Use of over-the-scope clip (OTSC) versus standard therapy for the prevention of rebleeding in large peptic ulcers (size ≥1.5 cm): an open-labelled, multicentre international randomised controlled trial.

INTRODUCTION: Over-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders. METHODS: This was a multicentre international randomised controlled trial from July 2017 to October 2020. All patients with Forest IIa or above peptic ulcers of ≥1.5 cm were included. Primary outcome was 30-day clinical rebleeding. Secondary endpoints include 3-day all-cause mortality, transfusion requirement, hospital stay, technical and clinical success, and further interventions. 100 patients are needed to yield a power of 80% to detect a difference of -0.15 at the 0.05 significance level (alpha) using a two-sided Z-test (pooled). RESULTS: 100 patients were recruited. Success in achieving primary haemostasis was achieved in 46/50 (92%) and 48/50 (96%) in the OTSC and conventional arm, respectively. Among patients who had success in primary haemostasis, 2/46 (4.35%) patients in the OTSC arm and 9/48 (18.75%) patients in the conventional arm developed 30-day rebleeding (p=0.03). However, in an intention-to-treat analysis, there was no difference in rebleeding within 30 days (5/50 (10%) OTSC vs 9/50 (18%) standard, p=0.23) or all-cause mortality (2/50 (4%) OTSC vs 4/50 (8%) standard, p=0.68; OR=2.09, 95% CI 0.37 to 11.95). There was also no difference in transfusion requirement, hospital stay, intensive care unit admission and further interventions. CONCLUSION: The routine use of OTSC as primary haemostasis in large bleeding peptic ulcers was not associated with a significant decrease in 30-day rebleeding. TRIAL REGISTRATION NUMBER: NCT03160911.

The comparative effects of metabolic surgery, SGLT2i, or GLP-1RA in patients with obesity and type 2 diabetes: a retrospective cohort study.

BACKGROUND: New antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes. OBJECTIVES: To compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months. SETTING: Hong Kong Hospital Authority database from 2006-2017. METHODS: This is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups. RESULTS: Patients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (-5.39, -.56, -.40 kg/m2, P < .001), % total weight loss (15.16%, 1.34%, 1.63%, P < .001), systolic (-2.21, -.59, 1.28 mm Hg, P < .001) and diastolic (-1.16, .50, -.13 mm Hg, P < .001) blood pressure, HbA1c (-1.80%, -.77%, -.80%, P < .001), triglycerides (-.64, -.11, -.09 mmol/L, P < .001), and estimated glomerular filtration rate (3.08, -1.37, -.41 mL/min/1.73m2, P < .001) after 12 months compared with patients with SGLT2i and GLP1-RA. Although the metabolic surgery group incurred the greatest direct medical costs (US$33,551, US$10,945, US$10,627, P < .001), largely due to the surgery itself and related hospitalization, the total monthly direct medical expenditure of metabolic surgery group became lower than that of SGLT2i and GLP-1RA groups at 7 months. CONCLUSION: Beneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.

Alterations in the Gut Virome in Obesity and Type 2 Diabetes Mellitus.

BACKGROUND & AIMS: Obesity and type 2 diabetes mellitus (T2DM) are associated with changes in the gut bacterial composition, but little is known about the role of the viral community (virome) in disease development. This study aims to characterize the gut virome alterations in obese subjects with or without T2DM. METHODS: There were 128 obese subjects (body mass index ≥28 kg/m2) and 101 lean controls (body mass index ≥18.5 and <23 kg/m2) recruited from 2 regions in China (Hong Kong and Kunming). Fecal virome and bacteriome were profiled by shotgun metagenomic sequencing. Gut virome, bacteriome, and viral-bacterial correlations were compared between obese subjects and lean controls. RESULTS: Obese subjects, especially those with T2DM (ObT2), had a decreased gut viral richness and diversity compared with lean controls in the Hong Kong cohort (P < .05), while no significant differences were observed in the Kunming cohort. Eleven viruses, including Escherichia phage, Geobacillus phage, and Lactobacillus phage were enriched in obese subjects (q < .1). Besides, 17 differentially abundant viruses were identified between ObT2 and lean controls (q < .1). Further ecologic analysis revealed that intensive transkingdom correlations between viruses and bacteria observed in lean controls were significantly decreased in ObT2 subjects (P < .001). CONCLUSIONS: Obesity is characterized by altered viral taxonomic composition and weakened viral-bacterial correlations compared with lean controls. Obesity accompanied with T2DM may aggravate the obesity-associated virus signatures, signifying that the gut virome may play an important role in the development of obesity and T2DM. Geographic factors also contributed to the variations of gut virome in obesity and T2DM.

