- Email: [email protected]
The role of endoscopy in dyspepsia
Clinical Update
American Society for Gastrointestinal Endoscopy
Editor: Ronnie Fass, MD
Vol. 15, No. 1 July 2007
Commentary: In practice, dyspepsia is commonly used as an indication for endoscopy to exclude upper-gut mucosal abnormalities. However, in this review, Dr Nicholas J. Talley offers a much more pragmatic approach for the diagnosis and management of dyspepsia. By using several systematic reviews, meta-analyses, and recently proposed practice guidelines for dyspepsia, Dr Talley provides a convincing argument that upper endoscopy in subjects younger than 55 years with dyspepsia but without alarm symptoms is a low-yield diagnostic strategy. In contrast, subjects with dyspepsia and who are older than 55 years and/or with alarm symptoms would benefit from upper endoscopy as the initial evaluative strategy. An easy-to-follow (and remember) diagnostic algorithm for uninvestigated dyspepsia is offered at the end of the monograph. – Ronnie Fass, MD, Editor
THE ROLE OF ENDOSCOPY IN DYSPEPSIA Nicholas J. Talley, MD, PhD Professor of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
yspepsia is a confusing term, poorly understood by patients and often misused by clinicians.1 Some physicians use the label dyspepsia to refer to any upper-GI-tract symptom, including classical symptoms of GERD, like heartburn or acid regurgitation.1 Gastroenterologists tend to use the term dyspepsia in a more restricted sense, referring to patients who have epigastric pain or meal-related symptoms, such as postprandial fullness or an inability to finish a normal meal (early satiation), consistent with the Rome working team definition.2 The focus here will be on the role of endoscopy in patients who present with epigastric pain or upper-abdominal meal-related discomfort.
D
IF AN EGD IS PERFORMED, WHAT IS LIKELY TO BE FOUND? The majority of patients who present with dyspepsia will have a normal EGD.1 In a Canadian study of patients with uninvestigated dyspepsia in primary care, the most common finding was esophagitis (defined as erosions or mucosal breaks), which occurred in 43% of cases.3 Peptic ulcer disease was rare in this population, which affected only 5% of patients, reflecting the disappearance of Helicobacter pylori and less use of nonsteroidal anti-inflammatory drugs. Gastric and esophageal adenocarcinoma remain feared diseases, but these will rarely be found in patients in
Copyright © 2007 by the American Society for Gastrointestinal Endoscopy 1520 Kensington Road, Suite 202, Oak Brook, IL 60523 Phone 630.573.0600, Fax 630.573.0691, www.asge.org, www.askasge.org To purchase additional copies, please contact the ASGE • ISSN 1070-7212 www.asge.org
primary care, affecting less than 1% of patients who were investigated in most series.1,3,4
SHOULD EVERYONE WHO PRESENTS WITH DYSPEPSIA HAVE AN ENDOSCOPY? Prompt endoscopy does have some clear advantages. In addition to making a firm diagnosis of clinically relevant abnormalities, like esophagitis or peptic ulcer, endoscopists hope that the test will improve patient satisfaction.1 There are some limited data to support the view that patient satisfaction may be greater after endoscopy, but the data are not convincing.5-8 One randomized trial of empiric H2 receptor blocker therapy vs prompt endoscopy found that satisfaction was greater 1 month after endoscopy in the endoscopy arm, but, because this study was not blinded, it is not possible to exclude bias.5 If reassurance does occur after endoscopy, the duration is unclear. In another study, after a normal endoscopy and reassurance by the endoscopist, there were improvements in health-related anxiety that persisted for 6 months.7 However, a Dutch study of 420 patients reported that anxiety, depression, and general health were similar before and after EGD for dyspepsia.9
Sponsored by:
Still, there are substantial disadvantages of performing a prompt endoscopy for all cases, aside from cost to both patients and society. The procedure does have a very small risk. Although, in the individual patient, this is unlikely to be an issue, if recommendations were made to promptly have an endoscopy for all patients with dyspepsia, then the risk-benefit ratio becomes more of a consideration in view of the large population burden.1 It is unlikely that endoscopy will identify a serious structural lesion, particularly in the younger patient who has no alarm features, such as weight loss or GI bleeding.1,3 Indeed, finding esophagitis usually does not lead to any change in management, which is the whole point of doing the procedure.10 Finally, there are alternative strategies to a prompt endoscopy, namely empiric therapy, as discussed below, which probably provides equivalent outcomes.1
