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Savarino V, Visaggi P, Marabotto E, Bertin L, Pasta A, Calabrese F, Zentilin P, Ghisa M, Ribolsi M, Mari A, Tolone S, de Bortoli N, Savarino EV. Topical Protection of Esophageal Mucosa as a New Treatment of GERD. J Clin Gastroenterol 2025:00004836-990000000-00405. [PMID: 39777899 DOI: 10.1097/mcg.0000000000002128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 12/08/2024] [Indexed: 01/11/2025]
Abstract
Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods, enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa
| | - Pierfrancesco Visaggi
- Department of Translational Research and New Technologies in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa
| | - Elisa Marabotto
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padua
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua
| | - Andrea Pasta
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa
| | - Francesco Calabrese
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa
| | - Patrizia Zentilin
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa
| | - Matteo Ghisa
- Department of Surgery, Oncology and Gastroenterology, University of Padua
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua
| | - Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Roma
| | - Amir Mari
- Department of Gastroenterology, Azrieli Faculty of Medicine, Nazareth EMMS Hospital, Bar Ilan University, Safed, Israel
| | - Salvatore Tolone
- School of Medicine Naples, Università degli Studi della Campania, Naples, Italy
| | - Nicola de Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa
| | - Edoardo V Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua
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Alhithlool AW, Almutlaq AS, Almulla SA, Alhamdan AB, Alotaibi ZB, AlHithlool AW, Kamal AH, Daoud MYI, Zakaria OM. How do medical students perceive the role of artificial intelligence in management of gastroesophageal reflux disease? MEDICAL TEACHER 2024:1-7. [PMID: 39436823 DOI: 10.1080/0142159x.2024.2407129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 09/17/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND Artificial intelligence (AI) has significantly revolutionized the diagnosis and treatment of various medical and surgical conditions, including gastroesophageal reflux disease (GORD). AI has the potential to enhance diagnostic and treatment capabilities, contributing to overall advancements in healthcare. The current study aimed to investigate the medical students' views regarding the use of AI in GORD management. METHODS An anonymous, self-administered questionnaire was distributed among undergraduate medical students of various grades within different national medical institutions. The questionnaire comprised three sections, addressing sociodemographic data, knowledge, and attitudes. Knowledge and attitudes were assessed through 5- and 7-item questionnaires, respectively. The knowledge scores constituted a scale of 0-5. This reflected varying levels of understanding. Categories include poor knowledge (two or less), moderate knowledge (three), and good knowledge (4 and 5). Attitudes were classified as negative, neutral, or positive based on 50% and 75% cutoff points, with scores below 50% indicating negative attitudes, 50-75% considered neutral, and scores above 75% reflecting positive attitudes. RESULTS A total of 506 medical students participated, including 273 females and 233 males, with a ratio of 1.2-1. The majority fell within the age range of 20-26 years. Additionally, 388 participants (76.7%) reported grade point averages (GPAs) higher than 4. Regarding knowledge, 9% demonstrated a poor score of knowledge, while 33% had a moderate knowledge score. However, 65% of the participating students held a neutral attitude toward the role of AI in GORD management, with 6.9% expressing a negative stance on the matter. CONCLUSION Although AI is highly involved in GORD management, the study revealed that medical students and interns possess a limited perception of this emerging technology. This may highlight the necessity for active involvement in AI education within the medical curricula.
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Affiliation(s)
| | | | - Sarah A Almulla
- College of Medicine, King Faisal University, Alhasa, Saudi Arabia
| | | | - Ziyad B Alotaibi
- College of Medicine, King Faisal University, Alhasa, Saudi Arabia
| | - Amjad W AlHithlool
- College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ahmed Hassan Kamal
- Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mohamed Yasser I Daoud
- Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Ossama M Zakaria
- Department of Surgery, College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia
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Angelica B, Tippett M, Lim A, Wong S, Kuo P. Utility of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index in clinical pH-impedance reflux study. Intern Med J 2024; 54:1523-1530. [PMID: 38530066 DOI: 10.1111/imj.16379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 02/26/2024] [Indexed: 03/27/2024]
Abstract
BACKGROUND AND AIMS Analysis of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) have been proposed to increase the diagnostic yield of pH-impedance studies in reflux disease. However, routine use of these indices in clinical studies is yet to be established, particularly with PSPWi, which requires laborious manual analysis. Our study aimed to assess the utility of MNBI and PSPWi and their potential for future incorporation into clinical practice. METHODS pH-impedance recordings from consecutive patients referred to the Motility Laboratory at Royal Adelaide Hospital for evaluation of gastro-oesophageal reflux disease (GORD) were prospectively collected and manually analysed. Baseline demographic characteristics, symptoms, acid exposure time (AET), number of reflux episodes, and MNBI and PSPWi were collected. RESULTS Eighty-nine patients were included in the study (age 50 ± 17 years, 35 males). MNBI and PSPWi inversely correlated with AET (R = -0.678, P < 0.0001 and R = -0.460, P < 0.0001 respectively) and with reflux episodes (R = -0.391, P = 0.0002 and R = -0.305, P = 0.0037 respectively). In patients with a negative pH study, but with typical reflux symptoms, 4/30 (13%) had pathologic MNBI and PSPWi. There was a positive correlation between MNBI and PSPWi values (R = 0.525, P < 0.0001). Performing analysis of PSPWi was substantially more laborious than MNBI. CONCLUSION MNBI and PSPWi are both useful adjuncts in the diagnosis of reflux disease, although in our cohort MNBI showed stronger correlation with AET with less time to analyse. The role of these indices remains to be further explored, particularly in patients with inconclusive AET and in those with positive compared to negative symptom association.
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Affiliation(s)
- Bianca Angelica
- Motility Laboratory, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Marcus Tippett
- Motility Laboratory, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Amanda Lim
- Motility Laboratory, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Stephanie Wong
- Motility Laboratory, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Paul Kuo
- Motility Laboratory, Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Reddy AT, Patel A, Leiman DA. Automated software-derived supine baseline impedance is highly correlated with manual nocturnal baseline impedance for the diagnosis of GERD. Neurogastroenterol Motil 2024; 36:e14861. [PMID: 38988098 DOI: 10.1111/nmo.14861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/12/2024]
Abstract
BACKGROUND Mean nocturnal baseline impedance (MNBI) can improve diagnostic accuracy for gastroesophageal reflux disease (GERD), but must be manually calculated and is not routinely reported. We aimed to determine how automated software-derived mean supine baseline impedance (MSBI), a potential novel GERD metric, is related to MNBI. METHODS Consecutively obtained pH-impedance studies were assessed. Manually extracted MNBI was compared to MSBI using paired t-test and Spearman's correlations. KEY RESULTS The correlation between MNBI and MSBI was very high (ρ = 0.966, p < 0.01). CONCLUSIONS & INFERENCES The ease of acquisition and correlation with MNBI warrant the routine clinical use and reporting of MSBI with pH-impedance studies.
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Affiliation(s)
- Alexander T Reddy
- Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina, USA
| | - Amit Patel
- Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina, USA
- Durham VA Medical Center, Durham, North Carolina, USA
| | - David A Leiman
- Division of Gastroenterology, Duke University Medical Center, Durham, North Carolina, USA
- Duke Clinical Research Institute, Durham, North Carolina, USA
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Kurylo CM, Noel J, Blumin JH, Bock JM. Esophageal Baseline Impedance is Associated with Laryngopharyngeal Reflux and Treatment Response. Laryngoscope 2024; 134:4071-4077. [PMID: 38775163 DOI: 10.1002/lary.31506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 04/23/2024] [Accepted: 05/01/2024] [Indexed: 08/09/2024]
Abstract
OBJECTIVE To evaluate the efficacy of distal esophageal mean nocturnal baseline impedance (MNBI), a general marker of esophageal mucosal barrier integrity, in predicting laryngopharyngeal reflux (LPR) and symptomatic response to acid reflux therapy. METHODS This retrospective study analyzed 173 patients who presented with symptoms of laryngopharyngeal reflux and underwent 24-h multichannel intraluminal impedance-pH (MII-pH) testing. Mean nocturnal baseline impedance values were calculated and assessed for their association and ability to predict LPR symptoms, MII-pH results, treatment response, and other markers of LPR. RESULTS Notably, 153 of the 173 patients were tested off acid suppression medication and included in statistical analysis. Based on the MII-pH probe data, 108 (71%) patients had LPR, 8 (5%) had gastroesophageal reflux disease (GERD), and 37 (24%) were without pathologic reflux. Distal esophageal MNBI of LPR patients was significantly lower in LPR patients than patients with negative studies (1332 ± 94.8 vs. 2158 ± 173.5, p = 0.001). Among 118 patients who trialed antireflux therapy, a distal esophageal MNBI cutoff value of <1580 Ω was an independent predictor of treatment response (OR = 4.148 [1.877-9.189]). This value better predicted improvement with antireflux therapy for LPR than other objective MII-pH probe data, which were not independent predictors of treatment response. CONCLUSION Distal esophageal MNBI values may have value in the diagnosis of LPR and potentially predict medication responsiveness in LPR patients. LEVEL OF EVIDENCE 3 Laryngoscope, 134:4071-4077, 2024.
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Affiliation(s)
- Christopher M Kurylo
- Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Jacob Noel
- Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Joel H Blumin
- Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Jonathan M Bock
- Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
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Lages RB, Fontes LHDS, Barbuti RC, Navarro-Rodriguez T. Esophageal Mucosal Impedance Assessment for the Diagnosis of Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2024; 30:352-360. [PMID: 38972870 PMCID: PMC11238107 DOI: 10.5056/jnm23063] [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: 04/26/2023] [Revised: 06/27/2023] [Accepted: 07/17/2023] [Indexed: 07/09/2024] Open
Abstract
Background/Aims Diagnosing gastroesophageal reflux disease (GERD) is sometimes challenging because the performance of available tests is not entirely satisfactory. This study aims to directly measure the esophageal mucosal impedance during upper gastrointestinal endoscopy for the diagnosis of GERD. Methods Sixty participants with typical symptoms of GERD underwent high-resolution esophageal manometry, 24-hour multichannel intraluminal impedance-pH monitoring, upper gastrointestinal endoscopy, and mucosal impedance measurement. Mucosal impedance measurement was performed at 2, 5, 10, and 18 cm above the esophagogastric junction during gastrointestinal endoscopy using a specific catheter developed based on devices described in the literature over the last decade. The patients were divided into groups A (acid exposure time < 4%) and B (acid exposure time ≥ 4%). Results The mucosal impedance was significantly lower in group B at 2 cm (2264.4 Ω ± 1099.0 vs 4575.0 Ω ± 1407.6 [group A]) and 5 cm above the esophagogastric junction (4221.2 Ω ± 2623.7 vs 5888.2 Ω ± 2529.4 [group A]). There was no significant difference in the mucosal impedance between the 2 groups at 10 cm and 18 cm above the esophagogastric junction. Mucosal impedance value at 2 cm > 2970 Ω resulted in a sensitivity of 96.4% and a specificity of 87.5% to exclude GERD. Conclusions Direct measurement of mucosal impedance during endoscopy is a simple and promising method for diagnosing GERD. Individuals with an abnormal acid exposure time have lower mucosal impedance measurements than those with a normal acid exposure time.