Accuracy of High-Resolution Manometry in Hiatal Hernia Diagnosis in Primary and Revision Bariatric Surgery.

PURPOSE: There is a complex association between obesity, hiatal hernia (HH), and reflux. There is a deficiency of literature on the accuracy of preoperative high-resolution manometry (HRM) in detecting HH before both primary and revision bariatric surgery. MATERIALS AND METHODS: A retrospective analysis of a prospective database of all HRM performed before bariatric surgery from 2014 to 2019. An electronic medical records review was conducted. Sensitivity, specificity, and global diagnostic test accuracy were calculated. RESULTS: Sixty-seven patients with HRM (mean age of 44.0 ± 11.3 years, body mass index 40.8 ± 6.9 kg/m2) were eligible. Intraoperative diagnosis of HH was made in 37 patients (55.2% prevalence). The HRM sensitivity was 48.7% (95% confidence interval (CI) 31.9-65.6%), specificity 90.0% (95% CI 73.5-97.9%), and accuracy was 67.2% (95% CI 54.6-78.2%). Comparing primary (28) and revision (39) surgery, the sensitivity (37.5% vs 57.1%), specificity (75.0% vs 100%), and diagnostic accuracy (54.3% vs 76.3%) were comparable, with overlapping 95% CI. Endoscopy performed in 30 patients had a sensitivity of 25.5% (95% CI 6.8-49.9%), specificity of 100% (95% CI 75.3-100%), and accuracy of 57.8% (95% CI 38.5-75.5%) and was comparable to HRM. CONCLUSION: High-resolution manometry for the detection of HH before bariatric surgery has a high specificity and maintains a high accuracy in both primary and revision bariatric surgery.

Association between bariatric surgery and risks of cancer among Chinese patients with type 2 diabetes mellitus: A retrospective cohort study.

BACKGROUND: To examine risks of cancers, obesity-related cancers (eg, cancers in digestive organs, breast, ovary, kidney, thyroid, and myeloma), cancer-related mortality, and all-cause mortality in patients with type 2 diabetes mellitus (T2DM) and obesity who underwent bariatric surgery. METHODS: A retrospective cohort of 1944 T2DM patients with obesity (345 bariatric surgery patients and 1599 matched controls) who were free of cancer from 2006 to 2017 was assembled. One-to-five propensity score matching followed by propensity score trimming was used to balance baseline covariates. RESULTS: During a mean follow-up period of 37 months, there are risks that in 3.2%, 1.4%, 0.9%, and 3.2% of bariatric patients cancer, obesity-related cancer, cancer-related mortality, and all-cause mortality, respectively, would occur. Surgical patients were found to have reduced incidence rates (IRs) of obesity-related cancer (0.531/100 person-years, 95% confidence interval [CI]: 0.172-1.238/100 person-years) and cancer of breast and genital organs (0.394/100 person-years, 95% CI: 0.048-1.424/100 person-years) than matched control patients whose IRs for obesity-related cancer and cancer of breast and genital organs were 0.627/100 person-years (95% CI: 0.426-0.889/100 person-years) and 0.521/100 person-years (95% CI: 0.277-0.891/100 person-years), respectively. Patients in the surgical group had a significant reduction in risk of all-cause mortality (hazard ratio [HR] = 0.508, P = .041). Effects of bariatric surgery on any cancers (HR = 1.254, P = .510), obesity-related cancers (HR = 0.843, P = .724), and cancer mortality (HR = 1.304, P = .694) were not significant. CONCLUSIONS: Bariatric surgery was not associated with risks of overall cancer, obesity-related cancer, and cancer mortality among T2DM patients with obesity at 3 years.

Effects of bariatric surgery on kidney diseases, cardiovascular diseases, mortality and severe hypoglycaemia among patients with Type 2 diabetes mellitus.

