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Uoti S, Andersson SEM, Robinson E, Räsänen J, Kytö V, Ilonen I. Epidemiology and Management of Zenker Diverticulum in a Low-Threshold Single-payer Health Care System. JAMA Otolaryngol Head Neck Surg 2021; 148:235-242. [PMID: 34913965 DOI: 10.1001/jamaoto.2021.3671] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
Importance The incidence of Zenker diverticulum has been established; previous estimates have been extrapolated from small institutional cohorts. Objective To describe the population-wide incidence of Zenker diverticulum over a 20-year period and characterize management strategies across specialties and treatment settings. Design, Setting, and Participants This retrospective national cohort study was conducted from January 1, 1996, through December 31, 2015, and reviewed patient records from the Care Register for Healthcare in Finland, from which patients with Zenker diverticulum were identified. The data were analyzed in October 2021. Exposures Zenker diverticulum. Main Outcome and Measure The incidence of Zenker diverticulum per 100 000 person-years. Results A total of 2736 patients (median [IQR] age at diagnosis 72.0 [19-106] years; 1278 women [46.7%]) were identified, making the annual incidence of Zenker diverticulum in Finland 2.9/100 000 person-years. Men had higher incidence (3.7/100 000 person-years) compared with women (2.3/100 000 person-years), with an incidence rate ratio of 1.61 (95% CI, 1.48-1.76; P < .001). Within the study population, 1044 patients (38.2%) underwent surgical treatment and 227 (8.3%) underwent 2 or more surgeries. The choice of initial operative approach depended on the medical specialty (Cramer V = 0.41) and on specific catchment area (Cramer V = 0.41). Overall, endoscopic approaches for initial operations were most popular. Conclusions and Relevance The cohort study results found that the incidence of Zenker diverticulum was 2.9/100 000 person-years. Most patients with Zenker diverticulum did not undergo definitive therapy. Some hospital districts and some medical specialties were more likely to opt for conservative treatment than others. The choice of operative approach depended more on physician-level factors rather than patient profiles.
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Affiliation(s)
- Sandra Uoti
- Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland
| | - Saana E-M Andersson
- Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland
| | - Eric Robinson
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jari Räsänen
- Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland
| | - Ville Kytö
- Heart Center, Turku University Hospital and University of Turku, Turku, Finland.,Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.,Center for Population Health Research, Turku University Hospital and University of Turku, Turku, Finland.,Administrative Center, Hospital District of Southwest Finland, Turku, Finland
| | - Ilkka Ilonen
- Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland
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Kasle DA, Torabi SJ, Boey H, Sasaki CT. Hypopharyngeal Diverticulum: Toward a Unified Understanding of Its Etiopathogenesis. Dysphagia 2019; 34:713-715. [PMID: 31230142 DOI: 10.1007/s00455-019-10030-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 05/16/2019] [Accepted: 06/10/2019] [Indexed: 11/30/2022]
Abstract
The etiopathogenesis of Zenker's diverticulum (ZD) remains uncertain. Increased hypopharyngeal pressure due to a hypertonic upper esophageal sphincter results in herniation proximal to the sphincter producing a pulsion diverticulum. Gastroesophageal reflux, which is known to induce shortening of the injured esophagus, likely plays a prominent role in ZD formation by pulling the cricopharyngeus muscle (CPM) away from the anchored inferior constrictor muscle. This creates a "weak zone" encouraging herniation. A bilobed diverticulum may originate from continuation of the fibrous midline raphe inferiorly to developmentally include part of the CPM. We report using laser endoscopy to divide the inter-diverticular septum followed by transmucosal cricopharyngeus myotomy. Presentation of a rare, bilobed diverticulum emphasizes the importance of the midline prevertebral raphe in anchoring the pharyngeal constrictor muscles with respect to the CPM. This lends support to the hypothesis that the etiopathogenesis of ZD is multifactorial while guiding us to a unified understanding of ZD.
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Affiliation(s)
- David A Kasle
- Department of Surgery (Section of Otolaryngology), Yale University School of Medicine, New Haven, CT, USA.,, New Haven, USA
| | - Sina J Torabi
- Department of Surgery (Section of Otolaryngology), Yale University School of Medicine, New Haven, CT, USA.,, New Haven, USA
| | - Howard Boey
- Department of Surgery (Section of Otolaryngology), Yale University School of Medicine, New Haven, CT, USA.,, New Haven, USA
| | - Clarence T Sasaki
- Department of Surgery (Section of Otolaryngology), Yale University School of Medicine, New Haven, CT, USA. .,, New Haven, USA.
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3
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Rengarajan A, Bolkhir A, Gor P, Wang D, Munigala S, Gyawali CP. Esophagogastric junction and esophageal body contraction metrics on high-resolution manometry predict esophageal acid burden. Neurogastroenterol Motil 2018; 30:e13267. [PMID: 29266647 DOI: 10.1111/nmo.13267] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Accepted: 11/27/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND 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). METHODS 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. KEY RESULTS 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). CONCLUSIONS & INFERENCES 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.
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Affiliation(s)
- A Rengarajan
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
| | - A Bolkhir
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
| | - P Gor
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
| | - D Wang
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
| | - S Munigala
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
| | - C P Gyawali
- Division of Gastroenterology, Washington University School of Medicine, Saint Louis, MO, USA
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4
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Bazin C, Benezech A, Alessandrini M, Grimaud JC, Vitton V. Esophageal Motor Disorders Are a Strong and Independant Associated Factor of Barrett's Esophagus. J Neurogastroenterol Motil 2018; 24:216-225. [PMID: 29605977 PMCID: PMC5885720 DOI: 10.5056/jnm17090] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 12/27/2017] [Accepted: 02/09/2018] [Indexed: 01/10/2023] Open
Abstract
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.
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Affiliation(s)
- Camille Bazin
- Service de Gastroentérologie, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France
| | - Alban Benezech
- Service de Gastroentérologie, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France
| | - Marine Alessandrini
- EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, Aix-Marseille Université, Marseille, France
| | - Jean-Charles Grimaud
- Service de Gastroentérologie, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France.,Plateforme d'Interface Clinique, CRN2M CNRS UMR 7286, Aix-Marseille Université, Marseille, France
| | - Veronique Vitton
- Service de Gastroentérologie, Hôpital Nord, Assistance Publique - Hôpitaux de Marseille, Marseille, France.,Plateforme d'Interface Clinique, CRN2M CNRS UMR 7286, Aix-Marseille Université, Marseille, France
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5
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Gyawali CP, Roman S, Bredenoord AJ, Fox M, Keller J, Pandolfino JE, Sifrim D, Tatum R, Yadlapati R, Savarino E. Classification of esophageal motor findings in gastro-esophageal reflux disease: Conclusions from an international consensus group. Neurogastroenterol Motil 2017; 29. [PMID: 28544357 DOI: 10.1111/nmo.13104] [Citation(s) in RCA: 151] [Impact Index Per Article: 18.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Accepted: 04/10/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND 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. METHODS 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. KEY RESULTS 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. CONCLUSIONS & INFERENCES 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.