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Affiliation(s)
- Rafael B Lages
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Luiz H de Souza Fontes
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Ricardo C Barbuti
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Tomas Navarro-Rodriguez
- Department of Gastroenterology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
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Olmos JA, Pandolfino JE, Piskorz MM, Zamora N, Díaz MAV, Troche JMR, Guzmán M, Hani A, García LRV, Lukashok HP, Domingues G, Vesco E, Rivas MM, Ovalle LFP, Cisternas D, Vela MF. Latin American consensus on diagnosis of gastroesophageal reflux disease. Neurogastroenterol Motil 2024; 36:e14735. [PMID: 38225792 PMCID: PMC11720354 DOI: 10.1111/nmo.14735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 12/05/2023] [Accepted: 12/18/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND Diagnosing gastroesophageal reflux disease (GERD) can be challenging given varying symptom presentations, and complex multifactorial pathophysiology. The gold standard for GERD diagnosis is esophageal acid exposure time (AET) measured by pH-metry. A variety of additional diagnostic tools are available. The goal of this consensus was to assess the individual merits of GERD diagnostic tools based on current evidence, and provide consensus recommendations following discussion and voting by experts. METHODS This consensus was developed by 15 experts from nine countries, based on a systematic search of the literature, using GRADE (grading of recommendations, assessment, development and evaluation) methodology to assess the quality and strength of the evidence, and provide recommendations regarding the diagnostic utility of different GERD diagnosis tools, using AET as the reference standard. KEY RESULTS A proton pump inhibitor (PPI) trial is appropriate for patients with heartburn and no alarm symptoms, but nor for patients with regurgitation, chest pain, or extraesophageal presentations. Severe erosive esophagitis and abnormal reflux monitoring off PPI are clearly indicative of GERD. Esophagram, esophageal biopsies, laryngoscopy, and pharyngeal pH monitoring are not recommended to diagnose GERD. Patients with PPI-refractory symptoms and normal endoscopy require reflux monitoring by pH or pH-impedance to confirm or exclude GERD, and identify treatment failure mechanisms. GERD confounders need to be considered in some patients, pH-impedance can identify supragrastric belching, impedance-manometry can diagnose rumination. CONCLUSIONS Erosive esophagitis on endoscopy and abnormal pH or pH-impedance monitoring are the most appropriate methods to establish a diagnosis of GERD. Other tools may add useful complementary information.
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Affiliation(s)
- Jorge A. Olmos
- Neurogastroenterology Sector, Hospital de Clinicas Jose de San Martin, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - John E. Pandolfino
- Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - María M. Piskorz
- Neurogastroenterology Sector, Hospital de Clinicas Jose de San Martin, Universidad de Buenos Aires, Buenos Aires, Argentina
| | | | - Miguel A. Valdovinos Díaz
- UNAM, Ciudad de Mexico, Mexico
- Department of Gastroenterology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José M. Remes Troche
- Institute of Medical Biological Research, Universidad Veracruzana, Veracruz, Mexico
| | - Mauricio Guzmán
- Neurogastroenterology Unit, Gastroenterology Service, Hospital San Martín de La Plata, Buenos Aires, Argentina
| | - Albis Hani
- Hospital San Ignacio-Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Hannah Pitanga Lukashok
- Digestive Motility Service, Instituto Ecuatoriano de Enfermedades Digestivas-IECED, Guayaquil, Ecuador
| | | | - Eduardo Vesco
- Neuromotility Unit, Clínica Angloamericana, Lima. Peru
- Universidad Nacional Mayor de San Marcos. Lima, Peru
| | - Mariel Mejia Rivas
- lnternal Medicine, Gastroenterology and Digestive Endoscopy Service, Hospital Vivian Pellas, Managua, Nicaragua
| | - Luis F. Pineda Ovalle
- Neurogastroenterology and Motility Service Motility Instituto Gut Médica, Bogotá, Colombia
| | - Daniel Cisternas
- Clínica Alemana de Santiago, School of Medicine, Universidad del Desarrollo, Clínica Alemana, Vitacura, Chile
| | - Marcelo F. Vela
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
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Kataria J, Rivera D, Grin A, Reed DE, Rodrigues DM. The role of histology in the diagnosis of non-erosive reflux disease: A systematic review and meta-analysis. Neurogastroenterol Motil 2023; 35:e14631. [PMID: 37448170 DOI: 10.1111/nmo.14631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 03/21/2023] [Accepted: 06/06/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND AND PURPOSE Non-erosive reflux disease (NERD) accounts for over half of all gastroesophageal reflux cases and is characterized by reflux symptoms with pathologic acid exposure on pH monitoring but no evidence of erosions on upper endoscopy. Ambulatory pH monitoring is limited by availability and patient tolerance. The utility of performing esophageal mucosal biopsies in diagnosing NERD is unclear. We conducted a systematic review and meta-analysis to determine the sensitivity of esophageal mucosal biopsies in diagnosing NERD. METHODS Data were obtained from Embase and Ovid MEDLINE from inception to April 2021. Studies were included if esophageal mucosal biopsies were taken and analyzed using conventional histopathologic analysis in symptomatic NERD patients. Relevant data was including histologic abnormalities and location of the biopsy. Sensitivity and specificity were calculated against healthy controls or those with functional heartburn. RESULTS The search yielded 2871 studies, of which 10 studies met our inclusion criteria and contained raw data. Histological abnormalities included histologic sum scores, papillary elongation, basal cell hyperplasia, and dilated intraepithelial spaces. When assessing for the presence of any abnormality, biopsies taken <3 cm from the lower esophageal sphincter (LES) had a pooled sensitivity of 0.71 (95% CI 0.64-0.77) and specificity of 0.64 (95% 0.54-0.73); however, analysis of individual histologic features such as the presence of eosinophils improved the sensitivity. CONCLUSIONS Although esophageal mucosal biopsies had poor sensitivity at diagnosing NERD, biopsies taken within 3 cm of the LES had higher sensitivity when pathologists reported upon eosinophils and dilated intraepithelial spaces.
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Affiliation(s)
- Jay Kataria
- Departments of Medicine, Queen's University, Kingston, Ontario, Canada
- Departments of Anatomy and Pathology, Queen's University, Kingston, Ontario, Canada
| | - Daniel Rivera
- Departments of Medicine, Queen's University, Kingston, Ontario, Canada
- Departments of Anatomy and Pathology, Queen's University, Kingston, Ontario, Canada
| | - Andrea Grin
- Departments of Medicine, Queen's University, Kingston, Ontario, Canada
- Departments of Anatomy and Pathology, Queen's University, Kingston, Ontario, Canada
| | - David Edward Reed
- Departments of Medicine, Queen's University, Kingston, Ontario, Canada
- Departments of Anatomy and Pathology, Queen's University, Kingston, Ontario, Canada
| | - David Mario Rodrigues
- Departments of Medicine, Queen's University, Kingston, Ontario, Canada
- Departments of Anatomy and Pathology, Queen's University, Kingston, Ontario, Canada
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Layne SJ, Lorsch ZS, Patel A. Novel Diagnostic Techniques in the Evaluation of Gastroesophageal Reflux Disease (GERD). Dig Dis Sci 2023; 68:2226-2236. [PMID: 37071244 DOI: 10.1007/s10620-023-07901-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Accepted: 02/21/2023] [Indexed: 04/19/2023]
Abstract
In our present clinical paradigm, patient symptoms and presentation in the setting of traditional findings from endoscopy (erosive esophagitis, Barrett's esophagus, reflux-mediated stenosis), esophageal high-resolution manometry, and/or ambulatory reflux monitoring (distal esophageal acid exposure time, numbers of reflux events, reflux-symptom association) guide the care of patients with suspected GERD. However, novel metrics and techniques acquired from or performed at endoscopy, manometry, or pH-impedance monitoring, beyond conventional evaluation, are of great interest to the gastroenterology community given the frequent (and sometimes challenging) presentation of suspected GERD. These novel and evolving diagnostic approaches have the potential to enhance the evaluation of these patients and optimize their management. In this invited review, we discuss the present evidence and potential clinical utility of selected GERD metrics and techniques of interest at endoscopy (dilated intercellular spaces, mucosal impedance), manometry (contractile integral, impedance analysis, straight leg raise, multiple rapid swallow maneuvers), and reflux monitoring (mean nocturnal baseline impedance, post-reflux swallow-induced peristaltic wave indices), and how these tools may be most optimally adopted and utilized for clinical care (Fig. 1).
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Affiliation(s)
- Sabrina J Layne
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - Zachary S Lorsch
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine and the Durham Veterans Affairs Medical Center, Box 3913, Durham, NC, 27710, USA.
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Wong MW, Rogers BD, Liu MX, Lei WY, Liu TT, Yi CH, Hung JS, Liang SW, Tseng CW, Wang JH, Wu PA, Chen CL. Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD. Diagnostics (Basel) 2023; 13:diagnostics13050960. [PMID: 36900104 PMCID: PMC10000892 DOI: 10.3390/diagnostics13050960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/24/2023] [Accepted: 02/27/2023] [Indexed: 03/06/2023] Open
Abstract
Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.
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Affiliation(s)
- Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Benjamin D. Rogers
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, KY 40292, USA
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Min-Xiang Liu
- AI Innovation Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
| | - Chiu-Wang Tseng
- NVIDIA AI Technology Center, NVIDIA Corporation, Taipei 11492, Taiwan
| | - Jen-Hung Wang
- Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan
| | - Ping-An Wu
- AI Innovation Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97004, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, 707, Section 3, Chung-Yang Road, Hualien 97004, Taiwan
- Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan
- Correspondence:
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Ilia S, Monica V, Daniel S. Mean nocturnal baseline impedance and endoscopic mucosal impedance measurements in patients with eosinophilic esophagitis: a new tool for follow up and management? Updates Surg 2023; 75:389-393. [PMID: 35840790 PMCID: PMC9852170 DOI: 10.1007/s13304-022-01331-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 07/05/2022] [Indexed: 01/24/2023]
Abstract
Eosinophilic esophagitis (EoE) is the second most common cause of chronic esophageal inflammation after GERD, with increasing incidence and prevalence across all age groups. Since current diagnosis and follow up of EoE require endoscopy with biopsies, there is an increased interest in non or less invasive tests for its diagnosis and follow up. Baseline mucosal impedance measurement allows evaluation of mucosal barrier properties and is widely accepted as an adjunct method in GERD diagnosis. As EoE is associated with increased mucosal permeability, the use of baseline impedance to evaluate mucosal integrity has been investigated in several studies. It was found that baseline mucosal impedance, measured either during 24 h reflux monitoring or during endoscopy, was significantly lower in all parts of the esophagus in EoE patients. Impedance measurement correlated with eosinophil counts on biopsies, offering a tool to monitor treatment response. Additionally, baseline impedance patterns differed between those responding to proton pump inhibitor (PPI) treatment and those resistant to PPI, potentially allowing to tailor future treatment to the individual patient. In summary, baseline impedance measurement offers a potential tool for diagnosis and follow up in EoE. Its exact place in EoE treatment is yet to be determined and requires further future studies.
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Affiliation(s)
- Sergeev Ilia
- Barts and the London School of Medicine and Dentistry, Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK
| | - Velosa Monica
- Barts and the London School of Medicine and Dentistry, Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK
| | - Sifrim Daniel
- Barts and the London School of Medicine and Dentistry, Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK
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12
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Ren Y, Guo X, Cai Y, Huo X, Ying X, Lu Q, Jiang X, Jiang B. Difference in meal-related esophageal intraluminal impedance change between gastroesophageal reflux disease and functional disorders. Scand J Gastroenterol 2022; 58:443-447. [PMID: 36314511 DOI: 10.1080/00365521.2022.2141073] [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] [Indexed: 11/07/2022]
Abstract
OBJECTIVES Gastroesophageal reflux disease (GERD) has overlapping symptoms with functional disorders such as functional heart burn. Twenty-four-hour pH with impedance monitoring is useful for differentiation. The intraluminal impedance change with meal in distal esophagus is not investigated. METHODS We performed a retrospective investigation of clinical files, 24-hour pH with intraluminal impedance monitoring in patients with GERD and functional disorders. The post-reflux swallow induced peristaltic wave (PSPW) index as well as the impedance in distal esophagus before the first meal and 30 min and 60 min after the meal were measured and analyzed. RESULTS A significant decrease of intraluminal impedance in distal esophagus was noted at 30 min (ΔI30min -301.5 [747.5] Ω, p = 0.018) and recovered at 60 min (ΔI60min -194.6 [766.0] Ω, p = 0.126) after meals in GERD patients. On the other hand, there was no significant change of impedance in patients with functional disorders. There were positive correlations between ΔI30min and PSPW index (correlation = 0.232, p = 0.038). Comparing GERD to functional disorders, the best cut-off value for ΔI30min was -212Ω with 74.4% sensitivity and 60.5% specificity. CONCLUSIONS The intraluminal impedance in distal esophagus was lowered after meals in GERD patients other than functional disorders. This impedance change was correlated with PSPW index and could help differentiate GERD from functional disorders.
