High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry

BACKGROUND AND AIMS: High-resolution manometry (HRM) is a recent development in oesophageal measurement; its value in the clinical setting remains a matter of controversy. (i) We compared the accuracy with which bolus transport could be predicted from conventional manometry and HRM. (ii) The clinical value of HRM was assessed in a series of patients with endoscopy-negative dysphagia in whom conventional investigations had been non-diagnostic. METHOD: (i) Control subjects and patients with endoscopy-negative dysphagia underwent concurrent HRM and video-fluoroscopy. Ninety-five records were reviewed using HRM with spatiotemporal plot and conventional line plots of the pressure data derived from the same recording. (ii) The HRM and notes of patients with endoscopy-negative dysphagia and abnormal bolus transport were analysed to identify additional information provided by the new technique. RESULTS: (i) Receiver operating characteristic analysis demonstrated that HRM predicts the presence of abnormal bolus transport more accurately than conventional manometry. (ii) HRM identified clinically important motor dysfunction not detected by manometry and radiography. These included localized disturbances of peristalsis and abnormal movement of the lower oesophageal sphincter during oesophageal spasm. CONCLUSION: The HRM predicts bolus movement more accurately than conventional manometry and identifies clinically relevant oesophageal dysfunction not detected by other investigations including conventional manometry.     

Effect of the 5-HT1 agonist sumatriptan on oesophageal motor pattern in patients with ineffective oesophageal motility

The 5-HT1 agonist sumatriptan (SUM) elicits an increase in amplitude of oesophageal motor waves and of lower oesophageal sphincter (LOS) tone in healthy subjects. The aim of the study was to evaluate whether such an effect occurs also in patients with ineffective oesophageal motility (IOM). 16 patients (nine males and seven females, age range 34-55 years) with chest pain and mild to moderate dysphagia were studied; all had undergone previous cardiologic, radiologic and upper gastrointestinal endoscopic exams that were normal. An oesophageal manometry was performed using an electronic probe to record swallows, oesophageal, LOS and gastric motility. The patients whose motor pattern were compatible with IOM (>30% of motor waves with amplitude <30 mmHg and/or non-transmitted) received SUM or placebo 6 mg s.c., injected in the morning and in the afternoon in a random order. The data analysis was limited to 1 h before and 1 h after the drug injections. Ten out of the 16 patients showed an IOM motor pattern. The administration of SUM caused a significant increase in the number of swallows (SUM 99.5 +/- 15.4 vs 78.6 +/- 16.1 basal, P = 0.03) and of primary oesophageal motor waves (SUM 89.6 +/- 13.4 vs 67.2 +/- 12.9 basal, P = 0.04) with no significant changes in the percentage of swallows associated with propagation. Placebo was not associated with increase in the number of swallows (80.3 +/- 14.6, P = 0.9) or of primary oesophageal motor waves (70.1 +/- 12.3, P = 0.7). The amplitude and the percentage of propagated oesophageal motor waves as well as the mean basal LOS tone were unaltered by SUM. There was no change in the symptoms reported after SUM. Although effective in healthy subjects, SUM 6 mg s.c. improves only the numbers but not the amplitude or propagation of oesophageal motility of patients with IOM. The 5-HT1 pathway and its acute stimulation seem to play only a minor role in the pathogenesis of such a disease.     

Segmental characteristics of oesophageal peristalsis in paediatric patients.

High-resolution manometry (HRM) in adults identifies a sequential chain of pressure segments that together form normal oesophageal peristalsis. HRM was performed in 40 neonates, infants/toddlers and children (age 1 day-14 years) to see if a similar segmental pattern could be identified in paediatric subjects. A chain of three pressure segments was found with inter-segmental troughs at 27.4 +/- 1.1%, 62.6 +/- 1.3% and 94.9 +/- 0.8% oesophageal length. The first and second pressure troughs were similarly distributed along the oesophagus across age groups; the third was 7.6-8.9% oesophageal length further from the lower oesophageal sphincter in neonates (P < 0.05 compared with other age groups). There were no significant differences in trough locations between subjects with or without oesophageal disease, controlling for age. Consistent presence of all three segments was less common in neonates, primarily because of fewer swallows demonstrating the first (proximal) and third (distal) segments compared with children. HRM in paediatric patients demonstrates, from neonates to children, the distinctive chain of pressure events that also characterizes oesophageal peristalsis in adults. The segmental character to oesophageal peristalsis should be taken into consideration in manometric investigation of all age groups - for example, in testing pharmacological responses and evaluating clearance mechanisms.     

