Peptic Ulcer Disease

Cengiz Pata,MDDept. Gastroenterology,

Yeditepe University, Medical center

Case

• 30 year old male• Epigatsric pain radiating to the back

Questions?

Possible diagnosis

Deferential diagnosis

Possible complications

Case • Pain: • What type of pain?

How often?Awakes at night? Relation to food?

• Complications:• Vomiting? (obstruction?)

Stools? (melena?)• Common deferential diagnosis:• Pnacreatobiliary disease

DyspepsiaTumors

Case

• Next diagnostic step? • Endoscopy

Abdominal USUGI?

• DU Ulcer detected- next step? • Test for H. pylori

Exclude NSAID use Rare – assess gastrin, mainly in unusual cases

Benign gastric ulcer (B)

Peptic Ulcer

• A defect in the gastrointestinal mucosa extending through the muscularis mucosa.

• Two main forms:1) Helicobacter associated 2) NSAID associated ( Steroids alone – no additional risk, Increased risk when combined with NSAIDS)

Peptic Ulceration : Additional Causes

• Acid hypersecretion:Gastrinoma ( ZE)Systemic mastocytosisBasophilia in myeloproliferative disorders

• ViralHerpes simplex CMV ( mainly in immune compromised)

Peptic Ulceration : Additional Causes• Vascular Insufficiency

( including due to crack cocaine)

• Radiation induced

• Chemotherapy induced

• Stress ulceration

Electron micrograph of H. pylori

Prevalence of Helicobacter pylori in peptic ulcer

Seroprevalence of H. pylori with increasing age in developed and developing countries

Developing countries Developed countries100

0

25

50

75

<20 40-50 <20 40-50

10-75%

64-96%

6-39%7-54%

Age range (years)

Prev

alen

ce (%

)

Adapted with permission from Heatley-Helicobacter pylori and Gastrointestinal Disease; Oxford, UK: Blackwell Scientific Publications

Risk factors for H. pylori infection

• Age

• Country of origin

• Socio-economic status poor housing

bed sharing

overcrowding

large families

Modes of transmission of H. pylori infection

• Zoonosis unlikely

• Environment unlikely

• Person-to-person oral-oral likely

gastro-oral likely

faecal-oral likely

H. pylori infection and disease associations

•Chronic gastritis

• Duodenal ulcer

• Benign gastric ulcer

• Gastric carcinoma

• Gastric MALT and non-Hodgkin‘s lymphoma

• Ménétrier‘s disease

Pattern of gastritis

Duodenal ulcer Gastric ulcer

*H. pylori colonizes areas of gastric metaplasia, leading to chronic duodenitis and eventually duodenal ulcer.

Antralgastritis

*

Corpusitis

NSAIDS

• In the USA 30 bil OTC 20 mil prescriptions• 3-4% ulcerations• 20,000 die of NSAID complications• 80% have no preceding dyspepsia• Important to identify at risk populations

Previous gastritisElderly

PD & Systemic Diseases

• COPD

• Renal Failure

• Cirrhosis

• Mastocytosis

Clinical Presentation

• Abdominal Pain: Epigastric dull “hunger pain”DU- 11/2 –3 hrs postprandial relived by foodMay awake at night GU – May occur with meals

• nausea weight loss more frequent in GU• Sudden pain – perforation?• Vomiting – obstruction?

Clinical Presentation

• Physical examination:• Poor predictive value, not specific• Pain may occur in RUQ ~ 20%• Detect complications:

Tachycardia, orthostasis- bleeding?Radiation to the back- perforation?Succussion splash – outlet obstruction?

Complications

• Bleeding ~ 15% ( More in >60 yrs –NSAID)20% - no warning sign

• Perforation 6-7% FreePenetration: DU posterior to pancreas

GU into Lt hepatic lobe Gastrocolic fistula

Complications

• Outlet obstruction 1-2%Inflammatory – reversible by TxScar tissue – balloon dilatation, Surgery

• Presentation : Gradual onsetSudden

Clinical manifestations of ulcer disease

Differential Diagnosis

• Non ulcer dyspepsia• Tumors of the UGIT• Biliary disease• Reflux disease• Vascular diseases• Pancreatitis • Coronary heart disease

Diagnosis

• Radiology:Single contrast 80% sensitivity Double 90%(worse for ulcers<0.5 cm, scar tissue)

• Endoscopy: examination of choice good for small ulcersbiopsy samples for HP and malignancytherapeutic

• Assay for HP infection

Diagnostic methods for H. pylori

Diagnostic method

Histology

Main indication

Diagnosis

Sensitivity (%)

90

Specificity (%)

90

Culture H. pylori antibiotic sensitivities

80-90 95

Rapid urease test

Endoscopy room diagnosis

90 90

Serology Screening and diagnosis

90 90

Urea breath test

To confirm eradication

95 100

The principle of the urease test

NH2

C

NH2

O + 2H2O + H+

2NH4+

+ HCO3-

Urease

Urea CLOtest

pH change

The principle of the 13C- or 14C-urea breath test

Reproduced with permission from Mr Phil Johnson, Bureau of Stable Isotope Analysis, Brentford, UK.

