Differential diagnosis and Differential diagnosis with functional gastric lesions

treatment of gastric dyspepsia
syndrome.
 
lead biliary apparatus, acute and chronic exogenous dyspepsia and gastric
dyspepsia. Modern methods of laboratory and instrumental examinations
and treatment of chronic gastritis. Early diagnosis of gastric
cancer. Algorithms for examination of patients with suspected peptic
ulcer. Methods for diagnosing the presence of Helicobacter
pylori. Modern aspects of peptic ulcer treatment.

Definition of dyspepsia

The concept of dyspepsia (from Greek. "dys" – bad and "pepsis" - digestion) includes many subjective
symptoms that accompany a digestive disorder. Russian gastroenterologists traditionally consider dyspepsia
in a broad sense, i.e. as manifestations of diseases of the esophagus, stomach and intestines. These include:
abdominal pain, epigastric discomfort (heaviness, fullness, early satiety), excessive gas formation in the
intestines, heartburn, belching, dysphagia, nausea, vomiting, diarrhea, constipation, loss of
appetite. Dyspepsia is divided into functional and organic. Functional dyspepsia (with the presence of
characteristic complaints) with a thorough examination of patients is not accompanied by organic changes in
the organs of the gastrointestinal tract (GIT). Organic dyspepsia is associated with a serious organic disease
of the digestive tract. Manifestations of dyspepsia can be associated with food intake, or not depend on
it. Currently, foreign researchers define dyspepsia as chronic or recurrent pain or unpleasant sensations in
the upper abdomen. Unpleasant sensations mean subjective discomfort, but not pain, and may include: a
wide variety of symptoms, such as rapid satiety, bloating, a feeling of fullness in the epigastrium and
nausea. Apart from dyspepsia, foreign authors distinguish heartburn and acid belching, which are
manifestations of gastroesophageal reflux disease. Symptoms associated with intestinal pathology (diarrhea,
constipation, flatulence), according to foreign authors, do not fall under the term "dyspepsia". From our
point of view, it is advisable to divide dyspepsia into esophageal, gastric and intestinal. This facilitates the
differential diagnosis of diseases. Next, we will separately consider the manifestations of esophageal and
gastric dyspepsia and the clinical approach to patients with these manifestations.

Clinical assessment of patients with esophageal dyspepsia

Esophageal dyspepsia is characterized by dysphagia, heartburn, and belching. These symptoms can be

combined with individual diseases of the esophagus, but they can also occur independently of each other.

Dysphagia - this is the feeling of an obstacle to the normal passage of ingested food. Dysphagia is
considered as difficulty at the beginning of swallowing (oropharyngeal dysphagia), or as a feeling of
obstruction to the passage of food or liquid from the mouth to the stomach (esophageal dysphagia).

Dysphagia should be distinguished from other symptoms associated with swallowing. Aphagia means a

complete blockage of the esophagus, which is usually caused by a food lump stuck in the esophagus and
requires urgent medical intervention. Difficulty in trying to start swallowing occurs when the forced phase
of swallowing is disrupted. However, once started, the act of swallowing is completed
normally. Odynophagia means painful swallowing. Often, odynophagia and dysphagia develop
simultaneously. Odynophagia often indicates dysphagia in achalasia, diffuse esophageal spasm, and
esophagitis. Globus hystericus - this is the seeming sensation of a lump stuck in the throat. However, in the
actual implementation of the act of swallowing, there are no difficulties. Phagophobia means fear of
swallowing, and in cases of hysteria, rabies, tetanus and paralysis of the pharynx, refusal to swallow may
occur due to fear of aspiration. Painful inflammatory disorders that cause odynophagia can also lead to
refusal to swallow. Some patients may feel the process of food passing down the esophagus. However, this
sensitivity of the esophagus is not associated with food getting stuck in the esophagus or with its
blockage. Dysphagia should not be confused with the feeling of fullness in the epigastric region that occurs
after eating or after swallowing air.

Heartburn – this is a feeling of heat or burning, localized behind the sternum or in the upper part of the
epigastric region, with radiation to the neck, and sometimes in the forearm. Intermittent heartburn is also
common in healthy people, but frequent and severe heartburn is usually a manifestation of esophageal
dysfunction. Heartburn can be the result of impaired motor activity or stretching of the esophagus, throwing
acid or bile into the esophagus, or direct irritation of the esophageal mucosa (esophagitis). Heartburn is most
often associated with gastroesophageal reflux. In this case, heartburn develops after a heavy meal, when
bending or bending the body, or when the patient is lying on his back. It can be accompanied by the
spontaneous appearance of a liquid in the mouth, which can be salty ("sour belching"), sour (stomach
contents) or bitter, having a green or yellow color (bile). Heartburn can occur after consuming certain foods
(such as citrus juices) or medications (such as alcohol and acetylsalicylic acid). Usually, heartburn can be
alleviated immediately (at least temporarily) by taking antacids.

Heartburn can also occur in the absence of visible pathological conditions or disorders of motor function. In
this case, it is often accompanied by aerophagia, which may reflect the patient's attempt to relieve the feeling
of discomfort, and it is often attributed to psychological factors for lack of another explanation.

Burp – this is an involuntary sudden release of gases through the mouth from the stomach or esophagus,
sometimes with an admixture of a small amount of stomach contents, not accompanied by nausea and
vomiting. Belching can accompany heartburn.