What is new in Chicago Classification version 4.0?

Since publication of Chicago Classification version 3.0 in 2015, the clinical and research applications of high‐resolution manometry (HRM) have expanded. In order to update the Chicago Classification, an International HRM Working Group consisting of 52 diverse experts worked for two years and utilized formally validated methodologies. Compared with the prior iteration, there are four key modifications in Chicago Classification version 4.0 (CCv4.0). First, further manometric and non‐manometric evaluation is required to arrive at a conclusive, actionable diagnosis of esophagogastric junction (EGJ) outflow obstruction (EGJOO). Second, EGJOO, distal esophageal spasm, and hypercontractile esophagus are three manometric patterns that must be accompanied by obstructive esophageal symptoms of dysphagia and/or non‐cardiac chest pain to be considered clinically relevant. Third, the standardized manometric protocol should ideally include supine and upright positions as well as additional manometric maneuvers such as the multiple rapid swallows and rapid drink challenge. Solid test swallows, postprandial testing, and pharmacologic provocation can also be considered for particular conditions. Finally, the definition of ineffective esophageal motility is more stringent and now encompasses fragmented peristalsis. Hence, CCv4.0 no longer distinguishes between major versus minor motility disorders but simply separates disorders of EGJ outflow from disorders of peristalsis.     

Multiple rapid swallowing in idiopathic achalasia: evidence for patients' heterogeneity.

In order to evaluate the function of inhibitory neural pathways in achalasia, we compared the response of the oesophageal body and lower oesophageal sphincter (LOS) to single swallows (SS) and multiple rapid swallowing (MRS) in 20 consecutive patients with untreated idiopathic achalasia (10 men, aged 23-81 years) and in 20 control patients without dysphagia (nine men, aged 31-73 years), using sleeve manometry; 277 SS and 85 MRS were analysed. In the control group, MRS inhibited motor activity in the oesophageal body and induced a slightly lower (P < 0.05) nadir LOS pressure compared with SS. In the achalasia patients, MRS induced a variable response: eight patients had simultaneous motor activity during all MRS although onset was delayed compared with SS [median (interquartile range), 3.5 s (1.7-6.1) vs 1.4 s (0.8-3.9); P < 0.05], whereas eight patients showed motor inhibition which occurred during all MRS in four of them, and the remaining four had no motor activity both after SS and during MRS. Overall MRS did not decrease nadir LOS pressure compared with SS [12 mmHg (5-20) vs 16 mmHg (7-22); P > 0.1]; however, it induced complete LOS relaxation in three of the patients. MRS gives further evidence of functional heterogeneity among achalasia patients.     

Effect of topical anaesthesia on oesophageal sensory and motor function in healthy subjects

Abstract Oesophageal hyperalgesia was demonstrated in the non-cardiac chest pain syndrome and suggests an altered perception of visceral stimuli in these patients. Data on oesophageal sensory function and its pharmacological manipulation, however, are fragmentary.
Using a randomized, double-blind, placebo-controlled, cross-over design, ten healthy male volunteers were manometrically examined for the effects of topical oesophageal anaesthesia with benzocaine 0.75% on (1) oesophageal perception of graded intra-luminal balloon distension, (2) oesophageal compliance and primary motility, and (3) rectal perception of graded intraluminal balloon distension.
It was demonstrated that topical benzocaine significantly increased oesophageal perception thresholds for intraluminal distension (P < 0.03), irrespective of them being correlated to distension volume or distension pressure. The level of first sensation increased from 4.3 ml (SD 2.8) and 24.8 mmHg (SD 9.1) to 7.4 ml (SD 4.4) and 32.1 mmHg (SD 8.3), respectively; pain perception increased from 11.O ml (SD 4.5) and 30.9 mmHg (SD 8.9) to 14.5 ml (SO 5.1) and 38.3 mmHg (SD 10.2), respectively. In contrast, oesophageal compliance, primary oesophageal motility and rectal perception were not altered.
It was concluded that topical anaesthesia decreases visceral sensitivity of the oesophagus to mechanical distension by action on intramural nervous afferents. It does not affect oesophageal motor function, nor does it exert systemic analgesic effects.     

