Nicholas J. Shaheen, MD, MPH; David S. Weinberg, MD, MSc; Thomas D. Denberg, MD, PhD; Roger Chou, MD; Amir Qaseem, MD, PhD, MHA; Paul Shekelle, MD, PhD; for the Clinical Guidelines Committee of the American College of Physicians*
Note: Best practice advice papers are “guides” only and may not apply to all patients and all clinical situations. Thus, they are not intended to override clinicians' judgment. All ACP best practice advice papers are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.
Disclaimer: The authors of this best practice advice paper are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of Veterans Affairs.
Financial Support: Financial support for the development of this best practice advice paper comes exclusively from the ACP's operating budget. Dr. Shaheen is supported by the National Cancer Institute (grant U54CA163060 and U54CA156733).
Potential Conflicts of Interest: Any financial and nonfinancial conflicts of interest of the group members were declared, discussed, and resolved according to ACP's conflicts of interest policy. A record of conflicts of interest is kept for each Clinical Guidelines Committee meeting and conference call and can be viewed at www.acponline.org/clinical_information/guidelines/guidelines/conflicts_cgc.htm. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M12-0618.
Requests for Single Reprints: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Current Author Addresses: Dr. Shaheen: University of North Carolina School of Medicine, CB#7080, Room 4150, 130 Mason Farm Road, Chapel Hill, NC 27599-7080.
Dr. Weinberg: Department of Medicine, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111.
Dr. Denberg: Harvard Vanguard Medical Associates, 275 Grove Street, Auburndale, MA 02466.
Dr. Chou: Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Mail Code: BICC, Portland, OR 97239.
Dr. Qaseem: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.
Dr. Shekelle: RAND Corporation, 1776 Main Street, Santa Monica, CA 90401.
Author Contributions: Conception and design: N.J. Shaheen, D.S. Weinberg, T.D. Denberg, R. Chou, A. Qaseem, P. Shekelle.
Analysis and interpretation of the data: N.J. Shaheen, D.S. Weinberg, T.D. Denberg, R. Chou, A. Qaseem.
Drafting of the article: N.J. Shaheen, D.S. Weinberg, T.D. Denberg, R. Chou, A. Qaseem.
Critical revision of the article for important intellectual content: N.J. Shaheen, D.S. Weinberg, T.D. Denberg, R. Chou, A. Qaseem, P. Shekelle.
Final approval of the article: N.J. Shaheen, D.S. Weinberg, T.D. Denberg, R. Chou, A. Qaseem, P. Shekelle.
Statistical expertise: A. Qaseem.
Obtaining of funding: D.S. Weinberg.
Administrative, technical, or logistic support: D.S. Weinberg, A. Qaseem.
Collection and assembly of data: N.J. Shaheen, D.S. Weinberg.
Shaheen NJ, Weinberg DS, Denberg TD, Chou R, Qaseem A, Shekelle P, et al. Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2012;157:808-816. doi: 10.7326/0003-4819-157-11-201212040-00008
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Published: Ann Intern Med. 2012;157(11):808-816.
Also available: Consumer Reports Patient Resource on High-Value Care for GERD
Upper endoscopy is commonly used in the diagnosis and management of gastroesophageal reflux disease (GERD). Evidence demonstrates that it is indicated only in certain situations, and inappropriate use generates unnecessary costs and exposes patients to harms without improving outcomes.
The Clinical Guidelines Committee of the American College of Physicians reviewed evidence regarding the indications for, and yield of, upper endoscopy in the setting of GERD, and to highlight how clinicians can increase the delivery of high-value health care.
Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting).
Upper endoscopy is indicated in men and women with:
Typical GERD symptoms that persist despite a therapeutic trial of 4 to 8 weeks of twice-daily proton-pump inhibitor therapy.
Severe erosive esophagitis after a 2-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus. Recurrent endoscopy after this follow-up examination is not indicated in the absence of Barrett esophagus.
History of esophageal stricture who have recurrent symptoms of dysphagia.
Upper endoscopy may be indicated:
In men older than 50 years with chronic GERD symptoms (symptoms for more than 5 years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus.
For surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than 3 to 5 years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia.
Cancer incidence as a function of age.
Estimated incidence of EAC in men and women with weekly GERD symptoms as a function of age, compared with other types of cancer, including BrCa in women and men and CRC in men and women. The green horizontal line represents incidence of CRC in women aged 50 years (an age at which endoscopic screening procedures are endorsed by many organizations) as a benchmark comparison. Note that the incidences of EAC in women with GERD and BrCa in men overlap (from reference 29). BrCa = breast cancer; CRC = colorectal cancer; EAC = esophageal adenocarcinoma; GERD = gastroesophageal reflux disease.
Summary of the ACP best practice advice: upper endoscopy in the setting of GERD.
BMI = body mass index; GERD = gastroesophageal reflux disease; PPI = proton-pump inhibitor.
Consumer Reports Patient Resource on High-Value Care for GERD
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Video News Release - Upper Endoscopy for GERD: Best Practice Advice from ACP
Gabor Kandel, MD, FRCP
Division of Gastroenterology, St. Michael's Hospital, Toronto.
December 26, 2012
Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians.
Annals of Internal Medicine
Re: Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians.
December 24, 2012
Dr. Shaheen and his colleagues (1) thoughtfully illuminate a perplexing problem. However, I believe two further indications for upper endoscopy evaluating reflux should be considered.
For those worried about cancer, endoscopy may be both more reassuring and cost—effective than explanation alone. In a study of gastric acid suppressants versus immediate gastroscopy for dyspepsia, Bytzer et al (2) found that the group randomized to endoscopy not only was more satisfied with medical care, but also had lower health care costs, in part because of decreased drug costs, sick-days, and physician follow-ups. Discussion, reassurance, and support without endoscopy ring hollow in light of articles demonstrating an increased incidence of cancer in reflux even without Barrett's esophagus (3), and the rarity of curing cancer once alarm symptoms have developed. Esophageal cancer may not even be that rare in the young: our center has reported 29 cases of Barrett's with early esophageal cancer or high grade dysplasia in patients age less than age 55 collected from the province of Ontario alone over 9 years without even delving into surgical files (4). As further justification, I use a survey of 1040 upper endoscopies done to investigate dyspepsia presenting to primary care physicians, the very group to which the Shaheen guidelines are directed. Thomson and his colleagues found two cases of malignancy (5), neither with alarm symptoms, both potentially curable, but no cancer was found in the in 29 with alarm symptoms.
Secondly, upper endoscopy before starting a proton pump inhibitor provides a logical basis to guide the length of continuing such gastric acid suppression therapy. For those with esophagitis, a compelling argument can be made to continue these drugs for months, perhaps indefinitely. However, if the esophageal mucosa appears normal, pointing toward either non-esophagitis reflux disease or functional dyspepsia, gastric acid suppression treatment can be less aggressive, even taken on demand. Since symptoms of reflux commonly develop after discontinuing a proton pump inhibitor (6,7) it is difficult to use clinical assessment alone to guide when proton pump inhibitors should be stopped when prescribed for reflux. Endoscopy after a course of proton pump inhibitor therapy, as recommended by Shaheen et al, is often not helpful in this regard: after treatment one cannot know if the esophageal mucosa appears normal because esophagitis has healed, or if there never was any esophagitis in the first place. Until the risks and costs of unduly long proton pump inhibitor therapy, including its potential complications of hip fractures, low serum magnesium levels, and infections are directly compared with endoscopy, it may be premature to exclude this dilemma when considering gastroscopy to investigate reflux.
With better anesthesia, and smaller endoscopes, the risk of upper endoscopy may have decreased since the 1991 survey quoted by Shaheen et al, just as the quoted risk of malignancy in Barrrett's esophagus has fallen during this time. Accordingly, wonder if offering without necessarily recommending upper endscopy should be considered for patients with reflux worried about malignancy and unnecessary long term proton pump inhibitor therapy.