Often in patients who complain of chronic, repeated burping, each act of regurgitation is preceded by
swallowing air, a large volume of which passes only part of the way down the esophagus, and then
regurgitates. Thus, an excessively intense belch occurs as a result of aerophagies (ingestion of air), and not
because of increased gas formation in the stomach or in the intestines. There is also a slight degree of
aerophagia in healthy people, but some people swallow excessive amounts of air due to a chronic state of
anxiety, rapid absorption of food, consumption of carbonated drinks, chewing gum, leakage of secretions
into the nasopharynx, or because of poorly fitted dentures. Because the belching that follows aerophagy can
give the patient a temporary sense of relief, a vicious cycle of swallowing air can develop, followed by
belching.

Diagnostic algorithm for dysphagia

The conclusion about the location of dysphagia should be made based on the patient's complaints; the lesion
will be located either in the place indicated by the patient's feelings, or below the specified location.

It is equally important to find out after taking what food (solid, liquid, or both) dysphagia occurs, whether it
is constant or intermittent. Determining the duration of symptoms is also important. Although they can often
occur together, it is important to rule out lonophagy (painful swallowing). Finally, differential diagnosis
based on the identification and analysis of symptoms should exclude the presence of Globus hystericus (a
lump in the throat), chest compression, difficulty breathing, and phagophobia (fear of swallowing).

When collecting complaints for dysphagia, it is necessary to find out:

• localization;

• nature of food and / or liquid;

• persistent or intermittent symptoms;

• duration of occurrence of symptoms.

The main question: is the dysphagia oropharyngeal or esophageal? This conclusion can be made with
confidence based on a very thorough examination, which provides an accurate assessment of the type of
dysphagia (oropharyngeal dysphagia compared to esophageal dysphagia occurs in 80-85% of cases).

Oropharyngeal dysphagia It can also be called "high" dysphagia if it is related to the oral cavity or
pharynx.

Patients have difficulty at the beginning of swallowing and they usually point to the cervical region as the
location of this difficulty.

Typical concomitant symptoms:

• difficulty at the beginning of swallowing;

• nasal regurgitation;

• cough;

• nasal speech;

• weakened cough reflex;

• choking attack;

• dysarthria or diplopia (may accompany neurological disorders that cause oropharyngeal dysphagia);

• bad breath may occur in patients with large Cenker diverticula containing residual food masses, as well as
with progressive achalasia or long-term obstruction of the lumen, leading to accumulation of decomposing
food.

An accurate diagnosis can be established after the neurological disorders accompanying oropharyngeal
dysphagia are clarified, these can be:

• hemiparesis caused by a stroke;

• ptosis of the eyelid;

• signs of myasthenia gravis in pregnant women (weakness by the end of the day);

• Parkinson's disease;

• other neurological diseases, including cervical dystonia, cervical hyperostosis, Arnold-Chiari

malformation (displacement of the brain in the caudal direction and pinching it in the large occipital
foramen);

• identification of a specific decrease in the number of brain nerves involved in the regulation of swallowing
can also help to accurately determine the cause of oropharyngeal disorders when making a diagnosis.

Esophageal dysphagia It can be called "lower" dysphagia, since it is mainly localized in the distal
esophagus, although it should be noted that some patients with esophageal dysphagia, such as achalasia, may
complain of difficulty swallowing in the cervical esophagus, which mimics oropharyngeal dysphagia. If
more than 2 seconds pass from the beginning of pharynx to signs of dysphagia, then this usually indicates
esophageal dysfunction.

The type of food consumed that causes dysphagia provides useful information. Difficulties that arise when
eating only solid food indicate the presence of mechanical dysphagia, in which the lumen is not narrowed so
much. A stuck food lump can be pushed through the narrowed area by drinking some liquid. With a
pronounced decrease in the lumen, dysphagia develops when eating both solid and liquid food. In contrast,
respiratory dysphagia caused by achalasia and diffuse esophageal spasm is equally affected by the use of
both solid and liquid food from the very beginning of the disease. Patients with scleroderma are susceptible
to developing dysphagia when eating solid food that is not related to the body position, while when eating
liquid food, dysphagia is observed in them in the supine position, but is absent when the body is upright. In
case of development of peptic strictures in such patients, dysphagia becomes more persistent.

Short-term transient dysphagia can be caused by any inflammatory processes. Progressive dysphagia over a
period of several weeks to several months suggests the presence of esophageal cancer. Episodic dysphagia
with solid food intake, which occurs for several years, indicates a benign disease and is characteristic of the
lower esophageal ring.

Establishing the location of dysphagia is of diagnostic value when it is described as tightness in the chest
area, where the location of dysphagia usually correlates with the location of esophageal
obstruction. However, the localization of dysphagia felt by the patient in the neck area has no diagnostic
value, since lesions of the pharynx, cervical esophagus, and even lower - lying areas of the esophagus can
cause dysphagia felt in the neck.

Concomitant symptoms have important diagnostic significance. Nasal regurgitation and tracheobronchial

