2DefinitionDisruption of mucosal and submucosal integrity of the stomach and/or duodenum >5 mm in size
3Epidemiology Peptic ulcer disease Duodenal ulcers Gastric ulcers Prevalence: 12% of men and 10% of women in U.S.Duodenal ulcers6–15% of the Western populationGastric ulcersLess common than DUoccur later in life than DU; peak in 6 decadeMore than half occur in males
4Epidemiology Helicobacter pylori infection Prevalence : 30% in U.S. 10% of Americans < 30 years80% in developing parts of the world
5Risk Factors Genetic predisposition First-degree relatives of patients with DU or GU are at 3-fold increased risk for ulcerPatients with blood group O may be at increased risk; the antigen may be a target of H. pylori .
6Risk Factors Psychological stress Evidence for causal effect is mainly anecdotal.Increased numbers of stressful events do not distinguish patients with DU from those without DU.
7Risk factors for H. pylori Birth or residence in a developing countryDomestic crowdingUnsanitary living conditionsUnclean food or waterExposure to gastric contentsPoor socioeconomic statusLess education
8Risk factors for NSAID-induced PUD Advanced ageHistory of ulcerConcomitant use of glucocorticoids or anticoagulantsHigh-dose NSAIDsMultiple NSAIDs useSerious or multisystem diseaseConcomitant infection with H. pyloriCigarette smokingAlcohol consumption
9Cigarette smoking Increase duodenal acid by: Increasing gastric acid secretionImpair duodenal and pancreatic bicarbonateSmokers are at increased risk for DU and GU
10Smoking in Hp-associated PUD is major risk factor for: OccurrencePersistenceRecurrence following Hp eradicationComplicationsImpairs ulcer healingIncreases the need for surgery
14Laboratory evaluation Routine laboratory studies are typically normal.Screening studies should include :CBCliver chemistriesserum creatinineserum calcium.A fasting serum gastrin level is indicated in ulcers refractory to therapy, with a positive family history, or in cases requiring surgery.
19ASGE Guidelines for endoscopy indication in dyspeptic patients New-onset dyspepsia in older than age 50Alarm features in any age that suggest significant structural disease or malignancy.Persistent dyspeptic symptoms
20Alarm features Family history of upper GI malignancy Weight loss Overt GI bleeding, iron deficiency anemiaProgressive dysphagia or odynophagiaPersistent vomitingPalpable massLymphadenopathy.
21Dyspeptic patients younger than 50 without alarm features Should be test for H. pyloriIf positive : H.pylori eradicationIf negative :short trial (4-8 weeks) PPI orEGDNSAID stopped, if possible.
22Endoscopy in DU (ASGE RECOMMENDATIONS) Endoscopy is not recommended in benign-appearing, uncomplicated duodenal ulcers identified on radiologic imagingDU are extremely unlikely malignant, and routine biopsy is not recommended
24Endoscopy in GU (ASGE RECOMMENDATIONS) Patients diagnosed with GU via radiologic imaging should undergo endoscopy.Although the presence of concurrent DU supports the diagnosis of a benign gastric ulcer, these radiologic criteria are not reliable.
26Endoscopy in GUIf a radiologic benign-appearing GU respond to medical therapy and has no alarm features, is reasonable to a medical therapy course for 8-12 weeks before an endoscopy.If has not healed within that period, at least four jumbo biopsies or seven regular biopsies should be obtained.
29Biopsy in GUBiopsy of all gastric ulcers was recommended in the past because older data suggested that 5% to 11% of GU represented malignancyThere are no recent data to recommend the need for biopsy of all GU.
30Routine biopsy may not be necessary in GU Ifhistory suggest a very low risk of malignancyIn young patient taking NSAIDs and endoscopic typical NSAID lesions (eg, shallow flat antral ulcer with associated erosions) biopsy is not necessary.
31Role of endoscopic surveillance in DU Is not recommended if symptoms resolve after a course of acid suppression with H Pylori eradication and discontinuation of NSAID.Is recommended in persistent symptoms forRule out refractory peptic ulcersRule out ulcers with nonpeptic etiologies
32surveillance endoscopy in GU May be unnecessary:When history suggest a low risk of cancer (eg, a young patient taking NSAIDs with endoscopic appearance of typical NSAID-associated lesions)In benign GU on EGD and biopsy with a defined etiology (eg, NSAID or H Pylori ) that is asymptomatic after a course of therapy
33Surveillance EGD indication in GU Endoscopically suspicious for malignancy, even if biopsy samples are benign.Symptomatic despite an appropriate therapy and previous benign biopsy(for detect refractory , benign nonpeptic etiologies and occult malignancy)Those did not biopsied at index EGD for any reason ( active GIB,coagulopathy, patien instability)Gastric ulcers without a clear etiology
34ASGE Recommendations in PUD 1. H Pylori testing should be performed in all PUD because it is a common etiology.2. DU is extremely unlikely to be malignant, and routine biopsy is not recommended.3. EGD is not recommended in benign-appearing, uncomplicated DU identified on radiologic imaging.
