1 - Front Cover [Seite 1]
2 - GASTROENTEROLOGYCLINICS OF NORTH AMERICA [Seite 2]
3 - Copyright page [Seite Copyright page]
- 3 [Seite 3]
4 - Contributors [Seite 4]
4.1 - Consulting Editor [Seite 4]
4.2 - Editor [Seite 4]
4.3 - Authors [Seite 4]
5 - Contents [Seite 6]
6 - Forthcoming Issues [Seite 10]
6.1 - Forthcoming Issues [Seite 10]
6.1.1 - June 2014 [Seite 10]
6.1.2 - September 2014 [Seite 10]
6.1.3 - December 2014 [Seite 10]
6.2 - Recent Issues [Seite 10]
6.2.1 - December 2013 [Seite 10]
6.2.2 - September 2013 [Seite 10]
6.2.3 - June 2013 [Seite 10]
7 - Gastroesophageal Reflux Disease [Seite Gastroesophageal Reflux Disease]
- 12 [Seite 12]
8 - What's New in Gastroesophageal Reflux Disease for 2014 [Seite 14]
9 - Epidemiology of Gastroesophageal Reflux Disease [Seite 16]
9.1 - Key points [Seite 16]
9.2 - Introduction [Seite 16]
9.3 - Trends in the prevalence of GERD and incidence of its complications [Seite 16]
9.4 - The economic impact of GERD [Seite 19]
9.4.1 - Direct Health Care Costs [Seite 19]
9.4.1.1 - Ambulatory care costs [Seite 20]
9.4.1.2 - Inpatient care costs [Seite 20]
9.4.1.3 - Diagnostic procedure costs [Seite 20]
9.4.1.4 - Pharmaceutical costs [Seite 21]
9.4.1.5 - Extraesophageal reflux [Seite 21]
9.4.2 - Indirect Costs of GERD [Seite 21]
9.5 - Risk factors for GERD [Seite 23]
9.6 - Summary [Seite 25]
9.7 - References [Seite 25]
10 - Pathophysiology of Gastroesophageal Reflux Disease [Seite 30]
10.1 - Key points [Seite 30]
10.2 - Introduction [Seite 30]
10.3 - The esophagogastric junction [Seite 31]
10.3.1 - TLESRs [Seite 31]
10.3.2 - Hiatal Hernia [Seite 32]
10.3.3 - Acid Pocket [Seite 33]
10.3.4 - Positive Pressure Gradient and Obesity [Seite 34]
10.3.5 - Gastric Motility [Seite 34]
10.3.6 - Esophageal Clearance [Seite 34]
10.4 - Perception of reflux episodes [Seite 35]
10.4.1 - Peripheral Sensitization [Seite 35]
10.4.2 - Central Sensitization and Psychoneuroimmune Interactions [Seite 35]
10.5 - Esophageal injury [Seite 36]
10.5.1 - Esophageal Defense and Mucosal Changes [Seite 36]
10.6 - Summary [Seite 37]
10.7 - References [Seite 37]
11 - Symptom Predictability in Gastroesophageal Reflux Disease and Role of Proton Pump Inhibitor Test [Seite 42]
11.1 - Key points [Seite 42]
11.2 - Symptom assessment [Seite 43]
11.3 - Issues in GERD symptom assessment [Seite 43]
11.4 - Evaluation of symptoms in GERD [Seite 44]
11.5 - Patient-reported outcomes in GERD symptom assessment [Seite 44]
11.6 - Sensitivity and specificity for heartburn in diagnosing GERD [Seite 47]
11.6.1 - Estimated Range Based on Recent Reviews [Seite 47]
11.7 - Difficulty with using heartburn as the primary means of diagnosing GERD: common occurrence of heartburn with other symptoms [Seite 48]
11.8 - Sensitivity and specificity of regurgitation in diagnosing GERD [Seite 48]
11.9 - PPI use in GERD [Seite 48]
11.10 - The PPI test [Seite 49]
11.11 - Regurgitation and acid suppression [Seite 51]
11.12 - References [Seite 51]
12 - Role of Endoscopy in GERD [Seite 54]
12.1 - Key points [Seite 54]
12.2 - Introduction [Seite 54]
12.3 - Esophagogastroduodenoscopy or upper endoscopy [Seite 55]
12.4 - Confocal laser endomicroscopy and optical coherence tomography [Seite 55]
12.5 - Wireless capsule endoscopy [Seite 56]
12.6 - Gastroesophageal reflux disease [Seite 56]
12.7 - Esophageal dilation [Seite 57]
12.8 - Barrett esophagus [Seite 58]
12.9 - Advance imaging [Seite 59]
12.10 - Eosinophilic esophagitis [Seite 59]
12.11 - Endoscopic therapies for GERD [Seite 60]
12.12 - Summary [Seite 60]
12.13 - References [Seite 60]
13 - Barium Esophagram [Seite 62]
13.1 - Key points [Seite 62]
13.2 - Esophagram: important general elements of the examination [Seite 63]
