Gastric Ulcer

Etiology

The most common etiologies of gastric ulcers include a bacterial infection with Helicobacter pylori and gastric prostaglandin loss associated with non-steroidal anti-inflammatory medications. Less common etiologies include hypergastrinemia (Zollinger-Ellison syndrome), viral infections such as CMV, chemotherapy and radiation, gastric outlet obstruction, gastric infiltrative disorders such as malignancy, cigarette smoking, and Crohn disease. The common factor in all of these etiologies is that they promote a breakdown in the mucosal barrier and expose the gastric mucosa to the damaging effects of acid.[1]

Epidemiology

Gastric ulcers are a part of peptic ulcer disease, which carries a lifetime prevalence of 5 to 10% of patients, which is likely an underestimation of the disease as some patients may remain asymptomatic. Studies have shown that the prevalence of gastric ulcers increases with age and with the chronicity of NSAID use. Research shows that smoking leads to a relative risk of 2.0 times that of non-smokers for developing gastric ulcers.  There is no difference between men and women in the prevalence of gastric ulcers. The prevalence of Helicobacter pylori infection at age 60 approximates 50% in the US population. Estimates are that 25% of chronic NSAID users will develop gastric ulcers.[2]

Pathophysiology

The pathophysiology of gastric ulcer development depends on the insult. Since about 80 to 90% of gastric ulcers result from either Helicobacter pylori and/or NSAID use, a detailed discussion will focus on each in detail.

First, regarding Helicobacter pylori - these bacteria colonize about 45-50% of the stomach mucosa worldwide. It is a bacterium that people are inoculated with at an early age, especially in developing countries with lower socioeconomic status and crowded households. These bacteria induce an inflammatory response in the host that leads to an epithelial response, degeneration, and injury, known as gastritis. Typically, patients with this infection develop pan-gastritis. This damages the antral somatostatin release, which leads to an increase in gastrin secretion, which stimulates increased acid production. Patients who develop gastric ulcers are those in whom the bacteria has remained in the antrum. Parietal cells of the more proximal gastric body still have full production capabilities preventing ulcer genesis in this area. Of note, not all patients with this infection are symptomatic; this depends on the virulence of the bacteria and other host risk factors. A common bacterial virulence factor is the production of cagA, which leads to more cytokine cell destruction and mucosal damage.[3]

NSAID medications are the other most common etiology causing gastric ulcers. Patients who use these medications have a relative risk of four for developing gastric ulcers when compared to people who don't. There are multiple mechanisms by which NSAID medications lead to ulceration. The drugs themselves are weak acids when they become exposed to gastric acid. They remain in the epithelial cells and lead to increased cellular permeability, which leads to physical cellular injury. The primary mechanism of NSAID-induced ulceration is the decrease in prostaglandin synthesis. NSAIDs inhibit the cyclooxygenase-1 enzyme, which usually increases prostaglandin synthesis, which in turn leads to gastric bicarbonate secretion, mucus barrier formation, increased mucosal blood flow, and accelerated epithelial cell restitution and repair after injury or cell death. NSAID medications allow the gastric mucosa to become more vulnerable to gastric acid and pepsin damage. Overall, the most harmful physiological damage results from the decrease in gastric blood flow and the mild ischemia it causes in the gastric mucosa.

Overall, the pathophysiology of gastric ulcer development depends on the etiology, but they all lead to the loss or damage of the gastric mucosal integrity. 

Histopathology

On histopathology, one will see an ulcer base with clear margins that penetrate the muscularis propria and into the submucosa. Inflammatory debris on the epithelial surface is often present. In the submucosa, one will see fibrosis and thickened blood vessels. 

History and Physical

The typical presentation of a patient with gastric ulcers is epigastric pain that is worse with eating. It often correlates with mild nausea and early satiety. They often describe this pain as a sharp or burning type of pain that typically doesn't radiate. The most common finding on the physical exam is epigastric tenderness. These symptoms may continue for weeks or months before patients seek medical help. Patients may present with upper GI bleeding. The clinician should ask if they are having any black tarry stools, hematemesis, coffee-ground emesis, or bright red blood per rectum. It is important to remember that up to 15% of patients who present with bright red rectal bleeding have a brisk upper GI bleed. 

During the interview with the patient, one should definitely ask about the use of NSAID, oral anticoagulation, and a history of peptic ulcer disease. 

Evaluation

When a gastric ulcer is suspected, evaluation for hemodynamic stability is critical as they often present with upper GI bleeding and may have hemorrhagic shock. Necessary labs include BMP, CBC, PT/INR, and lipase. A chest X-ray should be obtained to test for other causes of epigastric pain. Many times patients are evaluated for pancreatitis with an abdominal CT scan.

During endoscopy, gastric ulcers are graded using the Forrest classification scheme; this provides the estimated risk of ulcer bleeding and helps to distinguish which ulcers need endoscopic management, such as injection therapy, cautery, or metal or absorbable clip placement. Below is a representation of the grading system.[3]

Forrest classification:

• Ia- jet arterial bleeding, 90% rebleeding risk
• Ib- oozing, 50% rebleeding risk
• IIa-visible vessel, 25 to 30% rebleeding risk
• IIb- adherent clot, 10 to 20% rebleeding risk
• IIc- black spot in the ulcer, 7 to 10% rebleeding risk
• III- clean based, 3 to 5% rebleeding risk

Treatment / Management

The goal of treatment and management of gastric ulcers is first to increase the gastric pH and allowing the gastric mucosa to heal, which is possible through administering proton pump inhibitors, such as pantoprazole. A decision to proceed with an EGD should be the next consideration. Alarm symptoms should be recognized, which would make the need for an EGD more urgent. Alarm symptoms include unintentional weight loss, bleeding, age over 50, nausea, and vomiting. If a gastric ulcer is present on EGD, biopsies of the mucosa surrounding the ulcer will b necessary to rule out gastritis, Helicobacter pylori infection, and malignancy. These patients need to be on PPI therapy twice daily for 8 weeks and then undergo a repeat endoscopy to confirm for healing.[4]

If the patient is on NSAID medications, these require immediate discontinuation. If the biopsies or lab testing are positive for Helicobacter pylori infection, this condition requires treatment with antibiotic therapy, and eradication needs to be confirmed. 

If the gastric ulcer is bleeding or has a higher Forrest classification, different modalities to stop and prevent future bleeding can be employed. Epinephrine injection with either cautery or metal or absorbable clip placement is usually effective. 

Surgical management may be needed when endoscopic therapy is inadequate or not indicated. Indications for surgical intervention include perforation, uncontrolled bleeding, severe gastric outlet obstruction, and ulcers not healed with medical therapy. 

Differential Diagnosis

The differential diagnosis includes other causes of dyspepsia, such as gastritis, chronic pancreatitis, acute pancreatitis, gastric cancer, and biliary disease. 

Prognosis

Overall, patients who have gastric ulcers do well when they continue medical treatment and avoid medications that worsen the disease. 

Complications

The most common complications associated with gastric ulcers include GI bleeding, perforation, penetration, and gastric outlet obstruction.