Peptic Ulcer

1. Peptic Ulcer Chaohui Yu ych623@sina.com 13957161659

2. Suggested readings • 消化性溃疡,内科学第二版,人民卫生出版社,434-445 • Acid peptic disease, Cecil medcine,24th edition,886-895 • Peptic ulcer disease, Lancet, 2009; 374: 1449-1461 • Helicobacter pylori infection, N Engl J Med,2010;363;1597-1604

3. Suggested readings • Challenges in the management of acute peptic ulcer bleeding , Lancet, 2013; 381: 2033-43 • Clinical effects of Helicobacter pylori outside the stomach, Nat Rev Gastroenterol Hepatol. 2014;11:234-42.

4. The self-digestion of GI mucosa • caused by gastric acid and pepsin • The rate is 10% in population

5. Why does the ulcer happen?- normal defense Bicarbonate Acid, pepsine mucus layer epithelial cell submucosa

6. Defensive barrier of gastric and duodenal mucosa mucus barrier physical defense chemical counteraction • mucosal barrier • quick refreshment of • epithelial cell • abundant circulation of blood • nutrition factor: PGE1,EGF • intercellular tight junction • abundant submucosal • blood vessel • HCO3- counteracts H+

7. Acid, pepsine attack factors defence factors Balance in attack and defence

8. Mucosal damage Pathogenesy of PU • Acid and Pepsine • Helicobacter pylori • NSAIDs • Motility disturbance • Stress • Systemic inflammatory disorders • Ischemia • Hypergastrinemic Syndromes • Hyperhistaminic Syndromes • Anastomotic or marginal Ulceration • Alcohol • Tobacco defence attack

9. Maximum activity of enzyme(%) 100 80 60 40 20 0 1 2 3 4 Gastric fluid pH Pathogenesy of PU—Acid & Pepsine Pepsine • rely on Acid • no acid,no ulcer • parietal cell mass 2 4 • parietal sensibility • feedback suppression • vagal tone

10. Pathogenesy of PU —Helicobacter Pylori • Biology • bostrychoid,have flegalla, • microamount requirement of oxygen • urase: urea NH3 • Vac A, Cag A • Evidence-based medicine • high positive rate of HP in PU • the eradication of Hp facilitate the healing of PU • the eradication of Hp degrades the recurrence of PU

11. 2005年10月

12. Pathogenesy of PU—Helicobacter Pylori • The colonization factor of HP • bostrychoid,have flegalla • urase • especial adherence factor • Invasive factor • urase ammoniacal toxicity • Vac A, Cag A and • phosphatidase A1 • chemotact and activate inflammatory cell • antigen imitate • Two theory: • hypothesis of leaking roof • gastrin-link hypothesis • D cell & somatostatin

13. Infection with H. pylori results in anacute inflammatory reaction Epithelial cell O2 radicals IL-8 Proteolyticenzymes Polymorph

14. Increasing proportion of H. pylori-negative ulcers 1995–2000 2000 1995 13% 33% 67% 87% H. pylori-negative gastroduodenal ulcers H. pylori-positive gastroduodenal ulcers Juhasz, Gut 2001; 49: A64.

15. guard gastric and duodenal mucosa Pathogenesy of PU— non-steroidal anti-inflammatory drugs, NSAID Arachidonic acid Cox1 Cox2 cycloxygenase antiinflammatory analgesia gastrointestinal damage nephrotoxicity X The synergistic affection of Hp and NSAID prostaglandin Maintain the function of kidney and platelet Inflammation、pain

16. PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

17. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

18. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

19. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

20. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

21. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

22. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

23. + Pathogenesis of NSAID-induced ulcers PROTECTIVE FACTORS AGGRESSIVE FACTORS Prostaglandins NSAIDs Acid + pepsin H. pylori Mucus layer Bicarbonate Surface epithelial cells Mucosal blood supply Seager & Hawkey, BMJ 2001; 323: 1236–9.

24. Ulcers related to NSAID use1995–2000 2000 1995 17% 31% 83% 59% NSAID-related ulcers Ulcers not related to NSAID use Juhasz, Gut 2001; 49: A64.

25. Aspirin correlated ulcer Large GU, which healed in 14Wk after stopping aspirin use Deep GU unhealed for 5 years with continued aspirin abuse Large DU, which healed after stopping aspirin

26. Location • DU: bulbar zone,antetheca • GU:lesser curvature side of sinus ventriculi,gastric corner • Especial denomination • complex ulcer: DU+GU • multiple ulcer: ≥two • two symmetria ulcers • enormous ulcer • DU>2cm,GU>3cm

27. Clinical manifestation—upper GI symptoms • Chronicity、periodicity、rhythmic • Pain • DU：pain in hanger/hypnalgia， • remittence after the meal • pain- foodintake-remittence • GU：pain after the meal • foodintake-pain-remittence • location/property • Other dyspepsia symptoms

28. Especial type of ulcer • Symptomless PU：15-35%，see a doctor after the appearance of the complications • PU in olders：most of superior positional/enormous ulcer ,often atypical symptoms • Complex ulcer：DU often happens earlier than GU, often atypical symptoms • Ulcer of pyloric canal：more gastric acid、bad curative effect、more complications • Post bulbar ulcer：night pain、radiating pain、more complications， bad curative effect. Difficult curable ulcer

29. Differential diagnosis of symptoms Chronic gastritis/functional dyspepsia •   have symptoms，but no evidence Chronic cholecystitis/cholelithiasis •   the discrimination is difficult，oily food，BUS Castric carcinoma •    the discrimination is difficult in symptoms,gastroscope and pathologicalexamination are critical • atypical+multiple+more • complications+diarrhea Hookworm infection Gastrin adenoma

30. Diagnosis—the existence of ulcer is true or untrue X –ray examination • Direct sign：niche sign • Indirect sign：spasmus、irritation • tenderness、deformation Gastroscopy：focus lesions+biopsy +Hp examination •  Active stage (A1,A2) •  Healing stage(H1,H2) •  Scar stage(S1,S2) A1 H1 S2

31. Diagnosis—Hp infection is yes or no? virulence—need taking gastric mucosa • (RUT): ammine • Histological examination • Cultivation • PCR Non –virulent examination—not need taking gastric mucosa • Breath test • Serology • Hp stool antigen Urase based test: RUT、UBT

33. Diagnose-if have complication upper GI hemorrhage (UGIH) •   the most common complication •   the first symptom of hemorrhage by • 10%-20% ulcer • activity symptom before hemorrhage • perforation •    acute perforation ：acute diffuse peritonitis •    penetrability perforation ： lesser bursa omentalis • subacute perforation pyloric obstruction：functionality/parenchymatous obstruction canceration：warning sings and symptoms • chronic patient history age>45(GU) • symptom has changed recently and curative effect badly • the appearance of hemorrhage :stool OB (+), • anemia • emaciation

34. PU cure-purpose Eliminate cause of a disease、relieve symptom、heal ulcer、prevent recurrence、avoid complication defend attack Factitiousness intervention to speed up ulcer healing

35. PU cure—degrade gastric acid Antacid：counteract gastric acid obviously rebound Acid-reducing Drugs ：H2RA，PPI H+ Omeprazole Lansoprazole pantoprazole Rabeprazole PPI DU:4-6 Wk GU:6-8 Wk Cimetidine Famotidine Nizatidine Ranitidine H2RA Ach Histamine Gastrin

36. PU cure—Eradication Hp Program • Trigeminy with the core of PPI • PPI+(Clarithromycin/amoxicillin )+(furazlidone /metronidazole), Bid, 7-14d • Trigeminy with the core of bismuth • To object: blind medication ,single/ double • medication Re-examination ? •  Eradication:after course of treatment to • end for 4 weeks,HP Negative • Generally do not request re-examination

38. Influence of successful eradication of H. pylori on ulcer healing Review of 60 trials; 4329 patients Ulcer healing rate according to post-treatment H. pylori status ***95 **88 H. pylori eradicated H. pylori persisted 100 76 73 **p<0.01 ***p<0.001 Healing rate (%) 0 Gastric ulcer Duodenal ulcer Treiber & Lambert, Gastroenterol 1998; 93: 1080–4.

39. H. pylori eradication reduces recurrence in gastric ulcer 100 Non-eradicated H. pylori infection Eradicated H. pylori infection 80 60 Gastric ulcer recurrence (%) 40 20 0 Labenz Sung Labenz Karita Seppälä & Borsch et al. & Borsch et al. et al. (n=11) (n=19) (n=18) (n=4) (n=42) Labenz Sung Labenz Karita Seppälä & Borsch et al. & Borsch et al. et al. (n=16) (n=26) (n=32) (n=26) (n=10) Hopkins et al., Gastroenterol 1996; 110: 1244–52.

40. Eradication of H. pylori almost eliminates duodenal ulcer recurrence H. pylori + ve H. pylori – ve ***96 ***95 ***95 ***92 100 58 Patients in remission (%) 40 30 25 0 0 Months 6 12 18 24 ***p<0.001 Huang et al., Am J Gastroenterol 1996, 91: 1914.

41. The treatment of complication Peptic Ulcer Hemorrhage

42. THANK YOU