1. peptic ulcer disease

2. Definition
Disruption of mucosal and submucosal integrity of the stomach and/or duodenum >5 mm in size

3. Epidemiology Peptic ulcer disease Duodenal ulcers Gastric ulcers
Prevalence: 12% of men and 10% of women in U.S.
Duodenal ulcers
6–15% of the Western population
Gastric ulcers
Less common than DU
occur later in life than DU; peak in 6 decade
More than half occur in males

4. Epidemiology Helicobacter pylori infection Prevalence : 30% in U.S.
10% of Americans < 30 years
80% in developing parts of the world

5. Risk Factors Genetic predisposition
First-degree relatives of patients with DU or GU are at 3-fold increased risk for ulcer
Patients with blood group O may be at increased risk; the antigen may be a target of H. pylori .

6. Risk 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.

7. Risk factors for H. pylori
Birth or residence in a developing country
Domestic crowding
Unsanitary living conditions
Unclean food or water
Exposure to gastric contents
Poor socioeconomic status
Less education

8. Risk factors for NSAID-induced PUD
Advanced age
History of ulcer
Concomitant use of glucocorticoids or anticoagulants
High-dose NSAIDs
Multiple NSAIDs use
Serious or multisystem disease
Concomitant infection with H. pylori
Cigarette smoking
Alcohol consumption

9. Cigarette smoking Increase duodenal acid by:
Increasing gastric acid secretion
Impair duodenal and pancreatic bicarbonate
Smokers are at increased risk for DU and GU

10. Smoking in Hp-associated PUD is major risk factor for:
Occurrence
Persistence
Recurrence following Hp eradication
Complications
Impairs ulcer healing
Increases the need for surgery

11. Etiology of PUD

12. Disease Associated with PUD
COPD
CRF
Cirrhosis
Organ transplant
Nephrolithiasis
α1 antitrypsin deficiency
Hyperparathyroidism
Systemic mastocytosis
Coronary artery disease
Polycythemia vera
Chronic pancreatitis

13. Symptoms of PUD

14. Laboratory evaluation
Routine laboratory studies are typically normal.
Screening studies should include :
CBC
liver chemistries
serum creatinine
serum calcium.
A fasting serum gastrin level is indicated in ulcers refractory to therapy, with a positive family history, or in cases requiring surgery.

19. ASGE Guidelines for endoscopy indication in dyspeptic patients
New-onset dyspepsia in older than age 50
Alarm features in any age that suggest significant structural disease or malignancy.
Persistent dyspeptic symptoms

20. Alarm features Family history of upper GI malignancy Weight loss
Overt GI bleeding, iron deficiency anemia
Progressive dysphagia or odynophagia
Persistent vomiting
Palpable mass
Lymphadenopathy.

21. Dyspeptic patients younger than 50 without alarm features
Should be test for H. pylori
If positive : H.pylori eradication
If negative :
short trial (4-8 weeks) PPI or
EGD
NSAID stopped, if possible.

22. Endoscopy in DU (ASGE RECOMMENDATIONS)
Endoscopy is not recommended in benign-appearing, uncomplicated duodenal ulcers identified on radiologic imaging
DU are extremely unlikely malignant, and routine biopsy is not recommended

24. Endoscopy 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.

26. Endoscopy in GU
If 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.

27. GU

28. HEALED ULCER

29. Biopsy in GU
Biopsy of all gastric ulcers was recommended in the past because older data suggested that 5% to 11% of GU represented malignancy
There are no recent data to recommend the need for biopsy of all GU.

30. Routine biopsy may not be necessary in GUIf
history suggest a very low risk of malignancy
In young patient taking NSAIDs and endoscopic typical NSAID lesions (eg, shallow flat antral ulcer with associated erosions) biopsy is not necessary.

31. Role 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 for
Rule out refractory peptic ulcers
Rule out ulcers with nonpeptic etiologies

32. surveillance 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

33. Surveillance 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

34. ASGE 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.

35. ASGE 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.

36. ASGE recommendation cont.
6. Surveillance endoscopy indication in GU:
Symptomatic despite a medical therapy.
Ulcer without a clear etiology
If 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.

