Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis.

PubMed

Bektas, Mehmet; Seven, Gulseren; Idilman, Ramazan; Yakut, Mustafa; Doğanay, Beyza; Kabacam, Gökhan; Ustun, Yusuf; Korkut, Esin; Kalkan, Çağdaş; Sahin, Günay; Cetinkaya, Hulya; Bozkaya, Hakan; Yurdaydin, Cihan; Bahar, Kadir; Cinar, Kubilay; Soykan, Irfan

2014-03-01

Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögren's syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögren's syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Esophageal motor activity in children with gastro-esophageal reflux disease and esophagitis.

PubMed

Chitkara, Denesh K; Fortunato, Christine; Nurko, Samuel

2005-01-01

To evaluate esophageal body motor contractions occurring during esophageal reflux in pediatric patients with gastro-esophageal reflux disease (GERD). Patients referred for the evaluation of GERD who were evaluated with combined 24-hour pH probe and esophageal manometry test (MP24) were included. Patients were separated into the following groups: Group C -- normal pH probe and normal EGD; Group 1 -- abnormal pH probe and normal EGD; and Group 2 -- abnormal pH probe and EGD with histologic esophagitis. Esophageal motor function during reflux episodes was analyzed. Twenty-five patients were included. All had a normal stationary esophageal manometry. Patients in Groups 1 and 2 had significantly more gastroesophageal reflux by pH probe than Group C (P < 0.01). During the MP24, patients in Group 1 and 2 had significantly fewer contractions per minute pre-, during, and post-GER (P < 0.05). There were significant differences in the number of isolated and prolonged contractions (>7 sec) during prolonged GERD episodes >5 minutes (P < 0.05). Children with GERD have a decreased number and abnormal esophageal body contractions with esophageal reflux. This suggests that children with GERD with and without esophagitis have impaired esophageal body acid clearance.

Functional Esophageal Disorders.

PubMed

Aziz, Qasim; Fass, Ronnie; Gyawali, C Prakash; Miwa, Hiroto; Pandolfino, John E; Zerbib, Frank

2016-02-15

Functional esophageal disorders consist of a disease category that present with esophageal symptoms (heartburn, chest pain, dysphagia, globus) not explained by mechanical obstruction (stricture, tumor, eosinophilic esophagitis), major motor disorders (achalasia, EGJ outflow obstruction, absent contractility, distal esophageal spasm, jackhammer esophagus), or gastroesophageal reflux disease (GERD). While mechanisms responsible are unclear, it is theorized that visceral hypersensitivity and hypervigilance play an important role in symptom generation, in the context of normal or borderline function. Treatments directed at improving borderline motor dysfunction or reducing reflux burden to sub-normal levels have limited success in symptom improvement. In contrast, strategies focused on modulating peripheral triggering and central perception are mechanistically viable and clinically meaningful. However, outcome data from these treatment options are limited. Future research needs to focus on understanding mechanisms underlying visceral hypersensitivity and hypervigilance so that appropriate targets and therapies can be developed. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Treatment implications of high-resolution manometry findings: options for patients with esophageal dysmotility.

PubMed

Bolkhir, Ahmed; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) has significantly impacted diagnosis and management of achalasia in particular, and has improved characterization of other motor disorders. Achalasia, the most profound esophageal motor disorder, is characterized by esophageal outflow obstruction from abnormal relaxation of the lower esophageal sphincter (LES) during swallowing, and presents with transit symptoms (dysphagia, regurgitation). Esophageal body motor disorders include both inhibitory nerve dysfunction associated with hypermotility or spasm, and hypomotility disorders with poor contraction. The implications of hypermotility disorders are both perceptive and obstructive. On the other hand, hypomotility disorders have reflux implications because of abnormal barrier function at the LES, and abnormal bolus clearance. Esophageal outflow obstruction in achalasia responds favorably to disruption of the LES, and outcome may be predicted by HRM subtyping of achalasia. Identification of dominant (perceptive vs. obstructive) mechanisms of symptom generation help direct therapy of hypermotility disorders, while hypomotility disorders typically require management of concurrent reflux disease.

Esophageal manometry in gastroesophageal reflux disease.

PubMed

Mello, Michael; Gyawali, C Prakash

2014-03-01

High-resolution manometry (HRM) allows nuanced evaluation of esophageal motor function, and more accurate evaluation of lower esophageal sphincter (LES) function, in comparison with conventional manometry. Pathophysiologic correlates of gastroesophageal reflux disease (GERD) and esophageal peristaltic performance are well addressed by this technique. HRM may alter the surgical decision by assessment of esophageal peristaltic function and exclusion of esophageal outflow obstruction before antireflux surgery. Provocative testing during HRM may assess esophageal smooth muscle peristaltic reserve and help predict the likelihood of transit symptoms following antireflux surgery. HRM represents a continuously evolving new technology that compliments the evaluation and management of GERD. Copyright © 2014 Elsevier Inc. All rights reserved.

Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

PubMed

Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

2013-08-01

Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P < 0.0001). Abnormal AET was noted in 56.5%, and was similar between ILD and OLD, but less frequent than in the ARS group (P = 0.04). Post-transplant chronic rejection trended towards association with pretransplant elevated AET in OLD (P = 0.08) but not ILD. Mortality was not predicted by esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

[Esophageal motor function of gastroesophageal reflux disease].

PubMed

Wang, Hong; Tian, Yuan; Ding, Yan

2010-08-01

To study the relationship between esophageal motor functional disorder [decreased lower esophageal sphincter pressure (LESP)and ineffective motility (IEM)] and gastroesophageal reflux disease (GERD). Totally 89 patients with GERD were enrolled in this study. All of them underwent 24-hour pH monitoring with dual-channel probe and stationary esophageal manometry. In addition, 77 of these patients underwent upper endoscopy. IEM and LES, 10 mmHg were common disturbances in patients with GERD (54% and 48%, respectively). The number of the acid reflux events of distal esophagus and prevalence of moderate or severe erosive esophagitis (EE) were significantly higher in patients with low LESP and IEM than patients without low LESP ( P<0.05). The number of the acid reflux events in distal esophagus was significantly correlated with the severity of esophagitis, distal esophagus amplitude, and LESP, while no such correlation was found between IEM and degree of esophageal acid exposure or esophagitis. The pathophysiology of GERD is probably multifactorial. Lower LESP or IEM is not a independent pathophysiological factor for GERD. However,one single factor is insufficient to explain all the pathogenic mechanism of GERD.

The 5-HT1A receptor agonist buspirone improves esophageal motor function and symptoms in systemic sclerosis: a 4-week, open-label trial.

PubMed

Karamanolis, George P; Panopoulos, Stylianos; Denaxas, Konstantinos; Karlaftis, Anastasios; Zorbala, Alexandra; Kamberoglou, Dimitrios; Ladas, Spiros D; Sfikakis, Petros P

2016-09-01

Acute administration of the oral 5-HT1A receptor agonist buspirone, which is commonly used as an anxiolytic drug, may improve compromised lower esophageal sphincter function. In an open-label trial we assessed the effects of buspirone on esophageal motor function and symptoms in patients with esophageal involvement associated with systemic sclerosis (SSc). Thirty consecutive patients with SSc and symptomatic esophageal involvement, despite treatment with proton pump inhibitors, underwent high resolution manometry and chest computed tomography for assessment of motor function and esophageal dilatation, respectively. Regurgitation, heartburn, dysphagia, and chest pain severity was subjectively scored by visual analog scales. Manometric parameters (primary endpoint) and symptom severity (secondary endpoint) were re-examined after 4-week daily administration of 20 mg buspirone. Other medications remained unchanged. Eight patients did not complete the trial because of buspirone-associated dizziness (n = 2), or nausea (n = 2), or reluctancy to undergo final manometry. In the remaining 22 patients lower esophageal sphincter (LES) resting pressure increased from 7.7 ± 3.9 to 12.2 ± 4.6 mmHg (p = 0.00002) after buspirone administration; other manometric parameters did not change. Statistical analysis revealed negative correlation between individual increases in resting LES pressure and supra-aortic esophageal diameter (r = -0.589, p = 0.017), suggesting a more beneficial effect in patients with less severely affected esophageal function. Heartburn and regurgitation scores decreased at 4 weeks compared to baseline (p = 0.001, and p = 0.022, respectively). Our findings warrant more conclusive evaluation with a double-blind controlled study; however, buspirone could potentially be given under observation for objective improvement in all patients with SSc who report reflux symptoms despite undergoing standard treatment. ClinicalTrials.gov Identifier: NCT02363478 Registered: 21-02-2014.

Medical and surgical management of esophageal and gastric motor dysfunction.

PubMed

Awad, R A

2012-09-01

he occurrence of esophageal and gastric motor dysfunctions happens, when the software of the esophagus and the stomach is injured. This is really a program previously established in the enteric nervous system as a constituent of the newly called neurogastroenterology. The enteric nervous system is composed of small aggregations of nerve cells, enteric ganglia, the neural connections between these ganglia, and nerve fibers that supply effectors tissues, including the muscle of the gut wall. The wide range of enteric neuropathies that includes esophageal achalasia and gastroparesis highlights the importance of the enteric nervous system. A classification of functional gastrointestinal disorders based on symptoms has received attention. However, a classification based solely in symptoms and consensus may lack an integral approach of disease. As an alternative to the Rome classification, an international working team in Bangkok presented a classification of motility disorders as a physiology-based diagnosis. Besides, the Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high-resolution esophageal pressure topography studies. This review covers exclusively the medical and surgical management of the esophageal and gastric motor dysfunction using evidence from well-designed studies. Motor control of the esophagus and the stomach, motor esophageal and gastric alterations, treatment failure, side effects of PPIs, overlap of gastrointestinal symptoms, predictors of treatment, burden of GERD medical management, data related to conservative treatment vs. antireflux surgery, and postsurgical esophagus and gastric motor dysfunction are also taken into account.

Effects of bariatric surgery on the esophagus.

PubMed

Savarino, Edoardo; Marabotto, Elisa; Savarino, Vincenzo

2018-07-01

Bariatric surgery is the best therapeutic approach to patients with morbid obesity, but there is mounting evidence that it is associated with esophageal dysfunctions, including gastroesophageal reflux disease (GERD) and motor disorders. In the present review, we summarize the existing information on the complex link between bariatric surgery and esophageal disorders. Although high-quality studies on these effects are lacking, because of evident methodological flaws and retrospective nature, the review of published investigations show that pure restrictive procedures, such as laparoscopic adjustable gastric banding (LAPG) and laparoscopic sleeve gastrectomy (LSG), are associated with de novo development or worsening of GERD. Moreover, LAGB is the procedure with the greatest frequency of esophageal motor disorders, including impairment of LES relaxation and ineffective esophageal peristalsis associated with esophageal dilation. LSG seems to be less associated with esophageal dysmotility, although evidence derived from studies with objective measurements of esophageal dysfunction is limited. Finally, RYGB seems to be the best procedure for improvement of GERD symptoms and preservation of esophageal function. Overall, the restrictive-malabsorptive approach represented by RYGB must be preferred to pure restrictive operations in order to avoid the negative consequences of bariatric surgery on esophageal functions.

The Potential Benefits of Applying Recent Advances in Esophageal Motility Testing in Patients with Esophageal Atresia

PubMed Central

Rommel, Nathalie; Rayyan, Maissa; Scheerens, Charlotte; Omari, Taher

2017-01-01

Infants and children with esophageal atresia commonly present with swallowing dysfunction or dysphagia. Dysphagia can lead to a range of significant consequences such as aspiration pneumonia, malnutrition, dehydration, and food impaction. To improve oral intake, the clinical diagnosis of dysphagia in patients with esophageal atresia should focus on both the pharynx and the esophagus. To characterize the complex interactions of bolus flow and motor function between mouth, pharynx, and esophagus, a detailed understanding of normal and abnormal deglutition is required through the use of adequate and objective assessment techniques. As clinical symptoms do not correlate well with conventional assessment methods of motor function such as radiology or manometry but do correlate with bolus flow, the current state-of-the-art diagnosis involves high-resolution manometry combined with impedance measurements to characterize the interplay between esophageal motor function and bolus clearance. Using a novel pressure flow analysis (PFA) method as an integrated analysis method of manometric and impedance measurements, differentiation of patients with impaired esophago-gastric junction relaxation from patients with bolus outflow disorders is clinically relevant. In this, pressure flow matrix categorizing the quantitative PFA measures may be used to make rational therapeutic decisions in patients with esophageal atresia. Through more advanced diagnostics, improved understanding of pathophysiology may improve our patient care by directly targeting the failed biomechanics of both the pharynx and the esophagus. PMID:28680874

The Potential Benefits of Applying Recent Advances in Esophageal Motility Testing in Patients with Esophageal Atresia.

PubMed

Rommel, Nathalie; Rayyan, Maissa; Scheerens, Charlotte; Omari, Taher

2017-01-01

Infants and children with esophageal atresia commonly present with swallowing dysfunction or dysphagia. Dysphagia can lead to a range of significant consequences such as aspiration pneumonia, malnutrition, dehydration, and food impaction. To improve oral intake, the clinical diagnosis of dysphagia in patients with esophageal atresia should focus on both the pharynx and the esophagus. To characterize the complex interactions of bolus flow and motor function between mouth, pharynx, and esophagus, a detailed understanding of normal and abnormal deglutition is required through the use of adequate and objective assessment techniques. As clinical symptoms do not correlate well with conventional assessment methods of motor function such as radiology or manometry but do correlate with bolus flow, the current state-of-the-art diagnosis involves high-resolution manometry combined with impedance measurements to characterize the interplay between esophageal motor function and bolus clearance. Using a novel pressure flow analysis (PFA) method as an integrated analysis method of manometric and impedance measurements, differentiation of patients with impaired esophago-gastric junction relaxation from patients with bolus outflow disorders is clinically relevant. In this, pressure flow matrix categorizing the quantitative PFA measures may be used to make rational therapeutic decisions in patients with esophageal atresia. Through more advanced diagnostics, improved understanding of pathophysiology may improve our patient care by directly targeting the failed biomechanics of both the pharynx and the esophagus.

Manometric evaluation of the esophagus in patients with Behçet's disease.

PubMed

Bektas, Mehmet; Altan, Mehmet; Alkan, Murat; Ormeci, Necati; Soykan, Irfan

2007-01-01

Gastrointestinal (GI) involvement in Behçet's disease (BD) mainly appears in mucosa and affects 5-40% of patients, however the effects of the disease on lower esophageal sphincter (LES) pressure and esophageal contractions are not well known. The aims of this study were to evaluate esophageal motor function and to identify whether there was any specific motility pattern for patients with BD who had upper GI symptoms without endoscopic abnormality. 25 patients with BD, with a mean age of 43.1 (range 20-66) years, were admitted to our clinic whose main complaints were dyspeptic such as reflux, epigastric pain, vomiting and bloating. 25 healthy and age-matched individuals were also included in the study as controls. After one night fasting, LES pressure and esophageal contractions were measured. Esophageal motor abnormalities were detected in 16% (4/25) of these patients with manometric studies (non-specific esophageal motor disorder in 1, esophageal hypomotility in 2, and LES hypotension in 1 patient); 16% (4/25) of these patients had endoscopic findings and overall 32% (8/25) of the cases showed esophageal pathology. All cases with esophageal motor abnormalities were suffering from reflux and endoscopy showed grade B esophagitis in 2 of these cases. Median LES pressure and LES relaxation were significantly lower in patients with BD compared to the control group (16.8 +/- 10.5 vs. 20.4 +/- 6.1, p = 0.02, and 92.1 +/- 10.1 vs. 96.4 +/- 4.5, p = 0.03 respectively). Esophageal involvement in BD is significantly high. We propose manometric studies are necessary to evaluate esophageal manifestations in BD patients with esophageal symptoms even without endoscopic findings.

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

PubMed

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p<0.01) and among patients with severe motor dysfunction (90% vs. 35%; p<0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

Esophageal hypomotility and spastic motor disorders: current diagnosis and treatment.

PubMed

Valdovinos, Miguel A; Zavala-Solares, Monica R; Coss-Adame, Enrique

2014-11-01

Esophageal hypomotility (EH) is characterized by abnormal esophageal peristalsis, either from a reduction or absence of contractions, whereas spastic motor disorders (SMD) are characterized by an increase in the vigor and/or propagation velocity of esophageal body contractions. Their pathophysiology is not clearly known. The reduced excitation of the smooth muscle contraction mediated by cholinergic neurons and the impairment of inhibitory ganglion neuronal function mediated by nitric oxide are likely mechanisms of the peristaltic abnormalities seen in EH and SMD, respectively. Dysphagia and chest pain are the most frequent clinical manifestations for both of these dysfunctions, and gastroesophageal reflux disease (GERD) is commonly associated with these motor disorders. The introduction of high-resolution manometry (HRM) and esophageal pressure topography (EPT) has significantly enhanced the ability to diagnose EH and SMD. Novel EPT metrics in particular the development of the Chicago Classification of esophageal motor disorders has enabled improved characterization of these abnormalities. The first step in the management of EH and SMD is to treat GERD, especially when esophageal testing shows pathologic reflux. Smooth muscle relaxants (nitrates, calcium channel blockers, 5-phosphodiesterase inhibitors) and pain modulators may be useful in the management of dysphagia or pain in SMD. Endoscopic Botox injection and pneumatic dilation are the second-line therapies. Extended myotomy of the esophageal body or peroral endoscopic myotomy (POEM) may be considered in highly selected cases but lack evidence.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers.

PubMed

Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

2016-01-31

Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm(2)/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults.

Effects of Metoclopramide on Esophageal Motor Activity and Esophagogastric Junction Compliance in Healthy Volunteers

PubMed Central

Mikami, Hironobu; Ishimura, Norihisa; Fukazawa, Kousuke; Okada, Mayumi; Izumi, Daisuke; Shimura, Shino; Okimoto, Eiko; Aimi, Masahito; Ishihara, Shunji; Kinoshita, Yoshikazu

2016-01-01

Background/Aims Prokinetic drugs such as metoclopramide are frequently used as second-line therapy for patients with gastroesophageal reflux disease. However, their beneficial effects remain unclear. Esophageal motor activities and compliance of the esophagogastric junction (EGJ) are important for prevention of gastroesophageal reflux. Although metoclopramide has been reported to increase lower esophageal sphincter (LES) pressure, its effects on EGJ compliance have not been evaluated. In the present study, we investigated the effects of metoclopramide on esophageal motor activities and EGJ compliance. Methods Nine healthy male volunteers without abdominal symptoms were enrolled. Peristaltic esophageal contractions and LES pressure were examined using high-resolution esophageal manometry, while EGJ compliance was evaluated with an endoluminal functional lumen-imaging probe. After obtaining baseline values for esophageal motor activities and EGJ compliance, metoclopramide (10 mg) was intravenously administered, then all measurements were repeated at 15 minutes after administration in each subject. Results Following administration of metoclopramide, mean resting LES pressure was significantly increased as compared with the baseline (13.7 ± 9.2 vs 26.7 ± 8.8 mmHg, P < 0.05). In addition, metoclopramide significantly augmented peristaltic contractions, especially in the distal esophageal segment (P < 0.05). On the other hand, distensibility index did not change after administration (4.5 ± 0.5 vs 4.1 ± 0.5 mm2/mmHg), suggesting no significant effect of metoclopramide on EGJ compliance. Conclusions Metoclopramide augmented esophageal contractions without changing EGJ compliance in healthy adults. PMID:26507875

Esophageal Motor Abnormalities in Patients With Scleroderma: Heterogeneity, Risk Factors, and Effects on Quality of Life.

PubMed

Crowell, Michael D; Umar, Sarah B; Griffing, W Leroy; DiBaise, John K; Lacy, Brian E; Vela, Marcelo F

2017-02-01

Systemic scleroderma (SSc) is associated with esophageal aperistalsis and hypotensive esophagogastric junction pressure, although there could be a gradation in esophageal motor dysfunction. We characterized esophageal motor function by high-resolution esophageal manometry (HRM) and assessed associations between SSc severity, health-related quality of life (HRQOL), and HRM findings in patients. We performed a prospective study of 200 patients with SSc and 102 patients without SSc (controls) who underwent HRM at Mayo Clinic Arizona from May 2006 through January 2015. We used data on integrated relaxation pressure, distal contractile integral, and distal latency to classify esophageal motility disorders according to the Chicago Classification v 3.0. A subset of subjects (n = 122) completed SSc-specific gastrointestinal symptom and HRQOL questionnaires. HRM findings, symptoms, and HRQOL data were compared among diffuse SSc, limited SSc, and control subjects. Categorical variables were compared by using the χ 2 or Fisher exact test; continuous variables were compared by using Mann-Whitney or Kruskal-Wallis test. Multivariable logistic regression was used to assess the association between severity of esophageal dysmotility and baseline clinical factors. Among patients with SSc, 83 had diffuse SSc (42%), and 117 had limited SSc (58%). Absent contractility was more frequent in patients with SSc than in controls (56% vs 13%; P < .001). HRM findings varied among the patients; absent contractility (56%) was the most frequent diagnosis, followed by normal motility (26%) and ineffective esophageal motility (10%). Classic scleroderma esophagus (esophagogastric junction pressure with absent contractility) was only observed in 33% of patients (34% with diffuse SSc vs 32% limited SSc) (P = .880). Severe esophageal dysmotility was associated with disease duration, interstitial lung disease, and higher gastrointestinal symptom scores (P < .001). HRQOL was decreased in patients with SSc and severe esophageal dysmotility. Although severe dysmotility is more common in patients with SSc than in controls, we observed the so-called scleroderma esophagus in only one-third of patients with SSc. Esophageal motor function appears to be heterogeneous in SSc. Esophageal dysmotility reduces HRQOL in patients with SSc. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Motility abnormalities in esophageal body in GERD: are they truly related to reflux?

PubMed

Ciriza de los Ríos, C; García Menéndez, L; Díez Hernández, A; Fernández Eroles, A L; Vega Fernández, A; Enguix Armada, A

2005-03-01

Esophageal motility abnormalities have been observed in patients with gastroesophageal reflux disease. The aim of the present study was to determine if esophageal motor disorders in patients with a positive response to the omeprazole test are related to the existence of reflux or they are concomitant findings. A 24-hour pH monitoring and a stationary manometry were performed on 128 patients: 49 of them had normal manometry, 31 hypotensive lower esophageal sphincter, 29 motor disorder in esophageal body, and 19 hypotensive lower esophageal sphincter and motor disorder in esophageal body. We found an association between the presence of abnormal reflux and motor disorder in esophageal body (chi test; P < 0.05). However, ineffective esophageal motility was the disorder most strongly related to reflux, whereas the hypercontractile disorders were not clearly attributed to it. Esophageal manometric abnormalities should be considered cautiously before considering a motor disorder as a consequence of abnormal reflux.

Longitudinal muscle of the esophagus: its role in esophageal health and disease.

PubMed

Mittal, Ravinder K

2013-07-01

The muscularis propria of the esophagus is organized into circular and longitudinal muscle layers. The function of the longitudinal muscle and its role in bolus propulsion are not clear. The goal of this review is to summarize what is known of the role of the longitudinal muscle in health, as well as in sensory and motor disorders of the esophagus. Simultaneous manometry and ultrasound imaging reveal that, during peristalsis, the two muscle layers of the esophagus contract in perfect synchrony. On the contrary, during transient lower esophageal sphincter (LES) relaxation, longitudinal muscle contracts independent of the circular muscle. Recent studies have provided novel insights into the role of the longitudinal muscle in LES relaxation and descending relaxation of the esophagus. In certain diseases (e.g. some motility disorders of the esophagus), there is discoordination between the two muscle layers, which likely plays an important role in the genesis of dysphagia and delayed esophageal emptying. There is close temporal correlation between prolonged contractions of the longitudinal muscles of the esophagus and esophageal 'angina-like' pain. Novel techniques to record longitudinal muscle contraction are reviewed. Longitudinal muscles of the esophagus play a key role in the physiology and pathophysiology of esophageal sensory and motor function. Neuro-pharmacologic controls of circular and longitudinal muscle are different, which provides an opportunity for the development of novel pharmacological therapies in the treatment of esophageal sensory and motor disorders.

[Differences between Chicago and traditional classifications in the diagnosis of esophageal motor disorders with high-resolution manometry and topography of esophageal pressure].

PubMed

Abreu-Y Abreu, A T; González Sánchez, C B; Villanueva Sáenz, E; Valdovinos Díaz, M A

2010-01-01

With the introduction of high resolution manometry (HRM) and esophageal topography a novel classification (Chicago Classification) has been proposed for the diagnosis of esophageal motor disorders (EMD). Clinical differences with the traditional classification are currently under evaluation. To investigate differences between the Chicago (CC) and traditional (TC) classifications in the diagnosis of EMD. Consecutive patients with indication for esophageal manometry were studied. HRM was performed with a 36 sensors solid-state catheter and Manoview software (V2.0).Conventional manometric tracings were analyzed by an investigator blinded to the results of HRM. Diagnosis by CC and CT were compared. Two hundred patients were studied, 106 (53%) of them women (53%) with a mean patient age of 43.4 (range 16 - 84) years. Preoperative evaluation for GERD 152 (76%) was the most frequent indication. Achalasia (8), scleroderma (2) and peristaltic dysfunction (60 vs. 59) were similarly diagnosed by CC and CT. Spastic disorders were more frequently identified by CC: nutcracker esophagus (NC) in 3, spastic NC in3 and segmental NC in 11 patients versus TC: NC 5. Three patients had spasm with CC and 1 with TC. Non specific motor disorder was diagnosed by TC and 2 patients had functional obstruction with CC. Hypotensive lower esophageal sphincter was identified in 63 patients with CC vs.57 with TC. Spastic disorders and functional obstruction were the EMD better identified by HRM and CC.

Long-term Outcomes of Patients With Normal or Minor Motor Function Abnormalities Detected by High-resolution Esophageal Manometry.

PubMed

Ravi, Karthik; Friesen, Laurel; Issaka, Rachel; Kahrilas, Peter J; Pandolfino, John E

2015-08-01

High-resolution manometry (HRM) expands recognition of minor esophageal motor abnormalities, but the clinical significance of these is unclear. We aimed to determine the outcomes of minor esophageal motor abnormalities. We reviewed HRM tracings from patients who underwent esophageal manometry at Northwestern Memorial Hospital from July 2004 through October 2005 by using the Chicago classification (version 2.0). We identified 301 patients with normal findings or minor manometric abnormalities (weak peristalsis, hypertensive peristalsis, frequent failed peristalsis, or rapid contractions with normal latency). Ninety-eight patients participated in a phone survey in which they were asked questions from the impact dysphagia questionnaire (mean follow-up period, 6 years 5 months). Of 301 patients assessed, 166 had normal findings from HRM, 82 had weak peristalsis, 34 had hypertensive peristalsis, 17 had frequent failed peristalsis, and 2 had rapid contractions with normal latency. The primary indications for HRM of dysphagia (44%) and gastroesophageal reflux disease (63%) were unrelated to manometric findings. There were no endoscopic or videofluoroscopic differences between patients with minor manometric abnormalities. Of 98 patients with follow-up, findings from HRM were normal in 63, weak peristalsis was observed in 23, hypertensive peristalsis was observed in 10, and frequent failed peristalsis was observed in 2. No patients underwent surgical myotomy, pneumatic dilation, or botulinum toxin injection. Use of proton pump inhibitors and rates of fundoplication were similar, regardless of manometric findings. Sixteen patients (16%) had significant dysphagia at follow-up; hypertensive peristalsis was the most likely to be symptomatic. Patients with normal and minor esophageal motor abnormalities report minimal symptoms and have few medical interventions related to esophageal dysfunction during long-term follow-up. Therefore, identification of normal and minor motor function is likely a good prognostic indicator. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Radiological evaluation of dysphagia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ott, D.J.; Gelfand, D.W.; Wu, W.C.

1986-11-21

Dysphagia is a common complaint in patients presenting for radiological or endoscopic examination of the esophagus and is usually due to functional or structural abnormalities of the esophageal body or esophagogastric region. The authors review the radiological evaluation of the esophagus and esophagogastric region in patients with esophageal dysphagia and discuss the roentgenographic techniques used, radiological efficacy for common structural disorders, and evaluation of esophageal motor function. Comparison is made with endoscopy in assessing dysphagia, with the conclusion that the radiological examination be used initially in patients with this complaint.

Minimally invasive surgery for esophageal achalasia

PubMed Central

Bonavina, Luigi

2006-01-01

Esophageal achalasia is the most commonly diagnosed primary esophageal motor disorder and the second most common functional esophageal disorder. Current therapy of achalasia is directed toward elimination of the outflow resistance caused by failure of the lower esophageal sphincter to relax completely upon swallowing. The advent of minimally invasive surgery has nearly replaced endoscopic pneumatic dilation as the first-line therapeutic approach. In this editorial, the rationale and the evidence supporting the use of laparoscopic Heller myotomy combined with fundoplication as a primary treatment of achalasia are reviewed. PMID:17009388

Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group.

PubMed

Gyawali, C P; Roman, S; Bredenoord, A J; Fox, M; Keller, J; Pandolfino, J E; Sifrim, D; Tatum, R; Yadlapati, R; Savarino, E

2017-12-01

High-resolution manometry (HRM) has resulted in new revelations regarding the pathophysiology of gastro-esophageal reflux disease (GERD). The impact of new HRM motor paradigms on reflux burden needs further definition, leading to a modern approach to motor testing in GERD. Focused literature searches were conducted, evaluating pathophysiology of GERD with emphasis on HRM. The results were discussed with an international group of experts to develop a consensus on the role of HRM in GERD. A proposed classification system for esophageal motor abnormalities associated with GERD was generated. Physiologic gastro-esophageal reflux is inherent in all humans, resulting from transient lower esophageal sphincter (LES) relaxations that allow venting of gastric air in the form of a belch. In pathological gastro-esophageal reflux, transient LES relaxations are accompanied by reflux of gastric contents. Structural disruption of the esophagogastric junction (EGJ) barrier, and incomplete clearance of the refluxate can contribute to abnormally high esophageal reflux burden that defines GERD. Esophageal HRM localizes the LES for pH and pH-impedance probe placement, and assesses esophageal body peristaltic performance prior to invasive antireflux therapies and antireflux surgery. Furthermore, HRM can assess EGJ and esophageal body mechanisms contributing to reflux, and exclude conditions that mimic GERD. Structural and motor EGJ and esophageal processes contribute to the pathophysiology of GERD. A classification scheme is proposed incorporating EGJ and esophageal motor findings, and contraction reserve on provocative tests during HRM. © 2017 John Wiley & Sons Ltd.

Advances in esophageal motor disorders.

PubMed

Smout, André Jpm

2008-07-01

Esophageal motor disorders, often leading to dysphagia and chest pain, continue to pose diagnostic and therapeutic problems. In the past 12 months important new information regarding esophageal motor disorders was published. This information will be reviewed in this paper. A number of studies have addressed the issue of heterogeneity in achalasia, the best defined esophageal motility disorder. The spastic esophageal motility disorders nutcracker esophagus and diffuse esophageal spasm may coexist with gastroesophageal reflux disease, which has consequences for the management of patients with these disorders. The entity labelled ineffective esophageal motility is associated with reflux esophagitis, but also with morbid obesity. For the detection of disordered transit caused by ineffective esophageal motility, application of intraluminal impedance monitoring in conjunction with manometry leads to improved diagnosis. New data on the effect of Nissen fundoplication on esophageal motility were published during the last year. Recent knowledge on the heterogeneity of achalasia and the association of spastic esophageal motor disorders and ineffective motility with reflux disease will help the clinician in the management of patients with these disorders.

Esophageal dysmotility in scleroderma: a prospective study of 183 cases.

PubMed

Lahcene, M; Oumnia, N; Matougui, N; Boudjella, M; Tebaibia, A; Touchene, B

2009-01-01

The goal of the study was to evaluate the prevalence and risk factors of esophageal motor disorders in systemic sclerosis. In 183 consecutive cases of scleroderma, as diagnosed by American College of Rheumatology criteria (1980). Patients' mean age was 40.6+/-13.3 years, the gender ratio was 0.13 and the average duration of disease was 6.8+/-7.5 years. A localized, cutaneous form was observed in 148 patients (81%) and a diffuse form in 35 (19%). All patients underwent upper gastrointestinal endoscopy and standard esophageal manometry. Esophageal symptoms and reflux esophagitis were found in 108 (59%) and 68 (37%) of patients, respectively. Esophageal motor disorders were present in 148 patients (81%), and were associated with a hypotensive lower esophageal sphincter in 114 (62%). The presence of these motor abnormalities was not related to age, gender, skin extension or duration of disease. Esophageal motor disorders were present in almost all patients with esophageal symptoms or esophagitis, and were also found in 48 (64%) of the asymptomatic patients. Esophageal motor disorders are frequently seen in scleroderma, especially in cases with clinical symptoms, but are not associated with a specific form of the disease.

High resolution vs conventional esophageal manometry in the assessment of esophageal motor disorders in patients with non-cardiac chest pain.

PubMed

Akinsiku, O; Yamasaki, T; Brunner, S; Ganocy, S; Fass, R

2018-06-01

High-resolution esophageal manometry (HREM) has become a leading tool in the assessment of esophageal motor disorders, replacing conventional manometry. However, there is limited data about the contribution of HREM as compared with conventional manometry to the assessment of esophageal motor disorders in patients with non-cardiac chest pain (NCCP). The aim of the study was to compare the distribution of esophageal motor disorders in patients with NCCP using HREM as compared with conventional manometry and to determine if HREM improved diagnosis of these disorders. In this study, we included 300 consecutive patients with NCCP who underwent either HREM or conventional manometry over a period of 10 years. A total of 150 patients had conventional manometry and the other 150 patients HREM. The Chicago 3.0 classification and the Castell and Spechler classification were used to determine the esophageal motor disorder of NCCP patients undergoing HREM and conventional manometry, respectively. In both HREM and the conventional manometry groups, normal esophageal motility was the most frequent finding (47% and 36%; respectively, P = .054). Hypotensive lower esophageal sphincter was the most common motility disorder identified by conventional manometry (27.3%), while ineffective esophageal motility was the most common esophageal motor disorder identified by HREM (25.3%). There is a discrepancy in the type of esophageal motor disorders identified by HREM as compared with conventional manometry in NCCP patients. Hypotensive motility disorders are the most commonly diagnosed by both manometric techniques. © 2017 John Wiley & Sons Ltd.

Distribution of Esophageal Motor Disorders in Diabetic Patients With Dysphagia.

PubMed

George, Nina S; Rangan, Vikram; Geng, Zhuo; Khan, Freeha; Kichler, Adam; Gabbard, Scott; Ganocy, Stephen; Fass, Ronnie

Diabetes mellitus can cause various gastrointestinal symptoms. Assessment of esophageal dysmotility in diabetic patients has been scarcely studied. The aim of this study was to determine the esophageal motor characteristics of diabetic versus nondiabetic patients who present with dysphagia. High-resolution esophageal manometries (HREMs) of 83 diabetic patients and 83 age and gender-matched nondiabetic patients with dysphagia from 2 medical centers were included in this study. Demographic information, medical comorbidities, and medication usage were recorded for each patient in a single registry. HREM of each patient was evaluated and the different functional parameters were recorded. Overall, 46% of diabetic patients were found to have an esophageal motor disorder. Diabetic patients with dysphagia were more likely to have failed swallows on HREM (50.6% vs. 33.7%; P=0.03) as compared with nondiabetic patients. Among diabetic patients, those being treated with insulin were more likely to have failed (69.0% vs. 40.7%; P=0.01) and weak (65.5% vs. 33.3%; P=0.005) swallows as compared with diabetic patients not on insulin. Among diabetic patients, those with abnormal manometry were more likely to demonstrate diabetic retinopathy (27.0% vs. 8.7%; P=0.04). There was a trend toward increased incidence of esophagogastric junction outflow obstruction in diabetic patients (10.8% vs. 2.4%; P=0.057) as compared with nondiabetic patients. Nearly half of diabetic patients with dysphagia have some type of an esophageal motility disorder. Diabetic retinopathy and the use of insulin are predictive of esophageal motor abnormalities among diabetic patients.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry.

PubMed

Krishnan, K; Lin, C-Y; Keswani, R; Pandolfino, J E; Kahrilas, P J; Komanduri, S

2014-08-01

Esophageal motor disorders are a heterogeneous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound (EUS) in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra-esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification. EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. © 2014 John Wiley & Sons Ltd.

Endoscopic ultrasound as an adjunctive evaluation in patients with esophageal motor disorders subtyped by high-resolution manometry

PubMed Central

Krishnan, Kumar; Lin, Chen-Yuan; Keswani, Rajesh; Pandolfino, John E; Kahrilas, Peter J; Komanduri, Srinadh

2015-01-01

Background and aims Esophageal motor disorders are a heterogenous group of conditions identified by esophageal manometry that lead to esophageal dysfunction. The aim of this study was to assess the clinical utility of endoscopic ultrasound in the further evaluation of patients with esophageal motor disorders categorized using the updated Chicago Classification. Methods We performed a retrospective, single center study of 62 patients with esophageal motor disorders categorized according to the Chicago Classification. All patients underwent standard radial endosonography to assess for extra esophageal findings or alternative explanations for esophageal outflow obstruction. Secondary outcomes included esophageal wall thickness among the different patient subsets within the Chicago Classification Key Results EUS identified 9/62 (15%) clinically relevant findings that altered patient management and explained the etiology of esophageal outflow obstruction. We further identified substantial variability in esophageal wall thickness in a proportion of patients including some with a significantly thickened non-muscular layer. Conclusions EUS findings are clinically relevant in a significant number of patients with motor disorders and can alter clinical management. Variability in esophageal wall thickness of the muscularis propria and non-muscular layers identified by EUS may also explain the observed variability in response to standard therapies for achalasia. PMID:25041229

Esophageal Reconstruction with the Stomach, a Functional Dilemma?

PubMed

Predescu, Dragoş; Constantinoiu, Silviu

2018-01-01

Background: A few decades ago, esophageal substitution was mainly dedicated particularly in postcaustic esophageal stenosis; currently, the reconstruction has expanded its palette of indications to other areas of benign esophageal pathology (severe motor disorders, esophageal achalasia with multiple relapses, peptic stenosis, etc.) but has also become a quasi-obligatory final time in the esophagectomy for cancer whenever it is possible. The techniques of esophageal reconstruction using the stomach, regardless of the indication and the chosen technical option, remain a valuable and effective method. A number of striking arguments advocate for one or another type of gastric graft: anatomic factors more than convenient (vascularization, sufficient length, a wall structure favorable for suture, etc.) and a sustainable surgical intervention (length, approach, complexity of the surgical steps digestive disorders after surgery, post-therapeutic functionality, etc.). Choosing a technique or another, beyond pathological arguments, should take into account remote functionality, with a clear impact on metabolic status and quality of life. So, according to this criterion, can we functionally justify a type or another of gastric restoration? Finally, the proof of an adequate solution is relatively easy to appreciate: has swallowing been restored and if so, the result has been maintained over time? For oncological cases, the assessment should also take into account the chronological criterion of the postoperative survival rate. Methods: The statistically rated lot ranged from 1981 to 2016 and included 268 patients with surgical interventions for esophageal stenosis, distributed according to etiopathogenesis and indication in 201 reconstructions for post-caustic stenosis, and 67 for post-esophagectomy replacement for neoplasm. The techniques used for remote functional evaluation included: barium swallow, endoscopy + biopsy, and in cases with obvious changes pH measurement/24 h and manometry and, only in exceptional cases, scintigraphy with marked foods. Results: two types of problems have been identified: a particular type of neuro-motor dysfunction of the esophageal substitute in 6 patients (1 patient with Gavriliu reconstruction and 5 with Nakayama reconstruction, using the whole stomach), with difficulty, delayed gastric graft evacuation, with major stasis and abdominal discomfort vomiting, inability to eat, aspiration phenomena) respectively a reflux pathology - 8 patients, being proved by a specific simptomatology, barium lunch, endoscopic examination and pH-metric examination. Reflux was alkaline in 7 patients, all with pyloroplasty, 5 with whole stomach and 2 with Akiyama procedure; in 1 case with Gavriliu procedure the reflux was acid. Conclusions: Stomach is a good option in esophageal substitution. Concerning the remote results, a good functionality is found with a reasonable metabolic status. The two phenomena on which the function of the graft depends - secretory activity and motor activity - seem to be restored in time but these does not occur concurrently, the recovery of the secretory function being much faster. Celsius.

Distension-evoked motility analysis in human esophagus.

PubMed

Liao, D; Villadsen, G E; Gregersen, H

2013-05-01

The major function of the esophagus is to transport food from the mouth to the stomach by peristaltic muscle action. However, only few techniques exist for detailed evaluation of motor activity of the esophagus in vivo. The aim of this study is to use distension combined with manometry and impedance planimetry [pressure-cross-sectional area (P-CSA) recordings] to assess esophageal peristaltic motor function in terms of the mechanical energy output, and to examine the change in the motor activity of the esophagus in response to butylscopolamine, an anticholinergic drug known to impair the smooth muscle contraction in the gastrointestinal tract. The probe with CSA measurements was positioned 7 cm above the lower esophageal sphincter in 16 healthy volunteers before and during butylscopolamine administration. Distension-evoked esophageal peristalsis was analyzed using P-CSA data during distension up to pressures of 5 kPa. The P-CSA, work output (area of the tension-CSA curves), and propulsive tension were analyzed. The wave-like peristalsis resulted in P-CSA loops consisting of relaxation and contraction phases. The work increased with the distension pressure (from 1311 ± 198 to 16 330 ± 1845 μJ before butylscopolamine vs from 2615 ± 756 to 11 404 ± 1335 μJ during butylscopolamine administration), and propulsive tension increased from 18.7 ± 1.9 to 88.5 ± 5.5 N m(-1) before the drug and from 23.1 ± 3.9 to 79.5 ± 3.3 N m(-1) during butylscopolamine administration). Significantly, lower values were found during butylscopolamine administration compared with the distension before using the drug (P < 0.01). Esophageal muscle properties during peristalsis can be assessed in vivo in terms of mechanical energy output parameters. Butylscopolamine impaired muscle contraction which could be detected as altered contraction parameters. The analysis can be further used as an adjunct tool of the combined manometry and impedance planimetry recordings to derive advanced esophageal motor function parameters for studying the physiological and pathophysiological mechanical consequences of esophageal contractions. © 2013 Blackwell Publishing Ltd.

The spectrum of motor function abnormalities in gastroesophageal reflux disease and Barrett's esophagus.

PubMed

Ang, D; Blondeau, K; Sifrim, D; Tack, J

2009-01-01

Barrett's esophagus has traditionally been regarded as the most severe end of the spectrum of gastroesophageal reflux disease and is of great clinical importance in view of the association with esophageal adenocarcinoma. Studies have documented high levels of esophageal acid exposure in Barrett's esophagus. Various pathogenetic mechanisms underlie this phenomenon. These include abnormalities in esophageal peristalsis, defective lower esophageal sphincter pressures, gastric dysmotility and bile reflux. Whilst these factors provide evidence for an acquired cause of Barrett's esophagus, an underlying genetic predisposition cannot be ruled out. Although the past decade has brought about many new discoveries in the pathogenesis of Barrett's esophagus, it has also added further controversy to this complex disorder. A detailed analysis of the gastrointestinal motor abnormalities occurring in Barrett's esophagus follows, with a review of the currently available literature and an update on this condition that continues to be of interest to the gastroenterologist.

Deterioration of muscle function in the human esophagus with age.

PubMed

Gregersen, Hans; Pedersen, Jan; Drewes, Asbjørn Mohr

2008-12-01

Most studies on the effect of aging on esophageal motor function have shown that peristaltic function deteriorates with age. Esophageal motor function is traditionally studied by means of manometry and radiography. Distension of the esophagus with evaluation of active and passive mechanical parameters have become available during recent years. In this study, we did a manometric swallow analysis and used the distension method to study esophageal properties and function during aging. An impedance planimetric probe with a bag for distension was placed in the distal esophagus of 25 healthy volunteers with a median age of 35 (range 23-86) years. Distensions were done at an infusion rate of 25 ml min(-1) with and without relaxation of neuromuscular activity with butylscopolamine. The infusion was reversed when moderate pain was experienced by the subjects. Swallow-induced contraction amplitudes decreased as function of age for persons older than 40 years (P < 0.05). The total and passive tension showed an exponential increase as function of the change in radius, whereas the active tension increased until it reached a local maximum point. The maximum active tension deteriorated as a function of age after the age of 40 years (P < 0.05). Furthermore, esophagus became stiffer with age. In conclusion, age-related changes of increased stiffness and reduced primary and secondary peristalsis were found in the human esophagus with a deterioration of esophageal function after the age of 40 years. Such changes may contribute to the high prevalence of reflux disease in elderly.

Evaluation of esophageal function in patients with esophageal motor abnormalities using multichannel intraluminal impedance esophageal manometry.

PubMed

Cho, Yu Kyung; Choi, Myung-Gyu; Park, Jae Myung; Oh, Jung Hwan; Paik, Chang Nyol; Lee, Joon Wook; Lee, In Seok; Kim, Sang Woo; Chung, In-Sik

2006-10-21

To evaluate the functional aspect of esophageal motility in healthy subjects and in patients who were referred for esophageal function testing using multichannel intraluminal impedance-esophageal manometry (MII-EM), and to assess the clinical utility of MII-EM. From September 2003 to January 2004, we performed the MII-EM on healthy volunteers and all the patients who were referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. We analyzed the results, the impedance and the manometric findings. Some of the subjects had additional ambulatory 24-h pH study performed to diagnose gastroesophageal reflux disease (GERD). Among 89 studied subjects, the MII-EM findings showed normal esophageal motility in 50 (56.17%), ineffective esophageal motility (IEM) in 17 (19.10%), nutcracker esophagus in 7 (7.86%), achalasia in 4 (4.49%), and scleroderma esophagus in 11 (12.35%) cases. The completeness and the speed of bolus transit were in the order of nutcracker esophagus, normal manometry and IEM. Some of the swallows showing normal manometry and IEM had incomplete transit. In the achalasia and scleroderma esophagus, almost all the swallows had incomplete transit. The body amplitudes were higher for the swallows with complete transit than for the swallows with incomplete transit. There was not a significant difference in the manometric and impedance findings between the subjects with and without GERD. MII-EM is a useful tool in assessing the esophageal function in the patients having esophageal motility abnormality. The primary factors influencing the bolus transit are the amplitude of the esophageal body and normal peristalsis.

Prevalence of esophageal disorders in patients with recurrent chest pain.

PubMed

Manterola, C; Barroso, M S; Losada, H; Muñoz, S; Vial, M

2004-01-01

The objective of this study is to determine the prevalence of esophageal disorders (ED) associated with recurrent chest pain (RCP) and the utility of esophageal functional tests (EFT) in the study of these patients. The cross-sectional study was conducted at Hospital Clínico de La Frontera, Chile. One hundred and twenty-three patients with RCP were studied using esophageal manometry, edrophonium stimulation and 24-h pH monitoring. The performance of EFT was considered acceptable when they were capable of finding ED. To state the probability that RCP had an esophageal origin, patients were classified according to whether their pain had a probable, possible or unlikely esophageal origin. The prevalence of ED was determined according to diagnoses obtained after applying EFT and a multivariate analysis was performed to examine the association between the esophageal origin of RCP and ED. Rates of correct diagnosis of 65.9%, 56.9% and 31.7% was verified for 24-h pH monitoring, esophageal manometry and edrophonium stimulation, respectively. In 38.2% of patients with RCP, the pain was probably of esophageal origin, in 42.3% there was a possible esophageal origin and in 19.5% an unlikely esophageal origin. A 44.7% prevalence of GERD, 26.8% of GERD with secondary esophageal motor dysfunction and 8.9% of pure esophageal motor dysfunction were verified. The multivariate analysis allowed us to verify the association between the probability of esophageal origin of RCP, the variables RCP duration, esophagitis and dysphagia coexistence (P= 0.037, P= 0.030 and P= 0.024, respectively), and a statistically significant association between ED and dysphagia coexistence (P= 0.028). A high prevalence of ED was identified in patients with RCP.

Digestive and respiratory tract motor responses associated with eructation

PubMed Central

Medda, Bidyut K.; Shaker, Reza

2013-01-01

We studied the digestive and respiratory tract motor responses in 10 chronically instrumented dogs during eructation activated after feeding. Muscles were recorded from the cervical area, thorax, and abdomen. The striated muscles were recorded using EMG and the smooth muscles using strain gauges. We found eructation in three distinct functional phases that were composed of different sets of motor responses: gas escape, barrier elimination, and gas transport. The gas escape phase, activated by gastric distension, consists of relaxation of the lower esophageal sphincter and diaphragmatic hiatus and contraction of the longitudinal muscle of the thoracic esophagus and rectus abdominis. All these motor events promote gas escape from the stomach. The barrier elimination phase, probably activated by rapid gas distension of the thoracic esophagus, consists of relaxation of the pharyngeal constrictors and excitation of dorsal and ventral upper esophageal sphincter distracting muscles, as well as rapid contraction of the diaphragmatic dome fibers. These motor events allow esophagopharyngeal air movement by promoting retrograde airflow and opening of the upper esophageal sphincter. The transport phase, possibly activated secondary to diaphragmatic contraction, consists of a retrograde contraction of the striated muscle esophagus that transports the air from the thoracic esophagus to the pharynx. We hypothesize that the esophageal reverse peristalsis is mediated by elementary reflexes, rather than a coordinated peristaltic response like secondary peristalsis. The phases of eructation can be activated independently of one another or in a different manner to participate in physiological events other than eructation that cause gastroesophageal or esophagogastric reflux. PMID:23578784

Esophageal motor disorders: how to bridge the gap between advanced diagnostic tools and paucity of therapeutic modalities?

PubMed

Clarke, John O; Pandolfino, John E

2012-07-01

High-resolution manometry has added significantly to our current understanding of esophageal motor function by providing improved detail and a data analysis paradigm that is more akin to an imaging format. Esophageal pressure topography provides a seamless dynamic representation of the pressure profile through the entire esophagus and thus, is able to eliminate movement artifact and also assess intrabolus pressure patterns as a surrogate for bolus transit mechanics. This has led to improved identification of anatomic landmarks and measurement of important physiological parameters (esophagogastric junction relaxation, distal latency, and contractile integrity). This research has bridged the gap into clinical practice by defining physiologically relevant phenotypes that may have prognostic significance and improve treatment decisions in achalasia, spasm, and hypercontractile disorders. However, more work is needed in determining the etiology of symptom generation in the context of normal or trivial motor dysfunction. This research will require new techniques to assess visceral hypersensitivity and alterations in central modulation of pain and discomfort.

Age and gender affect likely manometric diagnosis: Audit of a tertiary referral hospital clinical esophageal manometry service.

PubMed

Andrews, Jane M; Heddle, Richard; Hebbard, Geoffrey S; Checklin, Helen; Besanko, Laura; Fraser, Robert J

2009-01-01

Awareness of patient demographics, common diagnoses and associations between these may improve the use and interpretation of manometric investigations. The aim of the present study therefore was to determine whether age and/or gender affect manometric diagnosis in a clinical motility service. An audit of all 452 clinical manometry reports issued from December 2003 to July 2005 with respect to age, gender and diagnosis was carried out. Patients were divided by age (17-24 years n = 14, 25-44 years n = 87, 45-64 years n = 216 and >or=65 years n = 135), and gender and data compared using contingency tables. Women were more commonly referred overall (59%) and in each age bracket except <25 years (64% male). Men were more likely to have 'hypotensive' motor problems P = 0.01. With aging, normal motor function became less common (P = 0.013), with non-specific motor disorder, ineffective/hypotensive peristalsis and 'achalasia-like' conditions each more common (individual P = NS). Increasing age showed a trend for increased spastic motor disorders (P = 0.06). Gender did not, however, influence whether motility was abnormal (P = 0.5), spastic (P = 0.7) or whether a non-specific motor disorder was present (P = 0.1). In the total cohort, the principal manometric diagnoses were: non-specific motor disorder 33%, normal motility 29%, low basal lower esophageal sphincter pressure 18%, hypotensive/ineffective peristalsis 10%, achalasia/achalasia-like 6%, diffuse esophageal spasm 3% and other 1%. Aging leads to increasing esophageal motor abnormalities. Men and women have similar rates of dysfunction, although 'low-pressure problems' were more common in men.

Modulation of activity in swallowing motor cortex following esophageal acidification: a functional magnetic resonance imaging study.

PubMed

Paine, Peter A; Hamdy, Shaheen; Chitnis, Xavier; Gregory, Lloyd J; Giampietro, Vincent; Brammer, Mick; Williams, Steve; Aziz, Qasim

2008-06-01

Esophageal acid exposure induces sensory and motility changes in the upper gastrointestinal tract; however, the mechanisms involved and the effects on activity in the brain regions that control swallowing are unknown. The aim of this study was to examine functional changes in the cortical swallowing network as a result of esophageal acidification using functional magnetic resonance imaging (fMRI). Seven healthy volunteers (3 female, age range=20-30 years) were randomized to receive either a 0.1 M hydrochloric acid or (control) saline infusion for 30 min into the distal esophagus. Postinfusion, subjects underwent four 8 min blocks of fMRI over 1 h. These alternated between 1 min swallowing water boluses and 1 min rest. Three-dimensional cluster analysis for group brain activation during swallowing was performed together with repeated-measures ANOVA for differences between acid and saline. After acid infusion, swallowing-induced activation was seen predominantly in postcentral gyrus (p<0.004). ANOVA comparison of acid with saline showed a significant relative reduction in activation during swallowing of the precentral gyrus (M1) BA 4 (p<0.008) in response to acid infusion. No areas of increased cortical activation were identified with acid vs. saline during swallowing. Esophageal acidification inhibits motor and association cortical areas during a swallowing task, probably via changes in vagal afferent or nociceptive input from the esophagus. This mechanism may play a protective role, facilitating acid clearance by reduced descending central motor inhibition of enteric/spinal reflexes, or by preventing further ingestion of injurious agents.

Motor and sensory function of the esophagus: revelations through ultrasound imaging.

PubMed

Mittal, Ravinder K

2005-04-01

Catheter based high frequency intraluminal ultrasound (HFIUS) imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It has provided a number of important insights into the longitudinal muscle function of the esophagus. Based on the ultrasound images and intraluminal pressure recordings, it is clear that there is synchrony in the timing as well as the amplitude of contraction between the circular and the longitudinal muscle layers of the esophagus in normal subjects. On the other hand, in patients with spastic disorders of the esophagus, there is an asynchrony of contraction related to the timing and amplitude of contraction of the two muscle layers during peristalsis. Achalasia, diffuse esophageal spasm, and nutcracker esophagus (spastic motor disorders of the esophagus) are associated with hypertrophy of the circular as well as longitudinal muscle layers. A sustained contraction of the longitudinal muscle of the esophagus is temporally related to chest pain and heartburn and may very well be the cause of symptoms. Longitudinal muscle function of the esophagus can be studied in vivo in humans using dynamic ultrasound imaging. Longitudinal muscle dysfunction appears to be important in the motor and sensory disorders of the esophagus.

Evaluation of Esophageal Functions by Manometry in Iron Deficiency Anemia Patients.

PubMed

Kubilay, Pinar; Doganay, Beyza; Bektas, Mehmet

2017-06-01

The aim of this study was to investigate whether any esophageal motor dysfunction exists in patients with iron deficiency anemia (IDA). The study included 39 patients (34 women, mean age: 44.17 ± 14.21 years) who met WHO diagnostic criteria for IDA. An additional 30 functional dyspepsia patients were also included as a control group. Esophageal motility testing was performed; esophagus contraction amplitude, peak velocity, contraction time, lower esophageal sphincter (LES) resting pressure, LES relaxation, and LES relaxation duration were assessed. A majority (76.4%) of patients had at least one IDA symptom, such as reflux, chest pain, or dysphagia. Manometric findings in IDA patients vs. controls were as follows: mean LES resting pressure (mm Hg): 25.41 ± 11.67 vs. 19.96 ± 6.58 (P = 0.025); mean esophageal contraction amplitude (mm Hg): 61.61 ± 24.21 vs. 63.23 ± 18.86 (P = 0.764); mean LES relaxation duration (s, x ± SD): 5.33 ± 1.61 vs. 8.75 ± 1.86 (P = 0.000); mean LES relaxation (%): 93.30 ± 9.88 vs. 95.53 ± 5.81 (P = 0.278); mean peak velocity (cm/s): 12.67 ± 37.95 vs. 3.50 ± 1.63 (P = 0.191). Esophageal dysmotility was found in 11 (28.2%) IDA patients. Non-specific esophageal motor disorder was found in three patients, hypomotility of the esophagus was found in three patients, achalasia was found in two patients, hypertensive LES was found in two patients, and hypotensive LES was found in one patient. LES resting pressure was higher and LES relaxation duration was shorter in patients with IDA. Esophageal dysmotility was present in 28.2% of the patients with IDA A little more than half of patients had dysphagia symptoms. IDA may contribute to esophageal motility dysfunction and esophageal symptoms.

Innervation of the mammalian esophagus.

PubMed

Neuhuber, Winfried L; Raab, Marion; Berthoud, Hans-Rudolf; Wörl, Jürgen

2006-01-01

Understanding the innervation of the esophagus is a prerequisite for successful treatment of a variety of disorders, e.g., dysphagia, achalasia, gastroesophageal reflux disease (GERD) and non-cardiac chest pain. Although, at first glance, functions of the esophagus are relatively simple, their neuronal control is considerably complex. Vagal motor neurons of the nucleus ambiguus and preganglionic neurons of the dorsal motor nucleus innervate striated and smooth muscle, respectively. Myenteric neurons represent the interface between the dorsal motor nucleus and smooth muscle but they are also involved in striated muscle innervation. Intraganglionic laminar endings (IGLEs) represent mechanosensory vagal afferent terminals. They also establish intricate connections with enteric neurons. Afferent information is implemented by the swallowing central pattern generator in the brainstem, which generates and coordinates deglutitive activity in both striated and smooth esophageal muscle and orchestrates esophageal sphincters as well as gastric adaptive relaxation. Disturbed excitation/inhibition balance in the lower esophageal sphincter results in motility disorders, e.g., achalasia and GERD. Loss of mechanosensory afferents disrupts adaptation of deglutitive motor programs to bolus variables, eventually leading to megaesophagus. Both spinal and vagal afferents appear to contribute to painful sensations, e.g., non-cardiac chest pain. Extrinsic and intrinsic neurons may be involved in intramural reflexes using acetylcholine, nitric oxide, substance P, CGRP and glutamate as main transmitters. In addition, other molecules, e.g., ATP, GABA and probably also inflammatory cytokines, may modulate these neuronal functions.

[Motility disorders of the esophagus].

PubMed

Bruder, E; Rougemont, A-L; Furlano, R I; Schneider, J F; Mayr, J; Haecker, F-M; Beier, K; Schneider, J; Weber, P; Berberich, T; Cathomas, G; Meier-Ruge, W A

2013-03-01

Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities.

PubMed

Rieder, Florian; Cheng, Ling; Harnett, Karen M; Chak, Amitabh; Cooper, Gregory S; Isenberg, Gerard; Ray, Monica; Katz, Jeffry A; Catanzaro, Andrew; O'Shea, Robert; Post, Anthony B; Wong, Richard; Sivak, Michael V; McCormick, Thomas; Phillips, Manijeh; West, Gail A; Willis, Joseph E; Biancani, Piero; Fiocchi, Claudio

2007-01-01

Gastroesophageal reflux disease is a condition frequently associated with esophagitis and motor abnormalities. Recent evidence suggests that proinflammatory cytokines, such as interleukin (IL)-1beta and IL-6, may be implicated because they reduce esophageal muscle contractility, but these results derive from in vitro or animal models of esophagitis. This study used human esophageal cells and tissues to identify the cellular source of cytokines in human esophagitis investigate whether cytokines can be induced by gastric refluxate, and examine whether esophageal tissue- or cell-derived mediators affect muscle contractility. Endoscopic mucosal biopsy specimens were obtained from patients with and without esophagitis, organ-cultured, and undernatants were assessed for cytokine content. The cytokine profile of esophageal epithelial, fibroblast, and muscle cells was analyzed, and esophageal mucosa and cell products were tested in an esophageal circular muscle contraction assay. The mucosa of esophagitis patients produced significantly greater amounts of IL-1beta and IL-6 compared with those of control patients. Cultured esophageal epithelial cells produced IL-6, as did fibroblasts and muscle cells. Epithelial cells exposed to buffered, but not denatured, gastric juice produced IL-6. Undernatants of mucosal biopsy cultures from esophagitis patients reduced esophageal muscle contraction, as did supernatants from esophageal epithelial cell cultures. The human esophagus produces cytokines capable of reducing contractility of esophageal muscle cells. Exposure to gastric juice is sufficient to stimulate esophageal epithelial cells to produce IL-6, a cytokine able to alter esophageal contractility. These results indicate that classic cytokines are important mediators of the motor disturbances associated with human esophageal inflammation.

Esophagogastric junction and esophageal body contraction metrics on high-resolution manometry predict esophageal acid burden.

PubMed

Rengarajan, A; Bolkhir, A; Gor, P; Wang, D; Munigala, S; Gyawali, C P

2018-05-01

Distal contractile integral (DCI) and esophagogastric junction contractile integral (EGJ-CI) are high-resolution manometry (HRM) software metrics assessing esophageal motor function in gastroesophageal reflux disease (GERD). Patients undergoing HRM and ambulatory pH monitoring off antisecretory therapy prospectively completed symptom questionnaires assessing symptom burden and a global symptom score (GSS) at baseline and after GERD therapy. DCI<450 mm Hg/cm/s in ≥5 swallows diagnosed ineffective esophageal motility (IEM); proportions of failed (DCI<100 mm Hg/cm/s) and weak (DCI 100-450 mm Hg/cm/s) sequences were separately assessed. EGJ-CI assessed vigor of the EGJ barrier. Univariate and multivariate analyses addressed performance of esophageal body and EGJ metrics in predicting abnormal esophageal reflux burden, and symptom outcome from antireflux therapy. Of 188 patients (55.2 ± 0.9 year, 64% F), 42.6% had low EGJ-CI, and 25.0% had IEM. While low EGJ-CI was associated with abnormal reflux burden (P = 0.003), IEM alone was not (P = 0.2). Increasing proportions of failed swallows predicted abnormal AET better than the current IEM definition. Combined low EGJ-CI and IEM segregated abnormal total and supine acid burden compared to patients with normal EGJ-CI and no IEM (P ≤ 0.007 for each comparison). Medical therapy and surgical antireflux therapy were similarly effective in improving symptom burden; surgery resulted in better outcomes with low EGJ-CI (P ≤ 0.04), especially with intact esophageal body motor function (P = 0.02). While abnormal EGJ and esophageal body metrics are collectively associated with elevated esophageal reflux burden, increasing proportions of failed swallows are better predictors of reflux burden and outcome compared to the current IEM definition. © 2017 John Wiley & Sons Ltd.

[Esophageal motor disorders in cirrhotic patients with esophageal varices non-submitted to endoscopic treatment].

PubMed

Flores, Priscila Pollo; Lemme, Eponina Maria de Oliveira; Coelho, Henrique Sérgio Moraes

2005-01-01

The hepatic cirrhosis has as one of the main morbid-mortality causes, the portal hypertension with the development of esophageal varices, the possibility of a digestive hemorrhage and worsening of hepatic insufficiency. It is important to identify causal predictive or aggravating factors and if possible to prevent them. In the last years, it has been observed the association of esophageal motor disorders and gastro-esophageal reflux in cirrhotic patients with esophageal varices. To study the prevalence of the esophageal motility disorders and among them, the ineffective esophageal motility, in patients with hepatic cirrhosis and esophageal varices, without previous endoscopic therapeutic and the predictive factors. Prospectively, it has been evaluate 74 patients suffering from liver cirrhosis and esophagic varices, without previous endoscopic treatment. All of them were submitted to a clinical protocol, esophageal manometry and 55 patients also held the ambulatory esophageal pHmetry. Esophageal motility disorders have been found in 44 patients (60%). The most prevalent was the ineffective esophageal motility, observed in 28%. The abnormal reflux disease was diagnosed through the pHmetry in 35% of the patients. There were no correlation between the manometrical abnormality in general and the ineffective esophageal motility in particular and the esophageal or gastroesophageal reflux disease symptoms, the abnormal reflux, the disease seriousness, the ascites presence and the gauge of the varices. The majority of cirrhotic patients with non-treated esophageal varices present esophageal motor disorders. No predictive factor was found. The clinical relevance of these findings need more researches in the scope to define the real meaning of theses abnormalities.

[Esophageal motor disorders in asymptomatic subjects with Trypanosoma cruzi infection].

PubMed

Torres-Aguilera, M; Remes-Troche, J M; Roesch-Dietlen, F; Vázquez-Jiménez, J G; De la Cruz-Patiño, E; Grube-Pagola, P; Ruiz-Juárez, I

2011-01-01

The indeterminate chronic or "asymptomatic" phase of Trypanosoma cruzi (Chagas' disease) infection is characterized by the absence of gastrointestinal symptoms, and has an estimated duration of 20 to 30 years. However, the intramural denervation that induces dysfunction of the gastrointestinal tract is progressive. Recently, epidemiological studies have shown that the seroprevalence for this infection in our area ranges between 2% and 3% of the population. To detect the presence of esophageal motor disorders in asymptomatic individuals chronically infected with Trypanosoma cruzi using standard esophageal manometry. A cross sectional study in 28 asymptomatic subjects (27 men, age 40.39 ± 10.79) with serological evidence of infection with Trypanosoma cruzi was performed. In all cases demographic characteristics, gastrointestinal symptoms and esophageal motility disorders using conventional manometry were analyzed. In this study 54% (n = 15) of asymptomatic subjects had an esophageal motor disorder: 5 (18%) had nutcracker esophagus, 5 (18%) nonspecific esophageal motor disorders, 3 (11%) hypertensive lower esophageal sphincter (LES), 1 (4%) an incomplete relaxation of the LES and 1 (4%) had chagasic achalasia. More than half of patients that course with Chagas' disease in the indeterminate phase and that are apparently asymptomatic have impaired esophageal motility. Presence of hypertensive LES raises the possibility that this alteration represents an early stage in the development of chagasic achalasia.

How to Diagnose and Treat Functional Chest Pain.

PubMed

Remes-Troche, Jose M

2016-12-01

Chest pain that is not explained by reflux disease or cardiac, musculoskeletal, mucosal, or motor esophageal abnormalities is classified as functional chest pain (FCP). Although several mechanisms are involved, esophageal hypersensitivity plays a major role and it could be considered a biomarker for FCP. Psychologic comorbidity such as anxiety, neuroticism, depression, and somatization is common. When the diagnosis of FCP is suspected, patients should undergo evaluation with esophageal motility testing, endoscopy, 24-h esophageal pH monitoring, and in some cases, sensory tests. Once the diagnosis of FCP has been established, treatment options rely on controlling patients' symptoms. Medical treatment has focused predominantly on medications that target pain, such as antidepressants and other pain neuromodulators. Non-pharmacologic interventions with complementary behavioral treatments, such as cognitive behavioral therapy, biofeedback, and hypnosis, have recently been recognized as useful in FCP patients. The latest findings on the evaluation and treatment of FCP are outlined herein.

Esophageal manometric characteristics and outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication for epiphrenic diverticula.

PubMed

Melman, Lora; Quinlan, Jessica; Robertson, Brian; Brunt, L M; Halpin, Valerie J; Eagon, J C; Frisella, Margaret M; Matthews, Brent D

2009-06-01

The purpose of this study is to characterize the esophageal motor and lower esophageal sphincter (LES) abnormalities associated with epiphrenic esophageal diverticula and analyze outcomes for laparoscopic esophageal diverticulectomy, myotomy, and partial fundoplication. The endoscopic, radiographic, manometric, and perioperative records for patients undergoing laparoscopic esophageal diverticulectomy, anterior esophageal myotomy, and partial fundoplication from 8/99 until 9/06 were reviewed from an Institutional Review Board (IRB)-approved outcomes database. Data are given as mean +/- standard deviation (SD). An esophageal body motor disorder and/or LES abnormalities were present in 11 patients with epiphrenic diverticula; three patients were characterized as achalasia, one had vigorous achalasia, two had diffuse esophageal spasm, and five had a nonspecific motor disorder. Presenting symptoms included dysphagia (13/13), regurgitation (7/13), and chest pain (4/13). Three patients had previous Botox injections and three patients had esophageal dilatations. Laparoscopic epiphrenic diverticulectomy with an anterior esophageal myotomy was completed in 13 patients (M:F; 3:10) with a mean age of 67.6 +/- 4.2 years, body mass index (BMI) of 28.1 +/- 1.9 kg/m2 and American Society of Anesthesiologists (ASA) 2.2 +/- 0.1. Partial fundoplication was performed in 12/13 patients (Dor, n = 2; Toupet, n = 10). Four patients had a type I and one patient had a type III hiatal hernia requiring repair. Mean operative time was 210 +/- 15.1 min and mean length of stay (LOS) was 2.8 +/- 0.4 days. Two grade II or higher complications occurred, including one patient who was readmitted on postoperative day 4 with a leak requiring a thoracotomy. After a mean follow-up of 13.6 +/- 3.0 months (range 3-36 months), two patients complained of mild solid food dysphagia and one patient required proton pump inhibitor (PPI) for gastroesophageal reflux disease (GERD) symptoms. The majority of patients with epiphrenic esophageal diverticula have esophageal body motor disorders and/or LES abnormalities. Laparoscopic esophageal diverticulectomy and anterior esophageal myotomy with partial fundoplication is an appropriate alternative with acceptable short-term outcomes in symptomatic patients.

Clinical, endoscopic and manometric features of the primary motor disorders of the esophagus.

PubMed

Martinez, Júlio César; Lima, Gustavo Rosa de Almeida; Silva, Diego Henrique; Duarte, Alexandre Ferreira; Novo, Neil Ferreira; da Silva, Ernesto Carlos; Pinto, Pérsio Campos Correia; Maia, Alexandre Moreira

2015-01-01

Significant incidence, diagnostic difficulties, clinical relevance and therapeutic efficacy associated with the small number of publications on the primary esophageal motor disorders, motivated the present study. To determine the manometric prevalence of these disorders and correlate them to the endoscopic and clinical findings. A retrospective study of 2614 patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric examinations diagnosed with primary esophageal motor disorder, were sought-clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic (hiatal hernia, erosive esophagitis, food waste) that motivated the performance of manometry. Were found 49 cases of achalasia, 73 diffuse spasm, 89 nutcracker esophagus, 82 ineffective esophageal motility, and six lower esophageal sphincter hypertension. In relation to the correlations, it was observed that in 119 patients clinical conditions were associated with dysphagia, found in achalasia more than in other conditions; in relationship between endoscopic findings and clinical conditions there was no statistical significance between data. The clinical and endoscopic findings have little value in the characterization of the primary motor disorders of the esophagus, showing even more the need for manometry, particularly in the preoperative period of gastroesophageal reflux disease.

What is the real impairment on esophageal motility in patients with gastroesophageal reflux disease?

PubMed

Falcão, Angela; Nasi, Ary; Brandão, Jeovana; Sallum, Rubens; Cecconello, Ivan

2013-04-01

Impairment of esophageal motility is a common finding in patients with gastroesophageal reflux disease (GERD) as reduced lower esophageal sphincter (LES) basal pressure. A very low LES pressure might facilitate the occurrence of more gastroesophageal reflux whereas abnormal esophageal peristalsis may contribute to impaired esophageal clearance after reflux. Evaluate the esophageal motor function of the lower esophageal sphincter and esophageal body in the various forms of gastroesophageal reflux disease. The manometrics records of 268 patients, who had evaluation of the esophageal motility as part of the diagnostic gastroesophageal reflux disease were split into four groups, as follows: 33 patients who had no esophagitis; 92 patients who had erosive esophagitis; 101 patients who had short Barrett's esophagus and 42 patients who had long Barrett's esophagus. The group who had long Barrett's esophagus showed smaller mean LES pressure and higher percentage of marked LES hypotonia; in the distal segment of the esophageal body the this group showed higher percentage of marked hypocontractility of the distal segment (<30 mm Hg); this same group showed higher percentage of esophageal motility disorders. The most intense esophageal motility disorders and lower pressure of lower esophageal sphincter were noted in the group with long Barrett's esophagus. Those with reflux esophagitis and short Barrett's esophagus had esophageal motility impairment, intermediate among patients with esophagitis and long Barrett's esophagus. Patients with typical symptoms of gastroesophageal reflux but without esophagitis by endoscopy study showed no impairment of esophageal motility.

Lack of correlation between HRM metrics and symptoms during the manometric protocol.

PubMed

Xiao, Yinglian; Kahrilas, Peter J; Nicodème, Frédéric; Lin, Zhiyue; Roman, Sabine; Pandolfino, John E

2014-04-01

Although esophageal motor disorders are associated with chest pain and dysphagia, minimal data support a direct relationship between abnormal motor function and symptoms. This study investigated whether high-resolution manometry (HRM) metrics correlate with symptoms. Consecutive HRM patients without previous surgery were enrolled. HRM studies included 10 supine liquid, 5 upright liquid, 2 upright viscous, and 2 upright solid swallows. All patients evaluated their esophageal symptom for each upright swallow. Symptoms were graded on a 4-point likert score (0, none; 1, mild; 2, moderate; 3, severe). The individual liquid, viscous or solid upright swallow with the maximal symptom score was selected for analysis in each patient. HRM metrics were compared between groups with and without symptoms during the upright liquid protocol and the provocative protocols separately. A total of 269 patients recorded symptoms during the upright liquid swallows and 72 patients had a swallow symptom score of 1 or greater. Of the 269 patients, 116 recorded symptoms during viscous or solid swallows. HRM metrics were similar between swallows with and without associated symptoms in the upright, viscous, and solid swallows. No correlation was noted between HRM metrics and symptom scores among swallow types. Esophageal symptoms are not related to abnormal motor function defined by HRM during liquid, viscous or solid bolus swallows in the upright position. Other factors beyond circular muscle contraction patterns should be explored as possible causes of symptom generation.

Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

PubMed Central

Hirano, Ikuo; Aceves, Seema S.

2014-01-01

In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGFβ1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity. PMID:24813517

High resolution manometry findings in patients with esophageal epiphrenic diverticula.

PubMed

Vicentine, Fernando P P; Herbella, Fernando A M; Silva, Luciana C; Patti, Marco G

2011-12-01

The pathophysiology of esophageal epiphrenic diverticula is still uncertain even though a concomitant motility disorder is found in the majority of patients in different series. High resolution manometry may allow detection of motor abnormalities in a higher number of patients with esophageal epiphrenic diverticula compared with conventional manometry. This study aims to evaluate the high resolution manometry findings in patients with esophageal epiphrenic diverticula. Nine individuals (mean age 63 ± 10 years, 4 females) with esophageal epiphrenic diverticula underwent high resolution manometry. A single diverticulum was observed in eight patients and multiple diverticula in one. Visual analysis of conventional tracings and color pressure plots for identification of segmental abnormalities was performed by two researchers experienced in high resolution manometry. Upper esophageal sphincter was normal in all patients. Esophageal body was abnormal in eight patients; lower esophageal sphincter was abnormal in seven patients. Named esophageal motility disorders were found in seven patients: achalasia in six, diffuse esophageal spasm in one. In one patient, a segmental hypercontractile zone was noticed with pressure of 196 mm Hg. High resolution manometry demonstrated motor abnormalities in all patients with esophageal epiphrenic diverticula.

Tissue resistance in the normal and diseased esophagus.

PubMed

Bellizzi, Andrew M; Nardone, Gerardo; Compare, Debora; Bor, Serhat; Capanoglu, Doga; Farré, Ricard; Neumann, Helmut; Neurath, Markus F; Vieth, Michael; Chen, Hao; Chen, Xiaoxin

2013-10-01

This paper presents commentaries on reflux-induced injury of human esophageal epithelium; inflammation in human reflux esophagitis; motor consequences of reflux-induced inflammation in esophageal epithelium; the microscopic morphology of esophageal squamous epithelium; intraluminal impedance in the evaluation of the esophageal mucosa; endoscopic tissue morphology of esophageal squamous epithelium; and the developmental biology of esophageal squamous epithelium. © 2013 New York Academy of Sciences.

Use of radioisotopic esophageal transit in the assessment of patients with symptoms of reflux and non-specific esophageal motor disorders.

PubMed

Iascone, C; Di Giulio, E; Maffi, C; Ruperto, M

2004-01-01

The purposes of this study were to assess the esophageal clearance of a radioisotopic bolus in patients with symptoms of reflux and evaluate the impact of manometric abnormalities on scintigraphic esophageal transit. Esophageal clearance was assessed in a supine position and indicated by the retained radioactivity in the esophagus at 10, 20, 30 and 40 s after the ingestion of a liquid bolus labeled with 2 mCi 99 mTc-SC. The study included 214 consecutive patients with symptoms of reflux and 11 normal controls. The results were compared to the motility findings detected on manometry performed on a separate occasion. Esophageal manometry was normal in 93 patients. Nonspecific esophageal motor disorders were identified in 121 patients and were classified into: 'predominantly nonpropagated activity', 'predominantly low-amplitude peristaltic contractions' and 'miscellaneous disorders' diagnosed in 27, 47 and 47 patients, respectively. The radionuclide clearance was significantly delayed in the overall group of patients compared with that of normal controls (P < 0.001); in patients with reflux symptoms and nonspecific esophageal motor disorders compared with patients with reflux symptoms and 'normal manometry' (P < 0.01 at 20 s); and in patients with reflux symptoms and 'normal manometry' compared with the control group (P < 0.01 at 20 s). Abnormal radioisotope clearances were detected in 88% of patients with 'predominantly nonpropagated activity', in 70% of patients with 'predominantly low-amplitude peristaltic contractions' and in 57% of patients with 'miscellaneous disorders'. Radioisotopic esophageal clearance abnormalities are frequently observed in patients with reflux symptoms and are more likely to be associated to hypomotility disorders, i.e. nonpropagated motor activity or low-amplitude contractions.

Architecture of Vagal Motor Units Controlling Striated Muscle of Esophagus: Peripheral Elements Patterning Peristalsis?

PubMed Central

Powley, Terry L.; Mittal, Ravinder K.; Baronowsky, Elizabeth A.; Hudson, Cherie N.; Martin, Felecia N.; McAdams, Jennifer L.; Mason, Jacqueline K.; Phillips, Robert J.

