PEPTIC ULCER

PEPTIC ULCER

GASTRIC ULCER
DUODENAL ULCER
ESOPHAGEAL ULCER
Patient Problem:
Suffer - recurrency / relaps,
- loss in the works,
- cost of medication
expensive

EPIDEMOLOGY
o Incidens in Western Countries:
Female 4 15 % & Male 10 15 %
Peptic Ulcer
CA Gastro
Dispepsia Non
Ulkus
Esofagitis

Medan

Jakarta

20,01 %

6,93 %

5,18 %

1,73 %

72,15 %

88,4 %

1,59 %

1,5 %

Common Causes of Death in U.S.

9

Death per 100,000

8
7
6
5
4
3
2
1
0
Leukemia

AIDS

NSAID-GI
disease

Melanoma

Asthma

Cervical
cancer

Wolfe et al. NEJM 1999

DEFINITION
Peptic Ulcer: Damage of mucosal
layer/muscularis mucosa or deeper
until submucosa of the
stomach/duodenum, ulcer edge
surounded by acute and chronic
inflamatory cells; the diameter 5 mm
Erosion: damage < 5 mm and the
depth not over than muscularis mucosa

HISTORY / PATHOGENESE
1.

NO ACID NO ULCER 1910 SCHWARTZ

2.

DEFENSIVE FACTOR (nucus,mucosal

resistance,local mucosal blood flow)/AGGRESIVE
FACTOR(acid,pepsin)

3.

NO HP NO ULCER WARREN AND MARSHALL

1983
GU : 60 80% HP, 25% OAINS, 5% ZES
DU : 90 - 95% HP,
5% OAINS, 5% ZES

BALANCE THEORY SHAY

& SUN
Ulcer
Healing
Aggressive
Factor
Defensive
Factor
Mucus, mucin
Fosfolipida
Ion bicarbonat
Prostaglandin
Mucous blood flow
Cell regeneration

BALANCE
Shay & Sun

Acid
Pepsin
Food
Alcohol
NSAIDs

H. Pylori (cont)
Faktor-faktor yang berperan merusak mukosa
gastroduodenal ialah:

urease,
catalase,
lipase,
adhesin,
platelet activating factor,
CagA (cytotoxin associated gene protein),
Pic B (protein induces cytokines),
Vac A (vacuolating cytotoxin).

(Peterson dkk, 2002).

Differences between NSAID and

H.pylori induced ulcers
NSAIDs
induced

H.pylori

Patients
demographics

Elderly more than

young
Women more often
than men

Young more often

than elderly
Men more often than
woman

Site of damage

Gastric more than

duodenal

Duodenal more than

gastric

Symptoms

More often
asymptomatic

Usually pain and or

dyspepsia

Histology

Surrounding mucosa
normal
(foveolar hyperplasia)

Surrounding mucosa
inflammed
(active chronic
gastritis)
Scarpignato,1997

List of NSAIDs Available by Prescription

NON-SALICYLATES

SALICYLATES

Diclofenac (Voltaren)
Diclofenac/Misoprostol (Arthrotec)b
Fenoprofen (Nalfon)
Flurbiprofen (Ansaid)
Ibuprofen (Motrin)a
Indomethacin (Indocin)
Ketoprofen (Orudis)a
Meclofenamate
Mefenamic acid (Ponstel)

Aspirina (Zorprin, Easprin)

Diflunisal (Dolobid)
Salsalate (Disalcid, Salflex)
Choline salicylate (Trilisate)
Magnesium salicylate (Magan)

COX-2 INHIBITORS
Celecoxib (Celebrex)
Valdecoxib (Bextra)

In Development
Etoricoxib
Parecoxibc

Nabumetone (Relafen)
Naproxen (Naprosyn, Anaprox)a
Oxaprozin (Daypro)
Piroxicam (Feldene)
Sulindac (Clinoril)
Tolmetin (Tolectin)

Lumiracoxib
Previously Available
Rofecoxib (Vioxx)

Also available as over-the-counter preparations in the U.S.

b
Combination tablet of NSAID/synthetic prostaglandin E1
c
Parenterally administered
2004 Physicians Desk Reference
a