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Affiliation(s)
- C P Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
| | - S Roman
- Digestive Physiology, Hospices Civils de Lyon and Lyon I University and Inserm U1032, LabTAU, Lyon, France
| | - A J Bredenoord
- Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - M Fox
- Department of Gastroenterology, Abdominal Center, St. Claraspital, Basel, Switzerland
| | - J Keller
- Department of Internal Medicine, Israelitic Hospital, University of Hamburg, Hamburg, Germany
| | - J E Pandolfino
- Division of Gastroenterology, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - D Sifrim
- Center for Digestive Diseases, Bart's and the London School and Dentistry, London, UK
| | - R Tatum
- Department of Surgery, University of Washington, Seattle, WA, USA
| | - R Yadlapati
- Division of Gastroenterology, Department of Medicine, Northwestern University, Chicago, IL, USA
| | - E Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, Padua, Italy
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6
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Triadafilopoulos G, Tandon A, Shetler KP, Clarke J. Clinical and pH study characteristics in reflux patients with and without ineffective oesophageal motility (IEM). BMJ Open Gastroenterol 2016; 3:e000126. [PMID: 28074151 PMCID: PMC5174815 DOI: 10.1136/bmjgast-2016-000126] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 11/21/2016] [Accepted: 11/22/2016] [Indexed: 12/28/2022] Open
Abstract
Background The aetiology and clinical impact of ineffective oesophageal motility (IEM) remain poorly understood, but the condition is thought to worsen supine gastro-oesophageal acid reflux (GERD). Aims In this retrospective cohort analysis of symptomatic patients with abnormal oesophageal acid exposure, we sought to determine any clinical or functional characteristics that would distinguish those with normal peristalsis from those with IEM, defined using the Chicago classification. We hypothesised that the impaired oesophageal clearance in IEM would be contributing to more severe degrees of pathological acid exposure, as well as clinical and endoscopic GERD severity. Methods Consecutive symptomatic patients with GERD underwent clinical, endoscopic and functional evaluation that included high-resolution impedance manometry (HRIM) and ambulatory pH monitoring performed ‘off’ acid suppressive therapy. Results Of the 114 patients with abnormal oesophageal acid exposure, 71 had normal oesophageal motility by HRIM and 43 were diagnosed with IEM (38% prevalence). Age, gender and symptom duration were similar between the two groups. Both groups had similar magnitude and frequency of symptoms, making a distinction clinically impossible. Endoscopically, the two groups had similar rates of erosive disease, hiatal hernia and Barrett's oesophagus. Ambulatory pH, proton pump inhibitor (PPI) dosage and PPI response rates were also similar. Nevertheless, patients with IEM had significantly more impairment of oesophageal clearance (mean 56.9±6.4) than those with normal motility (mean 32.4±5.0) (p<0.003). Conclusions Symptomatic patients with IEM exhibit significant impairment of oesophageal clearance but are otherwise clinically indistinguishable from those with normal oesophageal motility and have a similar prevalence of erosive disease and pathological acid exposure.
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Affiliation(s)
- George Triadafilopoulos
- Silicon Valley Gastroenterology, Mountain View, California, USA; Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Apurva Tandon
- Silicon Valley Gastroenterology , Mountain View, California , USA
| | - Katerina P Shetler
- Department of Gastroenterology , Palo Alto Medical Foundation , Mountain View, California , USA
| | - John Clarke
- Division of Gastroenterology and Hepatology , Stanford University School of Medicine , Stanford, California , USA
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7
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Kawami N, Iwakiri K, Sano H, Tanaka Y, Sakamoto C. Effects of aging and acid reflux on esophageal motility. Digestion 2015; 91:181-6. [PMID: 25765546 DOI: 10.1159/000367650] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 08/15/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUNDS It is generally thought that esophageal motility decreases with age; however, a decrease in esophageal motility may also be caused by esophagitis. The aim of this study is to investigate the effects of aging and acid reflux on esophageal motility. METHODS 40 young (under 45) healthy subjects (HS), 40 elderly (over 65) HS, and 40 elderly (over 65) patients with mild reflux esophagitis (RE), underwent esophageal high-resolution manometry (HRM). Lower esophageal sphincter pressure (LESP), primary peristalsis (PP), and secondary peristalsis (SP) were evaluated. RESULTS There was no difference in the LESP and also in the success rate of PP between young and elderly HS or between elderly HS and RE. There was no difference in the distal contractile integral (DCI) of PP and SP between the young and elderly HS, but in the elderly RE, it was significantly lower than in the elderly HS. There was no difference in the success rate of SP between elderly HS and RE, but in elderly HS it was significantly lower than in young HS. CONCLUSIONS Aging may cause a decrease in the success rate of SP, and acid reflux itself may cause a decrease of the DCI in PP and SP.
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Affiliation(s)
- Noriyuki Kawami
- Department of Gastroenterology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan
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8
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Abstract
Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett's esophagus [BE]) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done, but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (ie, changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia-EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel therapeutic targets.
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Affiliation(s)
- Antonio Galvao Neto
- Department of Pathology, New York University School of Medicine, New York, NY, USA
| | - April Whitaker
- Department of Pathology, New York University School of Medicine, New York, NY, USA
| | - Zhiheng Pei
- Department of Veterans Affairs New York Harbor Healthcare System, New York, NY, USA; Departments of Medicine and Pathology, New York University School of Medicine, New York, NY, USA.
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Ravi K, Katzka DA. Diagnosis and medical management of esophageal dysmotility. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2015. [DOI: 10.1016/j.tgie.2015.03.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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10
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Lee YY, Whiting JGH, Robertson EV, Derakhshan MH, Smith D, McColl KEL. Measuring movement and location of the gastroesophageal junction: research and clinical implications. Scand J Gastroenterol 2013. [PMID: 23205940 DOI: 10.3109/00365521.2012.746394] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Understanding the physiology of gastroesophageal junction (GEJ) is important as failure of its function is associated with reflux disease, hiatus hernia, and cancer. In recent years, there have been impressive developments in high resolution technologies allowing measurement of luminal pressure, pH, and impedance. One obvious deficiency is the lack of technique to monitor the movement and location of the GEJ over a prolonged period of time. Proximal movement of the GEJ during peristalsis and transient lower esophageal sphincter relaxations (TLESRs) is due to shortening of the longitudinal muscle of the esophagus. Techniques for measuring shortening include fluoroscopic imaging of mucosal clip, high-frequency intraluminal ultrasound, and high resolution manometry, but these techniques have limitations. Short segment reflux is recently found to be more common than traditional reflux and may account for the high prevalence of intestinal metaplasia and cancer seen at GEJ. While high resolution pHmetry is available, there is no technique that can reliably and continuously measure the position of the squamocolumnar junction. A new technique is recently reported allowing a precise and continuous measurement of the GEJ based on the principle of Hall effect. Reported studies have validated its accuracy both on the bench and against the gold standard, fluoroscopy. It has been used alongside high resolution manometry in studying the behavior of the GEJ during TLESRs and swallows. While there are challenges associated with this new technique, there are promising ongoing developments. There is exciting time ahead in research and clinical applications for this new technique.
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Affiliation(s)
- Yeong Yeh Lee
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
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Penagini R, Bravi I. The role of delayed gastric emptying and impaired oesophageal body motility. Best Pract Res Clin Gastroenterol 2010; 24:831-45. [PMID: 21126697 DOI: 10.1016/j.bpg.2010.09.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2010] [Revised: 08/30/2010] [Accepted: 09/01/2010] [Indexed: 01/31/2023]
Abstract
Delayed gastric emptying in a variable proportion of patients with gastro-oesophageal reflux disease has been observed in most series, however a relationship between delayed gastric emptying and increased gastro-oesophageal reflux has not been convincingly demonstrated. Enhanced postprandial accommodation and delayed emptying of the proximal stomach have been described, but some controversy exists. Impaired primary peristalsis is often present especially in patients with oesophagitis and its prevalence increases with increasing severity of inflammatory mucosal lesions. Patients with gastro-oesophageal reflux disease often have defective triggering of secondary peristalsis independently of presence of oesophagitis. It is presently unclear if impaired oesophageal motility is a primary defect or an irreversible consequence of inflammation. Attempts at pharmacological improvement of impaired oesophageal motility have been so far disappointing. Patients with partially preserved neuromuscular structures need to be identified in order to select them for new prokinetic therapy.
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Affiliation(s)
- Roberto Penagini
- Department of Gastroenterology, Università degli Studi and Fondazione IRCCS Cà Granda - Ospedale Maggiore Policlinico, Milan, Italy.