13.3 - The preoperative barium esophagram [Seite 64]
13.3.1 - Initial Upright Phase [Seite 64]
13.3.2 - Semiprone or Right Anterior Oblique Phase [Seite 66]
13.3.3 - Reflux Identification Phase [Seite 69]
13.3.4 - Solid Food Ingestion Phase [Seite 70]
13.3.5 - Feline Esophagus [Seite 70]
13.3.6 - Distal Mucosal Ring (Schatzki Ring) [Seite 70]
13.4 - Outcome of the preoperative examination [Seite 71]
13.5 - Alternative diagnoses to GERD [Seite 72]
13.6 - Diagnosis of esophagitis and Barrett esophagus with the barium esophagram [Seite 74]
13.7 - The barium esophagram after antireflux procedures [Seite 75]
13.7.1 - Initial Upright Phase [Seite 75]
13.7.2 - Semiprone or Right Anterior Oblique Examination [Seite 75]
13.7.3 - Reflux Identification Examination [Seite 76]
13.7.4 - Solid Food Ingestion Examination [Seite 76]
13.7.5 - Gastric Motility Assessment [Seite 76]
13.7.6 - Normal Nissen Fundoplication [Seite 76]
13.7.7 - Normal Toupet Fundoplication [Seite 76]
13.7.8 - Collis Gastroplasty-Nissen Fundoplication [Seite 77]
13.7.9 - Abnormal or Failed Fundoplication [Seite 78]
13.8 - Outcome of the postoperative examination [Seite 80]
13.9 - Summary [Seite 81]
13.10 - Acknowledgments [Seite 81]
13.11 - References [Seite 81]
14 - Esophageal Manometry in Gastroesophageal Reflux Disease [Seite 84]
14.1 - Key points [Seite 84]
14.2 - Introduction [Seite 84]
14.3 - Advances in esophageal manometry [Seite 84]
14.4 - Pathophysiologic correlates of GERD on HRM [Seite 85]
14.4.1 - Transient Lower Esophageal Sphincter Relaxations [Seite 85]
14.4.2 - Barrier Function of the Esophagogastric Junction [Seite 87]
14.4.2.1 - EGJ opening with reflux events [Seite 87]
14.4.2.2 - Pressure inversion point and hiatus hernia [Seite 87]
14.4.2.3 - LES hypotension [Seite 88]
14.4.3 - Esophageal Clearance [Seite 88]
14.4.4 - Esophageal Length and Other Anatomic Considerations [Seite 92]
14.5 - HRM software tools and metrics [Seite 93]
14.6 - Clinical application of HRM metrics [Seite 94]
14.6.1 - Presurgical Assessment of Peristaltic Function [Seite 95]
14.7 - Provocative maneuvers [Seite 97]
14.8 - Summary [Seite 98]
14.9 - References [Seite 99]
15 - Acid and Nonacid Reflux Monitoring [Seite 104]
15.1 - Key points [Seite 104]
15.2 - Introduction [Seite 104]
15.3 - Indications for esophageal reflux monitoring [Seite 105]
15.3.1 - Before Antireflux Surgery [Seite 105]
15.3.2 - PPI-Refractory GERD Symptoms [Seite 105]
15.3.3 - Noncardiac Chest Pain [Seite 106]
15.3.4 - Extraesophageal GERD Symptoms [Seite 106]
15.3.5 - Assessing Effectiveness of Reflux Therapy [Seite 106]
15.4 - Performance of esophageal reflux monitoring [Seite 106]
15.4.1 - Sensor Placement and Positioning [Seite 108]
15.4.1.1 - Limitation of conventional placement location [Seite 108]
15.4.2 - Test Duration [Seite 109]
15.4.2.1 - Patient tolerance [Seite 109]
15.4.3 - Comparisons of Esophageal Reflux Monitoring Modalities [Seite 110]
15.4.3.1 - Other limitations [Seite 110]
15.4.4 - On or Off PPIs? [Seite 111]
15.5 - Test interpretation [Seite 112]
15.5.1 - Normal Values [Seite 113]
15.5.2 - Symptom Association Assessment [Seite 114]
15.6 - Summary [Seite 115]
15.7 - References [Seite 115]
16 - Extraesophageal Presentations of GERD [Seite 120]
16.1 - Key points [Seite 120]
16.2 - Pathophysiology, or what might be going on? [Seite 121]
16.3 - Diagnosis, or how might the association be established? [Seite 123]
16.3.1 - What is the Value of Laryngoscopy in Assessing Patients with Suspected EER? [Seite 123]
16.3.2 - What is the Value of Endoscopy in Assessing Patients with Suspected EER? [Seite 124]
16.3.3 - What is the Value of Esophageal Reflux Studies in Assessing Patients with Suspected EER? [Seite 125]
