Prospective clinical cohort study: low incidence of Barrett esophagus but high rate of reflux disease at 5-year follow-up after sleeve gastrectomy versus Roux-en-Y gastric bypass.

BACKGROUND: Gastroesophageal reflux disease seems more frequent after laparoscopic sleeve gastrectomy (LSG) than Roux-en-Y gastric bypass (LRYGB). Retrospective case series have raised concerns about a high incidence of Barrett esophagus (BE) after LSG. OBJECTIVE: This prospective clinical cohort study compared the incidence of BE ≥5 years after LSG and LRYGB. SETTING: St. Clara Hospital, Basel, and University Hospital, Zürich, Switzerland. METHODS: Patients were recruited from 2 bariatric centers where preoperative gastroscopy is standard practice and LRYGB is preferred for patients with preexisting gastroesophageal reflux disease. At follow-up ≥5 years after surgery, patients underwent gastroscopy with quadrantic biopsies from the squamocolumnar junction and metaplastic segment. Symptoms were assessed using validated questionnaires. Wireless pH measurement assessed esophageal acid exposure. RESULTS: A total of 169 patients were included, with a median 7.0 ± 1.5 years after surgery. In the LSG group (n = 83), 3 patients had endoscopically and histologically confirmed de novo BE; in the LRYGB group (n = 86), there were 2 patients with BE, 1 de novo and 1 preexisting (de novo BE, 3.6% versus 1.2%; P = .362). At follow-up, reflux symptoms were reported more frequently by the LSG group than by the LRYGB group (51.9% versus 10.5%). Similarly, moderate-to-severe reflux esophagitis (Los Angeles grade B-D) was more common (27.7% versus 5.8%) despite greater use of proton pump inhibitors (49.4% versus 19.7%), and pathologic acid exposure was more frequent in patients who underwent LSG than in patients who underwent LRYGB. CONCLUSIONS: After at least 5 years of follow-up, a higher incidence of reflux symptoms, reflux esophagitis, and pathologic esophageal acid exposure was found in patients who underwent LSG compared with patients who underwent LRYGB. However, the incidence of BE after LSG was low and not significantly different between the 2 groups.

Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.

AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS: We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.

Effect of the Natural Sweetener Xylitol on Gut Hormone Secretion and Gastric Emptying in Humans: A Pilot Dose-Ranging Study.

Sugar consumption is associated with a whole range of negative health effects and should be reduced and the natural sweetener xylitol might be helpful in achieving this goal. The present study was conducted as a randomized, placebo-controlled, double-blind, cross-over trial. Twelve healthy, lean volunteers received intragastric solutions with 7, 17 or 35 g xylitol or tap water on four separate days. We examined effects on: gut hormones, glucose, insulin, glucagon, uric acid, lipid profile, as well as gastric emptying rates, appetite-related sensations and gastrointestinal symptoms. We found: (i) a dose-dependent stimulation of cholecystokinin (CCK), active glucagon-like peptide-1 (aGLP-1), peptide tyrosine tyrosine (PYY)-release, and decelerated gastric emptying rates, (ii) a dose-dependent increase in blood glucose and insulin, (iii) no effect on motilin, glucagon, or glucose-dependent insulinotropic peptide (GIP)-release, (iv) no effect on blood lipids, but a rise in uric acid, and (v) increased bowel sounds as only side effects. In conclusion, low doses of xylitol stimulate the secretion of gut hormones and induce a deceleration in gastric emptying rates. There is no effect on blood lipids and only little effect on plasma glucose and insulin. This combination of properties (low-glycemic sweetener which stimulates satiation hormone release) makes xylitol an attractive candidate for sugar replacement.

Long-Term Effects of Laparoscopic Sleeve Gastrectomy and Roux-en-Y Gastric Bypass on Body Composition and Bone Mass Density.

