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Gastroesophageal Reflux DiseaseA Review

Educational Objective
To review the clinical management of gastroesophageal reflux disease.
1 Credit CME
Abstract

Importance  Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.

Observations  GERD can influence patients’ health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established.

Conclusions and Relevance  The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Jesper Lagergren, MD, PhD, Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Retzius St 13a, Karolinska Institutet, 171 77 Stockholm, Sweden (jesper.lagergren@ki.se).

Accepted for Publication: October 12, 2020.

Author Contributions: Dr Lagergren had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Maret-Ouda, Markar.

Critical revision of the manuscript for important intellectual content: Markar, Lagergren.

Statistical analysis: Maret-Ouda.

Obtained funding: Lagergren.

Administrative, technical, or material support: Maret-Ouda.

Supervision: Markar, Lagergren.

Conflict of Interest Disclosures: No disclosures were reported.

Funding/Support: Dr Maret-Ouda was supported by the Centre for Clinical Research Sormland. Dr Markar was supported by the National Institute for Health Research. Dr Lagergren was supported by the Distinguished Professor Award at Karolinska Institutet and the United European Gastroenterology (UEG) Research Prize.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

References
1.
Vakil  N , van Zanten  SV , Kahrilas  P , Dent  J , Jones  R ; Global Consensus Group.  The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus.   Am J Gastroenterol. 2006;101(8):1900-1920. doi:10.1111/j.1572-0241.2006.00630.x PubMedGoogle ScholarCrossref
2.
Richter  JE , Rubenstein  JH .  Presentation and epidemiology of gastroesophageal reflux disease.   Gastroenterology. 2018;154(2):267-276. doi:10.1053/j.gastro.2017.07.045 PubMedGoogle ScholarCrossref
3.
Eusebi  LH , Ratnakumaran  R , Yuan  Y , Solaymani-Dodaran  M , Bazzoli  F , Ford  AC .  Global prevalence of, and risk factors for, gastro-oesophageal reflux symptoms: a meta-analysis.   Gut. 2018;67(3):430-440. doi:10.1136/gutjnl-2016-313589 PubMedGoogle ScholarCrossref
4.
Scida  S , Russo  M , Miraglia  C ,  et al.  Relationship between Helicobacter pylori infection and GERD.   Acta Biomed. 2018;89(8-S):40-43.PubMedGoogle Scholar
5.
El-Serag  HB , Sweet  S , Winchester  CC , Dent  J .  Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review.   Gut. 2014;63(6):871-880. doi:10.1136/gutjnl-2012-304269 PubMedGoogle ScholarCrossref
6.
Kulig  M , Leodolter  A , Vieth  M ,  et al.  Quality of life in relation to symptoms in patients with gastro-oesophageal reflux disease: an analysis based on the ProGERD initiative.   Aliment Pharmacol Ther. 2003;18(8):767-776. doi:10.1046/j.1365-2036.2003.01770.x PubMedGoogle ScholarCrossref
7.
Becher  A , El-Serag  H .  Systematic review: the association between symptomatic response to proton pump inhibitors and health-related quality of life in patients with gastro-oesophageal reflux disease.   Aliment Pharmacol Ther. 2011;34(6):618-627. doi:10.1111/j.1365-2036.2011.04774.x PubMedGoogle ScholarCrossref
8.
Savarino  E , Bredenoord  AJ , Fox  M , Pandolfino  JE , Roman  S , Gyawali  CP ; International Working Group for Disorders of Gastrointestinal Motility and Function.  Expert consensus document: advances in the physiological assessment and diagnosis of GERD.   Nat Rev Gastroenterol Hepatol. 2017;14(11):665-676. doi:10.1038/nrgastro.2017.130 PubMedGoogle ScholarCrossref
9.
Mikami  DJ , Murayama  KM .  Physiology and pathogenesis of gastroesophageal reflux disease.   Surg Clin North Am. 2015;95(3):515-525. doi:10.1016/j.suc.2015.02.006 PubMedGoogle ScholarCrossref
10.
Poddar  U .  Gastroesophageal reflux disease (GERD) in children.   Paediatr Int Child Health. 2019;39(1):7-12. doi:10.1080/20469047.2018.1489649 PubMedGoogle ScholarCrossref
11.
Jacobson  BC , Somers  SC , Fuchs  CS , Kelly  CP , Camargo  CA  Jr .  Body-mass index and symptoms of gastroesophageal reflux in women.   N Engl J Med. 2006;354(22):2340-2348. doi:10.1056/NEJMoa054391 PubMedGoogle ScholarCrossref
12.
