Peptic Ulcer Disease

Peptic ulcers are focal defects in the gastric or duodenal mucosa which extend into the submucosa or deeper, as seen under laboratory microscopes. They may be acute or chronic, and ultimately are caused by an imbalance be¬tween the action of peptic acid and mucosal defenses. Peptic ulcer remains a common outpatient diagnosis, but the number of physician visits, hospital admissions and elective operations for peptic ulcer disease has decreased steadily and dramatically over the past 3 decades. These trends all predated the advent of fiber optic endoscopy, highly selective vagotomy, and the use of H2-blockers. However, the incidence of emergency surgery and the death rate associated with peptic ulcers are fairly stable. These epidemiologic trends probably represent the net effect of sev¬eral factors, including decreasing prevalence of H. pylori bacteria infection, better medical therapy, increases in outpatient management, and the use of NSAIDs and aspirin (with and without ulcer prophylaxis).

These epidemiologic facts notwithstanding, it is important to re¬iterate that peptic ulcer is a common disease in the U.S. In 2000, the total direct costs (hospital, physicians, and drugs) of peptic ulcer disease were about $3.3 billion, with indirect costs (lost work and productivity) of over $6 billion. The prevalence of peptic ulcer in the U.S. is about 2%, and the lifetime risk is about 10%. In 1998, the crude mortality rate for peptic ulcer was 1.7 per 100,000 individuals. Gastric ulcer has a higher mortality than duodenal ul¬cer because of its increased prevalence in the elderly. Recent studies have shown an increase in the rates of hospitalization and mortality in elderly patients for the peptic ulcer complications of bleeding and perforation. Presumably this is due to the increasingly common use of NSAIDs and aspirin in this elderly cohort, many of whom have H. pylori bacteria infection.

Pathophysiology and Etiology

A variety of factors may contribute to the development of peptic ulcer disease. Although it is now recognized that the large major¬ity of duodenal and gastric ulcers are caused by H. pylori bacteria infection and/or NSAID use, the final common pathway to ul¬cer formation is peptic acid injury of the gastroduodenal mucosal barrier, as seen under laboratory microscopes. Thus the adage “no acid, an ulcer” remains true¬ even today. Acid suppression, either with medication or surgery, remains a mainstay in healing both duodenal and gastric ulcers and in prevent¬ing recurrence. It generally is thought that the bacteria H. pylori predisposes to ulceration, both by acid hypersecretion, and by compromise of mu¬cosal defense mechanisms. NSAID use is thought to lead to peptic ulcer disease predominantly by compromise of mucosal defenses. Duodenal ulcer has typically been thought of as a disease of in¬creased peptic acid action on the duodenal mucosa, whereas gastric ulcer has been viewed as a disease of weakened mucosal defenses in the face of relatively normal action of peptic acid, as seen under laboratory microscopes. However, increased understanding of the pathophysiology of peptic ulcer has blurred this distinction. Clearly, weakened mucosal defenses play a role in many duodenal and most gastric ulcers (e.g., duodenal ul¬cer in an H. pylori-negative patient on NSAIDs or a patient with a typical type I gastric ulcer with acid hyposecretion), whereas in¬creased aggressive activity of peptic acid may result in a duodenal or gastric ulcer in the setting of normal mucosal defenses (e.g., a duodenal ulcer in a patient with Zollinger-Ellison syndrome, or a gastric ulcer in a patient with gastric outlet obstruction, antral stasis, and acid hypersecretion).

Elimination of H. pylori bacteria infection or NSAID use is important for optimal ulcer healing, and perhaps is even more important in preventing ulcer recurrence and/or complications. A variety of other diseases are known to cause peptic ulcer, including Zollinger-Ellison syndrome (gastrinoma), antral G-cell hyperfunction and/or enlargement because of an increase in number of cells, systemic mastocytosis, trauma, burns, and major physiologic stress. Other causative agents include drugs (all NSAIDs, aspirin, and cocaine), smoking, alcohol, and psychologic stress. In the U.S., probably more than 90% of serious peptic ulcer complications can be attributed to H. pylori infection, NSAID use, or cigarette smoking.

Clinical Manifestations

Over 90% of patients with peptic ulcer disease complain of abdom¬inal pain. The pain is typically nonradiating, burning in quality, and located in the epigastrium. The mechanism of the pain is unclear. Patients with duodenal ulcer usually experience pain 2 to 3 hours after a meal and at night. Two thirds of patients with duodenal ulcers will complain of pain that awakens them from sleep. The pain of gastric ulcer more commonly occurs with eating and is less likely to awaken the patient at night. A history of peptic ulcer disease, use of NSAIDs, over-the-counter antacids, or antisecretory drugs, is Suggestive of the diagnosis. Other signs and symptoms include nausea, bloating, weight loss, stool positive for occult blood, and anemia. Duodenal ulcer is about twice as common in men compared to women, but the incidence of gastric ulcer is similar in men and women. On average, gastric ulcer patients are 10 years older than duodenal ulcer patients, and the incidence is increasing in the el¬derly, probably because of increasing NSAID use in this cohort with a high incidence of H. pylori infection.

