC, p = 0.0006). The optimal cut-off value for differential diagnosis was confirmed as 17.14 after propensity score matching. CONCLUSIONS: We provided the optimal cut-off SR values for differential diagnosis between MFP and PDAC. EUS-EG can be used as a supplementary diagnostic method in the diagnosis of SPLs. (Clinical trial registration number: https://cris.nih.go.kr/cris: KCT0002082).

Prevalence of Regional Lymph Node Metastasis of Mucosal Gastric Signet Ring Cell Carcinoma: Analysis of the Collaborative Stage Data Survey of the Korean Central Cancer Registry.

INTRODUCTION: Patients with very early-stage gastric signet ring cell carcinoma (SRC) are eligible for minimally invasive treatment, like endoscopic submucosal dissection. However, population-based data on regional lymph node metastasis (LNM) and distant metastasis of gastric SRC are lacking. This study aimed to identify the prevalence of LNM and distant metastasis in mucosal cancer (T1a) of gastric SRC. METHODS: The Collaborative Stage Data Survey was performed by the Korean Center of Cancer Registry between 2010 and 2015 to establish collaborative stage data of the stomach, colon, rectum, rectosigmoid junction, and breast. From the survey data, information on patients with gastric SRC was extracted for analysis. Variables including age, sex, diagnosis date, primary site, tumor size, histology, American Joint Committee on Cancer staging system scores, and Surveillance, Epidemiology, and End Results summary stage were analyzed. RESULTS: A total of 1,335 (65.7%) patients had mucosal gastric SRC, and 1,189 (89.1%) patients had surgery and 134 (10%) had endoscopic treatment. Of them, 1,283 (96.1%) patients did not have regional LNM, and 52 (3.9%) patients had regional LNM and 6 (0.4%) had distant metastasis. The hazard ratios of LNM and distant metastasis were 14.98 (95% CI: 4.18-53.2) and 10.09 (95% CI: 2.30-44.17). CONCLUSIONS: Reginal LNM and distant metastasis occur very less in mucosal gastric SRC, but they are associated with an increased risk of cancer-related death. Even in early stage, surgery should be considered as a standard treatment of mucosal gastric SRC.

Comparison of contrast-enhanced versus conventional EUS-guided FNA/fine-needle biopsy in diagnosis of solid pancreatic lesions: a randomized controlled trial.

BACKGROUND AND AIMS: Contrast-enhanced harmonic EUS (CEH-EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). However, there is lack of verification about the usefulness of CEH-EUS-guided FNA/fine-needle biopsy (FNB) sampling. This study aimed to investigate the usefulness of CEH-EUS-guided FNA/FNB sampling without on-site cytopathology. METHODS: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to 2 parallel groups, the interventional group (CEH-EUS) or the control group (conventional EUS). The diagnostic sensitivity and optimal number of needle passes for pathologic diagnosis were investigated and compared between groups. RESULTS: Two hundred forty patients were enrolled from March 2016 to September 2019, with 120 patients assigned to each group. Pancreatic malignancies and neuroendocrine tumors were found in 202 (90.83%) and 9 (3.75%) patients, respectively. There was no statistically significant difference between the groups in terms of age, sex, lesion size (30.96 ± 12.09 mm in the CEH-EUS group vs 33.09 ± 16.39 mm in the conventional EUS group; P = .252), lesion location, adverse event rate, and disease distribution. The diagnostic sensitivity values in the CEH-EUS and conventional EUS groups were 85.8% and 88.3%, respectively (P = .564). All patients in the conventional EUS group and most in the CEH-EUS group received a pathologic diagnosis within 3 needle passes. CONCLUSIONS: Diagnostic sensitivity for SPLs was not different between the CEH-EUS and conventional EUS groups, and no independent factors were found that could improve diagnostic sensitivity. CEH-EUS-guided FNA/FNB sampling does not need to be used routinely and may be selectively considered for small, indeterminate lesions. (Clinical trial registration number: KCT 0001840.).

The Association between Nonalcoholic Fatty Liver Disease and Stroke: Results from the Korean Genome and Epidemiology Study (KoGES).

