45 ACID-PEPTIC ULCER DISEASE
Frank H. Chae M.D.

DUODENAL ULCER DISEASE

1. What is the risk of duodenal ulcer disease?

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The lifetime risk for duodenal ulcer is about 1 in 14. It usually occurs between ages 20 and 60 years, with peak incidence in the fourth decade of life. It is more common in males. Hemorrhage is the most common cause of hospital admission. The annual number of deaths in the United States is about 10,000 deaths caused by duodenal ulcers.

2. What is the role of Helicobacter pylori in duodenal ulcer?

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Helicobacter pylori, a gram-negative bacillus, is strongly associated with peptic ulcer disease. It is isolated from antral mucosa in 80% of patients with peptic ulcer disease. Ulcers may occur in the absence of H. pylori. These ulcers occur in the setting of hyperacid secretion, normal acid secretion, or after acid reduction operations such as vagotomy. Recurrent or multiple ulcerations may indicate an underlying endocrine disease. The breakdown of the duodenal mucosal barrier probably also contributes to ulcerogenesis.

3. Is acid hypersecretion necessary for peptic ulcer disease?

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No. Gastric hypersecretion of acid and pepsin plays an important role in ulcer formation; however, only 40% of ulcer sufferers manifest acid hypersecretion.

4. What are the clinically important complications of H. pylori infection?

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Peptic ulcer disease: As noted, H. pylori is present in 80% of peptic ulcers. Conversely, 50% of the general population harbors this organism, but only a small percentage of people develop ulcers. H. pylori may be part of the indigenous human gastric flora; antigens were detected in pre-Columbian Central American mummies whose last meal was 1700 years ago.
Gastric carcinoma: H. pylori is strongly linked to gastric cancer and is now classified as a group I carcinogen. It may also cause mucosa-associated lymphoid tissue lymphoma.
Barrett’s esophagus is a possible H. pylori-associated disease, although it is more commonly associated with chronic gastroesophageal reflux.
H. pylori probably synergizes with nonsteroidal anti-inflammatory drug (NSAID) use.

5. What is the most commonly used test for H. pylori?

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The CLO test detects the presence of H. pylori. H. pylori releases urease, which breaks down urea to ammonia and bicarbonate, thus increasing the pH. The CLO test can be performed at the time of endoscopy by obtaining scrapings from the antral mucosa.
If endoscopy is not available, the enzyme-linked immunosorbent assay (ELISA) may be used to detect anti-H. pylori IgA and IgG antibody titers.
Direct culture of the organism should be reserved for cases in which antibiotic resistance becomes the issue.

6. What other risk factors are associated with duodenal ulcer disease?

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* Cigarette smoking is a major risk factor; its cessation is a key component of ulcer therapy.
* Blood group O is associated with higher incidence of duodenal ulcer, as are leukocyte antigens HLA-B5, B12, and BW35.
* NSAIDs promote ulcer formation by suppressing systemic prostaglandin production.
* Chronic pancreatitis, cirrhosis, emphysema, and alpha-1 antitrypsin deficiency are also associated with the condition.

7. Which endocrine disorder is associated with severe ulcer disease?

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Patients with multiple endocrine neoplasia (MEN) type I have a 75% incidence of gastrinoma with severe ulcer diathesis.

8. What other endocrine disorders should be screened?

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Pituitary tumor and hyperparathyroidism should be suspected when MEN type I is considered.

9. What are the clinical presentations of peptic ulcer disease?

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* Pain is usually epigastric in origin, although radiation to the back may indicate pancreatic involvement. It is often relieved by food or antacid ingestion. Nausea and vomiting may occur.
* Upper gastrointestinal (GI) bleeding.
* Gastric outlet obstruction (GOO) may result from pyloric spasm, inflammatory mass constriction, duodenal scarring, or fibrosis.
* Perforation is a surgical emergency with a mortality rate as high as 10%. Perforation may occur without a history of peptic ulcer disease, especially if the ulcer is situated on the anterior surface of the duodenum.

