Peptic ulcer of the stomach and duodenum: etiology, pathogenesis, methods of treatment. Symptoms of gastric and duodenal ulcers Gastric ulcer and 12 pc

peptic ulcer stomach and duodenum is a fairly common pathology. According to statistics, 5-10% of the population of various countries suffer from it, and men are 3-4 times more likely than women. An unpleasant feature of this disease is that it often affects people of a young, working age, for some, and quite a long time, depriving them of their ability to work. In this article, we will look at the symptoms of stomach and duodenal ulcers, the causes of the disease and how to diagnose it.

What is a peptic ulcer?

This is a recurrent chronic disease of the stomach and duodenum, characterized by the formation of one or more ulcers on the mucous membrane of these organs.

The peak incidence occurs at the age of 25-50 years. In all likelihood, this is due to the fact that it is during this period of life that a person is most susceptible to emotional stress, often leads an unhealthy lifestyle, and eats irregularly and irrationally.

Causes and mechanism of occurrence

Defects in the mucous membrane of the stomach and duodenum occur under the influence of the so-called aggression factors (these include hydrochloric acid, the proteolytic enzyme pepsin, bile acids and a bacterium called Helicobacter pylori) if their number prevails over mucosal protective factors (local immunity, adequate microcirculation, prostaglandin levels and other factors).

Factors predisposing to the disease are:

• infection with Helicobacter pylori (this microbe causes inflammation in the mucous membrane, destroying protective factors and increasing acidity);
• taking certain medications (non-steroidal anti-inflammatory drugs, steroid hormones);
• irregular meals;
• bad habits(smoking, drinking alcohol);
• acute and chronic stress;
• heredity.

Symptoms

For peptic ulcer of the stomach and duodenum, a chronic, undulating course is characteristic, that is, from time to time the period of remission is replaced by an exacerbation (the latter are noted mainly in the spring and autumn period). Patients complain during the period of exacerbation, the duration of which can vary within 4-12 weeks, after which the symptoms regress for a period of several months to several years. Many factors can cause an exacerbation, the main of which are a gross error in the diet, excessive physical activity, stress, infection, taking certain medicines.

In most cases, peptic ulcer debuts acutely with the appearance of intense pain in the stomach.

The time of onset of pain depends on in which department the ulcer is localized:

• “early” pains (appear immediately after eating, decrease as the contents of the stomach enter the duodenum - 2 hours after eating) are characteristic of ulcers located in the upper part of the stomach;
• “Late” pains (occur about 2 hours after eating) disturb people suffering from an antral ulcer;
• "Hunger" or night pains (occur on an empty stomach, often at night and decrease after eating) are a sign of duodenal ulcer.

The pains do not have a clear localization and can be of a different nature - aching, cutting, boring, dull, cramping.

Since the acidity gastric juice and sensitivity of the gastric mucosa to it in persons suffering from peptic ulcer disease are usually increased,. It can occur both simultaneously with pain and precede it.

Approximately half of the patients complain of belching. This is a non-specific symptom, arising from the weakness of the cardiac sphincter of the esophagus, combined with the phenomena of anti-peristalsis (movements against the course of food) of the stomach. Belching is often sour, accompanied by salivation and regurgitation.

Frequent symptoms of exacerbation this disease are nausea and vomiting, and usually they are combined with each other. Vomiting often occurs at the height of pain and brings significant relief to the patient - it is for this reason that many patients themselves try to cause this condition in themselves. The vomit is usually made up of acidic contents mixed with recently eaten food.

As for appetite, in persons suffering from peptic ulcer, it is often not changed or increased. In some cases - usually with intense pain - there is a decrease in appetite. Often there is a fear of eating food due to the expected subsequent occurrence of a pain syndrome - sitophobia. This symptom can lead to severe weight loss of the patient.

On average, 50% of patients have complaints of defecation disorders, namely constipation. They can be so persistent that they disturb the patient much more than the pain itself.

Diagnosis and treatment of peptic ulcer

Complaints and palpation of the patient's abdomen will help the doctor to suspect the disease, and the most accurate method of confirming the diagnosis is esophagogastroduodenoscopy, or EFGDS.

It depends on the degree of its severity and can be either conservative (with optimization of the patient's regimen, adherence to dietary recommendations, use of antibiotics and antisecretory drugs) or surgical (usually with complicated forms of the disease).

At the stage of rehabilitation, the most important role is played by diet therapy, physiotherapy, psychotherapy.

Which doctor to contact

Treatment of peptic ulcer of the stomach and duodenum is carried out by a gastroenterologist, and in case of complications (for example, bleeding or perforation of the ulcer), it is necessary surgical intervention. An important stage of diagnosis is FGDS, which is performed by an endoscopist. It is also useful to visit a nutritionist, undergo a course of physiotherapy, consult a psychologist and learn how to properly cope with stressful situations.

Peptic ulcer of the stomach and duodenum is a chronic disease, the main expression of which is a recurrent gastric or duodenal ulcer that occurs against the background of gastritis.

According to classical concepts, an ulcer is formed as a result of an imbalance between the aggressive and protective mechanisms of the gastrointestinal mucosa.

Aggressive factors include

• hydrochloric acid,
• digestive enzymes,
• bile acids;

to protective

• mucus secretion,
• cellular renewal of the epithelium,
• adequate blood supply to the mucosa.

The causal significance of H. Pylori for chronic gastritis determines the most important place of the microorganism in the development of gastric ulcer and duodenal ulcer. It turned out that H. Pylori is closely related to the factors of aggression in peptic ulcer disease. The most important result of its destruction is a decrease in the frequency of relapses of the disease.

Manifestations of peptic ulcer

With a duodenal ulcer, pain appears one and a half hours after eating, there are nightly, hungry (that is, arising on an empty stomach) pain in the pancreas or in the right hypochondrium, which disappear after eating, taking antacids, ranitidine, omeprazole.

Vomiting of acidic contents of the stomach can occur at the height of pain, after vomiting the patient experiences relief (some patients self-induce vomiting to reduce pain).

Pain that occurs 30 minutes - 1 hour after eating is more typical for the localization of an ulcer in the stomach.

Manifestations of peptic ulcer also include nausea, heartburn, and belching.

Naturally, there are cases with atypical symptoms: the absence of a characteristic connection between pain syndrome and food intake, the absence of seasonal exacerbations do not exclude this diagnosis. The so-called silent exacerbations of the disease are difficult to suspect and correctly recognize.

