Gastroesophageal reflux disease (GERD) is a prevalent condition arising from the backward flow of stomach contents into the esophagus, manifesting as either non-erosive reflux disease or erosive esophagitis. This educational article provides an in-depth review of GERD evaluation and treatment, emphasizing the crucial role of an interprofessional healthcare team in optimizing patient care for this common ailment.
Objectives:
- Detail the underlying mechanisms of gastroesophageal reflux disease.
- Recognize the diverse signs and symptoms associated with gastroesophageal reflux disease.
- Outline the diagnostic tests employed in identifying gastroesophageal reflux disease.
- Underscore the significance of enhanced collaboration among interprofessional team members to improve patient outcomes in gastroesophageal reflux disease management.
Access free multiple choice questions on this topic.
Introduction
Gastroesophageal reflux disease (GERD) is a chronic gastrointestinal condition defined by the recurring reflux of stomach contents into the esophagus. As one of the most frequently diagnosed digestive disorders in the United States, GERD affects approximately 20% of the adult population, leading to substantial direct and indirect healthcare costs and a diminished quality of life.[1, 2] The development of GERD is attributed to a combination of factors, including intrinsic and structural abnormalities that compromise the esophagogastric junction barrier. This breakdown allows for the esophageal mucosa to be exposed to the corrosive effects of gastric acid. While heartburn and regurgitation are classic GERD symptoms, the condition can also present atypically, featuring extra-esophageal manifestations such as chest pain, dental erosion, chronic cough, laryngitis, or asthma.[3, 4] GERD is further categorized into three phenotypes based on endoscopic and histopathologic findings: non-erosive reflux disease (NERD), erosive esophagitis (EE), and Barrett’s esophagus (BE).[5] NERD represents the majority of cases (60-70%), followed by erosive esophagitis (30%), and Barrett’s esophagus (6-12%). [1, 5, 6] While lifestyle adjustments and proton pump inhibitors (PPIs) have traditionally been the cornerstone of GERD management, medically refractory GERD is increasingly encountered, necessitating a more personalized treatment strategy.
Etiology of GERD
The precise cause of GERD remains elusive, but several risk factors have been identified as contributing to its development. Motor impairments, such as esophageal dysmotility that hinders acid clearance, reduced lower esophageal sphincter (LES) tone, transient LES relaxations (TLESRs), and delayed gastric emptying are implicated in GERD pathogenesis.[7] Anatomical factors, such as hiatal hernia and increased intra-abdominal pressure, commonly seen in obesity, also elevate GERD risk.[7] A meta-analysis by Hampel H et al. established a link between obesity and increased susceptibility to GERD symptoms, erosive esophagitis, and esophageal adenocarcinoma.[8] The ProGERD study by Malfertheiner et al. in over 6000 GERD patients confirmed a rising odds ratio for erosive disease with increasing body mass index (BMI).[9] Other independent risk factors for GERD symptoms include age ≥50 years, low socioeconomic status, tobacco and alcohol consumption, connective tissue disorders, pregnancy, postprandial supination, and certain medications like anticholinergics, benzodiazepines, NSAIDs, nitroglycerin, albuterol, calcium channel blockers, antidepressants, and glucagon.[10, 11, 12]
Epidemiology of GERD
GERD is a highly prevalent gastrointestinal disorder, affecting approximately 20% of adults in Western populations. A systematic review by El-Serag et al. estimated GERD prevalence in the US to range from 18.1% to 27.8%. However, the actual prevalence may be higher due to the widespread availability of over-the-counter acid-reducing medications.[2, 13, 2] While some studies suggest a slightly higher prevalence in men,[14] a large meta-analysis by Eusebi et al. indicated marginally higher pooled prevalence of GERD symptoms in women (16.7%) compared to men (15.4%).[12] Interestingly, women with GERD are more likely to present with NERD, whereas men are more prone to erosive esophagitis.[15] However, men with long-standing GERD symptoms exhibit a higher incidence of Barrett’s esophagus (23%) compared to women (14%).[16]
Pathophysiology of GERD
The pathophysiology of GERD is complex and involves multiple interacting mechanisms. Key factors include LES dysfunction, hiatal hernia, esophageal mucosal defense mechanisms, and esophageal motility.
