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Savarino V, Marabotto E, Zentilin P, De Bortoli N, Visaggi P, Furnari M, Bodini G, Giannini E, Savarino E. How safe are heartburn medications and who should use them? Expert Opin Drug Saf 2023; 22:643-652. [PMID: 37477199 DOI: 10.1080/14740338.2023.2238592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
INTRODUCTION Heartburn is a frequent symptom occurring in daily clinical practice and is mainly associated with gastroesophageal reflux disease (GERD). However, it can be stimulated by various factors and diseases other than GERD can present with heartburn. Therefore, physicians must be very careful in distinguishing GERD from non-GERD conditions in their patients, particularly when heartburn is refractory to anti-reflux medications. AREAS COVERED The aim of this narrative review was to analyze the medical literature regarding the prevalence of heartburn and the various clinical disorders which can be present with this symptom. The type of medications usually adopted for treating heartburn and their grade of safety have been reviewed using an extensive computerized (Medline/PubMed) search with particular focus on the last 20 years. EXPERT OPINION Many drugs can be used for relieving heartburn in patients with GERD, although PPIs are the pharmacological agents with the greatest efficacy. However, it must be highlighted that many non-GERD conditions may present clinically with this symptom whose intensity does not differ between GERD and functional esophageal disorders, which represent about 50% of all patients with suspected GERD. It is very important to identify these functional conditions because their treatment differs completely from that of GERD.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Manuele Furnari
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Giannini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Alleleyn AM, Keszthelyi D, Rinsma NF, Csekő K, Kajtár B, Helyes Z, Winkens B, Masclee AA, Conchillo JM. The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study. Clin Transl Gastroenterol 2022; 13:e00488. [PMID: 35351835 PMCID: PMC9132534 DOI: 10.14309/ctg.0000000000000488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 03/15/2022] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION Esophageal pain is mediated by sensory nerves, most importantly by the activation of the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor. TRPV1 is activated and sensitized by a broad range of pungent compounds, as well as inflammatory mediators and tissue irritants. Luminal stressors are suggested to impair the barrier function, which results in consequent activation of these sensory nerve terminals and pain. In this study, we investigated the effect of the perfusion of capsaicin, a TRPV1 agonist, on mucosal impedance and pain in asymptomatic volunteers. METHODS Thirteen asymptomatic volunteers completed a single-blind, saline-controlled, randomized crossover study. Capsaicin or saline was perfused for 30 minutes in the distal esophagus. Visual analog scale pain intensity scores and intraluminal impedance indicating mucosal integrity were determined. Distal and proximal biopsies were obtained 10 minutes later to measure TRPV1 messenger RNA and TRPV1 immunopositivity, as well as the intercellular space area. RESULTS Capsaicin perfusion resulted in significantly greater pain intensity (P = 0.047) and impaired recovery of the mucosal impedance compared with saline-treated controls (P = 0.027). Pain response was significantly associated with decreased mucosal impedance. Similar dynamics were seen in the proximal esophagus, but mucosal impedance recovered entirely to the preinfusion values there. There was a significant association between mucosal impedance and intercellular space width in the distal esophagus. TRPV1 transcription and expression were not significantly altered within this observation period. DISCUSSION Esophageal capsaicin perfusion results in pain, which is likely to be explained by impaired mucosal impedance and defective restoration capacity in the distal esophagus.
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Affiliation(s)
- Annick M.E. Alleleyn
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands;
| | - Daniel Keszthelyi
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands;
| | - Nicolaas F. Rinsma
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands;
| | - Kata Csekő
- Department of Pharmacology and Pharmacotherapy, Medical School, Janos Szentagothai Research Centre & Centre for Neuroscience, University of Pécs, Pécs, Hungary;
| | - Béla Kajtár
- Department of Pathology, Medical School, Clinical Centre, University of Pécs, Pécs, Hungary; and
| | - Zsuzsanna Helyes
- Department of Pharmacology and Pharmacotherapy, Medical School, Janos Szentagothai Research Centre & Centre for Neuroscience, University of Pécs, Pécs, Hungary;
| | - Bjorn Winkens
- Department of Methodology and Statistics, Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, the Netherlands.
| | - Adrian A.M. Masclee
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands;
| | - José M. Conchillo
- Division of Gastroenterology-Hepatology, Department of Internal Medicine, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands;
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Determinants of reflux perception in patients with non-erosive reflux disease who have reflux-related symptoms on potassium-competitive acid blocker therapy. Esophagus 2022; 19:367-373. [PMID: 34655001 DOI: 10.1007/s10388-021-00889-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Accepted: 10/09/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND This study investigated potential determinants of reflux perception in patients with non-erosive reflux disease (NERD) who had reflux-related symptoms on potassium-competitive acid blocker (P-CAB) therapy. METHODS This study included 23 patients with reflux-related symptoms despite P-CAB therapy. Esophageal impedance-pH monitoring was performed on P-CAB and the following potential determinants of reflux perception were investigated: reflux nadir pH value; change in pH (baseline-nadir); bolus clearance time; reflux extent; proportions of acid, weakly acidic, and weakly alkaline reflux episodes; and proportions of liquid and mixed reflux episodes. RESULTS Overall, ≥ 90% of all and symptomatic reflux episodes were weakly acidic reflux and 63% of symptomatic reflux episodes were reflux episodes with pH ≥ 5. There were no significant differences regarding potential determinants between symptomatic and asymptomatic reflux episodes. However, the proportion of symptomatic reflux episodes was significantly greater with pH < 5 (13.8%) than with pH ≥ 5 (9.5%) (P = 0.0431). In reflux episodes with pH < 5, the proportion of symptomatic reflux episodes was significantly greater in proximal sites (20.6%) than in distal sites (10.6%) (P = 0.0178). Conversely, in reflux episodes with pH ≥ 5, there was no significant difference regarding reflux perception according to reflux extent (proximal: 9.6% vs. distal: 9.0%, P = 0.9337). CONCLUSIONS In patients with P-CAB-resistant NERD, reflux symptoms were mainly caused by reflux episodes with pH ≥ 5 on P-CAB therapy. The proportions of symptomatic reflux episodes among reflux sites differed according to reflux pH value; thus, the mechanisms of reflux perception may differ according to reflux pH value.
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Mittal RK. Montreal, Rome, and Lyon Consensus: Will They Resolve the Conundrum of Gastroesophageal Reflux Disease. Gastroenterology 2021; 161:1776-1779. [PMID: 34461054 DOI: 10.1053/j.gastro.2021.08.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 08/11/2021] [Indexed: 12/02/2022]
Affiliation(s)
- Ravinder K Mittal
- Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, California
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Kang SG, Hwang HJ, Kim Y, Lee J, Oh JH, Kim J, Lim CH, Youn SB, Jung SH. Reflux Esophagitis and Fatigue: Are They Related? J Clin Med 2021; 10:jcm10081588. [PMID: 33918665 PMCID: PMC8069331 DOI: 10.3390/jcm10081588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/02/2021] [Accepted: 04/07/2021] [Indexed: 01/18/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a chronic, recurrent disease. Reflux esophagitis can interfere with sleep via acid reflux, which can cause daytime sleepiness or fatigue. However, little is known about the association between reflux esophagitis and fatigue. Objectives: We evaluated the association between fatigue and reflux esophagitis in subjects seen at health check-ups. Methods: Consecutive patients who were scheduled for screening endoscopies were enrolled prospectively at the Comprehensive Medical Examination Center of St. Vincent Hospital and Eunpyeong St. Mary’s Hospital, Korea. Three validated questionnaires were used to assess fatigue, daytime hypersomnolence, anxiety, and depression: the Multidimensional Fatigue Inventory—Korean version (MFI-K), Epworth Sleepiness Scale (ESS), and Hospital Anxiety and Depression Scale (HADS). Results: We investigated 497 consecutive eligible subjects. The reflux esophagitis and symptomatic GERD groups comprised 103 (20.7%) and 92 (18.5%) subjects, respectively. The MFI-K total, ESS, HADS-anxiety, and HADS-depression scores did not differ between the esophagitis and non-esophagitis groups (50.0 ± 11.5 vs. 49.7 ± 10.9, p = 0.661; 6.2 ± 2.8 vs. 6.1 ± 3.1, p = 0.987; 5.8 ± 3.1 vs. 5.2 ± 3.2, p = 0.060; 6.2 ± 3.6 vs. 6.0 ± 3.3, p = 0.561). However, the MFI-K total, ESS, HADS-anxiety, and HADS-depression scores were higher in the symptomatic group than in the non-symptomatic group (54.7 ± 12.7 vs. 48.6 ± 10.3, p < 0.001; 7.1 ± 3.5 vs. 5.9 ± 2.9, p = 0.002; 6.4 ± 3.3 vs. 5.1 ± 3.1, p < 0.001; 7.5 ± 4.0 vs. 5.7 ± 3.1, p < 0.001). Multiple regression analysis showed that the MFI-K total was correlated with GERD symptoms (p = 0.021), women (p = 0.001), anxiety (p < 0.001), and depression (p < 0.001). Conclusion: There was no statistically significant association in which reflux esophagitis could cause daytime sleepiness, fatigue, anxiety, or depression. However, fatigue was associated with GERD symptoms, women, anxiety, and depression. Further studies should clarify the association between fatigue and reflux esophagitis.