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12
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Liu H, Miller DV, Lourenssen S, Wells RW, Blennerhassett MG, Paterson WG. Proteinase-activated receptor-2 activation evokes oesophageal longitudinal smooth muscle contraction via a capsaicin-sensitive and neurokinin-2 receptor-dependent pathway. Neurogastroenterol Motil 2010; 22:210-6, e67. [PMID: 19740117 DOI: 10.1111/j.1365-2982.2009.01394.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Intraluminal acid evokes sustained oesophageal longitudinal smooth muscle (LSM) contraction and oesophageal shortening, which may play a role in oesophageal pain and the aetiology of hiatus hernia. In the opossum model, this reflex has been shown to involve mast cell activation and release of neurokinins from capsaicin-sensitive neurons. The aim of this study was to determine whether proteinase-activated receptor-2 (PAR-2) activation evokes reflex LSM contraction via similar mechanisms. METHODS Tension recording studies were performed using opossum oesophageal LSM strips in the presence and absence of pharmacological agents. In addition, the effect of trypsin on single isolated LSM cells was determined using videomicroscopy, and the expression of PAR-2 in oesophageal tissue was examined using immunohistochemistry. KEY RESULTS The PAR-2 agonist trypsin evoked sustained, concentration-dependent contraction of LSM muscle strips, but had no effect on isolated LSM cells. The trypsin-induced contraction was blocked by capsaicin desensitization, substance P (SP) desensitization or application of the selective neurokinin-2 (NK-2) receptor antagonist MEN 10376. Immunohistochemistry revealed co-localization of SP, calcitonin gene-related peptide and PAR-2 in axons of opossum oesophageal LSM. CONCLUSIONS & INFERENCES Longitudinal smooth muscle contraction induced by trypsin involves capsaicin-sensitive neurons and subsequent activation of NK-2, which is identical to the pathway involved in acid-induced LSM contraction and oesophageal shortening. This suggests that acid-induced LSM contraction may involve mast cell-derived mediators that activate capsaicin-sensitive neurons via PAR-2.
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Affiliation(s)
- H Liu
- Gastrointestinal Diseases Research Unit, Kingston General Hospital Queens University, Kingston, ON, Canada
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13
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BALDI F, LONGANESI A, FERRARINI F, MICHIELETTI G, MORSELLI-LABATE AM. Oesophageal motor function and outcome of treatment with H2-blockers in erosive oesophagitis. Neurogastroenterol Motil 2008. [DOI: 10.1111/j.1365-2982.1992.tb00157.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
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Abstract
In 1987, Richter and colleagues published the results of an esophageal motility study conducted on 95 normal healthy volunteers between the ages of 22 and 79. In accordance with these results, abnormal esophageal motility was defined on the basis of the percentage of manometric normal, ineffective, and simultaneous swallows and on lower esophageal sphincter dynamics during liquid swallows. For example, Richter and colleagues found that the mean amplitude of contraction in the distal body of the esophagus >180 mm Hg in association with wet swallows was above the 95% confidence interval of normal. Richter's study also showed a wide variation among individuals and that the mean distal esophageal contractile amplitude increased with age without sex predominance. Likewise, as no subjects had >20% simultaneous contractions (though a considerable number, 4%, had 10% simultaneous contractions), esophageal spasm was defined at the >20% mark.
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Fornari F, Blondeau K, Durand L, Rey E, Diaz-Rubio M, De Meyer A, Tack J, Sifrim D. Relevance of mild ineffective oesophageal motility (IOM) and potential pharmacological reversibility of severe IOM in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2007; 26:1345-54. [PMID: 17892523 DOI: 10.1111/j.1365-2036.2007.03525.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Several studies showed high prevalence of ineffective oesophageal motility (IOM) in gastro-oesophageal reflux disease (GERD) and suggested an important role for ineffective oesophageal motility in increased acid exposure. However, impedance-manometric studies proposed that only severe ineffective oesophageal motility might affect oesophageal clearance. OBJECTIVES (i) To re-assess the relevance of mild IOM in GERD and (ii) to test the reversibility of IOM. METHODS Oesophageal motility, clearance and acid exposure were assessed in 191 GERD patients: 99 without IOM; 58 with mild IOM (30-80% ineffective contractions) and 34 with severe IOM (>80% ineffective contractions). In 30 patients with oesophagitis, the potential reversibility of IOM was evaluated with edrophonium intravenously. RESULTS Patients with mild IOM had identical oesophageal clearance and acid exposure in comparison with those without IOM. Patients with severe IOM had a higher probability of prolonged supine clearance and acid exposure [odds ratio: 2.88 (1.16-7.17); 2.48 (0.99-6.17)]. This effect was independent of the presence of hiatal hernia and male sex. Severe IOM could be transiently reverted in 55% of patients. CONCLUSIONS Mild IOM does not affect oesophageal clearance. Only severe IOM is associated with prolonged clearance and acid exposure, particularly in supine periods. The edrophonium test might be useful to predict severe IOM response to prokinetic medications.
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Affiliation(s)
- F Fornari
- Center for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium
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Fornari F, Callegari-Jacques SM, Scussel PJ, Madalosso LF, Barros EF, Barros SGS. Is ineffective oesophageal motility associated with reflux oesophagitis? Eur J Gastroenterol Hepatol 2007; 19:783-7. [PMID: 17700264 DOI: 10.1097/meg.0b013e3282748ecf] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVE To evaluate the association between ineffective oesophageal motility and reflux oesophagitis controlling for hiatal hernia, hypotensive lower oesophageal sphincter and male sex in patients with gastro-oesophageal reflux disease. METHODS A total of 387 patients with reflux disease (mean age, 46 years, 42% men) were consecutively selected from a database. All patients underwent upper endoscopy, oesophageal manometry and 24 h oesophageal pH-metry in accordance with a standardized protocol. Reflux disease was confirmed either by endoscopy (oesophagitis grade I-IV according to Savary-Miller) or by pH-metry (increased acid exposure). Hiatal hernia was diagnosed endoscopically, whereas ineffective oesophageal motility and hypotensive lower oesophageal sphincter were characterized during manometry testing. The association between ineffective oesophageal motility and reflux oesophagitis was assessed by logistic regression analysis. RESULTS A total of 166 patients with oesophagitis (mean age 45 years, 49% men) and 221 without oesophagitis (mean age 46 years, 37% men) were present. Prevalences of ineffective oesophageal motility, hiatal hernia, hypotensive lower oesophageal sphincter and male sex were significantly higher in patients with oesophagitis compared with those without oesophagitis (P<0.05). Ineffective oesophageal motility was independently associated with oesophagitis after multivariate logistic regression analysis (odds ratio=1.68; 95% confidence interval=1.04-2.70). CONCLUSION Ineffective oesophageal motility is associated with reflux oesophagitis, independently of hiatal hernia, hypotensive lower oesophageal sphincter and male sex.
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Affiliation(s)
- Fernando Fornari
- Sciences in Gastroenterology, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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17
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Abstract
Motor abnormalities of the oesophagus are characterised by a chronic impairment of the neuromuscular structures that co-ordinate oesophageal function. The best-defined entity is achalasia, which is discussed in a separate chapter. Other motor disorders with clinical relevance include diffuse oesophageal spasm, oesophageal dysmotility associated with scleroderma, and ineffective oesophageal motility. These non-achalasic motor disorders have variable prevalence but they could be associated with invalidating symptoms such as dysphagia, chest pain and gastro-oesophageal reflux disease. New oesophageal diagnostic techniques, including high-resolution manometry, high-frequency intraluminal ultrasound and intraluminal impedance, allow (1) better definition of peristalsis and sphincter function, (2) assessment of changes in oesophageal wall thickness, and (3) evaluation of pressure gradients within the oesophagus and across the sphincters that can produce normal or abnormal patterns of bolus transport. This chapter discusses recent advances in physiology, pathophysiology, diagnosis and treatment of non-achalasic oesophageal motor disorders.
