Diagnosis of supra‐esophageal gastric reflux: correlation of oropharyngeal pH with esophageal impedance monitoring for gastro‐esophageal reflux

Background Oropharyngeal (OP) pH monitoring has been developed as a new way to diagnose supra‐esophageal gastric reflux (SEGR), but has not been well validated. Our aim was to determine the correlation between OP pH and gastro‐esophageal reflux (GER) events detected by multichannel intraluminal impedance‐pH (MII‐pH). Methods Fifteen patients (11 males, median age 10.8 years) with suspected GER were prospectively evaluated with ambulatory 24‐h OP pH monitoring (positioned at the level of the uvula) and concomitant esophageal MII‐pH monitoring. Potential OP events were identified by the conventional pH threshold of <4 and by the following alternative criteria: (i) relative pH drop >10% from 15‐min baseline and (ii) absolute pH drop below thresholds of <5.5, 5.0, and 4.5. The 2‐min window preceding each OP event was analyzed for correlation with an episode of GER detected by MII‐pH. Key Results A total of 926 GER events were detected by MII‐pH. Application of alternative pH criteria increased the identification of potential OP pH events; however, a higher proportion of OP events had no temporal correlation with GER (45–81%), compared with the conventional definition of pH < 4 (40%). A total of 306 full‐column acid reflux episodes were detected by MII‐pH, of which 10 (3.3%) were also identified by OP pH monitoring. Conclusions & Inferences Use of extended pH criteria increased the detection of potential SEGR events, but the majority of decreases in OP pH were not temporally correlated with GER. Oropharyngeal pH monitoring without concurrent esophageal measurements may overestimate the presence of SEGR in children.     

Assessment of esophageal function in patients with myasthenia gravis

Background: Myasthenia gravis (MG) is an autoimmune disease in which impairment of neuromuscular transmission results in a pathological fatigability of striated muscles. Dysphagia is a common symptom in MG. It is caused by a weakness of the striated muscles in the pharynx and esophagus. The purpose of our study was to evaluate the role of esophageal scintigraphy in the assessment of esophageal function in MG. Methods: In 15 patients with clinically proven MG (oculopharyngeal manifestation in 6/15 patients, generalized weakness in 9/15 patients) esophageal transit was investigated scintigraphically with a multiple swallow test protocol. 10/15 patients had a history of dysphagia. Patients were studied twice: under baseline conditions, and immediately after pharmacological stimulation with 10 mg of edrophonium chloride (EC), a short-acting acetylcholinesterase inhibitor. Results: Under baseline conditions all patients showed an impaired esophageal function (emptying [%]= 58 % ± 21; normal range > 85 %). In 14/15 individuals esophageal transit improved after administration of EC (emptying [%]= 75 % ± 18; p < 0.01), reaching the normal range in 6 patients. One patient showed no effect attributable to EC. Conclusions: Esophageal transit is often compromised in MG. Functional abnormalities may be also present in patients without a history of dysphagia. Inhibition of cholinesterase positively affects striated muscles in the pharynx and upper esophagus, thus improving esophageal transit. Esophageal scintigraphy may be considered as a simple, non-invasive method for diagnosing impairment of esophageal function in MG and to monitor the changes under pharmacological stimulation. Received: 20 August 2002, Received in revised form: 11 December 2002, Accepted: 18 December 2002 Correspondence to Rainer Linke, MD     

Failure to respond to physiologic challenge characterizes esophageal motility in erosive gastro‐esophageal reflux disease