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Affiliation(s)
- Sung-Goo Kang
- Department of Family Medicine, St. Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea;
| | - Hyun jee Hwang
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Youngwoo Kim
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Junseak Lee
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Jung Hwan Oh
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Jinsu Kim
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Chul-Hyun Lim
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Seung Bae Youn
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
| | - Sung Hoon Jung
- Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea; (H.j.H.); (Y.K.); (J.L.); (J.H.O.); (J.K.); (C.-H.L.); (S.B.Y.)
- Correspondence: ; Tel.: +82-10-5141-7306
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Kichloo A, Albosta M, Aljadah M, El-Amir Z, Goldar G, Khan MZ, Dahiya DS, Vallabhaneni S, Wani F, Singh J. Marijuana: A systems-based primer of adverse effects associated with use and an overview of its therapeutic utility. SAGE Open Med 2021; 9:20503121211000909. [PMID: 33786179 PMCID: PMC7958160 DOI: 10.1177/20503121211000909] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/12/2021] [Indexed: 12/18/2022] Open
Abstract
Marijuana use is on the rise in the United States. By the end of 2019, 33 states have legalized marijuana use and marijuana byproduct use for medical purposes. However, marijuana use does not come without side effects. This manuscript reviews the increasing usage of marijuana and the different forms (natural and synthetic) that patients may use when presenting to clinicians. It also addresses the biochemical and behavioral changes observed with marijuana use, including the location and changes associated with cannabinoid receptors (abbreviated CB1 and CB2). These two topics lead into an extensive review of the side effects of marijuana use. This manuscript discusses gastrointestinal side-effects, such as Cannabinoid Hyperemesis Syndrome, pancreatitis, and hepatotoxicity. It also briefly reviews cardiovascular, neurologic, and pulmonary side effects. This article provides an overview of therapeutic effects of marijuana including the antiemetic effect, its medical utility as an appetite stimulant, and usefulness in cancer patients post-chemotherapy. A thorough social history pertaining to marijuana use is an important consideration for clinicians in patients presenting with a variety of symptoms, including those effecting the gastrointestinal, cardiovascular, pulmonary, or neurologic systems.
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Affiliation(s)
- Asim Kichloo
- Department of Internal Medicine,
Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Michael Albosta
- Department of Internal Medicine,
Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Michael Aljadah
- Department of Internal Medicine,
Medical College of Wisconsin, Milwaukee, WI, USA
| | - Zain El-Amir
- Department of Internal Medicine,
Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Ghazaleh Goldar
- Department of Internal Medicine,
Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Muhammed Zatmar Khan
- Department of Internal Medicine,
Central Michigan University College of Medicine, Saginaw, MI, USA
| | - Dushyant Singh Dahiya
- Department of Internal Medicine,
Central Michigan University College of Medicine, Saginaw, MI, USA
| | | | - Farah Wani
- Department of Family Medicine,
Samaritan Medical Center, Watertown, NY, USA
| | - Jagmeet Singh
- Department of Nephrology, Guthrie
Robert Packer Hospital, Sayre, PA, USA
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Zheng M, Arora N, Bhatt N, O'Dell K, Johns M. Factors Associated With Tolerance for In-Office Laryngeal Laser Procedures. Laryngoscope 2021; 131:E2292-E2297. [PMID: 33405311 DOI: 10.1002/lary.29370] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/13/2020] [Accepted: 12/28/2020] [Indexed: 11/08/2022]
Abstract
OBJECTIVES/HYPOTHESIS A variety of laryngeal pathologies are increasingly being managed with in-office KTP laser (IOKTP) endoscopic procedures. The primary goal of this study was to identify patient characteristics and disease-related features that correlated with tolerance for IOKTP. STUDY DESIGN Retrospective chart review. METHODS The study was a retrospective review of adult patients undergoing office-based laryngeal laser procedures between November 2016 and December 2019 at a tertiary care center. Two blinded otolaryngologist reviewers scored videotaped recordings of IOKTP procedures and assessed severity and distribution of disease using a modified Derkay score, and evaluated procedure tolerance using a visual analog scale. RESULTS A total of 56 patients who received IOKTP procedures for laryngeal pathology were reviewed, 42 male and 14 female, with a mean age of 61 years. Gender, age, and BMI were not correlated with tolerance. There was a moderate, negative correlation between tolerance and total number of pathological anatomic laryngeal subsites (rs(56) = -0.35, P = .01). There was a weak, negative correlation between tolerance and total modified Derkay score (rs(56) = -0.29, P = .03). The median tolerance score was lower for patients with posterior lesions (Mdn = 6.4) compared with patients with non-posterior lesions (Mdn = 7.4), P = .04, and lower for current or former smokers (Mdn = 6.5) compared with never smokers (Mdn = 7.3), P = .04. CONCLUSION Patients with large disease burden or posterior lesions and patients with smoking history may exhibit poorer tolerance of IOKTP procedures, factors which can help guide pre-procedural counseling and management decisions. LEVEL OF EVIDENCE IV Laryngoscope, 131:E2292-E2297, 2021.
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Affiliation(s)
- Melissa Zheng
- Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, U.S.A
| | - Nikhil Arora
- Keck School of Medicine, University of Southern California, Los Angeles, California, U.S.A
| | - Neel Bhatt
- Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, U.S.A
| | - Karla O'Dell
- Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, U.S.A
| | - Michael Johns
- Department of Otolaryngology-Head and Neck Surgery, University of Southern California, Los Angeles, California, U.S.A
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Spechler SJ. Evaluation and Treatment of Patients with Persistent Reflux Symptoms Despite Proton Pump Inhibitor Treatment. Gastroenterol Clin North Am 2020; 49:437-450. [PMID: 32718563 DOI: 10.1016/j.gtc.2020.04.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Despite the exceptional efficacy of proton pump inhibitors (PPIs) in healing reflux esophagitis complicating gastroesophageal reflux disease (GERD), up to 40% of patients who take PPIs for GERD complain of persistent GERD symptoms. There is no clear consensus on the type, dosing, and duration of PPI therapy required to establish a diagnosis of PPI-refractory GERD symptoms, but most authorities do not consider patients "PPI-refractory" unless they have been on double-dose PPIs. This article discusses the mechanisms that might underlie heartburn that does not respond PPIs and an approach to the management of patients with PPI-refractory GERD symptoms.
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Affiliation(s)
- Stuart Jon Spechler
- Division of Gastroenterology, Center for Esophageal Diseases, Baylor University Medical Center, Center for Esophageal Research, Baylor Scott & White Research Institute, 3500 Gaston Avenue, 2 Hoblitzelle, Suite 250, Dallas, TX 75246, USA.
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9
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Spechler SJ. Refractory Gastroesophageal Reflux Disease and Functional Heartburn. Gastrointest Endosc Clin N Am 2020; 30:343-359. [PMID: 32146950 DOI: 10.1016/j.giec.2019.12.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This report discusses the potential mechanisms that might underlie refractory GERD and functional heartburn, and how to distinguish among those mechanisms using a systematic evaluation that includes careful medical history, endoscopy with esophageal biopsy, esophageal manometry, and esophageal multichannel intraluminal impedance-pH monitoring. The report provides an approach to patient management that depends on the underlying mechanism identified by this systematic evaluation.
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Affiliation(s)
- Stuart Jon Spechler
- Division of Gastroenterology, Center for Esophageal Diseases, Baylor University Medical Center at Dallas, The Center for Esophageal Research, Baylor Scott & White Research Institute, 3500 Gaston Avenue, 2 Hoblitzelle, Suite 250, Dallas, TX 75246, USA.
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10
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Morozova YN, Pogromov AP, Mnatsakanyan MG, Tashchyan OV, Kolosova KY. Esophageal disorders in patients with irritable bowel syndrome. TERAPEVT ARKH 2020; 92:19-23. [DOI: 10.26442/00403660.2020.02.000483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Indexed: 11/22/2022]
Abstract
Aim.To study the whole range of esophageal disorders in patients with irritable bowel syndrome (IBS) using high-tech methods.
Materials and methods.102 IBS patients (47 males, mean age 40.8, diagnosis of IBS was established according to Rome III criteria) with esophageal symptoms (heartburn, belching, globus sensation and noncardiac chest pain) were examined in gastroenterology department. All patients underwent endoscopy, with biopsies if required, X-ray examination of upper gastrointestinal tract; 24-hour pH-impedance monitoring;13C-urea breath test. Evaluation of esophageal symptoms was carried out on the basis of Rome IV criteria.
Results.21 (20.6%) individuals had esophagitis (ERD). According to 24-hour pH-monitoring data, 7 of them had overlap between GERD and functional esophageal disorders (FED). 27 (26.5%) individuals had nonerosive reflux disease (NERD). In 54 (52.9%) individuals endoscopy and pH-impedance monitoring data did not differ from normal, suggesting this group as group of patients with FED. There was no significant difference for age, sex and IBS subtypes in GERD, NERD and FED groups.
Conclusion.Comorbid esophageal disorders in patients with IBS are different and represented by organic diseases, FED and overlap between them. Methods such as 24-h pH-impedance measurement and esophageal manometry should be used to assess comorbid esophageal disorders in IBS patients.
