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Kahrilas PJ, Keefer L, Yadlapati R, Anastasiou F, Heidelbaugh JJ, Howden CW, Mendive JM, Savarino EV, Udrescu M, Hungin APS. Review Article: Individualised Management of Reflux-Like Symptoms-Strategies Beyond Acid Suppression. Aliment Pharmacol Ther 2025. [PMID: 40166851 DOI: 10.1111/apt.70115] [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: 01/28/2025] [Revised: 02/09/2025] [Accepted: 03/23/2025] [Indexed: 04/02/2025]
Abstract
BACKGROUND Reflux-like symptoms and reflux oesophagitis are often perceived as having the same acid-related aetiology and responsiveness to antisecretory therapy. However, the frequency of residual symptom reporting on proton pump inhibitor (PPI) therapy suggests the two entities have some differential pathophysiological determinants requiring distinct management approaches. AIMS To examine the complexities of reflux-like symptom pathophysiology and strategies that may be used to target contributing factors beyond acid reflux. METHODS A panel of ten expert clinicians (primary care, gastroenterology and psychology) held a series of online meetings to share perspectives on the underlying contributors to, and management of, reflux-like symptoms when PPIs are ineffective or provide partial relief. This review summarises the agreed key themes that emerged from the expert discussions. RESULTS While degradation of the anti-reflux barrier dominates in reflux oesophagitis, cognitive-affective, behavioural, and other psychosocial factors can play a major role in symptom persistence. These require individualised management strategies, beginning with education on the gut-brain connection and expectation setting with regard to PPI therapy. A detailed clinical history and patient-reported outcome tools that measure symptom burden and associated anxiety/hypervigilance can help guide management using brain-gut behavioural therapies, supported diet/lifestyle modification, diaphragmatic breathing, weight loss, and/or on-demand symptom control measures according to a patient's specific needs. CONCLUSIONS A paradigm shift in reflux-like symptom management is required such that acid suppression is viewed as one of several interventions that can be utilised as part of a phenotype-driven, individualised approach to care that acknowledges the multiple contributors to symptom burden.
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Affiliation(s)
| | - Laurie Keefer
- Icahn School of Medicine at Mount Sinai, New York, New York State, USA
| | - Rena Yadlapati
- University of California San Diego, La Jolla, California, USA
| | - Foteini Anastasiou
- 4th Local Health Team (TOMY), Municipality Practice, Academic Practice of Heraklion, Heraklion, Greece
| | - Joel J Heidelbaugh
- Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Colin W Howden
- University of Tennessee College of Medicine, Memphis, Tennessee, USA
| | - Juan M Mendive
- La Mina Primary Health Care Academic Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | - A Pali S Hungin
- Emeritus Professor of General Practice, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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Chen J, Dong P, Chen S, Zhuang Q, Zhang M, Sun K, Tang F, Wang Q, Xiao Y. The Los Angeles-B esophagitis is a conclusive diagnostic evidence for gastroesophageal reflux disease: the validation of Lyon Consensus 2.0. Gastroenterol Rep (Oxf) 2025; 13:goaf004. [PMID: 40083682 PMCID: PMC11904300 DOI: 10.1093/gastro/goaf004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 10/27/2024] [Accepted: 12/06/2024] [Indexed: 03/16/2025] Open
Abstract
Background and Aims Recently, Lyon Consensus 2.0 recommended Los Angeles (LA)-B esophagitis as conclusive evidence and LA-A esophagitis as borderline evidence for gastroesophageal reflux disease (GERD). This study aimed to investigate the diagnostic value of LA-B and LA-A esophagitis. Methods Patients with typical reflux symptoms who underwent endoscopy examination and received acid-suppressive therapy from two tertiary hospitals [the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, P. R. China) and the Third People's Hospital of Chengdu (Chengdu, P. R. China)] were retrospectively included. Acid-suppression response rates, endoscopy results, motility, and reflux parameters were compared between patients with different grades of esophagitis. Results In total, 401 patients were enrolled, among whom 254 were without reflux esophagitis (RE), 51 had LA-A esophagitis, 44 had LA-B esophagitis, and 52 had LA-C/D esophagitis. Patients with LA-B esophagitis and LA-C/D esophagitis had significantly higher acid-suppressive response rates than non-RE patients (P < 0.05), whereas no significant difference was found between patients with LA-A esophagitis and non-RE patients (non-RE vs LA-A vs LA-B vs LA-C/D: 52.4% vs 70.6% vs 75.0% vs 82.7%). Among patients with LA-A esophagitis, those with a number of reflux episodes that exceeded 80 per day (90.0% vs 52.4%, P = 0.044) or hypotensive esophagogastric junction (72.4% vs 52.4%, P = 0.040) had significantly higher acid-suppressive response rates than non-RE patients. Conclusions LA-B esophagitis can be regarded as conclusive evidence for GERD and initiate acid-suppressive therapy. LA-A esophagitis did not establish a definite GERD diagnosis alone. When combined with adjunctive or supportive evidence, the acid-suppressive therapy response rate of LA-A esophagitis improved.
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Affiliation(s)
- Jing Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Peiwen Dong
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Songfeng Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Qianjun Zhuang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Mengyu Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Kaidi Sun
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Feng Tang
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Qiong Wang
- Department of Gastroenterology, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, P. R. China
| | - Yinglian Xiao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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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; 59:197-205. [PMID: 39777899 DOI: 10.1097/mcg.0000000000002128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [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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Farah A, Savarino EV, Abboud W, Tatakis A, Mari A. The Contemporary Diagnostic Approaches to Esophageal Symptomatology. Cureus 2025; 17:e78804. [PMID: 40078269 PMCID: PMC11897839 DOI: 10.7759/cureus.78804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Esophageal symptoms, including dysphagia, heartburn, and non-cardiac chest pain, are prevalent concerns in gastroenterology. This review examines the roles of advanced diagnostic modalities such as high-resolution manometry (HRM), pH-impedance monitoring, and EndoFLIP in understanding esophageal physiology and pathology. Here, we discuss the clinical presentations of common esophageal symptoms and explore how structural abnormalities like strictures and motility disorders, including achalasia and esophageal spasms, are assessed using these tools. The diagnostic utility of endoscopy in visualizing mucosal and structural changes is highlighted alongside emerging technologies like artificial intelligence in enhancing detection capabilities. Complementary techniques, such as barium esophagrams and reflux monitoring, provide additional functional and anatomical insights, crucial for comprehensive patient evaluation. The integration of these diagnostic approaches fosters a deeper understanding of esophageal disorders, guiding effective management strategies and improving patient outcomes. This review aimed to highlight the importance of adopting a multimodal diagnostic approach in modern gastroenterological practice.
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Affiliation(s)
- Amir Farah
- Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - Edoardo V Savarino
- Surgery, Oncology, and Gastroenterology, University of Padua, Padua, ITA
| | - Wisam Abboud
- General Surgery, Nazareth Hospital Edinburgh Medical Missionary Society (EMMS), Nazareth, ISR
| | - Anna Tatakis
- General Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - Amir Mari
- Gastroenterology and Hepatology, Nazareth Hospital Edinburgh Medical Missionary Society (EMMS), Nazareth, ISR
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Tietto A, Faggin S, Scarpignato C, Savarino EV, Giron MC. Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease. Expert Opin Drug Metab Toxicol 2025; 21:53-68. [PMID: 39189409 DOI: 10.1080/17425255.2024.2397433] [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: 05/23/2024] [Revised: 07/13/2024] [Accepted: 08/23/2024] [Indexed: 08/28/2024]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively). AREAS COVERED This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed. EXPERT OPINION P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.
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Affiliation(s)
- Angela Tietto
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
- School of Specialization in Clinical Pharmacology and Toxicology, University of Ferrara, Ferrara, Italy
| | - Sofia Faggin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | | | - Maria Cecilia Giron
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
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Ivashkin VT, Trukhmanov AS, Maev IV, Drapkina OM, Livzan MA, Martynov AI, Lapina TL, Paraskevova AV, Andreev DN, Alexeeva OP, Alekseenko SA, Baranovsky AY, Zayratyants OV, Zolnikova OY, Dronova OB, Kliaritskaia IL, Korochanskaya NV, Kucheryavyy YA, Mammaev SN, Osipenko MF, Pirogov SS, Poluektova EA, Rumyantseva DE, Sayfutdinov RG, Storonova OA, Uspenskiy YP, Khlynov IB, Tsukanov VV, Sheptulin AA. Diagnosis and Treatment of Gastroesophageal Reflux Disease (Clinical Guidelines of the Russian Gastroenterological Association, Russian Scientific Medical Society of Internal Medicine, Russian Society for the Prevention of Noncommunicable Diseases, Scientific Community for Human Microbiome Research). RUSSIAN JOURNAL OF GASTROENTEROLOGY, HEPATOLOGY, COLOPROCTOLOGY 2024; 34:111-135. [DOI: 10.22416/1382-4376-2024-34-5-111-135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Aim. These recommendations are developed for practitioners in order to familiarize them with modern diagnostic methods, management features and pharmacotherapy of patients with gastroesophageal reflux disease (GERD).General provisions. GERD is the most common reason for patients to visit clinics. There are esophageal and extraesophageal manifestations of GERD. Patients' complaints of heartburn and regurgitation remain the most sensitive and specific clinical manifestations of GERD. The diagnosis of GERD is established on the basis of anamnestic data, instrumental examination (detection of reflux esophagitis during upper gastrointestinal endoscopy, detection of pathological gastroesophageal reflux with 24-hour pH-metry or/and 24-hour pH-impedance monitoring). Patients with suspected GERD and the absence of erosive and ulcerative changes in the mucous membrane of the esophagus or the presence of erosive esophagitis of Grade A according to Los Angeles Classification of Gastroesophageal Reflux Disease are recommended to conduct 24-hour pH-metry on PPI off to exclude or confirm the diagnosis of GERD. Patients with extraesophageal manifestations of GERD without classic symptoms (heartburn, regurgitation) are recommended to undergo 24-hour pH-impedance monitoring with discontinuation of proton pump inhibitor therapy. When deciding on surgical treatment, all patients need to perform high-resolution esophageal manometry and 24-hour pH-impedance monitoring. Complications of GERD include bleeding, strictures, Barrett’s esophagus and esophageal adenocarcinoma. The main groups of medications used in the treatment of GERD are proton pump inhibitors (PPIs), potassium-competitive acid blockers (P-CABs), alginates, antacids, and prokinetics. PPIs are the drugs of choice in the treatment of both symptoms of gastroesophageal reflux disease and existing erosive esophagitis. Combination therapy Rebamipide with PPIs increases the effectiveness of relief of GERD symptoms, as well as reduces the frequency of relapses.Conclusion. These clinical recommendations will improve the quality of medical care for patients with GERD.
