PEPTIC ULCER

PEPTIC ULCERPEPTIC ULCER

GASTRIC ULCER DUODENAL ULCER ESOPHAGEAL ULCER Patient Problem:

Suffer ←→ - recurrency / relaps, - loss in the works, - cost of medication expensive

EPIDEMOLOGYEPIDEMOLOGYo Incidens in Western Countries:

Female 4 – 15 % & Male 10 – 15 %

MedanMedan JakartaJakartaPeptic UlcerPeptic Ulcer 20,01 %20,01 % 6,93 %6,93 %

CA GastroCA Gastro 5,18 %5,18 % 1,73 %1,73 %

Dispepsia Non Dispepsia Non UlkusUlkus

72,15 %72,15 % 88,4 %88,4 %

EsofagitisEsofagitis 1,59 %1,59 % 1,5 %1,5 %

Common Causes of Death in Common Causes of Death in U.S. U.S.

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DEFINITIONDEFINITIONPeptic 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 / PATHOGENESEHISTORY / PATHOGENESE1. “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% ZESDU : 90 - 95% HP, 5% OAINS, 5% ZES

BALANCE THEORY SHAY & SUN

Mucus, mucinFosfolipida

Ion bicarbonatProstaglandin

Mucous blood flowCell regeneration

AcidPepsinFood

AlcoholNSAIDs

BALANCEShay & Sun

AggressiveFactor

DefensiveFactor

UlcerHealing

H. Pylori (cont…)Faktor-faktor yang berperan merusak mukosagastroduodenal 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). (Peterson dkk, 2002).

Differences between NSAID Differences between NSAID and H.pylori induced ulcersand H.pylori induced ulcers

NSAIDs NSAIDs inducedinduced

H.pyloriH.pylori

Patients Patients demographicsdemographics

Elderly more than Elderly more than youngyoungWomen more often Women more often than menthan men

Young more often Young more often than elderlythan elderlyMen more often than Men more often than womanwoman

Site of damageSite of damage Gastric more than Gastric more than duodenalduodenal

Duodenal more than Duodenal more than gastricgastric

SymptomsSymptoms More often More often asymptomaticasymptomatic

Usually pain and or Usually pain and or dyspepsiadyspepsia

HistologyHistology Surrounding mucosa Surrounding mucosa normalnormal(foveolar hyperplasia)(foveolar hyperplasia)

Surrounding mucosa Surrounding mucosa inflammedinflammed(active chronic (active chronic gastritis)gastritis)

Scarpignato,1997

List of NSAIDs Available by PrescriptionList of NSAIDs Available by PrescriptionNON-SALICYLATESNON-SALICYLATES SALICYLATES SALICYLATES COX-2 INHIBITORS COX-2 INHIBITORS

Diclofenac (Voltaren)Diclofenac (Voltaren) AspirinAspirinaa (Zorprin, Easprin) (Zorprin, Easprin) Celecoxib (Celebrex) Celecoxib (Celebrex)Diclofenac/Misoprostol (Arthrotec)Diclofenac/Misoprostol (Arthrotec)bb Diflunisal (Dolobid)Diflunisal (Dolobid) Valdecoxib (Bextra) Valdecoxib (Bextra)Fenoprofen (Nalfon) Fenoprofen (Nalfon) Salsalate (Disalcid, Salflex)Salsalate (Disalcid, Salflex) Flurbiprofen (Ansaid) Flurbiprofen (Ansaid) Choline salicylate (Trilisate)Choline salicylate (Trilisate)Ibuprofen (Motrin)Ibuprofen (Motrin)aa Magnesium salicylate (Magan)Magnesium salicylate (Magan)Indomethacin (Indocin) Indomethacin (Indocin) Ketoprofen (Orudis)Ketoprofen (Orudis)aa In DevelopmentIn DevelopmentMeclofenamate Meclofenamate Etoricoxib EtoricoxibMefenamic acid (Ponstel) Mefenamic acid (Ponstel) Parecoxib Parecoxibcc

