2DefinitionPUD is a disease of multiple etiology that characteristic of local gastric or duodenal damage and ulceration
3EpidemiologyThe annual incidence in USA 1.8% or new cases per year.There are 4 million ulcer recurrences yearly.More than operation for PUD performed yearly.About 4000 patient die from complication of their PUD yearly
4PathogenesisDisbalance between aggressive factors and defenisive factors cause ulcerProtective factor (defensive) – mucous bicarbonate secretion ,blood flow, grwoth factors, cell renewal, endogenous prostaglandineDamaging(aggressive ) factors-HCL secretion, ethanol, smoking, reflux of bile, NSAID, hypoxia, HP
5cause 1. H.PYLORI infection (most common cause) 2.NSAID (second most common cause)3.stress4. incrased pepsin and acid secretion
6Role of HP90% of duodenal ulcer and 70% of gastric ulcer are associated with H.Pylori infectionH.Pylori is a gram-negative rod with 6 flagella.
7HP HP is a chronic infection that found worldwide Person is infected, usually in childhood.Developing countries have a higher rate of HP infection.
8HP infection varies with racial and ethnic group- in USA white tend to have lowest rates of infection, African American rates of infection at each age is doubled those of white.This difference in prevalence is related to lower socioeconomic status during childhood.
9Rout of transmissionHP infection in one household member is associated with greater chance of infection in other members.This mean that infection is transmitted person- to- person route and acquired early in life
10HPHP resides in gastric type epithelium within or beneath the mucus layer which is protect it from acid and antibiotic.It shape and flagella aid it movement within through the mucus layerHP produce variety of enzymes that help it adapt to hostile environment
11HP HP most potent producer of urease Urease an enzyme that split urea into ammonia and bicarbonate creating an alkaline microenvironment in the sitting of acidic gastric milieuThis facilitate DS in laboratory test
12Mechanism of gastric injury by HP 1. production of toxic product to case local tissue injury2. induction of local mucosal immune response3. increased gastrin levels with a resultant increase in acid secretion.
131.Toxic product -local injury HP locally produce toxic product include:* breakdown product from urease activity (ammonia).* cytotoxins : - a mucinase that degrades mucus and glycoprotein's , phospholipases that damage epithelial and mucus cells* platelet-activating factor-known to cause mucusal injury and thrombosis in microcalcification
142. Local Immune Injury d/t HP HP known to case local inflammatory reaction in gastric mucusa and to produce chemotactic factors that attract neutrophils and monocytesActivated monocytes and neutrophils in turn produce a number of proinflamatory cytokines and reactive oxygen metabolites
153.Gastrine and HPIn patient with HP infection basal and stimulated gastrine level are increased secondry to reduction in antral D cells caused by infection with HP.HP-infected patient with duodenal ulcer did have a marked increase in acid secretion
16HP and other GI disorder HP is present in most case of chronic gastritisHP most gastric cancer patient show evidence of past HP infection.There is strong association between mucosa-associated lymphoid tissue( MALT) lymphoma and HP infectionEradication of HP infection cause regression of these MALT lymphoma
17Gastritis and PUD PUD strongly associated with antral gastritis. All patient with PUD have histologic evidence of antral gastritis (95%)The only patient with gastric ulcer and no gastritis those ingesting aspirin or NSAID25% of patient with NSAID- associated ulcer have evidence of antral gastritis.
19after HP infection NSAID is the most common cause of PUD. Risk of complication and bleeding in patient taking NSAID is increased with age >60 , patient having prior GI event or use of steroid and anticoagulant
20Epidemiology of PUD and NSAID 3 million people in USA take daily NSAID1 in 10patient taking NSAID have an acute ulcer2%-4% of NSAID user have GI complication each yearMore than 3000 death and hospitalization per year are attributed to NSAID induced GI complication
21NSAID injury NSAID can cause acute gastroduodenal injury or chronic. Acute injury occur within 2 week of use and range from hyperemia to erosionChronic injury occur after month of use and range from erosion to ulceration
22Characteristic of NSAID ulcer NSAID ulcer more frequently found in stomach whereas HP- ulcer found in duodenumChronic active gastritis always associated with HP and not found in NSAID associated ulcerWhen NSAID is stopped the ulcer not recur but HP – associated ulcer recurrence is 50%-80% in 1 year unless the organism is eradicated
23DU pathophisiology Is a disease of multiple ethiology Absolute requirement: acid and pepsin secretion in combination of H.Pylori infection or NSAIDs ingestionSecretor abnormalities such as : bicarbonate secretion, nocturnal acid secretion, daytime acid secretionDU associated with parietal cell number
24Pathophysiology of gastric ulcer GU may occur anywhere in stomachGU rarely develop before age of 40, peak incidence yearsPredispose condition: age>40, sex f:m 2:1, ingestion of barrier breaking drug (aspirin), abnormalities in acid and pepsin secretion, gastric stasis, delayed gastric emptying, coexisting DU, duodenal gastric reflux of bile, infection with HP, smoking, alcohol intake
25TYPE I of GU Account for 60% of GU Occur within 1.5cm of the histologic transition zone between the fundic and and antral mucosa (in the lesser curvature near the incisura)Are not associated with excessive acid secretionNot associated with DU or prepyloric ,pyloric mucosal abnormalitiesMalignancy are major concern
26TYPE II of GUAbout 15%Are located in the body of stomach in combination with a duodenal ulcerAssociated with excess acid secretion
27TYPE III of GU About 20% Located in the preylorus Are associated with excess of acid secretion
28TYPE IV of GUABOUT 10%Occur hiegh in the lesser curvature near the gasroesophageal junctionAre not associated with excessive acid secretion
29clinical feature Abdominal midepigastric pain. Pain is well localized Tolerable and relieve by food in DU and exagerated by food in GUPain irradiation to back suggest pentration to pancreasOther magnifestation: perforation, bleeding, obstruction
30PerforationAbout 5% of the time ulcer perforated into free peritoneal cavity and elicit chemical peritonitis.The patient recall the exact time of onset of pain.Pain accompanied by fever, tachycardia, dehydration and ileus.