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Affiliation(s)
- Yutang Ren
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Xiaojuan Guo
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Yunting Cai
- Department of Thoracic Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Xueru Huo
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Xiaofang Ying
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Qiuxiang Lu
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Xuan Jiang
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Bo Jiang
- Department of Gastroenterology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
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13
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Zhang T, Zhang B, Tian W, Wei Y, Wang F, Yin X, Wei X, Liu J, Tang X. Trends in gastroesophageal reflux disease research: A bibliometric and visualized study. Front Med (Lausanne) 2022; 9:994534. [PMID: 36250094 PMCID: PMC9556905 DOI: 10.3389/fmed.2022.994534] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 09/06/2022] [Indexed: 11/19/2022] Open
Abstract
Background Gastroesophageal reflux disease (GERD), a disorder resulting from the retrograde flow of gastric contents into the esophagus, affects an estimated 10-30% of the Western population, which is characterized by multifactorial pathogenesis. Over the past few decades, there have been many aspects of uncertainty regarding GERD leading to an ongoing interest in the field as reflected by a large number of publications, whose heterogeneity and variable quality may present a challenge for researchers to measure their scientific impact, identify scientific collaborations, and to grasp actively researched themes in the GERD field. Accordingly, we aim to evaluate the knowledge structure, evolution of research themes, and emerging topics of GERD research between 2012 and 2022 with the help of bibliometric approaches. Methods The literature focusing on GERD from 2012 to 2022 was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The overall publication performance, the most prolific countries or regions, authors, journals and resources-, knowledge- and intellectual-networking, as well as the co-citation analysis of references and keywords, were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer. Results A total of 8,964 publications were included in the study. The USA published the most articles (3,204, 35.74%). Mayo Clin ranked first in the number of articles published (201, 2.24%). EDOARDO SAVARINO was the most productive author (86, 0.96%). The most productive journal in this field was SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES (304, 3.39%). AMERICAN JOURNAL OF GASTROENTEROLOGY had the most co-citations (4,953, 3.30%). Keywords with the ongoing strong citation bursts were transoral incision less fundoplication, eosinophilic esophagitis, baseline impedance, and functional heartburn. Conclusion For the first time, we obtained deep insights into GERD research through bibliometric analysis. Findings in this study will be helpful for scholars seeking to understand essential information in this field and identify research frontiers.
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Affiliation(s)
- Tai Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Beihua Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wende Tian
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yuchen Wei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Fengyun Wang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaolan Yin
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiuxiu Wei
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiali Liu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Traditional Chinese Medical Sciences, Beijing, China
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xudong Tang
- Traditional Chinese Medicine Research Institute of Spleen and Stomach Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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14
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Wu Y, Guo Z, Zhang C, Zhan Y. Mean nocturnal baseline impedance, a novel metric of multichannel intraluminal impedance-pH monitoring in diagnosing gastroesophageal reflux disease. Therap Adv Gastroenterol 2022; 15:17562848221105195. [PMID: 35983222 PMCID: PMC9379274 DOI: 10.1177/17562848221105195] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 05/18/2022] [Indexed: 02/04/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a common disease with increasing prevalence worldwide. However, the diagnosis of GERD is challenging because there are no definite gold standard criteria. Recently, a novel impedance parameter, namely mean nocturnal baseline impedance (MNBI), has been proposed, which reflects the burden of longitudinal reflux and the integrity of esophageal mucosa. MNBI has shown an immense promise for increasing the diagnostic rate of multichannel intraluminal impedance-pH (MII-pH) monitoring and predicting the response to proton pump inhibitor (PPI) or anti-reflux intervention in patients with reflux symptoms. The present paper reviews the association between baseline impedance and esophageal mucosal integrity, the acquisition of MNBI in 24-h MII-pH monitoring, the clinical utilization of MNBI in improving the diagnosis rate of GERD in patients with typical reflux symptoms, predicting the response to PPI or anti-reflux treatment in these patients, the utilization of MNBI in diagnosing patients with atypical symptoms or extra-esophageal symptoms, and the correlation between reflux burden and MNBI. MNBI should be routinely assessed using MII-pH monitoring.
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Affiliation(s)
| | | | | | - Yutao Zhan
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing 100730, P. R. China
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15
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Maev IV, Barkalova EV, Ovsepian MA, Andreev DN. Phenotypes of gastroesophageal reflux disease: classification, pathogenesis and diagnostic criteria: A review. CONSILIUM MEDICUM 2022. [DOI: 10.26442/20751753.2022.5.201703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
The literature review focuses on the current understanding of visceral hypersensitivity mechanisms in the esophagus. Mechanisms of peripheral and central sensitization and their relation to heartburn symptoms are covered in detail. Diagnostic criteria and algorithms for non-erosive reflux disease, functional heartburn, and esophagus hypersensitivity based on pH-impedance testing and high-resolution esophageal manometry data are presented.
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16
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Savarino E, Marabotto E, Savarino V. Recent insights on functional heartburn and reflux hypersensitivity. Curr Opin Gastroenterol 2022; 38:417-422. [PMID: 35762702 PMCID: PMC10810351 DOI: 10.1097/mog.0000000000000846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
PURPOSE OF REVIEW Rome IV experts have proposed that gastroesophageal reflux disease (GERD) should be diagnosed only in patients with abnormal esophageal acid exposure, and that reflux hypersensitivity (RH) and functional heartburn (FH) both should be considered functional conditions separate from GERD. Although past and recent evidence support that FH can be completely distinguished from GERD, the concept that RH is not GERD is highly questionable. This review attempts to provide current data on these issues. RECENT FINDINGS Many recent investigations have provided new data on the different pathophysiological features characterizing RH and FH. Major differences have emerged from analyses of impedance-pH monitoring studies using the novel impedance metrics of baseline impedance (an index of mucosal integrity) and the rate of postreflux swallow-induced peristaltic waves (a reflection of the integrity of esophageal chemical clearance). SUMMARY The better ability to interpret impedance-pH tracings together with earlier data on the different prevalence of microscopic esophagitis in RH and FH patients, and recent studies documenting poor therapeutic efficacy of pain modulators and good results of antireflux surgery for RH support recategorization of RH within the GERD world. Further research is needed to correctly phenotype patients who have heartburn without mucosal breaks, and to guide their effective management.
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Affiliation(s)
- Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy
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17
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Ullal TV, Marks SL, Belafsky PC, Conklin JL, Pandolfino JE. A Comparative Assessment of the Diagnosis of Swallowing Impairment and Gastroesophageal Reflux in Canines and Humans. Front Vet Sci 2022; 9:889331. [PMID: 35754550 PMCID: PMC9228035 DOI: 10.3389/fvets.2022.889331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Accepted: 05/05/2022] [Indexed: 11/24/2022] Open
Abstract
Swallowing impairment is a highly prevalent and clinically significant problem affecting people and dogs. There are myriad causes of swallowing impairment of which gastroesophageal reflux is the most common in both species. Similarities in anatomy and physiology between humans and canines results in analogous swallowing disorders including cricopharyngeus muscle achalasia, esophageal achalasia, hiatal herniation, and gastroesophageal reflux with secondary esophagitis and esophageal dysmotility. Accordingly, the diagnostic approach to human and canine patients with swallowing impairment is similar. Diagnostic procedures such as swallowing fluoroscopy, high-resolution manometry, pH/impedance monitoring, and endolumenal functional luminal imaging probe can be performed in both species; however, nasofacial conformation, increased esophageal length, and the difficulty of completing several of these procedures in awake dogs are inherent challenges that need to be considered. Human patients can convey their symptoms and respond to verbal cues, whereas veterinarians must rely on clinical histories narrated by pet owners followed by comprehensive physical examination and observation of the animal eating different food consistencies and drinking water. Dogs may also be unwilling to drink or eat in the hospital setting and may be resistant to physical restraint during diagnostic procedures. Despite the species differences and diagnostic challenges, dogs are a natural animal model for many oropharyngeal and esophageal disorders affecting people, which presents a tremendous opportunity for shared learnings. This manuscript reviews the comparative aspects of esophageal anatomy and physiology between humans and canines, summarizes the diagnostic assessment of swallowing impairment in both species, and discusses future considerations for collaborative medicine and translational research.
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Affiliation(s)
- Tarini V Ullal
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
| | - Stanley L Marks
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States
| | - Peter C Belafsky
- Department of Otolaryngology, Center for Voice and Swallowing, School of Medicine, University of California, Davis, Davis, CA, United States
| | - Jeffrey L Conklin
- The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, UCLA Robert G. Kardashian Center for Esophageal Health, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - John E Pandolfino
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States
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18
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Liang SW, Wong MW, Yi CH, Liu TT, Lei WY, Hung JS, Lin L, Rogers BD, Chen CL. Current advances in the diagnosis and management of gastroesophageal reflux disease. Tzu Chi Med J 2022; 34:402-408. [PMID: 36578634 PMCID: PMC9791847 DOI: 10.4103/tcmj.tcmj_323_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 01/10/2022] [Accepted: 02/23/2022] [Indexed: 12/31/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is very common and defined as troublesome symptoms owing to excessive acid reflux. The spectrum of GERD is broad, including not only erosive esophagitis and Barrett's esophagus but also nonerosive reflux disease (NERD), reflux hypersensitivity, and functional heartburn. Patients with reflux symptoms despite normal endoscopy remain common clinical presentation, can be heterogeneous overlapping with functional gastrointestinal disorders. Ambulatory esophageal pH monitoring with and without impedance helps the diagnosis of NERD. Metrics such as baseline impedance and postreflux swallow induced peristaltic wave enhance diagnostic accuracy in patients with inconclusive diagnoses. The major treatment of all manifestations of GERD is acid suppression with proton pump inhibitors, while other therapies, such as reflux-reducing agents and adjunctive medications, can be individualized where the response to traditional management is incomplete. GERD patients often need long-term treatment due to frequent relapses. Anti-reflux surgery can be effective too. Endoscopic therapies have some promising results, but long-term outcomes remain to be determined.
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Affiliation(s)
- Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Ming-Wun Wong
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan,School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Tso-Tsai Liu
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Jui-Sheng Hung
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Lin Lin
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Benjamin D. Rogers
- Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky, USA,Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan,Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan,Address for correspondence: Dr. Chien-Lin Chen, Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien, Taiwan. E-mail:
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19
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Snyder DL, Katzka DA. Complex Gastroesophageal Reflux Disease. GASTRO HEP ADVANCES 2022; 1:420-430. [PMID: 39131678 PMCID: PMC11307939 DOI: 10.1016/j.gastha.2022.02.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Accepted: 02/15/2022] [Indexed: 08/13/2024]
Abstract
Gastroesophageal reflux disease (GERD) is the most prevalent gastrointestinal disorder posing diagnostic and therapeutic challenges. Diagnosis should be objectively defined with endoscopy and pH testing, while novel metrics may augment diagnosis for inconclusive GERD cases, including the postreflux swallow-induced peristaltic wave index and esophageal mucosal impedance. Conditions that overlap with or mimic GERD should be considered such as achalasia, rumination, and eosinophilic esophagitis. Genetic testing for proton pump inhibitor metabolism is an option for precision therapy in complex persistent GERD. Proton pump inhibitor refractory GERD may require medical, surgical, or endoscopic therapies. The presence of GERD should be objectively evaluated in achalasia patients treated with peroral endoscopic myotomy, and further studies are needed to determine timing of this evaluation. Patients with scleroderma are at a high risk for GERD owing to abnormal esophageal motility and should be managed with aggressive medical therapy and lifestyle changes given the high prevalence of esophagitis and Barrett's esophagus in this population. Further studies are needed to understand the complex mechanisms of GERD in idiopathic pulmonary fibrosis and lung transplantation.
