Yield of endoscopy in dyspepsia and concurrent treatment with proton pump inhibitors: The blind leading the blind?

Abstract

Esophagogastroduodenoscopy (EGD) remains the “gold standard” test in dyspepsia; physicians inherently believe the views obtained provide the truth. It is further assumed valid decisions are made after the test and the results alter practice appropriately. Smith et al.1Smith T Verzola E Mertz H. Low yield of endoscopy for persistent dyspepsia on proton pump inhibitors.Gastrointest Endosc. 2003; 58: 9-13Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar in this issue of the Journal, however, sound an important warning bell about the interpretation of EGD findings in dyspepsia. They evaluated the diagnostic yield in 100 patients with dyspepsia referred for EGD; regardless of whether patients continued to have symptoms while undergoing antisecretory therapy, significantly fewer endoscopic findings were present in the proton pump inhibitor (PPI)-treated group compared with those not receiving treatment. A similar trend was apparent for the H2 blocker-treated patients. The detection of esophagitis and peptic ulcers accounted for the differences observed. A larger retrospective audit reached similar conclusions; antisecretory use seems to blind us at least in some cases.2Mitchell RM Collins JS Watson RG Tham TC. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists.Endoscopy. 2002; 34: 524-526Crossref PubMed Scopus (11) Google Scholar Mitchell et al.2Mitchell RM Collins JS Watson RG Tham TC. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists.Endoscopy. 2002; 34: 524-526Crossref PubMed Scopus (11) Google Scholar reported that among over 4000 patients undergoing EGDs for uncomplicated dyspepsia, one third were undergoing acid suppression treatment; there were dramatic differences in terms of the rates of esophagitis among those taking PPIs (31%), H2 receptor antagonists (30%,) or no therapy (63%).Others have bemoaned the overuse of antisecretory therapy in dyspepsia because this may hide really serious disease during EGD. Wayman et al.3Wayman J Hayes N Raimes SA Griffin SM. Prescription of proton pump inhibitors before endoscopy. A potential cause of missed diagnosis of early gastric cancers.Arch Fam Med. 2000; 9: 385-388Crossref PubMed Scopus (27) Google Scholar reported a series of 7 patients in primary care with gastric ulcer cancers that became asymptomatic in response to treatment with a PPI before EGD, and the diagnosis was not made during the procedure. However, such a report is not particularly illuminating in terms of quantifying the magnitude of the problem. Bramble et al.4Bramble MG Suvakovic Z Hungin AP. Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy.Gut. 2000; 46: 464-467Crossref PubMed Scopus (90) Google Scholar reviewed 133 patients from a representative district in the United Kingdom who had died of upper GI cancer, mostly gastric adenocarcinoma. They noted that 22 of 62 patients treated with acid suppression were falsely given a diagnosis of benign disease at the index EGD, compared with only 1 of 54 patients taking antacids or no therapy.4Bramble MG Suvakovic Z Hungin AP. Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy.Gut. 2000; 46: 464-467Crossref PubMed Scopus (90) Google Scholar However, some perspective is needed. Gastric cancer is an unusual cause of dyspepsia, and in the absence of any alarm features (such as older age at onset, vomiting, bleeding, anemia, or weight loss), it is extremely uncommon. Breslin et al.5Breslin NP Thomson AB Bailey RJ Blustein PK Meddings J Lalor E et al.Gastric cancer and other endoscopic diagnoses in patients with benign dyspepsia.Gut. 2000; 46: 93-97Crossref PubMed Scopus (78) Google Scholar found that among all upper endoscopies in Alberta, Canada in patients without alarm features under age 45 years over a 3-year period, just 3 cancers were found (0.08%). Canga and Vakil6Canga III, C Vakil N. Upper GI malignancy, uncomplicated dyspepsia, and the age threshold for early endoscopy.Am J Gastroenterol. 