Peptic Ulcer Disease

Peptic ulcer disease includes both duodenal and gastric ulcers. Tobacco smoking, alcohol, and
steroids by themselves do not cause ulcer disease, although tobacco and alcohol can delay
healing and are associated with the development of gastritis.
• NSAIDs can cause ulcer formation because they decrease the normal production of the
mucous barrier protecting the epithelial cells of the gastric mucosa. Prostaglandins, the major
stimulant for mucous production that forms this protective barrier, are inhibited by NSAIDs and
hence diminish the protective barrier of the stomach lining.
• Steroid use by itself does not cause peptic ulcer disease and is therefore not a routine
indication for stress ulcer prophylaxis.
Parietal cells in the stomach produce acid. The 3 stimulants to the production of acid from
the parietal cells are gastrin, acetylcholine, and histamine.
• Gastrin is produced by G cells in the stomach, and its release is stimulated by distention
of the stomach, the presence of amino acids, and vagal stimulation. Vagal
stimulation also releases acetylcholine and gastrin-releasing peptide. However, the
single most important stimulant to gastrin release is distention of the stomach.
• Histamine is released by enterochromaffin-like cells present in the same glandular elements
of the stomach that have the parietal and chief cells. Chief cells release pepsinogen,
which is converted to pepsin by the acid environment of the gastric lumen.
Histamine directly stimulates the parietal cells to both release acid and potentiate the
effects of acetylcholine and gastrin on the parietal cells. This is why H2 blockers such
as cimetidine, famotidine, and ranitidine inhibit acid release.
Zollinger-Ellison syndrome is the excessive production and release of gastrin from the
pancreas. Somatostatin is the counterbalance to this system, inhibiting the release of gastrin
and histamine, as well as having a direct inhibitory effect on the production of acid from the
parietal cells. Secretin is released from the S cells of the duodenal lining. The main stimulant to
the release of secretin is the presence of acid in the duodenum. Secretin inhibits the production
of gastrin, as well as stimulates pancreatic and biliary bicarbonate production and release.
The most common cause of ulcer disease is Helicobacter pylori followed by the use of
NSAIDs; 80–90% of duodenal ulcers and 70–80% of gastric ulcers are associated with
H. pylori. Overall, 10–20% of ulcers are idiopathic, and no clear etiology is ever identified.

Clinical Presentation. The most common presentation of ulcer disease is midepigastric pain.
There is no definite way to distinguish between duodenal and gastric ulcer simply by symptoms.
Gastric ulcer is often associated with pain on eating (frequently leading to weight loss),
while duodenal ulcer is thought to be relieved by eating. However, these associations
are only rough approximations, and endoscopy is still required for a definite diagnosis.
Tenderness of the abdomen is unusual with ulcer disease. More than 80% are not associated
with abdominal tenderness in the absence of a perforation. Nausea and vomiting are
occasionally found with both of them.
Complications of PUD: All patients with the following complications need special care at
referral hospitals
• Haemorrhage
o Is the most common complication of PUD, and patients present with hematemesis, passage
of tarry stools, weakness, hypotension, syncope, thirst and sweating resulting from associated
blood loss.
o Immediate treatment can be given via endoscopy or surgery.
• Penetration (confined perforation)
ο Is entering of adjacent confined space (e.g. lesser sac) or organ (e.g. pancreas, liver).
ο Adhesions prevent leakage into peritoneal cavity.
ο Radiographic evaluation with contrast study is usually needed to confirm the diagnosis.
ο When medical therapy does not produce healing, surgery is recommended.
• Free perforation
ο Usually presents as acute abdomen with sudden, intense, steady epigastric pain.
ο Diagnosis is confirmed with upright or lateral decubitus x-ray of abdomen.
• Gastric outlet obstruction (GOO)
ο May be caused by scarring, spasm, or inflammation.
ο Symptoms include recurrent large volume vomiting, persistent bloating, fullness
after eating, loss of appetite; weight loss, dehydration and alkalosis due to prolonged vomiting.
ο Succussion splash for over 6 hrs after a meal, gastric aspiration or x - rays may help in the
diagnosis.
ο Treat such patients with nasogastric tube aspiration and acid suppression if causes are
temporary. But if the pyloric canal scarred, do endoscopic pyloric balloon dilatation or surgical
relief of obstruction.
• Stomach cancer
ο Is intestinal type adenocarcinoma of gastric body and antrum and commonly
associated with H. pylori infection.
ο Moreover, the incidence of MALT lymphoma (MALT=mucosa-associated
lymphatic tissue) is increased in PUD.
ο Treating H. pylori might cure lymphoma, but chemotherapy or radical surgery
must be used when such treatment fails to cure the tumour.
ο For adenocarcinoma, surgery is always treatment of choice

Diagnosis. Ulcer disease is best diagnosed with upper endoscopy. Barium studies are inferior.
• If patient age <50 and has no alarm symptoms, test and treat for H. pylori. If H. pylori
is negative, give trail of proton-pump inhibitors (PPIs). If symptoms persist, perform
endoscopy.
• If patient age >50 or has alarm symptoms (weight loss, anemia, heme-positive stools,
or dysphagia), perform endoscopy.
The diagnosis of H. pylori is based on urea breath testing, stool antigen testing, or biopsy with
histology or rapid urease testing. The first 2 tests are non-invasive. Before testing for H. pylori,
make sure the patient is off PPIs for 2 weeks and antibiotics for 4 weeks, as they can
cause false-negatives. Biopsy with histology can be done on treatment. Biopsy with rapid
urease testing can also be false-negative on treatment.
Do not check serum antibodies as they will not indicate whether this is a past or present
infection.
Note Gastric ulcers must be biopsied to exclude cancer.