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20
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Kandulski A, Zimmermann D, Weidlich S, Schulz C. [Beningn disesases of the esophagus]. MMW Fortschr Med 2022; 164:20-28. [PMID: 35359289 DOI: 10.1007/s15006-022-0829-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Affiliation(s)
- Arne Kandulski
- Klinik und Poliklinik für Innere Medizin I, Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany.
| | | | - Simon Weidlich
- Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technische Universität München, Ismaninger Str. 22, 81675, München, Germany
| | - Christian Schulz
- Medizinische Klinik und -Poliklinik II, Medizinische Klinik und -Poliklinik II, Marchioninistr. 15, 81377, München, Germany
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21
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Visaggi P, Mariani L, Svizzero FB, Tarducci L, Sostilio A, Frazzoni M, Tolone S, Penagini R, Frazzoni L, Ceccarelli L, Savarino V, Bellini M, Gyawali PC, Savarino EV, de Bortoli N. Clinical use of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index for the diagnosis of gastro-esophageal reflux disease. Esophagus 2022; 19:525-534. [PMID: 35768671 PMCID: PMC9436885 DOI: 10.1007/s10388-022-00933-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/07/2022] [Indexed: 02/03/2023]
Abstract
The clinical diagnosis of gastro-esophageal reflux disease (GERD) is based on the presence of typical esophageal troublesome symptoms. In clinical practice, heartburn relief following a proton pump inhibitor (PPI) trial or endoscopy can confirm a diagnosis of GERD. In cases of diagnostic uncertainty or before anti-reflux interventions, combined impedance-pH monitoring (MII-pH) provides a comprehensive assessment of both physical and chemical properties of the refluxate, allowing to achieve a conclusive diagnosis of GERD. Recently, the Lyon Consensus proposed the use of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPW-I) as novel MII-pH metrics to support the diagnosis of GERD. The calculation of MNBI and PSPW-I currently needs to be performed manually, but artificial intelligence systems for the automated analysis of MII-pH tracings are being developed. Several studies demonstrated the increased diagnostic yield MNBI and PSPW-I for the categorization of patients with GERD at both on- and off-PPI MII-pH monitoring. Accordingly, we performed a narrative review on the clinical use and diagnostic yield of MNBI and PSPW-I when the diagnosis of GERD is uncertain. Based on currently available evidence, we strongly support the evaluation of PSPW-I and MNBI as part of the standard assessment of MII-pH tracings for the evaluation of GERD, especially in patients with endoscopy-negative heartburn.
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Affiliation(s)
- Pierfrancesco Visaggi
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Lucia Mariani
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Federica Baiano Svizzero
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Luca Tarducci
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Andrea Sostilio
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit, Baggiovara Hospital, Modena, Italy
| | - Salvatore Tolone
- General and Bariatric Surgery Unit, Department of Surgery, University of Caserta Luigi Vanvitelli, Caserta, Italy
| | - Roberto Penagini
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Leonardo Frazzoni
- Gastroenterology Unit, Department of Medical and Surgical Sciences, Sant'Orsola Hospital, University of Bologna, Bologna, Italy
| | - Linda Ceccarelli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine "DiMI", University of Genoa, Genoa, Italy
| | - Massimo Bellini
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy
| | - Prakash C Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, USA
| | - Edoardo V Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Nicola de Bortoli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy.
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22
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Rettura F, Bronzini F, Campigotto M, Lambiase C, Pancetti A, Berti G, Marchi S, de Bortoli N, Zerbib F, Savarino E, Bellini M. Refractory Gastroesophageal Reflux Disease: A Management Update. Front Med (Lausanne) 2021; 8:765061. [PMID: 34790683 PMCID: PMC8591082 DOI: 10.3389/fmed.2021.765061] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/04/2021] [Indexed: 12/12/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) is one of the most frequent gastrointestinal disorders. Proton pump inhibitors (PPIs) are effective in healing lesions and improving symptoms in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, some patients unresponsive to PPIs who experience symptoms potentially related to GERD may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic and pH-impedance investigations. The management strategies regarding rGERD, apart from a careful check of patient's compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginates, antacids and mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and metabotropic glutamate receptor-5 (mGluR5) antagonists, and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux option remains laparoscopic antireflux surgery (LARS), even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient. The aim of this paper is to review the different management options available to successfully deal with rGERD.
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Affiliation(s)
- Francesco Rettura
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Francesco Bronzini
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Michele Campigotto
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
| | - Christian Lambiase
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Andrea Pancetti
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Ginevra Berti
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Santino Marchi
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Nicola de Bortoli
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Frank Zerbib
- CHU de Bordeaux, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Massimo Bellini
- Division of Gastroenterology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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Wang Y, Ye B, Wang M, Lin L, Jiang L. Esophageal Nocturnal Baseline Impedance and Post-reflux Swallow-induced Peristaltic Wave Index in Identifying Proton Pump Inhibitor-refractory Non-erosive Reflux Disease. J Neurogastroenterol Motil 2021; 27:525-532. [PMID: 34642272 PMCID: PMC8521464 DOI: 10.5056/jnm20073] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 04/15/2021] [Accepted: 04/15/2021] [Indexed: 12/12/2022] Open
Abstract
Background/Aims Esophageal mean nocturnal baseline impedance (MNBI) levels and post-reflux swallow-induced peristaltic wave (PSPW) index could increase the diagnostic value of 24-hour multichannel intraluminal impedance and pH monitoring in patients with gastroesophageal reflux disease. This study aims to compare the MNBI and PSPW index in patients with no evidence of erosive reflux disease. Methods Impedance-pH monitoring tracings from 70 patients, 50 with non-erosive reflux disease (NERD) and 20 with functional heartburn (FH), were reviewed. According to proton pump inhibitors (PPI) treatment response, NERD patients were divided into NERD/PPI responders and NERD/PPI nonresponders. MNBI, PSPW index, and intercellular spaces were measured and compared among each group. Results MNBI values and PSPW index were lower in NERD patients than in FH (P < 0.01 and P < 0.05, respectively). MNBI positively correlated with PSPW index (r = 0.525, P < 0.001). NERD/PPI responders had lower MNBI values and PSPW index compared to NERD/PPI nonresponders (both P < 0.01). MNBI and PSPW index distinguished NERD from FH patients with an area under the curve of 0.914 and 0.677, respectively. Wider intercellular space could be identified in patients with NERD (P < 0.01). Conclusion MNBI and PSPW index may differentiate NERD from FH patients and relate to PPI treatment efficacy in patients with NERD.
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Affiliation(s)
- Yan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Bixing Ye
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Meifeng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Liuqin Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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24
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Guo Z, Wu Y, Zhan Y, Zhang C. Correlation between gastroesophageal flap valve abnormality and novel parameters in patients with gastroesophageal reflux disease symptoms by the lyon consensus. Sci Rep 2021; 11:15076. [PMID: 34301972 PMCID: PMC8302560 DOI: 10.1038/s41598-021-94149-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 07/07/2021] [Indexed: 11/25/2022] Open
Abstract
Gastroesophageal flap valve (GEFV) grading is a simple and reproducible parameter. There is limited information about the association between GEFV abnormality and novel parameters in patients with gastroesophageal reflux disease(GERD) symptoms by the Lyon Consensus. To investigate the value of GEFV grading in GERD, the clinical data of 320 patients with GERD symptoms who underwent endoscopy, 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, and high-resolution manometry (HRM) were retrospectively analyzed. The percentage of acid exposure time (AET%)(4.2 [1.5–7.4] vs. 1.3 [0.3–4.2], P < 0.001) and the proportion of abnormal esophagogastric junction (EGJ) morphology (71 [87.7%] vs. 172 [72.0%], P = 0.011) were significantly higher, while the mean nocturnal baseline impedance (MNBI) (2068.3 [1658.4–2432.4] vs. 2228.5 [1794.8–2705.3]Ω, P = 0.012) and post-reflux swallow-induced peristaltic wave index (PSPWI) (19.7 [13.9–29.0] vs. 33.3 [25.0–44.0]%, P < 0.001) were significantly lower in the abnormal GEFV group compared with the normal GEFV group. AET% and EGJ morphology showed positive correlations with GEFV grade, while PSPWI and MNBI showed negative correlations. Patients with an abnormal GEFV had a significantly greater risk of conclusive evidence of GERD compared to those with a normal GEFV (OR 3.035, 95% CI 1.758–5.240, P < 0.001). Further, when identifying patients with conclusive evidence of GERD, abnormal GEFV had a specificity of 80.4% (95% CI 75.3–85.5%). GEFV grading might be regarded as supportive evidence for GERD diagnosis.
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Affiliation(s)
- Zihao Guo
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, China
| | - Yanhong Wu
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, China
| | - Yutao Zhan
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, China.
| | - Chuan Zhang
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, No.1, Dongjiaominxiang, Dongcheng District, Beijing, 100730, China.
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Patel D, Fass R, Vaezi M. Untangling Nonerosive Reflux Disease From Functional Heartburn. Clin Gastroenterol Hepatol 2021; 19:1314-1326. [PMID: 32246998 DOI: 10.1016/j.cgh.2020.03.057] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 03/23/2020] [Accepted: 03/23/2020] [Indexed: 02/07/2023]
Abstract
Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.
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Affiliation(s)
- Dhyanesh Patel
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Ronnie Fass
- Division of Gastroenterology and Hepatology, MetroHealth System, Case Western Reserve University, Cleveland, Ohio
| | - Michael Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee
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Gomes AC, Sousa M, Lopes R, Afecto E, Correia J, Freitas T, Carvalho J. Gastroesophageal Reflux Disease Diagnosis by New Consensus in Clinical Practice: The Additional Value of Mean Basal Impedance. Dig Dis 2021; 40:261-265. [PMID: 34348287 DOI: 10.1159/000517987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 06/18/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Recently, Lyon consensus and ROME IV were published as there was a need to create a more objective evaluation for gastroesophageal reflux disease (GERD) in order to better predict treatment outcomes. However, with classical pH-impedance measures, some patients would still have diagnostic uncertainty, and new metrics, such as mean nocturnal basal impedance (MNBI), have emerged to corroborate with GERD diagnosis. The aim of the present study was to describe the prevalence of GERD, functional heartburn (FH), reflux hypersensitivity (RH), and undetermined diagnosis using current consensuses and to evaluate if MNBI could be considered a supportive measure for the diagnosis of GERD. METHODS Patients who underwent pH-multichannel intraluminal impedance (MII-pH) for suspected GERD between 2013 and 2018 were included. Subjects with previous diagnosis of GERD (e.g., esophagitis grade C or D according to Los Angeles classification, Barrett's esophagus, or peptic stricture), atypical symptoms, major esophageal motor disorder, eosinophilic esophagitis, or under proton pump inhibitor were excluded from the analysis. RESULTS We included 75 patients. The prevalence of GERD, FH, RH and undetermined diagnosis was 44%, 14.7%, 12%, and 29.3%, respectively. MNBI was lower in patients with GERD (GERD: 1,307.5 ± 817.9 Ω vs. FH: 3,039.6 ± 1,040.8 Ω, RH: 2,617.1 ± 1,342.2 Ω, undetermined: 2,351.9 ± 1,018.2, p < 0.001), although it was similar between patients with FH and RH (p = 0.44) or between undetermined diagnosis and FH/RH (p = 0.15). More patients with a GERD diagnosis had a MNBI under 2,292 Ω (GERD: 93.9% vs. non-GERD: 31.7%, p < 0.001). CONCLUSION In our study, using MII-pH criteria, less than half of the patients had a GERD diagnosis. MNBI showed additional value as another metric for the diagnosis of GERD.