37. ASGE recommendation cont.
8. Endoscopy should be performed early in the course of hospitalization in bleeding PUD
9. 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.

38. ASGE 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.

39. Giant 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

41. Rol 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 craters
Ruling out malignancy , Crohn's , eosinophilic gastroenteritis
Surveillance and documentation of healing

42. prepyloric ulcers
Distal antral ulcers, especially 2 to 3 cm of the pylorus:
Heal more slowly
Recur more likely

43. Refractory ulcers Fail to heal despite 8 to 12 weeks of PPI
Surveillance EGD should be considered until:
Healing is documented or
Etiology is defined (eg, surreptitious NSAID use, high gastrin states, ischemia).
Surgical consultation may be considered for persistent nonhealing PUD.

44. Upper gastrointestinal radiography
Barium within an ulcer niche, (round or oval ; by smooth edema) .
Folds radiating to the crater, and deformities in the
region 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

46. CT Scan
Spiral and multislice contrast CT is clearly the most valuable test for penetrating or perforated ulcer
Free air
Fluid collections
Inflammatory changes in surrounding soft tissues
Extravasation or sinus tracks
Localizing the site of perforation or penetration

47. AGA Guideline on the Management of H. pylori Infection
H. pylori Infection is one of the most common worldwide human infections
Is associated with a number of important upper GI conditions :
Chronic gastritis
Peptic ulcer disease
Gastric malignancy.

48. DIAGNOSING AND TREATING H.PYLORI
CLEAR INDICATIONS ?
CONTROVERSY ?

49. Clear indication for H.P test-and-treat
Active peptic ulcer disease
2. Past history of documented peptic ulcer
3. Gastric MALT lymphoma.
4. Uninvestigated dyspepsia in:
Under the age of 55 yr and no “alarm features”

50. Contraversy indication for H.P test-and-treat
Functional dyspepsia
Small but significant clinical benefit from H.pylori eradication.
GERD
H. 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

51. Contraversy indication for H.P test-and-treat
NSAIDs
Regardless of NSAID, all patients with a PUD
should be tested and treated for H.pylori.
Iron deficiency
Data support an association but do not prove cause and effect.

52. Contraversy indication for H.P test-and-treat
Gastric adenocarcinoma
Curing H. pylori may prevent progression of metaplasia to gastric adenocarcinoma, there is no definitive population based data

53. Diagnosting tests for H.pylori
Endoscopic:
Rapid urease test
Histology
Culture
Non endoscopic:
Sreology
Urese breath test
Fecal antigen test

54. Rapid urease test (RUT)
Base: PH↑ due to H. pylori urease
Biopsy for RUT should be done from two site
Sensitivity>90% and specificity >95%
Acute ulcer bleeding at the time of testing may decrease the sensitivity

55. False negative RUT Unfortunately, most patients referred for EGD
are taking PPI or have recently received
antibiotics or bismuth.
This cause 20% False negative RUT

56. What is your plan after a negative RUT?
histology of same RUT biopsies Or
UBT or FAT at a later date

57. Histology for H.pylori
Is imperfect gold standard because detection of H. pylori is related to site, number and size of gastric biopsies
Three biopsies must be obtained:
One from anglularis
One from greater curvature of corpus
3. One from greater curvature of antrum
Sensitivity and specificity >95%

58. Antibody Tests
Is present 21 days after infection and remain long after eradication
Only IgG is recomended
Poor PPV limits its usefulness in clinical practice in low prevalence area.

