Proliferation of the integumentary pit epithelium: possible causes, symptoms, diagnosis and treatment

The wall of the stomach consists of 4 layers: the inner mucosa, the submucosa, the muscular layer and the outer serosa. The mucous membrane (MS) is normally folded, it has depressions - pits, flat areas (fields) and folds.

The mucosal epithelium is highly prismatic (columnar) cells that line the entire stomach and all its folds in one layer. The cells of this epithelium secrete special mucus; it forms a layer up to 1-1.5 mm thick. During the production of enzymes and hydrochloric acid, temporary channels are formed in this layer. Mucus protects the wall from digestion by stomach juice and various damage. The epithelium is renewed every 1-3 days.

What is proliferation

Cell proliferation is a normal process necessary for the body to renew itself. In other words, this is the physiological reproduction of cells with the result in the form of an increase in tissue volume. This process is controlled by hormones. Proliferation occurs in any organ and tissue. It controls the state of the immune system, leads to the destruction of tissue defects, regenerates them and restores the previous functioning of organs. Due to proliferation, connective tissue grows, new vessels are formed, burns are scarred, damage is eliminated and tissue is replaced with new cells or connective tissue. This applies to blood cells, epithelium and mucous membranes, cartilage, myocardial walls, etc. The most active process occurs in the gastric mucosa.

But proliferation under certain conditions can become pathological, that is, excessive. For example, with increased concentrations of somatropin, it leads to enlargement of organs and limbs. If cell differentiation is disrupted during the process of proliferation, this becomes the beginning of oncology with the appearance of atypical growths. This uncontrolled active (abnormal) cell division is called hyperproliferation or hyperplasia. This can also be explained by the predominance of proliferation over differentiation of mucosal cells. Then the number of narrowly differentiated cells decreases and the epithelium begins to lose its “legal properties” due to immature cells. Proliferation of the integumentary epithelium can and is often accompanied by processes of intestinal metaplasia of the stomach.

Glandular hyperplasia of the endometrium

The endometrium is the inner mucous layer that lines the uterine cavity. The endometrium is subject to monthly changes that occur depending on the period of the menstrual cycle. Normally, the endometrium increases during the menstrual cycle under the influence of hormones and reaches the required thickness during the ovulatory phase for embryo implantation. If fertilization does not occur, the endometrium begins to thin and is excreted from the body during menstruation. The process begins again with a new menstrual cycle. With hyperplasia, the tissue of the inner layer grows too much, which turns into pathology.

Glandular hyperplasia of the endometrium is characterized by an increase in glandular cells due to disruption of their structures. During normal functioning, the endometrial glands look like vertical straight stripes. With the development of hyperplasia, the glands begin to change appearance, twisting and intertwining with each other. When the hormonal balance is disturbed due to excess estrogen, the endometrial glandular cells grow, but their volume does not decrease, which leads to the appearance of hyperplasia.

Hyperplasia

Proliferation of the integumentary pitted epithelium of the stomach is one of the subtypes of mucosal proliferation. The name is given because as a result of tissue growth, corkscrew-shaped pits are formed. This proliferation means hyperplasia of mucus-producing cells (goblet cells), which play a protective role. The integumentary epithelium undergoes mutation, the content of mucin in the cells increases, pushing the nuclei to the base of the cell, pathological cells begin to replace healthy ones. Pits form in the mucosa, which are shaped like a corkscrew pin. The process is a harbinger of oncology.

Most often, proliferation of the integumentary pitted epithelium occurs with hyperplastic gastritis, peptic ulcer disease, and ulcer-like cancer. Clinically and morphologically, they are identical, so a biopsy is required. Cytological examination can reveal pronounced proliferation of the integumentary pitted epithelium of the stomach. In fact, this is a precancerous condition, and such patients should be registered with an oncologist and undergo a systematic examination.

Modern strategy for managing patients with precancerous diseases of the stomach

Despite advances in diagnosis and treatment, gastric cancer remains a serious problem worldwide, ranking sixth in terms of incidence and second in the structure of mortality from cancer [1–2]. The highest rates are observed in the countries of East and Central Asia and Latin America, the lowest in North America. In East Asia, the incidence of stomach cancer is 32.1 per 100,000 in men, 13.2 in women, in South Korea - 57.8 and 23.5 per 100,000, in Japan 40.7 and 16.0 per 100,000 for men and women, respectively [1–2]. The lowest incidence is observed in North America and most parts of Africa. Thus, in the United States of America (5.5 per 100,000 in men; 2.8 in women) [1]. Russia is one of the countries with a moderate risk of stomach cancer, along with Portugal, Singapore, and Estonia. At the end of 2022, according to Russian statistics, in the structure of general morbidity, the proportion of stomach tumors reached 20.4 per 100,000 population in men and 8.8 in women [3]. An improvement in the epidemiological situation regarding gastric cancer is observed, as a rule, in countries where preventive measures have been developed, a high level of public awareness, and national programs for screening and management of patients with precancerous diseases have been in place for a long time [4].