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Affiliation(s)
- Ana Catarina Gomes
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - Mafalda Sousa
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - Rita Lopes
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - Edgar Afecto
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - João Correia
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - Teresa Freitas
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
| | - João Carvalho
- Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal
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27
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Ye B, Wang Y, Lin L, Jiang L, Wang M. Sex-Based Differences in pH Parameters and Esophageal Impedance of Patients With Gastroesophageal Reflux Disease. Front Med (Lausanne) 2021; 8:629302. [PMID: 34124085 PMCID: PMC8192704 DOI: 10.3389/fmed.2021.629302] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Accepted: 04/23/2021] [Indexed: 12/22/2022] Open
Abstract
Background/Aims: The incidence of reflux esophagitis (RE) has a striking predominance in males. Conversely, non-erosive reflux disease (NERD) is more common in females. This imbalance of gastroesophageal reflux disease (GERD) implies sex-related differences in its pathogenesis. However, limited studies have analyzed the sex-based differences in pH parameters and esophageal impedance of GERD patients. Methods: This study evaluated sex-based pathogenesis differences by comparing reflux episodes, mean nocturnal baseline impedance (MNBI) values, and post-reflux swallow-induced peristaltic wave (PSPW) index values of males with GERD and females with GERD using 24-h multichannel intraluminal impedance and pH monitoring. Results: We analyzed 181 patients (102 males and 79 females) with GERD. Reflux symptom index (RSI) scores were higher in females than that in males (P < 0.05). Males had significantly longer acid exposure times, higher DeMeester scores, and more acid reflux episodes than females (P < 0.05). Females had more instances of weakly acidic reflux than males (P < 0.01). The PSPW index values of males and females were similar (P > 0.05). Compared with females, males had lower MNBI values for the mid and distal esophagus (P < 0.05). However, with increasing age, the MNBI values of females decreased more rapidly than those of males. MNBI values of elderly patients of both sexes older than 60 years were similar. Conclusions: Acid reflux is more likely to occur in males; however, females tend to have more instances of weakly acid reflux. The integrity of the esophageal mucosa is more fragile in males than in females; however, the esophageal mucosal barrier attenuates more rapidly with increasing age in females than in males.
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Affiliation(s)
- Bixing Ye
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yanjuan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Liuqin Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Meifeng Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Ustaoglu A, Sawada A, Lee C, Lei WY, Chen CL, Hackett R, Sifrim D, Peiris M, Woodland P. Heartburn sensation in nonerosive reflux disease: pattern of superficial sensory nerves expressing TRPV1 and epithelial cells expressing ASIC3 receptors. Am J Physiol Gastrointest Liver Physiol 2021; 320:G804-G815. [PMID: 33655767 DOI: 10.1152/ajpgi.00013.2021] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The underlying causes of heartburn, characteristic symptom of gastroesophageal reflux disease (GERD), remain incompletely understood. Superficial afferent innervation of the esophageal mucosa in nonerosive reflux disease (NERD) may drive nociceptive reflux perception, but its acid-sensing role has not yet been established. Transient receptor potential vanilloid subfamily member-1 (TRPV1), transient receptor potential melastatin 8 (TRPM8), and acid-sensing ion channel 3 (ASIC3) are regulators of sensory nerve activity and could be important reflux-sensing receptors within the esophageal mucosa. We characterized TRPV1, TRPM8, and ASIC3 expression in esophageal mucosa of patients with GERD. We studied 10 patients with NERD, 10 with erosive reflux disease (ERD), 7 with functional heartburn (FH), and 8 with Barrett's esophagus (BE). Biopsies obtained from the distal esophageal mucosa were costained with TRPV1, TRPM8, or ASIC3, and CGRP, CD45, or E-cadherin. RNA expression of TRPV1, TRPM8, and ASIC3 was assessed using qPCR. Patients with NERD had significantly increased expression of TRPV1 on superficial sensory nerves compared with ERD (P = 0.028) or BE (P = 0.017). Deep intrapapillary nerve endings did not express TRPV1 in all phenotypes studied. ASIC3 was exclusively expressed on epithelial cells most significantly in patients with NERD and ERD (P ≤0.0001). TRPM8 was expressed on submucosal CD45+ leukocytes. Superficial localization of TRPV1-immunoreactive nerves in NERD, and increased ASIC3 coexpression on epithelial cells in NERD and ERD, suggests a mechanism for heartburn sensation. Esophageal epithelial cells may play a sensory role in acid reflux perception and act interdependently with TRPV1-expressing mucosal nerves to augment hypersensitivity in patients with NERD, raising the enticing possibility of topical antagonists for these ion channels as a therapeutic option.NEW & NOTEWORTHY We demonstrate for the first time that increased pain perception in patients with nonerosive reflux disease likely results from expression of acid-sensitive channels on superficial mucosal afferents and esophageal epithelial cells, raising the potential for topical therapy.
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Affiliation(s)
- Ahsen Ustaoglu
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Akinari Sawada
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Chung Lee
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Richard Hackett
- Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Madusha Peiris
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
| | - Philip Woodland
- Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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Zerbib F, Bredenoord AJ, Fass R, Kahrilas PJ, Roman S, Savarino E, Sifrim D, Vaezi M, Yadlapati R, Gyawali CP. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil 2021; 33:e14075. [PMID: 33368919 DOI: 10.1111/nmo.14075] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/11/2020] [Accepted: 12/13/2020] [Indexed: 02/08/2023]
Abstract
Up to 40% of patients with symptoms suspicious of gastroesophageal reflux disease (GERD) do not respond completely to proton pump inhibitor (PPI) therapy. The term "refractory GERD" has been used loosely in the literature. A distinction should be made between refractory symptoms (ie, symptoms may or may not be GERD-related), refractory GERD symptoms (ie, persisting symptoms in patients with proven GERD, regardless of relationship to ongoing reflux), and refractory GERD (ie, objective evidence of GERD despite adequate medical management). The present ESNM/ANMS consensus paper proposes use the term "refractory GERD symptoms" only in patients with persisting symptoms and previously proven GERD by either endoscopy or esophageal pH monitoring. Even in this context, symptoms may or may not be reflux related. Objective evaluation, including endoscopy and esophageal physiologic testing, is requisite to provide insights into mechanisms of symptom generation and evidence of true refractory GERD. Some patients may have true ongoing refractory acid or weakly acidic reflux despite PPIs, while others have no evidence of ongoing reflux, and yet others have functional esophageal disorders (overlapping with proven GERD confirmed off therapy). In this context, attention should also be paid to supragastric belching and rumination syndrome, which may be important contributors to refractory symptoms.
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Affiliation(s)
- Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Gastroenterology Department, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | | | - Ronnie Fass
- Digestive Health Center, MetroHealth System, Cleveland, OH, USA
| | - Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University, Chicago, IL, USA
| | - Sabine Roman
- Hospices Civils de Lyon, Hôpital E Herriot, Digestive Physiology, Université de Lyon, Inserm U1032, LabTAU, Lyon, France
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University Hospital of Padua, Padua, Italy
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University, Nashville, TN, USA
| | - Rena Yadlapati
- Division of Gastroenterology, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, MO, USA
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30
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Advances in the diagnosis of GERD. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MÉDECINE INTERNE 2021; 59:3-9. [PMID: 33010143 DOI: 10.2478/rjim-2020-0027] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Indexed: 12/22/2022]
Abstract
Gastroesophageal reflux disease (GERD) is considered one of the most frequent chronic gastrointestinal diseases globally with high costs due to treatment and investigations.First line therapy is with proton pump inhibitors, those who do not respond to initial treatment usually require further investigations such as upper gastrointestinal endoscopy or ambulatory 24-hours esophageal pH monitoring. The total time of exposure to acid and the DeMeester score represent the most useful parameters associated with conventional pH-metry, because they can identify gastroesophageal reflux disease.Although pH-metry is considered the gold standard for the evaluation of gastroesophageal reflux disease, new impedance-based parameters have been introduced in recent years with the role of increasing the accuracy of diagnosing gastroesophageal reflux disease and characterizing the type of reflux. The development of multichannel intraluminal pH-impedance has improved the ability to detect and quantify gastroesophageal reflux. New parameters such as post-reflux swallowing peristaltic wave (PSPW) index and the mean nocturnal basal impedance (MNBI) have recently been introduced to assess GERD phenotypes more accurately. This review evaluates current GERD diagnotic tools while also taking a brief look at newer diagnostic parameters like PSPW and MNBI.
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31
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Roh SS, Shin MR, Lee J, Kim M, Park HJ. Rhei rhizoma and citri pericarpium mixture regulates oxidative stress and tight junction proteins on acute reflux esophagitis. Pharmacogn Mag 2021. [DOI: 10.4103/pm.pm_207_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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32
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Horton A, Posner S, Sullivan B, Cornejo J, Davis A, Fields M, McIntosh T, Gellad Z, Shimpi R, Gyawali CP, Patel A. Esophageal contractile segment impedance from high-resolution impedance manometry correlates with mean nocturnal baseline impedance and acid exposure time from 24-hour pH-impedance monitoring. Dis Esophagus 2020; 33:5865407. [PMID: 32607563 DOI: 10.1093/dote/doaa063] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/10/2020] [Accepted: 06/01/2020] [Indexed: 12/11/2022]
Abstract
Esophageal baseline impedance (BI) acquired during esophageal contraction (contractile segment impedance [CSI]) is proposed to improve BI accuracy in gastroesophageal reflux disease (GERD). We evaluated associations between CSI and conventional and novel GERD metrics. We analyzed high-resolution impedance manometry (HRIM) and ambulatory pH-impedance studies from 51 patients (58.6 ± 1.5 years; 26% F) with GERD symptoms studied off antisecretory therapy. Patients with achalasia or absent contractility were excluded. CSI (averaged across 10 swallows) and BI-HRIM (from the resting landmark phase) were acquired from the distal impedance sensors (distal sensor and 5 cm above the lower esophageal sphincter). Acid exposure time (AET) and mean nocturnal baseline impedance (MNBI) were calculated. Associations between CSI, BI-HRIM, MNBI, and AET were evaluated using correlation (Pearson) and receiver operating characteristic (ROC) analysis. Presenting symptoms included heartburn (67%), regurgitation (12%), cough (12%), and chest pain (10%). CSI-distal and CSI-5 each correlated with BI-HRIM, AET, and distal MNBI. Associations with AET were numerically stronger for CSI-distal (r = -0.46) and BI-HRIM-distal (r = -0.44) than CSI-5 (r = -0.33), BI-HRIM-5 (r = -0.28), or distal MNBI (r < -0.36). When compared to AET <4%, patients with AET >6% had significantly lower CSI-distal and BI-HRIM-distal values but not CSI-5, BI-HRIM-5, or MNBI. ROC areas under the curve for AET >6% were numerically higher for CSI-distal (0.81) than BI-HRIM-distal (0.77), distal MNBI (0.68-0.75), CSI-5 (0.68), or BI-HRIM-5 (0.68). CSI from HRIM studies inversely correlates with pathologic AET and has potential to augment the evaluation of GERD.