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Affiliation(s)
- V. T. Ivashkin
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - A. S. Trukhmanov
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | - O. M. Drapkina
- National Research Center for Therapy and Preventive Medicine
| | | | | | - T. L. Lapina
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | - O. P. Alexeeva
- Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
| | | | | | | | - O. Yu. Zolnikova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | | | | | | | | | | | - S. S. Pirogov
- Moscow Research Oncological Institute named after P.A. Gertsen — Branch of National Medical Research Radiological Center
| | - E. A. Poluektova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | | | - R. G. Sayfutdinov
- Kazan State Medical Academy — Branch Campus of the Russian Medical Academy of Continuous Professional Education
| | - O. A. Storonova
- I.M. Sechenov First Moscow State University (Sechenov University)
| | - Yu. P. Uspenskiy
- First Saint Petersburg State Medical University named after Academician I.P. Pavlov; Saint Petersburg State Pediatric Medical University
| | | | - V. V. Tsukanov
- Federal Research Center “Krasnoyarsk Science Center of Siberian Branch of the Russian Academy of Sciences”, Separate Division “Scientific Research Institute of Medical Problems of the North”
| | - A. A. Sheptulin
- I.M. Sechenov First Moscow State University (Sechenov University)
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Marabotto E, Calabrese F, Pasta A, Visaggi P, de Bortoli N, Mari A, Tolone S, Ghisa M, Bertin L, Savarino V, Savarino EV. Evaluating Vonoprazan for the treatment of erosive GERD and heartburn associated with GERD in adults. Expert Opin Pharmacother 2024; 25:2319-2325. [PMID: 39503620 DOI: 10.1080/14656566.2024.2427335] [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: 08/31/2024] [Accepted: 11/05/2024] [Indexed: 11/12/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a common debilitating chronic disease presenting in two main forms based on esophageal mucosal appearance, the erosive reflux disease (ERD) and the non-erosive reflux disease (NERD). Acid secretion is a key factor in the disease pathogenesis and management. Potent acid-suppressant drugs have been manufactured since the mid of 1970s, initially with histamine-H2-receptors antagonists, and later, inhibitors of the proton pump (H+-K+-ATPase).More recently, potassium-competitive acid blockers (p-CABs), particularlyVonoprazan, have been introduced. Vonoprazan has shown high efficacy and safety profiles and exhibits several advantages that allow to overcome shortcomings of proton pump inhibitors (PPIs). AREAS COVERED In this review, we provide an updated summary of Vonoprazan pharmacodynamics and its role in clinical practice for the management of erosive esophagitis and GERD-related heartburn. Moreover, we discuss characteristics of Vonoprazan that allow to bypass some limitations of the older PPIs. EXPERT OPINION Long-term safety and efficacy of Vonoprazan have already been demonstrated for the induction and maintenance of ERD, preventing nocturnal acid breakthrough, reducing reflux symptoms in non-responder to standard therapy. Ongoing and future studies are expected to further elucidate its long-term benefits and potential applications in other acid-related disorders.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Francesco Calabrese
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Amir Mari
- Gastroenterology Unit, Nazareth Hospital EMMS, Azrieli Faculty of Medicine, Bar Ilan University, Ramat Gan, Israel
| | - Salvatore Tolone
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Matteo Ghisa
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
- Gastroenterology Unit, Azienda Ospedale Università Padova, Padova, Italy
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Han F, Li X, Song Z, Xie J, Wang N, Yao J. The association between salivary pepsin and gastroesophageal reflux disease: A meta-analysis. Neurogastroenterol Motil 2024; 36:e14905. [PMID: 39223797 DOI: 10.1111/nmo.14905] [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: 06/07/2024] [Revised: 07/18/2024] [Accepted: 08/18/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND AND PURPOSE The definitive diagnosis of gastroesophageal reflux disease (GERD) often requires invasive investigations like upper gastrointestinal endoscopy or reflux monitoring. We aimed to explore the relationship between salivary pepsin and GERD and its value as a non-invasive diagnostic tool. METHODS Databases (PubMed, Web of Science, Cochran Library, and EMBASE) were searched from their inception to January 22, 2024 to explore the correlation of salivary pepsin with GERD. The meta-analysis data retrieved were summarized, including the salivary pepsin concentration, sensitivity of diagnosis (SEN), specificity of diagnosis (SPE), negative likelihood ratio, positive likelihood ratio, diagnostic odds ratio, and receiver operating characteristic (ROC) curve. RESULTS The meta-analysis comparing salivary pepsin concentration in two groups (proven GERD and non-GERD) with 18 studies revealed that the proven GERD group had higher salivary pepsin concentration than the non-GERD group (SMD = 1.74 [95% CI 1.14-2.34]). The meta-analysis of salivary pepsin diagnostic value for proven GERD incorporated 23 studies. The results showed pooled SEN (0.73 [95% CI 0.66-0.80]), SPE (0.72 [95% CI 0.65-0.78]), positive likelihood ratio (2.61 [95% CI 2.02-3.39]), negative likelihood ratio (0.37 [95% CI 0.28-0.50]), diagnostic odds ratio (7.03 [95% CI 4.24-11.66]) and area under the SROC curve (0.79 [95% CI 0.75-0.82]). CONCLUSION GERD patients presented a higher salivary pepsin concentration. Salivary pepsin is both sensitive and specific in identifying GERD, making it a promising non-invasive marker for diagnosis.
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Affiliation(s)
- Fei Han
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiangyu Li
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhaoxiang Song
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinlin Xie
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Nan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianning Yao
- Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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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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10
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Wei MH, Chen CC, Lee HC, Lee YC, Wang HP, Wu MS, Wu JF, Tseng PH. Prevalence of functional esophageal disorders and associated clinical characteristics in patients with proton-pump-inhibitor-unresponsive reflux symptoms. J Gastroenterol Hepatol 2024; 39:2097-2104. [PMID: 38860301 DOI: 10.1111/jgh.16654] [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: 02/08/2024] [Revised: 05/08/2024] [Accepted: 05/29/2024] [Indexed: 06/12/2024]
Abstract
BACKGROUND AND AIM Patients with proton-pump-inhibitor (PPI)-unresponsive reflux symptoms, often caused by functional esophageal disorders (FED), are frequently encountered in clinical practice. We aimed to investigate the prevalence of FED and its associated clinical characteristics in patients with PPI-unresponsive reflux symptoms. METHODS We retrospectively identified patients who were evaluated for persistent typical reflux symptoms, despite ≥8 weeks of PPI treatment, at the National Taiwan University Hospital from 2014 to 2023. All patients underwent a comprehensive evaluation comprising validated gastroesophageal reflux disease (GERD) symptom questionnaires, 5-item Brief Symptom Rating Scale (BSRS-5), Pittsburgh Sleep Quality Index (PSQI), esophagogastroduodenoscopy, high-resolution impedance manometry, and 24-h impedance-pH monitoring off PPI therapy. Diagnosis of FED and non-erosive reflux disease (NERD) was based on the Rome IV criteria. RESULTS We analyzed 190 patients [46.8% male, median age 52 (interquartile range, 42-61) years], of whom 32 (16.8%) had NERD and 158 (83.2%) had FED (57.9% with functional heartburn and 25.3% with reflux hypersensitivity). Patients with FED had a lower body mass index than those with NERD and a higher prevalence of psychological comorbidities and poor sleep quality than healthy volunteers. The severity of reflux symptoms among FED patients was significantly associated with the severity of psychological comorbidities and sleep quality. CONCLUSIONS A notably high prevalence (83.2%) of FED was observed among patients experiencing PPI-unresponsive reflux symptoms. Patients with FED had a higher level of psychological distress and diminished sleep quality, both of which were associated with reflux symptom severity.
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Affiliation(s)
- Ming-Han Wei
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Zhubei City, Taiwan
| | - Chien-Chuan Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hui-Chuan Lee
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
| | - Yi-Chia Lee
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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11
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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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12
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Visaggi P, Bertin L, Pasta A, Calabrese F, Ghisa M, Marabotto E, Ribolsi M, Savarino V, de Bortoli N, Savarino EV. Pharmacological management of gastro-esophageal reflux disease: state of the art in 2024. Expert Opin Pharmacother 2024; 25:2077-2088. [PMID: 39392340 DOI: 10.1080/14656566.2024.2416585] [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: 06/30/2024] [Revised: 10/03/2024] [Accepted: 10/10/2024] [Indexed: 10/12/2024]
Abstract
INTRODUCTION Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma. AREAS COVERED Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients. EXPERT OPINION PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.
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Affiliation(s)
- Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Luisa Bertin
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Andrea Pasta
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | | | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
- IRCCS Policlinico San Martino, Genoa, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | | | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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13
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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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14
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Pop RS, Pop D, Chiperi LE, Nechita VI, Man SC, Dumitrașcu DL. Utility of the Post-Reflux Swallow-Induced Peristaltic Wave Index and Mean Nocturnal Baseline Impedance for the Diagnosis of Gastroesophageal Reflux Disease Phenotypes in Children. CHILDREN (BASEL, SWITZERLAND) 2024; 11:773. [PMID: 39062223 PMCID: PMC11275132 DOI: 10.3390/children11070773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/19/2024] [Accepted: 06/25/2024] [Indexed: 07/28/2024]
Abstract
(1) Objectives: Assessment of novel impedance parameters such as the post-reflux swallow-induced peristaltic wave (PSPW) index and mean nocturnal baseline impedance (MNBI) have been proposed to enhance the accuracy of gastroesophageal reflux disease (GERD) diagnosis. We aimed to evaluate the clinical value of MNBI and the PSPW index in discerning different phenotypes of GERD in children. (2) Methods: We conducted a prospective, observational study that included 49 children aged 5-18 years, referred for MII-pH monitoring due to negative endoscopy and persisting gastroesophageal reflux symptoms despite acid-suppressant treatment. The PSPW index and MNBI were assessed along with conventional metrics. (3) Results: Using a receiver operating characteristic (ROC) curve analysis, MNBI (AUC 0.864) and the PSPW index (AUC 0.83) had very good performance in differentiating between non-erosive reflux disease (NERD) and functional phenotypes. The PSPW index (AUC 0.87) discriminated better between functional heartburn (FH) and reflux hypersensitivity (RH) compared to the MNBI (AUC 0.712). A PSPW cut-off value of 65% provided a sensitivity of 76.9% and a specificity of 90% in distinguishing FH and RH. The PSPW index (AUC 0.87) proved to have better performance than the MNBI (AUC 0.802) in differentiating between FH and non-FH patients. MNBI diagnosed FH with a sensitivity of 84% and a specificity of 80.6% at a cut-off value of 2563 Ω. (4) Conclusions: The PSPW index and MNBI are useful to distinguish between GERD phenotypes in pediatric patients.