Diagnostics

The symptomatology of the disease is quite bright, and the diagnosis is not difficult in a typical case. Be sure to conduct esophagogastroduodenoscopy.

A complete diagnosis of peptic ulcer should include objective evidence of the presence of H. Pylori infection. Many laboratories perform a urea breath test with urea.

For analysis, only 2 samples of exhaled air are needed, the method allows you to control the success of the treatment.

A polymerase method has been developed chain reaction(PCR) to determine H. Pylori in feces. The method has sufficient sensitivity and specificity.

Treatment of gastric and duodenal ulcers

Principles of treatment of peptic ulcer:

• the same approach to the treatment of gastric and duodenal ulcers;
• mandatory basic therapy that reduces acidity;
• choosing an acid-reducing drug that maintains intragastric acidity >3 for about 18 hours per day;
• the appointment of an acid-reducing drug in a strictly defined dose;
• endoscopic control with a 2-week interval;
• duration of therapy depending on the timing of ulcer healing;
• antihelicobacter therapy according to indications;
• mandatory monitoring of the effectiveness of therapy after 4-6 weeks;
• repeated courses of therapy with its ineffectiveness;
• maintenance anti-relapse therapy.

The protocol for the treatment of peptic ulcer involves, first of all, basic therapy, the purpose of which is to eliminate pain and digestive disorders, as well as to achieve scarring of the ulcer in the shortest possible time.

Drug treatment involves the appointment of a drug that reduces the acidity of gastric juice, in a strictly defined dose. The duration of treatment depends on the results of endoscopic control, which is carried out at two-week intervals (i.e. after 4, 6, 8 weeks).

In each patient with a stomach ulcer or duodenal ulcer, in which H. pylori is found in the gastric mucosa, by one method or another (rapid urease test, morphological method, using DNA detection by polymerase chain reaction, etc.), antimicrobial therapy is carried out. This therapy involves a combination of several antimicrobials.

Eradication therapy 2 lines

• Proton pump blockers 2 times a day;
• Colloidal bismuth subcitrate 120 mg x 4 times;
• Tetracycline 500 mg x 4 times;
• Metronidazole 250 mg x 4 times;
• The duration of treatment is 7 days.

An alternative regimen was a combination of pyloride (ranitidine) at a dose of 400 mg 2 times a day with one of the antibiotics - clarithromycin (250 mg 4 times or 500 mg 2 times a day) or amoxicillin (at a dose of 500 mg 4 times a day) .

The protocol of eradication therapy involves mandatory monitoring of its effectiveness, which is carried out 4-6 weeks after its completion (during this period, the patient does not take antimicrobials) using the breath test or polymerase chain reaction. If H. pylori persists in the gastric mucosa, a second course of eradication therapy is carried out using 2nd line therapy, followed by monitoring of its effectiveness also after 4-6 weeks.

The ineffectiveness of conservative treatment of patients with a stomach ulcer or duodenal ulcer can manifest itself in two ways: a frequently relapsing course of peptic ulcer (i.e., with an exacerbation frequency of 2 times a year or more) and the formation of refractory gastroduodenal ulcers (ulcers that do not scar within 12 weeks ongoing treatment).

The factors that determine the frequently relapsing course of peptic ulcer disease are:

• contamination of the gastric mucosa by N. pylori;
• taking non-steroidal anti-inflammatory drugs (diclofenac, ortofen, ibuprofen, etc.);
• the presence in the past of ulcerative bleeding and perforation of the ulcer;
• low "compliance", i.e. lack of readiness of the patient to cooperate with the doctor, manifested in the refusal of patients to stop smoking and drinking alcohol, irregular intake of medications.

The main symptoms of a stomach ulcer (peptic ulcer) are pain and dyspeptic syndromes (a syndrome is a stable set of symptoms characteristic of a given disease).

Pain is the most typical symptom of peptic ulcer of the stomach and duodenum. It is necessary to find out the nature, frequency, time of occurrence and disappearance of pain, the connection with the intake of food.

Up to 75% of patients complain of pain in the upper abdomen (more often in the epigastric region). Approximately 50% of patients experience pain of low intensity, and about a third of patients experience pronounced pain. The pain may appear or increase with physical activity, eating spicy food, a long break in eating, drinking alcohol. In a typical course of peptic ulcer, pains have a clear connection with food intake, they occur during an exacerbation of the disease and are characterized by seasonality - they occur more often in spring and autumn. In addition, a decrease or even disappearance of pain after taking soda, food, antisecretory (omez, famotidine, etc.) and antacid (almagel, gastal, etc.) drugs is quite characteristic.

Early pain occurs 0.5-1 hour after eating, gradually increases in intensity, persists for 1.5-2 hours, decreases and disappears as gastric contents move into the duodenum; characteristic of gastric ulcers. With the defeat of the cardiac, subcardial and fundal departments, pain occurs immediately after eating.

Late pain occurs 1.5-2 hours after eating, gradually intensifies as the contents are evacuated from the stomach; characteristic of ulcers of the pyloric stomach and duodenal bulb.

"Hungry" (night) pains occur 2.5-4 hours after eating, disappear after the next meal; characteristic of duodenal ulcers and pyloric stomach. The combination of early and late pain is observed with combined or multiple ulcers.

The intensity of pain may depend on age (more pronounced in young people), the presence of complications.

The most typical projection of pain, depending on the localization of the ulcerative process, is the following:

• with ulcers of the cardiac and subcardial sections of the stomach - the region of the xiphoid process;
• with ulcers of the body of the stomach - the epigastric region to the left of midline;
• with ulcers of the pyloric and duodenal ulcers - the epigastric region to the right of the midline.

Palpation of the epigastric region may be painful.

The absence of the typical nature of pain does not contradict the diagnosis of peptic ulcer.

Dyspeptic syndrome is characterized by heartburn, belching, nausea, vomiting, stool disturbance, as well as a change in appetite, a feeling of fullness or bloating of the stomach, a feeling of discomfort in the epigastric region. Heartburn occurs in 30-80% of patients, it can be persistent and usually appears 1.5-3 hours after eating. At least 50% of patients complain of belching. Nausea and vomiting are not uncommon in peptic ulcer disease, most often vomiting develops at the height of pain and brings relief to the patient, so patients can induce vomiting artificially. Almost 50% of patients suffer from constipation, which is more often observed with an exacerbation of the process. Diarrhea is not typical. Severe disturbances of appetite in peptic ulcer, as a rule, are not observed. The patient may restrict himself in nutrition with severe pain, which happens during an exacerbation.

