Charlotte Scheerens

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.

Buspirone, a new drug for the management of patients with ineffective esophageal motility?:

Ineffective esophageal motility (IEM) is the most frequently encountered esophageal motility disorder. Patients may present with a variety of symptoms, such as dysphagia, heartburn, odynophagia, and regurgitation. Over the past years, the landscape of esophageal motility testing has been revolutionized; however, our current treatment options for IEM still remain limited. Previous studies have suggested that buspirone, a serotonin receptor agonist, enhances esophageal peristalsis and lower esophageal sphincter (LES) function. Recent work provides the first evidence that buspirone may influence LES resting pressure in patients with systemic sclerosis. Future research should evaluate whether the beneficial effects of buspirone also apply to the broad clinical entity of esophageal dysphagia patients with IEM.

The effect of intravenous corticotropin-releasing hormone administration on esophageal sensitivity and motility in health

Esophageal hypersensitivity is important in gastroesophageal reflux disease (GERD) patients who are refractory to acid-suppressive therapy. Stress affects visceral sensitivity and exacerbates heartburn in GERD. Peripheral CRH is a key mediator of the gut stress response. We hypothesize that CRH increases esophageal sensitivity and alters esophageal motility in health. Esophageal sensitivity to thermal, mechanical, electrical, and chemical stimuli was assessed in 14 healthy subjects after administration of placebo or CRH (100 μg iv). Perception scores were assessed for first perception, pain perception threshold (PPT), and pain tolerance threshold (PTT). Esophageal motility was investigated by high-resolution impedance manometry, before and after CRH and evaluated by distal contractile integral (DCI) and intrabolus pressure (IBP). Pressure flow analysis assessed bolus clearance (impedance ratio), degree of pressurization needed to propel bolus onward (IBP slope), and pressure flow (pressure flow index, PFI). Stress and mood were assessed during the study. Sensitivity to mechanical distention was increased after CRH compared with placebo (PPT: P = 0.0023; PTT: P = 0.0253). CRH had no influence on the other stimulations. DCI was increased for all boluses (liquid, P = 0.0012; semisolid, P = 0.0017; solid, P = 0.0107). Impedance ratio for liquid (P < 0.0001) and semisolid swallows (P = 0.0327) decreased after CRH. IBP slope increased after CRH for semisolid (P = 0.0041) and solid (P = 0.0003) swallows. PFI increased for semisolid (P = 0.0017) and solid swallows (P = 0.0031). CRH increased esophageal sensitivity to mechanical distention, not to the other stimulation modalities. CRH increased esophageal contractility and tone, decreased LES relaxation, increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow.NEW & NOTEWORTHY This is the first study to address the effect of corticotropin-releasing hormone (CRH) on esophageal sensitivity and alterations in motility in health. CRH administration increased esophageal sensitivity to mechanical distention. This effect is accompanied by an increase in esophageal contractility and tone and a decrease in lower esophageal sphincter relaxation. CRH increased esophageal bolus pressurization, improved esophageal bolus clearance, and increased pressure flow. The changes in esophageal contractile properties may underlie the increased sensitivity to mechanical distention after CRH.

The Potential Benefits of Applying Recent Advances in Esophageal Motility Testing in Patients with Esophageal Atresia

Infants and children with esophageal atresia commonly present with swallowing dysfunction or dysphagia. Dysphagia can lead to a range of significant consequences such as aspiration pneumonia, malnutrition, dehydration, and food impaction. To improve oral intake, the clinical diagnosis of dysphagia in patients with esophageal atresia should focus on both the pharynx and the esophagus. To characterize the complex interactions of bolus flow and motor function between mouth, pharynx, and esophagus, a detailed understanding of normal and abnormal deglutition is required through the use of adequate and objective assessment techniques. As clinical symptoms do not correlate well with conventional assessment methods of motor function such as radiology or manometry but do correlate with bolus flow, the current state-of-the-art diagnosis involves high-resolution manometry combined with impedance measurements to characterize the interplay between esophageal motor function and bolus clearance. Using a novel pressure flow analysis (PFA) method as an integrated analysis method of manometric and impedance measurements, differentiation of patients with impaired esophago-gastric junction relaxation from patients with bolus outflow disorders is clinically relevant. In this, pressure flow matrix categorizing the quantitative PFA measures may be used to make rational therapeutic decisions in patients with esophageal atresia. Through more advanced diagnostics, improved understanding of pathophysiology may improve our patient care by directly targeting the failed biomechanics of both the pharynx and the esophagus.

Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals

Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals.

Automatische Impedantie Manometrie (AIM): objectieve diagnostiek van oro-faryngale dysfagie

Automated Impedance Manometry (AIM): objective diagnosis of oropharyngeal dysphagiaThis review article aims to demonstrate the clinical potential of Automated Impedance Manometry (AIM) as a new, non-radiological technique for screening and diagnosis of oro-pharyngeal dysphagia. An integrated – rather than separate – analysis of pressure and impedance patterns generated in the pharynx when swallowing a food bolus, can be a useful complement to the radiological investigations considered as gold standard today. Major advantages are the objective nature of this technique and the fully automated calculation of various swallow parameters. A global measure of swallowing function can be derived (a Swallow Risk Index, SRI) and is related to (the severity of) the risk of aspiration and the presence of pharyngeal post-swallow residue. It was shown that aspiration on videofluoroscopy was accurately detected by using AIM with a sensitivity of 0.88 and a specificity of 0.96. AIM analysis can be performed quickly and is reliable in the hands of different end users. Various parameters are sufficiently sensitive to detect changes in bolus consistency and – as was recently found – are influenced by swallowing manoeuvers. Furthermore, different patterns of deviant swallow parameters can be found in different patient populations. Whether this observation can provide specific diagnoses and – as a consequence – more targeted treatments is currently under investigation.SamenvattingDit overzichtsartikel wil het klinisch potentieel aantonen van Automatische Impedantie Manometrie (AIM) als nieuwe, niet-radiologische techniek voor screening en diagnostiek van faryngale dysfagie, zijnde slikstoornissen in de mond, keelholte en bovenste slokdarm. Deze AIM-techniek maakt gebruik van een katheter met druksensoren en impedantie-elektroden om slikken kwantitatief te beschrijven. Een geïntegreerde – eerder dan afzonderlijke – analyse van de gemeten druk- en impedantiepatronen die ontstaan bij het doorslikken van een voedselbolus, kan een zinvolle aanvulling zijn op de dynamische beeldvormingsonderzoeken die vandaag de dag als gouden standaard worden gezien. Belangrijke voordelen zijn het objectieve karakter van de techniek en de geautomatiseerde berekening van diverse slikparameters. Een globale maat voor de slikfunctie kan worden bekomen (Slik Risico Index, SRI) en houdt verband met (de ernst van) het aspiratierisico van de patiënt en de aanwezigheid van bolusresidu. Zo kan een accurate detectie van aspiratie met een sensitiviteit van 0,88 en specificiteit van 0,96 niet via radiologisch onderzoek bereikt worden. Verschillende slikparameters zijn ook voldoende gevoelig om veranderingen in voedselconsistentie te detecteren en om de effecten van slikmanoeuvres objectief te beschrijven. Recent werd ook aangetoond dat deze AIM-analyse snel en betrouwbaar kan worden uitgevoerd door clinici met variërende ervaring en opleiding. Bovendien worden in verschillende patiëntengroepen andere patronen van afwijkende slikparameters aangetroffen. Of deze observatie aanleiding kan geven tot specifieke slikdiagnoses en dus meer gerichte behandelingen is momenteel onderwerp van onderzoek.