2002; 97: 600-603Crossref PubMed Google Scholar noted that among patients with upper GI malignancies who presented to 2 teaching hospitals in Milwaukee with uncomplicated dyspepsia, only 1 patient was under age 45. Moreover, a delay in diagnosis of several weeks usually does not alter the ultimate prognosis because most cancers are advanced and incurable anyway (although extremely unlucky patients and the courts may be unimpressed by this argument).7Talley NJ Silverstein MD Agreus L Nyren O Sonnenberg A Holtmann G. AGA technical review: evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (392) Google ScholarEGD is undertaken to not only exclude malignancy, but also identify other relevant causes of dyspepsia.7Talley NJ Silverstein MD Agreus L Nyren O Sonnenberg A Holtmann G. AGA technical review: evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar However, the yield of EGD in those presenting with dyspepsia is highly variable and depends on a number of factors in addition to prior antisecretory medication use. The background prevalence of Helicobacter pylori is clearly important. In those places in which H pylori infection is now rare, such as among higher socioeconomic groupings in the United States, ulcer disease is relatively uncommon but esophagitis is prevalent.8Sharma P Vakil N. Helicobacter pylori and reflux disease.Aliment Pharmacol Ther. 2003; 17: 297-305Crossref PubMed Scopus (100) Google Scholar, 9Malfertheiner P Megraud F O'Morain C Hungin AP Jones R Axon A et al.The European Helicobacter pylori Study Group (EHPSG). Current concepts in the management of Helicobacter pylori infection—the Maastricht 2-2000 Consensus Report.Aliment Pharmacol Ther. 2002; 16: 167-180Crossref PubMed Scopus (6) Google Scholar Indeed, peptic ulcer disease is rapidly disappearing in many parts of the United States,10Quan C Talley NJ. Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs.Am J Gastroenterol. 2002; 97: 2950-2961Crossref PubMed Google Scholar and in these regions it is difficult to mount any reasonable cost-effectiveness argument to support doing EGD to detect ulcer disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) including the Cox-2 inhibitors can cause dyspepsia11Hawkey CJ. Nonsteroidal anti-inflammatory drug gastropathy.Gastroenterology. 2000; 119: 521-535Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 12Bytzer P Talley NJ. Dyspepsia.Ann Intern Med. 2001; 134: 815-822Crossref PubMed Google Scholar but discontinuation of the medication without resorting to EGD in otherwise low-risk cases seems reasonable. Esophagitis is now the most frequent abnormality detected by EGD in dyspepsia.2Mitchell RM Collins JS Watson RG Tham TC. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists.Endoscopy. 2002; 34: 524-526Crossref PubMed Scopus (11) Google Scholar, 13Voutilainen M Sipponen P Mecklin JP Juhola M Farkkila M. Gastroesophageal reflux disease: prevalence, clinical, endoscopy and histopathological findings in 1128 consecutive patients referred for endoscopy due to dyspeptic and reflux symptoms.Digestion. 2000; 61: 6-13Crossref PubMed Scopus (166) Google ScholarThe 2001 American Society for Gastrointestinal Endoscopy (ASGE) guidelines on the role of endoscopy in dyspepsia suggest that in the absence of alarm features, medical management or endoscopy represent equally reasonable options.14Eisen GM Dominitz JA Faigel DO Goldstein JA Kalloo AN Petersen BT et al.The role of endoscopy in dyspepsia.Gastrointest Endosc. 2001; 54: 815-817Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar Current first-line medical management for dyspepsia in H pylori-negative cases essentially comprises antisecretory therapy since the withdrawal of cisapride. It is unrealistic however, to expect antisecretory therapy will not be given to many patients with dyspepsia before EGD. Moreover, guidelines recommending early EGD are hard to support based on current evidence.Although there is universal agreement that prompt EGD is indicated in the setting of alarm features,7Talley NJ Silverstein MD Agreus L Nyren O Sonnenberg A Holtmann G. AGA technical review: evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar, 14Eisen GM Dominitz JA Faigel DO Goldstein JA Kalloo AN Petersen BT et al.The role of endoscopy in dyspepsia.Gastrointest Endosc. 