It is imperative to clarify with the patient the presence of episodes of vomiting of blood or black stools (melena). In addition, physical examination should purposefully try to identify signs of a possible malignant nature of ulceration or the presence of complications of peptic ulcer.

With a favorable course, the disease proceeds without complications, with alternating periods of exacerbation lasting from 3 to 8 weeks, and periods of remission, the duration of which can vary from several months to several years. An asymptomatic course of the disease is also possible: the diagnosis of peptic ulcer during life is not established in 24.9-28.8% of cases.

Symptoms of peptic ulcer depending on the localization of the ulcer

Symptoms of an ulcer of the cardiac and subcardial stomach

These ulcers are localized either directly at the esophageal-gastric junction or distal to it, but not more than 5-6 cm.

Characteristic for cardiac and subcardial ulcers are the following features:

• men over the age of 45 are more likely to get sick;
• pain occurs early, 15-20 minutes after eating and is localized high in the epigastrium at the xiphoid process itself;
• Pain quite often radiates to the region of the heart and can be mistakenly regarded as angina pectoris. In differential diagnosis, it should be borne in mind that pain in coronary disease hearts appear when walking, at a height physical activity and disappear in peace. Pain in cardiac and subcardial ulcers is clearly associated with food intake and does not depend on physical wear, walking, does not calm down after taking nitroglycerin under the tongue, as with angina pectoris, but after taking antacids, milk;
• weak expressiveness of a pain syndrome is characteristic;
• pain is often accompanied by heartburn, belching, vomiting due to insufficiency of the cardiac sphincter and the development of gastroesophageal reflux;
• often ulcers of the cardial and subcardial stomach are combined with a hernia of the esophageal opening of the diaphragm, reflux esophagitis;
• the most characteristic complication is bleeding, ulcer perforation is very rare.

Symptoms of an ulcer of the lesser curvature of the stomach

The lesser curvature is the most frequent localization stomach ulcers. The characteristic features are the following:

• the age of patients usually exceeds 40 years, often these ulcers occur in the elderly and the elderly;
• pains are localized in the epigastric region (slightly to the left of the midline), occur 1-1.5 hours after eating and stop after the evacuation of food from the stomach; sometimes there are late, "night" and "hungry" pains;
• pains are usually aching in nature, their intensity is moderate; however, in the acute phase, very intense pain may occur;
• often observed heartburn, nausea, rarely vomiting;
• gastric secretion is most often normal, but in some cases it is also possible to increase or decrease the acidity of gastric juice;
• in 14% of cases they are complicated by bleeding, rarely by perforation;
• in 8-10% of cases, malignancy of the ulcer is possible, and it is generally accepted that malignancy is most characteristic of ulcers located at the bend of the lesser curvature. Ulcers, localized in the upper part of the lesser curvature, are mostly benign.

Symptoms of an ulcer of the greater curvature of the stomach

Ulcers of the greater curvature of the stomach have the following clinical features:

• are rare;
• older men predominate among patients;
• the symptomatology differs little from the typical clinical picture of a stomach ulcer;
• in 50% of cases, ulcers of the greater curvature of the stomach are malignant, so the doctor should always consider an ulcer of this localization as potentially malignant and make repeated multiple biopsies from the edges and bottom of the ulcer.

Symptoms of an antral ulcer

Ulcers of the antrum of the stomach ("prepyloric") account for 10-16% of all cases of peptic ulcer and have the following clinical features:

• occur predominantly in young people;
• the symptomatology is similar to the symptomatology of duodenal ulcer, late, “nightly”, “hungry” pains in the epigastrium are characteristic; heartburn; vomiting of sour contents; high acidity of gastric juice; positive symptom Mendel on the right in the epigastrium;
• it is always necessary to carry out a differential diagnosis with a primary ulcerative form of cancer, especially in the elderly, since the antrum is a favorite localization of gastric cancer;
• in 15-20% of cases are complicated by gastric bleeding.

Symptoms of a pyloric canal ulcer

Pyloric canal ulcers account for about 3-8% of all gastroduodenal ulcers and are characterized by the following features:

• persistent course of the disease;
• a pronounced pain syndrome is characteristic, the pains are paroxysmal in nature, last about 30-40 minutes, in 1/3 of patients the pains are late, nocturnal, "hungry", but in many patients they are not associated with food intake;
• pains are often accompanied by vomiting of sour contents;
• persistent heartburn, paroxysmal excessive salivation, a feeling of fullness and fullness in the epigastrium after eating are characteristic;
• with many years of recurrence, ulcers of the pyloric canal are complicated by pyloric stenosis; other frequent complications are bleeding (the pyloric canal is abundantly vascularized), perforation, penetration into the pancreas; 3-8% have malignancy.

Symptoms of a duodenal ulcer

Ulcers of the duodenal bulb are more often localized on the anterior wall. The clinical picture of the disease has the following features:

• the age of patients is usually younger than 40 years;
• men are more often ill;
• epigastric pain (more on the right) appears 1.5-2 hours after eating, there are often night, early morning, and “hungry” pains;
• vomiting is rare;
• seasonal exacerbations are characteristic (mainly in spring and autumn);
• a positive symptom of Mendel is determined in the epigastrium on the right;
• the most common complication is ulcer perforation.

When the ulcer is located on the back wall of the duodenal bulb, the following manifestations are most characteristic in the clinical picture:

• the main symptoms are similar to the symptoms described above, which are characteristic of the localization of an ulcer on the anterior wall of the duodenal bulb;
• often there is a spasm of the sphincter of Oddi, dyskinesia of the gallbladder of the hypotonic type (feeling of heaviness and dull pain in the right hypochondrium with irradiation to the right subscapular region);
• the disease is often complicated by ulcer penetration into the pancreas and hepatoduodenal ligament, the development of reactive pancreatitis.

Duodenal ulcers, unlike gastric ulcers, are not malignant.