Manometric abnormalities of the oesophagus in patients with Parkinson's disease.

Dysphagia in Parkinson's disease (PD) is known to correlate with abnormalities of oropharyngeal function. Oesophageal abnormalities have not been previously demonstrated to correlate with dysphagia. The aim of the study was to determine if motor dysfunction of the oesophageal body correlates with dysphagia or disease severity in PD. Twenty-two patients with PD were assessed for the severity of their dysphagia (scale of 1-7) and severity of PD (Hoehn and Yahr scale 1-4). All underwent oesophageal manometry. Dysphagia was present daily in 10 patients (45%). Parkinson's disease was graded as severe (Hoehn and Yahr > or =3) in eight (36%) patients. Oesophageal manometry was abnormal in 16 (73%) patients. Thirteen patients had either complete aperistalsis or multiple simultaneous contractions (diffuse oesophageal spasm). These findings were significantly more common in patients with daily dysphagia (90% vs. 33%; P < 0.005), and were not related to duration or severity of PD. We conclude that the presence of aperistalsis or multiple simultaneous contractions in the oesophagus does correlate with dysphagia and is independent of PD severity or duration. This may reflect selective involvement of either the dorsal motor nucleus of the vagus or the oesophageal myenteric plexus.     

Oesophageal peristaltic transition zone defects: real but few and far between

Abstract This study analysed the association between oesophageal transition zone (TZ) defects [characterized by a delay and/or spatial gap between the terminus of the proximal oesophageal (striated muscle) contraction and the initiation of the distal oesophageal (smooth muscle) contraction] and dysphagia in a large patient cohort. Four hundred consecutive patients (178 with dysphagia) and 75 controls were studied with 36‐channel high‐resolution manometry (HRM). The resultant pressure topography plots were first analysed for impaired oesophagogastric junction (OGJ) relaxation, distal segment contractile abnormalities, and proximal contractile abnormalities using normal values from the 75 controls. If these aspects of oesophageal motility were deemed normal, the TZ was characterized by length and duration between the proximal and distal contractions using a 20 mmHg isobaric contour to establish the segment boundaries. Patients were then classified according to whether or not they exhibited TZ defects (spatial separation or delay) and the occurrence of unexplained dysphagia. Of the 400 patients, 267 were suitable for TZ analysis and of these 55 had a spatial or temporal TZ measurement exceeding the 95th percentile of the controls (2 cm, 1 s). Exactly 34.6% of the patients (n = 19) with spatial and/or temporal TZ defects had unexplained dysphagia, which was significantly more than seen with normal TZ dimensions (19.8%). Although far less common than distal peristaltic or OGJ abnormailites, TZ defects may be related to dysphagia in a minority of patients (<4% in this series) and should be considered a distinct oesophageal motility disorder.     

Multiple rapid swallowing: a complementary test during standard oesophageal manometry