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is associated with various cardiometabolic diseases. However, the association between NAFLD and stroke is not well known. The purpose of our study is to reveal the relationship between NAFLD and Stroke incidence. (2) Methods: Using data from a Korean prospective cohort study, we excluded participants with heavy alcohol consumption and a history of stroke; hence, 7964 adults aged 40-69 years were included in this study. According to their fatty liver index (FLI), participants were divided into three groups: <30 (n = 4550, non-NAFLD), 30-59.9 (n = 2229, intermediate), and ≥60 (n = 1185, NAFLD). The incidence of stroke according to the degree of FLI was evaluated using the Cox proportional hazard model. (3) Results: During the 12-year follow-up period, 168 strokes occurred. A graded association between NAFLD and stroke incidence was observed, i.e., 1.7% (n = 76), 2.5% (n = 56), and 3.0% (n = 36) for non-NAFLD, intermediate, and NAFLD FLI groups, respectively. After adjusting for confounding variables and compared to the risk of stroke in the non-NAFLD group, the risk of stroke in the NAFLD group was the highest (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.17-3.34), followed by the risk of stroke in the intermediate group (HR: 1.41, 95% CI: 0.94-2.21) (p for trend < 0.001). However, the level of aspartate aminotransferase, alanine aminotransferase, or gamma-glutamyltransferase alone did not show any significant association with stroke. (4) Conclusions: This study demonstrated that the risk of stroke incidence gradually increased with the degree of FLI. Individuals with NAFLD should be properly counseled and monitored for risk for stroke.

Upregulation of Peroxiredoxin-2 in Well-Differentiated Pancreatic Neuroendocrine Tumors and Its Utility as a Biomarker for Predicting the Response to Everolimus.

Pancreatic neuroendocrine neoplasms (pNENs) account for 2-3% of pancreatic malignancies. Peroxiredoxins (Prdxs), which are major cellular antioxidants, are involved in multiple oncogenic signaling pathways. We investigated the role of peroxiredoxin-2 in QGP-1 human pNEN cell line and patient-derived pNEN tissue. To validate the cancer stem cell-like cell characteristics of QGP-1 cells in spheroid culture, in vitro analyses and xenografting were performed. Furthermore, immunohistochemical staining was conducted to verify the overexpression of Prdx2 in pNEN tissue. Prdx2 expression was high at the mRNA and protein levels in QGP-1 cells. Prdx2 was also overexpressed in patient-derived pNEN tissue. Silencing of Prdx2 using siRNA induced overexpression and phosphorylation of ERK and AKT in QGP-1. Cell proliferation was increased by treating QGP-1 cells with siPrdx2, and the IC50 of everolimus increased suggesting resistance to everolimus. Interestingly, QGP-1 spheroid cells, which exhibited cancer stem cell-like features, exhibited lower expression of Prdx2 and mTOR. The results suggest that Prdx2 expression level and its activity may be a potential predictive biomarker for therapeutic response or resistance to everolimus in pNEN.

Trends of Incidence and Survival Rates of Mucosa-associated Lymphoid Tissue Lymphoma in the Korean Population: Analysis of the Korea Central Cancer Registry Database.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) is an extranodal lymphoma that occurs at various sites in the body. There is a limited understanding of the incidence and survival rates of MALT-lymphoma. To investigate the nation-wide incidence and survival rates of MALT-lymphoma in Korea during 1999-2017, the data on MALT-lymphoma were retrieved from the Korea Central Cancer Registry. METHODS: During the time period of 1999-2017, 11,128 patients were diagnosed with MALT-lymphoma. The age and sex of the patients and the Surveillance, Epidemiology, and End Results (SEER) summary stage of the tumor were analyzed, and the relative survival rates (RSRs) were calculated. RESULTS: The age-standardized incidence rates of MALT-lymphoma in 2017 among males and females were 1.53 and 1.61 per 100,000 individuals, respectively, whereas those in 1999 among males and females were 0.21 and 0.20, respectively in Korea. The RSRs were more than 97% at 10 years post-diagnosis between 1993 and 2017. The 5-year RSRs were 87.4%, 94.8%, 97.8%, and 98.6% during 1996-2000, 2001-2005, 2006-2010, and 2013-2017, respectively. Based on SEER summary staging, the 5-year RSRs during 2013-2017 were 100.3%, 90.8%, 91.3%, and 97.9% for patients with localized, regional, distant, and unknown stages of MALT-lymphoma, respectively. CONCLUSION: Although the incidence of MALT-lymphoma is low in Korea, it has been increasing in recent years. The prognosis of MALT-lymphoma is good even at advanced stages. These findings provide useful insights to clinicians about MALT-lymphoma and inform patients about the survival rate.