Impaired Lower Esophageal Sphincter (LES) Function and Transient Lower Esophageal Sphincter Relaxations (TLESRs)
The LES, a 3-4 cm segment of smooth muscle at the esophagogastric junction (EGJ), along with the crural diaphragm, forms a critical barrier preventing gastric acid reflux into the esophagus.[17] In healthy individuals, the LES maintains a high-pressure zone above intragastric pressure, with transient relaxations (TLESRs) occurring physiologically after meals to allow food passage into the stomach. In GERD patients, more frequent TLESRs, not associated with swallowing, can occur, leading to gastric pressure exceeding LES pressure and subsequent reflux.[18] The exact causes of increased TLESRs are not fully understood, but they are implicated in 48-73% of GERD symptoms.[19] Factors influencing LES tone and TLESRs include alcohol, smoking, caffeine, pregnancy, and medications like nitrates and calcium channel blockers.[18]
Hiatal Hernia
Hiatal hernia, a common condition where part of the stomach protrudes into the chest cavity, frequently coexists with GERD and can exacerbate it. While hiatal hernias can exist without causing symptoms, they can impair LES function and promote reflux.[20] Patti et al. found similar LES dysfunction and acid clearance in GERD patients with and without small hiatal hernias. However, larger hiatal hernias were associated with weaker LES and increased reflux episodes, along with more severe esophagitis.[21] Ott et al. reported a high prevalence of hiatal hernia (94%) in patients with reflux esophagitis, highlighting the strong association between these conditions.[22]
Impaired Esophageal Mucosal Defense
The esophageal mucosa has inherent protective mechanisms against refluxate. Prolonged exposure to refluxate, containing both acidic (hydrochloric acid, pepsin) and alkaline (bile salts, pancreatic enzymes) components, can overwhelm these defenses and cause mucosal damage.[18] The role of gastroparesis in GERD is still being investigated, but delayed gastric emptying is thought to contribute to GERD symptoms by increasing gastric distension and reflux exposure.[18]
Defective Esophageal Peristalsis
Normal esophageal peristalsis clears refluxed gastric contents and salivary bicarbonate neutralizes residual acid.[23, 18] Diener et al. found that 21% of GERD patients had impaired esophageal peristalsis, resulting in reduced reflux clearance, more severe symptoms, and mucosal damage.[24]
Histopathology of GERD
The esophageal squamous epithelium acts as a protective barrier against refluxate. Disruption of this barrier is common in both GERD and NERD.[25] Histopathological findings in GERD are not always specific due to variable diagnostic criteria and sensitivity.[26] Diagnosis often relies on a combination of microscopic features including inflammation, basal cell hyperplasia, papilla elongation, and dilated intercellular spaces.[26]
History and Physical Examination in GERD
Typical GERD symptoms include heartburn and regurgitation. Heartburn is described as a retrosternal burning sensation, often radiating to the neck, typically occurring postprandially or when reclining.[28] Regurgitation involves the reflux of acidic gastric contents into the mouth or hypopharynx.[28] Atypical GERD presentations involve extra-esophageal symptoms such as chest pain, chronic cough, asthma, laryngitis, dental erosions, dysphonia, hoarseness, and globus sensation.[3, 4] These atypical symptoms often complicate the Differential Diagnosis Of Gerd.
Evaluation and Differential Diagnosis of GERD
Diagnosing GERD can be challenging as no single gold standard test exists. Diagnosis relies on symptom presentation, response to acid-suppressing therapy, esophagogastroduodenoscopy (EGD), and ambulatory reflux monitoring. Critically, when considering GERD, healthcare providers must consider a range of differential diagnoses to ensure accurate patient management.
