Clinical outcome of non-curative endoscopic submucosal dissection for early gastric cancer.

Background: Early gastric cancer (EGC) is defined as cancer cells confined to the mucosal or submucosal layer, irrespective of size or presence of lymph node metastasis. The recent EGC endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) guidelines (2021 Japan Gastroenterological Endoscopy Society (JGES) guidelines, 2nd edition) revised the concept from "endoscopic curative/non-curative resection" (NCR) to "endoscopic curability (eCura)". Under this, eCuraA and eCuraB signify curative resections (CRs), while eCuraC (including eCuraC-1 and eCura-C2) indicate NCRs. This study retrospectively analyzes clinical and pathological data from EGC patients who underwent endoscopic resection, assessing the long-term clinical outcomes in a substantial cohort after undergoing NCR. Methods: We retrospectively analyzed clinical and pathological data from 443 EGC patients, encompassing 478 lesions, who received endoscopic treatment. The long-term clinical outcomes of patients who underwent NCR were statistically evaluated. Characteristics of the NCR group were compared with those of the surgical group, employing single- and multi-factor logistic regression analyses to identify risk factors that necessitate further surgical intervention. Prognostically, the Kaplan-Meier method and Log-Rank test determined the impact of risk factors on recurrence-free survival post-surgery in NCR patients. Differences were assessed using a method incorporating statistically significant differences in the multi-factor Cox regression analysis, evaluating the hazard ratio (HR) for disease recurrence following NCR. Results: In this study, 443 EGC cases were pathologically diagnosed, comprising a total of 478 lesions. Of these, 127 cases underwent non-curative endoscopic resection, resulting in a NCR rate of 24.4%. Long-term follow-up was achieved for 117 (92.12%) patients. The metastasis/recurrence rate at 6 months stood at 23.1%. Multivariate Cox regression analysis identified lesion size ≥2.0 and <3 cm [P=0.02, HR =0.12, 95% confidence interval (CI): 0.02-0.67], presence of ulceration (P=0.03, HR =5.48, 95% CI: 1.23-24.33), lymphatic invasion (P=0.05, HR =17.51, 95% CI: 1.07-286.23), positive vertical margins (P=0.09, HR =3.77, 95% CI: 0.81-17.53), and flat macroscopic morphology (P=0.048, HR =4.8, 95% CI: 1.01-22.73) as independent risk factors for recurrence-free survival post non-curative endoscopic resection in EGC patients. Conclusions: The recurrence/metastasis rate in patients who underwent NCR is notably higher compared to the control group. Significant prognostic risk factors include tumor size ≥2.0 and <3 cm, positive vertical margins, lymphatic invasion, and flat type (one of pathological gross classification). Patients in the eCuraC-2 category of NCR should consider further surgical intervention. The necessity for additional surgical intervention in these patients warrants further investigation.

Effect of smoking-related features and 731 immune cell phenotypes on esophageal cancer: a two-sample and mediated Mendelian randomized study.

Introduction: Numerous observational studies have indicated that smoking is a substantial risk factor for esophageal cancer. However, there is a shortage of research that delves into the specific causal relationship and potential mediators between the two. Our study aims to validate the correlation between smoking-related traits and esophageal cancer while exploring the possible mediating effects of immune factors. Methods: Initially, we conducted bidirectional univariate Mendelian Randomization (MR) analyses to forecast the causal effects linking smoking-related traits and esophageal cancer. Subsequently, we employed a two-step MR analysis to scrutinize immune cell phenotypes that could mediate these effects. Finally, the coefficient product method was employed to determine the precise mediating impact. Additionally, we have refined our sensitivity analysis to ensure the reliability of the outcomes. Results: After analysis, Smoking status: Never had a significant negative association with the incidence of esophageal cancer (inverse-variance weighted (IVW) method, p=1.82e-05, OR=0.10, 95%CI=0.04~0.29). Ever smoked (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) and Current tobacco smoking (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) showed the promoting effect on the pathogenesis of esophageal cancer. Through further examination, researchers discovered 21 immune cell phenotypes that have a causal relationship with esophageal cancer. After careful screening, two immune cell phenotypes were found to have potential mediating effects. In particular, it was observed that in the case of the preventive effect of Smoking status: Never on esophageal cancer, the absolute count of CD62L plasmacytoid dendritic cells mediated a reduction of 4.21%, while the mediating effect of CD27 in CD20-CD38-B cells was -4.12%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy. Conclusion: The study provides new evidence for the causal relationship between smoking-related features and esophageal cancer and proposes immune factors with potential mediating effects. However, this finding needs to be further demonstrated by more extensive clinical studies.