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Affiliation(s)
- Radu Samuel Pop
- 3rd Department of Pediatrics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania; (D.P.); (S.C.M.)
| | - Daniela Pop
- 3rd Department of Pediatrics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania; (D.P.); (S.C.M.)
- 3rd Pediatric Clinic, Clinical Emergency Hospital for Children, 400217 Cluj-Napoca, Romania
| | - Lăcrămioara Eliza Chiperi
- Department of Pediatrics, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, 540136 Târgu Mureș, Romania;
| | - Vlad-Ionuț Nechita
- Department of Medical Informatics and Biostatistics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania;
| | - Sorin Claudiu Man
- 3rd Department of Pediatrics, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400217 Cluj-Napoca, Romania; (D.P.); (S.C.M.)
- 3rd Pediatric Clinic, Clinical Emergency Hospital for Children, 400217 Cluj-Napoca, Romania
| | - Dan Lucian Dumitrașcu
- 2nd Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
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15
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de Bortoli N, Visaggi P, Penagini R, Annibale B, Baiano Svizzero F, Barbara G, Bartolo O, Battaglia E, Di Sabatino A, De Angelis P, Docimo L, Frazzoni M, Furnari M, Iori A, Iovino P, Lenti MV, Marabotto E, Marasco G, Mauro A, Oliva S, Pellegatta G, Pesce M, Privitera AC, Puxeddu I, Racca F, Ribolsi M, Ridolo E, Russo S, Sarnelli G, Tolone S, Zentilin P, Zingone F, Barberio B, Ghisa M, Savarino EV. The 1st EoETALY Consensus on the Diagnosis and Management of Eosinophilic Esophagitis - Definition, Clinical Presentation and Diagnosis. Dig Liver Dis 2024; 56:951-963. [PMID: 38423918 DOI: 10.1016/j.dld.2024.02.005] [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: 01/03/2024] [Revised: 01/26/2024] [Accepted: 02/09/2024] [Indexed: 03/02/2024]
Abstract
Eosinophilic esophagitis (EoE) is a chronic type 2-mediated inflammatory disease of the esophagus that represents the most common eosinophilic gastrointestinal disease. Experts in the field of EoE across Italy (i.e., EoETALY Consensus Group) including gastroenterologists, endoscopists, allergologists/immunologists, and paediatricians conducted a Delphi process to develop updated consensus statements for the management of patients with EoE and update the previous position paper of the Italian Society of Gastroenterology (SIGE) in light of recent evidence. Grading of the strength and quality of the evidence of the recommendations was performed using accepted GRADE criteria. The guideline is divided in two documents: Part 1 includes three chapters, namely 1) definition, epidemiology, and pathogenesis; 2) clinical presentation and natural history, and 3) diagnosis, while Part 2 includes two chapters: 4) treatment and 5) monitoring and follow-up. This document has received the endorsement of three Italian national societies including the SIGE, the Italian Society of Neurogastroenterology and Motility (SINGEM), and the Italian Society of Allergology, Asthma, and Clinical Immunology (SIAAIC). With regards to patients' involvement, these guidelines involved the contribution of members of ESEO Italia, the Italian Association of Families Against EoE.
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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
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Roberto Penagini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome 00189, Italy
| | - Federica Baiano Svizzero
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Giovanni Barbara
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | | | - Edda Battaglia
- Gastroenterology Unit ASLTO4, Chivasso - Ciriè - Ivrea, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia 27100, Italy
| | - Paola De Angelis
- Digestive Endoscopy Unit - Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Ludovico Docimo
- Department of Advanced Medical and Surgical Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marzio Frazzoni
- Digestive Pathophysiology Unit and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria di Modena, Ospedale Civile di Baggiovara, Modena, Italy
| | - Manuele Furnari
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Andrea Iori
- Gastroenterology and Digestive Endoscopy Unit,' Santa Chiara' Hospital, Trento, Italy
| | - Paola Iovino
- Gastrointestinal Unit, Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi 84084, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia 27100, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy; IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Giovanni Marasco
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Aurelio Mauro
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Policlinico San Matteo, Pavia 27100, Italy
| | - Salvatore Oliva
- Maternal and Child Health Department, Pediatric Gastroenterology and Liver Unit, Sapienza - University of Rome, Italy
| | - Gaia Pellegatta
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Humanitas University, Via Rita Levi Montalcini 4, 20090 Pieve Emanuele, Milan, Italy
| | - Marcella Pesce
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | | | - Ilaria Puxeddu
- Immunoallergology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy
| | - Francesca Racca
- Personalized Medicine, Asthma and Allergy Clinic, IRCCS Humanitas Research Hospital, Rozzano - Milan, Italy
| | - Mentore Ribolsi
- Unit of Gastroenterology and Digestive Endoscopy, Campus Bio Medico University, Rome, Italy
| | - Erminia Ridolo
- Allergy Unit, Department of Internal Medicine, University Hospital of Parma, Parma, Italy
| | - Salvatore Russo
- Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliera Universitaria of Modena, Modena, Italy
| | - Giovanni Sarnelli
- Department of clinical medicine and surgery, University of Naples Federico II, Naples, Italy
| | - Salvatore Tolone
- Division of General, Oncological, Mini-Invasive and Obesity Surgery, University of Campania "Luigi Vanvitelli", Naples 80131, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy
| | - Edoardo Vincenzo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Via Giustiniani 2, Padua 35128, Italy.
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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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17
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Antequera CM, Orleck K, Jacob R, Kenneally A, Wright WL. Potassium-competitive acid blockers: rethinking acid suppression for gastroesophageal reflux disease and Helicobacter pylori. Postgrad Med 2024; 136:131-140. [PMID: 38385191 DOI: 10.1080/00325481.2024.2320081] [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: 10/18/2023] [Accepted: 02/13/2024] [Indexed: 02/23/2024]
Abstract
Gastroesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection are different disease states that are united by the core role of acid suppression in their management. In GERD, proton pump inhibitors (PPIs) have long been standard therapy based on abundant positive clinical trial data supporting their efficacy and safety. In H. pylori, PPIs are also a critical element of therapy in combination with 1 or more antibiotics to achieve and maintain a pH that maximizes the efficacy of therapy. Despite the considerable clinical success and widespread use of PPIs, room remains for agents with differentiated pharmacokinetic and pharmacodynamic profiles. The potassium-competitive acid blockers (PCABs) are mechanistically distinct from PPIs but are acid-stable and do not require activation of the proton pump by coadministration of food. In pharmacodynamic studies, these agents have shown greater durations of acid suppression above the critical threshold of pH 4 (for GERD) and pH 6 (for H. pylori), which have been shown to optimize therapeutic efficacy in these settings. These results have translated in clinical studies to similar and, in some cases, improved outcomes relative to PPIs in these disease states. This review summarizes current knowledge on the physiology of acid secretion, pathophysiology and management of GERD and H. pylori, and key characteristics and clinical trial data for PPIs and PCABs.
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Affiliation(s)
| | | | - Rinu Jacob
- Phathom Pharmaceuticals, Florham Park, NJ, USA
| | | | - Wendy L Wright
- Wright & Associates Family Healthcare PLLC, Amherst, NH, USA
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Kongkam P, Khongkha W, Lopimpisuth C, Chumsri C, Kosarussawadee P, Phutrakool P, Khamsai S, Sawanyawisuth K, Sura T, Phisalprapa P, Buamahakul T, Siwamogsatham S, Angsusing J, Poonniam P, Wanaratna K, Teerachaisakul M, Pongpirul K. Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial. BMJ Evid Based Med 2023; 28:399-406. [PMID: 37696679 DOI: 10.1136/bmjebm-2022-112231] [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] [Accepted: 07/10/2023] [Indexed: 09/13/2023]
Abstract
OBJECTIVE To compare the efficacy of curcumin versus omeprazole in improving patient reported outcomes in people with dyspepsia. DESIGN Randomised, double blind controlled trial, with central randomisation. SETTING Thai traditional medicine hospital, district hospital, and university hospitals in Thailand. PARTICIPANTS Participants with a diagnosis of functional dyspepsia. INTERVENTIONS The interventions were curcumin alone (C), omeprazole alone (O), or curcumin plus omeprazole (C+O). Patients in the combination group received two capsules of 250 mg curcumin, four times daily, and one capsule of 20 mg omeprazole once daily for 28 days. MAIN OUTCOME MEASURES Functional dyspepsia symptoms on days 28 and 56 were assessed using the Severity of Dyspepsia Assessment (SODA) score. Secondary outcomes were the occurrence of adverse events and serious adverse events. RESULTS 206 patients were enrolled in the study and randomly assigned to one of the three groups; 151 patients completed the study. Demographic data (age 49.7±11.9 years; women 73.4%), clinical characteristics and baseline dyspepsia scores were comparable between the three groups. Significant improvements were observed in SODA scores on day 28 in the pain (-4.83, -5.46 and -6.22), non-pain (-2.22, -2.32 and -2.31) and satisfaction (0.39, 0.79 and 0.60) categories for the C+O, C, and O groups, respectively. These improvements were enhanced on day 56 in the pain (-7.19, -8.07 and -8.85), non-pain (-4.09, -4.12 and -3.71) and satisfaction (0.78, 1.07, and 0.81) categories in the C+O, C, and O groups, respectively. No significant differences were observed among the three groups and no serious adverse events occurred. CONCLUSION Curcumin and omeprazole had comparable efficacy for functional dyspepsia with no obvious synergistic effect. TRIAL REGISTRATION NUMBER TCTR20221208003.