aspiration during swallowing are signs of paralysis of the pharyngeal muscles or the presence of a
tracheoesophageal fistula. Non-swallowing tracheobronchial aspiration may be secondary in the presence of
achalasia, Cenker's diverticulum, or gastro-esophageal reflux. A pronounced decrease in body weight, not
proportional to the severity of dysphagia, is very characteristic of esophageal cancer. If dysphagia is
preceded by hoarseness, the primary lesion is usually localized in the larynx. Hoarseness that occurs after
the development of dysphagia, it may indicate involvement of the laryngeal recurrent nerve through the
spread of esophageal cancer beyond the walls of the esophagus. Sometimes hoarseness can be caused by
laryngitis, secondary to gastro-esophageal reflux. The combination of symptoms of laryngeal damage with
dysphagia is also observed in various neuromuscular disorders. Hiccups suggest a lesion of the distal
esophagus. Unilateral wheezing, combined with dysphagia, indicates a mediastinal process affecting the
esophagus and large bronchus. Chest pain the disease associated with dysphagia develops with diffuse
esophageal spasm and associated motor disorders. Chest pain, similar to the pain experienced with diffuse
esophageal spasms, can also occur in acute aphagia caused by too large a food lump. The presence in the
anamnesis of long-term heartburn and reflux preceding dysphagia indicates a peptic stricture. Similarly, a
history of prolonged nasogastric intubation, ingestion of caustic substances, previous radiation therapy, or
concomitant mucocutaneous diseases may indicate the cause of esophageal stricture. If the patient has
odynophagia, it should be assumed that he has candida or herpetic esophagitis, especially in weakened
cancer patients or in patients receiving immunosuppressive therapy.

Physical examination is important for motor dysphagia caused by skeletal muscle damage, neurological
diseases and diseases of the oropharynx. Carefully check for signs of bulbar or pseudobulbar paralysis, such
as dysarthria, dysphonia, ptosis, tongue atrophy, and overactive jaw muscle contractions, in addition to signs
of generalized neuromuscular disease. It is necessary to examine the neck area to make sure that there is no
enlargement of the thyroid gland or spinal disorders. Thorough examination the oral and pharyngeal cavity
should identify lesions that may prevent further passage of food from the mouth or esophagus due to pain or
obstruction. Changes in the skin or limbs may suggest a diagnosis of scleroderma and other collagen
diseases, or mucocutaneous diseases such as pemphigus or congenital epidermolysis bullosa, which can
cause damage to the esophagus. In addition, some patients with scleroderma and secondary peptic strictures
may have CREST syndrome (calcification, Raynaud's disease, esophageal motility disorders, sclerodactyly,
telangiectasia). There may be signs of metastatic damage to the lymph nodes and liver, as well as pulmonary
complications due to acute aspiration pneumonia or chronic aspiration of stomach contents.

Causes of esophageal dysphagia

Mucosal damage:

• gastroesophageal reflux disease (peptic stricture);

• esophageal rings and tissues (sideropenic dysphagia or Plummer-Vinson syndrome);

• esophageal tumors;

• caustic lesions of the esophagus (alkali ingestion, medicinal esophagitis, sclerotherapy of varicose veins);

• radiation damage;

• infectious esophagitis (candidiasis, herpes, cytomegalovirus).

Mediastinal diseases:

• tumors (including lung cancer, lymphoma);

• infections (including tuberculosis, histoplasmosis);

• cardiovascular diseases (left atrial dilatation, aortic aneurysm).

Diseases affecting the smooth muscles of the esophagus and its innervation:

• achalasia of the cardia;

• scleroderma;

• other motor disorders;

• condition after surgical operations (after fundoplication, antireflux operations, implantation of mechanical
devices).

The combination of progressive dysphagia when taking solid food and heartburn indicates the presence of
peptic stricture of the esophagus, and the combination of progressive dysphagia when taking liquid and solid
food with heartburn characterizes progressive systemic sclerosis (scleroderma). Foreign bodies in the
esophageal lumen usually cause acute dysphagia.

Symptoms of anxiety in esophageal and gastric dyspepsia

In addition to being over 50 years old, unexplained weight loss, anorexia, rapid satiety, vomiting,
progressive dysphagia, pain when swallowing, bleeding, anemia, jaundice, bulky formations in the
abdominal cavity, enlarged lymph nodes, cancer of the upper extremities are traditionally considered to be
alarming symptoms that indicate a possible serious disease, primarily a malignant neoplasm. GIT
departments in the next of kin, as well as data on past peptic ulcer disease, gastric surgery, or stomach
malignancies. In young patients in the absence of anxiety disorders malignancies of the upper
gastrointestinal tract are rare, but the predictive value of detecting alarming symptoms remains extremely
low. If the symptoms of dyspepsia have been observed for a long time, a malignant neoplasm is unlikely, but
what time period is meant when it comes to the prescription of symptoms, the literature does not
specify. Antisecretory therapy can mask a malignant tumor during esophagogastroduodenoscopy (EGDS),
but it does not affect the outcome of the disease. Although alarming symptoms do not always indicate a
serious illness, patients younger than 50 years of age with malignant neoplasms of the upper gastrointestinal
tract rarely do not have such symptoms. Alarming symptoms, and in patients over 50 years of age-any new
symptoms of dyspepsia, are indications for urgent EGDS to exclude a malignant tumor.

Instrumental diagnosis of esophageal dysphagia

The main task in the case of esophageal dysphagia is to exclude the malignant process.

Signs of malignancy of the process:

• the duration of the disease is short (less than 4 months);

• the disease is progressing;

• dysphagia is more pronounced when taking solid rather than liquid food.;

• there is weight loss.

The presence of the following signs indicates achalasia:

• dysphagia occurs after both solid and liquid food intake;

• the problem has existed for many years;

• no weight loss.

There are some disagreements regarding the choice of diagnostic tests, which relate to the choice of the
primary examination method – either endoscopy or barium ingestion.

Barium-contrast esophagogram

Barium esophagogram is performed in the supine position on the right side and allows you to identify
irregularities in the lumen of the esophagus and identify areas of obstruction, places of tissue damage and
rings. Barium testing of the oropharynx and esophagus during ingestion is the most appropriate initial test; it
may be useful for detecting achalasia and diffuse esophageal spasm, although this pathology can be more
accurately diagnosed by manometry. Such a study can be carried out using a barium tablet, which allows
you to identify even minor strictures. Examination of the esophagus after ingesting a barium tablet may also
be useful in patients with dysphagia in cases where the endoscopy results were negative.