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Affiliation(s)
- Daniel Sifrim
- Centre for Gastroenterological Research, Catholic University of Leuven, Faculty of Medicine, Belgium.
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18
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Oh DS, Hagen JA, Fein M, Bremner CG, Dunst CM, Demeester SR, Lipham J, Demeester TR. The impact of reflux composition on mucosal injury and esophageal function. J Gastrointest Surg 2006; 10:787-96; discussion 796-7. [PMID: 16769534 DOI: 10.1016/j.gassur.2006.02.005] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2005] [Accepted: 02/01/2006] [Indexed: 02/06/2023]
Abstract
The components of refluxed gastric juice are known to cause mucosal injury, but their effect on esophageal function is less appreciated. Our aim was to determine the effect of acid and/or bile on mucosal injury and esophageal function. From 1993-2004, 402 patients with reflux symptoms had 24-hour pH and Bilitec monitoring, manometry, and endoscopy with biopsies. Mucosal injury (esophagitis or Barrett's esophagus) and esophageal function (lower esophageal sphincter [LES] characteristics and body contractility) in patients with acid reflux, bile reflux, or both were compared with patients without reflux. Reflux was present in 273/402 patients; of these, 37 (13.5%) had increased exposure to bile, 82 (30.0%) had increased exposure to acid, and 154 (56.4%) had increased exposure to both. Mucosal injury was most common with increased mixed acid and bile exposure, followed by acid alone, and was uncommon with bile alone (P < 0.0001). Functional deterioration paralleled mucosal injury (P < 0.0001). Mixed acid and bile exposure was present in more than half of patients with reflux and was associated with the most severe mucosal injury and the greatest deterioration of esophageal function. This suggests that composition of gastric juice is the primary determinant of inflammatory mucosal injury and subsequent loss of esophageal function.
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Affiliation(s)
- Daniel S Oh
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA
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19
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Reddy H, Arendt-Nielsen L, Staahl C, Pedersen J, Funch-Jensen P, Gregersen H, Drewes AM. Gender differences in pain and biomechanical responses after acid sensitization of the human esophagus. Dig Dis Sci 2005; 50:2050-8. [PMID: 16240214 DOI: 10.1007/s10620-005-3006-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2005] [Accepted: 02/18/2005] [Indexed: 01/01/2023]
Abstract
Our aims were to investigate gender differences to multimodal stimulations of the esophagus after experimentally induced sensitization. Thirty healthy age-matched subjects, 13 males and 17 females, were included. Pain evoked by mechanical and thermal stimuli was assessed before and after perfusion of the lower esophagus with 0.1 N hydrochloric acid. Males were more sensitive to the baseline mechanical stimuli (P < 0.01) and tolerated a lower volume of acid (P = 0.04). After acid perfusion, males were more sensitive than females to distensions (cross-sectional area P = 0.001 and volume P = 0.001). Acid perfusion sensitized both males (P = 0.03) and females (P = 0.04) to heat stimulation but not to cold stimulation (males, P = 0.09; females, P = 0.8). The referral areas for pain evoked by mechanical and thermal stimuli were larger in females compared with males both before and after acid perfusion (P = 0.002). In females only the referred pain area increased to heat stimulations (P = 0.02). Acid infusion resulted in a more hyperreactive esophagus (P = 0.03) but the hyperreactivity was not gender-dependent. In conclusion, males were more sensitive to mechanical and chemical esophageal stimuli and showed acid-evoked mechanical hyperalgesia. Females had significantly larger referred pain areas to the stimulations. The differentiated response to peripheral and central pain mechanisms may explain the gender-related differences seen in several gastrointestinal disorders.
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Affiliation(s)
- Hariprasad Reddy
- Center for Biomechanics and Pain, University Hospital Aalborg, DK-9000, Aalborg, Denmark
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20
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Drewes AM, Reddy H, Staahl C, Pedersen J, Funch-Jensen P, Arendt-Nielsen L, Gregersen H. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid. World J Gastroenterol 2005; 11:4367-74. [PMID: 16038036 PMCID: PMC4434664 DOI: 10.3748/wjg.v11.i28.4367] [Citation(s) in RCA: 34] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus. The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.
METHODS: Thirty healthy subjects were included. Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area, volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.
RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.
CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions. The new model can be used to study abnormal sensory-motor mechanisms in visceral organs.
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Affiliation(s)
- Asbjørn-Mohr Drewes
- Center for Biomechanics and Pain, Department of Medical Gastroenterology, Aalborg Hospital, DK-9000 Aalborg, Denmark.
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21
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Zhang X, Geboes K, Depoortere I, Tack J, Janssens J, Sifrim D. Effect of repeated cycles of acute esophagitis and healing on esophageal peristalsis, tone, and length. Am J Physiol Gastrointest Liver Physiol 2005; 288:G1339-46. [PMID: 15637176 DOI: 10.1152/ajpgi.00492.2004] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Severe esophagitis is associated with motor abnormalities in the esophageal body and lower esophageal sphincter. Reflux disease involves repeated episodes of mucosal inflammation and spontaneous or treatment-induced healing. The aims of this study were 1) to further assess changes induced by acute esophagitis on esophageal peristalsis, tone, and shortening and 2) to assess the effect of repeated sequences of acute esophagitis-healing on these motor parameters. Experiments were performed on adult cats. Esophageal manometry and barostat were performed before, 24 h after, and every 7 days after intraesophageal acid perfusion (0.1 N HCl, 80 min). Esophageal length was measured during manometry, and compliance of the esophageal body was assessed with barostat. The identical protocol was performed 8 and 16 wk after the first acid perfusion. The degree of esophageal mucosal damage was evaluated by endoscopy, histopathology, and myeloperoxidase activity. Acid perfusion induced severe esophagitis. At 24 h, distal peristaltic contractions disappeared, lower esophageal sphincter pressure was reduced by 60%, the esophagus length was 1-2 cm shorter, and esophageal compliance was reduced by 30%. Most parameters recovered in 4 wk. Subsequent repeated acute injuries induced similar endoscopic esophagitis but a different pattern of inflammatory infiltration and fibrosis in the mucosa and muscle layers, resulting in milder motor disturbances. Acute experimental esophagitis provokes severe but reversible hypomotility. Spaced repeated acute injuries provoke milder motor effects, suggesting an adaptive response.
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Affiliation(s)
- X Zhang
- Faculty of Medicine KU Leuven, Lab G-I Physiopathology, O and N Gasthuisberg, 7th floor, Herestraat 49, 3000 Leuven, Belgium
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22
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Vicente Y, da Rocha C, Perez-Mies B, Madero R, Tovar JA. Effect of reflux and esophagitis on esophageal volume and acid clearance in piglets. J Pediatr Gastroenterol Nutr 2004; 38:328-37. [PMID: 15076636 DOI: 10.1097/00005176-200403000-00019] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND/AIMS The study investigates esophageal motor function and esophageal clearance immediately after surgical induction of reflux in piglets and 8 weeks later after peptic esophagitis has developed. METHODS Twenty-four sedated, nonintubated piglets were divided into three groups: sham (laparotomy only), reflux (distal esophageal myotomy), and reflux + esophagitis (8 weeks after myotomy). All animals underwent stationary manometry of the esophagus with a four-lumen perfused assembly after injection of 1-, 2-, and 3-mL boluses of saline and acid into the proximal esophagus. Simultaneous pH monitoring allowed assessment of acid clearance. Wave features and clearance times after saline and acid were compared among groups. RESULTS There were minor changes in peristaltic activity of the esophagus after saline boluses in animals with reflux. Acid clearance time was prolonged, especially the time to re-establish resting esophageal pH, in animals with esophagitis. These changes, which were volume-dependent, were related to the loss of peristaltic organization of the esophageal waves. The esophageal wave frequency, amplitude, and duration were only slightly changed by the induction of reflux and by esophagitis. CONCLUSIONS The esophagus affected by acid reflux, with or without esophagitis, was capable of near-normal motor responses after boluses of saline. Reflux impaired the peristaltic response to acid, and the effect was more pronounced when reflux and esophagitis were both present. The acid clearance time was also strikingly prolonged in the presence of reflux and esophagitis. The results suggest that long episodes of reflux seen on pH tracings from individuals with esophagitis might be secondary both to acid-related motor dysfunction and large volumes of refluxate.