2001; 54: 815-817Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 15Talley NJ Axon A Bytzer P Holtmann G Lam SK Van Zanten S. Management of uninvestigated and functional dyspepsia: a Working Party report for the World Congresses of Gastroenterology 1998.Aliment Pharmacol Ther. 1999; 13: 1135-1148Crossref PubMed Scopus (102) Google Scholar EGD arguably has little to offer the remainder who represent the majority of cases. First, management trials have convincingly shown that the clinical outcomes in those with dyspepsia randomized to empiric H pylori “test and treat” therapy are highly similar to those undergoing prompt endoscopy.16Lassen AT Pedersen FM Bytzer P Schaffalitzky de Muckadell OB. Helicobacter pylori test-and-eradication versus prompt endoscopy for management of dyspepsia patients: a randomised trial.Lancet. 2000; 356: 455-460Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar, 17McColl KE Murray LS Gillen D Walker A Wirz A Fletcher J et al.Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia.BMJ. 2002; 324: 999-1002Crossref PubMed Google Scholar, 18Heaney A Collins JS Watson RG McFarland RJ Bamford KB Tham TC. A prospective randomised trial of a “test and treat” policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic.Gut. 1999; 45: 186-190Crossref PubMed Scopus (134) Google Scholar, 19Delaney BC Innes MA Deeks J Wilson S Cooner MK Moayyedi P et al.Initial management strategies for dyspepsia (Cochrane Review).Cochrane Database Syst Rev. 2001; 3: CD001961PubMed Google Scholar Second, decision analyses have consistently reported that EGD fails to make the grade in terms of cost-effectiveness unless the true cost of the test drops dramatically below current costs in the United States.20Spiegel BMR Vakil NB Ofman JJ. Dyspepsia management in primary care: a reappraisal of competing strategies.Gastroenterology. 2002; 122: 1270-1285Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 21Ofman JJ Etchason J Fullerton S Kahn KL Soll AH. Management strategies for Helicobacter pylori-seropositive patients with dyspepsia: clinical and economic consequences.Ann Intern Med. 1997; 126: 280-291Crossref PubMed Scopus (162) Google Scholar, 22Silverstein MD Petterson T Talley NJ. Initial endoscopy or empirical therapy with or without testing for Helicobacter pylori for dyspepsia: a decision analysis.Gastroenterology. 1996; 110: 72-83Abstract Full Text PDF PubMed Scopus (175) Google Scholar The analysis by Silverstein et al.,22Silverstein MD Petterson T Talley NJ. Initial endoscopy or empirical therapy with or without testing for Helicobacter pylori for dyspepsia: a decision analysis.Gastroenterology. 1996; 110: 72-83Abstract Full Text PDF PubMed Scopus (175) Google Scholar for example, reported that the decision to choose EGD versus empiric therapy was a “toss-up,” but if the cost of EGD was much higher than $500 the results change and EGD starts to become the “loser” in terms of cost-effectiveness in sensitivity analyses. Of course many clinicians are rightly suspicious of decision analyses; their results are driven by the assumptions included, many of which are in reality based on inspired (and sometimes uninspired or plain biased) guess work.Third, there are other practical issues to consider for those physicians who support prompt EGD for almost all patients with dyspepsia. Dyspepsia represents a huge workload in primary care7Talley NJ Silverstein MD Agreus L Nyren O Sonnenberg A Holtmann G. AGA technical review: evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar, 23Bodger K Eastwood PG Manning SI Daly MJ Heatley RV. Dyspepsia workload in urban general practice and implication of the British Society of Gastroenterology Dyspepsia guidelines (1996).Aliment Pharmacol Ther. 2000; 14: 413-420Crossref PubMed Scopus (33) Google Scholar; endoscopy facilities would be overwhelmed if all cases were referred for EGD. If patients have to wait for an