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11
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Fass R, Shibli F, Tawil J. Diagnosis and Management of Functional Chest Pain in the Rome IV Era. J Neurogastroenterol Motil 2019; 25:487-498. [PMID: 31587539 PMCID: PMC6786446 DOI: 10.5056/jnm19146] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 08/07/2019] [Indexed: 12/13/2022] Open
Abstract
Functional chest pain accounts for about a third of the patients with noncardiac chest pain. It is a very common functional esophageal disorder that remains even today a management challenge to the practicing physician. Based on the definition offered by the Rome IV criteria, diagnosis of functional chest pain requires a negative workup of noncardiac chest pain patients that includes, proton pump inhibitor test or empirical proton pump inhibitor trial, endoscopy with esophageal mucosal biopsies, reflux testing, and esophageal manometry. The mainstay of treatment are neuromodulators that are primarily composed of anti-depressants. Alternative medicine and psychological interventions may be provided alone or in combination with other therapeutic modalities.
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Affiliation(s)
- Ronnie Fass
- The Esophageal and Swallowing Center, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH, USA
| | - Fahmi Shibli
- The Esophageal and Swallowing Center, MetroHealth Medical Center and Case Western Reserve University, Cleveland, OH, USA
| | - Jose Tawil
- Departamento de Trastornos Funcionales Digestivos, Gedyt-Gastroenterología Diagnóstica y Terapéutica, BuenosAires, Argentina
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Reflux esophagitis, functional and non-functional. Best Pract Res Clin Gastroenterol 2019; 40-41:101649. [PMID: 31594653 DOI: 10.1016/j.bpg.2019.101649] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Revised: 08/07/2019] [Accepted: 08/12/2019] [Indexed: 01/31/2023]
Abstract
The pathogenesis of gastroesophageal reflux disease has been explained by acid-peptic model. However, related with the progress of the diagnostic modalities, another phenotypical group of patients were defined and called "functional disorders of the esophagus". These patients are important because diagnosis is particularly difficult, co-morbid disorders especially psychiatric diseases are common, proton pump inhibitor response is low, and surgical results are very poor. Simpler and translational science studies are required in functional groups in order to differentiate from acid-peptic disorders. New and more accurate diagnostic modalities as well as therapeutic approaches are strongly needed in this particularly new and exciting era, especially in the effect of neuromodulators. Current diagnostic modalities should also be evaluated and in fact, normal values should be established. New medications, especially acting at the level of esophageal epithelium and intercellular spaces, might shift the paradigm.
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Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis JM, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García ES. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:344-356. [PMID: 31239096 DOI: 10.1016/j.rgmx.2019.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/26/2019] [Accepted: 04/30/2019] [Indexed: 06/09/2023]
Abstract
Proton pump inhibitors are the reference standards for the treatment of acid-related diseases. Acid suppression in gastroesophageal reflux disease is associated with a high rate of mucosal cicatrization, but symptom response differs among endoscopic phenotypes. Extraesophageal manifestations have a good clinical response in patients that present with abnormal acid exposure (diagnostic test) in the esophagus. Proton pump inhibitors have shown their effectiveness for reducing symptom intensity in nighttime reflux and sleep disorders, improving quality of life and work productivity. That can sometimes be achieved through dose modifications by splitting or increasing the dose, or through galenic formulation. Proton pump inhibitors are not exempt from controversial aspects related to associated adverse events. Technological development is directed at improving proton pump inhibitor performance through increasing the half-life, maximum concentration, and area under the curve of the plasma concentrations through galenic formulation, as well as creating safer and more tolerable drugs. The present review is focused on the mechanisms of action, pharmacokinetic properties, and technological advances for increasing the pharmacologic performance of a proton pump inhibitor.
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Affiliation(s)
- S Sobrino-Cossío
- Hospital Ángeles del Pedregal, Ciudad de México, México; Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México.
| | - O Teramoto-Matsubara
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Centro Médico ABC, Ciudad de México, México
| | - G Mateos-Pérez
- Hospital Ángeles del Pedregal, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J M Abdo-Francis
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital Ángeles Acoxpa, Ciudad de México, México
| | - J Tawil
- Departamento de Trastornos Funcionales Digestivos, Gedyt-Gastroenterología Diagnóstica y Terapéutica, Buenos Aires, Argentina
| | - C Olguín-Ramírez
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México
| | - A Orozco-Gamiz
- Gastrolab Laboratorio de Fisiología Gastrointestinal, Guadalajara, Jalisco, México
| | - E S Galvis-García
- Gástrica, Centro Avanzado en Endoscopia y Estudios Funcionales, Ciudad de México, México; Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
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14
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Sobrino-Cossío S, Teramoto-Matsubara O, Mateos-Pérez G, Abdo-Francis J, Tawil J, Olguín-Ramírez C, Orozco-Gamiz A, Galvis-García E. In search of the grail: A race for acid suppression. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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15
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Cannata’ A, Artico J, De Paris V, Cristallini J, Gentile P, Naso P, Ortis B, Fabris E, Sinagra G. Thoracic Pain: Clinical Features. PAIN IMAGING 2019:159-170. [DOI: 10.1007/978-3-319-99822-0_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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16
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17
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Duricek M, Nosakova L, Zatko T, Pecova R, Hyrdel R, Banovcin P. Cough reflex sensitivity does not correlate with the esophageal sensitivity to acid in patients with gastroesophageal reflux disease. Respir Physiol Neurobiol 2018; 257:25-29. [DOI: 10.1016/j.resp.2018.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 03/17/2018] [Accepted: 03/21/2018] [Indexed: 01/23/2023]
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18
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Heinrich H, Sweis R. The role of oesophageal physiological testing in the assessment of noncardiac chest pain. Ther Adv Chronic Dis 2018; 9:257-267. [PMID: 30719270 PMCID: PMC6348533 DOI: 10.1177/2040622318791392] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 05/14/2018] [Indexed: 12/15/2022] Open
Abstract
Oesophageal physiology testing plays an important role in the diagnosis of noncardiac chest pain (NCCP) after cardiac, structural and mucosal abnormalities have been ruled out. Endoscopy can establish the presence of structural causes of chest pain such as cancer, oesophageal webs and diverticula. Even if macroscopically normal, eosinophilic oesophagitis is a common cause of chest pain and needs to be ruled out with an adequate biopsy regimen. In the remaining cases, diagnosis is focused on the identification of often subtle mechanisms that lead to NCCP. The most common oesophageal aetiologies for NCCP are gastro-oesophageal reflux disease (GORD), oesophageal dysmotility and functional chest pain. Ambulatory pH studies (with or without impedance or wireless measurements) can establish the presence of GORD, nonerosive reflux as well any association with symptoms of chest pain. High-resolution manometry, particularly with the inclusion of adjunctive testing, can rule out major motility disorders such as spasm, hypercontraction or achalasia. The EndoFLIP device can help define disorders with reduced distensibility, not easily appreciated with endoscopy or manometry. When all tests remain negative, a diagnosis of oesophageal hypersensitivity is normally made and therapy is shifted from targeting a disease to treating symptoms and patient affect.
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Affiliation(s)
- Henriette Heinrich
- University Hospital Zuerich, Department for Gastroenterology and Hepatology, Zuerich, Switzerland St Claraspital, Bauchzentrum, Basel, Switzerland
| | - Rami Sweis
- GI Services, University College London Hospital, Ground floor west, 250 Euston Road, London, NW1 2 PG, London, UK
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19
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Sinclair CF, Téllez MJ, Ulkatan S. Human laryngeal sensory receptor mapping illuminates the mechanisms of laryngeal adductor reflex control. Laryngoscope 2018; 128:E365-E370. [PMID: 30194722 DOI: 10.1002/lary.27248] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/30/2018] [Indexed: 11/12/2022]
Affiliation(s)
| | - Maria J. Téllez
- Department of Intraoperative Neurophysiology; Mount Sinai West Hospital; New York New York U.S.A
| | - Sedat Ulkatan
- Department of Intraoperative Neurophysiology; Mount Sinai West Hospital; New York New York U.S.A
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20
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Gregersen H, Lo KM. What Is the Future of Impedance Planimetry in Gastroenterology? J Neurogastroenterol Motil 2018; 24:166-181. [PMID: 29605974 PMCID: PMC5885717 DOI: 10.5056/jnm18013] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/09/2018] [Indexed: 12/13/2022] Open
Abstract
The gastrointestinal (GI) tract is efficient in transporting ingested material to the site of delivery in healthy subjects. A fine balance exists between peristaltic forces, the mixing and delivery of the contents, and sensory signaling. This fine balance is easily disturbed by diseases. It is mandatory to understand the pathophysiology to enhance our understanding of GI disorders. The inaccessibility and complex nervous innervation, geometry and mechanical function of the GI tract make mechanosensory evaluation difficult. Impedance planimetry is a distension technology that assesses luminal geometry, mechanical properties including muscle dynamics, and processing of nociceptive signals from the GI tract. Since standardized models do not exist for GI muscle function in vivo, models, concepts, and terminology must be borrowed from other medical fields such as cardiac mechanophysiology. The review highlights the impedance planimetric technology, muscle dynamics assessment, and 3 applied technologies of impedance planimetry. These technologies are the multimodal probes that assesses sensory function, the functional luminal imaging probe that dynamically measures the geometry of the lumen it distends, and Fecobionics that is a simulated feces providing high-resolution measurements during defecation. The advanced muscle analysis and 3 applied technologies can enhance the quality of future interdisciplinary research for gaining more knowledge about mechanical function, sensory-motor disorders, and symptoms. This is a step in the direction of individualized treatment for GI disorders based on diagnostic subtyping. There seems to be no better alternatives to impedance planimetry, but only the functional luminal imaging probe is currently commercially available. Wider use depends on commercialization of the multimodal probe and Fecobionics.