10. How does the location of the ulcer affect its clinical presentation?

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Anterior wall ulcers (usually first portion of duodenum) may perforate and cause peritonitis with free air in the abdomen. Posterior ulcers may erode into the gastroduodenal artery or pancreas.

11. What are the differential diagnoses of epigastric pain?

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In addition to peptic ulcer disease, gastroesophageal reflux disease, gastritis, gastric carcinoma, biliary tract disease, pancreatitis or pancreatic carcinoma, aortic aneurysm, intestinal angina (ischemia), and myocardial ischemia should be considered.

12. What initial test should be performed when evaluating epigastric pain of presumed GI origin?

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Flexible esophagogastroduodenoscopy (EGD) is preferred, although the upper GI contrast study with barium may be acceptable. The CLO test can be performed at the time of the EGD if indicated. Ultrasound should be performed if gallbladder or vascular diseases are suspected. A lateral-view angiogram for intestinal angina, computed tomography (CT) scan for aneurysm, and a baseline electrocardiogram should be obtained because ischemic heart disease is always possible.

13. How are patients with duodenal ulcer treated?

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* Diet: Aspirin and NSAIDs must be discontinued. Alcohol and nicotine should be avoided.
* Antacids: Neutralizing gastric pH may alleviate symptoms, but its impact on ulcer healing is not well defined.
* H2 receptor antagonists: The use of cimetidine or ranitidine prevents gastric acid secretions by blocking the H2 histamine receptor.
* Sucralfate: A protective-barrier medicine adheres to the ulcer base, providing a protective coating. Medications that decrease acid secretion should not be used at the same time because sucralfate requires an acidic environment to be activated.
* Proton pump inhibitors: Omeprazole blocks the hydrogen-potassium adenosine triphosphatase pump in the gastric parietal cells and inhibits hydrogen ion release. It usually is reserved for failures of first-line therapy (i.e., H2 receptor antagonists).
* H. pylori eradication: If H. pylori infection is diagnosed, the combination of triple therapy (bismuth, tetracycline, and metronidazole) with an H2 receptor antagonist regimen appears to provide a 90% cure rate. Erythromycin, amoxicillin-omeprazole, or erythromycin-omeprazole may be added for initial failures.

14. What are the recurrence rates after medical therapy?

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Approximately 80% of duodenal ulcers heal in 6 weeks. The recurrence rate within 1 year of treatment is 70%; thus, repeated treatment may be necessary.

15. What complications are associated with medical therapy?

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H2 receptor antagonists may induce mental status changes and gynecomastia. Cimetidine, in particular, may affect hepatic metabolism of warfarin, phenytoin, theophylline, propranolol, and digoxin, leading to abnormal serum levels. Omeprazole may cause hypergastrinemia by blocking gastric acid secretion. H. pylori resistance to antibiotics may develop, especially to metronidazole; therefore, a triple combination of at least two antimicrobials with an acid inhibitory drug is recommended as initial therapy.

16. How should recurrent or multiple ulcers be evaluated?

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In addition to the previously mentioned workup, serum gastrin levels should be obtained to evaluate for possible endocrine disorder. Patients should not be taking omeprazole when gastrin levels are measured. In Zollinger-Ellison syndrome, gastrin hypersecretion from the pancreatic islet tumor results in multiple or intractable ulcers (normal serum gastrin, < 200 pg/mL; Zollinger-Ellison syndrome, usually > 500 pg/mL).

17. How do you evaluate a borderline serum gastrin value (200-500 pg/mL)?

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The secretin stimulation test may be used to diagnose Zollinger-Ellison syndrome. An intravenous bolus of secretin (2 U/kg) should result in an increase of gastrin of 150 pg/mL within 15 minutes if the patient has this syndrome.