Differential Diagnosis of GERD:
When evaluating patients presenting with symptoms suggestive of GERD, it is crucial to consider and exclude other conditions that can mimic GERD. The differential diagnosis of GERD includes:
- Coronary Artery Disease: Chest pain is a common symptom in both GERD and cardiac conditions. Angina can be mistaken for heartburn. Key differentiators include the nature of the pain (crushing, squeezing chest pain radiating to the left arm or jaw in cardiac pain vs. burning retrosternal pain in GERD), associated symptoms (shortness of breath, sweating in cardiac pain vs. acid regurgitation in GERD), and response to antacids (minimal relief in cardiac pain vs. potential relief in GERD). ECG and cardiac enzyme tests are essential to rule out cardiac ischemia.
- Achalasia: This esophageal motility disorder can present with dysphagia and regurgitation, similar to GERD. However, achalasia typically involves dysphagia to both solids and liquids, and regurgitation is often of undigested food, without heartburn. Manometry is the diagnostic gold standard for achalasia.
- Eosinophilic Esophagitis (EoE): EoE is characterized by esophageal inflammation due to eosinophil infiltration, causing dysphagia, food impaction, and sometimes heartburn-like symptoms. EoE is more common in patients with allergies and atopic conditions. Endoscopy with esophageal biopsies is necessary to diagnose EoE. Histopathology showing high eosinophil counts differentiates EoE from GERD.
- Non-ulcer Dyspepsia (Functional Dyspepsia): This condition involves upper abdominal discomfort, bloating, and nausea, which can overlap with GERD symptoms. However, non-ulcer dyspepsia lacks typical heartburn and regurgitation. Diagnosis is often made after excluding organic causes, including GERD, through endoscopy and other investigations.
- Rumination Syndrome: This disorder involves effortless regurgitation of recently ingested food, which may be re-chewed and re-swallowed or expelled. It can be mistaken for GERD-related regurgitation. Rumination syndrome is often associated with psychological factors and can be differentiated from GERD through careful history taking and esophageal pH monitoring.
- Esophageal Diverticula: Zenker’s diverticulum, in particular, can cause regurgitation of undigested food, dysphagia, and halitosis. Symptoms can resemble GERD, but diverticula are typically diagnosed with barium swallow studies or endoscopy.
- Gastroparesis: Delayed gastric emptying can lead to nausea, vomiting, and upper abdominal discomfort, and may exacerbate GERD. However, gastroparesis symptoms are broader than typical GERD symptoms. Gastric emptying studies can confirm gastroparesis.
- Esophageal and Gastric Neoplasm: Esophageal or gastric cancers can present with dysphagia, weight loss, and upper abdominal pain, which can be mistaken for GERD, particularly in older adults. Alarm symptoms like weight loss, anemia, and persistent dysphagia necessitate prompt endoscopic evaluation to rule out malignancy.
- Peptic Ulcer Disease (PUD): Gastric or duodenal ulcers can cause epigastric pain that may be burning in nature, similar to heartburn. However, PUD pain is often related to meals (worsened or relieved by food, depending on ulcer location). Endoscopy is crucial for diagnosing PUD and differentiating it from GERD. H. pylori testing and treatment are essential in PUD management.
Diagnostic Tests for GERD:
- Proton Pump Inhibitor (PPI) Trial: In patients with typical heartburn and regurgitation without alarm symptoms (dysphagia, odynophagia, anemia, weight loss, hematemesis), an empiric trial of PPI therapy can be initiated.[29] Symptom improvement in response to PPIs can support a GERD diagnosis. However, the accuracy of PPI trials as a diagnostic strategy is debated.[30]
- Esophagogastroduodenoscopy (EGD): EGD is recommended for patients with GERD symptoms and alarm features to exclude GERD complications (erosive esophagitis, Barrett’s esophagus, strictures, adenocarcinoma) and peptic ulcer disease.[29] While distal esophageal biopsies are not routinely required for GERD diagnosis, EGD is vital for visualizing mucosal damage and obtaining biopsies when Barrett’s esophagus or EoE is suspected.