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Affiliation(s)
- Yvone Vicente
- Section of Pediatric Surgery, Universidade de Sao Paulo-Ribeirao Preto, Brazil
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23
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Sasaki CT, Ross DA, Hundal J. Association between Zenker diverticulum and gastroesophageal reflux disease: development of a working hypothesis. Am J Med 2003; 115 Suppl 3A:169S-171S. [PMID: 12928096 DOI: 10.1016/s0002-9343(03)00218-3] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
A cause-and-effect relation between gastroesophageal reflux disease and Zenker diverticulum remains unclear. Convincing evidence exists demonstrating that patients with Zenker diverticula have increased resting tone of the cricopharyngeus muscle, and that this may be an important initiating factor for the development of Zenker diverticula. Yet some patients with cricopharyngeus hypertonicity never develop Zenker diverticulum. In this context, we hypothesize that acid-induced esophageal shortening may be an important cofactor. We suggest that acid reflux induces longitudinal esophageal shortening, which in turn increases the risk for the development of herniation between 2 spatially related structures, the pharyngeal constrictors and cricopharyngeus muscles, leading to the development of Zenker diverticulum. This hypothesis awaits clinical verification.
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Affiliation(s)
- Clarence T Sasaki
- Section of Otolaryngology, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA
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24
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Wells RW, Morris GP, Blennerhassett MG, Paterson WG. Effects of acid-induced esophagitis on esophageal smooth muscle. Can J Physiol Pharmacol 2003; 81:451-8. [PMID: 12774851 DOI: 10.1139/y03-051] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.
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Affiliation(s)
- R W Wells
- Gastrointestinal Diseases Research Unit, Hotel Dieu Hospital, and Department of Biology, Queen's University, Kingston, ON K7L 5G2, Canada
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25
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Abstract
Reflux of acidic gastric contents through the esophagogastric junction into the esophageal lumen occurs in everyone nearly every day. The esophagogastric junction is composed of several structural components that contribute to its function as the primary antireflux barrier. Only when 1 or more of these components fail does reflux esophagitis develop. The initial focus of this review is on transient lower esophageal sphincter relaxations, a vagally mediated reflex arc that accounts for almost all reflux events in healthy individuals and the majority of reflux events in those with reflux esophagitis. The association of erosive esophagitis with low or absent (incompetent) lower esophageal sphincter (LES) pressure and anatomic disruptions of the esophagogastric junction, such as hiatal hernia, are also important, especially with respect to whether the LES dysfunction and hernia are the cause or the consequence of erosive disease.
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Affiliation(s)
- R C Orlando
- Department of Gastroenterology and Hepatology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA
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26
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White RJ, Zhang Y, Morris GP, Paterson WG. Esophagitis-related esophageal shortening in opossum is associated with longitudinal muscle hyperresponsiveness. Am J Physiol Gastrointest Liver Physiol 2001; 280:G463-9. [PMID: 11171629 DOI: 10.1152/ajpgi.2001.280.3.g463] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Acute intraluminal acid perfusion induces esophageal shortening in humans and opossums. Lower esophageal sphincter (LES) hypotension and peristaltic dysfunction occur in patients and animal models of reflux esophagitis. This study examined whether similar shortening and motor dysfunction occur in anesthetized opossums after repeated esophageal acid exposure and whether this is associated with longitudinal muscle (LM) hyperresponsiveness. Manometry used before and after 3 consecutive days of 45-min perfusion with 100 mmol/l HCl or normal saline measured esophageal length and motor responses to induced swallows. LM electrical and mechanical responses were assessed using standard isometric tension and intracellular recording techniques. Compared with controls, repeated acid perfusion induced erosive esophagitis and significant esophageal shortening, associated with enhanced LM responses to carbachol, a significantly depolarized resting membrane potential, and abnormal spike patterns. LES resting pressure and swallow-induced peristalsis were unaffected. In this model of reflux esophagitis, marked persistent esophageal shortening and associated LM hyperresponsiveness occur before significant LES or peristaltic dysfunction, suggesting that esophageal shortening is the earliest motor disorder induced by acid injury.
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Affiliation(s)
- R J White
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada K7L 3N6
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27
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Chrysos E, Tzovaras G, Epanomeritakis E, Tsiaoussis J, Vrachasotakis N, Vassilakis JS, Xynos E. Erythromycin enhances oesophageal motility in patients with gastro-oesophageal reflux. ANZ J Surg 2001; 71:98-102. [PMID: 11413601 DOI: 10.1046/j.1440-1622.2001.02005.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Intravenous (i.v.) erythromycin enhances gastric emptying and oesophageal motility in both healthy and disease situations, acting either as a motilin or acetylcholine agonist. The purpose of the present paper was to investigate any possible effect of i.v. erythromycin on oesophageal motility in patients with gastro-oesophageal reflux (GOR). METHODS In 15 patients with GOR (proven on 24-h ambulatory oesophageal pH measurement), standard oesophageal manometry was performed after i.v. injection of placebo and 200 mg erythromycin, in a random blind fashion. RESULTS Erythromycin significantly increased lower oesophageal sphincter (LOS) pressure from 17 +/- 5 to 41 +/- 10 mmHg (P < 0.001), without affecting the postdeglutition relaxation of LOS. Erythromycin also increased the amplitude (from 79 +/- 34 to 97 +/- 40 mmHg; P < 0.001), duration (from 3.4 +/- 0.6 to 3.8 +/- 0.6 s; P = 0.005), velocity (from 3.1 +/- 0.8 to 3.5 +/- 1.15 cm/s; P = 0.0047) and strength (from 149 +/- 84 to 201 +/- 103 mmHg.s; P < 0.001) of peristalsis at 5 cm proximal to the LOS. Similarly, the drug increased the amplitude of peristalsis at 10 and 15 cm proximal to the LOS (from 70 +/- 39 to 77.4 +/- 37 mmHg; P = 0.049 and from 36 +/- 20 to 49 +/- 36 mmHg; P = 0.004, respectively) and the duration of peristalsis at the same levels (from 3.1 +/- 0.6 to 3.3 +/- 0.5 s; P = 0.011, and from 2.7 +/- 0.6 to 3 +/- 0.5 s; P = 0.003, respectively). CONCLUSION Intravenously administered erythromycin improves impaired oesophageal motility in patients with GOR. This observation might be of clinical use.
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Affiliation(s)
- E Chrysos
- Department of General Surgery, University Hospital of Heraklion, Heraklion, Crete GR-711 10, Greece.
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28
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Shiino Y, Filipi CJ, Tomonaga T, Awad ZT, Marsh RE. Does the duration of gastroesophageal reflux disease and degree of acid reflux correlate with esophageal function? A retrospective analysis of 768 patients. J Clin Gastroenterol 2000; 30:56-60. [PMID: 10636211 DOI: 10.1097/00004836-200001000-00010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
To reconfirm that the duration of symptoms is not associated with esophageal motility in patients with gastroesophageal reflux disease (GERD), esophageal manometric data from 768 patients with GERD were retrospectively analyzed with relation to the duration of symptoms. GERD was defined by positive acid reflux test results monitored by ambulatory 24-hour pH monitoring. Correlation of the duration of symptoms with esophageal body pressures, the presence of dysmotility determined by simultaneous waves, average resting pressure of the lower esophageal sphincter (LES), and abdominal and overall lengths of the LES were statistically analyzed. The median duration of the symptoms was 60 months (range, 1-600). Duration of symptoms was not associated with contraction pressures of the esophageal body at 3 and 8 cm above the LES (r = -0.070 and -0.063, respectively). There was no correlation between LES pressures, LES lengths, or the percentage of simultaneous waves and duration of symptoms. Stricture formation is related to decreased distal esophageal function in GERD patients. In conclusion, the duration of GERD has little influence on esophageal body and LES function.
