Lower Esophageal Sphincter In Achalasia Research Articles

Imbalance of Innate and Adaptive Immunity in Esophageal Achalasia.

Previous studies reveal that immune-mediated neuroinflammation plays a key role in the etiology of esophageal achalasia. However, the understanding of leucocyte phenotype and proportion is limited. This study aim to evaluate the phenotypes of leukocytes and peripheral blood mononuclear cells transcriptomes in esophageal achalasia. We performed high-dimensional flow cytometry to identified subsets of peripheral leukocytes, and further validated in lower esophageal sphincter histologically. RNA sequencing was applied to investigate the transcriptional changes in peripheral blood mononuclear cells of patients with achalasia. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) was used for estimating the immune cell types. A differential gene expression analysis was performed and the differential expressed genes were subjected to gene ontology, Kyoto Encyclopedia of Genes and Genomes network, protein-protein interaction network construction. An imbalance between innate and adaptive immune cells occurred in achalasia. Specifically, neutrophils and CD8+ T cells increased both in peripheral blood and lower esophageal sphincter in achalasia. Eosinophils decreased in peripheral blood but massively infiltrated in lower esophageal sphincter. CIBERSORT analysis of peripheral blood mononuclear cells RNA sequencing displayed an increased prevalence of CD8+ T cells. 170 dysregulated genes were identified in achalasia, which were enriched in immune cells migration, immune response, etc. Proton pump inhibitor analysis revealed the intersections and gained 7 hub genes in achalasia, which were IL-6, Toll-like receptor 2, IL-1β, tumor necrosis factor, complement C3, and complement C1q A chain. Patients with achalasia exhibited an imbalance of systematic innate and adaptive immunity, which may play an important role in the development of achalasia.

EsoFLIP for esophageal dilation: proposed advantages.

The EsoFLIP integrates impedance planimetry technology into a dilator balloon capable of dilating from diameters between 10 and 30 mm via controlled volumetric distension while providing real-time visualization and objective measurement during the dilation procedure, potentially negating the need for fluoroscopy. This review aims to describe the use and application of EsoFLIP and the potential advantages this novel technology may afford. Small pilot and retrospective studies demonstrate EsoFLIP feasibility and safety, but larger studies are needed to understand its impact on clinical outcomes. EsoFLIP is an appealing new technology that offers advantages in therapeutic dilation of the lower esophageal sphincter in achalasia or of esophageal strictures because of previous surgery, gastroesophageal reflux disease, or radiation.

High-resolution manometric features of achalasia of the cardia

Background: Achalasia of the cardia is a common esophageal motility disorder. High-resolution manometry is the gold standard for the diagnosis of achalasia. The body of the esophagus and the lower esophageal sphincter (LOS) exhibits various motility characteristics that are typical to achalasia. Aims and Objectives: The study was conducted to study the physiology of the LOS in achalasia with a 16-channel water perfusion high-resolution esophageal manometer. Materials and Methods: High-resolution esophageal manometry was performed in 13 adult patients of achalasia and the functional patterns were evaluated. Results: 12 of 13 cases of achalasia had a high basal LOS pressure (BLOSP), while one had reduced pressure. All cases of achalasia had an elevated LOS nadir pressure, indicating an incomplete relaxation of the LOS. All 13 cases of achalasia showed the absence of peristalsis. Conclusion: A reduced BLOSP is rare in achalasia and so is a normal BLOSP; however, they have been described in literature, and hence, the BLOSP as such cannot be considered as a diagnostic feature of achalasia on manometry.

Tu1842 Fibrosis of the Lower Esophageal Sphincter in Achalasia Is Associated With an Insertion in HLA-DQB1

Tu1842 Fibrosis of the Lower Esophageal Sphincter in Achalasia Is Associated With an Insertion in HLA-DQB1