Kaltenbach  T , Crockett  S , Gerson  LB .  Are lifestyle measures effective in patients with gastroesophageal reflux disease? an evidence-based approach.   Arch Intern Med. 2006;166(9):965-971. doi:10.1001/archinte.166.9.965 PubMedGoogle ScholarCrossref
13.
Mohammed  I , Cherkas  LF , Riley  SA , Spector  TD , Trudgill  NJ .  Genetic influences in gastro-oesophageal reflux disease: a twin study.   Gut. 2003;52(8):1085-1089. doi:10.1136/gut.52.8.1085 PubMedGoogle ScholarCrossref
14.
Cameron  AJ , Lagergren  J , Henriksson  C , Nyren  O , Locke  GR  III , Pedersen  NL .  Gastroesophageal reflux disease in monozygotic and dizygotic twins.   Gastroenterology. 2002;122(1):55-59. doi:10.1053/gast.2002.30301 PubMedGoogle ScholarCrossref
15.
Böhmer  AC , Schumacher  J .  Insights into the genetics of gastroesophageal reflux disease (GERD) and GERD-related disorders.   Neurogastroenterol Motil. 2017;29(2):1-5. doi:10.1111/nmo.13017 PubMedGoogle ScholarCrossref
16.
Patel  A , Hasak  S , Nix  BD , Sayuk  GS , Newberry  RD , Gyawali  CP .  Genetic risk factors for perception of symptoms in GERD: an observational cohort study.   Aliment Pharmacol Ther. 2018;47(2):289-297. doi:10.1111/apt.14414 PubMedGoogle ScholarCrossref
17.
Sugimoto  M , Murata  M , Mizuno  H ,  et al.  Endoscopic reflux esophagitis and reflux-related symptoms after Helicobacter pylori eradication therapy: meta-analysis.   J Clin Med. 2020;9(9):E3007. doi:10.3390/jcm9093007 PubMedGoogle Scholar
18.
Katz  PO , Gerson  LB , Vela  MF .  Guidelines for the diagnosis and management of gastroesophageal reflux disease.   Am J Gastroenterol. 2013;108(3):308-328. doi:10.1038/ajg.2012.444 PubMedGoogle ScholarCrossref
19.
Sidhwa  F , Moore  A , Alligood  E , Fisichella  PM .  Diagnosis and treatment of the extraesophageal manifestations of gastroesophageal reflux disease.   Ann Surg. 2017;265(1):63-67. doi:10.1097/SLA.0000000000001907 PubMedGoogle ScholarCrossref
20.
Kellerman  R , Kintanar  T .  Gastroesophageal reflux disease.   Prim Care. 2017;44(4):561-573. doi:10.1016/j.pop.2017.07.001 PubMedGoogle ScholarCrossref
21.
Johnston  BT .  Oesophageal dysphagia: a stepwise approach to diagnosis and management.   Lancet Gastroenterol Hepatol. 2017;2(8):604-609. doi:10.1016/S2468-1253(17)30001-8 PubMedGoogle ScholarCrossref
22.
Kahrilas  PJ , Shaheen  NJ , Vaezi  MF ,  et al; American Gastroenterological Association.  American Gastroenterological Association medical position statement on the management of gastroesophageal reflux disease.   Gastroenterology. 2008;135(4):1383-1391, 1391.e1-1391.e5. doi:10.1053/j.gastro.2008.08.045PubMedGoogle ScholarCrossref
23.
Revicki  DA , Wood  M , Maton  PN , Sorensen  S .  The impact of gastroesophageal reflux disease on health-related quality of life.   Am J Med. 1998;104(3):252-258. doi:10.1016/S0002-9343(97)00354-9 PubMedGoogle ScholarCrossref
24.
Hansen  AN , Bergheim  R , Fagertun  H , Lund  H , Wiklund  I , Moum  B .  Long-term management of patients with symptoms of gastro-oesophageal reflux disease: a Norwegian randomised prospective study comparing the effects of esomeprazole and ranitidine treatment strategies on health-related quality of life in a general practitioners setting.   Int J Clin Pract. 2006;60(1):15-22. doi:10.1111/j.1368-5031.2006.00768.x PubMedGoogle ScholarCrossref
25.