BACKGROUND: Bariatric surgery has been widely indicated for the management of obesity and related comorbidities. However, there are uncertainties pertaining to the risks of post-bariatric severe hypoglycaemia (SH), cardiovascular diseases (CVDs), end-stage kidney diseases (ESKDs) and all-cause mortality in obese patients with Type 2 diabetes mellitus (T2DM), especially among Asian populations. METHODS: A retrospective population-based cohort of 1702 obese T2DM patients who were free of CVD and ESKD were assembled based on the 2006-17 Hospital Authority database. One-to-five propensity-score matching was used to balance baseline covariates between patients in bariatric surgery and control groups. Incidence rates (IRs) of SH, CVD, Stage 4/5 chronic kidney diseases (CKD), ESKD and all-cause mortality events for two groups were calculated. Hazard ratios (HR) for SH, CVD and Stage 4/5 CKD events were assessed using Cox-proportional hazard models. Changes in estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) were measured up to 60 months. RESULTS: Over a mean follow-up period of 32 months with 5725 person-years, cumulative incidences of mortality, CVD, Stage 4/5 CKD, ESKD and SH were 0, 0.036, 0.050, 0.017 and 0.020, respectively. The surgery group had a significant reduction in risk of CVD events (HR = 0.464, P = 0.015) and no occurrence of mortality events. However, there were no significant differences in risks of SH [HR = 0.469, 95% confidence interval (CI): 0.204-1.081], Stage 4/5 CKD (HR =0.896, 95% CI: 0.519-1.545) and ESKD (HR = 0.666, 95% CI: 0.264-1.683) between two groups, although IRs were lower in the surgery group. Surgical patients had significantly higher eGFR within 12 months and had significantly lower UACR until 48 months. CONCLUSIONS: Among obese T2DM patients, bariatric surgery lowered the risk of CVD and mortality, and was beneficial towards the kidney outcomes.

Outcomes with Intra-gastric Balloon Therapy in BMI < 35 Non-morbid Obesity: 10-Year Follow-Up Study of an RCT.

PURPOSE: Intra-gastric balloon (IGB) therapy is the most established endoscopic treatment of obesity, but there is a paucity of literature on long-term efficacy. This study aims to evaluate the short- and long-term weight loss efficacy of IGB. MATERIALS AND METHODS: Double-blinded RCT with 6-month IGB vs with sham endoscopy, in body mass index (BMI) 27-35 patients. Anthropometric, fasting glucose, and lipid profile measurement as early outcomes (up to 2 years) and 10-year follow-up. Primary outcomes were total body weight loss (kg) and BMI. Secondary outcomes were new-onset diabetes mellitus, other new comorbidities, and willingness for further intervention. RESULTS: Initial RCT recruited 99 patients (50 IGB vs 49 sibutramine group). Forty-nine patients (26 IGB vs 23 control group) participated in a 10-year review (follow-up rate of 51.6%). Total body weight loss at 6 (9.75 vs 7.48 kg, p = 0.03), 12 (6.52 vs 4.42 kg, p = 0.05), 18 (5.42 vs 3.57, p = 0.32), and 24 months (4.07 vs 2.93 kg, p = 0.56) favored the IGB group. Total weight loss (TWL) at 10 years (0.03 vs - 2.32 kg, p = 0.05) and %TWL (- 0.16 ± 12.8% vs - 2.84 ± 5.6%, p = 0.39) were not significantly different between groups. Follow-up BMI (30.97 ± 1.6 vs 30.38 ± 1.8 kg/m2, p = 1.00) was similar. At 10 years, new-onset diabetes mellitus, sleep apnoea, metabolic syndrome, and arthralgia were not significant (p > 0.05). Twenty-three (81%) IGB group vs 13 (56%) control expressed a willingness for further intervention (p < 0.01). CONCLUSION: IGB delivers weight loss to 2 years and is superior to control. However, new comorbidity development is not significantly different at 10 years. Patient that received IGB therapy were subsequently more willing for further bariatric metabolic intervention.

Accuracy of hiatal hernia diagnosis in bariatric patients: Preoperative endoscopy versus intraoperative reference.

