Peptic ulcer

A peptic ulcer is a peptic defect in the gastrointestinal mucosa, usually in the stomach (gastric ulcer) or the first part of the duodenum (duodenal ulcer), that penetrates the muscular layer. Almost all ulcers are caused by Helicobacter infection or by the use of nonsteroidal anti-inflammatory drugs. Symptoms of a peptic ulcer usually include a burning pain in the epigastric region, which often decreases after eating. The diagnosis of "peptic ulcer" is established by endoscopy and testing for Helicobacter pylori. Treatment of peptic ulcer is aimed at suppressing acidity, destroying H. pylori (if infection is verified), and eliminating the use of nonsteroidal anti-inflammatory drugs.

The size of an ulcer can vary from a few millimeters to several centimeters. An ulcer differs from an erosion by the depth of the lesion; erosions are more superficial and do not affect the muscle layer. An ulcer can develop at any age, including infancy and childhood, but is most common in middle-aged individuals.

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What causes peptic ulcers?

Helicobacter pylori and nonsteroidal anti-inflammatory drugs destroy the normal protective layer of the mucosa and impair its regeneration, making the mucosa more susceptible to acid. Helicobacter pylori infection is present in 80-90% of patients with duodenal ulcers and in 70-90% of patients with gastric ulcers. With Helicobacter pylori eradication, only 10-20% of patients experience recurrence of peptic ulcer, compared with 70% recurrence of ulcer in patients treated with acid-suppressing drugs alone.

Smoking is a risk factor for the development of ulcers and their complications. In addition, smoking impairs the healing process of the ulcer and increases the risk of recurrence. The risk of ulcer recurrence correlates with the number of cigarettes smoked per day. Although alcohol is a strong stimulant of gastric secretion, no definitive relationship has been established between moderate amounts of alcohol and the development or delay of ulcer healing. Very few patients have hypersecretion of gastrin (Zollinger-Ellison syndrome).

A family history is present in 50-60% of children with duodenal ulcer.

Symptoms of peptic ulcer

The symptoms of peptic ulcers depend on the location of the ulcer and the age of the patients; many patients, especially the elderly, have no or mild symptoms. Pain is the most common symptom, usually localized in the epigastric region and relieved by food or antacids. The pain is described as burning and excruciating, and sometimes with a feeling of hunger. The course of the ulcer is usually chronic and recurrent. Only about half of the patients experience the characteristic systemic symptoms.

The symptoms of gastric ulcers are often inconsistent with the findings (e.g., eating sometimes makes the pain worse rather than better). This is especially true for pyloric ulcers, which are often associated with symptoms of stenosis (e.g., bloating, nausea, vomiting) caused by swelling and scarring.

Duodenal ulcers usually cause persistent stomach pain. Stomach pain is absent in the morning upon awakening, but appears in the middle of the morning, disappears after eating, but returns again after 2-3 hours. Pain that appears at night is very characteristic of duodenal ulcer. In newborns, perforation and bleeding may be the first manifestation of duodenal ulcer. Bleeding may also be the first manifestation of ulcer in later infancy and early childhood, although frequent vomiting and abdominal pain may be clues to the diagnosis.

Complications of peptic ulcer

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Bleeding

Moderate to severe bleeding is the most common complication of peptic ulcer. Symptoms of gastrointestinal bleeding include hematemesis (vomiting fresh blood or "coffee ground" type of blood); bloody or tarry stools (melena); weakness, orthostatic collapse, syncope, thirst, and sweating caused by blood loss.

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Penetration (limited perforation)

A peptic ulcer may penetrate the wall of the stomach. If the adhesive process prevents the contents from entering the abdominal cavity, free penetration does not occur and a limited perforation develops. However, the ulcer may grow into the duodenum and penetrate into an adjacent limited space (smaller cavity) or another organ (e.g., pancreas, liver). The pain may be intense, constant, radiate to other parts of the body except the abdomen (usually the back in the case of penetration of a duodenal ulcer into the pancreas), and change with a change in body position. Abdominal CT or MRI is usually necessary to confirm the diagnosis. If conservative therapy is ineffective, surgical treatment is indicated.

