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Ribolsi M, Marchetti L, Olmi LM, Cicala M, Savarino E. Esophageal chest pain resembles heartburn in reflux metrics and response to proton pump inhibitor therapy. Neurogastroenterol Motil 2025; 37:e14953. [PMID: 39485991 DOI: 10.1111/nmo.14953] [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: 06/24/2024] [Revised: 10/14/2024] [Accepted: 10/19/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND Gastro-esophageal reflux disease (GERD) is the most common cause for noncardiac chest pain (NCCP), with an estimated prevalence rate ranging between 30% and 60%. Heartburn and NCCP may share common mechanisms. AIMS/METHODS To assess whether particular patterns of impedance-pH variables characterize patients with dominant heartburn, regurgitation, or NCCP and their ability to predict proton pump inhibitor (PPI) response for each symptom, GERD patients, evaluated with high-resolution manometry (HRM) and impedance-pH, were included. RESULTS In total, 109 NCCP, 68 heartburn, and 64 regurgitation patients were included. Pathological reflux episodes were observed in 28%, 19%, and 56% (p < 0.001). Pathological mean nocturnal baseline impedance (MNBI) values were observed in 55%, 53%, and 34% (p < 0.05). Hypomotility was more frequent in NCCP compared to heartburn patients (p < 0.05). When comparing NCCP with heartburn, hypomotility was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). When comparing NCCP with regurgitation, >80 refluxes and type 2/3 esophagogastric junction (EGJ) were associated with regurgitation perception (OR: 0.31, 95% CI: 0.16-0.59; p < 0.001, and OR: 0.5, 95% CI: 0.27-0.93; p < 0.05), while pathological MNBI was associated with NCCP perception (OR: 2.34, 95% CI: 1.23-4.43; p < 0.01). 45.5% NCCP patients, 45.6% with heartburn, and 36% with regurgitation responded to PPIs (p < 0.05). At multivariate analysis, pathological MNBI or PSPW index were associated with PPI responsiveness in patients with NCCP or heartburn, while in patients with regurgitation, pathological MNBI was associated with PPI responsiveness and a reflux number >80 to PPI refractoriness. CONCLUSIONS We highlight the usefulness of an accurate clinical and functional evaluation of GERD patients, allowing to discriminate particular characteristics in patients with dominant heartburn, NCCP, or regurgitation, which may benefit of distinct therapeutic strategies.
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Affiliation(s)
- Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Lorenzo Marchetti
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Lucrezia Maria Olmi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Michele Cicala
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
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Marabotto E, Pasta A, Calabrese F, Ribolsi M, Mari A, Savarino V, Savarino EV. The Clinical Spectrum of Gastroesophageal Reflux Disease: Facts and Fictions. Visc Med 2024; 40:242-249. [PMID: 39398395 PMCID: PMC11466451 DOI: 10.1159/000536583] [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: 12/19/2023] [Accepted: 01/30/2024] [Indexed: 07/05/2024] Open
Abstract
BACKGROUND This review addresses the intricate spectrum of gastroesophageal reflux disease (GERD), a condition affecting 10-30% of the Western population. GERD is characterized by the backflow of gastric contents into the esophagus, causing typical and atypical symptoms. Its pathophysiology involves various factors such as hiatal hernia, esophageal motor disorders, and dietary triggers. The review explores the complexities of GERD spectrum, including nonerosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). SUMMARY The diagnostic process for GERD, based on the Lyon Consensus 2.0 criteria, encompasses clinical evaluation, endoscopy, and functional tests, including pH-impedance and wireless-pH monitoring. NERD, a significant subset of GERD, is defined by reflux symptoms and abnormal reflux burden without mucosal damage. RH, classified under functional esophageal disorders by Rome IV criteria, presents with typical esophageal symptoms associated with reflux but lacks of structural, inflammatory, or motor causes. FH is identified by heartburn with normal endoscopy, reflux testing, and esophageal manometry results. The management of RH and FH, focusing on reducing esophageal hypersensitivity, varies from standard GERD treatments. KEY MESSAGES The review emphasizes the necessity of personalized treatment strategies due to the complexity and overlap of GERD subtypes. It highlights the importance of a multidisciplinary approach, involving gastroenterologists, psychologists, and other specialists, to improve patient outcomes and quality of life. The article underscores that understanding the distinctions and overlaps among NERD, RH, and FH is crucial for effective management, and the need for innovative approaches in diagnosis and treatment to address the unique challenges of each subtype.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Francesco Calabrese
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Amir Mari
- Israel Institute of Technology, Hadera, Israel and Nazareth Hospital EMMS, Nazareth, Israel
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università of Padua, Padua, Italy
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Voulgaris TA, Karamanolis GP. Mean nocturnal baseline impedance in gastro-esophageal reflux disease diagnosis: Should we strictly follow the Lyon 2 Consensus? World J Gastroenterol 2024; 30:3253-3256. [PMID: 39086632 PMCID: PMC11287407 DOI: 10.3748/wjg.v30.i26.3253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 05/27/2024] [Accepted: 06/13/2024] [Indexed: 07/09/2024] Open