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Affiliation(s)
- Pradermchai Kongkam
- Department of Internal Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | | | - Chawin Lopimpisuth
- Department of Internal Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Chitsanucha Chumsri
- Department of Preventive and Social Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- Center of Excellence in Preventive & Integrative Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
| | - Prach Kosarussawadee
- Department of Internal Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Phanupong Phutrakool
- Center of Excellence in Preventive & Integrative Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- Chula Data Management Centre, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
| | | | | | - Thanyachai Sura
- Ramathibodi Hospital, Mahidol University Faculty of Medicine, Bangkok, Thailand
| | | | | | - Sarawut Siwamogsatham
- Department of Internal Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- King Chulalongkorn Memorial Hospital, Bangkok, Thailand
| | - Jaenjira Angsusing
- Department of Thai Traditional and Alternative Medicine, Royal Thai Government Ministry of Public Health, Bangkok, Thailand
| | - Pratchayanan Poonniam
- Department of Thai Traditional and Alternative Medicine, Royal Thai Government Ministry of Public Health, Bangkok, Thailand
| | - Kulthanit Wanaratna
- Department of Thai Traditional and Alternative Medicine, Royal Thai Government Ministry of Public Health, Bangkok, Thailand
| | - Monthaka Teerachaisakul
- Department of Thai Traditional and Alternative Medicine, Royal Thai Government Ministry of Public Health, Bangkok, Thailand
| | - Krit Pongpirul
- Department of Preventive and Social Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- Center of Excellence in Preventive & Integrative Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand
- Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
- Department of Infection Biology & Microbiomes, University of Liverpool Faculty of Health and Life Sciences, Liverpool, UK
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Corazziari ES, Gasbarrini A, D'Alba L, D'Ovidio V, Riggio O, Passaretti S, Annibale B, Cicala M, Repici A, Bassotti G, Ciacci C, Di Sabatino A, Neri M, Bragazzi MC, Ribichini E, Radocchia G, Iovino P, Marazzato M, Schippa S, Badiali D. Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial. Am J Gastroenterol 2023; 118:2014-2024. [PMID: 37307528 PMCID: PMC10617666 DOI: 10.14309/ajg.0000000000002360] [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: 12/03/2022] [Accepted: 05/09/2023] [Indexed: 06/14/2023]
Abstract
INTRODUCTION In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure. METHODS In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed. RESULTS A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm. DISCUSSION Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).
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Affiliation(s)
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, CEMAD Centro Malattie Dell'Apparato Digerente, Università Cattolica Del Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli IRCCS. Rome, Italy
| | - Lucia D'Alba
- Department of Gastroenterology and Digestive Endoscopy, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy
| | - Valeria D'Ovidio
- Unit of Gastroenterology and Digestive Endoscopy, S. Eugenio Hospital, Rome, Italy
| | - Oliviero Riggio
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza University of Rome, Rome, Italy
| | - Sandro Passaretti
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Bruno Annibale
- Dipartimento Scienze Medico-Chirurgiche e Medicina Traslazionale, Universita' Sapienza Roma, Ospedale Universitario Sant'Andrea, Rome, Italy
| | - Michele Cicala
- Department of Digestive Diseases, Campus Bio Medico University, Rome, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Gabrio Bassotti
- Gastroenterology & Hepatology Section, Department of Medicine & Surgery, University of Perugia, Perugia, Italy
| | - Carolina Ciacci
- PO di Malattie Dell'Apparato Digerente, Università di Salerno, AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | | | - Matteo Neri
- Department of Medicine and Ageing Sciences and Center for Advanced Studies and Technology (CAST), “G. D'Annunzio” University of Chieti-Pescara, Chieti-Pescara, Italy
| | | | - Emanuela Ribichini
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giulia Radocchia
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Paola Iovino
- PO di Malattie Dell'Apparato Digerente, Università di Salerno, AOU San Giovanni di Dio e Ruggi D'Aragona, Salerno, Italy
| | - Massimiliano Marazzato
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Serena Schippa
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy
| | - Danilo Badiali
- Dipartimento di Medicina Traslazionale e di Precisione, Sapienza University of Rome, Rome, Italy
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Zhang M, Wu T, Tan N, Chen S, Zhuang Q, Luo Y, Xiao Y. Clinical relevance of salivary pepsin detection in diagnosing gastroesophageal reflux disease subtypes. Gastroenterol Rep (Oxf) 2023; 11:goad053. [PMID: 37720194 PMCID: PMC10500079 DOI: 10.1093/gastro/goad053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Revised: 07/25/2023] [Accepted: 08/09/2023] [Indexed: 09/19/2023] Open
Abstract
Background Gastroesophageal reflux disease (GERD) is heterogeneous with a varied symptom spectrum and reflux profiles. Its definite diagnosis often requires invasive tools including endoscopy or reflux monitoring. The aim of this study was to investigate the clinical relevance of salivary pepsin detection as a non-invasive screening tool to diagnose GERD of different subtypes. Methods A total of 77 patients with suspected GERD symptoms and 12 asymptomatic controls were analysed. All participants performed symptom evaluation, upper endoscopy, esophageal manometry, and 24-hour multichannel intraluminal impedance-dual pH probe monitoring. Saliva was self-collected across three different time points: at early fasting, postprandially, and at symptom occurrence. Salivary pepsin levels were measured via Peptest. The optimal threshold of salivary pepsin for diagnosing distal or proximal reflux was determined according to a receiver-operating characteristic curve. Results The average salivary pepsin concentration of suspected GERD patients was significantly higher than that of controls (100.63 [68.46, 141.38] vs 67.90 [31.60, 115.06] ng/mL, P = 0.044), although no difference was found among patients with different symptom spectrums. The distal reflux group had a higher average pepsin concentration than non-reflux patients (170.54 [106.31, 262.76] vs 91.13 [63.35, 127.63] ng/mL, P = 0.043), while no difference was observed between the distal reflux group and the proximal reflux group. The optimal cut-off value of salivary pepsin concentration for diagnosing pathological distal reflux was 157.10 ng/mL, which was higher than that for diagnosing pathological proximal reflux (122.65 ng/mL). The salivary pepsin concentration was significantly correlated with distal and proximal reflux parameters. Conclusions Salivary pepsin measurement can help in identifying true GERD with pathological distal reflux or proximal reflux, regardless of different symptom spectrums. A higher threshold should be applied for diagnosing distal reflux than for proximal reflux.
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Affiliation(s)
- Mengyu Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Tingting Wu
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Niandi Tan
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Songfeng Chen
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Qianjun Zhuang
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yu Luo
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Yinglian Xiao
- Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Sugihartono T, Hidayat AA, Lusida MAP, Kuntaman, Aftab H, Miftahussurur M. Comparison of RDQ and GERDQ for Predicting Erosive Esophagitis in Patients with Typical GERD Symptoms. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:84-90. [PMID: 37621243 DOI: 10.4166/kjg.2023.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/02/2023] [Accepted: 06/19/2023] [Indexed: 08/26/2023]
Abstract
Background/Aims The management decisions regarding gastroesophageal reflux disease (GERD) may differ according to the presence of erosive esophagitis. On the other hand, the availability of upper endoscopy in Indonesia is relatively limited. This study compared the Reflux Disease Questionnaire (RDQ) and the GERD questionnaire (GERDQ) performance in predicting the presence of clinically significant erosive esophagitis and determined the validity and reliability of the Indonesian-translated version of RDQ. Methods Ninety-two adults with GERD suspicion were recruited. All patients completed RDQ and GERDQ. Receiver operating curve analysis was conducted on RDQ and GERDQ to evaluate their performance in discriminating LA GERD B or higher esophagitis from others. The translated RDQ preserved its main structure and was culturally adapted. Results The patients were 66.3% female and 73.9% Javanese. Only 22 (23.9%) patients presented with LA grade B or higher erosive esophagitis. The RDQ showed a higher AUC than the GERDQ (0.602 vs. 0.589). A cutoff point of 20 was selected for the RDQ with sensitivity and specificity of 73% and 50%, respectively, whereas the optimal cutoff point of GERDQ was 8, with a sensitivity and specificity of 77% and 43%, respectively. The r-value greater than the critical value table (r>0.205, p<0.01) confirmed the construct validity of our translated RDQ. The questionnaire also demonstrated excellent reliability (α=0.900) and moderate similarity with the Indonesian version of GERDQ (κ=0.459, p<0.01). Conclusions The RDQ is slightly superior to GERDQ in predicting the presence of clinically significant erosive esophagitis (LA grade B or higher). The Indonesian-translated RDQ is valid and reliable.
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Affiliation(s)
- Titong Sugihartono
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Amal Arifi Hidayat
- Internal Medicine Department, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | - Kuntaman
- Department of Medical Microbiology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Hafeza Aftab
- Department of Gastroenterology, Dhaka Medical College and Hospital, Dhaka, Bangladesh
| | - Muhammad Miftahussurur
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
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Mari A, Marabotto E, Ribolsi M, Zingone F, Barberio B, Savarino V, Savarino EV. Encouraging appropriate use of proton pump inhibitors: existing initiatives and proposals for the future. Expert Rev Clin Pharmacol 2023; 16:913-923. [PMID: 37632213 DOI: 10.1080/17512433.2023.2252327] [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: 07/09/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 08/27/2023]
Abstract
INTRODUCTION Proton pump inhibitors (PPIs) have revolutionized the management of acid-related disorders, representing today the mainstay treatment of these conditions. However, despite their large range of indications and usefulness, the remarkable expansion of their use in the last two decades cannot be explained by the increasing prevalence of acid-related diseases only. An inappropriate prescription for clinical conditions in which the pathogenetic role of acid has not been documented has been described, with the natural consequence of increasing the costs and the potential risk of iatrogenic harm due to adverse events and complications recently emerged. AREAS COVERED In this review, we summarize current indications of PPIs administration, potential adverse events associated with their chronic utilization, and misuse of PPIs. Moreover, we describe existing and possible initiatives for improving the use of PPIs, and some proposals for the future. EXPERT OPINION PPI deprescribing is the preferred and most effective approach to reduce the use of PPIs, rather than adopting sharp discontinuation, probably due to fewer withdrawal symptoms. Nonetheless, large knowledge gaps still exist in clinical practice regarding the optimal approach of PPI deprescribing in various clinical scenarios. Further prospective well-designed international studies are eagerly warranted to improve our perspectives on controlling global PPI inappropriate use.