EGD, even if it is only for a few weeks, it is difficult for clinicians to deny any prescription therapy. With the availability of over-the-counter H2 blockers and PPIs, the decision to take effective symptomatic therapy before EGD is often out of the physicians' hands anyway.Does performing an EGD in uncomplicated dyspepsia change management and for the better? This is a critical question, but unfortunately support here is extremely thin at best. Some have suggested an EGD may in itself be therapeutic because it offers firm reassurance, although clearly this will much depend on the patient-physician interaction. Wiklund et al.24Wiklund I Glise H Jerndal P Carlsson J Talley NJ. Does endoscopy have a positive impact on quality of life in dyspepsia?.Gastrointest Endosc. 1998; 47: 449-454Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar reported the effect of EGD on quality of life before and 1 week after the test in a clinical trial; despite symptoms remaining unchanged, quality of life improved toward normal after an EGD. However, the duration of any benefit is uncertain. Quadri and Vakil25Quadri A Vakil N. Health-related anxiety and the effect of open-access endoscopy in US patients with dyspepsia.Aliment Pharmacol Ther. 2003; 17: 1-6Crossref Scopus (35) Google Scholar reported that among those patients with high anxiety presenting for EGD in primary care, anxiety significantly improved after the procedure. This persisted for 6 months, although the clinical significance remains unclear. Others have observed that any reassurance after EGD was extremely short-lived.26Lucock MP Morley S White C Peake MD. Responses of consecutive patients to reassurance after gastroscopy: results of self administered questionnaire survey.BMJ. 1997; 315: 572-575Crossref PubMed Scopus (121) Google Scholar The benefits of negative testing in non-ulcer dyspepsia (NUD) has been modeled but this is highly complex; assuming negative tests improve quality of life, any benefit is likely to depend on an interaction of multiple influences including symptom severity and its response to therapy, and fear of serious disease including cancer.27Sonnenberg A Vakil N. The benefit of negative tests in non-ulcer dyspepsia.Med Decis Making. 2002; 22: 199-207PubMed Google Scholar Bytzer at al.28Bytzer P Hansen JM Schaffalitzky de Muchadell OB. Empirical H2-blocker therapy or prompt endoscopy in management of dyspepsia.Lancet. 1994; 343: 811-816Abstract PubMed Scopus (315) Google Scholar randomized 414 patients to either prompt endoscopy or empirical H2 antagonist therapy; patients with NUD at EGD received no antisecretory therapy. Among those who underwent endoscopy, one third had organic disease, mainly peptic ulcer disease; at 12 months' follow-up, no differences in symptoms or quality of life emerged in the two treatment groups. In favor of EGD, however, two thirds in the empiric therapy group underwent endoscopy, and patients were more satisfied in the prompt EGD arm.28Bytzer P Hansen JM Schaffalitzky de Muchadell OB. Empirical H2-blocker therapy or prompt endoscopy in management of dyspepsia.Lancet. 1994; 343: 811-816Abstract PubMed Scopus (315) Google Scholar However, patients could not be blinded to management and may have expected to have an EGD on entry, accounting for the results. A management trial of empiric H pylori “test and treat” versus EGD in 500 patients, on the other hand, did not demonstrate any convincing benefit of early EGD in terms of most outcomes assessed, although 12% were dissatisfied with “test and treat” compared with only 4% in the endoscopy arm.16Lassen AT Pedersen FM Bytzer P Schaffalitzky de Muckadell OB. Helicobacter pylori test-and-eradication versus prompt endoscopy for management of dyspepsia patients: a randomised trial.Lancet. 