Ingrid Demedts

Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett's esophagus : acid reflux, bile reflux, or both?

OBJECTIVES:Studies using ambulatory pH and esophageal bile reflux monitoring (Bilitec®) have shown that both acid reflux and duodeno-gastro-esophageal reflux (DGER) frequently occur in patients with gastroesophageal reflux disease (GERD). A subset of patients with GERD has persistent reflux symptoms in spite of standard doses of proton pump inhibitors (PPIs). The aim of the present study was to investigate the role of acid and DGER in patients with reflux disease poorly responsive to PPIs.METHODS:Sixty-five patients (32 men, 44 ± 2 yr) without Barretts esophagus and with persistent heartburn or regurgitation during standard PPI doses were studied. They underwent upper gastrointestinal endoscopy and simultaneous 24-h ambulatory pH and Bilitec® monitoring while PPIs were continued.RESULTS:Thirty-three patients (51%) had persistent esophagitis. Seven patients (11%) had only pathological acid exposure, 25 (38%) had only pathological DGER exposure, and 17 (26%) had pathological exposure to both acid and DGER. Acid exposure under PPI was positive in only 37%, but adding Bilitec® increased the diagnoses of persistent reflux to 75%. Patients with persistent esophagitis had similar acid exposure, but significantly higher DGER exposure than those without esophagitis. The highest prevalence of esophagitis was found in patients with pathological exposure to both acid and DGER; symptoms did not differ according to the type of reflux.CONCLUSIONS:Combined pH and Bilitec® monitoring is superior to pH monitoring alone in demonstrating ongoing pathological reflux in patients with medically poorly responsive reflux disease.

Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans

Aims: In humans, impaired gastric accommodation is associated with early satiety and weight loss. In animals, accommodation involves activation of gastric nitrergic neurones. Our aim was to study involvement of nitric oxide in gastric accommodation and in meal induced satiety in humans. Methods: The effect of NG-monomethyl-l-arginine (l-NMMA) 4 mg/kg/h and 8 mg/kg/h on gastric compliance, on sensitivity to distension, and on gastric accommodation was studied with a barostat in double blind, randomised, placebo controlled studies. The effect of l-NMMA 8 mg/kg/h on meal induced satiety was studied using a drinking test. Results:l-NMMA had no significant effect on fasting compliance and sensitivity. Ingestion of a meal induced a relaxation of 274 (15) ml which was significantly smaller after l-NMMA 4 mg/kg/h (132 (45) ml; p=0.03) or l-NMMA 8 mg/kg/h (82 (72) ml; p=0.03). l-NMMA 8 mg/kg/h significantly decreased the amount of food ingested at maximum satiety from 1058 (67) to 892 (73) kcal (p<0.01). Conclusion: In humans, fasting gastric tone and sensitivity to distension are not influenced by nitric oxide synthase inhibition, but the gastric accommodation reflex involves activation of nitrergic neurones. Inhibition of nitric oxide synthase impairs accommodation and enhances meal induced satiety.

Long Term outcome of endoscopic dilatation in patients with Crohn’s disease is not affected by disease activity or medical therapy

Background Endoscopic dilatation of Crohns disease-related strictures is an alternative to surgical resection in selected patients. The influence of disease activity and concomitant medical therapy on long-term outcomes is largely unknown. Aim and methods To study the long-term safety and efficacy of stricture dilatation in a single centre cohort. Results Between 1995 and 2006, 237 dilatations where performed in 138 patients (mean age 50.6±13.4, 56% female) for a clinically obstructive stricture (<5 cm, 84% anastomotic). Immediate success of a first dilatation was 97% with a 5% serious complication rate. After a median follow-up of 5.8 years (IQR 3.0–8.4), recurrent obstructive symptoms led to a new dilatation in 46% or surgery in 24%. Niether elevated levels of C-reactive protein nor endoscopic disease activity predicted the need for new intervention. None of the concomitant therapies influenced the outcome. Conclusion This largest series ever reported confirms that long term efficacy of endoscopic dilatation of Crohns disease outweighs the complication risk. Neither active disease at the time of dilatation nor medical therapy afterwards predict recurrent dilatation or surgery.

