Peptic ulcer

Peptic ulcer is a peptic defect of the site of the gastrointestinal mucosa, usually in the stomach (gastric ulcer) or in the initial part of the duodenum (duodenal ulcer) that penetrates the muscle layer. Almost all ulcers are caused by Helicobacter infection or when using non-steroidal anti-inflammatory drugs. Symptoms of peptic ulcers usually include a burning pain in the epigastric region, which often decreases after eating. The diagnosis of "peptic ulcer" is established by endoscopy and examination of Helicobacter pylori (Helicobacter pylori). Treatment of peptic ulcer is aimed at suppressing acidity, destruction of H. Pylori (if infection is verified) and exclusion of non-steroidal anti-inflammatory drugs.

The size of the ulcer can vary from a few millimeters to several centimeters. Ulcer differs from erosion by the depth of the lesion; Erosion is more superficial and does not affect the muscular layer. Ulcer can develop at any age, including infancy and childhood, but is most common in middle-aged people.

[1], [2], [3], [4], [5], [6]

What causes a peptic ulcer?

Helicobacter pylori and non-steroidal anti-inflammatory drugs destroy the normal protective layer of the mucosa and disrupt 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 the eradication of Helicobacter pylori, only 10-20% of patients experience a relapse of peptic ulcers, compared to 70% relapse of ulcers in patients treated with acid-suppressing drugs alone.

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

Family history can be traced in 50-60% of children with duodenal ulcers.

Symptoms of peptic ulcer

Symptoms of peptic ulcers depend on the location of the ulcer and the age of the patients; in many patients, especially the elderly, the symptoms are not expressed or absent. Pain is the most common symptom, usually it is localized in the epigastric region and decreases when eating food or antacids. The pain is described as burning and agonizing and sometimes with a feeling of hunger. The course of the ulcer is usually chronic and recurrent. Only about half of patients have characteristic common symptoms.

Symptoms of stomach ulcers often do not coincide with the results obtained (eg, eating sometimes strengthens, but does not reduce pain). This is especially true for pyloric ulcers, which are often associated with symptoms of stenosis (eg, bloating, nausea, vomiting) caused by swelling and scarring.

Duodenal ulcers, as a rule, cause constant pain in the stomach. Pain in the stomach is absent in the morning after waking up, but appears in the middle of the morning, disappears after eating, but again recurs after 2-3 hours. Pain that appears at night is very typical of duodenal ulcers. In newborns, perforation and bleeding may be the first manifestation of a duodenal ulcer. Bleeding can also be the first manifestation of an ulcer in later infancy and early childhood, although the key to the diagnosis may be frequent vomiting and abdominal pain.

Complications of peptic ulcer

[7], [8], [9], [10], [11], [12],

Bleeding

Moderate and severe bleeding is the most common complication of peptic ulcer. Symptoms of gastrointestinal bleeding include hematomesis (vomiting with fresh blood or the type of "coffee grounds"); bloody or tarry stool (melena); weakness, orthostatic collapse, fainting, thirst and sweating caused by blood loss.

[13], [14], [15]

Penetration (delimited perforation)

Peptic ulcer can penetrate through the wall of the stomach. If the adhesive process prevents the entry of the contents into the abdominal cavity, there is no free penetration and a limited perforation develops. However, the ulcer can sprout the duodenum and penetrate into the adjacent confined space (smaller cavity) or other organ (eg, pancreas, liver). The pain can be intense, constant, irradiating to other parts of the body, except the abdomen (usually the back in case of penetration of the duodenal ulcer into the pancreas) and change with the change in the position of the body. Usually CT scan of the abdominal cavity or MRI is required to confirm the diagnosis. If the conservative therapy is ineffective, surgical treatment is indicated.

Free perforation

Peptic ulceration perforating into the free abdominal cavity is usually located on the anterior wall of the duodenum or, more rarely, in the stomach. The patient develops a symptom complex of an acute abdomen. There is a sudden strong constant pain in the epigastric region, rapidly spreading throughout the abdomen, often becoming most pronounced in the right lower quadrant and from time to time radiating into one or both shoulders. The patient usually lies motionless, since even deep breathing increases pain. Palpation of the abdomen is painful, peritoneal symptoms are determined, abdominal wall muscles are strained (washing board), intestinal peristalsis is reduced or absent. Shock may develop, manifested by an increase in heart rate, a decrease in blood pressure and urine production. Symptoms may be less pronounced in elderly or agonizing patients, as well as those taking glucocorticoids or immunosuppressants.