Esophagogastroduodenoscopy  It is performed using a fibrooptic endoscope passed through the mouth into
the stomach with detailed visualization of the upper gastrointestinal tract. The process of introducing an
endoscope into the stomach cavity is very important to exclude pseudoachalasia associated with a tumor of
the esophageal-gastric junction.

Esophageal manometry

This diagnostic method is less accessible than contrast/barium X-ray and endoscopy, but may be useful in
some cases. The method is based on measuring the pressure in the lumen of the esophagus using solid or
hydraulic measuring equipment.
Manometry is indicated for use in cases where it is assumed that the cause of esophageal dysphagia cannot
be detected either by X-ray examination or by endoscopy, and adequate anti-reflux therapy has been
performed (with the treatment of esophagitis, which is detected during endoscopy).

The three main causes of dysphagia that can be detected by manometry are: achalasia of the cardia,
scleroderma (ineffective peristalsis of the esophagus) and esophageal spasm.

Esophageal radionuclide scintigraphy

The patient swallows a liquid containing a radioactive label (for example, water mixed with Tc).99 and
colloidal sulfur) and then the radioactivity of the esophagus is measured. In patients with esophageal
contractility disorders, a slow release of the radioactive label from the esophagus is typical. This technique
was originally used for research purposes, but is now beginning to be used for clinical purposes in some
specialized institutes.

Diagnosis and treatment of diseases manifested by esophageal dyspepsia

In clinical practice, esophageal dyspepsia is most often found in gastroesophageal reflux disease, achalasia
of the cardia and esophageal cancer.

Gastroesophageal reflux disease and Barrett's esophagus

Gastroesophageal reflux disease (GERD) is a disease that manifests itself as a complex of characteristic
symptoms with the presence of inflammatory changes in the distal part of the esophagus, resulting from
repeated throwing of gastric and/or duodenal contents into the esophagus, or the presence of gastro-
esophageal reflux without concomitant inflammation of the esophagus.

Erosive gastroesophageal reflux disease is a type of reflux esophagitis (RE) that is accompanied by the
appearance of erosions on the surface of the esophageal mucosa.

Non-erosive gastroesophageal reflux disease (GERD) is characterized by the presence of reflux with or
without endoscopic manifestations of catarrhal RE. In non-erosive reflux disease, the diagnosis is
established on the basis of a typical clinical picture, taking into account data obtained with additional
research methods (pH-metric, X-ray, manometric). In the general population of patients with GERD,
individuals with NERD account for more than 60%. The severity of clinical symptoms and decreased quality
of life in patients with GERD are comparable to those in patients with erosive GERD.

Epidemiology

The prevalence of GERD among the adult population of Russia is up to 40-60%. In Western Europe and the
USA – up to 40%. The incidence of severe esophagitis in the general population is 5 cases per 100,000
population per year. The prevalence of Barrett's esophagus among individuals with esophagitis is close to
8%, with variations ranging from 5 to 30%. The presence of Barrett's esophagus increases the risk of
subsequent development of esophageal adenocarcinoma tenfold.

The formation of esophageal strictures was noted in 7-23% of patients with erosive-ulcerative esophagitis,
the occurrence of bleeding – in 2% of patients. Erosions and ulcers of the esophagus were the cause of
gastrointestinal bleeding in 21% of cases among people over 80 years of age, and in 25% of cases among
patients in intensive care units who underwent surgery.

Pathogenesis
The main pathogenetic factors for the development of clinical symptoms and morphological manifestations
of GERD are hydrochloric acid of the stomach and insufficiency of the lower esophageal sphincter. GERD
develops as a result of:

1) decrease in the function of the anti-reflux barrier, which can occur in three ways:: a) due to a primary
decrease in pressure in the lower esophageal sphincter; b) as a result of an increase in the number of
episodes of its spontaneous relaxation; c) due to its complete or partial destructurization, for example, with a
hernia of the esophageal opening of the diaphragm; d) other causes of insufficiency of the lower esophageal
sphincter: scleroderma, pregnancy, smoking, the use of drugs that reduce smooth muscle tone (nitrates,
calcium channel blockers, beta-adrenergic agents, eufillin), surgery on the sphincter;

2) reduced esophageal clearance: a) chemical – due to a decrease in the neutralizing effect of saliva and
bicarbonates of esophageal mucus; b) volumetric – due to inhibition of secondary peristalsis and a decrease
in the tone of the thoracic esophagus wall;

3) the damaging properties of refluktate (hydrochloric acid, pepsin, bile acids); 4) the inability of the
esophageal mucosa to resist the damaging effect of the thrown contents;

5) disorders of gastric emptying;

6) increased intra-abdominal pressure.

Clinical picture

The main symptoms of GERD are heartburn, belching, regurgitation, painful and difficult passage of
food. The quality of life of patients with GERD, who have clinical symptoms of the disease observed at
night, is particularly significantly reduced.

Heartburn is the most common symptom, occurs in 83 % of patients and occurs due to prolonged contact of
acidic (pH<4) gastric contents with the esophageal mucosa. Typical for this symptom is considered to
increase with errors in diet, alcohol intake, carbonated drinks, physical exertion, inclinations and in a
horizontal position. Belching, as one of the leading symptoms of GERD, is quite common and is found in
52% of patients. Belching, as a rule, increases after eating, taking carbonated drinks.

