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Poor Sensitivity of Fecal Gluten Immunogenic Peptides and Serum Antibodies to Detect Duodenal Mucosal Damage in Celiac Disease Monitoring.
Laserna-Mendieta, EJ, Casanova, MJ, Arias, Á, Arias-González, L, Majano, P, Mate, LA, Gordillo-Vélez, CH, Jiménez, M, Angueira, T, Tébar-Romero, E, et al
Nutrients. 2020;(1)
Abstract
A lifelong gluten-free diet (GFD) is the only current treatment for celiac disease (CD), but strict compliance is complicated. Duodenal biopsies are the "gold standard" method for diagnosing CD, but they are not generally recommended for disease monitoring. We evaluated the sensitivity and specificity of fecal gluten immunogenic peptides (GIPs) to detect duodenal lesions in CD patients on a GFD and compared them with serum anti-tissue transglutaminase (tTG) IgA antibodies. A prospective study was conducted at two tertiary centers in Spain on a consecutive series of adolescents and adults with CD who maintained a long-lasting GFD. Adherence to a GFD and health-related quality of life were scored with validated questionnaires. Mucosal damage graded according to the Marsh-Oberhüber classification (Marsh 1/2/3) was used as the reference standard. Of the 97 patients included, 27 presented duodenal mucosal damage and 70 had normal biopsies (Marsh 0). The sensitivity (33%) and specificity (81%) of GIPs were similar to those provided by the two assays used to measure anti-tTG antibodies. Scores in questionnaires showed no association with GIP, but an association between GIPs and patients' self-reported gluten consumption was found (p = 0.003). GIP displayed low sensitivity but acceptable specificity for the detection of mucosal damage in CD.
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Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study.
van Baar, ACG, Holleman, F, Crenier, L, Haidry, R, Magee, C, Hopkins, D, Rodriguez Grunert, L, Galvao Neto, M, Vignolo, P, Hayee, B, et al
Gut. 2020;(2):295-303
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Abstract
BACKGROUND The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. METHODS International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. RESULTS Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p<0.001), FPG (-1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (-2.9±1.1, p<0.001), weight was modestly reduced (-2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly. CONCLUSIONS In this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further. TRIAL REGISTRATION NUMBER NCT02413567.
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Randomized Comparison of Gastric Tube Reconstruction With and Without Duodenal Diversion Plus Roux-en-Y Anastomosis After Esophagectomy.
Yano, M, Sugimura, K, Miyata, H, Motoori, M, Tanaka, K, Omori, T, Ohue, M, Sakon, M
Annals of surgery. 2020;(1):48-54
Abstract
OBJECTIVE This prospective randomized phase-II trial examined whether gastric reconstruction with duodenal diversion plus Roux-en-Y anastomosis(RY) minimized gastroduodenal reflux and delayed gastric emptying compared with standard gastric reconstruction. SUMMARY BACKGROUND DATA There is no established standard surgical procedure to prevent both gastroduodenal reflux and delayed gastric emptying simultaneously. METHODS Sixty patients with thoracic esophageal cancer scheduled to undergo esophagectomy with retrosternal gastric tube reconstruction were randomly allocated to standard gastric reconstruction (non-RY, n = 31) or gastric reconstruction with duodenal diversion plus RY (n = 29) groups. Primary endpoint was quality of life assessed by DAUGS-32 score 1 year after surgery. Secondary endpoints were the extent of postoperative duodenal juice reflux into the gastric tube, postoperative morbidity, endoscopic findings, body weight changes, and nutritional status. RESULTS Preoperative clinicopathological characteristics and postoperative morbidity did not differ significantly between groups. However, operation time and blood loss volume were significantly higher in the RY group. Pancreatic amylase concentrations in the gastric conduit on postoperative days 2, 3, and 7 were higher in the non-RY group. Postoperative endoscopic examination showed residual gastric content in 7 of 17 patients in the non-RY group but in none in the RY group (P = 0.012). Quality of life was significantly favorable in the RY group with regard to reflux symptoms and food passage dysfunction. Postoperative body weight changes, serum albumin levels, and peripheral blood lymphocyte counts were not significantly different between groups. CONCLUSION Gastric reconstruction with duodenal diversion plus RY is effective in improving both gastroduodenal reflux and delayed gastric emptying.