Symptoms of extrabulbar (postbulbar) ulcers

Extrabulbous (postbulbar) ulcers are ulcers located distal to the duodenal bulb. They make up 5-7% of all gastroduodenal ulcers and have characteristic features:

• most common in men aged 40-60 years, the disease begins 5-10 years later compared to duodenal ulcer;
• in the acute phase, intense pain in the right upper quadrant of the abdomen, radiating to the right subscapular region and back, is very characteristic. Often the pain is paroxysmal in nature and may resemble an attack of urolithiasis or cholelithiasis;
• pains appear 3-4 hours after eating, and eating, in particular milk, stops the pain syndrome not immediately, but after 15-20 minutes;
• the disease is often complicated by intestinal bleeding , the development of perivisceritis, perigastritis, penetration and stenosis of the duodenum 12;
• perforation of the ulcer, in contrast to localization on the anterior wall of the duodenal bulb, is observed much less frequently;
• in some patients, mechanical (subhepatic) jaundice may develop, which is caused by compression of the common bile duct by an inflammatory periulcerous infiltrate or connective tissue.

Symptoms of combined and multiple gastroduodenal ulcers

Combined ulcers occur in 5-10% of patients with peptic ulcer. At the same time, a duodenal ulcer initially develops, and after a few years - a stomach ulcer. The proposed mechanism for this sequence of ulcer development is as follows.

With a duodenal ulcer, mucosal edema, intestinal spasm, and often cicatricial stenosis develop initial department 12 duodenal ulcer. All this complicates the evacuation of gastric contents, stretching of the astral region (antral stasis) occurs, which stimulates gastrin hyperproduction and, accordingly, causes gastric hypersecretion. As a result, prerequisites are created for the development of a secondary gastric ulcer, which is more often localized in the region of the stomach angle. The development of an ulcer initially in the stomach and then in the duodenum is extremely rare and is considered an exception. It is also possible to develop them simultaneously.

Combined gastroduodenal ulcer has the following characteristic clinical features:

• the accession of a gastric ulcer rarely worsens the course of the disease;
• epigastric pains become intense, along with late, nocturnal, “hungry” pains, early pains appear (arising shortly after eating);
• the zone of localization of pain in the epigastrium becomes more common;
• after eating, there is a painful feeling of fullness in the stomach (even after taking a small amount of food), severe heartburn, vomiting is often disturbing;
• in the study of the secretory function of the stomach, pronounced hypersecretion is observed, while the production of hydrochloric acid can become even higher compared to the values ​​that were available with an isolated duodenal ulcer;
• the development of such complications as cicatricial pyloric stenosis, pylorospasm, gastrointestinal bleeding, perforation of an ulcer (usually duodenal) is characteristic;
• in 30-40% of cases, the attachment of a stomach ulcer to a duodenal ulcer does not significantly change the clinical picture of the disease, and a gastric ulcer can only be detected during gastroscopy.

Multiple ulcers are called 2 or more ulcers, simultaneously localized in the stomach or duodenum 12. Multiple ulcers are characterized by the following features:

• tendency to slow scarring, frequent recurrence, development of complications;
• in a number of patients clinical course may not differ from the course of a single gastric or duodenal ulcer.

Symptoms of giant ulcers of the stomach and duodenum 12

According to E. S. Ryss and Yu. I. Fishzon-Ryss (1995), ulcers with a diameter of more than 2 cm are called giant. A. S. Loginov (1992) classifies ulcers with a diameter of more than 3 cm as giant.

Giant ulcers are characterized by the following features:

• located mainly on the lesser curvature of the stomach, less often - in the subcardiac region, on greater curvature and very rarely - in the duodenum;
• pains are significantly pronounced, their periodicity often disappears, they can become almost constant, which requires differential diagnosis with stomach cancer; in rare cases, the pain syndrome may be mild;
• characterized by rapid onset of exhaustion;
• very often complications develop - massive gastric bleeding, penetration into the pancreas, less often - ulcer perforation;
• careful differential diagnosis of a giant ulcer with a primary ulcerative form of gastric cancer is required; possible malignancy of giant gastric ulcers.

Symptoms of long-term non-healing ulcers

According to A. S. Loginov (1984), V. M. Mayorov (1989), ulcers that do not scar within 2 months are called long-term non-healing. The main reasons for the sharp lengthening of the healing time of the ulcer are:

• hereditary burden;
• age over 50;
• smoking;
• alcohol abuse;
• the presence of pronounced gastroduodenitis;
• cicatricial deformity of the stomach and duodenum;
• persistence of Helicobacter pylori infection.

For long-term non-healing ulcers, the symptoms are erased, and the severity of pain decreases during therapy. However, quite often such ulcers are complicated by perivisceritis, penetration, and then the pain becomes persistent, constant, monotonous. There may be a progressive drop in body weight of the patient. These circumstances dictate the need for careful differential diagnosis of a long-term non-healing ulcer with a primary ulcerative form of gastric cancer.

Peptic ulcer in old age

Under the senile understand ulcers that first developed after the age of 60 years. Ulcers in old people or the elderly are called ulcers that first appeared at a young age, but remain active until old age.

Features of peptic ulcer in these age groups are:

• an increase in the number and severity of complications, primarily bleeding, compared with the age when the ulcer first formed;
• tendency to increase the diameter and depth of the ulcer;
• poor healing of ulcers;
• pain syndrome is mild or moderate;
• acute development of "senile" ulcers, their predominant localization in the stomach, frequent complication bleeding;
• the need for careful differential diagnosis with gastric cancer.

Peptic ulcer of the 12th duodenal ulcer- This is a disease of the duodenum of a chronic relapsing nature, accompanied by the formation of a defect in its mucous membrane and the tissues located under it. Manifested by severe pain in the left epigastric region, occurring 3-4 hours after eating, bouts of "hungry" and "night" pain, heartburn, acid belching, often vomiting. The most formidable complications are bleeding, perforation of the ulcer and its malignant degeneration. Diagnosis includes gastroscopy with biopsy, radiography of the stomach, urease breath test. The main directions of treatment are the eradication of H. pylori infection, antacid and gastroprotective therapy.

General information

Peptic ulcer of the duodenum is a chronic disease characterized by the occurrence of ulcerative defects in the duodenal mucosa. It proceeds for a long time, alternating periods of remission with exacerbations. Unlike erosive lesions of the mucosa, ulcers are deeper defects penetrating into the submucosal layer of the intestinal wall. Duodenal ulcer occurs in 5-15% of the population (statistics vary depending on the region of residence), more common in men. Duodenal ulcer is 4 times more common than gastric ulcer.

The reasons

The modern theory of the development of peptic ulcer considers an infectious lesion of the stomach and duodenum by Helicobacter pylori bacteria as a key factor in its occurrence. This bacterial culture is sown during bacteriological examination of gastric contents in 95% of patients with duodenal ulcer and in 87% of patients with gastric ulcer.

