Ambulatory high-resolution manometry, lower esophageal sphincter lift and transient lower esophageal sphincter relaxation

Background Lower esophageal sphincter (LES) lift seen on high‐resolution manometry (HRM) is a possible surrogate marker of the longitudinal muscle contraction of the esophagus. Recent studies suggest that longitudinal muscle contraction of the esophagus induces LES relaxation. Aim Our goal was to determine: (i) the feasibility of prolonged ambulatory HRM and (ii) to detect LES lift with LES relaxation using ambulatory HRM color isobaric contour plots. Methods In vitro validation studies were performed to determine the accuracy of HRM technique in detecting axial movement of the LES. Eight healthy normal volunteers were studied using a custom designed HRM catheter and a 16 channel data recorder, in the ambulatory setting of subject’s home environment. Color HRM plots were analyzed to determine the LES lift during swallow‐induced LES relaxation as well as during complete and incomplete transient LES relaxations (TLESR). Key Results Satisfactory recordings were obtained for 16 h in all subjects. LES lift was small (2 mm) in association with swallow‐induced LES relaxation. LES lift could not be measured during complete TLESR as the LES is not identified on the HRM color isobaric contour plot once it is fully relaxed. On the other hand, LES lift, mean 8.4 ± 0.6 mm, range: 4–18 mm was seen with incomplete TLESRs (n = 80). Conclusions & Inferences Our study demonstrates the feasibility of prolonged ambulatory HRM recordings. Similar to a complete TLESR, longitudinal muscle contraction of the distal esophagus occurs during incomplete TLESRs, which can be detected by the HRM. Using prolonged ambulatory HRM, future studies may investigate the temporal correlation between abnormal longitudinal muscle contraction and esophageal symptoms.     

Validation of a Fully Automated Analysis of Esophageal Body Contractility and Lower Esophageal Sphincter Function: A Study on the Effect of the PGEI Analogue Rioprostil on Human Esophageal Motility

A new method for automatic analysis of resting lower esophageal sphincter pressure and postdeglutitive motor activity of esophageal body and lower esophageal sphincter (LES) is validated by comparing the results obtained with automatic and manual analysis of 11,700 esophageal body pressure peaks, 390 resting LES pressure measurements, and 3900 LES relaxations. The automatic analysis is based on the on-line transformation of pressure recordings into a mathematical formula using B-spline functions, which allows one to use the same parameters as those generally applied in manual analysis of esophageal manometric recordings. Statistical evaluation of the results indicates that this method provides a faithful analysis of the pressure tracings. The difference between manual and automatic analysis (mean ± SD) was only + 1.49 ± 4.26 mm Hg for wave amplitude, -0.15 ± 0.61 seconds for wave duration, +0.37 ± 1.05 cm/second for progression velocity, +0.95 ± 1.38 mm Hg for resting LES pressure, and -2.0 ± 1.67 mm Hg for residual LES pressure after deglutition. Wave form was correctly recognized in 95.3% of the waves. Pressure recordings were obtained from a study on the effect of the PGE₁ analogue rioprostil (600 and 300 μg), administered orally on esophageal motor function in 10 normal volunteers. The drug increased both the resting LES pressure and the amplitude of esophageal body contractions and decreased the completeness of LES relaxation after swallowing.     

Multiple rapid swallow responses segregate achalasia subtypes on high‐resolution manometry