Ness-Jensen  E , Gottlieb-Vedi  E , Wahlin  K , Lagergren  J .  All-cause and cancer-specific mortality in GORD in a population-based cohort study (the HUNT study).   Gut. 2018;67(2):209-215. doi:10.1136/gutjnl-2016-312514 PubMedGoogle ScholarCrossref
26.
Ronkainen  J , Aro  P , Storskrubb  T ,  et al.  High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: a Kalixanda study report.   Scand J Gastroenterol. 2005;40(3):275-285. doi:10.1080/00365520510011579 PubMedGoogle ScholarCrossref
27.
Zagari  RM , Fuccio  L , Wallander  MA ,  et al.  Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano-Monghidoro study.   Gut. 2008;57(10):1354-1359. doi:10.1136/gut.2007.145177 PubMedGoogle ScholarCrossref
28.
Armstrong  D , Bennett  JR , Blum  AL ,  et al.  The endoscopic assessment of esophagitis: a progress report on observer agreement.   Gastroenterology. 1996;111(1):85-92. doi:10.1053/gast.1996.v111.pm8698230 PubMedGoogle ScholarCrossref
29.
Lundell  LR , Dent  J , Bennett  JR ,  et al.  Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification.   Gut. 1999;45(2):172-180. doi:10.1136/gut.45.2.172 PubMedGoogle ScholarCrossref
30.
Pregun  I , Hritz  I , Tulassay  Z , Herszényi  L .  Peptic esophageal stricture: medical treatment.   Dig Dis. 2009;27(1):31-37. doi:10.1159/000210101 PubMedGoogle ScholarCrossref
31.
Poincloux  L , Rouquette  O , Abergel  A .  Endoscopic treatment of benign esophageal strictures: a literature review.   Expert Rev Gastroenterol Hepatol. 2017;11(1):53-64. doi:10.1080/17474124.2017.1260002 PubMedGoogle ScholarCrossref
32.
Spechler  SJ , Souza  RF .  Barrett’s esophagus.   N Engl J Med. 2014;371(9):836-845. doi:10.1056/NEJMra1314704 PubMedGoogle ScholarCrossref
33.
Hayeck  TJ , Kong  CY , Spechler  SJ , Gazelle  GS , Hur  C .  The prevalence of Barrett’s esophagus in the US: estimates from a simulation model confirmed by SEER data.   Dis Esophagus. 2010;23(6):451-457. doi:10.1111/j.1442-2050.2010.01054.x PubMedGoogle ScholarCrossref
34.
Eusebi  LH , Cirota  GG , Zagari  RM , Ford  AC .  Global prevalence of Barrett’s oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: a systematic review and meta-analysis.   Gut. Published online July 30, 2020. doi:10.1136/gutjnl-2020-321365PubMedGoogle Scholar
35.
Singh  S , Manickam  P , Amin  AV ,  et al.  Incidence of esophageal adenocarcinoma in Barrett’s esophagus with low-grade dysplasia: a systematic review and meta-analysis.   Gastrointest Endosc. 2014;79(6):897-909.e4. doi:10.1016/j.gie.2014.01.009PubMedGoogle ScholarCrossref
36.
Krishnamoorthi  R , Singh  S , Ragunathan  K ,  et al.  Factors associated with progression of Barrett’s esophagus: a systematic review and meta-analysis.   Clin Gastroenterol Hepatol. 2018;16(7):1046-1055.e8. doi:10.1016/j.cgh.2017.11.044PubMedGoogle ScholarCrossref
37.
Bennett  C , Moayyedi  P , Corley  DA ,  et al; BOB CAT Consortium.  BOB CAT: a large-scale review and Delphi consensus for management of Barrett’s esophagus with no dysplasia, indefinite for, or low-grade dysplasia.   Am J Gastroenterol. 2015;110(5):662-682. doi:10.1038/ajg.2015.55 PubMedGoogle ScholarCrossref
38.
Spechler  SJ , Sharma  P , Souza  RF , Inadomi  JM , Shaheen  NJ ; American Gastroenterological Association.  American Gastroenterological Association medical position statement on the management of Barrett’s esophagus.   Gastroenterology. 2011;140(3):1084-1091. doi:10.1053/j.gastro.2011.01.031 PubMedGoogle ScholarCrossref
39.
Fitzgerald  RC , di Pietro  M , Ragunath  K ,  et al; British Society of Gastroenterology.  British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus.   Gut. 2014;63(1):7-42. doi:10.1136/gutjnl-2013-305372 PubMedGoogle ScholarCrossref
40.