A Pilot Study on Duodenal Acid Exposure and Its Relationship to Symptoms in Functional Dyspepsia with Prominent Nausea

BACKGROUND:Duodenal hypersensitivity to acid and decreased duodenal clearance of exogenous acid have been reported in functional dyspepsia (FD). However, the relevance of these abnormalities to spontaneous duodenal acid exposure and dyspeptic symptoms in FD is unknown.AIMS:To determine spontaneous duodenal acid exposure and its relationship with symptoms, duodenal sensitivity to acid, and the effects of a 5-HT3 receptor antagonist on duodenal responses to acid in FD.METHODS:Eleven FD patients with prominent nausea and 11 healthy controls underwent 24-h ambulatory duodenal pH monitoring with assessment of dyspeptic symptoms. On the next day, duodenal bolus infusions of 5 ml of acid and normal saline were given in a randomized double-blind manner and repeated after ondansetron or a placebo.RESULTS:Nighttime duodenal acid exposure was similar, but FD patients had lower duodenal pH and higher duodenal % time (pH < 4) than controls during the daytime and in the second postprandial 2 h (p < 0.05). Seven patients (64%) with duodenal acid exposure above the normal range had higher severity scores for several dyspeptic symptoms including nausea. However, the symptom severity was poorly or weakly correlated to duodenal pH, and brief duodenal acid infusion did not affect any symptoms. Duodenal responses to exogenous acid were unaffected by 5-HT3 receptor antagonism.CONCLUSIONS:Spontaneous duodenal acid exposure is increased in a subset of FD patients with prominent nausea, and this is associated with more severe dyspeptic symptoms. However, a direct relationship between duodenal acid exposure and symptom severity is lacking.

The Yield of Upper Gastrointestinal Endoscopy in Patients with Suspected Reflux-Related Chronic Ear, Nose, and Throat Symptoms

OBJECTIVES:It is well established that various ENT disorders and symptoms may be a manifestation of gastroesophageal reflux disease (GERD). Erosive esophagitis is considered a rare finding in ENT patients and therefore upper gastrointestinal (GI) endoscopy is not recommended in the diagnostic work-up. However, large prospective studies underscoring this policy are lacking. The aim of the present study was to investigate the prevalence and severity of esophagitis in patients with suspected GERD-related chronic ENT symptoms.METHODS:Endoscopy was performed in 405 ENT patients with suspected GERD and 545 typical GERD patients. The presence of erosive esophagitis, Barretts esophagus, hiatal hernia, peptic ulcer, and Helicobacter pylori infection on biopsies was determined and compared with the results of a symptom questionnaire.RESULTS:The prevalence of erosive esophagitis (52.3%vs 38.4%; p < 0.05), mainly grade 1 (31.9%vs 22.7%; p < 0.05), and of peptic ulcer (8.4%vs 4.3%; p < 0.05) was significantly higher in patients with GERD-related ENT symptoms compared to typical GERD. Barretts mucosa occurred in, respectively, 4.9% and 4.5% of the patients (NS). Esophagitis prevalence was highest in patients with predominant cough and lowest in globus pharyngeus and throat symptoms. The presence of esophagitis was associated with significantly higher rates of symptom relief during the first 8 wk of proton pump inhibitor (PPI) therapy.CONCLUSIONS:Patients with suspected GERD-related ENT symptoms have a high prevalence of esophagitis and this is associated with better response to antisecretory therapy.