Background Multiple rapid swallows (MRS) inhibit esophageal peristalsis and lower esophageal sphincter (LES) tone; a rebound excitatory response then results in an exaggerated peristaltic sequence. Multiple rapid swallows responses are dependent on intact inhibitory and excitatory neural function and could vary by subtype in achalasia spectrum disorders. Methods Consecutive subjects with incomplete LES relaxation on high‐resolution manometry (HRM) (Sierra Scientific, Los Angeles, CA, USA) in the absence of mechanical obstruction were prospectively identified. Achalasia spectrum disorders were classified and HRM plots reviewed according to Chicago criteria. Esophageal peristaltic performance and LES function were assessed after 10 wet swallows and MRS (five 2 mL water swallows 2–3 s apart). Findings were compared with 18 healthy controls (28.5 ± 0.6 years, 44% women). Key Results A total of 46 subjects (57.1 ± 2.1 years, 52.2% women) met inclusion criteria. There was complete failure of peristalsis with MRS in all subjects with achalasia subtypes 1 and 2. In contrast, 80% of achalasia subtype 3 and incomplete LES relaxation (EGJ outflow obstruction) with preserved esophageal body peristalsis had a contractile response to MRS (P < 0.001 compared with subtypes 1 and 2); controls demonstrated 94.4% peristalsis. Percent decrease in LES residual pressure during MRS (compared to wet swallows) segregated achalasia subtypes; those with aperistalsis (subtypes 1 and 2) had a lesser decline (22.6%) compared to those with retained esophageal body peristalsis (40.5%) and controls (51.3%, P < 0.001 across groups). Conclusions & Inferences Multiple rapid swallow responses segregate achalasia spectrum disorders into two patterns differentiated by presence or absence of esophageal body contraction response to wet swallows. These findings support subtyping of achalasia, with pathophysiologic implications.     

Short-term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease

Background Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD). Methods A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24‐h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5–15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7‐days after stimulation. Continuous cardiac monitoring was performed during and after stimulation. Key Results All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1–13.1) to 16.6 mmHg (95% CI 10.8–19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0–16.3) to 16.5 mmHg (95% CI 2.7–30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation. Conclusions & Inferences Short‐term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.     

Slow esophageal propagation velocity: association with dysphagia for solids

Background Spastic disorders of the esophagus, associated with rapid esophageal propagation velocity, are classically associated with dysphagia and/or chest pain. The aim of this study was to characterize patients with slow esophageal propagation velocity (SPV) on high‐resolution esophageal manometry (HRM). Methods A review of patients undergoing HRM was conducted during 1‐year study period. Patients with achalasia, aperistalsis, and diffuse esophageal spasm were excluded. Patients with contractile front velocity (CFV) ≤2.3 cm s^?1 were defined as having SPV, whereas normal propagation velocity (NPV) was defined as ≥2.6 cm s^?1. A composite isobaric contour of all swallows for each patient was generated to determine composite distal contraction latency (cDL). Key Results A total of 650 HRMs were reviewed and 552 met inclusion criteria. 173 patients had SPV and 339 had NPV. There was a greater female predominance in the SPV group compared with NPV (75.7%vs 66.4%, P = 0.03). Patients in the SPV group reported more dysphagia for solids (66.3%vs 53.3%; P = 0.004) and nausea (68.6%vs 59.0%; P = 0.04) than NPV group. Dysphagia for solids was the only symptom significantly associated with SPV group (OR = 2.21, CI = 1.21–4.02; P = .01). There was a negative correlation between CFV and cDL, r = ?0.494, P < 0.001. Conclusions & Inferences Patients with SPV have a higher prevalence of dysphagia for solids and nausea when compared with NPV. Dysphagia for solids was the only symptom significantly associated with SPV group. Thus, abnormal esophageal propagation velocity (both slow and rapid) is associated with dysphagia.     

Normative values and inter‐observer agreement for liquid and solid bolus swallows in upright and supine positions as assessed by esophageal high‐resolution manometry

Background High‐resolution manometry (HRM) with spatiotemporal representation of pressure data is a recent advance in esophageal measurement. At present, normal values are available for 5 mL water swallows in the supine position. This study provides reference values for liquid and solid bolus swallows in the upright seated and supine positions. Methods A total of 23 asymptomatic volunteers (11M : 12F, age 20–56) underwent HRM (Manoscan 360; Sierra Scientific Instruments) with 5 mL water and 1 cm³ bread swallows in the upright and supine positions. Normal values for primary parameters associated with effective bolus transport [proximal transition zone length (PTZ, assesses peristaltic coordination], contraction front velocity (CFV), distal contractile index (DCI) and integrated relaxation pressure (IRP)] are presented. For each parameter, median values along with the 5–95th percentile range are reported. Inter‐observer agreement between independent observers is reported using the intra‐class correlation coefficient. Key Results A higher proportion of swallows were peristaltic for liquids than solids in both the upright and supine positions (both P < 0.05). As workload increases with solid bolus and on moving from the upright to the supine position the esophageal contractile response resulted in a shorter PTZ, a slower CFV, and a more vigorous DCI. Also IRP increased during solid bolus transit (all P < 0.01). There was significant agreement between independent observers for HRM parameters. Conclusions & Inferences Normative values for esophageal function for solids as well as liquids and in the ‘physiologic’, upright position will optimize the utility of HRM studies. The high level of inter‐observer agreement indicates that these can be applied as reference values in clinical practice.     