Spechler  SJ .  Barrett esophagus and risk of esophageal cancer: a clinical review.   JAMA. 2013;310(6):627-636. doi:10.1001/jama.2013.226450 PubMedGoogle ScholarCrossref
41.
Lagergren  J , Bergström  R , Lindgren  A , Nyrén  O .  Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.   N Engl J Med. 1999;340(11):825-831. doi:10.1056/NEJM199903183401101 PubMedGoogle ScholarCrossref
42.
Coleman  HG , Xie  SH , Lagergren  J .  The epidemiology of esophageal adenocarcinoma.   Gastroenterology. 2018;154(2):390-405. doi:10.1053/j.gastro.2017.07.046 PubMedGoogle ScholarCrossref
43.
Gavin  AT , Francisci  S , Foschi  R ,  et al; EUROCARE-4 Working Group.  Oesophageal cancer survival in Europe: a EUROCARE-4 study.   Cancer Epidemiol. 2012;36(6):505-512. doi:10.1016/j.canep.2012.07.009 PubMedGoogle ScholarCrossref
44.
Njei  B , McCarty  TR , Birk  JW .  Trends in esophageal cancer survival in United States adults from 1973 to 2009: a SEER database analysis.   J Gastroenterol Hepatol. 2016;31(6):1141-1146. doi:10.1111/jgh.13289 PubMedGoogle ScholarCrossref
45.
Launoy  G , Bossard  N , Castro  C , Manfredi  S ; GRELL EUROCARE-5 Working Group.  Trends in net survival from esophageal cancer in six European Latin countries: results from the SUDCAN population-based study.   Eur J Cancer Prev. 2017;26:S24-S31. doi:10.1097/CEJ.0000000000000308PubMedGoogle ScholarCrossref
46.
Lagergren  J , Lagergren  P .  Recent developments in esophageal adenocarcinoma.   CA Cancer J Clin. 2013;63(4):232-248. doi:10.3322/caac.21185 PubMedGoogle ScholarCrossref
47.
Hu  Q , Sun  TT , Hong  J , Fang  JY , Xiong  H , Meltzer  SJ .  Proton pump inhibitors do not reduce the risk of esophageal adenocarcinoma in patients with Barrett’s esophagus: a systematic review and meta-analysis.   PLoS One. 2017;12(1):e0169691. doi:10.1371/journal.pone.0169691 PubMedGoogle Scholar
48.
Jankowski  JAZ , de Caestecker  J , Love  SB ,  et al; AspECT Trial Team.  Esomeprazole and aspirin in Barrett’s oesophagus (AspECT): a randomised factorial trial.   Lancet. 2018;392(10145):400-408. doi:10.1016/S0140-6736(18)31388-6 PubMedGoogle ScholarCrossref
49.
Maret-Ouda  J , Santoni  G , Wahlin  K ,  et al.  Esophageal adenocarcinoma after antireflux surgery in a cohort study from the 5 Nordic countries.   Ann Surg. Published online November 27, 2019. doi:10.1097/SLA.0000000000003709PubMedGoogle Scholar
50.
Maret-Ouda  J , Konings  P , Lagergren  J , Brusselaers  N .  Antireflux surgery and risk of esophageal adenocarcinoma: a systematic review and meta-analysis.   Ann Surg. 2016;263(2):251-257. doi:10.1097/SLA.0000000000001438 PubMedGoogle ScholarCrossref
51.
Markar  SR , Arhi  C , Leusink  A ,  et al.  The influence of antireflux surgery on esophageal cancer risk in England: national population-based cohort study.   Ann Surg. 2018;268(5):861-867. doi:10.1097/SLA.0000000000002890 PubMedGoogle ScholarCrossref
52.
Stefanidis  D , Hope  WW , Kohn  GP , Reardon  PR , Richardson  WS , Fanelli  RD ; SAGES Guidelines Committee.  Guidelines for surgical treatment of gastroesophageal reflux disease.   Surg Endosc. 2010;24(11):2647-2669. doi:10.1007/s00464-010-1267-8 PubMedGoogle ScholarCrossref
53.
National Institute for Clinical Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. 2019.
54.
Spechler  SJA .  A 59-year-old woman with gastroesophageal reflux disease and Barrett esophagus.   JAMA. 2003;289(4):466-475. doi:10.1001/jama.289.4.466 PubMedGoogle ScholarCrossref
55.