Risk factors and a nomogram for predicting local recurrence in adult patients with early gastric cancer after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is an effective treatment method for early gastric cancers. The aim of this study was to evaluate the risk factors of recurrence for patients with early gastric cancer after ESD and construct a nomogram for predicting recurrence. METHODS: A retrospective observational study was conducted on patients with early gastric cancer who underwent ESD at Beijing Friendship Hospital between 2013 and 2018. The risk factors of gastric cancer recurrence after ESD were analyzed by univariate and multivariate Cox regression. RESULTS: A total of 238 patients with a median follow-up period of 70.5-month were enrolled in the study. Risk factors for recurrence included diabetes (HR = 3.68), alcohol consumption history (HR = 5.73), complications (HR = 5.22), lymphatic invasion (HR = 13.09) and multiple lesions (HR = 4.34). The analysis of the receiver operating characteristic curve, calibration curve, and model consistency index demonstrates that the graphical representation exhibits a good predictive capability. CONCLUSIONS: Based on identified risk factors, this study developed the first nomogram with high accuracy to predict the recurrence of early gastric cancer after ESD. This model offers valuable guidance to clinicians for identifying high-risk patient groups and planning more intensive follow-up strategies.

RIOK3 sustains colorectal cancer cell survival under glucose deprivation via an HSP90α-dependent pathway.

Glucose oxidation via the pentose phosphate pathway serves as the primary cellular mechanism for generating nicotinamide adenine dinucleotide phosphate (NADPH). The central regions of solid tumors typically experience glucose deficiency, emphasizing the need for sustained NADPH production crucial to tumor cell survival. This study highlights the crucial role of RIOK3 in maintaining NADPH production and colorectal cancer (CRC) cell survival during glucose deficiency. Our findings revealed upregulated RIOK3 expression upon glucose deprivation, with RIOK3 knockout significantly reducing cancer cell survival. Mechanistically, RIOK3 interacts with heat shock protein 90α (HSP90α), a chaperone integral to various cellular processes, thereby facilitating HSP90α binding to isocitrate dehydrogenase 1 (IDH1). This interaction further upregulates IDH1 expression, enhancing NADPH production and preserving redox balance. Furthermore, RIOK3 inhibition had no discernible effect on intracellular NADPH levels and cell death rates in HSP90α-knockdown cells. Collectively, our findings suggest that RIOK3 sustains colon cancer cell survival in low-glucose environments through an HSP90α-dependent pathway. This highlights the significance of the RIOK3-HSP90α-IDH1 cascade, providing insights into potential targeted therapeutic strategies for CRC in metabolic stress conditions.

No potential causal link between HP infection and IBD: A 2way Mendelian randomization study.