31Perforation Examination reveal: tenderness, rigidity and rebound Diagnosis is established by free air in upright chest X-Ray underneath the diaphragm.Treatment is operative after fluid resuscitation
32BleedingThe most common cause of death with PUD is bleeding in those who have medical problems or are older than 60 yearsIn DU bleeding usually from GDAMost case of massive GI bleeding are DU following penetration of ulcer in GDABleeding can manifests as melena or bloody vomiting
33ObstructionActive inflamation of duodenum can cause mechanical obstruction and functional gastric outlet obstructionDelayed gastric emptying lead to nausea and vomitingCan lead to hypochloremic hypokalemic metabolic alkalosis secondry to loss of gastric juice and H+, CL-, K
34Zollinger –Ellison Syndrome ZES clinical triade:1 .Gastric acid hyper secretion2. Severe PUD3. Non-b islet cell tumorsZES are known to produce gastrin and called gastrinomas
35ZESZES usually localized to the head of pancreas, duodenal wall or regional LN.½ of ZES are multiple2/3 of ZES are malignant¼ of ZES are associated with MEN1
36ZES Clinically- abdominal pain and PUD in 80% of case. ½ of patient have diarrhea secondary to increase gastric acid secretion (Gastrin stimulation secretion of acid)Weight loss and steatorrhea occur secondary to decreased duodenal and jeujenal PH and inactivation of lipaseEsophagitis is common
37When consider ZESIn a ptient with recurrent or intractable PUD despite eradication of H.Pylori.In patient with multiple or atypically located ulcer.PUD associated with significant diarrheaPUD associated with symptom of MEN1: hyperparthyroidismPatient with other pancreatic endocrine tumorsLarge gastric rugae in endoscopy
38How to diagnose ZESElevated serum gastrin > 200 pg/ml, value >1000 is diagnosticSecretin test: give secretine 2u/kg and measure serum gastrin before and after gastrin administration evrey 5 minute for 30 minute: an increase of serum gastrin of greater than 200pg/ml above basal level is specific for gastrinoma.
40History and physical examination. Laboratory to R/O other condition: CBC, Liver chimistry, cre, elecgtrolytes, amylaseSerum Gastrin in refractory ulcerChest- X-ray- to rule out perforationEndoscopy or contrast radiographyH.pylori testing
41H.Pylori testingSerology- HP ilicites a local as a systemic immunoglonulin G mediated immune response that can measured by ELISASerology is test of choice when endoscopy is not indicatedSensitivity 90%Limitation: the test remain high for year or more thus cannot used to assess eradication
42Urease breath test Carbon- labeled urea breath test Based in ability of HP to hydrolyze urea to ammonia and bicarbonatePatient ingest 14C or 13C Isotope after carbone ingestion urea metabolized to ammonia and bicarbonate if HP present
43Urease breath testThe bicarbonate is excreted in the breath as labeled carbon dioxideNegative result occur if the test done early after treatment , , 4 weak.Is the method of choice to documment erradication,Test not expensive
44Rapid urease assayThe urease catalize urea to ammonia and bicarbonate creating an alkaline environmentThis environment can measured by PH indicatorEndoscopy is performed and gastric mucosal biopsied to perform the testSensitivity 90%, specificity 98%.
45Diagnosis of HP by histology Endoscopy performed and biopsy obtainedDiagnosis is by visualization of HP by hematoxyline and eosin stainSensitivity is 90%, specificity is 99%HP can cultured – diagnosis required 3-5 days and expensive, sensitivity 80%, specificity is 99%
46Upper GI radiographyThe barium is demonstrated within the ulcer crater which is round or oval and may or may not surrounded by edemaWith single contrast 50% of ulcer may be missedWith double contrast 80-90% of ulcer carter can be detectedCan asses the depth and penetrationLimitation- cannot r/o malignancy
48Endoscopy The most reliable method of diagnosis Ability to diagnose malignancyBenign ulcer have smooth ulcer baseMalignant ulcer associated with mass and protrude into the lumen or have fold surrounding the ulcer carterBiopsy can performed with endoscopy .