Abstract  Multiple rapid swallowing (MRS) stimulates neural inhibition resulting in abolition of contractions in the oesophageal body (OB) and complete lower oesophageal sphincter (LOS) relaxation which is followed by peristalsis and LOS contraction. The aim of this study was to evaluate the yield of MRS to detect abnormalities in inhibitory or excitatory oesophageal mechanisms in patients with oesophageal symptoms and either normal standard manometry or ineffective oesophageal motility (IOM). MRS (five water swallows, 2 mL, separated by 2–3 s) was evaluated in 23 healthy subjects, 109 symptomatic patients with normal standard sleeve manometry and in 48 patients with IOM. Healthy subjects had complete inhibition of OB motility during MRS and a strong motor response after MRS, i.e. amplitude of OB contractions in the oesophageal body and LOS tone being higher than after single swallows. Almost 70% of patients with oesophageal symptoms and normal manometry had abnormal MRS, mainly consistent on inability to increase amplitude of OB contractions after MRS. Nearly, half of the patients with IOM were able to normalize OB contractions after MRS. MRS is a simple complementary test that can be added to standard oesophageal manometry. Two-thirds of patients with normal manometry show abnormal MRS that could potentially underlie their symptoms. A normal response to MRS in patients with severe IOM might be used to predict response to prokinetic treatment.     

Effect of interval between swallows on oesophageal pressures and bolus movement in normal subjects – Studies with combined multichannel intraluminal impedance and oesophageal manometry

The effect of closely spaced swallows to decrease peristalsis ('deglutitive inhibition') is believed to be due to both central inhibitory impulses and smooth muscle refractoriness. Ten volunteers (three females, age 26-65) were given both four pairs and two series of four swallows at 5-, 10-, 15-s intervals and control swallows at 30-s intervals. Oesophageal function was assessed using combined multichannel intraluminal impedance and oesophageal manometry (MII-OM). Swallows were considered manometrical effective if distal oesophageal pressures >/=30 mmHg. Complete bolus transit was defined as bolus exiting from all three distal impedance segments. During swallowing at 5-s intervals the majority of initial swallows were ineffective with incomplete bolus transit while the last swallow in both series and pairs was manometrically effective with complete bolus transit. During swallowing at 10-15-s intervals the number of manometric ineffective swallows and swallows with incomplete bolus transit progressively increased with the number of swallows. The functional information obtained by MII-OM indicates pooling of liquid in the distal oesophagus that is cleared by the last swallow determined by, previously reported, neural inhibition occurring during swallowing spaced 5 s apart whereas incomplete bolus transit is related to manometrically ineffective swallows resulting from muscle refractoriness occurring during swallowing at 10-15-s intervals.     

Effect of successive swallows on oesophageal motility of normal volunteers, patients with Chagas'' disease and patients with idiopathic achalasia

Most frequently, ten swallows of a 5-mL bolus of water are performed during oesophageal manometry. Our hypothesis is that five swallows may produce the same results. We studied the oesophageal contraction parameters of 40 volunteers, 75 patients with Chagas' disease and 14 patients with idiopathic achalasia. Motility was recorded at 5, 10 and 15 cm above the lower oesophageal sphincter. The subjects performed ten swallows of a 5-mL bolus of water alternated with ten dry swallows with an interval of at least 30 s. We measured the amplitude, duration, peristaltic velocity, number of failed and number of simultaneous contractions of the initial five and final five dry and wet swallows. The comparison of dry and wet swallows showed the differences already known. The comparison of the parameters of the initial five swallows with those of the final five swallows showed no differences. Thus, when the initial five or the final five swallows were considered, there was no change in the conclusions reached by the comparison of patients and volunteers and of dry and wet swallows. We conclude that five swallows may be sufficient for the manometric examination of oesophageal parameters in Chagas' disease and idiopathic achalasia.     

Disposable balloon-based oesophageal motility catheters: comparison with solid-state transducers.

BACKGROUND: Current oesophageal manometry systems use either water-perfused or solid-state pressure transducers. Recently developed single-use disposable catheters use small balloons prefilled with air that transmit the pressure of oesophageal contractions to external transducers. AIM: To compare data obtained from single-use disposable balloon catheters to data from solid-state systems. METHODS: Healthy volunteers, patients with ineffective oesophageal motility and nutcracker oesophagus were studied to include a broad range of pressures. A single-use disposable Clinical Innovations (CI) catheter was placed adjacent to a solid-state Konigsberg Instruments (KI) catheter with pressure transducers at 5, 10, 15 and 20 cm above the lower oesophageal sphincter (LOS). Subjects received liquid and viscous swallows at 30-s intervals. Healthy volunteers received additional sets of swallows while having only one catheter in the oesophagus. RESULTS: When both catheters were present in the oesophagus, no differences were noted between mean pressure measurements in the distal oesophagus and there was good correlation between pressures recorded in response to individual swallows. When present alone in the oesophagus the CI catheter recorded lower mean pressures compared with the KI catheter. Overall there was good agreement in classifying swallows as normal, ineffective and simultaneous. CONCLUSION: Single-use oesophageal manometry catheters are promising alternatives to solid-state manometry systems in measuring intra-oesophageal pressures.     