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Affiliation(s)
- Amir Mari
- Gastroenterology Unit, Nazareth EMMS Hospital, Nazareth, Israel
- The Azrieli Faculty of Medicine, Bar Ilan University, Nazareth, Israel
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Mentore Ribolsi
- Department of Digestive Diseases, Campus Bio Medico University of Rome, Rome, Italy
| | - Fabiana Zingone
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | | | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Azienda Ospedale Università di Padova, Padua, ItalyI
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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Savarino V, Marabotto E, Zentilin P, De Bortoli N, Visaggi P, Furnari M, Bodini G, Giannini E, Savarino E. How safe are heartburn medications and who should use them? Expert Opin Drug Saf 2023; 22:643-652. [PMID: 37477199 DOI: 10.1080/14740338.2023.2238592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Accepted: 07/17/2023] [Indexed: 07/22/2023]
Abstract
INTRODUCTION Heartburn is a frequent symptom occurring in daily clinical practice and is mainly associated with gastroesophageal reflux disease (GERD). However, it can be stimulated by various factors and diseases other than GERD can present with heartburn. Therefore, physicians must be very careful in distinguishing GERD from non-GERD conditions in their patients, particularly when heartburn is refractory to anti-reflux medications. AREAS COVERED The aim of this narrative review was to analyze the medical literature regarding the prevalence of heartburn and the various clinical disorders which can be present with this symptom. The type of medications usually adopted for treating heartburn and their grade of safety have been reviewed using an extensive computerized (Medline/PubMed) search with particular focus on the last 20 years. EXPERT OPINION Many drugs can be used for relieving heartburn in patients with GERD, although PPIs are the pharmacological agents with the greatest efficacy. However, it must be highlighted that many non-GERD conditions may present clinically with this symptom whose intensity does not differ between GERD and functional esophageal disorders, which represent about 50% of all patients with suspected GERD. It is very important to identify these functional conditions because their treatment differs completely from that of GERD.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Nicola De Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Pierfrancesco Visaggi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Manuele Furnari
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Giorgia Bodini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Giannini
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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ANDERLONI A, SAVARINO E, ZAGARI RM, ARAGONA SE, CIPRANDI G. The practical management of patients with gastroesophageal reflux: an Italian survey. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2023; 182. [DOI: 10.23736/s0393-3660.23.05039-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2023]
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Hu Z, Wu J, Wang Z, Bai X, Lan Y, Lai K, Kelimu A, Ji F, Ji Z, Huang D, Hu Z, Hou X, Hao J, Fan Z, Chen X, Chen D, Chen S, Li J, Li J, Li L, Li P, Li Z, Lin L, Liu B, Liu DG, Lu Y, Lü B, Lü Q, Qiu M, Qiu Z, Shen H, Tai J, Tang Y, Tian W, Wang Z, Wang B, Wang JA, Wang J, Wang Q, Wang S, Wang W, Wang Z, Wei W, Wu Z, Wu W, Wu Y, Wu Y, Wu J, Xiao Y, Xu W, Xu X, Yang F, Yang H, Yang Y, Yao Q, Yu C, Zhang P, Zhang X, Zhou T, Zou D. Chinese consensus on multidisciplinary diagnosis and treatment of gastroesophageal reflux disease 2022. GASTROENTEROLOGY & ENDOSCOPY 2023; 1:33-86. [DOI: 10.1016/j.gande.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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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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Ambulatory pH-Impedance Findings Confirm That Grade B Esophagitis Provides Objective Diagnosis of Gastroesophageal Reflux Disease. Am J Gastroenterol 2023; 118:794-801. [PMID: 36633477 DOI: 10.14309/ajg.0000000000002173] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/13/2022] [Indexed: 01/13/2023]
Abstract
INTRODUCTION The Lyon Consensus designates Los Angeles (LA) grade C/D esophagitis or acid exposure time (AET) >6% on impedance-pH monitoring (MII-pH) as conclusive for gastroesophageal reflux disease (GERD). We aimed to evaluate proportions with objective GERD among symptomatic patients with LA grade A, B, and C esophagitis on endoscopy. METHODS Demographics, clinical data, endoscopy findings, and objective proton-pump inhibitor response were collected from symptomatic prospectively enrolled patients from 2 referral centers. Off-therapy MII-pH parameters included AET, number of reflux episodes, mean nocturnal baseline impedance, and postreflux swallow-induced peristaltic wave index. Objective GERD evidence was compared between LA grades. RESULTS Of 155 patients (LA grade A: 74 patients, B: 61 patients, and C: 20 patients), demographics and presentation were similar across LA grades. AET >6% was seen in 1.4%, 52.5%, and 75%, respectively, in LA grades A, B, and C. Using additional MII-pH metrics, an additional 16.2% with LA grade A and 47.5% with LA grade B esophagitis had AET 4%-6% with low mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index; there were no additional gains using the number of reflux episodes or symptom-reflux association metrics. Compared with LA grade C (100% conclusive GERD based on endoscopic findings), 100% of LA grade B esophagitis also had objective GERD but only 17.6% with LA grade A esophagitis ( P < 0.001 compared with each). Proton-pump inhibitor response was comparable between LA grades B and C (74% and 70%, respectively) but low in LA grade A (39%, P < 0.001). DISCUSSION Grade B esophagitis indicates an objective diagnosis of GERD.
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Barberio B, Visaggi P, Savarino E, de Bortoli N, Black CJ, Ford AC. Comparison of acid-lowering drugs for endoscopy negative reflux disease: Systematic review and network Meta-Analysis. Neurogastroenterol Motil 2023; 35:e14469. [PMID: 36153790 PMCID: PMC10078414 DOI: 10.1111/nmo.14469] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/29/2022] [Accepted: 09/12/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND The comparative efficacy and safety of medical therapies for gastro-esophageal reflux symptoms in endoscopy-negative reflux disease is unclear. We conducted a network meta-analysis to evaluate efficacy and safety of proton pump inhibitors (PPIs), histamine-2-receptor antagonists, potassium-competitive acid blockers (PCABs), and alginates in patients with endoscopy-negative reflux disease. METHODS We searched MEDLINE, EMBASE, EMBASE Classic, and the Cochrane central register of controlled trials from inception to February 1, 2022. We included randomized controlled trials (RCTs) comparing efficacy of all drugs versus each other, or versus a placebo, in adults with endoscopy-negative reflux disease. Results were reported as pooled relative risks with 95% confidence intervals to summarize effect of each comparison tested, with treatments ranked according to P-score. KEY RESULTS We identified 23 RCTs containing 10,735 subjects with endoscopy-negative reflux disease. Based on failure to achieve complete relief of symptoms between ≥2 and <4 weeks, omeprazole 20 mg o.d. (P-score 0.94) ranked first, with esomeprazole 20 mg o.d. or 40 mg o.d. ranked second and third. In achieving adequate relief, only rabeprazole 10 mg o.d. was significantly more efficacious than placebo. For failure to achieve complete relief at ≥4 weeks, dexlansoprazole 30 mg o.d. (P-score 0.95) ranked first, with 30 ml alginate q.i.d. combined with omeprazole 20 mg o.d., and 30 ml alginate t.i.d. second and third. In terms of failure to achieve adequate relief at ≥4 weeks, dexlansoprazole 60 mg o.d. ranked first (P-score 0.90), with dexlansoprazole 30 mg o.d. and rabeprazole 20 mg o.d. second and third. All drugs were safe and well-tolerated. CONCLUSIONS & INFERENCES Our results confirm superiority of PPIs compared with most other drugs in treating endoscopy-negative reflux disease. Future RCTs should aim to better classify patients with endoscopy-negative reflux disease, and to establish the role of alginates and PCABs in achieving symptom relief in both the short- and long-term.
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Affiliation(s)
- Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Christopher J Black
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK.,Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
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Patankar M, Li M, Khalatbari A, Castle JD, Hu L, Zhang C, Shaker A. Inflammatory and Proliferative Pathway Activation in Human Esophageal Myofibroblasts Treated with Acidic Bile Salts. Int J Mol Sci 2022; 23:ijms231810371. [PMID: 36142285 PMCID: PMC9498994 DOI: 10.3390/ijms231810371] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 09/01/2022] [Accepted: 09/04/2022] [Indexed: 11/16/2022] Open
Abstract
Subepithelial human esophageal myofibroblasts (HEMFs) in gastroesophageal reflux disease (GERD) are exposed to luminal contents via impaired squamous epithelium barrier integrity. The supernatant of HEMFs treated with acidic bile salts reflective of in vivo reflux increases squamous epithelial thickness. We aimed to identify the involved mechanisms using an unbiased approach. Acidic-bile-salt-treated primary HEMF cultures (n = 4) were submitted for RNA-Seq and analyzed with Partek Flow followed by Ingenuity Pathway Analysis (IPA). A total of 1165 molecules (579 downregulated, 586 upregulated) were differentially expressed, with most top regulated molecules either extracellular or in the plasma membrane. Increases in HEMF CXCL-8, IL-6, AREG, and EREG mRNA, and protein secretion were confirmed. Top identified canonical pathways were agranulocyte and granulocyte adhesion and diapedesis, PI3K/AKT signaling, CCR5 signaling in macrophages, and the STAT3 pathway. Top diseases and biological functions were cellular growth and development, hematopoiesis, immune cell trafficking, and cell-mediated response. The targets of the top upstream regulator ErbB2 included CXCL-8, IL-6, and AREG and the inhibition of CXCL-8 in the HEMF supernatant decreased squamous epithelial proliferation. Our work shows an inflammatory/immune cell and proliferative pathways activation in HEMFs in the GERD environment and identifies CXCL-8 as a HEMF-derived chemokine with paracrine proliferative effects on squamous epithelium.
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Affiliation(s)
- Madhura Patankar
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Meng Li
- USC Libraries Bioinformatics Services, University of Southern California, Los Angeles, CA 90007, USA
| | - Atousa Khalatbari
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Joshua D. Castle
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Liping Hu
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Chunying Zhang
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
| | - Anisa Shaker
- Department of Internal Medicine, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine of USC, Los Angeles, CA 90033, USA
- Correspondence: ; Tel.: +1-323-442-2084
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30
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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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31
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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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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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Hungin APS, Scarpignato C, Keefer L, Corsetti M, Anastasiou F, Muris JWM, Mendive JM, Kahrilas PJ. Review article: rethinking the "ladder" approach to reflux-like symptom management in the era of PPI "resistance" - a multidisciplinary perspective. Aliment Pharmacol Ther 2022; 55:1492-1500. [PMID: 35460095 PMCID: PMC9324949 DOI: 10.1111/apt.16930] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 01/26/2021] [Accepted: 04/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Despite widespread adoption of potent acid suppression treatment with proton pump inhibitors (PPI) for reflux-like symptoms, persistent symptoms are commonly reported in primary care and community studies. AIMS This multidisciplinary review critically evaluates how the management of reflux-like symptoms could better reflect their multifactorial pathophysiology. METHODS A panel of experts (from general practice, gastroenterology and gastropsychology) attended a series of workshops to review current management and propose a framework for the provision of more individualised care. RESULTS It was agreed that the perceptual (as well as the physiological) causes of reflux-like symptoms should be considered at the start of management, not as a last resort when all else has failed. A short course of PPI is a pragmatic approach to address reflux-like symptoms, but equally important is counselling about the gut-brain axis and provision of symptom-specific behavioural interventions for those who show signs of somatisation, hypervigilance or co-existing disorders of gut-brain interaction. Other low-harm interventions such as lifestyle and dietary advice, should also be better integrated into care at an early stage. Multidisciplinary care management programmes (including dietary, weight loss, exercise and behavioural intervention) should be developed to promote greater self-management and take advantage of the general shift toward the use of remotely accessed health care resources. CONCLUSIONS Management of reflux-like symptoms should be adapted to reflect the advances in knowledge about the multifactorial aetiology of these symptoms, addressing both acid-related and behavioural components early in management. The time has come to treat the patient, not the "disease".