The diagnosis is confirmed radiologically when free air is detected under the diaphragm or in the free abdominal cavity. Radiography of the chest and abdomen is preferred in the vertical position of the body. The most informative is lateral radiography of the chest. In the case of a serious condition of the patient and the impossibility of performing radiographs in an upright position, a lateral examination of the abdomen in the supine position is indicated. The absence of free gas does not exclude a diagnosis.

Emergency surgical intervention is necessary. The longer the delay with the operation, the more unfavorable the prognosis. If contraindicated to surgical treatment, the alternative is continuous nasogastric aspiration and broad-spectrum antibiotics.

Stenosis of the outlet stomach

Stenosis can be caused by scarring. Spasm and inflammation in the area of ulcers can cause disruption of evacuation, but they succumb to conservative therapy. Symptoms include repetitive copious vomiting that occurs mainly at the end of the day and often 6 hours after the last meal. Loss of appetite with a constant bloating or a feeling of overflow after eating suggests stenosis of the outlet stomach. Long-term vomiting can cause weight loss, dehydration and alkalosis.

If the patient's anamnesis involves stenosis, physical examination, aspiration of gastric contents, or X-ray examination can provide evidence of gastric retention. Noise of the splash, heard after more than 6 hours after eating or aspiration more than 200 ml of liquid or food residues after its reception the day before, involves a delay in gastric contents. If aspiration of the gastric contents indicates a delay, it is necessary to empty the stomach and perform endoscopy or fluoroscopy of the stomach to determine the affected area, the cause and degree of stenosis.

Edema or spasm in the ulcer of the pyloric canal is subject to gastric decompression by nasogastric aspiration and suppression of acidity (eg, in / in H ₂ -blockers). Dehydration and electrolyte imbalance due to prolonged vomiting or prolonged nasogastric aspiration require rapid diagnosis and correction. Prokinetic agents are not shown. As a rule, within 2-5 days after treatment, the phenomena of evacuation violation are resolved. Extensive obstruction can be the result of peptic cicatrization of the ulcer and is resolved by endoscopic balloon dilatation of the pyloric canal. Surgical treatment to remove the obstruction is indicated in individual cases.

Relapse of peptic ulcer

Factors causing recurrence of ulcers include ineffective treatment with Helicobacter pylori, the use of non-steroidal anti-inflammatory drugs and smoking. More rarely, the cause may be gastrinoma (Zollinger-Ellison syndrome). During the year relapse of gastric and duodenal ulcers is less than 10% in case of complete destruction of Helicobacter pylori, but more than 60% if the infection persists. Thus, the patient with recurrence of the disease should be examined for H. Pylori and, once the infection is confirmed, again undergo a course of therapy.

Although prolonged treatment with H ₂ -blockers, proton pump inhibitors or misoprostol reduces the risk of recurrence, their routine use for this purpose is not recommended. However, patients who need non-steroidal anti-inflammatory drugs in the presence of peptic ulcers are candidates for long-term therapy, as well as patients with large ulcers or previous perforation or bleeding.

Stomach cancer

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

Diagnosis of peptic ulcer

The diagnosis of "peptic ulcer" can be assumed with careful collection of anamnesis and confirmed by endoscopy. Empirical therapy is often prescribed without a definitive diagnosis. However, endoscopy with biopsy or cytological examination makes it possible to differentiate the lesions of the stomach and esophagus between simple ulceration and gastric ulcer. Cancer of the stomach may show similar signs and should be excluded, especially in patients older than 45 years with complaints of weight loss or expressed, non-treatable peptic ulcer symptoms. Malignancy of the duodenal ulcer is rare, so a biopsy of lesions in this area is usually not necessary. Endoscopy can also be used for the final diagnosis of H. Pylori infection, which must be investigated if an ulcer is detected.

For multiple ulcers, or for ulceration of atypical localization (eg, postbulbary department), as well as ineffective treatment, weight loss or severe diarrhea, one should keep in mind the malignant secretion of gastrin and the Zollinger-Ellison syndrome. These patients should be assessed serum gastrin levels.

[16], [17], [18], [19], [20],

Treatment of peptic ulcer

Treatment of gastric and duodenal ulcers provides, in case of detection, eradication of Helicobacter pylori and a decrease in gastric acidity. With duodenal ulcers, it is especially important to suppress nighttime gastric secretion.

Acid-lowering methods include many medications, most of which are quite effective, but differ in cost, duration of therapy, and dosage convenience. In addition, drugs that have protective properties for the mucous membrane (eg, sucralfate), as well as surgical procedures that reduce acid production, can be used.