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Affiliation(s)
- Anthony Horton
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Shai Posner
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Brian Sullivan
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Jennifer Cornejo
- Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Andrea Davis
- Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Monika Fields
- Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Thasha McIntosh
- Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Ziad Gellad
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Rahul Shimpi
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, MO, USA
| | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Division of Gastroenterology, Durham Veterans Affairs Medical Center, Durham, NC, USA
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de Bortoli N, Gyawali CP, Frazzoni M, Tolone S, Frazzoni L, Vichi E, Visaggi P, Bellini M, Marabotto E, Penagini R, Savarino V, Marchi S, Savarino EV. Bile reflux in patients with nerd is associated with more severe heartburn and lower values of mean nocturnal baseline impedance and chemical clearance. Neurogastroenterol Motil 2020; 32:e13919. [PMID: 32573065 DOI: 10.1111/nmo.13919] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 05/10/2020] [Accepted: 05/19/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Mean nocturnal baseline impedance (MNBI) and postreflux swallow-induced peristaltic wave (PSPW) index are novel impedance-based markers of reflux, but the effect of bile reflux on these metrics is unknown. The aim of this study was to evaluate bile reflux, MNBI, and PSPW index in patients with endoscopy-negative GERD partially responsive to PPI therapy. METHODS All patients underwent off-PPI endoscopy, esophageal manometry, multichannel intraluminal impedance pH (MII-pH), and bile reflux monitoring. Abnormal esophageal acid exposure time (AET) was required for inclusion. Symptom intensity (using 10-cm visual analog scales), and conventional and novel MII-pH metrics were compared between patients with and without abnormal bile reflux. KEY RESULTS We evaluated 42 NERD patients (29 males, mean age: 53.4 ± 13. years), mean AET 6.1 ± 2%, of which 21 had abnormal bile reflux (Group A, 10.2 ± 4.9%), and 21 had normal bile reflux (Group B, 0.4 ± 0.1%, P < .05 compared with Group A). Heartburn reporting on PPI was higher in Group A (7.2 ± 2.1 vs 5.8 ± 0.9; P = .002), but AET, number of reflux events (acidic and weakly acidic), did not differ between the two groups. However, both PSPW index and MNBI were lower in Group A (P < .001). A strong inverse linear correlation was found between bile reflux and both MNBI (Pearson's test; R = -0.714; P < .001) and PSPW index (R = -0.722; P < .001). CONCLUSIONS AND INFERENCES Compared to acid reflux alone, the presence of bile in an acidic esophageal environment is associated with more severe heartburn, lesser relief from PPI therapy, higher impairment of esophageal mucosal integrity and less effective chemical clearance.
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Affiliation(s)
- Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - C Prakash Gyawali
- Department of Gastroenterology, Washington University School of Medicine, St Louis, MO, USA
| | - Marzio Frazzoni
- Gastroenterology Digestive Pathophysiology Unit, Baggiovara Hospital, Modena, Italy
| | - Salvatore Tolone
- Surgery Unit, Department of Surgery, University of Campania Luigi Vanvitelli, Caserta, Italy
| | - Leonardo Frazzoni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Eleonora Vichi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Massimo Bellini
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine (DIMI), Universitry of Genoa, Genoa, Italy
| | - Roberto Penagini
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine (DIMI), Universitry of Genoa, Genoa, Italy
| | - Santino Marchi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo V Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Savarino V, Marabotto E, Zentilin P, Demarzo MG, Pellegatta G, Frazzoni M, De Bortoli N, Tolone S, Giannini EG, Savarino E. Esophageal reflux hypersensitivity: Non-GERD or still GERD? Dig Liver Dis 2020; 52:1413-1420. [PMID: 33097427 DOI: 10.1016/j.dld.2020.10.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 09/29/2020] [Accepted: 10/01/2020] [Indexed: 12/11/2022]
Abstract
The most recent iteration of the classifications for functional esophageal disorders, Rome IV, proposed relevant modifications of the previous definitions for Rome III. They specifically considered increased esophageal acid exposure as the marker of gastroesophageal reflux disease (GERD), including the remaining part of non-erosive reflux disease patients with normal acid in the group with functional alterations, considering both reflux hypersensitivity and functional heartburn. However, recent pathophysiological and therapeutic data suggest the need for a return to including reflux hypersensitivity in the GERD spectrum. Indeed, physiologic alterations in esophageal mucosal integrity and chemical clearance, the presence of microscopic esophagitis, and strict symptom-reflux association support the concept that reflux hypersensitivity pertains to GERD. Surgical anti-reflux therapy has resulted in positive outcomes, even in the long term, in patients with reflux hypersensitivity and not in those with functional heartburn. Moreover, clinical trials using neuromodulators have been scarce and provided conflicting results. As a result, the real progress of the Rome IV classifications is in dispute. This article aims to summarize the most recent knowledge of non-erosive reflux disease and reflux hypersensitivity to discuss the utility of Rome IV criteria in the identification and management of functional esophageal disorders.
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Affiliation(s)
- Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Maria Giulia Demarzo
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gaia Pellegatta
- Digestive Endoscopy Unit, Division of Gastroenterology, Humanitas, Rozzano, Milan, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit, Baggiovara Hospital, Modena, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Salvatore Tolone
- General and Bariatric Surgery Unit, Department of Surgery, Università della Campania Luigi Vanvitelli, Naples, Italy
| | - Edoardo Giovanni Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.
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Gyawali CP, Sonu I, Becker L, Sarosiek J. The esophageal mucosal barrier in health and disease: mucosal pathophysiology and protective mechanisms. Ann N Y Acad Sci 2020; 1482:49-60. [PMID: 33128243 DOI: 10.1111/nyas.14521] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Revised: 10/09/2020] [Accepted: 10/10/2020] [Indexed: 12/13/2022]
Abstract
Diseases of the esophagus, such as gastroesophageal reflux (GER), can result in changes to mucosal integrity, neurological function, and the microbiome. Although poorly understood, both age and GER can lead to changes to the enteric nervous system. In addition, the esophagus has a distinct microbiome that can be altered in GER. Mucosal integrity is also at risk due to persistent damage from acid. Diagnostic tools, such as ambulatory pH/impedance testing and esophageal mucosal impedance, can assess short-term and longitudinal GER burden, which can also assess the risk for mucosal compromise. The quality of the mucosal barrier is determined by its intercellular spaces, tight junctions, and tight junction proteins, which are represented by claudins, occludins, and adhesion molecules. Fortunately, there are protective factors for mucosal integrity that are secreted by the esophageal submucosal mucous glands and within saliva that are augmented by mastication. These protective factors have potential as therapeutic targets for GER. In this article, we aim to review diagnostic tools used to predict mucosal integrity, aging, and microbiome changes to the esophagus and esophageal mucosal defense mechanisms.
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Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology and Hepatology, Washington University School of Medicine, St. Louis, Missouri
| | - Irene Sonu
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Laren Becker
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California
| | - Jerzy Sarosiek
- Division of Gastroenterology and Hepatology, Molecular Medicine Research Laboratory, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso, Texas
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Zikos TA, Triadafilopoulos G, Kamal A, Podboy A, Sonu IS, Regalia KA, Nandwani MC, Nguyen LA, Fernandez-Becker NQ, Clarke JO. Baseline impedance via manometry and ambulatory reflux testing are not equivalent when utilized in the evaluation of potential extra-esophageal gastroesophageal reflux disease. J Thorac Dis 2020; 12:5628-5638. [PMID: 33209395 PMCID: PMC7656325 DOI: 10.21037/jtd-20-1623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Background Esophageal baseline impedance (BI) shows promise for the diagnosis of gastroesophageal reflux disease (GERD), but means of acquisition and relevance to extra-esophageal manifestations of GERD (EE-GERD) remain unclear. In this study we aim to (I) evaluate concordance between BI as measured by 24-hour pH-impedance (pH-MII) and high-resolution impedance manometry (HRIM), and (II) assess relationship to potential EE-GERD symptoms. Methods In this prospective open cohort study, patients presenting for outpatient HRIM and pH-MII studies were prospectively enrolled. All patients completed the GERD-HRQL, NOSE, and respiratory symptom index questionnaire (RSI), plus questions regarding wheezing and dental procedures. HRIM and pH-MII were evaluated with calculation of BI. Correlations were assessed using either Pearson’s correlation or Spearman’s rank coefficients. Results 70 HRIM patients were enrolled, 35 of whom underwent pH-MII. There was no correlation between BI measurements as assessed by HRIM and pH-MII proximally, but there was moderate-weak correlation distally (r=0.34 to 0.5). Distal acid exposure time correlated with distal BI only for measurements by pH-MII (rho= −0.5 to −0.65), and not by HRIM. There was no relationship between proximal acid exposure time and proximal BI. There were no correlations when comparing proximal or distal BI measurements, acid exposure times, and impedance events to symptoms. Conclusions Concordance between BI as measured by HRIM and pH-MII is poor, especially proximally, suggesting that these two methods are not interchangeable. There is no correlation between BI both distally/proximally and symptoms of either GERD/EE-GERD, suggesting that many symptoms are unrelated to acid or that BI is not an adequate marker to assess EE-GERD symptoms.
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Affiliation(s)
- Thomas A Zikos
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - George Triadafilopoulos
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Afrin Kamal
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Alexander Podboy
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Irene S Sonu
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Kirsten A Regalia
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Monica C Nandwani
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Linda A Nguyen
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Nielsen Q Fernandez-Becker
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - John O Clarke
- Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Kim YG, Noh CK, Lee KJ. The Usefulness of Esophageal Baseline Impedance Levels for the Diagnosis of Nonerosive Reflux Disease and the Proper Time for Measurement in Endoscopy-negative Korean Patients With Esophageal or Supraesophageal Symptoms. J Neurogastroenterol Motil 2020; 26:463-470. [PMID: 32595173 PMCID: PMC7547184 DOI: 10.5056/jnm20019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 03/29/2020] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Low baseline impedance levels (BILs) have been suggested to be evidence of GERD. The aim of this study is to investigate the usefulness of esophageal BILs for the diagnosis of nonerosive reflux disease (NERD) and the proper time for measurement in endoscopy-negative Korean patients with esophageal or supraesophageal symptoms. Methods Endoscopy-negative patients with esophageal or supraesophageal symptoms who underwent esophageal multichannel intraluminal impedance-pH monitoring were included. BILs were measured in the proximal and distal esophagus around 10 minutes before meals, 10 minutes and 30 minutes after meals, 30 minutes before the start of nighttime sleep, and 30 minutes and 60 minutes after the start of nighttime sleep. Results A total of 104 patients were included in the study. Distal and proximal esophageal BILs were decreased after meal ingestion. The BILs of the distal esophagus were significantly lower at all time points in the NERD group, but not in the reflux hypersensitivity (RH) group, compared with the functional group. The area under the receiver operating characteristic curve for the diagnosis of NERD was significant at all time points, but that for the diagnosis of RH was not. The cut-off value of 2375 Ω or 2125 Ω measured around 30 minutes before or 60 minutes after the start of nighttime sleep, respectively, were appropriate for the diagnosis of NERD. Conclusion The BILs of the distal esophagus measured at time points before or after the start of nighttime sleep appear to be useful for the diagnosis of NERD, but not for the diagnosis of RH, in endoscopy-negative Korean patients with esophageal or supraesophageal symptoms.