BACKGROUND AND AIM: Obesity is becoming increasingly prevalent in Asia. Bariatric surgery in the region is growing in popularity to reflect increasing demand. Hiatal hernia (HH) is common among the obese population. There is a lack of evidence comparing preoperative endoscopy against intraoperative findings as a standard of reference for HH diagnosis. METHODS: This was a retrospective analysis of a bariatric procedure database from a single tertiary teaching hospital and high-volume endoscopy center. Electronic medical records were reviewed. Endoscopy results were compared to intraoperative findings, and subgroup analysis of >2 cm hernias was performed. Sensitivity, specificity, predictive values, likelihood ratios, and global diagnostic test accuracy were calculated. RESULTS: A total of 434 patients were eligible for this study, of which HH was detected in 37 patients (prevalence rate 8.55%). Mean age was 41.51 ± 11.07 years, and body mass index was 39.37 ± 5.67 kg/m2. Endoscopy sensitivity was 75.68% (95% confidence interval, 58.80-88.23%) and specificity 91.44% (88.24-94.00%). Positive likelihood ratio was 8.53 (6.11-12.79) and negative likelihood ratio 0.27 (0.15-0.47). Positive predictive value was 45.16% (36.27-54.38%) and negative predictive value 97.58% (95.80-98.62%). Accuracy of endoscopy for preoperative HH diagnosis was 90.09% (86.89-92.74%). CONCLUSION: Endoscopy can have a high diagnostic accuracy of preoperative HH diagnosis in obese Asian patients using intraoperative diagnosis as the reference standard.

Mesenchymal Stem Cells Combined with Tissue Fusion Technology Promoted Wound Healing in Porcine Bowel Anastomosis.

OBJECTIVE: To evaluate the possible biological effect of allogenic mesenchymal stem cells (MSCs) combined with tissue fusion technology on the anastomosis. METHODS: Sixteen pigs were divided into a 7 d group and 14 d group, each of which was further subdivided into an MSC-treated group and a control group. Five anastomoses per animal were established using LigaSure ForceTriad (Covidien, MA, USA), a tissue sealing system. Cell migration and tissue-specific differentiation potency, in addition to potential cytokine and genetic changes, were investigated. RESULTS: There were no significant between-group differences in postoperative complications and anastomosis burst pressure. The number of proliferating cell nuclear antigen- (PCNA-) positive cells was significantly higher in the MSC-treated group as compared with that in the control group (P = 0.021). Labeled MSCs were found in the mucosal layer, villus, and lamina propria, as well as in the lamina muscularis mucosae, where they exhibited characteristics of smooth muscle cells. CONCLUSIONS: Grafted MSCs significantly promoted epithelial and connective cell proliferation and maintained their cell migration capacity and differentiation potential in the fused anastomotic tissues, without causing severe postoperative complications.

Utility of a standardized training program for endoscopic diagnosis of early gastrointestinal neoplasia.

Background and study aims Image enhanced endoscopy (IEE) allows endoscopists to improve recognition and characterization of gastrointestinal neoplasia. The Asian Novel Bio-Imaging and Intervention Group (ANBIG) conducted a standardized training program in endoscopic diagnosis and treatment of early gastrointestinal cancers in Asia. We embarked on a study to investigate the effect of this module on endoscopic diagnosis of early gastrointestinal neoplasia. Methods This prospectively collected database was from workshops conducted on training for endoscopic diagnosis of early gastrointestinal neoplasia. All workshops were conducted in a standardized format, which included a pretest, a learning phase consisting of didactic lectures, case discussion, and live demonstration followed by a post-test to assess knowledge gained. The pretest and post-training tests were standardized questions addressing four domains, including basic knowledge of imaging and diagnosis of esophageal, gastric, and colonic neoplasia. Results From November 2013 to November 2016, 41 ANBIG workshops were conducted in 13 countries. A total of 1863 delegates and 40 faculty participated in these workshops. Of the delegates, 627 completed both tests. There was a significant improvement after training in all domains of the tests. There was a trend in general lack of knowledge across all domains for delegates from "low" healthcare cost countries before training. All delegates demonstrated significant improvement in knowledge of all domains after the workshop irrespective of whether they were from "high" or "low" healthcare cost per capita countries. Conclusion A standardized teaching program on IEE improved the diagnostic ability and quality of endoscopists in recognizing early gastrointestinal neoplasia in Asia.

Observed changes in brown, white, hepatic and pancreatic fat after bariatric surgery: Evaluation with MRI.