NRF2 Knockdown Resensitizes 5-Fluorouracil-Resistant Pancreatic Cancer Cells by Suppressing HO-1 and ABCG2 Expression.

Chemoresistance is a leading cause of morbidity and mortality in patients with pancreatic cancer and remains an obstacle to successful treatment. The antioxidant transcription factor nuclear factor (erythroid-derived 2)-related factor 2 (NRF2), which plays important roles in tumor angiogenesis and invasiveness, is upregulated in pancreatic ductal adenocarcinoma (PDAC), where it correlates with poor survival. Here, we investigated the role of NRF2 in two 5-Fluourouracil-resistant (5-FUR) PDAC cell lines: BxPC-3 and CFPAC-1. Levels of NRF2 and antioxidants, such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), and superoxide dismutase 2 (SOD2), were higher in the chemoresistant cells than in their chemosensitive counterparts. Expression of epithelial mesenchymal transition (EMT) markers, stemness markers, including Nanog, Oct4, and CD133, and that of the drug transporter ATP binding cassette, subfamily G, member A2 (ABCG2) was also upregulated in 5-FUR PDAC cells. NRF2 knockdown reversed 5-FU resistance of PDAC cells via suppression of ABCG2 and HO-1. In summary, these data indicate that NRF2 is a potential target for resensitizing 5-FUR PDAC cells to 5-FU to improve treatment outcomes in patients with pancreatic cancer.

The Effects of Sulglycotide on the Adhesion and the Inflammation of Helicobacter Pylori.

Helicobacter pylori (H. pylori) is a primary etiologic factor in gastric diseases. Sulglycotide is a glycopeptide derived from pig duodenal mucin. Esterification of its carbohydrate chains with sulfate groups creates a potent gastroprotective agent used to treat various gastric diseases. We investigated the inhibitory effects of sulglycotide on adhesion and inflammation after H. pylori infection in human gastric adenocarcinoma cells (AGS cells). H. pylori reference strain 60190 (ATCC 49503) was cultured on Brucella agar supplemented with 10% bovine serum. Sulgylcotide-mediated growth inhibition of H. pylori was evaluated using the broth dilution method. Inhibition of H. pylori adhesion to AGS cells by sulglycotide was assessed using a urease assay. Effects of sulglycotide on the translocation of virulence factors was measured using western blot to detect cytotoxin-associated protein A (CagA) and vacuolating cytotoxin A (VacA) proteins. Inhibition of IL-8 secretion was measured using enzyme-linked immunosorbent assay (ELISA) to determine the effects of sulglycotide on inflammation. Sulglycotide did not inhibit the growth of H. pylori, however, after six and 12 hours of infection on AGS cells, H. pylori adhesion was significantly inhibited by approximately 60% by various concentrations of sulglycotide. Sulglycotide decreased H. pylori virulence factor (CagA and VacA) translocation to AGS cells and inhibited IL-8 secretion. Sulglycotide inhibited H. pylori adhesion and inflammation after infection of AGS cells in vitro. These results support the use of sulglycotide to treat H. pylori infections.

Clinical Features of Intra-Abdominal Abscess and Intestinal Free-Wall Perforation in Korean Patients with Crohn's Disease: Results from the CONNECT Study.