Treatment. The treatment of ulcer disease centers largely on the treatment of H. pylori. Use a
proton pump inhibitor (PPI) combined with clarithromycin and amoxicillin. The PPIs omeprazole,
lansoprazole, pantoprazole, rabeprazole, and esomeprazole are all equal in efficacy.
The PPI/clarithromycin/amoxicillin regimen should be effective in >90% of patients. The
other 2 choices of antibiotics are tetracycline and metronidazole.
• Bismuth subsalicylate is not necessary (USA).
• Regimens that contain PPIs are superior to those that use H2 blockers, such as
ranitidine or cimetidine.
• The duration of therapy is 10−14 days, but sometimes the PPI is continued for a few
months in order to heal the gastric mucosa.
• Repeat endoscopy for gastric ulcers is needed only if symptoms persist or if biopsies
were not done the first time. Follow-up endoscopy for duodenal ulcers is not required.
Testing for eradication is indicated only for persistent symptoms, ulcers, or malignancy.
• Wait 4−8 weeks after treatment to check for eradication. Do not use serology to test
for eradication.
• If the organism was not eradicated, then repeat treatment with different antibiotics,
plus bismuth subsalicylate. Explore sensitivity testing for the organism.
• If the organism was eradicated and the ulcer persists or worsens, consider evaluating
the patient for Zollinger-Ellison syndrome.
Ordinary ulcers not related to Helicobacter can be treated with PPIs alone. Stop NSAIDs. If
unable to stop aspirin or NSAIDs, add a PPI, although COX-2 inhibitors are just as good as
NSAIDs plus PPI. Sucralfate does not help and should not be used.

Give PPI for prophylaxis if patient is high risk. Risk factors include:
• History of PUD or GI bleed
• Age 65 years or older
• Chronic comorbid illness
• High-dose NSAID use
• Concomitant use of aspirin (of any dose), anticoagulants, other NSAIDs, or glucocorticoids

Indications for surgery in peptic ulcer disease (PUD):

• UGI bleed not amenable to endoscopic procedures
• Perforation
• Refractory ulcers
• Gastric outlet obstruction (can change endoscopic dilation)

Treatment
WHO:
Quadruple therapy (more effective):
1. bismuth subcitrate 240 mg twice daily (or 120 mg four times daily) or bismuth
subsalicylate (534 mg four times daily) or proton pump inhibitor
2. proton pump inhibitor (omeprazole 20 mg twice daily, lansoprazole 30 mg twice daily,
pantoprazole 40 mg twice daily, or rabeprazole 20 mg twice daily)
3. amoxicillin (1 g twice daily)
4. clarithromycin (500 mg twice daily). Or (alternative) levofloxacin 500 mg twice daily
In some countries:
Triple therapy:
1. proton pump inhibitor (omeprazole 20 mg twice daily, lansoprazole 30 mg twice daily,
pantoprazole 40 mg twice daily, or rabeprazole 20 mg twice daily)
2. amoxicillin (1 g twice daily)
3. clarithromycin (500 mg twice daily). Or (alternative) levofloxacin 500 mg twice daily
10- day, or 14- day therapy are comparable. The differences between proton pump inhibitors
are minimal. H. pylori is rarely resistant to amoxicillin. Metronidazole can be used to substitute
amoxicillin in penicillin- allergic patients.
Quadruple therapy:
1. bismuth subsalicylate (534 mg four times daily) or bismuth subcitrate 240 mg twice daily
(or 120 mg four times daily)
2. proton pump inhibitor
3. metronidazole 500 mg 3 times daily
4. tetracycline 500mg four times daily given for 10 to 14 days
Stage сlassification of gastric ulcer by Sakita-Miwa

• Active stageA1 The surrounding mucosa is edematously swollen and no regenerating

epithelium is seen endoscopically
• A2 The surrounding edema has decreased, the ulcer margin is clear, and a slight
amount of regenerating epithelium is seen in the ulcer margin. A red halo in the marginal
zone and a white slough circle in the ulcer margin are frequently seen. Usually,
converging mucosal folds can be followed right up to the ulcer margin
• Healing stageH1 The white coating is becoming thin and the regenerating epithelium is
extending into the ulcer base. The gradient between the ulcer margin and the ulcer floor
is becoming flat. The ulcer crater is still evident and the margin of the ulcer is sharp. The
diameter of the mucosal defect is about one-half to two thirds that of A1
• H2 The defect is smaller than in H1 and the regenerating epithelium covers most of the
ulcer floor. The area of white coating is about a quarter to one-third that of A1
• Scarring stageS1 The regenerating epithelium completely covers the floor of ulcer. The
white coating has disappeared. Initially, the regenerating region is markedly red. Upon
close observation, many capillaries can be seen. This is called ‘‘red scar’’
• S2 In several months to a few years, the redness is reduced to the color of the
surrounding mucosa. This is called ‘‘white scar’’