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 us to give a visual assessment of the esophagus and the zone of the esophageal-gastric transition and to take a biopsy material for carrying out a histological and, if necessary, immunohistochemical study.

Obligatory biopsy during endoscopic examination in pediatric practice is shown:

1. patients of any age with an endoscopic picture of Barrett's esophagus;
2. patients with radiological 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 gastroesophageal reflux of a high degree;
6. patients who have a history of surgical intervention on the esophagus and stomach, if the GERD clinic is preserved or appeared.

Endoscopic markers of possible ectopy of the epithelium include:

• "islands" of foreign cylindrical epithelium,
• so-called. High longitudinal slit-like erosion,
• a variety of papillomas located at a distance of 2 or more cm proximal to the Z-line.

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

• "tongues of flame" as an extension of the gastric mucosa in the lower part of the esophagus,
• a circular cuff with a Z-line offset,
• fuzzy cuff with "malpighian islets".

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

For the diagnosis of the barrett's epithelium, chromoso-esophagogastroscopy can be used. Toluidine blue, indigo carmine or methylene blue selectively stain metaplastic mucous, leaving the esophagus epithelium unpainted. Lugol's solution selectively stains the multilayered flat epithelium of the esophagus, leaving intact the cylindrical epithelium.

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

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

There are recommendations according to which it is necessary to conduct a biopsy of a whole segment of the mucous membrane of the Barrett's esophagus with an interval of 2 seconds. 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 esophageal-gastric transition does not coincide with that found endoscopically. In connection with this, for reliable diagnosis of the state of the esophagus it is necessary to take biopsy specimens 2 and more cm proximal to the Z-line.

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

1. foundation;
2. transitional or nardial;
3. cylinder cell.

It is also possible to isolate the fourth variant, an intermediate type of epithelium.

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

1. characteristic form, which is inherent in the villous-mucosal surface of the mucous membrane, the presence in the integument epithelium of the cylinders with mucus and goblet cells, and in the epithelium of the glands - parietal (non-permanent) and all neuroendocrine cells (NEC);
2. the cardiac form is characterized by the absence of goblet cells in the integument epithelium, as well as the main, parietal and goblet cells in the epithelium of the glands while preserving all types of neuroendocrine cells;
3. the base form differs from the cardial mainly by the presence in the epithelium of glands of the main and parietal cells;
4. The indifferent form or "variegated" includes focal features of all the forms mentioned above.

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

In children, cardiac (50% of cases) and characteristic (38%) forms of Barrett's esophagus are more often encountered, less often - fundal (3.5%) and indifferent (2.5%),

Particular attention is paid to detecting dysplasia in metaplastic titelia and determining its degree, since it is known that dysplasia, especially of "high" degree, is a morphological marker of possible malignancy. At present, there are criteria for verifying the degrees of dysplasia, well known to morphologists. Usually distinguish three degrees of dysplasia. Sometimes there are two options: high and low dysplasia. The frequency of detection of dysplasia in the Barrett's esophagus, according to different authors, ranges from 12.9% to 45% of cases. The most common malignancy of the dysplastic epithelium of Barrett's esophagus occurs in individuals with a prior indifferent form - 77.2%.

Proceeding from the foregoing, it is not difficult to imagine the risk situation for the development of malignancy in the Barrett's esophagus: an indifferent form with dysplasia of the 3rd (high) degree.

Analyzing the obtained morphological data, one should remember about possible overdiagnosis of the Barrett's esophagus and exaggeration of the risk of development of adenocarcinoma of the esophagus. So in one of the studies it was found that in 95% of patients with gastroesophageal reflux the cylindrical epithelium is determined at a distance of 3 cm or more above the Z-line. These data allow us to ask a logical question: is always the detection in the esophagus of the gastric epithelium of the fundal (and, especially, of the cardiac) type predictive for us in the aspect of carcinogenesis?

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

3. Additionally, immunohistochemical and histochemical methods of investigation, which are carried out in a number of cases, also help in diagnosis, acting as prognostic markers for possible malignancy. So in the parenchyma in 86.3% of patients with adenocarcinoma of the esophagus were found sulphomucins, the production of which was fixed and at the third degree of dysplasia in retrospective study. In addition, it has been proven that malignantiation leads to the displacement (or suppression) of neuroendocrine cell lines by tumor cells.

To specific markers of the epithelium, Barrett is also referred to as Saccharra-isomaltase.

In the work of MacLennan AJ.etal. 100% expression of villin in patients with Barrett's esophagus is shown. Willin is a marker of cell differentiation in the small intestine and his research is very promising in terms of diagnosing intestinal metaplasia in the Barrett's esophagus.

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

4. X-ray examination allows you to confidently diagnose the "classic" version of Barrett's esophagus, which suggests the presence of stricture in the middle part of the esophagus, Barrett's ulcer and large hiatal hernia. The variant of the "short" esophagus has its own clear radiographic criteria. With double contrasting, two types of mucosal relief are distinguished: meshy and smooth. However, a number of authors indicate a low sensitivity and specificity of this finding and note that every third patient with Barrett's esophagus has no deviations on the roentgenogram.

X-ray examination remains one of the decisive methods in the diagnosis of gastroesophageal reflux and GERD, since it allows confident enough to diagnose reflux as such, reflux-eeophagitis and hernia of the esophageal aperture of the diaphragm. Indirect signs of gastroesophageal reflux can be a decrease in the size of the gas bubble of the stomach and rectification of the angle of the Hisnia. 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. With this technique, it is possible not only to fix a modification of the esophagus (lowering the pH below 4.0), but also to determine the severity of the GER, to determine the effect of various provoking factors on its occurrence. Despite the fact that this method does not allow "directly" to suspect Barrett's esophagus, it rightfully remains one of the components of the algorithm for examining a child with GERD, whose complication is Barrett's esophagus.
6. Radioisotope methods are used in clinical practice much less often than the above.
7. Genetic Screening. Over the past two decades, foreign literature has published papers suggesting the possible family character of Barrett's esophagus, in particular, several families have been described in which Barrett's esophagus was found in more than one generation in several people. So V.Jochem et aL. Barrett's esophagus was observed in 6 members of the same family in three generations. The authors put forward the theory of the genetic predisposition of 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 adenocarcinoma of the esophagus. Carcinogenesis in the Barrett's epithelium is associated with a series of genetic disorders that activate oncogenes and render incompetent tumor suppressor genes. The marker of the development of this pathology in the Barrett's esophagus is the loss of hetero-eutogenicity of a number of genes, primarily tumor-suppressor genes p53, p21 and erbB-2. Disturbance of the structure of DNA (aneuploidy) of the cells of the epithelium of the esophagus is the second most important marker of possible carcinogenesis.

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