However, infection with Helicobacter pylori does not always lead to the development of the disease, in most cases there is an asymptomatic carriage. Factors contributing to the development of duodenal ulcer:

• alimentary disorders - improper, irregular nutrition;
• frequent stress;
• increased secretion of gastric juice and reduced activity of gastroprotective factors (gastric mucoproteins and bicarbonates);
• smoking, especially on an empty stomach;
• long-term use of drugs that have an ulcerogenic (ulcerogenic) effect (most often these are drugs from the group of non-steroidal anti-inflammatory drugs - analgin, aspirin, diclofenac, etc.);
• gastrin-producing tumor (gastrinoma).

Duodenal ulcers resulting from ingestion medicines or concomitant gastrinoma, are symptomatic and are not included in the concept of peptic ulcer.

Classification

Peptic ulcer differs in localization:

• Peptic ulcer of the stomach (cardia, subcardiac department, body of the stomach);
• peptic post-resection ulcer of the pyloric canal (anterior, posterior wall, lesser or greater curvature);
• duodenal ulcer (bulbous and postbulbar);
• ulcer of unspecified localization.

By clinical form allocate acute (for the first time identified) and chronic peptic ulcer. According to the phase, periods of remission, exacerbation (relapse) and incomplete remission or fading exacerbation are distinguished. Peptic ulcer can occur:

• latently (without a pronounced clinic),
• easy (with rare relapses),
• moderate (1-2 exacerbations during the year)
• severe (with regular exacerbations up to 3 or more times a year).

Directly duodenal ulcer is different:

1. According to the morphological picture: acute or chronic ulcer.
2. In size: small (up to half a centimeter), medium (up to a centimeter), large (from one to three centimeters) and giant (more than three centimeters) in size.

Stages of ulcer development: active, scarring, "red" scar and "white" scar. With concomitant functional disorders of the gastroduodenal system, their nature is also noted: violations of motor, evacuation or secretory function.

Symptoms

In children and the elderly, the course of peptic ulcer is sometimes almost asymptomatic or with minor manifestations. Such a course is fraught with the development of severe complications, such as perforation of the duodenal wall with subsequent peritonitis, occult bleeding and anemia. A typical clinical picture of duodenal ulcer is a characteristic pain syndrome.

The pain is usually mild and dull. The severity of pain depends on the severity of the disease. Localization, as a rule, from the epigastrium, under the sternum. Sometimes the pain can be diffused in the upper half of the abdomen. Occurs often at night (1-2 hours) and after long periods without food, when the stomach is empty. After eating, milk, antacids, relief comes. But most often the pain resumes after the evacuation of the contents of the stomach.

Pain may occur several times a day for several days (weeks), after which it will pass on its own. However, over time, without proper therapy, relapses become more frequent, and the intensity of the pain syndrome increases. Seasonality of relapses is characteristic: exacerbations often occur in spring and autumn.

Complications

The main complications of duodenal ulcer are penetration, perforation, bleeding and narrowing of the intestinal lumen. Ulcerative bleeding occurs when the pathological process affects the vessels of the gastric wall. Bleeding can be latent and manifest only with increasing anemia, or it can be pronounced, blood can be found in vomiting and appear during bowel movements (black or bloody stools). In some cases, bleeding can be stopped during endoscopic examination, when the source of bleeding can sometimes be cauterized. If the ulcer is deep and the bleeding is profuse, surgical treatment is prescribed, in other cases they are treated conservatively, correcting iron deficiency. With ulcerative bleeding, patients are prescribed strict hunger, parenteral nutrition.

Perforation of the duodenal ulcer (usually the anterior wall) leads to the penetration of its contents into the abdominal cavity and inflammation of the peritoneum - peritonitis. When the intestinal wall is perforated, a sharp cutting-stabbing pain in the epigastrium usually occurs, which quickly becomes diffuse, intensifies with a change in body position, deep breathing. The symptoms of peritoneal irritation (Shchetkin-Blumberg) are determined - with pressure on abdominal wall, and then a sharp release of the pain intensifies. Peritonitis is accompanied by hyperthermia. This is an emergency condition that, without proper medical care leading to shock and death. Perforation of the ulcer is an indication for urgent surgical intervention.

Forecast and prevention

Measures to prevent the development of duodenal ulcer:

• timely detection and treatment of Helicobacter pylori infection;
• normalization of the mode and nature of nutrition;
• quitting smoking and alcohol abuse;
• control over the drugs taken;
• harmonious psychological environment, avoidance of stressful situations.

Uncomplicated peptic ulcer disease, with proper treatment and adherence to dietary and lifestyle recommendations, has a favorable prognosis, with high-quality eradication, ulcer healing and cure. The development of complications in peptic ulcer worsens the course and can lead to life threatening states.

Peptic ulcer (PU) is a chronic relapsing disease that occurs with alternating periods of exacerbation and remission, the leading manifestation of which is the formation of a defect (ulcer) in the wall of the stomach and duodenum.

Etiology and pathogenesis

Of great importance is hereditary burden (genetically determined high density of parietal cells, their hypersensitivity to gastrin, deficiency of trypsin inhibitors, congenital deficiency of antitrypsin, etc.) Under the influence of adverse factors (infection with Helicobacter pylori, prolonged nutritional error, psycho-emotional stress, bad habits), a genetic predisposition to the development of ulcer is realized.

The pathogenesis of PU is based on an imbalance between the factors of acid-peptic aggression of gastric contents and the protective elements of the mucous membrane (SO) of the stomach and duodenum.

Strengthening of factors of aggression or weakening of factors of protection lead to disturbance of this balance and emergence of an ulcer.

Factors of aggression include hyperproduction of hydrochloric acid, increased excitability of parietal cells due to vagotonia, infectious factors (Helicobacter pylori), impaired blood supply to the mucous membrane of the stomach and duodenum, impaired antroduodenal acid brake, bile acids and lysolecithin.

The protective factors are the mucous barrier, mucin, sialic acids, bicarbonates - back diffusion of hydrogen ions, regeneration, sufficient blood supply to the mucous membrane of the stomach and duodenum, and antroduodenal acid brake.

