Charles Cock

Topical Steroid Therapy for the Treatment of Eosinophilic Esophagitis (EoE): A Systematic Review and Meta-Analysis

OBJECTIVES:Current guidelines recommend topical steroids as first-line treatment for patients with eosinophilic esophagitis (EoE). However, the evidence for this approach has been inconsistent in earlier reports. This meta-analysis aimed to clarify the efficacy of topical steroid treatment in active EoE using updated evidence.METHODS:CENTRAL, MEDLINE and EMBASE databases were searched for randomized controlled trials (RCTs) published up to May 2014 that compared topical steroids with control treatments for active EoE. Study bias was assessed using the Cochrane Collaboration Tool, and outcomes were pooled using random effects models. The primary outcome was the mean change in eosinophil counts. Secondary outcomes were symptom responses and adverse events.RESULTS:In total, seven RCTs (226 patients) were included. Topical steroids were associated with a significant reduction in esophageal mucosal eosinophil counts compared with control therapy although substantial heterogeneity between studies was observed (weighted mean difference (WMD) −27.2, 95% confidence interval (CI) −45.3 to −9.1, I2=56.2%). Subgroup analysis indicated the reduction in eosinophil counts was only present in studies where a proton pump inhibitor (PPI) trial was used to exclude other diagnoses (WMD −46.3, 95% CI −61.3 to −31.4, I2=0.0%). Subdivision of studies on the use of a PPI trial also accounted for the majority of heterogeneity among RCTs. No clear trends in symptom resolution were observed. Eleven out of 127 patients who received topical steroids developed asymptomatic esophageal candidiasis.CONCLUSIONS:These data provide updated high-quality evidence that support current guidelines for first-line EoE treatment with topical steroids after an initial PPI trial to exclude non-EoE pathologies (PROSPERO ID: CRD42014008828).

Swallowing dysfunction in healthy older people using pharyngeal pressure-flow analysis

Age‐related loss of swallowing efficiency may occur for multiple reasons. Objective assessment of individual dysfunctions is difficult and may not clearly differentiate these from normal. Pharyngeal pressure‐flow analysis is a novel technique that allows quantification of swallow dysfunction predisposing to aspiration risk based on a swallow risk index (SRI). In this study, we examined the effect of ageing on swallow function.

Applying the Chicago Classification criteria of esophageal motility to a pediatric cohort: effects of patient age and size

Applying the 2012 Chicago Classification (CC) of esophageal motility disorders to pediatric patients is problematic as it relies upon adult‐derived criteria. As shorter esophageal length and smaller esophago‐gastric junction (EGJ) diameter may influence CC metrics, we explored the potential for age‐ and size‐adjustment of diagnostic criteria.

Upper esophageal sphincter mechanical states analysis: a novel methodology to describe UES relaxation and opening

The swallowing muscles that influence upper esophageal sphincter (UES) opening are centrally controlled and modulated by sensory information. Activation of neural inputs to these muscles, the intrinsic cricopharyngeus muscle and extrinsic suprahyoid muscles, results in their contraction or relaxation, which changes the diameter of the lumen, alters the intraluminal pressure and ultimately inhibits or promotes flow of content. This relationship that exists between the changes in diameter and concurrent changes in intraluminal pressure has been used previously to calculate the “mechanical states” of the muscle; that is when the muscles are passively or actively, relaxing or contracting. Diseases that alter the neural pathways to these muscles can result in weakening the muscle contractility and/or decreasing the muscle compliance, all of which can cause dysphagia. Detecting these changes in the mechanical state of the muscle is difficult and as the current interpretation of UES motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during swallow can be missed. We hypothesized that quantification of mechanical states of the UES and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern the timing and extent of UES opening during swallowing. To achieve this we initially analyzed swallows captured by simultaneous videofluoroscopy and UES pressure with impedance recording. From these data we demonstrated that intraluminal impedance measurements could be used to determine changes in the internal diameter of the lumen when compared to videofluoroscopy. Then using a database of pressure-impedance studies, recorded from young and aged healthy controls and patients with motor neuron disease, we calculated the UES mechanical states in relation to a standardized swallowed bolus volume, normal aging and dysphagia pathology. Our results indicated that eight different mechanical states were almost always seen during healthy swallowing and some of these calculated changes in muscle function were consistent with the known neurally dependent phasic discharge patterns of cricopharyngeus muscle activity during swallowing. Clearly defined changes in the mechanical states were observed in motor neuron disease when compared to age matched healthy controls. Our data indicate that mechanical state predictions were simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.

New insights into pharyngo-esophageal bolus transport revealed by pressure-impedance measurement

Background  Pharyngeal propulsion, strength of peristalsis and esophago–gastric junction (EJG) resistance are determinants of esophageal bolus transport. This study used pressure‐impedance methods to correlate pharyngo‐esophageal function with the esophageal bolus trajectory pathway and pressures generated during bolus transport.