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Affiliation(s)
- A. Pali S. Hungin
- Primary Care and General Practice, Faculty of Medical SciencesNewcastle UniversityNewcastle upon TyneUK
| | | | - Laurie Keefer
- Icahn School of Medicine at Mount SinaiNew York CityNew YorkUSA
| | - Maura Corsetti
- NIHR Nottingham Biomedical Research CentreNottingham University Hospitals NHS TrustNottinghamUK,School of Medicine, University of Nottingham and Translational Medical Science – Nottingham Digestive Diseases CentreUniversity of NottinghamNottinghamUK
| | - Foteini Anastasiou
- 4th Local Primary Care TeamMunicipality Practice and Academic Practice of HeraklionCreteGreece
| | - Jean W. M. Muris
- Department of Family MedicineCare and Public Health Research Institute (CAPHRI)Maastricht UniversityMaastrichtThe Netherlands
| | - Juan M. Mendive
- La Mina Primary Care Academic Centre, Catalan Health InstituteUniversity of BarcelonaBarcelonaSpain
| | - Peter J. Kahrilas
- Division of Gastroenterology, Feinberg School of MedicineNorthwestern UniversityChicagoIllinoisUSA
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Savarino V, Antonioli L, Fornai M, Marabotto E, Demarzo MG, Zingone F, Ghisa M, Barberio B, Zentilin P, Ribolsi M, Savarino E. An update of pharmacology, efficacy, and safety of vonoprazan in acid-related disorders. Expert Rev Gastroenterol Hepatol 2022; 16:401-410. [PMID: 34550866 DOI: 10.1080/17474124.2021.1984878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Patients with acid-related disorders (ARDs) of the upper digestive tract remain highly prevalent and need to be continuously investigated to improve their management. AREAS COVERED This review provides a summary of the most recent advancements in the treatment of ARDs with particular focus on the new drugs available to overcome the unmet needs of traditional therapies. EXPERT OPINION Proton pump inhibitors remain the best therapy in treating ARDs, but a consistent proportion of these patients continues to present mucosal lesions or to experience symptoms despite treatment. These cases pertain mainly to the most severe forms of erosive esophagitis or to non-erosive reflux disease. Also, the increasing rate of patients with H. pylori infection not responding to eradication therapy represents a difficult clinical condition. The recent advent of a new class of antisecretory drugs, such as the potassium competitive acid blockers and, among them the most studied vonoprazan, which are characterized by a better pharmacological profile than PPIs (rapid onset of action, longer lasting acid suppression, control of nocturnal acidity), has the potential to overcome the above-mentioned unmet needs. More research should be done to assess their efficacy in Western populations and their safety in patients treated in the long term.
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Affiliation(s)
- Vincenzo Savarino
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Luca Antonioli
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Matteo Fornai
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Maria Giulia Demarzo
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Fabiana Zingone
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Matteo Ghisa
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Brigida Barberio
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Patrizia Zentilin
- Division of Gastroenterology, Department of Internal Medicine, University of Genoa, Genoa, Italy
| | - Mentore Ribolsi
- Gastroenterology Unit, Departmental Faculty of Medicine and Surgery, Università Campus Bio-Medico Di Roma, Rome, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
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35
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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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Efficacy of Endoscopic Radiofrequency Ablation for Treatment of Reflux Hypersensitivity: A Study Based on Rome IV Criteria. Gastroenterol Res Pract 2022; 2022:4145810. [PMID: 35386530 PMCID: PMC8977342 DOI: 10.1155/2022/4145810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/14/2022] [Accepted: 03/10/2022] [Indexed: 11/17/2022] Open
Abstract
Objective. Effective therapies for reflux hypersensitivity are lacking. Endoscopic radiofrequency ablation may reduce the sensitivity of the distal esophagus through direct interference with nociceptors or vagal afferent fibers and thus may be useful in reflux hypersensitivity. The aim of this study is to assess the effectiveness and possible mechanisms of endoscopic radiofrequency ablation in reflux hypersensitivity patients. Methods. Patients with reflux hypersensitivity who fulfilled the Rome IV criteria and who wished to receive further treatment were recruited. Endoscopic radiofrequency ablation was delivered to the gastroesophageal junction. Data were collected by questionnaire using a 6-point Likert scale. The primary outcome measure was effect on symptoms including heartburn, regurgitation, and chest pain. The secondary outcomes were degree of satisfaction, medication use, acid exposure time (AET), low esophageal sphincter (LES) pressure, and total reflux episodes. We also assessed positive cell density of transient receptor potential vanilloid type 1 receptor (TRPV1) and calcitonin gene-related peptide (CGRP), both of which are biomarkers of afferent fibers, in biopsies obtained from esophageal mucosa 0.5 cm-1 cm above the Z line. These scales will be administered at baseline, 3-month follow-up, 6-month follow-up, and 12-month follow-up. Results. A total of 22 reflux hypersensitivity patients were enrolled (14 males, median age 50.0 years). A significant improvement in symptom scores (heartburn, regurgitation, and chest pain) was noted at 3 months, 6 months, and 12 months (
). Satisfaction with life increased to 72.7% (16/22), 72.7% (16/22), and 68.2% (15/22) at 3, 6, and 12 mo, respectively, compared with baseline (
). Nineteen patients reduced their medication use after treatment. Of these, 22.7% (5/22), 31.8% (7/22), and 40.9% (9/22) subjects stopped medication use at 3 mo, 6 mo, and 12 mo, respectively. No statistical differences were noted in AET, LES pressure, or total reflux episodes from preoperation to 12 mo postoperation. After treatment, the positive cell density of both TRPV1 and CGRP decreased significantly; however, only TRPV1 had a positive correlation with heartburn (
,
) and chest pain (
,
). Conclusion. Endoscopic radiofrequency ablation was an effective and safe therapeutic option in reflux hypersensitivity patients. Further studies with large sample size are required to validate the role of radiofrequency in reflux hypersensitivity.
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Nikaki K, Sifrim D. Pathophysiology of Pediatric Gastroesophageal Reflux Disease: Similarities and Differences With Adults. J Clin Gastroenterol 2022; 56:99-113. [PMID: 34560757 DOI: 10.1097/mcg.0000000000001604] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Gastroesophageal reflux (GOR) is defined as "the passage of gastric contents into the esophagus with or without regurgitation and vomiting" and gastroesophageal reflux disease (GORD) is defined "when GOR leads to troublesome symptoms affecting the daily functioning and/or complications." This definition was first developed in 2006 by the Montreal consensus group (1) and later on adopted by pediatric gastroenterology societies such as ESPGHAN and NASPGHAN in 2009 (2). The definition of gastroesophageal reflux reveals little about its pathophysiology and is focused on symptomatology. In this way, it acts as an umbrella term for the multifactorial causes of the disease and the various phenotypes encountered; from functional heartburn to hypersensitive esophagus and nonerosive reflux disease, to erosive esophagitis and Barrett's esophagus. This article is devoted to the pathophysiology of pediatric GORD in comparison to adult GORD and is divided in 2 parts. In the first part, we will systematically describe the different mechanisms for the generation and clearance of reflux events, while on the second part we will discuss the mechanisms involved in symptoms generation. Finally, we will discuss the similarities and differences between pediatric and adult GORD.
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Affiliation(s)
- Kornilia Nikaki
- Gastroenterology Department, Great Ormond Street Hospital for Children
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, The Blizard Institute, QMUL, London, UK
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Lee JY, Kim N, Park JH, Yu JE, Song YJ, Yoon JW, Lee DH. Sex and Gender Differences in Overlap Syndrome of Functional Gastrointestinal Disorder and Effect of Genetic Polymorphisms in South Korea: A Long-term Follow-up Study. J Neurogastroenterol Motil 2022; 28:145-158. [PMID: 34980697 PMCID: PMC8748849 DOI: 10.5056/jnm21047;] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 10/02/2021] [Accepted: 10/11/2021] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND/AIMS Overlap functional gastrointestinal disorder (FGID) is associated with more severe gastrointestinal symptoms and lower quality of life. The aim of this study is to evaluate clinical features of non-erosive reflux disease (NERD), functional dyspepsia, irritable bowel syndrome, their overlap in terms of sex and gender, and to assess the risk factors, including genetic polymorphisms. METHODS A total of 494 FGIDs and 239 controls were prospectively enrolled between 2004 and 2020. FGIDs were diagnosed based on the Rome III criteria and symptoms were evaluated using a questionnaire. Follow-up questionnaires were conducted to determine the change of symptoms during the 75.8-month mean observation period. Risk factors including genetic polymorphisms in neurotransmitter receptor (SLC6A4 5-HTTLPR, GNB3, ADRA2A, CCKAR, and TRPV1) and cytokine (TNFA and IL10) genes. RESULTS NERD was more prevalent in men, and functional dyspepsia in women. Overlap FGIDs (n = 239) were more prevalent than nonoverlap FGIDs (n = 255) in women (P = 0.019). Anxiety and depression scores were higher in the overlaps (P = 0.012 and P < 0.001, respectively). Symptoms were more frequent and severe in the overlap FGIDs than in the non-overlaps (P < 0.001). During followup, symptoms progressed more frequently in the overlap FGIDs, especially in patients with the L/S genotype of SLC6A4 5-HTTLPR and anxiety/depression. CONCLUSIONS Overlap FGID patients need attention given their association with anxiety/depression and more severe symptoms, especially in women. Genetic polymorphisms also may be associated with certain symptoms of overlap FGIDs.
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Affiliation(s)
- Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Yun Jeong Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Jung Won Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Lee JY, Kim N, Park JH, Yu JE, Song YJ, Yoon JW, Lee DH. Sex and Gender Differences in Overlap Syndrome of Functional Gastrointestinal Disorder and Effect of Genetic Polymorphisms in South Korea: A Long-term Follow-up Study. J Neurogastroenterol Motil 2022; 28:145-158. [PMID: 34980697 PMCID: PMC8748849 DOI: 10.5056/jnm21047] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 10/02/2021] [Accepted: 10/11/2021] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Overlap functional gastrointestinal disorder (FGID) is associated with more severe gastrointestinal symptoms and lower quality of life. The aim of this study is to evaluate clinical features of non-erosive reflux disease (NERD), functional dyspepsia, irritable bowel syndrome, their overlap in terms of sex and gender, and to assess the risk factors, including genetic polymorphisms. Methods A total of 494 FGIDs and 239 controls were prospectively enrolled between 2004 and 2020. FGIDs were diagnosed based on the Rome III criteria and symptoms were evaluated using a questionnaire. Follow-up questionnaires were conducted to determine the change of symptoms during the 75.8-month mean observation period. Risk factors including genetic polymorphisms in neurotransmitter receptor (SLC6A4 5-HTTLPR, GNB3, ADRA2A, CCKAR, and TRPV1) and cytokine (TNFA and IL10) genes. Results NERD was more prevalent in men, and functional dyspepsia in women. Overlap FGIDs (n = 239) were more prevalent than non-overlap FGIDs (n = 255) in women (P = 0.019). Anxiety and depression scores were higher in the overlaps (P = 0.012 and P < 0.001, respectively). Symptoms were more frequent and severe in the overlap FGIDs than in the non-overlaps (P < 0.001). During follow-up, symptoms progressed more frequently in the overlap FGIDs, especially in patients with the L/S genotype of SLC6A4 5-HTTLPR and anxiety/depression. Conclusions Overlap FGID patients need attention given their association with anxiety/depression and more severe symptoms, especially in women. Genetic polymorphisms also may be associated with certain symptoms of overlap FGIDs.