35ASGE recommendation cont. 4. Surveillance EGD be considered in DU with persistent symptoms.5.Most GU need biopsy because malignant GU may appear benign in EGD.However, in young patients taking NSAIDs with multiple benign-appearing GU, malignancy is very low.Therefore, biopsy and surveillance endoscopy should be individualized.
36ASGE recommendation cont. 6. Surveillance endoscopy indication in GU:Symptomatic despite a medical therapy.Ulcer without a clear etiologyIf biopsy was not obtained at the index EGD.7. In refractory PUD, surveillance endoscopy should be performed until the ulcer has healed or the etiology has been defined.
37ASGE recommendation cont. 8. Endoscopy should be performed early in the course of hospitalization in bleeding PUD9. In rebleeding after initial endoscopic hemostasis, repeat endoscopic therapy is recommended before considering surgical or radiologic intervention.10. Endoscopy is not recommend in clinical evidence of acute perforation.
38ASGE recommendation cont. 11. Endoscopy recommended for evaluation of gastric outlet obstruction.12. Endoscopic balloon dilation be considered for the management of benign gastric outlet obstruction.
39Giant ulcers (>2cm)patients with giant ulcers tend to be older and may present with atypical symptoms including anorexia and weight loss.Is aggressive disease, with a higher incidence of bleeding, penetration, perforation, mortality rates , and greater need for urgent surgery
41Rol of EGD in giant ulcer EGD is important for the diagnosis of giant GU because barium studies may miss these ulcers due to their large, shallow cratersRuling out malignancy , Crohn's , eosinophilic gastroenteritisSurveillance and documentation of healing
42prepyloric ulcersDistal antral ulcers, especially 2 to 3 cm of the pylorus:Heal more slowlyRecur more likely
43Refractory ulcers Fail to heal despite 8 to 12 weeks of PPI Surveillance EGD should be considered until:Healing is documented orEtiology is defined (eg, surreptitious NSAID use, high gastrin states, ischemia).Surgical consultation may be considered for persistent nonhealing PUD.
44Upper gastrointestinal radiography Barium within an ulcer niche, (round or oval ; by smooth edema) .Folds radiating to the crater, and deformities in theregion secondary to spasm, edema, and scarring.Radiographic signs suggesting gastric malignancy : (1) Ulcer within a definitive mass(2) Fused, or nodular mucosal folds as they approach the margin of the crater(3) Irregular filling defects in ulcer crater
46CT ScanSpiral and multislice contrast CT is clearly the most valuable test for penetrating or perforated ulcerFree airFluid collectionsInflammatory changes in surrounding soft tissuesExtravasation or sinus tracksLocalizing the site of perforation or penetration
47AGA Guideline on the Management of H. pylori Infection H. pylori Infection is one of the most common worldwide human infectionsIs associated with a number of important upper GI conditions :Chronic gastritisPeptic ulcer diseaseGastric malignancy.
48DIAGNOSING AND TREATING H.PYLORI CLEAR INDICATIONS ?CONTROVERSY ?
49Clear indication for H.P test-and-treat Active peptic ulcer disease2. Past history of documented peptic ulcer3. Gastric MALT lymphoma.4. Uninvestigated dyspepsia in:Under the age of 55 yr and no “alarm features”
50Contraversy indication for H.P test-and-treat Functional dyspepsiaSmall but significant clinical benefit from H.pylori eradication.GERDH. pylori eradication not worsens nor improves GERD symptoms.Treatment of H. pylori should not be withheld related to concerns of creating or worsening of GERD
51Contraversy indication for H.P test-and-treat NSAIDsRegardless of NSAID, all patients with a PUDshould be tested and treated for H.pylori.Iron deficiencyData support an association but do not prove cause and effect.
52Contraversy indication for H.P test-and-treat Gastric adenocarcinomaCuring H. pylori may prevent progression of metaplasia to gastric adenocarcinoma, there is no definitive population based data
53Diagnosting tests for H.pylori Endoscopic:Rapid urease testHistologyCultureNon endoscopic:SreologyUrese breath testFecal antigen test
54Rapid urease test (RUT) Base: PH↑ due to H. pylori ureaseBiopsy for RUT should be done from two siteSensitivity>90% and specificity >95%Acute ulcer bleeding at the time of testing may decrease the sensitivity
55False negative RUT Unfortunately, most patients referred for EGD are taking PPI or have recently receivedantibiotics or bismuth.This cause 20% False negative RUT
56What is your plan after a negative RUT? histology of same RUT biopsiesOrUBT or FAT at a later date
57Histology for H.pyloriIs imperfect gold standard because detection of H. pylori is related to site, number and size of gastric biopsiesThree biopsies must be obtained:One from anglularisOne from greater curvature of corpus3. One from greater curvature of antrumSensitivity and specificity >95%
58Antibody TestsIs present 21 days after infection and remain long after eradicationOnly IgG is recomendedPoor PPV limits its usefulness in clinical practice in low prevalence area.