Free perforation

A peptic ulcer that perforates into the free abdominal cavity is usually located on the anterior wall of the duodenum or, less commonly, in the stomach. The patient develops a symptom complex of acute abdomen. There is sudden, severe, persistent pain in the epigastric region, rapidly spreading throughout the abdomen, often becoming most pronounced in the right lower quadrant and occasionally radiating to one or both shoulders. The patient usually lies motionless, since even deep breathing increases the pain. Palpation of the abdomen is painful, peritoneal signs are determined, the abdominal wall muscles are tense (washboard), intestinal peristalsis is decreased or absent. Shock may develop, manifested by an increase in pulse rate, a decrease in blood pressure and urine production. Symptoms may be less pronounced in elderly or moribund patients, as well as in individuals taking glucocorticoids or immunosuppressants.

The diagnosis is confirmed radiologically by detecting free air under the diaphragm or in the free abdominal cavity. Chest and abdominal radiography in a vertical body position is preferable. The most informative is lateral chest radiography. In case of a serious patient condition and impossibility to perform radiographs in a vertical position, a lateral abdominal examination in a supine position is indicated. The absence of free gas does not exclude the diagnosis.

Urgent surgical intervention is required. The longer the delay with surgery, the more unfavorable the prognosis. If surgical treatment is contraindicated, continuous nasogastric aspiration and broad-spectrum antibiotics are alternatives.

Stenosis of the gastric outlet

Stenosis may be caused by scarring. Spasm and inflammation in the ulcer area may cause evacuation problems, but they respond to conservative therapy. Symptoms include recurrent profuse vomiting, occurring mainly at the end of the day and often 6 hours after the last meal. Loss of appetite with persistent bloating or a feeling of fullness after meals suggests gastric outlet stenosis. Prolonged vomiting may cause weight loss, dehydration, and alkalosis.

If the patient's history suggests stenosis, physical examination, gastric aspiration, or radiography may reveal evidence of gastric retention. A splashing sound heard more than 6 hours after a meal or aspiration of more than 200 mL of fluid or food debris from the previous meal suggests gastric retention. If gastric aspiration suggests retention, gastric emptying and gastric endoscopy or fluoroscopy should be performed to determine the site of the lesion, cause, and extent of stenosis.

Edema or spasm due to pyloric ulceration requires gastric decompression by nasogastric aspiration and acid suppression (e.g., intravenous H2 _blockers ). Dehydration and electrolyte imbalance due to prolonged vomiting or prolonged nasogastric aspiration require prompt diagnosis and correction. Prokinetic agents are not indicated. Evacuation dysfunction usually resolves within 2 to 5 days after treatment. Extended obstruction may result from peptic ulcer scarring and is resolved by endoscopic balloon dilation of the pyloric canal. Surgical treatment to remove the obstruction is indicated in selected cases.

Recurrence of peptic ulcer

Factors that cause ulcer recurrence include failure of treatment against Helicobacter pylori, use of nonsteroidal anti-inflammatory drugs, and smoking. Less commonly, gastrinoma (Zollinger-Ellison syndrome) may be the cause. The annual recurrence of gastric and duodenal ulcers is less than 10% if Helicobacter pylori is completely eradicated, but more than 60% if the infection persists. Therefore, a patient with recurrent disease should be tested for H. pylori and, if infection is confirmed, undergo a new course of therapy.

Although long-term treatment with H2 _blockers, proton pump inhibitors, or misoprostol reduces the risk of recurrence, their routine use for this purpose is not recommended. However, patients requiring nonsteroidal anti-inflammatory drugs for peptic ulcer disease are candidates for long-term therapy, as are patients with a large ulcer or previous perforation or bleeding.

Stomach cancer

Patients with Helicobacter pylori-associated ulcers have a 3-6 times higher risk of malignancy in the future. There is no increased risk of malignancy of ulcers of other etiologies.