Long-Term Outcome of Transcatheter Embolotherapy for Acute Lower Gastrointestinal Hemorrhage

OBJECTIVES:We sought to assess the safety, short- and long-term efficacy, and durability of transcatheter embolization for lower gastrointestinal hemorrhage (LGH) unresponsive to endoscopic therapy and to analyze the overall survival of the embolized patients.METHODS:Between January 1997 and January 2008, 122 patients were referred for angiographic evaluation to control major LGH. Overall, 43 patients (35.3%) presented with angiographic signs of contrast extravasation. In 39 patients (26 men, 13 women; mean age 67.7 years), a transcatheter embolization was performed to stop the bleeding.RESULTS:In all 39 patients, no contrast extravasation could be depicted on completion of angiography after embolization. Rebleeding occurred in eight patients (20%), in six of them within the first 30 days after embolization. Ischemic intestinal complications requiring surgery occurred in four patients (10%) within 24 h after embolization. Long-term follow-up depicted estimated survival rates of 70.6, 56.5, and 50.8% after 1, 3, and 5 years, respectively.CONCLUSIONS:Transcatheter embolotherapy to treat lower gastrointestinal bleeding is very effective, with a relatively low rebleeding and ischemic complication rate, mostly occurring within the first month after the embolization. Long-term follow-up shows a very low late rebleeding rate, and half of the embolized patients survive more than 5 years. This study shows that the majority of patients presenting with lower gastrointestinal bleeding, unresponsive to endoscopic therapy, do not benefit from transcatheter embolization. In cases of angiography extravasation, a good immediate clinical outcome—defined as high immediate success with acceptable rebleeding—and ischemic complication rate may be obtained.

Neural mechanisms of early postinflammatory dysmotility in rat small intestine

Abstract  Although human postinflammatory dysmotility is known, so far animal studies have primarily investigated changes during inflammation. Here, we focused on postinflammatory changes in rat jejunal myenteric plexus and jejunal motility. Evolution of ethanol/2,4,6‐tri‐nitrobenzene sulphonic acid (TNBS)‐induced inflammation was assessed histologically and by measuring myeloperoxidase activity (MPO). Electromyography and immunohistochemistry were performed 1 week after ethanol/TNBS and also after NG‐nitro‐l‐arginine methyl ester (l‐NAME) administration. Ethanol/TNBS induced a transient inflammation, with normalization of MPO and histological signs of an early phase of recovery after 1 week. The number of cholinergic neurones was not altered, but myenteric neuronal nitric oxide synthase (nNOS)‐immunoreactivity was significantly lower in the early phase of recovery after TNBS compared with water (1.8 ± 0.2 vs 3.5 ± 0.2 neurones ganglion−1, P < 0.001). Interdigestive motility was disrupted with a loss of phase 1 quiescence, an increase of migrating myoelectric complex cycle length, a higher number of non‐propagated activity fronts and a decrease of adequately propagated phase 3 s after TNBS. Administration of l‐NAME resulted in a similar disruption of interdigestive motility patterns. In the early phase of recovery after ethanol/TNBS‐induced jejunal inflammation, a loss of motor inhibition occurs due to a decrease of myenteric nNOS activity. These observations may provide a model for early postinflammatory dysmotility syndromes.

Gastrointestinal motility changes and myenteric plexus alterations in spontaneously diabetic biobreeding rats

Background/Aims Type 1 diabetes is often accompanied by gastrointestinal motility disturbances. Vagal neuropathy, hyperglycemia, and alterations in the myenteric plexus have been proposed as underlying mechanism. We therefore studied the relationship between vagal function, gastrointestinal motiliy and characteristics of the enteric nervous system in the biobreeding (BB) rat known as model for spontaneous type 1 diabetes. Methods Gastric emptying breath test, small intestinal electromyography, relative risk-interval variability, histology and immunohistochemistry on antral and jejunal segments were performed at 1, 8 and 16 weeks after diabetes onset and on age-matched controls. Results We observed no consistent changes in relative risk-interval variability and gastric emptying rate. There was however, a loss of phases 3 with longer duration of diabetes on small intestinal electromyography. We found a progressive decrease of nitrergic neurons in the myenteric plexus of antrum and jejunum, while numbers of cholinergic nerve were not altered. In addition, a transient inflammatory infiltrate in jejunal wall was found in spontaneous diabetic BB rats at 8 weeks of diabetes. Conclusions In diabetic BB rats, altered small intestinal motor control associated with a loss of myenteric nitric oxide synthase expression occurs, which does not depend on hyperglycemia or vagal dysfunction, and which is preceded by transient intestinal inflammation.