Ultimately, the formation of a peptic ulcer is due to the action of hydrochloric acid (the rule of K. Schwarz "No acid - no ulcer") on the mucous membrane of the stomach and duodenum, which allows us to consider antisecretory therapy as the basis for the treatment of exacerbations of peptic ulcer.

The decisive etiological role in the development of PU is currently assigned to H. pylori microorganisms. These bacteria produce a number of enzymes (urease, protease, phospholipases) that damage the protective mucosal barrier, as well as various cytotoxins. Seeding of the gastric mucosa with H. pylori is accompanied by the development of superficial antral gastritis and duodenitis and leads to an increase in the level of gastrin, followed by increased secretion of hydrochloric acid.

Excessive intake of hydrochloric acid into the lumen of the duodenum in conditions of relative deficiency of pancreatic bicarbonates contributes to increased duodenitis, the occurrence of intestinal metaplasia and the spread of H. pylori.

In the presence of a hereditary predisposition and the action of additional etiological factors (malnutrition, neuropsychic stress, etc.), an ulcerative defect is formed.

In children, unlike adults, infection with H. pylori is much less often accompanied by ulceration of the mucous membrane of the stomach and duodenum.

Classification

AT pediatric practice use the classification of peptic ulcer proposed by Professor Mazurin A.V. (Table 2) with additions .
The domestic medical school separates peptic ulcer and symptomatic ulcers - ulceration of the mucous membrane (SO) of the stomach and duodenum that occurs in various diseases and conditions. For example, ulcers with stress, taking non-steroidal anti-inflammatory drugs (NSAIDs). In the English-language literature, the term "peptic ulcer" is often used to refer to the actual peptic ulcer and symptomatic lesions of the mucous membrane of the stomach and duodenum.

Clinical picture

-Pain syndrome
Usually the pain is localized in the epigastric or paraumbilical region, sometimes it is diffused throughout the abdomen.
In a typical case, the pain occurs regularly, becomes intense, takes on a nocturnal and “hungry” character, and decreases with food intake. With duodenal ulcer, the so-called Moinigan rhythm of pain appears (hunger - pain - food intake - light gap - hunger - pain).
- Dyspeptic disorders(heartburn, belching, vomiting, nausea) are less common in children than in adults. With an increase in the duration of the disease, the frequency of dyspeptic symptoms increases. Appetite is reduced in some patients. They may have a delay in physical development (weight loss). Patients with PU often have a tendency to constipation or loose stools.
- Asthenic syndrome. As the ulcer progresses, emotional lability increases, due to pain sleep is disturbed, increased fatigue appears, an asthenic condition may develop. There may be hyperhidrosis of the palms and feet, arterial hypotension, a change in the nature of dermographism, sometimes bradycardia, which indicates a violation of the activity of the autonomic nervous system, with a predominance of the activity of the parasympathetic division.

Complications of PU in childhood

observed in 7-10% of patients. In boys, complications are observed more often than in girls in the case of duodenal ulcer.

The structure of complications is dominated by bleeding (80%), stenosis (11%), perforation (8%) and ulcer penetration (1.5%) are less common.
Bleeding is characterized by blood in the vomit (scarlet or coffee grounds vomit), black tarry stools.

With a large blood loss, weakness, nausea, pallor, tachycardia, a decrease in blood pressure, and sometimes fainting are characteristic. With hidden bleeding in the feces, a positive reaction to occult blood.

Stenosis of the pylorobulbar zone usually develops in the process of ulcer healing. As a result of food delay in the stomach, its expansion occurs, followed by the development of intoxication, exhaustion. Clinically, this is manifested by vomiting of food eaten the day before, increased peristalsis of the stomach, especially on palpation, and "splash noise", determined by jerky palpation of the abdominal wall.

Penetration (penetration of an ulcer into neighboring organs) usually occurs against the background of a long and severe course of the disease, inadequate therapy. It is accompanied by an increase in pain syndrome with irradiation to the back. There is vomiting that does not bring relief, fever is possible.

Ulcer perforation is 2 times more common in gastric localization of the ulcer. Basic clinical sign perforation - a sharp sudden (“dagger”) pain in the epigastric region and in the right hypochondrium, often accompanied by state of shock. There is a weak pulse, a sharp pain in the pyloroduodenal zone, the disappearance of hepatic dullness due to the release of air into the free abdominal cavity. Nausea, vomiting, stool retention

Diagnostics

On examination, it is often found white coating on the tongue, on palpation - soreness in the pyloroduodenal zone. Regardless of the localization of the ulcer in children, pain in the epigastric region and in the right hypochondrium is very often noted. The symptom of muscular protection is rare, more often during severe pain. In the exacerbation phase, a positive Mendel symptom is determined
Clinical manifestations of PU are diverse, a typical picture is not always observed, which greatly complicates the diagnosis. Yes, in children early age the disease is often atypical. Moreover, the younger the child, the less specific the complaints. At an older age, the symptoms of duodenal ulcer are similar to those in adults, although they may be more blurred. Often there is no characteristic ulcerative anamnesis, which is partly due to the fact that children quickly forget the pains, do not know how to differentiate them, cannot indicate their localization and the cause that caused them.
The increase in the number of atypical forms of the disease, the lack of alertness in the formation of the ulcerative process, especially in children with aggravated heredity for the pathology of APTO, contributes to an increase in the percentage of patients with late diagnosis of PU. This leads to a more frequent recurrence of the disease in this category of patients and the early formation of its complications, leading to a decrease in the quality of life of children with PU.

Examination plan for gastric and duodenal ulcers:

History and physical examination.
Mandatory laboratory tests
 general analysis blood;
 General analysis of urine;
 general analysis of feces;
 analysis of feces for occult blood;
levels of total protein, albumin, cholesterol, glucose, serum iron in blood;
 blood type and Rh factor;

Mandatory instrumental research
 FEGDS. When the ulcer is localized in the stomach - taking 4-6 biopsies from the bottom and edges of the ulcer with their histological examination in order to exclude cancer (more often in adults);
 Ultrasound of the liver, pancreas, gallbladder.
 determination of Helicobacter pylori infection by endoscopic urease test, morphological method, enzyme immunoassay or breath test;
Additional laboratory tests
 determination of the level of serum gastrin.

Additional instrumental studies (according to indications)
 intragastric pH-metry;
 endoscopic ultrasonography;
 x-ray examination of the stomach;
 computed tomography.