OBJECTIVES: To study the change in brown and white adipose tissue (BAT and WAT), as well as fat content in the liver and pancreas, in patients with morbid obesity before and after bariatric surgery. METHODS: Twelve patients with morbid obesity (F=8, M=4, age: 45.4 years (38.4-51.2), BMI: 35.2 kg/m2 (32.5-38.6)) underwent pre-op MRI at baseline and two post-op scans at 6-month and 12-month intervals after bariatric surgery. Co-registered water, fat, fat-fraction and T2* image series were acquired. Supraclavicular BAT and abdominal WAT were measured using in-house algorithms. Intrahepatic triglyceride (IHTG) was measured using MR spectroscopy and pancreatic fat was measured using a region-of-interest approach. Fat contents were compared between baseline and the first and second 6-month intervals using non-parametric analysis of Friedman's test and Wilcoxon's signed-rank test. Level of significance was selected at p=0.017 (0.05/3). Threshold of non-alcoholic fatty liver disease was set at 5.56%. RESULTS: Results indicated that BMI (p=0.005), IHTG (p=0.005), and subcutaneous (p=0.005) and visceral adipose tissues (p=0.005) were significantly reduced 6 months after surgery. Pancreatic fat (p=0.009) was significantly reduced at 12 months. Most reduction became stable between the 6-month and 12-month interval. No significant difference was observed in BAT volume, fat-fraction and T2* values. CONCLUSION: The results of this study suggest that bariatric surgery effectively reduced weight, mainly as a result of the reduction of abdominal WAT. Liver and pancreatic fat were deceased below the threshold possibly due to the reduction of free fatty acid. BAT volume, fat-fraction and T2* showed no significant changes, probably because surgery itself might not have altered the metabolic profile of the patients. KEY POINTS: • No significant changes were observed in fat-fraction, T2* and volume of brown adipose tissue after bariatric surgery. • Non-alcoholic fatty liver disease was resolved after surgery. • Abdominal white fat and liver fat were significantly reduced 6 months after surgery and become stable between 6 and 12 months while pancreatic fat was significantly reduced between 0 and 12 months.

How I do it: Flexible 3-D endoscope for endoscopic submucosal dissection.

Endoscopic submucosal dissection (ESD) is technically challenging as a result of a lack of depth perception. The present article investigated the 3-D endoscope for carrying out ESD and translated the technique from bench to clinical use. In a preclinical porcine experiment, ESD using a 3-D endoscope was compared between an experienced and a novice endoscopist. All ESD were completed without perforation. Median operative time per surface area was significantly lower for the experienced endoscopist than for the novice (197.9 s/cm2 vs 434.7 s/cm2 ; P = 0.05). The second part was a prospective clinical experience to evaluate use of the 3-D endoscope for carrying out ESD. Ten patients received ESD using the 3-D endoscope. Four patients had gastric ESD, two had duodenal ESD and four had sigmoid and rectal ESD. There were no complications, whereas ESD failed in one patient who had gastric neoplasia at anastomosis. Mean operative time was 99.4 min, and operative time per surface area resection was 391 s/cm2 . The operating endoscopist did not complain of motion sickness, whereas the assistants had some dizziness upon prolonged ESD procedure. This study showed that carrying out ESD was safe and effective using a 3-D endoscope with an excellent 3-D view enhancing depth perception. Future study should be conducted to compare 3-D against 2-D endoscopes for ESD.

Validation of water-fat MRI and proton MRS in assessment of hepatic fat and the heterogeneous distribution of hepatic fat and iron in subjects with non-alcoholic fatty liver disease.