Patel  A , Posner  S , Gyawali  CP .  Esophageal high-resolution manometry in gastroesophageal reflux disease.   JAMA. 2018;320(12):1279-1280. doi:10.1001/jama.2018.8694 PubMedGoogle ScholarCrossref
56.
Gyawali  CP , Kahrilas  PJ , Savarino  E ,  et al.  Modern diagnosis of GERD: the Lyon Consensus.   Gut. 2018;67(7):1351-1362. doi:10.1136/gutjnl-2017-314722 PubMedGoogle ScholarCrossref
57.
Ness-Jensen  E , Lagergren  J .  Tobacco smoking, alcohol consumption and gastro-oesophageal reflux disease.   Best Pract Res Clin Gastroenterol. 2017;31(5):501-508. doi:10.1016/j.bpg.2017.09.004 PubMedGoogle ScholarCrossref
58.
Ness-Jensen  E , Hveem  K , El-Serag  H , Lagergren  J.   Lifestyle intervention in gastroesophageal reflux disease.   Clin Gastroenterol Hepatol. 2016;14(2):175-182.Google ScholarCrossref
59.
Zalvan  CH , Hu  S , Greenberg  B , Geliebter  J .  A comparison of alkaline water and Mediterranean diet vs proton pump inhibition for treatment of laryngopharyngeal reflux.   JAMA Otolaryngol Head Neck Surg. 2017;143(10):1023-1029. doi:10.1001/jamaoto.2017.1454 PubMedGoogle ScholarCrossref
60.
Rotman  SR , Bishop  TF .  Proton pump inhibitor use in the US ambulatory setting, 2002-2009.   PLoS One. 2013;8(2):e56060. doi:10.1371/journal.pone.0056060 PubMedGoogle Scholar
61.
Bustillos  H , Leer  K , Kitten  A , Reveles  KR .  A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015.   PLoS One. 2018;13(11):e0208461. doi:10.1371/journal.pone.0208461 PubMedGoogle Scholar
62.
Pratt  NL , Kalisch Ellett  LM , Sluggett  JK ,  et al.  Use of proton pump inhibitors among older Australians: national quality improvement programmes have led to sustained practice change.   Int J Qual Health Care. 2017;29(1):75-82. doi:10.1093/intqhc/mzw138 PubMedGoogle ScholarCrossref
63.
Nishtala  PS , Soo  L .  Proton pump inhibitors utilisation in older people in New Zealand from 2005 to 2013.   Intern Med J. 2015;45(6):624-629. doi:10.1111/imj.12757 PubMedGoogle ScholarCrossref
64.
Proulx  J , Hunt  J .  Drug use among seniors on public drug programs in Canada, 2012.   Healthc Q. 2015;18(1):11-13. doi:10.12927/hcq.2015.24250 PubMedGoogle ScholarCrossref
65.
Graham  DY , Tansel  A .  Interchangeable use of proton pump inhibitors based on relative potency.   Clin Gastroenterol Hepatol. 2018;16(6):800-808.e7. doi:10.1016/j.cgh.2017.09.033PubMedGoogle ScholarCrossref
66.
Pottegård  A , Broe  A , Hallas  J , de Muckadell  OB , Lassen  AT , Lødrup  AB .  Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study.   Therap Adv Gastroenterol. 2016;9(5):671-678. doi:10.1177/1756283X16650156 PubMedGoogle ScholarCrossref
67.
Hálfdánarson  OO , Pottegård  A , Björnsson  ES ,  et al.  Proton-pump inhibitors among adults: a nationwide drug-utilization study.   Therap Adv Gastroenterol. 2018;11:1756284818777943. doi:10.1177/1756284818777943 PubMedGoogle Scholar
68.
Freedberg  DE , Kim  LS , Yang  YX .  The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association.   Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031 PubMedGoogle ScholarCrossref
69.
Pasternak  B , Hviid  A .  Use of proton-pump inhibitors in early pregnancy and the risk of birth defects.   N Engl J Med. 2010;363(22):2114-2123. doi:10.1056/NEJMoa1002689 PubMedGoogle ScholarCrossref
70.
Majithia  R , Johnson  DA .  Are proton pump inhibitors safe during pregnancy and lactation? evidence to date.   Drugs. 2012;72(2):171-179. doi:10.2165/11597290-000000000-00000 PubMedGoogle ScholarCrossref
71.
Patel  A , Gyawali  CP .  Gastroesophageal reflux monitoring.   JAMA. 2018;319(12):1271-1272. doi:10.1001/jama.2018.1144 PubMedGoogle ScholarCrossref
72.