Esophageal Disorders Not Yet Addressed by High-resolution Manometry

TO THE EDITOR: We greatly appreciate the insight provided by Wang et al1 regarding their recent review of the esophageal disorders not assessed by the Chicago classification of motility disorders of the esophagus. This is an important issue as many people still fail to understand that the Chicago classification was designed to describe and categorize distal esophageal motor disorders focused on dysphagia and was not meant to be a global classification across the entire spectrum of esophageal disorders. All patients undergoing manometry will have a Chicago classification diagnosis, however, there may be other motor abnormalities of the upper esophageal sphincter, proximal esophagus or esophagogastric junction and proximal stomach that may be important in the patients presenting complaints and these need to be described separately from the Chicago classification diagnosis. To utilize the Chicago classification, one has to follow specific rules and calculate specific metrics in a predefined order and the analysis is confined to an assessment during 10 supine 5 mL water swallows.2 We experienced that changing position elicited a change in diagnosis in about 10% of studies, and that provocative bolus challenges modified the diagnoses by increasing the number of patients classified with an esophagogastric junction outflow obstruction.3 However, this did require utilization of different standard values and thresholds to allow for a refined characterization and represents one aspect where the Chicago classification diagnosis can be complemented. Similarly, the Chicago classification is also restricted to assessing patients before definitive treatment and although the Chicago classification can be modified to assess patients after antireflux procedures, bariatric surgery or treatments focused on disrupting the lower esophageal sphincter in achalasia; there are no reference ranges to define what is normal in the post-operative state. Nevertheless, the Chicago classification metrics, such as the integrated relaxation pressure and intrabolus pressure pattern, can help one discern whether there is an outflow obstruction after intervention and continued abnormal peristalsis.4,5 Thus, it is likely that the metrics described in the Chicago classification can be utilized, or modified, to help define disorders outside of those that are focused on distal esophageal motor function. Moving forward, the next steps in the evolution of high resolution manometry and esophageal pressure topography should focus on describing specific disease related processes highlighted in the review published by Wang et al,1 such as disorders related to gastroesophageal reflux, upper esophageal sphincter and proximal esophageal dysfunction in dysphagia, post-prandial complaints of regurgitation/possible rumination syndrome and postoperative assessment of symptomatic patients. This will require rigorous evaluation with careful description of normal thresholds and will require outcome data. This is no easy task as the evolution of the Chicago classification to its final version took almost 5 years and it is still being refined. Initial steps in the process of categorizing esophageal motor dysfunction as it relates to gastroesophageal reflux, are currently underway. Hoshino et al6 have described new metrics of defining esophagogastric junction function as an antireflux barrier using modifications of the Chicago classification metrics and correlates of ineffective motility have been defined for esophageal pressure topography.7 Additionally, more emphasis on post-prandial assessments and provocative meals are also being studied to help elucidate mechanism of reflux that may be contributing to the patients underlying symptoms and there are new definitions for the assessment of transient lower esophageal sphincter relaxation using high resolution manometry.8,9 These are promising advances, however, we are only in the preliminary stages and although many have described motor abnormalities in the upper sphincter and post-prandial state, there is a paucity of reference data and consensus regarding terminology and definitions to help define new classifications for these disorders. Thus, the Chicago classification should be utilized as it was intended and designed with the idea that it can be complemented by an assessment of motor function that extends beyond the distal esophagus and 10 supine water swallows. We look forward to future work that may lead to a parallel classification scheme for other disorders not covered by the Chicago classification and we look forward to another great city taking over where Chicago left off.

PNEUMATIC DILATION FOR ACHALASIA CARDIA: REDUCTION IN LOWER ESOPHAGEAL SPHINCTER PRESSURE IN ASSESSING RESPONSE AND FACTORS ASSOCIATED WITH RECURRENCE DURING LONG‐TERM FOLLOW UP

Data on utility of post-pneumatic dilation (PD) lower esophageal sphincter (LES) pressure measurement in evaluating short and long-term efficacy of dilation, which tears the non-relaxing LES in achalasia, are scanty. Post-PD LES pressure was measured in 72/98 patients with achalasia. The best cut-off pressure classifying responders and non-responders was determined by receiver operating characteristic (ROC) curve. Factors associated with non-response and recurrence were evaluated. Of 98 patients (41.1 ± 13.3 years, 58 male), 75 improved, three had perforation requiring surgery, and 20 did not respond to the first PD session. Of 18/20 patients undergoing a second PD, 11 improved and six non-responders needed myotomy. 37/58 (71%) male and 17/40 (42.5%) female patients had a first PD with a 35-mm balloon (P = 0.03). Age and gender of patients did not influence outcome. LES pressure was lower in responders or in those having recurrence than in non-responders (17 mmHg [6.4-75], 11 mmHg [4.6-31]vs 25 mmHg [13-55]). On the ROC curve, 22.5 mmHg was the best cut-off value differentiating responders and non-responders (area under curve [AUC] 0.73). Of the 86 patients responding to PD, 20 had recurrence. Patients who responded to one session of PD or had LES pressure <10 mmHg after the procedure recurred less often, although there was no relationship with age and gender. Post-PD LES pressure measurement is useful to assess treatment response. Patients responding to the first session and those with post-PD LES pressure <10 mmHg tended to recur less. Age and gender did not influence outcome, which might be related to preferential use of a 35-mm balloon, particularly for male patients, during the first session.