KEY POINTS: HELICOBACTER PYLORI

1. H. pylori is a gram-negative urease-producing bacillus.
2. It has a strong association with peptic ulcer disease (80% of ulcer patients).
3. It is linked to development of mucosa-associated lymphoid tissue lymphoma (MALT).
4. Is is associated with development of gastric carcinoma.
5. H. pylori infection is diagnosed by EGD biopsy and CLO test.
6. Treatment includes triple antibiotic therapy supplemented with acid-reduction medication (90% cure rate).

18. What are the indications for operative treatment of duodenal ulcers?

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Failure of medical management to control pain, bleeding (< 6 units of packed red blood cell transfusions in 24 hours or, better yet, two thirds of the patients calculated blood volume loss in 24 hours), and obstruction are the usual indications. Perforation of the ulcer is usually treated surgically unless the patient presents 24 hours after the event without peritonitis and the Gastrografin upper GI series confirms that the perforation has been well sealed (usually with omentum).

19. What operations are used to treat duodenal ulcers?

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* Truncal vagotomy and pyloroplasty (V and P) or gastrojejunostomy
* Truncal vagotomy and antrectomy with Billroth I or II anastomosis
* Subtotal gastrectomy with Billroth I or II anastomosis
* Selective vagotomy (just the vagal branches to the parietal cells in the stomach)
* Total gastrectomy

20. What are Billroth I and Billroth II anastomoses?

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The Billroth I operation is an anastomosis between the duodenum and the gastric remnant (gastroduodenostomy). The Billroth II operation is constructed by sewing a loop of jejunum to the gastric remnant (gastrojejunostomy). Either method is acceptable.
21. Which procedure is preferred, Billroth I or Billroth II? Show answer
Billroth I has the advantages of eliminating the duodenal stump and requiring only one suture line instead of two (as in Billroth II). Duodenal stump blowout is a critical surgical emergency that requires immediate laparotomy. Afferent loop syndrome (i.e., sludging of stuff in the loop that is not in the enteric stream) is also a complication of Billroth II. Bile reflux gastritis may occur in both procedures. Billroth I is more physiologic; thus, it results in better protein and fat digestion. Billroth I is more susceptible to gastric outlet obstruction with ulcer or tumor recurrence; therefore, a Billroth I hook-up is not recommended for patients with gastric carcinoma.

22. What is afferent loop syndrome?

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Postprandial abdominal pain often is relieved by bilious vomiting. A narrowing at the junction of the stomach and duodenal side of a Billroth II anastomosis leads to biliary and pancreatic fluid build-up within the afferent limb of the intestine. Pain is relieved when the fluid content is emptied into the stomach, which may result in bilious vomiting and severe reflux gastritis.

23. How is afferent loop syndrome prevented?

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Prevention requires avoidance of a long or twisted afferent limb with too narrow an anastomosis during Billroth II construction. A Billroth I procedure eliminates this possible problem.

24. Who was Billroth?

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Christian Albert Theodor Billroth (1829-1894) was an Austrian surgeon credited with performing the first successful gastric resection in 1881 and introducing innovations to intestinal bypass surgery. The father of modern American surgery, William Halsted, was once an apprentice to Billroth in Vienna.

25. How does alkaline or bile reflux gastritis occur?

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Reflux of bile and pancreatic secretions into the stomach after a Billroth II (sometimes Billroth I) anastomosis may cause marked gastric irritation, leading to chronic postprandial pain. Persistent pain should be evaluated with endoscopy, and surgical reconstruction should be considered, usually with a Rouxen-Y gastrojejunostomy from a 40-cm efferent jejunal limb.

26. What is selective vagotomy?

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In this limited proximal vagotomy, the gastric parietal cells are selectively denervated. Fibers to antrum, pylorus, liver, biliary tract, and the rest of the intestinal tract are left intact, thereby precluding the need for a gastric emptying procedure. Recurrence of ulcer disease may be 10% or greater, but its side effects, namely dumping (caused by resection of the pylorus) or diarrhea (caused by the vagotomy), are minimized to 2%.