Moayyedi  P , Eikelboom  JW , Bosch  J ,  et al; COMPASS Investigators.  Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin.   Gastroenterology. 2019;157(3):682-691.e2. doi:10.1053/j.gastro.2019.05.056PubMedGoogle ScholarCrossref
73.
Nochaiwong  S , Ruengorn  C , Awiphan  R ,  et al.  The association between proton pump inhibitor use and the risk of adverse kidney outcomes: a systematic review and meta-analysis.   Nephrol Dial Transplant. 2018;33(2):331-342. doi:10.1093/ndt/gfw470 PubMedGoogle ScholarCrossref
74.
Hart  E , Dunn  TE , Feuerstein  S , Jacobs  DM .  Proton pump inhibitors and risk of acute and chronic kidney disease: a retrospective cohort study.   Pharmacotherapy. 2019;39(4):443-453. doi:10.1002/phar.2235 PubMedGoogle ScholarCrossref
75.
Cao  F , Chen  CX , Wang  M ,  et al.  Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection.   J Hosp Infect. 2018;98(1):4-13. doi:10.1016/j.jhin.2017.08.017 PubMedGoogle ScholarCrossref
76.
Nguyen  PA , Islam  M , Galvin  CJ ,  et al.  Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.   Int J Qual Health Care. 2020;32(5):292-299. doi:10.1093/intqhc/mzaa041 PubMedGoogle ScholarCrossref
77.
Mortensen  SJ , Mohamadi  A , Wright  CL ,  et al.  Medications as a risk factor for fragility hip fractures: a systematic review and meta-analysis.   Calcif Tissue Int. 2020;107(1):1-9. doi:10.1007/s00223-020-00688-1 PubMedGoogle ScholarCrossref
78.
Brusselaers  N , Lagergren  J , Engstrand  L .  Duration of use of proton pump inhibitors and the risk of gastric and oesophageal cancer.   Cancer Epidemiol. 2019;62:101585. doi:10.1016/j.canep.2019.101585 PubMedGoogle Scholar
79.
Cheung  KS , Chan  EW , Wong  AYS , Chen  L , Wong  ICK , Leung  WK .  Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study.   Gut. 2018;67(1):28-35. doi:10.1136/gutjnl-2017-314605 PubMedGoogle ScholarCrossref
80.
Liu  P , McMenamin  UC , Johnston  BT ,  et al.  Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.   Br J Cancer. 2020;123(2):307-315. doi:10.1038/s41416-020-0860-4 PubMedGoogle ScholarCrossref
81.
Lee  JK , Merchant  SA , Schneider  JL ,  et al.  Proton pump inhibitor use and risk of gastric, colorectal, liver, and pancreatic cancers in a community-based population.   Am J Gastroenterol. 2020;115(5):706-715. doi:10.14309/ajg.0000000000000591 PubMedGoogle ScholarCrossref
82.
Oxford Centre for Evidence-based Medicine. Levels of evidence. Accessed June 17, 2020. https://www.cebm.net/2009/06/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/
83.
Food and Drug Administration. FDA drug safety communication: Clostridium difficile associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). Accessed June 15, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-clostridium-difficile-associated-diarrhea-can-be-associated-stomach
84.
Food and Drug Administration. FDA drug safety communication: possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. Accessed June 18, 2020. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wrist-and-spine-use-proton-pump
85.
Helgadottir  H , Bjornsson  ES .  Problems associated with deprescribing of proton pump inhibitors.   Int J Mol Sci. 2019;20(21):5469. doi:10.3390/ijms20215469 PubMedGoogle ScholarCrossref
86.
Targownik  L .  Discontinuing long-term PPI therapy: why, with whom, and how?   Am J Gastroenterol. 2018;113(4):519-528. doi:10.1038/ajg.2018.29 PubMedGoogle ScholarCrossref
87.
Gyawali  CP , Fass  R .  Management of gastroesophageal reflux disease.   Gastroenterology. 2018;154(2):302-318. doi:10.1053/j.gastro.2017.07.049 PubMedGoogle ScholarCrossref
88.
Food and Drug Administration. FDA requests removal of all ranitidine products (Zantac) from the market. Accessed May 31, 2020. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-all-ranitidine-products-zantac-market
89.
European Medicines Agency. Suspension of ranitidine medicines in the EU. Accessed May 31, 2020. https://www.ema.europa.eu/en/news/suspension-ranitidine-medicines-eu
90.