2013-01-01

Little is known about the architecture of the vagal motor units that control esophageal striated muscle, in spite of the fact that these units are necessary, and responsible, for peristalsis. The present experiment was designed to characterize the motor neuron projection fields and terminal arbors forming esophageal motor units. Nucleus ambiguus compact formation neurons of the rat were labeled by bilateral intracranial injections of the anterograde tracer dextran biotin. After tracer transport, thoracic and abdominal esophagi were removed and prepared as whole mounts of muscle wall without mucosa or submucosa. Labeled terminal arbors of individual vagal motor neurons (n = 78) in the esophageal wall were inventoried, digitized and analyzed morphometrically. The size of individual vagal motor units innervating striated muscle, throughout thoracic and abdominal esophagus, averaged 52 endplates per motor neuron, a value indicative of fine motor control. A majority (77%) of the motor terminal arbors also issued one or more collateral branches that contacted neurons, including nitric oxide synthase-positive neurons, of local myenteric ganglia. Individual motor neuron terminal arbors co-innervated, or supplied endplates in tandem to, both longitudinal and circular muscle fibers in roughly similar proportions (i.e., two endplates to longitudinal for every three endplates to circular fibers). Both the observation that vagal motor unit collaterals project to myenteric ganglia and the fact that individual motor units co-innervate longitudinal and circular muscle layers are consistent with the hypothesis that elements contributing to peristaltic programming inhere, or are “hardwired,” in the peripheral architecture of esophageal motor units. PMID:24044976

Architecture of vagal motor units controlling striated muscle of esophagus: peripheral elements patterning peristalsis?

PubMed

Powley, Terry L; Mittal, Ravinder K; Baronowsky, Elizabeth A; Hudson, Cherie N; Martin, Felecia N; McAdams, Jennifer L; Mason, Jacqueline K; Phillips, Robert J

2013-12-01

Little is known about the architecture of the vagal motor units that control esophageal striated muscle, in spite of the fact that these units are necessary, and responsible, for peristalsis. The present experiment was designed to characterize the motor neuron projection fields and terminal arbors forming esophageal motor units. Nucleus ambiguus compact formation neurons of the rat were labeled by bilateral intracranial injections of the anterograde tracer dextran biotin. After tracer transport, thoracic and abdominal esophagi were removed and prepared as whole mounts of muscle wall without mucosa or submucosa. Labeled terminal arbors of individual vagal motor neurons (n=78) in the esophageal wall were inventoried, digitized and analyzed morphometrically. The size of individual vagal motor units innervating striated muscle, throughout thoracic and abdominal esophagus, averaged 52 endplates per motor neuron, a value indicative of fine motor control. A majority (77%) of the motor terminal arbors also issued one or more collateral branches that contacted neurons, including nitric oxide synthase-positive neurons, of local myenteric ganglia. Individual motor neuron terminal arbors co-innervated, or supplied endplates in tandem to, both longitudinal and circular muscle fibers in roughly similar proportions (i.e., two endplates to longitudinal for every three endplates to circular fibers). Both the observation that vagal motor unit collaterals project to myenteric ganglia and the fact that individual motor units co-innervate longitudinal and circular muscle layers are consistent with the hypothesis that elements contributing to peristaltic programming inhere, or are "hardwired," in the peripheral architecture of esophageal motor units. © 2013.

Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry.

PubMed

Patel, A; Cassell, B; Sainani, N; Wang, D; Shahid, B; Bennett, M; Mirza, F A; Munigala, S; Gyawali, C P

2017-07-01

The Chicago Classification (CC) uses high-resolution manometry (HRM) software tools to designate esophageal motor diagnoses. We evaluated changes in diagnostic designations between two CC versions, and determined motor patterns not identified by either version. In this observational cohort study of consecutive patients undergoing esophageal HRM over a 6-year period, proportions meeting CC 2.0 and 3.0 criteria were segregated into esophageal outflow obstruction, hypermotility, and hypomotility disorders. Contraction wave abnormalities (CWA), and 'normal' cohorts were recorded. Symptom burden was characterized using dominant symptom intensity and global symptom severity. Motor diagnoses, presenting symptoms, and symptom burden were compared between CC 2.0 and 3.0, and in cohorts not meeting CC diagnoses. Of 2569 eligible studies, 49.9% met CC 2.0 criteria, but only 40.3% met CC 3.0 criteria (P<.0001). Between CC 2.0 and 3.0, 82.8% of diagnoses were concordant. Discordance resulted from decreasing proportions of hypermotility (4.4%) and hypomotility (9.0%) disorders, and increase in 'normal' designations (13.0%); esophageal outflow obstruction showed the least variation between CC versions. Symptom burden was higher with CC 3.0 diagnoses (P≤.005) but not with CC 2.0 diagnoses (P≥.1). Within 'normal' cohorts for both CC versions, CWA were associated with higher likelihood of esophageal symptoms, especially dysphagia, regurgitation, and heartburn, compared to truly normal studies (P≤.02 for each comparison). Despite lower sensitivity, CC 3.0 identifies esophageal motor disorders with higher symptom burden compared to CC 2.0. CWA, which are associated with both transit and perceptive symptoms, are not well identified by either version. © 2017 John Wiley & Sons Ltd.

[Transient lower esophageal sphincter relaxation and the related esophageal motor activities].

PubMed

Han, Seung Hyo; Hong, Su Jin

2012-03-01

Transient lower esophageal sphincter (LES) relaxation (TLESR) is defined as LES relaxation without a swallow. TLESRs are observed in both of the normal individuals and the patients with gastroesophageal reflux disorder (GERD). However, TLESR is widely considered as the major mechanism of the GERD. The new equipments such as high resolution manometry and impedance pH study is helped to understand of TLESR and the related esophageal motor activities. The strong longitudinal muscle contraction was observed during development of TLESR. Most of TLESRs are terminated by TLESR related motor events such as primary peristalsis and secondary contractions. The majority of TLESRs are associated with gastroesophageal reflux. Upper esophageal sphincter (UES) contraction is mainly associated with liquid reflux during recumbent position and UES relaxation predominantly related with air reflux during upright position. The frequency of TLESR in GERD patients seems to be not different compared to normal individuals, but the refluxate of GERD patients tend to be more acidic during TLESR.

Transient lower esophageal sphincter relaxation and esophageal motor response.

PubMed

Schneider, Joachim H; Küper, Markus A; Königsrainer, Alfred; Brücher, Björn L D M

2010-04-01

Gastroesophageal reflux is caused by transient lower esophageal sphincter relaxations (TLESRs) in healthy individuals and in most patients with gastroesophageal reflux disease (GERD). Refluxate is normally propelled by pharyngeally induced swallowing events, but TLESRs may also be accompanied by retrograde esophageal motor responses (EMRs). These contractions have not previously been investigated and their effect on esophageal clearance is not known. The aim of this study was to assess the frequency of EMRs after TLESR in healthy individuals and GERD patients and to develop an animal model for further investigation of EMRs. The frequency of TLESRs and esophageal body contractions after TLESRs was assessed using ambulatory manometry in five healthy individuals and five GERD patients. An animal model was developed for reproducible provocation of TLESRs and subsequent EMRs. Patients with GERD have significantly more TLESRs than healthy individuals. However, post-TLESR EMRs were not more frequent in the GERD group. All post-TLESR EMRs presented as simultaneous contractions of the esophagus. The feline model allowed reproducible initiation of the esophageal motor response after TLESR, showing that EMRs can be induced by external mechanoreceptor stimulation simultaneously with LES relaxation. This experimental design imitates the conditions after fundoplication in humans. The study demonstrated that GERD patients have significantly more TLESRs in comparison with healthy individuals, but these were only incidental to EMRs. Further research is needed to improve our understanding of esophageal motility disorders. The animal model presented offers a feasible tool for investigating TLESR-induced esophageal motility.

A functional study of the esophagus in patients with non-cardiac chest pain and dysphagia.

PubMed

Gullo, Roberto; Inviati, Angela; Almasio, Piero Luigi; Di Paola, Valentina; Di Giovanni, Silvia; Scerrino, Gregorio; Gulotta, Gaspare; Bonventre, Sebastiano

2015-03-01

Nutcracker esophagus and non-specific motility disorders are the main causes of non-cardiac chest pain (NCCP), with gastroesophageal reflux in 60% of cases. Achalasia and diffuse esophageal spasm are the most frequent anomalies described in patients with dysphagia. The goal of this study was to evaluate the occurrence of esophageal body and lower esophageal sphincter motor abnormalities in patients with dysphagia, NCCP, or both. This study is a retrospective analysis of 716 patients with NCCP and/or dysphagia tested between January 1994 and December 2010. 1023 functional studies were performed, 707 of which were esophageal manometries, 225 esophageal pH-meters, and 44 bilimetries. We divided the patients into three groups: group 1 was composed of patients affected with dysphagia, group 2 with NCCP and group 3 with NCCP and dysphagia. Manometric anomalies were detected in 84.4% of cases (p<0.001). The most frequent esophageal motility alteration was achalasia (36%). The lower esophageal sphincter was normal in 45.9% of patients (p<0.001). In all 3 groups, 80.9%, 98.8%, and 93.8, respectively, of patients showed normal upper esophageal sphincter (p=0.005). Our data differs from those of other studies because they were collected from and analyzed by a single tertiary level referral center by a single examiner. This could have eliminated the variability found in different hands and different experiences. The high percentage of symptomatic patients with non-pathologic esophageal motility pattern suggests an unclear origin of the disease, with possible neuromuscular involvement. As a result, these patients may need more-detailed diagnostic studies.

Value of preoperative esophageal function studies before laparoscopic antireflux surgery.

PubMed

Chan, Walter W; Haroian, Laura R; Gyawali, C Prakash

2011-09-01

The value of esophageal manometry and ambulatory pH monitoring before laparoscopic antireflux surgery (LARS) has been questioned because tailoring the operation to the degree of hypomotility often is not required. This study evaluated a consecutive cohort of patients referred for esophageal function studies in preparation for LARS to determine the rates of findings that would alter surgical decisions. High-resolution manometry (HRM) was performed for each subject using a 21-lumen water-perfused system, and motor function was characterized. Gastroesophageal reflux disease (GERD) was evident from ambulatory pH monitoring if thresholds for acid exposure time and/or positive symptom association probability were passed. Of 1,081 subjects (age, 48.4 ± 0.4 years; 56.7% female) undergoing preoperative HRM, 723 (66.9%) also had ambulatory pH testing performed. Lower esophageal sphincter (LES) hypotension (38.9%) and nonspecific spastic disorder (NSSD) of the esophageal body (36.1%) were common. Obstructive LES pathophysiology was noted in 2.5% (achalasia in 1%; incomplete LES relaxation in 1.5%), and significant esophageal body hypomotility in 4.5% (aperistalsis in 3.2%; severe hypomotility in 1.3%) of the subjects. Evidence of GERD was absent in 23.9% of the subjects. Spastic disorders were more frequent in the absence of GERD (43.9% vs. 23.1% with GERD; p < 0.0001), whereas hypomotility and normal patterns were more common with GERD. Findings considered absolute or relative contraindications for standard 360º fundoplication are detected in 1 of 14 patients receiving preoperative HRM. Additionally, spastic findings associated with persistent postoperative symptoms are detected at esophageal function testing that could be used in preoperative counseling and candidate selection. Physiologic testing remains important in the preoperative evaluation of patients being considered for LARS.

The Esophagiome: concept, status, and future perspectives.

PubMed

Gregersen, Hans; Liao, Donghua; Brasseur, James G

2016-09-01

The term "Esophagiome" is meant to imply a holistic, multiscale treatment of esophageal function from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. The development and application of multiscale mathematical models of esophageal function are central to the Esophagiome concept. These model elements underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease by quantitatively contrasting normal and pathophysiological function. Functional models incorporate anatomical details with sensory-motor properties and functional responses, especially related to biomechanical functions, such as bolus transport and gastrointestinal fluid mixing. This brief review provides insight into Esophagiome research. Future advanced models can provide predictive evaluations of the therapeutic consequences of surgical and endoscopic treatments and will aim to facilitate clinical diagnostics and treatment. © 2016 New York Academy of Sciences.

Beneficial effect of the 5-HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study.

PubMed

Karamanolis, George P; Panopoulos, Stylianos; Karlaftis, Anastasios; Denaxas, Konstantinos; Kamberoglou, Dimitrios; Sfikakis, Petros P; Ladas, Spiros D

2015-06-01

Esophageal involvement in systemic sclerosis (SSc) carries significant morbidity and is empirically managed with domperidone, albeit with questionable efficacy. The oral 5-HT1A receptor agonist buspirone may enhance esophageal peristalsis and lower esophageal sphincter (LES) function in healthy volunteers. We aimed to test the hypothesis that buspirone may exert a beneficial acute effect on esophageal motor dysfunction in symptomatic patients with SSc. Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined. Esophageal hypomotility and hypotensive LES was found in 63% and 67% of patients, respectively. Demographic and clinical characteristics, including baseline manometric parameters, were comparable between groups. Resting pressure of LES increased after buspirone from 9.42 ± 2.6 to 11.53 ± 3.4 mmHg (p = 0.0002 by paired t-test), but not after domperidone; a trend for increase of amplitude of contractions was also observed after buspirone (p = 0.09). Comparison of the individual changes revealed that buspirone was superior to domperidone in enhancing LES pressure ( + 2.11 ± 2.0 versus -0.45 ± 2.3 mmHg, p = 0.006). No significant effects of either drug were noted on other examined parameters of esophageal function. The beneficial acute effect of buspirone on impaired LES function associated with SSc suggests a role of 5-HT1A receptor-mediated interactions in these patients. Prospective studies to examine whether buspirone is of long-term therapeutic value for SSc-associated esophageal disease are warranted.

Nonerosive reflux disease: clinical concepts.

PubMed

Gyawali, C Prakash; Azagury, Dan E; Chan, Walter W; Chandramohan, Servarayan M; Clarke, John O; de Bortoli, Nicola; Figueredo, Edgar; Fox, Mark; Jodorkovsky, Daniela; Lazarescu, Adriana; Malfertheiner, Peter; Martinek, Jan; Murayama, Kenric M; Penagini, Roberto; Savarino, Edoardo; Shetler, Katerina P; Stein, Ellen; Tatum, Roger P; Wu, Justin

2018-05-15

Esophageal symptoms can arise from gastroesophageal reflux disease (GERD) as well as other mucosal and motor processes, structural disease, and functional esophageal syndromes. GERD is the most common esophageal disorder, but diagnosis may not be straightforward when symptoms persist despite empiric acid suppressive therapy and when mucosal erosions are not seen on endoscopy (as for nonerosive reflux disease, NERD). Esophageal physiological tests (ambulatory pH or pH-impedance monitoring and manometry) can be of value in defining abnormal reflux burden and reflux-symptom association. NERD diagnosed on the basis of abnormal reflux burden on ambulatory reflux monitoring is associated with similar symptom response from antireflux therapy for erosive esophagitis. Acid suppression is the mainstay of therapy, and antireflux surgery has a definitive role in the management of persisting symptoms attributed to NERD, especially when the esophagogastric junction is compromised. Adjunctive approaches and complementary therapy may be of additional value in management. In this review, we describe the evaluation, diagnosis, differential diagnosis, and management of NERD. © 2018 New York Academy of Sciences.

Specific movement of esophagus during transient lower esophageal sphincter relaxation in gastroesophageal reflux disease.

PubMed

Kim, Hoon Il; Hong, Su Jin; Han, Jae Pil; Seo, Jung Yeon; Hwang, Kyoung Hwa; Maeng, Hyo Jin; Lee, Tae Hee; Lee, Joon Seong

2013-07-01

Transient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastroesophageal reflux disease (GERD). The aim of this study was to investigate the characteristics of transient lower esophageal sphincter movement in patients with or without gastroesophageal reflux by high-resolution manometry (HRM). From June 2010 to July 2010, we enrolled 9 patients with GERD (GERD group) and 9 subjects without GERD (control group), prospectively. The manometry test was performed in a semi-recumbent position for 120 minutes following ingestion of a standardized, mixed liquid and solid meal. HRM was used to identify the frequency and duration of TLESR, esophageal shortening length from incomplete TLESR, upper esophageal sphincter (UES) response, and the related esophageal motor responses during TLESR. TLESR occurred in 33 in the GERD group and 34 in the control group after 120 minutes following food ingestion. Duration of TLESR and length of esophageal shortening did not differ between 2 groups. UES pressure increase during TLESR was mostly detected in patients with GERD, and UES relaxation was observed frequently in the control group during TLESR. TLESR-related motor responses terminating in TLESR were predominantly observed in the control group. Increased UES pressure was noted frequently in the GERD group, suggesting a mechanism for preventing harmful reflux, which may be composed mainly of fluid on the larynx or pharynx. However, patients with GERD lacked the related motor responses terminating in TLESR to promote esophageal emptying of refluxate.

Radionuclide Esophageal Transit Scintigraphy in Primary Hypothyroidism.

PubMed

Khan, Shoukat H; P, Madhu Vijay; Rather, Tanveer A; Laway, Bashir A

2017-01-30

Esophageal dysmotility is associated with gastrointestinal dysmotility in various systemic and neuroregulatory disorders. Hypothyroidism has been reported to be associated with impaired motor function in esophagus due to accumulation of glycosaminoglycan hyaluronic acid in its soft tissues, leading to changes in various contraction and relaxation parameters of esophagus, particularly in the lower esophageal sphincter. In this study we evaluated esophageal transit times in patients of primary hypothyroidism using the technique of radionuclide esophageal transit scintigraphy. Thirty-one patients of primary hypothyroidism and 15 euthyroid healthy controls were evaluated for esophageal transit time using 15-20 MBq of Technetium-99m sulfur colloid diluted in 10-15 mL of drinking water. Time activity curve was generated for each study and esophageal transit time was calculated as time taken for clearance of 90% radioactive bolus from the region of interest encompassing the esophagus. Esophageal transit time of more than 10 seconds was considered as prolonged. Patients of primary hypothyroidism had a significantly increased mean esophageal transit time of 19.35 ± 20.02 seconds in comparison to the mean time of 8.25 ± 1.71 seconds in healthy controls ( P < 0.05). Esophageal transit time improved and in some patients even normalized after treatment with thyroxine. A positive correlation ( r = 0.39, P < 0.05) albeit weak existed between the serum thyroid stimulating hormone and the observed esophageal transit time. A significant number of patients with primary hypothyroidism may have subclinical esophageal dysmotility with prolonged esophageal transit time which can be reversible by thyroxine treatment. Prolonged esophageal transit time in primary hypothyroidism may correlate with serum thyroid stimulating hormone levels.

Esophageal sensation in premature human neonates: temporal relationships and implications of aerodigestive reflexes and electrocortical arousals

PubMed Central

Parks, Vanessa N.; Peng, Juan; Dzodzomenyo, Samuel; Fernandez, Soledad; Shaker, Reza; Splaingard, Mark

2012-01-01

Electrocortical arousal (ECA) as an effect of visceral provocation or of its temporal relationships with aerodigestive reflexes in premature neonates is not known. We tested the hypothesis that esophageal provocation results in both esophageal reflex responses and ECAs during sleep and that ECAs are dependent on the frequency characteristics of esophageal neuromotor responses. We defined the spatiotemporal relationship of ECAs in relation to 1) spontaneous pharyngoesophageal swallow sequences and gastroesophageal reflux (GER) events and 2) sensory-motor characteristics of esophageal reflexes. Sixteen healthy premature neonates born at 27.9 ± 3.4 wk were tested at 36.8 ± 1.9 wk postmenstrual age. Ninety-five midesophageal and 31 sham stimuli were given in sleep during concurrent manometry and videopolysomnography. With stimulus onset as reference point, we scored the response latency, frequency occurrence and duration of arousals, peristaltic reflex, and upper esophageal sphincter contractile reflex (UESCR). Changes in polysomnography-respiratory patterns and esophageal sensory-motor parameters were scored by blinded observers. Significantly (for each characteristic listed, P < 0.05), swallow sequences were associated with arousals and sleep state changes, and arousals were associated with incomplete peristalsis, response delays to lower esophageal sphincter relaxation, and prolonged esophageal clearance. GER events (73.5%) provoked arousals, and arousals were associated with response delays to peristaltic reflexes or clearance, sleep state modification, and prolonged respiratory arousal. Midesophageal stimuli (54%) provoked arousals and were associated with increased frequency, prolonged latency, prolonged response duration of peristaltic reflexes and UESCR, and increased frequency of sleep state changes and respiratory arousals. In human neonates, ECAs are provoked upon esophageal stimulation; the sensory-motor characteristics of esophageal reflexes are distinct when accompanied by arousals. Aerodigestive homeostasis is defended by multiple tiers of aerodigestive safety mechanisms, and when esophageal reflexes are delayed, cortical hypervigilance (ECAs) occurs. PMID:21852361

Effect of aging on the esophageal motor functions.

PubMed

Nishimura, N; Hongo, M; Yamada, M; Kawakami, H; Ueno, M; Okuno, Y; Toyota, T

1996-04-01

To clarify the changes of esophageal motility along with age, we performed esophageal manometry on 47 healthy volunteers, and compared the values of four groups under 49 years old (n = 11), 50 to 59 (n = 15), 60 to 69 (n = 11), and over 70 years old (n = 10). Resting lower esophageal sphincter (LES) pressure in the group over 70 years old showed the tendency of decrease, but not statistically significant. Nadir LES pressure on swallow-induced relaxation was not statistically different among 4 groups. On esophageal body testing, percentage of non-conduction sequence in the group 60 to 69 and over 70 years old was statistically higher compared with that of the group under 49 years old (p < 0.05) but spared in some elderly subjects. Percentage of simultaneous contractions was not statistically different among 4 groups. Peristaltic contraction amplitude in the group over 70 years old was significantly lower than that of the group under 49 years old both at the level of 5 cm above (p < 0.01) and 10 cm above LES (p < 0.05). We speculate that the influence of aging on esophageal motility is the reduced transmission sequence of peristalsis and contractility of esophageal body. This alteration along with age may differ from the pathological condition of scleroderma or diffuse esophageal spasm.

Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease.

PubMed

Mittal, Ravinder K

2016-09-01

Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic reflex, respectively. Studies in patients with various types of esophageal motor disorders reveal temporal disassociation between the circular and longitudinal muscle layers. We suggest that the discoordination between the two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain. Certain pathologies may selectively target one and not the other muscle layer, e.g., in eosinophilic esophagitis there is a selective dysfunction of the longitudinal muscle layer. In achalasia esophagus, swallows are accompanied by the strong contraction of the longitudinal muscle without circular muscle contraction. The possibility that the discoordination between two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain are discussed. The purpose of this review is to summarize the regulation and dysregulation of peristalsis by the coordinated and discoordinated function of circular and longitudinal muscle layers in health and diseased states.

Regulation and dysregulation of esophageal peristalsis by the integrated function of circular and longitudinal muscle layers in health and disease

PubMed Central

2016-01-01

Muscularis propria throughout the entire gastrointestinal tract including the esophagus is comprised of circular and longitudinal muscle layers. Based on the studies conducted in the colon and the small intestine, for more than a century, it has been debated whether the two muscle layers contract synchronously or reciprocally during the ascending contraction and descending relaxation of the peristaltic reflex. Recent studies in the esophagus and colon prove that the two muscle layers indeed contract and relax together in almost perfect synchrony during ascending contraction and descending relaxation of the peristaltic reflex, respectively. Studies in patients with various types of esophageal motor disorders reveal temporal disassociation between the circular and longitudinal muscle layers. We suggest that the discoordination between the two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain. Certain pathologies may selectively target one and not the other muscle layer, e.g., in eosinophilic esophagitis there is a selective dysfunction of the longitudinal muscle layer. In achalasia esophagus, swallows are accompanied by the strong contraction of the longitudinal muscle without circular muscle contraction. The possibility that the discoordination between two muscle layers plays a role in the genesis of esophageal symptoms, i.e., dysphagia and esophageal pain are discussed. The purpose of this review is to summarize the regulation and dysregulation of peristalsis by the coordinated and discoordinated function of circular and longitudinal muscle layers in health and diseased states. PMID:27445346

Primary Esophageal Motility Disorders: Beyond Achalasia.

PubMed

Schlottmann, Francisco; Patti, Marco G

2017-06-30

The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders. The Chicago classification introduced new manometric parameters and better defined esophageal motility disorders. Motility disorders beyond achalasia with the current classification are: esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility) and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). The aim of this study was to review the current diagnosis and management of esophageal motility disorders other than achalasia.

Primary Esophageal Motility Disorders: Beyond Achalasia

PubMed Central

Schlottmann, Francisco; Patti, Marco G.

2017-01-01

The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders. The Chicago classification introduced new manometric parameters and better defined esophageal motility disorders. Motility disorders beyond achalasia with the current classification are: esophagogastric junction outflow obstruction, major disorders of peristalsis (distal esophageal spasm, hypercontractile esophagus, absent contractility) and minor disorders of peristalsis (ineffective esophageal motility, fragmented peristalsis). The aim of this study was to review the current diagnosis and management of esophageal motility disorders other than achalasia. PMID:28665309

Esophageal Dysmotility in Patients following Total Laryngectomy.

PubMed

Zhang, Teng; Maclean, Julia; Szczesniak, Michal; Bertrand, Paul P; Quon, Harry; Tsang, Raymond K; Wu, Peter I; Graham, Peter; Cook, Ian J

2018-02-01

Objectives Dysphagia is common in total laryngectomees, with some symptoms suggesting esophageal dysmotility. Tracheoesophageal (TE) phonation requires effective esophagopharyngeal air passage. Hence, esophageal dysmotility may affect deglutition or TE phonation. This study aimed to determine (1) the characteristics of esophageal dysmotility in laryngectomees, (2) whether clinical history is sensitive in detecting esophageal dysmotility, and (3) the relationship between esophageal dysmotility and TE prosthesis dysfunction. Study Design Multidisciplinary cross-sectional study. Setting Tertiary academic hospital. Subjects and Methods For 31 participants undergone total laryngectomy 1 to 12 years prior, clinical histories were taken by a gastroenterologist and a speech pathologist experienced in managing dysphagia. Esophageal high-resolution manometry was performed and analyzed using Chicago Classification v3.0. Results Interpretable manometric studies were obtained in 23 (1 normal manometry). Esophageal dysmotility patterns included achalasia, esophagogastric junction outflow obstruction, diffuse esophageal spasm, and other major (30%) and minor (50%) peristaltic disorders. The sensitivity of predicting any esophageal dysmotility was 28%, but it is noteworthy that patients with achalasia and diffuse esophageal spasm (DES) were predicted. Two of 4 participants with TE puncture leakage had poor esophageal clearance. Of 20 TE speakers, 12 had voice problems, no correlation between poor voice, and any dysmotility pattern. Conclusions Peristaltic and lower esophageal sphincter dysfunction are common in laryngectomees. Clinical history, while not predictive of minor motor abnormalities, predicted correctly cases with treatable spastic motor disorders. Dysmotility was not associated with poor phonation, although TE puncture leakage might be linked to poor esophageal clearance. Esophageal dysmotility should be considered in the laryngectomees with persisting dysphagia or leaking TE puncture.

Esophageal motor abnormalities in eosinophilic esophagitis identified by high-resolution manometry.

PubMed

Martín Martín, Leticia; Santander, Cecilio; Lopez Martín, Mari Carmen; Espinoza-Ríos, Jorge; Chavarría-Herbozo, Carlos; Gisbert, Javier P; Moreno-Otero, Ricardo

2011-09-01

Esophageal motility abnormalities, as measured by conventional manometry (CM), are non-specific in the majority of patients with eosinophilic esophagitis (EoE). Moreover, the study of CM is limited by poor interobserver agreement. The aims of the present study were: (i) to assess the esophageal patterns in EoE by a topographic analysis of high-resolution manometry (HRM) data; and (ii) to establish a relationship between motility abnormalities and symptoms of EoE, such as dysphagia and bolus impaction. All adult patients with EoE diagnosed according to histological criteria, and controls with gastroesophageal reflux disease symptoms and dysphagia, were included. HRM was done in EoE patients and controls. For the analysis of data, the Chicago classification was followed. HRM was performed in 21 patients with EoE, as well as in 21 controls. Of the 21 patients with EoE, 10 (48%) showed pan-esophageal pressurization, six (28%) showed peristaltic dysfunction, and in five cases (24%), HRM was normal. There was no pan-esophageal pressurization in controls. Nine of 10 patients with pan-esophageal pressurization required endoscopic bolus removal (P < 0.05); none had obstructive endoscopy findings. The most frequent esophageal motor abnormality measured by HRM was a pan-esophageal pressurization. Bolus impaction in patients with EoE was associated with pan-esophageal pressurization. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

The esophagiome: integrated anatomical, mechanical, and physiological analysis of the esophago-gastric segment.

PubMed

Zhao, Jingbo; McMahon, Barry; Fox, Mark; Gregersen, Hans

2018-06-10

Esophageal diseases are highly prevalent and carry significant socioeconomic burden. Despite the apparently simple function of the esophagus, we still struggle to better understand its physiology and pathophysiology. The assessment of large data sets and application of multiscale mathematical organ models have gained attention as part of the Physiome Project. This has long been recognized in cardiology but has only recently gained attention for the gastrointestinal(GI) tract. The term "esophagiome" implies a holistic assessment of esophageal function, from cellular and muscle physiology to the mechanical responses that transport and mix fluid contents. These anatomical, mechanical, and physiological models underlie the development of a "virtual esophagus" modeling framework to characterize and analyze function and disease. Functional models incorporate anatomical details with sensory-motor responses, especially related to biomechanical functions such as bolus transport. Our review builds on previous reviews and focuses on assessment of detailed anatomical and geometric data using advanced imaging technology for evaluation of gastro-esophageal reflux disease (GERD), and on esophageal mechanophysiology assessed using technologies that distend the esophagus. Integration of mechanics- and physiology-based analysis is a useful characteristic of the esophagiome. Experimental data on pressures and geometric characteristics are useful for the validation of mathematical and computer models of the esophagus that may provide predictions of novel endoscopic, surgical, and pharmaceutical treatment options. © 2018 New York Academy of Sciences.

Esophageal manifestations of celiac disease.

PubMed

Lucendo, A J

2011-09-01

Celiac disease (CD) may often be associated with various motor disorders affecting the different segments of the digestive tract, including the esophagus. Although it has not been universally reported, some available evidences indicate that pediatric and adult celiac patients could manifest a higher frequency of esophagitis and gastroesophageal reflux disease-related symptoms compared to nonceliac patients. In addition, several published studies have consistently shown the efficacy of a gluten-free diet in rapidly controlling esophageal symptoms and in preventing their recurrence. Since the participation of gluten in the esophageal symptoms of CD seems clear, its intimate mechanisms have yet to be elucidated, and several hypothesis have been proposed, including the specific immune alterations characterizing CD, the reduction in nutrient absorption determining the arrival of intact gluten to distal gastrointestinal segments, and various dysregulations in the function of gastrointestinal hormones and peptides. Recent studies have suggested the existence of a possible relationship between CD and eosinophilic esophagitis, which should be more deeply investigated. © 2011 Copyright the Author. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Longitudinal muscle dysfunction in achalasia esophagus and its relevance.

PubMed

Mittal, Ravinder K; Hong, Su Jin; Bhargava, Valmik

2013-04-01

Muscularis propria of the esophagus is organized into circular and longitudinal muscle layers. Goal of this review is to summarize the role of longitudinal muscle in physiology and pathophysiology of esophageal sensory and motor function. Simultaneous manometry and ultrasound imaging that measure circular and longitudinal muscle contraction respectively reveal that during peristalsis 2 layers of the esophagus contract in perfect synchrony. On the other hand, during transient relaxation of the lower esophageal sphincter (LES), longitudinal muscle contracts independently of circular muscle. Recent studies provide novel insights, i.e., longitudinal muscle contraction of the esophagus induces LES relaxation and possibly descending relaxation of the esophagus. In achalasia esophagus and other motility disorders there is discoordination between the 2 muscle layers. Longitudinal muscle contraction patterns are different in the recently described three types of achalasia identified by high-resolution manometry. Robust contraction of the longitudinal muscle in type II achalasia causes pan-esophageal pressurization and is the mechanism of whatever little esophageal emptying that take place in the absence of peristalsis and impaired LES relaxation. It may be that preserved longitudinal muscle contraction is also the reason for superior outcome to medical/surgical therapy in type II achalasia esophagus. Prolonged contractions of longitudinal muscles of the esophagus is a possible mechanism of heartburn and "angina like" pain seen in esophageal motility disorders and possibly achalasia esophagus. Novel techniques to record longitudinal muscle contraction are on the horizon. Neuro-pharmacologic control of circular and longitudinal muscles is different, which provides an important opportunity for the development of novel pharmacological therapies to treat sensory and motor disorders of the esophagus.

Longitudinal Muscle Dysfunction in Achalasia Esophagus and Its Relevance

PubMed Central

Hong, Su Jin; Bhargava, Valmik

2013-01-01

Muscularis propria of the esophagus is organized into circular and longitudinal muscle layers. Goal of this review is to summarize the role of longitudinal muscle in physiology and pathophysiology of esophageal sensory and motor function. Simultaneous manometry and ultrasound imaging that measure circular and longitudinal muscle contraction respectively reveal that during peristalsis 2 layers of the esophagus contract in perfect synchrony. On the other hand, during transient relaxation of the lower esophageal sphincter (LES), longitudinal muscle contracts independently of circular muscle. Recent studies provide novel insights, i.e., longitudinal muscle contraction of the esophagus induces LES relaxation and possibly descending relaxation of the esophagus. In achalasia esophagus and other motility disorders there is discoordination between the 2 muscle layers. Longitudinal muscle contraction patterns are different in the recently described three types of achalasia identified by high-resolution manometry. Robust contraction of the longitudinal muscle in type II achalasia causes pan-esophageal pressurization and is the mechanism of whatever little esophageal emptying that take place in the absence of peristalsis and impaired LES relaxation. It may be that preserved longitudinal muscle contraction is also the reason for superior outcome to medical/surgical therapy in type II achalasia esophagus. Prolonged contractions of longitudinal muscles of the esophagus is a possible mechanism of heartburn and "angina like" pain seen in esophageal motility disorders and possibly achalasia esophagus. Novel techniques to record longitudinal muscle contraction are on the horizon. Neuro-pharmacologic control of circular and longitudinal muscles is different, which provides an important opportunity for the development of novel pharmacological therapies to treat sensory and motor disorders of the esophagus. PMID:23667744

Effects of Age on Esophageal Motility: Use of High-resolution Esophageal Impedance Manometry

PubMed Central

Shim, Young Kwang; Kim, Nayoung; Park, Yo Han; Lee, Jong-Chan; Sung, Jihee; Choi, Yoon Jin; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Lee, Dong Ho

2017-01-01

Background/Aims Disturbances of esophageal motility have been reported to be more frequent the aged population. However, the physiology of disturbances in esophageal motility during aging is unclear. The aim of this study was to evaluate the effects of age on esophageal motility using high-resolution esophageal impedance manometry (HRIM). Methods Esophageal motor function of 268 subjects were measured using HRIM in 3 age groups, < 40 years (Group A, n = 32), 40–65 years (Group B, n = 185), and > 65 years (Group C, n = 62). Lower esophageal sphincter (LES) and upper esophageal sphincter (UES) pressures, integrated relaxation pressure, distal contractile integral, contractile front velocity, distal latency, and pressures and duration of contraction on 4 positions along the esophagus, and complete bolus transit were measured. Results Basal UES pressure was lower in Group C (P < 0.001) but there was no significant difference in the LES pressure among groups. Contractile duration on position 3 (10 cm from proximal LES high pressure zone) was longer in Group C (P = 0.001), and the contractile amplitude on position 4 (5 cm from proximal LES high pressure zone) was lower in Group C (P = 0.005). Distal contractile integral was lower in Group C (P = 0.037). Contractile front velocity (P = 0.015) and the onset velocity (P = 0.040) was lower in Group C. There was no significant difference in impedance values. Conclusions The decrease of UES pressure, distal esophageal motility, and peristaltic velocity might be related with esophageal symptoms in the aged population. PMID:28163259

The effect of esophageal and gastric distension on the crural diaphragm.

PubMed

Shafik, Ahmed; Shafik, Ismail; El Sibai, Olfat; Mostafa, Randa M

2006-02-01

The mechanism of prevention of gastric reflux into the esophagus is not exactly known. The lower esophagus has a barrier function provided by the lower esophageal sphincter. We investigated the hypothesis that the crural diaphragm shares in the barrier function not only mechanically but also actively through a crural-esophageal-gastric reflex action. The study was performed during repair of abdominal ventral and incisional hernias in 20 subjects (11 men, 9 women; age 38.6+/-4.8 years). The electromyographic response of the crural diaphragm to individual balloon distension of esophagus and stomach was recorded by means of a needle electrode inserted into the crural diaphragm and connected to an electromyographic apparatus. The recordings were repeated after separate crural, esophageal, and gastric anesthetization. The crural diaphragm exhibited basal motor unit action potentials, which decreased on esophageal distension (P<0.001) after a mean latency of 17.3+/-2.8 SD ms. The crural diaphragm response to esophageal distension did not occur after the crural diaphragm or esophagus was anesthetized. Gastric distension effected an increase of crural diaphragm electromyographic activity with a mean latency of 18.4+/-4.6 ms; this effect could not be achieved after the crural diaphragm or stomach was anesthetized. The crural diaphragm has a resting tone that relaxes after esophageal distension and contracts after gastric distension. This sphincter-like action of the crural diaphragm appears to be a reflex and is mediated through the esophagocrural inhibitory and gastrocrural excitatory reflexes. The crural diaphragm seems to share actively in the gastroesophageal competence mechanism.

Impact of thoracic surgery on esophageal motor function-Evaluation by high resolution manometry.

PubMed

Wäsche, Anja; Kandulski, Arne; Malfertheiner, Peter; Riedel, Sandra; Zardo, Patrick; Hachenberg, Thomas; Schreiber, Jens

2017-06-01

Alteration of esophageal function is a potential risk factor for postoperative complications in thoracic surgery. This prospective study investigates esophageal motility and function during and after thoracic procedures via high resolution manometry (HRM) and impedance technology with spatiotemporal representation of pressure data. Twelve consecutive patients eligible for elective thoracic surgery underwent preoperative and postoperative (48 hours and 7 days) esophageal HRM. Swallowing acts were carried out with 5 mL of water, 10 mL of water and 1 cm 3 bread in physiological posture to evaluate distal contraction integral (DCI). Length and location of contractile integrity breaks were measured by investigators blinded to the form of surgical intervention. The impact of surgical procedures on esophageal motility was quantified according to current Chicago Classification (CC) criteria. Pre-, intra- and postoperative 24-hour multi-channel impedance pH-metry (MII-pH) was performed to further analyze gastroesophageal reflux patterns. All patients were investigated 48 hours prior to and 7 days after thoracic procedures, with a total of n=675 swallowing acts being included in our study. Increased motility patterns of the tubular esophagus occurred temporally 48 hours postoperatively. DCI 48 hours after surgery increased significantly (5 mL, P=0.049; solid, P=0.014) and returned to baseline values after seven days (5 mL, P=0.039; solid, P=0.039). Break length was significantly reduced 48 hours postoperatively, especially in the proximal esophageal segment (transition zone). Follow-up measurements after another week were comparable to preoperative baseline findings. The perioperative MII-pH measurement showed numerous artifacts caused by intubation and ventilation during surgery also with increasing short and frequent acidic reflux episodes. Thoracic procedures cause a transient modulation of esophageal peristalsis with postoperative increased contractility of the tubular esophagus, presumably without affecting intraesophageal reflex arcs. Although limited by the number of patients, we can conclude on our data that postoperative esophageal hypomotility is unlikely to promote secondary pulmonary complications.

Esophageal motility in eosinophilic esophagitis.

PubMed

Weiss, A H; Iorio, N; Schey, R

2015-01-01

Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration of the esophagus and is a potential cause of dysphagia and food impaction, most commonly affecting young men. Esophageal manometry findings vary from normal motility to aperistalsis, simultaneous contractions, diffuse esophageal spasm, nutcracker esophagus or hypotonic lower esophageal sphincter (LES). It remains unclear whether esophageal dysmotility plays a significant role in the clinical symptoms of EoE. Our aim is to review the pathogenesis, diagnosis, and effect of treatment on esophageal dysmotility in EoE. A literature search utilizing the PubMed database was performed using keywords: eosinophilic esophagitis, esophageal dysmotility, motility, manometry, impedance planimetry, barium esophagogram, endoscopic ultrasound, and dysphagia. Fifteen studies, totaling 387 patients with eosinophilic esophagitis were identified as keeping in accordance with the aim of this study and included in this review. The occurrence of abnormal esophageal manometry was reported to be between 4 and 87% among patients with EoE. Esophageal motility studies have shown reduced distensibility, abnormal peristalsis, and hypotonicity of the LES in patients with EoE, which may also mimic other esophageal motility disorders such as achalasia or nutcracker esophagus. Studies have shown conflicting results regarding the presence of esophageal dysmotility and symptoms with some reports suggesting a higher rate of food impaction, while others report no correlation between motor function and dysphagia. Motility dysfunction of the esophagus in EoE has not been well reported in the literature and studies have reported conflicting evidence regarding the clinical significance of dysmotility seen in EoE. The correlation between esophageal dysmotility and symptoms of EoE remains unclear. Larger studies are needed to investigate the incidence of esophageal dysmotility, clinical implications, and effect of treatment on patients with EoE. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Esophageal motor disorders in adults with eosinophilic esophagitis.

PubMed

Moawad, Fouad J; Maydonovitch, Corinne L; Veerappan, Ganesh R; Bassett, John T; Lake, Jason M; Wong, Roy K H

2011-05-01

An association between eosinophilic esophagitis (EoE) and esophageal motility disorders has been described in small studies. The aim of this study was to describe the prevalence of esophageal motor disorders in a large cohort of adults with EoE and examine whether an association exists between esophageal dysmotility and dysphagia. A retrospective review of esophageal manometry studies in adult EoE patients was performed. Tracings were reviewed for abnormalities including nutcracker esophagus and ineffective swallows, defined as low amplitude peristalsis (<30 mmHg) or non-propagating contractions. Ineffective esophageal motility (IEM) was categorized as mild (30-40% ineffective swallows), moderate (50-60% ineffective swallows), and severe (≥70% ineffective swallows). Dysphagia was graded on a 0-3 scale for frequency and severity. Seventy-five tracings from EoE patients were reviewed (85% male, mean age 41 ± 12 years). IEM was identified in 25 patients and categorized as mild (n = 13), moderate (n = 6), and severe (n = 6). Nutcracker esophagus was found in three patients. There was no significant difference in eosinophil count among the motility groups: normal 46.5 ± 3.1, mild IEM 56.9 ± 36.9, moderate IEM 45.5 ± 23.7, severe IEM 34.3 ± 12.6 (P = 0.157). In this cohort of EoE patients, the majority had normal esophageal motility studies, although a subset of these patients had some esophageal dysmotility. It is unlikely that esophageal dysmotility is a major contributing factor to dysphagia, although it is reasonable to consider esophageal manometry testing in EoE patients to identify potential abnormalities of the smooth muscle esophagus.

Indications of 24-h esophageal pH monitoring, capsule pH monitoring, combined pH monitoring with multichannel impedance, esophageal manometry, radiology and scintigraphy in gastroesophageal reflux disease?

PubMed

Vardar, Rukiye; Keskin, Muharrem

2017-12-01

Ambulatory esophageal pH monitoring is an essential method in patients exhibiting signs of non-erosive reflux disease (NERD) to make an objective diagnosis. Intra-esophageal pH monitoring is important in patients who are non-responsive to medications and in those with extraesophageal symptoms, particularly in NERD, before surgical interventions. With the help of the wireless capsule pH monitoring, measurements can be made under more physiological conditions as well as longer recordings can be performed because the investigation can be better tolerated by patients. Ambulatory esophageal pH monitoring can be detected within normal limits in 17%-31.4% of the patients with endoscopic esophagitis; therefore, normal pH monitoring cannot exclude the diagnosis of gastroesophageal reflux disease (GERD). Multi-channel intraluminal impedance pH (MII-pH) technology have been developed and currently the most sensitive tool to evaluate patients with both typical and atypical reflux symptoms. The sensitivity of a pH catheter test is 58% for the detection of acid reflux compared with MII-pH monitoring; further, its sensitivity is 28% for the detection of weak acid reflux compared with MII-pH monitoring. By adding impedance to pH catheter in patients with reflux symptoms, particularly in those receiving PPIs, it has been demonstrated that higher rates of diagnoses and symptom analyses can be obtained than those using only pH catheter. Esophageal manometry is used in the evaluation of patients with functional dysphagia and unexplained noncardiac chest pain and prior to antireflux surgery. The use of esophageal manometry is suitable for the detection of esophageal motor patterns and extreme motor abnormalities (e.g., achalasia and extreme hypomotility). Esophageal manometry and ambulatory pH monitoring are often used in assessments prior to laparoscopic antireflux surgery and in patients with reflux symptoms refractory to medical treatment. Although the esophageal motility is predominantly normal in patients with non-acid reflux, ineffective esophageal motility is often monitored in patients with acid reflux. In the literature, there are contradictory and an insufficient number of studies regarding radiological methods for the diagnosis of GERD. There are inconsistent values for sensitivity and specificity among the barium studies. There are inadequate studies in the literature involving scintigraphic examinations in the diagnosis of GERD, and a majority of existing studies have been conducted in the pediatric group. The results of a few studies do not provide sufficient contribution toward the implementation in clinical practice.

Deglutitive Inhibition, Latency Between Swallow and Esophageal Contractions and Primary Esophageal Motor Disorders

PubMed Central

Jafari, Jafar

2012-01-01

Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm. PMID:22323983

Deglutitive inhibition, latency between swallow and esophageal contractions and primary esophageal motor disorders.

PubMed

Sifrim, Daniel; Jafari, Jafar

2012-01-01

Swallowing induces an inhibitory wave that is followed by a contractile wave along the esophageal body. Deglutitive inhibition in the skeletal muscle of the esophagus is controlled in the brain stem whilst in the smooth muscle, an intrinsic peripheral control mechanism is critical. The latency between swallow and contractions is determined by the pattern of activation of the inhibitory and excitatory vagal pathways, the regional gradients of inhibitory and excitatory myenteric nerves, and the intrinsic properties of the smooth muscle. A wave of inhibition precedes a swallow-induced peristaltic contraction in the smooth muscle part of the human oesophagus involving both circular and longitudinal muscles in a peristaltic fashion. Deglutitive inhibition is necessary for drinking liquids which requires multiple rapid swallows (MRS). During MRS the esophageal body remains inhibited until the last of the series of swallows and then a peristaltic contraction wave follows. A normal response to MRS requires indemnity of both inhibitory and excitatory mechanisms and esophageal muscle. MRS has recently been used to assess deglutitive inhibition in patients with esophageal motor disorders. Examples with impairment of deglutitive inhibition are achalasia of the LES and diffuse esophageal spasm.

Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

PubMed

Zerbib, Frank; Roman, Sabine

2015-07-01

With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

Esophageal motor and sensory disorders: presentation, evaluation, and treatment.

PubMed

Massey, Benson T

2007-09-01

Esophageal motor and sensory disorders are relatively rare conditions in the general population and afflicted patients are often initially misdiagnosed as having gastroesophageal reflux disease. Tests for these disorders have imperfect gold standards and are adjuncts to sound diagnostic reasoning. Treatments are palliative and have not been rigorously evaluated for some disorders. Symptoms and complications from disease progression and relapse are common, so that patients need continued follow-up.

Esophageal dysfunction in different stages of Parkinson's disease.

PubMed

Suttrup, I; Suttrup, J; Suntrup-Krueger, S; Siemer, M-L; Bauer, J; Hamacher, C; Oelenberg, S; Domagk, D; Dziewas, R; Warnecke, T

2017-01-01

Dysphagia is a clinically relevant symptom in patients with Parkinson's disease (PD) leading to pronounced reduction in quality of life and other severe complications. Parkinson's disease-related dysphagia may affect the oral and pharyngeal, as well as the esophageal phase of swallowing. To examine the nature and extend of esophageal dysphagia in different stages of PD and their relation to oropharyngeal dysfunction, we examined 65 PD patients (mean age 66.3±9.7 years, mean disease duration 7.9±5.8 years, mean Hoehn & Yahr [H&Y] stage 2.89±0.91) and divided into three groups (early [H&Y I+II; n=21], intermediate [H&Y III; n=25], and advanced stadium [H&Y IV+V; n=19]), using esophageal high-resolution manometry (HRM) to detect esophageal motor disorders. Oropharyngeal impairment was assessed using fiberoptic endoscopic evaluation of swallowing. Major esophageal motor disorders were detected in nearly one third of the PD patients. Minor impairment of the esophageal body was present in 95% of participants and throughout all disease stages with pathological findings especially in peristalsis and intrabolus pressure (IBP). The IBP was found to significantly increase in the advanced stadium. Although dysfunction of the upper and lower esophageal sphincters was observed in individual patients, alterations in these esophageal segments revealed no statistical significance compared with normative data. No clear association was found between the occurrence of oropharyngeal dysphagia and esophageal impairment. Esophageal body impairment in PD is a frequent phenomenon during all disease stages, which possibly reflects α-synucleinopathy in the enteric nervous system. © 2016 John Wiley & Sons Ltd.

Esophageal Motility and Rikkunshito Treatment for Proton Pump Inhibitor-Refractory Nonerosive Reflux Disease: A Prospective, Uncontrolled, Open-Label Pilot Study Trial.

PubMed

Odaka, Takeo; Yamato, Shigeru; Yokosuka, Osamu

2017-01-01

Only a few reports focused on esophageal motility in patients with proton pump inhibitor (PPI)-refractory nonerosive reflux disease (NERD) and there has been no established strategy for treatment. To clarify the characteristics of esophageal motility in patients with PPI-refractory NERD, we evaluated esophageal function using combined multichannel intraluminal impedance and esophageal manometry (MII-EM). In addition, we evaluated the efficacy of rikkunshito (RKT), which is a gastrointestinal prokinetic agent. Thirty patients with NERD were enrolled and underwent MII-EM. After 8 weeks of RKT (7.5 g/d) treatment, MII-EM was repeated on patients with PPI-refractory NERD. Symptoms were assessed by the Gastrointestinal Symptom Rating Scale. In patients with PPI-refractory NERD, measures of complete bolus transit, peristaltic contractions, and residual pressure of the lower esophageal sphincter during swallowing deviated from the standard values and esophageal clearance was found to be deteriorated. RKT significantly improved the peristaltic contractions ( P < 0.05), the complete bolus transit ( P < 0.01), and the residual pressure of lower esophageal sphincter ( P < 0.05) in these patients. The overall score ( P < 0.01) and the subscale scores of acid reflux syndrome ( P < 0.05), abdominal pain ( P < 0.05), and indigestion syndrome ( P < 0.01) in the Gastrointestinal Symptom Rating Scale were significantly improved by the 8-week RKT treatment. In the pilot study, patients with PPI-refractory NERD had disorders of esophageal and lower esophageal sphincter motility that were improved by RKT. Further studies examining esophageal motor activity of RKT in PPI-refractory NERD are required. University hospital Medical Information Network (UMIN) Clinical Trial Registry identifier: UMIN000003092.

Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett's Esophagus.

PubMed

Bazin, Camille; Benezech, Alban; Alessandrini, Marine; Grimaud, Jean-Charles; Vitton, Veronique

2018-04-30

Esophageal motor disorder (EMD) has been shown to be associated with gastroesophageal reflux disease (GERD). However, the association of EMD with a Barrett's esophagus (BE) is controversial. Our objective was to evaluate whether the presence of EMD was an independent factor associated with BE. A retrospective case-control study was conducted in GERD patients who all had oeso-gastroduodenal endoscopy and high-resolution esophageal manometry. The clinical data collected was known or potential risk factors for BE: male gender, smoking and alcohol consumption, age, body mass index, presence of hiatal hernia, frequency, and age of GERD. EMD were classified according to the Chicago classification into: ineffective motor syndrome, fragmented peristalsis and absence of peristalsis, lower esophageal sphincter hypotonia. Two hundred and one patients (101 in the GERD + BE group and 100 in the GERD without BE) were included. In univariate analysis, male gender, alcohol consumption, presence of hiatal hernia, and EMD appeared to be associated with the presence of BE. In a multivariate analysis, 3 independent factors were identified: the presence of EMD (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.71-9.28; P = 0.001), the presence of hiatal hernia (OR, 5.60; 95% CI, 2.45-12.76; P ＜ 0.001), Helicobacter pylori infection (OR, 0.08; 95% CI, 0.01-0.84; P = 0.035). The presence of EMD (particularly ineffective motor syndrome and lower esophageal sphincter hypotonia) is a strong independent associated factor of BE. Searching systematically for an EMD in patients suffering from GERD could be a new strategy to organize the endoscopic follow-up.

Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal dysmotility patients.

PubMed

Santander, Cecilio; Perea, Elena; Caldas, María; Clave, Pere

2017-05-01

High-resolution manometry (HRM) is currently the most important diagnostic test for esophageal motility disorders, providing information on the contraction pattern of the circular muscle layer, which helps classify these esophageal motor diseases. However, with the increasing development of ultrasound, other techniques, such as high-frequency intraluminal ultrasound (HFIUS), have gained importance. This technique uses a flexible shaft with a central wire integrated into a standard endoscope, which facilitates real-time sonography. Its main utility is to provide anatomical information on the structure of the esophageal wall, including both the circular and longitudinal layers that constitute the esophageal muscularis propria. Increasing knowledge about these motility disorders has led to the hypothesis that, in addition to an abnormal contraction pattern of the circular muscle, an overall increased muscle thickness and an abnormal longitudinal muscle contraction could be added as pathophysiological factors. The increase in muscle thickness could be an important indicator of the severity of diseases, such as achalasia, distal esophageal spasm, or hypercontractile esophagus. More studies are required before definitive conclusions can be reached, but HFIUS employed simultaneously with HRM could provide a more complete and precise evaluation of these esophageal motor disorders. © 2017 New York Academy of Sciences.

Mechanisms of repetitive retrograde contractions in response to sustained esophageal distension: a study evaluating patients with postfundoplication dysphagia.

PubMed

Carlson, Dustin A; Kahrilas, Peter J; Ritter, Katherine; Lin, Zhiyue; Pandolfino, John E

2018-03-01

Repetitive retrograde contractions (RRCs) in response to sustained esophageal distension are a distinct contractility pattern observed with functional luminal imaging probe (FLIP) panometry that are common in type III (spastic) achalasia. RRCs are hypothesized to be indicative of either impaired inhibitory innervation or esophageal outflow obstruction. We aimed to apply FLIP panometry to patients with postfundoplication dysphagia (a model of esophageal obstruction) to explore mechanisms behind RRCs. Adult patients with dysphagia after Nissen fundoplication ( n = 32) or type III achalasia ( n = 25) were evaluated with high-resolution manometry (HRM) and upper endoscopy with FLIP. HRM studies were assessed for outflow obstruction and spastic features: premature contractility, hypercontractility, and impaired deglutitive inhibition during multiple-rapid swallows. FLIP studies were analyzed to determine the esophagogastric junction (EGJ)-distensibility index and contractility pattern, including RRCs. Barium esophagram was evaluated when available. RRCs were present in 8/32 (25%) fundoplication and 19/25 (76%) achalasia patients ( P < 0.001). EGJ outflow obstruction was detected in 21 (67%) fundoplication patients by HRM, FLIP, or esophagram [6 (29%) had RRCs]. On HRM, none of the fundoplication patients had premature contractility, whereas 3/4 with defective inhibition on multiple-rapid swallows and 2/4 with hypercontractility had RRCs. Regression analysis demonstrated HRM with spastic features, but not esophageal outflow obstruction, as a predictor for RRCs. RRCs in response to sustained esophageal distension appear to be a manifestation of spastic esophageal motility. Although future study to further clarify the significance of RRCs is needed, RRCs on FLIP panometry should prompt evaluation for a major motor disorder. NEW & NOTEWORTHY Repetitive retrograde contractions (RRCs) are a common response to sustained esophageal distension among spastic achalasia patients when evaluated with the functional luminal imaging probe. We evaluated patients with postfundoplication dysphagia, i.e., patients with suspected mechanical obstruction, and found that RRCs occasionally occurred among postfundoplication patients, but often in association with manometric features of esophageal neuromuscular imbalance. Thus, RRCs appear to be a manifestation of spastic esophageal dysmotility, likely from neural imbalance resulting in excess excitation.

Impact of thoracic surgery on esophageal motor function—Evaluation by high resolution manometry

PubMed Central

Kandulski, Arne; Malfertheiner, Peter; Riedel, Sandra; Zardo, Patrick; Hachenberg, Thomas; Schreiber, Jens

2017-01-01

Background Alteration of esophageal function is a potential risk factor for postoperative complications in thoracic surgery. This prospective study investigates esophageal motility and function during and after thoracic procedures via high resolution manometry (HRM) and impedance technology with spatiotemporal representation of pressure data. Methods Twelve consecutive patients eligible for elective thoracic surgery underwent preoperative and postoperative (48 hours and 7 days) esophageal HRM. Swallowing acts were carried out with 5 mL of water, 10 mL of water and 1 cm3 bread in physiological posture to evaluate distal contraction integral (DCI). Length and location of contractile integrity breaks were measured by investigators blinded to the form of surgical intervention. The impact of surgical procedures on esophageal motility was quantified according to current Chicago Classification (CC) criteria. Pre-, intra- and postoperative 24-hour multi-channel impedance pH–metry (MII-pH) was performed to further analyze gastroesophageal reflux patterns. Results All patients were investigated 48 hours prior to and 7 days after thoracic procedures, with a total of n=675 swallowing acts being included in our study. Increased motility patterns of the tubular esophagus occurred temporally 48 hours postoperatively. DCI 48 hours after surgery increased significantly (5 mL, P=0.049; solid, P=0.014) and returned to baseline values after seven days (5 mL, P=0.039; solid, P=0.039). Break length was significantly reduced 48 hours postoperatively, especially in the proximal esophageal segment (transition zone). Follow-up measurements after another week were comparable to preoperative baseline findings. The perioperative MII-pH measurement showed numerous artifacts caused by intubation and ventilation during surgery also with increasing short and frequent acidic reflux episodes. Conclusions Thoracic procedures cause a transient modulation of esophageal peristalsis with postoperative increased contractility of the tubular esophagus, presumably without affecting intraesophageal reflex arcs. Although limited by the number of patients, we can conclude on our data that postoperative esophageal hypomotility is unlikely to promote secondary pulmonary complications. PMID:28740669

Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett’s Esophagus

PubMed Central

Bazin, Camille; Benezech, Alban; Alessandrini, Marine; Grimaud, Jean-Charles; Vitton, Veronique

2018-01-01

Background/Aims Esophageal motor disorder (EMD) has been shown to be associated with gastroesophageal reflux disease (GERD). However, the association of EMD with a Barrett’s esophagus (BE) is controversial. Our objective was to evaluate whether the presence of EMD was an independent factor associated with BE. Methods A retrospective case-control study was conducted in GERD patients who all had oeso-gastroduodenal endoscopy and high-resolution esophageal manometry. The clinical data collected was known or potential risk factors for BE: male gender, smoking and alcohol consumption, age, body mass index, presence of hiatal hernia, frequency, and age of GERD. EMD were classified according to the Chicago classification into: ineffective motor syndrome, fragmented peristalsis and absence of peristalsis, lower esophageal sphincter hypotonia. Results Two hundred and one patients (101 in the GERD + BE group and 100 in the GERD without BE) were included. In univariate analysis, male gender, alcohol consumption, presence of hiatal hernia, and EMD appeared to be associated with the presence of BE. In a multivariate analysis, 3 independent factors were identified: the presence of EMD (odds ratio [OR], 3.99; 95% confidence interval [CI], 1.71–9.28; P = 0.001), the presence of hiatal hernia (OR, 5.60; 95% CI, 2.45–12.76; P < 0.001), Helicobacter pylori infection (OR, 0.08; 95% CI, 0.01–0.84; P = 0.035). Conclusions The presence of EMD (particularly ineffective motor syndrome and lower esophageal sphincter hypotonia) is a strong independent associated factor of BE. Searching systematically for an EMD in patients suffering from GERD could be a new strategy to organize the endoscopic follow-up. PMID:29605977

Treatment of esophageal motility disorders based on the chicago classification.

PubMed

Maradey-Romero, Carla; Gabbard, Scott; Fass, Ronnie

2014-12-01

The Chicago Classification divides esophageal motor disorders based on the recorded value of the integrated relaxation pressure (IRP). The first group includes those with an elevated mean IRP that is associated with peristaltic abnormalities such as achalasia and esophagogastric junction outflow obstruction. The second group includes those with a normal mean IRP that is associated with esophageal hypermotility disorders such as distal esophageal spasm, hypercontractile esophagus (jackhammer esophagus), and hypertensive peristalsis (nutcracker esophagus). The third group includes those with a normal mean IRP that is associated with esophageal hypomotility peristaltic abnormalities such as absent peristalsis, weak peristalsis with small or large breaks, and frequent failed peristalsis. The therapeutic options vary greatly between the different groups of esophageal motor disorders. In achalasia patients, potential treatment strategies comprise medical therapy (calcium channel blockers, nitrates, and phosphodiesterase 5 inhibitors), endoscopic procedures (botulinum toxin A injection, pneumatic dilation, or peroral endoscopic myotomy) or surgery (Heller myotomy). Patients with a normal IRP and esophageal hypermotility disorder are candidates for medical therapy (nitrates, calcium channel blockers, phosphodiesterase 5 inhibitors, cimetropium/ipratropium bromide, proton pump inhibitors, benzodiazepines, tricyclic antidepressants, trazodone, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors), endoscopic procedures (botulinum toxin A injection and peroral endoscopic myotomy), or surgery (Heller myotomy). Lastly, in patients with a normal IRP and esophageal hypomotility disorder, treatment is primarily focused on controlling the presence of gastroesophageal reflux with proton pump inhibitors and lifestyle modifications (soft and liquid diet and eating in the upright position) to address patient's dysphagia.

Foreign body impaction in the esophagus: are there underlying motor disorders?

PubMed

Mazzadi, S; Salis, G B; García, A; Iannicillo, H; Fucile, V; Chiocca, J C

2017-11-01

Compared with the control group, the impacted subjects presented marked reduction in amplitude and duration of esophageal contraction in the proximal esophagus. These motor disorders could be responsible for the foreign body impaction in the esophagus. However, we believe this patient group should be further studied by 24-hour esophageal manometry to reach a more accurate diagnosis by studying each patient's entire circadian cycle. © 1998 International Society for Diseases of the Esophagus/Harcourt Brace & Co. Ltd

[Clinical and pathogenetic features of esophageal spasm].

PubMed

Firsova, L D; Pichugina, I M; Yanova, O B; Berezina, O I; Bordin, D S

2015-01-01

To comparatively analyze clinical manifestations in patients with primary esophageal spasm (ES) and its concurrence with gastroesophageal reflux disease (GERD) and the results of their instrumental examinations and psychodiagnostic tests. A total of 104 patients with the clinical and manometric signs of ES were examined and divided into two groups: 1) 42 patients with primary ES; 2) 62 patients with ES concurrent with GERD. The examination encompassed esophageal manometry, esophagogastroduodenoscopy, 24-hour pH metry, and an interview using a questionnaire to identify autonomic disorders, and the Mini-Mult test. The patients with primary ES compared to those with ES concurrent with GERD significantly more frequently showed severe pain syndrome (p = 0.009) and a paradoxical dysphagia pattern (p = 0.03); manometry revealed an incoordination in the motility of the entire esophagus (p = 0.001). Comparison of the statistical series of values for contraction amplitude and duration in the distal esophagus found no significant difference in the patients of both groups. Autonomic disturbances were detected in 76.0% of the patients with ES; but the intergroup differences were insignificant. Mental maladaptation was observed in 81.7% of the patients in the absence of intergroup differences. The etiopathogenetic factor of ES is a psychoautonomic response to chronic stress in both primary ES and its concurrence with GERD. The reflux of gastric contents into the esophagus does not appear to be one of the leading causes of ES. In primary ES, esophageal motor function is generally impaired to a much greater extent than that in ES concurrent with GERD. The degree of motor disorders is embodied in the specific clinical features of the disease.

Esophageal epiphrenic diverticulum associated with diffuse esophageal spasm.

PubMed

Matsumoto, Hideo; Kubota, Hisako; Higashida, Masaharu; Manabe, Noriaki; Haruma, Ken; Hirai, Toshihiro

2015-01-01

Esophageal diverticulum, a relatively rare condition, has been considered to be associated with motor abnormalities such as conditions that cause a lack of coordination between the distal esophagus and lower esophageal sphincter. We herein report a case of esophageal epiphrenic diverticulum associated with diffuse esophageal spasm. A 73-year-old woman presented with dysphagia and regurgitation. Imaging examinations revealed a right-sided esophageal diverticulum located about 10cm above the esophagogastric junction. High-resolution manometry revealed normal esophageal motility. However, 24-h pH monitoring revealed continuous acidity due to pooling of residue in the diverticulum. An esophageal epiphrenic diverticulum was diagnosed and resected thoracoscopically. Her dysphagia recurred 2 years later. High-resolution manometry revealed diffuse esophageal spasm. The diverticulum in the present case was considered to have been associated with diffuse esophageal spasm. The motility disorder was likely not identified at the first evaluation. In this case, the patient's symptoms spontaneously resolved without any treatment; however, longer-term follow-up is needed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus.

PubMed

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C; Pasricha, Pankaj J; Li, Xingde; Yu, Shaoyong

2015-03-15

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. Copyright © 2015 the American Physiological Society.

Allergen challenge sensitizes TRPA1 in vagal sensory neurons and afferent C-fiber subtypes in guinea pig esophagus

PubMed Central

Liu, Zhenyu; Hu, Youtian; Yu, Xiaoyun; Xi, Jiefeng; Fan, Xiaoming; Tse, Chung-Ming; Myers, Allen C.; Pasricha, Pankaj J.; Li, Xingde

2015-01-01

Transient receptor potential A1 (TRPA1) is a newly defined cationic ion channel, which selectively expresses in primary sensory afferent nerve, and is essential in mediating inflammatory nociception. Our previous study demonstrated that TRPA1 plays an important role in tissue mast cell activation-induced increase in the excitability of esophageal vagal nodose C fibers. The present study aims to determine whether prolonged antigen exposure in vivo sensitizes TRPA1 in a guinea pig model of eosinophilic esophagitis (EoE). Antigen challenge-induced responses in esophageal mucosa were first assessed by histological stains and Ussing chamber studies. TRPA1 function in vagal sensory neurons was then studied by calcium imaging and by whole cell patch-clamp recordings in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal vagal nodose and jugular neurons. Extracellular single-unit recordings were performed in vagal nodose and jugular C-fiber neuron subtypes using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Antigen challenge significantly increased infiltrations of eosinophils and mast cells in the esophagus. TRPA1 agonist allyl isothiocyanate (AITC)-induced calcium influx in nodose and jugular neurons was significantly increased, and current densities in esophageal DiI-labeled nodose and jugular neurons were also significantly increased in antigen-challenged animals. Prolonged antigen challenge decreased esophageal epithelial barrier resistance, which allowed intraesophageal-infused AITC-activating nodose and jugular C fibers at their nerve endings. Collectively, these results demonstrated that prolonged antigen challenge sensitized TRPA1 in esophageal sensory neurons and afferent C fibers. This novel finding will help us to better understand the molecular mechanism underlying esophageal sensory and motor dysfunctions in EoE. PMID:25591867

[Analyses of the characteristics of esophageal motility in patients with pharyngeal paraesthesia who visit the Department of gastroenterology].

PubMed

Wang, Zhenjiang; Chen, Yuping; Guo, Tingting

2015-07-01

To investigate the influence of the local sensory abnormality in throat while the change of motility in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), as well as the change of esophageal body in pharyngeal paraesthesia. From January 2014 to January 2015 there were sixty-four patients who had pharyngeal susceptible syndrome (PSS) but without confirmed organic disease were enrolled as the PSS group, forty healthy volunteers as the control group. High resolution manometry (HRM) was utilized to distinguish esophageal motility patterns of PSS, including the muscular tension of LES and UES, the integrity, adaptability, amplitude, speed and duration of esophageal peristalsis at 10 swallows. The resting LES and UES pressures and the distal contractile integral (DCI) of esophagus in PSS group were lower than that in control group (P < 0.05). The esophageal peristalsis was decelerated and shortened in duration, and amplitude of contraction notably lower in PSS group compared with its counterpart (P < 0.05). The integrity of esophageal peristalsis was impaired in PSS with remarkable changes in motility patterns, involving ratio of major and minor interrupts, and synchronous contraction rate (P < 0.05). As for the time course from relaxation to the lowest pressure point of UES and time for restoration, no definite difference was noticed between the two groups (P > 0.05). The average peak pressure was similar in two groups (P > 0.05). Muscle tension around the UES has no obvious change when pharyngeal paraesthesia occurred, but the reduction of esophageal motor function, clearance ability, anti-reflux gastroesophageal junction, causing the abnormal reflux which hurt the pharyngeal surface mucosa maybe one of the most important reasons leading to pharyngeal paresthesia.

Mechanical characteristics of distension-evoked peristaltic contractions in the esophagus of systemic sclerosis patients.

PubMed

Gregersen, Hans; Villadsen, Gerda E; Liao, Donghua

2011-12-01

Systemic sclerosis (SS) patients with severe esophageal affection have impaired peristalsis. However, motor function evaluated in vivo by manometry and fluoroscopy does not provide detailed information about the individual contraction cycles. To apply, for the first time in gastrointestinal (GI) patients, a method and principles modified from cardiac research to study esophageal muscle behavior in SS patients. Muscle contraction cycles were analyzed using pressure-cross-sectional area (P-CSA) loops during distension pressure up to 5 kPa. The probe with bag and electrodes for CSA measurements was positioned 7 and 15 cm above the lower esophageal sphincter (LES) in eleven healthy volunteers and eleven SS patients. The P-CSA, the wall tension, Δtension (afterload tension - preload tension), contraction velocity, work output (area of the tension-CSA loops), and power output (preload tension × CSA rate) were analyzed. The P-CSA loops consisted of phases with relaxation and contraction behavior. The tension-stretch ratio loops in patients were shifted to the left at both distension sites, indicative of a stiffer wall in patients. Lower contraction amplitudes and smaller P-CSA loops were observed for the SS patients. The work output, power output, Δtension, and contraction velocity were lower in patients (P < 0.001). Association was found between disease duration and the work output, Δtension, and velocity at pressure steps higher than 3 kPa (P < 0.05). Distension-evoked esophageal contraction can be studied in vivo and analyzed with advanced methods. Increased esophageal stiffness and impaired muscle function that depended on disease duration were observed for SS patients. The analysis may be useful for characterization of other diseases affecting GI function.

Elevated Temperature and 6-7 Year Outcome of Neonatal Encephalopathy

PubMed Central

Laptook, Abbot R.; McDonald, Scott A.; Shankaran, Seetha; Stephens, Bonnie E.; Vohr, Betty R.; Guillet, Ronnie; Higgins, Rosemary D.; Das, Abhik

2013-01-01

OBJECTIVE Determine if higher temperature after hypoxia-ischemia is associated with death or IQ < 70 at 6-7 yr among infants treated with intensive care without hypothermia. DESIGN/METHODS Control infants (non-cooled, n=106) of the NICHD Neonatal Research Network hypothermia trial had serial esophageal and skin temperatures over 72hrs. Each infant's temperature was ranked to derive an average of the upper and lower quartile, and median of each site. Temperatures were used in logistic regressions to determine adjusted associations with death or IQ < 70 at 6-7yrs. Secondary outcomes were death, IQ < 70, and moderate/severe CP. IQ and motor function were assessed with Wechsler Scales for Children and Gross Motor Function Classification System. Results are odds ratio (OR, per °C increment within the quartile or median) and 95% confidence interval (CI). RESULTS Primary outcome was available for 89 infants. At 6-7yrs death or IQ < 70 occurred in 54 infants (37 deaths, 17 survivors with IQ < 70) and moderate/severe CP in 15 infants. Death or IQ < 70 was associated with the upper quartile average of esophageal (OR 7.3, 95% CI 2.0-26.3) and skin temperature (OR 3.5, 95% 1.2-10.4). CP was associated with the upper quartile average of esophageal (OR 12.5, 95% CI 1.02-155) and skin temperature (OR 10.3, 95% 1.3-80.2). CONCLUSIONS Among non-cooled infants of a randomized trial, elevated temperatures during the first post-natal days are associated with increase odds of a worse outcome at 6-7yrs. PMID:23595408

Physiology of Normal Esophageal Motility

PubMed Central

Goyal, Raj K; Chaudhury, Arun

2009-01-01

The esophagus consists of two different parts. In humans, the cervical esophagus is composed of striated muscles and the thoracic esophagus is composed of phasic smooth muscles. The striated muscle esophagus is innervated by the lower motor neurons and peristalsis in this segment is due to sequential activation of the motor neurons in the nucleus ambiguus. Both primary and secondary peristaltic contractions are centrally mediated. The smooth muscle of esophagus is phasic in nature and is innervated by intramural inhibitory (nitric oxide releasing) and excitatory (acetylcholine releasing) neurons that receive inputs from separate sets of preganglionic neurons located in the dorsal motor nucleus of vagus. The primary peristalsis in this segment involves both central and peripheral mechanisms. The primary peristalsis consist of inhibition (called deglutitive inhibition) followed by excitation. The secondary peristalsis is entirely due to peripheral mechanisms and also involves inhibition followed by excitation. The lower esophageal sphincter (LES) is characterized by tonic muscle that is different from the muscle of the esophageal body. The LES, like the esophageal body smooth muscle, is also innervated by the inhibitory and excitatory neurons. The LES maintains tonic closure due to its myogenic property. The LES tone is modulated by the inhibitory and the excitatory nerves. Inhibitory nerves mediate LES relaxation and the excitatory nerves mediate reflex contraction or rebound contraction of the LES. Clinical disorders of esophageal motility can be classified on the basis of disorders of the inhibitory and excitatory innervations and the smooth muscles. PMID:18364578

Esophageal motor disorders are frequent during pre and post lung transplantation. Can they influence lung rejection?

PubMed

Ciriza de Los Ríos, Constanza; Canga Rodríguez-Valcárcel, Fernando; de Pablo Gafas, Alicia; Castel de Lucas, Isabel; Lora Pablos, David; Castellano Tortajada, Gregorio

2018-06-01

lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx. the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection. HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0. EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group. significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure.

Backflow prevention mechanism of laparoscopic Toupet fundoplication using high-resolution manometry.

PubMed

Hoshino, Masato; Omura, Nobuo; Yano, Fumiaki; Tsuboi, Kazuto; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-07-01

The use of multichannel intraluminal impedance pH (MII-pH) and high-resolution manometry (HRM), which are new devices used to examine the esophageal function, has recently become common in Europe and the USA, thus garnering much attention. There have not been enough studies as of yet, however, on the esophageal motor function and the benefits of treatment after these devices have been used in laparoscopic fundoplication. To use MII-pH and HRM to study the treatment effectiveness of laparoscopic fundoplication and consider a backflow prevention mechanism for laparoscopic Toupet fundoplication. The study looked at 27 of a total of 60 patients undergoing laparoscopic fundoplication due to reasons of either gastroesophageal reflux disease or esophageal hiatal hernia between October 2012 and February 2014, who underwent a postsurgical HRM examination. Of these, 25 patients whose symptoms disappeared following surgery and who were not orally administered gastric secretion inhibitor (of whom nine were male, average age 55.9 ± 14.9 years, and of whom 76 % underwent MII-pH) were taken as the subjects of the study. The postsurgical evaluation was conducted 3 months after the operation. Using HRM, although no change was noted in the lower esophageal sphincter pressure (LESP) (p = 0.943), an increase in lower esophageal sphincter pressure integral (p = 0.024) and extensions in both overall length and abdominal length were noted (both p < 0.001), while a significant improvement was noted in the lower esophageal sphincter (LES). Furthermore, the cases subjected to MII-pH demonstrated a reduced gastroesophageal reflux time, total number of liquid reflux episodes, and total number of reflux episodes (p < 0.001, p = 0.008, p = 0.009). Backflow prevention mechanism of laparoscopic Toupet fundoplication is thus considered to improve the overall LES function without elevating LESP.

Scintigraphic Evaluation of Mild to Moderate Dysphagia in Motor Neuron Disease.

PubMed

Szacka, Katarzyna; Potulska-Chromik, Anna; Fronczewska-Wieniawska, Katarzyna; Spychała, Andrzej; Kròlicki, Leszek; Kuźma-Kozakiewicz, Magdalena

2016-04-01

Approximately 30% of patients with motor neuron disease (MND) present swallowing difficulties even in early disease stages. The aim of this study was to examine the usefulness of esophageal scintigraphy in detecting early stage of dysphagia in MND. Esophageal scintigraphy (ES) including mean transit time (MTT) estimation was performed in 121 MND patients presenting various levels of upper (UMN) and lower motor neuron (LMN) degeneration. ES detected dysphagia in more than 80% of MND patients who had referenced swallowing difficulties. In MND patients with ES-confirmed dysphagia, the MTT was increased approximately 2-fold without significant differences between the clinical phenotypes. The MTT was significantly longer in patients with bulbar-pseudobulbar syndrome in comparison to patients with isolated pseudobulbar syndrome, which indicates a higher involvement of the LMN deficiency in developing dysphagia in MND. The esophageal passage in MND was not dependent on age, sex, disease duration, or diagnosis delay. Interestingly, ES was also able to detect dysphagia in almost 70% of MND individuals who had no swallowing complaints (subclinical dysphagia). A more benign disease course and a higher percentage of male patients characterized this group. Esophageal scintigraphy is a helpful screening tool in determining early swallowing impairment in a high percent of patients with MND of various clinical phenotypes.

Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects.

PubMed

Kessing, B F; Smout, A J P M; Bennink, R J; Kraaijpoel, N; Oors, J M; Bredenoord, A J

2014-08-01

The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and gastro-esophageal reflux in man. In this double-blind, placebo-controlled, randomized, crossover study, we included 21 healthy volunteers who received 4 mg prucalopride or placebo per day for 6 days. We performed high-resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric emptying for solids. Prucalopride decreased (median [IQR]) total acid exposure time (3.4 [2.5-5.6] vs 1.7 [0.8-3.5] %, p < 0.05). The total number of reflux events was unaffected by prucalopride, however, the number of reflux events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8-25.5] vs 10.5 [5.3-17.5], p < 0.05). Furthermore, prucalopride improved acid clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p < 0.05). Prucalopride did not affect the number of transient lower esophageal sphincter (LES) relaxations or their association with reflux events. Esophageal motility and basal pressure of the LES were not affected by prucalopride. Prucalopride increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p < 0.05) and decreased residue after 120 min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p < 0.05). Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia. © 2014 John Wiley & Sons Ltd.