- Radiographic Studies: Barium swallow studies can detect hiatal hernia, strictures, and tumors, but are not recommended for diagnosing GERD itself.[29] Their role is limited to evaluating structural abnormalities.
- Ambulatory Esophageal Reflux Monitoring: This is crucial for patients with medically refractory GERD or extra-esophageal symptoms suggestive of GERD. Ambulatory pH or pH-impedance monitoring assesses esophageal acid exposure, reflux frequency, and symptom correlation with reflux episodes.[29] It is essential preoperatively in patients without erosive esophagitis considering anti-reflux surgery.
Image alt text: Endoscopic view illustrating erosive esophagitis in a patient with GERD, characterized by visible breaks in the esophageal mucosa.
Treatment and Management of GERD
GERD management aims to alleviate symptoms and prevent complications like esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Treatment strategies include lifestyle modifications, medical therapy, surgical intervention, and endoluminal procedures.
Lifestyle Modifications for GERD:
Lifestyle adjustments are fundamental to GERD management. Weight loss is crucial for overweight or obese individuals as obesity is a significant GERD risk factor.[32] Patients should avoid meals within 3 hours of bedtime and practice good sleep hygiene, as sleep disturbances can increase reflux episodes.[27, 33] Elevating the head of the bed can also improve nocturnal GERD symptoms. Dietary modifications, such as avoiding chocolate, caffeine, spicy foods, citrus fruits, and carbonated beverages, are often suggested, although current guidelines do not routinely recommend them.[29]
Medical Therapy for GERD:
Medical therapy is indicated when lifestyle changes are insufficient. Options include antacids, histamine-2 receptor antagonists (H2RAs), PPIs, and prokinetic agents. PPIs are considered the most effective medical treatment for both erosive and non-erosive GERD, demonstrating superior symptom control, esophagitis healing, and reduced relapse rates compared to H2RAs.[34, 35] ACG guidelines recommend once-daily PPI dosing before the first meal.[29] Twice-daily dosing or adjusting administration timing can be considered for incomplete responders, especially those with nighttime symptoms.[29] Bedtime H2RAs can be added for nighttime symptom control in patients on maximal PPI therapy.[29] Prokinetic agents have limited roles in GERD due to limited efficacy and potential side effects.
Surgical Therapy for GERD:
Surgical management is considered for medically refractory GERD, medication intolerance, large hiatal hernia, or patient preference to avoid long-term medication.[36] Surgical options include laparoscopic Nissen fundoplication, laparoscopic anterior 180° fundoplication, and bariatric surgery in obese patients.[29] Laparoscopic Nissen fundoplication has been the traditional gold standard. However, with increasing obesity prevalence, gastric bypass surgery is becoming more common for GERD, particularly in obese patients.[29] Preoperative ambulatory pH monitoring is recommended in patients without erosive esophagitis, and esophageal manometry is needed to exclude achalasia before surgery.[29] While some meta-analyses suggest symptom improvement after surgery compared to medical therapy, others indicate uncertainty in surgical benefits.[37] Postoperative complications like bloating and dysphagia are potential risks. Roux-en-Y gastric bypass (RYGB) is particularly effective in reducing GERD symptoms in obese patients undergoing bariatric surgery and is the preferred procedure for those with severe GERD.[36]
Endoluminal Therapy for GERD:
Minimally invasive endoscopic therapies for GERD have evolved. Current options include magnetic sphincter augmentation (MSA) and transoral incisionless fundoplication (TIF) using EsophyX.[29] Meta-analyses suggest TIF 2.0 procedures can improve esophageal pH, reduce PPI use, and enhance quality of life for up to three years.[38] MSA has shown comparable short-term outcomes to Nissen fundoplication in some studies.[39]
Complications of GERD
Untreated or poorly managed GERD can lead to several complications:
- Erosive Esophagitis (EE): Characterized by esophageal mucosal erosions or ulcers, EE can range from asymptomatic to causing worsening GERD symptoms.[28] The Los Angeles classification system grades esophagitis severity based on endoscopic findings.[40]
- Esophageal Strictures: Chronic acid exposure can cause esophageal scarring and stricture formation, leading to dysphagia and food impaction. Esophageal dilation and ongoing PPI therapy are recommended to manage strictures and prevent recurrence.[29]
- Barrett Esophagus (BE): Chronic reflux can induce metaplastic changes in the distal esophageal mucosa, replacing squamous epithelium with columnar epithelium. BE increases the risk of esophageal adenocarcinoma and requires periodic endoscopic surveillance.[28, 41]
Image alt text: Endoscopic view of Barrett’s esophagus, demonstrating the characteristic salmon-pink columnar epithelium lining the distal esophagus, a complication of chronic GERD.