Risk Factors for NSAIDs Induced

Gastroduodenal Ulceration
Established

Possible

Advanced age
Concomitant infection with
History of ulcer
H. pylori
Concomitant use of glucocorticoids
Cigarette smoking
High-dose NSAIDs
Alcohol consumption
Multiple NSAIDs
Concomitant use of anticoagulants
Serious or multisystem disease

H. pylori, NSAID use and risk of PUD:

a meta-analysis
Both H. pylori infection and NSAID
use independently and significantly
increase the risk of peptic ulcer and
ulcer bleeding
H. pylori infection and NSAID use
are synergistic for peptic ulcer
development and ulcer bleeding

Huang et al., Lancet 2002; 359: 14

22.

Proportion with peptic ulcers (%)

Hp increase risk of NSAID

Ulcers
Meta-analysis of 16 studies consisting of 1633 patients
100
80

OR 3.55
OR 3.53

OR 19.4

60

HP+, NSAI D+
HP-, NSAI D+
HP+, NSAI DHP-, NSAI D-

OR 18.1

40
20
0
HP+,
NSAI D+

HP-,
NSAI D+

HP+,
NSAI D-

HP-,
NSAI D-

Huang et al. Lancet 200

Peptic Ulcer Clinical

Manifestation
HISTORY OF ILLNESS
None
Dyspeptic Symptom:
Epigastric Pain, Nausea,
Vomiting,anorexia, epigastric
discomfort, etc
Epigastric Pain
Episodic, Nocturnal, Pain-Food- Relief
pattern can be pointed at
Loss of body weight
Hematemesis and Melena

DIFFERENTIALS
Biliary colic
Cholecystitis
Cholelithiasis
Gastritis Acute
Gastritis Chronic
Gastroesophageal Reflux Disease
Mesenteric Artery Ischemia
Myocardial Ischemia
Pancreatic Cancer
Pancreatitis Acute
Pancreatitis Chronic

DIAGNOSTIC
1. Simptom 25 % mild, 50 % moderate, 25
% severe with/without complication.
Cardinal simptom epigastric pain or
dyspepsia.
2. Physical Examination and Laboratory
tests are typically normal.
3. Radiology/OMDF (Crater-Niche -->TL)
4. Endoscopy : gold standard diagnostic
peptic ulcer

Indication of Upper Gastrointestinal/

Esophago-gastro-duodenoscopy

Age over 45 years old

Alarm signs
Therapy failure
History of Peptic ulcer + Complication
Patient enquery
The use of aspirin or NSAID
Abnormality in Upper GI X-Ray (OMD)

Diagnosis of
Helicobacter Pylori Infection
NON-INVASIVE
Urea Breath Test
Serum serology for
Hp antibody test
Whole blood serology
for Hp antibody test
Saliva Assay for Hp
antibody test
Helicobacter Pylori
stool antigent (HpSA)
test

INVASIVE
(biopsy &
endoscopy)
Culture test
Histopatology test
Urease test
PCR

Peptic Ulcer in OAINS

patients
Large
Multiple
GU>DU
Painless
19

Ulkus
Gaster
RSH

Lokasi
90 % pada
daerah antrum
dan kurvatura
minor

Ulkus Duodenum

Definition and Causes

Duodenal ulcer is an epithelial defect in the
bulbar or descending duodenum that
penetrates the muscularis mucosae and
extends into the submucosa. The precipitating
causes include Helicobacter pylori infection
(detectable in more than 90% of cases) and
the ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs). Additional risk
factors include ni- cotine abuse, alcohol abuse,
and stress.

Clinical Aspects
A duodenal ulcer cannot be diagnosed from
the clinical presentation alone. The symptoms
range from typical nocturnal pain and vague or
crampy abdominal discomfort to an almost
complete absence of complaints, particularly
with NSAID-induced ulcers.

Location
Ninety percent of duodenal ulcers occur in
the duodenal bulb. Ulcers are usually located
on the anterior wall of the bulb, less
commonly on the posterior wall and lesser
curvature. Ulcers on the greater curvature are
rare. Multiple kissing ulcers are found on the
anterior and posterior walls in 1020 % of
cases. Ulcers located distal to the bulb should
raise suspicion of ZollingerEllison syndrome.