WHEN SHOULD YOU REFER A PATIENT WITH DYSPEPSIA FOR AN ENDOSCOPY? There are guidelines for clinical practice that have been endorsed by the American Gastroenterological Association1 and the American College of Gastroenterology.11 Firstly, there is evidence that the risk of detecting malignancy is increased in those patients of advanced age.12-15 Indeed, in the United States, the risk of malignancy begins to rapidly rise after the age of 55, and, because of this, recommendations have been made to proceed with endoscopy rather than empiric therapy in older individuals who develop the new onset of dyspepsia.1,11 Previously, the American College of Physicians in 1985 suggested that the age threshold should be 45 years,12 but this is probably too young based on the relative rarity of cancer in those in their early 50s and younger. No age threshold is absolute, and the decision whether to perform an endoscopy should also factor into account other symptoms, family history, and patient anxiety about malignancy. Traditionally, another useful clinical parameter has been to search for symptoms and signs that may suggest underlying serious disease.1,13 These are usually referred to as red flag or alarm features. Typical alarm features have included recurrent vomiting, progressive difficulty swallowing or painful swallowing, evidence of GI bleeding or anemia, unexplained weight loss, presence of jaundice, abdominal mass or abnormal lymph nodes, or family history of upper-GI malignancy. However, the literature supporting the utility of using these alarm features is more limited than many clinicians realize.4 A systematic review found only 15 studies that assessed the diagnostic accuracy of alarm features in predicting malignancy.4 Overall, the sensitivity of alarm symptoms was inadequate, varying from 0% to 83%. The specificity was only slightly better, varying from 40% to 98%. Moreover, much of the literature was flawed by a lack of careful characterization of alarm symptoms. For example, having trouble swallowing is common in the general population, but progressive dysphagia is rare and probably a better signal of something serious.4 The other problem is that alarm features, if present, usually indicate that the cancer is advanced and incurable. A study in the United Kingdom prospectively evaluated over 4000 patients who underwent EGD; 3% had malignancy.16 Overall, 85% of these patients had alarm features, but there were more curable cancers in the 15% with no alarm features.16 2
www.asge.org
Based on the available data, it seems reasonable to conclude that younger patients who have no alarm features are unlikely to have a malignancy.13-15 However, in older patients with new symptoms or in those who have alarm features, a prompt endoscopy is recommended. However, the chances of finding serious disease, including malignancy, still remains relatively low in this setting.1,4 Older patients deserve a prompt endoscopy. There is some evidence that a prompt endoscopy in older patients is actually a reasonable strategy, even if finding malignancy is not the goal. In a randomized trial from the United Kingdom, 422 patients over the age 50 years either had an endoscopy or received usual care.17 The endoscopy arm did better than usual care in this study, and these patients also used less acid-suppression therapy. Notably, the costs of an endoscopy in the United Kingdom are much lower than in the United States, which may have favored the costeffectiveness conclusions of this study, but the results still indicate that EGD is reasonable in older patients, even if there are no alarm features.
DOES EUS HAVE A ROLE? Occasionally, patients with pancreatic or biliary pathology will present with dyspepsia, (typically epigastric pain), but a diagnosis may be delayed in this setting.1 In a study of 200 patients from Hong Kong, the EUS identified pancreatic or biliary lesions in 48 patients and led to a change in management in 25% of cases.18 In a study from the United States, pancreatic disease was also found to be an atypical presentation of dyspepsia.19 Notably, however, these studies were done in tertiary referral centers and are unlikely to reflect the situation in primary care or even general gastroenterology practice.