3D‐high resolution manometry of the esophagogastric junction

Background The esophagogastric junction (EGJ) is a complex structure that challenges accurate manometric recording. This study aimed to define EGJ pressure morphology relative to the squamocolumnar junction (SCJ) during respiration with 3D‐high resolution manometry (3D‐HRM). Methods A 7.5‐cm long 3D‐HRM array with 96 independent solid‐state pressure sensors (axial spacing 0.75 cm, radial spacing 45°) was used to record EGJ pressure in 15 normal subjects. Concurrent videofluoroscopy was used to localize the SCJ marked with an endoclip. Ex vivo experiments were done on the effect of bending the probe to match that seen fluoroscopically. Key Results 3D‐high resolution manometry EGJ pressure recordings were dominated by an asymmetric pressure peak superimposed on the lower esophageal sphincter (LES) attributable to the crural diaphragm (CD). Median peak CD pressure at expiration and inspiration (51 and 119 mmHg, respectively) was much greater in 3D‐HRM than evident in HRM with circumferential pressure averaging. Esophagogastric junction length, defined as the zone of circumferential pressure exceeding that of adjacent esophagus or stomach was also substantially shorter (2.4 cm) than evident in conventional HRM. No consistent circumferential EGJ pressure was evident distal to the SCJ in 3D‐HRM recordings and ex vivo experiments suggested that the intra‐gastric pressure peak seen contralateral to the CD related to bending the assembly rather than the sphincter per se. Conclusions & Inferences 3D‐high resolution manometry demonstrated a profoundly asymmetric and vigorous CD component to EGJ pressure superimposed on the LES. Esophagogastric junction length was shorter than evident with conventional HRM and the distal margin of the EGJ sphincteric zone closely correlated with the SCJ.     

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.     

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.     

Identifying hiatal hernia with impedance planimetry during esophageal distension testing

Introduction

Functional luminal imaging probe (FLIP) Panometry evaluates the esophageal response to distension involving biomechanics and motility. We have observed that hiatus hernia (HH) is evident during FLIP studies as a separation between the crural diaphragm (CD) and lower esophageal sphincter (LES) like what is seen with high-resolution manometry (HRM). The aim of this study was to compare FLIP findings to endoscopy and HRM in the detection of HH.

Methods

A total of 100 consecutive patients that completed FLIP during sedated endoscopy and HRM were included. LES-CD separation was assessed on FLIP and HRM with the presence of HH defined as LES-CD ≥1 cm. The agreement was evaluated using the kappa (κ) statistic.

Results

Hiatal hernia was detected in 32% of patients on HRM and 44% of patients on FLIP with a substantial agreement between studies (84% agreement; κ = 0.667). On FLIP, a ‘new’ HH (i.e. HH not observed on HRM) occurred in 14 patients and an “enlarged” HH (i.e., LES-CD ≥2 cm larger than on HRM) occurred in 11 patients. Among patients that also completed, timed barium esophagogram (TBE), delayed esophageal emptying on TBE was more common in patients with new or enlarged HH on FLIP than those without: 7/11 (64%) versus 2/12 (17%); p = 0.017.

Conclusion

FLIP can detect HH with a substantial agreement with HRM, though esophageal distension with FLIP testing appeared to elicit and/or enlarge a HH in an additional 25% of patients. Although this unique response to esophageal distension may represent a mechanism of dysphagia or susceptibility to reflux, additional study is needed to clarify its significance.     