The purpose of this review is to summarize existing international recommendations for the management of patients with atrophic gastritis, intestinal metaplasia and gastric dysplasia.

In 2012, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), the European Society of Pathologists (ESP) and the Portuguese Society of Gastrointestinal Endoscopy (SPED) developed the first international guidelines for the treatment of precancerous conditions and changes in the stomach ( MAPS I). An updated version of the recommendations, called MAPS II, was published in 2022 [4]. These recommendations have been submitted for consideration in different countries.

Different forms of cancer have their own specific characteristics, knowledge of which will allow optimizing the diagnosis of gastric cancer in the early stages. The vast majority of gastric cancers are adenocarcinomas (AC, about 90%), which originate from the glands of the gastric mucosa. Gastric adenocarcinomas (GAC) are divided into cardiac and non-cardiac. There are two main histological types of non-cardiac ACJ: diffuse and intestinal. The cardiac form of gastric cancer is non-cardiac intestinal-type adenocarcinoma (90% of AGC). The latter has a tumor structure similar to that of colon cancer. They are characterized by distinct glandular structures consisting of highly differentiated columnar epithelium with a developed brush border. The diffuse type of tumor is represented by weakly organized groups or single cells with a high content of mucin (signet ring cells) and is characterized by diffuse infiltrative growth. A mixed type is possible—the tumor contains areas of intestinal and diffuse type [5]. The differentiated type is more common in older men and develops slowly, while the diffuse type is more common in younger women and has a worse prognosis [5].

The review of the presented recommendations does not apply to hereditary/familial diffuse gastric cancer, for which special recommendations have been developed [6].

Intestinal-type gastric adenocarcinoma represents the final outcome of the inflammation-atrophy-metaplasia-dysplasia-carcinoma sequence known as the Correa cascade [7–11].

Recommendation 1 (MAPS II). Patients with chronic atrophic gastritis or intestinal metaplasia are at risk of developing gastric adenocarcinoma (high level of evidence) [4].

Chronic atrophic gastritis and intestinal metaplasia (IM) are considered precancerous conditions, since they themselves are associated with the risk of developing gastric cancer and against their background the development of dysplasia and adenocarcinoma is possible [7–11].

Recommendation 2 (MAPS II). Histologically confirmed intestinal metaplasia is the most reliable marker of atrophy of the gastric mucosa (high level of evidence) [4].

Recommendation 3 (MAPS II). Patients with advanced gastritis, i.e., atrophy and/or intestinal metaplasia, of both the gastric antrum and corpus mucosa should be identified as they are considered to be at higher risk of developing gastric adenocarcinoma (moderate quality of evidence) , strong recommendation).

Recommendation 4 (MAPS II). Severe dysplasia and invasive carcinoma should be considered outcomes to be prevented when treating patients with chronic atrophic gastritis or intestinal metaplasia (moderate level of evidence, strong recommendation).

Recommendation 5 (MAPS II). In patients with endoscopic findings suggestive of mild to severe dysplasia or carcinoma, disease should be staged and treated (high level of evidence, strong recommendation).

Recommendation 6 (MAPS II). High-resolution endoscopy combined with chromoendoscopy is more effective than high-resolution white light endoscopy in diagnosing early gastric precancerous lesions and neoplastic lesions (high quality of evidence).

Recommendation 7 (MAPS II). When available and after adequate training, virtual chromoendoscopy with or without magnification should be used to diagnose gastric precancerous lesions, which allows for guided biopsy of areas of atrophic and metaplastic changes and also helps identify neoplastic lesions (moderate level of evidence, strong recommendation).

Recommendation 8 (MAPS II). To properly stage gastric precancerous lesions, the first diagnostic upper gastrointestinal endoscopy should include gastric biopsies to determine the presence of Helicobacter pylori infection and to detect advanced atrophic gastritis (moderate quality of evidence, strong recommendation) [4].

Recommendation 9 (MAPS II). A biopsy should be performed in at least two topographic areas (along the lesser and greater curvature, both in the antrum and in the body of the stomach). An additional biopsy of visible suspected neoplastic lesions should be performed (moderate level of evidence, strong recommendation) [4].

Recommendation 10 (MAPS II). Histopathological staging systems (eg, the operative gastritis grading system (OLGA) and the operative gastritis intestinal metaplasia-based (OLGIM) grading system) can be used to identify patients with advanced gastritis. Stages III and IV may indicate patients at higher risk of developing gastric cancer [12].

An additional biopsy from the gastric angle should be considered (moderate level of evidence, weak recommendation). This approach allows for the maximum degree of identification of patients with precancerous conditions, especially in cases where the use of chromoendoscopy for targeted biopsy is impossible [4].

If a pathological change is detected and the results of endoscopic evaluation indicate the presence of dysplasia, it is recommended to perform resection of the pathological area without additional biopsy [4].

