Peptic Ulcer Disease (PUD)

Peptic Ulcer Disease (PUD) represents a spectrum of disease characterized by ulceration of the stomach or proximal duodenum due to an imbalance between acid secretion and mucosal defense mechanisms.

A. Epidemiology

In the United States, there are approximately 500,000 new cases of PUD each year, with an annual incidence of 1% to 2% and a lifetime prevalence between 8% and 14%. Although there has been a steady decline in the incidence of peptic ulcer disease since the 1960s, ulcer-related mortality remains approximately 10,000 cases annually.

B. Pathogenesis

Four etiologic factors are responsible for the vast majority of PUD.

Helicobacter pylori (H. pylori) infection is associated with 90% to 95% of duodenal ulcers and 70% to 90% of gastric ulcers. Infection produces chronic antral gastritis, increased acid and gastrin secretion, and decreased mucosal resistance to acid.

Nonsteroidal anti-inflammatory drug (NSAID) use confers an 8-fold increase in risk of duodenal ulcers and a 40-fold increase in risk of gastric ulcers due to suppression of prostaglandin production.

Cigarette smoking

Acid hypersecretion occurs in the majority of patients with duodenal ulcers.

C. Presentation

Presentation in uncomplicated ulcer disease is usually burning, gnawing intermittent epigastric pain that is relieved by food or antacid ingestion for duodenal ulcers but exacerbated by intake for gastric ulcers. Pain may be accompanied by nausea,

vomiting, and mild weight loss. Differential diagnosis is broad and includes gastroesophageal reflux disease, biliary colic and related biliary tract disease, inflammatory and neoplastic pancreatic disease, and gastric neoplasms.

D. Diagnosis

Diagnosis can be made by barium contrast radiography or upper gastrointestinal endoscopy. Esophagogastroduodenoscopy (EGD) is more sensitive and specific than contrast examination for peptic ulcer disease (Ann Intern Med 1984;101:538). In addition, EGD offers therapeutic options (ligation of bleeding vessels) and diagnostic options (biopsy for malignancy, antral biopsy for H. pylori). Once the diagnosis of PUD is confirmed, further testing should be carried out to determine its etiology.

H. pylori infection can be detected noninvasively by radiolabeled urea breath test or serologic antibody testing. Antral tissue obtained during endoscopy can be subjected to direct histologic examination or rapid urease testing using the cod liver oil (CLO) test.

Fasting serum gastrin levels should be obtained in patients who have no history of NSAID use and are H. pylori-negative or who have recurrent ulcers despite adequate treatment, multiple ulcers, ulcers in unusual locations (such as the second and third portions of the duodenum), or complicated PUD (hemorrhage, perforation, obstruction). Such atypical presentations suggest the possibility of Zollinger-Ellison syndrome, a rare entity causing PUD in 0.1% to 1% of patients. This syndrome is discussed further in Chapter 21.

Endoscopic biopsy of gastric ulcers is mandatory to exclude malignancy.

E. Treatment

Treatment of PUD has changed dramatically with the development of antisecretory drugs [histamine2-receptor blockers and proton-pump inhibitors (PPIs)], and H. pylori –eradication regimens have greatly diminished the role of elective surgery for PUD.

Medical therapy

H. pylori eradication is the cornerstone of medical therapy for PUD. Regimens typically consist of a PPI combined with two antibiotics administered for 10 to 14 days. These regimens are 85% to 90% effective in eradicating H. pylori. Antisecretory therapy is then continued until ulcer healing is complete.

NSAID-associated PUD is treated by discontinuing the offending medication and initiating antisecretory therapy. If the NSAID must be continued, PPIs are most effective for facilitating ulcer healing.

Smoking cessation greatly facilitates ulcer healing, but compliance rates are low.

Follow-up endoscopy to ensure healing is essential for gastric ulcers because up to 3% harbor malignancy.

Surgical therapy for uncomplicated peptic ulcer disease is exceedingly rare. Indications for elective operation for PUD include failure of medical therapy and inability to exclude malignancy.

Duodenal ulcers are treated by one of three acid-reducing operations: (1) truncal vagotomy with pyloroplasty, (2) truncal vagotomy with antrectomy and Billroth I (gastroduodenostomy) or Billroth II (gastrojejunostomy) reconstruction, or (3) highly selective vagotomy (HSV). Truncal vagotomy with antrectomy yields maximal acid suppression with lowest ulcer recurrence rates (1% to 2%) but carries the highest postoperative morbidity (15% to 30%) and mortality (1% to 2%) rates. HSV has the lowest postoperative morbidity (3% to 8%) and mortality rates but is technically demanding to perform and has higher recurrence rates (5% to 15%).