16.4 - Treatment, or how well a therapeutic trial with antireflux therapy might help? [Seite 126]
16.4.1 - Reflux Cough Syndrome [Seite 126]
16.4.2 - Reflux Asthma Syndrome [Seite 127]
16.4.3 - Reflux Laryngitis Syndrome [Seite 128]
16.4.4 - Dental Erosions (Reflux Dental Erosion Syndrome) [Seite 129]
16.4.5 - Other Suspected Extraesophageal Conditions [Seite 129]
16.5 - Summary and final recommendations [Seite 130]
16.6 - References [Seite 131]
17 - Medical Treatments of GERD [Seite 136]
17.1 - Key points [Seite 136]
17.2 - Introduction [Seite 136]
17.3 - A pathophysiology-based approach to the medical treatment of GERD [Seite 137]
17.3.1 - Neutralization of Gastric Contents [Seite 137]
17.3.1.1 - Comparative effectiveness of H2RAs versus PPIs [Seite 138]
17.3.1.2 - Comparative effectiveness of different PPIs [Seite 139]
17.3.1.3 - Comparative effectiveness of PPIs versus anti-reflux surgery [Seite 139]
17.3.1.4 - Potassium-competitive acid blockers [Seite 140]
17.3.2 - Augmentation of the Antireflux Barrier Function [Seite 140]
17.3.2.1 - GABA-B agonists [Seite 141]
17.3.2.2 - Metabotropic glutamate receptor-5 antagonists [Seite 141]
17.3.2.3 - Other TLESR inhibitors [Seite 141]
17.3.3 - Enhancement of Mucosal Defense and Repair Mechanisms [Seite 142]
17.3.3.1 - Prokinetics [Seite 142]
17.3.3.2 - Mucosal repair [Seite 142]
17.3.4 - Modulating Sensation [Seite 143]
17.3.4.1 - Nociceptor blockade [Seite 143]
17.3.4.2 - Visceral analgesia and cortical modulation [Seite 143]
17.4 - Summary [Seite 143]
17.5 - References [Seite 144]
18 - Surgical Treatment of GERD [Seite 150]
18.1 - Key points [Seite 150]
18.2 - Historical review [Seite 150]
18.3 - Development of laparoscopic antireflux surgery [Seite 152]
18.4 - Keys in patient selection [Seite 154]
18.5 - Predictors of success [Seite 155]
18.6 - Keys in operative technique [Seite 155]
18.7 - Endoscopic antireflux surgery [Seite 156]
18.8 - Future developments [Seite 158]
18.9 - Summary [Seite 159]
18.10 - References [Seite 159]
19 - Gastroesophageal Reflux Disease and the Elderly [Seite 162]
19.1 - Key points [Seite 162]
19.2 - Introduction [Seite 162]
19.3 - Esophageal physiology and aging [Seite 163]
19.3.1 - Structural Studies [Seite 163]
19.3.2 - Esophageal Motility Studies [Seite 163]
19.3.2.1 - Lower esophageal sphincter [Seite 163]
19.3.2.2 - Esophageal body [Seite 164]
19.3.2.3 - Upper esophageal sphincter dysfunction [Seite 166]
19.3.3 - Sensory Changes [Seite 166]
19.3.4 - Other Changes [Seite 166]
19.4 - Age and GERD prevalence [Seite 167]
19.5 - Clinical presentation [Seite 167]
19.5.1 - Complications [Seite 169]
19.6 - Treatment [Seite 170]
19.6.1 - Medical Therapy [Seite 170]
19.6.2 - Surgical Therapy [Seite 171]
19.7 - Summary [Seite 172]
19.8 - References [Seite 172]
20 - Obesity and GERD [Seite 176]
20.1 - Key points [Seite 176]
20.2 - Introduction [Seite 176]
20.2.1 - Disease Description [Seite 176]
20.3 - Prevalence/Incidence [Seite 176]
20.4 - World-wide incidence rates [Seite 177]
20.5 - Clinical correlation [Seite 178]
20.5.1 - Complications of GERD [Seite 178]
20.5.2 - Pathophysiology [Seite 180]
20.5.3 - Weight Loss and GERD [Seite 182]
20.5.4 - Bariatric Surgery and GERD [Seite 182]
20.6 - Summary [Seite 184]
20.7 - References [Seite 184]
21 - Index [Seite 190]
21.1 - A [Seite 190]
21.2 - B [Seite 190]
21.3 - C [Seite 191]
21.4 - D [Seite 191]
21.5 - E [Seite 192]
21.6 - F [Seite 193]
21.7 - G [Seite 193]
21.8 - H [Seite 194]
21.9 - I [Seite 195]
21.10 - J [Seite 195]
21.11 - L [Seite 195]
21.12 - M [Seite 195]
21.13 - N [Seite 196]
21.14 - O [Seite 196]
21.15 - P [Seite 196]
21.16 - Q [Seite 197]
21.17 - R [Seite 197]
21.18 - S [Seite 198]