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Affiliation(s)
- Y Shiino
- Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska 68131, USA
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Homan CS, Singer AJ, Thomajan C, Henry MC, Thode HC. Thermal characteristics of neutralization therapy and water dilution for strong acid ingestion: an in-vivo canine model. Acad Emerg Med 1998; 5:286-92. [PMID: 9562189 DOI: 10.1111/j.1553-2712.1998.tb02706.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE To determine whether in-vivo neutralization therapy for acid ingestions will superimpose a thermal injury upon tissue already damaged by acid. METHODS An in-vivo canine model was used with repeated measures of tissue and luminal temperatures. All dogs were placed under halothane general anesthesia. The stomach was exteriorized and temperature probes were placed in the lumen and mucosa. 25 mL of 0.5 N HCl (25 degrees C) was placed in the gastric lumen followed 5 minutes later by 75 mL of either 8% NaHCO3 neutralization (25 degrees C, n = 10) or water dilution (25 degrees C, n = 10). Temperature measurements were recorded at specified intervals for 5 minutes post HCl acid exposure and for 30 minutes post treatment. Temperature profiles were analyzed by repeated-measures ANOVA. Post-treatment changes were evaluated using signed-rank tests. RESULTS In both treatment groups, treatment resulted in significant decreases in initial mucosa and intraluminal temperatures. Both the mucosa and intraluminal temperatures decreased immediately after treatment with HCO3 by an average of 1.6 degrees C (p = 0.05). In the water dilution treatment group, both temperatures decreased by 1.1 degrees C (p = 0.05). Ensuing post-treatment temperatures increased but did not reach baseline temperatures at any time up to 30 minutes post treatment. CONCLUSIONS In the in-vivo setting, there is no evidence of hazardous temperature elevation when a weak alkali or dilution therapy is used to neutralize strong acid-induced injury. Contraindication of this form of emergency treatment should not be based on the preconceived idea that a resultant exothermic reaction will cause a superimposed thermal injury. Further clinical study is needed to determine the clinical utility of this emergency therapeutic modality.
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Affiliation(s)
- C S Homan
- Department of Emergency Medicine, State University of New York at Stony Brook, University Medical Center, 11794-7400, USA.
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30
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Paterson WG. Role of mast cell-derived mediators in acid-induced shortening of the esophagus. THE AMERICAN JOURNAL OF PHYSIOLOGY 1998; 274:G385-8. [PMID: 9486193 DOI: 10.1152/ajpgi.1998.274.2.g385] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
It has recently been demonstrated that acid-induced esophageal mucosal injury leads to esophageal shortening, raising the possibility that reflux esophagitis per se may contribute to the development of hiatal hernia. The aim of the present study was to determine whether mast cell-derived mediators are involved in this acid-induced esophageal shortening. Changes in esophageal length were continuously monitored in anesthetized opossums while the esophageal lumen was perfused with 100 mmol/l HCl or normal saline. Changes in esophageal length were compared between animals perfused with acid, with or without pretreatment with the mast cell stabilizers doxantrazole or disodium cromoglycate (DSCG), and animals perfused with normal saline, with or without pretreatment with DSCG. In separate in vitro studies the effect of the mast cell stabilizers on electrical field stimulation-induced esophageal longitudinal muscle contraction was determined. Gradual esophageal lengthening occurred during saline perfusion, irrespective of whether animals were pretreated with DSCG. In contrast, acid perfusion induced esophageal shortening, which was abolished by pretreatment with either doxantrazole or DSCG in doses sufficient to attenuate the acid-induced mucosal histamine release. In vitro, the mast cell stabilizers had no effect on electrical field stimulation-induced esophageal shortening. This study suggests that esophageal shortening associated with acute acid-induced esophageal mucosal injury in the opossum is dependent on mast cell-derived mediators.
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Affiliation(s)
- W G Paterson
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
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31
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Abstract
Despite the increasing emphasis that is placed on both pH measurement and oesophageal manometry, there is little consensus about their usefulness in the clinical setting. These tests are far from infallible and it is difficult to support their universal application in patients with gastrooesophageal reflux disease. Nevertheless, these imperfect tests are useful in certain situations and clinicians must strive to use them intelligently for those most likely to benefit.
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Affiliation(s)
- G McLauchlan
- Department of Surgery, West Coast General Hospital, Port Albemi, British Columbia, Canada
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32
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Shirazi S, Schulze-Delrieu K. Role of altered responsiveness of hypertrophic smooth muscle in manometric abnormalities of the obstructed opossum oesophagus. Neurogastroenterol Motil 1996; 8:111-9. [PMID: 8784795 DOI: 10.1111/j.1365-2982.1996.tb00251.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The movements of the obstructed oesophagus are abnormal, but whether this relates to the disease causing the obstruction, to the altered load conditions or to abnormal neuromuscular functions in hypertrophic smooth muscle is unclear. In an opossum model of chronic oesophageal obstruction, we compared the mechanical responsiveness of hypertrophic smooth muscle in vitro to in vivo manometric function. Related to their greater thickness, strips of hypertrophic muscle generated greater force in response to electrical stimulation and to stretch than control strips. Hypertrophic muscle often generated repetitive contractions; spread of contractions orad from the stimulus site was common in hypertrophic oesophageal bands. On manometry, the obstructed oesophagus generated abnormally high pressures proximally, and highly variable pressure amplitudes in the middle and distally; pressure waves often occurred simultaneously throughout the oesophagus, were repetitive or multi-peaked and led to a lasting rise of oesophageal pressure. Alterations in the intrinsic neuromuscular functions of hypertrophic smooth muscle including generation of greater force, repetitive or spontaneous contractions, and retrograde spread of contractions explain many, but not all, of the manometric abnormalities seen in the chronically obstructed oesophagus.
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Affiliation(s)
- S Shirazi
- Research Laboratories, Veterans Administration Medical Centre, Iowa City, IA 55224, USA
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33
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Homan CS, Maitra SR, Lane BP, Thode HC, Finkelshteyn J, Davidson L. Effective treatment for acute alkali injury to the esophagus using weak-acid neutralization therapy: an ex-vivo study. Acad Emerg Med 1995; 2:952-8. [PMID: 8536120 DOI: 10.1111/j.1553-2712.1995.tb03121.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVE 1) To evaluate whether neutralization therapy with weak acid is effective in reducing observed histopathologic esophageal tissue injury secondary to liquid alkali, 2) to quantify the temperature change of the neutralizing agent, and 3) to determine the effect of interval to therapy on injury severity. METHODS Harvested Sprague-Dawley rat esophagi were catheterized and placed in an oxygenated saline bath (37 degrees C) for 60 minutes and then fixed in 10% formalin. Nine groups (n = 10) were perfused with 50% sodium hydroxide (NaOH). Six of the groups were treated by neutralization with cooled orange juice (OJ) or cola that was maintained between 2 degrees C and 4 degrees C. This was performed at 0, 5, or 30 minutes after injury. In addition, two positive control groups were exposed to OJ or cola at time 0 and were not exposed to strong alkali. A third control group was exposed to strong alkali but was not administered any subsequent treatment. The temperature of the neutralizing agent was recorded prior to instillation and after exiting the esophagus. Blinded pathologic scoring of 0 (no injury) to 3 (severe) was recorded performed for six histopathologic categories: epithelial cell viability, cornified epithelial cell differentiation, granular cell differentiation, epithelial cell nuclei, muscle cells, and muscle cell nuclei. Comparisons were made among treatment times using the Kruskal-Wallis test and linear trend analysis. RESULTS For each histopathologic category and each treatment mode, the Kruskal-Wallis test showed significant differences between the groups (p < 0.002) over time. Trend analyses showed more severe injury with delayed neutralization therapy (p < 0.05) for each treatment mode and histopathologic category. CONCLUSION Early neutralization therapy with OJ or cola reduces acute esophageal alkali injury. Additional in-vivo study is needed before neutralization therapy is adopted for clinical use.