Laboratory examination
There are no laboratory signs pathognomonic for peptic ulcer disease. Studies should be carried out in order to exclude complications, primarily ulcerative bleeding - a complete blood count and a fecal occult blood test.
Instrumental diagnosis of gastric and duodenal ulcers
 FEGDS allows you to reliably diagnose and characterize the ulcer. Additionally, FEGDS allows you to control its healing, conduct a cytological and histological assessment of the morphological structure of the gastric mucosa, and exclude the malignant nature of ulceration.
Endoscopic picture of the stages of ulcerative lesions:
Aggravation phase:
Stage I - acute ulcer. Against the background of pronounced inflammatory changes in the gastric mucosa and duodenum, a defect (defects) of a rounded shape, surrounded by an inflammatory shaft; pronounced edema. The bottom of the ulcer with a layer of fibrin.
Stage II - the beginning of epithelialization. The hyperemia decreases, the inflammatory shaft is smoothed out, the edges of the defect become uneven, the bottom of the ulcer begins to clear from fibrin, and convergence of the folds to the ulcer is outlined. Phase of incomplete remission:
Stage III - healing of the ulcer. At the site of repair, there are remnants of granulations, red scars of various shapes, with or without deformation. Signs of gastroduodenitis activity persist.
Remission:
Complete epithelialization of the ulcerative defect (or "calm" scar), there are no signs of concomitant gastroduodenitis.
 Contrast x-ray examination of the upper gastrointestinal tract also reveals an ulcer, however, in terms of sensitivity and specificity X-ray method inferior to endoscopic.
 Intragastric pH-metry. In case of peptic ulcer, an increased or preserved acid-forming function of the stomach is most often found.
 Ultrasound of organs abdominal cavity to rule out comorbidities.

Detection of Helicobacter pylori

Invasive diagnostics:
 Cytological method - staining of bacteria in smears-imprints of biopsy specimens of the gastric mucosa according to Romanovsky-Giemsa and Gram (currently considered insufficiently informative).
 Histological method - sections are stained according to Romanovsky-Giemsa, Wartin-Starry, etc. This is the most objective method for diagnosing H. pylori, as it allows not only to detect bacteria, but also to determine their location on the mucous membrane, the degree of contamination, to assess the nature of the pathological process
 Bacteriological method - determination of a strain of a microorganism, identification of its sensitivity to the drugs used, is little used in routine clinical practice.
 Immunohistochemical method using monoclonal antibodies: more sensitive because the antibodies used selectively stain H. pylori. Little used in routine clinical practice for the diagnosis of H. pylori.
 Biochemical method (rapid urease test) - the presence of bacteria in the biopsy specimen is confirmed by a change in the color of the medium, which reacts to the decomposition of urea by urease secreted by H. pylori.
 Detection of H.pylori in the mucous membrane of the stomach and duodenum by polymerase chain reaction. This method has the highest specificity.
Non-invasive diagnostics:
 Serological methods: detection of antibodies to H. pylori in blood serum. The method is most informative when conducting epidemiological studies. The clinical application of the test is limited by the fact that it does not allow to differentiate the fact of infection in history from the presence of H. pylori at the moment and to control the effectiveness of eradication. Not all serological tests are equal. Due to the variability in the accuracy of different commercial tests, only validated IgG serological tests should be used (level of evidence: 1b, grade of recommendation: B). Validated serological examination can be used to guide decisions about antimicrobial and antisecretory drugs, for ulcer bleeding, atrophy, and gastric tumors (level of evidence: 1b, grade of recommendation: B, expert opinion(5D).
 Urease breath test (URT) - determination of elevated ammonia concentration in the exhaled air of a patient after oral urea loading as a result of the metabolic activity of H. pylori.
 Isotope urease breath test - determination in the exhaled air of a patient of CO2 labeled with the isotope 14C or 13C, which is released under the action of H. pylori urease as a result of the splitting of labeled urea in the stomach. Allows you to effectively diagnose the result of eradication therapy.
 Determination of H. pylori antigen in feces using monoclonal antibodies. The diagnostic accuracy of the antigen stool test is equal to that of the urease breath test when validated first by a monoclonal laboratory test (LE: 1a; Grade of recommendation: A).
In patients treated with inhibitors proton pump(PPI): 1) If possible, PPIs should be suspended for 2 weeks before testing by bacteriological, histological methods, rapid urease test, UDT, or detection of H. pylori in feces (level of evidence: 1b, grade of recommendation: A);
2) If this is not possible, a validated serological diagnosis(level of evidence: 2b, grade of recommendation: B).
In pediatric practice, preference should be given to non-invasive methods for detecting H. pylori.

DIFFERENTIAL DIAGNOSIS
Peptic ulcer must be differentiated from symptomatic ulcers, the pathogenesis of which is associated with certain background diseases or specific etiological factors (Table 3). The clinical picture of exacerbation of these ulcers is erased, there is no seasonality and periodicity of the disease.
Gastric and duodenal ulcers in Crohn's disease, sometimes also referred to as symptomatic gastroduodenal ulcers, are an independent form of Crohn's disease affecting the stomach and duodenum.
Differential diagnosis of peptic ulcer with functional disorders gastrointestinal tract, chronic gastroduodenitis, chronic diseases liver, biliary tract and pancreas is carried out according to the anamnesis, examination, the results of laboratory, endoscopic, x-ray and ultrasound studies.

TREATMENT

Goals of therapy:
 H. pylori eradication (if available).
 Healing of the ulcer and rapid elimination of the symptoms of the disease.
 Achievement of stable remission.
 Prevention of development of complications.