1. Shaheen, NJ, Weinberg DS, Denberg, TD, Chou R, Qaseem A, Shekelle P. for the Clinical Guidelines Committeee of the MAerican College of Physicians. Upper Endoscopy for Gastroesophageal Reflux disease: Best Practice Advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2012; 157:808-816
2. Bytzer P, Hansen JM, Schaffalitzky de Muckadell 0B. Empirical H2- blocker therapy or prompt endoscopy in management of dyspepsia, Lancet 1994; 343:811-816
3. Lagergren J, Bergstrom R, Lindgren A, Nyren 0. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma N Eng J Med 1999;340: 825-31
4. James P, Cirocco M, Kandel G, Kortan P, May G, Marcon N. Early adenocarcinoma and high grade dysplasia among adults less than 55 years of age. Can J Gastroenterol 2012; 26: Suppl 26 A227
5. Thomson, ABR, Barkun AN, Armstrong D, Chiba N, Whites RJ, Daniels S, et al. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia: the Canadian Adult Dyspepsia Empiric Treatment-Prompt Endoscopy (CADET-PE) study.
6. Niklasson A, Lindstr8m L, Simren M, Lindberg G, Bjornsson E. Dyspeptic symptoms development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial. Am .1 Gastroenterol 2010; 105:1531-37
7, Reimer C, Sondergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009;137:80-87
Nicholas Shaheen MD, David Weinberg MD
January 9, 2013
We thank Dr. Kandel for his interest in our work.1 Regarding the use of upper endoscopy to dispel fears of esophageal cancer, we recognize the value of patient reassurance and peace of mind. However, it is better to address the underlying misunderstanding of the risk of developing cancer in low-risk individuals, as opposed to providing a service of dubious and unproven value to assuage an inappropriately-elevated concern. While a consultation addressing these concerns in a meaningful way may actually take longer than performing an endoscopy itself, it promotes understanding of the real risks involved, and averts the risks and costs associated with endoscopy. Such a consultation may also forestall subsequent requests for endoscopy after an initial negative exam, since the need for the initial exam was not endorsed.
Dr. Kandel suggests the performance of upper endoscopy on every patient prior to initiating PPI therapy. Fortunately, data exist as to whether endoscopy or empiric therapy with acid suppression is the best initial approach to subjects with routine GERD symptoms. Giannini et al randomized 612 subjects with typical GERD symptoms to a strategy of either early endoscopy or initial empiric treatment with PPI.2 An almost identical proportion in each arm responded to therapy at both 4 and 24 weeks. Unsurprisingly, the empiric treatment arm was more cost-effective, with 90% fewer endoscopies. Initial endoscopic management was associated with an overall cost which was 44% higher than empiric therapy. Interestingly, assessment of health-related quality of life (HRQOL) demonstrated essentially identical HRQOL in each arm, suggesting that any “re-assuring” effect of endoscopy is either transient or miniscule. In short, these investigators found no additional value in the early endoscopy strategy.
Dr. Kandel mentions some of the putative risks of long-term PPI use. It is important to put the magnitude of these risks, and the quality of the data supporting them, in context for our patients. The data come largely from cohort and case-control studies, subject to confounding by unmeasured variables. Some show an inconsistent relationship, and/or a very small increase in the absolute risk of the putative side effect. Finally, some of these side effects may be related to both dose and chronicity of usage, supporting our suggestions regarding limited durations of therapy. The primary utility of this literature may be to remind us that everyone should have a good reason for the medications they use, and that no medication is free of side effects.
Nicholas J. Shaheen, MD, MPH
David S. Weinberg, MD, MSc
1. Shaheen NJ, Weinberg DS, Denberg TD, Chou R, Qaseem A, Shekelle P. Upper Endoscopy for Gastroesophageal Reflux Disease: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Annals of Internal Medicine 2012;157(11).
2. Giannini EG, Zentilin P, Dulbecco P, Vigneri S, Scarlata P, Savarino V. Management strategy for patients with gastroesophageal reflux disease: a comparison between empirical treatment with esomeprazole and endoscopy-oriented treatment. Am J Gastroenterol 2008;103(2):267-275.
Gastroenterology/Hepatology, Guidelines, High Value Care, Peptic Disease, Gastroesophageal Reflux Disease.
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