BACKGROUND: Currently, the two most common bariatric procedures are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Long-term data comparing the two interventions in terms of their effect on body composition and bone mass density (BMD) are scarce. OBJECTIVE: The aim of this study was to assess body composition and BMD at least 5 years after LSG and LRYGB. SETTING: Department of Endocrinology and Nutrition, St. Claraspital Basel and St. Clara Research Ltd., Basel, Switzerland. METHODS: Bariatric patients at least 5 years after surgery (LSG or LRYGB) were recruited, and body composition and BMD were measured by means of dual-energy X-ray absorptiometry. Data from body composition before surgery were included in the analysis. Blood samples were taken for determination of plasma calcium, parathyroid hormone, vitamin D3, alkaline phosphatase, and C-terminal telopeptide, and the individual risk for osteoporotic fracture assessed by the Fracture Risk Assessment Tool score was calculated. After surgery, all patients received multivitamins, vitamin D3, and zinc. In addition, LRYGB patients were prescribed calcium. RESULTS: A total of 142 patients were included, 72 LSG and 70 LRYGB, before surgery: median body mass index 43.1, median age 45.5 years, 62.7% females. Follow-up after a median of 6.7 years. For LRYGB, the percentage total weight loss at follow-up was 26.3% and for LSG 24.1% (p = 0.243). LRYGB led to a slightly lower fat percentage in body composition. At follow-up, 45% of both groups had a T score at the femoral neck below -1, indicating osteopenia. No clinically relevant difference in BMD was found between the groups. CONCLUSIONS: At 6.7 years after surgery, no difference in body composition and BMD between LRYGB and LSG was found. Deficiencies and bone loss remain an issue after both interventions and should be monitored.

First-Phase Insulin and Amylin after Bariatric Surgery: A Prospective Randomized Trial on Patients with Insulin Resistance or Diabetes after Gastric Bypass or Sleeve Gastrectomy.

BACKGROUND: Most patients with severe obesity show glucose intolerance. Early after sleeve gastrectomy (LSG) or gastric bypass (LRYGB), a marked amelioration in glycemic control occurs. The underlying mechanism is not yet clear. OBJECTIVE: To determine whether the improvement in glycemic control on the level of endocrine pancreatic function is due to an increased first-phase insulin secretion comparing LRYGB to LSG. SETTING: University of Basel Hospital and St. Clara Research Ltd., Basel, Switzerland. METHODS: Sixteen morbidly obese patients with severe obesity and different degrees of insulin resistance were randomized to LSG or LRYGB, and islet cell functions were tested by intravenous glucose and intravenous arginine administration before and 4 weeks after surgery. RESULTS: Fasting insulin and glucose levels and homeostasis model assessment insulin resistance were significantly lower in both groups after surgery compared to baseline, while no change was seen in fasting C-peptide, amylin, and glucagon. After intravenous glucose stimulation, no statistically significant pre- to postoperative change in area under the curve (AUC 0-60 min) was seen for insulin, glucagon, amylin, and C-peptide. No statistically significant pre- to postoperative change in incremental AUC for first-phase insulin release (AUC 0-10 min), second-phase insulin secretion (AUC 10-60 min), and insulin/glucose ratio could be shown in either group. Arginine-stimulated insulin and glucagon release showed no pre- to postoperative change. CONCLUSION: Intravenous glucose and arginine administrations show no pre- to postoperative changes of insulin release, amylin, glucagon, or C-peptide concentrations, and no differences between LRYGB and LSG were found. The postoperative improvement in glycemic control is not caused by changes in endocrine pancreatic hormone secretion.

Impact of laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy on gut microbiota: a metagenomic comparative analysis.