Abstract
Clinical practice guidelines drive clinical practice and clinicians rely to them when trying to answer their most common questions. One of the most important position papers in the field of gastro-esophageal reflux disease (GERD) is the one produced by the Lyon Consensus. Recently an updated second version has been released. Mean nocturnal baseline impedance (MNBI) was proposed by the first Consensus to act as supportive evidence for GERD diagnosis. Originally a cut-off of 2292 Ohms was proposed, a value revised in the second edition. The updated Consensus recommended that an MNBI < 1500 Ohms strongly suggests GERD while a value > 2500 Ohms can be used to refute GERD. The proposed cut-offs move in the correct direction by diminishing the original cut-off, nevertheless they arise from a study of normal subjects where cut-offs were provided by measuring the mean value ± 2SD and not in symptomatic patients. However, data exist that even symptomatic patients with inconclusive disease or reflux hypersensitivity (RH) show lower MNBI values in comparison to normal subjects or patients with functional heartburn (FH). Moreover, according to the data, MNBI, even among symptomatic patients, is affected by age and body mass index. Also, various studies have proposed different cut-offs by using receiver operating characteristic curve analysis even lower than the one proposed. Finally, no information is given for patients submitted to on-proton pump inhibitors pH-impedance studies even if new and extremely important data now exist. Therefore, even if MNBI is an extremely important tool when trying to approach patients with reflux symptoms and could distinguish conclusive GERD from RH or FH, its values should be interpreted with caution.
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Affiliation(s)
- Theodoros A Voulgaris
- Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Georgios P Karamanolis
- Department of Gastroenterology, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
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Voulgaris T, Hoshino S, Sifrim D, Yazaki E. Effect of aging and obesity on esophageal mucosal integrity as measured by baseline impedance. Neurogastroenterol Motil 2023; 35:e14626. [PMID: 37332225 DOI: 10.1111/nmo.14626] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2023] [Revised: 05/26/2023] [Accepted: 05/29/2023] [Indexed: 06/20/2023]
Abstract
AIM Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI. METHODS In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%. RESULTS Mean BMI was 26.6 ± 5.9 kg/cm2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm. CONCLUSION According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used.
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Affiliation(s)
- Theodoros Voulgaris
- Barts and The London School of Medicine and Dentistry, Upper GI Physiology Unit Royal London Hospital, Wingate Institute of Neurogastroenterology, Blizard Institute, Queen Mary University of London, London, UK
| | - Shintaro Hoshino
- Barts and The London School of Medicine and Dentistry, Upper GI Physiology Unit Royal London Hospital, Wingate Institute of Neurogastroenterology, Blizard Institute, Queen Mary University of London, London, UK
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Upper GI Physiology Unit Royal London Hospital, Wingate Institute of Neurogastroenterology, Blizard Institute, Queen Mary University of London, London, UK
| | - Etsuro Yazaki
- Barts and The London School of Medicine and Dentistry, Upper GI Physiology Unit Royal London Hospital, Wingate Institute of Neurogastroenterology, Blizard Institute, Queen Mary University of London, London, UK
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Ribolsi M, Savarino E. Towards a better diagnosis of gastro esophageal reflux disease. Expert Rev Gastroenterol Hepatol 2023; 17:999-1010. [PMID: 37800858 DOI: 10.1080/17474124.2023.2267435] [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: 04/30/2023] [Accepted: 10/03/2023] [Indexed: 10/07/2023]
Abstract
INTRODUCTION GERD is a common disorder and is characterized by the presence of typical or atypical symptoms. In GERD patients, the presence of mucosal alterations in endoscopy is detected in up to 30% of individuals. The clinical presentation of GERD patients may be complex and their management is challenging, due to the heterogeneous clinical presentation. The present review has been performed searching all relevant articles in this field, over the past years, using PubMed database. AREAS COVERED The diagnosis and management of GERD have been significantly improved in the last years due to the increasing availability of reflux monitoring techniques and the implementation of new procedures in the therapeutic armamentarium. Beside traditional impedance-pH variables, new metrics have been developed, increasing the diagnostic yield of reflux monitoring and better predicting the treatment response. Traditional pharmacological treatments include acid-suppressive-therapy and/or anti-acid. On the other hand, surgical treatment and, more recently, endoscopic procedures represent a promising field in the therapeutic approach. EXPERT OPINION Diagnosis and treatment of GERD still represent a challenging area. However, we believe that an accurate upfront evaluation is, nowadays, necessary in addressing patients with GERD to a more accurate diagnosis as well as to the best treatment options.