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No Difference Between Latiglutenase and Placebo in Reducing Villous Atrophy or Improving Symptoms in Patients With Symptomatic Celiac Disease.
Murray, JA, Kelly, CP, Green, PHR, Marcantonio, A, Wu, TT, Mäki, M, Adelman, DC, ,
Gastroenterology. 2017;(4):787-798.e2
Abstract
BACKGROUND & AIMS Gluten ingestion leads to symptoms and small intestinal mucosal injury in patients with celiac disease. The only option is the strict lifelong exclusion of dietary gluten, which is difficult to accomplish. Many patients following a gluten-free diet continue to have symptoms and have small intestinal mucosal injury. Nondietary therapies are needed. We performed a phase 2 study of the ability of latiglutenase, an orally administered mixture of 2 recombinant gluten-targeting proteases, to reduce mucosal morphometric measures in biopsy specimens from patients with celiac disease. METHODS We performed a double-blind, placebo-controlled, dose-ranging study to assess the efficacy and safety of latiglutenase in 494 patients with celiac disease (with moderate or severe symptoms) in North America and Europe, from August 2013 until December 2014. Participants reported following a gluten-free diet for at least 1 year before the study began. Patients with documented moderate or severe symptoms and villous atrophy (villous height:crypt depth ratio of ≤2.0) were assigned randomly to groups given placebo or 100, 300, 450, 600, or 900 mg latiglutenase daily for 12 or 24 weeks. Subjects completed the Celiac Disease Symptom Diary each day for 28 days and underwent an upper gastrointestinal endoscopy with duodenal biopsy of the distal duodenum at baseline and at weeks 12 and 24. The primary end point was a change in the villous height:crypt depth ratio. Secondary end points included numbers of intraepithelial lymphocytes, serology test results (for levels of antibodies against tissue transglutaminase-2 and deamidated gliadin peptide), symptom frequencies, and safety. RESULTS In a modified intent-to-treat population, there were no differences between latiglutenase and placebo groups in change from baseline in villous height:crypt depth ratio, numbers of intraepithelial lymphocytes, or serologic markers of celiac disease. All groups had significant improvements in histologic and symptom scores. CONCLUSIONS In a phase 2 study of patients with symptomatic celiac disease and histologic evidence of significant duodenal mucosal injury, latiglutenase did not improve histologic and symptom scores when compared with placebo. There were no significant differences in change from baseline between groups. ClinicalTrials.gov no: NCT01917630.
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Ethanol concentrations in the human gastrointestinal tract after intake of alcoholic beverages.
Rubbens, J, Brouwers, J, Wolfs, K, Adams, E, Tack, J, Augustijns, P
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2016;:91-5
Abstract
INTRODUCTION The goal of this study was to monitor gastric and duodenal ethanol concentrations arising from the consumption of commonly used alcoholic beverages. MATERIALS AND METHODS In a cross-over study, five fasting volunteers were asked to drink two standard consumptions of commercially available alcoholic beverages, including beer (Stella Artois®, 500 mL, 5.2% ethanol), wine (Blanc du Blanc®, 200 mL, 11% ethanol) and whisky (Gallantry Whisky®, 80 mL, 40% ethanol). The volunteers finished drinking beer within 10 min and wine or whisky within 5 min. Ethanol concentrations in gastric and duodenal fluids, aspirated as a function of time, were analyzed by headspace gas chromatography. RESULTS In all three conditions, the average gastric profile shows a maximum ethanol concentration (Cmax) at 7 min, while the mean duodenal profiles have a Tmax at 20, 7 and 12 min for beer, wine and whisky, respectively. The median gastric ethanol Cmax (min-max) for the beer, wine and whisky conditions amounts to 4.1% (3.1-4.1), 4.1% (2.6-7.3) and 11.4% (6.3-21.1), respectively. The mean duodenal profiles follow the same pattern as their corresponding gastric profiles, albeit with lower percentages of ethanol. Median duodenal ethanol Cmax (min-max) for beer, wine and whisky are 1.97% (0.89-4.3), 2.39% (2.02-5.63) and 5.94% (3.55-17.71), respectively. Intraluminal ethanol concentrations appear to decline relatively rapidly in fasting conditions: both stomach and duodenum contained less than 0.05% of ethanol after 120 min. CONCLUSIONS This in vivo study is the first to present intraluminal ethanol concentrations in man after the intake of alcoholic beverages. Relatively low and fast declining gastric ethanol concentrations were observed, contrasting with the current Food and Drug Administration guidelines for the in vitro testing of formulations with respect to ethanol resistance. The presented gastric and duodenal ethanol concentrations and their variation may serve as reference data to design relevant models for predicting (i) ethanol resistance of drug formulations and (ii) ethanol effects on drug solubility and permeability.