BACKGROUND: Bariatric surgery is an effective therapeutic procedure for morbidly obese patients. The 2 most common interventions are sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). OBJECTIVES: The aim of this study was to compare microbiome long-term microbiome after SG and LRYGB surgery in obese patients. SETTING: University Hospital, France; University Hospital, United States; and University Hospital, Switzerland. METHODS: Eighty-nine and 108 patients who underwent SG and LRYGB, respectively, were recruited. Stools were collected before and 6 months after surgery. Microbial DNA was analyzed with shotgun metagenomic sequencing (SOLiD 5500 xl Wildfire). MSPminer, a novel innovative tool to characterize new in silico biological entities, was used to identify 715 Metagenomic Species Pan-genome. One hundred forty-eight functional modules were analyzed using GOmixer and KEGG database. RESULTS: Both interventions resulted in a similar increase of Shannon's diversity index and gene richness of gut microbiota, in parallel with weight loss, but the changes of microbial composition were different. LRYGB led to higher relative abundance of aero-tolerant bacteria, such as Escherichia coli and buccal species, such as Streptococcus and Veillonella spp. In contrast, anaerobes, such as Clostridium, were more abundant after SG, suggesting better conservation of anaerobic conditions in the gut. Enrichment of Akkermansia muciniphila was also observed after both surgeries. Function-level changes included higher potential for bacterial use of supplements, such as vitamin B12, B1, and iron upon LRYGB. CONCLUSION: Microbiota changes after bariatric surgery depend on the nature of the intervention. LRYGB induces greater taxonomic and functional changes in gut microbiota than SG. Possible long-term health consequences of these alterations remain to be established.

Quantification of Liver, Subcutaneous, and Visceral Adipose Tissues by MRI Before and After Bariatric Surgery.

BACKGROUND: Morbid obesity is a worldwide epidemic and is increasingly treated by bariatric surgery. Fatty liver is a common finding; almost half of all patients with non-alcoholic steatohepatitis develop steatohepatitis. Bariatric surgery improves steatohepatitis documented by liver biopsy and single voxel magnetic resonance imaging (MRI) techniques. OBJECTIVE: To investigate changes before and after bariatric surgery using whole organ MRI quantification of liver, visceral, and subcutaneous fat. SETTING: University of Basel Hospital and St. Clara Research Ltd, Basel, Switzerland. METHODS: Sixteen morbidly obese patients were evaluated by abdominal MRI-scanning before and 3, 6, 12, and 24 months after bariatric surgery to measure percentage liver fat (%-LF), total liver volume (TLV) and visceral and subcutaneous adipose tissues (VAT and SAT). Fasting plasma samples were taken for measurement of glucose, insulin, blood lipids, and liver biomarkers. In a control group of 12 healthy lean volunteers, the liver biomarker was also measured. RESULTS: The reproducibility of fat quantification by use of MRI was excellent. LF decreased significantly faster than VAT and SAT (%-LF vs. VAT p < 0.001 and %-LF vs. SAT p < 0.001). At certain time points, %-LF, VAT, and SAT were associated with changes in blood lipids and insulin. CONCLUSIONS: MRI quantification offers excellently reproducible results in measurement of liver fat and visceral and subcutaneous adipose tissues. Liver fat decreased significantly faster than visceral or subcutaneous adipose tissue. Decrease in %-LF and VAT is associated with decrease in total cholesterol, LDL, and plasma insulin.

The impact of preoperative investigations on the management of bariatric patients; results of a cohort of more than 1200 cases.

BACKGROUND: Despite the increasing use of bariatric surgery as the most effective treatment of morbid obesity, there is still no consensus on its preoperative diagnostic workup. The aim of this study was to identify the pathologies of the endoscopic and radiologic investigations before performing bariatric surgery and to evaluate their impact on the patient management. METHODS: Retrospective analysis of prospectively collected data of 1225 consecutive patients who underwent laparoscopic Roux-en-Y gastric bypass (n = 834) or sleeve gastrectomy (n = 391) at our institution. An abdominal ultrasound was performed in 1188 patients, 1190 patients underwent upper gastrointestinal (GI) endoscopy, 1178 patients underwent upper GI series, and 610 patients underwent esophageal manometry. SETTING: Private hospital, Switzerland. RESULTS: Gallstones were detected in 222 (21.0%) patients, and a synchronous cholecystectomy was performed in 220 (18.0%) patients. The upper GI series indicated hiatal hernias in 325 (27.6%) patients. The most common findings of the upper GI endoscopy were type-C gastritis (224 patients, 18.8%), reflux esophagitis (229 patients, 19.2%), Helicobacter pylori-positive gastritis (158, 13.3%), and hiatal hernia (55 patients, 4.6%). Additionally, we detected 1 Barrett's high-grade dysplasia, 2 Barrett's carcinomas, and 1 stomach cancer in asymptomatic patients, who were scheduled to have a sleeve gastrectomy. Esophageal motility disorders were detected in 104 (17.0%) individuals, who underwent esophageal manometry. CONCLUSIONS: We recommend performing abdominal sonography and upper GI endoscopy before bariatric surgery as they reveal findings, which influence the therapeutic approach. Upper GI series and esophageal manometry help to define patients not suitable for sleeve gastrectomy.