27. What is dumping syndrome?

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Resection of the pylorus can lead to uncontrolled, rapid emptying of hyperosmolar gastric contents into the proximal small bowel. The osmotic and glucose load in the intestine sucks intravascular volume into the gut, making the patient transiently hypovolemic. The physiologically appropriate adrenergic response to this volume shift produces tachycardia, sweating, flushing, weakness, nausea, abdominal cramps, and even syncope. Ingesting a small, dry, low-carbohydrate meal (to limit the available osmols) may prevent this syndrome. Anticholinergic drugs also may help. As many as 20% of patients experience the dumping syndrome in the early postoperative period, but only 2% develop chronic problems.

28. What must accompany truncal vagotomy?

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Truncal vagotomy denervates the stomach, resulting in gastric hypomotility. Some gastric emptying procedure such as a pyloroplasty or a side-to-side gastroduodenostomy should be performed.

29. What is a Heinecke-Mikulicz pyloroplasty?

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A pyloduodenal incision along the longitudinal axis followed by a transverse closure flops the pylorus open and promotes gastric emptying.

30. What is a Finney pyloroplasty?

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A side-to-side gastroduodenal anastomosis that transects and defunctionalizes the pylorus and promotes gastric emptying

31. What is a Jaboulay pyloroplasty?

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This gastric emptying procedure comprises a side-to-side gastroduodenal anastomosis that does not transect the pylorus. It is ideal if severe pyloric scarring is present.

32. What are the rates of ulcer recurrence after surgical treatment?

Vagotomy and pyloroplasty: 10%
Vagotomy and antrectomy: 2%
Highly selective vagotomy: 10%
Subtotal gastrectomy: 1%
Total gastrectomy: < 1%

33. What is the mortality rate of these operations?

Vagotomy and pyloroplasty: 1%
Vagotomy and antrectomy: 2%
Highly selective vagotomy: 0.1%
Subtotal gastrectomy: 2%
Total gastrectomy: 5%

34. How are patients with perforated duodenal ulcers treated?

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The patient must be resuscitated first, following the ABCs of airway, breathing, and circulation. The stomach contents are emptied via nasogastric tube. Surgical closure by omental patch (Graham closure) is widely practiced. For hemodynamically stable patients, oversewing of the ulcer followed by a selective vagotomy is appropriate. Antrectomy with vagotomy to remove the ulcer is appropriate if the patient has an intractable peptic ulcer.

35. What (ulcer-specific question) should you always ask before you proceed to the operating room?

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Past history of ulcer disease. Choice of operation will depend on acute versus chronic ulcer disease.
36. What is the long-term result after Graham closure of a perforated ulcer? Show answer
One third of patients remain asymptomatic, one third have symptoms controlled by medical treatment, and one third require an additional ulcer operation.

37. What are the complications of surgery for duodenal ulcers?

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Duodenal stump leakage may occur within the first week after antral resection and Billroth anastomosis. Treatment consists of prompt reoperation to drain and control the leak. Total parenteral nutrition may be required as a “bowel rest” adjunct.
Gastric retention may occur because of edema at the anastomosis or atony of the stomach after vagotomy. It usually resolves spontaneously in 3-4 weeks.
Bleeding may occur from a suture line, a missed ulcer, or other gastric mucosal lesions. Most postgastrectomy bleeding ceases spontaneously, but endoscopy may be necessary in some cases.

38. Where do ulcers recur after operation?

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Ulcers usually recur adjacent to the gastric anastomosis on the intestinal side (i.e., jejunum, duodenum).

39. Why do they recur?

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The responsible factors are inadequate gastric resection, incomplete vagotomy, inadequate drainage of the gastric remnant (stasis of gastric contents proximal to the anastomosis), or retained gastric antrum (gastrin-producing cells) after a Billroth II procedure.

40. How do you treat pyloric stenosis?

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Fluid resuscitation and nasogastric tube decompression should be initiated. Metabolic alkalosis may result from prolonged vomiting (loss of hydrogen ions) and should be corrected with normal saline infusion. Either vagotomy with gastrojejunostomy or resection of the stenosis with a Billroth II bypass is acceptable. Partial gastrectomy is required less often.