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A novel dynamic scintigraphic technique for assessing duodenal contractions during gastric emptying in humans: a feasibility study.
Kubo, TT, Moraes, ER, Secaf, M, Troncon, LE
Nuclear medicine communications. 2015;(1):95-101
Abstract
Duodenal contractions are thought to play a role in the control of gastric emptying. Although noninvasive techniques, such as ultrasonography and MRI, have been proposed for studying duodenal contractile activity in humans, there are no reports on the use of scintigraphy for this purpose. This work aimed to describe a novel scintigraphic technique for assessing duodenal contractility during gastric emptying in humans, and to present preliminary data on the frequency and amplitude of contractions detected in three different duodenal segments. Fasted young healthy volunteers (N=12) were given either a liquid or a solid test meal of similar calorie content (400 kcal) labeled with 99mTc-phytate. Static images were collected to determine gastric emptying. Dynamic images of the anterior aspect of the abdomen (1 frame/s) were also acquired periodically in a standard position for 256 s at 15-30 min intervals. 'Activity versus time' curves were generated for regions of interest corresponding to the proximal, middle, and distal duodenal segments. Curves were digitally filtered and processed to estimate both dominant frequency (fast Fourier transform) and amplitude (mean ejection fraction) of postprandial duodenal contractions. There were no significant differences regarding dominant frequency among proximal, middle, and distal duodenal regions of interest. In addition, there were no significant differences between the liquid and the solid meal in terms of either frequency or amplitude of duodenal contractions. Characterization of duodenal contractions in humans using scintigraphy is feasible and yields consistent data for both the frequency and the amplitude of postprandial contractions, which seems to be rather independent of meal consistency.
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Response to glucose tolerance testing and solid high carbohydrate challenge: comparison between Roux-en-Y gastric bypass, vertical sleeve gastrectomy, and duodenal switch.
Roslin, MS, Dudiy, Y, Brownlee, A, Weiskopf, J, Shah, P
Surgical endoscopy. 2014;(1):91-9
Abstract
BACKGROUND Hyperinsulinemic hypoglycemia is common after Roux-en-Y gastric bypass (RYGB) and may result in weight regain. The purpose of our investigation was to compare the effect of RYGB, vertical sleeve gastrectomy (VSG), and duodenal switch (DS) on insulin and glucose response to carbohydrate challenge. METHODS Patients meeting National Institutes of Health criteria for bariatric surgery selected their bariatric procedure after evaluation and education in this prospective nonrandomized study. Preoperatively and at 6, 9, and 12 months' follow-up, patients underwent blood draw to determine levels of fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), C-peptide, and 2-h oral glucose challenge test. Homoeostatic Model Assessment (HOMA)-IR, fasting to 1-h and 1- to 2-h ratios of glucose and insulin, were calculated. Statistical analysis was performed using ANOVA and Student's paired t test. All procedures were performed via a laparoscopic technique at a single institution. RESULTS Data from a total of 38 patients (13 RYGB, 12 VSG, 13 DS) were available for analysis. At baseline, all groups were similar; the only statistically significant difference was that DS patients had a higher preoperative weight and body mass index (BMI). All operations caused weight loss (BMI 47.7 ± 10-30.7 ± 6.4 kg/m(2) in RYGB; 45.7 ± 8.5-31.1 ± 5.5 kg/m(2) in VSG; 55.9 ± 11.4-27.5 ± 5.6 kg/m(2) in DS), reduction of fasting glucose, and improved insulin sensitivity. RYGB patients had a rapid rise in glucose with an accompanying rise in 1-h insulin to a level that exceeded preoperative levels. This was followed by a rapid decrease in glucose level. In comparison, DS patients had a lower increase in glucose and 1-h insulin, and the lowest HbA1c. These differences were statistically significant at various data points. For VSG, the results were intermediary. CONCLUSIONS Compared to gastric bypass, DS results in greater weight loss and improves insulin sensitivity and glucose homeostasis without causing a hyperinsulinemic response. Because the response to challenge after VSG is intermediary, pyloric preservation alone cannot account for this difference.