Diagnosis of peptic ulcer

The diagnosis of peptic ulcer may be suggested by careful history taking and confirmed by endoscopy. Empirical therapy is often prescribed without a definitive diagnosis. However, endoscopy with biopsy or cytology can differentiate gastric and esophageal lesions between simple ulceration and gastric ulcer-cancer. Gastric cancer may present with similar features and should be excluded, especially in patients over 45 years of age with weight loss or severe, intractable peptic ulcer symptoms. Malignancy of duodenal ulcers is rare, so biopsy of lesions in this area is usually unnecessary. Endoscopy can also be used to definitively diagnose H.pylori infection, which should be investigated if an ulcer is detected.

In cases of multiple ulcers or in cases of ulcer development in an atypical location (e.g., postbulbar region), as well as in case of treatment failure, weight loss, or severe diarrhea, malignant gastrin secretion and Zollinger-Ellison syndrome should be kept in mind. Serum gastrin levels should be determined in these patients.

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Treatment of peptic ulcer

Treatment of gastric and duodenal ulcers includes, if detected, eradication of Helicobacter pylori and reduction of gastric acidity. In case of duodenal ulcers, it is especially important to suppress nocturnal gastric secretion.

Methods to reduce acidity include many medications, most of which are quite effective, but differ in cost, duration of therapy, and ease of dosing. In addition, drugs with protective properties for the mucous membrane (e.g., sucralfate) and surgical procedures that reduce acid production can be used.

Adjunctive treatment for peptic ulcer

Smoking should be avoided, and alcohol consumption should be either discontinued or limited in diluted form. There is no substantiated evidence that dieting will help ulcers heal more quickly or prevent recurrence. For this reason, many doctors recommend eliminating only foods that cause distress.

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Surgical treatment of peptic ulcer

With the introduction of drug therapy, the number of patients requiring surgical treatment of peptic ulcer has decreased dramatically. Indications for surgical treatment include perforation, stenosis, profuse or recurrent bleeding, and persistent symptoms that do not respond to drug therapy.

Surgical treatment of peptic ulcer is aimed at reducing gastric secretion, often combined with gastric drainage operations. The recommended operation for duodenal ulcer is highly selective (proximal) or parietal cell vagotomy (the operation involves denervation of the body of the stomach while preserving innervation of the antrum, which eliminates the need for drainage surgery). This procedure has a very low mortality rate and eliminates the complications associated with resection and traditional vagotomy. Other surgical methods that reduce acid production include antrectomy, hemigastrectomy, partial gastrectomy, and subtotal gastrectomy (i.e., resection of 30-90% of the distal stomach). They are usually combined with truncal vagotomy. Resection methods or interventions for stenosis include gastric drainage operations through gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II).

The development and nature of disorders after surgical treatment of peptic ulcer depend on the type of operation. After resection operations, 30% of patients develop severe symptoms, including weight loss, indigestion, anemia, dumping syndrome, reactive hypoglycemia, nausea and vomiting, passage disorders and ulcer recurrence.

Weight loss is typical for subtotal gastrectomy; the patient limits his/her food intake due to the feeling of rapid satiety (due to the small gastric stump), the possibility of developing dumping syndrome and other postprandial syndromes. Due to the small stomach, a feeling of distension or discomfort may occur even when eating small amounts of food; patients are forced to eat less, but more often.

Indigestion and steatorrhea caused by pancreaticobiliary bypass, especially with the Billroth II anastomosis, may contribute to weight loss.

Anemia is common (usually due to iron deficiency, but sometimes due to vitamin B ₁₂ deficiency caused by loss of intrinsic factor or development of bacterial infection) in Billroth II operations; osteomalacia may also develop. Additionally, intramuscular injections of vitamin B are recommended for all patients after total gastrectomy, but may also be given to patients after subtotal gastrectomy if vitamin B ₁₂ deficiency is suspected.

Dumping syndrome develops after gastric surgery, especially after resection. Weakness, dizziness, sweating, nausea, vomiting, and palpitations occur shortly after eating, especially after hyperosmolar foods. This phenomenon is referred to as early dumping, the cause of which remains unclear, but is most likely related to an autonomic response, intravascular volume depletion, and the release of vasoactive peptides from the small intestine. A volume-reducing, more frequent, and carbohydrate-restricted diet is usually effective.