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Affiliation(s)
- Hans Gregersen
- GIOME, Department of Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong.,California Medical Innovations Institute, San Diego, California, USA
| | - Kar Man Lo
- GIOME Doublecove, Wu Kai Sha, New Territories, Hong Kong
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21
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Luk SWY, Chiu PWY. Surgical Treatment for Gastroesophageal Reflux Disease (GERD) in Asia. THE RISE OF ACID REFLUX IN ASIA 2018:113-122. [DOI: 10.1007/978-81-322-0846-4_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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22
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Tack J, Pandolfino JE. Pathophysiology of Gastroesophageal Reflux Disease. Gastroenterology 2018; 154:277-288. [PMID: 29037470 DOI: 10.1053/j.gastro.2017.09.047] [Citation(s) in RCA: 209] [Impact Index Per Article: 29.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 09/07/2017] [Accepted: 09/08/2017] [Indexed: 12/13/2022]
Abstract
The pathogenesis of gastroesophageal reflux disease (GERD) is complex and involves changes in reflux exposure, epithelial resistance, and visceral sensitivity. The gastric refluxate is a noxious material that injures the esophagus and elicits symptoms. Esophageal exposure to gastric refluxate is the primary determinant of disease severity. This exposure arises via compromise of the anti-reflux barrier and reduced ability of the esophagus to clear and buffer the refluxate, leading to reflux disease. However, complications and symptoms also occur in the context of normal reflux burden, when there is either poor epithelial resistance or increased visceral sensitivity. Reflux therefore develops via alterations in the balance of aggressive and defensive forces.
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Affiliation(s)
- Jan Tack
- Translational Research Center for Gastrointestinal Disorders, University of Leuven, Belgium.
| | - John E Pandolfino
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Yamasaki T, Tomita T, Takimoto M, Kondo T, Tozawa K, Ohda Y, Oshima T, Fukui H, Watari J, Miwa H. Intravenous Corticotropin-releasing Hormone Administration Increases Esophageal Electrical Sensitivity in Healthy Individuals. J Neurogastroenterol Motil 2017; 23:526-532. [PMID: 28992676 PMCID: PMC5628984 DOI: 10.5056/jnm17067] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2017] [Revised: 07/12/2017] [Accepted: 08/16/2017] [Indexed: 12/13/2022] Open
Abstract
Background/Aims When a person is experiencing stress, corticotropin-releasing hormone (CRH) can modulate gut physiologies, such as visceral sensation or gastrointestinal motility, and its intravenous administration mimics stress-induced physiological changes. However, the influence of CRH on the esophagus is yet unknown. Accordingly, we investigated whether intravenous CRH administration increases esophageal sensitivity to electrical stimulation in healthy Japanese subjects. Methods Twenty healthy subjects were recruited. We quantified the initial perception threshold (IPT) every 15 minutes after CRH injection. Venous blood was collected with a cannula, and both plasma adrenocorticotropic hormone (ACTH) and cortisol were measured at pre-stimulation, 0, 30, 60, 90, and 120 minutes. The results from each time point were compared against a baseline IPT obtained before electrical stimulation was initiated. Results When compared to the baseline IPT value (16.9 ± 4.5), CRH significantly decreased electrical threshold of the esophagus at 30, 45, 60, 75 minutes (14.1 ± 4.2, 13.1 ± 5.0, 12.1 ± 5.7, 14.0 ± 5.8 minutes, P 〈 0.01, respectively) after CRH injection, suggesting that CRH increased esophageal sensitivity to the electrical stimulus. CRH also significantly increased plasma ACTH levels at 30 minutes (50.3 ± 17.7, P 〈 0.01), and cortisol levels at 30 minutes (22.0 ± 6.7 minutes, P 〈 0.01) and 60 minutes (20.3 ± 6.7 minutes, P 〈 0.01) after CRH injection, when compared to the pre-stimulation ACTH and cortisol values. Conclusion Intravenous CRH administration increased esophageal electrical sensitivity in normal subjects, emphasizing the important role of stress in esophageal sensitivity.
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Affiliation(s)
- Takahisa Yamasaki
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Mayu Takimoto
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Takashi Kondo
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Katsuyuki Tozawa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Yoshio Ohda
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Jiro Watari
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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24
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Kondo T, Sei H, Yamasaki T, Tomita T, Ohda Y, Oshima T, Fukui H, Watari J, Miwa H. A novel prostanoid EP1 receptor antagonist, ONO-8539, reduces acid-induced heartburn symptoms in healthy male volunteers: a randomized clinical trial. J Gastroenterol 2017; 52:1081-1089. [PMID: 28120127 DOI: 10.1007/s00535-017-1308-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 01/11/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND Patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) have unmet clinical needs. Recently, we reported that esophageal prostaglandin E2 (PGE2) plays a crucial role in the generation of heartburn. In the present study, we focused on the PGE2 receptor, EP1, and investigated the effects of ONO-8539, a novel EP1 receptor antagonist, on heartburn symptoms in healthy male volunteers. METHODS This prospective, double-blind, placebo-controlled, two-period crossover study was performed in 20 healthy male subjects. The novel prostanoid EP1 receptor antagonist, ONO-8539 (450 mg), was administered once 4 h prior to acid perfusion test. During the test, hydrochloric acid (0.15 mol l-1) was perfused into the lower esophagus for 30 min. Acid perception threshold was quantified by the time to first sensation of heartburn and intensity of GI symptoms determined using a validated categorical rating scale, and the area under the curve (AUC) as the total symptom score. RESULTS ONO-8539 significantly reduced a total heartburn symptom score, not other upper GI symptom scores, during acid perfusion compared with placebo (AUC for heartburn, 85.0 ± 10.6 for placebo and 56.5 ± 7.2 for ONO-8539; P < 0.01), and significantly extended the time to first sensation of heartburn compared with placebo (5.7 ± 4.3 min for placebo and 9.7 ± 7.2 min for ONO-8539; P < 0.05). CONCLUSIONS ONO-8539 attenuated acid-induced heartburn in healthy male subjects, suggesting that EP1 receptors play a role in generation of heartburn symptoms. ONO-8539 is a potential novel therapeutic option for controlling heartburn symptoms in GERD patients. Clinical Trials Registry No: UMIN000015753.
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Affiliation(s)
- Takashi Kondo
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroo Sei
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Takahisa Yamasaki
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yoshio Ohda
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Jiro Watari
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
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Abstract
Functional heartburn (FH) is defined as a functional esophageal disorder characterized by symptoms of chronic heartburn with no apparent correlation to acid or nonacid reflux. In addition, its symptoms persist despite the lack of organic abnormalities or inflammation, esophageal motility disorders, or metabolic disorders. Although conditions presenting with esophageal symptoms without endoscopic abnormalities were previously categorized as nonerosive reflux disease, such conditions are now classified into 3 categories under Rome IV criteria: nonerosive reflux disease, reflux hypersensitivity, and FH. Although many aspects of FH remain unclear, its onset mechanism is considered to be strongly associated with peripheral or central sensitization, given the fact that its symptoms seem to be unrelated to gastroesophageal reflux. In addition, the cause of such hypersensitivity is an interesting topic in itself, and psychological factors, such as stress followed by increasing esophageal permeability are gaining attention as factors that can potentially influence this condition. There is a great unmet clinical need for therapeutic drugs that can be used to treat FH, and the development of novel drugs, diagnostic tests and biomarkers is eagerly awaited.
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26
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Weijenborg PW, Smout AJPM, Krishnadath KK, Bergman JGHM, Verheij J, Bredenoord AJ. Esophageal sensitivity to acid in patients with Barrett's esophagus is not related to preserved esophageal mucosal integrity. Neurogastroenterol Motil 2017; 29. [PMID: 28370911 DOI: 10.1111/nmo.13066] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2016] [Accepted: 02/19/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with Barrett's esophagus (BE) usually have severe gastroesophageal reflux. However, they often have surprisingly few reflux symptoms. We hypothesized that BE patients are less sensitive to acid than gastroesophageal reflux disease (GERD) patients without Barrett and that this is due to an unusual preservation of mucosal integrity of the squamous epithelium prohibiting transepithelial acid diffusion. METHODS We prospectively analyzed esophageal sensitivity and esophageal mucosal integrity in GERD patients with and without BE and healthy subjects. An acid perfusion test was performed and mucosal integrity was assessed in vivo by electrical tissue impedance spectroscopy and ex vivo by Ussing chamber experiments with biopsy specimens. KEY RESULTS Gastroesophageal reflux disease patients with BE were less sensitive to acid than GERD patients without BE, but more sensitive to acid than healthy controls (time to perception Barrett's 14.0 minutes, GERD 4.6 minutes, controls 17.5 minutes). However, extracellular impedance (6.2 and 5.7 vs 8.4×103 Ω/m) and transepithelial resistance (94.0 and 89 vs 118 Ω/cm2 ) was similar in BE and GERD patients and significantly lower than in healthy subjects. Transepithelial fluorescein flux was equally increased in GERD patients with and without BE (1.6 and 1.7×103 vs 0.6×103 nmol/cm2 /h). CONCLUSIONS & INFERENCES Esophageal hypersensitivity to acid is less pronounced in BE patients than in GERD patients without Barrett. However, mucosal integrity of the squamous epithelium is equally impaired in GERD patients with and without Barrett, indicating that factors other than esophageal mucosal barrier integrity explain the difference in acid sensitivity between those with BE and those without.