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Effect of amoxicillin/clavulanate on gastrointestinal motility in children.
Gomez, R, Fernandez, S, Aspirot, A, Punati, J, Skaggs, B, Mousa, H, Di Lorenzo, C
Journal of pediatric gastroenterology and nutrition. 2012;(6):780-4
Abstract
AIM: The aim of the present study was to evaluate the effect of amoxicillin/clavulanate (A/C) on gastrointestinal motility. METHODS Twenty consecutive pediatric patients referred for antroduodenal manometry received 20 mg/kg of A/C into the small bowel lumen. In 10 patients (group A), A/C was given 1 hour after and in 10 (group B), 1 hour before ingestion of a meal. Characteristics of the migrating motor complex, including presence, frequency, amplitude, and propagation of duodenal phase III and phase I duration and phase II motility index (MI), were evaluated 30 minutes before and after A/C administration. RESULTS There were no statistically significant differences in age and sex between the 2 groups. Manometry studies were considered normal in 8 patients in each group. In group A, 2 patients developed duodenal phase III after receiving A/C, and no significant difference was found in the MI before and after the drug administration. In group B, 9 patients developed duodenal phase III (P <0.05 vs group A). All phase III occurred within a few minutes from the medication administration. Most duodenal phase III contractions were preceded by an antral component during fasting but never after the medication was administered in either of the 2 groups (P<0.001 vs fasting). In group B, the duration of duodenal phase I was shorter after drug administration (P<0.05). There was no significant difference in duodenal phase II MI before and after A/C administration for the 2 study groups. CONCLUSIONS In children, administration of A/C directly into the small bowel before a meal induces phase III-type contractions in the duodenum, with characteristics similar to those present in the fasting state. These data suggest the possible use of A/C as a prokinetic agent. Further studies are needed to clarify its specific mechanism of action and the group of patients most likely to benefit from its use.
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The innovative potential of Lactobacillus rhamnosus LR06, Lactobacillus pentosus LPS01, Lactobacillus plantarum LP01, and Lactobacillus delbrueckii Subsp. delbrueckii LDD01 to restore the "gastric barrier effect" in patients chronically treated with PPI: a pilot study.
Del Piano, M, Anderloni, A, Balzarini, M, Ballarè, M, Carmagnola, S, Montino, F, Orsello, M, Pagliarulo, M, Tari, R, Soattini, L, et al
Journal of clinical gastroenterology. 2012;:S18-26
Abstract
BACKGROUND Gastroesophageal reflux disease is a very widespread condition. In Europe, it is estimated that about 175 million people suffer from this disease and have to chronically take drugs to increase gastric pH. The proton pump inhibitors (PPIs) such as omeprazole, lansoprazole, and esomeprazole are the most widely used drug typology in this regard. However, the inhibition of normal gastric acid secretion has important side effects, the most important being bacterial overgrowth in the stomach and duodenum with a concentration of >10⁵ viable cells/mL. As a major consequence of this, many harmful or even pathogenic bacteria contained in some foods could survive the gastric transit and colonize either the stomach itself, the duodenum, or the gut, where they could establish acute and even chronic infections with unavoidable consequences for the host's health. In other words, the "gastric barrier effect" is strongly reduced or even disrupted. To date, there are no real strategies to deal with this widespread, although still relatively little known, problem. The aim of this study was to confirm the gastric bacterial overgrowth in long-term PPI consumers and to assess the efficacy of some probiotic bacteria, belonging to both genera Lactobacillus and Bifidobacterium, in the reduction of gastric and duodenal bacterial overgrowth, therefore partially restoring the gastric barrier effect against foodborne pathogenic bacteria. METHODS For this purpose, probiotics with a strong demonstrated inhibitory activity on gram-negative bacteria, such as Escherichia coli, were tested in a human intervention trial involving a total of 30 subjects treated with PPIs for either 3 to 12 consecutive months (short-term) or >12 consecutive months (long-term). An additional 10 subjects not taking PPIs were enrolled and used as a control group representing the general population. Four selected probiotics Probiotical SpA (Novara, Italy), namely Lactobacillus