The Application of the Rome IV Criteria to Functional Esophagogastroduodenal Disorders in Asia

PubMed Central

Suzuki, Hidekazu

2017-01-01

The Rome criteria were amended as Rome IV. For functional esophageal disorders, the exclusion criteria have been more specifically revised based on further understanding of other esophageal disorders, including eosinophilic esophagitis and spastic and hypercontractile motor disorders. Another revised point is the more restrictive definition of gastroesophageal reflux disease, indicating that sensitivity to a physiological reflux burden may be placed more firmly within the functional group. For functional dyspepsia (FD), only minor changes were introduced, mainly to improve specificity. Among the major symptoms of FD, not only postprandial fullness, but also epigastric pain, epigastric burning, and early satiation should be “bothersome.” Investigation on the effect of meal ingestion on symptom generation has indicated that not only postprandial fullness and early satiety, but also epigastric pain, epigastric burning sensation and nausea (not vomiting) may increase after meals. Helicobacter pylori infection is considered a possible cause of dyspepsia if successful eradication leads to sustained resolution of symptoms for more than 6 months, and such status can be termed as “H. pylori–associated dyspepsia.” Prompt esophagogastroduodenoscopy and H. pylori testing and treatment would be more beneficial, especially in Asia, which has a high prevalence of gastric cancer. Acotiamide, tandospirone, and rikkunshito are the newly listed as treatment options for FD. For further therapeutic development, clinical studies based on the strict Rome IV criteria should be performed. PMID:28672431

Characterization of esophageal pressure-flow abnormalities in patients with non-obstructive dysphagia and normal manometry findings.

PubMed

Chen, Chien-Lin; Yi, Chih-Hsun; Liu, Tso-Tsai; Hsu, Ching-Sheng; Omari, Taher I

2013-06-01

Patients with non-obstructive dysphagia (NOD) report symptoms of impaired esophageal bolus transit without evidence of bolus stasis. In such patients, manometric investigation may diagnose esophageal motility disorders; however, many have normal motor patterns. We hypothesized that patients with NOD would demonstrate evidence of high flow-resistance during bolus passage which in turn would relate to the reporting of bolus hold up perception. Esophageal pressure-impedance recordings of 5 mL liquid and viscous swallows from 18 NOD patients (11 male; 19-71 years) and 17 control subjects (9 male; 25-60 years) were analyzed. The relationship between intrabolus pressure and bolus flow timing in the esophagus was assessed using the pressure flow index (PFI). Bolus perception was assessed swallow by swallow using standardized descriptors. NOD patients were characterized by a higher PFI than controls. The PFI defined a pressure-flow abnormality in all patients who appeared normal based on the assessment esophageal motor patterns and bolus clearance. The PFI was higher for individual swallows during which subjects reported perception of bolus passage. Bolus flow-resistance is higher in NOD patients compared with controls as well as higher in relation to perception of bolus transit, suggesting the presence of an esophageal motility disorder despite normal findings on conventional analysis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Reproducibility patterns of multiple rapid swallows during high resolution esophageal manometry provide insights into esophageal pathophysiology.

PubMed

Price, L H; Li, Y; Patel, A; Gyawali, C Prakash

2014-05-01

Multiple rapid swallows (MRS) during esophageal high resolution manometry (HRM) assess esophageal neuromuscular integrity by evaluating postdeglutitive inhibition and rebound contraction, but most reports performed only a single MRS sequence. We assessed patterns of MRS reproducibility during clinical HRM in comparison to a normal cohort. Consecutive clinical HRM studies were included if two separate MRS sequences (four to six rapid swallows ≤4 s apart) were successfully performed. Chicago Classification diagnoses were identified; contraction wave abnormalities were additionally recorded. MRS-induced inhibition (contraction ≤3 cm during inhibition phase) and rebound contraction was assessed, and findings compared to 18 controls (28.0 ± 0.7 year, 50.0% female). Reproducibility consisted of similar inhibition and contraction responses with both sequences; discordance was segregated into inhibition and contraction phases. Multiple rapid swallows were successfully performed in 89.3% patients and all controls; 225 subjects (56.2 ± 0.9 year, 62.7% female) met study inclusion criteria. Multiple rapid swallows were reproducible in 76.9% patients and 94.4% controls (inhibition phase: 88.0% vs 94.4%, contraction phase 86.7% vs 100%, respectively, p = ns). A gradient of reproducibility was noted, highest in well-developed motor disorders (achalasia spectrum, hypermotility disorders, and aperistalsis, 91.7-100%, p = ns compared to controls); and lower in lesser motor disorders (contraction wave abnormalities, esophageal body hypomotility) or normal studies (62.2-70.8%, p < 0.0001 compared to well-developed motor disorders). Inhibition phase was most discordant in contraction wave abnormalities, while contraction phase was most discordant when studies were designated normal. Multiple rapid swallows are highly reproducible, especially in well-developed motor disorders, and complement the standard wet swallow manometry protocol. © 2014 John Wiley & Sons Ltd.

Association between Minimal Change Esophagitis and Gastric Dysmotility: A Single-Center Electrogastrography and Endoscopy Study in Children.

PubMed

Lim, Kyung In; Shim, Sung Bo; Tchah, Hann; Ryoo, Eell

2018-01-01

Minimal change esophagitis (MCE) is a reflux disease without mucosal breaks, known to be partially associated with abnormal gastric motor function. Electrogastrography (EGG) is commonly applied to assess gastric motor function in a noninvasive fashion. We aimed to determine the relationship between MCE and gastric myoelectrical activity (GME) recorded on EGG in children. We retrospectively assessed the records of 157 children without underlying disease who underwent both EGG and upper gastrointestinal endoscopy at Gachon University Gil Medical Center between January 2010 and June 2015. The children were stratified according to the appearance of the esophagus (normal vs. MCE). Between-group differences in EGG parameters and their correlation with each MCE finding were statistically analyzed. Only the power ratio, one of the EGG parameters analyzed, differed significantly between the two groups (MCE, 1.68±3.37 vs. normal, 0.76±1.06; p <0.05), whereas the other parameters, such as dominant frequency, dominant power, and the ratio of abnormal rhythm, showed no differences. Among children with MCE, significant correlations were noted between erythema and power ratio ( p <0.05), friability and postprandial dominant frequency ( p <0.05), and edema and/or accentuation of mucosal folds and pre-prandial frequency ( p <0.05). Helicobacter pylori infection correlated with postprandial arrhythmia (MCE, 33.59±15.52 vs. normal, 28.10±17.23; p <0.05). EGG parameters did not differ between children with normal esophagus and those with biopsy-proven chronic esophagitis. In children with MCE, gastric dysmotility may affect the development of MCE, manifesting as EGG abnormalities. H. pylori infection may also affect GME. However, larger prospective investigations are needed to confirm these findings.

Esophageal motility and 24-h pH profiles of patients with heterotopic gastric mucosa in the cervical esophagus.

PubMed

Korkut, Esin; Bektaş, Mehmet; Alkan, Murat; Ustün, Yusuf; Meco, Cem; Ozden, Ali; Soykan, Irfan

2010-02-01

Heterotopic gastric mucosa occurs as a flat island of red mucosa in the proximal third of the esophagus where it gives rise to the cervical inlet patch. The aims of this study were to investigate the esophageal motility pattern and 24-h pH profiles of patients with cervical inlet patch. Thirty patients (16 women, mean age: 44.9 years, range: 23-72) diagnosed as having heterotopic gastric mucosa in the cervical esophagus with upper gastrointestinal symptoms had undergone esophageal motility testing and 24-h pH monitorisation with a double-channel pH probe. Manometric investigation was abnormal in 7 patients (non-specific esophageal motor disorder in 4 patients, esophageal hypomotility in 1 patient, and hypotensive LES in 2 patients). Pathological acid reflux (pH<4) was found in 9 (30%) of 30 heterotopic gastric mucosa patients during pH monitorisation from the distal probe. Pathological acid reflux in the proximal esophagus (percentage of total time of pH<4) was seen in four of these nine patients. Only four of the 30 patients (13.3%) presented with "acid independent episodes" during the 24-h esophageal pH monitorisation. Manometric investigation and 24-h pH monitorisation revealed that some of the patients with HGM have signs of esophageal motor dysfunction and "acid independent episodes" from the patches. These abnormalities may be responsible for some of the symptoms of HGM patients. Copyright 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Frequency of motor alterations detected through manometry in patients with esophageal symptoms and scleroderma.

PubMed

Pérez Y López, N; Lugo-Zamudio, G; Barbosa-Cobos, R E; Wong-Lam, A; Torres-López, E

Scleroderma can present with esophageal involvement causing important morbidity. To describe the manometric findings and clinical characteristics of patients with scleroderma and esophageal symptoms. Patients with scleroderma and esophageal symptoms were evaluated through esophageal manometry within the time frame of one year. Descriptive statistics were carried out and the continuous variables were expressed as means and standard deviation. Frequencies were expressed as percentages. The study included 24 female patients with a mean age of 53.5 years and mean disease progression of 7.84 years. The most frequent findings were short and hypotonic lower esophageal sphincter (mean length 1.58cm and mean tone 9.49mmHg) and ineffective esophageal motility (mean non-transmitted waves 92.91%, mean effective primary peristalsis 40.05%, and mean amplitude 13.11mmHg). The most frequent symptom was dysphagia. Scleroderma is associated with lower esophageal sphincter alterations and symptomatic ineffective esophageal motility. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Esophageal motility in children with suspected gastroesophageal reflux disease.

PubMed

Hoffman, Ilse; De Greef, Toon; Haesendonck, Nancy; Tack, Jan

2010-06-01

Motility abnormalities in adults with gastroesophageal reflux disease (GERD) include nontransmitted contractions, reduced distal esophageal contraction amplitude, and simultaneous contractions. Information on esophageal body motility in children with GERD is scarce. Our aim was to study esophageal motility patterns in children with GERD, taking into account the presence of anatomical abnormalities and neurological impairment, the effect of age on esophageal motility in GERD, and the relation between esophageal manometry and GERD severity parameters (acid exposure and presence of esophagitis). Consecutive children referred for severe GER(D) symptoms underwent a barium swallow, upper endoscopy, pH monitoring, and stationary water-perfused esophageal manometry. Mean lower esophageal sphincter (LES) pressure and velocity of propagation in the proximal and distal esophagus decreased with age in this group of children with GERD (all P < 0.01). Severely disturbed esophageal motility was found in children with previous esophageal atresia. Patients with psychomotor retardation had significantly lower occurrence of peristaltic waves (94% +/- 21% vs 79% +/- 38%; P = 0.001), distal propagation velocity (0.8 +/- 0.4 vs 0.6 +/- 0.5 cm/s; P = 0.05), and distal contraction duration (3.1 +/- 0.8 vs 3.4 +/- 1 seconds; P = 0.05). None of the manometric characteristics differed between patients with normal or abnormal esophageal pH monitoring or with or without erosive esophagitis. LES pressure and esophageal velocity decreased with increasing age. Esophageal manometry is severely impaired in children with esophageal atresia and psychomotor retardation. No specific esophageal motor abnormalities related to the presence of endoscopic esophagitis or abnormal pH monitoring were found.

Effect of methylnaltrexone and naloxone on esophageal motor function in man.

PubMed

Scarpellini, E; Pauwels, A; Vos, R; Rommel, N; Tack, J

2017-03-01

Endogenous opioids (EO) acting on μ-opiod receptors in central and enteric nervous system (ENS) control gastrointestinal motility but it is still unclear whether EO in ENS may control esophageal function in man, thus we will study the effects of methylnaltrexone (MNTX), a peripherally selective, and naloxone (NA), a non-selective μ-opiod receptor antagonist, on esophageal motility in healthy subjects. Fifteen HV (6 M; 34.1 ± 0.6 years; BMI: 22.1 ± 0.1 kg/m 2 ) underwent three esophageal high-resolution manometry impedance (HRiM) studies with 10 saline swallows administered every 30 minutes: drug was administered after 30 minutes (MNTX subcutaneously/NA or saline intravenously), a solid meal after 90 minutes; measurements continued for 120 minutes postprandially. Methylnaltrexone did not significantly decrease the upper esophageal sphincter (UES) percentage of relaxation preprandially (72.5 ± 5 vs 66.9 ± 4.6 and 73 ± 3.8%, ANOVA between placebo, MNTX and NA, P=NS) and postprandially (60 minutes: 68.2 ± 5.6 vs 61 ± 5.5 and 67.1 ± 5.6%; 120 minutes: 68 ± 5.9 vs 59.3 ± 5.2 and 67.7 ± 4.7%; ANOVA between placebo, MNTX and NA, P=NS). MNTX and NA did not significantly alter preprandial and postprandial LES resting pressures and integrated relaxation pressure (ANOVA between placebo, MNTX and NA, all P=NS). Peak front velocity and distal contractile integral were not altered pre- and postprandially by MNTX and NA (ANOVA between placebo, MNTX and NA, P=NS). Transient lower esophageal sphincter relaxations (TLESRs') number was not altered by MNTX and NA (ANOVA between placebo, MNTX and NA, all P=NS). The peripheral selective and non-selective μ-opioid receptor antagonists MNTX and NA, respectively, do not alter TLESRs occurrence and esophageal peristalsis. © 2017 John Wiley & Sons Ltd.

Does Chicago Classification address Symptom Correlation with High-resolution Esophageal Manometry?

PubMed Central

Srinivas, Melpakkam; Bawane, Piyush; Venkataraman, Jayanthi

2017-01-01

Aim: To assess the correlation of symptoms with findings on esophageal high-resolution manometry (HRM) in Indian patients. Materials and methods: Prospective data collection of all patients undergoing esophageal manometry was done at two centers in India—Indore and Chennai—over a period of 18 months. Symptom profile of the study group was divided into four: Motor dysphagia, noncardiac chest pain (NCCP), gastroesophageal reflux (GER), and esophageal belchers. The symptoms were correlated with manometric findings. Results: Of the study group (154), 35.71% patients had a normal study, while major and minor peristaltic disorders were noted in 31.16 and 33.76% respectively. In patients with symptoms of dysphagia, achalasia cardia was the commonest cause (45.1%), followed by ineffective esophageal motility (IEM) (22.53%) and normal study (19.71%). In patients with NCCP, normal peristalsis (50%) and ineffective motility (31.25%) formed the major diagnosis. Of the 56 patients with GER symptoms, 26 (46.4%) had normal manometry. An equal number had ineffective motility. Of the 11 esophageal belchers, 7 (63.6%) of these had a normal study and 3 had major motility disorder. Dysphagia was the only symptom to have a high likelihood ratio and positive predictive value to pick up major motility disorder. Conclusion: Dysphagia correlates with high chance to pick up a major peristaltic abnormality in motor dysphagia. The role of manometry in other symptoms in Indian setting needs to be ascertained by larger studies. Clinical significance: The present study highlights lack of symptom correlation with manometry findings in Indian patients. How to cite this article: Jain M, Srinivas M, Bawane P, Venkataraman J. Does Chicago Classification address Symptom Correlation with High-resolution Esophageal Manometry? Euroasian J Hepato-Gastroenterol 2017;7(2):122-125. PMID:29201792

Does Chicago Classification address Symptom Correlation with High-resolution Esophageal Manometry?

PubMed

Jain, Mayank; Srinivas, Melpakkam; Bawane, Piyush; Venkataraman, Jayanthi

2017-01-01

To assess the correlation of symptoms with findings on esophageal high-resolution manometry (HRM) in Indian patients. Prospective data collection of all patients undergoing esophageal manometry was done at two centers in India-Indore and Chennai-over a period of 18 months. Symptom profile of the study group was divided into four: Motor dysphagia, noncardiac chest pain (NCCP), gastroesophageal reflux (GER), and esophageal belchers. The symptoms were correlated with manometric findings. Of the study group (154), 35.71% patients had a normal study, while major and minor peristaltic disorders were noted in 31.16 and 33.76% respectively. In patients with symptoms of dysphagia, achalasia cardia was the commonest cause (45.1%), followed by ineffective esophageal motility (IEM) (22.53%) and normal study (19.71%). In patients with NCCP, normal peristalsis (50%) and ineffective motility (31.25%) formed the major diagnosis. Of the 56 patients with GER symptoms, 26 (46.4%) had normal manometry. An equal number had ineffective motility. Of the 11 esophageal belchers, 7 (63.6%) of these had a normal study and 3 had major motility disorder. Dysphagia was the only symptom to have a high likelihood ratio and positive predictive value to pick up major motility disorder. Dysphagia correlates with high chance to pick up a major peristaltic abnormality in motor dysphagia. The role of manometry in other symptoms in Indian setting needs to be ascertained by larger studies. The present study highlights lack of symptom correlation with manometry findings in Indian patients. How to cite this article: Jain M, Srinivas M, Bawane P, Venkataraman J. Does Chicago Classification address Symptom Correlation with High-resolution Esophageal Manometry? Euroasian J Hepato-Gastroenterol 2017;7(2):122-125.

Dysphagia among adult patients who underwent surgery for esophageal atresia at birth.

PubMed

Huynh Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickeal

2015-03-01

Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and⁄or anatomical anomalies. To determine the motor and anatomical causes of dysphagia. A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, nonpropagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14%, diverticula in 14% and stenosis in 7% of patients. There was more than one anomaly in 14% of patients. Dysphagia was a highly prevalent symptom in adults who underwent surgery for esophageal atresia. The present study is the first to demonstrate that motor and anatomical abnormalities may be implicated in causes of dysphagia in this population. Furthermore, these anomalies may be demonstrated with simple investigations such as endoscopy, manometry and barium swallow.

Dysphagia among adult patients who underwent surgery for esophageal atresia at birth

PubMed Central

Huynh-Trudeau, Valérie; Maynard, Stéphanie; Terzic, Tatjana; Soucy, Geneviève; Bouin, Mickael

2015-01-01

BACKGROUND: Clinical experiences of adults who underwent surgery for esophageal atresia at birth is limited. There is some evidence that suggests considerable long-term morbidity, partly because of dysphagia, which has been reported in up to 85% of adult patients who undergo surgery for esophageal atresia. The authors hypothesized that dysphagia in this population is caused by dysmotility and/or anatomical anomalies. OBJECTIVE: To determine the motor and anatomical causes of dysphagia. METHODS: A total of 41 adults, followed at the Esophageal Atresia Clinic at Hôpital Saint-Luc (Montreal, Quebec), were approached to particpate in the present prospective study. Evaluation was completed using upper endoscopy, manometry and barium swallow for the participants who consented. The medical charts of respondents were systematically reviewed from the neonatal period to 18 years of age to assess medical and surgical history. RESULTS: All 41 patients followed at the clinic consented and were included in the study. Dysphagia was present in 73% of patients. Esophagogastroduodenoscopy was performed in 32 patients: hiatal hernia was present in 62% (n=20); esophageal diverticulum in 13% (n=4); macroscopic Barrett esophagus in 31% (n=10); and esophagitis in 19% (n=6). Histological esophagitis was present in 20% and intestinal metaplasia in 10%. There were no cases of dysplagia or adenocarcinoma. Esophageal manometry was performed on 56% of the patients (n=23). Manometry revealed hypomotility in 100% of patients and included an insufficient number of peristaltic waves in 96%, non-propagating peristalsis in 78% and low-wave amplitude in 95%. Complete aperistalsis was present in 78%. The lower esophageal sphincter was abnormal in 12 (52%) patients, with incomplete relaxation the most common anomaly. Of the 41 patients, 29 (71%) consented to a barium swallow, which was abnormal in 13 (45%). The anomalies found were short esophageal dilation in 28%, delay in esophageal emptying in 14%, diverticula in 14% and stenosis in 7% of patients. There was more than one anomaly in 14% of patients. CONCLUSION: Dysphagia was a highly prevalent symptom in adults who underwent surgery for esophageal atresia. The present study is the first to demonstrate that motor and anatomical abnormalities may be implicated in causes of dysphagia in this population. Furthermore, these anomalies may be demonstrated with simple investigations such as endoscopy, manometry and barium swallow. PMID:25803019

Nonspecific motility disorders, irritable esophagus, and chest pain.

PubMed

Krarup, Anne Lund; Liao, Donghua; Gregersen, Hans; Drewes, Asbjørn Mohr; Hejazi, Reza A; McCallum, Richard W; Vega, Kenneth J; Frazzoni, Marzio; Frazzoni, Leonardo; Clarke, John O; Achem, Sami R

2013-10-01

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic- and gender-based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high-resolution manometry in noncardiac chest pain; whether pH-impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain. © 2013 New York Academy of Sciences.

Effects of transcranial direct current stimulation on esophageal motility in patients with gastroesophageal reflux disease.

PubMed

Vigneri, Simone; Bonventre, Sebastiano; Inviati, Angela; Schifano, Domenico; Cosentino, Giuseppe; Puma, Angela; Giglia, Giuseppe; Paladino, Piera; Brighina, Filippo; Fierro, Brigida

2014-09-01

To evaluate the effects of transcranial direct current stimulation (tDCS) on esophageal peristalsis in patients with gastroesophageal reflux disease (GERD). Patients with GERD preliminary diagnosis were included in a randomized double-blind sham-controlled study. Esophageal manometry was performed before and during transcranial direct current stimulation (tDCS) of the right precentral cortex. Half of patients were randomly assigned to anodal, half to sham stimulation. Distal waves amplitude and pathological waves percentage were measured, after swallowing water boli, for ten subsequent times. Last, a 24h pH-bilimetry was done to diagnose non-erosive reflux disease (NERD) or functional heartburn (FH). The values obtained before and during anodal or sham tDCS were compared. Sixty-eight patients were enrolled in the study. Distal waves mean amplitude increased significantly only during anodal tDCS in NERD (p=0.00002) and FH subgroups (p=0.008) while percentage of pathological waves strongly decreased only in NERDs (p=0.002). Transcranial stimulation can influence cortical control of esophageal motility and improve pathological motor pattern in NERD and FH but not in erosive reflux disease (ERD) patients. Pathophysiological processes in GERD are not only due to peripheral damage but to central neural control involvement as well. In ERD patients dysfunctions of the cortico-esophageal circuit seem to be more severe and may affect central nervous system physiology. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Involvement of catecholaminergic neurons in motor innervation of striated muscle in the mouse esophagus.

PubMed

van der Keylen, Piet; Garreis, Fabian; Steigleder, Ruth; Sommer, Daniel; Neuhuber, Winfried L; Wörl, Jürgen

2016-05-01

Enteric co-innervation is a peculiar innervation pattern of striated esophageal musculature. Both anatomical and functional data on enteric co-innervation related to various transmitters have been collected in different species, although its function remains enigmatic. However, it is unclear whether catecholaminergic components are involved in such a co-innervation. Thus, we examined to identify catecholaminergic neuronal elements and clarify their relationship to other innervation components in the esophagus, using immunohistochemistry with antibodies against tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), choline acetyltransferase (ChAT) and protein gene product 9.5 (PGP 9.5), α-bungarotoxin (α-BT) and PCR with primers for amplification of cDNA encoding TH and dopamine-β-hydroxylase (DBH). TH-positive nerve fibers were abundant throughout the myenteric plexus and localized on about 14% of α-BT-labelled motor endplates differing from VAChT-positive vagal nerve terminals. TH-positive perikarya represented a subpopulation of only about 2.8% of all PGP 9.5-positive myenteric neurons. Analysis of mRNA showed both TH and DBH transcripts in the mouse esophagus. As ChAT-positive neurons in the compact formation of the nucleus ambiguus were negative for TH, the TH-positive nerve varicosities on motor endplates are presumably of enteric origin, although a sympathetic origin cannot be excluded. In the medulla oblongata, the cholinergic ambiguus neurons were densely supplied with TH-positive varicosities. Thus, catecholamines may modulate vagal motor innervation of esophageal-striated muscles not only at the peripheral level via enteric co-innervation but also at the central level via projections to the nucleus ambiguus. As Parkinson's disease, with a loss of central dopaminergic neurons, also affects the enteric nervous system and dysphagia is prevalent in patients with this disease, investigation of intrinsic catecholamines in the esophagus may be worthwhile to understand such a symptom.

Esophageal motor dysfunction plays a key role in GERD with globus sensation--analysis of factors promoting resistance to PPI therapy.

PubMed

Tsutsui, Hideaki; Manabe, Noriaki; Uno, Masako; Imamura, Hiroshi; Kamada, Tomoari; Kusunoki, Hiroaki; Shiotani, Akiko; Hata, Jiro; Harada, Tamotsu; Haruma, Ken

2012-09-01

Patients with gastroesophageal reflux disease (GERD) also have various extra-esophageal symptoms. Laryngopharyngeal reflux disease (LPRD) is a subtype of GERD associated with globus sensation, but proton pump inhibitor (PPI) therapy achieves disappointing results. This study investigated esophageal motility in GERD patients with globus sensation who were resistant to PPI therapy. The subjects were 350 patients with globus sensation. All patients underwent both laryngoscopy and upper gastrointestinal endoscopy to exclude organic disease. After 4 weeks of treatment with rabeprazole sodium (20 mg daily), the patients were divided into PPI-responsive and PPI-resistant groups. Then we investigated esophageal motility in the PPI-resistant group by a multichannel intraluminal impedance and manometry study. A total of 119 patients (55.6%) were resistant to PPI therapy, among whom 57 patients (47.9%) had abnormal esophageal motility. They included 36 patients (66.4%) with ineffective esophageal motility, 9 patients (14.4%) with achalasia, 6 patients (9.6%) with diffuse esophageal spasm, 5 patients (8%) with nutcracker esophagus, and 1 patient (1.6%) with hypertensive lower esophageal sphincter. There were significant differences of upper esophageal sphincter pressure and esophageal body peristalsis between the patients with PPI-resistant LPRD and healthy controls matched for age and sex. Among patients with PPI-resistant LPRD, 47.9% had abnormal esophageal motility.

Current Status of Peroral Endoscopic Myotomy

PubMed Central

Cho, Young Kwan; Kim, Seong Hwan

2018-01-01

Peroral endoscopic myotomy (POEM) has been established as an optional treatment for achalasia. POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including Botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm, jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, gastric peroral endoscopic pyloromyotomy. POEM has been widely accepted as a treatment for all types of achalasia, even for specific cases such as achalasia with failed prior treatments, and hypertensive motor disorders. PMID:29397656

Current Status of Peroral Endoscopic Myotomy.

PubMed

Cho, Young Kwan; Kim, Seong Hwan

2018-01-01

Peroral endoscopic myotomy (POEM) has been established as an optional treatment for achalasia. POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue first attempted to use POEM for the treatment of achalasia in humans. Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including Botulinum toxin injection, endoscopic balloon dilation, laparoscopic Heller myotomy, and hypertensive motor disorders such as diffuse esophageal spasm, jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, gastric peroral endoscopic pyloromyotomy. POEM has been widely accepted as a treatment for all types of achalasia, even for specific cases such as achalasia with failed prior treatments, and hypertensive motor disorders.

The Role of Esophageal Hypersensitivity in Functional Esophageal Disorders.

PubMed

Farmer, Adam D; Ruffle, James K; Aziz, Qasim

2017-02-01

The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.

Esophageal Sensorimotor Function and Psychological Factors Each Contribute to Symptom Severity in Globus Patients.

PubMed

Rommel, Nathalie; Van Oudenhove, Lukas; Arts, Joris; Caenepeel, Philip; Tack, Jan; Pauwels, Ans

2016-10-01

Altered upper esophageal sphincter (UES) and esophageal body (EB) sensorimotor function and psychosocial factors may both be involved in symptom generation in globus, but their common impact is not yet assessed. The aim of the study is (1) to compare UES and EB sensitivity and compliance of globus patients with healthy controls (HC); (2) to study the association of globus symptom severity (GSS) with UES and EB sensitivity and compliance, UES motor function and psychosocial factors. In 58 globus patients, GSS, somatization, and anxiety disorders were determined using validated questionnaires. In 26 HC and 42/58 patients, UES and EB sensitivity and compliance were assessed twice using barostat measurements. UES function of 27 globus patients was evaluated using high-resolution manometry. Bivariate correlations and a general linear model tested the association of these factors with GSS. UES and EB compliance did not differ between globus patients and HC. Upon repeated distension, UES habituation was seen in both groups, whereas EB sensitization (23.3±1.3 vs. 19.5±1.5 mm Hg, P<0.0001) only occurred in globus patients, (P=0.038). UES compliance (ρ=0.37, P=0.04), change in EB compliance upon repeated distension (ρ=0.45, P=0.007), somatization (ρ=0.43, P=0.003), panic disorder (t=3.04, P=0.004), and post-traumatic stress severity (ρ=0.40, P=0.005) were associated with GSS. UES compliance and somatization were independently associated with GSS. A trend (P=0.061) was found for the association of GSS with change in EB compliance. UES compliance, change in EB compliance, and somatization explain 40% of the variance in GSS. This indicates that globus is a complex disorder of the brain-gut axis rather than a "psychosomatic" disorder or a peripheral esophageal disorder.

An appraisal of current dysphagia diagnosis and treatment strategies.

PubMed

Kaindlstorfer, Adolf; Pointner, Rudolph

2016-08-01

Dysphagia is a common, serious health problem with a wide variety of etiologies and manifestations. This review gives a general overview of diagnostic and therapeutic options for oropharyngeal as well as esophageal swallowing disorders respecting the considerable progress made over recent years. Diagnosis can be challenging and requires expertise in interpretation of symptoms and patient history. Endoscopy, barium radiography and manometry are still the diagnostic mainstays. Classification of esophageal motor-disorders has been revolutionized with the introduction of high-resolution esophageal pressure topography and a new standardized classification algorithm. Automated integrated impedance manometry is a promising upcoming tool for objective evaluation of oropharyngeal dysphagia, in non-obstructive esophageal dysphagia and prediction of post fundoplication dysphagia risk. Impedance planimetry provides new diagnostic information on esophageal and LES-distensibility and allows controlled therapeutic dilatation without the need for radiation. Peroral endoscopic myotomy is a promising therapeutic approach for achalasia and spastic motility disorders.

[Gastric and duodenal secretory and motor-evacuatory activity in patients with gastroesophageal reflux disease associated with different types of reflux].

PubMed

Dzhulay, G S; Sekareva, E V

2016-01-01

To estimate esophageal and gastric pH values on an empty stomach and after stimulation of gastric secretion and gastric and duodenal motor-evacuatory activity in patients with gastroesophageal reflux disease (GERD) associated with pathological refluxes, such as gastroesophageal reflux (GER) and duodenogastroesophageal reflux (DGER). The observational cross-sectional study was conducted to investigate and compare the parameters of intraesophageal and intragastric pH metry and peripheral electrogastroenterography in 103 GERD patients with endoscopically positive distal reflux esophagitis in GER and DGER. The patients with GERD developed pathological esophageal refluxes (both GER and DGER) in various degrees of impaired gastric production, from anacidity to hyperacidity. The patients with predominant DGER were found to have gastric hyperacidity and normal acidity slightly less frequently than those with predominant GER. The patients with GERD developing in the presence of predominant GER had moderate gastric stasis with discoordinated antroduodenal propulsion resulting from hypomotor dyskinesia of the stomach and duodenum. When DGER was predominant in the patients with GERD, the signs of gastric stasis and duodenal hyperkinesia were concurrent with discoordinated antroduodenal and duodenojejunal propulsion. The specific features of the esophagogastroduodenal secretory and motor evacuatory disorders found create conditions for the pathological refluxes into the esophagus, which differ in the composition of refluxate.

Pressure-flow characteristics of normal and disordered esophageal motor patterns.

PubMed

Singendonk, Maartje M J; Kritas, Stamatiki; Cock, Charles; Ferris, Lara F; McCall, Lisa; Rommel, Nathalie; van Wijk, Michiel P; Benninga, Marc A; Moore, David; Omari, Taher I

2015-03-01

To perform pressure-flow analysis (PFA) in a cohort of pediatric patients who were referred for diagnostic manometric investigation. PFA was performed using purpose designed Matlab-based software. The pressure-flow index (PFI), a composite measure of bolus pressurization relative to flow and the impedance ratio, a measure of the extent of bolus clearance failure were calculated. Tracings of 76 pediatric patients (32 males; 9.1 ± 0.7 years) and 25 healthy adult controls (7 males; 36.1 ± 2.2 years) were analyzed. Patients mostly had normal motility (50%) or a category 4 disorder and usually weak peristalsis (31.5%) according to the Chicago Classification. PFA of healthy controls defined reference ranges for PFI ≤142 and impedance ratio ≤0.49. Pediatric patients with pressure-flow (PF) characteristics within these limits had normal motility (62%), most patients with PF characteristics outside these limits also had an abnormal Chicago Classification (61%). Patients with high PFI and disordered motor patterns all had esophagogastric junction outflow obstruction. Disordered PF characteristics are associated with disordered esophageal motor patterns. By defining the degree of over-pressurization and/or extent of clearance failure, PFA may be a useful adjunct to esophageal pressure topography-based classification. Copyright © 2015 Elsevier Inc. All rights reserved.

A fully resolved active musculo-mechanical model for esophageal transport

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

2015-10-01

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multi-layered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function.

A fully resolved active musculo-mechanical model for esophageal transport

PubMed Central

Kou, Wenjun; Bhalla, Amneet Pal Singh; Griffith, Boyce E.; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

2015-01-01

Esophageal transport is a physiological process that mechanically transports an ingested food bolus from the pharynx to the stomach via the esophagus, a multilayered muscular tube. This process involves interactions between the bolus, the esophagus, and the neurally coordinated activation of the esophageal muscles. In this work, we use an immersed boundary (IB) approach to simulate peristaltic transport in the esophagus. The bolus is treated as a viscous fluid that is actively transported by the muscular esophagus, and the esophagus is modeled as an actively contracting, fiber-reinforced tube. Before considering the full model of the esophagus, however, we first consider a standard benchmark problem of flow past a cylinder. Next a simplified version of our model is verified by comparison to an analytic solution to the tube dilation problem. Finally, three different complex models of the multi-layered esophagus, which differ in their activation patterns and the layouts of the mucosal layers, are extensively tested. To our knowledge, these simulations are the first of their kind to incorporate the bolus, the multi-layered esophagus tube, and muscle activation into an integrated model. Consistent with experimental observations, our simulations capture the pressure peak generated by the muscle activation pulse that travels along the bolus tail. These fully resolved simulations provide new insights into roles of the mucosal layers during bolus transport. In addition, the information on pressure and the kinematics of the esophageal wall resulting from the coordination of muscle activation is provided, which may help relate clinical data from manometry and ultrasound images to the underlying esophageal motor function. PMID:26190859

Esophageal perforation due to blunt chest trauma: Difficult diagnosis because of coexisting severe disturbance of consciousness.

PubMed

Mezuki, Satomi; Shono, Yuji; Akahoshi, Tomohiko; Hisanaga, Kana; Saeki, Hiroshi; Nakashima, Yuichiro; Momii, Kenta; Maki, Jun; Tokuda, Kentaro; Maehara, Yoshihiko

2017-11-01

Esophageal perforation due to blunt trauma is a rare clinical condition, and the diagnosis is often difficult because patients have few specific symptoms. Delayed diagnosis may result in a fatal clinical course due to mediastinitis and subsequent sepsis. In this article, we describe a 26-year-old man with esophageal perforation due to blunt chest trauma resulting from a motor vehicle accident. Because a severe disturbance of consciousness masked the patient's trauma-induced thoracic symptoms, we required 11h to diagnose the esophageal perforation. Therefore, the patient developed septic shock due to mediastinitis. However, his subsequent clinical course was good because of prompt combined therapy involving surgical repair and medical treatment after the diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases.

PubMed

Menezes, Mariano A; Herbella, Fernando A M; Patti, Marco G

2016-04-01

Different connective tissue diseases (CTDs), such as dermatomyositis, mixed CTD, rheumatoid arthritis, polymyositis, lupus, and Behçet's, may affect the esophagus, impairing its motor function. The muscular atrophy and fibrosis caused by the autoimmune vasculitis and neuronal dysfunction affect the esophageal body and the lower esophageal sphincter, leading to a clinical presentation of dysphagia and gastroesophageal reflux disease (GERD). The belief that the impaired esophageal motility may negatively affect surgical outcome has led to the common recommendation of avoiding laparoscopic antireflux surgery (LARS) for fear of creating or worsening dysphagia. This review focuses on the evaluation of the outcome of LARS in patients with CTD. Specifically, this review shows that the literature on LARS and CTDs is scarce and most studies have a small number of patients and a short follow-up. Furthermore, a subanalysis of the outcome based on the type of CTD or the manometric profile is still elusive. In the setting of these limitations, it appears that results are good and comparable to those of patients with GERD and without a CTD. Morbidity and mortality are insignificant even considering the systemic manifestations of the CTD. LARS should not be denied to patients with CTD and GERD.

Novel association of achalasia with hereditary sensory and motor neuropathy with sensorineural deafness.

PubMed

Asthana, A K; Lubel, J S; Kohn, G P

2016-08-01

Achalasia is a primary esophageal motility disorder. Unlike diffuse esophageal spasm, it has not previously been described in association with hereditary sensory and motor neuropathy (HSMN). An 18-year-old-male with HSMN with sensorineural deafness presented with a 2-day history of dysphagia to solids and liquids. Achalasia was diagnosed after extensive investigations, and his symptoms resolved with endoscopic and definitive surgical management. His monozygotic twin brother had also been diagnosed with HSMN and suffered from chronic dysphagia, which was also subsequently diagnosed with achalasia. This is the first case to illustrate an association between HSMN with sensorineural deafness and achalasia. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

The Chicago classification of motility disorders: an update.

PubMed

Roman, Sabine; Gyawali, C Prakash; Xiao, Yinglian; Pandolfino, John E; Kahrilas, Peter J

2014-10-01

The Chicago Classification defines esophageal motility disorders in high resolution manometry. This is based on individual scoring of 10 swallows performed in supine position. Disorders of esophago-gastric junction (EGJ) outflow obstruction are defined by a median integrated relaxation pressure above the limit of normal and divided into 3 achalasia subtypes and EGJ outflow obstruction. Major motility disorders (aperistalsis, distal esophageal spasm, and hypercontractile esophagus) are patterns not encountered in controls in the context of normal EGJ relaxation. Finally with the latest version of the Chicago Classification, only two minor motor disorders are considered: ineffective esophageal motility and fragmented peristalsis. Copyright © 2014 Elsevier Inc. All rights reserved.

High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion.

PubMed

Liu, Xinyang; Wang, Zhichao; Zhang, Guoliang; Zhu, Qikun; Zeng, Hui; Wang, Tao; Gao, Feng; Qi, Zhan; Zhang, Jinwen; Wang, Rui

2017-04-14

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

Evaluation and management of esophageal manifestations in systemic sclerosis.

PubMed

Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

Evaluation and management of esophageal manifestations in systemic sclerosis

PubMed Central

Denaxas, Konstantinos; Ladas, Spyros D.; Karamanolis, George P.

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities. PMID:29507463

Relationship between esophageal clinical symptoms and manometry findings in patients with esophageal motility disorders: a cross-sectional study.

PubMed

FakhreYaseri, Hashem; FakhreYaseri, Ali Mohammad; Baradaran Moghaddam, Ali; Soltani Arabshhi, Seyed Kamran

2015-01-01

Manometry is the gold-standard diagnostic test for motility disorders in the esophagus. The development of high-resolution manometry catheters and software displays of manometry recordings in color-coded pressure plots have changed the diagnostic assessment of esophageal disease. The diagnostic value of particular esophageal clinical symptoms among patients suspected of esophageal motor disorders (EMDs) is still unknown. The aim of this study was to explore the sensitivity, specificity, and predictive accuracy of presenting esophageal symptoms between abnormal and normal esophageal manometry findings. We conducted a cross-sectional study of 623 patients aged 11-80 years. Data were collected from clinical examinations as well as patient questionnaires. The sensitivity, specificity, and accuracy were calculated after high-resolution manometry plots were reviewed according to the most recent Chicago Criteria. The clinical symptoms were not sensitive enough to discriminate between EMDs. Nevertheless, dysphagia, noncardiac chest pain, hoarseness, vomiting, and weight loss had high specificity and high accuracy to distinguish EMDs from normal findings. Regurgitation and heartburn did not have good accuracy for the diagnosis of EMDs. Clinical symptoms are not reliable enough to discriminate between EMDs. Clinical symptoms can, however, discriminate between normal findings and EMDs, especially achalasia.

Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function.

PubMed

Shi, Huijuan; Shi, Dongxuan; Wu, Yansong; Shen, Qiang; Li, Jing

2016-09-28

Qigesan (QGS), a well-known traditional Chinese medicinal formula, has long been used to treat patients with esophageal cancer. However, the anticancer mechanisms of action of QGS remain unknown. This study aims to determine whether QGS regulates gap junction (GJ) function and affects the invasiveness of esophageal cancer cells. Our results demonstrate that QGS markedly inhibits the migration and invasion of esophageal cancer cells in vitro. We further show that QGS enhances the function of GJ in esophageal cancer cells. We therefore hypothesized that enhanced connexin expression leads to enhanced GJ function and inhibition of metastasis. We found that QGS enhances expression of connexin 26 and connexin 43 in esophageal cancer cells. This study suggests that QGS increases GJ function via enhancing the expression of connexins, resulting in reduced esophageal cancer cell migration and invasion. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of two high-resolution manometry software systems in evaluating esophageal motor function.

PubMed

Rengarajan, A; Drapekin, J; Patel, A; Gyawali, C P

2016-12-01

High-resolution manometry (HRM) utilizes software tools to diagnose esophageal motor disorders. Performance of these software metrics could be affected by averaging and by software characteristics of different manufacturers. High-resolution manometry studies on 86 patients referred for antireflux surgery (61.6 ± 1.4 year, 70% F) and 20 healthy controls (27.9 ± 0.7 year, 45% F) were first subject to standard analysis (Medtronic, Duluth, GA, USA). Coordinates for each of 10 test swallows were exported and averaged to generate a composite swallow. The swallows and averaged composites were imported as ASCII file format into Manoview (Medtronic) and Medical Measurement Systems database reporter (MMS, Dover, NH, USA), and analyses repeated. Comparisons were made between standard and composite swallow interpretations. Correlation between the two systems was high for mean distal contractile integral (DCI, r 2 ≥ 0.9) but lower for integrated relaxation pressure (IRP, r 2 = 0.7). Excluding achalasia, six patients with outflow obstruction (mean IRP 23.2 ± 2.1 with 10-swallow average) were identified by both systems. An additional nine patients (10.5%) were identified as outflow obstruction (15 mmHg threshold) with MMS 10-swallow and four with MMS composite swallow evaluation; only one was confirmed. Ineffective esophageal motility was diagnosed by 10-swallow evaluation in 19 (22.1%) with Manoview, and 20 (23.3%) with MMS. On Manoview composite, 17 had DCI <450 mmHg/cm/s, and on MMS composite, 21, (p ≥ 0.85 for each comparison) but these did not impact diagnostic conclusions. Comparison of 10 swallow and composite swallows demonstrate variability in software metrics between manometry systems. Our data support use of manufacturer specific software metrics on 10-swallow sequences. © 2016 John Wiley & Sons Ltd.

A physiological model for the investigation of esophageal motility in healthy and pathologic conditions.

PubMed

Carniel, Emanuele Luigi; Frigo, Alessandro; Costantini, Mario; Giuliani, Tommaso; Nicoletti, Loredana; Merigliano, Stefano; Natali, Arturo N

2016-07-15

Recent technological advances in esophageal manometry allowed the definition of new classification methods for the diagnosis of disorders of esophageal motility and the implementation of innovative computational tools for the autonomic, reliable and unbiased detection of different disorders. Computational models can be developed aiming to interpret the mechanical behavior and functionality of the gastrointestinal tract and to summarize the results from clinical measurements, as high-resolution manometry pressure plots, into model parameters. A physiological model was here developed to interpret data from esophageal high-resolution manometry. Such model accounts for parameters related to specific physiological properties of the biological structures involved in the peristaltic mechanism. The identification of model parameters was performed by minimizing the discrepancy between clinical data from high-resolution manometry and model results. Clinical data were collected from both healthy volunteers (n = 35) and patients with different motor disorders, such as achalasia patterns 1 (n = 13), 2 (n = 20) and 3 (n = 5), distal esophageal spasm (n = 69), esophago-gastric junction outflow obstruction (n = 25), nutcracker esophagus (n = 11) and normal motility (n = 42). The physiological model that was formulated in this work can properly explain high-resolution manometry data, as confirmed by the evaluation of the coefficient of determination R 2  = 0.83 - 0.96. The study finally led to identify the statistical distributions of model parameters for each healthy or pathologic conditions considered, addressing the applicability of the achieved results for the implementation of autonomic diagnosis procedures to support the medical staff during the traditional diagnostic process. © IMechE 2016.

Ineffective esophageal motility phenotypes following fundoplication in gastroesophageal reflux disease.

PubMed

Mello, M D; Shriver, A R; Li, Y; Patel, A; Gyawali, C P

2016-02-01

Ineffective esophageal motility (IEM) is associated with reflux disease, but its natural history is unclear. We evaluated patients undergoing repeat esophageal high resolution manometry (HRM) for symptomatic presentations after antireflux surgery (ARS) to understand the progression of IEM. Patients with repeat HRM after ARS were included. Ineffective esophageal motility was diagnosed if ≥5 sequences had distal contractile integral (DCI) <450 mmHg cm s. Augmentation of DCI following multiple rapid swallows (MRS) was assessed. The esophagogastric junction (EGJ) was interrogated using the EGJ contractile integral (EGJ-CI). Esophageal motor function was compared between patients with and without IEM. Sixty-eight patients (53.9 ± 1.8 years, 66.2% female) had pre- and post-ARS HRM studies 2.1 ± 0.19 years apart. Esophagogastric junction-CI augmented by a mean of 26.3% following ARS. Four IEM phenotypes were identified: 14.7% had persistent IEM, 8.8% resolved IEM after ARS, 19.1% developed new IEM, and 57.4% had no IEM at any point. Patients with IEM had a lower DCI pre- and post-ARS, lower pre-ARS EGJ CI, and lower pre-ARS-integrated relaxation pressure (p ≤ 0.02 for all comparisons); presenting symptoms and other EGJ metrics were similar (p ≥ 0.08 for all comparisons). The IEM phenotypes could be predicted by MRS DCI response patterns (p = 0.008 across groups); patients with persistent IEM had the least DCI augmentation (p = 0.007 compared to no IEM), while those who resolved IEM had DCI augmentation comparable to no IEM (p = 0.08). Distinct phenotypes of IEM exist among symptomatic reflux patients following ARS. Provocative testing with MRS may help identify these phenotypes pre-ARS. © 2015 John Wiley & Sons Ltd.

Reflux Hypersensitivity: A New Functional Esophageal Disorder.

PubMed

Yamasaki, Takahisa; Fass, Ronnie

2017-10-30

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients' heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity.

Hypertrophy of the muscularis propria of the lower esophageal sphincter and the body of the esophagus in patients with primary motility disorders of the esophagus.

PubMed

Mittal, Ravinder K; Kassab, Ghassan; Puckett, James L; Liu, Jianmin

2003-08-01

Patients with diffuse esophageal spasm (DES) and nutcracker esophagus/high amplitude esophageal contraction (HAEC) have a thicker esophageal muscularis propria than do healthy subjects. The goals of this study were to determine the esophageal muscle cross-sectional area (MCSA), a measure of muscle mass, in patients with achalasia of the esophagus; and to compare it with that in patients with DES, patients with HAEC, and normal subjects. Using a high-frequency ultrasound probe catheter, concurrent manometry and ultrasound images of the esophagus were recorded in four subject groups: normal volunteers, patients with HAEC, patients with DES, and patients with achalasia of the esophagus. Recordings were obtained from the lower esophageal sphincter (LES) and multiple sites in the esophagus 2, 4, 6, 8, and 10 cm above the LES. The LES and esophageal muscle thickness as well as esophageal MCSA were greater in all three patient groups than in the normal subject group. Muscle thickness and MCSA were observed to be greatest in patients with achalasia, which were greater than in patients with DES, which were greater than in those with HAEC, which in turn were greater than in normal subjects. We propose that an increase in the MCSA is an important feature of patients with primary motility disorders of the esophagus. The degree of increase in muscle mass may be an important determinant of the type and the severity of esophageal motor dysfunction.

Multiple huge epiphrenic esophageal diverticula with motility disease treated with video-assisted thoracoscopic and hand-assisted laparoscopic esophagectomy: a case report.

PubMed

Taniguchi, Yoshiki; Takahashi, Tsuyoshi; Nakajima, Kiyokazu; Higashi, Shigeyoshi; Tanaka, Koji; Miyazaki, Yasuhiro; Makino, Tomoki; Kurokawa, Yukinori; Yamasaki, Makoto; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-12-01

Epiphrenic esophageal diverticulum is a rare condition that is often associated with a concomitant esophageal motor disorder. Some patients have the chief complaints of swallowing difficulty and gastroesophageal reflux; traditionally, such diverticula have been resected via right thoracotomy. Here, we describe a case with huge multiple epiphrenic diverticula with motility disorder, which were successfully resected using a video-assisted thoracic and laparoscopic procedure. A 63-year-old man was admitted due to dysphagia, heartburn, and vomiting. An esophagogram demonstrated an S-shaped lower esophagus with multiple epiphrenic diverticula (75 × 55 mm and 30 × 30 mm) and obstruction by the lower esophageal sphincter (LES). Esophageal manometry showed normal peristaltic contractions in the esophageal body, whereas the LES pressure was high (98.6 mmHg). The pressure vector volume of LES was 23,972 mmHg 2  cm. Based on these findings, we diagnosed huge multiple epiphrenic diverticula with a hypertensive lower esophageal sphincter and judged that resection might be required. We performed lower esophagectomy with gastric conduit reconstruction using a video-assisted thoracic and hand-assisted laparoscopic procedure. The postoperative course was uneventful, and the esophagogram demonstrated good passage, with no leakage, stenosis, or diverticula. The most common causes of mid-esophageal and epiphrenic diverticula are motility disorders of the esophageal body; appropriate treatment should be considered based on the morphological and motility findings.

Effects of pacifier and taste on swallowing, esophageal motility, transit, and respiratory rhythm in human neonates.

PubMed

Shubert, T R; Sitaram, S; Jadcherla, S R

2016-04-01

Pacifier use is widely prevalent globally despite hygienic concerns and uncertain mechanistic effects on swallowing or airway safety. The effects of pacifier and taste interventions on pharyngo-esophageal motility, bolus transit, and respiratory rhythms were investigated by determining the upper esophageal sphincter (UES), esophageal body, esophagogastric junction (EGJ) motor patterns and deglutition apnea, respiratory rhythm disturbances, and esophageal bolus clearance. Fifteen infants (six males; median gestation 31 weeks and birth weight 1.4 kg) underwent high-resolution impedance manometry at 43 (41-44) weeks postmenstrual age. Manometric, respiratory, and impedance characteristics of spontaneous swallows, pacifier-associated dry swallowing and taste (pacifier dipped in 3% sucrose)-associated swallowing were analyzed. Linear mixed and generalized estimating equation models were used. Data are presented as mean ± SEM, %, or median (IQR). Pharyngo-esophageal motility, respiratory, and impedance characteristics of 209 swallows were analyzed (85 spontaneous swallows, 63 pacifier- swallows, 61 taste- swallows). Basal UES and EGJ pressures decreased upon pacifier (p < 0.05) and taste interventions (p < 0.05); however, esophageal motility, respiratory rhythm, and impedance transit characteristics were similar with both interventions. Oral stimulus with pacifier or taste interventions decreases UES and EGJ basal pressure, but has no effects on pharyngo-esophageal motility, airway interactions, or esophageal bolus transit. A decrease in central parasympathetic-cholinergic excitatory drive is likely responsible for the basal effects. © 2016 John Wiley & Sons Ltd.

Progression of diffuse esophageal spasm to achalasia: incidence and predictive factors.

PubMed

Fontes, L H S; Herbella, F A M; Rodriguez, T N; Trivino, T; Farah, J F M

2013-07-01

The progression of certain primary esophageal motor disorders to achalasia has been documented; however, the true incidence of this decay is still elusive. This study aims to evaluate: (i) the incidence of the progression of diffuse esophageal spasm to achalasia, and (ii) predictive factors to this progression. Thirty-five patients (mean age 53 years, 80% females) with a manometric picture of diffuse esophageal spasm were followed for at least 1 year. Patients with gastroesophageal reflux disease confirmed by pH monitoring or systemic diseases that may affect esophageal motility were excluded. Esophageal manometry was repeated in all patients. Five (14%) of the patients progressed to achalasia at a mean follow-up of 2.1 (range 1-4) years. Demographic characteristics were not predictive of transition to achalasia, while dysphagia (P= 0.005) as the main symptom and the wave amplitude of simultaneous waves less than 50 mmHg (P= 0.003) were statistically significant. In conclusion, the transition of diffuse esophageal spasm to achalasia is not frequent at a 2-year follow-up. Dysphagia and simultaneous waves with low amplitude are predictive factors for this degeneration. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Reflux Hypersensitivity: A New Functional Esophageal Disorder

PubMed Central

Yamasaki, Takahisa; Fass, Ronnie

2017-01-01

Reflux hypersensitivity, recently introduced by Rome IV as a new functional esophageal disorder, is currently considered as the presence of typical heartburn symptoms in patients with normal upper endoscopy and esophageal biopsies, normal esophageal pH test and with evidence of a close correlation between patients’ heartburn and reflux events. Reflux hypersensitivity is very common and together with functional heartburn accounts for more than 90% of the heartburn patients who failed treatment with proton pump inhibitor twice daily. In addition, reflux hypersensitivity affects primarily young to middle aged women, commonly overlaps with another functional gastrointestinal disorders, and is often associated with some type of psychological comorbidity. Diagnosis is made by using endoscopy with esophageal biopsies, pH-impedance, and high-resolution esophageal manometry. Reflux hypersensitivity is primarily treated with esophageal neuromodulators, such as tricyclic anti-depressants and selective serotonin reuptake inhibitors among others. Surgical anti-reflux management may also play an important role in the treatment of reflux hypersensitivity. PMID:28992673

patients

PubMed

Hernández-Mondragón, Oscar Víctor; Solórzano-Pineda, Omar Michel; Blancas-Valencia, Juan Manuel; González-Martínez, Marina Alejandra

2017-01-01

Esophageal achalasia is a primary motor disorder of the esophagus characterized by impair relaxation of the lower esophageal sphincter and absent of esophageal peristalsis. Per-oral endoscopic myotomy is an alternative treatment to surgical Heller myotomy in patients over 65 years old. The aim of this paper was to describe the results of peroral endoscopic myotomy (POEM) or the treatment of achalasia in geriatric patients. We included patients over 65 years old with POEM, from retrospective cohort review, in which POEM was performed with a standardized technique in our department. 12 patients were included, the procedure was successful in 98% of patients, minor adverse events occurred without mortality. POEM is a safe and effective technique for the treatment of achalasia, the results of the study are similar to those reported in The literature.

The role of Heller myotomy and POEM for nonachalasia motility disorders.

PubMed

Schlottmann, F; Shaheen, N J; Madanick, R D; Patti, M G

2017-04-01

The best-defined primary esophageal motor disorder is achalasia. However, symptoms such as dysphagia, regurgitation and chest pain can be caused by other esophageal motility disorders such as Diffuse Esophageal Spasm (DES), Nutcracker Esophagus (NE) and the Hypertensive Lower Esophageal Sphincter (HTN-LES). Most patients with DES and HTN-LES who complain of dysphagia improve after a myotomy. Patients with NE whose main complaint is chest pain, often do not have relief of the pain and can even develop dysphagia as a consequence of the myotomy. POEM is a relatively new procedure, and there are no studies with long-term follow-up and no prospective and randomized trials comparing it to surgical myotomy. Overall, the key to success is based on a complete evaluation and a careful patient selection. The best results, regardless of the technique, are in fact obtained in patients with outflow obstruction and impaired esophageal emptying, a picture similar to achalasia. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Abnormal cerebral functional connectivity in esophageal cancer patients with theory of mind deficits in resting state.

PubMed

Cao, Yin; Xiang, JianBo; Qian, Nong; Sun, SuPing; Hu, LiJun; Yuan, YongGui

2015-01-01

To explore the function of the default mode network (DMN) in the psychopathological mechanisms of theory of mind deficits in patients with an esophageal cancer concomitant with depression in resting the state. Twenty-five cases of esophageal cancer with theory of mind deficits (test group) that meet the diagnostic criteria of esophageal cancer and neuropsychological tests, including Beck depression inventory, reading the mind in the eyes, and Faux pas, were included, Another 25 cases of esophageal cancer patients but without theory of mind deficits (control group) were enrolled. Each patient completed a resting-state functional magnetic resonance imaging. The functional connectivity intensities within the cerebral regions in the DMN of all the enrolled patients were analyzed. The results of each group were compared. The functional connectivity of the bilateral prefrontal central region with the precuneus, bilateral posterior cingulate gyrus and bilateral ventral anterior cingulate gyrus in the patients of the test group were all reduced significantly (P < 0.05). In the resting state, the functional connectivity is abnormal in the cerebral regions in the DMN of esophageal cancer patients with theory of mind deficits. The theory of mind deficits might have an important function in the pathogenesis of esophageal cancer.

Functional heartburn: definition and management strategies.

PubMed

Zerbib, Frank; Bruley des Varannes, Stanislas; Simon, Mireille; Galmiche, Jean Paul

2012-06-01

Functional heartburn (FH) is a functional gastro-intestinal disorder characterized by symptoms of heartburn not related to gastro-esophageal reflux. The absence of evidence of reflux-related symptoms relies on absence of esophagitis at endoscopy (including biopsies to exclude eosinophilic esophagitis), a normal esophageal acid exposure during esophageal pH-monitoring together with a negative symptom-reflux association analysis and an unsatisfactory response to proton pump inhibitor therapy. Addition of impedance measurement to pH-monitoring is likely to increase the number of patients with recognized reflux-related symptoms. The pathophysiology of functional heartburn remains largely unknown but involves disturbed esophageal perception and psychological factors such as depression, anxiety and somatization. The treatment of FH remains largely empirical and an individual approach is therefore recommended. The clinician should provide reassurance and refrain from performing too many invasive tests or therapeutic procedures. The use of pain modulators is recommended by most experts despite the lack of appropriate clinical trials to support it.

[Long-term result of total versus partial fundoplication following esophagomyotomy for primary esophageal motor disorders].

PubMed

Zhu, Zi-jiang; Chen, Long-qi; Duranceau, Andre

2008-02-15

To compare the long-term results of total and partial fundoplication on esophagus myotomy. From January 1978 to October 1998, 64 patients with achalasia or diffuse esophageal spasm underwent esophagomyotomy and antireflux operation via left thoracotomy. Twenty-one patients underwent Nissen total fundoplication (Nissen group) and 43 patients underwent Belsey Marker IV partial fundoplication (Belsey group). Clinical, radiologic, radionuclide transit, manometric, 24-hour pH monitoring and endoscopic assessments were performed before and after the operation. There was no operative death and major complications for either group. At over 6 years follow-up and compared to Belsey group, patients in Nissen group revealed a higher frequency of dysphagia (P = 0.025) and more radionuclide material retention (P = 0.044). Both operative procedures reduced the lower esophageal sphincter pressure gradient. However, in Nissen group, the esophageal diameter observed on radiology was significantly increased from 3.9 cm preoperatively to 5.5 cm postoperatively (P = 0.012), while it kept the same for Belsey group (from 5.4 to 5.3 cm, P = 0.695). Reoperation in order to relieve the recurrent dysphagia and esophageal obstruction was performed on 8 patients in Nissen group and 1 in Belsey group (P < 0.01). When treating achalasia or diffuse esophageal spasm by esophageal myotomy and an antireflux operation, a total fundoplication is not appropriate, whereas a partial fundoplication provides proper antireflux effect without significant esophageal emptying difficulty.

Anxiety can significantly explain bolus perception in the context of hypotensive esophageal motility: Results of a large multicenter study in asymptomatic individuals.

PubMed

Cisternas, D; Scheerens, C; Omari, T; Monrroy, H; Hani, A; Leguizamo, A; Bilder, C; Ditaranto, A; Ruiz de León, A; Pérez de la Serna, J; Valdovinos, M A; Coello, R; Abrahao, L; Remes-Troche, J; Meixueiro, A; Zavala, M A; Marin, I; Serra, J

2017-09-01

Previous studies have not been able to correlate manometry findings with bolus perception. The aim of this study was to evaluate correlation of different variables, including traditional manometric variables (at diagnostic and extreme thresholds), esophageal shortening, bolus transit, automated impedance manometry (AIM) metrics and mood with bolus passage perception in a large cohort of asymptomatic individuals. High resolution manometry (HRM) was performed in healthy individuals from nine centers. Perception was evaluated using a 5-point Likert scale. Anxiety was evaluated using Hospitalized Anxiety and Depression scale (HAD). Subgroup analysis was also performed classifying studies into normal, hypotensive, vigorous, and obstructive patterns. One hundred fifteen studies were analyzed (69 using HRM and 46 using high resolution impedance manometry (HRIM); 3.5% swallows in 9.6% of volunteers were perceived. There was no correlation of any of the traditional HRM variables, esophageal shortening, AIM metrics nor bolus transit with perception scores. There was no HRM variable showing difference in perception when comparing normal vs extreme values (percentile 1 or 99). Anxiety but not depression was correlated with perception. Among hypotensive pattern, anxiety was a strong predictor of variance in perception (R 2 up to .70). Bolus perception is less common than abnormal motility among healthy individuals. Neither esophageal motor function nor bolus dynamics evaluated with several techniques seems to explain differences in bolus perception. Different mechanisms seem to be relevant in different manometric patterns. Anxiety is a significant predictor of bolus perception in the context of hypotensive motility. © 2017 John Wiley & Sons Ltd.

Ineffective esophageal motility and the vagus: current challenges and future prospects

PubMed Central

Chen, Ji-Hong

2016-01-01

Ineffective esophageal motility (IEM) is characterized by low to very low amplitude propulsive contractions in the distal esophagus, hence primarily affecting the smooth muscle part of the esophagus. IEM is often found in patients with dysphagia or heartburn and is commonly associated with gastroesophageal reflux disease. IEM is assumed to be associated with ineffective bolus transport; however, this can be verified using impedance measurements or evaluation of a barium coated marshmallow swallow. Furthermore, water swallows may not assess accurately the motor capabilities of the esophagus, since contraction amplitude is strongly determined by the size and consistency of the bolus. The “peristaltic reserve” of the esophagus can be evaluated by multiple rapid swallows that, after a period of diglutative inhibition, normally give a powerful peristaltic contraction suggestive of the integrity of neural orchestration and smooth muscle action. The amplitude of contraction is determined by a balance between intrinsic excitatory cholinergic, inhibitory nitrergic, as well as postinhibition rebound excitatory output to the musculature. This is strongly influenced by vagal efferent motor neurons and this in turn is influenced by vagal afferent neurons that send bolus information to the solitary nucleus where programmed activation of the vagal motor neurons to the smooth muscle esophagus is initiated. Solitary nucleus activity is influenced by sensory activity from a large number of organs and various areas of the brain, including the hypothalamus and the cerebral cortex. This allows interaction between swallowing activities and respiratory and cardiac activities and allows the influence of acute and chronic emotional states on swallowing behavior. Interstitial cells of Cajal are part of the sensory units of vagal afferents, the intramuscular arrays, and they provide pacemaker activity to the musculature that can generate peristalsis in the absence of innervation. This indicates that a low-amplitude esophageal contraction, observed as IEM, can be caused by a multitude of factors, and therefore many pathways can be potentially explored to restore normal esophageal peristalsis. PMID:27703389

Ineffective esophageal motility and the vagus: current challenges and future prospects.

PubMed

Chen, Ji-Hong

2016-01-01

Ineffective esophageal motility (IEM) is characterized by low to very low amplitude propulsive contractions in the distal esophagus, hence primarily affecting the smooth muscle part of the esophagus. IEM is often found in patients with dysphagia or heartburn and is commonly associated with gastroesophageal reflux disease. IEM is assumed to be associated with ineffective bolus transport; however, this can be verified using impedance measurements or evaluation of a barium coated marshmallow swallow. Furthermore, water swallows may not assess accurately the motor capabilities of the esophagus, since contraction amplitude is strongly determined by the size and consistency of the bolus. The "peristaltic reserve" of the esophagus can be evaluated by multiple rapid swallows that, after a period of diglutative inhibition, normally give a powerful peristaltic contraction suggestive of the integrity of neural orchestration and smooth muscle action. The amplitude of contraction is determined by a balance between intrinsic excitatory cholinergic, inhibitory nitrergic, as well as postinhibition rebound excitatory output to the musculature. This is strongly influenced by vagal efferent motor neurons and this in turn is influenced by vagal afferent neurons that send bolus information to the solitary nucleus where programmed activation of the vagal motor neurons to the smooth muscle esophagus is initiated. Solitary nucleus activity is influenced by sensory activity from a large number of organs and various areas of the brain, including the hypothalamus and the cerebral cortex. This allows interaction between swallowing activities and respiratory and cardiac activities and allows the influence of acute and chronic emotional states on swallowing behavior. Interstitial cells of Cajal are part of the sensory units of vagal afferents, the intramuscular arrays, and they provide pacemaker activity to the musculature that can generate peristalsis in the absence of innervation. This indicates that a low-amplitude esophageal contraction, observed as IEM, can be caused by a multitude of factors, and therefore many pathways can be potentially explored to restore normal esophageal peristalsis.

Recovery of normal esophageal function in a kitten with diffuse megaesophagus and an occult lower esophageal stricture.

PubMed

Schneider, Jaycie; Ames, Marisa; DiCicco, Michael; Savage, Mason; Atkins, Clarke; Wood, Michael; Gookin, Jody L

2015-06-01

An 8-week-old male domestic shorthair was presented to the Internal Medicine Service at North Carolina State University for regurgitation. Radiographic diagnosis of generalized esophageal dilation and failure of esophageal peristalsis were compatible with diagnosis of congenital megaesophagus. Endoscopic examination of the esophagus revealed a fibrous stricture just orad to the lower esophageal sphincter. Conservative management to increase the body condition and size of the kitten consisted of feeding through a gastrostomy tube, during which time the esophagus regained normal peristaltic function, the stricture orifice widened in size and successful balloon dilatation of the stricture was performed. Esophageal endoscopy should be considered to rule out a stricture near the lower esophageal sphincter in kittens with radiographic findings suggestive of congenital megaesophagus. Management of such kittens by means of gastrostomy tube feeding may be associated with a return of normal esophageal motility and widening of the esophageal stricture, and facilitate subsequent success of interventional dilation of the esophageal stricture. © ISFM and AAFP 2014.

Prosthetic rehabilitation in patient with achalasia cardia — A rare case report

PubMed Central

Kondaka, Sudheer; Rao, Bathala L.; Reddy, Juturi R.; Akula, Rajesh

2016-01-01

Achalasia Cardia is an idiopathic esophageal motor disorder distinguished by the loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter. The oral manifestation of the disease is dental erosion caused by the regurgitation of the gastric contents and vomiting. A female patient aged 14 years reported to the Department of Prosthodontics, Lenora Institute of Dental Sciences, with complaints concerning aesthetics and pain in relation to several teeth. Patient gave history of loss of tooth structure over the past few years with associated sensitivity and pain in several teeth. Patient also gave history of inability to consume sufficient amount of food owing to the repeated vomiting. This paper aims to present a rare case report of achalasia cardia by rehabiliting the remaining teeth with overlay denture. PMID:27583229

[Functional methods of the esophagus examination].

PubMed

Valitova, E R; Bordin, D S; Ianova, O B; Vasnev, O S; Masharova, A A

2010-01-01

Manometry of the esophagus is the "gold standard" in diagnosing diseases of the esophagus associated with motor disorders. The combination of manometry with impedance gives an indication of violation of bolus transport along the esophagus. High resolution manometry is new method that provides the most accurate information about the functional anatomy of the esophagus and its sphincters, as well as accurately characterizes the esophageal-gastric junction. We can increase the diagnostic value of daily pH-monitoring by analyzing communication with reflux symptoms. The combination of pH and impedance can identify different types of reflux (acid, sour, gas, liquid and mixed) in patients with symptoms of GERD and related Ahil, after gastric resection in children and infants, to evaluate the effectiveness of antireflux therapy.

Minimally invasive surgery for esophageal achalasia.

PubMed

Chen, Huan-Wen; Du, Ming

2016-07-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow's relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia.

Minimally invasive surgery for esophageal achalasia

PubMed Central

Chen, Huan-Wen

2016-01-01

Esophageal achalasia is due to the esophagus of neuromuscular dysfunction caused by esophageal functional disease. Its main feature is the lack of esophageal peristalsis, the lower esophageal sphincter pressure and to reduce the swallow’s relaxation response. Lower esophageal muscular dissection is one of the main ways to treat esophageal achalasia. At present, the period of muscular layer under the thoracoscope esophagus dissection is one of the treatment of esophageal achalasia. Combined with our experience in minimally invasive esophageal surgery, to improved incision and operation procedure, and adopts the model of the complete period of muscular layer under the thoracoscope esophagus dissection in the treatment of esophageal achalasia. PMID:27499977

The course of lung inflation alters the central pattern of tracheobronchial cough in cat-The evidence for volume feedback during cough.

PubMed

Poliacek, Ivan; Simera, Michal; Veternik, Marcel; Kotmanova, Zuzana; Pitts, Teresa; Hanacek, Jan; Plevkova, Jana; Machac, Peter; Visnovcova, Nadezda; Misek, Jakub; Jakus, Jan

2016-07-15

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered (via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CTI), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered (via the ventilator) during the first half of inspiratory period (at CTI/2-early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CTI, and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CTE1). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CTE1, the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing. Copyright © 2016. Published by Elsevier B.V.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

PubMed

Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

2017-12-16

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Esophageal manometry findings and degree of acid exposure in short and long Barrett's esophagus.

PubMed

Helman, Laura; Biccas, Beatriz Nunes; Lemme, Eponina M O; Novais, Paula; Fittipaldi, Viviane

2012-01-01

Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (<3 cm - SSBE) or long-segment (>3 cm - LSSBE). It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. Barrett's esophagus patients identified by upper endoscopy and confirmed by histopathology were, retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter basal pressure, prevalence of esophageal body abnormalities and acid exposure times were evaluated. Forty-six patients with SSBE (24 males - 52.2%, mean age of 55.2 years) and 28 patients with LSBE (18 males - 64.3%, mean age of 50.5 years). Mean symptom duration was 9.9 years for SSBE and 12.9 years for LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE 34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%, LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE 0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any of these values (P<0.05). Average % total time pH<4 in SSBE 9.12, LSBE 17.27 (P<0.000); % time pH<4 upright in SSBE 11.91; LSBE 24.29 (P=0.003); % time pH<4 supine in SSBE 10.86, LSBE 33.26 (P = 0.000). There was no difference between the prevalence of motor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.

Diagnosis and management of esophageal achalasia.

PubMed

Stavropoulos, Stavros N; Friedel, David; Modayil, Rani; Parkman, Henry P

2016-09-13

Achalasia is a rare esophageal motility disorder that is usually idiopathic in origin. It is characterized by dysphagia, and patients often have chest pain, regurgitation, weight loss, and an abnormal barium radiograph showing esophageal dilation with narrowing at the gastroesophageal junction. Abnormal or absent esophageal peristalsis and impaired relaxation of the lower esophageal sphincter (LES) are typically seen on esophageal manometry. The advent of high resolution manometry (HRM) has allowed more precise diagnosis of achalasia, subtype designation, and differentiation from other esophageal motor disorders with an initial seminal publication in 2008 followed by further refinements of what has been termed the Chicago classification. Potential treatments include drugs, endoscopic botulinum toxin injection, balloon dilation, traditional surgery (usually laparoscopic Heller myotomy; LHM), and a novel, less invasive, natural orifice transluminal endoscopic surgery (NOTES) approach to Heller myotomy termed peroral endoscopic myotomy (POEM). The first human POEM was performed in 2008, with the first publication appearing in 2010 and evidence now rapidly accumulating showing POEM to be comparable to traditional surgery in terms of clinical success and radiologic and manometric post-therapy outcomes. This review discusses the diagnosis and management of achalasia with particular emphasis on the recent developments of HRM and POEM, which arguably represent the most important advances in the field since the advent of laparoscopic Heller myotomy in the 1990s. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The effect of water bolus temperature on esophageal motor function as measured by high-resolution manometry.

PubMed

Choi, Y J; Park, M I; Park, S J; Moon, W; Kim, S E; Kwon, H J; Kim, J H; Jeon, W S

2014-11-01

Ingestion of cold fluids may induce pain in patients with esophageal motility disorders. Hot fluids, on the other hand, may help to relieve pain. We studied changes in esophageal motility as a variable of water bolus temperature using high-resolution manometry (HRM) in healthy human. Thirty-two healthy subjects were recruited at Kosin University Hospital. HRM was performed in a sitting position, with room temperature (RT, 25 °C), hot (45 °C), and cold (2 °C) water swallowed in that order. This exam included single swallowing (10 swallows of 5 mL water, 30 s intervals) and multiple water swallows (MWS; 100 mL water within 30 s). In the single swallowing, hot water caused a decrease in lower esophageal sphincter (LES) residual pressure (5.87 ± 4.20 mmHg vs 7.45 ± 4.17 mmHg (RT), p = 0.001) and duration of esophageal body (EB) contraction (3.01 ± 0.80 s vs 3.15 ± 1.16 s (RT), p = 0.009). Cold water caused an increase in the duration of EB contraction (3.52 ± 0.87 s vs 3.15 ± 1.16 s (RT), p = 0.001) and a decrease in contractile front velocity (CFV) (4.43 ± 1.50 cm/s vs 4.90 ± 2.53 cm/s (RT), p = 0.007). Similarly, in the MWS, hot water caused a decrease in the duration of EB contraction (12.95 ± 5.02 s vs 16.33 ± 5.94 s (RT), p = 0.024) and an increase in the amplitude of EB contraction (114.27 ± 83.36 mmHg vs 82.70 ± 46.77 mmHg (RT), p = 0.007). Cold water caused an increase in the duration of EB contraction (27.38 ± 2.89 s vs 16.33 ± 5.94 s (RT), p = 0.03) and a decrease in the amplitude of EB contraction (51.68 ± 33.94 mmHg vs 82.70 ± 46.77 mmHg (RT), p = 0.001). This study showed changes in esophageal motility to be dependent on water temperature. Especially, MWS showed clear changes in esophageal motility at different temperatures of water. © 2014 John Wiley & Sons Ltd.

Utilization of wireless pH monitoring technologies: a summary of the proceedings from the esophageal diagnostic working group.

PubMed

Richter, J E; Pandolfino, J E; Vela, M F; Kahrilas, P J; Lacy, B E; Ganz, R; Dengler, W; Oelschlager, B K; Peters, J; DeVault, K R; Fass, R; Gyawali, C P; Conklin, J; DeMeester, T

2013-01-01

Gastroesophageal reflux disease (GERD) can be difficult to diagnose - symptoms alone are often not enough, and thus, objective testing is often required. GERD is a manifestation of pathologic levels of reflux into the esophagus of acidic, nonacidic, and/or bilious gastric content. However, in our current evidence-based knowledge approach, we only have reasonable outcome data in regards to acid reflux, as this particular type of refluxate predictably causes symptoms and mucosal damage, which improves with medical or surgical therapy. While there are data suggesting that nonacid reflux may be responsible for ongoing symptoms despite acid suppression in some patients, outcome data about this issue are limited. Therefore, this working group believes that it is essential to confirm the presence of acid reflux in patients with 'refractory' GERD symptoms or extraesophageal symptoms thought to be caused by gastroesophageal reflux before an escalation of antireflux therapy is considered. If patients do not have pathologic acid reflux off antisecretory therapy, they are unlikely to have clinically significant nonacid or bile reflux. Patients who do not have pathologic acid gastroesophageal reflux parameters on ambulatory pH monitoring then: (i) could attempt to discontinue antisecretory medications like proton pump inhibitors and H2-receptor antagonists (which are expensive and which carry risks - i.e. C. diff, etc.); (ii) may undergo further evaluation for other causes of their esophageal symptoms (e.g. functional heartburn or chest pain, eosinophilic esophagitis, gastroparesis, achalasia, other esophageal motor disorders); and (iii) can be referred to an ear, nose, and throat/pulmonary/allergy physician for assessment of non-GERD causes of their extraesophageal symptoms. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Esophageal function testing: Billing and coding update.

PubMed

Khan, A; Massey, B; Rao, S; Pandolfino, J

2018-01-01

Esophageal function testing is being increasingly utilized in diagnosis and management of esophageal disorders. There have been several recent technological advances in the field to allow practitioners the ability to more accurately assess and treat such conditions, but there has been a relative lack of education in the literature regarding the associated Common Procedural Terminology (CPT) codes and methods of reimbursement. This review, commissioned and supported by the American Neurogastroenterology and Motility Society Council, aims to summarize each of the CPT codes for esophageal function testing and show the trends of associated reimbursement, as well as recommend coding methods in a practical context. We also aim to encourage many of these codes to be reviewed on a gastrointestinal (GI) societal level, by providing evidence of both discrepancies in coding definitions and inadequate reimbursement in this new era of esophageal function testing. © 2017 John Wiley & Sons Ltd.

Idiopathic (primary) achalasia

PubMed Central

Farrokhi, Farnoosh; Vaezi, Michael F

2007-01-01

Idiopathic achalasia is a primary esophageal motor disorder characterized by esophageal aperistalsis and abnormal lower esophageal sphincter (LES) relaxation in response to deglutition. It is a rare disease with an annual incidence of approximately 1/100,000 and a prevalence rate of 1/10,000. The disease can occur at any age, with a similar rate in men and women, but is usually diagnosed between 25 and 60 years. It is characterized predominantly by dysphagia to solids and liquids, bland regurgitation, and chest pain. Weight loss (usually between 5 to 10 kg) is present in most but not in all patients. Heartburn occurs in 27%–42% of achalasia patients. Etiology is unknown. Some familial cases have been reported, but the rarity of familial occurrence does not support the hypothesis that genetic inheritance is a significant etiologic factor. Association of achalasia with viral infections and auto-antibodies against myenteric plexus has been reported, but the causal relationship remains unclear. The diagnosis is based on history of the disease, radiography (barium esophagogram), and esophageal motility testing (esophageal manometry). Endoscopic examination is important to rule out malignancy as the cause of achalasia. Treatment is strictly palliative. Current medical and surgical therapeutic options (pneumatic dilation, surgical myotomy, and pharmacologic agents) aimed at reducing the LES pressure and facilitating esophageal emptying by gravity and hydrostatic pressure of retained food and liquids. Although it cannot be permanently cured, excellent palliation is available in over 90% of patients. PMID:17894899

High resolution esophageal manometry--the switch from "intuitive" visual interpretation to Chicago classification.