HOW DOES EMPIRIC THERAPY STACK UP AGAINST AN ENDOSCOPY? An updated Cochrane Review of initial management strategies for dyspepsia carefully reviewed this issue.20 It was reported in the review that there was no significant difference in the outcome between an endoscopy (the criterion standard) vs H pylori testing and treatment. Similarly, an early endoscopy compared with acid suppression showed no significant difference in the overall effectiveness. Based on the available data, the American College of Gastroenterology recommended that, in populations where the prevalence of H pylori is likely to be low (using under 10% as a rough rule of thumb), then first-line empiric antisecretory therapy for 4 to 8 weeks should be prescribed for younger patients with no alarm features (Fig. 1). If a patient does not respond, it is then recommended that a urea breath test or a stool antigen test to check for H pylori status be performed after ceasing acid-suppression therapy for a week. If H pylori infection is detected, it should be treated empirically. If the patient still remains symptomatic, then referral for EGD is recommended, although it was also recognized that the yield of endoscopy in this setting is low. In populations where the prevalence of H pylori is likely to be high, such as in African Americans, Hispanics, or recent immigrants from developing countries, then testing for H pylori and treating the infection if present is considered the appropriate initial empiric strategy.11 The Cochrane Review concluded that proton pump inhibitor therapy is probably the most cost-effective treatment for dyspepsia.20 However, an excellent Vol. 15, No. 1 July 2007
Danish randomized controlled trial in primary care observed that H pylori eradication significantly reduced the endoscopy workload compared with antisecretory treatment.21
Dyspepsia (uninvestigated)
DO NOT FORGET THE COLON Many patients with dyspepsia also complain of bowel-habit disturbances.22 Indeed, there is a significant overlap of irritable bowel syndrome with nonulcer (functional) dyspepsia, as well as GERD.1 Rarely, colon cancer can present with dyspepsia-type symptoms.1 If the patient is 50 years old or older and has not had a screening colonoscopy, consider adding a colonoscopy to the workup. It can be cheekily suggested that if all patients with dyspepsia had a colonoscopy rather than an EGD, then, in fact, the community benefit would be significantly greater because of the prevention benefits for colon cancer (and the lack of benefit of EGD for cancer prevention, although this is unproven)!
WHAT TO DO IN PRACTICE
Age > 55 or alarm features
EGD
Age ≤ 55 No alarm features
HP prevalence <10%
HP prevalence >10%
PPI trial
Test and treat for H pylori
FAILS Test and treat for H pylori FAILS Re-evaluate the history: consider other causes
FAILS
FAILS
PPI trial
FAILS Re-evaluate the history: consider other causes
FAILS
Many patients who present with new PPI - proton pump inhibitor Consider EGD Consider EGD onset dyspepsia are under age 55 years EGD - esophagogastroduodenoscopy old and have no alarm features. In this setting, a trial of acid-suppression therFigure 1. Approaching testing and treatment in dyspepsia. Based on the American College of Gastroenterology apy is reasonable. If standard doses of guideline (ref 11). HP prevalence refers to the estimated H pylori prevalence in the clinicans region of practice. proton pump inhibitor therapy fail, then consider doubling the dose, although there is no good empiric evidence that this works in dyspepsia DISCLOSURE (but in GERD it can be helpful, and sometimes distinguishing dyspepsia The author discloses consulting for Takeda, GlaxoSmithKline AstraZeneca, from GERD is difficult).23 If acid suppression fails, then check H pylori and TAP Pharmaceuticals. status off antisecretory therapy, preferably by using the stool antigen or urea breath test, and treat positive cases.24 Serology is not a great test, and REFERENCES false positives will be common, particularly in areas where the background 1. Talley NJ, Vakil N, Moayyedi P. AGA technical review on the evaluation prevalence of H pylori is relatively high.25 If the patient is older and with of dyspepsia. Gastroenterology 2005;129:1756-80. new symptoms or has alarm features, then certainly do a prompt endos2. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology 2006;130:1466-79. copy to rule out malignancy.1,11 At that time, obtain a biopsy specimen for identifying H pylori and treat the patient if the infection is present, 3. Thomson A, Barkun A, Armstrong D, et al. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestiregardless of the endoscopic findings. There is now convincing evidence gated dyspepsia: the Canadian adult dyspepsia empiric treatment-prompt that H pylori eradication provides a benefit, albeit small, in endoscopy negendoscopy (CADET-PE) study. Aliment Pharmacol Ther 2003;17:1481-91. ative (or functional) dyspepsia.26 Avoid an immediate endoscopy if the 4. Vakil N, Moayyedi P, Fennerty MB, et al. Limited value of alarm features patient is concurrently taking acid-suppression therapy: the yield is lower in the diagnosis of upper gastrointestinal malignancy: systematic review 27 then and the result may even be misleading. If there is still a concern and meta-analysis. Gastroenterology 2006;131:390-401. about the diagnosis after the initial endoscopy, carefully reevaluate the his5. Bytzer P, Hansen JM, Schaffalitzky de Muckadell OB. Empirical H2tory, looking for any evidence that might suggest a biliary or pancreatic blocker therapy or prompt endoscopy in management of dyspepsia. Lancet 1994;343:811-6. problem, symptoms related to drug ingestion, or some other rare cause. www.asge.org
Vol. 15, No. 1 July 2007
3
6. Wiklund I, Glise H, Jerndal P, et al. Does endoscopy have a positive impact on quality of life in dyspepsia? Gastrointest Endosc 1998;47:44954.
17. Delaney BC, Wilson S, Roalfe A, et al. Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care. Lancet 2000;356:1965-9.
7. Quadri A, Vakil N. Health-related anxiety and the effect of open-access endoscopy in US patients with dyspepsia. Aliment Pharmacol Ther 2003;17:835-40.
18. Lee YT, Lai AC, Hui Y, et al. EUS in the management of uninvestigated dyspepsia. Gastrointest Endosc 2002;56:842-8.
8. Hungin A, Thomas P, Bramble M, et al. What happens to patients following open access gastroscopy? An outcome study from general practice. Br J Gen Pract 1994;44:519-21. 9. van Kerkhoven LA, van Rossum LG, van Oijen MG, et al. Upper gastrointestinal endoscopy does not reassure patients with functional dyspepsia. Endoscopy 2006;38:879-85.
19. Sahai AV, Mishra G, Penman ID, et al. EUS to detect evidence of pancreatic disease in patients with persistent or nonspecific dyspepsia. Gastrointest Endosc 2000;52:153-9. 20. Delaney BC, Moayyedi P, Forman D, et al. Initial management strategies for dyspepsia (Review). Cochrane Database Syst Rev 2005;2:CD001961. 21. Jarbol DE, Kragstrup J, Stovring H, et al. Proton pump inhibitor or testing for Helicobacter pylori as the first step for patients presenting with dyspepsia? A cluster-randomized trial. Am J Gastroenterol 2006;101:1200-8.
10. Blustein PK, Beck PL, Meddings JB, et al. The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms. Am J Gastroenterol 1998;93:2508-12.
22. Hammer J, Talley NJ. Disturbed bowel habits in patins with non-ulcer dyspepsia. Aliment Pharmacol Ther 2006;24:405-10.
11. Talley NJ, Vakil N, Practice Parameters Committee of the American College of Gastroenterology. Guidelines for the management of dyspepsia. Am J Gastroenterol 2005;100:2324-37.
23. Moayyedi P, Delaney B, Vakil N, et al. The efficacy of proton pump inhibitors in non-ulcer dyspepsia: a systematic review and economic analysis. Gastroenterology 2004;127:1329-37.
12. Endoscopy in the evaluation of dyspepsia. Health and Public Policy Committee, American College of Physicians. Ann Intern Med 1985;102:266-9.