21.19 - T [Seite 198]
21.20 - U [Seite 198]
21.21 - V [Seite 198]
21.22 - W [Seite 198]
Epidemiology of Gastroesophageal Reflux Disease
Joel H. Rubenstein, MD, MScab∗jhr@umich.edu and Joan W. Chen, MDb, aVeterans Affairs Center for Clinical Management Research, Ann Arbor, MI, USA; bDivision of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA
∗Corresponding author. VA Ann Arbor Healthcare System, 2215 Fuller Road, Mail Stop 111-D, Ann Arbor, MI 48105.
The prevalence of gastroesophageal reflux disease (GERD) symptoms increased approximately 50% until the mid-1990s, when it plateaued. The incidence of complications related to GERD including hospitalization, esophageal strictures, esophageal adenocarcinoma, and mortality also increased during that time period, but the increase in esophageal adenocarcinoma has since slowed, and the incidence of strictures has decreased since the mid-1990s. GERD is responsible for the greatest direct costs in the United States of any gastrointestinal disease, and most of those expenditures are for pharmacotherapy. Risk factors for GERD include obesity, poor diet, lack of physical activity, consumption of tobacco and alcohol, and respiratory diseases.
Keywords
Prevalence
Incidence
Risk factors
Esophageal strictures
Esophageal neoplasms
Cost
Key points
• Frequent GERD symptoms are encountered in 20% of North Americans.
• The prevalence of GERD symptoms rose, and then plateaued in the mid-1990s.
• GERD incurs the highest annual direct costs of all digestive diseases in the United States.
• Pharmaceutical cost is responsible for most of the direct cost of GERD management.
• Risk factors for GERD include obesity, poor diet, lack of leisure physical activity, consumption of tobacco and alcohol, and respiratory disease.
Introduction
Gastroesophageal reflux disease (GERD) is a condition that develops when the reflux of gastric contents causes troublesome symptoms or complications.1 GERD is responsible for some of the most common symptoms leading to presentation for medical care. The prevalence of GERD symptoms and the incidence of some of its complications have risen strikingly over the last few decades, leading to substantial economic impact. There are several potential explanations for these rising trends.
Trends in the prevalence of GERD and incidence of its complications
Symptoms of GERD seem to be more common now than 25 years ago. In systematic reviews of population-based studies, El-Serag and colleagues2,3 found that the prevalence of at least weekly symptoms of GERD rose approximately 50% until 1995, and that the prevalence has remained relatively constant since then (Fig. 1). The weighted-mean prevalence of at least weekly GERD symptoms is greatest in North America (19.8%), lowest in East Asia (5.2%), and intermediate in Europe and the Middle East (15.2% and 14.4%, respectively) (Fig. 2).3 The rate of increase in the prevalence of symptoms seems to be similar across all geographic regions studied.3
Fig. 1 Prevalence of at least weekly heartburn and/or acid regurgitation, or heartburn, with regard to the publication date of the 17 studies included in the Poisson regression analysis. Studies are categorized by geographic region (continent). (From El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol 2007;5:21; with permission.)
Fig. 2 Global distribution of the burden of gastroesophageal reflux disease. Sample-size weighted mean estimates of the prevalence of at least weekly heartburn and/or regurgitation in each country. (From El-Serag HB, Sweet S, Winchester CC, et al. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2013. http://dx.doi.org/10.1136/gutjnl-2012-304269; with permission.)