High‐resolution manometric characteristics help differentiate types of distal esophageal obstruction in patients with peristalsis

Background High‐resolution manometry (HRM) can identify obstructive motor features at the esophagogastric junction and abnormalities in esophageal bolus transit. We sought to determine if HRM patterns can differentiate functional from organic mechanical lower esophageal sphincter (LES) obstruction. Methods Segmental characteristics of peristalsis were examined using HRM in symptomatic subjects with elevated postdeglutitive residual pressure gradients across the LES (≥5 mmHg). Sixteen consecutive patients with non‐achalasic mechanical fixed obstruction were compared with 13 patients with elevated pressure gradients yet no mechanical obstruction and 14 asymptomatic controls. Pressure volumes were determined in mmHg cm s for peristaltic segments defined on HRM Clouse plots using an on‐screen pressure volume measurement tool. Key Results Residual pressure gradients were similarly elevated in both patient groups. A visually conspicuous and distinctive shift in the proportionate pressure strengths of the second and third peristaltic segments was apparent across groups. Whereas the ratios of peak pressures and pressure volumes between second and third segments approached 1 in controls (0.92, 0.98), pressures shifted to the second segment in mechanical obstruction (peak pressure ratio: 1.2 ± 0.4; pressure volume ratio: 1.8 ± 0.9) and to the third segment in functional obstruction (peak ratio: 0.7 ± 0.2; volume ratio: 0.5 ± 0.2; P < 0.02 for any comparison of either group with controls). A threshold volume ratio of 1.0 correctly segregated 93% of obstruction (P < 0.0001); visual pattern inspection was equally effective. Conclusions & Inferences When elevated residual pressure gradients are present in non‐achalasic patients, topographic characteristics of peristalsis can differentiate fixed mechanical obstruction from functional obstruction.     

Increasing body weight enhances prevalence and proximal extent of reflux in GERD patients ‘on’ and ‘off’ PPI therapy

Background Increased body weight is associated with higher intragastric pressure. Proximal extent of reflux is a determinant of symptoms in patients with gastro‐esophageal reflux disease (GERD). We aimed to investigate the association between body mass index (BMI) and abdominal circumference on the incidence and proximal extent of reflux. Methods A total of 95 patients [37 men, age 51(16–82) years] with typical and/or atypical GERD symptoms underwent 24 h impedance‐pH monitoring. Forty‐nine patients were studied ‘off’ and 46 ‘on’ proton pump inhibitors (PPI) treatment. Reflux was classified as acid (pH < 4) or weakly acidic (pH 4–7). Proximal extent was defined as the number of reflux events reaching ≥15 cm above the lower esophageal sphincter. Body mass index and abdominal circumference (cm) were assessed. Key Results In patients ‘off’ PPI, there was a correlation between BMI and esophageal acid exposure (ρ = 0.53, P < 0.001), volume exposure (ρ = 0.48, P < 0.001), total number of reflux events (ρ = 0.47, P < 0.001) and number of acid reflux events (ρ = 0.49, P < 0.001). In patients ‘on’ PPI there was a correlation between BMI and esophageal acid exposure (ρ = 0.32, P = 0.03), volume exposure (ρ = 0.46, P < 0.01) and total number of reflux events (ρ = 0.33, P = 0.03). Similar correlations were found between abdominal circumference and reflux. A correlation between BMI and proximal extent of reflux was present in patients ‘off’ PPI (ρ = 0.32, P = 0.03). In patients ‘on’ PPI, we found a correlation between abdominal circumference and proximal extent (ρ = 0.31, P = 0.03). Conclusions & Inferences Body mass index and abdominal circumference may contribute to GER and its proximal extent, in patients ‘on and ‘off’ PPI. Further studies investigating the role of weight reduction in the control of GERD symptoms are warranted.     

Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia

Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1mmHg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Results: Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5min. Basal LES pressure averaged (+/-SD) 9.2+/-4.8mmHg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2mmHg. Mean LES pressure was inversely correlated with age (r=0.7, P=0.02). The total number of reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0mmHg in 98% of reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Conclusions: Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.     

