Dr. Abdullah Al Mdani Consultant G/I Hepatology PUD Dr. Abdullah Al Mdani Consultant G/I Hepatology

INTRODUCTION • Peptic ulcers are defects in the gastrointestinal mucosa that extend through the muscularis Mucosae • (PUD) is an important and common cause of morbidity and health care costs • Estimates of expenditures related to work loss, hospitalization, and outpatient care (excluding medication costs) are $5.65 billion per year in the United States

NATURAL HISTORY —  • The NH of PU ranges from resolution without intervention to the development of complication with the potential for significant morbidity and mortality, such as bleeding and perforation • Data from the pre-H. pylori, pre-proton pump inhibitor (PPI) era provide important to insights into the natural history of PUD. • Untreated, peptic ulcers have a widely variable natural history . Some heal spontaneously, but recur within months or sometimes within a year or two.

NATURAL HISTORY Relapse occurred in 74 percent of cases; 33 percent had one recurrence, 24 percent two recurrences, 17 ‰ experienced three or more recurrences . Other reports a 50 to 80 ‰ recurrence rate during the 6 to 12 months following initial ulcer healing, although relapses are not always symptomatic .

— Those with a history of complications have an increased risk of future complications. —Ulcers that take longer to heal initially are more likely to recur rapidly — Ulcers that have recurred frequently are likely to continue to do so, unless the underlying cause (eg, H. pylori or [NSAIDs]) is removed

— A long duration of symptoms prior to presentation is more likely to be associated with a poor response to medical therapy.

Epidemiology and etiology of peptic ulcer disease Peptic ulcers were rare before the 1800s The pathology of gastric ulcers (GUs) was first described in 1835 During the late 1800s the prominent form was GUs in young women. Duodenal ulcers (DUs) were rare until about 1900 and then became a prevalent condition during the first half of the 20th century

However, in developed countries the mortality from peptic ulcer disease has fallen dramatically for birth cohorts born after the turn of the 20th century [3].

Incidence  — Uncomplicated peptic ulcer disease range from 0.09 to 0.3 percent per patient-year — The pooled incidence rates for uncomplicated DUs and GUs were comparable — Rates for bleeding from GUs and DUs were also comparable (0.019 and 0.024, respectively) — In contrast, incidence rates for perforated DUs were higher as compared with perforated GUs (0.0055 and 0.0014 percent, respectively).

— Ulcer incidence increases with age for both DUs and GUs, but DUs emerge two decades earlier than GUs, particularly in males — The incidence of bleeding from PUD is 13-fold higher in individuals >70 years as compared with those <40 years — The ulcer incidence in H. pylori-infected individuals is about 1 percent per year, a rate that is 6- to 10-fold higher than for uninfected subjects

Prevalence • A population-based one-year prevalence of PUD of 0.12 to 1.5 percent based on physician diagnosis — 0.1 to 0.19 percent based on hospitalization data . A study in the United States reported an endoscopic point prevalence for peptic ulcers in asymptomatic, H. pylori-positive adults of 2 percent

— Much higher rates are found in countries where H — Much higher rates are found in countries where H. pylori infection is higher . —The lifetime prevalence is also higher in H. pylori-positive subjects (approximat ely 10 to 20 percent compared to 5 to 10 percent in the general population) .

Time trends — Peptic ulcer disease and gastric cancer have been steadily falling over the past several decades Rates of DUs have fallen more dramatically than for Gus — The overall ulcer complication rates are also falling in developed countries — Peptic ulcer hemorrhage and perforation rapidly declined in younger individuals but have been relatively stable in older individuals

These overall trends are due to the interplay of several factors •The incidence of H. pylori in patients younger than 60 years is falling dramatically in developed countries due in part to improved hygiene and socioeconomic conditions •NSAID use increases as a function of age and is an independent risk factor for ulcers •Smoking clearly exacerbates at least H. pylori associated ulcer disease

●Other factors, such as the extreme psychological stress associated with traumatic events, are associated with a transient increase in ulcer disease • Diet has also been hypothesized to account for regional differences

ETIOLOGY ●H. pylori the United States and parts of Europe, the prevalence of H. pylori in PUD (with NSAID use excluded) now ranges from 50 to 75 percent and is continuing to fall rapidly • NSAIDs, including aspirin increase the risk of peptic ulcer disease

ETIOLOGY The Food and Drug Administration (FDA) estimated that nonselective NSAIDs were associated with a 1 to 4 percent per year risk of a clinically significant NSAID-induced G/I event, including gastrointestinal bleeding, perforation, or pyloric obstruction

Risk factors : —A prior history of clinical ulcer disease or ulcer complications — Dose; duration of action; duration of therapy of the NSAIDs; advanced age of the patient (generally above 75 years); co-therapy with drugs that enhance toxicity, and comorbidity, especially with cardiovascular disease —Genetic predisposition

Drug interactions Co-therapy of NSAIDs with steroids, anticoagulants, other NSAIDs, low dose aspirin, selective serotonin reuptake inhibitors (SSRI), and alendronate dramatically increase the risk of ulcer complications

Clopidogrel  The anti-platelet agent clopidogrel was associated with a 12 month rebleeding rate of 8.6 percent, compared to 0.7 percent with aspirin plus a PPI in a study of high-risk patients with a prior history of GI bleeding

