A comprehensive analysis of gastroesophageal reflux disease: Pathophysiology, clinical manifestations, and diagnostic approaches
Keywords:
gastroesophageal reflux disease, pathophysiology, prevalence, complications, therapeutic strategiesAbstract
Background: Gastroesophageal reflux disease (GERD) is a common condition characterized by the reflux of stomach contents, leading to troublesome symptoms and potential complications. The Montreal definition emphasizes symptom severity, while the Lyon Consensus focuses on physiological aspects, and the Rome IV Conference highlights functional syndromes resembling GERD. This article aims to provide a comprehensive analysis of GERD, consolidating various definitions and perspectives. Aim: The study seeks to clarify the multifaceted nature of GERD, including its pathophysiology, clinical manifestations, diagnostic approaches, and therapeutic strategies. Methods: This narrative review synthesizes existing literature, examining prevalence, morbidity, and mortality associated with GERD, as well as its pathogenesis and the impact of lifestyle factors such as obesity. Data from various studies were analyzed to assess the global prevalence of GERD and its complications. Results: GERD prevalence varies globally, from 2.5% in China to 51.2% in Greece, with significant associations between obesity and GERD-related complications, including esophageal adenocarcinoma (EAC). The economic burden of GERD is substantial, with significant healthcare costs reported in multiple countries. The review also highlights the dual role of Helicobacter pylori, which may both exacerbate and protect against GERD symptoms.
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Vakil, N., van Zanten, S. V., Kahrilas, P., Dent, J., Jones, R., & Global Consensus Group. (2006). The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. American Journal of Gastroenterology, 101(8), 1900–1920. https://doi.org/10.1111/j.1572-0241.2006.00630.x DOI: https://doi.org/10.1111/j.1572-0241.2006.00630.x
Gyawali, C. P., Kahrilas, P. J., Savarino, E., et al. (2018). Modern diagnosis of GERD: The Lyon Consensus. Gut, 67(9), 1351–1362. https://doi.org/10.1136/gutjnl-2017-314722 DOI: https://doi.org/10.1136/gutjnl-2017-314722
Drossman, D. A., & Hasler, W. L. (2016). Rome IV-functional GI disorders: Disorders of gut-brain interaction. Gastroenterology, 150(6), 1257–1261. https://doi.org/10.1053/j.gastro.2016.03.035 DOI: https://doi.org/10.1053/j.gastro.2016.03.035
Richter, J. E., & Rubenstein, J. H. (2018). Presentation and epidemiology of gastroesophageal reflux disease. Gastroenterology, 154(1), 267–276. https://doi.org/10.1053/j.gastro.2017.07.045 DOI: https://doi.org/10.1053/j.gastro.2017.07.045
Eusebi, L. H., Ratnakumaran, R., Yuan, Y., Solaymani-Dodaran, M., Bazzoli, F., & Ford, A. C. (2018). Global prevalence of, and risk factors for, gastroesophageal reflux symptoms: A meta-analysis. Gut, 67(4), 430–440. https://doi.org/10.1136/gutjnl-2016-313589 DOI: https://doi.org/10.1136/gutjnl-2016-313589
El-Serag, H. B., Sweet, S., Winchester, C. C., & Dent, J. (2014). Update on the epidemiology of gastro-oesophageal reflux disease: A systematic review. Gut, 63(6), 871–880. https://doi.org/10.1136/gutjnl-2012-304269 DOI: https://doi.org/10.1136/gutjnl-2012-304269
Yamasaki, T., Hemond, C., Eisa, M., Ganocy, S., & Fass, R. (2018). The changing epidemiology of gastroesophageal reflux disease: Are patients getting younger? Journal of Neurogastroenterology and Motility, 24(4), 559–569. https://doi.org/10.5056/jnm18140 DOI: https://doi.org/10.5056/jnm18140
Sawas, T., Manrique, G. C., Iyer, P. G., Wang, K. K., & Katzka, D. A. (2019). Young adults with esophageal adenocarcinoma present with more advanced stage tumors and have shorter survival times. Clinical Gastroenterology and Hepatology, 17(9), 1756–1762. https://doi.org/10.1016/j.cgh.2018.09.031 DOI: https://doi.org/10.1016/j.cgh.2018.09.031