Regurgitation of food, which is observed in some GERD patients, increases with physical exertion and in a
position that promotes regurgitation. Dysphagia and lonophagia occur in 19% of patients with GERD. A
characteristic feature of these symptoms is their intermittent nature. Their occurrence is based on
hypermotor dyskinesia of the esophagus, which violates its peristaltic function, and the cause of
odynophagia can also be erosive and ulcerative lesions of the mucous membrane. The appearance of more
persistent dysphagia and a simultaneous decrease in heartburn may indicate the formation of esophageal
stricture.

One of the most characteristic symptoms of GERD is pain in the epigastric region, which appears in the
projection of the xiphoid process shortly after eating and increases when bending down.

Other symptoms of GERD include a lump in the throat when swallowing, pain in the lower jaw, and burning
of the tongue.

Extraesophageal manifestations of GERD

Among the extraesophageal manifestations of GERD, chest pain, similar to angina, and bronchopulmonary
symptoms are most common. Extraesophageal manifestations are very characteristic for non-erosive forms
of GERD.
Chest pains, including those similar to angina, occur in patients with GERD due to hypermotor dyskinesia of
the esophagus (secondary esophagospasm), which may be caused by a defect in the system of the inhibitory
transmitter – nitric oxide. The trigger point for the occurrence of esophagospasm and, accordingly, pain,
however, is always pathological (i.e. prolonged) gastro-esophageal reflux. In some cases, there is an
increased sensitivity of the receptors of the esophageal mucosa, the so-called "irritated"
esophagus. Abnormal reflux can also lead to cardiac arrhythmias.

Bronchopulmonary and laryngological manifestations of GERD include chronic cough, pneumonia,

bronchial asthma, obstructive pulmonary diseases, dysphonia, and laryngitis. Numerous foreign and
domestic studies have shown an increase in the risk of bronchial asthma, as well as the severity of its course
in patients with GERD. Gastroesophageal reflux is detected in 30-90% of patients with bronchial asthma,
predisposing to its more severe course. The causes of bronchial obstruction in GERD are: 1) vago-vagal
reflex, 2) microaspiration. Bronchopulmonary manifestations may be the only clinical sign of
gastroesophageal reflux and cause insufficient effectiveness of treatment of bronchial asthma. On the
contrary, the inclusion of drugs prescribed for GERD in complex therapy in such cases increases the
effectiveness of treatment of bronchial asthma.

Differential diagnosis

Clinical symptoms of GERD occur when tilted, in a horizontal position, combined with heartburn, belching,
stop when taking antacids, a sip of water.

The association of extraesophageal symptoms of GERD with episodes of pathological reflux can be most
accurately verified by 24-hour intraesophageal pH-metry. This method allows you to establish the presence
of a correlation between the appearance of pain and reflux episodes (symptom index > 50%). If pain
increases during exercise, combined pH and ECG monitoring can be performed (to exclude CHD). An
affordable method of differential diagnosis that has recently appeared can be considered the rabeprazole test,
the essence of which is the disappearance of the corresponding symptoms (heartburn, chest pain or
bronchopulmonary manifestations) within a day after taking 20 mg of rabeprazole. This method is based on
the ability of rabeprazole, unlike other PPIs, to stop the symptoms of GERD within the first 24 hours after
the start of use.

Complications

Complications of GERD include esophageal strictures, bleeding from esophageal ulcers, and Barrett's
esophagus. Strictures require further expensive surgical and endoscopic (and often repeated) procedures
(augmentation, surgical treatment, etc.). Bleeding caused by erosive and ulcerative lesions of the esophagus
can complicate the course of cirrhosis of the liver, and is also observed in patients who have undergone
surgery, and elderly patients. Among people over 80 years of age with gastrointestinal bleeding, erosions
and ulcers of the esophagus cause them in 20% of cases, and among patients in intensive care units who
have undergone surgery-in 25%.

Barrett's esophagus – this is a disease characterized by the replacement of the squamous epithelium of the
esophagus, normally lining its distal part, with a metaplastic cylindrical one. The name of the disease is
ironic and is given by the name of an English surgeon who claimed in his work that the esophagus cannot be
lined with cylindrical epithelium. Barrett's esophagus is pathogenetically closely associated with gastro-
esophageal reflux, as well as with esophageal adenocarcinoma and esophago-gastric junction. In Barrett's
esophagus, esophageal cancer is 40 times more common than in the rest of the population. Exposure of
hydrochloric acid in the esophagus, with On the one hand, it increases the activity of protein kinases that
initiate the mitogenic activity of cells and, accordingly, their proliferation, and, on the other hand, inhibits
apoptosis in the affected areas of the esophagus. Esophageal adenocarcinoma has a low 5-year survival rate,
not exceeding 11%. Survival of patients depends on the stage of the disease, and one of the unfavorable
characteristics of esophageal adenocarcinoma should be considered early germination of the walls of the
organ and metastasis, which can occur long before the first clinical symptoms appear. Approximately 95%
of cases of esophageal adenocarcinoma are diagnosed in patients with Barrett's esophagus. Therefore, the
main role in the prevention and early diagnosis of esophageal cancer is played by the diagnosis and effective
treatment of Barrett's esophagus. After the use of proton pump inhibitors (PPIs) in patients with Barrett's
esophagus, a decrease in the level of proliferation markers is noted, which is absent in those patients with
persistent pathological acid reflux (pH<4). Proliferation activity also increases in those patients who use H
antagonists.2- histamine receptors (drugs that have much lower antisecretory activity compared to PPIs). In
turn, long-term use of PPIs leads to partial regression of a limited area of intestinal metaplasia.