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Affiliation(s)
- P W Weijenborg
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - A J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - K K Krishnadath
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - J G H M Bergman
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - J Verheij
- Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
| | - A J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
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Psychological Comorbidity and Chronic Heartburn: Which Is the Chicken and Which Is the Egg? Dig Dis Sci 2017; 62:823-825. [PMID: 28205110 DOI: 10.1007/s10620-017-4475-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Accepted: 01/24/2017] [Indexed: 12/09/2022]
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Abstract
The Rome IV diagnostic criteria delineates 5 functional esophageal disorders which include functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia. These are a heterogenous group of disorders which, despite having characteristic symptom profiles attributable to esophageal pathology, fail to demonstrate any structural, motility or inflammatory abnormalities on standard clinical testing. These disorders are associated with a marked reduction in patient quality of life, not least considerable healthcare resources. Furthermore, the pathophysiology of these disorders is incompletely understood. In this narrative review we provide the reader with an introductory primer to the structure and function of esophageal perception, including nociception that forms the basis of the putative mechanisms that may give rise to symptoms in functional esophageal disorders. We also discuss the provocative techniques and outcome measures by which esophageal hypersensitivity can be established.
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29
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Lottrup C, Krarup AL, Gregersen H, Ejstrud P, Drewes AM. Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett's Esophagus Than in Healthy Controls. J Neurogastroenterol Motil 2016; 22:630-642. [PMID: 27557545 PMCID: PMC5056572 DOI: 10.5056/jnm16019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Revised: 05/09/2016] [Accepted: 05/18/2016] [Indexed: 01/15/2023] Open
Abstract
Background/Aims Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett’s esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett’s esophagus to that in healthy controls. Methods A total of 26 patients with histology-confirmed Barrett’s esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. Results Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pH-measurement and acid clearance test were not correlated (all P > 0.3). Conclusions More frequent swallowing and thus faster acid clearance in Barrett’s esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes.
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Affiliation(s)
- Christian Lottrup
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Medicine, Vendsyssel Hospital, Hjørring, Denmark
| | - Anne L Krarup
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Medicine, Vendsyssel Hospital, Hjørring, Denmark
| | - Hans Gregersen
- GIOME, Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong SAR
| | - Per Ejstrud
- Department of Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Asbjørn M Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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31
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Brock C, Gregersen H, Gyawali CP, Lottrup C, Furnari M, Savarino E, Novais L, Frøkjaer JB, Bor S, Drewes AM. The sensory system of the esophagus--what do we know? Ann N Y Acad Sci 2016; 1380:91-103. [DOI: 10.1111/nyas.13205] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Revised: 07/19/2016] [Accepted: 07/19/2016] [Indexed: 12/13/2022]
Affiliation(s)
- Christina Brock
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute; Aalborg University; Aalborg Denmark
| | - Hans Gregersen
- GIOME and the Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering; Chongqing University; Chongqing China
| | - C. Prakash Gyawali
- Division of Gastroenterology; Washington University School of Medicine; St. Louis Missouri
| | - Christian Lottrup
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute; Aalborg University; Aalborg Denmark
- Department of Medicine; North Jutland Regional Hospital; Hjørring Denmark
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine; University of Genoa; Genoa Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology; University of Padua; Padua Italy
| | - Luis Novais
- Neurogastroenterology and Gastrointestinal Motility Laboratory, Nova Medical School; Universidade Nova de Lisboa; Lisbon Portugal
| | - Jens Brøndum Frøkjaer
- Mech-Sense, Department of Radiology, Aalborg University Hospital and Clinical Institute; Aalborg University; Aalborg Denmark
| | - Serhat Bor
- Department of Gastroenterology; Ege University School of Medicine; Bornova Izmir Turkey
| | - Asbjørn Mohr Drewes
- Mech-Sense, Department of Gastroenterology & Hepatology, Aalborg University Hospital and Clinical Institute; Aalborg University; Aalborg Denmark
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Farmer AD, Brock C, Frøkjaer JB, Gregersen H, Khan S, Lelic D, Lottrup C, Drewes AM. Understanding the sensory irregularities of esophageal disease. Expert Rev Gastroenterol Hepatol 2016; 10:907-14. [PMID: 26890720 DOI: 10.1586/17474124.2016.1155984] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Symptoms relating to esophageal sensory abnormalities can be encountered in the clinical environment. Such sensory abnormalities may be present in demonstrable disease, such as erosive esophagitis, and in the ostensibly normal esophagus, such as non-erosive reflux disease or functional chest pain. In this review, the authors discuss esophageal sensation and the esophageal pain system. In addition, the authors provide a primer concerning the techniques that are available for investigating the autonomic nervous system, neuroimaging and neurophysiology of esophageal sensory function. Such technological advances, whilst not readily available in the clinic may facilitate the stratification and individualization of therapy in disorders of esophageal sensation in the future.
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Affiliation(s)
- Adam D Farmer
- a Mech-Sense , University Hospital Aalborg , Aalborg , Denmark.,b Centre for Digestive Diseases, Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and the London School of Medicine & Dentistry, Queen Mary University of London , London , UK.,c Department of Gastroenterology , University Hospitals of North Midlands , Stoke on Trent , UK
| | - Christina Brock
- a Mech-Sense , University Hospital Aalborg , Aalborg , Denmark
| | - Jens Brøndum Frøkjaer
- a Mech-Sense , University Hospital Aalborg , Aalborg , Denmark.,d Department of Radiology , Aalborg University Hospital , Aalborg , Denmark
| | - Hans Gregersen
- e GIOME, Key Laboratory for Biorheological Science and Technology , College of Bioengineering, Chongqing University , Chongqing , China
| | - Sheeba Khan
- c Department of Gastroenterology , University Hospitals of North Midlands , Stoke on Trent , UK
| | - Dina Lelic
- a Mech-Sense , University Hospital Aalborg , Aalborg , Denmark
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Gastroesophageal reflux disease-related and functional heartburn: pathophysiology and treatment. Curr Opin Gastroenterol 2016; 32:344-52. [PMID: 27206157 DOI: 10.1097/mog.0000000000000282] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Patients who continue to experience heartburn symptoms despite adequate-dose proton pump inhibitor therapy have unmet clinical needs. In this review, we focus on the most recent findings related to the mechanism of heartburn symptom generation, and on the treatment of gastroesophageal reflux disease-related and functional heartburn. RECENT FINDINGS The immunological mechanism in the esophageal mucosa has been addressed as a potential mechanism of the onset of esophageal mucosa damage and the generation of heartburn symptoms. Peripheral or central hypersensitivity in viscera is a potentially unifying pathophysiological concept in functional heartburn. Vonoprazan, a novel and potent first-in-class potassium-competitive acid blocker, is expected to prove useful in the treatment of reflux disease. SUMMARY New findings in the mechanisms of heartburn symptom generation are emerging, including the immunological mediation of esophageal mucosal damage and the development of visceral hypersensitivity in functional heartburn. In the future, we anticipate the emergence of new and specific therapeutic options based on these mechanisms, with less dependence on acid-suppressing agents.
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van Hoeij FB, Weijenborg PW, van den Bergh Weerman MA, van den Wijngaard RMJGJ, Verheij J, Smout AJPM, Bredenoord AJ. Mucosal integrity and sensitivity to acid in the proximal esophagus in patients with gastroesophageal reflux disease. Am J Physiol Gastrointest Liver Physiol 2016; 311:G117-22. [PMID: 27198192 DOI: 10.1152/ajpgi.00134.2016] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 05/15/2016] [Indexed: 01/31/2023]
Abstract
Acid reflux episodes that extend to the proximal esophagus are more likely to be perceived. This suggests that the proximal esophagus is more sensitive to acid than the distal esophagus, which could be caused by impaired mucosal integrity in the proximal esophagus. Our aim was to explore sensitivity to acid and mucosal integrity in different segments of the esophagus. We used a prospective observational study, including 12 patients with gastroesophageal reflux disease (GERD). After stopping acid secretion-inhibiting medication, two procedures were performed: an acid perfusion test and an upper endoscopy with electrical tissue impedance spectroscopy and esophageal biopsies. Proximal and distal sensitivity to acid and tissue impedance were measured in vivo, and mucosal permeability and epithelial intercellular spaces at different esophageal levels were measured in vitro. Mean lag time to heartburn perception was much shorter after proximal acid perfusion (0.8 min) than after distal acid perfusion (3.9 min) (P = 0.02). Median in vivo tissue impedance was significantly lower in the distal esophagus (4,563 Ω·m) compared with the proximal esophagus (8,170 Ω·m) (P = 0.002). Transepithelial permeability, as measured by the median fluorescein flux was significantly higher in the distal (2,051 nmol·cm(-2)·h(-1)) than in the proximal segment (368 nmol·cm(-2)·h(-1)) (P = 0.033). Intercellular space ratio and maximum heartburn intensity were not significantly different between the proximal and distal esophagus. In GERD patients off acid secretion-inhibiting medication, acid exposure in the proximal segment of the esophagus provokes symptoms earlier than acid exposure in the distal esophagus, whereas mucosal integrity is impaired more in the distal esophagus. These findings indicate that the enhanced sensitivity to proximal reflux episodes is not explained by increased mucosal permeability.