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Affiliation(s)
- Young-Gun Kim
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Choong-Kyun Noh
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
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Horton A, Sullivan B, Charles K, McIntosh T, Davis A, Gellad Z, Shimpi R, Gyawali CP, Patel A. Esophageal Baseline Impedance From High-resolution Impedance Manometry Correlates With Mean Nocturnal Baseline Impedance From pH-impedance Monitoring. J Neurogastroenterol Motil 2020; 26:455-462. [PMID: 32388941 PMCID: PMC7547185 DOI: 10.5056/jnm19142] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 11/04/2019] [Accepted: 12/30/2019] [Indexed: 12/20/2022] Open
Abstract
Background/Aims Esophageal baseline impedance (BI) can be extracted from pH-impedance tracings as mean nocturnal baseline impedance (MNBI), and from high-resolution impedance manometry (HRIM), but it is unknown if values are similar between acquisition methods across HRIM manufacturers. We aim to assess correlations between MNBI and BI from HRIM (BI-HRIM) from 2 HRIM manufacturers in the setting of physiologic acid exposure time (AET). Methods HRIM and pH-impedance monitoring demonstrating physiologic AET (< 4%) off proton pump inhibitors were required. BI-HRIM was extracted as the average from 5 cm and 10 cm above the lower esophageal sphincter. Distal BI-HRIM (DBI-HRIM) was also extracted from the most distal channel (Medtronic studies). MNBI was extracted from 6 channels. Concordance between BI-HRIM across manufacturers with MNBI was analyzed. Results Thirty-six patients met the inclusion criteria (59.6 ± 1.7 years; 22% female; body mass index 30.5 ± 0.7; AET 1.6 ± 0.2%). Although MNBI was similar at all channels (P ≥ 0.18), Diversatek BI-HRIM was lower than Medtronic BI-HRIM (P = 0.003). Overall, BI-HRIM correlated with MNBI at corresponding recording sites, 7 cm and 9 cm (P < 0.05), but not at other sites (P ≥ 0.19). Pearson’s correlations > 0.5 were seen at MNBI at 7 cm for both systems, and at 9 cm for Medtronic. DBI-HRIM correlated with MNBI at 3 cm and 5 cm (P < 0.03), but not at other locations (P > 0.1). Conclusions While numeric differences exist between manufacturers, BI-HRIM correlates with MNBI from corresponding channels in patients with physiologic AET. Comparison with AET elevation is needed to determine correlations between pathologic MNBI with BI-HRIM across manufacturers. The optimal HRIM channels from which BI values should be extracted also warrants further study.
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Affiliation(s)
- Anthony Horton
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - Brian Sullivan
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Katie Charles
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | | | - Andrea Davis
- Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Ziad Gellad
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Durham Veterans Affairs Medical Center, Durham, NC, USA
| | - Rahul Shimpi
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, MO, USA
| | - Amit Patel
- Division of Gastroenterology, Duke University School of Medicine, Durham, NC, USA.,Durham Veterans Affairs Medical Center, Durham, NC, USA
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Aksionchyk M, Marakhouski K, Svirsky A. Gastroesophageal reflux disease in pediatric esophageal atresia: Assessment of clinical symptoms and pH-impedance data. World J Clin Pediatr 2020; 9:29-43. [PMID: 33014720 PMCID: PMC7515750 DOI: 10.5409/wjcp.v9.i2.29] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/28/2020] [Accepted: 09/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Esophageal atresia (EA) is the most common congenital anomaly of the gastrointestinal tract. Gastroesophageal reflux disease (GERD) is a frequent and lifelong problem in these patients. GERD can be asymptomatic and the incidence of esophageal gastric and intestinal metaplasia (Barrett’s esophagus) is increased in adults with EA compared with the general population. Timely and accurate diagnosis of GERD is important to reduce long-term problems and this may be achieved by pH-impedance testing.
AIM To assess symptoms and pH-impedance data in children after EA, in order to identify their specific features of GERD.
METHODS This study was conducted from November 2017 to February 2020 and involved 37 children who had undergone EA via open surgical repair (51.35% boys, 48.65% girls; age range: 1-14 years, median: 4.99 years). GERD diagnosis was made based on multichannel intraluminal impedance/pH study and two groups were established: EA without GERD, n = 17; EA with GERD, n = 20. A control group was established with 66 children with proven GERD (68.18% boys, 31.82% girls; median age: 7.21 years), composed of a nonerosive reflux disease (referred to as NERD) group (n = 41) and a reflux esophagitis group (n = 25). Upper gastrointestinal endoscopy with a mucosal esophageal biopsy was performed on all patients.
RESULTS The most frequently observed symptom in EA patients with GERD and without GERD was cough (70% and 76.5% respectively). The number of patients with positive symptom association probability in the EA groups was significantly larger in the EA without GERD group (P = 0.03). In the control reflux esophagitis group, prevalence of gastrointestinal symptoms was significantly higher than in the NERD group (P = 0.017). For both EA groups, there was strong correlation with index of proximal events (IPE) and total proximal events (EA with GERD: 0.96, P < 0.001; EA without GERD: 0.97, P < 0.001) but level of IPE was significantly lower than in GERD patients without any surgical treatment (P < 0.001). Data on distal mean nocturnal baseline impedance were significantly different between the EA with GERD group (P < 0.001) and the two control groups but not between EA without GERD and the two control groups.
CONCLUSION Mean nocturnal baseline impedance may have diagnostic value for GERD in EA children after open surgical repair. IPE might be an additional parameter of pH-impedance monitoring.
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Affiliation(s)
- Marina Aksionchyk
- Department of Pediatric Gastroenterology, Diagnostic Division, Republican Scientific and Practical Center for Pediatric Surgery, Minsk 220013, Belarus
| | - Kirill Marakhouski
- Department of Endoscopy, Republican Scientific and Practical Center of Pediatric Surgery, Minsk 220013, Belarus
| | - Aliaksandr Svirsky
- Department of Pediatric surgery, Republican Scientific and Practical Center of Pediatric Surgery, Minsk 220013, Belarus
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Abstract
Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram. Functional lumen imaging probe (FLIP) has recently been approved for the evaluation of esophageal pressure and dimensions using volumetric distension of a catheter-mounted balloon and as an adjunctive test for the evaluation of symptoms suggestive of motor dysfunction. Targeted utilization of esophageal physiologic tests can lead to definitive diagnosis of esophageal disorders but can also help rule out organic disorders while making a diagnosis of functional esophageal disorders. Esophageal physiologic tests can evaluate obstructive symptoms (dysphagia and regurgitation), typical and atypical GERD symptoms, and behavioral symptoms (belching and rumination). Certain parameters from esophageal physiologic tests can help guide the management of GERD and predict outcomes. In this ACG clinical guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to describe performance characteristics and clinical value of esophageal physiologic tests and provide recommendations for their utilization in routine clinical practice.
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Kataria R, Rosenfeld B, Malik Z, Harrison M, Smith MS, Schey R, Parkman HP. Distal Esophageal Impedance Measured by High-resolution Esophageal Manometry With Impedance Suggests the Presence of Barrett's Esophagus. J Neurogastroenterol Motil 2020; 26:344-351. [PMID: 32325542 PMCID: PMC7329159 DOI: 10.5056/jnm19105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 07/03/2019] [Accepted: 12/18/2019] [Indexed: 11/20/2022] Open
Abstract
Background/Aims Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus. The aims of this study are to: (1) Compare baseline distal esophageal impedance (DEI) using high-resolution esophageal manometry with impedance (HREMI) in patients with BE, esophagitis, and healthy volunteers and (2) Correlate length of low impedance on HREMI in patients with BE to the length of endoscopic BE. Methods Patients with BE or esophagitis who underwent HREMI were included. Ten volunteers had HREMI. Baseline DEI was calculated from HREMI using the landmark segment. In patients with BE, the impedance was plotted to measure the extent of plotted low impedance (PLI) and visual low impedance (VLI). Lengths of VLI and PLI were correlated to endoscopic length of BE by Prague score. Results Forty-five patients were included (16 BE; 19 esophagitis; 10 volunteers). BE patients had lower baseline DEI at the first, second, and third sensors above the lower esophageal sphincter (mean ± SEM: 1.37 ± 0.45, 0.97 ± 0.27, and 0.81 ± 0.20) compared to volunteers (8.73 ± 0.60, 8.20 ± 0.73, and 6.94 ± 0.99; P < 0.001). Baseline DEI was lower in BE than esophagitis patients (2.98 ± 0.65, 2.49 ± 0.56, and 2.01 ± 0.51) at the first, second, and third sensors (P < 0.052 for second and third sensors); ie, BE < esophagitis < controls. PLI and VLI had a stronger correlation to circumferential score (r2 = 0.84 and 0.83) than maximal score (r2 = 0.76 and 0.68). Conclusions Baseline DEI is lower in BE compared with esophagitis and healthy volunteers. The length of low impedance correlates to the endoscopic extent of BE. Thus, impedance values during HREMI may help suggest the presence and extent of BE or esophagitis.
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Affiliation(s)
- Rahul Kataria
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
| | - Benjamin Rosenfeld
- Department of Internal Medicine, Temple University Hospital, Philadelphia, PA, USA
| | - Zubair Malik
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
| | - Martha Harrison
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
| | - Michael S Smith
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
| | - Ron Schey
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
| | - Henry P Parkman
- Division of Gastroenterology, Temple University Hospital, Philadelphia, PA, USA
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Abstract
Various esophageal functional abnormalities have been described in patients with Barrett's esophagus (BE). A significantly higher esophageal acid exposure especially in the supine position has been documented in BE, as compared with the other gastroesophageal reflux disease phenotypes. In addition, weakly acidic reflux and duodenogastroesophageal reflux are more common in BE patients. The presence of Barrett's mucosa reduces esophageal mucosal impedance, occasionally to a level that prevents detection of reflux episodes. Reduced amplitude contractions and lower esophageal sphincter basal pressure are more common in BE patients as compared with the other gastroesophageal reflux disease groups. Ineffective esophageal motility is the most commonly defined motor disorder in BE. Reduced chemoreceptor and mechanoreceptor sensitivity to acid and balloon distention, respectively, have been suggested to explain lack or significantly less reports of reflux-related symptoms by BE patients.
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Wu PI, Sloan JA, Kuribayashi S, Gregersen H. Impedance in the evaluation of the esophagus. Ann N Y Acad Sci 2020; 1481:139-153. [PMID: 32557676 DOI: 10.1111/nyas.14408] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/09/2020] [Accepted: 05/14/2020] [Indexed: 12/16/2022]
Abstract
The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms.
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Affiliation(s)
- Peter I Wu
- Department of Gastroenterology and Hepatology, St George Hospital, University of New South Wales, Sydney, New South Wales, Australia
| | - Joshua A Sloan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology, Gunma University Hospital, Maebashi, Japan
| | - Hans Gregersen
- GIOME, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China
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Low-Cost Method and Biochip for Measuring the Trans-Epithelial Electrical Resistance (TEER) of Esophageal Epithelium. MATERIALS 2020; 13:ma13102354. [PMID: 32443854 PMCID: PMC7288155 DOI: 10.3390/ma13102354] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 05/13/2020] [Accepted: 05/18/2020] [Indexed: 12/13/2022]
Abstract
Trans-epithelial electrical resistance (TEER) is a good indicator of the barrier integrity of epithelial tissues and is often employed in biomedical research as an effective tool to assess ion transport and permeability of tight junctions. The Ussing chamber is the gold standard for measuring TEER of tissue specimens, but it has major drawbacks: it is a macroscopic method that requires a careful and labor intensive sample mounting protocol, allows a very limited viability for the mounted sample, has large parasitic components and low throughput as it cannot perform multiple simultaneous measurements, and this sophisticated and delicate apparatus has a relatively high cost. This paper demonstrates a low-cost home-made “sandwich ring” method which was used to measure the TEER of tissue specimens effectively. This method inspired the subsequent design of a biochip fabricated using standard soft lithography and laser engraving technologies, with which the TEER of pig epithelial tissues was measured. Moreover, it was possible to temporarily preserve the tissue specimens for days in the biochip and monitor the TEER continuously. Tissue responses after exposure tests to media of various pH values were also successfully recorded using the biochip. All these demonstrate that this biochip could be an effective, cheaper, and easier to use Ussing chamber substitute that may have relevant applications in clinical practice.