Leiman  DA , Riff  BP , Morgan  S ,  et al.  Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis.   Dis Esophagus. 2017;30(5):1-9. doi:10.1093/dote/dow020 PubMedGoogle ScholarCrossref
91.
Vaezi  MF , Fass  R , Vakil  N ,  et al.  IW-3718 reduces heartburn severity in patients with refractory gastroesophageal reflux disease in a randomized trial.   Gastroenterology. 2020;158(8):2093-2103. doi:10.1053/j.gastro.2020.02.031 PubMedGoogle ScholarCrossref
92.
Nissen  R .  [A simple operation for control of reflux esophagitis].   Schweiz Med Wochenschr. 1956;86(suppl 20):590-592.PubMedGoogle Scholar
93.
Garg  SK , Gurusamy  KS .  Laparoscopic fundoplication surgery versus medical management for gastro-oesophageal reflux disease (GORD) in adults.   Cochrane Database Syst Rev. 2015;(11):CD003243. doi:10.1002/14651858.CD003243.pub3 PubMedGoogle Scholar
94.
Håkanson  BS , Lundell  L , Bylund  A , Thorell  A .  Comparison of laparoscopic 270° posterior partial fundoplication vs total fundoplication for the treatment of gastroesophageal reflux disease: a randomized clinical trial.   JAMA Surg. 2019;154(6):479-486. doi:10.1001/jamasurg.2019.0047 PubMedGoogle ScholarCrossref
95.
Maret-Ouda  J , Brusselaers  N , Lagergren  J .  What is the most effective treatment for severe gastro-oesophageal reflux disease?   BMJ. 2015;350:h3169. doi:10.1136/bmj.h3169 PubMedGoogle ScholarCrossref
96.
Galmiche  JP , Hatlebakk  J , Attwood  S ,  et al; LOTUS Trial Collaborators.  Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial.   JAMA. 2011;305(19):1969-1977. doi:10.1001/jama.2011.626 PubMedGoogle ScholarCrossref
97.
Yadlapati  R , Hungness  ES , Pandolfino  JE .  Complications of antireflux surgery.   Am J Gastroenterol. 2018;113(8):1137-1147. doi:10.1038/s41395-018-0115-7 PubMedGoogle ScholarCrossref
98.
Maret-Ouda  J , Wahlin  K , El-Serag  HB , Lagergren  J .  Association between laparoscopic antireflux surgery and recurrence of gastroesophageal reflux.   JAMA. 2017;318(10):939-946. doi:10.1001/jama.2017.10981 PubMedGoogle ScholarCrossref
99.
Funch-Jensen  P , Bendixen  A , Iversen  MG , Kehlet  H .  Complications and frequency of redo antireflux surgery in Denmark: a nationwide study, 1997-2005.   Surg Endosc. 2008;22(3):627-630. doi:10.1007/s00464-007-9705-y PubMedGoogle ScholarCrossref
100.
Zhou  T , Harnsberger  C , Broderick  R ,  et al.  Reoperation rates after laparoscopic fundoplication.   Surg Endosc. 2015;29(3):510-514. doi:10.1007/s00464-014-3660-1 PubMedGoogle ScholarCrossref
101.
Patti  MG , Allaix  ME , Fisichella  PM .  Analysis of the causes of failed antireflux surgery and the principles of treatment: a review.   JAMA Surg. 2015;150(6):585-590. doi:10.1001/jamasurg.2014.3859 PubMedGoogle ScholarCrossref
102.
Richards  WO , Scholz  S , Khaitan  L , Sharp  KW , Holzman  MD .  Initial experience with the Stretta procedure for the treatment of gastroesophageal reflux disease.   J Laparoendosc Adv Surg Tech A. 2001;11(5):267-273. doi:10.1089/109264201317054546 PubMedGoogle ScholarCrossref
103.
Triadafilopoulos  G .  Stretta: a valuable endoscopic treatment modality for gastroesophageal reflux disease.   World J Gastroenterol. 2014;20(24):7730-7738. doi:10.3748/wjg.v20.i24.7730 PubMedGoogle ScholarCrossref
104.
Fass  R , Cahn  F , Scotti  DJ , Gregory  DA .  Systematic review and meta-analysis of controlled and prospective cohort efficacy studies of endoscopic radiofrequency for treatment of gastroesophageal reflux disease.   Surg Endosc. 2017;31(12):4865-4882. doi:10.1007/s00464-017-5431-2 PubMedGoogle ScholarCrossref
105.