If possible, virtual chromoendoscopy with or without image magnification should be used to diagnose precancerous conditions of the stomach, which allows for controlled biopsy in areas of atrophic and metaplastic changes, and also ensures the identification of neoplastic lesions. High-resolution endoscopy combined with chromoendoscopy is more effective than high-resolution white light endoscopy in diagnosing gastric precancerous lesions and neoplastic lesions at an early stage. If such high-resolution endoscopy does not reveal pathological changes, it is recommended to perform a biopsy to determine the stage of gastritis (if not previously performed) and endoscopic observation for 6 months (for severe dysplasia) to 12 months (for mild dysplasia) [4 ].

Gastric dysplasia represents the penultimate stage in the sequence of gastric carcinogenesis. It is defined as histologically confirmed neoplastic changes in the epithelium without signs of tissue invasion, which indicates an immediate neoplastic precancerous change [13]. The World Health Organization has confirmed the classification of dysplasia/intraepithelial neoplasia [14]:

• Intraepithelial neoplasia/dysplasia includes obvious epithelial and tumor proliferations characterized by variable cellular and architectural atypia, but without convincing signs of invasion.
• Mild intraepithelial neoplasia/dysplasia is characterized by minimal architectural disorder and mild to moderate cytologic atypia.
• Severe intraepithelial neoplasia/dysplasia is characterized by the presence of tumor cells that are usually cuboidal rather than columnar, with a high nuclear-cytoplasmic ratio, defined by amphophilic nucleoli, greater architectural disorder, and numerous mitoses that may be atypical. It is important to note that nucleoli often reach the luminal surface of the cell, and nuclear polarity is usually lost. Most patients with lesions classified as high-grade dysplasia are at high risk for concurrent or rapid development of invasive carcinoma.
• Intramucosal invasive neoplasia/intramucosal carcinoma includes types of carcinoma that grow into the lamina propria and are distinguished from intraepithelial neoplasia/dysplasia not only by the presence of desmoplastic changes, which may be minimal or absent, but also by the presence of characteristic structural abnormalities, such as marked crowding of glands, excessive branching, sprouting, and fusion or cribriform gland structures. A diagnosis of intramucosal carcinoma indicates an increased risk of lymphatic invasion and lymph node metastasis.

The diagnosis of indeterminate dysplasia/neoplasia should not initially be viewed as benign, although most patients will have a good prognosis. In fact, one study found that 26.8% of resected lesions classified as indeterminate dysplasia/neoplasia on preresection biopsy were actually neoplastic lesions (5.0% adenoma and 21.8% early gastric cancer ) [15].

It should be remembered that even mild dysplasia can represent a malignancy [16].

In the case of visible pathological changes, endoscopic biopsy alone is not enough to diagnose a malignant neoplasm; in the presence of any endoscopically detectable pathological change with any neoplastic changes, it is necessary to perform endoscopic resection[4].

Inspection of histological specimens and immediate (as soon as possible) re-evaluation using high-resolution endoscopy and chromoendoscopy is recommended [4].

In the absence of endoscopically detectable pathological changes in patients with dysplasia, immediate re-evaluation using high-resolution endoscopy and chromoendoscopy (virtual or dye) is recommended [4].

Patients with undetermined dysplasia, dysplasia, as well as carcinoma, diagnosed based on the results of a non-targeted biopsy, require further examination and treatment only in clinics specializing in the diagnosis and endoscopic treatment of gastric cancer [4].

Non-invasive methods for diagnosing precancerous changes in the gastric mucosa

A low serum level of pepsinogen I and/or a low pepsinogen I/II ratio allows the identification of patients with late-stage atrophic gastritis. In such patients, endoscopy is recommended, especially if the serological test for H. pylori is negative. The limit values ​​are pepsinogen I level < 70 ng/ml and pepsinogen I/II ratio < 3. The sensitivity and specificity for diagnosing gastric cancer at these indicator values ​​is 0.69 (95% CI 0.60–0.76) and 0 .73 (95% CI 0.62–0.82), respectively [24]. These cutoff values ​​are widely used in gastric cancer screening in Japan [25].

Family history

Despite the fact that in most cases the development of intestinal-type gastric adenocarcinoma is sporadic, in 10% of cases its familial accumulation is observed to some extent [17].

As shown above [12], patients with dysplasia, extensive atrophy/CM and/or OLGA/OLGIM stage III/IV are at significantly higher risk of cancer and are recommended to undergo endoscopic surveillance, optimally with high-resolution endoscopy . Meanwhile, the risk of developing gastric cancer also increases, although to a lesser extent, in patients with less severe stages of precancerous changes, for example, with focal CM (stage I/II according to OLGIM), especially in the presence of CM and/or gastric cancer in family history [4].