Two meta-analyses of case-controlled studies have found synergism between H. pylori and NSAIDs in producing both peptic ulcer and ulcer bleeding

Prevalence of H.pylori infection in Saudia Arabia, and comparison of those with and without upper G.I symptoms. — The prevalence of H. pylori infection increased rapidly with age: from 40% of those ages 5-10 yr, to more than 70% of those 20 or older. — H. pylori infection occurred with significantly more frequency in adults with less than 12 yr of schooling, compared with adults who had attended college. Moagel study 1990 Am.j.Gastro

Diagnosis of peptic ulcer disease • C/F •Blood test •Endoscopy _ Detection of Ulcer _ Differentiation benign or Malign. _ F/ UP to exclude malignant GU

DU

BARIUM RADIOGRAPHY •Detection of ulcer disease- Image • Radiographic differentiation of benign versus malignant lesions

Acute gastric ulcer This image from an upper GI series demonstrates a small ulcer crater (arrow) with smooth folds radiating into the center of the ulcer. This feature suggests benignity, which was confirmed by biopsy. The patient responded to conventional antiulcer therapy. Courtesy of Jonathan Kruskal, MD.

ENDOSCOPY VERSUS BARIUM RADIOGRAPHY — Endoscopy is the appropriate first test for evaluating gastric malignancy. • The use of glucagon or anticholinergic agents to reduce spasm increases the endoscopic and the radiographic yield.

HELICOBACTER PYLORI TESTING • Indications and diagnostic tests for H pylori And when to test 1 — ACG recommendations : — Testing for H. pylori should be performed only if the clinician plans to offer treatment for positive results — Testing is indicated in patients with gastric MALT lymphoma, active peptic ulcer disease, or a past history of documented peptic ulcer

Indications and diagnostic tests for H pylori 2— Peptic ulcer ⁻ Uncomplicated duodenal ulcers ⁻ Uncomplicated gastric ulcer ⁻ Recently bleeding gastric or duodenal ulcers ⁻ Past history of peptic ulcer

3—Long-term PPI therapy: The Maastricht III consensus report recommends that H. pylori testing be considered in patients who are receiving or are to receive long-term maintenance therapy with PPIs 4― Functional dyspepsia : There is evidence from randomized controlled trials that eradication of H. pylori results in relief of dyspepsia in a minority of patients

Other indications • Prior to treatment with chronic use of NSAIDs, • In patients with immune thrombocytopenia, as platelet counts may improve in patients treated for H. pylori Am J Hematol. 2008 • In patients with otherwise unexplained iron deficiency anemia Am J Gastroenterol. 2005 • In patients with otherwise unexplained vitamin B-12 deficiency Gut. 2012 May;61(5)

ENDOSCOPIC TESTING  Three methods: • biopsy urease test : The sensitivity of biopsy urease tests is approximately 90 to 95 percent, and specificity is 95 to 100 percent — Rapid urease testing • histology • Bacterial culture and sensitivity testing

NONINVASIVE TESTING  • Urea breath testing hydrolysis of urea by H. pylori to produce CO2 and ammonia The sensitivity and specificity of UBT are approximately 88 to 95 percent and 95 to 100 percent, respectively • Serology : ELISA technology to detect IgG antibodies , low accuracy , testing for active infection with stool antigen assay or UBT is recommended in these populations

Stool antigen assay  • The sensitivity and specificity of the test were 94 and 86 percent, respectively • The sensitivity and specificity for determining eradication after four weeks was 90 and 95 percent , respectively •False positive results have also been described in patients with acute upper gastrointestinal bleeding, possibly because of cross-reactivity with blood constituents

Rapid stool antigen tests — A rapid H. pylori stool antigen test that can be performed during a clinic visit is available — The sensitivities for initial diagnosis were 93 and 95 percent; the specificities for initial diagnosis were 89 and 87 percent. — The sensitivities following eradication were 94 and 100 percent; the specificities following eradication were 97 and 91 percent.

CONFIRMATION OF ERADICATION A 2007 guideline from the ACG recommends confirming eradication in the following settings ●Any patient with an H. pylori-associated ulcer ●Individuals with persistent dyspeptic sympt. ●Those with H. pylori-ass. MALT lymphoma ●Individuals who have undergone resection of early gastric cancer

TREATMENT • General approach: — All patients with PUD should receive antisecretory therapy — Patients with PUD should be tested for H.P —Patients with H. pylori should be treated with a goal of H. pylori eradication —It is essential to withdraw potential offending or contributing agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), cigarettes, and excess alcohol —No firm dietary recommendations are necessary, though patients should avoid any foods that precipitate symptoms

Eradication of H. pylori •Triple therapy •Quadruple therapy (PPI,Bismuth,Tetracycline,Flagyl) A combination capsule containing bismuth subcitrate 140 mg, metronidazole 125 mg, and tetracycline 125 mg . the combination capsule (three capsules four times daily plus PPI twice daily) Other regimens : levofloxacin, omeprazole, nitazoxanide and doxycycline (LOAD) for 7 or 10 days had significantly higher eradication rates compared to triple therapy

Sequential therapy : a PPI (twice daily) and amoxicillin (1 g twice daily) for five days, followed by a PPI (twice daily) plus clarithromycin (500 mg twice daily) and tinidazole/metronidazole (500 mg twice daily) for five days.