Pan-Colonic Pressurizations Associated With Relaxation of the Anal Sphincter in Health and Disease: A New Colonic Motor Pattern Identified Using High-Resolution Manometry

Objectives:Only a few studies have applied high-resolution manometry (HRM) to the study of colonic motility in adults and none of them have concurrently evaluated colonic and anal motor activity. The aim of the study was to evaluate colonic and anal motor activity by means of HRM in healthy subjects. As the present study revealed the presence of a new colonic motor pattern (pan-colonic pressurizations) in healthy subjects, three additional studies were conducted: the first and the second to exclude that this motor event results from an artifact due to abdominal wall contraction and to confirm its modulation by cholinergic stimulation, and the third, as pilot study, to test the hypothesis that this colonic pattern is defective in patients with chronic constipation refractory to current pharmacological treatments.Methods:In both volunteers and patients the HRM catheter was advanced proximally during colonoscopy.Results:In all subjects, pressure increases of 15±3 mm Hg and 24±4 s simultaneously occurring in all colonic sensors (pan-colonic pressurizations) and associated with anal sphincter relaxation were identified. Subjects had 85±38 pan-colonic pressurizations, which increased significantly during meal (P=0.007) and decreased afterward (P=0.01), and were correlated with feelings of and desire to evacuate gas. The mean number of propagating sequences was 47±39, and only retrograde increased significantly postprandially (P=0.01). Pan-colonic pressurizations differed from strain artifacts and significantly increased after prostigmine. In patients pan-colonic pressurizations were significantly reduced as compared with volunteers.Conclusions:Pan-colonic pressurizations associated with relaxations of the anal sphincter represent a new colonic motor pattern that seems to be defective in patients with treatment-refractory chronic constipation and may have a role in the transport of colonic gas and in the facilitation of the propagating sequence-induced colonic transport.

Chromoendoscopy versus narrow band imaging in UC: a prospective randomised controlled trial

Background Patients with long-standing UC have an increased risk for the development of colonic neoplastic lesions. Chromoendoscopy (CE) has been proven to enhance neoplasia detection while the role of virtual chromoendoscopy (VC) is still to be defined. Objective To compare the performance of CE to VC for the detection of neoplastic lesions in patients with long-standing UC. Design A multicentre prospective randomised controlled trial. 131 patients with long-standing UC were randomised between CE with methylene blue 0.1% (n=66) or VC with narrow band imaging (NBI) (n=65). Biopsies were taken from visible lesions and surrounding mucosa. No random biopsies were performed. The primary outcome was the difference in total number of neoplastic lesions detected in each group. Results There was no significant difference between NBI and CE for neoplasia detection. Mean number of neoplastic lesions per colonoscopy was 0.47 for CE and 0.32 for NBI (p=0.992). The neoplasia detection rate was not different between CE (21.2%) and NBI (21.5%) (OR 1.02 (95% CI 0.44 to 2.35, p=0.964). Biopsies from the surrounding mucosa yielded no diagnosis or dysplasia. The per lesion neoplasia detection was 17.4% for CE and 16.3% for NBI (OR 1.09 (95% CI 0.59 to 1.99, p=0.793). The total procedural time was on average 7 min shorter in the NBI group. Conclusion CE and NBI do not differ significantly for detection of colitis-associated neoplasia. Given the longer withdrawal time for CE and easier applicability, NBI may possibly replace classical CE. Trial registration number NCT01882205; Results.