Background Non‐specific esophageal dysmotility with impaired clearance is often present in patients with gastro‐esophageal reflux disease (GERD), especially those with erosive disease; however the physio‐mechanic basis of esophageal dysfunction is not well defined. Methods Retrospective assessment of patients with erosive reflux disease (ERD; n = 20) and endoscopy negative reflux disease (ENRD; n = 20) with pathologic acid exposure on pH studies (>4.2% time/24 h) and also healthy controls (n = 20) studied by high resolution manometry. Esophageal motility in response to liquid and solid bolus swallows and multiple water swallows (MWS) was analyzed. Peristaltic dysfunction was defined as failed peristalsis, spasm, weak or poorly coordinated esophageal contraction (>3 cm break in 30 mmHg isocontour). Key Results Peristaltic dysfunction was present in 33% of water swallows in controls, 56% ENRD and 76% ERD respectively (P < 0.023 vs controls, P = 0.185 vs ENRD). The proportion of effective peristaltic contractions improved with solid compared to liquid bolus in controls (18%vs 33%, P = 0.082) and ENRD (22%vs 54%, P = 0.046) but not ERD (62%vs 76%, P = 0.438). Similarly, MWS was followed by effective peristalsis in 83% of controls and 70% ENRD but only 30% ERD patients (P < 0.017 vs controls and P < 0.031 vs ENRD). The association between acid exposure and dysmotility was closer for solid than liquid swallows (r = 0.52 vs 0.27). Conclusions & Inferences Peristaltic dysfunction is common in GERD. ERD patients are characterized by a failure to respond to the physiologic challenge of solid bolus and MWS that is likely also to impair clearance following reflux events and increase exposure to gastric refluxate.     

Refining the criterion for an abnormal Integrated Relaxation Pressure in esophageal pressure topography based on the pattern of esophageal contractility using a classification and regression tree model

Background The Integrated Relaxation Pressure (IRP) is the esophageal pressure topography (EPT) metric used for assessing the adequacy of esophagogastric junction (EGJ) relaxation in the Chicago Classification of motility disorders. However, because the IRP value is also influenced by distal esophageal contractility, we hypothesized that its normal limits should vary with different patterns of contractility. Methods Five hundred and twenty two selected EPT studies were used to compare the accuracy of alternative analysis paradigms to that of a motility expert (the ‘gold standard’). Chicago Classification metrics were scored manually and used as inputs for MATLAB? programs that utilized either strict algorithm‐based interpretation (fixed abnormal IRP threshold of 15 mmHg) or a classification and regression tree (CART) model that selected variable IRP thresholds depending on the associated esophageal contractility. Key Results The sensitivity of the CART model for achalasia (93%) was better than that of the algorithm‐based approach (85%) on account of using variable IRP thresholds that ranged from a low value of >10 mmHg to distinguish type I achalasia from absent peristalsis to a high value of >17 mmHg to distinguish type III achalasia from distal esophageal spasm. Additionally, type II achalasia was diagnosed solely by panesophageal pressurization without the IRP entering the algorithm. Conclusions & Inferences Automated interpretation of EPT studies more closely mimics that of a motility expert when IRP thresholds for impaired EGJ relaxation are adjusted depending on the pattern of associated esophageal contractility. The range of IRP cutoffs suggested by the CART model ranged from 10 to 17 mmHg.     

High‐resolution esophageal pressure topography is superior to conventional sleeve manometry for the detection of transient lower esophageal sphincter relaxations associated with a reflux event

Background Transient lower esophageal sphincter relaxations (TLESRs) are the main mechanism underlying gastro‐esophageal reflux and are detected during manometric studies using well defined criteria. Recently, high‐resolution esophageal pressure topography (HREPT) has been introduced and is now considered as the new standard to study esophageal and lower esophageal sphincter (LES) function. In this study we performed a head‐to‐head comparison between HREPT and conventional sleeve manometry for the detection of TLESRs. Methods A setup with two synchronized MMS‐solar systems was used. A solid state HREPT catheter, a water‐perfused sleeve catheter, and a multi intraluminal impedance pH (MII‐pH) catheter were introduced in 10 healthy volunteers (M6F4, age 19–56). Subjects were studied 0.5 h before and 3 h after ingestion of a standardized meal. Tracings were blinded and analyzed by the three authors according to the TLESR criteria. Key Results In the HREPT mode 156 TLESRs were scored, vs 143 during sleeve manometry (P = 0.10). Hundred and twenty‐three TLESRs were scored by both techniques. Of all TLESRs (177), 138 were associated with reflux (78%). High‐resolution esophageal pressure topography detected significantly more TLESRs associated with a reflux event (132 vs 119, P = 0.015) resulting in a sensitivity for detection of TLESRs with reflux of 96% compared to 86% respectively. Analysis of the discordant TLESRs associated with reflux showed that TLESRs were missed by sleeve manometry due to low basal LES pressure (N = 5), unstable pharyngeal signal (N = 4), and residual sleeve pressure >2 mmHg (N = 10). Conclusions & Inferences The HREPT is superior to sleeve manometry for the detection of TLESRs associated with reflux. However, rigid HREPT criteria are awaited.     