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Ang D, Lee Y, Clarke JO, Lynch K, Guillaume A, Onyimba F, Kamal A, Gyawali CP. Diagnosis of gastroesophageal reflux: an update on current and emerging modalities. Ann N Y Acad Sci 2020; 1481:154-169. [DOI: 10.1111/nyas.14369] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 04/17/2020] [Accepted: 04/22/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Daphne Ang
- Department of Gastroenterology Changi General Hospital Singapore Singapore
| | - Yeong‐Yeh Lee
- Department of Gastroenterology, Hepatology and Internal Medicine, School of Medical Sciences Universiti Sains Malaysia Kota Bharu Malaysia
- Gut Research Group, Faculty of Medicine National University of Malaysia Kuala Lumpur Malaysia
- St George and Sutherland Clinical School University of New South Wales Sydney New South Wales Australia
| | - John O. Clarke
- Division of Gastroenterology and Hepatology Stanford University Stanford California
| | - Kristle Lynch
- Division of Gastroenterology, Department of Medicine Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania
| | - Alexandra Guillaume
- Division of Gastroenterology and Hepatology, Stony Brook Medicine Stony Brook University Hospital Stony Brook New York
| | - Frances Onyimba
- Division of Gastroenterology and Hepatology University of Maryland School of Medicine Baltimore Maryland
| | - Afrin Kamal
- Division of Gastroenterology and Hepatology Stanford University Stanford California
| | - C. Prakash Gyawali
- Division of Gastroenterology Washington University School of Medicine St. Louis Missouri
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Hoshikawa Y, Sawada A, Sonmez S, Nikaki K, Woodland P, Yazaki E, Sifrim D. Measurement of Esophageal Nocturnal Baseline Impedance: A Simplified Method. J Neurogastroenterol Motil 2020; 26:241-247. [PMID: 32235031 PMCID: PMC7176501 DOI: 10.5056/jnm19183] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Revised: 12/06/2019] [Accepted: 12/12/2019] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Mean nocturnal baseline impedance (MNBI) during multichannel intraluminal impedance pH-monitoring (MII-pH) reflects the status of esophageal mucosal integrity. MNBI is suggested as an adjunctive method to distinguish patients with true gastroesophageal reflux disease (GERD) from functional heartburn (FH) and might predict outcomes for anti-reflux treatment. However, current methodology for calculation of MNBI is time-consuming and subject to operator-dependent selection bias. We aim to simplify and provide a more objective method to calculate MNBI. Methods We retrospectively analyzed 100 MII-pH tracings from 20 patients with erosive reflux disease, 20 with non-erosive reflux disease (NERD), 20 with reflux hypersensitivity, 20 with functional heartburn (FH), and 20 healthy asymptomatic volunteers. We compared the current “conventional” MNBI analysis with our “simple” MNBI analysis measured by selecting the whole supine period using the impedance average calculation function in the MII-pH software. Results Absolute values were very similar and there was a strong correlation between conventional and simple MNBI values in the most distal channel in all groups (r ≥ 0.8, P < 0.001) including patients with increased supine acid reflux. Distal esophageal simple MNBI negatively correlated with acid exposure time (r = –0.695, P < 0.001). Patients with erosive reflux disease and NERD had lower simple MNBI values in the most distal channel compared to other groups (P < 0.001). With a cutoff value of 1785 ohms, simple MNBI can discriminate patients with GERD from those with reflux hypersensitivity and FH (sensitivity 80.0% and specificity 89.7%). Conclusion Simple MNBI analysis provides very similar values and has an excellent correlation with conventional MNBI analysis.
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Affiliation(s)
- Yoshimasa Hoshikawa
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Akinari Sawada
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Shirley Sonmez
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Kornilia Nikaki
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Philip Woodland
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Etsuro Yazaki
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
| | - Daniel Sifrim
- Barts and the London School of Medicine and Dentistry, Queen Mary University of London
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Zachariah RA, Goo T, Lee RH. Mechanism and Pathophysiology of Gastroesophageal Reflux Disease. Gastrointest Endosc Clin N Am 2020; 30:209-226. [PMID: 32146942 DOI: 10.1016/j.giec.2019.12.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Gastroesophageal reflux (GER) describes a process in which gastric contents travel retrograde into the esophagus. GER can be either a physiologic phenomenon that occurs in asymptomatic individuals or can potentially cause symptoms. When the latter occurs, this represents GER disease (GERD). The process by which GER transforms into GERD begins at the esophagogastric junction. Impaired clearance of the refluxate also contributes to GERD. Reflux causes degradation of esophageal mucosal defense. The refluxate triggers sensory afferents leading to symptom generation.
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Affiliation(s)
- Robin A Zachariah
- H.H. Chao Comprehensive Digestive Disease Center, 333 City Boulevard West, Suite 400, Room 459, Orange, CA 92868, USA
| | - Tyralee Goo
- Tibor Rubin Veterans' Affairs Medical Center, 5901 E. Seventh Street, Long Beach, CA 90822, USA
| | - Robert H Lee
- H.H. Chao Comprehensive Digestive Disease Center, 333 City Boulevard West, Suite 400, Room 459, Orange, CA 92868, USA; Tibor Rubin Veterans' Affairs Medical Center, 5901 E. Seventh Street, Long Beach, CA 90822, USA.
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48
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Katzka DA, Pandolfino JE, Kahrilas PJ. Phenotypes of Gastroesophageal Reflux Disease: Where Rome, Lyon, and Montreal Meet. Clin Gastroenterol Hepatol 2020; 18:767-776. [PMID: 31319183 PMCID: PMC6960363 DOI: 10.1016/j.cgh.2019.07.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2019] [Revised: 06/25/2019] [Accepted: 07/03/2019] [Indexed: 02/07/2023]
Abstract
Gastroesophageal reflux disease (GERD) is now one of the most common diagnoses made in a gastroenterology practice. From a conventional pathophysiological perspective, GERD is conceptualized as incompetence of the antireflux barrier at the esophagogastric junction; the more severe that incompetence, the worse the disease. However, it is increasingly clear that many presentations of GERD represent distinct phenotypes with unique predisposing cofactors and pathophysiology outside of this paradigm. Three major consensus initiatives have grappled with this dilemma (the Montreal Consensus, The Rome Foundation, and the Lyon Consensus), each from a different perspective. Montreal struggled to define the disease, Rome sought to characterize its functional attributes, while Lyon examined its physiological attributes. Here, we merge the 3 perspectives, developing the concept that what has come to be known as GERD is actually a family of syndromes with a complex matrix of contributing pathophysiology. A corollary to this is that the concept of one size fits all to therapeutics does not apply, and that although escalating treatment with proton pump inhibitors (PPIs) may be pertinent to healing esophagitis, its applicability beyond that is highly questionable. Similarly, failing to recognize the modulating effects of anxiety, hypervigilance, and visceral and central hypersensitivity on symptom severity has greatly oversimplified the problem. That oversimplification has led to excessive use of PPIs for everything captured under the GERD umbrella and shown a broad spectrum of syndromes less amenable to PPI therapy in any dose. It is with this in mind that we delineate this precision medicine concept of GERD.
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Affiliation(s)
- David A Katzka
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - John E Pandolfino
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Peter J Kahrilas
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
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49
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Rengarajan A, Savarino E, Della Coletta M, Ghisa M, Patel A, Gyawali CP. Mean Nocturnal Baseline Impedance Correlates With Symptom Outcome When Acid Exposure Time Is Inconclusive on Esophageal Reflux Monitoring. Clin Gastroenterol Hepatol 2020; 18:589-595. [PMID: 31163276 DOI: 10.1016/j.cgh.2019.05.044] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 05/16/2019] [Accepted: 05/24/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Abnormal acid exposure time (AET) is associated with good outcomes of symptoms from antireflux therapy. Low esophageal mean nocturnal baseline impedance (MNBI) is an additional marker of reflux disease. We aimed to evaluate the value of MNBI when analysis of AET produces borderline or inconclusive results. METHODS We studied a retrospective cohort of 371 patients (mean age, 54.5 ± 0.7 y; 60.0% female) who had persistent reflux symptoms after treatment and underwent ambulatory pH-impedance monitoring off antisecretory therapy at 1 tertiary center in Europe or 1 in the United States. Total AET was determined from pH impedance studies (pathologic, >6%; physiologic, <4%; borderline or inconclusive, 4%-6%). Baseline impedance values were calculated at the 5-cm impedance channel at 3 nocturnal 10-minute periods and averaged to yield MNBI (abnormal, <2292 ohms). The primary outcome was response to antireflux therapy, defined as global symptom improvement of 50% or greater on patients' answers on standardized visual analog scales. RESULTS Among the 371 patients, 107 (28.8%) had pathologic AET and 234 (63.1%) had abnormal MNBI. Low MNBI was concordant in 99.1% of patients with pathologic AET, in 91.2% with borderline AET, and in 33.7% with physiologic AET. During 38.7 ± 0.8 months of follow-up evaluation, 43.0% of patients had improved symptoms with medical therapy and 76.2% had improved symptoms with surgical antireflux therapy (P < .0001). When MNBI was low, response to medical therapy did not differ significantly between patients with borderline AET and patients with pathologic AET (P = .44), but did differ significantly when each group was compared with patients with physiologic AET, regardless of whether MNBI was normal or low (P < .0001 for each comparison). CONCLUSIONS When low, MNBI identifies patients with pathologic and borderline AET who respond to antireflux therapy. MNBI analysis complements AET in defining esophageal reflux burden. MNBI correlates with response of symptoms to antireflux therapy.
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Affiliation(s)
- Arvind Rengarajan
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Marco Della Coletta
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Amit Patel
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri; Division of Gastroenterology, Durham Veterans Administration Hospital, Duke University, Durham, North Carolina
| | - C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri.
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50
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Baseline Impedance Measured During High-resolution Esophageal Impedance Manometry in Patients With Rumination Syndrome is as Abnormal as in Patients With GERD. J Clin Gastroenterol 2020; 54:28-34. [PMID: 30575633 DOI: 10.1097/mcg.0000000000001159] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
GOALS AND BACKGROUND Baseline impedance measured during high-resolution impedance manometry (HRIM) can distinguish patients with gastroesophageal reflux disease (GERD) from controls, presumably due to differences in esophageal acid exposure. The characteristics of regurgitation and reflux in rumination syndrome and GERD are very different, and thus we investigated whether baseline esophageal impedance would differ in these 2 patient groups compared with controls. STUDY We compared 20 patients with rumination syndrome with 20 patients who had GERD and 40 controls. Baseline impedance was measured over 15 seconds during the landmark period of HRIM in all 18 impedance sensors on a HRIM catheter. RESULTS The mean distal baseline impedance measured in ohms during HRIM was 1336 Ω [95% confidence interval (CI)=799, 1873) in patients with GERD, 1536 Ω in rumination syndrome (95% CI=1012, 2061), and 3379 Ω in controls (95% CI=2999, 3759) (P<0.0001). Proximal impedance was significantly lower in the GERD and rumination groups compared with controls; rumination syndrome (2026; 95% CI=1493, 2559 Ω), GERD (2572; 95% CI=2027, 3118 Ω), and controls (3412; 95% CI=3026, 3798 Ω) (P<0.001). CONCLUSIONS Baseline impedance measured during HRIM in patients with rumination syndrome is significantly lower than controls and appears similar to patients with GERD both in the proximal and distal esophagus. These findings suggest that the postprandial regurgitation in rumination syndrome alters both the distal and proximal esophageal mucosal barrier.
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