2000; 356: 455-460Abstract Full Text Full Text PDF PubMed Scopus (212) Google Scholar Application of H pylori testing to select patients for EGD (assuming those infected are more likely to have an ulcer and benefit from antibiotics but other infected cases will not) might seem to make sense (the “test and endoscope” strategy). However, Delaney et al.29Delaney BC Wilson S Roalfe A Roberts L Redman V Wearn A et al.Randomised controlled trial of Helicobacter pylori testing and endoscopy for dyspepsia in primary care.Br Med J. 2001; 332: 898-901Crossref Scopus (69) Google Scholar in a trial of “test and endoscope” in 478 patients under age 50 in primary care showed all this strategy achieved was an increase in EGD rates for no significant gain in terms of reduced symptoms, quality of life, prescribing, consultations, or referrals. Lewin van den Broek et al.30Lewin van den Broek NT Numans ME Buskens E Verheij TJ de Wit NJ Smout AJ. A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome.Br J Gen Pract. 2001; 51: 619-624PubMed Google Scholar in a management trial randomized 349 patients to either empiric treatment in which therapy was based on the presenting symptoms, or empiric treatment with omeprazole or cisapride regardless of the presenting symptoms, or prompt endoscopy followed by appropriate treatment; no differences among the strategies were detected although the study was underpowered.Detection of reflux esophagitis if severe (LA grades C and D) will change dyspepsia management (because these patients usually require long-term full-dose PPI therapy or surgery to maintain healing and symptom control).31Dent J Jones R Kahrilas P Talley NJ. Management of gastro-oesophageal reflux disease in general practice.BMJ. 2001; 322: 344-347Crossref PubMed Scopus (100) Google Scholar However, most patients with dyspepsia caused by GERD have no or only mild esophagitis. Moreover, there is evidence that EGD does not substantially change the clinical management in patients with GERD anyway; Blustein et al.32Blustein PK Beck PL Meddings JB Van Rosendaal GM Bailey RJ Lalor E et al.The utility of endoscopy in the management of patients with gastroesophageal reflux symptoms.Am J Gastroenterol. 1998; 93: 2508-2512Crossref PubMed Scopus (50) Google Scholar reported that among 742 patients undergoing endoscopy for GERD, most patients were maintained or switched to PPI regardless of the findings. Barrett's esophagus detection remains a highly controversial reason to perform endoscopy in all patients with dyspepsia; Barrett's esophagus is uncommon in this setting, and although it has been argued it may be cost-effective to screen 50-year-old men with primarily GERD symptoms, subsequent surveillance, even at 5-year intervals, is costly and of questionable benefit.33Nandurkar S Talley NJ. Surveillance in Barrett's oesophagus: a need for reassessment?.J Gastroenterol Hepatol. 1998; 13: 990-996Crossref PubMed Scopus (14) Google Scholar, 34Inadomi JM Sampliner R Lagergren J Lieberman D Fendrick AM Vakil N. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis.Ann Intern Med. 2003; 138: 176-186Crossref PubMed Scopus (346) Google Scholar Ofman and Rabeneck35Ofman JJ Rabeneck L. The effectiveness of endoscopy in the management of dyspepsia: a qualitative systematic review.Am J Med. 1999; 106: 335-346Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar concluded in a systematic review that there was a lack of convincing evidence that EGD improves patient outcomes, reduces subsequent use of resources, improves decision making, or is cost effective in dyspepsia management. Of course a lack of evidence is not the same as evidence of no benefit, and better studies are required.It is reasonably clear that use of antisecretory therapy before EGD should be strongly discouraged if the yield is to be maximized. How long should antisecretory therapy be held before undertaking EGD? Here the data are indeed scarce. Mild esophagitis and peptic ulcer will heal in at least 70% to 80% of cases within 4 weeks of beginning treatment with a PPI, but relapse once therapy is stopped is extremely variable.31Dent J Jones R Kahrilas P Talley NJ. Management of gastro-oesophageal reflux disease in general practice.BMJ. 2001; 322: 344-347Crossref PubMed Scopus (100) Google Scholar Moreover, some patients may develop acid rebound after discontinuing a PPI, and theoretically could then develop more symptoms, although the magnitude and duration of this problem is unclear.36Gillen D McColl KE. Problems related to acid rebound and tachyphylaxis.Best Pract Res Clin Gastroenterol. 