Enhancing Healthcare Team Outcomes in GERD Management
Most GERD patients are initially managed in primary care settings. Complex cases, medically refractory GERD, and those with alarm symptoms are typically referred to gastroenterologists. Optimal GERD management necessitates a collaborative interprofessional approach involving primary care physicians, gastroenterologists, otolaryngologists, pulmonologists, bariatric surgeons, and pharmacists. Primary care providers play a vital role in initial assessment, identifying alarm symptoms, and ruling out cardiac causes of chest pain. Lifestyle modification counseling is crucial. Bariatric surgery should be considered and discussed with morbidly obese GERD patients. Otolaryngologists and pulmonologists should consider GERD in the differential diagnosis of atypical symptoms like chronic cough and laryngitis. Medically refractory GERD cases benefit from multidisciplinary team discussions involving surgeons, pharmacists, and endoscopy nurses. Prompt recognition and management of GERD complications are essential to minimize long-term morbidity. This interprofessional strategy improves patient outcomes and enhances quality of life in GERD management.
Review Questions
(Note: Review questions are available via the provided StatPearls link)
References
1.Fass R, Frazier R. The role of dexlansoprazole modified-release in the management of gastroesophageal reflux disease. Therap Adv Gastroenterol. 2017 Feb;10(2):243-251. [PMC free article: PMC5298478] [PubMed: 28203282]
2.El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80. [PMC free article: PMC4046948] [PubMed: 23853213]
3.Hom C, Vaezi MF. Extraesophageal manifestations of gastroesophageal reflux disease. Gastroenterol Clin North Am. 2013 Mar;42(1):71-91. [PubMed: 23452632]
4.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 Aug;101(8):1900-20; quiz 1943. [PubMed: 16928254]
5.Fass R, Ofman JJ. Gastroesophageal reflux disease–should we adopt a new conceptual framework? Am J Gastroenterol. 2002 Aug;97(8):1901-9. [PubMed: 12190152]
6.Fass R. Erosive esophagitis and nonerosive reflux disease (NERD): comparison of epidemiologic, physiologic, and therapeutic characteristics. J Clin Gastroenterol. 2007 Feb;41(2):131-7. [PubMed: 17245209]
7.Argyrou A, Legaki E, Koutserimpas C, Gazouli M, Papaconstantinou I, Gkiokas G, Karamanolis G. Risk factors for gastroesophageal reflux disease and analysis of genetic contributors. World J Clin Cases. 2018 Aug 16;6(8):176-182. [PMC free article: PMC6107529] [PubMed: 30148145]
8.Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005 Aug 02;143(3):199-211. [PubMed: 16061918]
9.Malfertheiner P, Nocon M, Vieth M, Stolte M, Jaspersen D, Koelz HR, Labenz J, Leodolter A, Lind T, Richter K, Willich SN. Evolution of gastro-oesophageal reflux disease over 5 years under routine medical care–the ProGERD study. Aliment Pharmacol Ther. 2012 Jan;35(1):154-64. [PubMed: 22070159]
10.El-Serag HB, Hashmi A, Garcia J, Richardson P, Alsarraj A, Fitzgerald S, Vela M, Shaib Y, Abraham NS, Velez M, Cole R, Rodriguez MB, Anand B, Graham DY, Kramer JR. Visceral abdominal obesity measured by CT scan is associated with an increased risk of Barrett’s oesophagus: a case-control study. Gut. 2014 Feb;63(2):220-9. [PMC free article: PMC3976427] [PubMed: 23408348]
