Diagnosis of Barrett's esophagus

Diagnostic methods

1. One of the main diagnostic methods that helps to suspect Barrett's esophagus is fibroesophagogastroduodenoscopy (FEGDS). This method allows for a visual assessment of the esophagus and the esophagogastric junction and for taking biopsy material for histological and, if necessary, immunohistochemical examination.

Mandatory biopsy during endoscopic examination in pediatric practice is indicated:

1. patients of any age with endoscopic picture of Barrett's esophagus;
2. patients with radiologically or endoscopically confirmed esophageal stricture;
3. patients with papillomas located at a distance of 2 cm and above the Z-line;
4. patients with a "short" esophagus,
5. patients with radiologically confirmed high-grade gastroesophageal reflux;
6. patients with a history of surgical interventions on the esophagus and stomach, in case of persistence or appearance of clinical GERD.

Endoscopic markers of possible ectopia of the epithelium include:

• "islands" of foreign columnar epithelium,
• the so-called high longitudinal slit-like erosions,
• various papillomas located at a distance of 2 cm or more proximal to the Z-line.

P.Spinelli and co-authors present the following endoscopic variants of Barrett's esophagus:

• "tongues of flame" as a continuation of the gastric mucosa in the lower part of the esophagus,
• Circular cuff with Z-line offset,
• indistinct cuff with "Malpighian islands".

Great importance is attached to the length of the emulated sections, since it is known that in long segments (length more than 3 cm) the risk of developing esophageal adenocarcinoma is 10 times higher than in short ones (length less than 3 cm). Short segments of Barrett's esophagus are 10 times more common than long ones.

Chromoesophagogastroscopy can be used to diagnose Barrett's epithelium. Toluidine blue, indigo carmine, or methylene blue selectively stain metaplastic mucosa, leaving the esophageal epithelium unstained. Lugol's solution selectively stains stratified squamous epithelium of the esophagus, leaving the columnar epithelium intact.

The introduction of video information endoscopic systems with digital registration and image analysis into practice, which make it possible to detect minimal pathological changes, should be considered very promising. In particular, the use of fluorescent endoscopy will allow for early diagnostics of Barrett's esophagus and esophageal adenocarcinoma.

2. The "gold standard" in the diagnosis of Barrett's esophagus is histological examination of esophageal biopsies. It is extremely important to follow the procedure for taking biopsy material if Barrett's esophagus is suspected: biopsies are taken from four quadrants, starting from the gastroesophageal junction and then proximally every 1-2 cm, as well as from any suspicious area.

There are recommendations that it is necessary to perform a biopsy of the entire segment of the mucosa of Barrett's esophagus at intervals of 2 s or 1 cm along the entire length of the visible segment, as well as all suspicious areas.

At the same time, it should be remembered that the anatomical zone of the esophagogastric junction does not coincide with that detected endoscopically. In this regard, for reliable diagnosis of the state of the esophagus, it is necessary to take biopsies 2 cm or more proximal to the Z-line.

There are various classifications of altered epithelium. Foreign authors distinguish three types of Barrett's epithelium:

1. fundamental;
2. transitional or nadir;
3. cylindrical cell.

It is also possible to distinguish a fourth variant - an intermediate type of epithelium.

There is also a classification that provides for four histological forms of metaplastic epithelium with specific morphological parameters for each form:

1. a characteristic form characterized by a villous-pitted surface of the mucous membrane, the presence of cylindrical cells with mucus and goblet cells in the integumentary epithelium, and parietal (inconstantly) and all neuroendocrine cells (NEC) in the epithelium of the glands;
2. the cardiac form is characterized by the absence of goblet cells in the integumentary epithelium, as well as chief, parietal and goblet cells in the epithelium of the glands, while all types of neuroendocrine cells are preserved;
3. The fundic form differs from the cardiac form mainly by the presence of chief and parietal cells in the epithelium of the glands;
4. The indifferent form or "variegated" includes focal features of all the forms indicated above.

According to research data, in adults the most common forms are characteristic (65%) and indifferent (25%), much less common are cardiac (6.5%) and fundic (3.5%).

In children, the cardiac (50% of cases) and characteristic (38%) forms of Barrett's esophagus are somewhat more common, while the fundal (3.5%) and indifferent (2.5%) forms are less common.