Fedorak, R. N., Veldhuyzen van Zanten, S., & Bridges, R. (2010). Canadian Digestive Health Foundation Public Impact Series: Gastroesophageal reflux disease in Canada: Incidence, prevalence, and direct and indirect economic impact. Canadian Journal of Gastroenterology, 24(7), 431–434. https://doi.org/10.1155/2010/296584 DOI: https://doi.org/10.1155/2010/296584
Rantanen, T. K., & Salo, J. A. (1999). Gastroesophageal reflux disease as a cause of death: Analysis of fatal cases under conservative treatment. Scandinavian Journal of Gastroenterology, 34(3), 229–233. https://doi.org/10.1080/00365529950173609 DOI: https://doi.org/10.1080/00365529950173609
Peery, A. F., Dellon, E. S., Lund, J., et al. (2012). Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology, 143(5), 1179–1187.e3. https://doi.org/10.1053/j.gastro.2012.08.002 DOI: https://doi.org/10.1053/j.gastro.2012.08.002
Miwa, H., Takeshima, T., Iwasaki, K., & Hiroi, S. (2016). Medical cost, incidence rate, and treatment status of gastroesophageal reflux disease in Japan: Analysis of claims data. Journal of Medical Economics, 19(11), 1049–1055. https://doi.org/10.1080/13696998.2016.1192551 DOI: https://doi.org/10.1080/13696998.2016.1192551
Singh, S., Sharma, A. N., Murad, M. H., et al. (2013). Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: A systematic review and meta-analysis. Clinical Gastroenterology and Hepatology, 11(11), 1399–1412.e7. https://doi.org/10.1016/j.cgh.2013.05.009 DOI: https://doi.org/10.1016/j.cgh.2013.05.009
Wildi, S. M., Tutuian, R., & Castell, D. O. (2004). The influence of rapid food intake on postprandial reflux: Studies in healthy volunteers. American Journal of Gastroenterology, 99(8), 1645–1651. https://doi.org/10.1111/j.1572-0241.2004.30273.x DOI: https://doi.org/10.1111/j.1572-0241.2004.30273.x
Blevins, C. H., Dierkhising, R. A., Geno, D. M., et al. (2018). Obesity and GERD impair esophageal epithelial permeability through two distinct mechanisms. Neurogastroenterology and Motility, 30(9), e13403. https://doi.org/10.1111/nmo.13403 DOI: https://doi.org/10.1111/nmo.13403
Atherton, J. C., & Blaser, M. J. (2009). Coadaptation of Helicobacter pylori and humans: Ancient history, modern implications. Journal of Clinical Investigation, 119(11), 2475–2487. https://doi.org/10.1172/JCI38605 DOI: https://doi.org/10.1172/JCI38605
Labenz, J., Jaspersen, D., Kulig, M., et al. (2004). Risk factors for erosive esophagitis: A multivariate analysis based on the ProGERD study initiative. American Journal of Gastroenterology, 99(8), 1652–1656. https://doi.org/10.1111/j.1572-0241.2004.30390.x DOI: https://doi.org/10.1111/j.1572-0241.2004.30390.x
Wang, Z., Shaheen, N. J., Whiteman, D. C., et al. (2018). Helicobacter pylori infection is associated with reduced risk of Barrett’s esophagus: An analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium. American Journal of Gastroenterology, 113(8), 1148–1155. https://doi.org/10.1038/s41395-018-0070-3 DOI: https://doi.org/10.1038/s41395-018-0070-3
Kulig, M., Leodolter, A., Vieth, M., et al. (2003). Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease: An analysis based on the ProGERD initiative. Alimentary Pharmacology and Therapeutics, 18(7), 767–776. https://doi.org/10.1046/j.1365-2036.2003.01770.x DOI: https://doi.org/10.1046/j.1365-2036.2003.01770.x
Moayyedi, P., Feltbower, R., Brown, J., et al., Leeds HELP Study Group. (2000). Effect of population screening and treatment for Helicobacter pylori on dyspepsia and quality of life in the community: A randomized controlled trial. Lancet, 355(9201), 1665–1669. https://doi.org/10.1016/S0140-6736(00)02236-4 DOI: https://doi.org/10.1016/S0140-6736(00)02236-4
Harvey, R. F., Lane, J. A., Murray, L. J., Harvey, I. M., Donovan, J. L., Nair, P., & Bristol Helicobacter Project. (2004). Randomised controlled trial of effects of Helicobacter pylori infection and its eradication on heartburn and gastro-oesophageal reflux: Bristol Helicobacter Project. BMJ, 328(7442), 1417–1420. https://doi.org/10.1136/bmj.38082.626725.EE DOI: https://doi.org/10.1136/bmj.328.7453.1417