Recent epidemiological research suggests a possible negative correlation between Helicobacter pylori infection and inflammatory bowel disease (IBD). However, conflicting studies have provided unclear evidence regarding these causal relationships. Therefore, recommending specific prevention and treatment strategies for H. pylori infection and IBD is challenging. We used various antibodies (anti-H. pylori IgG, VacA, and GroEl) related to H. pylori infection as indicators. We acquired relevant genetic variants from public databases within the Genome-wide Association Studies (GWAS) dataset using IBDs tool variables from 2 different GWAS datasets. We thoroughly examined the data and screened for IVs that fulfilled these criteria. Subsequently, Bidirectional Mendelian randomization (MR) was conducted to predict the potential causality between the 2. To ensure the accuracy and robustness of our results, we conducted a series of sensitivity analyses. Based on our comprehensive MR analysis, no potential causal relationship was observed between H. pylori infection and IBD. Across various methodologies, including IVW, MR-Egger, and weighted median, our findings showed P values > .05. The only exception was observed in the reverse MR analysis using the MR-Egger method, which yielded a P value of < .05. However, because the IVW method is considered the most statistically significant method for MR, and its P value was > .05, we do not believe that a potential causal relationship exists between them. Our sensitivity analysis did not suggest significant horizontal pleiotropism. Although heterogeneity was detected in the analysis of IBD (IIBDGC source) versus H. pylori GroEL antibody levels (MR-Egger, Qp = 0.038; IVW, Qp = 0.043), the results remained reliable because we selected IVW as a random-effects model in our MR analysis method. Based on our MR research, no direct correlation was observed between H. pylori infection and IBD risk. This implies that eradicating H. pylori may not provide substantial benefits in preventing or treating regional IBD, and vice versa. Nevertheless, the use of H. pylori serological index substitution has limitations, and further research using histological diagnosis and additional MR studies is required to comprehensively assess the link between H. pylori infection and IBD.

Effect of 3-Dimensional Imaging Device on Polyp and Adenoma Detection During Colonoscopy: A Randomized Controlled Trial.

INTRODUCTION: To evaluate the effect of 3-dimensional (3D) imaging device on polyp and adenoma detection during colonoscopy. METHODS: In a single-blind, randomized controlled trial, participants aged 18-70 years who underwent diagnostic or screening colonoscopy were consecutively enrolled between August 2019 and May 2022. Each participant was randomized in a 1:1 ratio to undergo either 2-dimensional (2D-3D) colonoscopy or 3D-2D colonoscopy through computer-generated random numbers. Primary outcome included polyp detection rate (PDR) and adenoma detection rate (ADR), defined as the proportion of individuals with at least 1 polyp or adenoma detected during colonoscopy. The primary analysis was intention-to-treat. RESULTS: Of 1,196 participants recruited, 571 in 2D-3D group and 583 in 3D-2D group were finally included after excluding those who met the exclusion criteria. The PDR between 2D and 3D groups was separately 39.6% and 40.5% during phase 1 (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.76-1.22, P = 0.801), whereas PDR was significantly higher in 3D group (27.7%) than that of 2D group (19.9%) during phase 2, with a 1.54-fold increase (1.17-2.02, P = 0.002). Similarly, the ADR during phase 1 between 2D (24.7%) and 3D (23.8%) groups was not significant (OR = 1.05, 0.80-1.37, P = 0.788), while ADR was significantly higher in 3D group (13.8%) than that of 2D group (9.9%) during phase 2, with a 1.45-fold increase (1.01-2.08, P = 0.041). Further subgroup analysis confirmed significantly higher PDR and ADR of 3D group during phase 2, particularly in midlevel and junior endoscopists. DISCUSSION: The 3D imaging device could improve overall PDR and ADR during colonoscopy, particularly in midlevel and junior endoscopists. Trial number: ChiCTR1900025000.

Comparison of endoscopic submucosal dissection outcomes between early gastric cardiac and non-cardiac cancers: a retrospective single-center study.

OBJECTIVES: This study aims to compare the efficacy of endoscopic submucosal dissection (ESD) between early gastric cardiac cancer (EGCC) and early gastric non-cardiac cancer (EGNCC), and investigate associated risk factors for non-curative resection. METHODS: Early gastric cancer (EGC) patients who underwent ESD from January 2015 to September 2020 in Beijing Friendship Hospital were consecutively enrolled. The clinical, histopathological and endoscopic data were retrospectively analyzed. The study was registered in Chinese Clinical Trial Registry (ChiCTR1800017117). RESULTS: Among 500 patients with 534 EGC lesions, 117 patients with 118 lesions were allocated to the EGCC group, and 383 patients with 416 lesions to the EGNCC group. The rates of en bloc resection, complete resection and curative resection in the EGCC group were 97.5%, 78.8% and 71.2%, respectively, significantly lower than those in the EGNCC group (99.8%, 94.5% and 90.4%, p = .010, <.001 and <.001). Among non-curative resected lesions, EGCC had more cases in both endoscopic curability (eCura) C-1 and C-2 groups than EGNCC (10.2% and 18.6% vs. 2.4% and 7.2%, p < .001). Multivariate analysis showed that tumor size (OR 2.393, 95% CI 1.388-4.126) and submucosal invasion (OR 11.498, 95% CI 3.759-35.175) were risk factors for non-curative resection in the EGCC group. For EGCC larger than 3 cm, none achieved curative resection, 86.7% were classified as eCura C-2 and 46.7% exhibited deep submucosal infiltration. CONCLUSIONS: The curative resection rate of ESD for EGCC was lower than that for EGNCC. ESD for EGCC larger than 3 cm should be cautiously considered.