Yang membedakannya dengan ulkus gastrikus,

Pada ulkus duodenum:
Rasa sakit timbul sewaktu pasien merasa lapar
Rasa sakit bisa membangunkan pasien tengah malam
Rasa sakit hilang setelah makan atau minum antasida
Rasa sakit dirasakan di kanan garis tengah perut
Hunger Pain Food Relief

MANAGEMENT

GENERAL/ SUPPORTIVE
SYMPTOM RELIEF
HEALING OF THE ULCER
PREVENTION OF RECURRENCE
PREVENT / THREAT COMPLICATION

H.PYLORI ERADICATION IS ESSENTIAL IN. H.PYLORY

POSITIVE PATIENTS
NSAID SHOULD BE DISCONTINUED OR REDUCED, IF
POSSIBLE
PPIs ARE THE MOST EFFECTIVE AGENTS FOR ACID
SUPPRESSION AND THE MOST APPROPRIATE FIRST
LINE THERAPY.

Table : Management of
peptic ulcer
Question:
What type of ulcer?
- Gastric ulcer

- Duodenal Ulcer

Action taken in the

management of ulcer
Requires biopsy to
exclude malignancy,
requires confirmation of
healing by endoscopy
If symptoms resolve
after adequate
treatment, endoscopy
generally not required
except for presentation
with bleeding

Table : Management of peptic

ulcer (Cont)
Question:

Action taken in the

management of ulcer

What the cause of ulcer

disease?

Evaluate for NSAID ingestion

and H pylori

- Has the patient used

NSAID?

If yes, evaluate indication for

NSAID; can this be stoped?

- Is H pylory infection
present?

Treat H Pylori

Any ulcerogenic risk factor?

- Aspirin or NSAID use

Stop if possible; evaluate

indication and consider nonulcerogenic substitutes: eg,
ticlopidine instead of aspirin
for cardiovascular
prophylaxis; non-NSAID
analgesiscs such as

THERAPY
- NON MEDICAMENT: Life style, Diiet
- MEDICAMENT:
. ANTACIDS
. CYTOPROTECTIVE AGENTS
Sucralfate, Misoprostol,Prostaglandin,Bismuth
subsalicylate,Treponene,Rebamipide.
. ACID SUPPRESSION
- ARH2 (Antagonis / Reseptor H2)
Cimetidin, Ranitidin, Famotidin.
- PPI (Proton Pump Inhibitors)
Omeprazole(20), Lansoprazole(30), Esomeprazole (20/40),
Rabeprazole(10), Pantoprazole(40).

Consensus of The Treatment H Pylori

Infection
First Line(Maastrich
Therapy For H
Pylori Eradication
III-2005)
PPI- Clarithromycin Amoxicillin or metronidazole therapy remains the recommended
first line Therapy In populations with less than 15-20% clarithromycin resistance
prevalence in population in Less than 40% Metronidazole resistance prevalence
PPI clarithromycin - metronidazole is preferable
Quadriple therapies are alternative first line therapy

In case of failure
Second line therapy
Bismuth based quadruple therapies remain the best second line therapy, if available,
if not, PPI Amoxicillin or tetracycline and metronidazole are recommended

Subsequent failures rescue therapy

The rescue therapy should be based on antimicrobial susceptibility testing

H Pylori Eradication
(KSHPI)
Tripple therapy (1 or 2 weeks):
PPI + Amoxicillin + Clarithromycin
PPI + Metronidazole + Clarithromycin
PPI + Metronidazole + Tetracyclin (Alergy to
clarithromycin)
Quadripple therapy ( 1 or 2 weeks):
If fail to therapy combination 3 drugs:
Bismuth + PPI + Amoxicillin + Clarithromycin
Bismuth + PPI + Metroniudazole + Clarithromycin
High resistency area:
PPI + Bismuth + Tetracyclin + Metronidazole
PPI 2 x/d: Omeprazole/Esomeprazole 20 mg, Lansoprazole 30
mg, Pantoprazole 40 mg, Rabeprazole 10 mg
Amoxicillin 2 x 1000 mg/d, Clarithromycin 2 x 500 mg/d,
metronidazole 3 x 500 mg/d, tetracyclin 4 x 250 mg/d,
Bismuth 4 x 120 mg/d

Management of Uncomplicated
Gastric Ulcer
**Gastric ulcer on endoscopy or barium meal
IS H PYLORI PRESENT?