The source studies for that systematic review were often limited because they did not account for the use of acid-reducing medications, which would be expected to mask GERD symptoms; because the use of such medications has increased, the true prevalence of GERD (including treated and untreated) may be greater than the estimates previously mentioned. In addition, the estimates were based primarily on studies of separate samples of populations obtained at different time points. One exception is the HUNT study, which administered surveys longitudinally to the same population over time; residents of a Norwegian county answered the questions between 1995 and 1997, and the same questions again between 2006 and 2009.4 The prevalence of at least weekly GERD symptoms increased from 12% to 17% during that time period. GERD symptoms became more common in men and women, and in all age groups.
The incidence of complications of GERD also seems to have risen, but may have plateaued or even decreased since the mid-1990s. The proportion of hospitalizations in the US Veterans Affairs health care system with a primary or secondary discharge diagnosis of GERD increased fourfold between 1970 and 1996.5 Mortality directly related to GERD is very rare, but analysis of US death certificates demonstrated an increase from 1 death per 1 million individuals per year to 2.1 per 1 million between 1979 and 1992.5 In two community hospitals, the incidence of new esophageal strictures increased from 1986 to 1993, then decreased from 1994 to 2001, coinciding with a large increase in prescriptions for proton pump inhibitors (PPIs).6 In the US Veterans Affairs health care system, the incidence of new esophageal strictures decreased 12% as a proportion of all upper endoscopies from 1998 to 2003, and the 1-year incidence rate of recurrent strictures decreased 36%.7 Similarly, within the US Medicare system, the proportion of upper endoscopies with a stricture declined 11% between 1992 and 2000, and the incidence of recurrent strictures decreased 30%, coinciding with the introduction of PPIs.8
The most feared complication of GERD is esophageal adenocarcinoma, a cancer that historically had been extremely rare. The cancer is fivefold as common in individuals with chronic GERD symptoms compared with those without GERD.9 In 1991, a seminal study by Blot and colleagues10 reported an alarming doubling of the incidence of esophageal adenocarcinoma from 1976 to 1987. The incidence of esophageal adenocarcinoma thereafter climbed to sevenfold the baseline incidence, and most recently occurs in the general US population in 2.6 per 100,000 patient-years.11 World-wide, the incidence of esophageal adenocarcinoma has risen in most industrialized countries where there is a majority white population.12,13 Despite the dramatic relative increase in the incidence of esophageal adenocarcinoma, it remains a rare disease in absolute terms. Indeed, even in men with chronic GERD symptoms, the incidence of colorectal cancer is likely threefold the incidence of esophageal adenocarcinoma, and women with GERD symptoms likely have an incidence of esophageal adenocarcinoma that is similar to the incidence of breast cancer in men.14 Furthermore, the rising incidence may be reaching a plateau, because the increase in incidence has slowed in the United States since around 1997.11,15 The plateauing of the incidence of esophageal adenocarcinoma might be in part related to the advent of PPIs.
Just as the incidence of esophageal adenocarcinoma has risen, there has been a dramatic rise in the incidence of diagnosed cases of Barrett's esophagus, the premalignant lesion associated with esophageal adenocarcinoma. For example, in a Dutch primary care database, the incidence of newly diagnosed cases of Barrett's esophagus rose from 11 per 100,000 patients in 1996 to 23 per 100,000 in 2003.16 Similarly, in a large integrated US health care system, the incidence of diagnosed cases of Barrett's esophagus rose from 15 per 100,000 patient-years in 1998 to 24 per 100,000 in 2006.17 In the same population, the prevalence of diagnosed Barrett's esophagus rose from less than 10 per 100,000 individuals in 1994 to 131 per 100,000 in 2006, with no sign of plateauing. These figures need to be interpreted with caution because estimating the changing incidence of Barrett's esophagus is more challenging than estimating the changing incidence of esophageal adenocarcinoma. Changes in the incidence of diagnosed Barrett's esophagus can be strongly influenced by changing patterns in the practice of upper endoscopy, both in terms of who gets referred for the procedure and which endoscopic and histologic findings are recognized as Barrett's esophagus. Hence, the proportion of individuals with Barrett's esophagus who are diagnosed with Barrett's esophagus has likely been increasing over the last few decades. Indeed, population-based studies of individuals invited to undergo upper endoscopy for research indicate that the true prevalence of Barrett's esophagus is much greater than suggested by the previously mentioned clinical studies, and at least...