2001; 15: 487-495Abstract Full Text PDF PubMed Scopus (54) Google Scholar Telling people to stop their PPI therapy for a few weeks before EGD is often impractical and may not greatly increase the diagnostic yield, although this needs to be studied formally.Current guidelines for management of dyspepsia recommend that patients with dyspepsia who fail to respond to an empiric course of PPI therapy should be referred promptly for an EGD,7Talley NJ Silverstein MD Agreus L Nyren O Sonnenberg A Holtmann G. AGA technical review: evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar, 14Eisen GM Dominitz JA Faigel DO Goldstein JA Kalloo AN Petersen BT et al.The role of endoscopy in dyspepsia.Gastrointest Endosc. 2001; 54: 815-817Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 15Talley NJ Axon A Bytzer P Holtmann G Lam SK Van Zanten S. Management of uninvestigated and functional dyspepsia: a Working Party report for the World Congresses of Gastroenterology 1998.Aliment Pharmacol Ther. 1999; 13: 1135-1148Crossref PubMed Scopus (102) Google Scholar but the observations by Smith et al.1Smith T Verzola E Mertz H. Low yield of endoscopy for persistent dyspepsia on proton pump inhibitors.Gastrointest Endosc. 2003; 58: 9-13Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar suggest that this may also need reconsideration. They noted that those who failed to respond to antisecretory therapy at all had no findings at endoscopy, in contrast to those who had excellent relief where 50% had endoscopic lesions.1Smith T Verzola E Mertz H. Low yield of endoscopy for persistent dyspepsia on proton pump inhibitors.Gastrointest Endosc. 2003; 58: 9-13Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar There is a lack of other good data on the yield of EGD in those who have failed to respond to initial empiric therapy, but because these tend to typically be younger patients with no other alarm features, it is not surprising little is usually found. Those with GERD causing dyspepsia, on the other hand, are likely to have a good response to empiric PPI. A recent decision analysis failed to support the cost-effectiveness of prompt EGD after initial empiric therapy had failed.20Spiegel BMR Vakil NB Ofman JJ. Dyspepsia management in primary care: a reappraisal of competing strategies.Gastroenterology. 2002; 122: 1270-1285Abstract Full Text Full Text PDF PubMed Scopus (114) Google ScholarIn conclusion, the management value of EGD in dyspepsia is limited whether done promptly or not, based on the available evidence. Worse, physicians must appreciate that they may inadvertently be misled by the EGD findings if the patient is taking concurrent antisecretory therapy or has recently stopped such therapy. There is the hope that new approaches might change the balance in favor of early EGD in the management of dyspepsia. Unsedated EGD with a small-caliber endoscope is feasible and cheaper than sedated endoscopy, and is reasonably well accepted by patients, but seems unlikely to be the answer.37Sorbi D Gostout CJ Henry J Lindor KD. Unsedated small-caliber esophagogastroduodenoscopy (EGD) versus conventional EGD: a comparative study.Gastroenterology. 1999; 117: 1307Abstract Full Text Full Text PDF Scopus (99) Google Scholar Novel technologies including EUS, the endoscopic video capsule, and endoscopic interventions for GERD and gastroparesis might increase the diagnostic and therapeutic value of early upper endoscopy, but seem unlikely to add enough to alter current management of dyspepsia in most cases.38Cappell MS Friedel D. The role of esophagogastroduodenoscopy in the diagnosis and management of upper gastrointestinal disorders.Med Clin North Am. 2002; 86: 1165-1216Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 39Sahai AV Penman ID Mishra G Williams D Pearson A Wallace MB et al.An assessment of the potential value of endoscopic ultrasound as a cost-minimizing tool in dyspeptic patients with persistent symptoms.Endoscopy. 