Background: In Crohn's disease (CD), intra-abdominal abscess (IA) and intestinal free-wall perforation (IP) have a common mechanism of transmural inflammation; however, their manifestation is different. Objective: This study aimed to investigate differences in the clinical features between IA and IP in Korean patients with Crohn's disease. Design: A retrospective cohort study. Setting: Thirty university hospitals and two local hospitals in Korea. Patients: Patients who were diagnosed with CD between July 1982 and December 2008 were enrolled. Main Outcome Measures: Clinical characteristics of IA and IP. Results: Among 1286 patients with CD, 147 (11.4%) had IA and 83 (6.5%) had IP. IA patients were younger than those of IP (24.2 ± 8.6 vs. 30.4 ± 11.1 years, p = 0.001). Location and behavior were significantly different between IA and IP (p = 0.035 and 0.021). In multivariate analyses, perianal fistula was not associated with increased risk of IA and IP, while intestinal stricture was associated with increased risk of IA (OR: 2.72, p < 0.0001) and IP (OR: 2.76, p < 0.0001). In subgroup analyses, 55 (36.5%) IA patients were diagnosed at the diagnosis of CD, and 92 (63.5%) during follow-up of CD, while 47 (56.6%) IP patients were diagnosed at the diagnosis of CD, and 36 (43.3%) during follow-up of CD. Conclusions: There are several differences in the clinical features of IA and IP in Korean patients with CD. The development mechanism is considered as identical, but further investigation should be needed for clinical implication.

Safety of esophagogastroduodenoscopy-guided forceps biopsy and the feasibility of esophagogastroduodenoscopy for evaluation of hypopharyngeal cancer.

BACKGROUND: There is currently no established standard tissue sampling method for hypopharyngeal cancer. The present study aimed to evaluate the feasibility of esophagogastroduodenoscopy (EGD) for the pretreatment evaluation of hypopharyngeal cancer and the safety of EGD-guided forceps biopsy. METHODS: We reviewed nine patients with hypopharyngeal cancer who underwent EGD for the evaluation of tumor extent and tissue biopsy from March 2014 to March 2017 at International St. Mary's Hospital. One experienced endoscopist performed all the EGD procedures in the presence of a head and neck surgeon. The procedure included determining tumor location, extent (presence of pyriform sinus apex involvement), and size, and passing the endoscope through the upper esophageal sphincter. The success rate of tissue sampling was assessed, and procedure-related complications were recorded. RESULTS: All patients were male, with a mean age of 69.9 ± 10.9 years (range 61-69 years). Tissue sampling using biopsy forceps was performed in 6/9 patients (66.7%). No complications related to moderate sedation or biopsy, including post-biopsy bleeding or respiratory distress, were reported. Histologic confirmation was successful in 5/6 patients (83.3%). Upper gastrointestinal lesions were evaluated in 7/9 (77.8%) patients in whom the scope passed through the lesion. CONCLUSIONS: EGD and EGD-guided forceps biopsy may be useful for the evaluation of hypopharyngeal cancer extent and tissue sampling, respectively.

Association between Peptic Ulcer Disease and Osteoporosis: The Population-Based Longitudinal Cohort Study in Korea.

OBJECTIVES: The association between peptic ulcer disease (PUD) and osteoporosis remains unclear. We investigated the association between PUD and osteoporosis by classifying individuals based on gender in a prospective study on 10,030 adults in Korea at a 12-year follow-up examination. DESIGN AND SETTING: The baseline survey of the Ansung-Ansan cohort studies was conducted from May 2001 to February 2003, and 10,030 participants (5018 from the Ansung study and 5012 from the Ansan study) completed the examination. PRIMARY OUTCOME MEASURES: The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group. RESULTS: At the 12-year follow-up, osteoporosis had developed in 11.1% (21/189) and 29.9% (56/187) of men and women in the PUD group, respectively. Meanwhile, in the control group, 4.8% (70/1464) and 16.5% (271/1639) of men and women, respectively, were presented with osteoporosis. The incidence rates per 1000 person-years were 20.5% and 68.5% in men and women in the PUD group and 11.2% and 42.3% of men and women in the control group, respectively. The risk of developing osteoporosis was higher in both men and women in the PUD group than in the control group (men: hazard ratio [HR] = 1.72, 95% confidence interval [CI] = 1.02-2.92; women: HR = 1.62, 95% CI = 1.20-2.18). CONCLUSION: The risk of developing osteoporosis was significantly higher in both men and women in the PUD group than in the control group.

Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway.

We developed a molecular beacon targeting miR-141-3p, aberrantly increased in 5-fluorouracil-resistant colorectal cancer cells (R-CRCCs). It consists of a fluorophore-labeled oligonucleotide, antisense to miR-141-3p, and a quencher. It detected R-CRCCs and recovered the chemosensitivity of them to 5-fluorouracil by hybridization with miR-141-3p, which is applicable to cancer treatment.

Fatty liver disease and the risk of erosive oesophagitis in the Korean population: a cross-sectional study.

OBJECTIVES: To investigate an association between fatty liver disease (FLD) and erosive oesophagitis. DESIGN AND SETTING: This was a cross-sectional study of subjects selected from examinees who underwent health check-up, including oesophagogastroduodenoscopy in one hospital between 2004 and 2011. Erosive oesophagitis was classified according to the Los Angeles classification and FLD was diagnosed with ultrasonography. The anthropometric and laboratory data of the subjects were analysed using χ2 test and multivariate logistic regression. Additionally, we have analysed our data with two-stage least square estimation using the Baltagi-Chang one-way model to clarify unobserved confounding variable. PRIMARY OUTCOME MEASURE: The effect of FLD on erosive oesophagitis. RESULTS: Among the 14 723 eligible subjects, 4232 (28.7%) subjects diagnosed with FLD were classified into the fatty liver group and 10 491 (71.3%) subjects without FLD were classified into the non-fatty liver group. The incidence rate of erosive oesophagitis was significantly higher in the fatty liver group than in the non-fatty liver group (10.4%vs6.1%, p<0.0001). The multivariate analysis revealed that the fatty liver group was significantly associated with erosive oesophagitis (OR 1.19, 95% CI 1.03 to 1.37, p=0.016). CONCLUSION: FLD diagnosed by ultrasonography is an independent risk factor of erosive oesophagitis. It suggests that FLD-related metabolic abnormality may be associated with erosive oesophagitis.

Body mass index and the risk of acute pancreatitis by etiology: A prospective analysis of Korean National Screening Cohort.

BACKGROUND: It is unclear whether obesity increases the incidence of acute pancreatitis (AP) in the general population. Further, no study has prospectively examined the associations of the risk of AP by etiology with measured body mass index (BMI) values. METHODS: A total of 512 928 Korean participants in routine health examinations during 2002-2003 were followed up until 2013 via linkage to national hospital discharge records to assess AP incidence. Multivariable-adjusted hazard ratios were calculated using BMI measurements. RESULTS: During 10.5 mean years of follow-up, 1656 persons developed AP (337 gallstone related and 1319 non-gallstone related). Nonlinear associations were found: U-curves for total and non-gallstone-related AP and a reverse L-curve for gallstone-related AP. Each 5 kg/m2 increment in BMI increased gallstone-related AP by 123% (95% confidence interval = 48-234%) and non-gallstone-related AP by 42% (9-84%) in the range ≥ 25 kg/m2 (Pheterogeneity  = 0.068). Obese persons had a doubled risk of gallstone-related AP compared with normal-weight persons. In the range < 25 kg/m2 , BMI had inverse association with non-gallstone-related AP but no association with gallstone-related AP (Pheterogeneity  < 0.001). In subgroup analyses, for non-gallstone-related AP, hazard ratios per each 5 kg/m2 BMI increment were 0.50 (men), 0.73 (women), 0.46 (alcohol drinkers), 0.69 (alcohol non-drinkers), 0.43 (ever smokers), and 0.73 (never smokers). CONCLUSIONS: Gallstone-related AP and non-gallstone-related AP have different nonlinear associations with BMI. Higher BMI increases the risk of both gallstone-related AP and non-gallstone-related AP but more strongly for gallstone-related AP. For non-gallstone-related AP, in the range < 25 kg/m2 , BMI has inverse associations that were stronger in men, current alcohol drinkers, and ever smokers than in their counterparts.