Diagnosis

In the young patient with dyspepsia and/or epigastric pain, it may be appropriate to initiate empiric therapy for peptic ulcer disease without confirmatory testing with the use of laboratory microscopes. All patients over 45 with the above symptoms should have an upper endoscopy, and all patients, re¬gardless of age, should have this study if any alarm symptoms are present. A double contrast upper GI x-ray study may be useful. All gastric ulcers should be adequately biopsied, and any sites of gastritis should be biopsied to rule out H. pylori bacteria, and for histologic evaluation. Additional testing for H. pylori bacteria may be indi¬cated. Although somewhat controversial, it is not unreasonable to test all peptic ulcer patients for H. pylori. A baseline serum gastrin level is appropriate to rule out gastrinoma.

Complications

The three most common complications of peptic ulcer disease, in decreasing order of frequency, are bleeding, perforation, and ob¬struction. Most peptic ulcer-related deaths in the US are due to bleeding. Bleeding peptic ulcers account for about half of the clin¬ically significant cases of upper GI bleeding at most medical cen¬ters. Patients with a bleeding peptic ulcer typically present with black tarry stools and/or vomiting out blood. Nasogastric aspiration is usually confirmatory of the upper GI bleeding. Abdominal pain is quite uncommon. Shock may be present, necessitating aggressive resuscitation and blood transfusion. Early endoscopy is important to diagnose the cause of the bleeding and to assess the need for hemostatic therapy.

Three quarters of the patients who come to the hospital with bleeding peptic ulcer will stop bleeding if given acid suppression and kept on nothing by mouth. However, one fourth will continue to bleed or will rebleed after an initial qui¬escent period, and virtually all the mortalities (and all the operations for bleeding) occur in this group. This group can be fairly well delin¬eated based on clinical factors related to the magnitude of the hemor¬rhage and endoscopic findings. Shock, hematemesis, transfusion requirement exceeding four units in 24 hours, and high-risk endoscopic stigmata define this high-risk group. These patients benefit from endoscopic ther¬apy to stop the bleeding. The most common endoscopic hemostatic modalities used are injection with epinephrine, and electrocautery. Persistent bleeding or rebleeding after endoscopic therapy is an indi¬cation for operation, although repeat endoscopic treatment has been successful in treating rebleeding. Elderly and high-risk patients do not tolerate repeated episodes of hemodynamically significant hem¬orrhage, and may benefit from early elective operation after initially successful endoscopic treatment, especially if they have one or more of the risk factors mentioned above or a high-risk ulcer. Planned surgery under controlled circumstances often yields better outcomes than emergent surgery performed in the middle of the night. Deep bleeding ulcers on the posterior duodenal bulb or lesser gastric cur¬vature are high-risk lesions, because they often erode large arteries not amenable to nonoperative treatment, and early operation should be considered.

Perforated peptic ulcer usually presents as an acute abdomen. The patient can often give the exact time of onset of the excruciat¬ing abdominal pain. Initially, a chemical peritonitis develops from the gastric and/or duodenal secretions, but within hours a bacterial peritonitis supervenes. Fluid sequestration into the third space of the inflamed peritoneum can be impressive, and fluid resuscitation is mandatory. The patient is in obvious distress, and the abdominal exam shows peritoneal signs. Usually marked involuntary guarding and rebound tenderness is evoked by a gentle examination. Upright chest x-ray shows free air in about 80% of patients. Once the diagnosis has been made, the patient is given analgesia and antibiotics, resuscitated with isotonic fluid, and taken to the op¬erating room. Rarely, the perforation has sealed spontaneously by the time of presentation, and surgery can be avoided. Non-opera¬tive management is appropriate only if there is objective evidence that the leak has sealed (i.e., radiologic contrast study), and in the absence of clinical peritonitis.

Gastric outlet obstruction occurs in no more than 5% of pa¬tients with peptic ulcer disease. It is usually due to duodenal or pre¬pyloric ulcer disease, and may be acute (from inflammatory swelling and peristaltic dysfunction) or chronic (from cicatrix). Patients typ¬ically present with nonbilious vomiting and may have a profound hypokalemic hypochloremic metabolic alkalosis. Pain or discom¬fort is common. Weight loss may be prominent, depending on the duration of symptoms. Initial treatment is nasogastric suction, intra¬venous hydration and electrolyte repletion, and antisecretory med¬ication. The diagnosis is confirmed by endoscopy. Cancer must be ruled out. Currently most natients admitted to the hospital with obstructing ulcer disease require intervention, either balloon dilation or operation.