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Affiliation(s)
- Froukje B van Hoeij
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and
| | - Pim W Weijenborg
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and
| | | | - René M J G J van den Wijngaard
- Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and
| | - J Verheij
- Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands;
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35
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Turan I, Kitapcioglu G, Tavmergen Goker E, Sahin G, Bor S. In vitro fertilization-induced pregnancies predispose to gastroesophageal reflux disease. United European Gastroenterol J 2016; 4:221-8. [PMID: 27087950 DOI: 10.1177/2050640615597836] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2015] [Accepted: 07/05/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Women conceiving following in vitro fertilization (IVF) likely have a variety of risk factors that predispose them to gastroesophageal reflux disease (GERD) in the future. OBJECTIVE We aimed to investigate whether pregnancy through IVF may predispose to subsequent GERD compared with pregnancies without IVF. We also evaluate whether twin IVF pregnancies lead to additional risk for having GERD compared with singleton IVF pregnancies. METHODS A validated reflux questionnaire was administered to 156 women with singleton (n = 102) or twin (n = 54) IVF birth (IVF group) and 111 women with a naturally conceived singleton birth (control group). All women included in the study were primiparas who had given birth at least 1 year prior to data collection. The diagnosis of GERD was based on the occurrence of typical symptoms (heartburn, regurgitation, or both) at least once a week. RESULTS The prevalence of GERD was 13.5% and 4.5% in IVF and control groups (p = 0.015); in the IVF group, this was slightly higher, but not statistically significant, in women with twin compared with singleton pregnancies (14.8% vs. 12.7%, p = 0.749). Logistic regression analysis showed that IVF was strongly associated with subsequent GERD (OR, 3.30; 95% CI 1.20-9.04; p = 0.02). CONCLUSION The risk of developing GERD at least 1 year after delivery increased following IVF. Long-term follow-up studies are required to determine whether therapy during pregnancy can prevent this risk.
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Affiliation(s)
- Ilker Turan
- Section of Gastroenterology, Ege University School of Medicine, Izmir, Turkey
| | - Gul Kitapcioglu
- Department of Biostatistics, Ege University School of Medicine, Izmir, Turkey
| | - Ege Tavmergen Goker
- Department of Obstetrics and Gynecology, Ege University School of Medicine, Izmir, Turkey; Family Planning and Infertility Treatment and Research Center, Ege University School of Medicine, Izmir, Turkey
| | - Gulnaz Sahin
- Family Planning and Infertility Treatment and Research Center, Ege University School of Medicine, Izmir, Turkey
| | - Serhat Bor
- Section of Gastroenterology, Ege University School of Medicine, Izmir, Turkey
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Lee K, Kwon HJ, Kim IY, Yoo KH, Lee S, Min YW, Rhee PL. Esophageal Mast Cell Infiltration in a 32-Year-Old Woman with Noncardiac Chest Pain. Gut Liver 2016; 10:152-5. [PMID: 26087786 PMCID: PMC4694748 DOI: 10.5009/gnl14294] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 11/30/2014] [Accepted: 01/02/2015] [Indexed: 12/13/2022] Open
Abstract
Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.
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Affiliation(s)
- Keol Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Hee Jin Kwon
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - In Young Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Kwai Han Yoo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Seulkee Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
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37
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Radulovic M, Schilero GJ, Yen C, Bauman WA, Wecht JM, Ivan A, La Fountaine MF, Korsten MA. Greatly increased prevalence of esophageal dysmotility observed in persons with spinal cord injury. Dis Esophagus 2015; 28:699-704. [PMID: 25224683 DOI: 10.1111/dote.12272] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The effects of spinal cord injury (SCI) on esophageal motility are largely unknown. Furthermore, due to the complete or partial loss of sensory innervation to the upper gastrointestinal tract, a symptom-based diagnosis of esophageal dysmotility is problematic in the SCI population. To determine the prevalence and characterize the type of motility disorders observed in persons with chronic SCI compared with that of able-bodied (AB) controls based on esophageal pressure topography isometrics acquired by high-resolution manometry and categorized by application of the Chicago Classification. High-resolution manometry of the esophagus was performed in 39 individuals: 14 AB, 12 with paraplegia (level of injury between T4-T12) and 13 with tetraplegia (level of injury between C5-C7). A catheter containing multiple pressure sensors arranged at 360° was introduced into the esophagi of subjects at a distance that allowed visualization of both the upper esophageal sphincters (UES) and lower esophageal sphincters (LES). After a period to acquire pressures at baseline, subjects were asked to perform 10 wet swallows with 5-mL boluses of isotonic saline while esophageal pressure and impedance were being recorded. No significant differences were noted for gender, age, or body mass index between AB and SCI groups. Twenty-one of 25 (84%) subjects with SCI had at least one motility abnormality: 12% with Type II achalasia, 4% with Type III achalasia, 20% with esophagogastric junction outflow obstruction, 4% with the hypercontractile esophagus, and 48% with peristaltic abnormalities (weak peristalsis with small or large defects or frequent failed peristalsis). In contrast, only 7% (1 out of 14) of the AB subjects had any type of esophageal motility disorder. Despite the lack of subjective complaints and clinical awareness, esophageal dysmotility appears to be a highly prevalent condition in persons with SCI. The use of new and improved techniques, as well as a more stringent classification system, permitted the identification of the presence of nonspecific motility disorders in almost all SCI subjects, including four individuals who were previously undiagnosed with achalasia. Future work in persons with SCI is required to clarify the clinical impact of this observation and to study potential associations between esophageal dysmotility, gastroesophageal reflux disease, and pulmonary function. An increased awareness of esophageal dysfunction in the SCI population may lead to the development of new clinical guidelines for the diagnosis, prevention, and treatment of these largely unrecognized disorders.
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Affiliation(s)
- M Radulovic
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,Medical Service, The James J. Peters VA Medical Center, Bronx, USA.,Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - G J Schilero
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,Medical Service, The James J. Peters VA Medical Center, Bronx, USA.,Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.,Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - C Yen
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA
| | - W A Bauman
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,Medical Service, The James J. Peters VA Medical Center, Bronx, USA.,Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA.,Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - J M Wecht
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,Department of Rehabilitation Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - A Ivan
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA
| | - M F La Fountaine
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,School of Health and Medical Sciences, Seton Hall University, Essex County, New Jersey, USA
| | - M A Korsten
- Rehabilitation Research & Development Service, National Center of Excellence for the Medical Consequences of Spinal Cord Injury, The James J. Peters VA Medical Center, Bronx, USA.,Medical Service, The James J. Peters VA Medical Center, Bronx, USA.,Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Kondo T, Oshima T, Tomita T, Fukui H, Okada H, Watari J, Miwa H. The Nonsteroidal Anti-inflammatory Drug Diclofenac Reduces Acid-Induced Heartburn Symptoms in Healthy Volunteers. Clin Gastroenterol Hepatol 2015; 13:1249-1255.e1. [PMID: 25632805 DOI: 10.1016/j.cgh.2015.01.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2014] [Revised: 12/31/2014] [Accepted: 01/06/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We investigated the effects of diclofenac, a nonsteroidal anti-inflammatory drug that inhibits prostaglandin production, on induction of esophageal sensation by acid perfusion in healthy men. METHODS We performed a prospective, double-blind, placebo-controlled, 2-period, cross-over study over 3 visits in 12 healthy men. Diclofenac was given 6 hours and 2 hours before an acid perfusion test. During the test, hydrochloric acid (0.15 mol/L) was perfused into the lower esophagus for 30 minutes; we evaluated upper gastrointestinal symptoms using a validated categoric rating scale. Then, we calculated and assessed the acid perfusion sensitivity score (APSS). Biopsy specimens were collected by endoscopy of the distal esophagus before and after acid perfusion; levels of prostaglandin E2 (PGE2) (pg/mg) were measured in the samples using an enzyme-linked immunosorbent assay. RESULTS Compared with placebo, diclofenac significantly reduced the APSS for heartburn (82.2 ± 12.2 for placebo and 47.5 ± 8.9 for diclofenac; P < .01). Of the upper gastrointestinal symptoms, only the APSS for heartburn was reduced significantly by diclofenac. Compared with placebo, diclofenac reduced the overproduction of PGE2 by esophageal tissues after acid perfusion (23.3 ± 5.2 for placebo and 11.4 ± 3.5 for diclofenac; P < .05). APSS correlated with the development of heartburn and esophageal levels of PGE2 (r = 0.53; P < .05 for heartburn vs PGE2). CONCLUSIONS Diclofenac attenuated acid-induced heartburn by inhibiting PGE2 overproduction in the esophagus. Esophageal PGE2 might be involved in producing heartburn symptoms. Clinical Trials Registry no: UMIN000014595.
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Affiliation(s)
- Takashi Kondo
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Tadayuki Oshima
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Toshihiko Tomita
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hirokazu Fukui
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroki Okada
- Minase Research Institute, Pharmacological Research Laboratories, Ono Pharmaceutical Co, Ltd, Osaka, Japan
| | - Jiro Watari
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroto Miwa
- Division of Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan.