3D view of the lower esophageal sphincter in achalasia

Modine-IBEPEGE, Săn Paolo, Brazil Special Issue of the 8th World Congress of OESO Avignon, September 3–6, 2006 Oral, Video and Poster Sessions

The minimally invasive surgical approach to achalasia: a new standard of care?

Achalasia is a rare primary motor disorder of the esophagus, characterized by the triad of esophageal aperistalsis, failure of the lower esophageal sphincter (LES) to completely relax with swallowing, and a hypertensive or sometimes normal pressure LES. The pathophysiology of achalasia results in progressive dysphagia and intermittent regurgitation as well as esophageal dilatation. The exact etiology of achalasia is uncertain, although the pathology has been distinguished in recent literature by the absence of post-inhibitory neurons in Auerbach’s myenteric plexus. Although the incidence of esophageal achalasia is low, occurring in 0.5 to 1 of 100,000 individuals in Western countries, achalasia represents the most frequent esophageal motility disorder. Ernest Heller, a pioneer in the surgical treatment of achalasia, is credited with the first performance of concomitant posterior and anterior cardiomyotomies in 1914. This surgical approach was modified by Groeneveldt in 1918, and by Zaaijer in 1923 to a single anterior cardiomyotomy. The largest experience with cardiomyotomy is in Brazil due to the prevalence of Chagas’s disease, which may progress to a motility disorder similar to achalasia. The treatment for achalasia lends itself well to a minimally invasive approach. The laparoscopic approach enables precise division of the esophageal and cardiac muscle fibers by offering a magnified view of the esophagus and gastroesophageal junction. Laparoscopic cardiomyotomy studies by Hunter and Ancona demonstrate outcomes comparable to conventional open cardiomyotomy. Thoracoscopic esophageal myotomy also provides good results in the treatment of achalasia. It is important to note that none of the current surgical or endoscopic treatments addresses the etiology of the disease itself; these procedures are merely palliative in nature. A full discussion of the diagnostic studies for achalasia, medical and endoscopic treatment, and open cardiomyotomy is presented in the companion article. Briefly, manometry can identify the poorly contractile esophagus and incompletely relaxing LES of achalasia. Achalasia patients also have tertiary, low-amplitude, simultaneous contractions. Vigorous achalasia is characterized by forceful contractions, as in diffuse esophageal spasm, combined with a contracted LES. A barium swallow study may complement the manometric findings by revealing a dilated, often tortuous, “sigmoid-shaped” esophagus tapering to a narrow “bird’s beak” proximal to the gastroesophageal junction. Esophageal endoscopy typically demonstrates a dilated esophagus that tapers distally and often reveals the presence of retained food or esophagitis. Yeast esophagitis should be aggressively treated preoperatively to avoid the catastrophic sequellae of fungal mediastinitis should a mucosal injury occur during esophageal myotomy. Importantly, the LES in achalasia yields to the endoscope to allow it to “pop” into the stomach. This endoscopic characteristic distinguishes achalasia from an esophageal stricture or “pseudoachalasia.” Pseudoachalasia, a condition in which a tumor exerts a mass effect on the distal esophagus, mimics the fluoroscopic and clinical findings of achalasia. If pseudoachalasia is suspected, a computed tomography scan should be performed to check for malignancy.

Vector volume analysis of the lower esophageal sphincter in achalasia and the effect of balloon dilation.