Non-drug treatment
1. Mode of physical activity. Protective mode with limitation of physical and emotional stress.
2. Diet.
Therapeutic nutrition of children with PU is aimed at reducing the effect of aggressive factors, mobilizing protective factors, and normalizing gastric and duodenal motility.
In the acute phase or in case of recurrence of peptic ulcer, diet No. 1 is prescribed, or a variant of the diet with mechanical and chemical sparing (according to the new nomenclature of diets). initially wiped version, as the condition improves - not wiped version. Highly effective modern antisecretory therapy made it possible to abandon the previously used physiologically unbalanced diets 1a, 1b.
Products that irritate the gastric mucosa and stimulate the secretion of hydrochloric acid are excluded: strong meat and fish broths, fried and spicy foods, smoked meats and canned food, seasonings and spices (onion, garlic, pepper, mustard), pickles and marinades, nuts, mushrooms, refractory animal fats, vegetables, fruits and berries without prior heat treatment, fermented milk and carbonated drinks, coffee, cocoa, chocolate, citrus fruits.
Products with pronounced buffering properties are recommended: meat and fish (boiled or steamed), steam omelet, milk, unleavened mashed cottage cheese. The diet includes soups based on vegetables and cereals, milk porridges (except for millet and barley), vegetables (potatoes, carrots, zucchini, cauliflower) boiled or in the form of mashed potatoes and steam soufflés; baked apples, mousses, jelly, jelly from sweet varieties of berries, weak tea with milk. Pasta, dried wheat bread, dry biscuit and dry cookies are also allowed. Dishes are served warm, a fractional diet is used, 5-6 times a day. Food is taken in a calm atmosphere, sitting, slowly, chewed thoroughly. This contributes to better impregnation of food with saliva, the buffering capabilities of which are quite pronounced.
The energy value of the diet should correspond to the physiological needs of the child. In order to influence the reparative processes, enhance the cytomucoprotection of the gastric mucosa, it is recommended to increase the quota of protein with a high biological value in the diet. It is advisable to supplement the diet with enteral nutrition - normocaloric or hypercaloric mixtures based on cow's milk proteins.
Diet #1 is recommended for 2-3 weeks, then the food ration is gradually expanded to match Diet #15 (or the main variant of the standard diet).

Medical treatment

Peptic ulcer of the stomach and duodenum associated with H. pylori Eradication therapy is shown.
According to the latest recommendations of the Maastricht Agreement IV (2010, Table 4, Table 5), ESPGHAN and NASPGHAN (2011), standard triple therapy:
PPI (esomeprazole, rabeprazole, omeprazole) 1-2 mg/kg/day + amoxicillin 50 mg/kg/day + clarithromycin 20 mg/kg/day
or
PPI + clarithromycin + metronidazole 20 mg/kg/day.
The duration of therapy is 10-14 days.
In order to increase the acceptability of therapy, it is possible to use the so-called. a "sequential" regimen where PPIs are given for 14 days and antibiotics are given consecutively for 7 days each.
Standard second-line quadruple therapy with bismuth: PPI + metronidazole + tetracycline + bismuth subcitrate 8 mg / kg / day - 7-14 days - is not used in children in Russia.
With the ineffectiveness of eradication therapy, an individual selection of the drug is carried out based on the sensitivity of H. pylori to antibacterial drugs - third-line therapy.
To assess the effectiveness of anti-Helicobacter therapy, standard non-invasive tests are used. Eradication efficiency control is determined after at least 6 weeks. after the end of treatment with tetracycline in children, according to the recommendations of Russian experts, the following schemes are used in children:
First line therapy.
 PPI + amoxicillin + clarithromycin
 PPI + amoxicillin or clarithromycin + nifuratel (30 mg/kg/day)
 PPI + amoxicillin + josamycin (50 mg/kg/day, not more than 2g/day).
It is possible to use a "serial" scheme.
 Quadrotherapy is used as second-line therapy:
 bismuth subcitrate + PPI + amoxicillin + clarithromycin
 bismuth subcitrate + PPI + amoxicillin or clarithromycin + nifuratel. The duration of treatment is 10-14 days.
In order to overcome the resistance of H. pylori to clarithromycin and reduce side effects from the application antibacterial drugs a scheme with sequential prescription of antibiotics is used: PPI + bismuth subcitrate + amoxicillin - 5 days, then PPI + bismuth subcitrate + josamycin - 5 days. For the prevention and treatment of antibiotic-associated diarrhea, along with eradication therapy, it is recommended to prescribe probiotic preparations (Saccharomyces boulardii 250 mg 2 times a day). in children.
Peptic ulcer not associated with H. pylori In case of peptic ulcer not associated with H. pylori. pylori, the aim of treatment is to stop clinical symptoms disease and ulcer scarring. In this regard, the appointment of antisecretory drugs is indicated.
Currently, the drugs of choice are proton pump inhibitors: esomeprazole, omeprazole, rabeprazole, which are prescribed at a dose of 1-2 mg/kg/day. The duration of the PPI course is 4 weeks for DU, 8 weeks for DU.
H2-blockers have lost their position and are now rarely used, mainly when it is impossible to use PPIs or in combination with them in order to enhance the antisecretory effect.
Antacids(aluminum hydroxide or phosphate, magnesium hydroxide) are used in complex therapy with a symptomatic purpose for the relief of dyspeptic complaints. To enhance cytoprotection, bismuth subcitrate 8 mg/kg/day is prescribed for up to 2-4 weeks. In case of violations of the motility of the gastrointestinal tract, prokinetics, antispasmodics are prescribed according to indications. The effectiveness of treatment for gastric ulcers is controlled by the endoscopic method after 8 weeks, with duodenal ulcers - after 4 weeks.
Further tactics drug therapy: Continuous maintenance therapy with PPI (duration is determined individually) is indicated for:  complications of PU;  the presence of concomitant diseases requiring the use of NSAIDs;  concomitant PU erosive and ulcerative reflux esophagitis. Therapy on demand:
The indication for this therapy is the appearance of symptoms of peptic ulcer after successful eradication of H. pylori. On-demand therapy provides for the appearance of symptoms characteristic of an exacerbation of PU, taking PPIs for 2 weeks. If symptoms persist, conduct FEGDS, examinations, as in an exacerbation.
Surgery
Indications for surgical treatment of gastric ulcer - complications of the disease: ulcer perforation, decompensated cicatricial-ulcerative pyloric stenosis, accompanied by severe evacuation disorders; profuse gastrointestinal bleeding that cannot be stopped by conservative methods, including the use of endoscopic hemostasis. When choosing a method surgical treatment preference is given to organ-preserving operations.
MANAGEMENT OF CHILDREN WITH ULCER
Indications for hospitalization:
 YAB with clinical picture pronounced exacerbation (pronounced pain syndrome).
 Signs of complications of PU.
 PU with a history of complications.
 PU with concomitant diseases.
 Detection of ulcers in the stomach, requiring differential diagnosis between benign ulcers and gastric cancer.
Children with exacerbation of peptic ulcer are treated in a pediatric or gastroenterological department.
The length of stay in the hospital averages 14-21 days at the debut and recurrence of peptic ulcer.
Children with uncomplicated peptic ulcer disease are subject to conservative treatment in outpatient settings.
Children in remission are observed on an outpatient basis (Table 7).
Deregistration is possible with complete remission within 5 years