Cadière  GB , Rajan  A , Germay  O , Himpens  J .  Endoluminal fundoplication by a transoral device for the treatment of GERD: a feasibility study.   Surg Endosc. 2008;22(2):333-342. doi:10.1007/s00464-007-9618-9 PubMedGoogle ScholarCrossref
106.
Jobe  BA , O’Rourke  RW , McMahon  BP ,  et al.  Transoral endoscopic fundoplication in the treatment of gastroesophageal reflux disease: the anatomic and physiologic basis for reconstruction of the esophagogastric junction using a novel device.   Ann Surg. 2008;248(1):69-76. doi:10.1097/SLA.0b013e31817c9630 PubMedGoogle ScholarCrossref
107.
Testoni  PA , Testoni  S , Distefano  G , Mazzoleni  G , Fanti  L , Passaretti  S .  Transoral incisionless fundoplication with EsophyX for gastroesophageal reflux disease: clinical efficacy is maintained up to 10 years.   Endosc Int Open. 2019;7(5):E647-E654. doi:10.1055/a-0820-2297 PubMedGoogle ScholarCrossref
108.
Trad  KS , Barnes  WE , Simoni  G ,  et al.  Transoral incisionless fundoplication effective in eliminating GERD symptoms in partial responders to proton pump inhibitor therapy at 6 months: the TEMPO randomized clinical trial.   Surg Innov. 2015;22(1):26-40. doi:10.1177/1553350614526788 PubMedGoogle ScholarCrossref
109.
Trad  KS , Barnes  WE , Prevou  ER ,  et al.  The TEMPO trial at 5 years: transoral fundoplication (TIF 2.0) is safe, durable, and cost-effective.   Surg Innov. 2018;25(2):149-157. doi:10.1177/1553350618755214 PubMedGoogle ScholarCrossref
110.
Witteman  BP , Conchillo  JM , Rinsma  NF ,  et al.  Randomized controlled trial of transoral incisionless fundoplication vs proton pump inhibitors for treatment of gastroesophageal reflux disease.   Am J Gastroenterol. 2015;110(4):531-542. doi:10.1038/ajg.2015.28 PubMedGoogle ScholarCrossref
111.
Ganz  RA , Peters  JH , Horgan  S ,  et al.  Esophageal sphincter device for gastroesophageal reflux disease.   N Engl J Med. 2013;368(8):719-727. doi:10.1056/NEJMoa1205544 PubMedGoogle ScholarCrossref
112.
Bonavina  L , Saino  GI , Bona  D ,  et al.  Magnetic augmentation of the lower esophageal sphincter: results of a feasibility clinical trial.   J Gastrointest Surg. 2008;12(12):2133-2140. doi:10.1007/s11605-008-0698-1 PubMedGoogle ScholarCrossref
113.
Zadeh  J , Andreoni  A , Treitl  D , Ben-David  K .  Spotlight on the Lin Reflux Management System for the treatment of gastroesophageal reflux disease: evidence and research.   Med Devices (Auckl). 2018;11:291-300. PubMedGoogle Scholar
114.
Kuckelman  JP , Phillips  CJ , Hardin  MO , Martin  MJ .  Standard vs expanded indications for esophageal magnetic sphincter augmentation for reflux disease.   JAMA Surg. 2017;152(9):890-891. doi:10.1001/jamasurg.2017.1606 PubMedGoogle ScholarCrossref
115.
Lipham  JC , Taiganides  PA , Louie  BE , Ganz  RA , DeMeester  TR .  Safety analysis of first 1000 patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease.   Dis Esophagus. 2015;28(4):305-311. doi:10.1111/dote.12199 PubMedGoogle ScholarCrossref
116.
Bell  R , Lipham  J , Louie  B ,  et al  Laparoscopic magnetic sphincter augmentation versus double-dose proton pump inhibitors for management of moderate-to-severe regurgitation in GERD: a randomized controlled trial.   Gastrointest Endosc. 2019;89(1):14-22.e11.PubMedGoogle ScholarCrossref
117.
Guidozzi  N , Wiggins  T , Ahmed  AR , Hanna  GB , Markar  SR .  Laparoscopic magnetic sphincter augmentation versus fundoplication for gastroesophageal reflux disease: systematic review and pooled analysis.   Dis Esophagus. 2019;32(9):doz031. doi:10.1093/dote/doz031 PubMedGoogle Scholar
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