BACKGROUND: Research studies demonstrated pathologic lesions were unevenly distributed in patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. As hepatic steatosis occurs prior to steatohepatitis and other late stage liver conditions, the distribution pattern of hepatic fat and iron concentration should be investigated to prevent sampling variability. The first purpose of this study was to perform comparison and validation of in-house hepatic fat measurements using water-fat MRI and MRS. The second objective was to quantify hepatic fat-fraction and T2* values in left and right liver lobes using water-fat MRI. METHOD: Fifty-four non-alcoholic adults (27 NAFLD, age: 42.8 ± 11.8), 27 non-NAFLD, age: 45.5 ± 11.2) and 46 non-alcoholic teenagers (23 NAFLD (age: 15.4 ± 2.6), 23 non-NAFLD (age: 13.9 ± 2.3) were recruited. All participants underwent chemical shift water-fat MRI and 1H MRS at 3 T. Hepatic steatosis was defined by intrahepatic triglyceride more than the threshold of 5.56% using MRS (clinical reference) and non-alcoholic was defined by alcohol ingestion of no more than 30 g and 20 g per day for male and female respectively. Hepatic fat-fractions in left and right liver lobes were measured using regions-of-interest (ROIs) approach. Three ROIs were drawn on the fat-fraction images and duplicated on to the co-registered T2* images at the inferior right, superior right and superior left liver lobes. Comparison and validation of water-fat MRI and MRS were performed using intraclass correlation coefficient (ICC) and Bland-Altman plot. Hepatic fat-fraction and T2* measured from the ROIs were compared using repeated measures ANOVA. Independent t-test was used for between groups analysis. RESULTS: Statistical analysis indicated good correlation (R = 0.987) and agreement (ICC = 0.982) between MRS and water-fat MRI in hepatic fat measurements. Results indicated that hepatic fat was significantly higher in the right lobe compared to the left in NAFLD adults (p < 0.001) and NAFLD teenagers (p < 0.001). For T2*, significant difference between left and right lobes was observed in NAFLD adults (p < 0.001) and non-NAFLD adults (p < 0.001) but not in teenagers. CONCLUSION: Hepatic fat measurements using MRS and water-fat MRI are statistically equivalent. In subjects with NAFLD regardless of their age, hepatic fat is stored preferentially in the right live lobe probably due to the streamline of blood flow to the right liver. T2* value is significantly higher in the right liver lobe in adults but not in the teenagers regardless of their hepatic fat contents probably due to the longer time span of hepatic iron accumulation.

Oncogenic microRNA signature for early diagnosis of cervical intraepithelial neoplasia and cancer.

Cervical cancer is one of the leading causes of cancer death in women globally, despite the widespread use of cytology/human papillomavirus (HPV) screening. In the present study, we aimed to identify the potential role of microRNA (miRNA) as a diagnostic biomarker in the detection of cervical pre-malignant lesions and cancer. In total, we recruited 582 patients with cervical diseases and 145 control individuals. The expression levels of six miRNAs (miR-20a, miR-92a, miR-141, miR-183*, miR-210 and miR-944) were found to be significantly up-regulated in cervical cancer and pre-malignant lesions compared to normal cervical samples, indicating that they are oncogenic miRNAs. Receiver operating characteristic curve analysis showed that these six miRNAs can be used to distinguish patients with cervical pre-malignant lesions or cancer from normal individuals and they also had a good predictive performance, particularly in cervical lesions. Combined use of these six miRNAs further enhanced the diagnostic accuracy over any single miRNA marker, with an area under the curve of 0.998, 0.996 and 0.959, a diagnostic sensitivity of 97.9%, 97.2% and 91.4%, and a specificity of 98.6%, 96.6% and 87.6% for low-grade lesions, high-grade lesions and cancer, respectively. This six oncogenic miRNA signature may be suitable for use as diagnostic marker for cervical pre-malignant lesions and cancer in the near future.

MicroRNA-125b Interacts with Foxp3 to Induce Autophagy in Thyroid Cancer.

Thyroid cancer is rapidly increasing in incidence worldwide. Although most thyroid cancer can be cured with surgery, radioactive iodine, and/or chemotherapy, thyroid cancers still recur and may become chemoresistant. Autophagy is a complex self-degradative process that plays a dual role in cancer development and progression. In this study, we found that miR-125b was downregulated in tissue samples of thyroid cancer as well as in thyroid cancer cell lines, and the expression of Foxp3 was upregulated. Further, we demonstrated that miR-125b could directly act on Foxp3 by binding to its 3' UTR and inhibit the expression of Foxp3. A negative relationship between miR-125b and Foxp3 was thus revealed. Overexpression of miR-125b markedly sensitized thyroid cancer cells to cisplatin treatment by inducing autophagy through an Atg7 pathway in vitro and in vivo. Taken together, our findings demonstrate a novel mechanism by which miR-125b has the potential to negatively regulate Foxp3 to promote autophagy and enhance the efficacy of cisplatin in thyroid cancer. miR-125 may be of therapeutic significance in thyroid cancer.

MiR-92 suppresses proliferation and induces apoptosis by targeting EP4/Notch1 axis in gastric cancer.