Circulating Tumor Cells as Diagnostic Markers of Early Gastric Cancer and Gastric Precancerous Lesions.

INTRODUCTION: Circulating tumor cells (CTCs) may be potential diagnostic biomarkers of various malignancies including gastric cancer. This study aimed to evaluate whether CTCs could be used to facilitate the diagnosis of early gastric cancer (EGC) or precancerous gastric lesions. METHODS: The diagnostic study included consecutive patients with EGC, gastric precancerous lesions, or fundic gland polyps admitted to the Gastroenterology Department, Beijing Friendship Hospital Affiliated to Capital Medical University (National Center for Digestive Diseases) between October 2016 and January 2018. RESULTS: A total of 92 patients were enrolled, including 57 patients with EGC, 14 patients with gastric precancerous lesions, and 21 patients with fundic gland polyps (control group). CTCs were detected in 47.89% (34/71) of patients with EGC/gastric precancerous lesions and 4.76% (1/21) of patients with fundic gland polyps (p < 0.001). CTC detection distinguished EGC/precancerous lesions from fundic gland polyps with an area under the receiver operating characteristic curve of 0.740 (95% confidence interval, 0.640-0.840; p = 0.001), a sensitivity of 49.10%, a specificity of 95.00%, a positive predictive value of 97.00%, and a negative predictive value of 64.90%. CONCLUSIONS: Peripheral blood CTCs are more common in patients with EGC or gastric precancerous lesions than in patients with fundic gland polyps. Measurement of CTCs may be a useful tool to aid in the diagnosis of EGC and precancerous lesions.

Case report: a precancerous lesion associated with HPV in the anal canal diagnosed by magnifying endoscopy with narrow-band imaging and resected by endoscopic submucosal dissection.

Although anal cancer remains rarely diagnosed in the world, its frequency is rising, especially in high-risk groups. The prognosis of advanced anal cancer is poor. However, there are still few reports on the endoscopic diagnosis and treatment of early anal cancer and its precancerous lesions. A 60-year-old woman was referred to our hospital for endoscopic treatment of a flat precancerous lesion in the anal canal, which was identified by narrow-band imaging (NBI) and confirmed by pathological examination in another hospital. The pathological results showed a high-grade squamous intraepithelial lesion (HSIL) in the biopsy specimen, and immunochemistry staining showed P16 positive, suggesting HPV infection. We performed pre-resection endoscopic examination for the patient. A lesion with a clear margin and tortuous dilated vessels was revealed under magnifying endoscopy with NBI (ME-NBI), which stayed unstained after iodine spraying. The lesion was successfully removed en bloc using ESD without complications, and the resected specimen was a low-grade squamous intraepithelial lesion (LSIL) with positive immunochemistry staining of P16. The patient underwent follow-up coloscopy a year after ESD, and the anal canal healed well with no suspicious lesions found. From this case, we can learn that ESD is safe and effective for curative resection of precancerous lesions of the anal canal.

Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

External validation of the BEST-J score and a new risk prediction model for ESD delayed bleeding in patients with early gastric cancer.