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Affiliation(s)
- C S Homan
- State University of New York-Stony Brook, Department of Emergency Medicine 11794-7400, USA
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34
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Paterson WG, Kolyn DM. Esophageal shortening induced by short-term intraluminal acid perfusion in opossum: a cause for hiatus hernia? Gastroenterology 1994; 107:1736-40. [PMID: 7958685 DOI: 10.1016/0016-5085(94)90814-1] [Citation(s) in RCA: 57] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
BACKGROUND/AIMS Reflux esophagitis and hiatal hernia commonly coexist, yet a cause and effect relationship remains unclear. This study examined whether acute acid-induced esophageal injury induces longitudinal esophageal shortening in the opossum model. METHODS Esophageal length was measured continuously using a specially designed strain gauge transducer in anesthetized opossums while the midesophagus was perfused intraluminally with either normal saline or 100 mmol/L HCl. After a stabilization period, the test solution was perfused for 150 minutes. The effect of bilateral cervical vagotomy and atropine (60 microns/kg intravenously) were determined in separate groups. Parallel studies in which resting lower esophageal sphincter pressure was measured before and after prolonged intraesophageal acid perfusion were performed. RESULTS Esophageal acid perfusion induced acute epithelial injury as determined histologically. This was associated with significant esophageal shortening compared with saline-perfused controls and was not affected by vagotomy or atropine. In contrast, acid perfusion invariably induced a decrease in resting lower esophageal sphincter pressure. CONCLUSIONS Acute acid-induced esophageal mucosal injury induces longitudinal esophageal shortening that does not involve vagal pathways or cholinergic neurons. This raises the possibility that esophagitis could contribute to the development of hiatal hernia by inducing esophageal long axis shortening.
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Affiliation(s)
- W G Paterson
- Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada
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35
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Fass J, Silny J, Braun J, Heindrichs U, Dreuw B, Schumpelick V, Rau G. Measuring esophageal motility with a new intraluminal impedance device. First clinical results in reflux patients. Scand J Gastroenterol 1994; 29:693-702. [PMID: 7973429 DOI: 10.3109/00365529409092496] [Citation(s) in RCA: 87] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The study was undertaken to determine the validity of intraluminal impedance measuring for the diagnosis of esophageal motility disorders in reflux patients. METHODS A new impedance device was used for the detection of esophageal motility patterns in a prospective study with 10 volunteers and 10 patients with reflux esophagitis grade II-III. Perfused manometry was correlated with the impedance tracings. Test meals were saline and curd in three different preparations with liquid to semisolid viscosity. RESULTS There was a marked delay in esophageal transport with increasing viscosity of the bolus (p < 0.01). A significant (p < 0.001) delay of the bolus transport in the inflamed esophageal areas was seen in reflux patients. A reduced contractility of the lower esophagus and the lower esophageal sphincter was detected by the impedance procedure in reflux patients, indicating that the pathologic motility patterns in reflux esophagitis are most likely secondary to the tissue inflammation. CONCLUSION We conclude that impedance procedures may give additional significant information about bolus transport and esophageal wall movements.
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Affiliation(s)
- J Fass
- Dept. of Surgery, Rheinisch Westphälische Technische Hochschule, Aachen, Germany
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36
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Homan CS, Maitra SR, Lane BP, Thode HC, Sable M. Therapeutic effects of water and milk for acute alkali injury of the esophagus. Ann Emerg Med 1994; 24:14-20. [PMID: 8010543 DOI: 10.1016/s0196-0644(94)70155-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
STUDY BACKGROUND Alkali ingestions cause progressive and devastating injury to the esophagus by liquefaction necrosis. However, the therapeutic efficacy of water or milk dilution for alkali-induced esophageal injury has not been determined. This study used our previously reported model of alkali-induced esophageal injury to evaluate the effectiveness of water and milk dilution. HYPOTHESIS Early dilution with water or milk is efficacious in decreasing esophageal damage from alkali exposure. METHODS The esopgagi of 75 Sprague-Dawley rats were harvested, and each end was cannulated with a 20-gauge catheter. Specimens were maintained in an oxygenated saline solution (at 37 degrees C) during a 60-minute experimental period and then fixed immediately in 10% Formalin solution for histologic examination. Esophagi from six experimental groups (total of 60) were perfused with 50% NaOH solution at time 0. Water or milk dilution was performed immediately at 0 minutes, 5 minutes after injury, and 30 minutes after injury. Blinded pathologic examination was performed using a score of 0 (no injury), 1 (minimal), 2 (moderate), or 3 (severe) for the following six histologic categories: epithelial viability, cornified epithelial cell differentiation, granular cell differentiation, epithelial cell nuclei, muscle cells, and muscle cell nuclei. RESULTS Positive and negative controls showed expected outcomes. Significant progressions of injury over time were seen for every histologic category for both water and milk dilution. The injury scores for the milk-treated group at 0 minutes were less than or equal to the injury score for the water-treated group for all categories. However, these differences were significant only for the cornified epithelial cells. CONCLUSION Early dilution therapy with water or milk reduces acute alkali injury of the esophagus and supports use of these forms of emergency treatment.
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Affiliation(s)
- C S Homan
- Department of Emergency Medicine, State University of New York Health Sciences Center, Stony Brook
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37
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Williams D, Thompson DG, Heggie L, O'Hanrahan T, Bancewicz J. Esophageal clearance function following treatment of esophagitis. Gastroenterology 1994; 106:108-16. [PMID: 8276171 DOI: 10.1016/s0016-5085(94)94713-9] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND/AIMS To investigate whether healing of the esophagitis was associated with an improvement in esophageal clearance function, 15 patients with endoscopic and histologically confirmed erosive esophagitis were studied both before and after 1-month treatment with 40 mg/day of omeprazole. METHODS All patients were studied before and after treatment by perfusion manometry to measure esophageal pressures, and a traction measuring device was used to record aboral forces generated by graded intraluminal distension. RESULTS Before treatment, standard manometry showed reduced lower esophageal sphincter pressures (4 mm Hg [range, 2-9] vs. a control of 12 mm Hg [range, 5-25]; P < 0.01) and distal peristaltic amplitudes (29 mm Hg [range, 5-57] vs. a control of 55 mg Hg [range, 32-90]; P < 0.01). Responses to distension were also abnormal with a higher threshold for induction of contractile activity (12 mL [range, 8.5-14] vs. control values of 5 mL [range, 3-10]; P < 0.01) and weaker clearance forces (5 g [range, 0-80] vs. control values of 20 g [range, 8-90]; P < 0.01). After treatment, all patients showed endoscopic and histological evidence of healing, but not consistent improvement in either lower esophageal sphincter pressure (5 mm Hg [range, 3-7]; P > 0.05 vs. pretreatment) or peristaltic amplitude (35 mm Hg [range, 10-55]) was found. However, responses to distension did improve, with a decrease in distension threshold to 10 mL (range, 7-14; P = 0.04) and enhancement of traction force to 14 g (range, 0-95; P < 0.01). Patients with the worst pretreatment distension responses showed the least improvement with therapy. CONCLUSIONS Improvement in esophageal clearance can be achieved by the healing of esophagitis, although the capacity for functional benefit appears to be related to the degree of dysfunction present before therapy.
