An approach to dyspeptic patients A Aljebreen, MD, FRCPC KKUH, Riyadh, Saudi Arabia March 2008

Learning objectives Definitions? Epidemiology? DDx and investigation? An approach to dyspepsia Endoscopy or not? Management recommendations

Case#1 A 44 yr old Male presented with a 1 y h/o intermittent epigastric pain, often 1hr after meals. No wt loss, vomiting or symptoms of GI bleeding. No history of constipation or bloating. What is your next step?

Definitions Dyspepsia is a nonspecific term to denote upper abdominal discomfort. Dyspepsia may encompass a variety of more specific symptoms, including epigastric discomfort, bloating, anorexia, early satiety, belching regurgitation, nausea, and heartburn.

Definitions The Rome III Committee defined dyspepsia as one or more of the following 3 symptoms: Postprandial fullness Early satiety Epigastric pain or burning Tack et al. Functional GI disorders. Gastroenterology 2006;130:1466-79.

epidemiology It occurs in approximately 25 percent of the population each year, but most affected people do not seek medical care. Dyspepsia is responsible for substantial health care costs and considerable time lost from work

causes? Symptoms of dyspepsia most commonly result from 1 of 4 underlying disorders: PUD (5-15%) GERD (heartburn and regurgitation) functional disorders (non-ulcer dyspepsia, 60%), and Malignancy (1-3%) Other problems, such as Medication intolerance, Pancreatitis, Biliary-tract disease, or Motility disorders (SOD) IBS (considerable overlap with functional dyspepsia) Vakil et al. Gastroenterology 2006;131:390-401.

CLINICAL APPROACH History Physical examination A thorough history can be useful for narrowing the differential diagnosis and helping to focus evaluation and management. Physical examination  The physical examination is usually normal. Routine laboratory tests  Routine blood counts and blood chemistry determinations are commonly obtained. These tests help to identify patients with "alarm symptoms" (eg, anemia) who require endoscopy.

Patients > 50 or with alarm symptoms Endoscopy Age > 50 y, with new onset symptoms Family history of upper-GI malignancy Unintended weight loss GI bleeding or iron deficiency anemia Progressive dysphagia Odynophagia Persistent vomiting Palpable mass or lymphadenopathy Jaundice

Alarm features Poor outcomes: Low diagnostic yield: In a prospective questionnaire study, patients with alarm symptoms and dyspepsia had a significant increase in both GI cancer and mortality over a 3-year period. Low diagnostic yield: In a meta-analysis of 15 studies that evaluated more than 57,000 patients with dyspepsia, alarm symptoms showed a PPVfor GI cancer of < 11% with 97% NPV ¼ of patients with malignancy and dyspepsia have no alarm symptoms. Vakil et al. Gastroenterology 2006;131:390-401. Fransen et al. Aliment Pharmacol Ther 2004;20:1045-52. Meineche-Schmidt et al. Scand J Gastroenterol 2002;37:999-1007.

PATIENTS WITHOUT ALARM FEATURES Noninvasive testing for Helicobacter pylori, with subsequent treatment if positive (the ‘‘test and- treat’’ approach); A trial of acid suppression; or An initial endoscopy. GI ENDOSCOPY. 2007

(1)Test-and-Treat approach Noninvasive testing options for H pylori include serology, urea breath testing (UBT), and stool antigen. Serologic testing has a sensitivity that ranges from 85% to 100%, with a specificity of 76-96%. The specificities of UBT and stool antigen are higher than serologic testing.

Pros of T & T approach Similar outcomes: It is more cost effective. Patients who undergo the test-and-treat approach have similar outcomes to those undergoing initial endoscopy. It is more cost effective. Results from a meta-analysis of 5 randomized studies of test-and-treat versus an initial endoscopy showed a negligible improvement of symptoms in the endoscopy group but a savings of $389 per patient in the test-and-treat group. Results from a large, randomized study that compared test-and-treat with initial endoscopy found no significant difference in dyspeptic symptoms at 1 year but with a 60% reduction in endoscopy utilization in the test-and treat group Lassen et al. Lancet 2000

Problems of the T & T approach Unsatisfaction: 12% of patients in the T & T group were dissatisfied with their treatment plan versus only 4% in the endoscopy group. At 6.7 years, reduction in endoscopy utilization was only 38%. Increase risk of Clostridium difficile-associated colitis and induction of antibiotic resistance. Lassen et al. Lancet 2000 Lassen et al. Gut 2004

(2)Acid-suppression therapy Proton pump inhibitors (PPI) are more effective than H2 blockers in this approach. Initiation of empiric acid suppression will not address underlying H pylori in those patients with H pylori–associated peptic ulcer disease, risking recurrent symptoms when acid suppression is withdrawn.