59. Urea Breath Tests(UBT)
C13/C14 labeled urea  labeled CO2
C14 UBT is safe. but C13 test is preferred in children and pregnancy
Sensitivity and specificity exceeding 95%
Accurate in post treatment eradication

60. Recommendation prior to the UBT
DC bismuth and antibiotics for 28 days
DC PPI for 7–14 days
DC H2RA for 24–48 hour before the UBT
Antacids do not affect the accuracy of UBT

61. Fecal Antigen Test (FAT)
Is approved by the FDA for:
H.pylory infection screening
Establishing cure following therapy(more than 4 or perhaps 8–12 wk after treatment)
Sensitivity is reduced by recent use of bismuth antibiotics, and PPI
Specificity is reduced in the setting of GIB

62. H.pylory tests in acute upper GIB
Sensitivity of RUT and histology may be low in GIB
Positive RUT or histology  H.P eradication
Negative RUT or histology  UBT or FAT at later date

63. AGA recommendations in Uninvestigated Dyspepsia
In regions with high prevalence of H. pylori :
Antibody testing is good screening test
In regions with low prevalence of H. pylori:
Negative result is acceptable
Positive result should be confirmed with a UBT or FAT that identifies active infection

64. Testing to Prove H.P Eradication After Antibiotic Therapy
Any H. pylori-associated ulcer
Persistent dyspeptic symptoms despite the a course of H.P treatment
H. pylori-associated MALT lymphoma
Individuals who have undergone resection of early gastric cancer

65. Testing to Prove H.P Eradication After Antibiotic Therapy
If EGD is clinically indicated :
Histology ± RUT
RUT alone has low sensitivity in the post treatment setting and is not recommended
: If EGD is not indicated:
UBT or FAT
Anti H.pylori Ab is not recomended

66. Empirical 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

67. Treatment of H. pylori Infection
Triple: PPI + Clarithro + Amoxi/Metro 14 day
Quadruple : PPI+ Bismuth + Metro +Tetra days
Sequential therapy :PPI + Amoxi (5 days)  PPI + Clarithro + Tinidazole (5 days)

69. Treatment of H. pylori Infection
PPI should be used b.i.d
H2RA can be substituted if a patient cannot tolerate PPI

70. Predictors of H. pylori Treatment Outcome
Most important predictors of failure are
Poor compliance
Antibiotic resistance.
There is limited evidence to suggest that smoking, alcohol , and diet may reduce successful eradication

71. Common side effects of drugs
PPI headache, diarrhea
Clarithro GI upset, diarrhea, altered taste
Amoxi GI upset, headache, diarrhea
Metro metallic taste, dyspepsia
Tetracycline GI upset, photosensitivity
Bismuth darkening of the tongue and stool, nausea, and GI upset

72. Antibiotic 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)

73. Antibiotic resistance
Previous treatment with a macrolide or metronidazole for any reason significantly increase resistance
In patients with persistent H. pylori ; avoidance from previously used antibiotics is recomended

74. culture 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.

75. Recommendations in persistent infection
If patient has not been previously treated with clarithro, triple therapy can be done
Levofloxacin-based triple therapy for 10 days is another option (Levofloxacin 500mg daily+ Amoxi 1gr BD+PPI)
Other antibiotic used include Rifabutin and Furazolidone.

76. Maintenance antisecretory therapy
Is recommended in :
High-risk patient who fail H. pylori eradication
H. pylori-negative ulcers
With:
PPI or
Cimetidine 400 mg / Ranitidine150 mg Famotidine20 mg / Nizatidine150 mg at bedtime

77. Maintenance antisecretory therapy
Uncomplicated recurrent disease; stopping therapy after two years
Complicated disease;
five-year may be more appropriate

78. Maintenance antisecretory therapy
Rebound acid-hypersecretion is important following abrupt cessation of PPI
stepping-down to low dose PPI and then to full dose H2RA is an appropriate caution

79. H. pylori negative ulcers
Special attention to ensure that H. pylori infection and NSAID has been excluded
In confirmed non-H. pylori, non-NSAID ulcers; excluding acid hypersecretory states, such as ZES (fasting serum Gastrin )

80. H. pylori test&treat in NSAID user
Before starting NSAIDs or aspirin (even at low dose), consider testing for H. pylori
In 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.