BACKGROUND: Delayed bleeding is an important adverse event after gastric endoscopic submucosal dissection (ESD). We aimed to externally validate the Bleeding after ESD Trend from Japan (BEST-J) score and subsequently develop a risk prediction model for bleeding in Chinese patients with early gastric cancer (EGC) after ESD. METHODS: The clinical data of patients who underwent ESD for EGC in Beijing Friendship Hospital from June 2013 to December 2019 were collected retrospectively. The BEST-J score was evaluated according to the clinical data. Through univariate and multivariate logistic regression analyses of the clinical data, the factors affecting delayed bleeding were identified, and a new risk prediction model for bleeding was established. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of the two prediction models. RESULTS: A total of 444 patients with EGC undergoing ESD were included, of whom 27 patients had delayed bleeding (6.1%). Multivariate logistic regression analysis showed that a history of smoking (P = 0.029), tumor size > 20 mm (P = 0.022), intraoperative use of hemoclips (P = 0.025), resection of multiple tumors (P = 0.027), and prolongation of activated partial thromboplastin time (APTT) (P = 0.020) were independent influencing factors for delayed bleeding. ROC curve analysis showed that the areas under the curves (AUCs) were different between the BEST-J score and the newly built prediction model (0.624 vs. 0.749, P = 0.012). CONCLUSIONS: The BEST-J score has moderately good discrimination for Chinese patients with EGC. However, for patients with EGC without severe comorbidities, the new risk prediction model may predict delayed bleeding better than the BEST-J score.

Systolic Blood Pressure Mediates Body Mass Index and Non-alcoholic Fatty Liver Disease: A Population-Based Study.

BACKGROUND: Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Systolic blood pressure (SBP) and body mass index (BMI) are associated with NAFLD. We aimed to evaluate the mediating effect of SBP in the association between BMI and NAFLD. METHODS: A total of 21 072 participants were enrolled. Multivariate logistic regression and linear regression models were used to describe the association between BMI, SBP, and NAFLD. The impact of SBP on the association between BMI and NAFLD was determined through mediation analysis. RESULTS: BMI was positively associated with incident NAFLD overall (odds ratio (OR) = 1.171, 95% CI (1.153-1.189)) and in the female (OR = 1.189, 95% CI (1.157-1.222)) and male groups (OR = 1.162, 95% CI (1.141-1.184)) (P < .001). SBP also showed positive effects in the general, female, and male groups (P < .001). The effect of BMI on SBP also indicated similar positive results in the general (ß = 0.913, 95% CI (0.799-1.026)), female (ß = 0.956, 95% CI (0.760-1.151)), and male (ß = 0.867, 95% CI (0.727-1.006)) groups (P < .001). Mediation analysis showed that SBP contributed to 14.23% of the relationship between BMI and NAFLD in the general group and 31.07 and 22.67% of the relationship in the female and male groups of individuals younger than 50 years old, respectively. The mediation effect appeared higher among females than among males, especially in participants younger than 50 years. CONCLUSION: SBP and BMI contribute to the development of NAFLD. SBP mediates a positive association between BMI and NAFLD among individuals younger than 50 years, especially among females.

Serum Uric Acid Is a Mediator of the Association Between Obesity and Incident Nonalcoholic Fatty Liver Disease: A Prospective Cohort Study.

Objective: Obesity has been demonstrated to show a consistent link with the increased possibility of nonalcoholic fatty liver disease (NAFLD). Since both serum uric acid (SUA) and obesity are essential components of metabolic syndrome (MetS), it is uncertain whether the incidence of NAFLD results from serum uric acid, obesity, or other potential factors based on previous studies. Patients and methods: This study enrolled 16,839 participants with no history of alcohol consumption and no fatty liver disease in 2010. All participants completed a survey which included health and lifestyle questionnaires, and underwent physical examination, ultrasonography, and laboratory examinations of blood samples. After the four-year follow up, 5,104 (30.31%) participants were diagnosed with NAFLD. The associations between SUA, BMI or obesity, and incident NAFLD were assessed by multivariate linear regression, logistic regression analysis, and mediation analysis, respectively. Results: By adjusting demographic and serum characteristics, linear correlation coefficients between obesity and SUA were 20.26 [95% confidence interval (CI)]: 15.74, 24.77), 13.31 (95% CI: 6.63, 19.99) and 22.21 (95% CI: 16.41, 28.02) in the total population, and in the female and male groups, respectively. The odds ratios were 2.49 (95% CI: 1.61, 3.87) in the total population, 5.71 (95% CI: 2.25, 14.45) in the female group and 1.99 (95% CI: 1.15, 3.45) in the male group for the correlation between obesity and incident NAFLD. The mediation analysis showed that SUA contributed to 10.03%, 0.58%, and 12.54% of obesity-related NAFLD development in the total population, females and males, respectively. Conclusion: The findings showed mediation linkages of both obesity and SUA with the incident NAFLD. The role of SUA as a mediator constitutes clinical significance that should be recognized and considered.

