Clinical case discussion

1. Clinical case discussion Zhi Hua Ran Department of gastroenterology Ren Ji Hospital

2. Questions What are the common causes of upper abdominal pain?

3. Answer Gastroesophageal reflux Biliary colic Functional dyspepsia Peptic ulcer (duodenal ulcer, gastric ulcer) Gastric cancer Irritable bowel syndrome

4. Questions How to differentiate the common causes of upper abdominal pain?

5. Answer --- the clinical features Gastroesophageal reflux typically produces “heart burn”, or burning epigastric or mid-chest pain after meals and worse with recumbency Biliary colic caused by gallstones typically has an acute onset of severe pain located in the right upper quadrant or epigastrium precipitated by meals, fatty foods in particular lasts 30~60 min with spontaneous resolution more common in women

6. Answer --- the clinical features Functional dyspepsia can be associated with fullness, early satiety, bloating or nausea can be intermittent or continuous may or may not be related to meals symptom persisting at least 12 weeks Irritable bowel syndrome is a diagnosis of exclusion suggested by chronic dysmotility symptoms --- bloating, cramping that is often relieved with defecation without weight loss or bleeding

7. Answer --- the clinical features Peptic ulcer (duodenal ulcer, gastric ulcer) DU: the classic symptoms of duodenal ulcers are caused by the presence of acid without food or other buffers symptoms are typically produced after the stomach is emptied but food- stimulated acid production still persists, typically 2~5 h after a meal pain wake patients at night, when circadian rhythms increase acid production it is typically relieved within minutes by neutralization of acid by food or antacids GU: are more variable in their presentation food may actually worsen symptoms pain might not be relieved by antacids

8. Answer --- the clinical features Gastric cancer >45y alarm symptoms: weight loss, recurrent vomiting, dysphagia, bleeding, anemia earlier satiety, pain

9. Answer --- Peptic Ulcer Disease Summary: A 37-year-old man presents complaining of chronic and recurrent upper abdominal pain with characteristics suggestive of duodenal ulcer: the pain is burning in quality, occurs when the stomach is empty, and is relieved within minutes by food or antacids. He doesn’t have evidence of gastrointestinal bleeding or anemia. He does not take nonsteroidal antiinflammatory drugs, which might cause ulcer formation, but he does have serological evidence of H. pylori infection.

10. Question What are the roles of Helicobacter pylori (H. pylori ) infection and how to diagnose H. pylori infection?

11. Answer H. pylori is associated with duodenal and gastric ulcers, chronic active gastritis, gastric adenocarcinoma, and gastric MALT (mucosa-associated lymphoid tissue) lymphoma.

12. Answer The diagnosis of H. pylori infection Diagnostic methods for H. pylori infection are categorized into two groups as: Invasive Noninvasive

13. Answer Noninvasive: does not need endoscopic procedure Urea breath test --- evidence of current active infection convenient method H. pylori antibody --- evidence of prior infection, will remain positive for life Stool antigen test

14. Answer Invasive: need endoscopic biopsy of gastric mucosal sample Pathology (using special staining: Giemsa staining, silver staining, Gimenez staining, immunohistochemistry, in addition to Hematoxylin-eosin staining) Rapid urease test (RUT): H. pylori splits the urea in the test container to yield ammonia. Elevation of the pH by ammonium hydroxide produced in detected by a color change of the pH indicator. Advantage: inexpensive, ease to use, rapid diagnostic methods Disadvantage: require endoscopy, false-negative

15. Answer Invasive: Microaerobic bacterial culture Advantage: perfect specificity (100%), allowing further characterization of the organisms (determining its sensitivity to antibiotics) Disadvantage: most difficult to use in clinical setting

16. Question What is the most common cause of duodenal and gastric ulcers?

17. Answer H. pylori infection and use of NSAIDs are the common causes of peptic ulcer

18. Question What are the roles of Helicobacter pylori infection in the etiology of peptic ulcer disease?

19. Proposed natural history of H. pylori infection in human Environmental factors Gastric Cancer 80%~90% Multifocal Atrophic Gastritis Gastric Ulcer lymphoma Acute Gastritis Chronic Active Gastritis 95%~100% Duodenal Ulcer Antral Predominant Gastritis lymphoma

20. Question What are the roles of NSAIDs use in the etiology of peptic ulcer disease?

21. Answer In endoscopic clinical research studies of patients who take NSAIDs, 10~ 20% of patients in the first 3 months of NASID use develop new gastric ulcers and 4% to 10% develop duodenal ulcers. They promote ulcer formation by inhibiting gastroduodenal prostaglandin synthesis, resulting in reduced secretion of mucus and bicarbonate and decreased mucosal blood flow. In short, they impair local defense against acid damage. The risk of ulcer formation caused by NASID use is dose-dependent, and can occur within days after treatment is initiated.