24. Spiegel BM, Vakil NB, Ofman JJ. Dyspepsia management in primary care: a decision analysis of competing strategies. Gastroenterology 2002; 122:1270-85.
13. Gillen D, McColl KE. Does concern about missing malignancy justify endoscopy in uncomplicated dyspepsia in patients aged less than 55? Am J Gastroenterol 1999;94:75-9. 14. Breslin NP, Thomson A, Bailey R, et al. Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia. Gut 2000;46:93-7.
25. Loy CT, Irwig LM, Katelaris PH, et al. Do commercial serological kits for Helicobacter pylori infection differ in accuracy? A meta-analysis. Am J Gastroenterol 1996;91:1138-44.
15. Canga C 3rd, Vakil N. Upper GI malignancy, uncomplicated dyspepsia, and the age threshold for early endoscopy. Am J Gastroenterol 2002;97:600-3.
26. Moayyedi P, Deeks J, Talley NJ, et al. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol 2003;98:2621-6.
16. Bowrey DJ, Griffin SM, Wayman J, et al. Use of alarm symptoms to select dyspeptics for endoscopy causes patients with curable esophagogastric cancer to be overlooked. Surg Endosc 2006;20:1725-8.
27. Talley NJ. Yield of endoscopy in dyspepsia and concurrent treatment with proton pump inhibitors: the blind leading the blind? Gastrointest Endosc 2003;58:89-92.
www.asge.org
CU-1501
Vol. 15, No. 1 July 2007
American Society for Gastrointestinal Endoscopy
Editor: Ronnie Fass, MD
Vol. 15, No. 1 July 2007
Commentary: In practice, dyspepsia is commonly used as an indication for endoscopy to exclude upper-gut mucosal abnormalities. However, in this review, Dr Nicholas J. Talley offers a much more pragmatic approach for the diagnosis and management of dyspepsia. By using several systematic reviews, meta-analyses, and recently proposed practice guidelines for dyspepsia, Dr Talley provides a convincing argument that upper endoscopy in subjects younger than 55 years with dyspepsia but without alarm symptoms is a low-yield diagnostic strategy. In contrast, subjects with dyspepsia and who are older than 55 years and/or with alarm symptoms would benefit from upper endoscopy as the initial evaluative strategy. An easy-to-follow (and remember) diagnostic algorithm for uninvestigated dyspepsia is offered at the end of the monograph. – Ronnie Fass, MD, Editor
THE ROLE OF ENDOSCOPY IN DYSPEPSIA Nicholas J. Talley, MD, PhD Professor of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota
yspepsia is a confusing term, poorly understood by patients and often misused by clinicians.1 Some physicians use the label dyspepsia to refer to any upper-GI-tract symptom, including classical symptoms of GERD, like heartburn or acid regurgitation.1 Gastroenterologists tend to use the term dyspepsia in a more restricted sense, referring to patients who have epigastric pain or meal-related symptoms, such as postprandial fullness or an inability to finish a normal meal (early satiation), consistent with the Rome working team definition.2 The focus here will be on the role of endoscopy in patients who present with epigastric pain or upper-abdominal meal-related discomfort.