59Urea Breath Tests(UBT) C13/C14 labeled urea labeled CO2C14 UBT is safe. but C13 test is preferred in children and pregnancySensitivity and specificity exceeding 95%Accurate in post treatment eradication
60Recommendation prior to the UBT DC bismuth and antibiotics for 28 daysDC PPI for 7–14 daysDC H2RA for 24–48 hour before the UBTAntacids do not affect the accuracy of UBT
61Fecal Antigen Test (FAT) Is approved by the FDA for:H.pylory infection screeningEstablishing cure following therapy(more than 4 or perhaps 8–12 wk after treatment)Sensitivity is reduced by recent use of bismuth antibiotics, and PPISpecificity is reduced in the setting of GIB
62H.pylory tests in acute upper GIB Sensitivity of RUT and histology may be low in GIBPositive RUT or histology H.P eradicationNegative RUT or histology UBT or FAT at later date
63AGA recommendations in Uninvestigated Dyspepsia In regions with high prevalence of H. pylori :Antibody testing is good screening testIn regions with low prevalence of H. pylori:Negative result is acceptablePositive result should be confirmed with a UBT or FAT that identifies active infection
64Testing to Prove H.P Eradication After Antibiotic Therapy Any H. pylori-associated ulcerPersistent dyspeptic symptoms despite the a course of H.P treatmentH. pylori-associated MALT lymphomaIndividuals who have undergone resection of early gastric cancer
65Testing to Prove H.P Eradication After Antibiotic Therapy If EGD is clinically indicated :Histology ± RUTRUT alone has low sensitivity in the post treatment setting and is not recommended: If EGD is not indicated:UBT or FATAnti H.pylori Ab is not recomended
66Empirical H. Pylori eradication in PUD In region that prevalence of H.pylori in DU is more than 90% H . Pylori eradication can be started without any H . pylori test
67Treatment of H. pylori Infection Triple: PPI + Clarithro + Amoxi/Metro 14 dayQuadruple : PPI+ Bismuth + Metro +Tetra daysSequential therapy :PPI + Amoxi (5 days) PPI + Clarithro + Tinidazole (5 days)
69Treatment of H. pylori Infection PPI should be used b.i.dH2RA can be substituted if a patient cannot tolerate PPI
70Predictors of H. pylori Treatment Outcome Most important predictors of failure arePoor complianceAntibiotic resistance.There is limited evidence to suggest that smoking, alcohol , and diet may reduce successful eradication
71Common side effects of drugs PPI headache, diarrheaClarithro GI upset, diarrhea, altered tasteAmoxi GI upset, headache, diarrheaMetro metallic taste, dyspepsiaTetracycline GI upset, photosensitivityBismuth darkening of the tongue and stool, nausea, and GI upset
72Antibiotic resistance Metronidazole:37%Clarithromycin:10%Both antibiotics:3.9%Amoxicillin :1.4% .Metronidazole resistance can be overcome by use of higher doses(500 mg tds)
73Antibiotic resistance Previous treatment with a macrolide or metronidazole for any reason significantly increase resistanceIn patients with persistent H. pylori ; avoidance from previously used antibiotics is recomended
74culture and antibiotic sensitivity Are typically not performed unless a patient has failed at least 2 courses of therapy.Even in this circumstance, the usefulness of such testing is arguable.
75Recommendations in persistent infection If patient has not been previously treated with clarithro, triple therapy can be doneLevofloxacin-based triple therapy for 10 days is another option (Levofloxacin 500mg daily+ Amoxi 1gr BD+PPI)Other antibiotic used include Rifabutin and Furazolidone.
76Maintenance antisecretory therapy Is recommended in :High-risk patient who fail H. pylori eradicationH. pylori-negative ulcersWith:PPIorCimetidine 400 mg / Ranitidine150 mg Famotidine20 mg / Nizatidine150 mg at bedtime
77Maintenance antisecretory therapy Uncomplicated recurrent disease; stopping therapy after two yearsComplicated disease;five-year may be more appropriate
78Maintenance antisecretory therapy Rebound acid-hypersecretion is important following abrupt cessation of PPIstepping-down to low dose PPI and then to full dose H2RA is an appropriate caution
79H. pylori negative ulcers Special attention to ensure that H. pylori infection and NSAID has been excludedIn confirmed non-H. pylori, non-NSAID ulcers; excluding acid hypersecretory states, such as ZES (fasting serum Gastrin )
80H. pylori test&treat in NSAID user Before starting NSAIDs or aspirin (even at low dose), consider testing for H. pyloriIn NSAID users with ulcer complications and evidence of H. pylori , curing H. pylori does not reduce high risk of ulcer complications if NSAIDs are continued.