Reactive hypoglycemia or late dumping syndrome (another form of the syndrome) develops due to rapid evacuation of carbohydrates from the gastric stump. A rapid rise in blood glucose levels stimulates the release of large amounts of insulin, which leads to symptomatic hypoglycemia several hours after eating. A high-protein, low-carbohydrate diet and adequate caloric intake (frequent meals, but in small doses) are recommended.

Passage disturbances (including gastrostasis and bezoar formation) may occur secondarily with the reduction of gastric motility in phase III, which changes after antrectomy and vagotomy. Diarrhea is especially characteristic of vagotomy, even without resection (pyloroplasty).

Ulcer recurrence occurs in 5-12% after highly selective vagotomy and 2-5% after resection operations. Ulcer recurrence is diagnosed by endoscopy and requires therapy with proton pump inhibitors or H2 _blockers. In case of ulcer recurrence, it is necessary to evaluate the completeness of vagotomy by studying gastric secretion, antibacterial therapy if Helicobacter pylori is detected, and serum gastrin level is studied if Zollinger-Ellison syndrome is suspected.

Drug treatment for high acidity

Acid-reducing drugs are used for peptic ulcers, gastroesophageal reflux disease, and various forms of gastritis. Some drugs are used in regimens to treat H. pylori infection. Drugs include proton pump inhibitors, H2 _blockers, antacids, and prostaglandins.

Proton pump inhibitors

The drugs are powerful inhibitors of H2, K-ATPase. This enzyme, located in the apical secretory membrane of parietal cells, plays a key role in the secretion of H (protons). These drugs can completely block acid production and have a long duration of action. They promote ulcer healing and are also key components of the drug complex for the eradication of H. pylori. Proton pump inhibitors are a favorable alternative to H2 _blockers in most clinical situations due to their rapid action and effectiveness.

Proton pump inhibitors for oral use only include omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole. Omeprazole is available in the Russian Federation as a powder for injection. For uncomplicated duodenal ulcers, omeprazole 20 mg orally once a day or lansoprazole 30 mg orally once a day is used for 4 weeks. Complicated duodenal ulcers (i.e. multiple ulcers, bleeding ulcers, ulcers larger than 1.5 cm, or ulcers with a severe clinical course) respond better to higher doses of drugs (omeprazole 40 mg once a day, lansoprazole 60 mg once a day, or 30 mg twice a day). Gastric ulcers require treatment for 6-8 weeks. Gastritis and GERD require treatment for 8-12 weeks; GERD additionally requires long-term maintenance therapy.

Long-term therapy with proton pump inhibitors causes an increase in gastrin levels, leading to hyperplasia of enterochromaffin-like cells. However, there are no data on the development of dysplasia or malignancy in patients receiving this treatment. Some patients may develop vitamin B12 malabsorption.

H2 blockers

These drugs (cimetidine, ranitidine, famotidine for oral and intravenous use and nizatidine for oral use) have competitive inhibition of H2 _- histamine receptors and, thus, suppress gastrin-stimulated acid secretion, proportionally reducing the volume of gastric juice. Secretion of histamine-stimulated pepsin is reduced.

H2 blockers are well absorbed in the gastrointestinal tract and their action begins 30-60 minutes after eating, and the peak of activity is 1-2 hours. Intravenous administration of drugs promotes a faster onset of action. The duration of action of the drugs is proportional to the dose and the time intervals between doses from 6 to 20 hours. Doses should be lower in elderly patients.

For duodenal ulcers, cimetidine 800 mg, ranitidine 300 mg, famotidine 40 mg, or nizatidine 300 mg orally once daily for 6 to 8 weeks at bedtime or after dinner. For gastric ulcers, the same regimen may be given but extended to 8 to 12 weeks so that nocturnal acid secretion is less important and morning administration may be equally or more effective. Children over 40 kg may be given adult doses. Below this weight, the oral dosage is ranitidine 2 mg/kg every 12 hours and cimetidine 10 mg/kg every 12 hours. For GERD, H2 blockers are used primarily for pain relief. Effective treatment of gastritis is achieved by oral administration of famotidine or ranitidine twice daily for 8-12 weeks.