Nabumetone (Relafen)Nabumetone (Relafen) Lumiracoxib LumiracoxibNaproxen (Naprosyn, Anaprox)Naproxen (Naprosyn, Anaprox)aa

Oxaprozin (Daypro)Oxaprozin (Daypro) Previously AvailablePreviously AvailablePiroxicam (Feldene)Piroxicam (Feldene) Rofecoxib (Vioxx)Rofecoxib (Vioxx)Sulindac (Clinoril)Sulindac (Clinoril)Tolmetin (Tolectin)Tolmetin (Tolectin)

a Also available as over-the-counter preparations in the U.S.b Combination tablet of NSAID/synthetic prostaglandin E1c Parenterally administered

2004 Physician2004 Physician’’s Desk References Desk Reference

Risk Factors for NSAIDs Induced Risk Factors for NSAIDs Induced Gastroduodenal UlcerationGastroduodenal Ulceration

Established Possible

Advanced age Concomitant infection withHistory of ulcer H. pyloriConcomitant use of glucocorticoids Cigarette smokingHigh-dose NSAIDs Alcohol consumptionMultiple NSAIDsConcomitant use of anticoagulantsSerious or multisystem disease

H. pylori, NSAID use and risk of PUD:H. pylori, NSAID use and risk of PUD:a meta-analysisa 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.

Hp increase risk of NSAID Hp increase risk of NSAID UlcersUlcers

Meta-analysis of 16 studies consisting of 1633 patients

Huang et al. Lancet 2002

Prop

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OR 18.1

OR 19.4

OR 3.55

OR 3.53

Peptic Ulcer Clinical Peptic Ulcer Clinical ManifestationManifestation

HISTORY OF ILLNESS– None– Dyspeptic Symptom:

Epigastric Pain, Nausea, Vomiting,anorexia, epigastric discomfort, etc

– Epigastric PainEpisodic, 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

DIAGNOSTICDIAGNOSTIC

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/Indication of Upper Gastrointestinal/Esophago-gastro-duodenoscopyEsophago-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 Diagnosis of Helicobacter Pylori InfectionHelicobacter 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 patientsPeptic Ulcer in OAINS patients

• LargeLarge

• MultipleMultiple

• GU>DUGU>DU

• PainlessPainless

19

Ulkus Gaster

RSH

Lokasi• 90 % pada daerah

antrum dan kurvatura minor

Ulkus Duodenum

Definition and CausesDuodenal 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-in- flammatory drugs (NSAIDs). Additional risk factors include ni- cotine abuse, alcohol abuse, and stress.

Clinical AspectsA 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.

LocationNinety 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 10−20 % of cases. Ulcers located distal to the bulb should raise suspicion of Zollinger−Ellison syndrome.

Yang membedakannya dengan ulkus gastrikus,

Pada ulkus duodenum:

Rasa sakit timbul sewaktu pasien merasa laparRasa sakit bisa membangunkan pasien tengah malamRasa sakit hilang setelah makan atau minum antasida Rasa sakit dirasakan di kanan garis tengah perut

Hunger Pain Food Relief

MANAGEMENTMANAGEMENT• 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 Table : Management of peptic ulcerpeptic ulcer

Question:Question: Action taken in the Action taken in the management of ulcermanagement of ulcer

What type of ulcer?What type of ulcer?- Gastric ulcer- Gastric ulcer Requires biopsy to Requires biopsy to

exclude malignancy, exclude malignancy, requires confirmation of requires confirmation of healing by endoscopyhealing by endoscopy

- - Duodenal UlcerDuodenal Ulcer If symptoms resolve If symptoms resolve after adequate after adequate treatment, endoscopy treatment, endoscopy generally not required generally not required except for presentation except for presentation with bleedingwith bleeding

Table : Management of peptic Table : Management of peptic ulcer (Cont…)ulcer (Cont…)Question:Question: Action taken in the Action taken in the

management of ulcermanagement of ulcerWhat the cause of ulcer What the cause of ulcer disease?disease?