Gastric ulcers are typically treated with either wedge excision or antrectomy with inclusion of the ulcer, depending on ulcer location. Concurrent truncal vagotomy is reserved for patients who are known to have refractory ulcer disease despite maximal medical management; this is rare today.

II. Complicated Peptic Ulcer Disease

Complicated Peptic Ulcer Disease refers to PUD complicated by hemorrhage, perforation, or obstruction. These complications represent the most common

indications for surgery in PUD. Although there has been a sharp decline in elective surgery for PUD, the rates of emergency surgery for complicated PUD have been stable over time.

A. Hemorrhage

Hemorrhage is the leading cause of death due to PUD, with associated 5% to 10% mortality. Evaluation and management begin with aggressive resuscitation and correction of any coagulopathy, followed by EGD. Although spontaneous cessation of bleeding occurs in 70% of patients, endoscopic therapy using thermal coagulation with or without epinephrine is warranted in individuals who present with hemodynamic instability, need for continuing transfusion, hematemesis or red stool, age greater than 60 years, and serious medical comorbidities, because these patients have a higher risk of recurrent bleeding. Endoscopic findings of a visible vessel or active bleeding also indicate high risk for rebleeding and require endoscopic hemostasis. Indications for surgery include repeated episodes of bleeding, continued hemodynamic instability, ongoing transfusion requirement of more than 6 units of packed red blood cells over 24 hours, and more than one unsuccessful endoscopic intervention.

Bleeding duodenal ulcers are usually located on the posterior duodenal wall within 2 cm of the pylorus and typically erode into the gastroduodenal artery. Bleeding is controlled by duodenotomy and oversewing of the bleeding vessel. In hemodynamically stable patients, consideration should be made for a concomitant acid-reducing procedure for those who have failed or are noncompliant with medical therapy. Postoperative H. pylori eradication is important to reduce the risk of recurrent bleeding.

Bleeding gastric ulcers present a diverse challenge because the patient’s condition, comorbidities, and previous ulcer and medication history all play a role in surgical decision making. In unstable patients, biopsy followed by oversewing or wedge excision of the ulcer should be performed. Stable patients may be candidates for antrectomy and vagotomy.

B. Perforated peptic ulcer

Perforated peptic ulcer typically presents with sudden onset of severe abdominal pain but may be less dramatic, particularly in hospitalized, elderly, and immunocompromised patients. The resulting peritonitis is often generalized but can be localized when the perforation is walled off by adjacent viscera and structures. Examination reveals fever, tachycardia, and abdominal wall rigidity, and laboratory evaluation typically demonstrates leukocytosis. Abdominal x-ray reveals free subdiaphragmatic gas in 80% to 85% of cases. Aggressive fluid resuscitation and broad-spectrum antibiotics followed by prompt operative repair is indicated in the vast majority of patients with perforated PUD. Nonoperative treatment of perforated duodenal ulcer can be considered in poor operative candidates in whom the perforation has been present for more than 24 hours, the pain is well localized, and there is no evidence of ongoing extravasation on upper GI water-soluble contrast studies (World J Surg 2000;24:256).

Perforated duodenal ulcers are best managed by simple omental patching and peritoneal débridement, followed by H. pylori eradication. An acid-reducing procedure (preferably truncal vagotomy and pyloroplasty) should be added in stable patients who are known to be H. pylori-negative or have failed medical therapy.

Perforated gastric ulcers are best treated by simple wedge resection to eliminate the perforation and exclude malignancy. If wedge resection of the ulcer cannot be performed due to its juxtapyloric location, multiple biopsies of the ulcer are taken and omental patching is performed.

C. Gastric outlet obstruction

Gastric outlet obstruction can occur as a chronic process due to fibrosis and scarring of the pylorus from chronic ulcer disease or as a consequence of acute inflammation superimposed on previous scarring of the gastric outlet. In general, gastric outlet obstruction secondary to PUD has become exceedingly rare with modern medical antisecretory therapy. Patients present with recurrent vomiting of poorly digested food, dehydration, and hypochloremic hypokalemic metabolic alkalosis. Management consists in correction of volume and electrolyte abnormalities, nasogastric suction, and intravenous antisecretory agents. EGD is necessary for evaluating the nature of the obstruction and for ruling out malignant etiology, and endoscopic hydrostatic balloon dilation can be performed at the same time. This is feasible in up to 85% of patients, but fewer than 40% have sustained improvement at 3 months (Gastrointest Endosc 1996;43:98). Indications for surgical therapy include persistent obstruction after 7 days of nonoperative management and recurrent obstruction. Antrectomy to include the ulcer and truncal vagotomy is the ideal operation for most patients. In exceptional instances, truncal vagotomy with gastrojejunostomy may be preferred in those patients whose pyloroduodenal inflammation precludes safe management with Billroth I or II reconstructions.