Insulin resistance causes inflammation in adipose tissue.

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized Clinical Trial.

Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. Objective: To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. Interventions: Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). Main Outcomes and Measures: The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. Results: Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and Relevance: Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. Trial Registration: clinicaltrials.gov Identifier: NCT00356213.

Deregulation of transcription factors controlling intestinal epithelial cell differentiation; a predisposing factor for reduced enteroendocrine cell number in morbidly obese individuals.

Morbidly obese patients exhibit impaired secretion of gut hormones that may contribute to the development of obesity. After bariatric surgery there is a dramatic increase in gut hormone release. In this study, gastric and duodenal tissues were endoscopically collected from lean, and morbidly obese subjects before and 3 months after laparoscopic sleeve gastrectomy (LSG). Tissue morphology, abundance of chromogranin A, gut hormones, α-defensin, mucin 2, Na+/glucose co-transporter 1 (SGLT1) and transcription factors, Hes1, HATH1, NeuroD1, and Ngn3, were determined. In obese patients, the total number of enteroendocrine cells (EEC) and EECs containing gut hormones were significantly reduced in the stomach and duodenum, compared to lean, and returned to normality post-LSG. No changes in villus height/crypt depth were observed. A significant increase in mucin 2 and SGLT1 expression was detected in the obese duodenum. Expression levels of transcription factors required for differentiation of absorptive and secretory cell lineages were altered. We propose that in obesity, there is deregulation in differentiation of intestinal epithelial cell lineages that may influence the levels of released gut hormones. Post-LSG cellular differentiation profile is restored. An understanding of molecular mechanisms controlling epithelial cell differentiation in the obese intestine assists in the development of non-invasive therapeutic strategies.

Extracellular vesicles in gastrointestinal cancer in conjunction with microbiota: On the border of Kingdoms.

Extracellular vesicle (EV) production is a universal feature of metazoan cells as well as prokaryotes (bMVs - bacterial microvesicles). They are small vesicles with phospholipid membrane carrying proteins, DNA and different classes of RNAs and are heavily involved in intercellular communication acting as vectors of information to target cells. For the last decade, the interest in EV research has exponentially increased though thorough studies of their roles in various pathologies that was not previously possible due to technical limitations. This review focuses on research evaluating the role of EV production in gastrointestinal (GI) cancer development in conjunction with GI microbiota and inflammatory diseases. We also discuss recent studies on the promising role of EVs and their content as biomarkers for early diagnosis of GI cancers. The bMVs have also been implicated in the pathogenesis of GI chronic inflammatory diseases, however, possible role of bMVs in tumorigenesis remains underestimated. We propose that EVs from eukaryotic cells as well as from different microbial, fungi, parasitic species and edible plants in GI tract act as mediators of intracellular and inter-species communication, particularly facilitating tumor cell survival and multi-drug resistance. In conclusion, we suggest that matching sequences from EV proteomes (available from public databases) with known protein sequences of microbiome gut bacteria will be useful in identification of antigen mimicry between evolutionary conservative protein sequences. Using this approach we identified Bacteroides spp. pseudokinase with activation loop and homology to PDGFRα, providing a proof-of-concept strategy. We speculate that existence of microbial pseudokinase that 'mimics' PDGFRα may be related to PDGFRα and Bacteroides spp. roles in colorectal carcinogenesis that require further investigation.