Tu1200 Swallow Function and Post-Swallow Residue in Dysphagic Patients With and Without a History of Pneumonia

BACKGROUND: Automated Impedance Manometry (AIM) analysis defines swallow metrics indicative of bolus timing and presence, contractile vigour and luminal diameter. The Swallow Risk Index (SRI) and integrated nadir impedance to impedance ratio (iZn/Z) are global indices correlating with aspiration risk and post-swallow residue respectively (Omari et al., Gastroenterology 2011; Omari et al., Neurogastro. Mot. 2012). This study compared the SRI and iZn/Z ratio for controls and dysphagic patients with and without a history of pneumonia. METHODS: 87 asymptomatic controls 20-91y (39M, mean 59y) and 201 dysphagic patients 17-91y (117 male, mean 67y) were investigated. 33 patients had history of pneumonia. Swallowing of 5-10ml liquid boluses was recorded by solid state manometryimpedance catheter (OD 3.2mm, 36 pressure at 1cm, 12 impedance at 2cm). AIMplot software was used to derive SRI and iZn/Z indices. RESULTS: 140 patients had abnormal swallow function (SRI>15). 123 patients had significant post-swallow residue (iZn/Z.500). The SRI and iZn/Z ratio were higher in relation to dysphagia. Furthermore, the iZn/Z ratio was higher in dysphagic patients with a history of pneumonia compared to those with no history (See Figure). The latency from bolus flow to pharyngeal contraction was shorter and pharyngeal bolus dwell time was longer in relation to pneumonia (ANOVA p,0.001, p,0.05 for all pairwise comparisons). Pharyngeal pressures and UES relaxation pressures were not significantly different in relation to pneumonia. CONCLUSIONS: Pharyngeal HRIM with AIM analysis can detect increased swallow dysfunction and post-swallow residue in dysphagic patients. Patients with a history of pneumonia have higher post swallow residues.

Tu1980 Radiological Correlates of Esophageal Pressure-Flow Variables Derived by Automated Impedance Manometry (AIM) Analysis

INTRODUCTION: Pressure-flow analysis may quantify the interactions between bolus transport and pressure generation during bolus swallowing. The functional relevance of pressure flow metrics is still to be fully elucidated and therefore we undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the EGJ. We hypothesise that differences in pressureflow metrics would correlate with changes in bolus clearance and reduced flow across the EGJ. METHODS: Videofluoroscopic images, impedance and pressure were recorded simultaneously in 16 control subjects (19-44y, 8m) tested with liquid (L), semi-solid (SS) and solid barium boluses (S). A 3.6mm diameter solid-state catheter with 36x1cm pressure/ 16x2cm impedance was used (Solar GI system, MMS). Swallowed bolus clearance was videofluroscopically assessed using a validated 7-point bolus transport scale; higher score = poor bolus clearance. The cumulative period of bolus flow across the EGJ was also measured (EGJ flow time). Pressure Flow Index (PFI) was used to integrate bolus pressurisation and flow timing and Impedance Ratio (IR) was used to assess the effectiveness of bolus clearance. Subjects were asked to report the level of perception of bolus transit using a 5 point scale. RESULTS: in total 92 swallows were simultaneously acquired. A higher transport score, indicating more severe levels of bolus transport failure, correlated with higher Impedance Ratios (L r = 0.617 p<0.001; SS r= 0.580 p<0.001; S 0.841 p<0.001). IR had strong prognostic value for detecting incomplete bolus clearance (ROC area for transport score ≥3 was L 0.902; SS 0.782; S 0.906). When subjects perceived bolus transit this was associated with a higher bolus transport score (2.0 vs. 4.6 for perception score 1 vs. score 2-5 respectively p=0.04). PFI and IR were used in combination to distinguish individual swallows on grounds of abnormal bolus pressurisation and/or clearance. Figure A demonstrates how solid swallows could be separated into 3 groups based on high or low PFI/IR : Group 1 Low PFI/ low IR, Group 2 low PFI /high IR and Group 3 high PFI. Comparisons among these groups in relation to fluoroscopic measures shows bolus transport abnormalities in Group 2 only (Fig B). EGJ flow time was shortest in Group 3 (Fig C). CONCLUSIONS: Different pressureflow signatures are associated with altered bolus clearance and/or flow across the EGJ. A high PFI pattern is associated with diminished flow across the EGJ, possibly due to increased flow resistance in the distal esophagus whilst a high IR is consistent with failed bolus transport to the EGJ. This study provides radiological confirmation that patterns of abnormal PFI and/or IR in dysphagia patients are consistent with abnormal flow patterns, possibly explaining patient symptoms.