Having a first-degree relative with gastric cancer is a consistent risk factor for developing this disease, with odds ratios ranging from 2 to 10, depending on geographic region and ethnicity [18]. Having a second-degree relative with stomach cancer also increases the risk of developing this disease, although to a lesser extent [19]. A strong family history of gastric cancer is due to inherited genetic predisposition, common environmental or lifestyle factors, common susceptibility to H. pylori infection, a common cytotoxic strain of H. pylori, or a combination of these factors. Accordingly, according to the results of a meta-analysis, first-degree relatives of patients with gastric cancer have an increased incidence of H. pylori infections (OR 1.93), gastric atrophy (OR 2.2) and CM (OR 1.98) [20]. In addition, first-degree relatives of patients with early gastric cancer have an increased incidence of severe gastritis (OLGA stage III/IV) and dysplasia, which is most likely due to the high virulence of H. pylori strains and proinflammatory host genotypes [21 ].

First-degree relatives of patients with gastric cancer have an increased incidence of H. pylori infection and precancerous lesions/changes, as well as an increased risk of developing gastric cancer [22, 23]. Although there is limited evidence that precancerous lesions in relatives of patients with gastric cancer progress to cancer more rapidly through the carcinogenic cascade compared with similar conditions in matched controls in the general population, it is suggested that more intensive follow-up in patients with extensive atrophy/CM may be advisable. and if there is a family history of stomach cancer in a close relative.

Patients with extensive CM, persistent H. pylori infection, or incomplete CM, or especially a family history of gastric cancer in a close relative, require more frequent endoscopic surveillance (every 1–2 years) [4]. These recommendations do not apply to hereditary/familial diffuse gastric cancer, for which special recommendations have been developed [6].

Within the framework of the MAPS II recommendations, approaches to cancer prevention of another form of chronic gastritis—autoimmune—were formulated for the first time. Autoimmune gastritis is a chronic progressive inflammatory disease that leads to the replacement of parietal cells with atrophic and metaplastic mucous membrane, resulting in the development of atrophic gastritis, mainly affecting the body of the stomach, the formation of hydrochloric acid and internal factor decreases or stops, which can lead to the development of severe anemia caused by vitamin B12 deficiency and known as pernicious anemia. Some existing evidence suggests that autoimmune gastritis is a precancerous condition for which endoscopic monitoring is warranted. However, the recommended follow-up interval has not been established at this time.

Because the greatest increased risk of gastric cancer in patients with pernicious anemia is observed during the first year of follow-up [26, 27], some evidence suggests that endoscopic evaluation should be recommended in all patients at the time of diagnosis. Given the heterogeneity of the reported cohorts and the lack of larger randomized clinical trials with longer follow-up, it is recommended that endoscopy be performed as part of follow-up at 3–5 year intervals in patients with autoimmune gastritis [4].

Treatment approaches

The main goal in treating patients with chronic atrophic gastritis or intestinal metaplasia is to prevent progression to dysplasia and invasive carcinoma.

Eradication of H. pylori

Eradication of H. pylori helps relieve chronic inflammation and can lead to regression of atrophic gastritis, reducing the risk of developing gastric cancer in patients with non-atrophic and atrophic gastritis [28].

In patients with severe CM, H. pylori eradication usually does not lead to a significant reduction in the risk of developing gastric cancer, at least in the short term, but it does reduce inflammation and atrophy, so its use should be considered in such patients [4].

H. pylori eradication is recommended for all patients with gastric neoplasia after endoscopic therapy [4].

However, eradication therapy alone does not completely eliminate the risk of developing stomach cancer. Residual inflammation along the lesser curvature of the gastric body after eradication of H. pylori is a risk factor for metachronous gastric cancer [4]. There is evidence that the use of rebamipide in the post-eradication period is advisable for potentiating the repair of the gastric mucosa and regression of inflammatory changes [4, 29, 30].

Correction of environmental factors

Excessive salt consumption and cigarette smoking have an additional carcinogenic effect in the presence of H. pylori infection [31, 32], the doctor’s task is to correct modifiable risk factors.

Endoscopic screening

In 2012, a study published in a Korean patient population concluded that for a population of patients aged 50–80 years, endoscopic examination annually in men and every two years in women represents the optimal screening option [33]. ]. Later, based on data from new studies, according to which a decrease in mortality rates was observed in individuals who were screened at least once every 3 years, the authors concluded that the frequency of screening could be increased to 2-3 years. The age for starting screening is set at 50 years [34]. In countries with a moderate risk of developing gastric cancer, endoscopic surveillance in patients with precancerous lesions performed every 3 years is cost-effective [35]. In Russia, economic studies are required to determine the optimal interval for endoscopic screening taking into account population characteristics, including a modeling approach.

Conclusion

Stomach cancer represents a serious medical and social problem both for most countries of the world and for Russia. Patients with chronic atrophic gastritis or intestinal metaplasia have an increased risk of developing gastric adenocarcinoma. In regions with moderate and high risk, identifying patients with precancerous conditions of the stomach by endoscopic screening is effective. Histopathological staging systems (Operational Gastritis Grading (OLGA) and Operative Gastritis Intestinal Metaplasia (OLGIM)) should be used to rank patients at risk. Another important area of ​​cancer prevention for gastric cancer is the eradication of H. pylori, which helps relieve the manifestations of chronic non-atrophic gastritis and partial regression of atrophic gastritis.