Risk Factors and Prediction Model for Non-curative Resection of Early Gastric Cancer With Endoscopic Resection and the Evaluation.

Background and Study Aim: EGC, also known as Early Gastric Cancer is known to lack the lymph node metastasis and confined along the mucosa, which is treated through an endoscopic resection procedure that includes ESD (Endoscopic Submucosal dissection) and EMR (Endoscopic Mucosal Resection). However, some cases underwent residual disease, recurrence, or additional gastrectomy because of non-curative resection. The following research aims to delineate the threat factors causing the non-curative resection as well as develop a predictive model. Patient and Methods: Effort was taken to collect all the records about the health history of pathologically diagnosed EGC who experienced endoscopic treatment in the Department of Endoscopy, the Capital Medical University, and Beijing Friendship Hospital from January 2012 to January 2020. Patients were grouped into two categories primarily; a curative resection group and finally a non-curative resection group based on the outcomes of the postoperative pathological and immunohistochemical examination results. The statistical methods used included single factor analysis, a multivariate logistic regression analysis and a chi-square test. A nomogram for the prediction of non-curative resection was constructed, which included information on age, gender, resection method, postoperative pathology, tumor size, ulcer, treatment, and infiltration depth. Receiver operating characteristic (ROC) curve analysis and calibration were performed to present the predictive accuracy of the nomogram. Results: Of 443 patients with 478 lesions who had undergone ESD or EMR for EGCs, 127 were identified as being treated non-curative resection. Older patients (>60 years), a large tumor size (>30 mm), submucosal lesion, piecemeal resection, EMR for treatment and undifferentiated tumor histology were associated with non-curative resection group. Our risk nomogram showed good discriminated performance in internal validation (bootstrap-corrected area under the receiver-operating characteristic curve, 0.881; P < 0.001). Conclusions: A validated prediction model was developed to identify people who were subject to undergoing a non-curative resection for ESD. The predictive model that we formulated is essential in providing reliable information to guide the decision-making process on the treatment for EGC before undertaking an endoscopic resection.

Triglycerides Mediate Body Mass Index and Nonalcoholic Fatty Liver Disease: A Population-Based Study.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is defined by the accumulation of triglycerides (TG). The body mass index (BMI) is associated with NAFLD. This large-scale cohort study was performed to evaluate and quantify the mediating effect of TG on the association between BMI and NAFLD. METHODS: In total, 15,943 participants in the Kailuan Group were recruited between 2010 and 2014. The impact of TG on the association between BMI and NAFLD was determined through a mediation analysis. RESULTS: BMI was an independent risk factor for incident NAFLD, with OR of 1.416 (95% CI 1.338-1.499) and 1.187 (95% CI 1.137-1.240) in the low-BMI and high-BMI groups, respectively (p < 0.001). The TG level was a risk factor for NAFLD in the high-BMI group, with an OR of 2.775 (95% CI 1.488-5.177; p = 0.001). Positive associations between BMI and the TG level remained in the 2 above mentioned groups after adjusting for confounders (ß = 0.072 and 0.032; p < 0.001). The mediation analysis revealed that TG contributed to 26.050% of incident NAFLD in the high-BMI group (p = 0.01). CONCLUSION: A high BMI was an independent risk factor for incident NAFLD, and a high TG level was a risk factor in the high-BMI group (BMI ≥24). TG contributes about 25% to incident NAFLD in people with obesity.

Ethyl pyruvate supplemented in drinking water ameliorates experimental nonalcoholic steatohepatitis.