Among the risk factors for developing complications of GERD, the most important are the frequency and
duration of symptoms, in particular, heartburn, the severity of erosive esophagitis, the presence of a hiatal
hernia, and obesity with a body mass index of more than 30.

Rapidly progressing dysphagia and weight loss may indicate the development of esophageal
adenocarcinoma, but these symptoms occur only in the late stages of the disease, so clinical diagnosis of
esophageal cancer is usually delayed. Therefore, prevention and early diagnosis of esophageal cancer
require timely detection and adequate treatment of Barrett's esophagus.

Instrumental diagnostics

Endoscopic examination and classification of reflux esophagitis (RE)

Endoscopic examination may show signs of RE of varying severity: hyperemia and looseness of the
esophageal mucosa (catarrhal esophagitis, which belongs to the non-erosive form of GERD), erosion and
ulcers (erosive esophagitis of varying severity-from the 1st to the 4th stage-depending on the area of the
lesion), the presence of exudate, fibrin or signs of bleeding. In addition, prolapse of the gastric mucosa into
the esophagus may occur, especially with vomiting movements, true shortening of the esophagus with the
location of the esophageal-gastric junction significantly higher than the diaphragm, throwing gastric or
duodenal contents into the esophagus. It is rather difficult to assess the closing function of the cardia during
esophagoscopy, since the cardia can be slightly opened reflexively in response to the introduction of an
endoscope and air insufflation.

According to the Los Angeles classification, 4 degrees of RE are distinguished endoscopically:

Grade A – one (or more) mucosal lesion (erosion or ulceration) with a length of less than 5 mm, limited to
the limits of the mucosal fold;

Grade B – one (or more) mucosal lesion with a length of more than 5 mm, limited to the limits of the
mucosal fold;

Grade C - the mucosal lesion extends to 2 or more folds of the mucosa, but occupies less than 75% of the
circumference of the esophagus;

Grade D - mucosal damage extends to 75% or more of the circumference of the esophagus.

When making a diagnosis of GERD, the severity of reflux esophagitis (RE) is determined by the Savary-
Miller classification, which provides for the allocation of 4 (sometimes 5) degrees of severity of the disease:

 RE of the first degree of severity - endoscopically isolated erosions that occupy less than 10% of the
surface of the mucosa of the distal esophagus;

 RE of the second degree of severity - erosions become draining and already capture 50% of the
surface of the mucous membrane of the distal esophagus;

 RE of the third degree of severity is characterized by the presence of circularly located drain erosions
that occupy almost the entire surface of the mucosa of the distal esophagus;
  RE of the IV degree of severity – the formation of peptic ulcers and strictures of the esophagus, as
well as the development of cylindrical metaplasia of the esophageal mucosa (Barrett's esophagus).

Some authors consider the last complication as V degree of severity of RE.

In many cases, the clinical symptoms of the disease are not accompanied by endoscopic and morphological
changes characteristic of erosive esophagitis (non-erosive form of the disease, NERD).

In case of torpid course of the disease (absence of clinical and endoscopic remission within 8 weeks of
standard adequate therapy), as well as the presence of complications of the disease (strictures, Barrett's
esophagus), it is necessary to conduct an examination in a specialized hospital or gastroenterological clinic,
including in outpatient departments of these institutions. If necessary, patients should undergo: histological
examination of esophageal mucosal biopsies to exclude Barrett's esophagus and adenocarcinoma,
esophageal manometry, pH-metric and X-ray studies.

Histological examination

More often, epithelial atrophy and thinning of the epithelial layer are detected, but occasionally, along with
atrophy, areas of epithelial layer hypertrophy can be detected. The stratification of the epithelium is
sometimes disturbed, while epithelial cells (epithelial cells) are in a state of dystrophy of varying degrees. In
some cases, dystrophy ends with necrosis of keratinocytes, especially pronounced in the surface layers of the
epithelium. The basement membrane of the epithelium in most cases retains its usual size, but in some
patients it may be thickened and sclerosed.

Along with pronounced dystrophic-necrotic changes in the epithelium, vascular hyperemia is noted, in all
cases the number of papillae is significantly increased. In the thickness of the epithelium and in the
subepithelial layer, focal (usually perivascular), and sometimes diffuse lymphoplasmocytic infiltrates with
an admixture of single eosinophils and polynuclear neutrophils are detected. In a small percentage of cases,
signs of active inflammation are not detected histologically. At the same time, the esophageal mucosa is
marked by an overgrowth of loose, and sometimes dense fibrous connective tissue (sclerosis). Fibroblasts
and destroyed macrophages are often found in the fields of sclerosis. Smooth muscle cells of the mucosal
lamina proper show signs of severe dystrophy or atrophy, and in rare cases a state of coagulation necrosis.

Histological examination may reveal metaplasia of the flat non-keratinizing epithelium of the esophagus,
which leads to the development of cylindrical epithelium with fundal glands (parietal, main and additional
cells in the glands are detected, and the integumentary epithelium forms typical rollers covered with
integumentary-pit epithelium). At the same time, the glands are not numerous, "squeezed" by connective
tissue growths and diffuse lymphoplasmocytic infiltrate.

If metaplasia leads to the development of cylindrical epithelium of the cardiac or fundal type of the gastric
mucosa, then the risk of developing esophageal adenocarcinoma does not increase. However, if metaplasia
leads to the appearance of specialized small intestinal cylindrical epithelium, the risk of malignancy
becomes clear. Specialized cylindrical epithelium is diagnosed as incomplete small bowel metaplasia with
the presence of goblet cells. The morphological substrate of NERD can be considered the expansion of
intercellular spaces in the basal layer of the epithelium of the esophageal mucosa, which is clearly
determined by electron microscopy.