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L. B. Lazebnik*, Doctor of Medical Sciences, Professor E. A. Lyalukova**, 1, Doctor of Medical Sciences, Professor G. V. Belova***, Doctor of Medical Sciences, Professor I. V. Dolgalev**** , Doctor of Medical Sciences N. V. Korochanskaya#, Doctor of Medical Sciences, Professor V. K. Kosenok**, Doctor of Medical Sciences, Professor, Academician of the Academy of Medical Sciences of the Russian Federation A. S. Lyalukova## E. V. Onuchina###, Doctor Medical Sciences, Professor M. M. Petrova#### , Doctor of Medical Sciences, Professor L. V. Prokhorova@ , Candidate of Medical Sciences A. S. Sarsenbaeva@@ , Doctor of Medical Sciences, Professor

* Federal State Budgetary Educational Institution of Higher Education MGMSU named after. A. I. Evdokimova Ministry of Health of Russia, Moscow ** Federal State Budgetary Educational Institution of Higher Education Omsk State Medical University of the Ministry of Health of the Russian Federation, Omsk *** MC Central Bank of the Russian Federation, Moscow **** Federal State Budgetary Educational Institution of Higher Education Siberian State Medical University of the Ministry of Health of Russia, Tomsk # Federal State Budgetary Educational Institution of Higher Education Kuban State Medical University of the Ministry of Health of the Russian Federation, Krasnodar ## State Budgetary Institution GB No. 3 Sochi Ministry of Health KK, Sochi ### IGMAPO - branch of the Federal State Educational Institution of Further Professional Education RMANPO of the Ministry of Health of Russia, Irkutsk #### Federal State Budgetary Educational Institution of Higher Education Krasnoyarsk State Medical University named after. prof. V.F. Voino-Yasenetsky Ministry of Health of Russia, Krasnoyarsk @ Federal State Budgetary Educational Institution of Higher Education Ural State Medical University of the Ministry of Health of Russia, Yekaterinburg @@ Federal State Budgetary Educational Institution of Higher Education South Ural State Medical University of the Ministry of Health of Russia, Chelyabinsk

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DOI: 10.26295/OS.2019.89.64.013

Modern strategy for the management of patients with precancerous diseases of the stomach / L. B. Lazebnik, E. A. Lyalukova, G. V. Belova, I. V. Dolgalev, N. V. Korochanskaya, V. K. Kosenok, A. S. Lyalukova, E. V. Onuchina, M. M. Petrova, L. V. Prokhorova, A. S. Sarsenbaeva For citation: Attending physician No. 9/2019; Page numbers in the issue: 60-64 Tags: chronic atrophic gastritis, intestinal metaplasia, gastric adenocarcinoma

Reasons for development

The main reason is chronic or long-term damage and irritation of the mucous membrane, which causes wounds and ulcers. In addition to the above pathologies, the cause may be:

• hereditary predisposition;
• hormonal imbalances;
• the presence of Helicobacter pylori - its metabolic products contaminate the entire body, which suppresses the immune system, destroys the mucous membrane and causes proliferation of the integumentary epithelium; this bacterium leads to inflammation of the gastric mucosa and the development of gastritis in 90% of cases;
• nutritional disorders, which contain a lot of E additives, preservatives, alcohol;
• taking NSAIDs;
• stress;
• changes in the functioning of the duodenum (it provokes excess gastrin, which irritates the gastric mucosa; backflow of bile during reflux) and the pancreas.

Glandular hyperplasia of the endometrium: causes

The main reason for the development of glandular endometrial hyperplasia is hormonal disorders, in which there is a significant production of estrogen and a decrease in the synthesis of progesterone. This disease can occur at any age. However, women are most susceptible to it during the transition period: puberty and menopause. This is due to significant hormonal changes in the body.

Hyperplasia can appear as a consequence of some gynecological diseases, which are also associated with hormonal imbalance:

• neoplasms in the ovaries;
• ovarian dysfunction;
• polycystic ovary syndrome;
• neoplasms in the uterus;
• endometritis and endometriosis.

The cause of the development of glandular endometrial hyperplasia can be abortion, curettage and other gynecological operations.

In most cases, hyperplasia occurs against the background of diseases such as diabetes, obesity, impaired functioning of the kidneys, liver and thyroid gland. These diseases are characterized by metabolic disorders and the occurrence of hormonal imbalances, which leads to the development of hyperplasia.