PPI vs Test and Treat approach In one study that compared PPI therapy with the test-and-treat approach in patients < 45 years of age, a higher endoscopy rate was seen in the PPI treatment group (88% vs 55%). A decision analysis showed that cost-effectiveness of the test-and-treat approach versus empiric acid suppression depends on the prevalence of H pylori. If the incidence of H pylori is <20%, then empiric acid-suppression therapy is more cost effective. Ladabaum et al. Aliment Pharmacol Ther 2002 Manes et al. BMJ 2003

PPI vs Endoscopy In a study that compared empiric H2 blockers with early endoscopy, endoscopy was eventually performed in 66% of the H2 blocker group. Costs were higher in this group. There are limited comparative studies of empiric PPI and endoscopy. It is unclear whether patients with dyspepsia who require prolonged PPI use should undergo an endoscopy. An endoscopy may still need to be considered in the group of non responders to exclude structural disease.

(3)Initial upper endoscopy One advantage of early endoscopy is the possibility of establishing a specific diagnosis, such as PUD or erosive esophagitis. The risk of malignancy is quite low in young patients without alarm features, however, many patients with early stage malignancy do not have alarm symptoms. Another advantage of a negative endoscopy is a reduction in anxiety and an increase in patient satisfaction. Most studies demonstrate an increased cost with the initial endoscopic approach compared with the test-and-treat method. Ford et al. Gastroenterology 2005 Delaney et al. Cochrane Database Syst Rev(4):2005;

Endoscopy Is Necessary Before Treating H pylori in patients with Dyspepsia??

Endoscopy Is Necessary Before Treating H pylori in patients with Dyspepsia We should look at the issue in three perspectives: (a) How effective is the treatment of H. pylori infection in curing dyspepsia? (b) Are we seeing the patient in a primary care setting or as a referral case to a gastroenterologist? (c) Does the patient come from a high-risk background?

How effective is treating H. pylori infection in curing dyspepsia? In a recent systematic review of the Cochrane Database, 18 trials that compared antisecretory dual or triple therapy against placebo showed only a modest (relative risk reduction 10%) reduction of dyspepsia after H. pylori eradication. The NNT is 14 (thus 13 pts remain symptomatic after curing H. pylori and require further investigations or empirical therapy) On the other hand, when six trials compared H. pylori testing and treatment versus endoscopy, initial endoscopy was associated with a 25% reduction in the risk of recurrent dyspeptic symptoms compared with H. pylori treatment. After the successful eradication of H. pylori, a patient may not be adequately reassured and quality of life may not be improved.

Primary care vs GI A trial enrolling 478 subjects from the United Kingdom showed that in patients under the age of 50 yr, applying a test-and-endoscopy strategy to H. pylori-positive dyspeptics increased the endoscopy load by 25–40%. There was no improvement in symptom score or quality of life of the patients. In Hong Kong, where 50% of the population are H. pylori positive and 10% of gastric cancer patients are below of 45 yr, a cohort study enrolled 1,017 subjects below 45 yr without alarm symptoms In this study, 0.4% of gastric cancers would have been missed if endoscopy had not been offered in the referral centers.

Guidelines in recommending endoscopy or H Guidelines in recommending endoscopy or H. pylori treatment are not always clear about the difference in the primary versus secondary level of consultation. No clear guidelines here, however patients who have gone through empirical therapy with acid suppression given by primary care physicians should not be probably observed in the specialist clinic for 3–12 months after H. pylori therapy and before endoscopy is considered.

Does the patient come from a high-risk background? In a high-prevalence country, one would expect to find more gastric and esophageal malignancy among dyspeptic patients above 50 yr and prompt endoscopy should not be withheld in these patients.

The cost effectiveness? The incremental cost-effectiveness is very sensitive to the cost of endoscopy. The cost-effectiveness ratio could be reduced to 1/10 if cost of endoscopy fell from £246 to £100. In high prevalent countries for H. pylori infection and gastric cancer, a more liberal approach to endoscopy would be necessary to avoid missing the diagnosis of cancers in the stomach.

RISKS OF MISSING CANCER Meineche-Schmidt and Jorgensen compared the incidence of upper gastrointestinal cancer over the subsequent 3 yr in 883 patients presenting with uncomplicated dyspepsia versus 988 population controls Incidence of cancer was 0.4% in pts with uncomplicated dyspepsia and similar at 0.5% in the controls. Would you do endoscopy to detect early gastric cancer in patients presenting with a sprained ankle or a headache?

IS IT NECESSARY TO DIAGNOSE PEPTIC ULCERS? There is evidence that eradication of H. pylori may be appropriate and beneficial in dyspeptic patients without as well as with peptic ulcer disease. A large meta-analysis indicates that eradication is cost-effective in the management of nonulcer dyspepsia.

Suggested algorithm for evaluation of dyspepsia

Management of functional dyspepsia

RECOMMENDATIONS ASGE Guidelines. GI ENDOSCOPY . 2007

RECOMMENDATIONS Patients with dyspepsia > 50 yrs and/or those with alarm features should undergo endoscopic evaluation. (1C) Patients with dyspepsia <50 yrs and without alarm features may undergo an initial test-and-treat approach for H pylori. (1B) Patients < 50 yrs and are H pylori negative can be offered an initial endoscopy or a short trial of PPI acid suppression. (2B) Patients with dyspepsia who do not respond to empiric PPI therapy or have recurrent symptoms after an adequate trial should undergo endoscopy. (3) ASGE Guidelines. GI ENDOSCOPY . 2007