Manometry

The study of the motor function of the esophagus allows you to study the indicators of movement of the
esophageal wall and the activity of its sphincters. In GERD, manometric examination reveals a decrease in
the pressure of the lower esophageal sphincter, the presence of a hiatal hernia, an increase in the number of
transient sphincter relaxes, and a decrease in the amplitude of peristaltic contractions of the esophageal wall.

pH-metric examination of the esophagus

The main method for diagnosing GERD is pH-metry.

The study can be performed both on an outpatient basis and in an inpatient setting. When diagnosing GERD,
the results of pH-metry are evaluated by the total time during which the pH takes values less than 4 units,
the total number of refluxes per day, the number of refluxes lasting more than 5 minutes, and the duration of
the longest reflux.

Daily pH measurement has a very high sensitivity (88-95 %) in the diagnosis of GERD and also helps in the
individual selection of medications.

X-ray examination

X-ray examination of the esophagus can be used for screening diagnosis of GERD and can detect hiatal
hernias (contrast examination is performed in the Trendelenburg position), esophageal strictures, diffuse
esophagospasm, and gastroesophageal reflux.

In the diagnosis of GERD, such methods as bilimetry, scintigraphy, and the Bernstein test can be
used. Bilimetry allows you to verify alkaline (bile) refluxes, scintigraphy reveals violations of the motor-
evacuation function of the esophagus. The Bernstein test consists of injecting 0.1 N HCl solution into the
esophagus, which leads to typical clinical symptoms in GERD. The introduction of chromoendoscopy helps
to detect metaplastic and dysplastic changes in the esophageal epithelium by applying substances to the
mucous membrane that color healthy and affected tissues differently.

Endoscopic ultrasound examination of the esophagus is the main technique for detecting endophytic
growing tumors.

GERD should be included in the differential diagnostic search for patients with chest pain, dysphagia,
gastrointestinal bleeding, or bronchial obstructive syndrome.

Treatment of GERD

Treatment goals: relief of clinical symptoms, healing of erosions, prevention or elimination of

complications, improvement of quality of life, prevention of relapse. Currently, the main principles of
GERD treatment can be considered as follows: the need to prescribe large doses of antisecretory drugs and
conduct long-term basic (at least 4-8 weeks) and maintenance (6-12 months) therapy. If these conditions are
not met, the probability of relapse of the disease is very high. Studies conducted in many countries around
the world have shown that more than 80% of patients who do not receive adequate supportive treatment will
relapse within the next 26 weeks, and within a year the probability of relapse is 90-98%. This implies the
mandatory need for maintenance treatment.

Lifestyle changes should be considered a prerequisite for effective anti-reflux treatment of patients with
GERD. First of all, it is necessary to eliminate smoking and normalize body weight.

You should avoid eating sour fruit juices, foods that increase gas formation, as well as fats, chocolate,
coffee, garlic, onions, peppers, tomatoes. It is necessary to exclude the use of alcohol, very spicy, hot or cold
food and carbonated drinks. Take food often (4-5 times a day), in small portions and chewing thoroughly.

Patients should avoid overeating; they should stop eating at least 3 hours before bedtime. You can not wear
tight belts, work in a slope. Sleep with the head end of the bed raised. Patients should be warned about the
side effects of drugs that reduce the tone of the lower esophageal sphincter (theophylline, progesterone,
antidepressants, nitrates, calcium antagonists), and can also cause inflammation (nonsteroidal anti-
inflammatory drugs, doxycycline, quinidine).

Drug treatment includes well-known groups of drugs. Antacids are effective in treating moderate to rare
symptoms, especially those associated with non-compliance with the recommended lifestyle. Antacids
(almagel, maalox, gastal, rutacid) should be taken frequently (depending on the severity of symptoms),
usually 1.5-2 hours after meals and at night. Antacids, creating a thick foam on the surface of the stomach
contents with each episode of reflux, return to the esophagus, having a therapeutic effect. The effect of
antacids is twofold: first, due to the content of antacids, they have an acid-neutralizing effect, and, secondly,
when they enter the esophagus, they form a protective film that creates a pH gradient between the mucous
membrane and the lumen of the esophagus and protects the mucosa from the aggressive influence of gastric
juice.

Prokinetics restore esophageal motility: they increase the tone of the lower esophageal sphincter, increase
esophageal motility and improve esophageal clearance.

Prokinetic drugs such as domperidone and itopride are considered pathogenetic treatments for GERD, as
they normalize the motor function of the upper digestive tract, restore active gastric motility, and improve
antroduodenal coordination. Prokinetics are prescribed at a dose of 10 mg (domperidone) or 50 ml (itopride)
3 times a day 30 minutes before meals.

Prokinetics are effective only in the complex therapy of erosive esophagitis together with proton pump
inhibitors (PPIs).

In the presence of erosive esophagitis, it is necessary to prescribe PPIs that very effectively control the pH
level in the lower third of the esophagus. Due to a decrease in the time of contact of hydrochloric acid with
the esophageal mucosa, the severity of the symptoms of the disease decreases and they quickly disappear
(within 3 days when omeprazole and esomeprazole are prescribed at a dose of 40 mg and during the first day
when rabeprazole is prescribed at a dose of 20 mg). This powerful inhibition of acid production is the main
factor contributing to the healing of erosive and ulcerative lesions of the esophageal mucosa in patients with
GERD. The use of PPIs should be the means of choice for the treatment of severe esophagitis. The course of
treatment for any of the PPIs should be at least 8 weeks (in the presence of stage 2 or more severe
esophagitis according to the Savary-Miller classification) and at least 4 weeks in the presence of stage 1
esophagitis. In the treatment of NERD, PPIs are used in half a dose (omeprazole group drugs-at a dose of 20
mg, rabeprazole-at a dose of 10 mg), and in the treatment of NERD, it is possible to use PPIs "on demand"
(when symptoms appear).