50The goals of treatment 1.symptom need to be relieved 2.The ulcer need to be healed3. Recurrence must be preventedThe antisecretory agent achieve the first 2 goalsWith NSAIDs related ulcer discontinuation of NSAIDs achieve the 3 goalEradication of HP achieve the 3 goal
51AntacidsAntacids reduce the gastric acidity by reacting with HCL forming a salt and waterIf taking on an empty stomach the antacids are emptied rapidly and have only transient effect ( for this take just after meal)Can result in 80% healing at 1 monthMagnesium antacids – the best buffers but can cause significant diarrheaAluminum antacis can bind phosporus and result in hypophospatemia and constipation
52H2-receptor antagonist Structurally similar to histamineUndergo hepatic metabolism and excreted by kidneyHalf-life hoursThe most potent is famotidineLess potent is cimetidine.Result in DU healing 70-80% after 4 weak and 80-90% after 8 weakContinuous IV infusion can produce more effect than intermittent administration
53Proton Pump Inhibitor Are the most potent antisecretory agent Bond to the catalytic alfa subunit of the proton pump and negate all types of acid secretionInhibition is more potent than H2 antagonist and more prolonged and irreversibleProduce more rapid healing of ulcer, healing rate 85% at 4 weeks , and 95% at 8 weeksPPI require an acidic environment within gastric lumen to become activated
54SucralafateStructurally related to heparin but not have anticoagulant effectAluminum salt of sulfated sucrose disassociates under acidic condition to sucrose polymerizes and bind protein in ulcer crater to produce a kind of protective coating that can last for 6 hoursDU healing after 4-6 weeks of treatment : 1g *4/dayEffect is compared to cimetidine
55Treatment of HPVery important, recurrence without eradication is 72%, after eradication is 2%.Use antibiotic:Moxypen 1gr*2 + clarythromycin 0.5 gr*2 for 14 daysOr Moxypen 1gr*2 for 10 days followed by clarythromycin 0.5*2 or metronidasole 0.5*3 for 5 days
57Indication for operation 1.intractability (failure of ulcer healing after 8-12 weeks of therapy)2.hemorrhage3.perforation4.obstruction
58The goals of operation Prevent of gastric acid secretion Achieved by: 1.anterctomy- removal of the gastrin-secretion portion of stomach2.vagotomy alone decrease the acid secretion by 50%3.Combination of vagotomy and anterectomy decrease acid secretion by 85%
59Truncal vagotomyDivision of RT and LT vagus nervus above the hepatic and celiac branches just above the GEJMost commonly used for DU .Performe drainage procedure mandatorydrainage operation: heineke-mikulicz, Finney, jaboulay pyloroplastySide effects- bile reflux after gastroduodenostomy, diarrhea after pyloroplasty
63Highly Selective Vagotomy (Parietal Cell Vagotyomy) Divide only the vagus nerve supplying the acid-producing portion of stomach within the corpus and fundusPreserve the vagal innervation of antrum , thus no need for drainage procedureThe nerve of latarjet devided and crows feet innervation of fundus and body devided until point 7 cm proximal to pylorus and to point 5 cm proximal to GEJ.Tow or three branchs to antrum and pylorus preserved
64The criminal nerve of Grassi represent a very proximal branch of the posterior trunk of vagus and great attention is take to avoid missing of them, because is cited predisposition for ulcer recurrenceRecurrence rate 10-15% and usually patient responsive to medical therapyThis not procedure of choice for pylorus ulcer but for duodenal ulcerPostvagotomy syndrome is rare
66Truncal Vagotomy and Antrectomy Indication- gastric ulcer and benign gastric tumoursContraindication- cirrhosis, previous operation on duodenumRecurrence rate 0-2%Postagstrectomy and postvagotomy syndrome occur in 20% .Reconstruction of GI tract done by biloroth 1 or 2 or Roux-En-Y
69Subtotal Gastrectomy Rarely used today for treatment of PUD Are preserved for malignancy
70Laparoscopy All previous procedure can performed laparoscopicaly Also omentopexy for perforation can performed laparoscopicaly.Taylor procedure- parietal cell vagotomy+posterior truncal vagotomy+seromyotomy
71Surgical Treatment Recommendations for Complications Related to Peptic Ulcer Disease
72Duodenal Ulcer Intractable: parietal cell vagotomy Bleeding: truncal vagotomy with pyloroplasty and oversewing of bleeding vesselPerforation: patch closure with treatment of H. pylori with or without parietal cell vagotomyObstruction: rule out malignancy and parietal cell vagotomy with gastrojejunostomy
73Gastric Ulcer Intractable Type I: distal gastrectomy with Billroth I Type II or III: distal gastrectomy with truncal vagotomy BleedingType II or III: distal gastrectomy with truncal vagotomy PerforatedType I, stable: distal gastrectomy with Billroth IType I, unstable: biopsy, patch, and treatment for H. pyloriType II or III: patch closure with treatment of H. pyloriObstruction:rule out malignancy and antrectomy with vagotomyType IV: depends on ulcer size, distance from the gastroesophageal junction, and degree of surrounding inflammation.Giant gastric ulcers: distal gastrectomy, with vagotomy reserved for type II and III gastric ulcers