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Affiliation(s)
- Ju Yup Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Yun Jeong Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Jung Won Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoungnam, Gyeonggi-do, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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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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Jung HK, Tae CH, Song KH, Kang SJ, Park JK, Gong EJ, Shin JE, Lim HC, Lee SK, Jung DH, Choi YJ, Seo SI, Kim JS, Lee JM, Kim BJ, Kang SH, Park CH, Choi SC, Kwon JG, Park KS, Park MI, Lee TH, Kim SY, Cho YS, Lee HH, Jung KW, Kim DH, Moon HS, Miwa H, Chen CL, Gonlachanvit S, Ghoshal UC, Wu JCY, Siah KTH, Hou X, Oshima T, Choi MY, Lee KJ. 2020 Seoul Consensus on the Diagnosis and Management of Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2021; 27:453-481. [PMID: 34642267 PMCID: PMC8521465 DOI: 10.5056/jnm21077] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.
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Affiliation(s)
- Hye-Kyung Jung
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Chung Hyun Tae
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Kyung Ho Song
- Division of Gastroenterology, Department of Internal Medicine, CHA Ilsan Medical Center, CHA University School of Medicine, Ilsan, Jeollabuk-do, Korea
| | - Seung Joo Kang
- Department of Internal Medicine, Seoul National University Hospital Gangnam Center, Seoul, Korea
| | - Jong Kyu Park
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Eun Jeong Gong
- Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Gangwon-do, Korea
| | - Jeong Eun Shin
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Chungcheongnam-do, Korea
| | - Hyun Chul Lim
- Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Gyeonggi-do, Korea
| | - Sang Kil Lee
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Da Hyun Jung
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Yoon Jin Choi
- Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seung In Seo
- Division of Gastroenterology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Joon Sung Kim
- Division of Gastroenterology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Korea
| | - Jung Min Lee
- Digestive Disease Center, CHA Gangnam Medical Center, CHA University, Seoul, Korea
| | - Beom Jin Kim
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Sun Hyung Kang
- Department of Gastroenterology, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Gyeonggi-do, Korea
| | - Suck Chei Choi
- Department of Internal Medicine and Digestive Disease Research Institute, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Korea
| | - Joong Goo Kwon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Kyung Sik Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Moo In Park
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Seung Young Kim
- Department of Internal Medicine, College of Medicine, Korea University, Seoul, Korea
| | - Young Sin Cho
- Division of Gastroenterology, Department of Internal Medicine, Soonchunhyang University Cheonan, Hospital, Cheonan, Chungcheongnamdo, Korea
| | - Han Hong Lee
- Department of Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kee Wook Jung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Do Hoon Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hee Seok Moon
- Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Korea
| | - Hirota Miwa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chien-Lin Chen
- Institute of Medical Sciences, Tzu Chi University, and Department of Public Health, College of Medicine, Tzu Chi University, Hualien City, Taiwan
| | - Sutep Gonlachanvit
- Center of Excellence on Neurogastroenterology and Motility, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Uday C Ghoshal
- Departments of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Science, Lucknow, India
| | - Justin C Y Wu
- Institute of Digestive Disease, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, China
| | - Kewin T H Siah
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Division of Gastroenterology and Hepatology, University Medicine Cluster, National University Hospital, Singapore
| | - Xiaohua Hou
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
| | - Tadayuki Oshima
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Mi-Young Choi
- Division of Healthcare Technology Assessment Research, National Evidence-based Healthcare Collaborating Agency, Seoul, Korea
| | - Kwang Jae Lee
- Department of Gastroenterology, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea
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Kahrilas PJ, Savarino E, Anastasiou F, Bredenoord AJ, Corsetti M, Lagergren J, Mendive J, Nelson S, Roman S, Zerbib F, Hungin P. The tapestry of reflux syndromes: translating new insight into clinical practice. Br J Gen Pract 2021; 71:470-473. [PMID: 34593403 PMCID: PMC8463155 DOI: 10.3399/bjgp21x717329] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Peter J Kahrilas
- Division of Gastroenterology, Feinberg School of Medicine, Northwestern University, Chicago, IL, US
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Foteini Anastasiou
- 4th Local Primary Health Care Unit, Academic Unit of Heraklion, Clinic of Social and Family Medicine, University of Crete, Greece
| | - Albert J Bredenoord
- Department of Gastroenterology, Amsterdam University Medical Center, Amsterdam, the Netherlands
| | - Maura Corsetti
- National Institute for Health Research Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust, UK; School of Medicine, University of Nottingham and Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, UK
| | - Jesper Lagergren
- School of Cancer and Pharmaceutical Sciences, King's College London, UK; Professor and Consultant of Surgery, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Juan Mendive
- La Mina Primary Care Academic Health Centre, University of Barcelona, Catalan Institute of Health, Barcelona, Spain
| | - Sophie Nelson
- Manchester University NHS Foundation Trust, Manchester, UK
| | - Sabine Roman
- Université Claude Bernard Lyon 1 and Hospices Civils de Lyon, Digestive Physiology, Hopital E Herriot, Lyon, France
| | - Frank Zerbib
- CHU de Bordeaux, Centre Medico-chirurgical Magellan, Hôpital Haut-Lévêque, Université de Bordeaux, INSERM CIC 1401, Bordeaux, France
| | - Pali Hungin
- Primary Care and General Practice, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
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Losa M, Manz SM, Schindler V, Savarino E, Pohl D. Increased visceral sensitivity, elevated anxiety, and depression levels in patients with functional esophageal disorders and non-erosive reflux disease. Neurogastroenterol Motil 2021; 33:e14177. [PMID: 34128293 DOI: 10.1111/nmo.14177] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 04/20/2021] [Accepted: 04/28/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Little is known about possible underlying psychological abnormalities and physiology of reflux hypersensitivity (RH) as defined in the recent Rome IV classification. We aimed to assess markers of psychological comorbidity as well as gastro-esophageal reflux measurements in RH patients compared to controls and also in patients with functional heartburn (FH) and non-erosive reflux disease (NERD) versus controls. METHODS Data of 304 patients visiting our Functional Diagnostics Centre from 2016 to 2018 were analyzed. We focused on a psychological assessment using validated questionnaires (visceral sensitivity index; VSI, hospital anxiety and depression score; HADS) as well as multichannel intraluminal impedance (MII) and pH-metry data from the diagnostic work-up. KEY RESULTS We found a decreased VSI of 57.8 ± 15.4 points (pts) among RH patients (n = 45) indicating higher visceral sensitivity compared to 85.7 ± 2.0 pts in the control group (n = 31, P < 0.001). Furthermore, a significant difference in VSI was found between the FH (60.8 ± 23.3 pts, n = 59, P < 0.001) and between the NERD (61.9 ± 20.8 pts, n = 67, P < 0.001) both compared to the control group. The HADS also displayed a significant difference between the RH (11.9 ± 6.0 pts, P < 0.001), FH (11.0 ± 7.4 pts, P < 0.001), respectively, NERD (11.3 ± 8.9 pts, P < 0.001) as compared to the control group (2.0 ± 1.4 pts). CONCLUSIONS AND INFERENCES Increased sensation to visceral stimuli as well as anxiety and depression appears to play an important role not only in reflux hypersensitivity and functional heartburn as defined by Rome IV but also in NERD. These findings are in line with the disease concept of disorders of gut-brain interaction in which psychological comorbidities and visceral hypersensitivity play a major role.
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Affiliation(s)
- Marco Losa
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
| | - Salomon M Manz
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
| | - Valeria Schindler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
| | - Edoardo Savarino
- Department of Gastroenterology, University of Padua, Padua, Italy
| | - Daniel Pohl
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
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Kim JY, Shin IS, Min YW, Kim K, Lee H, Min BH, Lee JH, Kim JJ, Rhee PL. Endoscopic Prediction for Acid Reflux in Patients without Hiatus Hernia. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 76:134-141. [PMID: 32969361 DOI: 10.4166/kjg.2020.76.3.134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Revised: 05/25/2020] [Accepted: 06/04/2020] [Indexed: 11/03/2022]
Abstract
Background/Aims A diagnosis of gastroesophageal reflux disease is challenging in patients who have reflux symptoms but do not respond to proton pump inhibitors nor have reflux esophagitis and hiatal hernia (HH) on endoscopy. This study examined the predictive role of the endoscopic findings, including the flap valve grade for pathologic acid exposure (PAE) to establish an endoscopic prediction model in patients with neither reflux esophagitis nor HH. Methods Five hundred seventy-eight patients who underwent upper endoscopy and 24 hours pH monitoring for reflux esophageal symptoms without evidence of reflux esophagitis and HH were analyzed. The gastroesophageal flap valve (GEFV), esophageal metaplasia, and chronic atrophic gastritis were assessed. The association between the endoscopic parameters and PAE was evaluated. Results Four hundred ninety-four patients were enrolled. The most common complaint was chest discomfort (42.3%) followed by globus (31.8%), dysphagia (7.9%), and heartburn (7.7%). PAE was present in 43 patients (8.7%). Multivariable analysis revealed PAE to be associated with the GEFV grade (p<0.001) and inversely associated with the chronic atrophic gastritis grade (p=0.005). Using these features, a predictive model was established and showed an area under the receiver operating characteristic curve of 0.705 (95% CI 0.619-0.790). The cutoff value of 12.0 had a sensitivity and specificity of 44.0% and 84.0%, respectively. Conclusions A loosened GEFV is associated with a risk of PAE in patients with neither reflux esophagitis nor HH, while atrophic gastritis is preventive. On the other hand, the endoscopic predictive model revealed a low sensitivity for detecting PAE. Thus, reflux testing needs to be performed further when gastroesophageal reflux disease is suspected, even without endoscopic evidence.