柱状球囊扩张术治疗脑卒中后食管上括约肌失弛缓致重度吞咽障碍临床研究

目的探讨柱状球囊扩张术治疗脑卒中后食管上括约肌失弛缓致重度吞咽障碍患者的作用机制及效果。方法共64例脑卒中后食管上括约肌失弛缓致重度吞咽障碍患者,随机接受脑卒中常规药物治疗和常规吞咽康复训练(对照组,32例)以及在此基础上联合柱状球囊扩张术(治疗组,32例),分别于治疗前和治疗终点或治疗4周时行吞咽动作影像学、食管上括约肌动力学和吞咽障碍程度评分。结果与治疗前相比,治疗后两组患者静息压(P=0.000)和残留压(P=0.000)降低、峰值压力升高(P=0.000)、松弛持续时间延长(P=0.000),吞咽障碍程度评分升高(P=0.000,0.000);与对照组相比,治疗后治疗组患者静息压(P=0.001)和残留压(P=0.000)降低、峰值压力升高(P=0.002)、松弛持续时间延长(P=0.000),吞咽障碍程度评分升高(P=0.000)。至治疗终点或治疗4周时,治疗组总有效率高于对照组[93.75%(30/32)对81.25%(26/32);χ~2=4.010,P=0.000]。结论柱状球囊扩张术有助于降低食管上括约肌张力、缓解痉挛,对食管上括约肌失弛缓具有明显的针对性治疗作用。     

Inspiration closure reflex: The effect of respiration on intrinsic sphincters

Introduction: The functions of the lower esophageal sphincter (LES) and internal urethral sphincter (IUS) have not been reported during voluntary and involuntary respiratory maneuvers. Methods: In this study we performed a prospective barium videofluoroscopy study (BSV) of the LES on 4 healthy adult men during voluntary cough (VC), laryngeal expiration reflex (LER), breath‐hold maneuvers, and normal inspiration. One subject had fiber‐optic pressure catheters placed in the LES and IUS, and electromyographic recording of the right T7–8 intercostals during respiration. Results: BSV showed closure and relaxation of the LES corresponding to the inspiration and expiration of VC. The LES was patent during the LER. There was closure of the LES during the deep inspiration/breath‐hold event. Pressure catheters in the LES and IUS showed increased pressure during inspiration. Conclusions: These observations suggest that pulmonary inspiration afferents elicit a patterned reflex motor response in the LES and IUS, referred to as the inspiration closure reflex (ICR). Muscle Nerve 47:424‐431, 2013     

Control of esophageal distension‐induced secondary peristalsis by the GABAB agonist baclofen in humans

Background Secondary peristalsis is important for the clearance of retained food bolus or refluxate from the esophagus. The effects of the gamma aminobutyric acid receptor type B (GABA_B) agonist on secondary peristalsis remain unclear in humans. We aimed to investigate the effect of a GABA_B agonist baclofen on esophageal secondary peristalsis. Methods After a baseline recording of esophageal motility, secondary peristalsis was generated by slow and rapid mid‐esophageal injections of air in 15 healthy subjects. Two separate sessions with 40 mg oral baclofen or placebo were randomly performed to test their effects on secondary peristalsis. Key Results Baclofen increased the threshold volume for triggering secondary peristalsis during slow air distension (P = 0.003) and rapid air distension (P = 0.002). Baclofen reduced the rate of secondary peristalsis by rapid air distension from 90% to 30% (P = 0.0002). Baclofen increased basal lower esophageal sphincter pressure (P = 0.03). Baclofen did not affect any of peristaltic parameters during primary or secondary peristalsis. Conclusions & Inferences This study provides an evidence for inhibitory modulation of esophageal secondary peristalsis by the GABA_B agonist baclofen. Activation of secondary peristalsis is probably modulated by GABA_B receptors; however, baclofen does not lead to any motility change in secondary peristalsis.     

Kinetics of transient hiatus hernia during transient lower esophageal sphincter relaxations and swallows in healthy subjects

Background Proximal displacement of the gastro‐esophageal junction (GEJ) is present in hiatus hernia but also occurs transiently during transient lower esophageal sphincter relaxations (TLESRs) and swallows. Using a novel magnetic‐based technique we have performed detailed examination of the GEJ movement during TLESRs and swallows in healthy subjects. Methods In 12 subjects, a magnet was endoscopically clipped to the GEJ and combined assembly of Hall‐Effect locator probe and 36 channel high‐resolution manometer passed nasally. After a test meal the subjects were studied for 90 min. Key Results The median amplitude of proximal movement of GEJ during TLESRs was 4.3 cm (1.6–8.8 cm) and this was substantially greater than during swallowing at 1.2 cm (0.4–2.7 cm), P = 0.002. With both TLESRs and swallows proximal GEJ movement coincided with lower esophageal sphincter (LES) relaxation and return to its original position occurred 4 s after return of LES tone. Kinetic modeling of the movement of the GEJ during TLESRs indicated two return phases with the initial return phase having the greater velocity (0.9 cm s^?1) and being strongly correlated with amplitude of proximal movement (r = 0.8, P < 0.001). Conclusions & Inferences The marked proximal GEJ migration during TLESRs represents very severe herniation of the GEJ. The rapid initial return of the GEJ following TLESRs when the crural diaphragm is relaxed and its correlation with amplitude suggest it is due to elastic recoil of the phreno‐esophageal ligament. The marked stretching of the phreno‐esophageal ligament during TLESRs may contribute to its weakening and development of established hiatus hernia.     