11.Mohammed I, Nightingale P, Trudgill NJ. Risk factors for gastro-oesophageal reflux disease symptoms: a community study. Aliment Pharmacol Ther. 2005 Apr 01;21(7):821-7. [PubMed: 15801917]
12.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 Mar;67(3):430-440. [PubMed: 28232473]
13.Patti MG. An Evidence-Based Approach to the Treatment of Gastroesophageal Reflux Disease. JAMA Surg. 2016 Jan;151(1):73-8. [PubMed: 26629969]
14.Nilsson M, Johnsen R, Ye W, Hveem K, Lagergren J. Prevalence of gastro-oesophageal reflux symptoms and the influence of age and sex. Scand J Gastroenterol. 2004 Nov;39(11):1040-5. [PubMed: 15545159]
15.Kim SY, Jung HK, Lim J, Kim TO, Choe AR, Tae CH, Shim KN, Moon CM, Kim SE, Jung SA. Gender Specific Differences in Prevalence and Risk Factors for Gastro-Esophageal Reflux Disease. J Korean Med Sci. 2019 Jun 02;34(21):e158. [PMC free article: PMC6543060] [PubMed: 31144481]
16.Lin M, Gerson LB, Lascar R, Davila M, Triadafilopoulos G. Features of gastroesophageal reflux disease in women. Am J Gastroenterol. 2004 Aug;99(8):1442-7. [PubMed: 15307857]
17.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 Nov;14(11):665-676. [PubMed: 28951582]
18.De Giorgi F, Palmiero M, Esposito I, Mosca F, Cuomo R. Pathophysiology of gastro-oesophageal reflux disease. Acta Otorhinolaryngol Ital. 2006 Oct;26(5):241-6. [PMC free article: PMC2639970] [PubMed: 17345925]
19.Mittal RK, McCallum RW. Characteristics and frequency of transient relaxations of the lower esophageal sphincter in patients with reflux esophagitis. Gastroenterology. 1988 Sep;95(3):593-9. [PubMed: 3396810]
20.Kahrilas PJ, Lin S, Chen J, Manka M. The effect of hiatus hernia on gastro-oesophageal junction pressure. Gut. 1999 Apr;44(4):476-82. [PMC free article: PMC1727465] [PubMed: 10075953]
21.Patti MG, Goldberg HI, Arcerito M, Bortolasi L, Tong J, Way LW. Hiatal hernia size affects lower esophageal sphincter function, esophageal acid exposure, and the degree of mucosal injury. Am J Surg. 1996 Jan;171(1):182-6. [PubMed: 8554137]
22.Ott DJ, Gelfand DW, Chen YM, Wu WC, Munitz HA. Predictive relationship of hiatal hernia to reflux esophagitis. Gastrointest Radiol. 1985;10(4):317-20. [PubMed: 4054494]
23.Richter J. Do we know the cause of reflux disease? Eur J Gastroenterol Hepatol. 1999 Jun;11 Suppl 1:S3-9. [PubMed: 10443906]
24.Diener U, Patti MG, Molena D, Fisichella PM, Way LW. Esophageal dysmotility and gastroesophageal reflux disease. J Gastrointest Surg. 2001 May-Jun;5(3):260-5. [PubMed: 11360049]
25.Kandulski A, Weigt J, Caro C, Jechorek D, Wex T, Malfertheiner P. Esophageal intraluminal baseline impedance differentiates gastroesophageal reflux disease from functional heartburn. Clin Gastroenterol Hepatol. 2015 Jun;13(6):1075-81. [PubMed: 25496815]
26.Allende DS, Yerian LM. Diagnosing gastroesophageal reflux disease: the pathologist’s perspective. Adv Anat Pathol. 2009 May;16(3):161-5. [PubMed: 19395879]
27.Sandhu DS, Fass R. Current Trends in the Management of Gastroesophageal Reflux Disease. Gut Liver. 2018 Jan 15;12(1):7-16. [PMC free article: PMC5753679] [PubMed: 28427116]