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Bouwense SAW, de Vries M, Schreuder LTW, Olesen SS, Frøkjær JB, Drewes AM, van Goor H, Wilder-Smith OHG. Systematic mechanism-orientated approach to chronic pancreatitis pain. World J Gastroenterol 2015; 21:47-59. [PMID: 25574079 PMCID: PMC4284360 DOI: 10.3748/wjg.v21.i1.47] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Revised: 08/23/2014] [Accepted: 11/19/2014] [Indexed: 02/07/2023] Open
Abstract
Pain in chronic pancreatitis (CP) shows similarities with other visceral pain syndromes (i.e., inflammatory bowel disease and esophagitis), which should thus be managed in a similar fashion. Typical causes of CP pain include increased intrapancreatic pressure, pancreatic inflammation and pancreatic/extrapancreatic complications. Unfortunately, CP pain continues to be a major clinical challenge. It is recognized that ongoing pain may induce altered central pain processing, e.g., central sensitization or pro-nociceptive pain modulation. When this is present conventional pain treatment targeting the nociceptive focus, e.g., opioid analgesia or surgical/endoscopic intervention, often fails even if technically successful. If central nervous system pain processing is altered, specific treatment targeting these changes should be instituted (e.g., gabapentinoids, ketamine or tricyclic antidepressants). Suitable tools are now available to make altered central processing visible, including quantitative sensory testing, electroencephalograpy and (functional) magnetic resonance imaging. These techniques are potentially clinically useful diagnostic tools to analyze central pain processing and thus define optimum management approaches for pain in CP and other visceral pain syndromes. The present review proposes a systematic mechanism-orientated approach to pain management in CP based on a holistic view of the mechanisms involved. Future research should address the circumstances under which central nervous system pain processing changes in CP, and how this is influenced by ongoing nociceptive input and therapies. Thus we hope to predict which patients are at risk for developing chronic pain or not responding to therapy, leading to improved treatment of chronic pain in CP and other visceral pain disorders.
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40
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Min YW, Rhee PL. Noncardiac Chest Pain: Update on the Diagnosis and Management. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2015; 65:76-84. [DOI: 10.4166/kjg.2015.65.2.76] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
After excluding a cardiac cause, potent anti-reflux therapy should be administered to patients with non-cardiac chest pain since gastroesophageal reflux disease (GERD) is the most common underlying mechanism of this disorder. If GERD is an unlikely cause of patient's symptoms, an esophageal motor disorder should be excluded. Spastic motility disorders can be treated with a smooth muscle relaxant (such as calcium channel blocker, nitrate, or phosphodiesterase 5 inhibitors). Alternatively, spastic motility disorders may respond to anti-spasmodics, pain modulators, botulinum toxin injection into the distal esophagus, and/or surgery. Patients with functional chest pain have recently seen an expanded treatment armamentarium including medications such as trazadone, tricyclic anti-depressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, pregabalin, and/or ramelteon.
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Affiliation(s)
- Carla Maradey-Romero
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, Case Western Reserve University, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH, 44109-1998, USA
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42
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Abstract
Dramatic progress has been made over the past decade in the sophistication and availability of equipment to test esophageal motility and sensation. High-resolution esophageal manometry and impedance have moved from the research clinic into clinical practice. Some of the testing is costly and time consuming, and requires extensive experience to perform the testing and properly interpret the results. These sensory studies are valuable in the interpretation of clinical problems, and provide important research information. Clinicians should evaluate the research studies to advance their understanding of the pathophysiology of the esophagus.
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Affiliation(s)
- Salman Nusrat
- Section of Digestive Disease and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Philip B Miner
- Division of Gastroenterology, Department of Medicine, Oklahoma Foundation for Digestive Research, Oklahoma University School of Medicine, 525 Northwest 9th Street, Suite 325, Oklahoma City, OK 73102, USA.
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Tominaga K, Kato M, Takeda H, Shimoyama Y, Umegaki E, Iwakiri R, Furuta K, Sakurai K, Odaka T, Kusunoki H, Nagahara A, Iwakiri K, Furuta T, Murakami K, Miwa H, Kinoshita Y, Haruma K, Takahashi S, Watanabe S, Higuchi K, Kusano M, Fujimoto K, Arakawa T. A randomized, placebo-controlled, double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: the G-PRIDE study. J Gastroenterol 2014; 49:1392-405. [PMID: 24535455 DOI: 10.1007/s00535-013-0896-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2013] [Accepted: 10/02/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to investigate the efficacy of rikkunshito (RKT), a traditional Japanese medicine, combined with proton pump inhibitor (PPI) in patients with PPI-refractory non-erosive reflux disease (NERD). METHODS Patients with PPI-refractory NERD (n = 242) were randomly assigned to the RKT group [rabeprazole (10 mg/day) + RKT (7.5 g/t.i.d.) for 8 weeks] or the placebo group (rabeprazole + placebo). After the 4- and 8-week treatments, we assessed symptoms and quality of life (QOL) using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG), Gastrointestinal Symptom Rating Scale (GSRS), and Short-Form Health Survey-8 (SF-8). RESULTS There were no significant differences in FSSG and GSRS score improvement between these groups after the 4- and 8-week treatments. The mental component summary (MCS) scores of the SF-8 improved more in the RKT group (from 45.8 ± 8.1 to 48.5 ± 7.4) than in the placebo group (from 47.7 ± 7.1 to 48.4 ± 7.5) after the 4-week treatment (P < 0.05). The 8-week treatment with RKT was more effective for improvement of the degree of MCS score in patients with a low body mass index (<22) (P < 0.05) and significantly improved the acid-related dysmotility symptoms of FSSG in female and elderly patients (≥ 65 years). CONCLUSION There were no significant differences in improvement of GERD symptoms in patients with PPI-refractory NERD between these groups. However, RKT may be useful for improving mental QOL in non-obese patients and acid-related dyspeptic symptoms, especially in women and the elderly.
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Affiliation(s)
- Kazunari Tominaga
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, Japan
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Emerenziani S, Ribolsi M, Guarino MPL, Balestrieri P, Altomare A, Rescio MP, Cicala M. Acid reflux episodes sensitize the esophagus to perception of weakly acidic and mixed reflux in non-erosive reflux disease patients. Neurogastroenterol Motil 2014; 26:108-14. [PMID: 24118616 DOI: 10.1111/nmo.12239] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 08/29/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND Non-erosive reflux disease (NERD) patients are more sensitive than erosive esophagitis patients to weakly acidic reflux and to the presence of gas in the refluxate. Intra-esophageal acid perfusion sensitizes esophageal receptors to mechanical and chemical stimuli. METHODS To establish whether acid sensitization plays a role in the perception of weakly acidic and mixed reflux episodes, 29 NERD patients, responders and 14 non-responders to proton pump inhibitors (PPIs), underwent pH-impedance monitoring. Non-responders repeated the study while on PPIs. To assess the effect of acid exposure on symptom perception, the time period with pH below 4 was measured in 15- and 30-minute time-windows preceding the onset of each reflux episode. KEY RESULTS Considering weakly acidic and mixed refluxes, both in responder and non-responder patients (off PPIs), the symptomatic refluxes were preceded by a significantly higher cumulative acid exposure than the asymptomatic refluxes. In all patients, following acid reflux, the percentage of symptomatic weakly acidic reflux episodes was significantly higher than that of asymptomatic refluxes. Non-responder patients, off-treatment, were characterized by a lower proportion of weakly acidic reflux and mixed reflux episodes. In the non-responder patients on PPI, only mixed and weakly symptomatic reflux episodes were preceded by a higher cumulative acid exposure. CONCLUSIONS & INFERENCES In NERD patients, spontaneous acid reflux enhances subsequent reflux perception, regardless of acidity or liquid/mixed composition of episodes; in non-responder patients on PPIs, only the perception of mixed and weakly acidic reflux episodes seems to be mediated by a preceding acid exposure.
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Affiliation(s)
- S Emerenziani
- Unit of Digestive Disease, Campus Bio Medico University, Roma, Italy
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Altomare A, Luca Guarino Sara Emerenziani MP, Cicala M, Drewes AM, Krarup AL, Brock C, Lottrup C, Frøkjaer JB, Souza RF, Nardone G, Compare D. Gastrointestinal sensitivity and gastroesophageal reflux disease. Ann N Y Acad Sci 2013; 1300:80-95. [PMID: 24117636 DOI: 10.1111/nyas.12236] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This paper reports on gastrointestinal sensitivity, including on the role of refluxate volume on the perception of reflux symptoms; experimental pain models that mimic mechanisms and symptoms of pain associated with esophageal diseases; the potential role of the acid receptor TRPV1 in the genesis of gastroesophageal reflux disease (GERD) symptoms; and roles for ATP and the purine and pyrimidine receptor subfamilies P1, P2X, and P2Y in the pathogenesis of GERD symptoms.