Laparoscopic Sleeve Gastrectomy Versus Roux-Y-Gastric Bypass for Morbid Obesity-3-Year Outcomes of the Prospective Randomized Swiss Multicenter Bypass Or Sleeve Study (SM-BOSS).

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is performed almost as often in Europe as laparoscopic Roux-Y-Gastric Bypass (LRYGB). We present the 3-year interim results of the 5-year prospective, randomized trial comparing the 2 procedures (Swiss Multicentre Bypass Or Sleeve Study; SM-BOSS). METHODS: Initially, 217 patients (LSG, n = 107; LRYGB, n = 110) were randomized to receive either LSG or LRYGB at 4 bariatric centers in Switzerland. Mean body mass index of all patients was 44 ±â€Š11 kg/m, mean age was 43 ±â€Š5.3 years, and 72% of patients were female. Minimal follow-up was 3 years with a rate of 97%. Both groups were compared for weight loss, comorbidities, quality of life, and complications. RESULTS: Excessive body mass index loss was similar between LSG and LRYGB at each time point (1 year: 72.3 ±â€Š21.9% vs. 76.6 ±â€Š20.9%, P = 0.139; 2 years: 74.7 ±â€Š29.8% vs. 77.7 ±â€Š30%, P = 0.513; 3 years: 70.9 ±â€Š23.8% vs. 73.8 ±â€Š23.3%, P = 0.316). At this interim 3-year time point, comorbidities were significantly reduced and comparable after both procedures except for gastro-esophageal reflux disease and dyslipidemia, which were more successfully treated by LRYGB. Quality of life increased significantly in both groups after 1, 2, and 3 years postsurgery. There was no statistically significant difference in number of complications treated by reoperation (LSG, n = 9; LRYGB, n = 16, P = 0.15) or number of complications treated conservatively. CONCLUSIONS: In this trial, LSG and LRYGB are equally efficient regarding weight loss, quality of life, and complications up to 3 years postsurgery. Improvement of comorbidities is similar except for gastro-esophageal reflux disease and dyslipidemia that appear to be more successfully treated by LRYGB.

Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.

The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.

Development and Clinical Validation of a Blood Test Based on 29-Gene Expression for Early Detection of Colorectal Cancer.

PURPOSE: A blood test for early detection of colorectal cancer is a valuable tool for testing asymptomatic individuals and reducing colorectal cancer-related mortality. The objective of this study was to develop and validate a novel blood test able to differentiate patients with colorectal cancer and adenomatous polyps (AP) from individuals with a negative colonoscopy. EXPERIMENTAL DESIGN: A case-control, multicenter clinical study was designed to collect blood samples from patients referred for colonoscopy or surgery. Predictive algorithms were developed on 75 controls, 61 large AP (LAP) ≥1 cm, and 45 colorectal cancer cases and independently validated on 74 controls, 42 LAP, and 52 colorectal cancer cases (23 stages I-II) as well as on 245 cases including other colorectal findings and diseases other than colorectal cancer. The test is based on a 29-gene panel expressed in peripheral blood mononuclear cells alone or in combination with established plasma tumor markers. RESULTS: The 29-gene algorithm detected colorectal cancer and LAP with a sensitivity of 79.5% and 55.4%, respectively, with 90.0% specificity. Combination with the protein tumor markers carcinoembryonic antigen (CEA) and CYFRA21-2 resulted in a specificity increase (92.2%) with a sensitivity for colorectal cancer and LAP detection of 78.1% and 52.3%, respectively. CONCLUSIONS: We report the validation of a novel blood test, Colox®, for the detection of colorectal cancer and LAP based on a 29-gene panel and the CEA and CYFRA21-1 plasma biomarkers. The performance and convenience of this routine blood test provide physicians a useful tool to test average-risk individuals unwilling to undergo upfront colonoscopy. Clin Cancer Res; 22(18); 4604-11. ©2016 AACR.

Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial.

BACKGROUND/OBJECTIVES: The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads. SUBJECTS/METHODS: The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water. RESULTS: Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects. CONCLUSIONS: It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT01875575.

Incretin effects, gastric emptying and insulin responses to low oral glucose loads in patients after gastric bypass and lean and obese controls.