Therapy• Treat H. pylori

• Healing by inhibition of acid secretion:H2 receptor antagonists (H2RA)Proton Pump inhibitors ( PPI)Anti Acid

• CytoprotectionSucralfateAnti AcidBismuth-BasedProstaglandin Analogs

Therapy of DU

• H2RA – Cure in 80% at 4 wks~95% at 8 wks Split and once daily equally effective

• PPI- Cure in 60-93% at 2 wks 80- 100 % at 4 wks

• Omeprazole Vs ranitidine 14% advantage at 2 wks 9% advantage 4 wks

Therapy of GU

• Suppress acid by H2RA or PPI• Advantage of PPI less apparent• Sucralfate comparable to H2RA

• Prepyloric ulcers may resemble more DU in terms of response to acid suppression

Risk stratification of Ulcer Pts

• Low risk:

Intermittent symptomsNonsmokerDiscontinued NSAIDUncomplicatedEasy healing

Risk stratification of Ulcer Pts• High risk:

Frequent recurrenceRefractory to TxSmokingContinued NSAIDGiant Ulcer ( DU >2 cm GU > 3 cm)AnticoagulationDeformity & scarringElderlyAcid hypersecretion

General Scheme• HP positive – Eradicate • If Non complicated – No further Tx• If high risk: • Follow by acid suppression for 4-6 wks• Withdraw –

NSAIDSmoking Excess Alcohol

• In GU – Biopsy? Cost and effect- Most CAs detected in first round of endoscopy

Refractory Ulcers

• Consider refractory after 8-12 wks of Tx• Ensure that refractory symptoms

= refractory ulcer ( endoscopy) • If no ulcer - investigate pain• Consider “silent” refractory ulcer in high risk

pts ( ~25% of refractory ulcers)

Refractory Ulcers - causes

• Persistent HP infection• Persistent NSAID use • Poor pt compliance• Giant ulcers ( healing at 3 mm/wk)• Smoking• Under laying pathology ( ZE, bands,

crohn’s,infections I.e. TB syphilis, Ly, scarcoidosis )• Impaired response to PPI ( 5% of population)

Refractory Ulcers - Approach

• Seek causes:DU- HP, NSAIDS, r/o ZE ( gastrin levels)

GU- main concern CARepeat multiple BxEvidence for malignancy: CT, EUS

No explanation - surgery

Surgery - DU

• Refractory bleeding (~5% of transfused Pts)• Perforation (2-3%)• Outlet obstruction

• Vagotomy + antrectomy Rec. (1%) Comp Vagotomy + pyloroplasty intermediate (10%)Highly selective vagotomy Rec. Comp

Zollinger Ellison Syndrome

• Severe peptic ulcer diathesis + gastric acid hypersecretion due to -cell endocrine tumor

• 0.1-1% of PUD patients

• Sporadic, or associated with MEN type I (25%)

Zollinger Ellison Syndrome

• >80% Localized to gastrinoma triangle:cystic & common bile ducts, duodenum, junction head and body of pancreas.

• 60 % malignant, up to 50% with metastasis

• Clinical: PUD >90% (recurrent, multiple, refractory, complicated)

Zollinger Ellison Syndrome

• Esophageal complaints ~60%

• Diarrhea ~50% (fluid overload, pancreatic enzyme dysfunction, epithelial dysfunction)

• Combination should raise clinical suspicion

Clinical features of Zollinger-Ellison syndrome

MEN I • Autosomal Dominant:

Parathyroid (~90%), Pancreas (40-80%)Pituitary (30-60%)

• Contributory effect of hyperparathyroidism, hypercalcemia hypergastrinemia acid secretion

• Higher incidence of carcinoids

• Smaller and multiple duodenal gastrinomas

Diagnosis of Gastrinoma

• Combination of clinical signs • Fasting gastrin levels (> 150 pg/ml) • Avoid confounding factors

(hypochlorhydria, PPIs, outlet obstruction, renal failure)

• Assess acid secretion (if low- excludes)• Provocative tests (calcium, secretin)

Treatment

• Localization (EUS, Oct scan, MRI, CT)

• Exclusion of metastasis

• If positive – symptomatic cure

• If negative attempt surgical resection ( less likely in MEN I ~ 6%)

Case -2

• 70 year old lady , RA

• Dizziness and weakness for the last week.

• Mild abdominal pain

• Questions?

Case-2

• Stools? • Melena • Drugs? • NSAIDS• Next action? • Gastroscopy

Gastric Ulcer with Stigma

Treatment

• H2RA

• Oral PPI

• Oral PPI + H2RA

• IV PPI

H2 RA

• Very safe drugs

• Tolerance after 48 hrs IV treatment

• Less effective than PPIs in suppressing acid secretion (block only histamin)

Treatment

• Heavy consumption of NSAID

• Should H. pylori be tested for? Treated?

• YES

Drugs for treatment of acid disorders and H. pylori infection• H2 Receptor antagonists

• PPI

• Anti H. pylori regimens

Overall Control of Acid Secretion

The parietal cell

The proton pump

Biologic mechanism of action of substituted benzimidazoles (proton pump inhibitors)

Kinetics of PPI Effect

Summary of PPI effects • Inhibit ~70% of acid secretion

• Need to coordinate pump activation & PPI availability (t/2~60-90 min)

• Pump re-synthesis (half life ~ 50 hours 25% synthesis between single day doses)

• Cysteins accessible to reducing activity of glutathione

• Spontaneous pump recycle every 60-120 min (Potential to block)

Optimization of acid control

Guidelines for use of antibiotic therapy in patients with Helicobacter pylori infection

Treatment regimens for eradication of Helicobacter pylori

Therapeutic options

clarithromycin2 x 250 - 500mg

metronidazole2 x 400 - 500mg

amoxycillin2 x 1000mg

PPI X 2eradic

ation

rate

90%

eradication rate

90%

eradication rate >80%

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Choice between treatments

Treatment failures