The lower esophageal sphincter

The lower esophageal sphincters (LES) together with the crural diaphragm are the major antireflux barriers protecting the esophagus from reflux of gastric content. However, reflux of gastric contents into the esophagus is a normal phenomenon in healthy individuals occurring primarily during episodes of transient lower esophageal sphincter relaxation (TLESR), defined as LES relaxation in the absence of a swallow. Transient lower esophageal sphincter relaxation is also the dominant mechanism of pathologic reflux in gastroesophageal reflux disorder (GERD) patients. Frequency of TLESR does not differ significantly between healthy individuals and those with GERD, but TLESRs are more likely to be associated with acid reflux in GERD patients. Understanding the mechanisms responsible for elicitation of a TLESR, using recently introduced novel technology is an area of intense interest. Pharmacologic and non‐pharmacologic manipulation of receptors involved in the control of TLESR has recently emerged as a potential target for GERD therapy.     

Localizing the contractile deceleration point (CDP) in patients with abnormal esophageal pressure topography

Background The contractile deceleration point (CDP) is an important landmark for interpreting esophageal pressure topography (EPT) plots. Previous analysis in normal subjects confirmed that the CDP could be localized using an algorithm that found the time during peristalsis at which a maximal length of the distal esophagus was contracting concurrently (tML method). This study aimed to test the tML method for localizing CDP in patients with abnormal motility. Methods High‐resolution manometry studies of 75 patients with normal and disordered peristalsis were analyzed. Two experts, JEP and YX, used the original tangent‐intersection method to score CDP coordinates for the first two swallows of each study. Alternative computerized algorithms tested against the expert were: (i) the tML method, (ii & iii) the intercept between the leading edge of the 30‐mmHg isobaric contour and a line 2.0 cm (or 10% of esophageal length) proximal to the esophagogastric junction (EGJ) at rest, or (iv) the ‘tML‐3 cm’ method, which added the stipulation that the CDP be within 3 cm of the EGJ. Key Results All tested algorithms were highly correlated with the expert. However, the tMl‐3 cm method was better in the sense that it eliminated outliers (>1 s discrepancy with the expert) that occurred with the other methods usually attributable to weak distal peristalsis. Conclusions & Inferences Optimal automated CDP localization was achieved in both normal and a spectrum of abnormal motility using the tML method with the added stipulation that the CDP be restricted to within the distal 3 cm of the EGJ at rest.     

Fragmented esophageal smooth muscle contraction segments on high resolution manometry: a marker of esophageal hypomotility

Background Esophageal peristalsis consists of a chain of contracting striated and smooth muscle segments on high resolution manometry (HRM). We compared smooth muscle contraction segments in symptomatic subjects with reflux disease to healthy controls. Methods High resolution manometry Clouse plots were analyzed in 110 subjects with reflux disease (50 ± 1.4 years, 51.5% women) and 15 controls (27 ± 2.1 years, 60.0% women). Using the 30 mmHg isobaric contour tool, sequences were designated fragmented if either smooth muscle contraction segment was absent or if the two smooth muscle segments were separated by a pressure trough, and failed if both smooth muscle contraction segments were absent. The discriminative value of contraction segment analysis was assessed. Key Results A total of 1115 swallows were analyzed (reflux group: 965, controls: 150). Reflux subjects had lower peak and averaged contraction amplitudes compared with controls (P < 0.0001 for all comparisons). Fragmented sequences followed 18.4% wet swallows in the reflux group, compared with 7.5% in controls (P < 0.0001), and were seen more frequently than failed sequences (7.9% and 2.5%, respectively). Using a threshold of 30% in individual subjects, a composite of failed and/or fragmented sequences was effective in segregating reflux subjects from control subjects (P = 0.04). Conclusions & Inferences Evaluation of smooth muscle contraction segments adds value to HRM analysis. Specifically, fragmented smooth muscle contraction segments may be a marker of esophageal hypomotility.     