Particular attention is paid to the detection of dysplasia in the metaplastic titelium and determination of its degree, since it is known that dysplasia, especially "high" degree, is a morphological marker of possible malignancy. Currently, there are criteria for verification of dysplasia degrees, well known to morphologists. Usually, three degrees of dysplasia are distinguished. Sometimes, two variants are distinguished: high and low degree dysplasia. The frequency of dysplasia detection in Barrett's esophagus, according to different authors, fluctuates in the range from 12.9% to 45% of cases. Most often, malignancy of the dysplastic epithelium of Barrett's esophagus occurs in individuals with a previous indifferent form - 77.2%.

Based on the above, it is not difficult to imagine a risk situation for the development of malignancy in Barrett's esophagus: an indifferent form with grade 3 (high) dysplasia.

When analyzing the obtained morphological data, one should remember about the possible hyperdiagnosis of Barrett's esophagus and exaggeration of the risk of developing esophageal adenocarcinoma. Thus, one study found that in 95% of patients with gastroesophageal reflux, cylindrical epithelium is determined at a distance of 3 cm or more above the Z-line. The presented data allow us to ask a logical question: should the detection of gastric epithelium of the fundic (and, especially, cardiac) type in the esophagus always alert us prognostically in terms of carcinogenesis?

According to a number of authors, the cylindrical cell type of mucosa is the least susceptible to malignancy, and the probability of the latter is highest with incomplete intestinal metaplasia, i.e. with the appearance of goblet cells in the esophageal epithelium. This point of view is currently dominant among specialists dealing with Barrett's esophagus.

3. Additionally, immunohistochemical and histochemical methods of research, which are conducted in a number of cases, also help in diagnostics, acting as prognostic markers of possible malignancy. Thus, sulfomucins were found in the parenchyma of 86.3% of patients with esophageal adenocarcinoma, the production of which was also recorded at grade 3 dysplasia during a retrospective study. In addition, it has been proven that during malignancy, the displacement (or suppression) of neuroendocrine cell lines by tumor cells occurs.

Specific markers of Barrett's epithelium also include sucrase-isomaltase.

In the work of MacLennan AJ.etal. 100% expression of villin was shown in patients with Barrett's esophagus. Villin is a marker of cell differentiation in the small intestine and its study is very promising in terms of diagnosing intestinal-type metaplasia in Barrett's esophagus.

The use of histochemical and immunohistochemical methods made it possible to note a significant increase in the glandular proliferation/apoptosis ratio in the progression of metaplasia - adenocarcinoma, which can also serve as a tumor marker.

4. X-ray examination allows for a fairly confident diagnosis of the "classic" variant of Barrett's esophagus, which involves the presence of a stricture in the middle part of the esophagus, Barrett's ulcer and a large hiatal hernia. The "short" esophagus variant has its own clear X-ray criteria. With double contrast, two types of mucosal relief are distinguished: reticular and smooth. However, a number of authors point to the low sensitivity and specificity of this finding and note that every third patient with Barrett's esophagus has no abnormalities on the X-ray.

X-ray examination remains one of the decisive methods in the diagnosis of gastroesophageal reflux and GERD, since it allows for a fairly confident diagnosis of reflux as such, reflux esophagitis and hernias of the esophageal opening of the diaphragm. Indirect signs of gastroesophageal reflux may include a decrease in the size of the gastric bubble and straightening of the His angle. In nominal cases, the use of a water-siphon test is recommended.

5. Daily pH monitoring is currently considered one of the most reliable methods for diagnosing GER. This method can not only record a modification of the esophagus (a decrease in pH below 4.0), but also determine the severity of GER, and find out the influence of various provoking factors on its occurrence. Despite the fact that this method does not allow "directly" suspecting Barrett's esophagus, it rightfully remains one of the components of the algorithm for examining a child with GERD, a complication of which is Barrett's esophagus.
6. Radioisotope methods are used in clinical practice much less frequently than those listed above.
7. Genetic screening. Over the past two decades, foreign literature has published papers suggesting a possible familial nature of Barrett's esophagus, in particular, several families have been described in which Barrett's esophagus occurred in more than one generation in several people. Thus, V. Jochem et al. observed Barrett's esophagus in 6 members of one family in three generations. The authors put forward a theory of genetic predisposition to Barrett's esophagus. It is assumed that the mechanism of hereditary transmission is compatible with the autosomal dominant model.

There are methods of genetic screening for the development of esophageal adenocarcinoma. Carcinogenesis in Barrett's epithelium is associated with a series of genetic disorders that activate oncogenes and make tumor suppressor genes inoperative. A marker for the development of this pathology in Barrett's esophagus is the loss of heteroeigosity of a number of genes, primarily the tumor suppressor genes p53, p21 and erbB-2. A violation of the DNA structure (aneuploidy) of esophageal epithelial cells is the second most important marker of possible carcinogenesis.

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