If heartburn rarely occurs and does not last for a long time, or if there is no history of erosive esophagitis, we
can recommend taking one of the PPIs in the "on-demand" mode, that is, only if complaints occur
(rabeprazole at a dose of 10 mg, omeprazole 20 ml, esomeprazole 10 mg, pantoprazole 20 mg, lansoprazole
30 mg 1-2 times a week, but at least once in 4 weeks). However, if these patients are obese, have a hiatal
hernia, or if heartburn occurs more often than 3 times a week, a constant intake of PPIs (rabeprazole 20 mg,
omeprazole 20 mg, esomeprazole 10-20 mg, pantoprazole 20-40 mg, lansoprazole 30 mg 1 time a day for 4
weeks) should be prescribed.

In the presence of isolated erosions of the esophagus (stage 1), the probability of their healing within 4
weeks of PPI treatment is high. Therefore, the main course in this case can be only 4 weeks (rabeprazole at a
dose of 20 mg 1 time a day, and omeprazole 20 mg, esomeprazole 10-20 mg, pantoprazole 20-40 mg,
lansoprazole 30 mg-2 times a day) with a control endoscopic examination. If multiple erosions of the
esophagus (stages 2-4 of esophagitis) are detected, as well as complications of GERD, the course of
treatment with any drug from the PPI group should be at least 8 weeks, since with this duration of therapy,
90-95% of the effectiveness can be achieved. With a 4-week course of treatment with any PPIs, the healing
rate of multiple esophageal erosions is significantly lower. In addition, such an unjustified reduction in the
duration of treatment of erosive forms of GERD can cause rapid subsequent relapse, as well as the
development of complications.

H Blockers2- histamine receptors (ranitidine, famotidine) can also be used to reduce the acidity of gastric
juice, but they are less effective than PPIs.
When reflux esophagitis is caused by the throwing of bile into the esophagus, ursodeoxycholic acid is
prescribed at a dose of 250 mg / day in combination with prokinetics.

Maintenance therapy after erosion healing should be performed for 16-24 weeks. In this case, both full and
half doses of PPIs can be used. So, after healing of single erosions of the esophagus after a 4-week course,
as well as successful healing of multiple erosions after an 8-week course, you can prescribe PPIs 1 time a
day (rabeprazole at a dose of 10 mg, omeprazole 20 ml, esomeprazole 10 mg, pantoprazole 20 mg,
lansoprazole 30 mg), including in the following cases: in "on demand" mode. If there are complications of
GERD, maintenance therapy should be performed with a full-dose PPIs.

Patients with GERD are subject to active medical supervision with a control examination conducted at least
once a year. In the presence of complications, it is necessary to examine such patients 2 times a year,
including with the use of endoscopic examination.

The highest percentage of effective treatment of GERD exacerbations and maintenance of remission is
achieved with the combined use of PPIs and prokinetics. In the presence of alkaline (bile) reflux, large doses
of enveloping drugs should be added to the combination of PPIs and prokinetics.

Patients whose clinical symptoms of the disease are not accompanied by the development of esophagitis
need to take medications in the "on-demand" mode. However, patients with erosive-ulcerative esophagitis
with this maintenance regimen will still have a high risk (80-90%) of developing a relapse of the disease
within a year. The likelihood of relapses increases in cases of resistance of the initial stages of esophagitis to
therapy with antisecretory drugs, as well as when low pressure in the lower esophageal sphincter is
detected. Such patients require the use of high doses of antisecretory drugs.

The decision on the duration of maintenance therapy for GERD should be made taking into account the
patient's age, the presence of concomitant diseases, existing complications, as well as the cost and safety of
treatment. Antireflux surgical treatment is considered indicated for a complicated course of the disease
(repeated bleeding, peptic strictures of the esophagus, development of Barrett's syndrome with high-grade
epithelial dysplasia), as well as for proven ineffectiveness of drug therapy. The question of surgical
treatment should be considered together with an experienced surgeon in this field, if long-term conservative
treatment of GERD, which was carried out very actively, was unsuccessful, all measures were taken to
normalize the lifestyle and the presence of pronounced gastro-esophageal reflux was proved (using pH-
metry).

Management of patients with Barrett's esophagus

The need for active dispensary monitoring of patients with Barrett's esophagus is due to the possibility of
preventing esophageal adenocarcinoma in cases of early diagnosis of epithelial dysplasia. Verification of the
diagnosis of Barrett's esophagus and determination of the degree of dysplasia is carried out by histological
examination. If low-grade dysplasia is detected, it is necessary to prescribe rabeprazole at a dose of at least
20 mg per day – or omeprazole group drugs at a dose of at least 40 mg per day, with a repeat of the
histological examination after 3 months. If low-grade dysplasia persists, patients are recommended to
continue the constant use of PPI at the same dose and conduct a histological examination after 3 and 6
months. Then a histological examination is performed annually. If a high degree of dysplasia is detected,
rabeprazole should be prescribed at a dose of at least 40 mg per day, and omeprazole, esomeprazole,
pantoprazole-40 mg 2 times a day, with a parallel assessment of the results of histological examination and
subsequent decision on endoscopic or surgical treatment of the patient.