Pandolfino, J. E., Kwiatek, M. A., Ho, K., Scherer, J. R., & Kahrilas, P. J. (2010). Unique features of esophagogastric junction pressure topography in hiatus hernia patients with dysphagia. Surgery, 147(1), 57–64. https://doi.org/10.1016/j.surg.2009.05.011 DOI: https://doi.org/10.1016/j.surg.2009.05.011
Kahrilas, P. J., Bredenoord, A. J., Fox, M., et al., International High Resolution Manometry Working Group. (2015). The Chicago Classification of esophageal motility disorders, v3.0. Neurogastroenterology and Motility, 27(2), 160–174. https://doi.org/10.1111/nmo.12469 DOI: https://doi.org/10.1111/nmo.12477
Daher, H. B., & Sharara, A. I. (2019). Gastroesophageal reflux disease, obesity and laparoscopic sleeve gastrectomy: The burning questions. World journal of gastroenterology, 25(33), 4805. DOI: https://doi.org/10.3748/wjg.v25.i33.4805
Emerenziani, S., Pier Luca Guarino, M., Trillo Asensio, L. M., Altomare, A., Ribolsi, M., Balestrieri, P., & Cicala, M. (2019). Role of overweight and obesity in gastrointestinal disease. Nutrients, 12(1), 111. DOI: https://doi.org/10.3390/nu12010111
Pandolfino, J. E., Shi, G., Trueworthy, B., & Kahrilas, P. J. (2003). Esophagogastric junction opening during relaxation distinguishes nonhernia reflux patients, hernia patients, and normal subjects. Gastroenterology, 125(4), 1018-1024. https://doi.org/10.1016/S0016-5085(03)01210-1 DOI: https://doi.org/10.1016/S0016-5085(03)01210-1
Clarke, A. T., Wirz, A. A., Manning, J. J., Ballantyne, S. A., Alcorn, D. J., & McColl, K. E. (2008). Severe reflux disease is associated with an enlarged unbuffered proximal gastric acid pocket. Gut, 57(3), 292-297. https://doi.org/10.1136/gut.2006.109421 DOI: https://doi.org/10.1136/gut.2006.109421
Kahrilas, P. J., McColl, K., Fox, M., et al. (2013). The acid pocket: A target for treatment in reflux disease? American Journal of Gastroenterology, 108(7), 1058-1064. https://doi.org/10.1038/ajg.2013.132 DOI: https://doi.org/10.1038/ajg.2013.132
Rohof, W. O., Bennink, R. J., Smout, A. J., Thomas, E., & Boeckxstaens, G. E. (2013). An alginate-antacid formulation localizes to the acid pocket to reduce acid reflux in patients with gastroesophageal reflux disease. Clinical Gastroenterology and Hepatology, 11(12), 1585-1591.e90. https://doi.org/10.1016/j.cgh.2013.04.046 DOI: https://doi.org/10.1016/j.cgh.2013.04.046
Souza, R. F., Huo, X., Mittal, V., et al. (2009). Gastroesophageal reflux might cause esophagitis through a cytokine-mediated mechanism rather than caustic acid injury. Gastroenterology, 137(5), 1776-1784. https://doi.org/10.1053/j.gastro.2009.07.055 DOI: https://doi.org/10.1053/j.gastro.2009.07.055
Dunbar, K. B., Agoston, A. T., Odze, R. D., et al. (2016). Association of acute gastroesophageal reflux disease with esophageal histologic changes. JAMA, 315(20), 2104-2112. https://doi.org/10.1001/jama.2016.5657 DOI: https://doi.org/10.1001/jama.2016.5657
Takashima, T., Iwakiri, R., Sakata, Y., et al. (2012). Endoscopic reflux esophagitis and Helicobacter pylori infection in young healthy Japanese volunteers. Digestion, 86(1), 55-58. https://doi.org/10.1159/000338849 DOI: https://doi.org/10.1159/000338849
Zagari, R. M., Fuccio, L., Wallander, M. A., et al. (2008). Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: The Loiano-Monghidoro study. Gut, 57(10), 1354-1359. https://doi.org/10.1136/gut.2007.145177 DOI: https://doi.org/10.1136/gut.2007.145177
Pandolfino, J. E., Kahrilas, P. J., & American Gastroenterological Association. (2005). American Gastroenterological Association medical position statement: Clinical use of esophageal manometry. Gastroenterology, 128(1), 207-208. https://doi.org/10.1053/j.gastro.2004.11.007 DOI: https://doi.org/10.1053/j.gastro.2004.11.007
Pandolfino, J. E., Kahrilas, P. J., & American Gastroenterological Association. (2005). AGA technical review on the clinical use of esophageal manometry. Gastroenterology, 128(1), 209-224. https://doi.org/10.1053/j.gastro.2004.11.008 DOI: https://doi.org/10.1053/j.gastro.2004.11.008