Assessment of the effect of balloon dilation of the lower esophageal sphincter in achalasia currently relies on symptom scores, radiologic studies, or manometry. We have used vector volume analysis which constructs a three-dimensional (3D) pressure profile to examine the effects of balloon dilation on the sphincter. Studies were performed in 26 normal subjects and in 11 patients with achalasia in whom vector volume was determined before and/or after balloon dilation. Vector volume analysis was performed using a multilumen manometry catheter with eight side-reading ports. The catheter was withdrawn through the sphincter using a continuous pull-through technique. A 3D pressure profile was constructed. Vector volume of the lower esophageal sphincter shows a marked radial and linear asymmetry in normal subjects. 3D pressure profiles showed a symmetrical increase in lower esophageal sphincter pressure in untreated achalasia. Mean vector volumes pre and postdilation fell from 254 to 88 cm3 respectively. This was associated with a fall in the mean radial symmetry index from 0.83 to 0.76. Improvement in dysphagia occurred in those patients in whom pressure fell to 15 mmHg or below in at least three adjacent segments. This technique may be a useful tool in the assessment of patients with achalasia and postdilation results may help to predict the long-term outcome of treatment.

Vector volume analysis of the lower esophageal sphincter in achalasia and the effect of balloon dilation*

Vector volume analysis of the lower esophageal sphincter in achalasia and the effect of balloon dilation*

Transnasal US of the esophagus: preliminary morphologic and function studies.

High-frequency catheter-based ultrasound (US) transducers can be inserted into the esophagus transnasally to evaluate esophageal wall structures. Studies were performed in two sheep esophagus specimens in vitro, in 17 healthy human subjects, and in 16 patients with esophageal abnormalities (eight with achalasia, four with scleroderma, three with esophageal carcinoma, and one with esophagitis). In the sheep specimens, endoluminal US delineated seven layers of the esophageal wall; these results correlated closely with histologic findings. Real-time US of the normal esophageal wall was performed during resting and swallowing. Muscles at the lower esophageal sphincter (LES) were shown to be thicker than muscles in the body of the esophagus. Thickening of the muscular layers at the LES in achalasia, dilated blood vessels within the submucosa in esophagitis, and fibrotic changes within the muscular layers in scleroderma were demonstrated. Extramural structures adjacent to the esophagus were also seen. These preliminary results suggest that transnasal esophageal US may become an important diagnostic tool in evaluation of the esophagus.

The effect of vasoactive intestinal polypeptide on the lower esophageal sphincter in achalasia

Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5,3, and 5 pmol · kg−1 · min−1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol · kg−1 · min−1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol · kg−1 · min−1 produced a maximal decrease of 51% in LESP. A β-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation.

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia: R.H. Holloway, W.J. Dodds, J.F. Helm, et al. Gastroenterology 90:924–929, (April), 1986

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia: R.H. Holloway, W.J. Dodds, J.F. Helm, et al. Gastroenterology 90:924–929, (April), 1986

Integrity of cholinergic innervation to the lower esophageal sphincter in achalasia

The human lower esophageal sphincter (LES) is believed to be innervated by nonadrenergic, noncholinergic inhibitory nerves, and cholinergic excitatory nerves. In idiopathic achalasia, LES relaxation is abnormal because the inhibitory nerves to the sphincter are either absent or functionally impaired. The integrity of cholinergic excitatory nerves to the LES, however, has not been thoroughly evaluated. In 27 patients with untreated idiopathic achalasia, and 21 healthy volunteers, we investigated the hypothesis that postganglionic cholinergic nerves to the LES are functionally intact in achalasia. The LES responses to atropine, edrophonium, methacholine, amyl nitrite, and pentagastrin were assessed. In 2 achalasia patients, patterns of fasting motor activity in the LES were investigated during overnight manometric studies. Resting LES pressure was significantly greater in the achalasia patients, 41 ± 4 mmHg (mean ± SE), than in the normal subjects, 20 ± 2 mmHg. Atropine significantly reduced LES pressure in both groups by 30%–75%. Edrophonium increased LES pressure in the achalasia patients but had negligible effect on the normal subjects. The LES in achalasia patients exhibited an increased sensitivity to both methacholine and pentagastrin compared with the normal subjects. In both patients who underwent an overnight manometric study, the LES exhibited cyclic phasic contractile activity synchronous with gastric contractions during the migrating motor complex. We conclude that the study findings support the hypothesis that postganglionic cholinergic LES innervation in achalasia patients is either normal or only minimally impaired, in contrast to the marked impairment of the inhibitory nerves governing LES relaxation.