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Affiliation(s)
- Jun Young Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - In Seub Shin
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yang Won Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyunga Kim
- Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung-Hoon Min
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jun Haeng Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Poong-Lyul Rhee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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45
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Wong MW, Hung JS, Liu TT, Yi CH, Lei WY, Liang SW, Orr WC, Chen CL. Esophageal acid burden in reflux patients with normal endoscopy: Does esophageal peristalsis matter? J Formos Med Assoc 2021; 121:388-394. [PMID: 34090788 DOI: 10.1016/j.jfma.2021.05.021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 05/13/2021] [Accepted: 05/17/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND A majority of patients with gastroesophageal reflux disease (GERD) have normal endoscopy. We aimed to investigate whether esophageal primary and secondary peristalsis influence esophageal reflux parameters in patients with normal endoscopy. METHODS We enrolled consecutive patients with typical reflux symptoms and normal endoscopy. All patients underwent High resolution manometry (HRM) and 24-h impedance-pH studies off therapy. During HRM, secondary peristalsis was evaluated using ten 20-mL rapid air infusions into the esophagus, while primary peristalsis was evaluated using ten 5-mL water swallows. RESULTS A total of 43 patients completed the study; 13 patients had normal motility, 20 had ineffective esophageal motility (IEM), and 10 had absent contractility. Acid exposure time (AET) (total, supine, and upright) was significantly higher in those with absent primary peristalsis (absent contractility) compared to normal motility (P = 0.001; 0.01; 0.007) and IEM (P = 0.002; 0.02; 0.03). Supine AET was significantly higher in patients without secondary peristalsis compared to those with secondary peristalsis (P = 0.04). CONCLUSION In the setting of normal endoscopy, acid reflux burden is more profound in patients with absent primary peristalsis, as well as in patients lacking a secondary peristaltic response to esophageal air distension.
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Affiliation(s)
- 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
| | - Jui-Sheng Hung
- 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
| | - Chih-Hsun Yi
- 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
| | - Shu-Wei Liang
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - William C Orr
- Lynn Institute for Healthcare Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 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.
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Jiang Y, Jiang L, Ye B, Lin L. Value of adjunctive evidence from MII-pH monitoring and high-resolution manometry in inconclusive GERD patients with AET 4-6. Therap Adv Gastroenterol 2021; 14:17562848211013484. [PMID: 34104208 PMCID: PMC8170342 DOI: 10.1177/17562848211013484] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 04/08/2021] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Gastro-esophageal reflux disease (GERD) is a common disease in gastroenterology outpatients. However, some patients with typical reflux symptoms does not satisfy diagnostic criteria. This study was to explore the value of adjunctive evidence from multichannel intraluminal impedance-pH (MII-pH) monitoring and esophageal high-resolution manometry (HRM) in inconclusive GERD patients with acid exposure time (AET) 4-6%. METHODS Endoscopy, MII-pH monitoring and esophageal HRM were retrospectively analyzed from consecutive patients with typical reflux symptoms in a tertiary hospital from 2013 to 2019. Patients were categorized as conclusive or inconclusive GERD according to AET. Adjunctive evidence for GERD diagnosis from Lyon Consensus were collected and analyzed. RESULTS Among 147 patients with typical reflux symptoms, conclusive GERD was found in only 31.97% of patients (N = 47). The remaining 100 patients (68.03%) were inconclusive GERD, of whom 28% (N = 28) had AET 4-6%. These patients suffered similar reflux burden and impaired esophageal movement. Inconclusive GERD patients with AET 4-6% had lots of positive adjunctive evidence from HRM and MII-pH monitoring. In receiver operating characteristic analysis, mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWI) had an area under the curve (AUC) of 0.839 (CI: 0.765-0.913, p < 0.001) and 0.897 (CI: 0.841-0.953, p < 0.001), respectively, better than total reflux episode (AUC of 0.55, p = 0.33). When MNBI was combined with PSPWI, the AUC was elevated to 0.910 (CI: 0.857-0.963, p < 0.001). CONCLUSIONS Inconclusive GERD patients with AET 4-6% have similar acid burden and esophagus motility dysfunction to GERD patients. MNBI and PSPWI are pivotal adjunctive evidence for diagnosing GERD when AET is borderline.
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Affiliation(s)
| | | | - Bixing Ye
- Department of Gastroenterology, the First
Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Lee SW, Chang CS. Impact of Overlapping Functional Gastrointestinal Disorders on the Quality of Life in Patients With Gastroesophageal Reflux Disease. J Neurogastroenterol Motil 2021; 27:176-184. [PMID: 33795540 PMCID: PMC8026382 DOI: 10.5056/jnm19006] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 05/04/2020] [Accepted: 01/02/2021] [Indexed: 12/13/2022] Open
Abstract
Gastroesophageal reflux disease (GERD) and functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome and functional dyspepsia, are common afflictions within the general population. Both conditions have a considerable impact on the daily health related quality of life (HRQoL) of affected individuals. Risk factors surrounding any impaired HRQoL in patients with GERD involve those of younger age, obesity, an increase in reflux symptom frequency, and overlapping FGIDs. The risk factors for subjects experiencing an overlap in FGIDs and GERD involve those who are female, younger age, cigarette smoking, non-erosive reflux disease, more GERD symptoms, and psychological performances including anxiety, somatization, and more frequent healthcareseeking behavior. The overlap of GERD and FGIDs is associated with a worsening of both physical and mental health, an increase in bothersome symptoms, impaired functional capacity, and a higher likelihood of consulting a physician. Acid secretion suppressors could offer therapeutic efficacy to some patients experiencing overlapping GERD and FGIDs.
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Affiliation(s)
- Shou-Wu Lee
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chi-Sen Chang
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan
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Savarino V, Marabotto E, Zentilin P, Demarzo MG, de Bortoli N, Savarino E. Pharmacological Management of Gastro-Esophageal Reflux Disease: An Update of the State-of-the-Art. Drug Des Devel Ther 2021; 15:1609-1621. [PMID: 33907381 PMCID: PMC8064680 DOI: 10.2147/dddt.s306371] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 04/06/2021] [Indexed: 12/12/2022] Open
Abstract
Gastro-esophageal reflux disease (GERD) is a highly prevalent, chronic disorder, whose knowledge remains limited and the management of these patients changes continuously. This review provides a summary of the most recent advancements in the pathogenesis of this disease and the new drugs introduced into the market to overcome some of the unmet needs of traditional therapies. Nowadays, the most fruitful diagnostic examinations are 24-hour impedance-pH monitoring, which allows us to separate true NERD from esophageal functional disorders and high-resolution manometry, which helps to exclude the existence of motility disorders sharing the same symptoms of GERD. Proton pump inhibitors (PPIs) remain the first-choice therapy in the treatment of GERD, but a consistent proportion of these patients continue to experience symptoms despite their intake. These cases pertain mainly to the subpopulation with non-erosive reflux disease (NERD) and represent very challenging clinical situations, because it is mandatory to understand the reasons for PPI failure. The management of these difficult patients requires necessarily to test them and avoid the use of empiric treatments that are often unsuccessful, costly and potentially dangerous. Recently, several new drugs have been used to increase the defensive properties of this mucosa with promising results in randomized clinical trials.
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Affiliation(s)
- Vincenzo Savarino
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Elisa Marabotto
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | - Patrizia Zentilin
- Department of Internal Medicine (DIMI), University of Genoa, Genoa, Italy
| | | | - Nicola de Bortoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
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Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study. Obes Surg 2021; 30:2667-2675. [PMID: 32193740 DOI: 10.1007/s11695-020-04545-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. METHODS Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. RESULTS A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (< 29%) and did not differ significantly between groups, while the proportions of patients with esophagitis were high both in the T2DM and non-T2DM group, 58% versus 47%, p = 0.16. The majority of patients with esophagitis did not have GERD-symptoms (68-80%). Further, 55% of the patients with T2DM had pathologic acid reflux. Among these, 71% also had erosive esophagitis, whereof 67% were asymptomatic. CONCLUSIONS The prevalence of GERD was similar in bariatric patients with or without T2DM, and the proportion of patients with asymptomatic GERD was high independent of the presence or absence of T2DM. Accordingly, GERD may be underdiagnosed in patients not undergoing a preoperative endoscopy or acid reflux assessment. TRIAL REGISTRATION Clinical Trials.gov number NCT01778738.
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Xie P, Yan J, Ye L, Wang C, Li Y, Chen Y, Li G. Efficacy of different endoscopic treatments in patients with gastroesophageal reflux disease: a systematic review and network meta-analysis. Surg Endosc 2021; 35:1500-1510. [PMID: 33650003 DOI: 10.1007/s00464-021-08386-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 02/09/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND Both transoral incisionless fundoplication (TIF) and radiofrequency ablation (Stretta) are representative endoscopic treatments for gastroesophageal reflux disease (GERD), but they have not been directly compared. This systematic review and network meta-analysis (NMA) evaluated the comparative effects of Stretta, TIF, and proton pump inhibitors (PPIs). METHODS PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase were searched for randomized controlled trials (RCTs) that compared the efficacy of either the Stretta, TIF, or PPIs/sham procedure for GERD treatment. The NMA was conducted using frequentist methods. RESULTS A total of 516 participants from 10 RCTs were included in this NMA. Both Stretta (mean difference, MD - 9.77, 95% confidence interval, CI - 12.85 to - 6.70) and TIF (MD - 12.22, 95% CI - 15.93 to - 8.52) were significantly superior to PPIs at improving health-related quality of life (HRQL) scores and heartburn scores (Stretta: MD - 1.53, 95% CI - 2.98 to - 0.08; TIF: MD - 9.60, 95% CI - 17.79 to - 1.41). Stretta (MD - 3.77, 95% CI - 6.88 to - 0.65) was less effective at increasing lower esophageal sphincter (LES) pressure than TIF. Stretta was significantly superior to TIF (MD - 3.25, 95% CI - 5.95 to - 0.56) at improving esophageal acid exposure. Regarding the decrease in PPIs utility and esophagitis incidence, no significant differences were found between TIF and Stretta. CONCLUSION In terms of short-term reduction of the HRQL score and heartburn score in patients with GERD, TIF and Stretta may be comparable to each other, and both may be more effective than PPIs. TIF may increase the LES pressure in comparison with Stretta and PPIs. PPIs may reduce the percentage of time pH < 4.0 when compared with TIF. This evidence should be interpreted with caution given the small number of included studies and inherent heterogeneity. Registration No. CRD42020188345.
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Affiliation(s)
- Peiwei Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Jing Yan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Ling Ye
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Chong Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Yuanyuan Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Youxiang Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China
| | - Guohua Li
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, 17 Yongwai Street, Nanchang, 30006, China.
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