BACKGROUND: After laparoscopic Roux-en-Y gastric bypass (LRYGB), many patients suffer from dumping syndrome. Oral glucose tolerance tests are usually carried out with 50-75 g of glucose. The aim of this study was to examine whether minimal glucose loads of 10 g and 25 g induce a reliable secretion of satiation peptides without dumping symptoms after LRYGB. In addition, lean and obese controls were examined. OBJECTIVE: The objective of this study was to determine the effects of low oral glucose loads on incretin release and gastric emptying. SETTING: All surgical procedures were performed by the same surgeon (RP) at the St. Claraspital Basel in Switzerland. Oral glucose challenges were carried out at the University Hospital of Basel (Phase 1 Research Unit). METHODS: Eight patients 10±.4 weeks after LRYGB (PostOP; body mass index [BMI]: 38.6 kg/m2±1.7) as well as 12 lean controls (LC; BMI: 21.8 kg/m2±.6) and 12 obese controls (OC; BMI 38.7 kg/m2±1.3) received 10 g and 25 g of oral glucose. We examined clinical signs of dumping syndrome; plasma glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, and peptide tyrosine tyrosine concentrations; and gastric emptying with a 13 C-sodium acetate breath test. RESULTS: No signs of dumping were seen in PostOP. Compared with OC, LC showed lower fasting glucose, insulin, and C-peptide, and lower homeostasis model assessment (HOMA) and AUC-180 for insulin and C-peptide. In PostOP, fasting insulin, HOMA and AUC-180 for insulin was lower and no difference was found in fasting C-peptide or AUC-180 for C-peptide compared to OC. There was no significant difference in fasting glucose, insulin, C-peptide, HOMA and AUC-180 for insulin in PostOP compared to LC, but AUC-180 for C-peptide was higher in PostOP. AUC-60 for gut hormones was similar in OC and LC and higher in PostOP compared to OC or LC. gastric emptying was slower in LC and OC compared with PostOP. CONCLUSION: After LRYGB, 25 g oral glucose is well tolerated and leads to reliable secretion of gut hormones. Fasting glucose, insulin and C-peptide are normalized, while glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine are overcorrected. Pouch emptying is accelerated after LRYGB.

Monitoring colonoscopy withdrawal time significantly improves the adenoma detection rate and the performance of endoscopists.

BACKGROUND AND STUDY AIMS: The recommended minimum withdrawal time for screening colonoscopy is 6 minutes. Adenoma detection rates (ADRs) increase with longer withdrawal times. We aimed to compare withdrawal times and ADRs of endoscopists unaware of being monitored vs. aware. PATIENTS AND METHODS: Seven experienced gastroenterologists prospectively performed 558 screening colonoscopies during a 9-month period in a Swiss University hospital. Colonoscopy withdrawal times were first measured without the gastroenterologists' knowledge of being monitored (n = 355 colonoscopies) and then with their knowledge (n = 203 colonoscopies). RESULTS: The median withdrawal time when gastroenterologists were unaware of being monitored was 4.5 minutes (interquartile range [IQR] 4 ­â€Š5.5 minutes) without intervention and 6 minutes (IQR 4 ­â€Š9 minutes) with intervention, increasing significantly to 7.3 minutes (IQR 6.5 ­â€Š9 minutes) and 8 minutes (IQR 7 ­â€Š11 minutes), respectively, when they were aware of being monitored (P < 0.001 both for colonoscopies with and without intervention). The ADR increased from 21.4 % when the gastroenterologists were unaware of being monitored to 36.0 % when they were aware (P < 0.001). In the multivariate regression model, the endoscopists knowing they were being monitored was the strongest factor associated with ADR (odds ratio 4.417; 95 % confidence interval [CI] 2.241 ­â€Š8.705; P < 0.001). CONCLUSIONS: Colonoscopy withdrawal time in unmonitored gastroenterologists is shorter than recommended and increases with awareness of monitoring. ADR significantly increases when gastroenterologists are aware of being monitored. Implementation of systematic monitoring, and analysis of withdrawal time and ADR for each endoscopist may help to increase the ADR.