D
IF AN EGD IS PERFORMED, WHAT IS LIKELY TO BE FOUND? The majority of patients who present with dyspepsia will have a normal EGD.1 In a Canadian study of patients with uninvestigated dyspepsia in primary care, the most common finding was esophagitis (defined as erosions or mucosal breaks), which occurred in 43% of cases.3 Peptic ulcer disease was rare in this population, which affected only 5% of patients, reflecting the disappearance of Helicobacter pylori and less use of nonsteroidal anti-inflammatory drugs. Gastric and esophageal adenocarcinoma remain feared diseases, but these will rarely be found in patients in
Copyright © 2007 by the American Society for Gastrointestinal Endoscopy 1520 Kensington Road, Suite 202, Oak Brook, IL 60523 Phone 630.573.0600, Fax 630.573.0691, www.asge.org, www.askasge.org To purchase additional copies, please contact the ASGE • ISSN 1070-7212 www.asge.org
primary care, affecting less than 1% of patients who were investigated in most series.1,3,4
SHOULD EVERYONE WHO PRESENTS WITH DYSPEPSIA HAVE AN ENDOSCOPY? Prompt endoscopy does have some clear advantages. In addition to making a firm diagnosis of clinically relevant abnormalities, like esophagitis or peptic ulcer, endoscopists hope that the test will improve patient satisfaction.1 There are some limited data to support the view that patient satisfaction may be greater after endoscopy, but the data are not convincing.5-8 One randomized trial of empiric H2 receptor blocker therapy vs prompt endoscopy found that satisfaction was greater 1 month after endoscopy in the endoscopy arm, but, because this study was not blinded, it is not possible to exclude bias.5 If reassurance does occur after endoscopy, the duration is unclear. In another study, after a normal endoscopy and reassurance by the endoscopist, there were improvements in health-related anxiety that persisted for 6 months.7 However, a Dutch study of 420 patients reported that anxiety, depression, and general health were similar before and after EGD for dyspepsia.9
Sponsored by:
Still, there are substantial disadvantages of performing a prompt endoscopy for all cases, aside from cost to both patients and society. The procedure does have a very small risk. Although, in the individual patient, this is unlikely to be an issue, if recommendations were made to promptly have an endoscopy for all patients with dyspepsia, then the risk-benefit ratio becomes more of a consideration in view of the large population burden.1 It is unlikely that endoscopy will identify a serious structural lesion, particularly in the younger patient who has no alarm features, such as weight loss or GI bleeding.1,3 Indeed, finding esophagitis usually does not lead to any change in management, which is the whole point of doing the procedure.10 Finally, there are alternative strategies to a prompt endoscopy, namely empiric therapy, as discussed below, which probably provides equivalent outcomes.1
WHEN SHOULD YOU REFER A PATIENT WITH DYSPEPSIA FOR AN ENDOSCOPY? There are guidelines for clinical practice that have been endorsed by the American Gastroenterological Association1 and the American College of Gastroenterology.11 Firstly, there is evidence that the risk of detecting malignancy is increased in those patients of advanced age.12-15 Indeed, in the United States, the risk of malignancy begins to rapidly rise after the age of 55, and, because of this, recommendations have been made to proceed with endoscopy rather than empiric therapy in older individuals who develop the new onset of dyspepsia.1,11 Previously, the American College of Physicians in 1985 suggested that the age threshold should be 45 years,12 but this is probably too young based on the relative rarity of cancer in those in their early 50s and younger. No age threshold is absolute, and the decision whether to perform an endoscopy should also factor into account other symptoms, family history, and patient anxiety about malignancy. Traditionally, another useful clinical parameter has been to search for symptoms and signs that may suggest underlying serious disease.1,13 These are usually referred to as red flag or alarm features. Typical alarm features have included recurrent vomiting, progressive difficulty swallowing or painful swallowing, evidence of GI bleeding or anemia, unexplained weight loss, presence of jaundice, abdominal mass or abnormal lymph nodes, or family history of upper-GI malignancy. However, the literature supporting the utility of using these alarm features is more limited than many clinicians realize.4 A systematic review found only 15 studies that assessed the diagnostic accuracy of alarm features in predicting malignancy.4 Overall, the sensitivity of alarm symptoms was inadequate, varying from 0% to 83%. The specificity was only slightly better, varying from 40% to 98%. Moreover, much of the literature was flawed by a lack of careful characterization of alarm symptoms. For example, having trouble swallowing is common in the general population, but progressive dysphagia is rare and probably a better signal of something serious.4 The other problem is that alarm features, if present, usually indicate that the cancer is advanced and incurable. A study in the United Kingdom prospectively evaluated over 4000 patients who underwent EGD; 3% had malignancy.16 Overall, 85% of these patients had alarm features, but there were more curable cancers in the 15% with no alarm features.16 2
www.asge.org
Based on the available data, it seems reasonable to conclude that younger patients who have no alarm features are unlikely to have a malignancy.13-15 However, in older patients with new symptoms or in those who have alarm features, a prompt endoscopy is recommended. However, the chances of finding serious disease, including malignancy, still remains relatively low in this setting.1,4 Older patients deserve a prompt endoscopy. There is some evidence that a prompt endoscopy in older patients is actually a reasonable strategy, even if finding malignancy is not the goal. In a randomized trial from the United Kingdom, 422 patients over the age 50 years either had an endoscopy or received usual care.17 The endoscopy arm did better than usual care in this study, and these patients also used less acid-suppression therapy. Notably, the costs of an endoscopy in the United Kingdom are much lower than in the United States, which may have favored the costeffectiveness conclusions of this study, but the results still indicate that EGD is reasonable in older patients, even if there are no alarm features.