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Affiliation(s)
- Annamaria Altomare
- Department of Digestive Disease, Campus Bio-medico University, Rome, Italy
| | | | - Michele Cicala
- Department of Digestive Disease, Campus Bio-medico University, Rome, Italy
| | - Asbjørn Mohr Drewes
- Mech-Sense, Departments of Gastroenterology & Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Anne Lund Krarup
- Mech-Sense, Departments of Gastroenterology & Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Departments of Gastroenterology & Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Christian Lottrup
- Mech-Sense, Departments of Gastroenterology & Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Jens Brøndum Frøkjaer
- Mech-Sense, Departments of Gastroenterology & Radiology, Aalborg University Hospital, Aalborg, Denmark
| | - Rhonda F Souza
- Departments of Medicine, University of Texas Southwestern Medical Center and the VA North Texas Health Care System, Dallas, Texas
| | - Gerardo Nardone
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University "Federico II,", Naples, Italy
| | - Debora Compare
- Department of Clinical and Experimental Medicine, Gastroenterology Unit, University "Federico II,", Naples, Italy
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Sun H, Chen Y, Zhao X, Wang X, Jiang Y, Wu P, Tang Y, Meng Q, Xu S. Abnormal activity of default mode network in GERD patients. BMC Neurosci 2013; 14:69. [PMID: 23844702 PMCID: PMC3717012 DOI: 10.1186/1471-2202-14-69] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2012] [Accepted: 07/01/2013] [Indexed: 01/24/2023] Open
Abstract
Background Abnormal processing of esophageal sensation at the level of the central nervous system has been proven to be involved in gastroesophageal reflux disease (GERD). However, most studies were focused on the possible functions of perceptual processing related network during task status, little attention has been paid to default mode network, which has been manifested to be important in the pathogenesis of many diseases. In our study, we compared the brain activity characteristic in GERD patients with the healthy subjects (HS) at baseline, looking for whether activities of default mode network were abnormal in GERD patients and attempting to identify their possible roles in GERD. In present study, fractional amplitude of low-frequency fluctuation was adopted to detect the brain activities at baseline. Group-level analyses were conducted by one-sample t test within groups (voxel thresholds were p < 0.001 and cluster level >42, corrected P < 0.05) and independent-samples t test between groups (p < 0.01 and cluster level >90, corrected P < 0.05) using SPM5. Results The predominant activity area in both groups mainly located in default mode network such as medial superior frontal gyrus, precuneus, posterior cingulate gyrus, etc. However, the activities of precuneus and posterior cingulate gyrus were significantly lower in GERD patients than those in the HS. Conclusions The activities of precuneus and posterior cingulate gyrus of default mode network in GERD patients were significantly lower compared to the HS, suggesting abnormal activities of brain regions in default mode network may be involved in pathophysiology of GERD symptom generation.
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Affiliation(s)
- Huihui Sun
- Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, No, 389 Xin Cun Road, Shanghai 200065, China
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Kim JY, Kim N, Seo PJ, Lee JW, Kim MS, Kim SE, Jo SY, Lee DH, Jung HC. Association of sleep dysfunction and emotional status with gastroesophageal reflux disease in Korea. J Neurogastroenterol Motil 2013; 19:344-54. [PMID: 23875102 PMCID: PMC3714413 DOI: 10.5056/jnm.2013.19.3.344] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2013] [Revised: 06/12/2013] [Accepted: 06/15/2013] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS Sleep disturbances and emotional dysfunction are commonly associated with gastroeophageal reflux disease (GERD). The aims of this study were to evaluate GERD symptoms and disturbance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD) patients, and to compare sleep dysfunction, depressive mood, anxiety and quality of life (QOL) among the control, ERD and NERD patients in Korea. METHODS The Korean subjects were enrolled between 2010 and 2012, classified into 3 groups; the control group with no symptom and normal endoscopic findings, the ERD group with erosive esophagitis and the NERD group with more than one episode of heartburn or acid regurgitation per week, positive response to proton pump inhibitor, and normal endoscopic findings. Questionnaire included GERD symptoms, GERD impact scale (GIS) and daytime pathological sleepiness (Epworth sleepiness scale), sleep dysfunction (Pittsburgh sleep quality index, PSQI), depression and anxiety (Hospital anxiety and depression scale, HADS) and QOL (WHO quality of life scale abbreviated version, WHOQOL-BREF). RESULTS A total of 217 subjects were enrolled as follows; control (n = 70), ERD (n = 70) and NERD (n = 77). Impact of symptom of GIS score was higher in the NERD (9.2 ± 0.4) than in the ERD (6.5 ± 0.3) group (P < 0.001). Sleep dysfunctions were more frequent in GERD than the control group (PSQI score [P = 0.021]). Anxiety subscale of HAD score was higher in NERD (7.0 ± 0.5, P = 0.002) and ERD (6.2 ± 0.7, P = 0.004) groups than control (4.3 ± 0.7) group. WHOQOL-BREF scores in NERD (54.9 ± 2.3) and ERD (57.8 ± 2.4) groups were significantly lower than those in the control group (63.8 ± 2.4) (P = 0.002; P = 0.014, respectively). CONCLUSIONS The patients with NERD than ERD suffered more from the symptoms and disturbance in Korea. Sleep dysfunction and anxiety mood were higher and QOL was decreased in GERD, especially in NERD, suggesting that those factors might affect the severity of NERD.
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Affiliation(s)
- Ji Yeon Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea. ; Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Weijenborg PW, Bredenoord AJ. How reflux causes symptoms: reflux perception in gastroesophageal reflux disease. Best Pract Res Clin Gastroenterol 2013; 27:353-64. [PMID: 23998974 DOI: 10.1016/j.bpg.2013.06.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2013] [Revised: 06/11/2013] [Accepted: 06/23/2013] [Indexed: 02/07/2023]
Abstract
In gastroesophageal reflux disease (GERD) symptoms arise due to reflux of gastric content into the oesophagus. However, the relation between magnitude and onset of reflux and symptom generation in GERD patients is far from simple; gastroesophageal reflux occurs several times a day in everyone and the majority of reflux episodes remains asymptomatic. This review aims to address the question how reflux causes symptoms, focussing on factors leading to enhanced reflux perception. We will highlight esophageal sensitivity variance between subtypes of GERD, which is influenced by peripheral sensitization of primary afferents, central sensitization of spinal dorsal horn neurons, impaired mucosal barrier function and genetic factors. We will also discuss the contribution of specific refluxate characteristics to reflux perception, including acidity, and the role of bile, pepsin and gas and proximal extent. Further understanding of reflux perception might improve GERD treatment, especially in current partial responders to therapy.
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Affiliation(s)
- Pim W Weijenborg
- Dept. of Gastroenterology and Hepatology, Academic Medical Center Amsterdam, Meibergdreef 9, Postbus 22660, 1100 DD Amsterdam, The Netherlands.
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Kondo T, Oshima T, Tomita T, Fukui H, Watari J, Okada H, Kikuchi S, Sasako M, Matsumoto T, Knowles CH, Miwa H. Prostaglandin E(2) mediates acid-induced heartburn in healthy volunteers. Am J Physiol Gastrointest Liver Physiol 2013; 304:G568-73. [PMID: 23370674 DOI: 10.1152/ajpgi.00276.2012] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Prostaglandin E(2) (PGE(2)) plays a major role in pain processing and hypersensitivity. This study investigated whether PGE(2) levels are increased in the esophageal mucosa after acid infusion and whether increases in PGE(2) are associated with heartburn. Furthermore, expression of the PGE(2) receptor EP1 was investigated in human esophageal mucosa. Fourteen healthy male volunteers were randomized to 30-min lower esophageal acid (1% HCl) or saline perfusion. Before and after acid perfusion, endoscopic biopsies were taken from the distal esophagus. PGE(2) concentration (pg/mg protein) and EP1 mRNA and protein in biopsy samples were measured by ELISA, RT-PCR, and Western blotting. Symptom status of heartburn was evaluated with a validated categorical rating scale with a higher values corresponding to increasing intensity. PGE(2) levels in the esophageal mucosa significantly increased after acid infusion (before vs. after acid infusion: 23.2 ± 8.6 vs. 68.6 ± 18.3, P < 0.05), but not after saline infusion (before vs. after saline infusion: 9.3 ± 2.5 vs. 9.0 ± 3.2, NS). Time to first sensation (min) after acid infusion was less than after saline (saline vs. acid infusion: 22.1 ± 4.1 vs. 5.4 ± 1.5, P < 0.05). Intensity of heartburn in the acid-infusion group was also significantly greater compared with saline (saline vs. acid infusion: 54.3 ± 13.1 vs. 178.5 ± 22.8, P < 0.01). Changes in PGE(2) levels in the esophagus correlated with symptom intensity score (r = 0.80, P = 0.029). EP1 mRNA and protein expression were observed in the normal human esophageal mucosa. Esophageal PGE(2) expression is associated with mucosal acid exposure and heartburn.
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Affiliation(s)
- Takashi Kondo
- Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
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Effect of age and correlation between esophageal visceral chemosensitivity and mechanosensitivity in healthy Japanese subjects. J Gastroenterol 2013; 48:360-5. [PMID: 23001250 DOI: 10.1007/s00535-012-0665-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2012] [Accepted: 08/12/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of this study was to examine the impact of age on esophageal sensation, and to determine whether esophageal mechanosensitivity and chemosensitivity are correlated in healthy Japanese subjects. METHODS To evaluate chemosensitivity, a catheter was inserted and placed 10 cm above the upper border of the lower esophageal sphincter (LES), which was determined with an esophageal manometric catheter. After saline had been infused into the esophagus at a rate of 10 mL/min for 2 min, 0.1 N hydrochloric acid, instead of saline-without the subjects' knowledge-was infused for 10 min at the same rate. The acid perfusion sensitivity score (APSS) was assessed. To evaluate mechanosensitivity, a barostat test was performed, with a balloon being placed 10 cm above the upper border of the LES. The initial perception threshold (IPT), pain threshold (PT), and maximal pain were quantified. RESULTS The APSS was significantly inversely correlated with age. IPT, PT, and mean maximal pain were significantly correlated with age. Body mass index, drinking, and smoking habits were not correlated with the esophageal perception threshold. The correlation of chemosensitivity and mechanosensitivity was also assessed, and the APSS was inversely correlated with IPT, PT, and maximal pain. CONCLUSIONS The thresholds of esophageal visceral chemosensitivity and mechanosensitivity in same individuals were significantly correlated and both of these thresholds were inversely correlated with age.
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