PubMed

Srinivas, M; Balakumaran, T A; Palaniappan, S; Srinivasan, Vijaya; Batcha, M; Venkataraman, Jayanthi

2014-03-01

High resolution esophageal manometry (HREM) has been interpreted all along by visual interpretation of color plots until the recent introduction of Chicago classification which categorises HREM using objective measurements. It compares HREM diagnosis of esophageal motor disorders by visual interpretation and Chicago classification. Using software Trace 1.2v, 77 consecutive tracings diagnosed by visual interpretation were re-analyzed by Chicago classification and findings compared for concordance between the two systems of interpretation. Kappa agreement rate between the two observations was determined. There were 57 males (74 %) and cohort median age was 41 years (range: 14-83 years). Majority of the referrals were for gastroesophageal reflux disease, dysphagia and achalasia. By "intuitive" visual interpretation, the tracing were reported as normal in 45 (58.4 %), achalasia 14 (18.2 %), ineffective esophageal motility 3 (3.9 %), nutcracker esophagus 11 (14.3 %) and nonspecific motility changes 4 (5.2 %). By Chicago classification, there was 100 % agreement (Kappa 1) for achalasia (type 1: 9; type 2: 5) and ineffective esophageal motility ("failed peristalsis" on visual interpretation). Normal esophageal motility, nutcracker esophagus and nonspecific motility disorder on visual interpretation were reclassified as rapid contraction and esophagogastric junction (EGJ) outflow obstruction by Chicago classification. Chicago classification identified distinct clinical phenotypes including EGJ outflow obstruction not identified by visual interpretation. A significant number of unclassified HREM by visual interpretation were also classified by it.

Laparoscopic Transhiatal Treatment of Large Epiphrenic Esophageal Diverticulum

PubMed Central

Casella, Giovanni; Recchia, Carlo Luigi; Bianchi, Ermanno; Lomartire, Nazzareno

2008-01-01

Background: Epiphrenic diverticulum is an uncommon disorder of the distal third of the esophagus. We report the case of a 73-year-old woman with a large symptomatic esophageal epiphrenic diverticulum, diffuse nonspecific esophageal dysmotility, and a hiatal hernia. Methods: Surgery was indicated by the patient's symptoms, the size of the diverticulum (maximum diameter 10 cm), and the associated esophageal motor disorder. Preoperative study included barium swallow, upper gastrointestinal endoscopy, and esophageal manometry. A laparoscopic transhiatal diverticulectomy associated with a Heller myotomy, hiatoplasty, and a Dor's fundoplication was carried out. The overall operative time was 230 minutes. Results: No intraoperative complications occurred. Gastrografin swallow performed on postoperative day 4 did not show any signs of leakage from the staple line. The postoperative hospital stay was 5 days. The patient was readmitted 10 days after discharge complaining of fever and chest pain. A new Gastrografin swallow demonstrated a small leak from the staple line successfully treated with 3 weeks of total enteral nutrition. Conclusion: The laparoscopic approach to epiphrenic diverticulum is feasible. Postoperative Gastrografin swallow is not 100% sensitive in detecting small suture-line leaks if a preexisting esophageal motility disorder is present. In case of late postoperative fever and pleural effusion, a suture-line leak should be suspected. Conservative management of the small suture-line leak should be considered as an effective therapeutic option. PMID:18402751

Management of acid-related disorders in patients with dysphagia.

PubMed

Howden, Colin W

2004-09-06

Dysphagia affects a large and growing number of individuals in the United States, particularly the elderly and those who are neurologically impaired. Swallowing difficulties may be due to age-related changes in oropharyngeal and esophageal functioning as well as central nervous system diseases such as stroke, Parkinson disease, and dementia. Among institutionalized individuals, dysphagia is associated with increased morbidity and mortality. An appreciation of the physiology of swallowing and the pathophysiology of dysphagia is necessary for proper patient management. Careful history, physical examination, and evaluation of radiologic and endoscopic studies should differentiate oropharyngeal and esophageal etiologies of dysphagia and distinguish mechanical (anatomic) disorders from functional (motor) disorders. A significant percentage of patients with dysphagia have concomitant acid-related disorders that are managed best with proton pump inhibitor (PPI) therapy. Three of the currently available PPIs are manufactured as capsules containing enteric-coated granules that may be mixed with soft foods or fruit juices before oral administration to those with swallowing difficulties. In addition, omeprazole and lansoprazole may be administered via gastrostomy or nasogastric feeding tubes as suspensions in sodium bicarbonate. Novel dosage formulations of lansoprazole that may be appropriate for patients with dysphagia include the commercially manufactured lansoprazole strawberry-flavored enteric-coated granules for suspension and lansoprazole orally disintegrating tablets.

Regenerative Medicine Strategies for Esophageal Repair

PubMed Central

Londono, Ricardo

2015-01-01

Pathologies that involve the structure and/or function of the esophagus can be life-threatening. The esophagus is a complex organ comprising nonredundant tissue that does not have the ability to regenerate. Currently available interventions for esophageal pathology have limited success and are typically associated with significant morbidity. Hence, there is currently an unmet clinical need for effective methods of esophageal repair. The present article presents a review of esophageal disease along with the anatomic and functional consequences of each pathologic process, the shortcomings associated with currently available therapies, and the latest advancements in the field of regenerative medicine with respect to strategies for esophageal repair from benchtop to bedside. PMID:25813694

Gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice

PubMed Central

Fang, Yu; Chen, Hao; Hu, Yuhui; Djukic, Zorka; Tevebaugh, Whitney; Shaheen, Nicholas J.; Orlando, Roy C.; Hu, Jianguo

2013-01-01

The barrier function of the esophageal epithelium is a major defense against gastroesophageal reflux disease. Previous studies have shown that reflux damage is reflected in a decrease in transepithelial electrical resistance associated with tight junction alterations in the esophageal epithelium. To develop novel therapies, it is critical to understand the molecular mechanisms whereby contact with a refluxate impairs esophageal barrier function. In this study, surgical models of duodenal and mixed reflux were developed in mice. Mouse esophageal epithelium was analyzed by gene microarray. Gene set enrichment analysis showed upregulation of inflammation-related gene sets and the NF-κB pathway due to reflux. Significance analysis of microarrays revealed upregulation of NF-κB target genes. Overexpression of NF-κB subunits (p50 and p65) and NF-κB target genes (matrix metalloproteinases-3 and -9, IL-1β, IL-6, and IL-8) confirmed activation of the NF-κB pathway in the esophageal epithelium. In addition, real-time PCR, Western blotting, and immunohistochemical staining also showed downregulation and mislocalization of claudins-1 and -4. In a second animal experiment, treatment with an NF-κB inhibitor, BAY 11-7085 (20 mg·kg−1·day−1 ip for 10 days), counteracted the effects of duodenal and mixed reflux on epithelial resistance and NF-κB-regulated cytokines. We conclude that gastroesophageal reflux activates the NF-κB pathway and impairs esophageal barrier function in mice and that targeting the NF-κB pathway may strengthen esophageal barrier function against reflux. PMID:23639809

Esophageal peristaltic defects in adults with functional dysphagia.

PubMed

Ratuapli, Shiva K; Hansel, Stephanie L; Umar, Sarah B; Burdick, George E; Ramirez, Francisco C; Fleischer, David E; Harris, Lucinda A; Lacy, Brian E; DiBaise, John K; Crowell, Michael D

2014-08-01

Functional dysphagia (FD) is characterized by the presence of dysphagia without evidence of mechanical esophageal obstruction, GERD, and histopathology-based esophageal motor disorders. Dysphagia is common in older patients; however, there is a paucity of information regarding the type and frequency of peristaltic abnormalities compared to younger patients. Based on recently validated criteria for classification of weak peristalsis using high-resolution manometry (HRM), we hypothesized that older patients with FD would have more peristaltic defects detected by HRM compared to younger FD patients. A retrospective review of our motility database yielded 65 patients that met inclusion criteria. Patients were divided into two groups based on age (younger: <70 years; older: ≥70 years). Patients were interviewed, completed a quality-of-life questionnaire, and underwent solid-state HRM. The two groups differed in age but in no other demographic characteristics, severity of dysphagia, or quality of life. Dyspeptic symptoms, including nausea (p < 0.001), early satiety (p = 0.01), bloating (p = 0.02), and belching (p = 0.01), were also more prevalent in younger FD patients. Older age was associated with weak peristalsis involving frequent failed peristalsis, small proximal peristaltic defects (2-5 cm), and large proximal peristaltic defects (>5 cm) (p < 0.001). The mean contraction amplitude was also lower in the older group (p < 0.05). These data support the hypothesis that older patients with FD have a higher frequency of peristaltic abnormalities on HRM compared to younger patients. Older age was associated with increased frequency of weak peristalsis with small and large peristaltic defects.

Surface modification of esophageal stent materials by a polyethylenimine layer aiming at anti-cancer function.

PubMed

Zhang, Kun; Bai, Yuxin; Wang, Xiaofeng; Li, Qian; Guan, Fangxia; Li, Jingan

2017-08-01

Esophageal cancer is difficult to cure globally and possesses high mortality rate, and it is generally accepted that palliative care such as stent implantation is the main therapy method for esophageal cancer in later period. However, the restenosis caused by tumor cells and inflammatory cells seriously interferes the stent clinical application and limits its long-term services. To solve this problem, series of drug delivery stents were developed and proven rather effective in the early stage of implantation, but more serious restenosis occurred after the drug delivery was over, which endangered the patients' life. Therefore, endowing the esophageal stent continuous anti-cancer function become an ideal strategy for inhibiting the restenosis. In this contribution, the functional layer composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10 3 , 1 × 10 4 , 2.5 × 10 4 and 7 × 10 4  Da) were fabricated onto the esophageal stent material 317L stainless steel (317L SS) surface. The surface characterization including amine quantitative, atomic force microscopy (AFM) and water contact angle measurement indicated successful preparation of the PDA/PEI layer. The Eca109 cells culture results proved that the PDA/PEI layers significantly improve Eca109 cells apoptosis and necrosis, suggesting excellent anti-cancer function. In addition, we also found that the anti-cancer function of the PDA/PEI layers was positively correlated to the immobilized PEIs' MW. All the results demonstrated the potential application of the PDA/PEI layers on the surface modification of esophageal stent for continuous anti-cancer function. It is generally accepted that the restenosis caused by tumor cells seriously interferes the esophageal stent clinical application. Thus, endowing the esophageal stent continuous anti-cancer function is the ideal strategy for inhibiting the restenosis. In this work, we fabricated functional layers composed of polydopamine (PDA) and Poly-ethylenimine (PEI) with series of molecular weights (MW, 1.8 × 10 3 , 1 × 10 4 , 2.5 × 10 4 and 7 × 10 4  Da) onto the esophageal stent material 317L stainless steel (317L SS) surface to inhibit the tumor cells growth, and this function was related to the PEIs' molecular weights. The functional PDA/PEI layers were expected potentially applied for surface modification of esophageal stent materials.

T-helper 2 cytokines, transforming growth factor β1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis.

PubMed

Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-05-01

Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEFs), human esophageal muscle cells (HEMCs), and esophageal muscle strips to eosinophil-derived products. Biopsy specimens were collected via endoscopy from the upper, middle, and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 by, and adhesion of human eosinophils to, HEFs and HEMCs. Eosinophil products were tested in an esophageal muscle contraction assay. Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were secreted spontaneously in mucosal biopsy specimens from patients with EoE than controls. Exposure of HEFs and HEMCs to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEFs and HEMCs to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor β1 and p38 mitogen-activated protein kinase signaling. Eosinophil binding to HEFs and HEMCs increased after incubation of mesenchymal cells with eosinophil-derived products, and decreased after blockade of transforming growth factor β1 and p38 mitogen-activated protein kinase blockade. Eosinophil products reduced electrical field-induced contraction of esophageal muscle strips, but not acetylcholine-induced contraction. In an analysis of tissues samples from patients with EoE, we linked the presence and activation state of eosinophils in EoE with altered fibrogenesis and motility of esophageal fibroblasts and muscle cells. This process might contribute to the development of dysphagia. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Esophageal cancer diagnosed by high-resolution manometry of the esophagus: A case report

PubMed Central

LIU, RONGBEI; CHU, HUA; XU, FEI; CHEN, SHUJIE

2016-01-01

A 48-year-old female who presented with a history of dysphagia for 5 months and regurgitation for 1 week was referred to the Sir Run Run Shaw Hospital (Hangzhou, China) for further evaluation, since the gastroscopy and endoscopic ultrasound performed in local hospitals did not reveal the presence of cancer. High-resolution manometry (HRM) of the esophagus was performed to determine the patient's condition, and revealed an abnormal high-pressure zone that was located 33 cm from the incisor and did not relax upon swallowing. Synchronous waves were observed, and the pressure of the esophageal lumen was found to increase with secondary synchronous peristaltic waves. The lower esophageal sphincter was 39 cm from the incisor and relaxed upon swallowing. The abnormal high-pressure zone could have been caused by an obstruction, and therefore an upper gastrointestinal series (barium swallow) test and gastroscopy were recommended to further pinpoint the cause. Following the two examinations, mid-esophageal cancer was considered as a possible diagnosis. A biopsy was performed and the final diagnosis was that of basaloid squamous cell carcinoma. The findings of the present study suggest that, for patients with evident symptoms of esophageal motor dysfunction without significant gastroscopy findings, HRM is recommended. PMID:27123076

Neurophysiology and new techniques to assess esophageal sensory function: an update.

PubMed

Brock, Christina; McCallum, Richard W; Gyawali, C Prakash; Farmer, Adam D; Frøkjaer, Jens Brøndum; McMahon, Barry P; Drewes, Asbjørn Mohr

2016-09-01

This review aims to discuss the neurophysiology of the esophagus and new methods to assess esophageal nociception. Pain and other symptoms can be caused by diseases in the mucosa or muscular or sphincter dysfunction, together with abnormal pain processing, either in the peripheral or central nervous systems. Therefore, we present new techniques in the assessment of esophageal function and the potential role of the mucosal barrier in the generation and propagation of pain. We discuss the assessment and role of esophageal sphincters in nociception, as well as imaging and electrophysiological techniques, with examples of their use in understanding the sensory system following noxious stimuli to the esophagus. Additionally, we discuss the mechanisms behind functional diseases of the esophagus. We conclude that the new methods have identified many of the mechanisms behind malfunction of the mucosa, disturbances of muscular and sphincter functions, and the central response to different stimuli. Taken together, this has increased our understanding of esophageal disorders and may lead to new treatment modalities. © 2016 New York Academy of Sciences.

De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux.

PubMed

Fujita, Atsushi; Isidor, Bertrand; Piloquet, Hugues; Corre, Pierre; Okamoto, Nobuhiko; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi

2016-09-01

MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change-specifically, an in-frame MEIS2 deletion-has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C>G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease.

PubMed

Cicala, Michele; Emerenziani, Sara; Guarino, Michele Pier Luca; Ribolsi, Mentore

2013-10-21

Gastro-esophageal reflux disease (GERD) is one of the most prevalent chronic diseases. Although proton pump inhibitors (PPIs) represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief, several studies have shown that up to 40% of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily. Several mechanisms have been proposed as involved in PPIs resistance, including ineffective control of gastric acid secretion, esophageal hypersensitivity, ultrastructural and functional changes in the esophageal epithelium. The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation, upper endoscopy, esophageal manometry and ambulatory pH-impedance monitoring, which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn. Treatment has been primarily based on doubling the PPI dose or switching to another PPI. Patients with proven disease, not responding to PPI twice daily, are eligible for anti-reflux surgery.

Comparison of Rectal and Esophageal Sensitivity in Women With Functional Heartburn.

PubMed

Freede, Margaret; Leasure, A Renee; Proskin, Howard M; Hatch, Daniel; Edwards, Karethy; Pascucci, MaryAnn; Smith, Patsy R

2016-01-01

This study tested the primary hypothesis that there is a correlation of maximum pain threshold (MPT) in the esophagus and rectum in persons with functional heartburn. Secondary aims evaluated correlations with initial perception threshold (IPT) and pain threshold (PT). This study explored objective sensory endpoints of IPT, PT, and MPT in the esophagus and rectum of 14 females with functional heartburn to determine whether visceral hypersensitivity is generalized or organ-specific. Data on volume and pressure measurements at IPT, PT, and MPT with esophageal and rectal barostat distention were collected. The relationship of sensation and pain to volume, pressure, and compliance was analyzed. Esophageal and rectal IPT balloon volume scores were highly and significantly correlated (r = .61, p = .02). Esophageal and rectal PT balloon volume scores were highly and significantly correlated (r = .6, p = .02). Esophageal and rectal MPT balloon volume scores were not correlated (r = .35, p = .26). The correlation of visceral sensitivity in the esophagus and rectum in persons with functional heartburn supports the hypothesis that visceral sensory changes in functional gastrointestinal disorders are not organ specific.

Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia.

PubMed

Siderits, Richard; Hanna, Iman; Baig, Zahid; Godyn, Janusz-J

2006-12-28

A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric (EG) junction and grade I erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and NSE were positive. This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type IIb (MEN IIb). Iansoprazole (Prevacid) was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild non-specific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease (GERD) and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient's reflux.

Baseline measure of health-related quality of life (Functional Assessment of Cancer Therapy-Esophagus) is associated with overall survival in patients with esophageal cancer.

PubMed

Kidane, Biniam; Sulman, Joanne; Xu, Wei; Kong, Qin Quinn; Wong, Rebecca; Knox, Jennifer J; Darling, Gail E

2016-06-01

Functional Assessment of Cancer Therapy-Esophagus is a health-related quality of life instrument validated in patients with esophageal cancer. It is composed of a general component and an esophageal cancer subscale. Our objective was to determine whether the baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores are associated with survival in patients with stage II and III cancer of the gastroesophageal junction or thoracic esophagus. Data from 4 prospective studies in Canadian academic hospitals were combined. These included consecutive patients with stage II and III esophageal cancer who received neoadjuvant therapy followed by surgery or chemoradiation/radiation alone. All patients completed baseline Functional Assessment of Cancer Therapy-Esophagus. Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale scores were dichotomized on the basis of median scores. Cox regression analyses were performed. There were 207 patients treated between 1996 and 2014. Mean age was 61 ± 10.6 years. Approximately 69.6% of patients (n = 144) had adenocarcinoma. All patients had more than 9 months of follow-up. In patients with stage II and III, 93 deaths were observed. When treated as continuous variables, baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were associated with survival with hazard ratios of 0.89 (95% confidence interval [CI], 0.81-0.96; P = .005) and 0.68 (95% CI, 0.56-0.82; P < .001), respectively. When dichotomized, they were also associated with survival with a hazard ratio of 0.58 (95% CI, 0.38-0.89; P = .01) and 0.43 (95% CI, 0.28-0.67; P < .001), respectively. In patients with stage II and III esophageal cancer being considered for therapy, higher baseline Functional Assessment of Cancer Therapy-Esophagus and esophageal cancer subscale were independently associated with longer survival, even after adjusting for age, stage, histology, and therapy received. Further study is needed, but Functional Assessment of Cancer Therapy-Esophagus may be useful as a prognostic tool to inform patient decision-making and patient selection criteria for studies. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Assessment and protection of esophageal mucosal integrity in patients with heartburn without esophagitis.

PubMed

Woodland, Philip; Lee, Chung; Duraisamy, Yasotha; Duraysami, Yasotha; Farré, Ricard; Dettmar, Peter; Sifrim, Daniel

2013-04-01

Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection. Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions. Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05). Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.

Current treatment options for the management of esophageal cancer

PubMed Central

Mawhinney, Mark R; Glasgow, Robert E

2012-01-01

In recent years, esophageal cancer characteristics and management options have evolved significantly. There has been a sharp increase in the frequency of esophageal adenocarcinoma and a decline in the frequency of squamous cell carcinoma. A more comprehensive understanding of prognostic factors influencing outcome has also been developed. This has led to more management options for esophageal cancer at all stages than ever before. A multidisciplinary, team approach to management in a high volume center is the preferred approach. Each patient should be individually assessed based on type of cancer, local or regional involvement, and his or her own functional status to determine an appropriate treatment regimen. This review will discuss management of esophageal cancer relative to disease progression and patient functional status. PMID:23152702

Generation and Characterization of an Immortalized Human Esophageal Myofibroblast Line.

PubMed

Niu, Chao; Chauhan, Uday; Gargus, Matthew; Shaker, Anisa

2016-01-01

Stromal cells with a myofibroblast phenotype present in the normal human esophagus are increased in individuals with gastro-esophageal reflux disease (GERD). We have previously demonstrated that myofibroblasts stimulated with acid and TLR4 agonists increase IL-6 and IL-8 secretion using primary cultures of myofibroblasts established from normal human esophagus. While primary cultures have the advantage of reflecting the in vivo environment, a short life span and unavoidable heterogeneity limits the usefulness of this model in larger scale in vitro cellular signaling studies. The major aim of this paper therefore was to generate a human esophageal myofibroblast line with an extended lifespan. In the work presented here we have generated and characterized an immortalized human esophageal myofibroblast line by transfection with a commercially available GFP-hTERT lentivirus. Immortalized human esophageal myofibroblasts demonstrate phenotypic, genotypic and functional similarity to primary cultures of esophageal myofibroblasts we have previously described. We found that immortalized esophageal myofibroblasts retain myofibroblast spindle-shaped morphology at low and high confluence beyond passage 80, and express α-SMA, vimentin, and CD90 myofibroblast markers. Immortalized human esophageal myofibroblasts also express the putative acid receptor TRPV1 and TLR4 and retain the functional capacity to respond to stimuli encountered in GERD with secretion of IL-6. Finally, immortalized human esophageal myofibroblasts also support the stratified growth of squamous esophageal epithelial cells in 3D organotypic cultures. This newly characterized immortalized human esophageal myofibroblast cell line can be used in future cellular signaling and co-culture studies.

Functional restoration of the esophagus after peroral endoscopic myotomy for achalasia.

PubMed

Huh, Cheal Wung; Youn, Young Hoon; Chung, Hyunsoo; Lee, Yong Chan; Park, Hyojin

2017-01-01

Peroral endoscopic myotomy (POEM) is a new efficacious treatment option for achalasia. We propose to define "esophageal remodeling" as the functional restoration of the esophagus that involves decreased lower esophageal sphincter (LES) pressure, recovery of esophageal body peristalsis, and reduction of luminal diameter. The aim of this study was to investigate "esophageal remodeling" after POEM for achalasia. We analyzed data from a prospectively collected database of POEM subjects, which included preoperative and 2-month postoperative Eckardt symptom scores, and results from esophageal high resolution manometry (HRM) and barium esophagogram (BE). We recruited 23 patients (13 male; mean age: 53.9 years) whose preoperative and postoperative HRM and BE results were available, from among 30 patients with achalasia who underwent POEM at two institutions between July 2013 and December 2015. All patients achieved clinical treatment success (Eckardt score≤3). Partial recovery of esophageal body peristalsis was noted in 1/5 patients with type I (20%), 6/11 with type II (54.5%), and 7/7 with type III (100%) achalasia after POEM. Pan-esophageal pressurization disappeared after POEM in 10/11 type II achalasia patients. The average diameter of the esophageal body after POEM was significantly decreased in all types of achalasia. POEM provided excellent clinical symptomatic relief and esophageal remodeling in terms of restoration of peristalsis and reduction in diameter of the esophageal body, especially in patients with type III achalasia.

Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer.

PubMed

Wang, Xingwei; Cao, Yan; Zhang, Shirong; Chen, Zhihui; Fan, Ling; Shen, Xiaochun; Zhou, Shiwen; Chen, Dongfeng

2017-05-30

Esophageal cancer is one of the most common malignant tumors of the digestive tract. The greatest obstacle to the curing of esophageal cancer is its propensity to spread and metastasize. Esophageal cancer stem cells are considered the source for recurrence and metastasis of the tumors. While clinical evidence suggested that continuous up-regulation of CXCL12/CXCR4 was significantly associated with poor prognosis in patients with esophageal cancer, but the role and mechanism of CXCL12/CXCR4 in the invasion and metastasis of esophageal cancer has not been reported by far. This study found that esophageal cancer stem cells not only autocrine a great amount of CXCL12, but also high expression of its corresponding receptor CXCR4. Most importantly, the ability of esophageal cancer stem cells to spread and metastasize could be inhibited by blockage of CXCR4 with inhibitors or shRNA approaches both in vivo and in vitro studies. The important role of CXCL12 in the invasion and metastasis of esophageal cancer stem cells was also confirmed by loss-of-function and gain-of-function strategies. Mechanistically, we demonstrated that CXCL12/CXCR4 activated the ERK1/2 pathway and thereby ultimately maintained the characteristics of high-level invasion and metastasis of esophageal cancer stem cells. Taken together, our findings suggested that autocrine CXCL12/CXCR4 was one of the major mechanisms underlying the metastatic property of esophageal cancer stem cells through ERK1/2 signaling pathway, and might serve as a therapeutic target for esophageal cancer patients.

In silico dissection of miRNA targetome polymorphisms and their role in regulating miRNA-mediated gene expression in esophageal cancer.

PubMed

Nariman-Saleh-Fam, Ziba; Bastami, Milad; Somi, Mohammad Hossein; Samadi, Naser; Abbaszadegan, Mohammad Reza; Behjati, Farkhondeh; Ghaedi, Hamid; Tavakkoly-Bazzaz, Javad; Masotti, Andrea

2016-12-01

Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribution of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer.

T-helper 2 Cytokines, Transforming Growth Factor β1, and Eosinophil Products Induce Fibrogenesis and Alter Muscle Motility in Patients with Eosinophilic Esophagitis

PubMed Central

Rieder, Florian; Nonevski, Ilche; Ma, Jie; Ouyang, Zhufeng; West, Gail; Protheroe, Cheryl; DePetris, Giovanni; Schirbel, Anja; Lapinski, James; Goldblum, John; Bonfield, Tracey; Lopez, Rocio; Harnett, Karen; Lee, James; Hirano, Ikuo; Falk, Gary; Biancani, Piero; Fiocchi, Claudio

2014-01-01

BACKGROUND & AIMS Patients with eosinophilic esophagitis (EoE) often become dysphagic from the combination of organ fibrosis and motor abnormalities. We investigated mechanisms of dysphagia, assessing the response of human esophageal fibroblasts (HEF), muscle cells (HEMC), and esophageal muscle strips to eosinophil-derived products. METHODS Biopsies were collected via endoscopy from the upper, middle and lower thirds of the esophagus of 18 patients with EoE and 21 individuals undergoing endoscopy for other reasons (controls). Primary cultures of esophageal fibroblasts and muscle cells were derived from 12 freshly resected human esophagectomy specimens. Eosinophil distribution was investigated by histologic analyses of full-thickness esophageal tissue. Active secretion of EoE-related mediators was assessed from medium underlying mucosal biopsy cultures. We quantified production of fibronectin and collagen I by HEF and HEMC in response to eosinophil products. We also measured expression of ICAM1 and VCAM1 by, and adhesion of human eosinophils to, HEF and HEMC. Eosinophil products were tested in an esophageal muscle contraction assay. RESULTS Activated eosinophils were present in all esophageal layers. Significantly higher concentrations of eosinophil-related mediators were spontaneously secreted in mucosal biopsies from patients with EoE than controls. Exposure of HEF and HEMC to increasing concentrations of eosinophil products or co-culture with eosinophils caused HEF and HEMC to increase secretion of fibronectin and collagen I; this was inhibited by blocking transforming growth factor (TGF)β1 and p38 mitogen-activated protein kinase (MAKP) signaling. Eosinophil binding to HEF and HEMC increased following incubation of mesenchymal cells with eosinophil-derived products, and decreased following blockade of TGFβ1 and p38MAPK blockade. Eosinophil products reduced electrical field-induced contraction of esophageal muscle strips, but not acetylcholine-induced contraction. CONCLUSION In an analysis of tissues samples from patients with EoE, we linked the presence and activation state of eosinophils in EoE with altered fibrogenesis and motility of esophageal fibroblasts and muscle cells. This process might contribute to the development of dysphagia. PMID:24486052

Impact of deep brain stimulation on pharyngo-esophageal motility: a randomized cross-over study.

PubMed

Derrey, S; Chastan, N; Maltete, D; Verin, E; Dechelotte, P; Lefaucheur, R; Proust, F; Freger, P; Leroi, A M; Weber, J; Gourcerol, G

2015-09-01

Bilateral subthalamic nucleus (STN) stimulation is used to alleviate Parkinson's disease (PD) motor symptoms. Recently, it has been shown that this therapeutic also increased gut cholinergic contractions. We therefore investigated the effect of STN stimulation on esophageal motility in an interventional randomized study. Sixteen humans PD patients (4 women, 12 men; age: 62.4 ± 9.3-years old) who underwent STN stimulation for at least 6 months were randomly evaluated with either stimulator turned OFF then ON, or inversely. Esophageal high resolution manometry was performed at the end of each ON and OFF period, with a 5 min resting period followed by ten swallows of 5 mL. During the ON, an increase in the distal contractility index was found (OFF: 1750 ± 629 vs ON: 2171 ± 755 mmHg/cm/s; p = 0.03), with no difference in the distal front velocity. A decrease in the integrative relaxation pressure of the lower esophageal sphincter (LES) was noted (OFF: 11.1 ± 1.8 mmHg vs ON: 7.2 ± 1.8 mmHg; p < 0.05) in ON. The LES resting pressure remained unchanged during the two periods. This resulted in a decrease in the intrabolus pressure (p = 0.03). No difference was observed for the upper esophageal sphincter, nor the pharyngeal contraction amplitude and velocity. In conclusion, STN stimulation in PD patients increased esophageal body contractions and enhanced the LES opening. This suggests that the nigrostriatal-striatonigral loop is involved in the control of esophageal motility. © 2015 John Wiley & Sons Ltd.

Functional restoration of the esophagus after peroral endoscopic myotomy for achalasia

PubMed Central

Huh, Cheal Wung; Youn, Young Hoon; Chung, Hyunsoo; Lee, Yong Chan; Park, Hyojin

2017-01-01

Purpose Peroral endoscopic myotomy (POEM) is a new efficacious treatment option for achalasia. We propose to define “esophageal remodeling” as the functional restoration of the esophagus that involves decreased lower esophageal sphincter (LES) pressure, recovery of esophageal body peristalsis, and reduction of luminal diameter. The aim of this study was to investigate “esophageal remodeling” after POEM for achalasia. Materials and methods We analyzed data from a prospectively collected database of POEM subjects, which included preoperative and 2-month postoperative Eckardt symptom scores, and results from esophageal high resolution manometry (HRM) and barium esophagogram (BE). We recruited 23 patients (13 male; mean age: 53.9 years) whose preoperative and postoperative HRM and BE results were available, from among 30 patients with achalasia who underwent POEM at two institutions between July 2013 and December 2015. Results All patients achieved clinical treatment success (Eckardt score≤3). Partial recovery of esophageal body peristalsis was noted in 1/5 patients with type I (20%), 6/11 with type II (54.5%), and 7/7 with type III (100%) achalasia after POEM. Pan-esophageal pressurization disappeared after POEM in 10/11 type II achalasia patients. The average diameter of the esophageal body after POEM was significantly decreased in all types of achalasia. Conclusion POEM provided excellent clinical symptomatic relief and esophageal remodeling in terms of restoration of peristalsis and reduction in diameter of the esophageal body, especially in patients with type III achalasia. PMID:28542509

Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

PubMed Central

Rinsma, Nicolaas F.; Farré, Ricard; Troost, Fred J.; Elizalde, Montserrat; Keszthelyi, Daniel; Helyes, Zsuzsanna; Masclee, Ad A.; Conchillo, José M.

2017-01-01

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients. PMID:28534850

SATB1 plays an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

PubMed

Song, Guiqin; Liu, Kang; Yang, Xiaolin; Mu, Bo; Yang, Junbao; He, Lang; Hu, Xin; Li, Qiujiang; Zhao, Yunxia; Cai, Xiaoming; Feng, Gang

2017-03-14

Esophageal cancer is a highly aggressive malignancy with very poor overall prognosis. Given the strong clinical relevance of SATB1 in esophagus cancer and other cancers suggested by previous studies, the exact function of SATB1 in esophagus cancer development is still unknown. Here we showed that the knockdown of SATB1 in esophageal cancer cell lines diminished the cell proliferation, survival and invasion. Whole genome transcriptome analysis of SATB1 knockdown cells revealed the different gene expression profiles between TE-1 cells and MDA-MB-231 cells. Network analysis and functional experiments further identified FN1 and PDGFRB to be key downstream genes regulated by SATB1 in esophageal cancer cells. Importantly, FN1 and PDGFRB were found to be highly expressed in human esophageal cancer. In summary, we provided the first molecular evidence that SATB1 played an oncogenic role in esophageal cancer by up-regulation of FN1 and PDGFRB.

Genesis of multipeaked waves of the esophagus: repetitive contractions or motion artifact?

PubMed

Sampath, Neha J; Bhargava, Valmik; Mittal, Ravinder K

2010-06-01

Multipeaked waves (MPW) in the distal esophagus occur frequently in patients with esophageal spastic motor disorders and diabetes mellitus and are thought to represent repetitive esophageal contractions. We aimed to investigate whether the relative motion between a stationary pressure sensor and contracted peristaltic esophageal segment that moves with respiration leads to the formation of MPW. We mathematically modeled the effect of relative movement between a moving pressure segment and a fixed pressure sensor on the pressure waveform morphology. We conducted retrospective analysis of 100 swallow-induced esophageal contractions in 10 patients, who demonstrated >30% MPW on high-resolution manometry (HRM) during standardized swallows. Finally, using HRM, we determined the effects of suspended breathing and hyperventilation on the waveform morphology in 10 patients prospectively. Modeling revealed that relative movement between a stationary pressure sensor and a moving contracted segment, contraction duration, contraction amplitude, respiratory frequency, and depth of respiration affects the waveform morphology. Retrospective analysis demonstrated a close temporal association with the onset of second and subsequent contractions in MPW with respiratory phase reversals. Numbers of peaks in MPW and respiratory phase reversals were closely related to the duration of contraction. In the prospective study, suspended breathing and hyperventilation resulted in a significant decrease and increase in the MPW frequency as well as the number of peaks within MPW respectively. We conclude that MPW observed during clinical motility studies are not indicative of repetitive esophageal contraction; rather they represent respiration-related movement of the contracted esophageal segment in relation to the stationary pressure sensor.

Variant allele of CHEK2 is associated with a decreased risk of esophageal cancer lymph node metastasis in a Chinese population.

PubMed

Gu, Haiyong; Qiu, Wanshan; Wan, Ying; Ding, Guowen; Tang, Weifeng; Liu, Chao; Shi, Yijun; Chen, Yijang; Chen, Suocheng

2012-05-01

Growing evidence suggests that the checkpoint kinase 2 (CHEK2) signaling pathway occupies a central position in the signaling networks of DNA-damage signaling. Many functional and molecular epidemiological studies have evaluated the association between genetic variants of CHEK2 and various cancers. To evaluate the relationship between CHEK2 functional genetic variants and esophageal cancer risk and the risk of lymph node metastasis among a Chinese population. We genotyped CHEK2 rs738722, rs2236141 and rs2236142 single nucleotide polymorphisms (SNPs) using the matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay in a case-controlled study, including 380 esophageal cancer cases and 380 healthy controls in a Chinese population. We found that none of the three polymorphisms achieved significant difference in their distributions between esophageal cancer cases and controls. Multiple logistic regression analyses revealed that esophageal cancer risk was not associated significantly with the variant genotypes of the three CHEK2 polymorphisms as compared with their wild-type genotypes. However, we found that functional variant rs738722 and rs2236142 in CHEK2 might contribute to susceptibility to lymph node metastasis. Our data did not support a significant association between CHEK2 SNPs and the risk of esophageal cancer. Functional variant CHEK2 rs738722 and rs2236142 might contribute to lymph node metastasis susceptibility. The CT allele of SNP rs738722 and the GC allele of SNP rs2236142 might be a protective factor of the risk for lymph node metastasis of esophageal cancer.

Pediatric esophageal scintigraphy. Results of 200 studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guillet, J.; Wynchank, S.; Basse-Cathalinat, B.

1983-09-01

Esophageal transit of a small volume of watery liquid has been observed scintigraphically in 200 studies performed on patients aged between 6 days and 16 years. Qualitative information concerning esophageal morphology and function in the various phases of deglutition, and scintigraphic features of achalasia, stenosis, and other pathologies are described. Measured esophageal transit time and its normal variation, its relevance to the diagnosis of esophagitis, and the monitoring of treatment are discussed. This technique observing distinct deglutitions has proven a useful diagnostic tool. Its advantages and limitations are discussed in comparison with other methods.

Evaluation of Esophageal Motility Utilizing the Functional Lumen Imaging Probe.

PubMed

Carlson, Dustin A; Kahrilas, Peter J; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A; Wong, Ian; Pandolfino, John E

2016-12-01

Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. In all, 145 patients (aged 18-85 years, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered "abnormal". FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered "abnormal" if EGJ-DI was <2.8 mm 2 /mm Hg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, and 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was "normal" in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. In all, 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia.

Evaluation of esophageal motility utilizing the functional lumen imaging probe (FLIP)

PubMed Central

Carlson, Dustin A.; Kahrilas, Peter J.; Lin, Zhiyue; Hirano, Ikuo; Gonsalves, Nirmala; Listernick, Zoe; Ritter, Katherine; Tye, Michael; Ponds, Fraukje A.; Wong, Ian; Pandolfino, John E.

2016-01-01

Background Esophagogastric junction (EGJ) distensibility and distension-mediated peristalsis can be assessed with the functional lumen imaging probe (FLIP) during a sedated upper endoscopy. We aimed to describe esophageal motility assessment using FLIP topography in patients presenting with dysphagia. Methods 145 patients (ages 18 – 85, 54% female) with dysphagia that completed upper endoscopy with a 16-cm FLIP assembly and high-resolution manometry (HRM) were included. HRM was analyzed according to the Chicago Classification of esophageal motility disorders; major esophageal motility disorders were considered ‘abnormal’. FLIP studies were analyzed using a customized program to calculate the EGJ-distensibility index (DI) and generate FLIP topography plots to identify esophageal contractility patterns. FLIP topography was considered ‘abnormal’ if EGJ-DI was < 2.8 mm2/mmHg or contractility pattern demonstrated absent contractility or repetitive, retrograde contractions. Results HRM was abnormal in 111 (77%) patients: 70 achalasia (19 type I, 39 type II, 12 type III), 38 EGJ outflow obstruction, and three jackhammer esophagus. FLIP topography was abnormal in 106 (95%) of these patients, including all 70 achalasia patients. HRM was ‘normal’ in 34 (23%) patients: five ineffective esophageal motility and 29 normal motility. 17 (50%) had abnormal FLIP topography including 13 (37%) with abnormal EGJ-DI. Conclusions FLIP topography provides a well-tolerated method for esophageal motility assessment (especially to identify achalasia) at the time of upper endoscopy. FLIP topography findings that are discordant with HRM may indicate otherwise undetected abnormalities of esophageal function, thus FLIP provides an alternative and complementary method to HRM for evaluation of non-obstructive dysphagia. PMID:27725650

TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells.

PubMed

Lim, Diana M; Narasimhan, Sneha; Michaylira, Carmen Z; Wang, Mei-Lun

2009-12-01

Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. In the present study, we investigated the inflammatory response and signaling pathways activated by TLR stimulation of human esophageal cells in vitro. Using quantitative RT-PCR, we profiled the expression pattern of human TLRs 1-10 in primary esophageal keratinocytes (EPC2), immortalized nontransformed esophageal keratinocytes (EPC2-hTERT), and normal human esophageal mucosal biopsies and found that TLRs 1, 2, 3, and 5 were expressed both in vivo and in vitro. Using the cytokine IL-8 as a physiological read out of the inflammatory response, we found that TLR3 is the most functional of the expressed TLRs in both primary and immortalized esophageal epithelial cell lines in response to its synthetic ligand polyinosinic polycytidylic acid [poly(I:C)]. Through reporter gene studies, we show that poly(I:C)-induced NF-kappaB activation is critical for the transactivation of the IL-8 promoter in vitro and that nuclear translocation of NF-kappaB occurs at an early time point following poly(I:C) stimulation of esophageal epithelial cells. Importantly, we also show that poly(I:C) stimulation induces the NF-kappaB-dependent esophageal epithelial expression of TLR2, leading to enhanced epithelial responsiveness of EPC2-hTERT cells to TLR2 ligand stimulation, suggesting an important regulatory role for TLR3-mediated NF-kappaB signaling in the innate immune response of esophageal epithelial cells. Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-kappaB signaling may play an important regulatory role in esophageal epithelial homeostasis.

[Experience of the surgical management of the esophageal achalasia in a tertiary care hospital].

PubMed

Barajas-Fregoso, Elpidio Manuel; Romero-Hernández, Teodoro; Sánchez-Fernández, Patricio Rogelio; Fuentes-Orozco, Clotilde; González-Ojeda, Alejandro; Macías-Amezcua, Michel Dassaejv

2015-01-01

Achalasia is a primary esophageal motor disorder. The most common symptoms are: dysphagia, chest pain, reflux and weight loss. The esophageal manometry is the standard for diagnosis. The aim of this paper is to determine the effectiveness of the surgical management in patients with achalasia in a tertiary care hospital. A case series consisting of achalasia patients, treated surgically between January and December of 2011. Clinical charts were reviewed to obtain data and registries of the type of surgical procedure, morbidity and mortality. Fourteen patients were identified, with an average age of 49.1 years. The most common symptoms were: dysphagia, vomiting, weight loss and pyrosis. Eight open approaches were performed and six by laparoscopy, with an average length of cardiomyotomy of 9.4 cm. Eleven patients received an antireflux procedure. The effectiveness of procedures performed was 85.7 %. Surgical management offered at this tertiary care hospital does not differ from that reported in other case series, giving effectiveness and safety for patients with achalasia.

Laparoscopic sleeve gastrectomy and gastroesophageal reflux disease: a systematic review and meta-analysis.

PubMed

Oor, Jelmer E; Roks, David J; Ünlü, Çagdas; Hazebroek, Eric J

2016-01-01

The effect of sleeve gastrectomy (SG) on the prevalence of gastroesophageal reflux disease (GERD) remains unclear. We aimed to outline the currently available literature. All relevant databases were searched for publications examining the effect of laparoscopic SG on GERD. Primary outcome measure was change in prevalence of GERD symptoms, antireflux medication use, and esophageal function tests. Secondary outcomes were prevalence of new-onset GERD and esophagitis. Thirty-three articles were included. Eleven studies used questionnaires to assess changes in the prevalence of GERD symptoms, with a risk difference in prevalence of 4.3%. Eight studies used esophageal function tests, with paradoxical results. Pooled incidence of new-onset GERD symptoms was 20%, with a strong suggestion of heterogeneity. New-onset esophagitis ranged from 6.3% to 63.3%. Because of high heterogeneity among available studies and paradoxical outcomes of objective esophageal function tests, the exact effect of laparoscopic SG on the prevalence of GERD remains unanswered. Surgeons should carefully evaluate preoperative GERD symptoms when choosing the proper bariatric technique. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Esophageal Hypersensitivity in Functional Heartburn.

PubMed

Kondo, Takashi; Miwa, Hiroto

2017-08-01

Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.

Altered cortical excitability in anorexia nervosa.

PubMed

Khedr, E M; El Fetoh, N A; El Bieh, E; Ali, A M; Karim, A A

2014-09-01

Recent EEG and positron emission tomography (PET) studies have reported hyperactivation of the right hemisphere in anorexia nervosa (AN). The aim of the present study was to test this notion by examining cortical excitability in subjects with AN using transcranial magnetic stimulation (TMS). We investigated thirteen patients meeting the DSM IV diagnostic criteria for AN and 14 controls age and sex matched. Each subject was assessed clinically using the Eating Disorder Inventory (EDI), the Eating Attitude Test (EAT) and Beck's Depression Inventory (BDI-II). TMS measures involved resting and active motor thresholds (RMT, AMT) as well as motor evoked potentials (MEP), cortical silent period duration (CSP), transcallosal inhibition (TCI), and short latency intracortical inhibition (SICI) of the first dorsal interosseous muscle (FDI) were assessed. Cortical esophageal MEP latencies (CL) were also recorded. The RMT and MEP onset latency of the FDI and the esophagus as well as duration of the TCI were significantly reduced in anorexic patients compared to the control group. There were no significant differences neither in AMT nor CSP between patients and controls. Moreover, we found significant negative correlations between the EAT scores and RMT, and TCI duration. Although anorexic patients had significantly higher BDI score, there was no correlation between it and cortical excitability. Anorexic individuals are characterized by pathologically increased motor and esophageal cortical excitability that significantly correlates with clinical symptoms of anorexia nervosa. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Morphofunctional analysis of experimental model of esophageal achalasia in rats.

PubMed

Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A

2010-10-01

We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.

Functional chest pain responds to biofeedback treatment but functional heartburn does not: what is the difference?

PubMed

Shapiro, Michael; Shanani, Ram; Taback, Hanna; Abramowich, Dov; Scapa, Eitan; Broide, Efrat

2012-06-01

Patients with functional esophageal disorders represent a challenging treatment group. The purpose of this study was to evaluate the role of biofeedback in the treatment of patients with functional esophageal disorders. In this prospective study, patients with typical/atypical symptoms of gastroesophageal reflux disease underwent upper endoscopy and 24-h pH monitoring. All patients filled out gastroesophageal Reflux Disease Symptom, Hospital Anxiety and Depression, and Symptom Stress Rating questionnaires. Patients with functional heartburn and those with functional chest pain were offered biofeedback treatment. A global assessment questionnaire was filled out at the end of treatment and then 2.8 (range 1-4) years later. From January 2006 to December 2009, 22 patients with functional esophageal diseases were included in the study. Thirteen had functional heartburn and nine had functional chest pain. Six patients from each group received biofeedback treatment. After treatment for 1-4 years, patients with functional chest pain showed significant improvements in symptoms compared with those who were not treated. Patients with functional heartburn showed no improvement. Patients with functional chest pain had a longer time of esophageal acid exposure than those with functional heartburn. Patients with functional chest pain have different central and intraesophageal factors associated with symptom generation in comparison with patients with functional heartburn. Biofeedback is a useful tool in the treatment of patients with functional chest pain, but not for those with functional heartburn.

Development and validation of the brief esophageal dysphagia questionnaire.

PubMed

Taft, T H; Riehl, M; Sodikoff, J B; Kahrilas, P J; Keefer, L; Doerfler, B; Pandolfino, J E

2016-12-01

Esophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy. 1638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split-half reliability, ceiling and floor effects, and construct validity. The BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split-half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter-item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant. The BEDQ represents a rapid, reliable, and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction. © 2016 John Wiley & Sons Ltd.

Development and Validation of the Brief Esophageal Dysphagia Questionnaire

PubMed Central

Taft, Tiffany H.; Riehl, Megan; Sodikoff, Jamie B.; Kahrilas, Peter J.; Keefer, Laurie; Doerfler, Bethany; Pandolfino, John E.

2017-01-01

Background Esophageal dysphagia is common in gastroenterology practice and has multiple etiologies. A complication for some patients with dysphagia is food impaction. A valid and reliable questionnaire to rapidly evaluate esophageal dysphagia and impaction symptoms can aid the gastroenterologist in gathering information to inform treatment approach and further evaluation, including endoscopy. Methods 1,638 patients participated over two study phases. 744 participants completed the Brief Esophageal Dysphagia Questionnaire (BEDQ) for phase 1; 869 completed the BEDQ, Visceral Sensitivity Index, Gastroesophageal Reflux Disease Questionnaire, and Hospital Anxiety and Depression Scale for phase 2. Demographic and clinical data were obtained via the electronic medical record. The BEDQ was evaluated for internal consistency, split-half reliability, ceiling and floor effects, and construct validity. Key Results The BEDQ demonstrated excellent internal consistency, reliability, and construct validity. The symptom frequency and severity scales scored above the standard acceptable cutoffs for reliability while the impaction subscale yielded poor internal consistency and split-half reliability; thus the impaction items were deemed qualifiers only and removed from the total score. No significant ceiling or floor effects were found with the exception of 1 item, and inter-item correlations fell within accepted ranges. Construct validity was supported by moderate yet significant correlations with other measures. The predictive ability of the BEDQ was small but significant. Conclusions & Inferences The BEDQ represents a rapid, reliable and valid assessment tool for esophageal dysphagia with food impaction for clinical practice that differentiates between patients with major motor dysfunction and mechanical obstruction. PMID:27380834

Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study.

PubMed

Kim, Yong Sung; Kim, Tae Hyeon; Choi, Chang Soo; Shon, Young Woo; Kim, Sang Wook; Seo, Geom Seog; Nah, Yong Ho; Choi, Myung Gyu; Choi, Suck Chei

2005-07-21

Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH<4) of more than 5% and mild esophagitis (Savary-Miller grades I, II) proven by endoscopy. Ambulatory 24-h pH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i.d.) for 30 d in random order, using an open label method. For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment. Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH<4, total time with pH<4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups. Itopride 100 mg t.i.d. is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease.

Effect of itopride, a new prokinetic, in patients with mild GERD: A pilot study

PubMed Central

Kim, Yong Sung; Kim, Tae Hyeon; Choi, Chang Soo; Shon, Young Woo; Kim, Sang Wook; Seo, Geom Seog; Nah, Yong Ho; Choi, Myung Gyu; Choi, Suck Chei

2005-01-01

AIM: Itopride is a newly developed prokinetic agent, which enhances gastric motility through both antidopaminergic and anti-acetylcholinesterasic actions. The importance of esophageal motor dysfunction in the pathogenesis of gastro-esophageal reflux disease (GERD) makes it interesting to examine the effect of itopride on esophageal acid exposure. METHODS: The effect of itopride on esophageal acid reflux variables for 24 h was studied in 26 patients with GERD symptoms, pre-entry total acid exposure time (pH<4) of more than 5% and mild esophagitis (Savary-Miller grades I, II) proven by endoscopy. Ambulatory 24-h pH-metry and symptom assessment were performed after treatments with 150 or 300 mg itopride thrice a day (t.i. d.) for 30 d in random order, using an open label method. For evaluating the safety of itopride, blood biochemical laboratory test was performed and the serum prolactin level was also examined before and after treatment. RESULTS: Total symptom score was significantly decreased after treatment in 150- or 300-mg group. Itopride 300 mg was significantly effective than 150 mg on decreasing the total per cent time with pH < 4, total time with pH < 4 and DeMeester score. No serious adverse effects were observed with administration of itopride in both groups. CONCLUSION: Itopride 100 mg t.i.d. is effective on decreasing pathologic reflux in patient with GERD and therefore it has the potential to be effective in the treatment of this disease. PMID:16015691

Feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn.

PubMed

Riehl, M E; Pandolfino, J E; Palsson, O S; Keefer, L

2016-07-01

Functional heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability, and clinical utility of 7 weekly sessions of esophageal-directed HYP (EHYP) on heartburn symptoms, quality of life, and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety, and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention. © 2015 International Society for Diseases of the Esophagus.

The feasibility and acceptability of esophageal-directed hypnotherapy for functional heartburn

PubMed Central

Riehl, M. E.; Pandolfino, J. E.; Palsson, O. S.; Keefer, L.

2015-01-01

SUMMARY Functional Heartburn (FH) is a benign but burdensome condition characterized by painful, burning epigastric sensations in the absence of acid reflux or symptom-reflux correlation. Esophageal hypersensitivity and its psychological counterpart, esophageal hypervigilance (EHv) drive symptom experience. Hypnotherapy (HYP) is an established and preferred intervention for refractory symptoms in functional gastrointestinal disorders (FGIDs) and could be applied to FH. The objective of this study was to determine the feasibility, acceptability and clinical utility of 7 weekly sessions of esophageal-directed hypnotherapy (EHYP) on heartburn symptoms, quality of life and EHv. Similar to other work in FGIDs and regardless of hypnotizability, there were consistent and significant changes in heartburn symptoms, visceral anxiety and quality of life and a trend for improvement in catastrophizing. We would recommend EHYP in FH patients who are either non-responsive to medications or who would prefer a lifestyle intervention. PMID:25824436

PP-8 ESOPHAGEAL HIGH RESOLUTION MANOMETRY IN NEUROLOGICALLLY IMPAIRED CHILDREN AND GASTRO-OESOPHAGEAL REFLUX DISEASE.

PubMed

Turco, R; Ummarino, D; Miele, E; Terrone, G; Del Giudice, E; Staiano, A

2015-10-01

Mechanism underlying the occurrence of Gastroesophageal reflux disease (GERD) in neurologically impaired children (NIC) is poorly understood. We sought to characterize, by Esophageal High Resolution Manometry (EHRM), alterations of esophageal motility associated with GERD in NIC and to compare with a group with a suspicion of GERD and normal psychomotor development (NDP). EHRM and multichannel intraluminal impedance/pH-metry (MII/pH) were conducted in 7 NIC and 9 patients with suspicion of GERD and NPD. Esophagogastric junction relaxation (EGJr), the presence/pressure troughs of the oesophageal segments, the distal contractile integral adjusted for esophageal length (DCIa) and the pressurization frontal velocity (PFV) were analyzed by EHRM. Three out of 7 NIC (42.8%) and 4 out of 9 patients with NPD (44.4%) resulted positive to MII/pH (p = 1). No statistical differences were observed for EGJr and PFV between NIC and NPD patients. DCIa was significantly lower in NIC subjects respect to NPD patients (p < 0.01). Comparing NIC with GERD and patients with GERD and NPD we found that third segment was absent in 2/3 (66,6 %) of NIC respect to NPD patients (p < 0.05) and that the third pressure trough was significantly lower in NIC respect to NPD patients (p < 0.05). There were no statistical differences with respect to the first and second pressure trough between NIC and NDP patients. NIC have esophageal motor dysfunction that can be detected by EHRM. Some esophageal manometric alterations could be predictive of GERD in NIC and could explain a different pathogenesis of GERD in NIC and in patients with NPD.

Vagal sensory innervation of the gastric sling muscle and antral wall: implications for gastro-esophageal reflux disease?

PubMed

Powley, T L; Gilbert, J M; Baronowsky, E A; Billingsley, C N; Martin, F N; Phillips, R J

2012-10-01

The gastric sling muscle has not been investigated for possible sensory innervation, in spite of the key roles the structure plays in lower esophageal sphincter (LES) function and gastric physiology. Thus, the present experiment used tracing techniques to label vagal afferents and survey their projections in the lesser curvature. Sprague-Dawley rats received injections of dextran biotin into the nodose ganglia. Fourteen days postinjection, animals were euthanized and their stomachs were processed to visualize the vagal afferent innervation. In different cases, neurons, muscle cells, or interstitial cells of Cajal (ICC) were counterstained. The sling muscle is innervated throughout its length by vagal afferent intramuscular arrays (IMAs) associated with ICC. In addition, the distal antral attachment site of the sling muscle is innervated by a novel vagal afferent terminal specialization, an antral web ending. The muscle wall of the distal antrum is also innervated by conventional IMAs and intraganglionic laminar endings, the two types of mechanoreceptors found throughout stomach smooth muscle. The innervation of sling muscle by IMAs, putative stretch receptors, suggests that sling sensory feedback may generate vago-vagal or other reflexes with vagal afferent limbs. The restricted distribution of afferent web endings near the antral attachments of sling fibers suggests the possibility of specialized mechanoreceptor functions linking antral and pyloric activity to the operation of the LES. Dysfunctional sling afferents could generate LES motor disturbances, or normative compensatory sensory feedback from the muscle could compromise therapies targeting only effectors. © 2012 Blackwell Publishing Ltd.

Abnormal intrinsic esophageal innervation in congenital diaphragmatic hernia: a likely cause of motor dysfunction.

PubMed

Pederiva, Federica; Rodriguez, Jose I; Ruiz-Bravo, Elena; Martinez, Leopoldo; Tovar, Juan A

2009-03-01

Patients with congenital diaphragmatic hernia (CDH) often have dilated esophagus and gastroesophageal reflux. Sparse intrinsic esophageal innervation has been described in rats with CDH, but this issue has not been investigated in patients with CDH. The present study tests the hypothesis that innervatory anomalies could account for motor dysfunction in human CDH. The esophagi of CDH (n = 6) and control babies dead of other causes (n = 6) were included in paraffin, transversally sectioned, and immunostained with antineurofilament and anti-S-100 antibodies. The proportion of the section surface occupied by neural structures, the ganglionar surface, and the number of neurons per ganglion were measured in 2 to 5 low-power fields from the proximal and distal esophagus with the assistance of image analysis software. Mann-Whitney tests were used for comparing the results using a threshold of significance of P < .05. The percentage of neural/muscle surface was similar in the upper esophagus in both groups, but it was significantly decreased in the lower esophagus of patients with CDH in comparison with controls. There was a relative scarcity of neural tissue in the intermuscular plexus of the lower esophagus. On the other hand, the ganglionar surface and the number of neurons per ganglion were identical in both groups. These results were similar with both immunostainings. Intrinsic innervation of the lower esophagus in CDH is abnormal in terms of decreased density of neural structures in the intermuscular plexus. These neural crest-derived anomalies could explain in part the esophageal dysfunction in survivors of CDH.

Esophageal replacement.

PubMed

Kunisaki, Shaun M; Coran, Arnold G

2017-04-01

This article focuses on esophageal replacement as a surgical option for pediatric patients with end-stage esophageal disease. While it is obvious that the patient׳s own esophagus is the best esophagus, persisting with attempts to retain a native esophagus with no function and at all costs are futile and usually detrimental to the overall well-being of the child. In such cases, the esophagus should be abandoned, and the appropriate esophageal replacement is chosen for definitive reconstruction. We review the various types of conduits used for esophageal replacement and discuss the unique advantages and disadvantages that are relevant for clinical decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

[Primary esophageal motility disorders; especially about esophageal achalasia].

PubMed

Miyazaki, Tatsuya; Sohda, Makoto; Sakai, Makoto; Tanaka, Naritaka; Suzuki, Shigemasa; Yokobori, Takehiko; Inose, Takanori; Nakajima, Masanobu; Fukuchi, Minoru; Kato, Hiroyuki; Kusano, Motoyasu; Kuwano, Hiroyuki

2011-07-01

Esophageal motility disorders are classified primary and secondary, and primary esophageal motility disorders are classified esophageal achalasia and other diseases by manometry. An esophageal emptying disorder associated with insufficient relaxation of the lower esophageal sphincter (LES) and elimination of peristaltic waves on the esophageal body is the major abnormality of achalasia. Esophagogram, endoscopy, and manometry are used for diagnosis. As pharmacological therapy, administration of a calcium channel blocker or nitrate is useful. The pharmacological therapy is not recommended as long-term basic therapy but as a temporary treatment. At 1st, the balloon dilation method is chosen in treatment of achalasia Surgical treatment is indicated in the following cases: (1) Patients uneffected by balloon dilation, (2) Flask type with grade II to III dilation, and sigmoid type, (3) the gradual progression to the pathophysiological stage, (4) young patients, (5) complicated with esophageal cancer. Laparoscopic Heller-Dor procedure is the most popular surgical procedure, recently. It is somewhat difficult to perform surgical treatment for this functional disease. We should select the most suitable individualized treatment with efficient comprehension of the pathophysiological situation.

PAQR3 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer Cells.

PubMed

Zhou, Fang; Wang, Shunchang; Wang, Jianjun

2017-05-24

Progestin and adipoQ receptor family member III (PAQR3), a member of the PAQR family, is frequently downregulated in different types of human cancer. However, its expression and functions in esophageal cancer are still unknown. This study aimed to explore the expression of PAQR3 in esophageal cancer cell lines and to investigate the role of PAQR3 in the development of esophageal cancer. Our data showed that PAQR3 is expressed in low amounts in human esophageal cancer cell lines. Overexpression of PAQR3 significantly suppressed the proliferation, migration, and invasion of esophageal cancer cells. In addition, overexpression of PAQR3 downregulated the protein expression levels of RAF1, p-MEK1, and p-ERK1/2 in esophageal cancer cells. Furthermore, overexpression of PAQR3 attenuated the tumor growth in a tumor xenograft model. In conclusion, we demonstrated that overexpression of PAQR3 suppresses cell proliferation, migration, and invasion in esophageal cancer in vitro and in vivo. Therefore, PAQR3 may act as a therapeutic target for human esophageal cancer.

Diagnostic outcome of contrast videofluoroscopic swallowing studies in 216 dysphagic dogs.

PubMed

Pollard, Rachel E; Marks, Stanley L; Cheney, Diane M; Bonadio, Cecily M

2017-07-01

Determining the anatomic and functional origin for dysphagia is critical for development of an appropriate therapeutic plan and determination of the prognosis. The purpose of this retrospective study was to report the quantitative and qualitative outcome of contrast videofluoroscopic swallowing studies in a large cohort of dysphagic dogs presenting to a tertiary veterinary care hospital. The videofluoroscopic swallowing studies were reviewed to generate values for pharyngeal constriction ratio, timing of swallowing events (maximum pharyngeal contraction, opening of upper esophageal sphincter, closing of upper esophageal sphincter, and reopening of epiglottis), type of esophageal peristalsis generated, and esophageal transit time. One or more anatomic locations for origin of dysphagia were assigned (pharyngeal, cricopharyngeal, esophageal (primary motility disorder), other esophageal (stricture, vascular ring anomaly, mass), lower esophageal sphincter/hiatus. Sixty-one of 216 studies (28%) were deemed unremarkable. Twenty-seven of 216 dogs (13%) had pharyngeal dysphagia, 17/216 dogs (8%) had cricopharyngeal dysphagia, 98/216 dogs (45%) had dysphagia secondary to esophageal dysmotility, 19/216 dogs (9%) had dysphagia secondary to focal esophageal disorders, and 97/216 dogs (45%) had dysphagia of lower esophageal sphincter/hiatus origin. Multiple abnormalities were present in 82/216 (38%) dogs. Elevated pharyngeal constriction ratio was associated with pharyngeal, cricopharyngeal, and esophageal motility disorders, delayed upper esophageal sphincter opening was associated with cricopharyngeal disorders, a lower percentage of primary esophageal peristaltic waves was associated with cricopharyngeal, pharyngeal, or primary esophageal motility disorders. In conclusion, videofluoroscopic swallowing studies was pivotal in the diagnosis of dysphagia with 155/216 (72%) dogs receiving a final diagnosis. © 2017 American College of Veterinary Radiology.

The Functional Lumen Imaging Probe Detects Esophageal Contractility not Observed with Manometry in Patients with Achalasia

PubMed Central

Carlson, Dustin A.; Lin, Zhiyue; Kahrilas, Peter J.; Sternbach, Joel; Donnan, Erica N.; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E.

2015-01-01

Background & Aims The functional lumen imaging probe (FLIP) could improve characterization of achalasia subtypes by detecting non-occlusive esophageal contractions not observed with standard manometry. We aimed to evaluate for esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Methods Fifty one treatment-naïve patients with achalasia, defined and sub-classified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intra-bag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were further characterized by propagation direction, repetitiveness, and based on whether they were occluding or non-occluding. Results Esophageal contractility was detected in all 10 controls: 8/10 had repetitive, antegrade, contractions and 9/10 had occluding contractions. Contractility was detected in 27% (4/15) of patients with type I achalasia and 65% (18/26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility not observed in controls (repetitive, retrograde contractions). Conclusions Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of pan-esophageal pressurization in patients with type II achalasia. These findings could have implications for additional sub-classification to supplement prediction of the achalasia disease course. PMID:26278501

The prevalence of gastro-esophageal reflux disease and esophageal dysmotility in Chinese patients with idiopathic pulmonary fibrosis.

PubMed

Gao, Feng; Hobson, Anthony Robert; Shang, Zhan Min; Pei, Yan Xiang; Gao, Yan; Wang, Jian Xin; Huang, Wan Nong

2015-02-19

The cause of idiopathic pulmonary fibrosis (IPF) remains unknown, yet gastro-esophageal reflux disease (GERD) is highly prevalent in this population. GERD prevalence was studied, and esophageal function tests (EFT) were assessed in Chinese IPF patients. We prospectively studied 69 IPF patients who undertook both stationary High Resolution esophageal Manometry/Impedance (HRiM) and 24-hour esophageal Multi-Channel Intraluminal Impedance with pH Recordings (MII/pH). Patients were divided into GERD+ and GERD- groups according to pH results. Controls were HRiM treated healthy volunteers, and patients without IPF received HRiM and MII/pH diagnosed with GERD. 69 IPF patients, 62 healthy volunteers, and 88 IPF negative GERD patients were selected. GERD prevalence in IPF was 43/69 (62.3%), and 58.1% of patients presented with at least one typical symptom. Symptoms had a sensitivity of 58.1%, a specificity of 61.6%, a positive predictive value of 71.4% and a negative predictive of 47.1%. Compared with healthy volunteers, IPF patients had significantly decreased lower esophageal sphincter pressure (LESP), upper esophageal sphincter pressure (UESP) and complete bolus transit rate (CBTR). By contrast, IPF patients had increased total bolus transit time and prevalence of weak peristalsis. MII/pH showed that one third of IPF patients had abnormal distal and proximal reflux, especially non-acid reflux. Compared with GERD patients without IPF, GERD patients with IPF had significantly decreased CBTR and UESP with increased bolus exposure time. GERD prevalence in IPF was high, but symptoms alone were an unreliable predictor of reflux. IPF patients had lower LESP and UESP, impaired esophageal peristalsis and bolus clearance function with more proximal reflux events.

Gastroesophageal reflux disease after peroral endoscopic myotomy: Analysis of clinical, procedural and functional factors, associated with gastroesophageal reflux disease and esophagitis.

PubMed

Familiari, Pietro; Greco, Santi; Gigante, Giovanni; Calì, Anna; Boškoski, Ivo; Onder, Graziano; Perri, Vincenzo; Costamagna, Guido

2016-01-01

Peroral endoscopic myotomy (POEM) does not include any antireflux procedure, resulting in a certain risk of iatrogenic gastroesophageal reflux disease (GERD). The aim of the present study was to evaluate the incidence of iatrogenic GERD after POEM and identify preoperative, perioperative and postoperative factors associated with GERD. All patients treated at a single center who had a complete GERD evaluation after POEM were included in the study. Demographics, preoperative and follow-up data, results of functional studies and procedural data were collected and analyzed. A total of 103 patients (mean age 46.6 years, 47 males) were included. Postoperative altered esophageal acid exposure was attested in 52 patients (50.5%). A total of 19 patients (18.4%) had heartburn and 21 had esophagitis (20.4%). Overall, a clinically relevant GERD (altered esophageal acid exposure, associated with heartburn and/or esophagitis) was diagnosed in 30 patients (29.1%). Correlation between the severity of esophageal acid exposure with heartburn and esophagitis after POEM was found. Patients with heartburn had a lower postoperative 4-second integrated relaxation pressure compared to patients without symptoms (7.6 ± 3.8 mmHg vs 10.01 ± 4.4 mmHg, p<0.05). No correlations were identified with patient sex, age, postoperative body mass index, esophageal shape (sigmoid vs non sigmoid), lower esophageal sphincter pressure, length of myotomy, previous therapies and type of achalasia at high-resolution manometry. Preoperative, perioperative or postoperative factors minimally correlated with GERD after POEM. Clinically relevant GERD was identified in less than one-third of patients, but all patients were well controlled with medical therapy. © 2015 The Authors Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

PubMed

Chen, Miao-Fen; Chen, Ping-Tsung; Chen, Wen-Cheng; Lu, Ming-Shian; Lin, Paul-Yang; Lee, Kuan Der

2016-02-16

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

Specific esophagogram to assess functional outcomes after Heller's myotomy and Dor's fundoplication for esophageal achalasia.

PubMed

Tsoukali, E; Gouvas, N; Tsiaoussis, J; Pechlivanides, G; Zervakis, N; Mantides, A; Xynos, E

2011-09-01

Esophageal emptying assessed at the 'timed barium' esophagogram correlates well with symptomatic outcomes after pneumatic dilation for esophageal achalasia, although 30% of patients with satisfactory outcome exhibit partial improvement in emptying. The aim of the study was to investigate any correlation of esophageal emptying to symptomatic response after laparoscopic Heller's myotomy and Dor's fundoplication. 'Bread and barium' (transit time of a barium opaque bread bolus) and 'timed barium' (height of esophageal barium column 5 minutes after ingestion of 200-250 mL of barium suspension) esophagogram was used to assess esophageal emptying in 73 patients with esophageal achalasia before 1 and 5 years (31 cases) after laparoscopic myotomy and anterior fundoplication. Symptoms assessment was based to a specific score. At 1-year follow-up, excellent and good symptomatic results were obtained in 95% of the cases. Esophageal maximum diameter, esophageal transit time, and esophageal barium column were significantly correlated to each other and to symptom score postoperatively (P < 0.001). Complete and partial (<90% and 50-90% postoperative reduction in barium column, respectively) emptying was seen in 55% and 31% of patients with excellent result. Patients with a pseudodiverticulum postoperatively had a more delayed esophageal emptying than those without. Symptomatic outcome and esophageal emptying did not deteriorate at 5-year follow-up. Esophageal emptying assessed by 'barium and bread' and 'timed barium' esophagogram correlated well with symptomatic outcome after laparoscopic myotomy for esophageal achalasia. Complete symptomatic relief does not necessarily reflect complete esophageal emptying. Outcomes do not deteriorate by time. Because of wide availability, esophagogram can be applied in follow-up of postmyotomy patients in conjunction with symptomatic evaluation. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients.

PubMed

Zifan, A; Jiang, Y; Mittal, R K

2017-02-01

The mechanism of esophageal pain in patients with nutcracker esophagus (NE) and other esophageal motor disorders is not known. Our recent study shows that baseline esophageal mucosal perfusion, measured by laser Doppler perfusion monitoring, is lower in NE patients compared to controls. The goal of our current study was to perform a more detailed analysis of esophageal mucosal blood perfusion (EMBP) waveform of NE patients and controls to determine the optimal EMBP biomarkers that combined with suitable statistical learning models produce robust discrimination between the two groups. Laser Doppler recordings of 10 normal subjects (mean age 43 ± 15 years, 8 males) and 10 patients (mean age 47 ± 5.5 years., 8 males) with NE were analyzed. Time and frequency domain features were extracted from the first twenty-minute recordings of the EMBP waveforms, statistically ranked according to four independent evaluation criterions, and analyzed using two statistical learning models, namely, logistic regression (LR) and support vector machines (SVM). The top three ranked predictors between the two groups were the 0.5 and 0.75 perfusion quantile values followed by the surface of the EMBP power spectrum in the frequency domain. ROC curve ranking produced a cross-validated AUC (area under the curve) of 0.93 for SVM and 0.90 for LR. We show that as a group NE patients have lower perfusion values compared to controls, however, there is an overlap between the two groups, suggesting that not all NE patients suffer from low mucosal perfusion levels. © 2016 John Wiley & Sons Ltd.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl.

PubMed

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal-bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER.

Quality of Life after Open or Minimally Invasive Esophagectomy in Patients With Esophageal Cancer-A Systematic Review.

PubMed

Taioli, Emanuela; Schwartz, Rebecca M; Lieberman-Cribbin, Wil; Moskowitz, Gil; van Gerwen, Maaike; Flores, Raja

2017-01-01

Although esophageal cancer is rare in the United States, 5-year survival and quality of life (QoL) are poor following esophageal cancer surgery. Although esophageal cancer has been surgically treated with esophagectomy through thoracotomy, an open procedure, minimally invasive surgical procedures have been recently introduced to decrease the risk of complications and improve QoL after surgery. The current study is a systematic review of the published literature to assess differences in QoL after traditional (open) or minimally invasive esophagectomy. We hypothesized that QoL is consistently better in patients treated with minimally invasive surgery than in those treated with a more traditional and invasive approach. Although global health, social function, and emotional function improved more commonly after minimally invasive surgery compared with open surgery, physical function and role function, as well as symptoms including choking, dysphagia, eating problems, and trouble swallowing saliva, declined for both surgery types. Cognitive function was equivocal across both groups. The potential small benefits in global and mental health status among those who experience minimally invasive surgery should be considered with caution given the possibility of publication and selection bias. Copyright © 2017 Elsevier Inc. All rights reserved.

Impacts of treatments on the quality of life among esophageal squamous cell carcinoma patients.

PubMed

Chen, C-Y; Hsieh, V C-R; Chang, C-H; Chen, P-R; Liang, W-M; Pan, S-C; Shieh, S-H

2017-10-01

This study aims to investigate the effects of treatments on the quality of life for patients with esophageal squamous cell carcinoma patients diagnosed at early and late stages. From a medical center in central Taiwan, patients who had been diagnosed with esophageal squamous cell carcinoma from February 2007 and March 2011 were recruited. Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Quality of Life Questionnaire Oesophageal 18 (QLQ-OES18), quality of life scores for 105 esophageal squamous cell carcinoma patients were obtained and assessed. Multivariate analysis was performed on the quality of life scores after stratification by cancer stage. Among early-stage esophageal squamous cell carcinoma patients, those received only surgery (S-only) performed better in physical and social functioning compared with patients who underwent surgery and concurrent chemoradiotherapy (S+CCRT) (β = 9.0, P = 0.03; β = 12.1, P = 0.04, respectively). For those that received only concurrent chemoradiotherapy (CCRT-only), they performed worse in role and emotional functioning relative to S+CCRT patients (β = -17.2, P = 0.02; β = -15.7, P = 0.05, respectively). Among late-stage patients, CCRT-only treatment gave insignificantly better global health status and functional scale scores and less severe symptoms compared to the S+CCRT option. Better functional scores and less aggravated symptoms are observed in early-stage esophageal squamous cell carcinoma patients who received surgery-only treatment relative to those that underwent both surgery and chemoradiotherapy. For late-stage esophageal cancer patients, the measured difference of quality of life is not significant between CCRT-only and S+CCRT treatments. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Gastro-Esophageal Reflux in Children.

PubMed

Rybak, Anna; Pesce, Marcella; Thapar, Nikhil; Borrelli, Osvaldo

2017-08-01

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines.

Gastro-Esophageal Reflux in Children

PubMed Central

Pesce, Marcella; Thapar, Nikhil; Borrelli, Osvaldo

2017-01-01

Gastro-esophageal reflux (GER) is common in infants and children and has a varied clinical presentation: from infants with innocent regurgitation to infants and children with severe esophageal and extra-esophageal complications that define pathological gastro-esophageal reflux disease (GERD). Although the pathophysiology is similar to that of adults, symptoms of GERD in infants and children are often distinct from classic ones such as heartburn. The passage of gastric contents into the esophagus is a normal phenomenon occurring many times a day both in adults and children, but, in infants, several factors contribute to exacerbate this phenomenon, including a liquid milk-based diet, recumbent position and both structural and functional immaturity of the gastro-esophageal junction. This article focuses on the presentation, diagnosis and treatment of GERD that occurs in infants and children, based on available and current guidelines. PMID:28763023

Magnetic resonance imaging for simultaneous morphological and functional evaluation of esophageal motility disorders.

PubMed

Miyazaki, Yasuhiro; Nakajima, Kiyokazu; Sumikawa, Mitsuhiro; Yamasaki, Makoto; Takahashi, Tsuyoshi; Miyata, Hiroshi; Takiguchi, Shuji; Kurokawa, Yukinori; Tomiyama, Noriyuki; Mori, Masaki; Doki, Yuichiro

2014-04-01

The purpose of this study was to evaluate the feasibility and safety of esophageal functional magnetic resonance imaging (fMRI) for the diagnosis of achalasia. Eleven patients with suspected achalasia and three normal subjects underwent fMRI while swallowing clear liquid with original sequences; "T2-weighed single-shot fast spin-echo" and "Fast Imaging Employing Steady-state Acquisition". The fMRI-based diagnosis was compared with that based on manometry. The luminal fluctuation index (LFI) and Dd/Ds ratio were used for the objective evaluation of the esophageal peristalsis and relaxation of the lower esophageal sphincter (LES). Functional MRI showed a dilated tortuous esophagus with no tumor, poor clearance, simultaneous waves, aperistalsis, and impaired LES relaxation in all but one case, allowing the diagnosis of achalasia with accuracy similar to that of manometry. The LFI (median 0.08, range 0.03-0.25) and Dd/Ds ratio (1.40, 1.0-2.3) of the patient group were significantly lower than those of the normal subjects [1.50, 2.32-4.05, and 2.59 (2.32-4.05)]. No severe adverse events directly related to fMRI were noted. Using our protocol, fMRI was considered to be safe and feasible for the diagnosis of achalasia. Given the widespread use of MRI, esophageal fMRI, which does not require exposure to radiation, could be a potentially useful diagnostic tool for patients with esophageal motility disorders.

Methylation of DACT2 accelerates esophageal cancer development by activating Wnt signaling

PubMed Central

Zhang, Meiying; Linghu, Enqiang; Zhan, Qimin; He, Tao; Cao, Baoping; Brock, Malcolm V.; Herman, James G.; Xiang, Rong; Guo, Mingzhou

2016-01-01

Esophageal cancer is one of the most common malignancies worldwide. DACT2 is frequently methylated in human lung, hepatic, gastric and thyroid cancers. The methylation status and function of DACT2 remain to be elucidated in human esophageal cancer. Ten esophageal cancer cell lines, 42 cases of dysplasia and 126 cases of primary esophageal cancer samples were analyzed in this study. The expression of DACT2 was detected in YES2 cells, while reduced DACT2 expression levels were found in TE8 and KYSE70 cells, and complete loss of DACT2 expression was found in KYSE30, KYSE140, KYSE150, KYSE410, KYSE450, TE3 and TE7 cells. Loss of expression or reduced expression of DACT2 correlated with promoter region hypermethylation in esophageal cancer cells. Restoration of DACT2 expression was induced by 5-aza-2′-deoxycytidine. In human primary esophageal squamous carcinoma, 69% (87/126) of samples were methylated. Methylation of DACT2 was significantly associated with tumor stage and metastasis (P < 0.01, P < 0.05). DACT2 suppressed colony formation, cell migration and invasion in esophageal cancer cells, and it also suppressed esophageal cancer cell xenograft growth. DACT2 inhibited Wnt signaling in human esophageal cancer cells. In conclusion, DACT2 is frequently methylated in human esophageal cancer and its expression is regulated by promoter region methylation. DACT2 suppresses esophageal cancer growth by inhibiting Wnt signaling. PMID:26919254

The calibrated laparoscopic Heller myotomy with fundoplication.

PubMed

Di Martino, Natale; Marano, Luigi; Torelli, Francesco; Schettino, Michele; Porfidia, Raffaele; Reda, Gianmarco; Grassia, Michele; Petrillo, Marianna; Braccio, Bartolomeo

2013-01-01

Esophageal achalasia is the most common primary esophageal motor disorder. Laparoscopic Heller's myotomy combined with fundoplication represents the treatment of choice for this disease, achieving good results in about 90% of patients. However, about 10% of treated patients refer persistent or recurrent dysphagia. Many Authors showed that this failure rate is related to inadequate myotomy. To verify, from experimental to clinical study, the modifications induced by Heller's myotomy of the esophago- gastric junction on LES pressure (LES-P profile, using a computerized manometric system. From 2002 to 2010 105 patients with achalasia underwent laparoscopic calibrated Heller myotomy followed by antireflux surgery. The calibrated Heller myotomy was extended for at least 2.5 cm on the esophagus and for 3 cm on the gastric side. Each step was evaluated by intraoperative manometry. Moreover, intraoperative manometry and endoscopy were used to calibrate the fundoplication. The preoperative mean LES-P was 37.73 ± 12.21. After esophageal and gastric myotomy the mean pressure drop was 21.3% and 91.9%, respectively. No mortality was reported. Laparoscopic calibrated Heller myotomy with fundoplication achieves a good outcome in the surgical treatment of achalasia. The use of intraoperative manometry enables an adequate calibration of myotomy, being effective in the evaluation of the complete pressure drop, avoiding too long esophageal myotomy and, especially, too short gastric myotomy, that may be the cause of surgical failure.