DOES EUS HAVE A ROLE? Occasionally, patients with pancreatic or biliary pathology will present with dyspepsia, (typically epigastric pain), but a diagnosis may be delayed in this setting.1 In a study of 200 patients from Hong Kong, the EUS identified pancreatic or biliary lesions in 48 patients and led to a change in management in 25% of cases.18 In a study from the United States, pancreatic disease was also found to be an atypical presentation of dyspepsia.19 Notably, however, these studies were done in tertiary referral centers and are unlikely to reflect the situation in primary care or even general gastroenterology practice.
HOW DOES EMPIRIC THERAPY STACK UP AGAINST AN ENDOSCOPY? An updated Cochrane Review of initial management strategies for dyspepsia carefully reviewed this issue.20 It was reported in the review that there was no significant difference in the outcome between an endoscopy (the criterion standard) vs H pylori testing and treatment. Similarly, an early endoscopy compared with acid suppression showed no significant difference in the overall effectiveness. Based on the available data, the American College of Gastroenterology recommended that, in populations where the prevalence of H pylori is likely to be low (using under 10% as a rough rule of thumb), then first-line empiric antisecretory therapy for 4 to 8 weeks should be prescribed for younger patients with no alarm features (Fig. 1). If a patient does not respond, it is then recommended that a urea breath test or a stool antigen test to check for H pylori status be performed after ceasing acid-suppression therapy for a week. If H pylori infection is detected, it should be treated empirically. If the patient still remains symptomatic, then referral for EGD is recommended, although it was also recognized that the yield of endoscopy in this setting is low. In populations where the prevalence of H pylori is likely to be high, such as in African Americans, Hispanics, or recent immigrants from developing countries, then testing for H pylori and treating the infection if present is considered the appropriate initial empiric strategy.11 The Cochrane Review concluded that proton pump inhibitor therapy is probably the most cost-effective treatment for dyspepsia.20 However, an excellent Vol. 15, No. 1 July 2007
Danish randomized controlled trial in primary care observed that H pylori eradication significantly reduced the endoscopy workload compared with antisecretory treatment.21
Dyspepsia (uninvestigated)
DO NOT FORGET THE COLON Many patients with dyspepsia also complain of bowel-habit disturbances.22 Indeed, there is a significant overlap of irritable bowel syndrome with nonulcer (functional) dyspepsia, as well as GERD.1 Rarely, colon cancer can present with dyspepsia-type symptoms.1 If the patient is 50 years old or older and has not had a screening colonoscopy, consider adding a colonoscopy to the workup. It can be cheekily suggested that if all patients with dyspepsia had a colonoscopy rather than an EGD, then, in fact, the community benefit would be significantly greater because of the prevention benefits for colon cancer (and the lack of benefit of EGD for cancer prevention, although this is unproven)!