2001; 33: 662-667Crossref PubMed Scopus (19) Google Scholar, 40Miller LS Szych GA Kantor SB Bromer MQ Knight LC Maurer AH et al.Treatment of idiopathic gastroparesis with injection of botulinum toxin into the pyloric sphincter muscle.Am J Gastroenterol. 2002; 97: 1653-1660Crossref PubMed Google Scholar, 41Triadafilopoulos G DiBaise JK Nostrant TT Stollman NH Anderson PK Wolfe MM et al.The Stretta procedure for the treatment of GERD: 6 and 12 month follow-up of the U.S. open label trial.Gastrointest Endosc. 2002; 55: 149-156Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar Although we as endoscopists tend to relish carefully viewing the upper GI tract in all patients with dyspepsia, our approach must be tempered by a realistic appraisal of the likely patient benefits. Esophagogastroduodenoscopy (EGD) remains the “gold standard” test in dyspepsia; physicians inherently believe the views obtained provide the truth. It is further assumed valid decisions are made after the test and the results alter practice appropriately. Smith et al.1Smith T Verzola E Mertz H. Low yield of endoscopy for persistent dyspepsia on proton pump inhibitors.Gastrointest Endosc. 2003; 58: 9-13Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar in this issue of the Journal, however, sound an important warning bell about the interpretation of EGD findings in dyspepsia. They evaluated the diagnostic yield in 100 patients with dyspepsia referred for EGD; regardless of whether patients continued to have symptoms while undergoing antisecretory therapy, significantly fewer endoscopic findings were present in the proton pump inhibitor (PPI)-treated group compared with those not receiving treatment. A similar trend was apparent for the H2 blocker-treated patients. The detection of esophagitis and peptic ulcers accounted for the differences observed. A larger retrospective audit reached similar conclusions; antisecretory use seems to blind us at least in some cases.2Mitchell RM Collins JS Watson RG Tham TC. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists.Endoscopy. 2002; 34: 524-526Crossref PubMed Scopus (11) Google Scholar Mitchell et al.2Mitchell RM Collins JS Watson RG Tham TC. Differences in the diagnostic yield of upper gastrointestinal endoscopy in dyspeptic patients receiving proton-pump inhibitors and H2-receptor antagonists.Endoscopy. 2002; 34: 524-526Crossref PubMed Scopus (11) Google Scholar reported that among over 4000 patients undergoing EGDs for uncomplicated dyspepsia, one third were undergoing acid suppression treatment; there were dramatic differences in terms of the rates of esophagitis among those taking PPIs (31%), H2 receptor antagonists (30%,) or no therapy (63%). Others have bemoaned the overuse of antisecretory therapy in dyspepsia because this may hide really serious disease during EGD. Wayman et al.3Wayman J Hayes N Raimes SA Griffin SM. Prescription of proton pump inhibitors before endoscopy. A potential cause of missed diagnosis of early gastric cancers.Arch Fam Med. 2000; 9: 385-388Crossref PubMed Scopus (27) Google Scholar reported a series of 7 patients in primary care with gastric ulcer cancers that became asymptomatic in response to treatment with a PPI before EGD, and the diagnosis was not made during the procedure. However, such a report is not particularly illuminating in terms of quantifying the magnitude of the problem. Bramble et al.4Bramble MG Suvakovic Z Hungin AP. Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastroscopy.Gut. 2000; 46: 464-467Crossref PubMed Scopus (90) Google Scholar reviewed 133 patients from a representative district in the United Kingdom who had died of upper GI cancer, mostly gastric adenocarcinoma. They noted that 22 of 62 patients treated with acid suppression were falsely given a diagnosis of benign disease at the index EGD, compared with only 1 of 54 patients taking antacids or no therapy.4Bramble MG Suvakovic Z Hungin AP. Detection of upper gastrointestinal cancer in patients taking antisecretory therapy prior to gastr