Utility of the transnasal esophagoscope in the management of chemoradiation-induced esophageal stenosis.

PubMed

Peng, Kevin A; Feinstein, Aaron J; Salinas, Jonathan B; Chhetri, Dinesh K

2015-03-01

This study aimed to describe management of esophageal stenosis after chemoradiation therapy for head and neck squamous cell carcinoma (HNSCC), with particular emphasis on techniques and outcomes with the use of the transnasal esophagoscope (TNE) in the office as well as operating room settings. Retrospective analysis of all patients with esophageal stenosis following head and neck cancer radiation, with or without chemotherapy, and managed with TNE-assisted esophageal dilation over a 5-year period. Preoperative and postoperative swallowing function were assessed objectively with the Functional Outcome Swallowing Scale (FOSS; ranging from score 0, a normal diet, to score 5, complete dependence on nonoral nutrition). Twenty-five patients met inclusion criteria. The mean pretreatment FOSS score was 4.4, whereas the mean posttreatment FOSS score was 2.7 (Wilcoxon signed-rank test, P<.001). Prior to dilation, 16 patients were completely gastrostomy-tube dependent (FOSS 5), of whom 12 (75%) were able to tolerate oral nutrition for a majority of their diet following treatment according to our protocol. No complications were noted. Dysphagia following chemoradiation therapy for HNSCC is often related to esophageal stenosis. With the aid of TNE, we have developed a successful treatment strategy for esophageal stenosis with improved success rates. © The Author(s) 2014.

Tachykinin receptor expression and function in human esophageal smooth muscle.

PubMed

Kovac, Jason R; Chrones, Tom; Preiksaitis, Harold G; Sims, Stephen M

2006-08-01

Tachykinins are present in enteric nerves of the gastrointestinal tract and cause contraction of esophageal smooth muscle; however, the mechanisms involved are not understood. Our aim was to characterize tachykinin signaling in human esophageal smooth muscle. We investigated functional effects of tachykinins on human esophageal smooth muscle using tension recordings and isolated cells, receptor expression with reverse transcription (RT)-polymerase chain reaction (PCR) and immunoblotting, intracellular Ca2+ responses using fluorescent indicator dyes, and membrane currents with patch-clamp electrophysiology. The mammalian tachykinins [substance P and neurokinin (NK) A and NKB] elicited concentration-dependent contractions of human esophageal smooth muscle. These responses were not affected by muscarinic receptor or neuronal blockade indicating a direct effect on smooth muscle cells (SMCs). Immunofluorescence and RT-PCR identified tachykinin receptors (NK1, NK2, and NK3) on SMCs. Contraction was mediated through a combination of Ca2+ release from intracellular stores and influx through L-type Ca2+ channels. NK2 receptor blockade inhibited the largest proportion of tachykinin-evoked responses. NKA evoked a nonselective cation current (I(NSC)) with properties similar to that elicited by muscarinic stimulation. The following paradigm is suggested: tachykinin receptor binding to SMCs releases Ca2+ from stores along with activation of I(NSC), which in turn results in membrane depolarization, L-type Ca2+ channel opening, rise of Ca2+ concentration, and contraction. These studies reveal new aspects of tachykinin signaling in human esophageal SMCs. Excitatory tachykinin pathways may represent targets for pharmacological intervention in disorders of esophageal dysmotility.

Intrinsic functional connectivity of the brain swallowing network during subliminal esophageal acid stimulation.

PubMed

Babaei, A; Siwiec, R M; Kern, M; Douglas Ward, B; Li, S-J; Shaker, R

2013-12-01

Intrinsic synchronous fluctuations of the functional magnetic resonance imaging signal are indicative of the underlying 'functional connectivity' (FC) and serve as a technique to study dynamics of the neuronal networks of the human brain. Earlier studies have characterized the functional connectivity of a distributed network of brain regions involved in swallowing, called brain swallowing network (BSN). The potential modulatory effect of esophageal afferent signals on the BSN, however, has not been systematically studied. Fourteen healthy volunteers underwent steady state functional magnetic resonance imaging across three conditions: (i) transnasal catheter placed in the esophagus without infusion; (ii) buffer solution infused at 1 mL/min; and (iii) acidic solution infused at 1 mL/min. Data were preprocessed according to the standard FC analysis pipeline. We determined the correlation coefficient values of pairs of brain regions involved in swallowing and calculated average group FC matrices across conditions. Effects of subliminal esophageal acidification and nasopharyngeal intubation were determined. Subliminal esophageal acid stimulation augmented the overall FC of the right anterior insula and specifically the FC to the left inferior parietal lobule. Conscious stimulation by nasopharyngeal intubation reduced the overall FC of the right posterior insula, particularly the FC to the right prefrontal operculum. The FC of BSN is amenable to modulation by sensory input. The modulatory effect of sensory pharyngoesophageal stimulation on BSN is mainly mediated through changes in the FC of the insula. The alteration induced by subliminal visceral esophageal acid stimulation is in different insular connections compared with that of conscious somatic pharyngeal stimulation. © 2013 John Wiley & Sons Ltd.

Hypnotherapy for Esophageal Disorders.

PubMed

Riehl, Megan E; Keefer, Laurie

2015-07-01

Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms--visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome.

Hypnotherapy for Esophageal Disorders

PubMed Central

Riehl, Megan E.; Keefer, Laurie

2015-01-01

Hypnotherapy is an evidence based intervention for the treatment of functional bowel disorders, particularly irritable bowel syndrome. While similar in pathophysiology, less is known about the utility of hypnotherapy in the upper gastrointestinal tract. Esophageal disorders, most of which are functional in nature, cause painful and uncomfortable symptoms that impact patient quality of life and are difficult to treat from a medical perspective. After a thorough medical workup and a failed trial of proton pump inhibitor therapy, options for treatment are significantly limited. While the pathophysiology is likely multifactorial, two critical factors are believed to drive esophageal symptoms—visceral hypersensitivity and symptom hypervigilance. The goal of esophageal directed hypnotherapy is to promote a deep state of relaxation with focused attention allowing the patient to learn to modulate physiological sensations and symptoms that are not easily addressed with conventional medical intervention. Currently, the use of hypnosis is suitable for dysphagia, globus, functional chest pain/non-cardiac chest pain, dyspepsia, and functional heartburn. In this article the authors will provide a rationale for the use of hypnosis in these disorders, presenting the science whenever available, describing their approach with these patients, and sharing a case study representing a successful outcome. PMID:26046715

The Functional Lumen Imaging Probe Detects Esophageal Contractility Not Observed With Manometry in Patients With Achalasia.

PubMed

Carlson, Dustin A; Lin, Zhiyue; Kahrilas, Peter J; Sternbach, Joel; Donnan, Erica N; Friesen, Laurel; Listernick, Zoe; Mogni, Benjamin; Pandolfino, John E

2015-12-01

The functional lumen imaging probe (FLIP) could improve the characterization of achalasia subtypes by detecting nonocclusive esophageal contractions not observed with standard manometry. We aimed to evaluate esophageal contractions during volumetric distention in patients with achalasia using FLIP topography. Fifty-one treatment-naive patients with achalasia, defined and subclassified by high-resolution esophageal pressure topography, and 10 asymptomatic individuals (controls) were evaluated with the FLIP during endoscopy. During stepwise distension, simultaneous intrabag pressures and 16 channels of cross-sectional areas were measured; data were exported to software that generated FLIP topography plots. Esophageal contractility was identified by noting periods of reduced luminal diameter. Esophageal contractions were characterized further by propagation direction, repetitiveness, and based on whether they were occluding or nonoccluding. Esophageal contractility was detected in all 10 controls: 8 of 10 had repetitive antegrade contractions and 9 of 10 had occluding contractions. Contractility was detected in 27% (4 of 15) of patients with type I achalasia and in 65% (18 of 26, including 9 with occluding contractions) of patients with type II achalasia. Contractility was detected in all 10 patients with type III achalasia; 8 of these patients had a pattern of contractility that was not observed in controls (repetitive retrograde contractions). Esophageal contractility not observed with manometry can be detected in patients with achalasia using FLIP topography. The presence and patterns of contractility detected with FLIP topography may represent variations in pathophysiology, such as mechanisms of panesophageal pressurization in patients with type II achalasia. These findings could have implications for additional subclassification to supplement prediction of the achalasia disease course. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms

PubMed Central

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-01

Background/Aims Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). Methods We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Results Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group (P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. Conclusions IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients. PMID:27599539

Esophageal Body Motility for Clinical Assessment in Patients with Refractory Gastroesophageal Reflux Symptoms.

PubMed

Jiang, Liuqin; Ye, Bixing; Wang, Ying; Wang, Meifeng; Lin, Lin

2017-01-30

Little data exists about esophageal body dysmotility and reflux patterns in refractory gastroesophageal reflux disease (RGERD) patients off therapy. We aimed to evaluate effects of esophageal body dysmotility on reflux parameters in RGERD patients by combining impedance-pH monitoring and high-resolution manometry (HRM). We retrospectively reviewed the impedance-pH data and HRM metrics in patients with refractory gastroesophageal reflux symptoms. Impedance-pH monitoring and manometric data were compared between 2 groups: ineffective esophageal motility (IEM) and normal motility. Forty-eight patients (30 males, mean age 54.5 years) were included (16 erosive esophagitis, 24 non-erosive reflux disease, and 8 functional heartburn), amongst which 24 subjects showed IEM, and others had normal motility. Number of patients who had a large break in the IEM group was significantly higher than that of normal motility patients. IEM group had more patients with weakly acid reflux and long term acid reflux than the normal group ( P = 0.008, P = 0.004, respectively). There was no statistical difference in baseine impedance levels from z4 to z6 between the 2 groups (2911 ± 1160 Ω vs 3604 ± 1232 Ω, 2766 ± 1254 Ω vs 3752 ± 1439 Ω, 2349 ± 1131 Ω vs 3038 ± 1254 Ω, all P > 0.05). Acid exposure time, numbers of long term acid reflux and weakly acid reflux showed strong negative correlation with esophageal body motility and/or lower esophageal sphincter function. IEM was associated more with acid exposure, abnormal weakly acid reflux, and long term acid reflux in RGERD patients. These data suggested the role of esophageal body dysmotility in the pathophysiological mechanisms of RGERD patients.

Esophageal motility pattern and gastro-esophageal reflux in chronic obstructive pulmonary disease.

PubMed

Gadel, Abil Ali; Mostafa, Mohamed; Younis, Ahmed; Haleem, Magdy

2012-01-01

The association of esophageal motility and gastroesophageal reflux symptoms with respiratory symptoms is not well established in patients with chronic obstructive pulmonary disease (COPD). The aim of this work is to study the abnormalities of esophageal function in COPD patients and study its relation to smoking index, body mass index and indices of hyperinflation. This study included 40 male COPD patients and 10 healthy controls. The patients and controls were subjected to spirometry, body plethysmography, esophageal manometry and 24hr pH-metry. Upper gastrointestinal symptoms were found in 55% of patients, hypotensive upper esophageal sphincter pressure in 65% of patients and hypotensive lower esophageal sphincter pressure in 52.5% of patients. Pathological acid reflux was found in 35% of patients. The severity of GERD increased with increased age, smoking index and body mass index, p<0.005. There was negative correlation between LESP and UESP compared with indices of hyperinflation, p<0.001. There was high prevalence of esophageal motility disorders in COPD patients, LESP and UESP were significantly negatively correlated to indices of hyperinflation. There was a high prevalence of GERD in COPD patents especially elderly, severe stage of COPD, high smoking index and high body mass index (BMI).

Reversal of lower esophageal sphincter hypotension and esophageal aperistalsis after treatment for hypothyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eastwood, G.L.; Braverman, L.E.; White, E.M.

1982-08-01

A 65-year-old woman suffered from both chronic gastroesophageal reflux, which was complicated by columnar metaplasia (Barrett's epithelium), and profound hypothyroidism. An esophageal motility tracing showed absence of peristalsis in the lower esophagus and the lower esophageal sphincter (LES) could not be identified. Thyroid replacement therapy, in conjunction with antacid and cimetidine treatment, was associated not only with improvement in the gastroesophageal reflux symptoms, but also with a return of esophageal peristalsis and LES pressure to normal. To support our clinical observations, we rendered four cats hypothyroid with /sup 131/I and documented a fall in LES pressure. We propose that abnormalmore » smooth-muscle function of the esophagus may be another manifestation of the gastrointestinal motility disturbances which are associated with hypothyroidism.« less

Esophageal achalasia: current diagnosis and treatment.

PubMed

Schlottmann, Francisco; Patti, Marco G

2018-05-27

Esophageal achalasia is a primary esophageal motility disorder of unknown origin, characterized by lack of peristalsis and by incomplete or absent relaxation of the lower esophageal sphincter in response to swallowing. The goal of treatment is to eliminate the functional obstruction at the level of the gastroesophageal junction Areas covered: This comprehensive review will evaluate the current literature, illustrating the diagnostic evaluation and providing an evidence-based treatment algorithm for this disease Expert commentary: Today we have three very effective therapeutic modalities to treat patients with achalasia - pneumatic dilatation, per-oral endoscopic myotomy and laparoscopic Heller myotomy with fundoplication. Treatment should be tailored to the individual patient, in centers where a multidisciplinary approach is available. Esophageal resection should be considered as a last resort for patients who have failed prior therapeutic attempts.

Characterization of Esophageal Physiology Using Mechanical State Analysis.

PubMed

Leibbrandt, Richard E; Dinning, Phil G; Costa, Marcello; Cock, Charles; Wiklendt, Lukasz; Wang, Guangsong; Tack, Jan; van Beckevoort, Dirk; Rommel, Nathalie; Omari, Taher I

2016-01-01

The esophagus functions to transport swallowed fluids and food from the pharynx to the stomach. The esophageal muscles governing bolus transport comprise circular striated muscle of the proximal esophagus and circular smooth muscle of the distal esophagus. Longitudinal smooth muscle contraction provides a mechanical advantage to bolus transit during circular smooth muscle contraction. Esophageal striated muscle is directly controlled by neural circuits originating in the central nervous system, resulting in coordinated contractions. In contrast, the esophageal smooth muscle is controlled by enteric circuits modulated by extrinsic central neural connections resulting in neural relaxation and contraction. The esophageal muscles are modulated by sensory information arising from within the lumen. Contraction or relaxation, which changes the diameter of the lumen, alters the intraluminal pressure and ultimately inhibits or promotes flow of content. This relationship that exists between the changes in diameter and concurrent changes in intraluminal pressure has been used previously to identify the "mechanical states" of the circular muscle; that is when the muscles are passively or actively, relaxing or contracting. Detecting these changes in the mechanical state of the muscle has been difficult and as the current interpretation of esophageal motility is based largely upon pressure measurement (manometry), subtle changes in the muscle function during peristalsis can be missed. We hypothesized that quantification of mechanical states of the esophageal circular muscles and the pressure-diameter properties that define them, would allow objective characterization of the mechanisms that govern esophageal peristalsis. To achieve this we analyzed barium swallows captured by simultaneous videofluoroscopy and pressure with impedance recording. From these data we demonstrated that intraluminal impedance measurements could be used to determine changes in the internal diameter of the lumen comparable with measurements from videofluoroscopy. Our data indicated that identification of mechanical state of esophageal muscle was simple to apply and revealed patterns consistent with the known neural inputs activating the different muscles during swallowing.

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer

PubMed Central

Ren, Zhipeng; Zhang, Guoliang

2017-01-01

Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer. PMID:28388588

Non-coding RNAs: new biomarkers and therapeutic targets for esophageal cancer.

PubMed

Hou, Xiaobin; Wen, Jiaxin; Ren, Zhipeng; Zhang, Guoliang

2017-06-27

Esophageal cancer is one of the most common gastrointestinal malignant diseases and there is still no effective treatment. The incidence of esophageal cancer in the world is relatively high and on the increase year by year. Thus, the elaboration on the carcinogenesis of esophageal cancer and the identification of new biomarkers and therapeutic targets is quite beneficial to optimizing the current therapeutic regimen for treating such deadly disease. More and more evidence has shown that non-coding RNAs play an important role in the development and progression of multiple human cancers, including esophageal cancer. microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two functional kinds of non-coding RNAs that have been well investigated. They exert tumor suppressive or promoting effect by specifically regulating the expression of certain downstream target genes, which is tumor specific. It is also proved that miRNAs and lncRNAs level in tissue and plasma from esophageal cancer patients are closely correlated with the survival and disease progression, which could be used as a prognostic factor and therapeutic target for esophageal cancer.

Does Nissen fundoplication improve deglutition in children?

PubMed

Soyer, Tutku; Yalçın, Şule; Demir, Numan; Karhan, Asuman Nur; Saltık-Temizel, İnci Nur; Demir, Hülya; Tanyel, Feridun Cahit

2017-01-01

Soyer T, Yalçın Ş, Demir N, Karhan AN, Saltık-Temizel İN, Demir H, Tanyel FC. Does Nissen fundoplication improve deglutition in children? Turk J Pediatr 2017; 59: 28-34. A prospective study was performed to evaluate the effect of Nissen fundoplication (NF) on deglutition in children. Children who underwent NF between 2011-2015 were evaluated for demographic features, clinical findings, diagnostic methods for gastroesophageal reflux (GER) and indications for NF. Penetration aspiration scale (PAS), functional oral intake scale (FOIS) and esophageal functions were evaluated by videoflouroscopy (VFS). Preoperative and postoperative VFS findings were compared to evaluate the effect of NF on clinical findings and deglutition. Twenty-three children with a mean age of 5.08 ± 3.7 years were included. Female to male ratio was 15:8. Recurrent respiratory infections (RTI) (n: 14, 60.8%), swallowing dysfunction (n:13, 56.5%) and vomiting (n:10, 43.4%) were the most common symptoms. Preoperatively GER was diagnosed with barium swallowing study (BSS) contrast graphs (n:20, 87%) and with 24-hour esophageal pH monitorization (n:8, 34.8%). In 39.1% of patients, medical treatment for GER was used with a mean duration of 8 ± 5.8 months. Indications for NF were swallowing dysfunction (n: 18, 78%), GER complications (n:6, 26%), associated anatomical problems (n:4, 17.3%) and unresponsiveness to medical treatment (n: 3, 13%). Postoperative barium swallowing study and 24-hour esophageal pH monitorization showed no GER after NF in 95% of patients. Number of RTI were significantly decreased after NF (preoperative vs postoperative infection rate 4.21 vs 1.6 respectively, p < 0.05). VFS findings showed that PAS was significantly decreased after NF during both liquid and semi-liquid swallowing (p < 0.05). After NF, upper esophageal opening (UEO) was decreased when compared to preoperative VFS findings (p < 0.05 Esophageal cleaning, esophageal motility, esophageal backflow and lower esophageal sphincter narrowing did not alter after NF (p > 0.05). FOIS were significantly improved after NF (p < 0.05). VFS findings showed that penetration and aspiration were significantly decreased after NF and children had less RTI. Although, esophageal motility evaluated by VFS did not changed after NF, functional oral intake significantly improved in children.

High-resolution manometry combined with impedance measurements discriminates the cause of dysphagia in children.

PubMed

Rommel, Nathalie; Omari, Taher I; Selleslagh, Margot; Kritas, Stamatiki; Cock, Charles; Rosan, Rachel; Rodriguez, Leonel; Nurko, Samuel

2015-12-01

Pressure-flow analysis allows assessing esophageal bolus transport in relation to esophageal pressures. This study aimed to characterize pressure-flow metrics in relation to dysphagia in paediatric patients. We analysed esophageal pressure-impedance recordings of 5 ml liquid and viscous swallows from 35 children (17 M, mean 10.5 ± 0.8 years). Primary indication for referral was gastroesophageal reflux disease (GERD) (9), post-fundoplication dysphagia (5), idiopathic dysphagia (16), trachea-esophageal fistula (2) and other (3). Peristaltic function was assessed using the 20 mmHg iso-contour defect and the timing between bolus pressure and flow was assessed using the Pressure Flow Index, a metric elevated in relation to dysphagia. Patients were stratified in relation to dysphagia and to peristaltic defect size. Dysphagia was characterized by a weaker peristalsis for liquids and higher Pressure Flow Index for viscous. When patients were stratified based on weak or normal peristalsis, dysphagia with weak peristalsis related to a larger iso-contour defect size and dysphagia with normal peristalsis related to higher Pressure Flow Index. Pressure-flow analysis enables differentiation of patients with dysphagia due to weak peristalsis (poor bolus clearance) from abnormal bolus flow resistance (esophageal outflow obstruction). This new dichotomous categorization of esophageal function may help guide the selection of optimal treatment such as pharmacological or endoscopic therapy. • Pressure-flow analysis (PFA) can detect abnormalities in esophageal motility using integrated analysis of bolus propulsion and bolus flow during swallowing. • AIM analysis has recently been reported to be useful in identifying subtle pre-operative esophageal dysfunction in adult patients who developed post-fundoplication dysphagia as well as in patients with non-obstructive dysphagia. • Pressure-flow parameters can distinguish the cause of dysphagia in paediatric patients. • Combined high-resolution manometry and impedance measurements with pressure-flow analysis can differentiate paediatric patients with dysphagia symptoms in relation to either weak peristalsis (poor bolus clearance) or over-pressurization (abnormal bolus flow resistance). HOW MIGHT IT IMPACT ON CLINICAL PRACTICE IN THE FUTURE? • This study supports the use of a novel objective analysis method on recordings that are readily used in paediatric clinical practice. • The pressure-flow approach allows discriminating esophageal dysfunction in relation to dysphagia symptoms in children. This has not been achieved in children with current analysis methods. • The new findings of this study allow a dichotomous categorization of esophageal function, which may help to guide the selection of the most optimal treatment such as pharmacological or endoscopic therapy.

The migrating myoelectric complex of the small intestine

NASA Astrophysics Data System (ADS)

Telford, Gordon L.; Sarna, Sushil K.

1991-10-01

Gastric and small intestinal myoelectric and motor activity is divided into two main patterns, fed and fasted. During fasting, the predominant pattern of activity is the migrating myoelectric complex (MMC), a cyclically occurring pattern of electric and mechanical activity that is initiated in the stomach and duodenum almost simultaneously and, from there, propagates the length of the small intestine. Cyclic motor activity also occurs in the lower esophageal sphincter, the gallbladder, and the sphincter of Oddi with a duration that is related to the MMC in the small intestine. Of the possible mechanisms for initiation of the MMC in the small intestine (extrinsic neural control, intrinsic neural control, and hormonal control), intrinsic neural control via a series of coupled is the most likely. The keep this sentence in! hormone motilin also plays a role in the initiation of MMCs. After a meal, in man the MMC is disrupted and replaced by irregular contractions. The physiologic role of the MMC is to clear the stomach and small intestine of residual food, secretions, and desquamated cells and propel them to the colon. Disruption of the MMC cycle is associated with bacterial overgrowth in some patients, an observation that supports the proposed cleansing function of the MMC cycle.

Axial force measurement for esophageal function testing

PubMed Central

Gravesen, Flemming H; Funch-Jensen, Peter; Gregersen, Hans; Drewes, Asbjørn Mohr

2009-01-01

The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the “golden standard” for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force (force in radial direction) whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal (axial) direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method. PMID:19132762

Reversal of asynchrony between circular and longitudinal muscle contraction in nutcracker esophagus by atropine.

PubMed

Korsapati, Hariprasad; Bhargava, Valmik; Mittal, Ravinder K

2008-09-01

Patients with high-amplitude esophageal contractions (nutcracker esophagus [NCE]) show asynchrony of circular muscle (CM) and longitudinal muscle (LM) contraction during peristalsis. The goal of our study was to determine if this asynchrony is related to an increase in the cholinergic receptor activity. High-frequency intraluminal ultrasound images and pressures of the esophagus were recorded simultaneously in 10 normal subjects and 10 patients with NCE. Recordings were obtained at 2 cm above the lower esophageal sphincter under 2 study conditions in normal subjects (before and after 80 microgm/kg of edrophonium), and under 3 study conditions in the NCE patients (control, 5 microgm and 10 microgm/kg of atropine). In normal subjects, edrophonium induced an increase in the CM and LM contraction amplitude, an increase in the contraction duration, and asynchrony of LM and CM contraction during peristalsis. On the other hand, increased contraction amplitude, duration, and asynchrony of LM and CM contraction observed at the baseline in the NCE patients were reversed by atropine in a dose-dependent fashion. These data prove that the esophageal motor abnormalities in patients with nutcracker esophagus, including asynchrony of CM and LM contraction, are related to a hypercholinergic state.

Mechanisms of acid reflux and how refluxed Acid extends proximally in patients with non-erosive reflux disease.

PubMed

Sano, Hirohito; Iwakiri, Katsuhiko; Kawami, Noriyuki; Tanaka, Yuriko; Sakamoto, Choitsu

2014-01-01

The mechanisms that cause acid reflux in patients with non-erosive reflux disease (NERD), including those that determine how acid extends proximally, are not yet clear. Concurrent esophageal manometry and pH monitoring were performed for 3 h after a meal in 13 patients with NERD, 12 with mild reflux esophagitis (RE), and 13 healthy subjects (HS). Transient lower esophageal sphincter (LES) relaxation (TLESR) was the major mechanism of acid reflux in all three groups. LES pressure did not differ between the groups. At 2 cm above the LES, there were no differences between the three groups in the number of TLESR-related acid reflux episodes, rate of TLESRs and rate of acid reflux during TLESR. However, at 7 cm above the LES, the rate of acid reflux during TLESRs was significantly higher in patients with NERD (mean ± SEM 42.3 ± 4.8) than in those with mild RE (28.0 ± 3.8) and HS (10.8 ± 2.5). TLESRs are the sole motor events underlying acid reflux episodes in patients with NERD. Acid extends proximally more readily in patients with NERD than in HS and those with mild RE.

Automated impedance-manometry analysis detects esophageal motor dysfunction in patients who have non-obstructive dysphagia with normal manometry.

PubMed

Nguyen, N Q; Holloway, R H; Smout, A J; Omari, T I

2013-03-01

Automated integrated analysis of impedance and pressure signals has been reported to identify patients at risk of developing dysphagia post fundoplication. This study aimed to investigate this analysis in the evaluation of patients with non-obstructive dysphagia (NOD) and normal manometry (NOD/NM). Combined impedance-manometry was performed in 42 patients (27F : 15M; 56.2 ± 5.1 years) and compared with that of 24 healthy subjects (8F : 16M; 48.2 ± 2.9 years). Both liquid and viscous boluses were tested. MATLAB-based algorithms defined the median intrabolus pressure (IBP), IBP slope, peak pressure (PP), and timing of bolus flow relative to peak pressure (TNadImp-PP). An index of pressure and flow (PFI) in the distal esophagus was derived from these variables. Diagnoses based on conventional manometric assessment: diffuse spasm (n = 5), non-specific motor disorders (n = 19), and normal (n = 11). Patients with achalasia (n = 7) were excluded from automated impedance-manometry (AIM) analysis. Only 2/11 (18%) patients with NOD/NM had evidence of flow abnormality on conventional impedance analysis. Several variables derived by integrated impedance-pressure analysis were significantly different in patients as compared with healthy: higher PNadImp (P < 0.01), IBP (P < 0.01) and IBP slope (P < 0.05), and shorter TNadImp_PP (P = 0.01). The PFI of NOD/NM patients was significantly higher than that in healthy (liquid: 6.7 vs 1.2, P = 0.02; viscous: 27.1 vs 5.7, P < 0.001) and 9/11 NOD/NM patients had abnormal PFI. Overall, the addition of AIM analysis provided diagnoses and/or a plausible explanation in 95% (40/42) of patients who presented with NOD. Compared with conventional pressure-impedance assessment, integrated analysis is more sensitive in detecting subtle abnormalities in esophageal function in patients with NOD and normal manometry. © 2012 Blackwell Publishing Ltd.

Esophageal acid sensitivity and mucosal integrity in patients with functional heartburn.

PubMed

Weijenborg, P W; Smout, A J P M; Bredenoord, A J

2016-11-01

Patients with functional heartburn (FH) experience troublesome heartburn that is not related to gastroesophageal reflux. The etiology of the heartburn sensation in FH patients is unknown. In patients with reflux disease, esophageal hypersensitivity seems associated with impaired mucosal integrity. We aimed to determine esophageal sensitivity and mucosal integrity in FH and non-erosive reflux disease (NERD) patients. In this prospective experimental study, we performed an acid perfusion test and upper endoscopy with biopsies in 12 patients with NERD and nine patients with FH. Mucosal integrity was measured during endoscopy using electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance and transepithelial permeability. Lag time to heartburn perception was significantly longer in FH patients (median 12 min) than in NERD patients (median 3 min). Once perceived, intensity of heartburn was scored equal with median visual analog scale 6.5 and 7.1 respectively. Esophageal mucosal integrity was also comparable between FH and NERD patients, both in vivo extracellular impedance and ex vivo transepithelial resistance and permeability were similar. Patients with FH did not show acid hypersensitivity as seen in patients with NERD. However, once perceived, intensity of heartburn is similar. Esophageal mucosal integrity is similar between NERD and FH patients, and is therefore unlikely to be the underlying cause of the observed difference in esophageal acid perception. © 2016 John Wiley & Sons Ltd.

The PER (Preoperative Esophagectomy Risk) Score: A Simple Risk Score to Predict Short-Term and Long-Term Outcome in Patients with Surgically Treated Esophageal Cancer.

PubMed

Reeh, Matthias; Metze, Johannes; Uzunoglu, Faik G; Nentwich, Michael; Ghadban, Tarik; Wellner, Ullrich; Bockhorn, Maximilian; Kluge, Stefan; Izbicki, Jakob R; Vashist, Yogesh K

2016-02-01

Esophageal resection in patients with esophageal cancer (EC) is still associated with high mortality and morbidity rates. We aimed to develop a simple preoperative risk score for the prediction of short-term and long-term outcomes for patients with EC treated by esophageal resection. In total, 498 patients suffering from esophageal carcinoma, who underwent esophageal resection, were included in this retrospective cohort study. Three preoperative esophagectomy risk (PER) groups were defined based on preoperative functional evaluation of different organ systems by validated tools (revised cardiac risk index, model for end-stage liver disease score, and pulmonary function test). Clinicopathological parameters, morbidity, and mortality as well as disease-free survival (DFS) and overall survival (OS) were correlated to the PER score. The PER score significantly predicted the short-term outcome of patients with EC who underwent esophageal resection. PER 2 and PER 3 patients had at least double the risk of morbidity and mortality compared to PER 1 patients. Furthermore, a higher PER score was associated with shorter DFS (P < 0.001) and OS (P < 0.001). The PER score was identified as an independent predictor of tumor recurrence (hazard ratio [HR] 2.1; P < 0.001) and OS (HR 2.2; P < 0.001). The PER score allows preoperative objective allocation of patients with EC into different risk categories for morbidity, mortality, and long-term outcomes. Thus, multicenter studies are needed for independent validation of the PER score.

Is there a role for high resolution manometry in GERD diagnosis?

PubMed

Tolone, Salvatore; Savarino, Edoardo; Docimo, Ludovico

2017-09-01

Gastroesophageal reflux disease (GERD) is a condition, which develops when the reflux of stomach contents causes troublesome symptoms and/or complications. In patients with alarm symptoms or signs or in those refractory to antiacid therapy, it is indicated to perform instrumental tests to correctly diagnose GERD presence. Esophageal manometry is currently considered the gold standard test for the diagnosis of esophageal dysmotility. However, it has shown limited capability in diagnosing GERD. With the advent of high resolution manometry (HRM), more accurate evaluations of esophageal motility are now possible. Furthermore, new metrics have been developed to investigate esophagogastric junction (EGJ) morphology and function. In particular, the antireflux barrier function of EGJ can now be assessed evaluating the contraction integral of the junction. Also, transient lower esophageal relaxations can be defined more precisely with HRM. Provocative tests with multiple swallows can give additional information on peristaltic reserve. Finally, adding impedance measurement to HRM allows to detect retrograde movements (e.g. reflux) in the esophagus and to measure the baseline impedance, a novel promising metric associated to esophageal mucosal integrity. The present review will discuss the recent progresses made in evaluation of GERD patients with HRM and its potential role in diagnosing pathological reflux presence.

Update on Functional Heartburn

PubMed Central

Yamasaki, Takahisa; O’Neil, Jessica

2017-01-01

The definition of functional heartburn has been refined over the years. It is currently described, based upon Rome IV criteria, as typical heartburn symptoms in the presence of normal upper endoscopy findings (including normal biopsies), normal esophageal pH testing, and a negative association between symptoms and reflux events. Functional heartburn is very common, affecting women more than men, and with reflux hypersensitivity makes up the majority of heartburn patients who fail twice-daily proton pump inhibitor therapy. These disorders overlap with other functional gastrointestinal disorders and are often accompanied by psychological comorbidities. Diagnosis is made by using endoscopy with esophageal biopsies, wireless pH capsule, pH-impedance monitoring, and high-resolution esophageal manometry. Additional diagnostic tools that may be of value include magnification endoscopy, chromoendoscopy, narrow-band imaging, autofluorescence imaging, mucosal impedance, impedance baseline values, and histopathology scores. Functional heartburn is primarily treated with neuromodulators. Psychological intervention and complementary and alternative medicine may also play important roles in the treatment of these patients. PMID:29339948

Protective Effect of Dietary Calcium Intake on Esophageal Cancer Risk: A Meta-Analysis of Observational Studies.

PubMed

Li, Qianwen; Cui, Lingling; Tian, Yalan; Cui, Han; Li, Li; Dou, Weifeng; Li, Haixia; Wang, Ling

2017-05-18

Although several epidemiological studies have investigated the association between dietary calcium intake and the risk of esophageal cancer, the results are inconsistent. This study aimed to make a comprehensive evaluation regarding the association between calcium intake and risk of esophageal cancer through a meta-analysis approach. We searched for all relevant articles from the inception to April 2017, using PUBMED, EMBASE, and Web of Knowledge. The pooled odds ratio (ORs) with the 95% confidence interval (95% CI) for the highest versus the lowest categories of calcium intake was calculated using a Mantel-Haenszel fixed-effect model. In total, 15 articles reporting 17 studies including 3396 esophageal cancer cases and 346,815 controls were selected for the meta-analysis. By comparing the highest vs. the lowest levels of dietary calcium intake, we found that dietary calcium intake was inversely associated with the risk of esophageal cancer (OR = 0.80, 95% CI: 0.71-0.91, I ² = 33.6%). The subgroup analysis indicated that the protective function of dietary calcium intake were observed in esophageal squamous cell cancer, but not in esophageal adenocarcinoma in the studies conducted in Asia, but not those in Europe and America. In conclusion, our results suggest that higher dietary calcium intake is associated with a lower risk of esophageal cancer-especially esophageal squamous cell cancer-in Asian populations, though more data from prospective cohort studies are needed.

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants.

PubMed

Jadcherla, Sudarshan R; Hasenstab, Kathryn A; Sitaram, Swetha; Clouse, Brian J; Slaughter, Jonathan L; Shaker, Reza

2016-06-01

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones. Copyright © 2016 the American Physiological Society.

New insights into the pathophysiology of achalasia and implications for future treatment.

PubMed

Furuzawa-Carballeda, Janette; Torres-Landa, Samuel; Valdovinos, Miguel Ángel; Coss-Adame, Enrique; Martín Del Campo, Luis A; Torres-Villalobos, Gonzalo

2016-09-21

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.

New insights into the pathophysiology of achalasia and implications for future treatment

PubMed Central

Furuzawa-Carballeda, Janette; Torres-Landa, Samuel; Valdovinos, Miguel Ángel; Coss-Adame, Enrique; Martín del Campo, Luis A; Torres-Villalobos, Gonzalo

2016-01-01

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter (LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents (herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient’s quality of life. PMID:27672286

Esophageal diverticula and cancer.

PubMed

Herbella, F A M; Dubecz, A; Patti, M G

2012-02-01

Esophageal diverticula are rare. The association of cancer and diverticula has been described. Some authors adopt a conservative non-surgical approach in selected patients with diverticula whereas others treat the symptoms by diverticulopexy or myotomy only, leaving the diverticulum in situ. However, the risk of malignant degeneration should be may be taken in account if the diverticulum is not resected. The correct evaluation of the possible risk factors for malignancy may help in the decision making process. We performed a literature review of esophageal diverticula and cancer. The incidence of cancer in a diverticulum is 0.3-7, 1.8, and 0.6% for pharyngoesophageal, midesophageal, and epiphrenic diverticula, respectively. Symptoms may mimic those of the diverticulum or underlying motor disorder. Progressive dysphagia, unintentional weight loss, the presence of blood in the regurgitated material, regurgitation of peaces of the tumor, odynophagia, melena, hemathemesis, and hemoptysis are key symptoms. Risk factors for malignancy are old age, male gender, long-standing history, and larger diverticula. A carcinoma may develop in treated diverticula, even after resection. Outcomes are usually quoted as dismal because of a delayed diagnosis but several cases of superficial carcinoma have been described. The treatment follows the same principals as the therapy for esophageal cancer; however, diverticulectomy is enough in cases of superficial carcinomas. Patients must be carefully evaluated before therapy and a long-term follow-up is advisable. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants

PubMed Central

Hasenstab, Kathryn A.; Sitaram, Swetha; Clouse, Brian J.; Slaughter, Jonathan L.; Shaker, Reza

2016-01-01

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones. PMID:27012774

Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

PubMed

Posner, S; Zheng, J; Wood, R K; Shimpi, R A; Hartwig, M G; Chow, S-C; Leiman, D A

2018-05-01

Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p < 0.01). Dysmotility was found in 98 (43%) patients, with major peristaltic or esophageal outflow disorders in 45 (20%) patients. Symptoms were not correlated with findings on esophageal high-resolution manometry. Fifteen of 25 (60%) asymptomatic patients had an abnormal manometry or pH-metry. These results demonstrate that in patients with advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

A fully coupled bolus-esophageal-gastric model for esophageal emptying based on the immersed boundary method

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Pandolfino, John E.; Kahrilas, Peter J.; Patankar, Neelesh A.

2016-11-01

In this work, we develop a fully coupled bolus-esophageal-gastric model to study esophageal emptying based on the immersed boundary method. The model includes an esophageal segment, an ellipsoid-shaped stomach, and a bolus. It can easily handle the passive and active function of the lower esophageal sphincter (LES). Two groups of case studies are presented. The first group is about the influence from tissue anisotropy. Simulation shows that the weaker (or more compliant) part suffers from a higher wall shear stress and higher pressure load when the bolus is filled in and emptied from the LES segment. This implies a degradation cycle in which a weaker tissue becomes much weaker due to an increased load, a possible pathway to the esophageal lower diverticulum. The second group is about bulge formation resulting from asymmetric anatomy and a compliant LES. In particular, we find a right bulge tends to develop for a compliant LES. The bulge is most pronounced with a highest stiffness of the gastric wall. This implies that the competition between the LES stiffness and gastric wall stiffness might be another factor related to the esophageal lower diverticulum. The support of Grant R01 DK56033 and R01 DK079902 from NIH is gratefully acknowledged.

Role of a health psychologist in the management of functional esophageal complaints.

PubMed

Riehl, M E; Kinsinger, S; Kahrilas, P J; Pandolfino, J E; Keefer, L

2015-07-01

Upper gastrointestinal complaints are common among patients in a gastrointestinal clinic. Outside of typical gastroesophageal reflux disease symptoms that are treated with medication, the symptom presentations of esophageal patients, particularly those with functional conditions, are often difficult to treat and account for high health-care utilization. This manuscript describes the role of a health psychologist in the treatment of esophageal disorders using behavioral medicine interventions. Observations over the course of a 1-year period indicate that the sample presents with a relatively low level of psychological distress but reports negative effects of their symptoms on health-related quality of life. Five case examples of commonly treated disorders (globus, non-cardiac chest pain, functional dysphagia, rumination syndrome, supragastric belching) are described to highlight how behavioral treatment can improve patients' symptoms, decrease health-care utilization, and improve overall quality of life in a timely and relatively simple manner. Successful treatment outcomes are associated with a collaborative working alliance between patient, health psychologist, and gastroenterologist. Results indicate the benefit of referring appropriate esophageal patients to a health psychologist with specialization in gastroenterology. © 2014 International Society for Diseases of the Esophagus.

Augment clinical measurement using a constraint-based esophageal model

NASA Astrophysics Data System (ADS)

Kou, Wenjun; Acharya, Shashank; Kahrilas, Peter; Patankar, Neelesh; Pandolfino, John

2017-11-01

Quantifying the mechanical properties of the esophageal wall is crucial to understanding impairments of trans-esophageal flow characteristic of several esophageal diseases. However, these data are unavailable owing to technological limitations of current clinical diagnostic instruments that instead display esophageal luminal cross sectional area based on intraluminal impedance change. In this work, we developed an esophageal model to predict bolus flow and the wall property based on clinical measurements. The model used the constraint-based immersed-boundary method developed previously by our group. Specifically, we first approximate the time-dependent wall geometry based on impedance planimetry data on luminal cross sectional area. We then fed these along with pressure data into the model and computed wall tension based on simulated pressure and flow fields, and the material property based on the strain-stress relationship. As examples, we applied this model to augment FLIP (Functional Luminal Imaging Probe) measurements in three clinical cases: a normal subject, achalasia, and eosinophilic esophagitis (EoE). Our findings suggest that the wall stiffness was greatest in the EoE case, followed by the achalasia case, and then the normal. This is supported by NIH Grant R01 DK56033 and R01 DK079902.

The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.

PubMed

Lubin, Daniel J; Mick, Rosemarie; Shroff, Stuti G; Stashek, Kristen; Furth, Emma E

2018-02-01

The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of peroral esophageal myotomy for achalasia treatment: A Chinese study.

PubMed

Lu, Bin; Li, Meng; Hu, Yue; Xu, Yi; Zhang, Shuo; Cai, Li-Jun

2015-05-14

To assess the safety and feasibility of peroral esophageal myotomy (POEM) in patients with achalasia. From January 2012 to March 2014, 50 patients (28 men, 22 women; mean age: 42.8 years, range: 14-70 years) underwent POEM. Pre- and postoperative symptoms were quantified using the Eckardt scoring system. Barium swallow and esophagogastroscopy were performed before and after POEM, respectively. Esophageal motility was evaluated in all patients, both preoperatively and one month after POEM treatment, using a high-resolution manometry system. Manometry data, Eckardt scores, lower esophageal sphincter pressure and barium swallow results were used to evaluate the effect of the procedure. POEM was successfully completed for all patients. The mean procedure time was 55.4 ± 17.3 min and the mean total length of myotomy of the circular esophagus was 10.5 ± 2.6 cm. No specific complications occurred, with the exception of two patients that developed asymptomatic pneumomediastinum and subcutaneous emphysema. Clinical improvement in symptoms was achieved in all patients. Approximately 77.5% of patients experienced weight gain 6 mo after POEM, with an average of 4.78 kg (range: 2-15 kg). The lower esophageal sphincter resting pressure, four second integrated relaxation pressure and Eckardt scores were all significantly reduced after POEM (Ps < 0.05). A small segment of proximal esophageal peristalsis appeared postoperatively in two patients, but without normal esophageal peristalsis. The average diameter of the esophageal lumen decreased significantly from 4.39 to 3.09 cm (P < 0.01). POEM can relieve achalasia symptoms, improve gastroesophageal junction relaxation and restore esophageal body motility function, but not normal esophageal peristalsis.

New endoscopic indicator of esophageal achalasia: "pinstripe pattern".

PubMed

Minami, Hitomi; Isomoto, Hajime; Miuma, Satoshi; Kobayashi, Yasutoshi; Yamaguchi, Naoyuki; Urabe, Shigetoshi; Matsushima, Kayoko; Akazawa, Yuko; Ohnita, Ken; Takeshima, Fuminao; Inoue, Haruhiro; Nakao, Kazuhiko

2015-01-01

Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia. This single-center retrospective study included 56 cases of esophageal achalasia without previous treatment. As a control, 60 non-achalasia subjects including reflux esophagitis and superficial esophageal cancer were also included in this study. Endoscopic findings were evaluated according to Descriptive Rules for Achalasia of the Esophagus as follows: (1) esophageal dilatation, (2) abnormal retention of liquid and/or food, (3) whitish change of the mucosal surface, (4) functional stenosis of the esophago-gastric junction, and (5) abnormal contraction. Additionally, the presence of the longitudinal superficial wrinkles of esophageal mucosa, "pinstripe pattern (PSP)" was evaluated endoscopically. Then, inter-observer diagnostic agreement was assessed for each finding. The prevalence rates of the above-mentioned findings (1-5) were 41.1%, 41.1%, 16.1%, 94.6%, and 43.9%, respectively. PSP was observed in 60.7% of achalasia, while none of the control showed positivity for PSP. PSP was observed in 26 (62.5%) of 35 cases with shorter history < 10 years, which usually lacks typical findings such as severe esophageal dilation and tortuosity. Inter-observer agreement level was substantial for food/liquid remnant (k = 0.6861) and PSP (k = 0.6098), and was fair for abnormal contraction and white change. The accuracy, sensitivity, and specificity for achalasia were 83.8%, 64.7%, and 100%, respectively. "Pinstripe pattern" could be a reliable indicator for early discrimination of primary esophageal achalasia.

Endoscopic mucosal autograft for treating esophageal caustic strictures: preliminary human experience.

PubMed

He, Kexin; Zhao, Lili; Bu, Shoushan; Liu, Li; Wang, Xiang; Wang, Min; Fan, Zhining

2018-06-11

 Esophageal caustic stricture is a stubborn disease and postoperative restenosis limits the clinical efficacy of endoscopic dilation. Autologous mucosal grafts have been successfully applied in the treatment of urethral stricture and in the prevention of stricture after extensive mucosal resection. We aimed to use mucosal autografting performed endoscopically to treat refractory esophageal stricture. METHODS : Three patients with intractable corrosive esophageal stricture were treated endoscopically by combining dilation with autologous mucosal transplantation. RESULTS : All procedures were successful with no severe complications. Mucosal regeneration was shown at the transplanted segments. One patient was able to maintain a normal diet with complete remission after 1 year of follow-up. Intraluminal stenosis and dysphagia were significantly improved in another two patients. CONCLUSIONS : Mucosal autografting can achieve esophageal re-epithelialization, inhibit undesired fibrosis, prevent restenosis, and promote functional regeneration. © Georg Thieme Verlag KG Stuttgart · New York.

The antiprotease SPINK7 serves as an inhibitory checkpoint for esophageal epithelial inflammatory responses.

PubMed

Azouz, Nurit P; Ynga-Durand, Mario A; Caldwell, Julie M; Jain, Ayushi; Rochman, Mark; Fischesser, Demetria M; Ray, Leanne M; Bedard, Mary C; Mingler, Melissa K; Forney, Carmy; Eilerman, Matthew; Kuhl, Jonathan T; He, Hua; Biagini Myers, Jocelyn M; Mukkada, Vincent A; Putnam, Philip E; Khurana Hershey, Gurjit K; Kottyan, Leah C; Wen, Ting; Martin, Lisa J; Rothenberg, Marc E

2018-06-06

Loss of barrier integrity has an important role in eliciting type 2 immune responses, yet the molecular events that initiate and connect this with allergic inflammation remain unclear. We reveal an endogenous, homeostatic mechanism that controls barrier function and inflammatory responses in esophageal allergic inflammation. We show that a serine protease inhibitor, SPINK7 (serine peptidase inhibitor, kazal type 7), is part of the differentiation program of human esophageal epithelium and that SPINK7 depletion occurs in a human allergic, esophageal condition termed eosinophilic esophagitis. Experimental manipulation strategies reducing SPINK7 in an esophageal epithelial progenitor cell line and primary esophageal epithelial cells were sufficient to induce barrier dysfunction and transcriptional changes characterized by loss of cellular differentiation and altered gene expression known to stimulate allergic responses (for example, FLG and SPINK5 ). Epithelial silencing of SPINK7 promoted production of proinflammatory cytokines including thymic stromal lymphopoietin (TSLP). Loss of SPINK7 increased the activity of urokinase plasminogen-type activator (uPA), which in turn had the capacity to promote uPA receptor-dependent eosinophil activation. Treatment of epithelial cells with the broad-spectrum antiserine protease, α1 antitrypsin, reversed the pathologic features associated with SPINK7 silencing. The relevance of this pathway in vivo was supported by finding genetic epistasis between variants in TSLP and the uPA-encoding gene, PLAU We propose that the endogenous balance between SPINK7 and its target proteases is a key checkpoint in regulating mucosal differentiation, barrier function, and inflammatory responses and that protein replacement with antiproteases may be therapeutic for select allergic diseases. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Dietary habits and esophageal cancer.

PubMed

Palladino-Davis, A G; Mendez, B M; Fisichella, P M; Davis, C S

2015-01-01

Cancer of the esophagus is an underestimated, poorly understood, and changing disease. Its overall 5-year survival is less than 20%, even in the United States, which is largely a function of a delay in diagnosis until its more advanced stages. Additionally, the epidemiologic complexities of esophageal cancer are vast, rendering screening and prevention limited at best. First, the prevalence of esophageal cancer is unevenly distributed throughout the world. Second, the two histological forms (squamous cell and adenocarcinoma) vary in terms of their geographic prevalence and associated risk factors. Third, some populations appear at particular risk for esophageal cancer. And fourth, the incidence of esophageal cancer is in continuous flux among groups. Despite the varied prevalence and risks among populations, some factors have emerged as consistent associations while others are only now becoming more fully recognized. The most prominent, scientifically supported, and long-regarded risk factors for esophageal cancer are tobacco, alcohol, and reflux esophagitis. Inasmuch as the above are regarded as important risk factors for esophageal cancer, they are not the sole contributors. Dietary habits, nutrition, local customs, and the environment may be contributory. Along these lines, vitamins, minerals, fruits, vegetables, meats, fats, salted foods, nitrogen compounds, carcinogens, mycotoxins, and even the temperature of what we consume are increasingly regarded as potential etiologies for this deadly although potentially preventable disease. The goal of this review is to shed light on the less known role of nutrition and dietary habits in esophageal cancer. © 2013 Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Gastroesophageal reflux disease-related and functional heartburn: pathophysiology and treatment.

PubMed

Miwa, Hiroto; Kondo, Takashi; Oshima, Tadayuki

2016-07-01

Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn. The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease. New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.

The value of early wireless esophageal pH monitoring in diagnosing functional heartburn in refractory gastroesophageal reflux disease.

PubMed

Park, Eun-Young; Choi, Myung-Gyu; Baeg, Meonggi; Lim, Chul-Hyun; Kim, Jinsu; Cho, Yukyung; Park, Jaemyung; Lee, Inseok; Kim, Sangwoo; Choi, Kyuyong

2013-10-01

It is difficult to differentiate functional heartburn from proton pump inhibitor (PPI) failure. The aims of this study were to assess the role of early wireless esophageal pH monitoring in patients referred with gastroesophageal reflux disease (GERD) and to identify differences in the clinical spectrum among GERD subtypes. We enrolled consecutive referred patients with suspected GERD. After endoscopy on the first visit, all underwent wireless esophageal pH monitoring when off the PPI. Two hundred thirty patients were enrolled. These patients were classified into a reflux esophagitis group (20, 8.7 %) and a normal endoscopic findings group (210, 91.3 %). Among the 210 patients in the normal endoscopic findings group, 63 (27.4 %) were diagnosed with pathological reflux, 35 (15.2 %) with hypersensitive esophagus, 87 (37.8 %) with normal acid exposure with negative symptom association, and 25 (10.9 %) with test failure. These groups did not differ in age, body mass index, smoking habit, alcohol consumption, symptom severity, quality of life, presence of atypical symptoms, overlap with irritable bowel syndrome, and the frequency of somatization, depression, and anxiety. PPI responses were evaluated in 135 patients. Fifty patients (37.0 %) were not responsive to the 4-week treatment; 26 (19.3 %) were diagnosed with refractory non-erosive gastroesophageal disease, and 24 (17.8 %) with functional heartburn. The demographics and clinical and psychological characteristics did not differ between the two groups. Demographic characteristics and symptom patterns alone cannot differentiate functional heartburn from various subtypes of GERD. Wireless esophageal pH monitoring should be considered for the initial evaluation of GERD in the tertiary referral setting.

Left colonic graft in esophageal reconstruction for caustic stricture: mortality and morbidity.

PubMed

Boukerrouche, A

2013-01-01

The adequacy of the blood supply to the left colon graft and its ability to transport food effectively from pharynx to stomach made it an esophageal substitute of choice, particularly in esophageal caustic stricture. From 1999 to 2009, 60 patients underwent colon interposition for esophageal caustic stricture (n= 57) and cancer (n= 3). An isoperistaltic colonic graft based on the left colonic artery could be used in all of these patients. The substernal route was used exclusively, and upper thoracic inlet was opened when necessary. The isoperistaltic left colonic graft interposed by substernal route represents the surgical procedure of choice in all operations performed for esophageal substitution during the study period. The operative mortality rate was 3.3%. A cervical fistula occurred in 10 patients (16.6%) and cervical anastomotic stricture in five patients (8.3%). Dilation was required in all the stricture of the esophageal colonic anastomosis with good response. The isoperistaltic left colic transplant supplied by the left colic pedicle is an excellent long-term replacement organ for the esophageal caustic stenosis. When performed by experienced surgeons, the left isoperistaltic esophagocoloplasty is a satisfactory surgical method for esophageal reconstruction with acceptable early morbidity and good long-term functional results. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Esophageal replacement by hydroxylated bacterial cellulose patch in a rabbit model.

PubMed

Zhu, Changlai; Liu, Fang; Qian, Wenbo; Wang, Yingjie; You, Qingsheng; Zhang, Tianyi; Li, Feng

2015-01-01

To repair esophageal defects by hydroxylated and kombucha-synthesized bacterial cellulose (HKBC) patch in a rabbit model. Semicircular esophageal defects 1 cm in length of the cervical esophagus were initially created in 18 Japanese big-ear rabbits and then repaired with HKBC patch grafts. The clinical outcomes including survival rate, weight change, food intake, and hematological and radiologic evaluation were observed. After X-ray evaluation, the rabbits were sacrificed sequentially at 1, 3, and 6 months for histopathologic analysis with light microscopy and scanning electron microscopy. Survival rate during the first month was 88.9% (n = 16). Two rabbits died from anastomotic leakage during the entire follow-up. Postoperatively, feeding function and body weight were gradually restored in the surviving animals. No hematological abnormalities were found, and no obvious anastomotic leakage, stenosis, or obstruction was observed under X-ray examination. The histopathologic results showed a progressive regeneration of the esophagus in the graft area, where the neo-esophagus tissue had characteristics similar to native esophageal tissue after 3 months of surgery. HKBC is beneficial for esophageal tissue regeneration and may be a promising material for esophageal reconstruction.

The pathogenesis of pseudoachalasia: a clinicopathologic study of 13 cases of a rare entity.

PubMed

Liu, Wendy; Fackler, William; Rice, Thomas W; Richter, Joel E; Achkar, Edgar; Goldblum, John R

2002-06-01

Pseudoachalasia is an esophageal motor disorder usually associated with malignancy that has clinical, radiographic, and manometric findings that are often indistinguishable from primary achalasia. There are few reports examining the histologic features of the associated neoplasms and their relationship with the esophageal myenteric plexus. We studied the clinical and pathologic features of 13 cases of pseudoachalasia seen at our institution between 1979 and 1999. Detailed clinical and radiographic data were obtained from medical records. In all cases available histologic material was reviewed to confirm the presence and type of associated neoplasm. When possible, the relationship of the neoplasm to the esophageal myenteric plexus was examined. In selected cases immunohistochemical stains were performed to further evaluate this relationship. All patients had clinical, radiographic, and manometric features similar to primary achalasia. The cohort included seven men and six women, age range 24-79 years (median 61 years). Associated neoplasms included esophageal adenocarcinoma arising in Barrett's esophagus (n = 1), adenocarcinoma of the esophagogastric junction (n = 7), metastatic renal cell carcinoma to the esophagogastric junction (n = 1), breast adenocarcinoma (n = 1), pulmonary small cell carcinoma (n = 1), pleural malignant mesothelioma (n = 1), and mediastinal fibrosis (n = 1). The mechanism of pseudoachalasia was consistent with neoplastic infiltration of the esophageal myenteric plexus in 11 cases. Neoplastic cells surrounded myenteric ganglion cells, which appeared normal in number and morphology. In the patient with pulmonary small cell carcinoma, there was no evidence of neoplastic infiltration of the esophagogastric junction, and anti-ANNA-1 antibody was detected, suggesting a paraneoplastic syndrome. Tissue obtained at the time of esophagomyotomy revealed lymphocytic myenteric inflammation and marked depletion of ganglion cells identical to that seen in primary achalasia. The mechanism pseudoachalasia in the patient with breast adenocarcinoma is uncertain, as there was no evidence of direct involvement of the esophagogastric junction. In summary, we describe 13 cases of pseudoachalasia resulting in a clinical syndrome indistinguishable from primary achalasia. The most common mechanism is direct involvement of the esophageal myenteric plexus by neoplastic cells. Rarely, a distant neoplasm may cause this syndrome as a paraneoplastic process.

Effect of peroral esophageal myotomy for achalasia treatment: A Chinese study

PubMed Central

Lu, Bin; Li, Meng; Hu, Yue; Xu, Yi; Zhang, Shuo; Cai, Li-Jun

2015-01-01

AIM: To assess the safety and feasibility of peroral esophageal myotomy (POEM) in patients with achalasia. METHODS: From January 2012 to March 2014, 50 patients (28 men, 22 women; mean age: 42.8 years, range: 14-70 years) underwent POEM. Pre- and postoperative symptoms were quantified using the Eckardt scoring system. Barium swallow and esophagogastroscopy were performed before and after POEM, respectively. Esophageal motility was evaluated in all patients, both preoperatively and one month after POEM treatment, using a high-resolution manometry system. Manometry data, Eckardt scores, lower esophageal sphincter pressure and barium swallow results were used to evaluate the effect of the procedure. RESULTS: POEM was successfully completed for all patients. The mean procedure time was 55.4 ± 17.3 min and the mean total length of myotomy of the circular esophagus was 10.5 ± 2.6 cm. No specific complications occurred, with the exception of two patients that developed asymptomatic pneumomediastinum and subcutaneous emphysema. Clinical improvement in symptoms was achieved in all patients. Approximately 77.5% of patients experienced weight gain 6 mo after POEM, with an average of 4.78 kg (range: 2-15 kg). The lower esophageal sphincter resting pressure, four second integrated relaxation pressure and Eckardt scores were all significantly reduced after POEM (Ps < 0.05). A small segment of proximal esophageal peristalsis appeared postoperatively in two patients, but without normal esophageal peristalsis. The average diameter of the esophageal lumen decreased significantly from 4.39 to 3.09 cm (P < 0.01). CONCLUSION: POEM can relieve achalasia symptoms, improve gastroesophageal junction relaxation and restore esophageal body motility function, but not normal esophageal peristalsis. PMID:25987787

New Endoscopic Indicator of Esophageal Achalasia: “Pinstripe Pattern”

PubMed Central

Minami, Hitomi; Isomoto, Hajime; Miuma, Satoshi; Kobayashi, Yasutoshi; Yamaguchi, Naoyuki; Urabe, Shigetoshi; Matsushima, Kayoko; Akazawa, Yuko; Ohnita, Ken; Takeshima, Fuminao; Inoue, Haruhiro; Nakao, Kazuhiko

2015-01-01

Background and Study Aims Endoscopic diagnosis of esophageal achalasia lacking typical endoscopic features can be extremely difficult. The aim of this study was to identify simple and reliable early indicator of esophageal achalasia. Patients and Methods This single-center retrospective study included 56 cases of esophageal achalasia without previous treatment. As a control, 60 non-achalasia subjects including reflux esophagitis and superficial esophageal cancer were also included in this study. Endoscopic findings were evaluated according to Descriptive Rules for Achalasia of the Esophagus as follows: (1) esophageal dilatation, (2) abnormal retention of liquid and/or food, (3) whitish change of the mucosal surface, (4) functional stenosis of the esophago-gastric junction, and (5) abnormal contraction. Additionally, the presence of the longitudinal superficial wrinkles of esophageal mucosa, “pinstripe pattern (PSP)” was evaluated endoscopically. Then, inter-observer diagnostic agreement was assessed for each finding. Results The prevalence rates of the above-mentioned findings (1–5) were 41.1%, 41.1%, 16.1%, 94.6%, and 43.9%, respectively. PSP was observed in 60.7% of achalasia, while none of the control showed positivity for PSP. PSP was observed in 26 (62.5%) of 35 cases with shorter history < 10 years, which usually lacks typical findings such as severe esophageal dilation and tortuosity. Inter-observer agreement level was substantial for food/liquid remnant (k = 0.6861) and PSP (k = 0.6098), and was fair for abnormal contraction and white change. The accuracy, sensitivity, and specificity for achalasia were 83.8%, 64.7%, and 100%, respectively. Conclusion “Pinstripe pattern” could be a reliable indicator for early discrimination of primary esophageal achalasia. PMID:25664812

A genome-wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer.

PubMed

Liu, Wenjia; Zhang, Yiyang; Chen, Min; Shi, Liangliang; Xu, Lei; Zou, Xiaoping

2018-06-21

Esophageal cancer is one of the most common cancers and a leading cause of cancer-related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence-free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein-coding genes involve with many known biological processes, such as cell cycle and cell-cell adherens junction. Further experimental validation revealed that knockdown of DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Esophageal leiomyoma in a dog causing esophageal distension and treated by transcardial placement of a self-expanding, covered, nitinol esophageal stent.

PubMed

Robin, Elisabeth M; Pey, Pascaline B; de Fornel-Thibaud, Pauline; Moissonnier, Pierre H M; Freiche, Valérie

2018-02-01

CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for evaluation because of a 2-month history of regurgitation and weight loss, despite no apparent change in appetite. The dog had received antiemetic and antacid treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a low body condition score (2/5), but other findings were unremarkable. Diffuse, global esophageal dilatation was noted on plain thoracic radiographs, and normal motility was confirmed through videofluoroscopic evaluation of swallowing. Transhepatic ultrasonographic and CT examination revealed a circumferential, intraparietal lesion in the distal portion of the esophagus causing distal esophageal or cardial subobstruction and no metastases. Incisional biopsy of the lesion was performed, and findings of histologic examination supported a diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous possible complications associated with esophageal surgery, the decision was made to palliatively treat the dog by transcardial placement of a self-expanding, covered, nitinol esophageal stent under endoscopic guidance. Two weeks after stent placement, radiography revealed complete migration of the stent into the gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in place. Twenty-four months after initial stent placement, the dog had a healthy body condition and remained free of previous clinical signs. CLINICAL RELEVANCE Diffuse benign muscular neoplasia should be considered as a differential diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the dog of this report, transcardial stent placement resulted in resolution of the clinical signs, with no apparent adverse effect on digestive function. The described procedure could be beneficial for nonsurgical treatment of benign esophageal tumors in dogs.

Dorsal Vagal Complex Modulates Neurogenic Airway Inflammation in a Guinea Pig Model With Esophageal Perfusion of HCl

PubMed Central

Chen, Zhe; Sun, Lejia; Chen, Hui; Gu, Dachuan; Zhang, Weitao; Yang, Zifeng; Peng, Tao; Dong, Rong; Lai, Kefang

2018-01-01

Neurogenic airway inflammation in chronic cough and bronchial asthma related to gastroesophageal reflux (GER) is involved in the esophageal–bronchial reflex, but it is unclear whether this reflex is mediated by central neurons. This study aimed to investigate the regulatory effects of the dorsal vagal complex (DVC) on airway inflammation induced by the esophageal perfusion of hydrochloric acid (HCl) following the microinjection of nuclei in the DVC in guinea pigs. Airway inflammation was evaluated by measuring the extravasation of Evans blue dye (EBD) and substance P (SP) expression in the airway. Neuronal activity was indicated by Fos expression in the DVC. The neural pathways from the lower esophagus to the DVC and the DVC to the airway were identified using DiI tracing and pseudorabies virus Bartha (PRV-Bartha) retrograde tracing, respectively. HCl perfusion significantly increased plasma extravasation, SP expression in the trachea, and the expression of SP and Fos in the medulla oblongata nuclei, including the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus (DMV). The microinjection of glutamic acid (Glu) or exogenous SP to enhance neuronal activity in the DVC significantly potentiated plasma extravasation and SP release induced by intra-esophageal perfusion. The microinjection of γ-aminobutyric acid (GABA), lidocaine to inhibit neuronal activity or anti-SP serum in the DVC alleviated plasma extravasation and SP release. In conclusion, airway inflammation induced by the esophageal perfusion of HCl is regulated by DVC. This study provides new insight for the mechanism of airway neurogenic inflammation related to GER. PMID:29867575

Per-oral endoscopic myotomy (POEM): a new endoscopic treatment for achalasia.

PubMed

Miranda García, Pablo; Casals Seoane, Fernando; Gonzalez, Jean-Michel; Barthet, Marc; Santander Vaquero, Cecilio

2017-10-01

Per-oral endoscopic myotomy (POEM) is a new minimally invasive technique to treat achalasia. We performed a review of the literature of POEM with a special focus on technical details and the results obtained with this technique in patients with achalasia and other esophageal motility disorders. Thousands of POEM procedures have been performed worldwide since its introduction in 2008. The procedure is based on the creation of a mucosal entry point in the proximal esophagus to reach the cardia through a submucosal tunnel and then perform a myotomy of the muscular layers of the cardia, esophagogastric junction and distal esophagus, as performed in a Heller myotomy. The clinical remission rate ranges from 82 to 100%. Although no randomized studies exist and available data are from single-center studies, no differences have been found between laparoscopic Heller myotomy (LHM) and POEM in terms of perioperative outcomes, short-term outcomes (12 months) and long-term outcomes (up to three years). Procedure time and length of hospital stay were lower for POEM. Post-POEM reflux is a concern, and controversial data have been reported compared to LHM. The technique is safe, with no reported deaths related to the procedure and an adverse event rate comparable to surgery. Potential complications include bleeding, perforation, aspiration and insufflation-related adverse events. Thus, this is a complex technique that needs specific training even in expert hands. The indication for this procedure is widening and other motor hypercontractil esophageal disorders have been treated by POEM with promising results. POEM can be performed in complicated situations such as in pediatric patients, sigmoid achalasia or after failure of previous treatments. POEM is an effective treatment for achalasia and is a promising tool for other motor esophageal disorders. It is a safe procedure but, due to its technical difficulty and possible associated complications, the procedure should be performed in referral centers by trained endoscopists.

Finding the Right Treatment for Achalasia Treatment: Risks, Efficacy, Complications.

PubMed

Moonen, An; Boeckxstaens, Guy

2016-12-01

Achalasia is a primary esophageal motor disorder of the esophagus that is characterized by the absence of esophageal peristalsis and a failure of the lower esophageal sphincter (LES) to relax upon swallowing. The defective relaxation leads to symptoms of dysphagia for solids and liquids, regurgitation, aspiration, chest pain, and weight loss. Achalasia is believed to result from a selective loss of enteric inhibitory neurons, most likely due to an autoimmune phenomenon in genetic susceptible individuals. As there is no curative treatment for achalasia, treatment is confined to disruption of the LES to improve bolus passage. The two most commonly used treatment modalities available are the endoscopic pneumodilation (PD) and the surgical laparoscopic Heller myotomy (LHM). A recent European randomized controlled trial showed that both treatment modalities have comparable success rates after a follow-up of at least 5 years. In view of these data, both treatments can be used as an initial therapy in achalasia and the choice should be based on the expertise available. Recently, a new endoscopic technique, peroral endoscopic myotomy (POEM), has been introduced with excellent short-term success rates. However, longer follow-up and data from randomized controlled trials are needed before accepting this technique as a new treatment option for achalasia in clinical practice.

Esophageal and anorectal involvement in systemic sclerosis: a systematic assessment with high resolution manometry.

PubMed

Luciano, Laure; Granel, Brigitte; Bernit, Emmanuelle; Harle, Jean-Robert; Baumstarck, Karine; Grimaud, Jean-Charles; Bouvier, Michel; Vitton, Véronique

2016-01-01

In systemic sclerosis (SSc), esophageal and anorectal involvements are frequent and often associated with each other. In clinical practice, esophageal explorations are often prescribed, while anorectal explorations are rarely proposed and therefore, under-recognised. However, it is well documented in the literature that early detection of anorectal dysfunction could delay and/or prevent the onset of symptoms such as fecal incontinence (FI). The main objective was the systematic evaluation and detection of esophageal and anorectal involvements in SSc patients. In this monocentric retrospective study, all patients with SSc addressed in the Department of Functional Digestive Explorations, North Hospital, Marseille for esophageal and anorectal explorations were included. Self-Questionnaires, evaluating the symptoms and quality of life, were filled by patients during their visit. Explorations were performed on the same day: high resolution esophageal manometry (EHRM), 3 Dimensional high resolution anorectal manometry (3DHRARM) and endo anal sonography (EUS). 44 patients (41 women), mean age 59.8±12 years, were included. With regard to the symptoms, 45.5% of patients had gastro-esophageal reflux disease (GERD), 66.9% dysphagia, 65.9% constipation and 77.3% FI. The incidence of esophageal dismotility was 65.9%, anorectal and both upper and lower dysfunction were 43.2%. More than 89% patients with abnormal explorations (EHRM, 3DHRARM or both) were symptomatic. Duration of SSc and altered quality of life was correlated with the severity of digestive involvement. Anorectal dysfunction appears to be closely linked to esophageal involvement in SSc. Their routine screening is undoubtedly essential to limit the occurrence of severe symptoms such as FI.

Mechanisms of Barrett’s esophagus (clinical): LES dysfunction, hiatal hernia, peristaltic defects

PubMed Central

Roman, Sabine; Kahrilas, Peter J

2014-01-01

Summary Barrett’s esophagus, with the potential to develop into esophageal adenocarcinoma (EAC), is a major complication of gastroesophageal reflux disease (GERD). However, about 50% of patients developing EAC had no known GERD beforehand. Hence, while GERD symptoms, esophagitis, and Barrett’s have a number of common determinants (esophagogastric junction (EGJ) incompetence, impaired esophageal clearance mechanisms, hiatus hernia) they also have some independent determinants. Further, although excess esophageal acid exposure plays a major role in the genesis of long-segment Barrett’s esophagus there is minimal evidence supporting this for short-segment Barrett’s. Hence, these may have unique pathophysiological features as well. Long-segment Barrett’s seems to share most, if not all, of the risk factors for esophagitis, particularly high-grade esophagitis. However, it is uncertain if EGJ function and acid clearance are more severely impaired in patients with long-segment Barrett’s compared to patients with high-grade esophagitis. With respect to short-segment Barrett’s, the acid pocket may play an important pathogenic role. Conceptually, extension of the acid pocket into the distal esophagus, also known as intra-sphincteric reflux, provides a mechanism or acid exposure of the distal esophageal mucosa without the occurrence of discrete reflux events, which are more likely to prompt reflux symptoms and lead to the development of esophagitis. Hence, intra-sphincteric reflux related to extension of the acid/no acid interface at the proximal margin of the acid pocket may be key in the development of short segment Barrett’s. However, currently this is still somewhat speculative and further studies are required to confirm this. PMID:25743453

Imipramine for Treatment of Esophageal Hypersensitivity and Functional Heartburn: A Randomized Placebo-Controlled Trial.

PubMed

Limsrivilai, Julajak; Charatcharoenwitthaya, Phunchai; Pausawasdi, Nonthalee; Leelakusolvong, Somchai

2016-02-01

Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.

The association between systemic sclerosis disease manifestations and esophageal high-resolution manometry parameters

PubMed Central

Kimmel, Jessica N.; Carlson, Dustin A.; Hinchcliff, Monique; Carns, Mary A.; Aren, Kathleen A; Lee, Jungwha; Pandolfino, John E.

2016-01-01

Background/Aims We aimed to evaluate the associations between SSc-related systemic manifestations and esophageal function using high-resolution manometry (HRM). Methods Patients with SSc that had undergone HRM between 1/2004 and 9/2014 were identified and HRMs were analyzed according to the Chicago Classification. Clinical characteristics were identified via retrospective chart review and compared among motility diagnoses while adjusting for age, gender, race, and SSc-disease duration. Results 79 patients (85% female, ages 25–77) were included. Clinical characteristics were compared between patients with absent contractility (AC, n = 40), ineffective esophageal motility (IEM; n = 15), and normal motility (n = 19); the 5 remaining patients met criteria for other motility diagnoses. Groups differed in severity of skin involvement measured by the modified Rodnan skin score (0–51): AC (adjusted mean 12.6), IEM (4.4), normal (4.3), p = 0.043. Pulmonary function tests [percent predicted FVC and DLCO) were lower in AC (adjusted mean, FVC: 70.3, DLCO 51.1), than IEM (FVC: 92.0; DLCO: 76.9) and normal motility (FVC: 80.0; DLCO: 67.2), p-values 0.057 (FVC) and 0.007 (DLCO). Groups did not differ by SSc-disease duration, autoantibodies, or reported symptoms of dysphagia or reflux. Conclusions In patients with SSc, absent esophageal contractility on HRM was associated with increased skin disease severity and worse lung function. Obtaining HRM to identify SSc patients with more severe esophageal dysfunction could be considered to enable implementation of management strategies in patients potentially at risk for increased morbidity and mortality. PMID:26921101

Pulmonary outcome of esophageal atresia patients and its potential causes in early childhood.

PubMed

Dittrich, René; Stock, Philippe; Rothe, Karin; Degenhardt, Petra

2017-08-01

The aim of this study was to illustrate the pulmonary long term outcome of patients with repaired esophageal atresia and to further examine causes and correlations that might have led to this outcome. Twenty-seven of 62 possible patients (43%) aged 5-20years, with repaired esophageal atresia were recruited. Body plethysmography and spirometry were performed to evaluate lung function, and the Bruce protocol treadmill exercise test to assess physical fitness. Results were correlated to conditions such as interpouch distance, gastroesophageal reflux or duration of post-operative mechanical ventilation. Seventeen participants (63%) showed abnormal lung function at rest or after exercise. Restrictive ventilatory defects (solely restrictive or combined) were found in 11 participants (41%), and obstructive ventilatory defects (solely obstructive or combined) in 13 subjects (48%). Twenty-two participants (81%) performed the Bruce protocol treadmill exercise test to standard. The treadmill exercise results were expressed in z-score and revealed to be significantly below the standard population mean (z-score=-1.40). Moreover, significant correlations between restrictive ventilatory defects and the interpouch distance; duration of post-operative ventilation; gastroesophageal reflux disease; plus recurrent aspiration pneumonia during infancy; were described. It was shown that esophageal atresia and associated early complications have significant impact on pulmonary long term outcomes such as abnormal lung function and, in particular restrictive ventilatory defects. Long-running and regular follow-ups of patients with congenital esophageal atresia are necessary in order to detect and react to the development and progression of associated complications such as ventilation disorders or gastroesophageal reflux disease. Prognosis study, Level II. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of the superior laryngeal nerve in esophageal reflexes

PubMed Central

Medda, B. K.; Jadcherla, S.; Shaker, R.

2012-01-01

The aim of this study was to determine the role of the superior laryngeal nerve (SLN) in the following esophageal reflexes: esophago-upper esophageal sphincter (UES) contractile reflex (EUCR), esophago-lower esophageal sphincter (LES) relaxation reflex (ELIR), secondary peristalsis, pharyngeal swallowing, and belch. Cats (N = 43) were decerebrated and instrumented to record EMG of the cricopharyngeus, thyrohyoideus, geniohyoideus, and cricothyroideus; esophageal pressure; and motility of LES. Reflexes were activated by stimulation of the esophagus via slow balloon or rapid air distension at 1 to 16 cm distal to the UES. Slow balloon distension consistently activated EUCR and ELIR from all areas of the esophagus, but the distal esophagus was more sensitive than the proximal esophagus. Transection of SLN or proximal recurrent laryngeal nerves (RLN) blocked EUCR and ELIR generated from the cervical esophagus. Distal RLN transection blocked EUCR from the distal cervical esophagus. Slow distension of all areas of the esophagus except the most proximal few centimeters activated secondary peristalsis, and SLN transection had no effect on secondary peristalsis. Slow distension of all areas of the esophagus inconsistently activated pharyngeal swallows, and SLN transection blocked generation of pharyngeal swallows from all levels of the esophagus. Slow distension of the esophagus inconsistently activated belching, but rapid air distension consistently activated belching from all areas of the esophagus. SLN transection did not block initiation of belch but blocked one aspect of belch, i.e., inhibition of cricopharyngeus EMG. Vagotomy blocked all aspects of belch generated from all areas of esophagus and blocked all responses of all reflexes not blocked by SLN or RLN transection. In conclusion, the SLN mediates all aspects of the pharyngeal swallow, no portion of the secondary peristalsis, and the EUCR and ELIR generated from the proximal esophagus. Considering that SLN is not a motor nerve for any of these reflexes, the role of the SLN in control of these reflexes is sensory in nature only. PMID:22403790

Peroral endoscopic myotomy for the treatment of achalasia in a patient with esophageal varices. A case report.

PubMed

Shen, Naning; Wang, Xin; Zhang, Xiaoyin; Yao, Liping; Xie, Huahong; Zhang, Hongbo

2017-06-01

Achalasia is very uncommon, and rarely does achalasia co-exist with esophageal varices. We present a 62-year-old woman who was diagnosed with both achalasia and esophageal varices in December 2014 and had a past history of hematemesis. The patient's achalasia symptoms' Eckardt score was 9, and her hepatic function was Child-Pugh grade A6. After comprehensive assessment of the patient's health and discussion of the pros and cons of various therapies for achalasia, the patient underwent a peroral endoscopic myotomy. She was symptom-free after the operation and had no recurrence of achalasia symptoms at 20-month follow-up. No adverse events were reported. Peroral endoscopic myotomy for achalasia with esophageal varices has not been previously reported in the English literature.

Progress on materials and scaffold fabrications applied to esophageal tissue engineering.

PubMed

Shen, Qiuxiang; Shi, Peina; Gao, Mongna; Yu, Xuechan; Liu, Yuxin; Luo, Ling; Zhu, Yabin

2013-05-01

The mortality rate from esophageal disease like atresia, carcinoma, tracheoesophageal fistula, etc. is increasing rapidly all over the world. Traditional therapies such as surgery, radiotherapy or chemotherapy have been met with very limited success resulting in reduced survival rate and quality of patients' life. Tissue-engineered esophagus, a novel substitute possessing structure and function similar to native tissue, is believed to be an effective therapy and a promising replacement in the future. However, research on esophageal tissue engineering is still at an early stage. Considerable research has been focused on developing ideal scaffolds with optimal materials and methods of fabrication. This article gives a review of materials and scaffold fabrications currently applied in esophageal tissue engineering research. Copyright © 2013 Elsevier B.V. All rights reserved.