Evaluate for NSAID ingestion Evaluate for NSAID ingestion and H pyloriand H pylori

- Has the patient used - Has the patient used NSAID?NSAID?

If yes, evaluate indication for If yes, evaluate indication for NSAID; can this be stoped?NSAID; can this be stoped?

- Is H pylory infection - Is H pylory infection present?present?

Treat H PyloriTreat H Pylori

Any ulcerogenic risk factor?Any ulcerogenic risk factor?- Aspirin or NSAID use- Aspirin or NSAID use Stop if possible; evaluate Stop if possible; evaluate

indication and consider non-indication and consider non-ulcerogenic substitutes: eg, ulcerogenic substitutes: eg, ticlopidine instead of aspirin ticlopidine instead of aspirin for cardiovascular for cardiovascular prophylaxis; non-NSAID prophylaxis; non-NSAID analgesiscs such as analgesiscs such as paracetamol or codein; COX-2 paracetamol or codein; COX-2 inhibitorsinhibitors

- Smoking- Smoking Advice to stop smokingAdvice to stop smoking

THERAPYTHERAPY

- NON MEDICAMENT: Life style, Diiet

- MEDICAMENT:. ANTACIDS. CYTOPROTECTIVE AGENTSSucralfate, 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).

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 therapyBismuth – 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

First Line Therapy For H Pylori Eradication

Consensus of The Treatment H Pylori Consensus of The Treatment H Pylori Infection Infection

(Maastrich III-2005)(Maastrich III-2005)

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

H Pylori Eradication H Pylori Eradication (KSHPI)(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

**Gastric ulcer on endoscopy or barium meal

IS H PYLORI PRESENT?

Successful

ANTI-SECRETORY TREATMENT 4-8 WEEKS

Healed

Follow-Up

Yes No

Eradication Treatment Is Patient taking NSAID?If so, Stop NSAID

*Unsuccessful

Repeat gastrocopy or barium meal to asses healing

Not Healed

Continue treatmentConsider repeat Bx To exclude cancer

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

Management of Uncomplicated Management of Uncomplicated Gastric UlcerGastric Ulcer

Management of Uncomplicated Management of Uncomplicated Duodenal UlcerDuodenal Ulcer

Duodenal Ulcer of Endoscopy or barium meal

Is H pylori Present

NoYes

Eradication Treatment Is patient taking NSAIDS?If so, stop NSAIDS

Successful & Symptoms resolve

Unsuccessful* or still symptomatic

optional Anti-secretory treatment 4-6 weeks

Low probability of recurenceNo maintenance treatment

Review symptomps And follow-up

COMPLICATIONCOMPLICATION

- HEMORRHAGECAUSED BY ULCER EROSING BLOOD VESSEL WALL;MAY RESULT IN DEATH

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

- OBSTRUCTIONSCARRING BLOCK STOMACH OUTLET, PREVENTING FOOD PASSAGE, PATIENT EXPERIANCE VOMITING AND WEIGHT LOSSCAVITY, REQUIRES HOSPITALISATION AND USUALLY SURGERY

- PENETRATIONADJACENT VISCUS,LIVER,PANCREAS OR BILLIARY SYSTEM

MANAGEMENT PUD WITH COMPLICATION

SURGICAL ULCERTOTAL GASTRECTOMYANTRECTOMYVAGOTOMYPYLOROPLASTYCLOSE PERFORATIONBILLROTH I AND II

RREFRACTER ULCEREFRACTER ULCER• Helicobacter Pylori resistency of antibiotics• NSAIDs• Zollinger Ellison Syndrome/Gastrinoma• Gastric Cancer (Adenocarcinoma &

Lymphoma)• Ischemic Gastropathy• Crohn’s 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 UlcerThe 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 ZOLLINGER –ELLISON SYNDROME (GASTRINOMA)(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.