Peptic Ulcer (peptic ulcer disease)

Shanghai Ren-Ji Hospital Shanghai Institute of Digestive Disease Wenzhong Liu

What is the peptic ulcer ?

Definition



Craters extending to below the muscularis mucosa of stomach (GU) or duodenum (DU).



A products of self-digestion.

Epidemiology

 Estimated life time prevalence :10%   Male: female =3- 4:1 Ratio of DU: GU = 3:1  DU emerges 10-20 years earlier than GU

Etiology & Pathogenesis

Barrier of Gastric Mucosa

Etiology & Pathogenesis



Helicobacter pylori infection



NSAIDs & Aspirin



Acid/Pepsin



Smoking



Genetics



Psychological factors

Nonsteroidal anti-inflammatory drugs, NSAIDs

Etiology & Pathogenesis

Aggressive Factors

Acid/Pepsin  H. pylori infection  NSAIDs  Smoking

Defensive Factors

 Mucus-bicarbonate barrier  Barrier of apical membrane  Mucosal blood flow  Prostaglandins  Epithelial cell restitution

I

Aggressive Factors  Defensive Factors

III

Aggressive Factors 

+

Defensive Factors  

II

Evolving Knowledge

Dictum    No acid, no ulcer No acid, no Hp, no ulcer No Hp, No NSAIDs, no ulcer

Under Electromicroscopy

Clinical Evidences That H.pylori Infection Plays Major Role in Peptic Ulcer  High prevalence of Hp infection in peptic ulcer.

 DU: 90-100%;  GU:70-90%  Eradication of Hp improves healing of ulcer.

 Healing refractory ulcer  Shortening treatment course: 4 - 6 weeks 1-2 weeks

Clinical Evidences That H.pylori Infection Plays Major Role in Peptic Ulcer  Eradication of Hp markedly reduces relapse and complication rates of ulcer.

 50 - 70%/yr < 5%/yr  Prospective study shows that individuals infected with Hp has higher risk of developing peptic ulcer.

 15 - 20%

Why anti-secretory agents can heal H.pylori associated peptic ulcer?

Acid   Anti-secretory agents Mucosal Barrier

“Leaking Roof ” Hypothesis Mucosal Barrier

The strongest evidence for the pathogenic role of

H. pylori

in peptic ulcer disease is the marked decrease in the recurrence rate of ulcers following the eradication of infection.

“for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease”

Why only a part of patients with H.pylori infection have peptic ulcer?

H.pylori

Virulence Host Factor IL-1B polymorphism Environment Factors

NSAIDs & Peptic Ulcer

Gastric acid plays a central role in NSAID-associated gastroduodenal damage

Bicarbonate layer Surface epithelial cells

NSAID Damage to the Gastric Mucosa

Scanning electron micrographs of normal gastric mucosa (left) and mucosal surface (right) 16 minutes after administration of aspirin Baskin et al 1976

 

Two Common Forms of Peptic Ulcer

H.pylori – associated: 70-85% NSAIDs – associated: 10-25% Non-Hp, Non-NSAID Ulcer: 5-30%

Acid /Pepsin

 By definition, peptic ulcer is caused by autodigestion of acid and pepsin  Activity of pepsin is pH-depedent  Pepsinogen pepsin pH< 4  Maintaining activity pH< 4  Usual therapy toward suppression of acid

The influence of pH on gastric pepsin activity

1 2 3 4 Adapted from Berstad 1970

Smoking & Peptic Ulcer

 Increasing incidence of peptic ulcer  Delaying healing of ulcer  Increasing relapse and complication  Mechanisms:  Facilitating bile reflux  Decreasing mucosal blood supply  Inhibiting synthesis of PGs

Genetics & Peptic Ulcer

 Familial Clustering  Genetic factors  Environment factor : H. pylori infection

Genetics & Peptic Ulcer

 Concordance of peptic ulcer is more common in monozygotic that dizygotic twins.

 Peptic ulcer occurs in a few rare inherited syndromes.

 Gastrinoma  Mastocytosis

Psychological Factor in Peptic Ulcer

 Controversial  Possible mechanisms through vagal mechanisms,  Stimulating acid secretion  Decreasing mucosal blood supply

Clinical Presentation

 Symptoms are neither specific nor sensitive  Silent Ulcer  Emergence of complications: bleeding, perforation  Discovered b y chance

Clinical Presentation



Acid dyspepsia in DU

 Epigastric “ hunger ” pain or discomfort ；  Occurred 2-4 hours after meal ， or at night;  Relieved by food or antacids; 

Acid dyspepsia in GU

 More severe pain ；   Occurred soon after meal ； Less relieved by food or antacids;

Physical Examination

 Limited value in patients with uncomplicated ulcer.  Epigastric tenderness on deep palpitation in active stage.

Sensitivity 50% Specificity 50%

Atypical Ulcers

 Giant Ulcer DU>2cm, GU>3cm  Pyloric Channel Ulcer  Pain occurring shortly after meal.

 Poor relief by antacids  Vomiting  Postbulbar Ulcers  Multiple Ulcers

Laboratory Examination

 Detection of H. pylori Infection Essential  Gastric Secretory Test For ruling out Zollinger-Ellison Syndrome  Determination of Serum Gastrin level For ruling out Zollinger-Ellison Syndrome  Fecal Occult Blood Test Nonspecific

Detection of H. pylori Infection

Direct smear PCR 13 C- Breath test

Warthin -Starry Stain Acridine orange stain

Endoscopy versus Radiography

 Endoscopy has a greater accuracy of establishing diagnosis than radiography.

 Endoscopy can take biopsies for histology, ruling out malignancy, and  detection of Hp.

Endoscopy can carry out therapy.  Cost  Risk

Endoscopy Gastric ulcers

Endoscopy Duodenal ulcer

Peptic ulcers

Staging of peptic ulcer under endoscopy

Barium Radiogram

Differential Diagnosis

 Functional dyspepsia: By Endoscopy  Zollinger Ellison Syndrome (Gastrinoma)  Gastric Malignant Ulcer: Endoscopy + Biopsy  Biliary or pancreatic diseases: Ultrosonography, MRCP, ERCP

Zollinger Ellison Syndrome



Clinical Characteristics

 Peptic ulcer with Diarrhea    Peptic ulceration in unusual location Multiple ulcers Refractory ulcer   Complications No H.pylori, no NSAIDs 

Gastric Secretory Test

 Basic acid output > 15mEq/hour 

Determination of Serum Gastrin level

 Fasting serum gastrin >500pg/ml

Complications

 Hemorrhage  Perforation  Pyloric Obstruction  Malignant Transformation(GU)

Free perforation

Gastric outlet obstruction (Pyloric obstruction)

Malignant Transformation 1

％

-3%

Medical Therapy

Aims of Treatment

 Removing underlying cause of peptic ulcer  Relieving symptoms  Healing ulcer  Preventing relapse of ulcer  Avoiding complications

Aggressive Factors

Acid/Pepsin  H. pylori infection  NSAIDs  Smoking

Defensive Factors

 Mucus-bicarbonate barrier  Barrier of apical membrane  Mucosal blood flow  Prostaglandins  Epithelial cell restitution

I

Aggressive Factors  Defensive Factors

III

Aggressive Factors 

+

Defensive Factors  

II

Strategies for healing ulcer



Eradicate H. pylori



Inhibit acid secretion



Improve mucosal defense

Eradicate H. pylori infection

PPI (H 2 -RA) or Bismuth

+

Two Antibiotics

Colloidal Bismuth Subcitrate ( CBS) 240mg Clarithromycin 250-500mg Amoxicillin 500-1000mg (Tetracycline) Metronidazole 400mg Furazolidone 100mg

Triple therapy, bid for 1 week

Inhibit acid secretion

 H 2 -Receptor Antagonists    Cimetidine 400mg bid Ranitidine 150mg bid Famotidine 20mg bid  Proton Pump Inhibitors  Omeprazole 20mg qd    Pantoprazole 40mg qd Rabeprazole 10mg qd  Lansoprazole 30mg qd Esomeprazole 20mg qd

DU

：

4 - 6 wks GU

：

6 - 8 wks

H 2 -RAs ATP PGs PPIs

Improve mucosal defense



Sucralfate

  Ulcer isolation Promoting PGs synthesis and release 

Colloidal Bismuth Subcitrate

 Ulcer isolation   Promoting PGs synthesis and release Anti-H.pylori

Healing Rates of DU After 4 Weeks Treatment with Various Anti-ulcer Agents

Placebo Misprostol Bismuth Sucralfate H2-RA PPIs 0 20 40 60 80 % 100

Preventing relapse of ulcer & Avoiding complication

 Eradication of H. pylori   Cost - effect Relapse rate < 5%/yr  Maintaining Therapy  Half dose of H 2 -RA q.n.

 6 months or longer  Relapse rate around 25%/yr

Treatment and prevention of NSAIDs-associated ulcer   Discontinuing NSAIDs  Medical Treatment  PPIs  Higher dose of H 2 -RA Prevention  Eradicating H.pylori ?

 Misoprostol (PGE 2 )  PPIs  Sucralfate ?

Surgical Therapy

  Rare event Indication for surgery    Perforation Intractable bleeding Gastric outlet obstruction   (Scaring) Malignant transformation Surgical options

Billroth I

Billroth II

Gastric ulcer biopsy, R/O cancer Establish the diagnosis (endoscopy or UGI) Duodenal ulcer Assess pathogenesis: H.pylori NSAIDs Smoking Family history Serum gastrin Endoscopic follow-up to healing Therapy: Treat H.pylori

Acid suppression Enhance mucosa defense Document H.pylori eradication Complications Surgery (obstruction, perforation, intractable bleeding, malignant transformation)

Thank You