Jumonji/Arid1b (Jarid1b) protein modulates human esophageal cancer cell growth

PubMed Central

KANO, YOSHIHIRO; KONNO, MASAMITSU; OHTA, KATSUYA; HARAGUCHI, NAOTSUGU; NISHIKAWA, SHIMPEI; KAGAWA, YOSHINORI; HAMABE, ATSUSHI; HASEGAWA, SHINICHIRO; OGAWA, HISATAKA; FUKUSUMI, TAKAHITO; NOGUCHI, YUKO; OZAKI, MIYUKI; KUDO, TOSHIHIRO; SAKAI, DAISUKE; SATOH, TAROH; ISHII, MASARU; MIZOHATA, EIICHI; INOUE, TAKESHI; MORI, MASAKI; DOKI, YUICHIRO; ISHII, HIDESHI

2013-01-01

Although esophageal cancer is highly heterogeneous and the involvement of epigenetic regulation of cancer stem cells is highly suspected, the biological significance of epigenetically modified molecules that regulate different subpopulations remains to be firmly established. Using esophageal cancer cells, we investigated the functional roles of the H3K4 demethylase Jumonji/Arid1b (Jarid1b) (Kdm5b/Plu-1/Rbp2-h1), an epigenetic factor that is required for continuous cell growth in melanoma. JARID1B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial marker expression. However, these inhibitory effects observed on tumor formation were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that JARID1B plays a role in maintaining cancer stem cells in the esophagus and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer. PMID:24649241

[Effect of EMP-1 gene on human esophageal cancer cell line].

PubMed

Wang, Hai-tao; Liu, Zhi-hua; Wang, Xiu-qin; Wu, Min

2002-03-01

EMP-1 was selected from a series of differential expressed genes obtained from cDNA microarray in the authors' lab. Epithelial membrane pnteiu-1 gene (EMP-1) was expressed 6 fold lower in esophageal cancer than in normal tissue. The authors further designed the experiment to study the effect of human EMP-1 gene on human esophageal cancer cell line in order to explain the function of this gene on the carcinogensis and progression esophageal cancer. EMP-1 gene was cloned into eukaryotic vector and transfected into the human esophageal cancer cell line. The transfection effect was qualified by Western blot and RT-PCR method. The cell growth curve was observed and the cell cycle was checked by FACS method. EMP-1 was transfected into EC9706 cell line and its expression was up-regulated. The cell growth is accelerated and expression of EMP-1 is linked to induction of S phase arrest. EMP-1 gene has some relationship with carcinogenesis of esophagus.

Advances in esophageal cancer: A new perspective on pathogenesis associated with long non-coding RNAs.

PubMed

Huang, Xiaomei; Zhou, Xi; Hu, Qing; Sun, Binyu; Deng, Mingming; Qi, Xiaolong; Lü, Muhan

2018-01-28

Esophageal cancer is a malignant digestive tract cancer with high mortality. Although studies have found that esophageal cancer is involved in a complex and important gene regulation network, the pathogenesis remains unclear. The recently described long non-coding RNAs (lncRNAs) are one effective part of the gene regulation network. However, in past decades, lncRNAs were thought to be "transcript noise" or "pseudogenes" and were thus ignored. Early studies indicated that lncRNAs play pivotal roles during evolution. However, in recent years, increasing research has revealed that many lncRNAs are associated with tumorigenesis. In particular, lncRNAs may act as important elements for epigenetic regulation, transcription, post-transcriptional regulation and post-translational modification of proteins. Additionally, they may be novel biomarkers for tumors and therapeutic targets in cancer. Here, we summarize the functions of lncRNAs in esophageal cancer, with an emphasis on lncRNA-mediated regulatory mechanisms that affect the biological characteristics of esophageal cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Weighted gene co-expression network analysis of gene modules for the prognosis of esophageal cancer.

PubMed

Zhang, Cong; Sun, Qian

2017-06-01

Esophageal cancer is a common malignant tumor, whose pathogenesis and prognosis factors are not fully understood. This study aimed to discover the gene clusters that have similar functions and can be used to predict the prognosis of esophageal cancer. The matched microarray and RNA sequencing data of 185 patients with esophageal cancer were downloaded from The Cancer Genome Atlas (TCGA), and gene co-expression networks were built without distinguishing between squamous carcinoma and adenocarcinoma. The result showed that 12 modules were associated with one or more survival data such as recurrence status, recurrence time, vital status or vital time. Furthermore, survival analysis showed that 5 out of the 12 modules were related to progression-free survival (PFS) or overall survival (OS). As the most important module, the midnight blue module with 82 genes was related to PFS, apart from the patient age, tumor grade, primary treatment success, and duration of smoking and tumor histological type. Gene ontology enrichment analysis revealed that "glycoprotein binding" was the top enriched function of midnight blue module genes. Additionally, the blue module was the exclusive gene clusters related to OS. Platelet activating factor receptor (PTAFR) and feline Gardner-Rasheed (FGR) were the top hub genes in both modeling datasets and the STRING protein interaction database. In conclusion, our study provides novel insights into the prognosis-associated genes and screens out candidate biomarkers for esophageal cancer.

Esophageal testing: What we have so far

PubMed Central

de Bortoli, Nicola; Martinucci, Irene; Bertani, Lorenzo; Russo, Salvatore; Franchi, Riccardo; Furnari, Manuele; Tolone, Salvatore; Bodini, Giorgia; Bolognesi, Valeria; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino; Savarino, Edoardo Vincenzo

2016-01-01

Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising. PMID:26909230

Esophageal tissue engineering: an in-depth review on scaffold design.

PubMed

Tan, J Y; Chua, C K; Leong, K F; Chian, K S; Leong, W S; Tan, L P

2012-01-01

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design. Copyright © 2011 Wiley Periodicals, Inc.

Reduced fitness and physical functioning are long-term sequelae after curative treatment for esophageal cancer: a matched control study.

PubMed

Gannon, J A; Guinan, E M; Doyle, S L; Beddy, P; Reynolds, J V; Hussey, J

2017-08-01

Reduced physical functioning is common following resections for esophageal cancer; however, objective data on physical performance outcomes in this cohort are rare. The aim of this study was to assess the physical performance and health related quality of life (HRQOL) of disease free survivors and compare findings in a case matched noncancer control group. Twenty-five males (mean (±SD) aged 63 (±6) years) who were over 6 months postesophagectomy and disease-free were compared with 25 controls (60 ± 6 years). Physical functioning was assessed through hand grip strength (dynamometry), exercise capacity (incremental shuttle walk test), physical activity levels (RT3 accelerometer), and body composition (bio-electrical impedance analysis). Health-related quality of life was measured using the EORTC QLQ-C30 questionnaire. Esophageal cancer survivors demonstrated significantly lower fitness (P < 0.001) and time spent in moderate (P < 0.001) and vigorous (P < 0.001) intensity physical activity compared with controls. Global health status and quality of life were similar in both groups (P = 0.245); however, physical and role functioning domains were lower in the cancer survivors (P < 0.001, and P = 0.001, respectively). These data show that disease-free survivors of curative esophageal cancer treatment demonstrate a significant compromise in physical functioning compared with controls, thus highlighting the multiple, complex rehabilitative needs of this cohort. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hypersensitivity to acid is associated with impaired esophageal mucosal integrity in patients with gastroesophageal reflux disease with and without esophagitis.

PubMed

Weijenborg, Pim W; Smout, André J P M; Verseijden, Caroline; van Veen, Henk A; Verheij, Joanne; de Jonge, Wouter J; Bredenoord, Albert J

2014-08-01

Increased esophageal sensitivity and impaired mucosal integrity have both been described in patients with gastroesophageal reflux disease, but the relationship between hypersensitivity and mucosal integrity is unclear. The aim of the present study was to investigate acid sensitivity in patients with erosive and nonerosive reflux disease and control subjects to determine the relation with functional esophageal mucosal integrity changes as well as to investigate cellular mechanisms of impaired mucosal integrity in these patients. In this prospective experimental study, 12 patients with nonerosive reflux disease, 12 patients with esophagitis grade A or B, and 11 healthy control subjects underwent an acid perfusion test and upper endoscopy. Mucosal integrity was measured during endoscopy by electrical tissue impedance spectroscopy and biopsy specimens were analyzed in Ussing chambers for transepithelial electrical resistance, transepithelial permeability and gene expression of tight junction proteins and filaggrin. Patients with nonerosive reflux disease and esophagitis were more sensitive to acid perfusion compared with control subjects, having a shorter time to perception of heartburn and higher perceived intensity of heartburn. In reflux patients, enhanced acid sensitivity was associated with impairment of in vivo and vitro esophageal mucosal integrity. Mucosal integrity was significantly impaired in patients with esophagitis, displaying higher transepithelial permeability and lower extracellular impedance. Although no significant differences in the expression of tight junction proteins were found in biopsies among patient groups, mucosal integrity parameters in reflux patients correlated negatively with the expression of filaggrin. In conclusion, sensitivity to acid is enhanced in patients with gastroesophageal reflux disease, irrespective of the presence of erosions, and is associated with impaired esophageal mucosal integrity. Mucosal integrity of the esophagus is associated with the expression of filaggrin. Copyright © 2014 the American Physiological Society.

Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation

PubMed Central

Patel, Nirali; Jiang, Yanfen; Mittal, Ravinder K.; Kim, Tae Ho; Ledgerwood, Melissa

2015-01-01

Esophageal axial shortening is caused by longitudinal muscle (LM) contraction, but circular muscle (CM) may also contribute to axial shortening because of its spiral morphology. The goal of our study was to show patterns of contraction of CM and LM layers during peristalsis and transient lower esophageal sphincter (LES) relaxation (TLESR). In rats, esophageal and LES morphology was assessed by histology and immunohistochemistry, and function with the use of piezo-electric crystals and manometry. Electrical stimulation of the vagus nerve was used to induce esophageal contractions. In 18 healthy subjects, manometry and high frequency intraluminal ultrasound imaging during swallow-induced esophageal contractions and TLESR were evaluated. CM and LM thicknesses were measured (40 swallows and 30 TLESRs) as markers of axial shortening, before and at peak contraction, as well as during TLESRs. Animal studies revealed muscular connections between the LM and CM layers of the LES but not in the esophagus. During vagal stimulated esophageal contraction there was relative movement between the LM and CM. Human studies show that LM-to-CM (LM/CM) thickness ratio at baseline was 1. At the peak of swallow-induced contraction LM/CM ratio decreased significantly (<1), whereas the reverse was the case during TLESR (>2). The pattern of contraction of CM and LM suggests sliding of the two muscles. Furthermore, the sliding patterns are in the opposite direction during peristalsis and TLESR. PMID:26045610

Upper esophageal sphincter abnormalities: frequent finding on high-resolution esophageal manometry and associated with poorer treatment response in achalasia.

PubMed

Chavez, Yamile H; Ciarleglio, Maria M; Clarke, John O; Nandwani, Monica; Stein, Ellen; Roland, Bani C

2015-01-01

Abnormalities of the upper esophageal sphincter (UES) on high-resolution esophageal manometry (HREM) have been observed in both symptomatic and asymptomatic individuals and are often interpreted as incidental findings of unclear clinical significance. Our primary aims were: (1) to assess the frequency of UES abnormalities in consecutive patients referred for HREM studies; and (2) to characterize the demographics, clinical symptoms, and manometric profiles associated with UES abnormalities as compared with those with normal UES function. We performed a retrospective study of 200 consecutive patients referred for HREM. Patients were divided into those with normal and abnormal UES function, including impaired relaxation (residual pressure >12 mm Hg), hypertensive (>104 mm Hg), and hypotensive (<34 mm Hg) resting pressure. Clinical and manometric profiles were compared. A total of 32.5% of patients had UES abnormalities, the majority of which were hypertensive (55.4%). Patients with achalasia were significantly more likely to have UES abnormalities as compared with normal UES function (57.2% vs. 42.9%, P=0.04), with the most frequent abnormality being a hypertensive UES (50%). In addition, patients with impaired lower esophageal sphincter (LES) relaxation (esophagogastric junction outflow obstruction or achalasia) were more likely to have an UES abnormality present as compared with those with normal LES relaxation (53.1% vs. 28.6%, P=0.01). When we assessed for treatment response among patients with achalasia, we found that subjects with evidence of UES dysfunction had significantly worse treatment outcomes as compared with those without UES abnormalities present (20% improved vs. 100%, P=0.015). This remained true even after adjusting for type of treatment received (surgical myotomy, per-oral endoscopic mytotomy, botulinum toxin injection, pneumatic dilatation, medical therapy, P=0.67) and achalasia subtype (P=1.00). UES abnormalities are a frequent finding on HREM studies, especially in patients with impaired LES relaxation, including both achalasia and esophagogastric junction outflow obstruction. Interestingly, the most common UES abnormality associated with achalasia was a hypertensive resting UES, despite the fact that achalasia is thought to spare striated muscle. Among patients with achalasia, we found a significant association between the lack of treatment response and the presence of UES dysfunction. The routine evaluation of UES function in patients referred for manometry may enhance our understanding of esophageal motility disorders and may yield important prognostic information, particularly in subjects with achalasia. Future prospective studies are needed to further delineate the underlying mechanism between UES dysfunction with achalasia and other esophageal motility disorders to predict treatment response and guide therapeutic treatment modalities.

LKB1 promotes radioresistance in esophageal cancer cells exposed to radiation, by suppression of apoptosis and activation of autophagy via the AMPK pathway.

PubMed

He, Qing; Li, Jing; Dong, Feng; Cai, Chuanshu; Zou, Xi

2017-08-01

Liver kinase B (LKB) 1 acts as a tumor suppressor in a broad spectrum of human cancers, and is important in chemoradiotherapy treatment of various tumor types. However, the potential function of LKB1 in esophageal cancer radiotherapy remains to be elucidated. The aim of the present study was to investigate the role of LKB1 in radiosensitivity of esophageal cancer in vivo and in vitro, and to explore its molecular mechanism. Eca‑109 cells transfected with LKB1 overexpression plasmid were xenografted into nude mice and subjected to irradiation and it was observed that the tumor volume was significantly increased in LKB1‑overexpressed tumors compared with that of the control tumors. The in vitro study revealed that LKB1 overexpression led to the radioresistance of Eca‑109 cells, as determined by MTT and colony formation assays. Furthermore, it was demonstrated that LKB1 overexpression inhibited apoptosis and activated autophagy of Eca‑109 cells following radiation treatment, as determined by flow cytometry and western blot analyses. AMP‑activated protein kinase (AMPK) inhibition attenuated LKB1‑induced radioresistance of Eca‑109 cells. To the best of our knowledge, the present study, for the first time, confirmed that LKB1 induces radioresistance of esophageal cancer cells to irradiation via suppression of apoptosis and activation of autophagy, and AMPK mediates this function of LKB1 in esophageal cancer radiotherapy. These findings suggest that LKB1 may act as a novel target in the future, to maximize the efficiency of esophageal cancer radiotherapy.

Esophageal tissue engineering: A new approach for esophageal replacement

PubMed Central

Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

2012-01-01

A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed. PMID:23322987

Esophageal tissue engineering: a new approach for esophageal replacement.

PubMed

Totonelli, Giorgia; Maghsoudlou, Panagiotis; Fishman, Jonathan M; Orlando, Giuseppe; Ansari, Tahera; Sibbons, Paul; Birchall, Martin A; Pierro, Agostino; Eaton, Simon; De Coppi, Paolo

2012-12-21

A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly suggest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.

Endoscopic approach to achalasia

PubMed Central

Müller, Michaela; Eckardt, Alexander J; Wehrmann, Till

2013-01-01

Achalasia is a primary esophageal motor disorder. The etiology is still unknown and therefore all treatment options are strictly palliative with the intention to weaken the lower esophageal sphincter (LES). Current established endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin injection. Both treatment approaches have an excellent symptomatic short term effect, and lead to a reduction of LES pressure. However, the long term success of botulinum toxin (BT) injection is poor with symptom recurrence in more than 50% of the patients after 12 mo and in nearly 100% of the patients after 24 mo, which commonly requires repeat injections. In contrast, after a single PD 40%-60% of the patients remain asymptomatic for ≥ 10 years. Repeated on demand PD might become necessary and long term remission can be achieved with this approach in up to 90% of these patients. The main positive predictors for a symptomatic response to PD are an age > 40 years, a LES-pressure reduction to < 15 mmHg and/or an improved radiological esophageal clearance post-PD. However PD has a significant risk for esophageal perforation, which occurs in about 2%-3% of cases. In randomized, controlled studies BT injection was inferior to PD and surgical cardiomyotomy, whereas the efficacy of PD, in patients > 40 years, was nearly equivalent to surgery. A new promising technique might be peroral endoscopic myotomy, although long term results are needed and practicability as well as safety issues must be considered. Treatment with a temporary self expanding stent has been reported with favorable outcomes, but the data are all from one study group and must be confirmed by others before definite recommendations can be made. In addition to its use as a therapeutic tool, endoscopy also plays an important role in the diagnosis and surveillance of patients with achalasia. PMID:23951393

PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma.

PubMed

Liu, Kang; Song, Guiqin; Zhang, Xuqian; Li, Qiujiang; Zhao, Yunxia; Zhou, Yuchuan; Xiong, Rong; Hu, Xin; Tang, Zhirong; Feng, Gang

2017-05-25

Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer. We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration. Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells. PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.

Esophageal dysphagia and reflux symptoms before and after oral IQoro(R) training.

PubMed

Hägg, Mary; Tibbling, Lita; Franzén, Thomas

2015-06-28

To examine whether muscle training with an oral IQoro(R) screen (IQS) improves esophageal dysphagia and reflux symptoms. A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (≥ 15 N), velopharyngeal closure test (≥ 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P < 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P < 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P < 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P < 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P < 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence.

Esophageal dysphagia and reflux symptoms before and after oral IQoroR training

PubMed Central

Hägg, Mary; Tibbling, Lita; Franzén, Thomas

2015-01-01

AIM: To examine whether muscle training with an oral IQoroR screen (IQS) improves esophageal dysphagia and reflux symptoms. METHODS: A total of 43 adult patients (21 women and 22 men) were consecutively referred to a swallowing center for the treatment and investigation of long-lasting nonstenotic esophageal dysphagia. Hiatal hernia was confirmed by radiologic examination in 21 patients before enrollment in the study (group A; median age 52 years, range: 19-85 years). No hiatal hernia was detected by radiologic examination in the remaining 22 patients (group B; median age 57 years, range: 22-85 years). Before and after training with an oral IQS for 6-8 mo, the patients were evaluated using a symptom questionnaire (esophageal dysphagia and acid chest symptoms; score 0-3), visual analogue scale (ability to swallow food: score 0-100), lip force test (≥ 15 N), velopharyngeal closure test (≥ 10 s), orofacial motor tests, and an oral sensory test. Another twelve patients (median age 53 years, range: 22-68 years) with hiatal hernia were evaluated using oral IQS traction maneuvers with pressure recordings of the upper esophageal sphincter and hiatus canal as assessed by high-resolution manometry. RESULTS: Esophageal dysphagia was present in all 43 patients at entry, and 98% of patients showed improvement after IQS training [mean score (range): 2.5 (1-3) vs 0.9 (0-2), P < 0.001]. Symptoms of reflux were reported before training in 86% of the patients who showed improvement at follow-up [1.7 (0-3) vs 0.5 (0-2), P < 0.001). The visual analogue scale scores were classified as pathologic in all 43 patients, and 100% showed improvement after IQS training [71 (30-100) vs 22 (0-50), P < 0.001]. No significant difference in symptom frequency was found between groups A and B before or after IQS training. The lip force test [31 N (12-80 N) vs 54 N (27-116), P < 0.001] and velopharyngeal closure test values [28 s (5-74 s) vs 34 s (13-80 s), P < 0.001] were significantly higher after IQS training. The oral IQS traction results showed an increase in mean pressure in the diaphragmatic hiatus region from 0 mmHg at rest (range: 0-0 mmHG) to 65 mmHg (range: 20-100 mmHg). CONCLUSION: Oral IQS training can relieve/improve esophageal dysphagia and reflux symptoms in adults, likely due to improved hiatal competence. PMID:26140003

[Marshmallow for investigating functional disturbances of the esophageal body].

PubMed

Keren, S; Argaman, E

1992-09-01

Manometric studies using water boluses do not always demonstrate disturbances in esophageal motility. We tested the use of a marshmallow bolus to induce abnormal manometric patterns in patients with dysphagia in whom manometric studies using water boluses were normal or nearly so. The study group included 12 normal volunteers and 22 patients with dysphagia and nearly normal manometric studies. Pressure was recorded along the esophageal body using 10 "wet" swallows followed by 10 "solid" swallows of marshmallow. In normal subjects there were fewer abnormal contractions after solid swallows than after wet swallows. In 15 patients solid swallows induced abnormal motility patterns which were not observed after wet swallows. The probability of inducing abnormal contractions in patients after solid swallows is significantly greater than after wet swallows (p < 0.0001). Solid swallowing is therefore useful in evaluating functional disturbances of the esophagus in patients with dysphagia.

Long non-coding RNA GAS5 is induced by interferons and plays an antitumor role in esophageal squamous cell carcinoma.

PubMed

Huang, Jianbing; Li, Yuan; Lu, Zhiliang; Che, Yun; Sun, Shouguo; Mao, Shuangshuang; Lei, Yuanyuan; Zang, Ruochuan; Li, Ning; Sun, Nan; He, Jie

2018-05-09

The long non-coding RNA GAS5 has been reported as a tumor suppressor in many cancers. However, its functions and mechanisms remain largely unknown in esophageal squamous cell carcinoma (ESCC). In this study, we found that GAS5 was over-expressed in ESCC tissue compared with that in normal esophageal tissue in a public database. Functional studies showed that GAS5 could inhibit ESCC cell proliferation, migration and invasion in vitro. Further analysis revealed that GAS5 was regulated by interferon (IFN) responses via the JAK-STAT pathway. Moreover, as an IFN-stimulated gene (ISG), GAS5 was a positive regulator of IFN responses. The feedback loop between GAS5 and the IFN signaling pathway plays an important antitumor role in ESCC, thus providing novel potential therapeutic targets. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Dysphagia in the elderly.

PubMed

Khan, Abraham; Carmona, Richard; Traube, Morris

2014-02-01

Dysphagia, or difficulty swallowing, is a common problem in the elderly. Based on the initial clinical history and physical examination, the dysphagia is assessed as either primarily oropharyngeal or esophageal in origin. Most oropharyngeal dysphagia is of neurologic origin, and management is coordinated with a clinical swallow specialist in conjunction with an ear, nose, and throat (ENT) physician if warning signs imply malignancy. Several structural and functional esophageal disorders can cause dysphagia. If a patient has likely esophageal dysphagia, a video barium esophagram is a good initial test, and referral to a gastroenterologist is generally warranted leading to appropriate treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

[Esophageal motility characteristics of refractory heartburn: a study based on high resolution manometry and 24 hour pH-impedance monitoring].

PubMed

Wang, Kun; Duan, Liping; Xia, Zhiwei; Xu, Zhijie; Ge, Ying

2014-09-16

To analyze the esophageal motility characteristics of refractory heartburn with different reflux patterns and preliminarily clarify the roles of esophageal disorder in refractory heartburn. A total of 176 refractory heartburn patients were enrolled from 2009 to 2013. After gastroscopy and 24 hour pH-impedance monitoring, they were divided into 4 groups of reflux esophagitis (RE, n = 29), non-erosive reflux disease with acid reflux (NERD-acid, n = 51), NERD with weakly acidic reflux (NERD-weakly acid, n = 51) and non-reflux associated heartburn (n = 45). All subjects undertake high resolution manometry test and their esophageal motility functions were analyzed by the Chicago classification criteria 2012. Among them, 60.23% (106/176) patients presented esophageal motility disorders. And 42.61% (75/176) fulfilled the criteria of weak peristalsis, 7.39% (13/176) distal esophageal spasm, 4.55% (8/176) rapid contraction, 3.98% (7/176) EGJ outflow obstruction, 1.14% (2/176) hiatus hernia and 1 Jackhammer esophagus. The detection rates of esophageal motility disorder were similar among 4 groups and weak peristalsis was the most common disorder in all groups (41.38% in RE, 37.25% in NERD-acid patients, 54.90% in NERD-weakly acid and 35.56% in non-reflux associated heartburn patients). However, hypertensive motility disorders in non-reflux associated heartburn group (31.11%, 14/45) were more than GERD subgroups (11.45%, 15/131) (P < 0.05) . The relax ratio of low esophagus sphincter (LES) in GERD subgroups were higher than that in non-reflux associated heartburn patients. And the relax ratio of NERD-weakly acid was significantly higher than that in non-reflux associated heartburn patients (65% (50%-80%) vs 58% (42%-67%) , P < 0.05). The integrated relaxation pressure in GERD subgroups were lower than that of non-reflux associated heartburn patients without significant differences (P > 0.05). Esophageal weak peristalsis is one of the most common motility disorders in refractory heartburn patients, and esophageal hypertensive motility disorders are common in non-reflux associated heartburn patients. Esophageal manometry is necessary for the diagnosis and treatment of refractory heartburn.

Diagnostic yield in the evaluation of dysphagia: experience at a single tertiary care center.

PubMed

Bill, J; Rajagopal, S; Kushnir, V; Gyawali, C P

2018-05-24

Evaluation of dysphagia typically starts with esophagogastroduodenoscopy (EGD); further testing is pursued if this is negative. When no mucosal, structural, or motor esophageal disorders are identified with persisting symptoms, functional dysphagia is considered. We evaluated outcomes in patients undergoing EGD for dysphagia, and estimated prevalence of functional dysphagia. The endoscopy database at single tertiary care center was interrogated to identify EGDs performed for an indication of 'dysphagia' over a 12-month period (2008-09). Electronic medical records were reviewed over the next 8 years to assess if an etiology was identified. Data were analyzed to assess the diagnostic yield of endoscopy and subsequent tests in the evaluation of dysphagia. Of 5486 EGDs, 822 (15.0%) were performed for dysphagia in 694 patients (58.4 ± 0.6 year, range: 18-95 year, 55.8% female). Of these, 529 (76.2%) had EGD findings that explained dysphagia; another 22 (3.2%) had findings on histopathology. Of the remainder 143 patients (20.6%) with normal index EGD, 38 (26.6%) patients underwent barium esophagram with 15 (39.5%) having abnormal studies. 19 patients (13.3%) underwent esophageal high resolution manometry with 12 (63.2%) being abnormal, and 7 had a mechanism for dysphagia on alternate testing. A repeat EGD was abnormal in 6 patients, while 45 patients were lost to follow-up. 42 patients had complete resolution of symptoms despite normal endoscopy, of which 30 were treated empirically with a proton pump inhibitor (PPI). Only 16 patients had no findings on evaluation, and had continued dysphagia symptoms, representing true functional dysphagia in 2.3% of all dysphagia patients and 11.2% of patients with normal EGD. Endoscopy remains the test with the highest yield (over 75%) for a diagnosis in patients presenting with dysphagia; secondary tests are useful when endoscopy does not provide a diagnosis. Benign strictures and GERD-related etiologies are leading causes; PPI therapy is useful even when testing is negative. Functional dysphagia is extremely rare, accounting for <2.5% of all dysphagia.

A novel pattern of longitudinal muscle contraction with subthreshold pharyngeal stimulus: a possible mechanism of lower esophageal sphincter relaxation.

PubMed

Leslie, Eric; Bhargava, Valmik; Mittal, Ravinder K

2012-03-01

A subthreshold pharyngeal stimulus induces lower esophageal sphincter (LES) relaxation and inhibits progression of ongoing peristaltic contraction in the esophagus. Recent studies show that longitudinal muscle contraction of the esophagus may play a role in LES relaxation. Our goal was to determine whether a subthreshold pharyngeal stimulus induces contraction of the longitudinal muscle of the esophagus and to determine the nature of this contraction. Studies were conducted in 16 healthy subjects. High resolution manometry (HRM) recorded pressures, and high frequency intraluminal ultrasound (HFIUS) images recorded longitudinal muscle contraction at various locations in the esophagus. Subthreshold pharyngeal stimulation was induced by injection of minute amounts of water in the pharynx. A subthreshold pharyngeal stimulus induced strong contraction and caudal descent of the upper esophageal sphincter (UES) along with relaxation of the LES. HFIUS identified longitudinal muscle contraction of the proximal (3-5 cm below the UES) but not the distal esophagus. Pharyngeal stimulus, following a dry swallow, blocked the progression of dry swallow-induced peristalsis; this was also associated with UES contraction and descent along with the contraction of longitudinal muscle of the proximal esophagus. We identify a unique pattern of longitudinal muscle contraction of the proximal esophagus in response to subthreshold pharyngeal stimulus, which we propose may be responsible for relaxation of the distal esophagus and LES through the stretch sensitive activation of myenteric inhibitory motor neurons.

A safe treatment option for esophageal bezoars

PubMed Central

Yaqub, Sheraz; Shafique, Muhammad; Kjæstad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njål; Røkke, Ola

2012-01-01

INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails. PMID:22609703

Ultrasonographic study of mechanosensory properties in human esophagus during mechanical distension

PubMed Central

Larsen, Ejnar; Reddy, Hariprasad; Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Gregersen, Hans

2006-01-01

AIM: To study the esophageal geometry and mechanosensation using endoscopic ultrasonography during volume-controlled ramp distensions in the distal esophagus. METHODS: Twelve healthy volunteers underwent distension of a bag. During distension up to moderate pain the sensory intensity was assessed on a visual analogue scale (VAS). The esophageal deformation in terms of multidimensional stretch ratios and strains was calculated at different volumes and VAS levels. Distensions were done before and during administration of the anti-cholinergic drug butylscopolamine. RESULTS: The stimulus-response (volume-VAS) curve did not differ without or with the administration of butylscopolamine. Analysis of stretch ratios demonstrated tensile stretch in circumferential direction, compression in radial direction and a small tensile stretch in longitudinal direction. A strain gradient existed throughout the esophageal wall with the largest circumferential deformation at the mucosal surface. The sensation intensity increased exponentially as function of the strains. CONCLUSION: The method provides information of esophageal deformation gradients that correlate to the sensation intensity. Hence, it can be used to study mechanosensation in the human esophagus. Further studies are needed to determine the exact deformation stimulus for the esophageal mechanoreceptors. PMID:16874864

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma.

PubMed

Sundaram, Gopinath M; Veera Bramhachari, Pallaval

2017-06-01

Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with non-coding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

Role of altered esophageal intraluminal baseline impedance levels in patients with gatroesophageal reflux disease refractory to proton pump inhibitors

PubMed Central

Jiang, Liuqin; Ye, Bixing; Lin, Lin; Wang, Ying; Wang, Meifeng

2016-01-01

Abstract Numerous studies have investigated utility of esophageal intraluminal baseline impedance levels (BILs) in gastroesophageal reflux disease (GERD). However, effect of BILs in refractory GERD (RGERD) has not been well investigated. The aim of this study is to evaluate role of BILs in RGERD patients. Total 62 subjects with refractory gastroesophageal reflux symptoms underwent 24-hour impedance-pH monitoring and gastroendoscopy. Distal BILs in acid reflux type were significantly lower than those in nonacid reflux type and functional heartburn (FH) group. Distal BILs of reflux esophagitis (RE) patients were lower than those of nonerosive reflux disease (NERD) patients, while there were no statistical significance between 2 groups. Patients with severe esophagitis had lower distal BILs than those with mild esophagitis and NERD patients, and patients with severe esophagitis in acid reflux type had the lowest distal BILs. Distal BILs were significantly negatively correlated with DeMeester score, episodes of acid reflux, and acid exposure time, but no correlated with episodes of nonacid reflux. Characteristics of BILs in RGERD patients were similar with those in GERD patients, but might be more complicated. Evaluating BILs in RGERD patients could achieve a better understanding of pathophysiology in RGERD. PMID:27537561

Angiotensin IV and the human esophageal mucosa: An exploratory study in healthy subjects and gastroesophageal reflux disease patients.

PubMed

Björkman, Eleonora; Edebo, Anders; Fändriks, Lars; Casselbrant, Anna

2015-09-01

The human esophageal mucosa expresses various components of the renin-angiotensin system (RAS), e.g. the main effector peptide angiotensin II (AngII). The aim of this study was to investigate the esophageal presence of angiotensin III (AngIII) and angiotensin IV (AngIV) forming enzymes and the AngIV receptor (AT4R). The aim was also to study the actions of AngIV and to look for aberrations in patients with gastroesophageal reflux disease (GERD). Esophageal biopsies were collected from healthy volunteers (n: 19) and individuals with erosive reflux disease (n: 14). Gene transcripts and protein expression of aminopeptidase A, -B and -M, and the AT4R were investigated by reverse transcriptase polymerase chain reaction (rt-PCR), western blot (WB) and immunohistochemistry (IHC). The functional impact of AngIV was examined in an Ussing chamber. Aminopeptidase A, -B and -M and the AT4R were expressed in the esophageal epithelium. The AT4R was less prominent in certain areas in the mucosa of reflux patients. AngIV influenced the esophageal epithelial ion transport. The impact was lower in patients with GERD. The AT4R and formation enzymes of AngIII and AngIV are present in the human esophageal epithelium. Moreover, the present results suggest that AngIV exert regulatory impact on the epithelium and that RAS is involved in mucosal aberrations associated with GERD. © The Author(s) 2014.

Motility alterations in celiac disease and non-celiac gluten sensitivity.

PubMed

Pinto-Sanchez, Maria Ines; Bercik, Premysl; Verdu, Elena F

2015-01-01

Regulation of gut motility is complex and involves neuromuscular, immune and environmental mechanisms. It is well established that patients with celiac disease (CD) often display gut dysmotility. Studies have shown the presence of disturbed esophageal motility, altered gastric emptying, and dysmotility of the small intestine, gallbladder and colon in untreated CD. Most of these motor abnormalities resolve after a strict gluten-free diet, suggesting that mechanisms related to the inflammatory condition and disease process are responsible for the motor dysfunction. Motility abnormalities are also a hallmark of functional bowel disorders such as irritable bowel syndrome (IBS), where it has been proposed as underlying mechanism for symptom generation (diarrhea, constipation, bloating). Non-celiac gluten sensitivity (NCGS) is a poorly defined entity, mostly self-diagnosed, that presents clinically with IBS symptoms in the absence of specific celiac markers. Patients with NCGS are believed to react symptomatically to wheat components, and some studies have proposed the presence of low-grade inflammation in these patients. There is little information regarding the functional characterization of these patients before and after a gluten-free diet. A study suggested the presence of altered gastrointestinal transit in NCGS patients who also have a high prevalence of nonspecific anti-gliadin antibodies. Results of an ongoing clinical study in NCGS patients with positive anti-gliadin antibodies before and after a gluten-free diet will be discussed. Elucidating the mechanisms for symptom generation in NCGS patients is important to find new therapeutic alternatives to the burden of imposing a strict gluten-free diet in patients who do not have CD. © 2015 S. Karger AG, Basel.

Leg raise increases pressure in lower and upper esophageal sphincter among patients with gastroesophageal reflux disease.

PubMed

Bitnar, P; Stovicek, J; Andel, R; Arlt, J; Arltova, M; Smejkal, M; Kolar, P; Kobesova, A

2016-07-01

The purpose of this study was to determine the relation between posturally increased intra-abdominal pressure and lower/upper esophageal sphincter pressure changes in patients with gastroesophageal reflux disease. We used high resolution manometry to measure pressure changes in lower and upper esophageal sphincter during bilateral leg rise. We also examined whether the rate of lower and upper esophageal sphincter pressure would increase during leg raise differentially in individuals with versus without normal resting pressure. Fifty eight patients with gastroesophageal reflux disease participated in the study. High resolution manometry was performed in relaxed supine position, then lower and upper esophageal sphincter pressure was measured. Finally, the subjects were instructed to keep their legs lifted while performing 90-degree flexion at the hips and knees and the pressure was measured again. Paired t-test and independent samples t-test were used. There was a significant increase in both lower (P < 0.001) and upper esophageal sphincter pressure (P = 0.034) during leg raise compared to the initial resting position. Individuals with initially higher pressure in lower esophageal sphincter (>10 mmHg) exhibited a greater pressure increase during leg raise than those with initially lower pressure (pressure ≤10 mmHg; P = 0.002). Similarly individuals with higher resting upper esophageal sphincter pressure (>44 mmHg) showed a greater pressure increase during leg raise than those with lower resting pressure (≤44 mmHg; P < 0.001). The results illustrate the influence of postural leg activities on intraesophageal pressure in patients with gastroesophageal reflux disease, indicating by means of high resolution manometry that diaphragmatic postural and sphincter function are likely interrelated in this population. Copyright © 2015 Elsevier Ltd. All rights reserved.

Overexpression of TRIM44 is related to invasive potential and malignant outcomes in esophageal squamous cell carcinoma.

PubMed

Kawaguchi, Tsutomu; Komatsu, Shuhei; Ichikawa, Daisuke; Hirajima, Shoji; Nishimura, Yukihisa; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

2017-06-01

Recent studies have shown that some members of the tripartite motif-containing protein family function as important regulators for carcinogenesis. In this study, we investigated whether tripartite motif-containing protein 44 acts as a cancer-promoting gene through its overexpression in esophageal squamous cell carcinoma. We analyzed esophageal squamous cell carcinoma cell lines to evaluate malignant potential and also analyzed 68 primary tumors to evaluate clinical relevance of tripartite motif-containing protein 44 protein in esophageal squamous cell carcinoma patients. Expression of the tripartite motif-containing protein 44 protein was detected in esophageal squamous cell carcinoma cell lines (8/14 cell lines; 57%) and primary tumor samples of esophageal squamous cell carcinoma (39/68 cases; 57%). Knockdown of tripartite motif-containing protein 44 expression in esophageal squamous cell carcinoma cells using several specific small interfering RNAs inhibited cell migration and invasion, but not cell proliferation. Immunohistochemical analysis demonstrated that the overexpression of the tripartite motif-containing protein 44 protein in the tumor infiltrated region was associated with the status of lymph node metastasis ( p = 0.049), and the overall survival rates were significantly worse among patients with tripartite motif-containing protein 44-overexpressing tumors than those with non-expressing tumors ( p = 0.029). Moreover, multivariate Cox regression model identified that overexpression of the tripartite motif-containing protein 44 protein was an independent worse prognostic factor (hazard ratio = 2.815; p = 0.041), as well as lymphatic invasion (hazard ratio = 2.735; p = 0.037). These results suggest that tripartite motif-containing protein 44 protein could play a crucial role in tumor invasion through its overexpression and highlight its usefulness as a predictor and potential therapeutic target in esophageal squamous cell carcinoma.

Nondestructive measurement of esophageal biaxial mechanical properties utilizing sonometry

NASA Astrophysics Data System (ADS)

Aho, Johnathon M.; Qiang, Bo; Wigle, Dennis A.; Tschumperlin, Daniel J.; Urban, Matthew W.

2016-07-01

Malignant esophageal pathology typically requires resection of the esophagus and reconstruction to restore foregut continuity. Reconstruction options are limited and morbid. The esophagus represents a useful target for tissue engineering strategies based on relative simplicity in comparison to other organs. The ideal tissue engineered conduit would have sufficient and ideally matched mechanical tolerances to native esophageal tissue. Current methods for mechanical testing of esophageal tissues both in vivo and ex vivo are typically destructive, alter tissue conformation, ignore anisotropy, or are not able to be performed in fluid media. The aim of this study was to investigate biomechanical properties of swine esophageal tissues through nondestructive testing utilizing sonometry ex vivo. This method allows for biomechanical determination of tissue properties, particularly longitudinal and circumferential moduli and strain energy functions. The relative contribution of mucosal-submucosal layers and muscular layers are compared to composite esophagi. Swine thoracic esophageal tissues (n  =  15) were tested by pressure loading using a continuous pressure pump system to generate stress. Preconditioning of tissue was performed by pressure loading with the pump system and pre-straining the tissue to in vivo length before data was recorded. Sonometry using piezocrystals was utilized to determine longitudinal and circumferential strain on five composite esophagi. Similarly, five mucosa-submucosal and five muscular layers from thoracic esophagi were tested independently. This work on esophageal tissues is consistent with reported uniaxial and biaxial mechanical testing and reported results using strain energy theory and also provides high resolution displacements, preserves native architectural structure and allows assessment of biomechanical properties in fluid media. This method may be of use to characterize mechanical properties of tissue engineered esophageal constructs.

A new endoscopic technique for suspension of esophageal prosthesis for refractory caustic esophageal strictures.

PubMed

Ancona, E; Guido, E; Cutrone, C; Bocus, P; Rampado, S; Vecchiato, M; Salvador, R; Donach, M; Battaglia, G

2008-01-01

There is no clear consensus concerning the best endoscopic treatment of benign refractory esophageal strictures due to caustic ingestion. Different procedures are currently used: frequent multiple dilations, retrievable self-expanding stent, nasogastric intubation and surgery. We describe a new technique to fix a suspended esophageal silicone prosthesis to the neck in benign esophageal strictures; this permits us to avoid the frequent risk of migration of the expandable metallic or plastic stents. Under general anesthesia a rigid esophagoscope was placed in the patient's hypopharynx. Using transillumination from the optical device, the patient's neck was pierced with a needle. A n.0 monofilament surgical wire was pushed into the needle, grasped by a standard foreign body forceps through the esophagoscope and pulled out of the mouth (as in percutaneous endoscopic gastrostomy procedure). After tying the proximal end of the silicone prosthesis with the wire, it was placed through the strictures under endoscopic view. This procedure was successfully utilized in four patients suffering from benign refractory esophageal strictures due to caustic ingestion. The prosthesis and its suspension from the neck were well-tolerated until removal (mean duration 4 months). A postoperative transitory myositis was diagnosed in only one patient. One of the most frequent complications of esophageal prostheses in refractory esophageal strictures due to caustic ingestion is distal migration. Different solutions were proposed. For example the suspension of a wire coming from the nose and then fixed behind the ear. This solution is not considered optimal because of patient complaints and moreover the aesthetic aspect is compromised. The procedure we utilized in four patients utilized the setting of a silicone tube hanging from the neck in a way similar to that of endoscopic pharyngostomy. This solution is a valid alternative both for quality of life and for functional results.

A novel murine model of esophageal nonerosive reflux disease: from inflammation to impairment in mucosal integrity.

PubMed

Silva, Renan O; Oliveira, Francisco Fábio B; Bingana, Rudy D; Arruda, Mailton O; Woodland, Philip; Lee, Chung; Souza, Miguel A N; Soares, Pedro M G; Santos, Armênio A; Sifrim, Daniel; Souza, Marcellus H L P

2017-06-01

Nonerosive reflux disease (NERD) is a highly prevalent phenotype of the gastroesophageal reflux disease. In this study, we developed a novel murine model of NERD in mice with microscopic inflammation and impairment in the epithelial esophageal barrier. Female Swiss mice were subjected to the following surgical procedure: the transitional region between the forestomach and the glandular portion of the stomach was ligated, and a nontoxic ring was placed around the duodenum near the pylorus. The control group underwent sham surgery. The animals were euthanized at 1, 3, 7, and 14 days after surgery. Survival and body weight were monitored daily. Esophageal wet weight, macroscopic lesion, histopathological alterations, myeloperoxidase (MPO) activity, cytokine levels, transepithelial electrical resistance (TEER), and mucosal permeability were evaluated. The survival rate was 78% at 14 days, with mild loss in body weight. Surgery did not induce erosive esophagitis but instead induced microscopic inflammation and increased esophageal wet weight, IL-6, keratinocyte-derived cytokine (KC) levels, and MPO activity with maximal peak between 3 and 7 days and resolution at 14 days postsurgery. Epithelial esophageal barrier was evaluated in operated mice at 7 and 14 days postsurgery; a decrease in TEER and increase in the esophageal epithelial permeability were observed compared with the sham-operated group. In addition, the inhibition of acid secretion with omeprazole significantly prevented the esophageal inflammation and impairment of barrier function at 7 days postsurgery. Thus we established a novel experimental model of NERD in mice, which can contribute to understanding the pathophysiological events associated with NERD. NEW & NOTEWORTHY In this study, we standardized an experimental model of nonerosive reflux disease (NERD) in mice. This model involves an acute inflammatory response followed by impaired esophageal mucosal integrity, even in the absence of inflammation. Thus this model can serve for evaluation of pathophysiological aspects of NERD and open new perspectives for therapeutic strategies for patients with this disorder. Copyright © 2017 the American Physiological Society.

Efficacy of peroral endoscopic myotomy compared with other invasive treatment options for the different esophageal motor disorders.

PubMed

Estremera-Arévalo, Fermín; Albéniz, Eduardo; Rullán, María; Areste, Irene; Iglesias, Rosa; Vila, Juan José

2017-08-01

Peroral endoscopic myotomy (POEM) has been performed since 2008 on more than 5,000 patients. It has proven to be highly effective in the treatment of achalasia and has shown promising outcomes for other esophageal motility spastic disorders. A literature review of the efficacy of POEM compared to the previous invasive treatments for different esophageal motility disorders was performed. The application in the pediatric and elderly populations and its role as a rescue therapy after other procedures are also outlined. Short-term outcomes are similar to laparoscopic Heller myotomy (LHM) and pneumatic endoscopic dilation (PD) (clinical success > 90%) for achalasia subtypes I and II. Mid-term outcomes are comparable to LHM and overcome the results obtained after PD (> 90% vs ~50%). With regard to type III achalasia, POEM efficacy is 98% compared to 80.8% for LHM and the PD success remains at 40%. With regard to spastic esophageal disorders (SED), POEM has an effectiveness of 88% and 70% for distal esophageal spasm (DES) and jackhammer esophagus (JE) respectively. A response of 95% in patients with sigmoid esophagus has been reported. POEM has been performed in pediatric and elderly populations and has obtained a higher efficacy than PD in pediatric series (100% vs 33%) without greater adverse events. Previous treatments do not seem to hinder POEM results with excellent response rates, including 97% in post LHM and 100% in a re-POEM series. Final considerations: POEM has shown excellent short and mid-term results for all subtypes of achalasia but long-term results are not yet available. The promising results in SED may make POEM the first-line treatment for SED. A high-safety profile and efficacy have been shown in elderly and pediatric populations. Previous treatments do not seem to diminish the success rate of POEM. Core tip: POEM has emerged as an efficient treatment option for all subtypes of achalasia and other scenarios (including previous treatments and elderly and pediatric populations). Short and mid-term results are comparable to LHM and are better than PD data. The clinical response rate of DES and JE may make POEM the first-line treatment for SED.

[Gastric emptying of a solid-liquid meal in gastroesophageal reflux in adults].

PubMed

Bost, R; Hostein, J; Gignoux, C; Busquet, G; Lachet, B; Fournet, J

1986-04-01

Several studies concerning the relationships between gastroesophageal reflux (GOR), gastric emptying and esophageal motility are available. So far, results have been contradictory. The purpose of this work was to study gastric emptying in patients with GOR; to search for simultaneous esophageal motility disorders and to specify their type and frequency; to establish a potential relationship between motor disorders of the esophagus and the stomach in these patients. Thirty-two consecutive patients were selected according to clinical criteria, i.e. presence of at least two of the three characteristic symptoms of GOR, and the data of a three-hour post-prandial pH-metry. Gastric stasis related clinical manifestations (nausea, post-prandial vomiting, sensation of abdominal distension or of post-prandial epigastric fullness) were also searched for in all patients. A gastroscopy allowed to score esophagitis in each case. All patients, including adult controls underwent an esophageal manometry as well as a radionuclide determination of gastric emptying, after isotopic labelling of the solid (S) and liquid (L) phases of a test meal. The results showed that there was no significant modification of gastric emptying of the S and L phases of the meal in the group of patients with GOR whatever the intensity of the reflux, judged on the pH-metry results and the endoscopic data. Thus the average time of gastric half-emptying of S and L was respectively 115 and 52 min for the patients vs 111 and 51 min for the control group. As well, no correlation was found between the gastric emptying parameters and the presence or absence of clinical signs of gastric stasis or the amplitude of esophageal contraction waves. On an individual basis, two patients showed a significant decrease in gastric emptying of either the S or L phases without any attendant modification in the kinetics of the other. These results suggest that, in the adult, gastric emptying cannot be considered to be a determining factor of GOR and there are no diffuse motility disorders of the upper digestive tract during this illness.

Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia.

PubMed

Fecteau, Ryan E; Kong, Jianping; Kresak, Adam; Brock, Wendy; Song, Yeunjoo; Fujioka, Hisashi; Elston, Robert; Willis, Joseph E; Lynch, John P; Markowitz, Sanford D; Guda, Kishore; Chak, Amitabh

2016-10-01

Esophageal adenocarcinoma and its precursor lesion Barrett esophagus have seen a dramatic increase in incidence over the past 4 decades yet marked genetic heterogeneity of this disease has precluded advances in understanding its pathogenesis and improving treatment. To identify novel disease susceptibility variants in a familial syndrome of esophageal adenocarcinoma and Barrett esophagus, termed familial Barrett esophagus, by using high-throughput sequencing in affected individuals from a large, multigenerational family. We performed whole exome sequencing (WES) from peripheral lymphocyte DNA on 4 distant relatives from our multiplex, multigenerational familial Barrett esophagus family to identify candidate disease susceptibility variants. Gene variants were filtered, verified, and segregation analysis performed to identify a single candidate variant. Gene expression analysis was done with both quantitative real-time polymerase chain reaction and in situ RNA hybridization. A 3-dimensional organotypic cell culture model of esophageal maturation was utilized to determine the phenotypic effects of our gene variant. We used electron microscopy on esophageal mucosa from an affected family member carrying the gene variant to assess ultrastructural changes. Identification of a novel, germline disease susceptibility variant in a previously uncharacterized gene. A multiplex, multigenerational family with 14 members affected (3 members with esophageal adenocarcinoma and 11 with Barrett esophagus) was identified, and whole-exome sequencing identified a germline mutation (S631G) at a highly conserved serine residue in the uncharacterized gene VSIG10L that segregated in affected members. Transfection of S631G variant into a 3-dimensional organotypic culture model of normal esophageal squamous cells dramatically inhibited epithelial maturation compared with the wild-type. VSIG10L exhibited high expression in normal squamous esophagus with marked loss of expression in Barrett-associated lesions. Electron microscopy of squamous esophageal mucosa harboring the S631G variant revealed dilated intercellular spaces and reduced desmosomes. This study presents VSIG10L as a candidate familial Barrett esophagus susceptibility gene, with a putative role in maintaining normal esophageal homeostasis. Further research assessing VSIG10L function may reveal pathways important for esophageal maturation and the pathogenesis of Barrett esophagus and esophageal adenocarcinoma.

Association Between Germline Mutation in VSIG10L and Familial Barrett Neoplasia

PubMed Central

Fecteau, Ryan E.; Kong, Jianping; Kresak, Adam; Brock, Wendy; Song, Yeunjoo; Fujioka, Hisashi; Elston, Robert; Willis, Joseph E.; Lynch, John P.; Markowitz, Sanford D.; Guda, Kishore; Chak, Amitabh

2016-01-01

IMPORTANCE Esophageal adenocarcinoma and its precursor lesion Barrett esophagus have seen a dramatic increase in incidence over the past 4 decades yet marked genetic heterogeneity of this disease has precluded advances in understanding its pathogenesis and improving treatment. OBJECTIVE To identify novel disease susceptibility variants in a familial syndrome of esophageal adenocarcinoma and Barrett esophagus, termed familial Barrett esophagus, by using high-throughput sequencing in affected individuals from a large, multigenerational family. DESIGN, SETTING, AND PARTICIPANTS We performed whole exome sequencing (WES) from peripheral lymphocyte DNA on 4 distant relatives from our multiplex, multigenerational familial Barrett esophagus family to identify candidate disease susceptibility variants. Gene variants were filtered, verified, and segregation analysis performed to identify a single candidate variant. Gene expression analysis was done with both quantitative real-time polymerase chain reaction and in situ RNA hybridization. A 3-dimensional organotypic cell culture model of esophageal maturation was utilized to determine the phenotypic effects of our gene variant. We used electron microscopy on esophageal mucosa from an affected family member carrying the gene variant to assess ultrastructural changes. MAIN OUTCOMES AND MEASURES Identification of a novel, germline disease susceptibility variant in a previously uncharacterized gene. RESULTS A multiplex, multigenerational family with 14 members affected (3 members with esophageal adenocarcinoma and 11 with Barrett esophagus) was identified, and whole-exome sequencing identified a germline mutation (S631G) at a highly conserved serine residue in the uncharacterized gene VSIG10L that segregated in affected members. Transfection of S631G variant into a 3-dimensional organotypic culture model of normal esophageal squamous cells dramatically inhibited epithelial maturation compared with the wild-type. VSIG10L exhibited high expression in normal squamous esophagus with marked loss of expression in Barrett-associated lesions. Electron microscopy of squamous esophageal mucosa harboring the S631G variant revealed dilated intercellular spaces and reduced desmosomes. CONCLUSIONS AND RELEVANCE This study presents VSIG10L as a candidate familial Barrett esophagus susceptibility gene, with a putative role in maintaining normal esophageal homeostasis. Further research assessing VSIG10L function may reveal pathways important for esophageal maturation and the pathogenesis of Barrett esophagus and esophageal adenocarcinoma. PMID:27467440

Diagnosis of Esophageal Motility Disorders: Esophageal Pressure Topography vs. Conventional Line Tracing.

PubMed

Carlson, Dustin A; Ravi, Karthik; Kahrilas, Peter J; Gyawali, C Prakash; Bredenoord, Arjan J; Castell, Donald O; Spechler, Stuart J; Halland, Magnus; Kanuri, Navya; Katzka, David A; Leggett, Cadman L; Roman, Sabine; Saenz, Jose B; Sayuk, Gregory S; Wong, Alan C; Yadlapati, Rena; Ciolino, Jody D; Fox, Mark R; Pandolfino, John E

2015-07-01

Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT. Forty previously completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder. The total group agreement was moderate (κ=0.57; 95% CI: 0.56-0.59) for EPT and fair (κ=0.32; 0.30-0.33) for CLT. Inter-rater agreement between attendings was good (κ=0.68; 0.65-0.71) for EPT and moderate (κ=0.46; 0.43-0.50) for CLT. Inter-rater agreement between fellows was moderate (κ=0.48; 0.45-0.50) for EPT and poor to fair (κ=0.20; 0.17-0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR: 3.3; 95% CI: 2.4-4.5; P<0.0001), and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than with EPT (OR: 3.4; 2.4-5.0; P<0.0001). Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses were demonstrated with analysis using EPT over CLT among our selected raters. On the basis of these findings, EPT may be the preferred assessment modality of esophageal motility.

Survival analysis of patients with esophageal cancer using parametric cure model.

PubMed

Rasouli, Mahboube; Ghadimi, Mahmood Reza; Mahmoodi, Mahmood; Mohammad, Kazem; Zeraati, Hojjat; Hosseini, Mostafa

2011-01-01

Esophageal cancer is a major cause of mortality and morbidity in the Caspian littoral north-eastern part of Iran. The aim of this study was to calculate cure function as well as to identify the factors that are related to this function among patients with esophageal cancer in this geographical area. Three hundred fifty nine cases of esophageal cancer registered in the Babol cancer registry during the period of 1990 to 1991 (inclusive) were followed up for 15 years up to 2006. Parametric cure model was used to calculate cure fraction and investigate the factors responsible for probability of cure among patients. Sample of subjects encompassed 62.7% men and 37.3% women, with mean ages of diagnosis was 60.0 and 55.3 years, respectively. The median survival time reached about 9 months and estimated survival rates in 1, 3, and 5 years following diagnosis were 23%, 15% and 13%, respectively. Results show the family history affects the cured fraction independently of its effect on early outcome and has a significant effect on the probability of uncured. The average cure fraction was estimated to be 0.10. As the proportionality assumption of Cox model does not meet in certain circumstances, a parametric cure model can provide a better fit and a better description of survival related outcome.

A case of alpha-fetoprotein-producing esophageal adenocarcinoma.

PubMed

Chen, Yi-Yu; Hsu, Wen-Hung; Hu, Huang-Ming; Wu, Deng-Chyang; Lin, Wen-Yi

2013-02-01

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma. Copyright © 2012. Published by Elsevier B.V.

Evaluation of Quality of Life Following Placement of Self-Expanding Plastic Stents as a Bridge to Surgery in Patients Receiving Neoadjuvant Therapy for Esophageal Cancer

PubMed Central

Cannon, Robert M.; Brown, Russell E.; Ellis, Susan F.; Williams, Sharon; Scoggins, C.R.; Abbas, Abbas E.

2014-01-01

Purpose. To determine whether self-expanding plastic stent (SEPS) placement significantly improves quality of life and maintains optimal nutrition while allowing full-dose neoadjuvant therapy (NAT) in patients with esophageal cancer. Patients and Methods. A prospective, dual-institution, single-arm, phase II (http://ClinicalTrials.gov: NCT00727376) evaluation of esophageal cancer patients undergoing NAT prior to resection. All patients had a self-expanding polymer stent placed prior to NAT. The European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-OG25, Functional Assessment of Cancer Therapy–Anorexia, and Functional Assessment of Cancer Therapy–General surveys were administered prior to stenting, within 1 week post-stent placement, and at the completion of neoadjuvant therapy. Results. Fifty-two patients were enrolled; 3 (5.8%) had stent migrations requiring replacement. There were no instances of esophageal erosion or perforation. All patients received some form of neoadjuvant therapy. Thirty-six (69%) received chemoradiation; 34 (93%) of these patients received the planned dose of chemotherapy, and 27 (75%) received the full planned dose of radiotherapy. There were 16 (31%) patients receiving chemotherapy alone; 12 (74%) of patients in the chemotherapy-alone group completed the planned dose of therapy. Conclusion. Placement of SEPS appears to provide significant improvement in quality of life related to dysphagia and eating restriction in patients with esophageal cancer undergoing neoadjuvant therapy. Consideration of SEPS instead of percutaneous feeding tube should be initiated as a first line in dysphagia palliation and NAT nutritional support. PMID:24567281

The gastro-esophageal reflux barrier: biophysical analysis on 3D models of anatomy from magnetic resonance imaging.

PubMed

Roy, S; Fox, M R; Curcic, J; Schwizer, W; Pal, A

2012-07-01

The function and structure of the gastro-esophageal junction (GEJ) determine its efficacy as a reflux barrier. This study presents a novel methodology for the quantitative assessment of GEJ and proximal gastric morphology from magnetic resonance (MR) imaging. Based on this data we propose a new conceptualization of the hypothesis that a flap valve mechanism contributes to reflux protection. 3D models of the GEJ and proximal stomach were reconstructed from MR images in 12 healthy volunteers during respiration and on eating a test meal to maximum satiation. A rotating plane analysis measured the gastro-esophageal insertion angle and span of contact. An ellipsoid fit provided quantitative assessment of gastric shape and orientation relative to a fixed anatomical reference point. Position of the esophageal insertion on the 'gastric ellipse' was noted. An ellipsoid-cylinder model was designed to analyze the relationships among parameters describing the GEJ morphology. The insertion angle became more acute on expiration, but did not change with meal ingestion. In contrast the span of contact did not vary with respiration, but increased with gastric filling. Changes in gastric morphology with distension further augmented the span of gastro-esophageal contact in almost 70% of the studies. Novel MR imaging and biophysical analysis of the GEJ and proximal stomach provide a quantitative description of structures contributing to the reflux barrier. Changes in these parameters during respiration and on eating support the hypothesis that structural components of a functional 'flap valve' like mechanism contribute to reflux protection. © 2012 Blackwell Publishing Ltd.

High-Resolution Manometry Evaluation of the Pharynx and Upper Esophageal Sphincter Motility in Patients with Achalasia.

PubMed

Menezes, Mariano A; Herbella, Fernando A M; Patti, Marco G

2015-10-01

The motility of the pharynx and upper esophageal sphincter (UES) is still poorly understood. It is also unclear if the motility of this area may be compromised in patients with achalasia. This study aims to evaluate the motility of the pharynx, UES, and proximal esophagus in patients with esophageal achalasia. Sixty patients with achalasia underwent high-resolution manometry (HRM) (52 % females, mean age 54 years). Esophageal dilatation was classified according to the radiologic diameter in Type I (<4 cm): 6 %; Type II (4-7 cm): 36 %; Type III (7-10 cm): 34 %; and Type IV (>10 cm): 24 %. HRM classified 43 % of the patients as Chicago Type I and 57 % as Type II. Manometric parameters were compared to normal values obtained from a previous study in volunteers. The motility of the velopharynx showed short, premature, and hypertonic contraction. The epiglottis also showed hypertonic contraction. The UES had increased residual pressure. Chicago classification Type II patients had higher UES residual pressure (p = 0.03). The degree of esophageal dilatation did not correlate with manometric parameters. Achalasia may affect the motility of the pharyngo-upper esophageal area. The changes observed may represent functional alterations to prevent aspiration, especially in patients with Chicago classification Type II achalasia.

RNA editing of SLC22A3 drives early tumor invasion and metastasis in familial esophageal cancer

PubMed Central

Fu, Li; Qin, Yan-Ru; Ming, Xiao-Yan; Zuo, Xian-Bo; Diao, Yu-Wen; Zhang, Li-Yi; Ai, Jiaoyu; Liu, Bei-Lei; Huang, Tu-Xiong; Cao, Ting-Ting; Tan, Bin-Bin; Xiang, Di; Zeng, Chui-Mian; Gong, Jing; Zhang, Qiangfeng; Dong, Sui-Sui; Chen, Juan; Liu, Haibo; Wu, Jian-Lin; Qi, Robert Z.; Xie, Dan; Wang, Li-Dong

2017-01-01

Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals. PMID:28533408

The tumor microenvironment in esophageal cancer.

PubMed

Lin, E W; Karakasheva, T A; Hicks, P D; Bass, A J; Rustgi, A K

2016-10-13

Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus, there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment (TME), which contains diverse cell populations, signaling factors and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Antitumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells and regulatory T cells, as well as immune checkpoints like programmed death-1. Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy.

The Tumor Microenvironment in Esophageal Cancer

PubMed Central

Lin, Eric W.; Karakasheva, Tatiana A.; Hicks, Philip D.; Bass, Adam J.; Rustgi, Anil K.

2016-01-01

Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy. PMID:26923327

Advances in Management of Esophageal Motility Disorders.

PubMed

Kahrilas, Peter J; Bredenoord, Albert J; Carlson, Dustin A; Pandolfino, John E

2018-04-24

The widespread adoption of high-resolution manometry (HRM) has led to a restructuring in the classification of esophageal motility disorder classification summarized in the Chicago Classification, currently in version 3.0. It has become apparent that the cardinal feature of achalasia, impaired lower esophageal sphincter relaxation, can occur in several disease phenotypes: without peristalsis, with premature (spastic) distal esophageal contractions, with panesophageal pressurization, or even with preserved peristalsis. Furthermore, despite these advances in diagnostics, no single manometric pattern is perfectly sensitive or specific for idiopathic achalasia and complimentary assessments with provocative maneuvers during HRM or interrogating the esophagogastric junction with the functional luminal imaging probe during endoscopy can be useful in clarifying equivocal or inexplicable HRM findings. Using these tools, we have come to conceptualize esophageal motility disorders as characterized by obstructive physiology at the esophagogastric junction, smooth muscle esophagus, or both. Recognizing obstructive physiology as a primary target of therapy has become particularly relevant with the development of a minimally invasive technique for performing a calibrated myotomy of the esophageal circular muscle, the POEM procedure. Now and going forward, optimal management is to render treatment in a phenotype-specific manner: e.g. POEM calibrated to patient-specific physiology for spastic achalasia and spastic disorders of the smooth muscle esophagus, more conservative strategies (pneumatic dilation) for the disorders limited to the sphincter. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

NRAGE is involved in homologous recombination repair to resist the DNA-damaging chemotherapy and composes a ternary complex with RNF8-BARD1 to promote cell survival in squamous esophageal tumorigenesis.

PubMed

Yang, Q; Pan, Q; Li, C; Xu, Y; Wen, C; Sun, F

2016-08-01

NRAGE, a neurotrophin receptor-interacting melanoma antigen-encoding gene homolog, is significantly increased in the nucleus of radioresistant esophageal tumor cell lines and is highly upregulated to promote cell proliferation in esophageal carcinomas (ECs). However, whether the overexpressed NRAGE promotes cell growth by participating in DNA-damage response (DDR) is still unclear. Here we show that NRAGE is required for efficient double-strand breaks (DSBs) repair via homologous recombination repair (HRR) and downregulation of NRAGE greatly sensitizes EC cells to DNA-damaging agents both in vitro and in vivo. Moreover, NRAGE not only regulates the stability of DDR factors, RNF8 and BARD1, in a ubiquitin-proteolytic pathway, but also chaperons the interaction between BARD1 and RNF8 via their RING domains to form a novel ternary complex. Additionally, the expression of NRAGE is closely correlated with RNF8 and BARD1 in esophageal tumor tissues. In summary, our findings reveal a novel function of NRAGE that will help to guide personalized esophageal cancer treatments by targeting NRAGE to increase cell sensitivity to DNA-damaging therapeutics in the long run.

Psychological traits influence autonomic nervous system recovery following esophageal intubation in health and functional chest pain.

PubMed

Farmer, A D; Coen, S J; Kano, M; Worthen, S F; Rossiter, H E; Navqi, H; Scott, S M; Furlong, P L; Aziz, Q

2013-12-01

Esophageal intubation is a widely utilized technique for a diverse array of physiological studies, activating a complex physiological response mediated, in part, by the autonomic nervous system (ANS). In order to determine the optimal time period after intubation when physiological observations should be recorded, it is important to know the duration of, and factors that influence, this ANS response, in both health and disease. Fifty healthy subjects (27 males, median age 31.9 years, range 20-53 years) and 20 patients with Rome III defined functional chest pain (nine male, median age of 38.7 years, range 28-59 years) had personality traits and anxiety measured. Subjects had heart rate (HR), blood pressure (BP), sympathetic (cardiac sympathetic index, CSI), and parasympathetic nervous system (cardiac vagal tone, CVT) parameters measured at baseline and in response to per nasum intubation with an esophageal catheter. CSI/CVT recovery was measured following esophageal intubation. In all subjects, esophageal intubation caused an elevation in HR, BP, CSI, and skin conductance response (SCR; all p < 0.0001) but concomitant CVT and cardiac sensitivity to the baroreflex (CSB) withdrawal (all p < 0.04). Multiple linear regression analysis demonstrated that longer CVT recovery times were independently associated with higher neuroticism (p < 0.001). Patients had prolonged CSI and CVT recovery times in comparison to healthy subjects (112.5 s vs 46.5 s, p = 0.0001 and 549 s vs 223.5 s, p = 0.0001, respectively). Esophageal intubation activates a flight/flight ANS response. Future studies should allow for at least 10 min of recovery time. Consideration should be given to psychological traits and disease status as these can influence recovery. © 2013 John Wiley & Sons Ltd.

Serotonin disrupts esophageal mucosal integrity: an investigation using a stratified squamous epithelial model.

PubMed

Wu, Liping; Oshima, Tadayuki; Tomita, Toshihiko; Ohda, Yoshio; Fukui, Hirokazu; Watari, Jiro; Miwa, Hiroto

2016-11-01

Serotonin regulates gastrointestinal function, and mast cells are a potential nonneuronal source of serotonin in the esophagus. Tight junction (TJ) proteins in the esophageal epithelium contribute to the barrier function, and the serotonin signaling pathway may contribute to epithelial leakage in gastroesophageal reflux disease. Therefore, the aim of this study was to investigate the role of serotonin on barrier function, TJ proteins, and related signaling pathways. Normal primary human esophageal epithelial cells were cultured with use of an air-liquid interface system. Serotonin was added to the basolateral compartment, and transepithelial electrical resistance (TEER) was measured. The expression of TJ proteins and serotonin receptor 7 (5-HT 7 ) was assessed by Western blotting. The involvement of 5-HT 7 was assessed with use of an antagonist and an agonist. The underlying cellular signaling pathways were examined with use of specific blockers. Serotonin decreased TEER and reduced the expression of TJ proteins ZO-1, occludin, and claudin 1, but not claudin 4. A 5-HT 7 antagonist blocked the serotonin-induced decrease in TEER, and a 5-HT 7 agonist decreased TEER. Inhibition of p38 mitogen-activated protein kinase (MAPK) reduced the serotonin-induced decrease in TEER. Inhibition of p38 MAPK blocked the decrease of ZO-1 levels, whereas extracellular-signal-regulated kinase (ERK) inhibition blocked the decrease in occludin levels. Cell signaling pathway inhibitors had no effect on serotonin-induced alterations in claudin 1 and claudin 4 levels. Serotonin induced phosphorylation of p38 MAPK and ERK, and a 5-HT 7 antagonist partially blocked serotonin-induced phosphorylation of p38 MAPK but not that of ERK. Serotonin disrupted esophageal squamous epithelial barrier function by modulating the levels of TJ proteins. Serotonin signaling pathways may mediate the pathogenesis of gastroesophageal reflux disease.

A disease-specific enteral nutrition formula improves nutritional status and functional performance in patients with head and neck and esophageal cancer undergoing chemoradiotherapy: results of a randomized, controlled, multicenter trial.

PubMed

Fietkau, Rainer; Lewitzki, Victor; Kuhnt, Thomas; Hölscher, Tobias; Hess, Clemens-F; Berger, Bernhard; Wiegel, Thomas; Rödel, Claus; Niewald, Marcus; Hermann, Robert M; Lubgan, Dorota

2013-09-15

In patients with head and neck and esophageal tumors, nutritional status may deteriorate during concurrent chemoradiotherapy (CRT). The aim of this study was to investigate the influence of enteral nutrition enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on body composition and nutritional and functional status. In a controlled, randomized, prospective, double-blind, multicenter study, 111 patients with head and neck and esophageal cancer undergoing concurrent CRT received either an enteral standard nutrition (control group) or disease-specific enteral nutrition Supportan®-containing EPA+DHA (experimental group) via percutaneous endoscopic gastrostomy. The primary endpoint was the change of body cell mass (BCM) following CRT at weeks 7 and 14 compared with the baseline value. Secondary endpoints were additional parameters of body composition, anthropometric parameters, and nutritional and functional status. The primary endpoint of the study, improvement in BCM, reached borderline statistical significance. Following CRT, patients with experimental nutrition lost only 0.82 ± 0.64 kg of BCM compared with 2.82 ± 0.77 kg in the control group (P = .055). The objectively measured nutritional parameters, such as body weight and fat-free mass, showed a tendency toward improvement, but the differences were not significant. The subjective parameters, in particular the Kondrup score (P = .0165) and the subjective global assessment score (P = .0065) after follow-up improved significantly in the experimental group, compared with the control group. Both enteral regimens were safe and well tolerated. Enteral nutrition with EPA and DHA may be advantageous in patients with head and neck or esophageal cancer by improving parameters of nutritional and functional status during CRT. © 2013 American Cancer Society.

Anatomical feasibility of vagus nerve esophageal branch transfer to the phrenic nerve☆

PubMed Central

Wang, Ce; Liu, Jun; Yuan, Wen; Zhou, Xuhui; Wang, Xinwei; Xu, Peng; Chen, Jian; Wu, Guoxin; Shi, Sheng

2012-01-01

This study measured the vagus and phrenic nerves from 12 adult cadavers. We found that the width and thickness of the vagus and phrenic nerves were different in the chest. The distance from the point of the vagus nerve and phrenic nerve on the plane of the inferior border of portal pulmonary arteries (T point) was approximately 7 cm to the diaphragm and was approximately 10 cm to the clavicle level. The number of motor fibers in the vagus nerves was 1 716 ± 362, and the number of nerve fibers was 4 473 ± 653. The number of motor fibers in the phrenic nerves ranged from 3 078 ± 684 to 4 794 ± 638, and the number of nerve fibers ranged from 3 437 ± 642 to 5 071 ± 723. No significant difference was found in the total number of nerve fibers. The results suggest that width, thickness, and total number of nerve fibers are similar between the vagus and phrenic nerves, but the number of motor fibers is different between them. PMID:25745467

New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

PubMed

Esfandiary, Ali; Ghafouri-Fard, Soudeh

2015-01-01

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

Idiopathic gastroesophageal reflux disease in an adult horse.

PubMed

Baker, Shannon J; Johnson, Philip J; David, Andrew; Cook, Cristi Reeves

2004-06-15

Chronic gastroesophageal reflux disease was diagnosed in a 22-year-old female Tennessee Walking Horse that had signs of bruxism and ptyalism. Esophageal ulceration was detected via endoscopy. Compared with the damage to the proximal portions of the esophagus, the severity of the ulceration increased toward the gastroesophageal junction. Esophageal ulceration attributable to chronic gastric acid reflux is usually secondary to pyloric outflow obstruction in horses. In the horse of this report, there was no evidence of either a chronic pyloric or duodenal obstruction that could have resulted in esophageal ulceration. Esophageal ulceration in this horse was attributed to gastroesophageal reflux disease, a common condition in humans in which the underlying abnormality is functional incompetence of the gastroesophageal junction. Treatment is directed at decreasing gastric acidity and protecting the ulcerated mucosa. In the horse of this report, treatment was unsuccessful and the horse was euthanatized; a physical cause of gastroesophageal reflux disease was not identified during an extensive postmortem examination.

TSLP-elicited basophil responses can mediate the pathogenesis of eosinophilic esophagitis

PubMed Central

Noti, Mario; Tait Wojno, Elia D.; Kim, Brian S.; Siracusa, Mark C.; Giacomin, Paul R.; Nair, Meera G.; Benitez, Alain J.; Ruymann, Kathryn R.; Muir, Amanda B.; Hill, David A.; Chikwava, Kudakwashe R.; Moghaddam, Amin E.; Sattentau, Quentin J.; Alex, Aneesh; Zhou, Chao; Yearley, Jennifer H.; Menard-Katcher, Paul; Kubo, Masato; Obata-Ninomiya, Kazushige; Karasuyama, Hajime; Comeau, Michael R.; Brown-Whitehorn, Terri; de Waal Malefyt, Rene; Sleiman, Patrick M.; Hakonarson, Hakon; Cianferoni, Antonella; Falk, Gary W.; Wang, Mei-Lun; Spergel, Jonathan M.; Artis, David

2014-01-01

Eosinophilic esophagitis (EoE) is a food allergy-associated inflammatory disease characterized by esophageal eosinophilia. EoE has become increasingly common, but current management strategies are nonspecific. Thus, there is an urgent need to identify specific immunological pathways that could be targeted to treat this disease. EoE is associated with polymorphisms in the gene that encodes thymic stromal lymphopoietin (TSLP), a cytokine that promotes allergic inflammation, but how TSLP might contribute to EoE disease pathogenesis remains unknown. Here, we describe a new mouse model of EoE-like disease that developed independently of IgE but was dependent on TSLP-elicited basophils. Therapeutic TSLP neutralization or basophil depletion also ameliorated established EoE-like disease. Critically, in human subjects with EoE, we observed elevated TSLP levels and exaggerated basophil responses in esophageal biopsies, and a gain-of-function TSLP polymorphism was associated with increased basophil responses. Together, these data suggest that the TSLP-basophil axis could be therapeutically targeted to treat EoE. PMID:23872715

Radiofrequency Catheter Ablation for Atrial Fibrillation Elicited "Jackhammer Esophagus": A New Complication Due to Vagal Nerve Stimulation?

PubMed

Tolone, Salvatore; Savarino, Edoardo; Docimo, Ludovico

2015-10-01

Radiofrequency catheter ablation (RFCA) is a potentially curative method for treatment of highly symptomatic and drug-refractory atrial fibrillation (AF). However, this technique can provoke esophageal and nerve lesion, due to thermal injury. To our knowledge, there have been no reported cases of a newly described motor disorder, the Jackhammer esophagus (JE) after RFCA, independently of GERD. We report a case of JE diagnosed by high-resolution manometry (HRM), in whom esophageal symptoms developed 2 weeks after RFCA, in absence of objective evidence of GERD. A 65-year-old male with highly symptomatic, drug-refractory paroxysmal AF was candidate to complete electrical pulmonary vein isolation with RFCA. Prior the procedure, the patient underwent HRM and impedance-pH to rule out GERD or hiatal hernia presence. All HRM parameters, according to Chicago classification, were within normal limits. No significant gastroesophageal reflux was documented at impedance pH monitoring. Patient underwent RFCA with electrical disconnection of pulmonary vein. After two weeks, patient started to complain of dysphagia for solids, with acute chest-pain. The patient repeated HRM and impedance-pH monitoring 8 weeks after RFCA. HRM showed in all liquid swallows the typical spastic hypercontractile contractions consistent with the diagnosis of JE, whereas impedance-pH monitoring resulted again negative for GERD. Esophageal dysmotility can represent a possible complication of RFCA for AF, probably due to a vagal nerve injury, and dysphagia appearance after this procedure must be timely investigated by HRM.

Effect of Maturation of the Magnitude of Mechanosensitive and Chemosensitive Reflexes in the Premature Human Esophagus

PubMed Central

Jadcherla, Sudarshan Rao; Hoffmann, Raymond G.; Shaker, Reza

2014-01-01

Objectives To investigate the effect of esophageal mechanosensitive and chemosensitive stimulation on the magnitude and recruitment of peristaltic reflexes and upper esophageal sphincter (UES)-contractile reflex in premature infants. Study design Esophageal manometry and provocation testing were performed in the same 18 neonates at 33 and 36 weeks postmenstrual age (PMA). Mechanoreceptor and chemoreceptor stimulation were performed using graded volumes of air, water, and apple juice (pH 3.7), respectively. The frequency and magnitude of the resulting esophago-deglutition response (EDR) or secondary peristalsis (SP), and esophago-UES-contractile reflex (EUCR) were quantified. Results Threshold volumes to evoke EDR, SP, or EUCR were similar. The recruitment and magnitude of SP and EUCR increased with volume increments of air and water in either study (P < .05). However, apple juice infusions resulted in increased recruitment of EDR in the 33 weeks group (P < .05), and SP in the 36 weeks group (P < .05). The magnitude of EUCR was also volume responsive (all media, P < .05), and significant differences between media were noted (P < .05). At maximal stimulation (1 mL, all media), sensory-motor characteristics of peristaltic and EUCR reflexes were different (P < .05) between media and groups. Conclusions Mechano- and chemosensitive stimuli evoke volume-dependent specific peristaltic and UES reflexes at 33 and 36 weeks PMA. The recruitment and magnitude of these reflexes are dependent on the physicochemical properties of the stimuli in healthy premature infants. PMID:16860132

A novel pattern of longitudinal muscle contraction with subthreshold pharyngeal stimulus: a possible mechanism of lower esophageal sphincter relaxation

PubMed Central

Leslie, Eric; Bhargava, Valmik

2012-01-01

A subthreshold pharyngeal stimulus induces lower esophageal sphincter (LES) relaxation and inhibits progression of ongoing peristaltic contraction in the esophagus. Recent studies show that longitudinal muscle contraction of the esophagus may play a role in LES relaxation. Our goal was to determine whether a subthreshold pharyngeal stimulus induces contraction of the longitudinal muscle of the esophagus and to determine the nature of this contraction. Studies were conducted in 16 healthy subjects. High resolution manometry (HRM) recorded pressures, and high frequency intraluminal ultrasound (HFIUS) images recorded longitudinal muscle contraction at various locations in the esophagus. Subthreshold pharyngeal stimulation was induced by injection of minute amounts of water in the pharynx. A subthreshold pharyngeal stimulus induced strong contraction and caudal descent of the upper esophageal sphincter (UES) along with relaxation of the LES. HFIUS identified longitudinal muscle contraction of the proximal (3–5 cm below the UES) but not the distal esophagus. Pharyngeal stimulus, following a dry swallow, blocked the progression of dry swallow-induced peristalsis; this was also associated with UES contraction and descent along with the contraction of longitudinal muscle of the proximal esophagus. We identify a unique pattern of longitudinal muscle contraction of the proximal esophagus in response to subthreshold pharyngeal stimulus, which we propose may be responsible for relaxation of the distal esophagus and LES through the stretch sensitive activation of myenteric inhibitory motor neurons. PMID:22173917

KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression.