Bakulin, I. G., Bordin, D. S., Drapkina, O. M., Zhuravleva, M. S., Kokovina, Y. V., Pavlova, E. Y., ... & Bakulina, N. V. (2019). Phenotypes of Gastroesophageal Reflux Disease in real clinical practice. Consilium Medicum, 21(8), 15-22. DOI: https://doi.org/10.26442/20751753.2019.8.190581
Drossman, D. A. (2016). Functional gastrointestinal disorders: History, pathophysiology, clinical features and Rome IV. Gastroenterology, 150(6), 1262-1279. https://doi.org/10.1053/j.gastro.2016.02.032 DOI: https://doi.org/10.1053/j.gastro.2016.02.032
Lagergren, J., Bergström, R., Lindgren, A., & Nyrén, O. (1999). Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. New England Journal of Medicine, 340(11), 825-831. https://doi.org/10.1056/NEJM199903183401101 DOI: https://doi.org/10.1056/NEJM199903183401101
Fitzgerald, R. C., di Pietro, M., Ragunath, K., et al. (2014). British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut, 63(1), 7-42. https://doi.org/10.1136/gutjnl-2013-305372 DOI: https://doi.org/10.1136/gutjnl-2013-305372
Weusten, B., Bisschops, R., Coron, E., et al. (2017). Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy, 49(2), 191-198. https://doi.org/10.1055/s-0042-122140 DOI: https://doi.org/10.1055/s-0042-122140
Spechler, S. J., Sharma, P., Souza, R. F., Inadomi, J. M., Shaheen, N. J., & American Gastroenterological Association. (2011). American Gastroenterological Association technical review on the management of Barrett’s esophagus. Gastroenterology, 140(3), e18-e52, quiz e13. https://doi.org/10.1053/j.gastro.2011.01.031 DOI: https://doi.org/10.1053/j.gastro.2011.01.031
Cohen, J., Desilets, D. J., Hwang, J. H., et al. (2019). Gastrointestinal Endoscopy Editorial Board top 10 topics: Advances in GI endoscopy in 2018. Gastrointestinal Endoscopy, 90(1), 35-43. https://doi.org/10.1016/j.gie.2019.03.020 DOI: https://doi.org/10.1016/j.gie.2019.03.020
Shaheen, N. J., Falk, G. W., Iyer, P. G., Gerson, L. B., & American College of Gastroenterology. (2016). ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus. American Journal of Gastroenterology, 111(1), 30-50, quiz 51. https://doi.org/10.1038/ajg.2015.322 DOI: https://doi.org/10.1038/ajg.2015.322
Whiteman, D. C., Appleyard, M., Bahin, F. F., et al. (2015). Australian clinical practice guidelines for the diagnosis and management of Barrett’s esophagus and early esophageal adenocarcinoma. Journal of Gastroenterology and Hepatology, 30(5), 804-820. https://doi.org/10.1111/jgh.12913 DOI: https://doi.org/10.1111/jgh.12913
Gaddam, S., Maddur, H., Wani, S., et al. (2011). Risk factors for nocturnal reflux in a large GERD cohort. Journal of Clinical Gastroenterology, 45(9), 764-768. https://doi.org/10.1097/MCG.0b013e318205e164 DOI: https://doi.org/10.1097/MCG.0b013e318205e164
Codipilly, D. C., Chandar, A. K., Singh, S., et al. (2018). The effect of endoscopic surveillance in patients with Barrett’s esophagus: A systematic review and meta-analysis. Gastroenterology, 154(8), 2068-2086.e2065. DOI: https://doi.org/10.1053/j.gastro.2018.02.022
Sawas, T., Killcoyne, S., Iyer, P. G., et al. (2018). Identification of prognostic phenotypes of esophageal adenocarcinoma in 2 independent cohorts. Gastroenterology, 155(6), 1720-1728.e1724. DOI: https://doi.org/10.1053/j.gastro.2018.11.026
Dulai, G. S., Guha, S., Kahn, K. L., Gornbein, J., & Weinstein, W. M. (2002). Preoperative prevalence of Barrett’s esophagus in esophageal adenocarcinoma: A systematic review. Gastroenterology, 122(1), 26-33. https://doi.org/10.1053/gast.2002.30297 DOI: https://doi.org/10.1053/gast.2002.30297
Visrodia, K., Singh, S., Krishnamoorthi, R., et al. (2016). Systematic review with meta-analysis: Prevalent vs. incident oesophageal adenocarcinoma and high-grade dysplasia in Barrett’s oesophagus. Alimentary Pharmacology & Therapeutics, 44(8), 775-784. https://doi.org/10.1111/apt.13783 DOI: https://doi.org/10.1111/apt.13783
Keller, J. A., & Soares, D. D. (2019). Barrett’s esophagus: A comprehensive review. World Journal of Gastroenterology, 25(36), 5520-5533. https://doi.org/10.3748/wjg.v25.i36.5520
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