Botulinum toxin injection in dysphagia syndromes with preserved esophageal peristalsis and incomplete lower esophageal sphincter relaxation

Background Botulinum toxin injection into the lower esophageal sphincter (LES) treats dysphagia syndromes with preserved peristalsis and incomplete LES relaxation (LESR). We evaluated clinical and esophageal motor characteristics predicting response, and compared duration of efficacy to similarly treated achalasia patients. Methods Thirty‐six subjects (59 ± 2.2 years, 19F/17M) with incomplete LESR on high resolution manometry (HRM) treated with botulinum toxin injection were identified. Individual and composite symptom indices were calculated, and HRM characteristics extracted. Symptom resolution for 6 months was a primary outcome measure, and repeat botulinum toxin injection, dysphagia recurrence or employment of alternate therapeutic approaches were secondary outcome measures. Duration of response was compared using Kaplan‐Meier survival curves to a historical cohort of similarly treated achalasia subjects. Key Results Response lasted a mean of 12.8 ± 2.3 months. Symptom relief for >6 months was seen in 58.3%; short (<6 months) response was associated with younger age, higher chest pain index, and esophageal body spastic features (P ≤ 0.04). On multivariate logistic regression, chest pain, younger age and contraction amplitudes >180 mmHg independently predicted <6 months relief (P < 0.05 for each). On survival analysis, relief with a single injection extended to 1 year in 54.8% and 1.5 years in 49.8%, statistically equivalent to that reported by 42 similarly treated achalasia subjects (59 ± 3.2 years, 24F/18M). Symptom relief was more prolonged compared to achalasia when repeat injections were performed on demand (P = 0.003). Conclusions & Inferences Botulinum toxin injections can provide lasting symptom relief in dysphagia syndromes with incomplete LESR. Prominent perceptive symptoms and non‐specific spastic features may predict shorter relief.     

Effects of lidocaine on esophageal secondary peristalsis in humans

Background Secondary peristalsis is important for the clearance of retained food bolus or refluxate from the esophagus. Lidocaine has been used to evaluate the role of mucosa‐mediating pathways of esophageal reflexes in animal model, but its effects on esophageal secondary peristalsis are yet unclear in humans. We aimed to investigate whether esophageal secondary peristalsis can be affected by intraluminal infusion of lidocaine into the esophagus. Methods After a baseline recording esophageal motility, secondary peristalsis was generated by slow and rapid mid‐esophageal injections of air in 13 healthy subjects. Two separate sessions with saline and lidocaine were randomly performed to test their effects on esophageal secondary peristalsis by mid‐esophageal air distension. Key Results Secondary peristalsis can be induced by slow or rapid air infusion. Secondary peristalsis was triggered less frequently in response to rapid air distension after lidocaine infusion (P = 0.001). After lidocaine infusion, the threshold volume to generate secondary peristalsis was significantly increased during rapid (P = 0.001), but not slow air infusions (P = NS). Infusion of lidocaine or saline did not affect pressure wave amplitude or duration during rapid and slow air infusions (P = NS). Conclusions & Inferences We have demonstrated selectively inhibitory effect of lidocaine on the triggering of esophageal secondary peristalsis during acute gaseous esophageal distension. The data suggest that part of the activation of secondary peristalsis is probably mediated by lidocaine‐sensitive mechanoreceptors; however, the infusion of lidocaine does not lead to any motility change in secondary peristalsis induced by either slow or rapid air infusions.