Endoscopic botulinum toxin injection for treatment of pharyngeal dysphagia in patients with cricopharyngeal dysfunction.

BACKGROUND: Dysphagia associated with neurologic disorders is a problem worldwide. However, few studies have assessed the efficacy of endoscopic botulinum toxin injections into the cricopharyngeal muscle using a pharyngoscope. METHODS: Fourteen patients who received an endoscopic botulinum toxin injection due to cricopharyngeal muscle dysfunction and a neurological disorder from 2006 to 2017 were retrospectively reviewed at a single tertiary medical center. The toxin was injected at a 100 international unit (IU) total dose under direct endoscopic vision. The success of the procedure was evaluated comprehensively using the following: clinical resolution of the previous symptoms, functional oral intake scale (FOIS) for the clinical evaluation of swallowing, and videofluoroscopic swallowing study (VFSS) to check decreased retention of barium at the pyriform sinus and the epiglottic vallecula. RESULTS: The study included 12 males and 2 females (mean age, 58 years old; range, 37-82 years). Three patients (21.4%) were confirmed clinically and eleven were confirmed by VFSS. Eleven patients (78.6%) were managed successfully with the injection. Three patients (21.4%) did not improve despite the injection. CONCLUSION: An endoscopic botulinum toxin injection may be a good treatment option for patients with dysphagia and cricopharyngeal dysfunction due to a neurological disorder. Large, prospective, long-term follow-up studies are needed in the future.

Body mass index and gastrointestinal cancer mortality in Korean adults: A prospective cohort study.

BACKGROUND: The association between body mass index (BMI) and mortality from gastrointestinal (GI) cancer remains unclear, especially in Asian populations. METHODS: A total of 510 148 Korean adults who participated in routine health examinations during the period 2002-2003 were followed up until 2013. RESULTS: During a mean follow up of 10.5 years, 7831 individuals died of GI cancer. Various associations with BMI were found: U-curve (overall GI, colorectal, liver, and gallbladder cancer), L-curve (stomach cancer), linear (esophageal, extrahepatic bile duct [EBD], and small intestine cancer), and none (pancreatic cancer). Overall GI cancer mortality was lowest at approximately 23.5-26 kg/m2 . For cancers with linear associations, the multivariable adjusted hazard ratios per each 5 kg/m2 higher BMI were 0.53 (95% confidence interval = 0.43-0.65, esophagus), 1.19 (1.02-1.40, EBD), and 0.64 (0.41-0.999, small intestine). For cancers with U-curve or L-curve associations, the corresponding hazard ratios ≥25 kg/m2 were 1.19 (1.08-1.32, overall GI), 1.30 (1.04-1.64, colorectal), 1.28 (1.07-1.53, liver), and 1.30 (0.85-1.97, gallbladder), while in the range of <25 kg/m2 , they were 0.81 (0.76-0.87, overall GI), 0.43 (0.32-0.58, esophagus), 0.70 (0.62-0.79, stomach), and 0.77 (0.65-0.90, colorectal), and these inverse associations did not weaken after excluding the first 7 years of follow up and ever smokers. CONCLUSIONS: Both low and high BMIs were associated with excess mortality from GI cancers in Korean adults. EBD cancer had a positive association, while esophageal and small intestine cancers had inverse associations. Above 25 kg/m2 , liver and colorectal cancers had positive associations with BMI, whereas below 25 kg/m2 , stomach and colorectal cancers had inverse associations.

Ursodeoxycholic acid suppresses epithelial-mesenchymal transition and cancer stem cell formation by reducing the levels of peroxiredoxin II and reactive oxygen species in pancreatic cancer cells.