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.     

Effect of sildenafil, a phosphodiesterase-5 inhibitor, on oesophageal peristalsis and lower oesophageal sphincter function in cats.

The propagation of oesophageal peristaltic contractions and lower oesophageal sphincter (LOS) relaxation depends on neural release of nitric oxide (NO) which acts to increase intracellular cGMP. Sildenafil, a phosphodiesterase-5 inhibitor that increases cGMP, reduces basal LOS pressure in patients with achalasia. We investigated the effect of sildenafil on the propagation of oesophageal contractions and LOS relaxation in the cat. Oesophageal manometry was performed in five cats under light sedation. Peristaltic contractions were monitored at 1, 2, 3, 4 and 8 cm proximal to the LOS, at the LOS using a Dent sleeve, and at 3 cm distal to the upper oesophageal sphincter. Swallow-induced oesophageal contractions and LOS relaxation were recorded during 30 min before and 30 min after intravenous administration of sildenafil. Sildenafil reduced the amplitude of oesophageal contractions only in the smooth muscle oesophagus. The latency from swallow to distal oesophageal contractions was significantly delayed. LOS pressure was significantly reduced but the relaxation nadir was not modified by sildenafil. Sildenafil has profound effects on oesophageal motility: it modifies propagation and amplitude of oesophageal contractions and reduces LOS pressure. Slowing down the propagation of contractions in the transitional zone between the striated and smooth muscle can be a useful tool in patients with segmental aperistalsis or intermittent simultaneous contractions, while the effect on the LOS can benefit patients with achalasia.     

Effect of baclofen on oesophageal motility and transient lower oesophageal sphincter relaxations in GORD patients: a 48-h manometric study

Abstract  Little is known about prolonged effect of baclofen on oesophageal and lower oesophageal sphincter (LOS) motility. We aimed at investigating the oesophageal motility in gastro-oesophageal reflux disease (GORD) patients 24 h before and after the administration of multiple doses of baclofen. Twenty-one GORD patients underwent a 48-h manometry recording the swallows, the oesophageal and the LOS motility. During the second 24-h period, patients received baclofen 10 mg or placebo four times per day in a double-blind randomized fashion. Baclofen increased the LOS basal tone in comparison with baseline ( P  = 0.02), with a concomitant reduction in the number of transient LOS relaxations (TLOSRs) ( P  = 0.01). Moreover, baclofen induced a decrease of the swallows ( P  = 0.02) and of primary oesophageal body waves ( P  = 0.04) with no changes in the amplitude. Multiple doses of baclofen determine a reduction in the number of TLOSRs and an increase in the LOS tone throughout the 24 h. The concomitant decreased number of swallows and of primary peristalsis could depend on the well-known lower amount of reflux episodes induced by the drug. The potential therapeutic effect of baclofen could be expressed not only postprandially, but also in the fasting state when reflux episodes are present as well.     

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.     