Sleep Disruption and Daytime Sleepiness Correlating with Disease Severity and Insulin Resistance in Non-Alcoholic Fatty Liver Disease: A Comparison with Healthy Controls.

BACKGROUND & AIMS: Sleep disturbance is associated with the development of obesity, diabetes and hepatic steatosis in murine models. Hepatic triglyceride accumulation oscillates in a circadian rhythm regulated by clock genes, light-dark cycle and feeding time in mice. The role of the sleep-wake cycle in the pathogenesis of human non-alcoholic fatty liver disease (NAFLD) is indeterminate. We sought to detail sleep characteristics, daytime sleepiness and meal times in relation to disease severity in patients with NAFLD. METHODS: Basic Sleep duration and latency, daytime sleepiness (Epworth sleepiness scale), Pittsburgh sleep quality index, positive and negative affect scale, Munich Chronotype Questionnaire and an eating habit questionnaire were assessed in 46 patients with biopsy-proven NAFLD and 22 healthy controls, and correlated with biochemical and histological parameters. RESULTS: In NAFLD compared to healthy controls, time to fall asleep was vastly prolonged (26.9 vs. 9.8 min., p = 0.0176) and sleep duration was shortened (6.3 vs. 7.2 hours, p = 0.0149). Sleep quality was poor (Pittsburgh sleep quality index 8.2 vs. 4.7, p = 0.0074) and correlated with changes in affect. Meal frequency was shifted towards night-times (p = 0.001). In NAFLD but not controls, daytime sleepiness significantly correlated with liver enzymes (ALAT [r = 0.44, p = 0.0029], ASAT [r = 0.46, p = 0.0017]) and insulin resistance (HOMA-IR [r = 0.5, p = 0.0009]) independent of cirrhosis. In patients with fibrosis, daytime sleepiness correlated with the degree of fibrosis (r = 0.364, p = 0.019). CONCLUSIONS: In NAFLD sleep duration was shortened, sleep onset was delayed and sleep quality poor. Food-intake was shifted towards the night. Daytime sleepiness was positively linked to biochemical and histologic surrogates of disease severity. The data may indicate a role for sleep-wake cycle regulation and timing of food-intake in the pathogenesis of human NAFLD as suggested from murine models.

Gastric emptying and disease activity in inflammatory bowel disease.

BACKGROUND: Gastric emptying (GE) is delayed in a subset of patients with inflammatory bowel disease (IBD). We have shown before that altered release of gastrointestinal hormones may contribute to GE disturbances, but overall effects of disease activity remain unclear. Thus, we aimed to evaluate GE in patients with IBD during active disease and following therapy. DESIGN: A total of 20 healthy subjects (HC) and 26 patients with IBD hospitalized because of an acute episode of their disease (Crohn's disease (CD) n = 13, ulcerative colitis (UC) n = 13) underwent a standardized (13) C-octanoic acid GE breath test (baseline test). Plasma glucose, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured periodically throughout the test. A total of 16 patients underwent a second GE test after 3-4 months of therapy. RESULTS: At baseline, nine patients with IBD had pathologically delayed GE half-time (T½ > 150 min) (P = 0·028 vs. HC). Moreover, T½ was significantly longer in the total group of patients with IBD than in HC (129 ± 12 min vs. 96 ± 7, P = 0·030). Postprandial GLP-1 responses were elevated in IBD (P = 0·002 vs. HC) and correlated with T½ (P = 0·05). Following therapy clinical activity indices and T½ were decreased in IBD (P ≤ 0·01 vs. baseline), and T½ no longer differed from HC (P > 0·5). Moreover, GLP-1 plasma levels decreased significantly (P = 0·031). CONCLUSIONS: Higher disease activity in IBD is associated with prolonged GE and increased release of GLP-1. Following effective therapy, GE is accelerated and GLP-1 release decreases significantly. Thus, increased release of GLP-1 from the inflamed mucosa might contribute to GE disturbances in IBD.