peptic ulcer disease cengiz pata,md dept. gastroenterology, yeditepe university, medical center
DESCRIPTION
Case Pain: What type of pain? How often? Awakes at night? Relation to food? Complications: Vomiting? (obstruction?) Stools? (melena?) Common deferential diagnosis: Pnacreatobiliary disease Dyspepsia TumorsTRANSCRIPT
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