PubMed

Fujita, Yuji; Masuda, Kiyoshi; Hamada, Junichi; Shoda, Katsutoshi; Naruto, Takuya; Hamada, Satoshi; Miyakami, Yuko; Kohmoto, Tomohiro; Watanabe, Miki; Takahashi, Rizu; Tange, Shoichiro; Saito, Masako; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Tangoku, Akira; Otsuji, Eigo; Imoto, Issei

2017-11-24

KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC.

Novel candidate genes may be possible predisposing factors revealed by whole exome sequencing in familial esophageal squamous cell carcinoma.

PubMed

Forouzanfar, Narjes; Baranova, Ancha; Milanizadeh, Saman; Heravi-Moussavi, Alireza; Jebelli, Amir; Abbaszadegan, Mohammad Reza

2017-05-01

Esophageal squamous cell carcinoma is one of the deadliest of all the cancers. Its metastatic properties portend poor prognosis and high rate of recurrence. A more advanced method to identify new molecular biomarkers predicting disease prognosis can be whole exome sequencing. Here, we report the most effective genetic variants of the Notch signaling pathway in esophageal squamous cell carcinoma susceptibility by whole exome sequencing. We analyzed nine probands in unrelated familial esophageal squamous cell carcinoma pedigrees to identify candidate genes. Genomic DNA was extracted and whole exome sequencing performed to generate information about genetic variants in the coding regions. Bioinformatics software applications were utilized to exploit statistical algorithms to demonstrate protein structure and variants conservation. Polymorphic regions were excluded by false-positive investigations. Gene-gene interactions were analyzed for Notch signaling pathway candidates. We identified novel and damaging variants of the Notch signaling pathway through extensive pathway-oriented filtering and functional predictions, which led to the study of 27 candidate novel mutations in all nine patients. Detection of the trinucleotide repeat containing 6B gene mutation (a slice site alteration) in five of the nine probands, but not in any of the healthy samples, suggested that it may be a susceptibility factor for familial esophageal squamous cell carcinoma. Noticeably, 8 of 27 novel candidate gene mutations (e.g. epidermal growth factor, signal transducer and activator of transcription 3, MET) act in a cascade leading to cell survival and proliferation. Our results suggest that the trinucleotide repeat containing 6B mutation may be a candidate predisposing gene in esophageal squamous cell carcinoma. In addition, some of the Notch signaling pathway genetic mutations may act as key contributors to esophageal squamous cell carcinoma.

CD163 as a marker of M2 macrophage, contribute to predicte aggressiveness and prognosis of Kazakh esophageal squamous cell carcinoma.

PubMed

Hu, Jian Ming; Liu, Kai; Liu, Ji Hong; Jiang, Xian Li; Wang, Xue Li; Chen, Yun Zhao; Li, Shu Gang; Zou, Hong; Pang, Li Juan; Liu, Chun Xia; Cui, Xiao Bin; Yang, Lan; Zhao, Jin; Shen, Xi Hua; Jiang, Jin Fang; Liang, Wei Hua; Yuan, Xiang Lin; Li, Feng

2017-03-28

M2 macrophages was domesticated by tumor microenvironment to produce some angiogenic molecules and protease, facilitating angiogenesis and matrix breakdown, promoting tumor invasive and metastasis. However, The function of M2 macrophages to progression of eophageal carcinoma, especially Kazakh esophageal carcinoma is still dimness. This study aims to investigate M2 macrophages correlated with matrix metalloproteinase-9 (MMP9) and microvessel density, and the role in the progression of Kazakh esophageal squamous cell carcinoma. CD163 and CD34 as the marker of M2 macrophages and endothelial cells, were used to identify the M2 macrophages density and microvessel density, respectively. Immunohistochemistry staining was evaluated the expression of MMP9. The number of infiltrated CD163-positive M2 macrophages in tumor islets and stroma was significantly higher than in cancer adjacent normal tissues. The increased of M2 macrophages and microvessel density were significantly correlated with more malignant phenotypes including lymph node metastasis and clinical stage progression. Meanwhile, the expression of MMP9 showed much higher level in esophageal squamous cell carcinoma than that in cancer adjacent normal tissues, and high expression of MMP9 in Kazakh esophageal squamous cell carcinoma was significantly associated with age, depth of tumor invasion, lymph node metastasis, and tumor clinical stage. The quantity of M2 macrophages in tumor stroma was positively associated with microvessel density and the expression of MMP9, and as an independent poorly prognostic factor for overall survival time of Kazakh esophageal squamous cell carcinoma. These findings suggest the increased number of M2 macrophages correlated with high expression of MMP9 and high microvessel density may contribute to the tumor aggressiveness and angiogenesis, promoting the progression of Kazakh esophageal squamous cell carcinoma.

Mechanisms underlying reflux symptoms and dysphagia in patients with joint hypermobility syndrome, with and without postural tachycardia syndrome.

PubMed

Fikree, A; Aziz, Q; Sifrim, D

2017-06-01

The joint hypermobility syndrome (JHS) is a common non-inflammatory connective tissue disorder which frequently co-exists with postural tachycardia syndrome (PoTS), a form of orthostatic intolerance. Gastrointestinal symptoms and dysmotility have been reported in PoTS. Dysphagia and reflux are common symptoms in JHS, yet no studies have examined the physiological mechanism for these, subdivided by PoTS status. Thirty patients (28 female, ages: 18-62) with JHS and symptoms of reflux (n=28) ± dysphagia (n=25), underwent high-resolution manometry and 24 hour pH-impedance monitoring after questionnaire-based symptom assessment. Esophageal physiology parameters were examined in JHS, subdivided by PoTS status. Fifty-three percent of JHS patients with reflux symptoms had pathological acid reflux, 21% had reflux hypersensitivity, and 25% had functional heartburn. Acid exposure was more likely to be increased in the recumbent than upright position (64% vs 43%). The prevalence of hypotensive lower esophageal sphincter (33%) and hiatus hernia (33%) was low. Forty percent of patients with dysphagia had minor disorders of motility, 60% had functional dysphagia. Eighteen (60%) patients had coexistent PoTS-they had significantly higher dysphagia (21 vs 11.5, P=.04) and reflux scores (24.5 vs 16.5, P=.05), and double the prevalence of pathological acid reflux (64% vs 36%, P=.1) and esophageal dysmotility (50% vs 25%, P=.2) though this was not significant. A large proportion of JHS patients with esophageal symptoms have true reflux-related symptoms or mild esophageal hypomotility, and this is more likely if they have PoTS. © 2017 John Wiley & Sons Ltd.

Transoral endoscopic esophageal myotomy based on esophageal function testing in a survival porcine model.

PubMed

Perretta, Silvana; Dallemagne, Bernard; Donatelli, Gianfranco; Diemunsch, Pierre; Marescaux, Jacques

2011-01-01

The most effective treatment of achalasia is Heller myotomy. To explore a submucosal endoscopic myotomy technique tailored on esophageal physiology testing and to compare it with the open technique. Prospective acute and survival comparative study in pigs (n = 12; 35 kg). University animal research center. Eight acute-4 open and 4 endoscopic-myotomies followed by 4 survival endoscopic procedures. Preoperative and postoperative manometry; esophagogastric junction (EGJ) distensibility before and after selective division of muscular fibers at the EGJ and after the myotomy was prolonged to a standard length by using the EndoFLIP Functional Lumen Imaging Probe (Crospon, Galway, Ireland). All procedures were successful, with no intraoperative and postoperative complications. In the survival group, the animals recovered promptly from surgery. Postoperative manometry demonstrated a 50% drop in mean lower esophageal sphincter pressure (LESp) in the endoscopic group (mean preoperative LESp, 22.2 ± 3.3 mm Hg; mean postoperative LESp, 11.34 ± 2.7 mm Hg; P < .005) and a 69% loss in the open procedure group (mean preoperative LESp, 24.2 ± 3.2 mm Hg; mean postoperative LESp, 7.4 ± 4 mm Hg; P < .005). The EndoFLIP monitoring did not show any distensibility difference between the 2 techniques, with the main improvement occurring when the clasp circular fibers were taken. Healthy animal model; small sample. Endoscopic submucosal esophageal myotomy is feasible and safe. The lack of a significant difference in EGJ distensibility between the open and endoscopic procedure is very appealing. Were it to be perfected in a human population, this endoscopic approach could suggest a new strategy in the treatment of selected achalasia patients. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

A randomized double-blind placebo-controlled crossover-style trial of buspirone in functional dysphagia and ineffective esophageal motility.

PubMed

Aggarwal, Nitin; Thota, Prashanthi Nagavenkata; Lopez, Rocio; Gabbard, Scott

2018-02-01

Studies suggest that Ineffective Esophageal Motility (IEM) is the manometric correlate of Functional Dysphagia (FD). Currently, there is no accepted therapy for either condition. Buspirone is a serotonin modulating medication and has been shown to augment esophageal peristaltic amplitude in healthy volunteers. We aimed to determine if buspirone improves manometric parameters and symptoms in patients with overlapping IEM/FD. We performed a prospective, double-blind, placebo-controlled, crossover-style trial of 10 patients with IEM/FD. The study consisted of two 2-week treatment arms with a 2-week washout period. Outcomes measured at baseline, end of week 2, and week 6 include high resolution esophageal manometry (HREM), the Mayo Dysphagia Questionnaire-14 (MDQ-14), and the GERD-HRQL. The mean age of our 10 patients was 53 ± 9 years and 70% were female. After treatment with buspirone, 30% of patients had normalization of IEM on manometry; however, there was 30% normalization in the placebo group as well. Comparing buspirone to placebo, there was no statistically significant difference in the HREM parameters measured. There was also no statistically significant difference in symptom outcomes for buspirone compared to placebo. Of note, patients had a statistically significant decrease in the total GERD-HRQL total score when treated with placebo compared to baseline levels. Despite previous data demonstrating improved esophageal motility in healthy volunteers, our study shows no difference in terms of HREM parameters or symptom scores in IEM/FD patients treated with buspirone compared to placebo. Further research is necessary to identify novel agents for this condition. © 2017 John Wiley & Sons Ltd.

Toll-like Receptor 2 Signalling and the Lysosomal Machinery in Barrett's Esophagus.

PubMed

Verbeek, Romy E; Siersema, Peter D; Vleggaar, Frank P; Ten Kate, Fiebo J; Posthuma, George; Souza, Rhonda F; de Haan, Judith; van Baal, Jantine W P M

2016-09-01

Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett's esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett's esophagus epithelium cell line. TLR2 expression in normal squamous esophagus, reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and immunohistochemistry. Barrett's esophagus epithelium cells (BAR-T) were incubated with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4 for a period up to 4 weeks. Morphological changes were assessed with electron microscopy, while Q-RT-PCR was used to determine the expression of lysosomal enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR) and autophagy (LC3 and Rab7). TLR2 was expressed in normal squamous esophagus, reflux esophagitis, Barrett's esophagus but was most prominent in esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T cells incubated with acid and bile salts but no TLR2 agonist. Factors associated with autophagy (LC3 and Rab7) expression remained largely unchanged. Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells resulted in an increased number of mitochondria and lysosomes and increased expression of lysosomal enzymes and factors involved in endocytosis.

Imaging and Clinicopathologic Features of Esophageal Gastrointestinal Stromal Tumors

PubMed Central

Winant, Abbey J.; Gollub, Marc J.; Shia, Jinru; Antonescu, Christina; Bains, Manjit S.; Levine, Marc S.

2016-01-01

OBJECTIVE The purpose of this article is to describe the imaging and clinicopathologic characteristics of esophageal gastrointestinal stromal tumors (GISTs) and to emphasize the features that differentiate esophageal GISTs from esophageal leiomyomas. MATERIALS AND METHODS A pathology database search identified all surgically resected or biopsied esophageal GISTs, esophageal leiomyomas, and esophageal leiomyosarcomas from 1994 to 2012. Esophageal GISTs were included only if imaging studies (including CT, fluoroscopic, or 18F-FDG PET/CT scans) and clinical data were available. RESULTS Nineteen esophageal mesenchymal tumors were identified, including eight esophageal GISTs (42%), 10 esophageal leiomyomas (53%), and one esophageal leiomyosarcoma (5%). Four patients (50%) with esophageal GIST had symptoms, including dysphagia in three (38%), cough in one (13%), and chest pain in one (13%). One esophageal GIST appeared on barium study as a smooth submucosal mass. All esophageal GISTs appeared on CT as well-marginated predominantly distal lesions, isoattenuating to muscle, that moderately enhanced after IV contrast agent administration. Compared with esophageal leiomyomas, esophageal GISTs tended to be more distal, larger, and more heterogeneous and showed greater IV enhancement on CT. All esophageal GISTs showed marked avidity (mean maximum standardized uptake value, 16) on PET scans. All esophageal GISTs were positive for c-KIT (a cell-surface transmembrane tyrosine kinase also known as CD117) and CD34. On histopathology, six esophageal GISTs (75%) were of the spindle pattern and two (25%) were of a mixed spindle and epithelioid pattern. Five esophageal GISTs had exon 11 mutations (with imatinib sensitivity). Clinical outcome correlated with treatment strategy (resection plus adjuvant therapy or resection alone) rather than risk stratification. CONCLUSION Esophageal GISTs are unusual but clinically important mesenchymal neoplasms. Although esophageal GISTs and esophageal leiomyomas had overlapping imaging features, esophageal GISTs tended to be more distal, larger, more heterogeneous, and more enhancing on CT and were markedly FDG avid on PET. Given their malignant potential, esophageal GISTs should be included in the differential diagnosis of intramural esophageal neoplasms. PMID:25055264

Barrett’s esophagus in 2016: From pathophysiology to treatment

PubMed Central

Martinucci, Irene; de Bortoli, Nicola; Russo, Salvatore; Bertani, Lorenzo; Furnari, Manuele; Mokrowiecka, Anna; Malecka-Panas, Ewa; Savarino, Vincenzo; Savarino, Edoardo; Marchi, Santino

2016-01-01

Esophageal complications caused by gastroesophageal reflux disease (GERD) include reflux esophagitis and Barrett’s esophagus (BE). BE is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). The carcinogenic sequence may progress through several steps, from normal esophageal mucosa through BE to EAC. A recent advent of functional esophageal testing (particularly multichannel intraluminal impedance and pH monitoring) has helped to improve our knowledge about GERD pathophysiology, including its complications. Those findings (when properly confirmed) might help to predict BE neoplastic progression. Over the last few decades, the incidence of EAC has continued to rise in Western populations. However, only a minority of BE patients develop EAC, opening the debate regarding the cost-effectiveness of current screening/surveillance strategies. Thus, major efforts in clinical and research practice are focused on new methods for optimal risk assessment that can stratify BE patients at low or high risk of developing EAC, which should improve the cost effectiveness of screening/surveillance programs and consequently significantly affect health-care costs. Furthermore, the area of BE therapeutic management is rapidly evolving. Endoscopic eradication therapies have been shown to be effective, and new therapeutic options for BE and EAC have emerged. The aim of the present review article is to highlight the status of screening/surveillance programs and the current progress of BE therapy. Moreover, we discuss the recent introduction of novel esophageal pathophysiological exams that have improved the knowledge of the mechanisms linking GERD to BE. PMID:27158534

[Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

PubMed

Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

2016-12-01

Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

Functional disorders of swallowing.

PubMed

Baumann, A; Katz, P O

2016-01-01

Swallowing involves complex coordination of the neuromuscular anatomy and physiology of the oropharynx and esophagus, controlled by the enteric and central nervous systems. Dysphagia is classified as either oropharyngeal or esophageal and results from mechanical or structural disturbances. Videofluoroscopy, fiberoptic endoscopic evaluation of swallowing, barium swallow, manometry, and endoscopy are common modalities utilized in diagnosis, but none is as important as a patient's history. Functional dysphagia is a diagnosis of exclusion and is based on Rome criteria. Its mechanism is unknown but potentially related to visceral hypersensitivity, inappropriate pain perception, or unidentified contraction abnormalities. Its management is mainly supportive; however, there is literature to suggest, but not confirm, benefit with the use of antidepressants. Continued understanding of functional dysphagia and other functional esophageal disorders, including globus sensation, will require further investigation into diagnostic algorithms and finding treatment methods. © 2016 Elsevier B.V. All rights reserved.

Nonsurgical management of severe esophageal and gastric injury following alkali ingestion

PubMed Central

Abaskharoun, Ramy D; Depew, William T; Hookey, Lawrence C

2007-01-01

The ingestion of caustic substances may result in significant gastrointestinal injury. Endoscopy can play a major role in the initial evaluation and subsequent therapy of such injuries. The case of a 50-year-old man who ingested an alkaline floor stripper is described, including the endoscopic management of esophageal and pyloric strictures, with good functional results. The role of endoscopy, steroids and acid suppression in the management of such patients is also explored. PMID:18026581

Diagnosis of esophageal motility disorders: esophageal pressure topography versus conventional line tracing

PubMed Central

Carlson, DA; Ravi, K; Kahrilas, PJ; Gyawali, CP; Bredenoord, AJ; Castell, DO; Spechler, SJ; Halland, M; Kanuri, N; Katzka, DA; Leggett, CL; Roman, S; Saenz, JB; Sayuk, GS; Wong, AC; Yadlapati, R; Ciolino, JD; Fox, MR; Pandolfino, JE

2015-01-01

Background Enhanced characterization of esophageal peristaltic and sphincter function provided by esophageal pressure topography (EPT) offers a potential diagnostic advantage over conventional line tracings (CLT). However, high-resolution manometry (HRM) and EPT require increased equipment costs over conventional systems and evidence demonstrating a significant diagnostic advantage of EPT over CLT is limited. Our aim was to investigate whether the inter-rater agreement and/or accuracy of esophageal motility diagnosis differed between EPT and CLT. Methods Forty previously-completed patient HRM studies were selected for analysis using a customized software program developed to perform blinded independent interpretation in either EPT or CLT (six pressure sensors) format. Six experienced gastroenterologists with a clinical focus in esophageal disease (attendings) and six gastroenterology trainees with minimal manometry experience (fellows) from three academic centers interpreted each of the 40 studies using both EPT and CLT formats. Rater diagnoses were assessed for inter-rater agreement and diagnostic accuracy, both for exact diagnosis and for correct identification of a major esophageal motility disorder. Results The total group agreement was moderate (κ = 0.57; 95% CI 0.56–0.59) for EPT and fair (κ = 0.32; 0.30–0.33) for CLT. Inter-rater agreement between attendings was good (κ = 0.68; 0.65–0.71) for EPT and moderate (κ = 0.46; 0.43–0.50) for CLT. Inter-rater agreement between fellows was moderate (κ = 0.48; 0.45–0.50) for EPT and poor to fair (κ = 0.20; 0.17–0.24) for CLT. Among all raters, the odds of an incorrect exact esophageal motility diagnosis were 3.3 times higher with CLT assessment than with EPT (OR 3.3; 95% CI 2.4–4.5; p<0.0001) and the odds of incorrect identification of a major motility disorder were 3.4 times higher with CLT than EPT (OR 3.4; 2.4–5.0; p<0.0001). Conclusions Superior inter-rater agreement and diagnostic accuracy of esophageal motility diagnoses was demonstrated with analysis using EPT over CLT among our selected raters. Based on these findings, EPT may be the preferred assessment modality of esophageal motility. PMID:26032151

The structural characteristics and expression of neuropeptides in the esophagus of patients with congenital esophageal atresia and tracheoesophageal fistula.

PubMed

Li, Kai; Zheng, Shan; Xiao, Xianmin; Wang, Qihong; Zhou, Yiming; Chen, Lian

2007-08-01

The aim of this study was to investigate the structural characteristics and the expression of a group of neuropeptides in the esophagus of patients with congenital esophageal atresia and tracheoesophageal fistula (EA-TEF), as well to elucidate the roles of these neuropeptides in the pathogenesis of postoperative incoordination of esophagus after successful surgical repair of EA-TEF. Twenty-four specimens from distal tracheoesophageal fistulas of patients with EA-TEF (EA-TEF group) and 10 esophageal specimens from neonates who died of nonesophageal diseases (control group) were studied. All of the specimens were subjected to routine pathologic study, ultrastructural observation, and immunohistochemical staining for neuron-specific enolase, substance P, vasoactive intestinal polypeptide, and nitric oxide synthase. In the EA-TEF group, mitochondria were distributed along the membrane of smooth muscle cell, whereas mitochondria in the control group were distributed along the karyotheca of the smooth muscle cells. The ratio of granulated vesicles to clear vesicles in the varicosity of the intramuscular motor nerve ending of the EA-TEF group (0.520 +/- 0.137) was much higher than that in the control group (0.192 +/- 0.020, P < .05). The percentages of specimens shown to have positive expression of neuron-specific enolase and substance P in the EA-TEF group (20.8% and 12.5%, respectively) were significantly lower than those in the control group (90% and 80% respectively, P < .05). The percentages of specimens shown to have positive expression of vasoactive intestinal polypeptide and nitric oxide synthase in the EA-TEF group (83.3% and 75%, respectively) were significantly higher than that in the control group (30% and 10% respectively, P < .05). Imbalance of neurotransmitters excretion in nerve vesicle, abnormal intrinsic dysplasia of nerve plexus and increased expression of certain neuropeptides were the main characteristics of esophagus with abnormal intrinsic innervation, which may be responsible for the postoperative esophageal dysfunction of EA-TEF.

Maximum upper esophageal sphincter (UES) admittance: a non-specific marker of UES dysfunction.

PubMed

Cock, C; Besanko, L; Kritas, S; Burgstad, C M; Thompson, A; Heddle, R; Fraser, R J L; Omari, T I

2016-02-01

Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. Sixty-six healthy subjects (n = 50 controls 20-80 years; n = 16 elderly >80 years), 11 patients with CPB (51-83 years) and 16 with MND (58-91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction. © 2015 John Wiley & Sons Ltd.

Unique features of esophagogastric junction pressure topography in hiatus hernia patients with dysphagia.

PubMed

Pandolfino, John E; Kwiatek, Monika A; Ho, Kim; Scherer, John R; Kahrilas, Peter J

2010-01-01

Our aim was to assess pressure dynamics within the esophagogastric junction (EGJ) in sliding hiatus hernia (HH) during normal peristalsis and to compare the pressure profiles of HH patients with gastroesophageal reflux disease (GERD) symptoms (HH-GERD) to HH patients with dysphagia (HH-dysphagia). High-resolution manometry studies in 230 consecutive patients and 68 controls were reviewed. HH patients were defined by a >or=1.5 cm separation between the lower esophageal sphincter (LES) and crural diaphragm (CD) on pressure topography plots. The HH population was further culled to eliminate those patients with motor disorders or stricture. The study groups were composed of 18 HH patients with only reflux symptoms and 10 HH patients with only dysphagia. Analysis of the pressure dynamics within the EGJ was performed at rest and after swallowing to independently quantify the LES and CD contributions to residual EGJ pressure, as well as the magnitude and genesis of distal esophageal intrabolus pressure (IBP). Differences among study groups were analyzed with analysis of variance. After swallows, HH-dysphagia patients had greater residual CD pressure (9 mmHg; standard deviation [SD], 4) and IBP pressure (19 mmHg; SD, 4) compared to HH-GERD patients (5 mmHg; SD, 2; and 12 mmHg; SD, 2, respectively; P<.001) or normal subjects (NA; 11 mmHg; SD, 3; P<.001). Sliding HH alters the pressure dynamics through the EGJ and can lead to a functional obstruction. Patients with HH and dysphagia have greater pressures through the CD compared to HH patients with GERD symptoms, supporting the hypothesis that sliding HH in and of itself may be responsible for dysphagia. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Molecular Phenotyping in Predicting Response in Patients With Stage IB-III Esophageal Cancer Receiving Combination Chemotherapy

ClinicalTrials.gov

2018-01-16

Stage IB Esophageal Adenocarcinoma; Stage IIA Esophageal Adenocarcinoma; Stage IIB Esophageal Adenocarcinoma; Stage IIIA Esophageal Adenocarcinoma; Stage IIIB Esophageal Adenocarcinoma; Stage IIIC Esophageal Adenocarcinoma

Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

PubMed

Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

2017-02-01

Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

Pathogenesis of Potassium-Competitive Acid Blocker-Resistant Non-Erosive Reflux Disease.

PubMed

Kawami, Noriyuki; Hoshino, Shintaro; Hoshikawa, Yoshimasa; Takenouchi, Nana; Umezawa, Mariko; Hanada, Yuriko; Kaise, Mitsuru; Iwakiri, Katsuhiko

2018-06-05

The present study examined the pathogenesis of potassium-competitive acid blocker (P-CAB)-resistant non-erosive reflux disease (NERD). Forty-three patients with NERD, who had persistent reflux symptoms despite the administration of P-CAB, were included in this study. After excluding eosinophilic esophagitis and primary esophageal motility disorders, esophageal impedance-pH monitoring was performed. In symptom index (SI)-positive patients, the mechanism of SI-positivity and percent time with intragastric pH > 4 and with esophageal pH < 4 were investigated according to the presence or absence of Helicobacter pylori infection. One (2.3%) of 43 patients had a primary esophageal motility disorder (Jackhammer esophagus). Eighteen (41.9%) and 3 (7%) patients were SI-positive for liquid and gas-only reflux, respectively, and the remaining 21 patients who were SI-negative (48.8%) had functional heartburn. All patients SI-positive for liquid reflux were SI-positive for weakly acidic reflux. Gastric acid was sufficiently suppressed by P-CAB, regardless of the presence or absence of H. pylori infection. The pathogenesis of -P-CAB-resistant NERD was elucidated in 51% of patients. Symptoms in all patients SI-positive for liquid reflux were related to weakly acidic reflux, and symptoms related to acid reflux may be ruled out by the administration of P-CAB. © 2018 S. Karger AG, Basel.

Clinical Study of Time Optimizing of Endoscopic Photodynamic Therapy on Esophageal and/or Gastric Cardiac Cancer

ClinicalTrials.gov

2015-12-10

Stage I Esophageal Adenocarcinoma; Stage II Esophageal Adenocarcinoma; Stage III Esophageal Adenocarcinoma; Stage I Esophageal Squamous Cell Carcinoma; Stage II Esophageal Squamous Cell Carcinoma; Stage III Esophageal Squamous Cell Carcinoma

Clinical significance of the correlation between PLCE 1 and PRKCA in esophageal inflammation and esophageal carcinoma

PubMed Central

Ma, Ming; Zhang, Shanshan; Zhang, Yongmeng; Yuan, Ming; Liu, Bing; Yang, Yiqiong; Cui, Wen; Ansong, Emmanuel; Dong, Huali; Macias, Virgilia; Yang, Wancai

2017-01-01

Esophagitis and Barrett's esophagus are linked to esophageal squamous cell carcinoma and adenocarcinoma, respectively. However, the underlying mechanisms are still unclear. This study analyzed the expression levels of and correlation between PLCE1 and PRKCA in human esophagitis, carcinogen NMBA-induced rat esophagus, PLCE1 genetic deficient mouse esophageal epithelial tissues and human esophageal cancer cell line, integrated with Online oncology data sets. We found that the expression levels of both PLCE1 and PRKCA were significantly elevated in human esophagitis, esophageal squamous cell carcinoma, Barrett's esophagus, esophageal adenocarcinoma and in NMBA-treated rat esophageal epithelia. However, PRKCA and cytokines were significantly downregulated in PLCE1-deficient mouse esophageal epithelia, and knockdown of PLCE1 in human esophageal cancer cells led to reduction of PRKCA and cytokines. Finally, high expression of both PLCE1 and PRKCA is significantly associated with poor outcomes of the patients with esophageal cancers. In conclusion, this study defined the initiation and progression of esophageal inflammation and malignant transformation, in which the positive correlation of PLCE1 and PRKCA exhibits critical clinical significance. PMID:28402280

Study of support vector machine and serum surface-enhanced Raman spectroscopy for noninvasive esophageal cancer detection

NASA Astrophysics Data System (ADS)

Li, Shao-Xin; Zeng, Qiu-Yao; Li, Lin-Fang; Zhang, Yan-Jiao; Wan, Ming-Ming; Liu, Zhi-Ming; Xiong, Hong-Lian; Guo, Zhou-Yi; Liu, Song-Hao

2013-02-01

The ability of combining serum surface-enhanced Raman spectroscopy (SERS) with support vector machine (SVM) for improving classification esophageal cancer patients from normal volunteers is investigated. Two groups of serum SERS spectra based on silver nanoparticles (AgNPs) are obtained: one group from patients with pathologically confirmed esophageal cancer (n=30) and the other group from healthy volunteers (n=31). Principal components analysis (PCA), conventional SVM (C-SVM) and conventional SVM combination with PCA (PCA-SVM) methods are implemented to classify the same spectral dataset. Results show that a diagnostic accuracy of 77.0% is acquired for PCA technique, while diagnostic accuracies of 83.6% and 85.2% are obtained for C-SVM and PCA-SVM methods based on radial basis functions (RBF) models. The results prove that RBF SVM models are superior to PCA algorithm in classification serum SERS spectra. The study demonstrates that serum SERS in combination with SVM technique has great potential to provide an effective and accurate diagnostic schema for noninvasive detection of esophageal cancer.

Diagnosis of digestive functional disease by the statistics of continuous monitoring of esophageal acidity

NASA Astrophysics Data System (ADS)

Rivera Landa, Rogelio; Cardenas Cardenas, Eduardo; Fossion, Ruben; Pérez Zepeda, Mario Ulises

2014-11-01

Technological advances in the last few decennia allow the monitoring of many physiological observables in a continuous way, which in physics is called a "time series". The best studied physiological time series is that of the heart rhythm, which can be derived from an electrocardiogram (ECG). Studies have shown that a healthy heart is characterized by a complex time series and high heart rate variability (HRV). In adverse conditions, the cardiac time series degenerates towards randomness (as seen in, e.g., fibrillation) or rigidity (as seen in, e.g., ageing), both corresponding to a loss of HRV as described by, e.g., Golberger et. al [1]. Cardiac and digestive rhythms are regulated by the autonomous nervous system (ANS), that consists of two antagonistic branches, the orthosympathetic branch (ONS) that accelerates the cardiac rhythm but decelerates the digestive system, and the parasympathetic brand (PNS) that works in the opposite way. Because of this reason, one might expect that the statistics of gastro-esophageal time series, as described by Gardner et. al. [2,3], reflects the health state of the digestive system in a similar way as HRV in the cardiac case, described by Minocha et. al. In the present project, we apply statistical methods derived from HRV analysis to time series of esophageal acidity (24h pHmetry). The study is realized on data from a large patient population from the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Our focus is on patients with functional disease (symptoms but no anatomical damage). We find that traditional statistical approaches (e.g. Fourier spectral analysis) are unable to distinguish between different degenerations of the digestive system, such as gastric esophageal reflux disease (GERD) or functional gastrointestinal disorder (FGID).

Quality of Life During Neoadjuvant Treatment and After Surgery for Resectable Esophageal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meerten, Esther van; Gaast, Ate van der; Looman, Caspar W.N.

2008-05-01

Purpose: Because of the trade-off between the potentially negative quality-of-life (QoL) effects and uncertain favorable survival effect of neoadjuvant chemoradiotherapy (CRT) in patients with resectable esophageal cancer, we assessed heath-related QoL (HRQoL) for up to 1 year postoperatively in these patients treated with preoperative CRT with a non-platinum-based outpatient regimen followed by esophagectomy. Methods and Materials: Patients undergoing neoadjuvant paclitaxel and carboplatin therapy concurrent with radiotherapy followed by surgery completed standardized HRQoL questionnaires before and after CRT and at regular times up to 1 year postoperatively. We analyzed differences in generic Qol core questionnaire [QLQ-C30] and condition-specific (esophageal site-specific [OES-18])more » HRQoL scores over time by using a linear mixed-effects model. Results: Mean scores of most HRQoL scales deteriorated significantly during neoadjuvant CRT. The largest deterioration was observed for physical and role-functioning scales. All except two symptom scores worsened significantly. Postoperatively, most mean HRQoL scores improved until recovery to baseline level. Speed of improvement varied. Average taste score returned to baseline 3 months postoperatively, whereas it took 1 year for the average role-functioning score to restore. The emotional-functioning score showed a different pattern; it was worst at baseline and increased over time during CRT and postoperatively. Dysphagia and pain scores worsened considerably during CRT, restored to baseline 3 months postoperatively, and were even significantly better 1 year postoperatively. Conclusions: Preoperative CRT with paclitaxel and carboplatin for patients with resectable esophageal cancer had a considerable temporary negative effect on most aspects of HRQoL. Nonetheless, all HRQoL scores were restored or even improved 1 year postoperatively.« less

Cleavage of E-Cadherin Contributes to Defective Barrier Function in Neosquamous Epithelium.

PubMed

Runge, Thomas M; Shaheen, Nicholas J; Djukic, Zorka; Hallquist, Suzanne; Orlando, Roy C

2016-11-01

After ablation of Barrett's esophagus (BE), the esophagus heals with neosquamous epithelium (NSE). Despite normal endoscopic appearance, NSE exhibits defective barrier function with similarities to defects noted in the distal esophageal epithelium in patients with gastroesophageal reflux disease (GERD). To determine whether patients with NSE, unlike patients with healthy esophageal epithelium, have C-terminal fragments (CTFs) of e-cad detectable on tissue biopsy. Secondly, to determine whether patients with NSE have elevated levels of N-terminal fragments (NTFs) of e-cad in the serum. Fifteen patients with ablated long-segment BE, who had healing with formation of NSE, were enrolled in this pilot study. Western blots for CTFs and NTFs were performed on biopsies of NSE. Venous blood was obtained to assess levels of NTFs. Endoscopic distal esophageal biopsies from patients without esophageal disease served as tissue controls. Control blood samples were obtained from healthy subjects. Blots of NSE were successful in 14/15 patients, and all 14 (100 %) had a 35-kD CTF of e-cad, while CTFs were absent in healthy control tissues. Despite CTFs in NSE, serum NTFs of e-cad in NSE were similar to controls, p > 0.05. However, unlike healthy controls, blots of NSE also showed NTFs with molecular weights of 70-90 kD. Cleavage of e-cad, as evidenced by the presence of CTFs and NTFs on biopsy, contributes to defective barrier function in NSE. However, unlike findings reported in GERD patients, serum NTFs are not elevated in NSE patients. This difference may reflect poor absorption with tissue entrapment of NTFs in previously ablated areas with poorly perfused NSE.

Radiation Therapy, Paclitaxel, and Carboplatin With or Without Trastuzumab in Treating Patients With Esophageal Cancer

ClinicalTrials.gov

2018-06-22

Esophageal Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Stage IB Esophageal Cancer AJCC v7; Stage IIA Esophageal Cancer AJCC v7; Stage IIB Esophageal Cancer AJCC v7; Stage IIIA Esophageal Cancer AJCC v7; Stage IIIB Esophageal Cancer AJCC v7

Perioperative Granulocyte Colony-Stimulating Factor Does Not Prevent Severe Infections in Patients Undergoing Esophagectomy for Esophageal Cancer

PubMed Central

Schaefer, Hartmut; Engert, Andreas; Grass, Guido; Mansmann, Georg; Wassmer, Gernot; Hubel, Kai; Loehlein, Dietrich; Ulrich, Bernward C.; Lippert, Hans; Knoefel, Wolfram T.; Hoelscher, Arnulf H.

2004-01-01

Objective: Esophagectomy for esophageal cancer is associated with substantial postoperative morbidity as a result of infectious complications. In a prior phase II study, granulocyte colony-stimulating factor (G-CSF) was shown to improve leukocyte function and to reduce infection rates after esophagectomy. The aim of the current randomized, placebo-controlled, multicenter phase III trial was to investigate the clinical efficacy of perioperative G-CSF administration in reducing infection and mortality after esophagectomy for esophageal cancer. Patients and Methods: One hundred fifty five patients with resectable esophageal cancer were randomly assigned to perioperative G-CSF at standard doses (77 patients) or placebo (76 patients), administered from 2 days before until day 7 after esophagectomy. The G-CSF and placebo groups were comparable as regards age, gender, risk, cancer stage, frequency of neoadjuvant radiochemotherapy, and type of esophagectomy (transthoracic or transhiatal esophageal resection). Results: Of 155 randomized patients, 153 were eligible for the intention-to-treat analysis. The rate of infection occurring within the first 10 days after esophagectomy was 43.4% (confidence interval 32.8–55.9%) in the placebo and 44.2% (confidence interval 32.1–55.3%) in the G-CSF group (P = 0.927). 30-day mortality amounted to 5.2% in the G-CSF group versus 5.3% in the placebo group (P = 0.985). Similar results were found in the per-protocol analysis. Conclusion: Perioperative administration of G-CSF failed to reduce postoperative morbidity, infection rate, or mortality in patients with esophageal cancer who underwent esophagectomy. PMID:15213620

Targeting CD47 Enhances the Efficacy of Anti-PD-1 and CTLA-4 in an Esophageal Squamous Cell Cancer Preclinical Model.

PubMed

Tao, Hua; Qian, Pudong; Wang, Feijiang; Yu, Hongliang; Guo, Yesong

2017-11-02

Esophageal squamous cell cancer is a highly aggressive cancer with a dismal 5-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presentation in the immune system. By interacting with signal regulatory protein-α expressed in antigen-presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APC-dependent antigen presentation. Overexpression of CD47 was found in various types of cancer. However, its role in esophageal squamous cell cancer is not yet clear. Anti-CD47 is an antagonist of CD47 signaling pathways by competing with its ligand. In the current study, we investigated the effects of anti-CD47 treatment on the antitumor immune response in an esophageal squamous cell cancer preclinical model. We found that anti-CD47 treatment enhanced proinflammatory responses and increased CD8+ T-cell infiltration in tumor tissue in the animal model. T cells in anti-CD47-treated tumors showed higher PD-1 and CTLA-4 expression, indicating T-cell activation and the rationale of combining anti-CD47 with anti-PD-1 and CLTA-4. The combinatory treatment showed the best antitumor response, implying a novel treatment strategy. The effects of anti-CD47 depended on dendritic cell function. In patient samples, expression of CD47 was negatively correlated with CD8+ T-cell infiltration in esophageal squamous cell cancer patients. Taken together, CD47 might be a novel target to enhance anti-PD-1 and CLTA-4 efficacy in esophageal squamous cell cancer.

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

PubMed

Li, C-Q; Huang, G-W; Wu, Z-Y; Xu, Y-J; Li, X-C; Xue, Y-J; Zhu, Y; Zhao, J-M; Li, M; Zhang, J; Wu, J-Y; Lei, F; Wang, Q-Y; Li, S; Zheng, C-P; Ai, B; Tang, Z-D; Feng, C-C; Liao, L-D; Wang, S-H; Shen, J-H; Liu, Y-J; Bai, X-F; He, J-Z; Cao, H-H; Wu, B-L; Wang, M-R; Lin, D-C; Koeffler, H P; Wang, L-D; Li, X; Li, E-M; Xu, L-Y

2017-02-13

Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

KH-type splicing regulatory protein is involved in esophageal squamous cell carcinoma progression

PubMed Central

Shoda, Katsutoshi; Naruto, Takuya; Hamada, Satoshi; Miyakami, Yuko; Kohmoto, Tomohiro; Watanabe, Miki; Takahashi, Rizu; Tange, Shoichiro; Saito, Masako; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Tangoku, Akira; Otsuji, Eigo; Imoto, Issei

2017-01-01

KH-type splicing regulatory protein (KHSRP) is a multifunctional RNA-binding protein, which is involved in several post-transcriptional aspects of RNA metabolism, including microRNA (miRNA) biogenesis. It affects distinct cell functions in different tissues and can have an impact on various pathological conditions. In the present study, we investigated the oncogenic functions of KHSRP and their underlying mechanisms in the pathogenesis of esophageal squamous cell carcinoma (ESCC). KHSRP expression levels were elevated in ESCC tumors when compared with those in non-tumorous tissues by immunohistochemistry, and cytoplasmic KHSRP overexpression was found to be an independent prognosticator for worse overall survival in a cohort of 104 patients with ESCC. KHSRP knockdown inhibited growth, migration, and invasion of ESCC cells. KHSRP knockdown also inhibited the maturation of cancer-associated miRNAs, such as miR-21, miR-130b, and miR-301, and induced the expression of their target mRNAs, such as BMP6, PDCD4, and TIMP3, resulting in the inhibition of epithelial-to-mesenchymal transition. Our findings uncover a novel oncogenic function of KHSRP in esophageal tumorigenesis and implicate its use as a marker for prognostic evaluation and as a putative therapeutic target in ESCC. PMID:29254151

Esophageal function testing using multichannel intraluminal impedance.

PubMed

Srinivasan, R; Vela, M F; Katz, P O; Tutuian, R; Castell, J A; Castell, D O

2001-03-01

Multichannel intraluminal impedance (MII) is a new technique for evaluation of bolus transport. We evaluated esophageal function using bolus transport time (BTT) and contraction wave velocity (CWV) of liquid, semisolid, and solid boluses. Ten healthy subjects underwent MII swallow evaluation with various boluses of sterile water (pH 5), applesauce, three different sized marshmallows, and iced and 130 degrees F water. The effect of bethanechol was also studied. There was no difference in BTT or CWV for all water volumes from 1 to 20 ml. There was significant linear increase of BTT with progressively larger volumes of applesauce, and BTT of applesauce was longer than for water. BTT was significantly longer with large marshmallows vs. small and medium and was longer than for water. BTT for iced water was similar to 130 degrees F water. Applesauce showed a significant linear decrease of CWV with progressively larger volumes and was slower than water. Marshmallow showed significantly slower CWV with the large vs. small, and CWV for ice water was significantly slower than 130 degrees F water. Therefore, BTT of liquid is constant, whereas BTT of semisolid and solid are volume dependent and longer than liquids. CWV of semisolids and solids are slower than liquids. CWV of cold liquids is slower than warm liquids. MII can be used as a discriminating test of esophageal function.

Complexity and diversity of gastroesophageal reflux disease phenotypes.

PubMed

Zentilin, Patrizia; Marabotto, Elisa; Pellegatta, Gaia; Coppo, Claudia; Furnari, Manuele; Savarino, Edoardo; Savarino, Vincenzo

2017-09-01

Gastroesophageal reflux disease (GERD) is defined as a condition which develops when the reflux of gastric contents causes troublesome symptoms, impairs quality of life, or leads to mucosal damage or complications. There are two main phenotypic presentations of GERD, the erosive (ERD) and non-erosive reflux disease (NERD), with the latter one representing up to 70% of GERD spectrum. Moreover, patients with GERD can be clinically subdivided into two distinct syndromes: patients with esophageal and extraesophageal symptoms. The diagnosis of NERD should be supported by the evidence that symptoms are due to reflux episodes on the basis of an excess of acid into the esophagus or a positive correlation between symptoms and acid and/or weakly acidic reflux episodes as evidenced by 24-hour impedance-pH monitoring. Patients with normal esophageal acid exposure and no correlation between heartburn and any kind of chemical reflux are considered affected by functional heartburn and do not pertain to the realm of NERD. They do not usually respond to PPI therapy as further empirical criterion and are included in the large group of functional digestive disorders with the expression of altered generation or perception of symptoms at the esophageal level and can often overlap with functional dyspepsia and irritable bowel syndrome.

Measuring Cell Free DNA During the Course of Treatment for Esophageal Cancer as a Marker of Response and Recurrence

ClinicalTrials.gov

2017-10-09

Esophageal Neoplasm; Esophageal Neoplasms Malignancy Unspecified; Esophageal Neoplasms Malignant; Cancer of Esophagus; Cancer of the Esophagus; Esophageal Cancer; Esophagus Cancer; Neoplasm, Esophageal

[The characteristics of esophagogastric junction contractile index in patients with gastroesophageal reflux disease or functional heartburn].

PubMed

Wang, K; Duan, L P; Ge, Y; Xia, Z W; Xu, Z J

2016-04-01

To study the role of esophagogastric junction contractile index (EGJ-CI) in evaluating the function of anti-reflux barrier, and in differentiating patients with gastroesophageal reflux disease (GERD) from those with functional heartburn (FH). A total of 115 patients presenting heartburn were enrolled in the study from January 2012 to June 2015.All subjects had completed Gerd-Q questionnaire and undergone gastroscopy, 24-hour pH-impedance monitoring and esophageal high-resolution manometry. GERD patients were divided into as reflux esophagitis, acid-nonerosive reflux disease (NERD) and weakly acid-NERD groups. Patients with normal esophageal mucosa, normal acid exposure and negative proton pump inhibitor test were enrolled in FH group. EGJ-CI (mmHg·cm) as well as EGJ rest pressure and 4s integrated relaxation pressure (IRP 4s) were measured. Among the 115 patients, 18 were reflux esophagitis [(49.0±18.9) years, M∶F=10∶8], 25 were acid-NERD [(48.7±14.4) years, M∶F=13∶12], 37 were weakly acid-NERD [(52.0±14.8) years, M∶F=15∶22] and 35 were FH [(53.6±14.8), M∶F=8∶27]. No differences of Gerd-Q scores were noticed between the four groups. (1)Negative correlations were demonstrated between EGJ-CI and esophageal acid exposure time (r=-0.283, P=0.002), EGJ-CI and acid reflux events (r=-0.233, P=0.012), EGJ-CI and weakly acid reflux events (r=-0.213, P=0.022), EGJ-CI and non-acid reflux events (r=-0.200, P=0.032). (2)The value of EGJ-CI was significantly higher in FH patients than in the three subgroups of GERD(all P<0.01). EGJ rest pressure of FH group was higher than that of acid-NERD (P<0.01). IRP 4s in acid-NERD group was lower than that of FH and weakly acid-NERD (P<0.05). (3)The area under curve (AUC) of EGJ-CI was higher than that of EGJ-CIT, EGJ rest pressure or IRP 4s(0.686 vs 0.678, 0.641 and 0.578). The cut-off value of EGJ-CI to differentiate GERD from FH was 9.74 mmHg·cm with sensitivity 82.86% and specificity 51.52%. The EGJ-CI values are negatively correlated with esophageal acid exposure time, weakly acid reflux events and non-acid reflux events. Thus it might be used as a metric to reflect the anti-reflux function of EGJ. According to the cut-off value of EGJ-CI 9.74 mmHg·cm, patients with GERD can be sensitively differentiated from patients with FH.

Esophageal Motility after Extensive Circumferential Endoscopic Submucosal Dissection for Superficial Esophageal Cancer.

PubMed

Kuribayashi, Yasutaka; Iizuka, Toshiro; Nomura, Kosuke; Furuhata, Tsukasa; Yamashita, Satoshi; Matsui, Akira; Kikuchi, Daisuke; Mitani, Toshifumi; Kaise, Mitsuru; Hoteya, Shu

2018-06-05

Endoscopic submucosal dissection (ESD) for superficial esophageal cancer is sometimes extensive, and in our experience, patients not infrequently present with dysphagia after ESD even in the absence of esophageal stricture. The aim of this study was to evaluate esophageal motility using high-resolution manometry (HRM) in patients with and without dysphagia after extensive circumferential ESD. HRM was performed in a total of 52 patients who had undergone ESD for superficial esophageal cancer and a mucosal defect after ESD exceeded more than two-thirds of the esophageal circumference. The frequency and type of esophageal dysmotility and the relationship between esophageal motility and dysphagia were evaluated. Esophageal dysmotility was observed in 13 patients (25%): jackhammer esophagus in 4, esophagogastric junction outflow obstruction in 4, absent contractility in 2, and distal esophageal spasm, ineffective esophageal motility, and fragmented peristalsis in 1 patient each. Of the 22 patients with dysphagia after ESD, 9 (41%) had esophageal dysmotility. Of the 30 patients without dysphagia after ESD, 4 (13%) had esophageal dysmotility. The relationship between dysmotility and dysphagia was significant (p = 0.025). Esophageal dysmotility exists in approximately one-quarter of patients after extensive circumferential ESD, which is associated with dysphagia in the absence of esophageal stricture. © 2018 S. Karger AG, Basel.

Biomechanical Quantification of Mendelsohn Maneuver and Effortful Swallowing on Pharyngoesophageal Function.

PubMed

Doeltgen, Sebastian Heinrich; Ong, Ellisa; Scholten, Ingrid; Cock, Charles; Omari, Taher

2017-11-01

Objective To quantify the effects of 2 swallowing maneuvers used in dysphagia rehabilitation-the Mendelsohn maneuver and effortful swallowing-on pharyngoesophageal function with novel, objective pressure-flow analysis. Study Design Evaluation of intervention effects in a healthy control cohort. Setting A pharyngoesophageal motility research laboratory in a tertiary education facility. Subjects Twelve young healthy subjects (9 women, 28.6 ± 7.9 years) from the general public, without swallowing impairment, volunteered to participate in this study. Methods Surface electromyography from the floor-of-mouth musculature and high-resolution impedance manometry-based pressure flow analysis were used to assess floor-of-mouth activation and pharyngoesophageal motility, respectively. Subjects each performed 10 noneffortful control swallows, Mendelsohn maneuver swallows, and effortful swallows, with a 5-mL viscous bolus. Repeated measures analyses of variance was used to compare outcome measures across conditions. Results Effortful and Mendelsohn swallows generated greater floor-of-mouth contraction ( P = .001) and pharyngeal pressure ( P < .0001) when compared with control swallows. There were no changes at the level of the upper esophageal sphincter, except for a faster opening to maximal diameter during maneuver swallows ( P = .01). The proximal esophageal contractile integral was reduced during Mendelsohn swallows ( P = .001). Conclusion Effortful and Mendelsohn maneuver swallows significantly alter the pharyngoesophageal pressure profile. Faster opening of the upper esophageal sphincter may facilitate bolus transfer during maneuver swallows; however, reduced proximal esophageal contractility during Mendelsohn maneuver swallows may impair bolus flow and aggravate dysphagic symptoms.

Experimental human pain models in gastro-esophageal reflux disease and unexplained chest pain

PubMed Central

Drewes, Asbjørn Mohr; Arendt-Nielsen, Lars; Funch-Jensen, Peter; Gregersen, Hans

2006-01-01

Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy. PMID:16718803

Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6

PubMed Central

Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

2017-01-01

AIM To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. METHODS Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ, as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. RESULTS After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend (P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age (P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues (P < 0.05). CONCLUSION Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation. PMID:28293090

Proteomic profiling of fetal esophageal epithelium, esophageal cancer, and tumor-adjacent esophageal epithelium and immunohistochemical characterization of a representative differential protein, PRX6.

PubMed

Guo, Jun-Hui; Xing, Guo-Lan; Fang, Xin-Hui; Wu, Hui-Fang; Zhang, Bo; Yu, Jin-Zhong; Fan, Zong-Min; Wang, Li-Dong

2017-02-28

To understand the molecular mechanism of esophageal cancer development and provide molecular markers for screening high-risk populations and early diagnosis. Two-dimensional electrophoresis combined with mass spectrometry were adopted to screen differentially expressed proteins in nine cases of fetal esophageal epithelium, eight cases of esophageal cancer, and eight cases of tumor-adjacent normal esophageal epithelium collected from fetuses of different gestational age, or esophageal cancer patients from a high-risk area of esophageal cancer in China. Immunohistochemistry (avidin-biotin-horseradish peroxidase complex method) was used to detect the expression of peroxiredoxin (PRX)6 in 91 cases of esophageal cancer, tumor-adjacent normal esophageal tissue, basal cell hyperplasia, dysplasia, and carcinoma in situ , as well as 65 cases of esophageal epithelium from fetuses at a gestational age of 3-9 mo. After peptide mass fingerprint analysis and search of protein databases, 21 differential proteins were identified; some of which represent a protein isoform. Varying degrees of expression of PRX6 protein, which was localized mainly in the cytoplasm, were detected in adult and fetal normal esophageal tissues, precancerous lesions, and esophageal cancer. With the progression of esophageal lesions, PRX6 protein expression showed a declining trend ( P < 0.05). In fetal epithelium from fetuses at gestational age 3-6 mo, PRX6 protein expression showed a declining trend with age ( P < 0.05). PRX6 protein expression was significantly higher in well-differentiated esophageal cancer tissues than in poorly differentiated esophageal cancer tissues ( P < 0.05). Development and progression of esophageal cancer result from interactions of genetic changes (accumulation or superposition). PRX6 protein is associated with fetal esophageal development and cancer differentiation.

Differential role of microRNAs in the pathogenesis and treatment of Esophageal cancer.

PubMed

Hemmatzadeh, Maryam; Mohammadi, Hamed; Karimi, Mohammad; Musavishenas, Mohammad Hossein; Baradaran, Behzad

2016-08-01

Esophageal cancer (EC) is the most invasive disease associated with inclusive poor prognosis. EC usually is found as either adenocarcinoma (EAC) or squamous cell carcinomas (ESCC). ESCC forms in squamous cells and highly occurs in the upper third of the esophagus. EAC appears in glandular cells and ordinarily develops in the lower one third of the esophagus near the stomach. Barrett's esophagus (BE) is a metaplastic precursor of EAC. There is a persistent need for improving our understanding of the molecular basis of this disease. MicroRNAs (miRNAs) demonstrate an uncovered class of small, non-coding RNAs that can negatively regulate the protein coding gene, and are associated with approximately all known physiological and pathological processes, especially cancer. MiRNAs can affect cancer pathogenesis, playing a crucial role as either oncogenes or tumor suppressors. The recent emergence of observations on the role of miRNAs in cancer and their functions has induced many investigations to examine their relevance to esophageal cancer. In esophageal cancer, miRNA dysregulation plays a crucial role in cancer prognosis and in patients' responsiveness to neo-adjuvant and adjuvant therapies. In this review, the oncogenic, tumor suppressive, and drug resistance related roles of miRNAs, and their involvement in the pathogenesis and treatment of esophageal cancer were summarized. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Video-assisted mediastinoscopic resection compared with video-assisted thoracoscopic surgery in patients with esophageal cancer.

PubMed

Wang, Qian-Yun; Tan, Li-Jie; Feng, Ming-Xiang; Zhang, Xiao-Ying; Zhang, Lei; Jiang, Nan-Qing; Wang, Zhong-Lin

2014-06-01

The purpose of this study was to explore the indications of radical vedio-assisted mediastinoscopic resection for esophageal cancer. The data of 109 patients with T1 esophageal cancer who underwent video-assisted mediastinoscopic resection (VAMS group) in Third Affiliated Hospital of Soochow University Hospital from December 2005 to December 2011 were collected in the study for comparison with the 58 patients with T1 esophageal cancer who underwent video-assisted thoracoscopic surgery (VATS group) in Zhongshan Hospital, Fudan University. The perioperative safety and survival were compared between the two groups. All operations were successful in both groups. One perioperative death was noted in the VATS group. The incidences of post-operative complications were not significantly different between these two groups, whereas the VAMS group was favorable in terms of operative time (P<0.001) and blood loss (P<0.001), and a significantly larger number of chest lymph nodes were dissected in the VATS group compared with the VAMS group (P<0.001). Long-term follow-up showed that the overall survival was not significantly different between these two groups (P=0.876). T1N0M0 esophageal cancer can be as the indication of VAMS radical resection. VAMS radical resection can be considered as the preferred option for patients with poor pulmonary and cardiac function or a history of pleural disease.

Video-assisted mediastinoscopic resection compared with video-assisted thoracoscopic surgery in patients with esophageal cancer

PubMed Central

Wang, Qian-Yun; Tan, Li-Jie; Feng, Ming-Xiang; Zhang, Xiao-Ying; Zhang, Lei; Jiang, Nan-Qing

2014-01-01

Objective The purpose of this study was to explore the indications of radical vedio-assisted mediastinoscopic resection for esophageal cancer. Methods The data of 109 patients with T1 esophageal cancer who underwent video-assisted mediastinoscopic resection (VAMS group) in Third Affiliated Hospital of Soochow University Hospital from December 2005 to December 2011 were collected in the study for comparison with the 58 patients with T1 esophageal cancer who underwent video-assisted thoracoscopic surgery (VATS group) in Zhongshan Hospital, Fudan University. The perioperative safety and survival were compared between the two groups. Results All operations were successful in both groups. One perioperative death was noted in the VATS group. The incidences of post-operative complications were not significantly different between these two groups, whereas the VAMS group was favorable in terms of operative time (P<0.001) and blood loss (P<0.001), and a significantly larger number of chest lymph nodes were dissected in the VATS group compared with the VAMS group (P<0.001). Long-term follow-up showed that the overall survival was not significantly different between these two groups (P=0.876). Conclusions T1N0M0 esophageal cancer can be as the indication of VAMS radical resection. VAMS radical resection can be considered as the preferred option for patients with poor pulmonary and cardiac function or a history of pleural disease. PMID:24976988

Follow-up of a cohort of children and adolescents with gastro-esophageal reflux disease who were free of reflux esophagitis at initial diagnosis.

PubMed

Ruigómez, Ana; Lundborg, Per; Johansson, Saga; Wallander, Mari-Ann; García Rodríguez, Luis A

2010-08-01

Few studies have examined the incidence of complications from gastro-esophageal reflux disease (GERD) in children and adolescents in primary care. Here we aimed to describe the natural history of GERD in a pediatric population with no reflux esophagitis at initial diagnosis, assessing diagnoses of new esophageal complications and extra-esophageal conditions. We used The Health Improvement Network UK primary care database (which includes data on more than 2 million patients) to identify individuals aged 1-17 years with a first diagnosis of gastro-esophageal reflux or heartburn in the period 2000-2005, via a computerized search followed by a manual review of the patient records. This search identified 1242 individuals with an incident diagnosis of GERD but no record of esophagitis. This cohort was followed-up to detect new diagnoses of esophageal complications and extra-esophageal conditions. During a mean follow-up period of almost 4 years, 40 children and adolescents had a confirmed new diagnosis of reflux esophagitis (incidence: 10.9 per 1000 person-years). No cases of Barrett's esophagus, esophageal stricture or esophageal ulcer were reported. Individuals with GERD had double the risk of an extra-esophageal condition such as asthma, pneumonia, cough or chest pain compared with children and adolescents with no diagnosis of GERD. Children and adolescents with GERD may be at risk of developing reflux esophagitis and a range of other extra-esophageal conditions, but more severe esophageal complications are rare.

Clinical and manometric characteristics of patients with Parkinson's disease and esophageal symptoms.

PubMed

Su, A; Gandhy, R; Barlow, C; Triadafilopoulos, G

2017-04-01

Dysphagia is a common problem in patients with Parkinson's disease (PD); its etiology is multifactorial and its management is challenging. In this retrospective cohort analysis using prospectively collected data, we aimed to objectively characterize dysphagia and/or other esophageal symptoms in patients with PD, assess the prevalence of outflow obstruction as well as major or minor disorders of esophageal peristalsis leading to impaired esophageal clearance and highlight objective parameters that can help in the current management algorithm. Thirty-three consecutive patients with PD presenting with dysphagia, odynophagia, heartburn, regurgitation, chest pain, and weight loss underwent clinical and functional evaluation by high-resolution manometry (HRM). Esophagogastric junction (EGJ) outflow obstruction and major as well as minor disorders of peristalsis were then assessed using the Chicago classification (v3). Thirty-three PD patients with esophageal symptoms were enrolled in the study; 12 of them reported weight loss that was considered as potentially reflecting underlying esophageal dysfunction. The median age of the patients was 70 years (range: 53-89 years), 24 (75%) were men. The majority (62%) experienced dysphagia, likely contributing to weight loss in 41% of patients. Odynophagia was rare (6%) while GER symptoms, such as heartburn, regurgitation, and chest pain were noted in 37%, 31%, and 28% of patients, respectively. Using the hierarchy of the Chicago classification, 12 patients (39%) exhibited EGJ outflow obstruction, 16 (48%) diffuse esophageal spasm (DES), 18 (55%), ineffective esophageal peristalsis (IEM), 16 (48%) fragmented peristalsis, and only 2 patients (6%) had normal HRM tracings. There were no patients with HRM features of achalasia. Dysphagia is common in patients with PD and is associated with a high prevalence of underlying motility disturbances as identified by HRM. The exact impact of these motility abnormalities on symptom induction and their role in influencing clinical management are unclear and will require further study. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Discovery and validation of vascular endothelial growth factor (VEGF) pathway polymorphisms in esophageal adenocarcinoma outcome.

PubMed

Eng, Lawson; Azad, Abul Kalam; Qiu, Xin; Kong, Qin Quinn; Cheng, Dangxiao; Ying, Nanjiao; Tse, Alvina; Kuang, Qin; Dodbiba, Lorin; Renouf, Daniel J; Marsh, Sharon; Savas, Sevtap; Mackay, Helen J; Knox, Jennifer J; Darling, Gail E; Wong, Rebecca K S; Xu, Wei; Liu, Geoffrey; Faluyi, Olusola O

2015-09-01

Polymorphisms in the vascular endothelial growth factor (VEGF)/angiogenesis pathway have been implicated previously in cancer risk, prognosis and response to therapy including in esophageal adenocarcinoma. Prior esophageal adenocarcinoma studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new VEGF pathway polymorphisms associated with esophageal adenocarcinoma prognosis and validated them in an independent cohort of esophageal adenocarcinoma patients. In 231 esophageal adenocarcinoma patients of all stages/treatment plans, 58 genetic polymorphisms (18 KDR, 7 VEGFA and 33 FLT1) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then validated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median OS and PFS were 20 and 12 months, respectively. KDR rs17709898 was found significantly associated with PFS (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). FLT1 rs3794405 and rs678714 were significantly associated with OS (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No VEGFA polymorphisms were found significantly associated with either outcome. Upon validation, FLT1 rs3794405 remained strongly associated with OS (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). FLT1 rs3794405 is significantly associated with OS in esophageal adenocarcinoma, whereby each variant allele confers a 45-60% increased risk of mortality. Validation and evaluation of this association in other cancer sites are warranted. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Self-Expandable Metal Stents for Persisting Esophageal Variceal Bleeding after Band Ligation or Injection-Therapy: A Retrospective Study.

PubMed

Müller, Martin; Seufferlein, Thomas; Perkhofer, Lukas; Wagner, Martin; Kleger, Alexander

2015-01-01

Despite a pronounced reduction of lethality rates due to upper gastrointestinal bleeding, esophageal variceal bleeding remains a challenge for the endoscopist and still accounts for a mortality rate of up to 40% within the first 6 weeks. A relevant proportion of patients with esophageal variceal bleeding remains refractory to standard therapy, thus making a call for additional tools to achieve hemostasis. Self-expandable metal stents (SEMS) incorporate such a tool. We evaluated a total number of 582 patients admitted to our endoscopy unit with the diagnosis "gastrointestinal bleeding" according to our documentation software between 2011 and 2014. 82 patients suffered from esophageal variceal bleeding, out of which 11 cases were refractory to standard therapy leading to SEMS application. Patients with esophageal malignancy, fistula, or stricture and a non-esophageal variceal bleeding source were excluded from the analysis. A retrospective analysis reporting a series of clinically relevant parameters in combination with bleeding control rates and adverse events was performed. The initial bleeding control rate after SEMS application was 100%. Despite this success, we observed a 27% mortality rate within the first 42 days. All of these patients died due to non-directly hemorrhage-associated reasons. The majority of patients exhibited an extensive demand of medical care with prolonged hospital stay. Common complications were hepatic decompensation, pulmonary infection and decline of renal function. Interestingly, we found in 7 out of 11 patients (63.6%) stent dislocation at time of control endoscopy 24 h after hemostasis or at time of stent removal. The presence of hiatal hernia did not affect obviously stent dislocation rates. Refractory patients had significantly longer hospitalization times compared to non-refractory patients. Self-expandable metal stents for esophageal variceal bleeding seem to be safe and efficient after failed standard therapy. Stent migration appeared to be a common incident that did not lead to reactivation of bleeding in any of our patients. SEMS should be considered a reasonable treatment option for refractory esophageal variceal bleeding after treatment failure of ligature and sclerotherapy and non-availability of or contraindication for other measures (e.g. TIPS).

Changes in Hyolaryngeal Movement and Swallowing Function After Neuromuscular Electrical Stimulation in Patients With Dysphagia

PubMed Central

Lee, Hoo Young; Hong, Ji Seong; Lee, Kil Chan; Shin, Yoon-Kyum

2015-01-01

Objective To investigate immediate changes in hyolaryngeal movement and swallowing function after a cycle of neuromuscular electrical stimulation (NMES) on both submental and throat regions and submental placement alone in patients with dysphagia. Methods Fifteen patients with dysphagia were recruited. First, videofluoroscopic swallowing study (VFSS) was performed before NMES. All patients thereafter received a cycle of NMES by 2 methods of electrode placement: 1) both submental and throat regions and 2) submental placement alone concomitant with VFSS. The Penetration-Aspiration Score (PAS) and the NIH-Swallowing Safety Scale (NIH-SSS) were measured for swallowing function. Results During swallowing, hyolaryngeal descent significantly occurred by NMES on both submental and throat regions, and anterior displacement of hyolaryngeal complex was significant on submental placement alone. NMES on submental placement alone did not change the PAS and NIH-SSS. However, NMES on both submental and throat regions significantly reduced the NIH-SSS, although it did not change the PAS. Patients with no brainstem lesion and with dysphagia duration of <3 months showed significantly improved the NIH-SSS. Conclusion Immediate hyolaryngeal movement was paradoxically depressed after NMES on both submental and throat regions with significant reductions in the NIH-SSS but not the PAS, suggesting improvement in pharyngeal peristalsis and cricopharyngeal functions at the esophageal entry rather than decreased aspiration and penetration. The results also suggested that patients with dysphagia should be carefully screened when determining motor-level NMES. PMID:25932416

Pressure-Flow Analysis for the Assessment of Pediatric Oropharyngeal Dysphagia.

PubMed

Ferris, Lara; Rommel, Nathalie; Doeltgen, Sebastian; Scholten, Ingrid; Kritas, Stamatiki; Abu-Assi, Rammy; McCall, Lisa; Seiboth, Grace; Lowe, Katie; Moore, David; Faulks, Jenny; Omari, Taher

2016-10-01

To determine which objective pressure-impedance measures of pharyngeal swallowing function correlated with clinically assessed severity of oropharyngeal dysphagia (OPD) symptoms. Forty-five children with OPD and 34 control children without OPD were recruited and up to 5 liquid bolus swallows were recorded with a solid-state high-resolution manometry with impedance catheter. Individual measures of pharyngeal and upper esophageal sphincter (UES) function and a swallow risk index composite score were derived for each swallow, and averaged data for patients with OPD were compared with those of control children without OPD. Clinical severity of OPD symptoms and oral feeding competency was based on the validated Dysphagia Disorders Survey and Functional Oral Intake Scale. Those objective measures that were markers of UES relaxation, UES opening, and pharyngeal flow resistance differentiated patients with and without OPD symptoms. Patients demonstrating abnormally high pharyngeal intrabolus pressures and high UES resistance, markers of outflow obstruction, were most likely to have signs and symptoms of overt Dysphagia Disorders Survey (OR 9.24, P = .05, and 9.7, P = .016, respectively). Pharyngeal motor patterns can be recorded in children by the use of HRIM and pharyngeal function can be defined objectively with the use of pressure-impedance measures. Objective measurements suggest that pharyngeal dysfunction is common in children with clinical signs of OPD. A key finding of this study was evidence of markers of restricted UES opening. Copyright © 2016 Elsevier Inc. All rights reserved.

Rare esophageal ulcers related to Behçet disease: A case report.

PubMed

Jia, Ning; Tang, Yanping; Liu, Huayi; Li, Yang; Liu, Simiao; Liu, Lei

2017-11-01

The fundamental pathogenesis of Behçet disease (BD) is still unclear and controversial. Many cases of oral aphthous ulcers and genital ulcers related to BD are reported; nevertheless, idiopathic giant esophageal ulcers related to BD are rare. A rare case for esophageal ulcers related to BD is presented. In China, BD is represented with esophageal involvement which is called esophageal BD (EBD). A 56-year-old man diagnosed to the Gastroenterology Department of Integrated Traditional Chinese and Western Medicine Hospital, for multiple discrete, elliptical esophageal ulcers related to BD. The esophageal ulcers were treated with corticosteroid treatment for 12 weeks. The esophageal ulcers were cured. Our report might give further strength to avoiding the erroneous diagnosis or missed diagnosis for EBD, which is different from esophageal carcinoma, esophageal tuberculosis and esophageal Crohns disease.

Structural equation modeling of motor impairment, gross motor function, and the functional outcome in children with cerebral palsy.

PubMed

Park, Eun-Young; Kim, Won-Ho

2013-05-01

Physical therapy intervention for children with cerebral palsy (CP) is focused on reducing neurological impairments, improving strength, and preventing the development of secondary impairments in order to improve functional outcomes. However, relationship between motor impairments and functional outcome has not been proved definitely. This study confirmed the construct of motor impairment and performed structural equation modeling (SEM) between motor impairment, gross motor function, and functional outcomes of regarding activities of daily living in children with CP. 98 children (59 boys, 39 girls) with CP participated in this cross-sectional study. Mean age was 11 y 5 mo (SD 1 y 9 mo). The Manual Muscle Test (MMT), the Modified Ashworth Scale (MAS), range of motion (ROM) measurement, and the selective motor control (SMC) scale were used to assess motor impairments. Gross motor function and functional outcomes were measured using the Gross Motor Function Measure (GMFM) and the Functional Skills domain of the Pediatric Evaluation of Disability Inventory (PEDI) respectively. Measurement of motor impairment was consisted of strength, spasticity, ROM, and SMC. The construct of motor impairment was confirmed though an examination of a measurement model. The proposed SEM model showed good fit indices. Motor impairment effected gross motor function (β=-.0869). Gross motor function and motor impairment affected functional outcomes directly (β=0.890) and indirectly (β=-0.773) respectively. We confirmed that the construct of motor impairment consist of strength, spasticity, ROM, and SMC and it was identified through measurement model analysis. Functional outcomes are best predicted by gross motor function and motor impairments have indirect effects on functional outcomes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fiber-enriched diet helps to control symptoms and improves esophageal motility in patients with non-erosive gastroesophageal reflux disease.

PubMed

Morozov, Sergey; Isakov, Vasily; Konovalova, Mariya

2018-06-07

To investigate the effect of dietary fiber on symptoms and esophageal function testing parameters in non-erosive gastroesophageal reflux disease (GERD) (NERD) patients. Thirty-six NERD patients with low (< 20 g/d) dietary fiber intake were enrolled in the study. They were examined with the use of symptom questionnaire (GERD-Q), high-resolution esophageal manometry, 24-h esophageal pH-impedance examinations, and food frequency questionnaire before and after 10 d of usual diet supplemented by psyllium 5.0 g TID. Complete data of 30 patients were available to the final analysis. The obtained results were analyzed with the use of non-parametric statistics (Wilcoxon matched pairs test). The number of patients experiencing heartburn was less (93.3% at baseline vs 40% at the end of the study, P < 0.001) and the GERD-Q score decreased (mean ± SD: 10.9 ± 1.7 vs 6.0 ± 2.3, P < 0.001) after the treatment period. Minimal resting lower esophageal sphincter (LES) pressure increased from 5.41 ± 10.1 to 11.3 ± 9.4 mmHg ( P = 0.023), but no change in residual LES pressure and mean resting pressure was found. Total number of gastroesophageal refluxes (GER) decreased from 67.9 ± 17.7 to 42.4 ± 13.5 ( P < 0.001) predominantly by acid and weak acid types of GERs. No significant change in mean esophageal pH and % of time pH < 4 was registered. Maximal reflux time decreased from 10.6 ± 12.0 min to 5.3 ± 3.7 min ( P < 0.05). Fiber-enriched diet led to a significant increase of minimal lower esophageal sphincter resting pressure, a decrease of number of gastroesophageal refluxes, and a decrease of heartburn frequency per week in NERD.

Acid sensitization of esophageal mucosal afferents: implication for symptom perception in patients across the gastroesophageal reflux disease spectrum.

PubMed

Szczesniak, Michal Marcin; Fuentealba, Sergio Enrique; Cook, Ian J

2013-01-01

Sensitization of esophageal chemoreceptors, either directly by intermittent acid exposure or indirectly through esophagitis-associated inflammatory mediators, is likely to be the mechanism underlying the perception of heartburn. To compare basal esophageal sensitivity with electrical stimulation and acid, and to compare the degree of acid-induced sensitization in controls and in patient groups across the entire spectrum of gastroesophageal reflux disease: erosive oesophagitis (EO), nonerosive reflux disease (NERD), and functional heartburn (FH). Esophageal sensory and pain thresholds to electrical stimulation were measured before, 30, and 60 minutes after an intraesophageal infusion of saline or HCl. Patients received a 30-minute infusion of 0.15 M HCl and controls were randomized to receive either HCl (n = 11) or saline (n = 10). After electrical sensory threshold testing, participants received another 30-minute infusion of HCl to determine whether sensitivity to acid is increased by prior acid exposure All patient groups had higher basal sensory thresholds than healthy controls (controls, 13 ± 1.4 mA; FH, 20 ± 5.1 mA; NERD, 21 ± 5.1 mA; EO, 23 ± 5.4 mA; P < 0.05). Acute esophageal acid exposure reduced sensory thresholds to electrical stimulation in FH and NERD patients (P < 0.05). The level of acid sensitivity during the first HCl infusion was comparable between all patient groups and controls. The secondary infusion caused increased discomfort in all participants (P < 0.01). This acid-induced sensitization to HCl was significantly elevated in the patient groups ( P < 0.05). (1) Esophageal acid infusion sensitizes it to subsequent electrical and chemical stimulation. (2) The acid-related sensitization is greater in gastroesophageal reflux disease than in controls and may influence in part symptom perception in this population. (3) Acid-related sensitization within the gastroesophageal reflux disease population is not dependant on mucosal inflammation.

Clinical Outcomes, Efficacy, and Adverse Events in Patients Undergoing Esophageal Stent Placement for Benign Indications: A Large Multicenter Study.

PubMed

Suzuki, Takayuki; Siddiqui, Ali; Taylor, Linda J; Cox, Kristen; Hasan, Raza A; Laique, Sobia N; Mathew, Arun; Wrobel, Piotr; Adler, Douglas G

2016-01-01

Esophageal stents are commonly used to treat benign esophageal conditions including refractory benign esophageal strictures, anastomotic strictures, fistulae, perforations and anastomotic leaks. Data on outcomes in these settings remain limited. We performed a retrospective multicenter study of patients who underwent fully or partially covered self-expandable stent placement for benign esophageal diseases. Esophageal stent placements were performed for the following indications: (1) benign refractory esophageal strictures, (2) surgical anastomotic strictures, (3) esophageal perforations, (4) esophageal fistulae, and (5) surgical anastomotic leaks. A total of 70 patients underwent esophageal stent placement for benign esophageal conditions. A total of 114 separate procedures were performed. The most common indication for esophageal stent placement was refractory benign esophageal stricture (48.2%). Global treatment success rate was 55.7%. Treatment success rate was 33.3% in refractory benign strictures, 23.1% in anastomotic strictures, 100% in perforations, 71.4% in fistulae, and 80% in anastomotic leaks. Stent migration was noted in 28 of 70 patients (40%), most commonly seen in refractory benign strictures. This is one of the largest studies to date of esophageal stents to treat benign esophageal diseases. Success rates are lowest in benign esophageal strictures. These patients have few other options beyond chronic dilations, feeding tubes, and surgery, and fully covered self-expandable metallic stent give patients a chance to have their problem fixed endoscopically and still eat by mouth. Perforations, fistulas, and leaks respond very well to esophageal stenting, and stenting should be considered as a first-line therapy in these settings.

Efficacy of Intensity Modulated Radiation Therapy After Surgery in Early Stage of Esophageal Carcinoma;

ClinicalTrials.gov

2018-02-22

Esophageal Neoplasm; Esophageal Cancer TNM Staging Primary Tumor (T) T2; Esophageal Cancer TNM Staging Primary Tumor (T) T3; Esophageal Cancer TNM Staging Regional Lymph Nodes (N) N0; Esophageal Cancer TNM Staging Distal Metastasis (M) M0

Upper Gastrointestinal Tract Motility Disorders in Women, Gastroparesis, and Gastroesophageal Reflux Disease.

PubMed

Zia, Jasmine K; Heitkemper, Margaret M

2016-06-01

This article reviews the sex differences in upper gastrointestinal (GI) motility for both healthy and common dysmotility conditions. It focuses on gastroesophageal reflux disease and other esophageal motor disorders for the esophagus and on gastroparesis and accelerated gastric emptying for the stomach. It also describes differences in upper GI motility signs and symptoms during each female hormonal stage (ie, menstrual cycle, pregnancy, perimenopause, menopause) for both healthy participants and those suffering from one of the aforementioned upper GI dysmotility conditions. More research still needs to be conducted to better understand sex differences in upper GI motility. Copyright © 2016 Elsevier Inc. All rights reserved.

Objectively Quantifying Radiation Esophagitis With Novel Computed Tomography–Based Metrics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niedzielski, Joshua S., E-mail: jsniedzielski@mdanderson.org; University of Texas Houston Graduate School of Biomedical Science, Houston, Texas; Yang, Jinzhong

Purpose: To study radiation-induced esophageal expansion as an objective measure of radiation esophagitis in patients with non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy. Methods and Materials: Eighty-five patients had weekly intra-treatment CT imaging and esophagitis scoring according to Common Terminlogy Criteria for Adverse Events 4.0, (24 Grade 0, 45 Grade 2, and 16 Grade 3). Nineteen esophageal expansion metrics based on mean, maximum, spatial length, and volume of expansion were calculated as voxel-based relative volume change, using the Jacobian determinant from deformable image registration between the planning and weekly CTs. An anatomic variability correction method wasmore » validated and applied to these metrics to reduce uncertainty. An analysis of expansion metrics and radiation esophagitis grade was conducted using normal tissue complication probability from univariate logistic regression and Spearman rank for grade 2 and grade 3 esophagitis endpoints, as well as the timing of expansion and esophagitis grade. Metrics' performance in classifying esophagitis was tested with receiver operating characteristic analysis. Results: Expansion increased with esophagitis grade. Thirteen of 19 expansion metrics had receiver operating characteristic area under the curve values >0.80 for both grade 2 and grade 3 esophagitis endpoints, with the highest performance from maximum axial expansion (MaxExp1) and esophageal length with axial expansion ≥30% (LenExp30%) with area under the curve values of 0.93 and 0.91 for grade 2, 0.90 and 0.90 for grade 3 esophagitis, respectively. Conclusions: Esophageal expansion may be a suitable objective measure of esophagitis, particularly maximum axial esophageal expansion and esophageal length with axial expansion ≥30%, with 2.1 Jacobian value and 98.6 mm as the metric value for 50% probability of grade 3 esophagitis. The uncertainty in esophageal Jacobian calculations can be reduced with anatomic correction methods.« less

Mucosal perforation during laparoscopic surgery for achalasia: impact of preoperative pneumatic balloon dilation.