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.     

The effects of intraduodenal nutrient infusion on serum CCK,LES pressure,and gastroesophageal reflux

Background Fats cause reflux symptoms in many patients and cholecystokinin (CCK) may play a role. This study was designed to evaluate the effects of intraduodenal nutrient infusion on serum CCK levels, lower esophageal sphincter (LES) pressure, and gastroesophageal reflux (GER). Methods Twenty‐four asymptomatic volunteers were studied. A Dent sleeve catheter assessed LES function while an impedance‐pH catheter measured reflux events. Participants were randomized to fat (F), carbohydrate (C) or protein (P) infusion. Serum CCK and LES pressures were measured at baseline and after nutrient infusion. Key Results Baseline LES pressures and CCK levels were similar in all three groups. A significant linear decrease was found in LES pressure during F, but not C or P, infusion (P = 0.004). A significant interaction effect was noted between the infusion groups and CCK levels (P = 0.002). A significant linear increase was noted in CCK levels during F but not during C or P infusion (P = 0.02). A significant inverse correlation was found between CCK levels and LES pressure (ρ = ?0.43; P = 0.04). Esophageal acid exposure was significantly increased in the F infusion group (median; interquartile range: 1.10%; 0.25–4.7%) compared to both the C (0.03%; 0.00–0.39%) and P infusion (0.03%; 0.00–0.39%) groups (P = 0.04). Conclusions & Inferences Intraduodenal F infusion was associated with an increase in CCK levels, while P and C were not. LES pressure decreased significantly after fat infusion and reflux events were more frequent. Fat‐induced CCK release is another mechanism that contributes to GER.     

High resolution manometry patterns distinguish acid sensitivity in non-cardiac chest pain

Background High resolution manometry (HRM) has demonstrated two distinct smooth muscle contraction segments in the esophageal body; changes in these segments typify certain esophageal disorders. We investigated segmental characteristics in subgroups of non‐cardiac chest pain (NCCP). Methods 32 NCCP subjects were segregated into a GERD group (ambulatory pH testing off antisecretory therapy showing elevated total acid exposure time, AET ≥ 4.0% and positive symptom association probability, SAP) and an acid sensitive group (normal AET and positive SAP). HRM Clouse plots were analyzed; smooth muscle segment lengths, pressure amplitude peaks were measured for segment 2 and segment 3 (proximal and distal smooth muscle segments). Pressure volumes were determined in mmHg cm^?1 s^?1 for each peristaltic segment, and ratios of segment 3 : segment 2 calculated. Values were compared to a cohort of 14 normal controls. Key Results A distinctive shift in peak contraction amplitude to segment 3 was evident in the acid sensitive group (segment 2, 100.03 ± 11.06 mmHg, segment 3, 145.23 ± 10.29 mmHg, P = 0.006). Pressure volumes were similarly shifted to segment 3 (segment 2: 855.3 ± 135.1 mmHg cm^?1 s^?1, segment 3: 2115.2 ± 218.6 mmHg cm^?1 s^?1, P < 0.005). In contrast, peak amplitude and pressure volume were near equal in the two segments in GERD and control groups. A threshold segment 3 : segment 2 pressure volume ratio of 1.9 had the best performance characteristic for segregating acid sensitivity subjects from all GERD and control subjects. Conclusions & Inferences Shift in contractile vigor to the third peristaltic segment may be seen in acid sensitive subjects. HRM characteristics of smooth muscle contraction segments are of value in making this determination.