The Reliability of Pharyngeal High Resolution Manometry with Impedance for Derivation of Measures of Swallowing Function in Healthy Volunteers

Purpose. We evaluated the intra- and interrater agreement and test-retest reliability of analyst derivation of swallow function variables based on repeated high resolution manometry with impedance measurements. Methods. Five subjects swallowed 10 × 10 mL saline on two occasions one week apart producing a database of 100 swallows. Swallows were repeat-analysed by six observers using software. Swallow variables were indicative of contractility, intrabolus pressure, and flow timing. Results. The average intraclass correlation coefficients (ICC) for intra- and interrater comparisons of all variable means showed substantial to excellent agreement (intrarater ICC 0.85–1.00; mean interrater ICC 0.77–1.00). Test-retest results were less reliable. ICC for test-retest comparisons ranged from slight to excellent depending on the class of variable. Contractility variables differed most in terms of test-retest reliability. Amongst contractility variables, UES basal pressure showed excellent test-retest agreement (mean ICC 0.94), measures of UES postrelaxation contractile pressure showed moderate to substantial test-retest agreement (mean Interrater ICC 0.47–0.67), and test-retest agreement of pharyngeal contractile pressure ranged from slight to substantial (mean Interrater ICC 0.15–0.61). Conclusions. Test-retest reliability of HRIM measures depends on the class of variable. Measures of bolus distension pressure and flow timing appear to be more test-retest reliable than measures of contractility.

Inter-observer agreement for Crohn's disease sub-phenotypes using the Montreal Classification: How good are we? A multi-centre Australasian study

BACKGROUND Crohns disease (CD) exhibits significant clinical heterogeneity. Classification systems attempt to describe this; however, their utility and reliability depends on inter-observer agreement (IOA). We therefore sought to evaluate IOA using the Montreal Classification (MC). METHODS De-identified clinical records of 35 CD patients from 6 Australian IBD centres were presented to 13 expert practitioners from 8 Australia and New Zealand Inflammatory Bowel Disease Consortium (ANZIBDC) centres. Practitioners classified the cases using MC and forwarded data for central blinded analysis. IOA on smoking and medications was also tested. Kappa statistics, with pre-specified outcomes of κ>0.8 excellent; 0.61-0.8 good; 0.41-0.6 moderate and ≤0.4 poor, were used. RESULTS 97% of study cases had colonoscopy reports, however, only 31% had undergone a complete set of diagnostic investigations (colonoscopy, histology, SB imaging). At diagnosis, IOA was excellent for age, κ=0.84; good for disease location, κ=0.73; only moderate for upper GI disease (κ=0.57) and disease behaviour, κ=0.54; and good for the presence of perianal disease, κ=0.6. At last follow-up, IOA was good for location, κ=0.68; only moderate for upper GI disease (κ=0.43) and disease behaviour, κ=0.46; but excellent for the presence/absence of perianal disease, κ=0.88. IOA for immunosuppressant use ever and presence of stricture were both good (κ=0.79 and 0.64 respectively). CONCLUSION IOA using MC is generally good; however some areas are less consistent than others. Omissions and inaccuracies reduce the value of clinical data when comparing cohorts across different centres, and may impair the ability to translate genetic discoveries into clinical practice.

Correlation of esophageal pressure-flow analysis findings with bolus transit patterns on videofluoroscopy

Pressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62-82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = -0.733, P < 0.05) and a higher IR (r = -0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ.Pressure-flow analysis quantifies the interactions between bolus transport and pressure generation. We undertook a pilot study to assess the interrelationships between pressure-flow metrics and fluoroscopically determined bolus clearance and bolus transport across the esophagogastric junction (EGJ). We hypothesized that findings of abnormal pressure-flow metrics would correlate with impaired bolus clearance and reduced flow across the EGJ. Videofluoroscopic images, impedance, and pressure were recorded simultaneously in nine patients with dysphagia (62-82 years, seven male) tested with liquid barium boluses. A 3.6 mm diameter solid-state catheter with 25 × 1 cm pressure/12 × 2 cm impedance was utilized. Swallowed bolus clearance was assessed using a validated 7-point radiological bolus transport scale. The cumulative period of bolus flow across the EGJ was also fluoroscopically measured (EGJ flow time). Pressure only parameters included the length of breaks in the 20 mmHg iso-contour and the 4 second integrated EGJ relaxation pressure (IRP4s). Pressure-flow metrics were calculated for the distal esophagus, these were: time from nadir impedance to peak pressure (TNadImp to PeakP) to quantify bolus flow timing; pressure flow index (PFI) to integrate bolus pressurization and flow timing; and impedance ratio (IR) to assess bolus clearance. When compared with controls, patients had longer peristaltic breaks, higher IRs, and higher residual EGJ relaxation pressures (break length of 8 [2, 13] vs. 2 [0, 2] cm, P = 0.027; IR 0.5 ± 0.1 vs. 0.3 ± 0.0, P = 0.019; IRP4s 11 ± 2 vs. 6 ± 1 mmHg, P = 0.070). There was a significant positive correlation between higher bolus transport scores and longer peristaltic breaks (Spearman correlation r = 0.895, P < 0.001) and with higher IRs (r = 0.661, P < 0.05). Diminished EGJ flow times correlated with a shorter TNadImp to PeakP (r = -0.733, P < 0.05) and a higher IR (r = -0.750, P < 0.05). Longer peristaltic breaks and higher IR correlate with failed bolus clearance on videofluoroscopy. The metric TNadImp to PeakP appears to be a marker of the period of time over which the bolus flows across the EGJ.

Inter-rater reliability and validity of automated impedance manometry analysis and fluoroscopy in dysphagic patients after head and neck cancer radiotherapy

Pharyngeal automated impedance manometry (AIM) analysis is a novel non‐radiological method to analyze swallowing function based on impedance‐pressure recordings. In dysphagic head and neck cancer patients, we evaluated the reliability and validity of the AIM‐derived swallow risk index (SRI) and a novel measure of postswallow residue (iZn/Z) by comparing it against videofluoroscopy as the gold standard.

Maximum Upper Esophageal Sphincter (UES) Admittance: A Non-Specific Marker of UES Dysfunction

Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2‐s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction.