Peptic Ulcer

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Peptic Ulcer (peptic ulcer disease)
Shanghai Ren-Ji Hospital Shanghai Institute of
Digestive Disease Wenzhong Liu
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What is the peptic ulcer ?
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Definition

• Craters extending to below the muscularis
• mucosa of stomach (GU) or duodenum (DU).
• A products of self-digestion.

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Epidemiology

• Estimated life time prevalence 10
• Male female 3- 41
• Ratio of DU GU 31
• DU emerges 10-20 years earlier
• than GU

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Etiology Pathogenesis
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Barrier of Gastric Mucosa
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Etiology Pathogenesis

• Helicobacter pylori infection
• NSAIDs Aspirin
• Acid/Pepsin
• Smoking
• Genetics
• Psychological factors

Nonsteroidal anti-inflammatory drugs, NSAIDs
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Etiology Pathogenesis
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• 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

Defensive Factors ?
Aggressive Factors ?
I
II
III
Aggressive Factors ? Defensive Factors ?
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Evolving Knowledge

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

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Under Electromicroscopy
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Clinical Evidences That H.pylori Infection
Plays Major Role in Peptic Ulcer

• High prevalence of Hp infection in peptic ulcer.
• ?DU 90-100
• ? GU70-90
• Eradication of Hp improves healing of ulcer.
• ? Healing refractory ulcer
• ? Shortening treatment course
• 4 - 6 weeks 1-2 weeks

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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 lt 5/yr
• Prospective study shows that individuals
  infected
• with Hp has higher risk of developing
  peptic ulcer.
• ? 15 - 20

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Why anti-secretory agents can heal H.pylori
associated peptic ulcer?
? Anti-secretory agents
Acid ?
Mucosal Barrier
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Leaking Roof Hypothesis
Mucosal Barrier
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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.
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for their discovery of the bacterium
Helicobacter pylori and its role in
gastritis and peptic ulcer disease
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Why only a part of patients with H.pylori
infection have peptic ulcer?
H.pylori Virulence
Host Factor
Environment Factors
IL-1B polymorphism
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NSAIDs Peptic Ulcer
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Gastric acid plays a central role
inNSAID-associated gastroduodenal damage
Bicarbonate layer
Surface epithelial cells
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NSAID Damage to the Gastric Mucosa
Scanning electron micrographs of normal gastric
mucosa (left) andmucosal surface (right) 16
minutes after administration of aspirin
Baskin et al 1976
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Two Common Forms of Peptic Ulcer

• H.pylori associated 70-85
• NSAIDs associated 10-25

Non-Hp, Non-NSAID Ulcer 5-30
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Acid /Pepsin

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

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The influence of pH on gastricpepsin activity
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Adapted from Berstad 1970
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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

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Genetics Peptic Ulcer

• Familial Clustering
• ? Genetic factors
• ? Environment factor H. pylori infection

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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

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Psychological Factor in Peptic Ulcer

• Controversial
• Possible mechanisms
• through vagal mechanisms,
• ? Stimulating acid secretion
• ? Decreasing mucosal blood supply

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Clinical Presentation

• Symptoms are neither specific
• nor sensitive
• Silent Ulcer
• ? Emergence of complications
• bleeding, perforation
• ? Discovered by chance

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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

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Physical Examination

• Limited value in patients with
• uncomplicated ulcer.
• Epigastric tenderness on deep
• palpitation in active stage.
• Sensitivity 50
• Specificity 50

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Atypical Ulcers

• Giant Ulcer
• DUgt2cm, GUgt3cm
• Pyloric Channel Ulcer
• ? Pain occurring shortly after meal.
• ? Poor relief by antacids
• ? Vomiting
• Postbulbar Ulcers
• Multiple Ulcers

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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

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Detection of H. pylori Infection
Direct smear PCR
13C- Breath test
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Warthin -Starry Stain Acridine orange
stain
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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

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Endoscopy
Gastric ulcers
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Endoscopy
Duodenal ulcer
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Peptic ulcers
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Staging of peptic ulcer under endoscopy
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Barium Radiogram
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Differential Diagnosis

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

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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 gt 15mEq/hour
• Determination of Serum Gastrin level
• ? Fasting serum gastrin gt500pg/ml

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Complications

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

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Free perforation
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Gastric outlet obstruction (Pyloric obstruction)
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Malignant Transformation
1-3
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Medical Therapy

• Aims of Treatment
• Removing underlying cause of
• peptic ulcer
• Relieving symptoms
• Healing ulcer
• Preventing relapse of ulcer
• Avoiding complications

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• 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

Defensive Factors ?
Aggressive Factors ?
I
II
III
Aggressive Factors ? Defensive Factors ?
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Strategies for healing ulcer

• Eradicate H. pylori
• Inhibit acid secretion
• Improve mucosal defense

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Eradicate H. pylori infection
PPI (H2-RA) or Bismuth
Two Antibiotics

Clarithromycin 250-500mg Amoxicillin
500-1000mg (Tetracycline) Metronidazole
400mg Furazolidone 100mg
Colloidal Bismuth Subcitrate ( CBS) 240mg
Triple therapy, bid for 1 week
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Inhibit acid secretion

• H2-Receptor Antagonists
• ? Cimetidine 400mg bid
• ? Ranitidine 150mg bid
• ? Famotidine 20mg bid
• Proton Pump Inhibitors
• ? Omeprazole 20mg qd
• ? Lansoprazole 30mg qd
• ? Pantoprazole 40mg qd
• ? Rabeprazole 10mg qd
• ? Esomeprazole 20mg qd

DU 4 - 6 wks GU 6 - 8 wks
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ATP
PGs
H2-RAs
PPIs
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Improve mucosal defense

• Sucralfate
• ? Ulcer isolation
• ? Promoting PGs synthesis and release
• Colloidal Bismuth Subcitrate
• ? Ulcer isolation
• ? Promoting PGs synthesis and release
• ? Anti-H.pylori

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

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Preventing relapse of ulcer Avoiding
complication

• Eradication of H. pylori
• ? Cost - effect
• ? Relapse rate lt 5/yr
• Maintaining Therapy
• ? Half dose of H2-RA q.n.
• ? 6 months or longer
• ? Relapse rate around 25/yr

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Treatment and prevention of NSAIDs-associated
ulcer

• Discontinuing NSAIDs
• Medical Treatment
• ? PPIs
• ? Higher dose of H2-RA
• Prevention
• ? Eradicating H.pylori ?
• ? Misoprostol (PGE2)
• ? PPIs
• ? Sucralfate ?

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Surgical Therapy

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

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Billroth I
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Billroth II
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Establish the diagnosis (endoscopy or UGI)
Gastric ulcer biopsy, R/O cancer
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)
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Thank You