Briefly about the types

There are the following types of pathology:

1. Foveal hyperplasia of the stomach. In this case, the folds and gastric pits are deformed, they are elongated and curved. The most common and harmless type. Develops when taking NSAIDs.
2. Antral - tissue grows at the junction of the gastric mucosa and duodenum. The cause is malnutrition. These changes look like multiple small growths.
3. Lymphofollicular - the mucous membrane thickens and grows due to the accumulation of lymphocytes that form follicles. Possible malignancy. With lymphoid hyperplasia, the antrum of the stomach is most often affected, when the number of lymphocytes in the lymph nodes increases. With an increase in lymphocytes, the mucous membrane thickens and hyperplasias. Moreover, the enlargement of lymph nodes in this case is not inflammatory in nature. Causes: peptic ulcer and infectious diseases of the digestive tract.
4. Glandular is the rarest form, with the proliferation of glandular cells and the formation of round and oval polyps. Occurs when the stomach stretches.
5. Polypoid – the appearance of multiple polyps in any part of the stomach. The reason is unknown.
6. Focal - “wart” - the appearance of additional tissue in one or several places. The process is observed in the initial stages of hyperplasia and is benign.

That is, we can say that the proliferation of cells of the integumentary pit epithelium is the proliferative growth of cells that produce mucus.

Glandular hyperplasia of the endometrium: diagnosis

A woman should consult a doctor if menstrual irregularities or acyclic bleeding occur. The doctor must be informed about when the disruptions and bleeding began, how often and for what duration they occur. To establish a diagnosis, the woman will be prescribed the following tests:

• Gynecological examination. During the gynecological examination, a bimanual (two-handed) vaginal examination will be performed, during which the gynecologist palpably determines the size of the uterus, cervix and ovaries, their ratio, the condition of the ligamentous apparatus of the appendage and uterus area, its mobility, soreness, etc.
• Ultrasound examination of the pelvic area. An ultrasound will help assess the condition of the uterus and appendages, as well as the size of the endometrium.
• Microscopic examination of a smear of vaginal discharge.
• Blood test for hormone levels in the first and second phases of the menstrual cycle: follicle-stimulating hormone, luteinizing hormone, progesterone, estradiol, testosterone, prolactin.
• Determination of the level of tumor markers CA 125, CA 15-3 in the blood.
• Diagnostic curettage of the uterine cavity and cervical canal followed by histological examination.
• Hysteroscopy. Using a hysteroscope allows you to examine the uterine cavity and collect the endometrium for biopsy.
• Therapeutic and diagnostic laparoscopy.

Degrees of proliferation

Today, hyperplasia is divided into 3 stages:

1. First degree – mucus production decreases, hyperchromatosis is noted. The process is initial, it is reversible with proper treatment.
2. The second degree is moderate proliferation of the integumentary pitted epithelium. The process is already more obvious, cell division accelerates and becomes more frequent, the number of Paneth and goblet cells decreases. The process can still be stopped with timely and modern treatment.
3. The third degree is pronounced proliferation of cells of the integumentary pit epithelium of the stomach. Large areas proliferate, mucus is not secreted, there is no protection, the process becomes precancerous.

Symptoms and signs

For a long time, a person does not realize that he has a pathology, he does not have any illness, which is why early diagnosis is so late. Then, as the process progresses, first after eating there is severe pain in the upper abdomen, nausea, loss of appetite, sour belching, and hiccups.

In advanced stages, vomiting, general weakness, bloating, and flatulence are observed. The pain can be cramping in nature - at first it is stabbing or in the form of a burning sensation, then it becomes aching. The stool is disturbed and prone to diarrhea. Signs of intoxication appear - pallor, headache, dizziness, fever, feeling of tense muscles. Symptoms are nonspecific and therefore often go unnoticed. Early diagnosis is of paramount importance: it is necessary to promptly identify and prescribe effective treatment for proliferation of the integumentary pitted epithelium of the stomach. It is dangerous, but in the early stages it is amenable to therapy.

Diagnostic measures

The main diagnostic method is gastroscopy. With such an examination, it is possible to perform a biopsy followed by histology. The gastric mucosa is thoroughly examined and the specialist can see all changes in it immediately.

During the examination, the doctor can see neoplasms, abnormalities of tissues and membranes.

Barium X-ray will reveal polyps, their shape and the size of their legs. When establishing the etiology, an analysis is performed for the presence of Helicobacter pylori. This includes a urea breath test and a blood test for antibodies.

If a diagnosis of “pronounced proliferation of the integumentary epithelium hp” with a certain number of crosses is made, then this indicates the presence of Helicobacter pylori in the mucosa. A biopsy can play a significant role; it is performed during gastroscopy. The study makes it possible to establish the presence of the disease and its subtype. It must be said that the combination of proliferation of the integumentary epithelium and Helicobacter is not such a rare phenomenon.

Simple glandular hyperplasia of the endometrium

Simple glandular hyperplasia of the endometrium is characterized by disruption of the mucous tissue of the inner layer of the uterus. In this case, there is an increase in the number and size of endometrial glandular cells without pathological changes in their structure. Gland cells can have different shapes and localization. With simple glandular hyperplasia of the endometrium, the boundaries between the basal and functional layers of the endometrium are blurred. The boundaries between the myometrium and endometrium are preserved. The endometrium grows to the maximum possible size and is then rejected. This is how intermenstrual (acyclic) bleeding occurs.