Cimetidine has a small antiandrogen effect, causing reversible gynecomastia and, rarely, erectile dysfunction with long-term use. Mental status changes, diarrhea, rash, drug fever, myalgia, thrombocytopenia, sinus bradycardia, and hypotension may occur in less than 1% of patients receiving all intravenous H2 blockers, more commonly in elderly patients.

Cimetidine and, to a lesser extent, other H2 _blockers interact with the microsomal P450 enzyme system and may delay the metabolism of other drugs eliminated via this system (eg, phenytoin, warfarin, theophylline, diazepam, lidocaine).

Antacids

These substances neutralize gastric acid and reduce the activity of pepsin (which decreases when the pH of the gastric contents increases above 4.0). In addition, some antacids absorb pepsin. Antacids may interfere with the absorption of other medications (e.g., tetracycline, digoxin, iron).

Antacids reduce symptoms, promote ulcer healing, and reduce the risk of recurrence. They are relatively inexpensive but must be used up to 5-7 times daily. The optimal antacid regimen for ulcer healing is 15-30 ml of liquid or 2-4 tablets 1 and 3 hours after each meal and at bedtime. The total daily dose of antacids should provide 200-400 mEq of neutralizing capacity. However, antacids have been replaced by acid-suppressing drugs in the treatment of peptic ulcers and are therefore used only for short-term symptomatic therapy.

In general, there are two types of antacids: absorbable and non-absorbable. Absorbable antacids (e.g., sodium bicarbonate, calcium carbonate) provide rapid and complete neutralization, but may cause alkalosis and should only be used for short periods (1 or 2 days). Non-absorbable antacids (e.g., aluminum or magnesium hydroxide) cause fewer systemic side effects and are preferred.

Aluminum hydroxide is a relatively safe agent and is commonly used as an antacid. With chronic use, phosphate deficiency sometimes develops as a result of aluminum phosphate binding in the gastrointestinal tract. The risk of phosphate deficiency is increased in alcoholics, in malnourished patients, and in patients with kidney disease (including patients on hemodialysis). Aluminum hydroxide causes constipation.

Magnesium hydroxide is a more effective antacid than aluminum, but may cause diarrhea. To reduce diarrhea, many antacids contain a combination of magnesium and aluminum antacids. Because small amounts of magnesium are absorbed, magnesium preparations should be used with caution in patients with kidney disease.

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Prostaglandins

Certain prostaglandins (especially misoprostol) inhibit acid secretion and enhance mucosal defenses. Synthetic prostaglandin derivatives are used primarily to reduce the risk of mucosal injury from nonsteroidal anti-inflammatory drugs. In patients at high risk of nonsteroidal drug-induced ulcers (i.e., elderly patients, patients with a history of ulcer or complications of ulcers, patients with glucocorticoid-induced ulcers), misoprostol 200 mg orally 4 times daily with meals is indicated along with nonsteroidal anti-inflammatory drugs. Common side effects of misoprostol are intestinal cramps and diarrhea, which occur in 30% of patients. Misoprostol is a potent abortifacient and its use is absolutely contraindicated in women of childbearing potential who are not using contraception.

Sucralfate

This drug is a sucrose-aluminum complex that dissociates in the acidic environment of the stomach and forms a physical barrier over the entire inflamed area, protecting it from the effects of acid, pepsin, and bile salts. This drug also inhibits pepsin-substrate interactions, stimulates mucosal prostaglandin production, and binds bile salts. It has no effect on acid production or gastrin secretion. Sucralfate may affect the trophism of the ulcerated mucosa, possibly by binding growth factors and concentrating them in the ulcer area. Systemic absorption of sucralfate is negligible. Constipation occurs in 3-5% of patients. Sucralfate may bind to other medications and interfere with their absorption.