Inflammation and oxidative stress play a significant role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Ethyl pyruvate (EP) is a novel anti-inflammatory agent and a potent reactive oxygen species (ROS) scavenger. Therefore, EP supplemented in drinking water may alleviate experimental NASH in this study (even though 0.3% of EP cannot attenuate the simple non-aggressive fatty liver). The methionine-choline-deficient (MCD) diet was given to the C57BL/6 male mice for 3 weeks to induce NASH. The NASH animals were randomized into 3 treatment groups: animals in the MCD alone group were treated with normal drinking water alone; animals in the delayed EP group were given 3% (v/v) of EP supplemented in normal drinking water, the treatment started 10 days after MCD diet feeding; animals in the early EP therapy group were treated the same as the delayed EP group except that EP treatment started the same day when MCD diet was given; the control mice were fed with normal chow and treated with normal drinking water (n = 10 for each group). Compared to MCD group with normal drinking water, early EP treatment significantly decreased serum ALT and improved NASH histopathology; delayed EP therapy only attenuated NASH in 50% (5/10) of the animals. The beneficial effects were associated with decreased hepatic TNF-a and IL-6 mRNA expression on early 5 days, inhibited NF-kB activation, reduced liver tissue malondialdehyde levels, and decreased intestinal bacterial translocation (BT). In conclusion: EP supplemented in drinking water attenuates experimental NASH.

Bile is a promising gut nutrient that inhibits intestinal bacterial translocation and promotes gut motility via an interleukin-6-related pathway in an animal model of endotoxemia.

OBJECTIVES: People who are critically ill have high rates of endotoxemia that can significantly decrease bile flow and increase bile cytokines, the latter of which might worsen their condition. Bile acids are nutrient-signaling hormones that have a significant impact on gut barrier function and motility, and the gut is considered the origin of systemic inflammation. Therefore, healthy exogenous bile could be a promising gut nutrient for critical illness, so the biomedical role of bile in endotoxemia was investigated in this study. METHODS: Twelve rats were injected with lipopolysaccharide (LPS) and randomized into a group with sham operation) and a group with bile external drainage (n = 6 for each group); six rats with sham operation served as the control group. In addition, interleukin-6 (IL-6) knockout mice and macrophages were treated with LPS. RESULTS: Compared to the control animals, the group with LPS injection and sham operation had significantly increased levels of gut permeability, gut bacterial translocation, gut mucosal tumor necrosis factor α, IL-6 transcripts, and serum tumor necrosis factor α and IL-6. Compared to group with sham operation and LPS injection, bile external drainage (in LPS-challenged rats) increased gut bacterial translocation by 10 times, and this detrimental effect was associated with prolonged intestinal transit time, increased serum IL-6 concentration, and up-regulated gut mucosal IL-6 transcripts. Moreover, bile selectively inhibited LPS-stimulated macrophages in IL-6 release, which can activate gastrointestinal submucosal neurons to promote motility. Knocking out IL-6 significantly reduced gut bacterial translocation in endotoxemic mice. CONCLUSIONS: Bile is a promising gut nutrient that inhibits gut bacterial translocation and promotes gut motility via an IL-6-related pathway in experimental endotoxemia.

Assessment of prevalence and risk factors of helicobacter pylori infection in an oilfield Community in Hebei, China.