22. Answer A rare cause of ulcer is the Zollinger – Ellison syndrome. It is the condition in which a gastrin-producing tumor (usually pancreatic) causes acid hypersecretion, peptic ulceration, and diarrhea. This condition should be suspected if ulcer disease occurs and the patient is H.pylori negative and does not use NSAIDs. To diagnose this condition, serum gastrin levels should be measured (>1000 pg/ml), and then try to localize the tumor with an imaging study.

23. Question What are the other clinical manifestations of peptic ulcer disease?

24. Answer---complications Hemorrhage: is the most common severe complication of peptic ulcer disease, and can present with hematemesis or melena. Freeperforation into the abdominal cavity may occur, with a sudden onset of pain and development of peritonitis Gastric outlet obstruction may develop in some patients with chronic ulcers, with persist vomiting and weight loss Perforation and obstruction are indications for surgical intervention

25. Question What is your next step?

26. Answer Eradication of H.pylori

27. Question Do you know any treatment regimen for H.pylori eradication?

28. Answer PPI based triple therapy omeprazole, lansoprazole, pantoprazole, rabeprazole Bismuth based triple therapy (colloidal bismuth subcitrate) Metronidazole: 400 mg bid Amoxicillin: 500 mg bid Clarithromycin: 250 ~ 500 mg bid Tetracycline: 500 ~1000mg bid Furazolidone: 100 mg bid Ranitidine Bismuth Citrate (RBC) 7~14 days

29. Answer Antisecretory treatment: lasts for 2~4 weeks

30. Comprehension questions (I) A 42-year-old overweight, though otherwise healthy, women presents with the sudden onset of right upper abdominal colicky pain 45 minutes after a meal of fried chicken. The pain is associated with nausea and vomiting, and any attempt to eat since has caused increased pain. The mostly cause is: A: Gastric ulcer B: Cholelithiasis C: Duodenal ulcer D: Acute hepatitis

31. Answer --- B Right upper abdominal pain that has an acute onset after the ingestion of a fatty meal and that is associated with nausea and vomiting is most suggestive of biliary colic as a result of gallstones. Duodenal ulcer pain is likely to be determined with food, and gastric ulcer pain is not likely to have the acute severe onset. Acute hepatitis is more likely to produce dull ache and tenderness

32. Comprehension questions (II) Which of the following is not true of H.pylori infection: A. It is more common in developing counties It is associated with the development of gastric lymphoma It is believed to be the cause of nonulcer dyspepsia The route of transmission is believed to be fecal – oral It is believed to be a cause of most duodenal and gastric ulcer

33. Answer --- C While H.pylori is clearly linked to gastric and duodenal ulcers, and probably to gastric carcinoma and lymphoma, it is unclear whether it is more common in patients with nonulcer dyspepsia, or whether treatment in those patients reduces symptoms.

34. Comprehension questions (III) A 45-year-old male was brought to the emergency room after vomiting bright red blood. He has a blood pressure of 88/46 mmHg and heart rate of 120 bpm. Which of the following is the best next step? IV fluid resuscitation and preparation for a transfusion Administration of a proton pump inhibitor Guaiac test the stool Treatment for H.pyroli

35. Answer --- A This patient is hemodynamically unstable with hypotension and tachycardia as a consequence of the acute blood loss. Volume resuscitation, immediately with crystalloid or colloid solution, followed by blood transfusion, if necessary, is the initial step to prevent irreversible shock and death. Later, after stabilization, acid suppression and H.pylori treatment might be useful to heal an ulcer, if one is present.

36. Comprehension questions (IV) Which one of the following patients should be promptly referred for endoscopy? A 65-year-old man with a new onset of epigastric pain and weight loss A 32-year-old whose symptoms are not relieved with ranitidine A 29-year-old H. pylori- positive patient with dyspeptic symptoms A 49-year-old women with intermittent right upper quadrant pain following meals

37. Answer --- A Patient “A” has a red flag: he is older than 45 years of age with new onset symptoms. Patient “B” may benefit from the reassurance of a negative endoscopic exam. Patient “C” may benefit from treatment of the her H.pylori first. Some studies indicate this approach may be cost-saving overall. This patient could be sent for an endoscopic examination if she doesn’t improve following therapy.