Reactive oxygen species (ROS) play a key role in cancer development and progression. Ursodeoxycholic acid (UDCA) may possess antioxidant, anti-inflammatory and chemoprophylatic effects. Therefore, we aimed to investigate the effects and mechanisms of UDCA treatment on pancreatic cancer cells. The pancreatic cancer cell lines HPAC and Capan-1 were treated with 0.2 mM UDCA. To examine alterations in the levels of intracellular ROS, the DCF-DA stain was used and both stemness and epithelial-mesenchymal transition (EMT)-related genes were quantified using qRT-PCR and western blot analysis. The pancreatic cancer sphere culture was performed following seven days of treatment with 0.2 mM UDCA, as an indicator of stemness. Following treatment with UDCA, the level of intracellular ROS was decreased in the pancreatic cancer cells. UDCA decreased both the phosphorylation of STAT3 and the expression of peroxiredoxin II (Prx2). Furthermore, the treatment resulted in the upregulation of E-cadherin and in the downregulation of N-cadherin. In addition, UDCA decreased the expression of sex determining region Y-box 2 (Sox2) and it diminished the number of pancreatic cancer spheres formed. In conclusion UDCA suppressed the levels of intracellular ROS and Prx2 and it decreased EMT and stem cell formation in pancreatic cancer cells. Therefore, UDCA may provide favorable therapeutic benefits, through its antioxidant effects, for patients with pancreatic cancer.

Predictive risk factors associated with synchronous multiple early gastric cancer.

The aim of this study was to elucidate the predictive risk factors of synchronous multiple early gastric cancer regardless of the treatment modality.Patients who underwent early gastric cancer treatment between July 2005 and June 2015 were retrospectively reviewed. In total, 1529 patients who were treated for early gastric cancer were included. We analyzed the patient's data to find predictive factors of synchronous multiple early gastric cancer compared to solitary early gastric cancer. Further analysis was performed to verify the difference between endoscopic and surgical treatment groups.Among the 1529 patients, synchronous multiple early gastric cancer was diagnosed in 68 (4.4%) patients. Significant differences in sex (P = .004), gross appearance (P = .038), depth of invasion (P = .007), and lymphovascular invasion (P = .039) were found between patients with solitary early gastric cancer and synchronous multiple early gastric cancer by univariate analysis. In multivariate analysis, male sex (odds ratio, 2.475; P = .011) and submucosal invasion (odds ratio, 1.850; P = .033) were independent predictive risk factors of synchronous multiple early gastric cancer. In addition, in multivariate analysis, significant differences in age, tumor size, longitudinal location, depth of invasion, and histology were found between patients groups depending on the mode of treatment.Male sex and submucosal invasion were predictive risk factors of synchronous multiple early gastric cancer. Patients with these factors should undergo more meticulous endoscopic surveillance.

Expression of MicroRNA in Host Cells Infected with Helicobacter pylori.

BACKGROUND/AIMS: MicroRNAs (miRNAs) regulate gene expression. We assess miRNA regulation by Helicobacter pylori infection and elucidate their role in H. pylori-infected gastric epithelial cells. METHODS: The relationship between miRNA expression and DNA methylation was examined. Cells were treated with the nuclear factor-kappaB (NF-κB) inhibitor Bay 11-7082 to determine the relationship between miRNA expression and NF-κB signal transduction. RESULTS: In the negative control cells infected with H. pylori 26695, the expression of six miRNAs was increased, whereas the expression of five miRNAs was decreased. The expression of upregulated miRNAs was increased when the host cells were treated with H. pylori and an NF-κB inhibitor. miR-127-5p, -155, and -181 were associated with increased interleukin 6 (IL-6) secretion in H. pylori infected cells treated with anti-miRNA. The expression of miR-155, -127-5p, -195, -216, -206, and -488 increased by approximately 3-fold following treatment with the methylation inhibitor Aza. CONCLUSIONS: We found novel miRNAs in H. pylori-infected negative control cells using miRNA microarrays. Upregulated miRNA expression was inversely related to the transcription of NF-κB. miR-195 and miR-488 appear to play a pivotal role in controlling IL-6 activity in H. pylori infection. miRNA expression in H. pylori infection was affected by methylation.