Acyclic bleeding sometimes coincides with menstruation. However, the discharge will be different. The volume of acyclic bleeding is uneven: discharge can be strong and weak. Often clots are found in the discharge, which are casts of immature endometrium. Immature endometrial cells are not rejected in full, as a result of which complete detachment of the functional layer of the endometrium does not occur. As a result, normal functioning of the endometrium is not restored.

With simple glandular hyperplasia of the endometrium, immature accumulations of endometrial cells remain in the uterine cavity, which constantly grow regardless of bleeding.

With any form of hyperplasia, a woman does not have a menstrual cycle as such, and reproductive system disorders occur. Accordingly, pregnancy does not occur with hyperplasia. Very rarely, simple glandular endometrial hyperplasia can transform into uterine cancer.

Principles of treatment

Therapy for the disease is multicomponent and aims to improve gastric motility and normalize the production of hydrochloric acid.

Treatment of proliferation of the integumentary pit epithelium, i.e. hyperplastic gastritis, depends on the etiology, subtype of proliferation, hypo- or hyperacidity, severity of the clinic and concomitant diseases. Self-prescription of drugs is strictly prohibited.

How to treat proliferation of the integumentary pitted epithelium of the stomach? The following groups of drugs are prescribed for therapy:

1. Antispasmodics - “No-shpa”, “Papaverine”, “Spazgan”, “Drotaverine”. Relieves spasm and pain.
2. Antibiotics - Amoxicillin, Tetracycline, Clarithromycin, etc.
3. Antimicrobial agent "Metronidazole" and bismuth preparations. Used to eradicate (remove) Helicobacter bacteria if present.
4. Enzyme preparations - “Festal”, “Creon”, “Mezim”, “Panzinorm”, etc. They are used to improve digestion.
5. Antacids - “Rennie”, “Almagel”, “Maalox”, etc. Relieve heartburn, pain, and protect the mucous membrane.
6. Amino acids - “Methionine”, “BCAA”, etc. – are necessary to compensate for protein deficiency.
7. Multivitamins - B vitamins, vit. S and R.
8. For hypoacid conditions, gastric juice preparations are prescribed - Pepsin, hydrochloric acid.
9. To reduce increased secretion - proton pump inhibitors. They are rarely prescribed and are effective in the initial stages. In recent years, hyperbaric oxygen therapy has been used for conservative therapy.

Endometrial hyperplasia - symptoms and treatment

Diagnosis is based on an analysis of the patient’s medical history (medical history), clinical picture of the disease (complaints and physical examination), as well as on the results of ultrasound and hysteroscopic examination with mandatory pathomorphological analysis of scrapings from the uterine cavity.

The diagnosis of “endometrial hyperplasia” is made only on the basis of histological examination of material obtained during diagnostic curettage of the uterine mucosa or removal of the uterus.

History and clinical picture

When collecting anamnesis, the gynecologist asks the patient questions:

• Did your mother, grandmother or other female relatives have any gynecological problems?
• What lifestyle does the patient lead?
• Are there any bad habits?
• What is the nature of the diet?
• How menstruation occurs: cycle length, nature and duration of menstruation.
• Is there abnormal uterine bleeding? If yes, what is their nature and duration.
• Have you ever been pregnant or given birth, or are you planning a pregnancy in the future? The inability to conceive a child and miscarriage can be a symptom of endometrial hyperplasia [18].
• Are there any concomitant diseases at risk for the development of endometrial hyperplasia?
• Does the patient take any hormonal medications?

Physical examination includes local examination of the external genitalia, speculum examination of the vagina and cervix, and bimanual (two-handed) examination of the uterus and appendages. An examination is carried out at the initial appointment to exclude inflammatory diseases and/or large tumor formations.

Instrumental diagnostics

Transvaginal ultrasound examination (TVUS) of the pelvic organs. Endometrial thickness according to ultrasound is not a reliable criterion for identifying endometrial hyperplasia in women of reproductive age [26]. The study is performed to exclude other causes of abnormal uterine bleeding or to evaluate endometrial thickness in postmenopausal women [23][27].

In women of reproductive and premenopausal age, if endometrial hyperplasia is suspected, TVUS of the pelvic organs is performed on the 5th–7th day of the menstrual cycle. Normally, at this time, the thickness of the endometrium does not exceed 6 mm. Endometrial pathology is suspected when its thickness does not correspond to a certain phase of the menstrual cycle:

• on the 5th–7th day of the cycle, the thickness of the endometrium is more than 6 mm (on average 8–15 mm);
• in the middle of the cycle (on the 14th–15th day of a 28-day cycle), the thickness of the endometrium is more than 15 mm [13][14].

In postmenopause, the normal thickness of the endometrium should be no more than 4–5 mm. Pathological thickening is diagnosed when this indicator exceeds 5 mm [12]. The permissible thickness of the endometrium while taking Tamoxifen is no more than 9 mm.