rhamnosus LR06 (DSM 21981), Lactobacillus pentosus LPS01 (DSM 21980), Lactobacillus plantarum LP01 (LMG P-21021), and Lactobacillus delbrueckii subsp. delbrueckii LDD01 (DSM 22106) were administered for 10 days to 10 subjects treated with PPIs for >12 months (group B). In the 60 mg formulation, N-acetylcysteine was included as well in light of its well-known mechanical effects on bacterial biofilms. Gastroscopies were performed at the beginning of the study (d0) in all the groups (A, B, C, and D) and after 10 days (d10) in group B only; that is, at the end of probiotics intake. The total viable cells and total Lactobacillus were quantified in gastric juice and duodenal brushing material from all subjects. The results were compared among all the groups and with the control subjects (group D) to confirm the bacterial overgrowth. A comparison was made also between d0 and d10 in group B to quantify the efficacy of the 4 probiotics administered for 10 days. Fecal samples were collected from all groups at d0, including subjects not treated with PPIs, and in group B only at d10. Specific bacterial classes, namely enterococci, total coliforms, E. coli, molds, and yeasts were quantified in all fecal specimens. RESULTS The results collected confirmed the strong bacterial overgrowth in the stomach and duodenum of people treated with PPIs compared with subjects with a normal intragastric acidity. It is also worth noting that the bacterial cell counts in subjects who underwent a long-term treatment with a PPI were greater than the results from subjects taking these drugs for 3 to 12 months. The intake of 4 specific probiotic strains with a marked antagonistic activity towards 5 E. coli bacteria, including the enterohaemorrhagic O157:H7 strain, and an effective amount of N-acetylcysteine (NAC) was able to significantly reduce bacterial overgrowth in long-term PPI-treated subjects. Total lactobacilli represented the major percentage of bacterial counts, thus demonstrating the ability of such bacteria to colonize the stomach and the duodenum, at least temporarily, and to consequently restore the gastric barrier effect. A significant decrease in fecal enterococci, total coliforms, E. coli, molds, and yeasts in subjects treated with PPIs was recorded at the end of probiotics supplementation (d10) compared with baseline (d0) in group B. This is a further confirmation of the barrier effect also exerted at the stomach level. CONCLUSIONS PPIs are the most widely sold and used drugs in the world. However, the chronic use of these pharmacological molecules exposes the subject to the risk of foodborne infections as most pathogens are able to survive the gastric transit in a condition of significantly decreased acidity.
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The delta-shaped anastomosis in laparoscopic distal gastrectomy: analysis of the initial 100 consecutive procedures of intracorporeal gastroduodenostomy.
Kanaya, S, Kawamura, Y, Kawada, H, Iwasaki, H, Gomi, T, Satoh, S, Uyama, I
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 2011;(4):365-71
Abstract
BACKGROUND We developed a new method of intracorporeal gastroduodenostomy, the delta-shaped anastomosis, in which only endoscopic linear staplers are used. In this report, we present the short- and long-term outcomes of our initial experience with this procedure. METHODS We retrospectively analyzed 100 consecutive gastric cancer patients who underwent the delta-shaped anastomosis procedure from May 2001 to November 2006. All of them underwent a laparoscopic distal gastrectomy with regional lymph node dissection. Quality of life was assessed with a questionnaire 6 months or more postoperatively, and the gastric remnant was evaluated by endoscopy one year following the surgery. RESULTS Eight surgeons successfully performed the delta-shaped anastomosis without any conversion to laparotomy. The learning curve for all surgeons was steep and the mean time for the anastomosis was 13 min. Only one patient developed an anastomotic leak, and the leak was minor. Sixty-five patients tolerated a 1500 kcal/day soft diet at the time of discharge. The mean follow-up period was 54.9 months. Only one patient reported symptoms indicative of dumping. Two patients were diagnosed with reflux esophagitis, and approximately 70% had evidence of bile reflux, but severe gastritis of the remnant stomach on endoscopy was uncommon. CONCLUSIONS The wide lumen of the delta-shaped anastomosis led to early, adequate postoperative oral intake without a significant incidence of dumping syndrome. The delta-shaped anastomosis is safe and simple and provides satisfactory postoperative results.