PEPTIC ULCER

DIVISI GASTROENTERO-HEPATOLOGI BAGIAN ILMU PENYAKIT DALAM RSUP. H. ADAM MALIK MEDAN

PEPTIC ULCER

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

EPIDEMOLOGY

Incidens in Western Countries: Female 4 15 % & Male 10 15 %

Medan Jakarta 6,93 % 1,73 % 88,4 % 1,5 % 20,01 % 5,18 % 72,15 % 1,59 %

Peptic Ulcer CA Gastro Dispepsia Non Ulkus Esofagitis

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

HISTORY / PATHOGENESE

1.

NO ACID NO ULCER 1910 SCHWARTZ

2.

DEFENSIVE FACTOR (mucus,mucosal resistance,local mucosal blood flow)/AGGRESIVE FACTOR(acid,pepsin) NO HP NO ULCER WARREN AND MARSHALL 1983
GU : 60 80% HP, 25% OAINS, 5% ZES DU : 90 - 95% HP, 5% OAINS, 5% ZES

3.

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

Differences between NSAID and H.pylori induced ulcers

NSAIDs induced
Patients demographics Elderly more than young Women more often than men Gastric more than duodenal More often asymptomatic

H.pylori
Young more often than elderly Men more often than woman Duodenal more than gastric Usually pain and or dyspepsia

Site of damage Symptoms Histology

Surrounding mucosa Surrounding mucosa normal inflammed (foveolar hyperplasia) (active chronic gastritis)
Scarpignato,1997

Risk Factors for NSAIDs Induced Gastroduodenal Ulceration

Established
Advanced age History of ulcer Concomitant use of glucocorticoids High-dose NSAIDs Multiple NSAIDs Concomitant use of anticoagulants Serious or multisystem disease

Possible
Concomitant infection with Cigarette smoking Alcohol consumption

H. pylori

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: 1422.

Hp increase risk of NSAID Ulcers

Meta-analysis of 16 studies consisting of 1633 patients
100 80 60 40 20 0 HP+, NSAID+ HP-, NSAID+ HP+, NSAIDHP-, NSAIDHuang et al. Lancet 2002 OR 3.55 OR 3.53 OR 19.4 OR 18.1

HP+, NSAID+ HP-, NSAID+ HP+, NSAIDHP-, NSAID-

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

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

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: 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

What type of ulcer? - Gastric ulcer

- Duodenal Ulcer

Table : Management of peptic ulcer (Cont)

Question: What the cause of ulcer disease? - Has the patient used NSAID? - Is H pylory infection present? Any ulcerogenic risk factor? Action taken in the management of ulcer Evaluate for NSAID ingestion and H pylori If yes, evaluate indication for NSAID; can this be stoped? Treat H Pylori

- Aspirin or NSAID use

Stop if possible; evaluate indication and consider non-ulcerogenic substitutes: eg, ticlopidine instead of aspirin for cardiovascular prophylaxis; non-NSAID analgesiscs such as paracetamol or codein; COX-2 inhibitors
Advice to stop smoking

- Smoking

THERAPY
-

NON MEDICAMENT: Life style, Diet 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 (Maastrich III-2005)

First Line Therapy For H Pylori Eradication
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

Peter Malfertheiner, The 6th western Pasific Helicobacter Congress, 2006

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 + Metronidazole + 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 Eradication Treatment Successful *Unsuccessful ANTI-SECRETORY TREATMENT ( P P I ) 4-8 WEEKS Repeat gastrocopy or barium meal to asses healing Healed Follow-Up Not Healed Continue treatment Consider repeat Bx To exclude cancer Consider Surgery No Is Patient taking NSAID? If so, Stop NSAID

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 Yes No Is patient taking NSAIDS? If so, stop NSAIDS

Eradication Treatment

Successful & Symptoms resolve optional

Unsuccessful* or still symptomatic Anti-secretory treatment 4-6 weeks Review symptomps And follow-up

Low probability of recurence No maintenance treatment

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

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) Hypergastrinemia and hypersecretion Ulcers solitary in distally duodenum, giant ulcers >2 cm Laboratory fasting serum gastrin >150 pg/mL (500-700 pg/mL)