PubMed

Souma, Yoshihito; Nakajima, Kiyokazu; Taniguchi, Eiji; Takahashi, Tsuyoshi; Kurokawa, Yukinori; Yamasaki, Makoto; Miyazaki, Yasuhiro; Makino, Tomoki; Hamada, Tetsuhiro; Yasuda, Jun; Yumiba, Takeyoshi; Ohashi, Shuichi; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

2017-03-01

Controversy remains whether preoperative pneumatic balloon dilation (PBD) influences the surgical outcome of laparoscopic esophagocardiomyotomy in patients with esophageal achalasia. The aim of this study was to evaluate whether preoperative PBD represents a risk factor for surgical complications and affects the symptomatic and/or functional outcomes of laparoscopic Heller myotomy with Dor fundoplication (LHD). A retrospective chart review was conducted on a prospectively compiled surgical database of 103 consecutive patients with esophageal achalasia who underwent LHD from November 1994 to September 2014. The following data were compared between the patients with preoperative PBD (PBD group; n = 26) and without PBD (non-PBD group; n = 77): (1) patients' demographics: age, gender, body mass index, duration of symptoms, maximum transverse diameter of esophagus; (2) operative findings: operating time, blood loss, intraoperative complications; (3) postoperative course: complications, clinical symptoms, postoperative treatment; and (4) esophageal functional tests: preoperative and postoperative manometric data and postoperative profile of 24-h esophageal pH monitoring. (1) No significant differences were observed in the patients' demographics. (2) Operative findings were similar between the two groups; however, the incidence of mucosal perforation was significantly higher in the PBD group (n = 8; 30.7 %) compared to the non-PBD group (n = 6; 7.7 %) (p = 0.005). (3) Postoperative complications were not encountered in either group. The differences were not significant for postoperative clinical symptoms, the incidence of gastroesophageal reflux disease, or necessity of postoperative treatments. (4) Lower esophageal sphincter pressure was effectively reduced in both groups, and no differences were observed in manometric data or 24-h pH monitoring profiles between the two groups. Multivariate logistic regression analysis showed that preoperative PBD and the maximum transverse diameter of esophagus were significantly associated with intraoperative mucosal perforation. Although postoperative outcomes were not affected, additional caution is recommended in identifying intraoperative mucosal perforation in patients with preoperative PBD when performing LHD.

Balloon dilation of the esophago-gastric junction affects lower and upper esophageal sphincter function in achalasia.

PubMed

Wauters, L; Van Oudenhove, L; Selleslagh, M; Vanuytsel, T; Boeckxstaens, G; Tack, J; Omari, T; Rommel, N

2014-01-01

Pneumatic dilation of the lower esophageal sphincter (LES) in achalasia has an unappreciated effect on upper esophageal sphincter (UES) function. We studied UES pressure patterns at baseline and alterations in UES parameters resulting from therapy. High-resolution manometry (HRM) tracings from 50 achalasia patients, seen at a tertiary center between January 2009 and July 2011, were reviewed. Manometric parameters studied were (i) LES: resting pressure (restP), 4-second integrated relaxation pressure (IRP4); (ii) UES: resting pressure (restP), minimal relaxation pressure (MRP), peak pressure (PP), relaxation interval (RI), intrabolus pressure (IBP), and deglutitive sphincter resistance (DSR). Mixed models analyses with LES and UES parameters as dependent variables and treatment stage as within-subject independent variable of interest were used. Correlations between treatment-induced changes in LES, UES, and esophageal body (EB) parameters were performed. Pre- and posttreatment HRM tracings were available from 50 patients (mean age 52.7 ± 18.6 years, 29 men). Upper esophageal sphincter parameters MRP (17.9 ± 1.2 vs 15.2 ± 0.9 mmHg; p = 0.02) and IBP (31.5 ± 1.5 vs 27.4 ± 1.2 mmHg; p = 0.009) were significantly reduced after initial balloon dilation and this effect was significant in type II achalasia (p = 0.002 and p = 0.0006). Peak pressure, RI, and DSR were not. The therapeutic effect on LES IRP4 correlated significantly with the change in UES MRP, statistically mediated by the change in EB deglutitive pressure (p = 0.004 and p = 0.0002). We present the first HRM study demonstrating that pneumatic dilation of the LES affects intraesophageal and UES pressures in patients with achalasia. © 2013 John Wiley & Sons Ltd.

Interleukin 1B rs16944 G>A polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population.

PubMed

Zheng, Liang; Yin, Jun; Wang, Liming; Wang, Xu; Shi, Yijun; Shao, Aizhong; Tang, Weifeng; Ding, Guowen; Liu, Chao; Chen, Suocheng; Gu, Haiyong

2013-10-01

Esophageal cancer is the sixth leading cause of cancer-associated deaths worldwide and represents a particularly aggressive type of cancer. Genetic polymorphisms may partly explain individual differences in esophageal cancer susceptibility. We conducted a hospital-based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 1 (IL1A and IL1B), IL1f7, IL3 and IL7Ra genes on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit. When the IL1B rs16944 GG homozygote genotype was used as the reference group, the GA genotype was associated with a significantly decreased risk of ESCC (GA vs. GG: adjusted OR=0.69, 95% CI=0.49-0.99, p=0.041). However, there were no significant associations between the other five SNPs and ESCC risk. Stratified analyses indicated no significantly different risks of ESCC associated with the IL1B rs16944 G>A polymorphism according to sex, age, smoking status or alcohol consumption. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher tumor, nodal, and metastatic (TNM) stages. These findings indicated that the functional IL1B rs16944 G>A polymorphism might contribute to ESCC susceptibility. IL3 rs2073506 G>A polymorphism was associated with an increased risk for ESCC higher TNM stages. However, the results were based on a limited sample size and larger well-designed studies are warranted to confirm these initial findings. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Esophagram findings in cervical esophageal stenosis: A case-controlled quantitative analysis.

PubMed

West, Jacob; Kim, Cherine H; Reichert, Zachary; Krishna, Priya; Crawley, Brianna K; Inman, Jared C

2018-01-04

Cervical esophageal stenosis is often diagnosed with a qualitative evaluation of a barium esophagram. Although the esophagram is frequently the initial screening exam for dysphagia, a clear objective standard for stenosis has not been defined. In this study, we measured esophagram diameters in order to establish a quantitative standard for defining cervical esophageal stenosis that requires surgical intervention. Single institution case-control study. Patients with clinically significant cervical esophageal stenosis defined by moderate symptoms of dysphagia (Functional Outcome Swallowing Scale > 2 and Functional Oral Intake Scale < 6) persisting for 6 months and responding to dilation treatment were matched with age, sex, and height controls. Both qualitative and quantitative barium esophagram measurements for the upper, mid-, and lower vertebral bodies of C5 through T1 were analyzed in lateral, oblique, and anterior-posterior views. Stenotic patients versus nonstenotic controls showed no significant differences in age, sex, height, body mass index, or ethnicity. Stenosis was most commonly at the sixth cervical vertebra (C 6) lower border and C7 upper border. The mean intraesophageal minimum/maximum ratios of controls and stenotic groups in the lateral view were 0.63 ± 0.08 and 0.36 ± 0.12, respectively (P < 0.0001). Receiver operating characteristic analysis of the minimum/maximum ratios, with a <0.50 ratio delineating stenosis, demonstrated that lateral view measurements had the best diagnostic ability. The sensitivity of the radiologists' qualitative interpretation was 56%. With application of lateral intraesophageal minimum/maximum ratios, we observed improved sensitivity to 94% of the esophagram, detecting clinically significant stenosis. Applying quantitative determinants in esophagram analysis may improve the sensitivity of detecting cervical esophageal stenosis in dysphagic patients who may benefit from surgical therapy. IIIb. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Influence of repeated infusion of capsaicin-contained red pepper sauce on esophageal secondary peristalsis in humans.

PubMed

Liu, T T; Yi, C H; Lei, W Y; Hung, X S; Yu, H C; Chen, C L

2014-10-01

The transient receptor potential vanilloid 1 has been implicated as a target mediator for heartburn perception and modulation of esophageal secondary peristalsis. Our aim was to determine the effect of repeated esophageal infusion of capsaicin-contained red pepper sauce on heartburn perception and secondary peristalsis in healthy adults. Secondary peristalsis was performed with mid-esophageal injections of air in 15 healthy adults. Two separate protocols including esophageal infusion with saline and capsaicin-contained red pepper sauce and 2 consecutive sessions of capsaicin-contained red pepper sauce were randomly performed. After repeated infusion of capsaicin-contained red pepper sauce, the threshold volume to activate secondary peristalsis was significantly increased during slow (p < 0.001) and rapid air injections (p = 0.004). Acute infusion of capsaicin-contained red pepper sauce enhanced heartburn perception (p < 0.001), but the intensity of heartburn perception was significantly reduced after repeated capsaicin-contained red pepper sauce infusion (p = 0.007). Acute infusion of capsaicin-contained red pepper sauce significantly increased pressure wave amplitudes of distal esophagus during slow (p = 0.003) and rapid air injections (p = 0.01), but repeated infusion of capsaicin-contained red pepper sauce significantly decreased pressure wave amplitude of distal esophagus during slow (p = 0.0005) and rapid air injections (p = 0.003). Repeated esophageal infusion of capsaicin appears to attenuate heartburn perception and inhibit distension-induced secondary peristalsis in healthy adults. These results suggest capsaicin-sensitive afferents in modulating sensorimotor function of secondary peristalsis in human esophagus. © 2014 John Wiley & Sons Ltd.

Nano Let‑7b sensitization of eliminating esophageal cancer stem‑like cells is dependent on blockade of Wnt activation of symmetric division.

PubMed

Pang, Yamei; Liu, Jian; Li, Xiang; Zhang, Yiwen; Zhang, Boxiang; Zhang, Jing; Du, Ning; Xu, Chongwen; Liang, Rui; Ren, Hong; Tang, Shou-Ching; Sun, Xin

2017-10-01

The poor therapy response and poor prognosis of esophageal cancer has made it one of the most malignant carcinoma, and the complicated multidisciplinary treatment failed to achieve a long-term disease-free survival. To diagnose esophageal cancer at an earlier stage, and to improve the effect of anticancer therapy would improve the therapeutic efficacy. After retrospective analysis of the cancer samples of patients who received esophagectomy, we found the relevance between ratio of either ALDH1 or CD133-positive cancer stem cells and 2-year recurrence. Higher ratios of cancer stem cells indicated later clinical stages, and Wnt signaling activation was more frequent in later esophageal carcinoma. Further in bench studies, we explored the suppressive roles and the mechanisms involved in Let‑7 on self-renewal in ECA‑109 and ECA‑9706 esophageal cancer stem cells. Isolated cancer stem cells naturally divide symmetrically and are therapy resistant. Therapy of fluorouracil and docetaxel both enriched the stem cells, proving the resistant characteristics of cancer stem cells. Wnt activation stimulated more symmetric division of stem cells, resulting in self-renewal promotion, which could be blocked by Let‑7 overexpression. Furthermore, enforced Let‑7 sensitized the stem cells to chemotherapies in a Wnt pathway inhibition-dependent manner, contributing to Let‑7 sensitization of chemotherapeutic response. Wnt activation weakened the suppressive Let‑7b through the sponge functions of CCAT-1, forming the negative feedback loop of Let‑7b/Wnt/CCAT1. These results identified the crucial participation of stem cells in esophageal cancer occurrence and progression as the potent indicator, and also indicate the potential powerful agent of Let‑7 nano-particles in treatment of cancer.

Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

ClinicalTrials.gov

2018-02-23

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

Epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China

PubMed Central

Liang, He; Fan, Jin-Hu; Qiao, You-Lin

2017-01-01

Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis. Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control. PMID:28443201

Update on Foregut Molecular Embryology and Role of Regenerative Medicine Therapies

PubMed Central

Perin, Silvia; McCann, Conor J.; Borrelli, Osvaldo; De Coppi, Paolo; Thapar, Nikhil

2017-01-01

Esophageal atresia (OA) represents one of the commonest and most severe developmental disorders of the foregut, the most proximal segment of the gastrointestinal (GI) tract (esophagus and stomach) in embryological terms. Of intrigue is the common origin from this foregut of two very diverse functional entities, the digestive and respiratory systems. OA appears to result from incomplete separation of the ventral and dorsal parts of the foregut during development, resulting in disruption of esophageal anatomy and frequent association with tracheo-oesophageal fistula. Not surprisingly, and likely inherent to OA, are associated abnormalities in components of the enteric neuromusculature and ultimately loss of esophageal functional integrity. An appreciation of such developmental processes and associated defects has not only enhanced our understanding of the etiopathogenesis underlying such devastating defects but also highlighted the potential of novel corrective therapies. There has been considerable progress in the identification and propagation of neural crest stem cells from the GI tract itself or derived from pluripotent cells. Such cells have been successfully transplanted into models of enteric neuropathy confirming their ability to functionally integrate and replenish missing or defective enteric nerves. Combinatorial approaches in tissue engineering hold significant promise for the generation of organ-specific scaffolds such as the esophagus with current initiatives directed toward their cellularization to facilitate optimal function. This chapter outlines the most current understanding of the molecular embryology underlying foregut development and OA, and also explores the promise of regenerative medicine. PMID:28503544

Update on Foregut Molecular Embryology and Role of Regenerative Medicine Therapies.

PubMed

Perin, Silvia; McCann, Conor J; Borrelli, Osvaldo; De Coppi, Paolo; Thapar, Nikhil

2017-01-01

Esophageal atresia (OA) represents one of the commonest and most severe developmental disorders of the foregut, the most proximal segment of the gastrointestinal (GI) tract (esophagus and stomach) in embryological terms. Of intrigue is the common origin from this foregut of two very diverse functional entities, the digestive and respiratory systems. OA appears to result from incomplete separation of the ventral and dorsal parts of the foregut during development, resulting in disruption of esophageal anatomy and frequent association with tracheo-oesophageal fistula. Not surprisingly, and likely inherent to OA, are associated abnormalities in components of the enteric neuromusculature and ultimately loss of esophageal functional integrity. An appreciation of such developmental processes and associated defects has not only enhanced our understanding of the etiopathogenesis underlying such devastating defects but also highlighted the potential of novel corrective therapies. There has been considerable progress in the identification and propagation of neural crest stem cells from the GI tract itself or derived from pluripotent cells. Such cells have been successfully transplanted into models of enteric neuropathy confirming their ability to functionally integrate and replenish missing or defective enteric nerves. Combinatorial approaches in tissue engineering hold significant promise for the generation of organ-specific scaffolds such as the esophagus with current initiatives directed toward their cellularization to facilitate optimal function. This chapter outlines the most current understanding of the molecular embryology underlying foregut development and OA, and also explores the promise of regenerative medicine.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

2012-04-01

To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Effects of gross motor function and manual function levels on performance-based ADL motor skills of children with spastic cerebral palsy.

PubMed

Park, Myoung-Ok

2017-02-01

[Purpose] The purpose of this study was to determine effects of Gross Motor Function Classification System and Manual Ability Classification System levels on performance-based motor skills of children with spastic cerebral palsy. [Subjects and Methods] Twenty-three children with cerebral palsy were included. The Assessment of Motor and Process Skills was used to evaluate performance-based motor skills in daily life. Gross motor function was assessed using Gross Motor Function Classification Systems, and manual function was measured using the Manual Ability Classification System. [Results] Motor skills in daily activities were significantly different on Gross Motor Function Classification System level and Manual Ability Classification System level. According to the results of multiple regression analysis, children categorized as Gross Motor Function Classification System level III scored lower in terms of performance based motor skills than Gross Motor Function Classification System level I children. Also, when analyzed with respect to Manual Ability Classification System level, level II was lower than level I, and level III was lower than level II in terms of performance based motor skills. [Conclusion] The results of this study indicate that performance-based motor skills differ among children categorized based on Gross Motor Function Classification System and Manual Ability Classification System levels of cerebral palsy.

The functional alterations associated with motor imagery training: a comparison between motor execution and motor imagery of sequential finger tapping

NASA Astrophysics Data System (ADS)

Zhang, Hang; Yao, Li; Long, Zhiying

2011-03-01

Motor imagery training, as an effective strategy, has been more and more applied to mental disorders rehabilitation and motor skill learning. Studies on the neural mechanism underlying motor imagery have suggested that such effectiveness may be related to the functional congruence between motor execution and motor imagery. However, as compared to the studies on motor imagery, the studies on motor imagery training are much fewer. The functional alterations associated with motor imagery training and the effectiveness of motor imagery training on motor performance improvement still needs further investigation. Using fMRI, we employed a sequential finger tapping paradigm to explore the functional alterations associated with motor imagery training in both motor execution and motor imagery task. We hypothesized through 14 consecutive days motor imagery training, the motor performance could be improved and the functional congruence between motor execution and motor imagery would be sustained form pre-training phase to post-training phase. Our results confirmed the effectiveness of motor imagery training in improving motor performance and demonstrated in both pre and post-training phases, motor imagery and motor execution consistently sustained the congruence in functional neuroanatomy, including SMA (supplementary motor cortex), PMA (premotor area); M1( primary motor cortex) and cerebellum. Moreover, for both execution and imagery tasks, a similar functional alteration was observed in fusiform through motor imagery training. These findings provided an insight into the effectiveness of motor imagery training and suggested its potential therapeutic value in motor rehabilitation.

Decellularized material as scaffolds for tissue engineering studies in long gap esophageal atresia.

PubMed

Lee, Esmond; Milan, Anna; Urbani, Luca; De Coppi, Paolo; Lowdell, Mark W

2017-05-01

Esophageal atresia refers to an anomaly in foetal development in which the esophagus terminates in a blind end. Whilst surgical correction is achievable in most patients, when a long gap is present it still represents a major challenge associated with higher morbidity and mortality. In this context, tissue engineering could represent a successful alternative to restore oesophageal function and structure. Naturally derived biomaterials made of decellularized tissues retain native extracellular matrix architecture and composition, providing a suitable bed for the anchorage and growth of relevant cell types. Areas covered: This review outlines the various strategies and challenges in esophageal tissue engineering, highlighting the evolution of ideas in the development of decellularized scaffolds for clinical use. It explores the interplay between clinical needs, ethical dilemmas, and manufacturing challenges in the development of a tissue engineered decellularized scaffold for oesophageal atresia. Expert opinion: Current progress on oesophageal tissue engineering has enabled effective repair of patch defects, whilst the development of a full circumferential construct remains a challenge. Despite the different approaches available and the improvements achieved, a gold standard for fully functional tissue engineered oesophageal constructs has not been defined yet.

Lymphocytic esophagitis: Report of three cases and review of the literature

PubMed Central

Jideh, Bilel; Keegan, Andrew; Weltman, Martin

2016-01-01

Lymphocytic esophagitis (LyE) is a rare condition characterised histologically by high numbers of esophageal intraepithelial lymphocytes without significant granulocytes infiltration, in addition to intercellular edema (“spongiosis”). The clinical significance and natural history of LyE is poorly defined although dysphagia is reportedly the most common symptom. Endoscopic features range from normal appearing esophageal mucosa to features similar to those seen in eosinophilic esophagitis, including esophageal rings, linear furrows, whitish exudates, and esophageal strictures/stenosis. Symptomatic gastroesophageal reflux disease is an inconsistent association. LyE has been associated in paediatric Crohn’s disease, and recently in primary esophageal dysmotility disorder in adults. There are no studies assessing effective treatment strategies for LyE; empirical therapies have included use of proton pump inhibitor and corticosteroids. Esophageal dilatation have been used to manage esophageal strictures. LyE has been reported to run a benign course; however there has been a case of esophageal perforation associated with LyE. Here, we describe the clinical, endoscopic and histopathological features of three patients with lymphocytic esophagitis along with a review of the current literature. PMID:28035315

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.

PubMed

Kottyan, Leah C; Davis, Benjamin P; Sherrill, Joseph D; Liu, Kan; Rochman, Mark; Kaufman, Kenneth; Weirauch, Matthew T; Vaughn, Samuel; Lazaro, Sara; Rupert, Andrew M; Kohram, Mojtaba; Stucke, Emily M; Kemme, Katherine A; Magnusen, Albert; He, Hua; Dexheimer, Phillip; Chehade, Mirna; Wood, Robert A; Pesek, Robbie D; Vickery, Brian P; Fleischer, David M; Lindbad, Robert; Sampson, Hugh A; Mukkada, Vincent A; Putnam, Phil E; Abonia, J Pablo; Martin, Lisa J; Harley, John B; Rothenberg, Marc E

2014-08-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replicating association of the 5q22 locus (meta-analysis P=1.9×10(-16)), we identified an association at 2p23 spanning CAPN14 (P=2.5×10(-10)). CAPN14 was specifically expressed in the esophagus, was dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to interleukin (IL)-13, and was located in an epigenetic hotspot modified by IL-13. Genes neighboring the top 208 EoE-associated sequence variants were enriched for esophageal expression, and multiple loci for allergic sensitization were associated with EoE susceptibility (4.8×10(-2)

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease

PubMed Central

Kottyan, Leah C.; Davis, Benjamin P.; Sherrill, Joseph D.; Liu, Kan; Rochman, Mark; Kaufman, Kenneth; Weirauch, Matthew T.; Vaughn, Samuel; Lazaro, Sara; Rupert, Andrew M.; Kohram, Mojtaba; Stucke, Emily M.; Kemme, Katherine A.; Magnusen, Albert; He, Hua; Dexheimer, Phillip; Chehade, Mirna; Wood, Robert A.; Pesek, Robbie D.; Vickery, Brian P.; Fleischer, David M.; Lindbad, Robert; Sampson, Hugh A.; Mukkada, Vince; Putnam, Phil E.; Abonia, J. Pablo; Martin, Lisa J.; Harley, John B.; Rothenberg, Marc E.

2014-01-01

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in European EoE cases and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replication of the 5q22 locus (meta-analysis p = 1.9×10−16), we identified association at 2p23 (encoding CAPN14, p = 2.5×10−10). CAPN14 was specifically expressed in the esophagus, dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to IL-13, and located in an epigenetic hotspot modified by IL-13. There was enriched esophageal expression for the genes neighboring the top 208 EoE sequence variants. Multiple allergic sensitization loci were associated with EoE susceptibility (4.8×10−2 < p < 5.1×10−11). We propose a model that elucidates the tissue specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14. PMID:25017104

The correlation between the first heart sound and cardiac output as measured by using digital esophageal stethoscope under anaesthesia.

PubMed

Duck Shin, Young; Hoon Yim, Kyoung; Hi Park, Sang; Wook Jeon, Yong; Ho Bae, Jin; Soo Lee, Tae; Hwan Kim, Myoung; Jin Choi, Young

2014-03-01

The use of an esophageal stethoscope is a basic heart sounds monitoring procedure performed in patients under general anesthesia. As the size of the first heart sound can express the left ventricle function, its correlation with cardiac output should be investigated. The aim of this study was to investigate the effects of cardiac output (CO) on the first heart sound (S1) amplitude. Methods : Six male beagles were chosen. The S1 was obtained with the newly developed esophageal stethoscope system. CO was measured using NICOM, a non-invasive CO measuring device. Ephedrine and beta blockers were administered to the subjects to compare changes in figures, and the change from using an inhalation anesthetic was also compared. The S1 amplitude displayed positive correlation with the change rate of CO (r = 0.935, p < 0.001). The heart rate measured using the esophageal stethoscope and ECG showed considerably close figures through the Bland-Altman plot and showed a high positive correlation (r = 0.988, p < 0,001). In beagles, the amplitude of S1 had a significant correlation with changes in CO in a variety of situations.

Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas

PubMed Central

Li, Yaqing; Li, Xiaoran; Kan, Quancheng; Zhang, Mingzhi; Li, Xiaoli; Xu, Ruiping; Wang, Junsheng; Yu, Dandan; Goscinski, Mariusz Adam; Wen, Jian-Guo; Nesland, Jahn M.; Suo, Zhenhe

2017-01-01

Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect. In addition, the HIF-1α expression and ROS production were also activated upon UK5099 application. It was further revealed that the UK5099-treated cells became significantly more resistant to chemotherapy and radiotherapy, and the UK5099-treated tumor cells also exhibited stronger invasive capacity compared to the parental cells. In contrast to esophageal squamous epithelium cells, decreased MPC protein expression was observed in a series of 157 human squamous cell carcinomas, and low/negative MPC1 expression predicted an unfavorable clinical outcome. All these results together revealed the potential connection of altered MPC expression/activity with the Warburg metabolic reprogramming and tumor aggressiveness in cell lines and clinical samples. Collectively, our findings highlighted a therapeutic strategy targeting Warburg reprogramming of human esophageal squamous cell carcinomas. PMID:27911865

[Use of esophageal small balloon or papillary sphincter knife in the treatment of stent implantation 
for colorectal malignant obstruction].

PubMed

Xiao, Dinghua; Liu, Shaojun; Yan, Hanguang; Wang, Xiaoyan

2018-05-28

To explore the function of esophageal small balloon or papillary sphincter knife in the treatment of stent implantation for colorectal malignant obstruction, and to improve the success rate of colonic stent placement in such patients.
 Methods: A total of 49 patients with colorectal cancer complicated with almost complete obstruction or colorectal cancer were enrolled for this study. The esophageal small balloon or papillary sphincter knife was used in the guide wires. The guide wires gradually crossed the tumor gap and they were placed in the contralateral intestinal cavity with balloon progression. X-ray was then used to confirm whether the guide wire was inserted in the lesion intestinal cavity, and then the metal bare stent was inserted.
 Results: The guide wires was successfully inserted with conventional methods in these 49 cases, while they were also successfully placed the guide wire and the stent in the new way.
 Conclusion: For the patients with colorectal cancer complicated with complete obstruction or colorectal cancer located in obviously angled location, the use of esophageal small balloon or papillary sphincter knife can help the guide wire insert. They greatly improve the success rate of stent implantation.

Treatments for achalasia in 2017: how to choose among them.

PubMed

Kahrilas, Peter J; Pandolfino, John E

2017-07-01

To review recent advances in achalasia diagnostics and therapeutics. The cardinal feature of achalasia, impaired lower esophageal sphincter (LES) relaxation, can occur in association with varied patterns of esophageal contractility. The Chicago Classification distinguishes among these as follows: without contractility (type I), with panesophageal pressurization (type II), with premature (spastic) distal esophageal contractions (type III), or even with preserved peristalsis [esophagogastric junction (EGJ) outlet obstruction]. Physiological testing also reveals achalasia-like syndromes that also benefit from achalasia therapies. Coincident with this has been the development of peroral endoscopic myotomy (POEM), an endoscopic technique for performing an esophageal myotomy. Hence, the option now exists to either selectively ablate the LES (pneumatic dilation, laparoscopic Heller myotomy, or POEM) or to ablate the sphincter and create a myotomy along some or the entire adjacent smooth muscle esophagus (POEM). Each achalasia syndrome has unique treatment considerations; type II achalasia responds well to all therapies, whereas type III responds best to POEM. Emerging data support the concept that optimal management of achalasia is phenotype-specific, guided by high-resolution manometry, and, in some instance, functional luminal imaging probe studies. This opinion article reviews the varied characteristic and treatment considerations of achalasia syndromes as currently understood.

Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD, NERD, NARD, esophageal hypersensitivity or dyspepsia?

PubMed Central

Bashashati, Mohammad; Hejazi, Reza A; Andrews, Christopher N; Storr, Martin A

2014-01-01

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy. PMID:24719900

Current advances in esophageal cancer proteomics.

PubMed

Uemura, Norihisa; Kondo, Tadashi

2015-06-01

We review the current status of proteomics for esophageal cancer (EC) from a clinician's viewpoint. The ultimate goal of cancer proteomics is the improvement of clinical outcome. The proteome as a functional translation of the genome is a straightforward representation of genomic mechanisms that trigger carcinogenesis. Cancer proteomics has identified the mechanisms of carcinogenesis and tumor progression, detected biomarker candidates for early diagnosis, and provided novel therapeutic targets for personalized treatments. Our review focuses on three major topics in EC proteomics: diagnostics, treatment, and molecular mechanisms. We discuss the major histological differences between EC types, i.e., esophageal squamous cell carcinoma and adenocarcinoma, and evaluate the clinical significance of published proteomics studies, including promising diagnostic biomarkers and novel therapeutic targets, which should be further validated prior to launching clinical trials. Multi-disciplinary collaborations between basic scientists, clinicians, and pathologists should be established for inter-institutional validation. In conclusion, EC proteomics has provided significant results, which after thorough validation, should lead to the development of novel clinical tools and improvement of the clinical outcome for esophageal cancer patients. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Repetition priming of motor activity mediated by a central pattern generator: the importance of extrinsic vs. intrinsic program initiators

PubMed Central

Siniscalchi, Michael J.; Jing, Jian; Weiss, Klaudiusz R.

2016-01-01

Repetition priming is characterized by increased performance as a behavior is repeated. Although this phenomenon is ubiquitous, mediating mechanisms are poorly understood. We address this issue in a model system, the feeding network of Aplysia. This network generates both ingestive and egestive motor programs. Previous data suggest a chemical coding model: ingestive and egestive inputs to the feeding central pattern generator (CPG) release different modulators, which act via different second messengers to prime motor activity in different ways. The ingestive input to the CPG (neuron CBI-2) releases the peptides feeding circuit activating peptide and cerebral peptide 2, which produce an ingestive pattern of activity. The egestive input to the CPG (the esophageal nerve) releases the peptide small cardioactive peptide. This model is based on research that focused on a single aspect of motor control (radula opening). Here we ask whether repetition priming is observed if activity is triggered with a neuron within the core CPG itself and demonstrate that it is not. Moreover, previous studies demonstrated that effects of modulatory neurotransmitters that induce repetition priming persist. This suggests that it should be possible to “prime” motor programs triggered from within the CPG by first stimulating extrinsic modulatory inputs. We demonstrate that programs triggered after ingestive input activation are ingestive and programs triggered after egestive input activation are egestive. We ask where this priming occurs and demonstrate modifications within the CPG itself. This arrangement is likely to have important consequences for “task” switching, i.e., the cessation of one type of motor activity and the initiation of another. PMID:27466134

Impaired Upper Esophageal Sphincter Reflexes in Patients with Supra-Esophageal Reflux Disease

PubMed Central

Babaei, Arash; Venu, Mukund; Naini, Sohrab Rahimi; Gonzaga, Jason; Lang, Ivan; Massey, Benson; Jadcherla, Sudarshan; Shaker, Reza

2015-01-01

Background & Aims Normal responses of the upper esophageal sphincter (UES) and esophageal body to liquid reflux events prevent esophagopharyngeal reflux and its complications, but abnormal responses have not been characterized. We investigated whether patients with supra-esophageal reflux disease (SERD) have impaired UES and esophageal body responses to simulated reflux events. Methods We performed a prospective study of 25 patients with SERD (19–82 y old, 13 female) and complaints of regurgitation and supra-esophageal manifestations of reflux. We also included 10 patients with gastroesophageal reflux disease (GERD; 32–60 y old, 7 female) without troublesome regurgitation and supra-esophageal symptoms and 24 healthy asymptomatic individuals (controls; 19–49 y old, 13 female). UES and esophageal body pressure responses, along with luminal distribution of infusate during esophageal rapid and slow infusion of air or liquid, were monitored by concurrent high-resolution manometry and intraluminal impedance. Results A significantly smaller proportion of patients with SERD had UES contractile reflexes in response to slow esophageal infusion of acid than controls or patients with GERD. Only patients with SERD had abnormal UES relaxation responses to rapid distension with saline. Diminished esophageal peristaltic contractions resulted in esophageal stasis in patients with GERD or SERD. Conclusions Patients with SERD and complaints of regurgitation have impaired UES and esophageal responses to simulated liquid reflux events. These patterns could predispose them to esophagopharyngeal reflux. PMID:26188682

MicroRNA-548-3p and MicroRNA-576-5p enhance the migration and invasion of esophageal squamous cell carcinoma cells via NRIP1 downregulation.

PubMed

Ni, X F; Zhao, L H; Li, G; Hou, M; Su, M; Zou, C L; Deng, X

2018-06-26

Nuclear receptor interacting protein (NRIP1), also known as RIP140, is a transcriptional coregulator that is required for the maintenance of energy homeostasis and ovulation. Although several studies have identified roles for NRIP1 in various cell processes, the biological functions of NRIP1 in esophageal squamous cell carcinoma (ESCC) remain unknown. In the present study, we demonstrate that NRIP1 inhibited the migration and invasion of ESCC cells. Further mechanistic studies revealed that NRIP1 is directly targeted by miR-548-3p and miR-576-5p. Next, we show that miR-548-3p and miR-576-5p regulated the migration and invasion of ESCC cells via inhibiting NRIP1 expression. Interestingly, in ESCC cell lines and ESCC tissues, expression of miR-548-3p and miR-576-5p was upregulated and NRIP1 was downregulated relative to the control. A statistically significant inverse association was found between the expression level of miR-548-3p/miR-576-5p and NRIP1. Taken together, our results reveal novel functions for miR-548-3p, miR-576-5p, and NRIP1 in regulating ESCC cell migration and invasion, important functions for the metastatic process in esophageal cancer.

A Functional Assessment of Handmouthing among Persons with Severe and Profound Intellectual Disability

ERIC Educational Resources Information Center

Swender, Stephen L.; Matson, Johnny L.; Mayville, Stephen B.; Gonzalez, Melissa L.; McDowell, Donald

2006-01-01

Background: The behavioural function of handmouthing has been assessed across various studies utilising analogue functional analyses. The aim of the current study was to expand upon research on this relatively understudied behaviour by examining the relationship between handmouthing and "Gastro-Esophageal Reflux Disorder" (GERD), and the potential…

Gender difference in gastro-esophageal reflux diseases.

PubMed

Asanuma, Kiyotaka; Iijima, Katsunori; Shimosegawa, Tooru

2016-02-07

The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Gender difference in gastro-esophageal reflux diseases

PubMed Central

Asanuma, Kiyotaka; Iijima, Katsunori; Shimosegawa, Tooru

2016-01-01

The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett’s esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen. PMID:26855539

Incidences of esophageal injury during esophageal temperature monitoring: a comparative study of a multi-thermocouple temperature probe and a deflectable temperature probe in atrial fibrillation ablation.

PubMed

Kuwahara, Taishi; Takahashi, Atsushi; Takahashi, Yoshihide; Okubo, Kenji; Takagi, Katsumasa; Fujino, Tadashi; Kusa, Shigeki; Takigawa, Masateru; Watari, Yuji; Yamao, Kazuya; Nakashima, Emiko; Kawaguchi, Naohiko; Hikita, Hiroyuki; Sato, Akira; Aonuma, Kazutaka

2014-04-01

The study aim was to compare the incidence of esophageal injuries between different temperature probes in the monitoring of esophageal temperature during atrial fibrillation (AF) ablation. One hundred patients with drug-resistant AF were prospectively and randomly assigned into two groups according to the esophageal temperature probe used: the multi-thermocouple probe group (n = 50) and the deflectable temperature probe group (n = 50). Extensive pulmonary vein (PV) isolation was performed with a 3.5-mm open irrigated tip ablation catheter by using a radiofrequency (RF) power of 25-30 W. In both groups, the esophageal temperature thermocouple was placed on the area of the esophagus adjacent to the ablation site. When the esophageal temperature reached 42 °C, the RF energy delivery was stopped. Esophageal endoscopy was performed 1 day after the catheter ablation. No differences existed between the two groups in terms of clinical background and various parameters related to the catheter ablation, including RF delivery time and number of RF deliveries at an esophageal temperature of >42 °C. Esophageal lesions, such as esophagitis and esophageal ulcers, occurred in 10/50 (20 %) and 15/50 (30 %) patients in the multi-thermocouple and deflectable temperature probe groups, respectively (P = 0.25). Most lesions were mild to moderate injuries, and all were cured using conservative treatment. The incidence of esophageal injury was almost equal between the multi-thermocouple temperature probe and the deflectable temperature probe during esophageal temperature monitoring. Most of the esophageal lesions that developed during esophageal temperature monitoring were mild to moderate and reversible.

Acid Secretion and Its Relationship to Esophageal Reflux Symptom in Patients with Subtotal Gastrectomy.

PubMed

Oh, Hyun Jin; Choi, Myung-Gyu; Park, Jae Myung; Song, Kyo Young; Yoo, Han Mo

2018-03-01

Esophageal reflux symptom has been reported as common in patients with subtotal gastrectomy. Management of postoperative esophageal reflux symptom is not satisfactory. The aim of this study is to investigate prevalence of esophageal reflux symptom after subtotal gastrectomy and assess factors affecting esophageal reflux symptom in subtotal gastrectomy patients. We prospectively enrolled 100 consecutive patients with subtotal gastrectomy who were regularly followed up by endoscopic examination. Acid secretory capacity was assessed by measuring messenger RNA (mRNA) expression of H + /K + -adenosine triphosphatase (ATPase) via real-time polymerase chain reaction (PCR) in biopsy specimens. In total, 47 % of patients had typical esophageal reflux symptom, where heartburn or regurgitation was experienced at least weekly. Age, sex, body mass index, and type of reconstruction did not differ between esophageal reflux and non-esophageal-reflux groups. The esophageal reflux group had longer duration from time of operation until study (median 5.0 versus 3.6 years; P = 0.017). Hill grade for gastroesophageal (GE) flap valve was higher in the esophageal reflux group than in the non-esophageal-reflux group (P = 0.027). H + /K + -ATPase mRNA expression was higher in the esophageal reflux group than in the non-esophageal-reflux group [3967.6 (± 7583.7) versus 896.2 (± 1456.0); P = 0.006]. Multivariate analysis revealed that postoperative duration, H + /K + -ATPase mRNA expression level, and GE flap valve disruption were significantly associated with esophageal reflux symptom development. Esophageal reflux symptom is common in patients after subtotal gastrectomy, possibly because of anti-reflux-barrier impairment and preservation of acid secretory capacity following surgery. Optimal acid suppression may be helpful in managing postoperative esophageal reflux symptom.

Clinical application of oral meglumine diatrizoate esophagogram in screening esophageal fistula during radiotherapy for esophageal cancer.

PubMed

Geng, Lidan; Wu, Rong; Hu, He; Zhao, Yu; Fan, Lingli; Zhao, Zhenhua; Liao, Dongbiao; Li, Musheng; Xiang, Miao; Ma, Ying; Du, Xiaobo

2018-05-01

Esophageal fistula is a serious and common complication of radiotherapy for esophageal cancer. Therefore, early diagnosis and treatment is necessary. Because of side effect of barium esophagography, it cannot be used to screening esophageal fistula during radiotherapy. Meglumine diatrizoate is an ionic contrast agent, its adverse reactions were rarely seen when it was used in the body cavity. The purpose of this trial is identified the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. This trial was a prospective, multicenter, diagnostic clinical trial. A total of 105 patients with esophageal cancer will swallowed meglumine diatrizoate and underwent a radiographic examination weekly during radiotherapy, medical personnel observed the esophageal lesions to determine whether an esophageal fistula formed. If an esophageal fistula was observed, esophagofiberoscopy and/or computer tomography was used to further confirm the diagnosis. And the sensitivity and specificity of meglumine diatrizoate should be calculated for screening esophageal fistula during radiotherapy. To our knowledge, this study protocol is the first to identify the sensitivity and specificity of oral meglumine diatrizoate in an esophagogram for screening esophageal fistula during radiotherapy. If oral meglumine diatrizoate can be used to screening esophageal fistula, more patients will benefit from early detection and treatment.

Prevention and Treatment of Esophageal Stenosis after Endoscopic Submucosal Dissection for Early Esophageal Cancer

PubMed Central

Wen, Jing; Lu, Zhongsheng; Liu, Qingsen

2014-01-01

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions is associated with a risk of esophageal stenosis, especially for near-circumferential or circumferential esophageal mucosal defects. Here, we review historic and modern studies on the prevention and treatment of esophageal stenosis after ESD. These methods include prevention via pharmacological treatment, endoscopic autologous cell transplantation, endoscopic esophageal dilatation, and stent placement. This short review will focus on direct prevention and treatment, which may help guide the way forward. PMID:25386186

Effect of proton pump inhibitor (PPI) treatment in obstructive sleep apnea syndrome: an esophageal impedance-pHmetry study.

PubMed

Ermis, Fatih; Akyuz, Filiz; Arici, Serpil; Uyanikoglu, Ahmet; Yakar, Fatih; Pinarbasi, Binnur; Demir, Kadir; Ozdil, Sadakat; Besisik, Fatih; Kaymakoglu, Sabahattin; Boztas, Gungor; Cuhadaroglu, Caglar; Mungan, Zeynel

2011-01-01

There is an increasing interest for a link between gastroesophageal reflux (GER) and obstructive sleep apnea syndrome (OSAS). There is no study in the literature which examines the relationship between OSAS and esophageal functions in adults with impedance. We first evaluated the role of reflux in OSAS with simultaneous polysomnography and impedance-pHmetry and then investigated whether the effect of proton pump inhibitor (PPI) treatment changes in these parameters. Twenty two OSAS patients who had applied to sleep laboratory between September 2007 and May 2008 were consecutively enrolled to the study. Twenty four hours esophageal impedance study was performed during polysomnographic recording. At least 50% of all apneas in patients must proceed with a reflux event in 2 minute intervals in order to be considered reflux related apnea patient. Pathologic reflux episodes were determined in 20 patients (8 were weakly acidic, 12 were acidic). Reflux dependent apnea was found in 6 patients. There was endoscopically esophagitis in all reflux related apnea patients. There was a negative correlation between initial mean SaO2 and gas reflux events at night (p=0.004, r =-0.588) and mixed reflux events at night (p=0.02, r=0.493). There was a statistically significant regression of AHI (apnea hypopnea index) after 3-months PPI treatment (p=0.012). Reflux may trigger apnea in some of the OSAS patients. Therefore, each OSAS patient must be inquired about esophageal and extraesophageal symptoms of reflux.

Laparoscopic surgery of esophageal hiatus hernia – single center experience

PubMed Central

Piątkowski, Jacek; Jackowski, Marek

2014-01-01

Introduction Esophageal hiatal hernias are the most frequent types of internal hernias. This condition involves disturbance of normal functioning of the stomach cardiac mechanism and reflux of the gastric contents to the esophagus. Aim: To evaluate postoperative results in our Clinic and the comparison of these results to data from the literature. Material and methods One hundred and seventy-eight patients underwent surgery due to esophageal hiatal hernia at the Clinic of General, Gastroenterological and Oncological Surgery, Collegium Medicum, Bydgoszcz, Nicolaus Copernicus University, Torun, Poland, from 2006 to 2011. All operations were performed using laparoscopy. Fundoplication by means of the Nissen-Rossetti method was carried out in 172 patients while Toupet's and Dor's methods were applied in 4 and 2 patients, respectively. Results Average time of the surgery was 82 min (55–140 min). Conversion was performed in 4 cases. No serious intraoperative complications were noted. In the postoperative period, dysphagia was reported in 20 patients (11.2%). Postoperative wound infection was observed in 1 patient (0.56%). Hernias in the trocar insertion area were reported in 3 patients (1.68%). Ailments recurred in 6 patients. The recurrence of esophageal hiatal hernia was confirmed in 2 patients. Patients with recurrent hernia were re-operated using a laparoscopic approach. Conclusions Laparoscopic surgery is a simple and effective approach for patients with gastroesophageal reflux symptoms due to diaphragmatic esophageal hiatus hernia. The number of complications is lower after laparoscopic procedures than after “open” operations. PMID:24729804

Inhibition of cyclin D1 enhances sensitivity to radiotherapy and reverses epithelial to mesenchymal transition for esophageal cancer cells.

PubMed

Su, Huafang; Jin, Xiance; Shen, Lanxiao; Fang, Ya; Fei, Zhenghua; Zhang, Xuebang; Xie, Congying; Chen, Xiaolei

2016-04-01

Acquired radioresistance during radiotherapy has significantly affected the treatment efficacy in esophageal cancer. Many of radioresistant cancer cells demonstrated epithelial-mesenchymal transition (EMT).We found in previous study that a radioresistant cell line (KYSE-150R) possessed EMT characteristic with cyclin D1 overexpression. Cyclin D1 has been demonstrated to affect the radiation sensitivity in cancer cells. To elucidate the molecular functions of cyclin D1 on EMT phenotypes and esophageal cancer radiosensitivity, we treated the radioresistant esophageal cancer cells (KYSE-150R) and parental cells (KYSE-150) with cyclin D1 small interfering RNA (siRNA). The cell proliferation rate of KYSE-150R and the radiation survival fraction were significantly decreased in cyclin D1 siRNA treatment group. Knocking down cyclin D1 resulted in G0/G1 arrest in KYSE-150R cells. The average number of irradiation-induced γ-H2AX foci increased in the cells treated with cyclin D1 siRNA, indicating impaired DNA double-strand break (DSB) repair in KYSE-150R cells. Cyclin D1 also reversed EMT phenotypes with significantly increased expression of E-cadherin in KYSE-150R cells. However, cyclin D1 siRNA have no radiosensitizing effects on KYSE-150 cells, with no obvious change in EMT marker expression .Our work showed that EMT phenotypes can be reduced and the radiosensitivity of esophageal cancer cells can be enhanced by inhibiting cyclin D1.

Postoperative esophageal leak management with the Polyflex esophageal stent.

PubMed

Freeman, Richard K; Ascioti, Anthony J; Wozniak, Thomas C

2007-02-01

Leak after esophageal anastomosis or perforation repair prolongs hospitalization, prevents oral hydration and nutrition, and can produce localized infection or sepsis. This investigation reviews our experience treating postoperative esophageal leaks with the Polyflex esophageal stent (Boston Scientific, Natick, Mass). Over a 30-month period, patients with a postoperative esophageal leak were treated with the Polyflex stent for leak occlusion. Leak occlusion was confirmed by means of esophagraphy. Patients were followed until their stent was removed and their esophageal leak had resolved. Twenty-one patients had 27 stents placed for leak occlusion after esophagectomy (n = 5), esophageal perforation (n = 5), surgical (n = 4) or endoscopic (n = 2) antireflux procedure, and esophageal diverticulectomy (n = 3) or myotomy (n = 2). The mean interval between surgical intervention and stent placement was 12 +/- 8 days (range, 3-31 days). Occlusion of the leak occurred in 20 patients. One patient experienced a dehiscence of the surgical esophageal perforation repair requiring esophageal diversion. Stent migration requiring repositioning (n = 3) or replacement (n = 4) occurred in 5 (24%) patients. Twenty (95%) stents were removed without residual leak (mean, 51 +/- 43 days; range, 15-175 days). One patient had a stricture after stent removal that required endoscopic dilatation. One patient in this series died. The Polyflex esophageal stent is an effective method for occluding a postoperative esophageal leak. It rapidly eliminates contamination of the mediastinum, pleura, and peritoneum; allows oral hydration and nutrition; and is easily removable. These stents also offer an appealing alternative to traditional esophageal diversion and subsequent reconstruction in patients with a persistent esophageal leak.

Laparoscopic treatment in achalasia of the cardia.

PubMed

Ursut, B; Alecu, L; Tulin, A; Enciu, O

2014-01-01

Achalasia, although a rare disease (an incidence of 1 100 000 individuals each year) is one of the common causes of motor dysphagia and is characterized by loss of peristalsis in the esophageal body and lack of relaxation of the lower esophageal sphincter. The aim of our study was to perform a clinical,therapeutic and evolution evaluation in patients diagnosed with achalasia and operated in our department between 1997 and 2013. We performed a retrospective study using the clinical charts, operatory protocols, imagistic and video database of the 17 patients with achalasia operated in our department. We encountered an equal repartition in women and men and a predominance of urban provenience. Ages were between 24 and 86 years (with an average age of 51). There were two cases of recurrent achalasia at 2, respectively 5 years after the first operation. In all cases, Heller myotomy was used, with the addition of a Dor fundoplication in 12 cases and Toupet fundoplication in five cases, as an antireflux procedure. Mean operation time was 117.6 minutes.There were three iatrogenic perforations of the esophageal mucosa, all of them recognized and treated in the same operative time. No postoperative complications related to the Heller-Dor Heller-Toupet procedure were encountered.The follow-up was between 3 and 72 months. Laparoscopic approach in the treatment of achalasia provides the advantages of minimally invasive surgery, but also and very important, a good visualization of the abdominal esophagus and gastroesophageal junction.Heller esocardiomyotomy is usually associated with anantireflux procedure. A Dor fundoplication is generally used,although the Toupet fundoplication may also be used with the same advantages. It is important to monitor these patients on a yearly basis, knowing the risk of dysplasia carcinoma in achalasia. Celsius.

Optimizing the high-resolution manometry (HRM) study protocol.

PubMed

Patel, A; Ding, A; Mirza, F; Gyawali, C P

2015-02-01

Intolerance of the esophageal manometry catheter may prolong high-resolution manometry (HRM) studies and increase patient distress. We assessed the impact of obtaining the landmark phase at the end of the study when the patient has acclimatized to the HRM catheter. 366 patients (mean age 55.4 ± 0.8 years, 62.0% female) undergoing esophageal HRM over a 1-year period were studied. The standard protocol consisted of the landmark phase, 10 5 mL water swallows 20-30 s apart, and multiple rapid swallows where 4-6 2 mL swallows were administered in rapid succession. The modified protocol consisted of the landmark phase at the end of the study after test swallows. Study duration, technical characteristics, indications, and motor findings were compared between standard and modified protocols. Of the 366 patients, 89.6% underwent the standard protocol (study duration 12.9 ± 0.3 min). In 10.4% with poor catheter tolerance undergoing the modified protocol, study duration was significantly longer (15.6 ± 1.0 min, p = 0.004) despite similar duration of study maneuvers. Only elevated upper esophageal sphincter basal pressures at the beginning of the study segregated modified protocol patients. The 95th percentile time to landmark phase in the standard protocol patients was 6.1 min; as many as 31.4% of modified protocol patients could not obtain their first study maneuver within this period (p = 0.0003). Interpretation was not impacted by shifting the landmark phase to the end of the study. Modification of the HRM study protocol with the landmark phase obtained at the end of the study optimizes study duration without compromising quality. © 2014 John Wiley & Sons Ltd.

Pros and cons of the gasless laparoscopic transhiatal esophagectomy for upper esophageal carcinoma.

PubMed

Yu, Lei; Wu, Ji-Xiang; Gao, Yu-Shun; Li, Jian-Ye; Zhang, Yun-Feng; Ke, Ji

2016-06-01

Controversies on how to treat upper esophageal carcinoma have existed for several decades. With the application of minimally invasive techniques, surgical treatment to upper esophageal carcinoma tends to show more advantages and attract more patients. Up to now, most hospitals adopted the combined thoracoscopic and laparoscopic esophagectomy (CTLE) as the way of minimally invasive surgery for upper esophageal carcinoma. But CTLE to treat upper esophageal carcinoma has its drawbacks, such as demanding certain pulmonary function and severe postoperative regurgitation. In 2011, we developed the gasless laparoscopic transhiatal esophagectomy (LTE) to treat upper esophageal carcinoma, which showed some advantages. The aim of this article was to compare LTE with CTLE in treating upper thoracic or cervical esophageal carcinoma and assess the value of LTE. From 2009 to 2014, esophagectomy has been performed by the introduction of minimally invasive surgery in a total of 83 patients with upper thoracic or cervical esophageal carcinoma. Among these patients, LTE was performed in 27 cases (Group 1), while CTLE was performed in the other 56 (Group 2). Neoadjuvant chemotherapy was done in patients of Group 1. There were no operation-related deaths and conversion to open procedure. There was no significant difference in postoperative complications, ventilation time, ICU stay, hospital stay, and anastomotic leak rates between the two groups. But LTE was associated with shorter operative time and less intraoperative blood loss. In Group 2, 21 (37.5 %) patients had postoperative pulmonary complications, while in Group 1, there were 6 (22.2 %) patients having pulmonary complications at least one time. Results of 24-h pH monitoring and manometry showed that postoperative laryngo-pharyngeal reflux (PLPR) was more severe in Group 2 patients than in Group 1; for Group 1, PLPR mainly occurred on sleep stage, while for Group 2, PLPR might exist all the day with short intervals and last longer at night. The median overall survival was 27.2 months after CTLE and 30.8 months after LTE (P = 0.962). There was no significant difference in survival at 2, 3 and 4 years between the two groups. Compared with CTLE, LTE is a more minimally invasive approach to effectively treat patients with upper esophageal carcinoma. Laryngo-pharyngeal reflux after LTE was less severe than that after CTLE, which might lower incidence of pulmonary complications. For the elderly patients, LTE seems more suitable.

BPC 157 therapy to detriment sphincters failure-esophagitis-pancreatitis in rat and acute pancreatitis patients low sphincters pressure.

PubMed

Petrovic, I; Dobric, I; Drmic, D; Sever, M; Klicek, R; Radic, B; Brcic, L; Kolenc, D; Zlatar, M; Kunjko, K; Jurcic, D; Martinac, M; Rasic, Z; Boban Blagaic, A; Romic, Z; Seiwerth, S; Sikiric, P

2011-10-01

Possibly, acute esophagitis and pancreatitis cause each other, and we focused on sphincteric failure as the common causative key able to induce either esophagitis and acute pancreatitis or both of them, and thereby investigate the presence of a common therapy nominator. This may be an anti-ulcer pentadecapeptide BPC 157 (tested for inflammatory bowel disease, wound treatment) affecting esophagitis, lower esophageal and pyloric sphincters failure and acute pancreatitis (10 μg/kg, 10 ng/kg intraperitoneally or in drinking water). The esophagitis-sphincter failure procedure (i.e., insertion of the tubes into the sphincters, lower esophageal and pyloric) and acute pancreatitis procedure (i.e., bile duct ligation) were combined in rats. Esophageal manometry was done in acute pancreatitis patients. In rats acute pancreatitis procedure produced also esophagitis and both sphincter failure, decreased pressure 24 h post-surgery. Furthermore, bile duct ligation alone immediately declines the pressure in both sphincters. Vice versa, the esophagitis-sphincter failure procedure alone produced acute pancreatitis. What's more, these lesions (esophagitis, sphincter failure, acute pancreatitis when combined) aggravate each other (tubes into sphincters and ligated bile duct). Counteraction occurred by BPC 157 therapies. In acute pancreatitis patients lower pressure at rest was in both esophageal sphincters in acute pancreatitis patients. We conclude that BPC 157 could cure esophagitis/sphincter/acute pancreatitis healing failure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atsumi, Kazushige; Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp; Arimura, Hidetaka

Purpose: To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Methods and Materials: The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors andmore » therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Results: Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Conclusion: Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer.« less

Comprehensive swallowing exercises to treat complicated dysphagia caused by esophageal replacement with colon: A case report.

PubMed

Jiang, Li; Wang, Yujue; Li, Na; Qiu, Weihong; Wu, Huixiang; Huo, Jianshan; Dai, Meng; Yu, Yong; Wan, Guifang; Dou, Zulin; Guo, Weiping

2017-02-01

Surgical procedures for colonic replacement of the esophagus are most commonly associated with anastomotic stricture which cause dysphagia. In this report, we describe a rare case of a patient who demonstrated dysphagia resulting from an anastomotic stricture following esophageal replacement with the colon. All the treatments to dilate the anastomotic stricture were ineffective. To investigate the new treatment strategy for a case with complicated dysphagia, clinical dysphagia evaluations, functional oral intake scale (FOIS), videofluoroscopic swallowing study as well as high-resolution manometry were used to evaluate the swallowing function of the patient before and after treatments. Comprehensive swallowing exercises included the protective airway maneuver, tongue pressure resistance feedback exercise, Masako Maneuver swallowing exercise, and the effortful swallowing exercise. Comprehensive swallowing exercises showed good effect in the patient. The FOIS score increased from level 1 to level 7. The videofluoroscopy digital analysis showed that the pharynx constriction rate was 23% and 50%, before and after treatment, respectively. The data from the high-resolution manometry displayed that: the value of the velopharyngeal pressure peak was 82.8 mmHg before treatment and 156.9 mmHg after treatment; the velopharyngeal contraction duration time was 310 milliseconds before treatment and 525 milliseconds after treatment; the value of the hypopharynx pressure peak was 53.7 mmHg before treatment and 103.2 mmHg after treatment; and the hypopharynx contraction duration time was 390 milliseconds before treatment and 1030 milliseconds after treatment. The swallowing visualization illustrated that a bolus could normally pass through the anastomotic stoma, and the bolus leakage was no longer present. The patient was able to eat various consistencies of food independently, and we were able to remove the jejunum nutrient catheter before discharging the patient. For patients with dysphagia caused by anastomotic stricture following esophageal replacement with colon, the swallowing function can be improved by enhancing the pharyngeal impetus when treatment using esophageal dilation is ineffective.

Comprehensive swallowing exercises to treat complicated dysphagia caused by esophageal replacement with colon

PubMed Central

Jiang, Li; Wang, Yujue; Li, Na; Qiu, Weihong; Wu, Huixiang; Huo, Jianshan; Dai, Meng; Yu, Yong; Wan, Guifang; Dou, Zulin; Guo, Weiping

2017-01-01

Abstract Introduction: Surgical procedures for colonic replacement of the esophagus are most commonly associated with anastomotic stricture which cause dysphagia. In this report, we describe a rare case of a patient who demonstrated dysphagia resulting from an anastomotic stricture following esophageal replacement with the colon. All the treatments to dilate the anastomotic stricture were ineffective. To investigate the new treatment strategy for a case with complicated dysphagia, clinical dysphagia evaluations, functional oral intake scale (FOIS), videofluoroscopic swallowing study as well as high-resolution manometry were used to evaluate the swallowing function of the patient before and after treatments. Interventions: Comprehensive swallowing exercises included the protective airway maneuver, tongue pressure resistance feedback exercise, Masako Maneuver swallowing exercise, and the effortful swallowing exercise. Outcomes: Comprehensive swallowing exercises showed good effect in the patient. The FOIS score increased from level 1 to level 7. The videofluoroscopy digital analysis showed that the pharynx constriction rate was 23% and 50%, before and after treatment, respectively. The data from the high-resolution manometry displayed that: the value of the velopharyngeal pressure peak was 82.8 mmHg before treatment and 156.9 mmHg after treatment; the velopharyngeal contraction duration time was 310 milliseconds before treatment and 525 milliseconds after treatment; the value of the hypopharynx pressure peak was 53.7 mmHg before treatment and 103.2 mmHg after treatment; and the hypopharynx contraction duration time was 390 milliseconds before treatment and 1030 milliseconds after treatment. The swallowing visualization illustrated that a bolus could normally pass through the anastomotic stoma, and the bolus leakage was no longer present. The patient was able to eat various consistencies of food independently, and we were able to remove the jejunum nutrient catheter before discharging the patient. Conclusion: For patients with dysphagia caused by anastomotic stricture following esophageal replacement with colon, the swallowing function can be improved by enhancing the pharyngeal impetus when treatment using esophageal dilation is ineffective. PMID:28178125

Value and limitations of transpulmonary pressure calculations during intra-abdominal hypertension.

PubMed

Cortes-Puentes, Gustavo A; Gard, Kenneth E; Adams, Alexander B; Faltesek, Katherine A; Anderson, Christopher P; Dries, David J; Marini, John J

2013-08-01

To clarify the effect of progressively increasing intra-abdominal pressure on esophageal pressure, transpulmonary pressure, and functional residual capacity. Controlled application of increased intra-abdominal pressure at two positive end-expiratory pressure levels (1 and 10 cm H2O) in an anesthetized porcine model of controlled ventilation. Large animal laboratory of a university-affiliated hospital. Eleven deeply anesthetized swine (weight 46.2 ± 6.2 kg). Air-regulated intra-abdominal hypertension (0-25 mm Hg). Esophageal pressure, tidal compliance, bladder pressure, and end-expiratory lung aeration by gas dilution. Functional residual capacity was significantly reduced by increasing intra-abdominal pressure at both positive end-expiratory pressure levels (p ≤ 0.0001) without corresponding changes of end-expiratory esophageal pressure. Above intra-abdominal pressure 5 mm Hg, plateau airway pressure increased linearly by ~ 50% of the applied intra-abdominal pressure value, associated with commensurate changes of esophageal pressure. With tidal volume held constant, negligible changes occurred in transpulmonary pressure due to intra-abdominal pressure. Driving pressures calculated from airway pressures alone (plateau airway pressure--positive end-expiratory pressure) did not equate to those computed from transpulmonary pressure (tidal changes in transpulmonary pressure). Increasing positive end-expiratory pressure shifted the predominantly negative end-expiratory transpulmonary pressure at positive end-expiratory pressure 1 cm H2O (mean -3.5 ± 0.4 cm H2O) into the positive range at positive end-expiratory pressure 10 cm H2O (mean 0.58 ± 1.2 cm H2O). Despite its insensitivity to changes in functional residual capacity, measuring transpulmonary pressure may be helpful in explaining how different levels of positive end-expiratory pressure influence recruitment and collapse during tidal ventilation in the presence of increased intra-abdominal pressure and in calculating true transpulmonary driving pressure (tidal changes of transpulmonary pressure). Traditional interpretations of respiratory mechanics based on unmodified airway pressure were misleading regarding lung behavior in this setting.

Differences in Normal Tissue Response in the Esophagus Between Proton and Photon Radiation Therapy for Non-Small Cell Lung Cancer Using In Vivo Imaging Biomarkers.

PubMed

Niedzielski, Joshua S; Yang, Jinzhong; Mohan, Radhe; Titt, Uwe; Mirkovic, Dragan; Stingo, Francesco; Liao, Zhongxing; Gomez, Daniel R; Martel, Mary K; Briere, Tina M; Court, Laurence E

2017-11-15

To determine whether there exists any significant difference in normal tissue toxicity between intensity modulated radiation therapy (IMRT) or proton therapy for the treatment of non-small cell lung cancer. A total of 134 study patients (n=49 treated with proton therapy, n=85 with IMRT) treated in a randomized trial had a previously validated esophageal toxicity imaging biomarker, esophageal expansion, quantified during radiation therapy, as well as esophagitis grade (Common Terminology Criteria for Adverse Events version 3.0), on a weekly basis during treatment. Differences between the 2 modalities were statically analyzed using the imaging biomarker metric value (Kruskal-Wallis analysis of variance), as well as the incidence and severity of esophagitis grade (χ 2 and Fisher exact tests, respectively). The dose-response of the imaging biomarker was also compared between modalities using esophageal equivalent uniform dose, as well as delivered dose to an isotropic esophageal subvolume. No statistically significant difference in the distribution of esophagitis grade, the incidence of grade ≥3 esophagitis (15 and 11 patients treated with IMRT and proton therapy, respectively), or the esophageal expansion imaging biomarker between cohorts (P>.05) was found. The distribution of imaging biomarker metric values had similar distributions between treatment arms, despite a slightly higher dose volume in the proton arm (P>.05). Imaging biomarker dose-response was similar between modalities for dose quantified as esophageal equivalent uniform dose and delivered esophageal subvolume dose. Regardless of treatment modality, there was high variability in imaging biomarker response, as well as esophagitis grade, for similar esophageal doses between patients. There was no significant difference in esophageal toxicity from either proton- or photon-based radiation therapy as quantified by esophagitis grade or the esophageal expansion imaging biomarker. Copyright © 2017 Elsevier Inc. All rights reserved.

Esophageal spasm

MedlinePlus

... foods if you get esophageal spasms. Alternative Names Diffuse esophageal spasm; Spasm of the esophagus; Distal esophageal spasm Images Digestive system Throat anatomy Esophagus References Falk GW, Katzka DA. ...

Genetic polymorphisms in TERT are associated with increased risk of esophageal cancer.

PubMed

Wu, Yifei; Yan, Mengdan; Li, Jing; Li, Jingjie; Chen, Zhengshuai; Chen, Peng; Li, Bin; Chen, Fulin; Jin, Tianbo; Chen, Chao

2017-02-07

Single nucleotide polymorphisms (SNPs) in TERT may be associated with susceptibility to esophageal cancer. In this study, we analyzed the association between TERT SNPs and risk of esophageal cancer in 386 esophageal cancer patients and 495 healthy subjects from the Xi'an area of China. Of the four SNPs examined, rs10069690 and rs2242652 were correlated with esophageal cancer risk. Additionally, after adjusting for age and gender, the "Trs10069690Ars2242652", "Trs10069690Grs2242652" haplotypes were associated with an increased risk of esophageal cancer, while the and "Crs10069690Grs2242652" haplotype was associated with a decreased risk of esophageal cancer. These findings suggest that TERT polymorphisms may contribute to the development of esophageal cancer.

Distal Esophageal Duplication Cyst with Gastro-Esophageal Reflux Disease: A Rare Association and a Management Challenge.

PubMed

Jan, Iftikhar Ahmad; Al Nuaimi, Asma; Al Hamoudi, Basma; Al Naqbi, Khalid; Bilal, Mohammad

2016-02-01

Esophageal duplication cysts are rare congenital abnormalities of the foregut and may be associated with other conditions. Association of esophageal duplication with Gastro-Esophageal Reflux Disease (GERD) has not been reported in children. We are reporting a case of a 16 months baby who had antenatal diagnosis of diaphragmatic hernia. Postnatal CTchest, however, suggested a distal esophageal duplication cyst and a contrast esophagogram showed grade-IV GER. A thoracoscopy in another hospital excluded esophageal duplication at that time. Later, he presented with hematemesis in our department and was re-evaluated. Repeat CTconfirmed a persistent 2.5 x 1.3 cm cyst in distal esophagus. Upper GI endoscopy suggested grade-II esophagitis with a wide patent gastro-esophageal junction. The child was treated with left thoracotomy, excision of the duplication cyst and thoracic fundoplication. He had an uneventful post-operative recovery and is doing well at 6 months follow-up.

Multimedia manuscript. Heller myotomy and intraluminal fundoplication: a NOTES technique.

PubMed

Perretta, Silvana; Dallemagne, Bernard; Allemann, Pierre; Alleman, Pierre; Marescaux, Jacques

2010-11-01

It is generally accepted that the most effective treatment of achalasia is a surgical myotomy. Nevertheless, if a myotomy alone is performed, reflux may occur in up to 30% of patients. The aim of this study was to explore a transoral incisionless stepwise approach to both esophageal Heller myotomy and fundoplication. The first step consisted of creating the esophageal myotomy. Under general anesthesia, with the pig supine, endoscopy was performed to assess the location of the esophagogastric junction (EGJ). The mucosa on the right posterolateral esophageal wall was cut with the needle-knife 15 cm above the lower esophageal sphincter (LES) and then dilated with blunt dissection to introduce the scope. A submucosal tunnel was created distally with CO(2) and blunt dissection. Once the gastroesophageal junction (GEJ) and the clasp fibers were identified, the muscular layer was cut. The scope was withdrawn into the lumen and the mucosal flap was sealed with endoscopic clips. The adequacy of the myotomy was evaluated using pre- and postoperative manometry and by comparing the EGJ distensibility before, during, and after the division of the esophageal muscular fibers using the functional lumen imaging probe, EndoFLIP®. The second step, consisted of building a transoral incisionless fundoplication 4 weeks postoperatively using the EsophyX™. Both Heller myotomy and endoscopic fundoplication were accomplished successfully with no injury to the esophageal mucosa. Postoperative manometry demonstrated a 50% loss in mean LES pressure (mean preoperative LES pressure = 22.2 mmHg; mean postoperative LES pressure = 10 mmHg, P < 0.005). The EndoFLIP® showed a preoperative minimal diameter of 6 mm with a cross-sectional area of 28 mm(2). Postoperatively, the junction was more compliant (minimal diameter = 15 mm; cross-sectional area = 177 mm(2)), with the main improvement in distensibility occurring when the clasps fibers were removed. A stepwise transoral incisionless approach to esophageal Heller myotomy and partial fundoplication is feasible and effective in the porcine model. A distensibility test such as the EndoFLIP® may provide better information on the opening and closing dynamics of the EGJ, rather than just relying on the sphincter tonic state as measured by manometry.

Effect of surface sensory and motor electrical stimulation on chronic poststroke oropharyngeal dysfunction.

PubMed

Rofes, L; Arreola, V; López, I; Martin, A; Sebastián, M; Ciurana, A; Clavé, P

2013-11-01

Chronic poststroke oropharyngeal dysfunction (OD) is a common condition, leading to severe complications, including death. Treatments for chronic poststroke OD are scarce. The aim of our study was to assess and compare the efficacy and safety of treatment with surface electrical stimulation (e-stim) at sensory and motor intensities in patients with chronic poststroke OD. Twenty chronic poststroke patients with OD were randomly assigned to (i) sensory e-stim (treatment intensity: 75% of motor threshold) or (ii) motor e-stim (treatment intensity: motor threshold). Patients were treated during 10 days, 1 h/day. Videofluoroscopy was performed at the beginning and end of the study to assess signs of impaired efficacy and safety of swallow and timing of swallow response. Patients presented advanced age (74.95 ± 2.18), 75% were men. The mean days poststroke was 336.26 ± 89.6. After sensory stimulation, the number of unsafe swallows was reduced by 66.7% (p < 0.001), the laryngeal vestibule closure time by 22.94% (p = 0.027) and maximal vertical hyoid extension time by 18.6% (p = 0.036). After motor stimulation, the number of unsafe swallows was reduced by 62.5% (p = 0.002), the laryngeal vestibule closure time by 38.26% (p = 0.009) and maximal vertical hyoid extension time by 24.8% (p = 0.008). Moreover, the motor stimulus reduced the pharyngeal residue by 66.7% (p = 0.002), the upper esophageal sphincter opening time by 39.39% (p = 0.009), and increased bolus propulsion force by 211.1% (p = 0.008). No serious adverse events were detected during the treatment. Surface e-stim is a safe and effective treatment for chronic poststroke dysphagic patients. © 2013 John Wiley & Sons Ltd.

Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

PubMed

Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

2017-07-01

Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was differentially expressed in a series of human esophageal tissues, and the aberrant c-MYC expression could be a potential factor in carcinogenesis and progression of esophageal squamous cell carcinoma. There was a statistical signification for c-MYC in esophageal squamous cell carcinoma patients to analyze clinicopathological features. It possibly becomes a new diagnostic indicator of esophageal squamous cell carcinoma.

The potential of photodynamic therapy to treat esophageal candidiasis coexisting with esophageal cancer.

PubMed

Qiu, Haixia; Mao, Yongping; Gu, Ying; Zhu, Jianguo; Wang, Ying; Zeng, Jing; Huang, Naiyan; Liu, Qingsen; Yang, Yunsheng

2014-01-05

Photodynamic therapy (PDT) has been used in recent years to deal with fungal infections because of the prevalence of fungi resistance to drugs. However, PDT for gastrointestinal fungal infection has not been reported. This study was conducted to assess the potential of PDT to deal with esophageal candidiasis. Two male patients with histological evidence of esophageal candidiasis coexisting with esophageal cancer were included in this retrospective study. Both patients were treated with PDT. This treatment was repeated at least 1month after the initial PDT if the patient still had residual cancer or esophageal candidiasis. Short-term efficacy was evaluated on the basis of endoscopy and histology findings. Further follow-up data were obtained from endoscopy results or telephone conversation. The esophageal candidiasis located 21-24cm and 25-28cm from the incisors of case 1 reached complete remission after one and two PDT sessions, respectively. The esophageal cancer coexisting with esophageal candidiasis located 21-24cm from the incisors reached complete remission after two PDT sessions. No recurrence was found at a 14-month follow-up. The esophageal cancer located 30-35cm from the incisors reached partial response after three PDT sessions. Both of the esophageal candidiasis and the coexisting esophageal cancer at 23-26cm from the incisors of case 2 reached complete remission and the esophageal cancer at 34-37cm from the incisors reached complete remission after one PDT session. No recurrence was found at a 24-month follow-up. There were no serious adverse events found in either of the two cases. Results of this preliminary study indicate that PDT may be a potential method to deal with esophageal candidiasis. Copyright © 2013 Elsevier B.V. All rights reserved.

Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

PubMed

Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

2014-12-01

We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p < 0.0001), while melena was less common in patients with esophagitis 38% (45/119) than in controls 68% (244/357) (p < 0.0001). Additionally, the more severe the esophagitis, the more frequent was melena. Patients with esophagitis had less abnormal vital signs, lesser decreases in hematocrit, and lesser increases in BUN. Both pre- and postRockall scores were lower in patients with esophagitis compared with controls (p = 0.01, and p < 0.0001, respectively). Length of hospital stay (p = 0.002), rebleeding rate at 42 days (p = 0.0007), and mortality were less in patients with esophagitis than controls. Finally, analysis of patients with esophagitis and cirrhosis suggested that this group of patients had more severe bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

[Evaluation of stents in treating childhood benign esophageal strictures].

PubMed

Reinshagen, K; Kähler, G; Manegold, B C; Waag, K-L

2009-01-01

Esophageal stenting is a popular of treatment of esophageal strictures in adults. It has also been described for children with benign strictures who did not respond to standard dilatation therapy. The aim of the study was to evaluate weather esophageal stents could be used safely and effectively in the treatment of benign esophageal strictures in children. From 1993 to 2005 stenting therapy was performed in 12 children with complicated esophageal strictures. Etiologies of the strictures were caustic burns in 9 patients, postoperative strictures due to complicated esophageal atresia in 2 patients and iatrogenic esophageal injury in 1 patient. Esophageal silicon tubi, covered retrievable expandable nitinol and plastic stents were placed endoscopically. The clinical course and the long term follow up were evaluated retrospectively The stents and tubi were placed in all patients without complications and were later removed successfully. 6 patients were treated with a self expanding plastic stent. The plastic stents showed a distinct tendency to migrate but in 5/6 patients esophageal stricture was treated successfully. 3 patients were treated by a covered self expanding nitinol stent. No migration occurred. One patient was asymptomatic after therapy, one required further dilatation therapy and the third had esophageal resection. 3 patients were treated by esophageal tubi. 2 patients required surgery in the follow up, one patient is asymptomatic. The use of stenting devices in children to treat benign esophageal strictures is safe and efficient. The self expanding plastic stents had the best long term results but required high compliance of parents and children due to the tendency of stent migration. Self expanding nitinol stents are more traumatic at the extraction procedure and are useful in patients with low compliance. Recurrence of strictures occurred most often after esophageal tubi possibly due to the lack of radial expansion.

[Non-neoplastic esophageal stenosis: not always so benign].

PubMed

Lorenz, Julie; Vollenweider, Peter; Vuilleumier, Henri; Schwab, Marcos

2013-10-02

Esophageal intramural pseudodiverticulosis is a rare pathology whose etiology is unknown, but which is frequently associated with three highly prevalent entities: esophageal reflux disease, esophageal candidosis and alcoholic esophagitis. With conservative treatment the course of these pathologies is usually benign. However, some severe cases are resistant to conservative treatment and may require more aggressive management. We here present the case of patient suffering from a severe esophagitis complicated by chronic mediastinitis with life-threatening repercussions, requiring esophagectomy as treatment.

Clinical outcome of using gastric remnant or jejunum or colon conduit in surgery for esophageal carcinoma with previous gastrectomy.

PubMed

Jun, Wang; Wei, Wen; Weibing, Wu; Jing, Xu; Fuxi, Zhen; Xiaoxiang, Xi; Bihong, Lu; Tong, Zhou; Liang, Chen; Jinhua, Luo

2017-05-01

For esophageal carcinoma patients with early gastrectomy, individualized surgical plans-including selection of replacement conduit and operation route based on patient's new lesion and surgical history-can achieve the desired therapeutic effect and improve postoperative life quality. We investigated the outcomes at our institution. The clinical data of 42 esophageal carcinoma patients with early gastrectomy were analyzed retrospectively. Esophagectomy was performed combining replacement with remnant stomach in 16 patients, jejunum in 17, and colon in 9. Esophagectomy combining replacement with gastric remnant got advantages of shorter operation time and less bleeding over that of replacement with jejunum or colon. Gastric remnant group scored higher on the QLQ-C30 questionnaire than jejunum or colon group with respect to overall quality of life, physical function, and social relationships. In QLQ-OES18 questionnaire, the scores of appetite recovery and reflux mitigation were more favorable in remnant stomach group than those in jejunum or colon group. Survival analysis showed no significant difference in survival rate among the patients undergoing replacement with gastric remnant, jejunum, or colon. For esophageal carcinoma patients with early gastrectomy, esophagus-gastric remnant anastomosis possesses advantages of shorter operation time, less surgical trauma, and greater life quality after surgery. © 2017 Wiley Periodicals, Inc.

Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

2014-02-01

The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma-Past, Present, and Future.

PubMed

Kapoor, Harit; Lohani, Kush Raj; Lee, Tommy H; Agrawal, Devendra K; Mittal, Sumeet K

2015-12-01

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long-standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5-year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett's esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett's esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett's esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett's carcinogenesis. © 2015 Wiley Periodicals, Inc.

Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia.

PubMed

Yamasaki, Yuki; Tsukada, Tomoya; Aoki, Tatsuya; Haba, Yusuke; Hirano, Katsuhisa; Watanabe, Toshifumi; Kaji, Masahide; Shimizu, Koichi

2017-01-01

We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a "0-IIb+IIa" lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage.

Thoracoscopic Surgery in a Patient with Multiple Esophageal Carcinomas after Surgery for Esophageal Achalasia

PubMed Central

Tsukada, Tomoya; Aoki, Tatsuya; Haba, Yusuke; Hirano, Katsuhisa; Watanabe, Toshifumi; Kaji, Masahide; Shimizu, Koichi

2017-01-01

We present a case in which we used a thoracoscopic approach for resection of multiple esophageal carcinomas diagnosed 33 years after surgery for esophageal achalasia. A 68-year-old Japanese man had been diagnosed with esophageal achalasia and underwent surgical treatment 33 years earlier. He was examined at our hospital for annual routine checkup in which upper gastrointestinal endoscopy showed a “0-IIb+IIa” lesion in the middle esophagus. Iodine staining revealed multiple irregularly shaped iodine-unstained areas, the diagnosis of which was esophageal carcinoma. Thoracoscopic subtotal esophagectomy was performed. Esophageal carcinoma may occur many years after surgery for esophageal achalasia, even if the passage symptoms have improved. So, long-term periodic follow-up is necessary for detection of carcinoma at an earlier stage. PMID:28951795

Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma

PubMed Central

Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei

2016-01-01

T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC. PMID:26958940