MiR-92a has been shown to be dysregulated in various cancers and exhibited differential role in carcinogenesis. In this study, we sought to delineate the functional role of miR-92a and its regulatory pathway in gastric cancer. MiR-92a expression were underexpressed in tissues of gastric cancer patients with the area under curve (AUC) of 0.78. Low expression in plasma was due to the increased promoter DNA methylation of miR-92a. Overexpression of miR-92a inhibited cell proliferation and invasion, and induced apoptosis. Furthermore, miR-92a reduced tumor growth in xenograft model. EP4 and Notch 1 were identified to be negatively regulated by miR-92a, and involved in cell growth. Moreover, NF-κB expression was inversely correlated with miR-92a in gastric cancer tissues and suppressed the expression of miR-92. This study unravels the tumor suppressive role of miR-92a involving EP4/Notch 1 signaling regulated by NF-κB in gastric cancer. Further studies on miR-92a and EP4/Notch1 may provide a new treatment strategy for gastric cancer.

Global Incidence and mortality of oesophageal cancer and their correlation with socioeconomic indicators temporal patterns and trends in 41 countries.

Oesophageal cancers (adenocarcinomas [AC] and squamous cell carcinomas [SCC]) are characterized by high incidence/mortality in many countries. We aimed to delineate its global incidence and mortality, and studied whether socioeconomic development and its incidence rate were correlated. The age-standardized rates (ASRs) of incidence and mortality of this medical condition in 2012 for 184 nations from the GLOBOCAN database; national databases capturing incidence rates, and the WHO mortality database were examined. Their correlations with two indicators of socioeconomic development were evaluated. Joinpoint regression analysis was used to generate trends. The ratio between the ASR of AC and SCC was strongly correlated with HDI (r = 0.535 [men]; r = 0.661 [women]) and GDP (r = 0.594 [men]; r = 0.550 [women], both p < 0.001). Countries that reported the largest reduction in incidence in male included Poland (Average Annual Percent Change [AAPC] = -7.1, 95%C.I. = -12,-1.9) and Singapore (AAPC = -5.8, 95%C.I. = -9.5,-1.9), whereas for women the greatest decline was seen in Singapore (AAPC = -12.3, 95%C.I. = -17.3,-6.9) and China (AAPC = -5.6, 95%C.I. = -7.6,-3.4). The Philippines (AAPC = 4.3, 95%C.I. = 2,6.6) and Bulgaria (AAPC = 2.8, 95%C.I. = 0.5,5.1) had a significant mortality increase in men; whilst Columbia (AAPC = -6.1, 95%C.I. = -7.5,-4.6) and Slovenia (AAPC = -4.6, 95%C.I. = -7.9,-1.3) reported mortality decline in women. These findings inform individuals at increased risk for primary prevention.

Serum microRNA-193b as a promising biomarker for prediction of chemoradiation sensitivity in esophageal squamous cell carcinoma patients.

Esophageal squamous cell carcinoma (ESCC) is the most predominantly occurring type of esophageal cancer worldwide. Locally advanced ESCC patients are treated by neoadjuvant chemoradiation for tumor downstaging prior to tumor resection. Patients receiving this treatment have an increased expectation of cure via the following tumor resection and have better survival outcomes. However, not all patients respond well to chemoradiation and poor responders suffer from treatment-associated toxicity and complications without benefits. No method is currently available to predict patient chemoradiation response and to exclude poor responders from ineffective treatment. To address this clinical limitation, the present study aimed to identify non-invasive biomarkers for predicting patient chemoradiation response. Due to the features of microRNA (miRNA) in cancer diagnosis, prognosis and treatment response prediction, serum miRNA arrays were performed to identify potential miRNA(s) that may be used for chemoradiation response prediction in ESCC. Using an miRNA array to compare pre-treatment serum sample pools from 10 good responders and 10 poor responders, the present study identified miR-193b, miR-942 and miR-629* as candidate miRNAs for predicting chemoradiation response. Subsequent validation using reverse transcription-quantitative polymerase chain reaction confirmed that miR-193b, however not miR-942 and miR-629*, were significantly increased in sera from 24 good responders, compared with 23 poor responders. Further analyses using the receiver operating characteristic curve revealed a strong predictive power of serum miR-193b on discriminating good responders from poor responders to chemoradiation. In addition, a high serum level of miR-193b was significantly associated with better survival outcomes. Therefore, serum miR-193b may be considered a promising biomarker for predicting chemoradiation response and post-therapy survival of ESCC patients.