Yes

No

Eradication Treatment

Is Patient taking NSAID?

If so, Stop NSAID

Successful

*Unsuccessful
ANTI-SECRETORY TREATMENT 4-8 WEEKS
Repeat gastrocopy or barium
meal to asses healing

Healed

Not Healed

Follow-Up

Continue treatment
Consider repeat Bx To exclude cancer

Consider Surgery
Notes: *Quadriple therapy given for failed triple
**Gastric ulcer should be biopsied to exclude malignancy

Management of Uncomplicated
Duodenal Ulcer
Duodenal Ulcer of Endoscopy or barium meal
Is H pylori Present
No

Yes

Is patient taking NSAIDS?

If so, stop NSAIDS

Eradication Treatment

Successful &
Symptoms resolve
optional

Unsuccessful* or
still symptomatic
Anti-secretory treatment 4-6 weeks

Low probability of recurence

No maintenance treatment

Review symptomps
And follow-up

COMPLICATION
- HEMORRHAGE
CAUSED BY ULCER EROSING BLOOD VESSEL WALL;MAY RESULT IN DEATH

- PERFORATION
CAUSES SUDDEN INTENSE PAIN AS GUT CONTENTS ESCAPE INTO
ABDOMINAL CAVITY;REQUIRES HOSPITALISATION AND USUALLY
SURGERY

- OBSTRUCTION
SCARRING BLOCK STOMACH OUTLET, PREVENTING FOOD
PASSAGE, PATIENT EXPERIANCE VOMITING AND WEIGHT LOSS
CAVITY, REQUIRES HOSPITALISATION AND USUALLY SURGERY

- PENETRATION
ADJACENT VISCUS,LIVER,PANCREAS OR BILLIARY SYSTEM

MANAGEMENT PUD WITH

COMPLICATION
SURGICAL ULCER
TOTAL GASTRECTOMY
ANTRECTOMY
VAGOTOMY
PYLOROPLASTY
CLOSE PERFORATION
BILLROTH I AND II

REFRACTER ULCER

Helicobacter Pylori resistency of antibiotics

NSAIDs
Zollinger Ellison Syndrome/Gastrinoma
Gastric Cancer (Adenocarcinoma &
Lymphoma)
Ischemic Gastropathy
Crohns Disease
Gastris Syphillis
Idiopathic Granulomatous Gastritis
Esinophilic Granulomatous Gastritis
Gastric Sarcoidosis
Gastric Tuberculosis
Viral infection: CMV & HSV
Amyloidosis

 REFRACTEC ULCER: 5 - 10% of ulcer

unhealed with conventional therapy.
Duodenal ulcer that not healed after 2
months of H2RA therapy or 6 weeks of PPI
or
Gastric ulcer that not healed after 3
months of H2RA therapy or 8 weeks of PPI
The majority of ulcer patients become
asymptomatic within a few days of
institution of treatment.
About 95% of all ulcer will heal if therapy
is continued for up to 12 weeks.

The Refractory Ulcer

> 12 weeks
compliance ?
optimal dose ?
Incorrect Diagnosis ( IBS / GC )
Eradication HP
Another cause : NSAID ?, cigarette ?, alcohol ?
Operation: perforation, Haemoragis, stenosis,
refractory

ZOLLINGER ELLISON SYNDROME

(GASTRINOMA)
Cause gastrin-secretin gut
neuroendocrine tumors
(gastrinomas)
Ulcers solitary in distally duodenum,
giant ulcers >2 cm
Laboratory fasting serum gastrin
>150 pg/mL (500-700 pg/mL),Bacal
acid output over 15 mEq/h.

THERAPY
PPIs, 40 120 mg/day,compelte
symptom relief,ulcer healing
Patient with isolated hepatic
metastase, surgical resection.
Role of surgery, patient do not respond
with aggresive medical therapy.
Total gastrectomy,highly selective
vagotomy.