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Affiliation(s)
- D Williams
- Department of Medicine, Hope Hospital, Salford, England
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38
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Pennathur A, Tran A, Cioppi M, Fayad J, Sieren GL, Little AG. Erythromycin strengthens the defective lower esophageal sphincter in patients with gastroesophageal reflux disease. Am J Surg 1994; 167:169-72; discussion 172-3. [PMID: 8311129 DOI: 10.1016/0002-9610(94)90069-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Motilin induces phase III activity of the gastrointestinal tract. Erythromycin has a motilin-like effect on the stomach and significantly increases the lower esophageal sphincter (LES) pressure in normal volunteers. This investigation was performed to evaluate the effects of erythromycin on esophageal function in patients with gastroesophageal reflux disease (GERD). Esophageal manometry was performed in 10 GERD patients before and after intravenous infusion of 500 mg of erythromycin. Values are expressed as mean +/- SEM. LES pressure increased from 13.9 +/- 2.9 mm Hg at baseline to 28.9 +/- 3.6 mm Hg after infusion of erythromycin (p < 0.01). The duration of contractions in the proximal, middle, and distal esophagus was significantly prolonged from 3.5 +/- 0.4 seconds, 3.8 +/- 0.4 seconds, and 4.1 +/- 0.5 seconds to 4.2 +/- 0.2 seconds, 4.6 +/- 0.5 seconds, and 5.6 +/- 0.6 seconds, respectively, after infusion of erythromycin (p < 0.05 for each comparison). Erythromycin did not effect esophageal body contraction amplitude or velocity, or the upper esophageal sphincter. Serum motilin decreased slightly after the administration of erythromycin. We concluded the following: (1) Erythromycin profoundly stimulates the defective LES in patients with GERD. This appears to be a direct motilin agonist-like effect rather than being mediated by release of endogenous motilin. (2) Erythromycin has less effect on the esophageal body, although it does prolong the duration of esophageal contractions.
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Affiliation(s)
- A Pennathur
- Department of Surgery, University of Nevada School of Medicine, Las Vegas
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39
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Salapatek AM, Diamant NE. Assessment of neural inhibition of the lower esophageal sphincter in cats with esophagitis. Gastroenterology 1993; 104:810-8. [PMID: 7680016 DOI: 10.1016/0016-5085(93)91017-c] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND The aim of this study was to investigate the inhibitory innervation of the lower esophageal sphincter in the presence of esophagitis. METHODS Esophagitis was produced in five anesthetized cats with intraesophageal perfusion of HCl. Sphincter pressure responses were assessed with a sleeve catheter after administration of bethanechol, cholecystokinin octapeptide, and McNeil-A343 and with intraesophageal balloon distension. RESULTS In the presence of esophagitis (1) resting lower esophageal sphincter pressure decreased; (2) the excitatory response to bethanechol was maintained; (3) there was a reduction in the excitatory response to McNeil-A343 and cholecystokinin at the highest dosages; (4) there was an increase in the potency of cholecystokinin and McNeil-A343 to produce an inhibitory response; (5) the inhibitory response to intraesophageal balloon distension was maintained; and (6) increased inhibitory responses took longer to normalize than the reduced excitatory responses. CONCLUSIONS Esophagitis decreases cholinergic excitation, but neural inhibition to the LES remains intact. These findings suggest that blocking intact inhibition may be a new therapeutic approach for esophagitis caused by gastroesophageal reflux.
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Affiliation(s)
- A M Salapatek
- Department of Medicine, University of Toronto, Playfair Neurosciences, Ontario, Canada
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40
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Williams D, Thompson DG, Marples M, Heggie L, O'Hanrahan T, Mani V, Bancewicz J. Identification of an abnormal esophageal clearance response to intraluminal distention in patients with esophagitis. Gastroenterology 1992; 103:943-53. [PMID: 1499944 DOI: 10.1016/0016-5085(92)90028-w] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Esophageal clearance responses were studied by a new technique comprising a miniature electronic strain gauge attached to an inflatable balloon in 30 normal volunteers and 48 patients with gastroesophageal reflux disease. The pressure changes around the balloon and traction forces acting on the balloon were measured during graded balloon distention (0-12 mL of air for 30 seconds each inflation) in the lower and midesophagus. All normal volunteers responded to distention with development of swallow independent contractions above the balloon [65 mm Hg/30 s (range, 45-100 mm Hg/30 s)] together with generation of an aboral traction force [15 g (range, 9-20 g)]. Patients with reflux esophagitis showed a higher distention threshold for initiation of these responses, induced fewer proximal contractions [24 mm Hg/30 s (range, 0-38 mm Hg/30 s); P less than 0.01 vs. normal], and generated weaker traction forces [4 g (range, 0-6 g) at 10 mL P less than 0.01 vs. normal]. Patients with the most severe esophagitis showed greatest impairment of the clearance response (correlation = 0.7, P less than 0.01) and the greatest esophageal residence of refluxed acid (correlation = 0.5, P less than 0.01). These abnormalities appear to be of relevance to the pathophysiology of esophageal reflux disease although it remains to be determined whether they are the cause, or the result, of the esophagitis.
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Affiliation(s)
- D Williams
- Department of Medicine, Hope Hospital, Salford, England
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41
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Ortiz Escandell A, Martinez de Haro LF, Parrilla Paricio P, Aguayo Albasini JL, Garcia Marcilla JA, Morales Cuenca G. Surgery improves defective oesophageal peristalsis in patients with gastro-oesophageal reflux. Br J Surg 1991; 78:1095-7. [PMID: 1933194 DOI: 10.1002/bjs.1800780919] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Postoperative manometry was carried out in 12 patients with gastro-oesophageal reflux associated with hypomotility of the oesophageal body. A Nissen fundoplication was carried out in all patients. After a median follow-up of 3.5 years, patients underwent clinical, endoscopic, radiological, manometric and pH-metric evaluation. Manometric results revealed an overall improvement in oesophageal motor function with an increase in the amplitude of deglutition waves and a decrease in the percentage of deglutitions without response. Six of the patients (one with complete motor failure) recovered normal peristaltic function. Non-specific oesophageal motor disorders may be secondary to gastro-oesophageal reflux and are reversible in nature.
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Affiliation(s)
- A Ortiz Escandell
- Department of Surgery, Virgen de la Arrixaca Hospital, University of Murcia, Spain
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42
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Jørgensen F, Elsborg L. Sucralfate versus cimetidine in the treatment of reflux esophagitis, with special reference to the esophageal motor function. Am J Med 1991; 91:114S-118S. [PMID: 1882896 DOI: 10.1016/0002-9343(91)90461-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Sixty patients entered a double-blind clinical trial comparing the effect of 1 g of sucralfate granulate given four times daily and cimetidine, 400 mg twice daily. Twenty-six patients treated with sucralfate and 26 treated with cimetidine were examined with short-term pH monitoring before and after 12 weeks of treatment. Thirty patients, 19 treated with cimetidine and 11 treated with sucralfate, had esophageal motility studied by a radionuclide test before and after 12 weeks of treatment. The efficacy of the treatments was judged by symptoms and endoscopic response after 4, 8, and 12 weeks of treatment. The endpoint healing rate was approximately 60% in both groups and symptoms were relieved in half of the patients in both groups (difference not significant). The effect of the treatments on pH and number of spikes reflected the different pharmacodynamic profiles of the drugs, whereas the mean transit time (MTT) was not changed by the treatments. The residual activity after radionuclide transit in the sitting position was significantly increased after treatment with cimetidine. The data support the hypothesis that primary dysmotility might be involved in the pathogenesis of reflux esophagitis in about 33% of the patients. Possibilities for a combination therapy with sucralfate and cimetidine are stressed.
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Affiliation(s)
- F Jørgensen
- Department of Internal Medicine and Gastroenterology B, Frederiksberg University Hospital of Copenhagen, Denmark
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