BACKGROUND: Only a paucity of large-scale perspective and cross-sectional studies on H. pylori infection in China have been published. The purpose of this study was to investigate the prevalence and risk factors for H. pylori infection among residents of Jidong community located in Hebei Province of China. METHODS: A perspective, cross-sectional study was conducted in Jidong community. Questionnaires and 13C-urea breath test were performed, and 10-ml blood samples were obtained for laboratory tests. RESULTS: Four thousand seven hundred ninety-six subjects were enrolled in this study, and 2506 (52.25%) were H. pylori positive. There was no difference in prevalence between both sexes (P = 0.5974). Age (P = 0.004) and education level (P = 0.0128) were significantly associated with H. pylori infection, and there were statistical trends in the prevalence across five age subgroups (χ2 test for trend = 23.5; P < 0.001) and education levels (χ2 test for trend = 19.50; P < 0.001). H. pylori infection was also associated with marital status (P = 0.0243), source of drinking water (P = 0.0433), frequency of eating raw garlic (P = 0.0310), alcohol drinking (P = 0.0207), knowledge about H. pylori transmission route (P = 0.0125) and related diseases (P = 0.0257). Age, alcohol drinking and knowledge about transmission route were found to be independent predictors of H. pylori infection. CONCLUSIONS: More than half of the population was infected with H. pylori in Jidong community. The socio-demographic profiles, socio-economic factors and lifestyle are worthy taking into consideration to prevent diseases associated with H. pylori infection. Understanding the prevalence and risk patterns for H. pylori infection in China will help in prioritizing public health efforts to better manage the H. pylori infection.

Cytoplasmic Asporin promotes cell migration by regulating TGF-ß/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer.

Previous studies revealed that Asporin (ASPN) is a potential mediator in the development of various types of cancer as a secreted stroma protein, but the function of ASPN inside the cancer cells remains largely unknown. Here, we demonstrated a higher expression level of ASPN in colorectal cancer (CRC) than matched normal tissues, and 25% (2/8) CRC showed copy number variation (CNV) gain/amplification in ASPN gene. Both higher ASPN expression levels and ASPN CNV gain/amplification indicated a worse prognosis in CRC patients. ASPN can promote proliferation, migration, and invasion of CRC cells, and inhibit apoptosis by activating Akt/Erk and TGF-ß/Smad2/3 signalings. Further investigations revealed that ASPN interacts with Smad2/3, facilitates its translocation into nucleus, and up-regulates the expression of Epithelial-mesenchymal transition (EMT) related genes. Rescue assays confirmed that TGF-ß signaling is essential for the effects of ASPN on promoting CRC cell migration and invasion. In conclusion, ASPN promotes the migration and invasion of CRC cells via TGF-ß/Smad2/3 pathway and could serve as a potential prognostic biomarker in CRC patients.

Associations of breast milk adiponectin, leptin, insulin and ghrelin with maternal characteristics and early infant growth: a longitudinal study.

Breast milk (BM) hormones have been hypothesised as a nutritional link between maternal and infant metabolic health. This study aimed to evaluate hormone concentrations in BM of women with and without gestational diabetes mellitus (GDM), and the relationship between maternal factors, BM hormones and infant growth. We studied ninety-six nulliparous women with (n 48) and without GDM and their exclusively breastfed term singletons. Women with GDM received dietary therapy or insulin injection for euglycaemia during pregnancy. Hormone concentrations in BM, maternal BMI and infant growth were longitudinally evaluated on postnatal days 3, 42 and 90. Mothers with GDM had decreased concentrations of adiponectin (P colostrum<0·001; P mature-milk=0·009) and ghrelin (P colostrum=0·011; P mature-milk<0·001) and increased concentration of insulin in BM (P colostrum=0·047; P mature-milk=0·021). Maternal BMI was positively associated with adiponectin (ß=0·06; 95 % CI 0·02, 0·1; P=0·001), leptin (ß=0·16; 95 % CI 0·12, 0·2; P<0·001) and insulin concentrations (ß=0·06; 95 % CI 0·02, 0·1; P<0·001), and inversely associated with ghrelin concentration in BM (ß=-0·08; 95 % CI -0·1, -0·06; P<0·001). Among the four hormones, adiponectin was inversely associated with infant growth in both the GDM (ß weight-for-height=-2·49; 95 % CI -3·83, -1·15; P<0·001; ß head-circumference=-0·39; 95 % CI -0·65, -0·13; P=0·003) and healthy groups (ß weight-for-height=-1·42; 95 % CI -2·38, -0·46; P=0·003; ß head-circumference=-0·15; 95 % CI -0·27, -0·03; P=0·007). Maternal BMI and GDM are important determinants of BM hormone concentrations. Milk-borne adiponectin is determined by maternal metabolic status and plays an independent down-regulating role in early infant growth.