WHAT TO DO IN PRACTICE
Age > 55 or alarm features
EGD
Age ≤ 55 No alarm features
HP prevalence <10%
HP prevalence >10%
PPI trial
Test and treat for H pylori
FAILS Test and treat for H pylori FAILS Re-evaluate the history: consider other causes
FAILS
FAILS
PPI trial
FAILS Re-evaluate the history: consider other causes
FAILS
Many patients who present with new PPI - proton pump inhibitor Consider EGD Consider EGD onset dyspepsia are under age 55 years EGD - esophagogastroduodenoscopy old and have no alarm features. In this setting, a trial of acid-suppression therFigure 1. Approaching testing and treatment in dyspepsia. Based on the American College of Gastroenterology apy is reasonable. If standard doses of guideline (ref 11). HP prevalence refers to the estimated H pylori prevalence in the clinicans region of practice. proton pump inhibitor therapy fail, then consider doubling the dose, although there is no good empiric evidence that this works in dyspepsia DISCLOSURE (but in GERD it can be helpful, and sometimes distinguishing dyspepsia The author discloses consulting for Takeda, GlaxoSmithKline AstraZeneca, from GERD is difficult).23 If acid suppression fails, then check H pylori and TAP Pharmaceuticals. status off antisecretory therapy, preferably by using the stool antigen or urea breath test, and treat positive cases.24 Serology is not a great test, and REFERENCES false positives will be common, particularly in areas where the background 1. Talley NJ, Vakil N, Moayyedi P. AGA technical review on the evaluation prevalence of H pylori is relatively high.25 If the patient is older and with of dyspepsia. Gastroenterology 2005;129:1756-80. new symptoms or has alarm features, then certainly do a prompt endos2. Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology 2006;130:1466-79. copy to rule out malignancy.1,11 At that time, obtain a biopsy specimen for identifying H pylori and treat the patient if the infection is present, 3. Thomson A, Barkun A, Armstrong D, et al. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestiregardless of the endoscopic findings. There is now convincing evidence gated dyspepsia: the Canadian adult dyspepsia empiric treatment-prompt that H pylori eradication provides a benefit, albeit small, in endoscopy negendoscopy (CADET-PE) study. Aliment Pharmacol Ther 2003;17:1481-91. ative (or functional) dyspepsia.26 Avoid an immediate endoscopy if the 4. Vakil N, Moayyedi P, Fennerty MB, et al. Limited value of alarm features patient is concurrently taking acid-suppression therapy: the yield is lower in the diagnosis of upper gastrointestinal malignancy: systematic review 27 then and the result may even be misleading. If there is still a concern and meta-analysis. Gastroenterology 2006;131:390-401. about the diagnosis after the initial endoscopy, carefully reevaluate the his5. Bytzer P, Hansen JM, Schaffalitzky de Muckadell OB. Empirical H2tory, looking for any evidence that might suggest a biliary or pancreatic blocker therapy or prompt endoscopy in management of dyspepsia. Lancet 1994;343:811-6. problem, symptoms related to drug ingestion, or some other rare cause. www.asge.org
Vol. 15, No. 1 July 2007
3
6. Wiklund I, Glise H, Jerndal P, et al. Does endoscopy have a positive impact on quality of life in dyspepsia? Gastrointest Endosc 1998;47:44954.
17. Delaney BC, Wilson S, Roalfe A, et al. Cost effectiveness of initial endoscopy for dyspepsia in patients over age 50 years: a randomised controlled trial in primary care. Lancet 2000;356:1965-9.
7. Quadri A, Vakil N. Health-related anxiety and the effect of open-access endoscopy in US patients with dyspepsia. Aliment Pharmacol Ther 2003;17:835-40.
18. Lee YT, Lai AC, Hui Y, et al. EUS in the management of uninvestigated dyspepsia. Gastrointest Endosc 2002;56:842-8.
8. Hungin A, Thomas P, Bramble M, et al. What happens to patients following open access gastroscopy? An outcome study from general practice. Br J Gen Pract 1994;44:519-21. 9. van Kerkhoven LA, van Rossum LG, van Oijen MG, et al. Upper gastrointestinal endoscopy does not reassure patients with functional dyspepsia. Endoscopy 2006;38:879-85.
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Vol. 15, No. 1 July 2007