Additive treatment of peptic ulcer

Smoking should be ruled out, and alcohol consumption either discontinued, or only in limited quantities in diluted form. There is no reasonable evidence that compliance with the diet promotes faster healing of the ulcer or prevents its recurrence. In this regard, many doctors recommend the exclusion of only food products that cause distress.

[21], [22]

Surgical treatment of peptic ulcer

With the introduction of drug therapy, the number of patients requiring surgical treatment of peptic ulcer decreased sharply. Indications for surgical treatment include perforation, stenosis, profuse or recurrent bleeding and the preservation of symptoms that can not be medicated.

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

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

Weight loss is typical for subtotal gastrectomy; the patient limits the diet due to a sense of rapid saturation (due to a small stump of the stomach), the possibility of developing dumping syndrome and other postprandial syndromes. Because of a small stomach, a feeling of bursting or discomfort can occur even when small amounts of food are taken; patients are forced to eat less, but more often.

Disturbance of digestion and steatorrhea caused by pancreaticabiliary bypass, especially when forming an anastomosis according to Billroth II, can contribute to weight loss.

Anemia characteristic (usually due to iron deficiency, but occasionally because of deficiency of vitamin B ₁₂ caused by loss of intrinsic factor or bacterial infection) for Billroth II operations; can also develop osteomalacia. Additionally recommended intramuscular injection of vitamin B for all patients after total gastrectomy, but can also be used in patients after subtotal gastrectomy in case of suspicion of deficiency of vitamin B ₁₂.

Dumping syndrome develops after operations on the stomach, especially after resection. Weakness, dizziness, sweating, nausea, vomiting and palpitation occur soon after eating, especially after taking hyperosmolar food. This phenomenon is referred to as early dumping, the cause of which remains unclear, but, most likely, its development is associated with vegetative response, intravascular volume reduction and the release of vasoactive peptides from the small intestine. Usually, a diet with a decrease in volume is effective, but more frequent intake of food and restriction of the use of carbohydrates.

Reactive hypoglycemia or late dumping syndrome (another form of the syndrome) develops due to rapid evacuation of carbohydrates from the stump of the stomach. Rapid rise in blood glucose levels stimulates the release of large amounts of insulin, which leads to symptomatic hypoglycemia several hours after ingestion. Recommended protein-rich, carbohydrate-poor diet and adequate calorie food (frequent meals, but in small doses).

Disturbances of the passage (including gastrostasis and formation of bezoar) can occur again with a decrease in gastric motility in phase III, which changes after antrumectomy and vagotomy. Diarrhea is especially characteristic of vagotomy, even without resection (pyloroplasty).

Recurrence of ulcers occurs in 5-12% after highly selective vagotomy and 2-5% after resection operations. Recurrence of the ulcer is diagnosed by endoscopy and requires therapy with proton pump inhibitors or H ₂ -blockers. With recurrence of ulcers, an evaluation of the completeness of vagotomy by gastric secretion testing, antibacterial therapy for the detection of Helicobacter pylori, and a study of serum gastrin level when suspicion of Zollinger-Ellison syndrome is necessary.

Medication at high acidity

Medicines that reduce acidity, are used in peptic ulcer, gastroesophageal reflux disease and various forms of gastritis. Some drugs are used in regimens for the treatment of H. Pylori infection. The drugs include proton pump inhibitors, H ₂ -blockers, antacids and prostaglandins.

Proton Pump Inhibitors

The drugs are potent 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 contribute to the healing of ulcers and are also key components of the medical complex of H. Pylori eradication. Proton pump inhibitors are a beneficial alternative to H ₂ -blockers in most clinical situations because of the speed of action and effectiveness.

Proton pump inhibitors, exclusively for oral use, include omeprazole, lansoprazole, rabeprazole, esomeprazole and pantoprazole. Omeprazole in the Russian Federation has a dosage form for injection. In uncomplicated duodenal ulcers, omeprazole 20 mg orally once a day or lansoprazole 30 mg orally once a day for 4 weeks. Complicated duodenal ulcers (ie, multiple ulcers, bleeding ulcers, ulcers greater than 1.5 cm, or ulcers with severe clinical course) are more amenable to treatment with higher doses of drugs (omeprazole 40 mg once a day, lansoprazole 60 mg once a day or 30 mg 2 times a day). Gastric ulcers require treatment within 6-8 weeks. Gastritis and GERD require treatment for 8-12 weeks; GERD additionally requires long-term maintenance therapy.