In addition to measuring the thickness, the ultrasound doctor evaluates the blood supply to the endometrium, as well as its contours, homogeneity and compliance with the cycle phase in women of reproductive age. Atypical hyperplasia is characterized by more pronounced thickening of the uterine mucosa, its heterogeneity, uneven tortuous contours and more intense vascularization (blood supply) [2][7].

In some cases, for example, with heavy bleeding that threatens the patient’s health, TVUS is not performed. A decision is immediately made about justified diagnostic curettage for health reasons [19].

Hysteroscopy with separate diagnostic curettage (RDC) of the uterus and cervical canal is an informative method in the diagnosis of endometrial hyperplastic processes. Using a hysteroscope (an endoscopic device for examining the uterine cavity), the doctor assesses the condition of the mucous membrane of the uterus and cervical canal. If necessary, removes local lesions and necessarily takes material for subsequent histological examination.

If curettage is performed as a therapeutic procedure for heavy uterine bleeding, the doctor completely removes the uterine mucosa under the control of hysteroscopy.

Cytological examination of aspirate from the uterine cavity. Pipelle biopsy. A special probe inserted into the uterine cavity “sucks up” fragments of the endometrium. Subsequently, the specialist evaluates the severity of its proliferative changes (i.e., new formations of cells and cellular structures). Pipelle endometrial biopsy is a highly sensitive method for diagnosing endometrial hyperplasia and cancer [28].

In women of reproductive age (15–49 years), an aspirate is taken on days 2–26 of the menstrual cycle. In premenopausal women (from 40–45 years of age until the onset of menopause) and menopausal women (timely menopause occurs at 46–54 years of age), a pipette biopsy can be done on any day [20][21].

Differential diagnosis of endometrial hyperplasia is carried out with endometrial polyp, submucous (submucosal) uterine fibroids, endometritis, interrupted pregnancy and endometrial cancer.

When is surgery needed?

Surgical treatment of hypertrophic gastritis is carried out when conservative therapy is ineffective. Indications for surgery are as follows:

• stomach bleeding;
• stomach polyps;
• presence or suspicion of malignancy of the process;
• severe course of the pathology.

Endoscopic removal of polyps (polypectomy) and gastric resection (complete or partial) are performed. Polyps are formed in all types of hyperplasia and can also be hereditary. The latter are more often malignant

Polyps larger than 1 cm are removed endoscopically. Small formations are not removed unless there is a suspicion of malignancy, but their development is monitored - examined once every six months.

Glandular endometrial hyperplasia: treatment

The first stage of treatment for glandular endometrial hyperplasia is the removal of its pathological areas. Removal can be done in two ways:

• separate curettage of the uterine cavity;
• removal of deformed areas using a hysteroscope.

The removed areas are sent for histological examination. Taking into account its results, as well as the patient’s age and concomitant diseases, the doctor determines further conservative treatment.

Drug treatment of glandular endometrial hyperplasia includes hormonal therapy, the effect of which is aimed at suppressing further pathological growth of the endometrium and restoring hormonal balance. For the treatment of glandular endometrial hyperplasia, combined oral contraceptives and drugs containing gestagens can be prescribed for a period of 3-6 months. Gonadotropin releasing hormone agonist drugs are effective in women over 35 years of age. They cause a temporary, reversible state of amenorrhea and menopause. In parallel with hormonal therapy, vitamin therapy and anemia correction are carried out.

Treatment of glandular endometrial hyperplasia is monitored after 3-6 months of hormonal therapy. A control biopsy is performed after completion of the course of treatment.

Special diet

Nutrition should be balanced. You should eat food in small portions (fractionally), preferably at the same time, every 3 hours.

It is advisable to completely avoid alcohol and any products that irritate the mucous membranes: pickles, smoked meats, marinades, preserves, fermented foods, fast foods, soda and semi-finished products. Salt must be minimized; canned food and red meat are prohibited. All food should only be boiled, everything fried is prohibited.

Table No. 2 is recommended. This nutritional system is prescribed for intestinal diseases and gastritis. Its purpose is to stop the development of inflammation and normalize the functioning of the secretory apparatus of the stomach.

Forecast depends on the subtype of hyperplasia and its intensity, timeliness and modernity of diagnosis.

Preventive actions

There is no specific prevention of gastric hyperplasia, but general recommendations for improving health have not been canceled. The diet should contain sufficient vitamins and minerals, smoking and alcohol should be stopped, negative emotions and stress should be avoided. Try to choose products with the least amount of preservatives and carcinogens. Get into the habit of drinking a glass of water before each meal so that your body receives at least 2 liters of clean water per day. Don't overuse anti-inflammatory drugs, even if they help you. An active lifestyle will also help get rid of many diseases. Don't forget to visit a gastroenterologist every six months. If you really don’t like the EGD method, you can simply undergo ultrasound.

Proliferation of the integumentary pit epithelium is a dangerous pathology, which in advanced cases provokes cancer. Early diagnosis is important to stop lesions in the initial stages.