28.Kellerman R, Kintanar T. Gastroesophageal Reflux Disease. Prim Care. 2017 Dec;44(4):561-573. [PubMed: 29132520]
29.Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013 Mar;108(3):308-28; quiz 329. [PubMed: 23419381]
30.Numans ME, Lau J, de Wit NJ, Bonis PA. Short-term treatment with proton-pump inhibitors as a test for gastroesophageal reflux disease: a meta-analysis of diagnostic test characteristics. Ann Intern Med. 2004 Apr 06;140(7):518-27. [PubMed: 15068979]
31.Hirano I, Richter JE., Practice Parameters Committee of the American College of Gastroenterology. ACG practice guidelines: esophageal reflux testing. Am J Gastroenterol. 2007 Mar;102(3):668-85. [PubMed: 17335450]
32.Jacobson BC, Somers SC, Fuchs CS, Kelly CP, Camargo CA. Body-mass index and symptoms of gastroesophageal reflux in women. N Engl J Med. 2006 Jun 01;354(22):2340-8. [PMC free article: PMC2782772] [PubMed: 16738270]
33.Fujiwara Y, Arakawa T, Fass R. Gastroesophageal reflux disease and sleep disturbances. J Gastroenterol. 2012 Jul;47(7):760-9. [PubMed: 22592763]
34.Zhang JX, Ji MY, Song J, Lei HB, Qiu S, Wang J, Ai MH, Wang J, Lv XG, Yang ZR, Dong WG. Proton pump inhibitor for non-erosive reflux disease: a meta-analysis. World J Gastroenterol. 2013 Dec 07;19(45):8408-19. [PMC free article: PMC3857466] [PubMed: 24363534]
35.Khan M, Santana J, Donnellan C, Preston C, Moayyedi P. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD003244. [PubMed: 17443524]
36.Chang P, Friedenberg F. Obesity and GERD. Gastroenterol Clin North Am. 2014 Mar;43(1):161-73. [PMC free article: PMC3920303] [PubMed: 24503366]
37.Garg SK, Gurusamy KS. Laparoscopic fundoplication surgery versus medical management for gastro-oesophageal reflux disease (GORD) in adults. Cochrane Database Syst Rev. 2015 Nov 05;2015(11):CD003243. [PMC free article: PMC8278567] [PubMed: 26544951]
38.Gerson L, Stouch B, Lobonţiu A. Transoral Incisionless Fundoplication (TIF 2.0): A Meta-Analysis of Three Randomized, Controlled Clinical Trials. Chirurgia (Bucur). 2018 Mar-Apr;113(2):173-184. [PubMed: 29733015]
39.Skubleny D, Switzer NJ, Dang J, Gill RS, Shi X, de Gara C, Birch DW, Wong C, Hutter MM, Karmali S. LINX® magnetic esophageal sphincter augmentation versus Nissen fundoplication for gastroesophageal reflux disease: a systematic review and meta-analysis. Surg Endosc. 2017 Aug;31(8):3078-3084. [PubMed: 27981382]
40.Lundell LR, Dent J, Bennett JR, Blum AL, Armstrong D, Galmiche JP, Johnson F, Hongo M, Richter JE, Spechler SJ, Tytgat GN, Wallin L. Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut. 1999 Aug;45(2):172-80. [PMC free article: PMC1727604] [PubMed: 10403727]
41.Wang KK, Sampliner RE., Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett’s esophagus. Am J Gastroenterol. 2008 Mar;103(3):788-97. [PubMed: 18341497]
Disclosures: Catiele Antunes declares no relevant financial relationships with ineligible companies.
Disclosures: Abdul Aleem declares no relevant financial relationships with ineligible companies.
Disclosures: Sean Curtis declares no relevant financial relationships with ineligible companies.