Prolonged therapy with proton pump inhibitors causes an increase in the level of gastrin, which leads to hyperplasia of enterochromaffin-like cells. However, there is no evidence of development of dysplasia or malignancy in patients receiving this treatment. In some patients, malabsorption of vitamin B12 may develop.

H2-blockers

These drugs (cimetidine, ranitidine, famotidine for oral and intravenous use and nisatidine for oral administration) have competitive inhibition of H ₂ -histamine receptors and thus inhibit gastrin-stimulated acid secretion, proportionately decreasing the volume of gastric juice. The secretion of histamine-stimulated pepsin is reduced.

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

With duodenal ulcers, oral administration before the sleep or after dinner of cimetidine 800 mg, ranitidine 300 mg, famotidine 40 mg or nizatidine 300 mg once a day for 6-8 weeks is effective. With gastric ulcers, the same regimen can be prescribed, but prolonged to 8-12 weeks, so night acid secretion becomes less important, and the morning use of drugs can be as or more effective. Adult doses can be administered to children weighing more than 40 kg. Below this weight, oral dosage is: ranitidine 2 mg / kg every 12 hours and cimetidine 10 mg / kg every 12 hours. With GERD, H2 blockers are used mainly to relieve pain. Effective treatment of gastritis is achieved by oral intake of 2 times per day of famotidine or ranitidine for 8-12 weeks.

Cimetidine has a slight antiandrogenic effect, causing reversible gynecomastia and, rarely, erectile dysfunction with prolonged use. In less than 1% of patients who received intravenous all the H2-blockers, more often in elderly patients, there may be changes in mental status, diarrhea, rash, drug fever, myalgia, thrombocytopenia, sinus bradycardia and hypotension.

Cimetidine and, to a lesser extent, other H ₂ -blockers interact with the microsomal system of the P450 enzyme and can delay the metabolism of other medications that are eliminated through this system (eg, phenytoin, warfarin, theophylline, diazepam, lidocaine).

Antacids

These substances neutralize the stomach acid and reduce the activity of pepsin (which decreases when the pH of the gastric contents is more than 4.0). In addition, some antacids absorb pepsin. Antacids may interfere with the absorption of other medicines (eg, tetracycline, digoxin, iron).

Antacids reduce symptoms, promote the healing of ulcers and reduce the risk of recurrence. They are relatively inexpensive, but should be used up to 5-7 times a day. The optimal mode of antacids for ulcer healing is 15-30 ml of liquid or 2-4 tablets at 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 in the treatment of peptic ulcers have been replaced with drugs that suppress acidity, and therefore are used only for short-term symptomatic therapy.

In general, there are two types of antacids: absorbed and not absorbed. Absorbable antacids (eg Na bicarbonate, Ca carbonate) provide rapid and complete neutralization, but can cause alkalosis and should only be used for a short time (1 or 2 days). Unabsorbed antacids (eg, aluminum or magnesium hydroxide) cause fewer systemic side effects and are more preferable.

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

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

[23], [24], [25], [26],

Prostaglandins

Certain prostaglandins (especially misoprostol) inhibit acid secretion and increase mucosal protection. Synthetic derivatives of prostaglandins are used primarily to reduce the risk of mucosal damage to non-steroidal anti-inflammatory drugs. Patients with a high risk of non-steroid drug-induced ulcers (ie, elderly patients, patients with a history of ulcer or ulcer complications, patients with glucocorticoid ulcers) showed the use of misoprostol 200 mg orally 4 times daily with meals along with non-steroidal anti-inflammatory drugs. The common side effects of misoprostol are intestinal spasms and diarrhea, which are observed in 30% of patients. Misoprostol - a powerful abortifacient and its use is absolutely contraindicated in women of childbearing age who do not use contraception.

Sucralfate

This drug is a sugar-aluminum complex that dissociates in the acidic environment of the stomach and forms a physical barrier throughout the inflamed area, protecting it from the effects of acid, pepsin and bile salts. This drug also inhibits the interaction of pepsin-substrate, stimulates the production of prostaglandin mucosa and binds bile salts. It has no effect on the production of acid or the secretion of gastrin. Sucralfate, perhaps, affects the trophic of ulcerated mucosa, possibly due to the binding of growth factors and their concentration in the area of the ulcer. Systemic absorption of sucralfate is negligible. Constipation is observed in 3-5% of patients. Sucralfate can bind to other medicines and disrupt their absorption.