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Affiliation(s)
- Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
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Ribolsi M, Savarino E, Frazzoni M, Cicala M. Prospective validation of reflux monitoring by impedance-pH in predicting PPI response in typical GERD. Dig Liver Dis 2023; 55:721-726. [PMID: 36572569 DOI: 10.1016/j.dld.2022.12.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 05/29/2023]
Abstract
BACKGROUND The Lyon Consensus proposed a hierarchical approach to GERD diagnosis based on conventional and new impedance-pH metrics, namely acid exposure time (AET), number of reflux episodes, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI). AIMS To define the value of conventional and new impedance-pH parameters as predictors of response to label-dose PPI in typical GERD. METHODS Consecutive adult patients with typical esophageal symptoms were prospectively studied with impedance-pH monitoring and treated with 8-week label-dose PPI. At the end of the PPI course, symptoms response was assessed. RESULTS Among 255 patients who entered the study, 168 (65.9%) reported symptom remission. At ROC analysis, both MNBI and PSPW index were significantly associated to PPI responsiveness with AUC of 0.783 and 0.801, respectively. Cut-off values of 1747Ω for MNBI and 50% for PSPW index were identified as discriminators between response and non-response to label-dose PPI. At multivariate analysis, MNBI, PSPW index, and AET >6% were efficient predictors of PPI responses (OR 3, 5.4 and 2.3, respectively). Number of reflux episodes did not predict PPI response. CONCLUSIONS The novel MII-pH variables together with pathological are highly predictive of response of the typical GERD syndrome to label-dose PPI.
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Affiliation(s)
- Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Via Alvaro del Portillo 200 - 00128, Roma, Italy.
| | - Edoardo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padova, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit, Baggiovara Hospital, Modena, Italy
| | - Michele Cicala
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Via Alvaro del Portillo 200 - 00128, Roma, Italy
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Li Y, Wang L, Yang D, Zhang Z, Sun X, Geng X, Lin J, Duan Z. Esophageal chemical clearance and mucosa integrity values in refractory gastroesophageal reflux disease patients with different esophageal dynamics. Scand J Gastroenterol 2023; 58:322-330. [PMID: 36259257 DOI: 10.1080/00365521.2022.2132534] [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: 02/04/2023]
Abstract
OBJECTIVES Esophageal post-reflux swallow-induced peristaltic wave index (PSPWI) and mean nocturnal baseline impedance (MNBI), novel impedance-based markers of reflux burden, are associated with esophageal dynamics. We aim to investigate the characteristics of PSPWI and MNBI in Chinese refractory gastroesophageal reflux disease (RGERD) patients with different esophageal dynamic changes. MATERIALS AND METHODS 201 RGERD and 76 functional heartburn patients, undergone off-PPI endoscopy, esophageal manometry and impedance-pH monitoring, were included. Comparisons of conventional and novel impedance-pH metrics were made among different esophageal dynamics groups. Receiver operating-characteristic analyses were utilized to evaluate the diagnostic efficacy of PSPWI and MNBI in differentiating abnormal esophageal dynamics. Correlations were used to investigate their associated factors. RESULTS PSPWI and MNBI of RGERD with esophagogastric junction (EGJ) injury and esophageal dysmotility were lower than EGJ injury alone or normal dynamics (p < 0.05 for both comparisons). PSPWI with esophageal peristalsis abnormality was lower than EGJ injury (p = 0.049), while MNBI showed no statistical difference. PSPWI, MNBI and their combination have auxiliary diagnostic values for esophageal peristalsis [area under the curves (AUCs): 0.683, 0.656, 0.708)] while only their combination for EGJ injury (AUC: 0.610). And they positively correlated with esophageal motility while negatively correlated with ineffective swallows and acid reflux events. CONCLUSIONS PSPWI and MNBI, indicating impairment of esophageal chemical clearance and mucosa integrity, were lower in RGERD patients with multiple esophageal dynamic injuries than single injuries or normal dynamics. Moreover, they provided useful contributing information for potential dynamic injuries if manometry has already been found normal or marginal.
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Affiliation(s)
- Yanqiu Li
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Lixia Wang
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dong Yang
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zhifeng Zhang
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiaoyu Sun
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Xiaoling Geng
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiarong Lin
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Zhijun Duan
- Second Gastroenterology Department, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Advancements in the use of 24-hour impedance-pH monitoring for GERD diagnosis. Curr Opin Pharmacol 2022; 65:102264. [PMID: 35797758 DOI: 10.1016/j.coph.2022.102264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 05/01/2022] [Accepted: 06/06/2022] [Indexed: 11/23/2022]
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