Increased swallowing frequency in GORD is likely to be caused by perception of reflux episodes

Abstract  Patients with gastro-oesophageal reflux disease (GORD) swallow air more frequently and have more gas-containing reflux episodes than healthy controls. One explanation for this phenomenon may be that GORD patients primarily swallow more frequently and, as a consequence, have more swallow- or transient lower oesophageal sphincter relaxation-associated reflux episodes. Another explanation may be that GORD patients swallow more often in response to perception of reflux episodes. The aim of this study was to differentiate between these two possible mechanisms. In 34 patients with typical reflux symptoms oesophageal 24-h pH-impedance monitoring was performed twice, once off and once on proton pump inhibitor (PPI) therapy. The number of reflux episodes and number of swallows and air swallows was evaluated. The symptom association probability (SAP) was used to distinguish patients with a good relationship between symptoms and reflux episodes (SAP+) from those who had not (SAP−). In both the SAP+ ( n  = 21) as SAP− patients ( n  = 13), the acid exposure time decreased during PPI therapy. In the SAP+ patients, the number of swallows decreased on PPI (829 ± 85 off vs 701 ± 79 on PPI, P  < 0.05), whereas in the SAP− patients, the incidence of swallows (802 ± 93 off vs 814 ± 69 on PPI, P  = NS) was not influenced by the PPI therapy. PPI therapy reduces the number of swallows in patients with a positive SAP, but not in those with a negative SAP. This finding supports the hypothesis that the increased incidence of swallows in GORD is brought about by responses to perceived reflux events.     

The lower oesophageal sphincter

Abstract  The lower oesophageal sphincter (LOS) is a specialized segment of the circular muscle layer of the distal oesophagus, accounting for approximately 90% of the basal pressure at the oesophago-gastric junction. Together with the crural diaphragm, it functions as an antireflux barrier protecting the oesophagus from the caustic gastric content. During swallowing or belching, the LOS muscle must relax briefly in order to allow passage of food or intragastric air. These swallow-induced and prolonged transient lower oesophageal sphincter relaxations (TLOSRs) respectively result from activation of the inhibitory motor innervation of the sphincter. Both in man and animals, the main neurotransmitter released by the inhibitory neurones is nitric oxide. The two typical examples of dysfunction of the LOS are achalasia and gastro-oesophageal reflux disease (GORD). Achalasia is characterized by reduction or even absence of the inhibitory innervation to the LOS, leading to impaired LOS relaxation with dysphagia and stasis of food in the oesophagus. On the contrary, GORD results from failure of the antireflux barrier, with increased exposure of the oesophagus to gastric acid. This leads to symptoms such as heartburn and regurgitation, and in more severe cases to oesophagitis, Barrett's oesophagus and even carcinoma. To date, TLOSRs are recognized as the main underlying mechanism, and may represent an important target for treatment. More insight in the pathogenesis of both diseases will undoubtedly lead to new treatments in the near future.     

Transient lower oesophageal sphincter relaxation in achalasia: everything but LOS relaxation

Abstract  In conducting clinical high-resolution oesophageal pressure topography (HROPT) studies we observed that after subjects sat upright between series of supine and upright test swallows, they frequently had a transient lower oesophageal sphincter relaxation (TLOSR). When achalasia patients were studied in the same protocol, they exhibited a similar HROPT event leading to the hypothesis that achalasics had incomplete TLOSRs. We reviewed clinical HROPT studies of 94 consecutive non-achalasics and 25 achalasics. Studies were analyzed for a TLOSR-like event during the study and, when observed, that TLOSR-like event was characterized for the degree and duration of distal oesophageal shortening, the degree of LOS relaxation, associated crural diaphragm (CD) inhibition, oesophageal pressurization and upper oesophageal sphincter (UOS) relaxation. About 64/94 (68%) non-achalasics and 15/24 (63%) of achalasics had a pressure topography event after the posture change characterized by a prolonged period of distal oesophageal shortening and/or LOS relaxation. Events among the non-achalasics and achalasics were similar in terms of magnitude and duration of shortening and all were associated with CD inhibition. Similar proportions had associated non-deglutitive UOS relaxations. The only consistent differences were the absence of associated LOS relaxation and the absence of HROPT evidence of reflux among the achalasics leading us to conclude that their events were incomplete TLOSRs. Achalasic patients exhibit a selective defect in the TLOSR response suggesting preservation of all sensory, central and efferent aspects of the requisite neural substrate with the notable exception of LOS relaxation, a function of inhibitory (nitrergic) myenteric plexus neurons.