Chromoendoscopy of the esophagus and stomach

Chromoendoscopy is a method of endoscopic examination of the gastrointestinal tract (GIT) with staining with various dyes safe for humans of suspected pathological superficial changes in the mucous membrane of the organs being examined, allowing to identify and differentiate minimal pathological changes in the epithelium of the mucous membrane by means of a comprehensive visual examination through an endofibroscope and histological examination of targeted biopsy materials. Sometimes the chromoendoscopy method is defined as a method of staining the epithelial structures of the GIT, used in examining patients during an endoscopic examination.

In order to increase the efficiency of cancer diagnostics, as well as differential diagnostics of benign and malignant lesions of the esophagus and stomach during endoscopic examinations of these organs, doctors from different countries, along with visual examination of the condition of the mucous membrane and multiple targeted biopsies to obtain more accurate material for histological and/or cytological examination, are now increasingly using so-called “vital” dyes, resorting to an additional method of examining patients - chromoendoscopy.

As early as 1966, a report was presented at the First World Congress of Gastroenterologists, the essence of which was to emphasize the expediency of using chromoendoscopy in examining patients by spraying methylene blue dye on the surface of probable pathological changes in the mucous membrane during gastroscopy with subsequent comprehensive assessment of these changes in the gastric mucosa. Later, chromoendoscopic examination of the esophagus and stomach began to be considered as an addition to the usual endoscopic examination, and was also increasingly used when examining other organs of the gastrointestinal tract. Currently, chromoendoscopy of the gastrointestinal tract is becoming increasingly widespread in the practice of examining patients.

Usually, when performing chromoendoscopy, depending on the available capabilities and contraindications for the use of various dyes when examining specific patients, Lugol's solutions, methylene blue, toluidine blue, Congo red or phenol red and others are used to diagnose gastrointestinal lesions, including the esophagus and/or stomach, among which absorbent dyes and reagents are sometimes distinguished.

Absorbent dyes (Lugol's solution, methylene blue, toluidine blue) are captured by special epithelial cells, which allows for the detection of pathologically altered areas of the gastrointestinal mucosa. The use of contrast dyes (Congo red, phenol red) in examining patients with the gastrointestinal tract makes it possible in a significant number of cases to distinguish pathologically altered areas of the epithelium from unaltered areas of the gastrointestinal mucosa; these dyes are most often used in endoscopy performed with magnification. Reactive substances allow for the detection of certain variants of the secretion, with which they enter into a chemical reaction, leading to a change in the color of the mucosa.

Chromoendoscopy of the esophagus makes it possible to detect squamous cell carcinoma of the esophagus, adenocarcinoma in the distal esophagus (the so-called "Barrett's cancer"), in the stomach - early cancer in risk groups (in patients with pernicious anemia, in patients with a history of squamous cell carcinoma of the ENT organs, with achalasia of the cardia, with chemical burns of the esophagus, as well as among people with an "operated" stomach). Chromoendoscopy is also indicated in the diagnosis of early cancer before endoscopic mucosectomy to accurately determine the tumor boundaries. In such cases, it is most justified to use Lugol's solution as a dye. Lugol's aqueous solution (10 ml of 1-4% potassium iodine solution) reacts with glycogen of the normal squamous multilayered epithelium of the esophageal mucosa and changes its color. Absorption of Lugol's solution by normal glycogen-containing cells helps to distinguish the boundaries of healthy tissue, dysplastic and neoplastic cells that do not contain glycogen and therefore are not stained with this dye. Before performing chromoendoscopy, it is advisable to rinse the organ being examined with water to wash away mucus, then apply the solution used to the mucous membrane.

Unchanged, non-keratinized epithelium after application of the dye acquires a black, dark brown or greenish-brown color after 2-3 seconds. The structure of the unchangeable mucous membrane is "wrinkled". The areas of leukoplakia localization become dark brown when stained. After 5-10 minutes, the stained areas of the mucous membrane (in the absence of additional effects on it) fade. It is necessary to remember that only healthy cells of the squamous epithelium of the esophagus are stained and cells with pronounced inflammation (in esophagitis), dysplasia and/or cancer are not stained. Due to this, staining with Lugol's solution allows to identify unchanged squamous epithelium of the mucous membrane (positive staining) against the background of malignant epithelium (no staining). The absence of staining of the mucosal epithelium indicates a decrease in glycogen in the cells of the nonkeratinizing epithelium in severe inflammation, dysplasia, metaplasia, and early cancer. Glandular epithelium or metaplasia of the epithelium of Barrett's esophagus are also not stained with Lugol's solution. This method increases the sensitivity, specificity, and accuracy of endoscopic detection of Barrett's esophagus by 89, 93, and 91%, respectively.

It is necessary, however, to remember that differential diagnostics of inflammation, dysplasia and cancer based on staining alone is impossible. Therefore, after chromoscopy, multiple targeted biopsy of the detected pathological areas of the mucous membrane is indicated (regardless of the organ being examined).

Indications for esophageal chromoendoscopy: suspected Barrett's esophagus; follow-up examination of patients with Barrett's esophagus to detect possible foci of dysplasia and cancer (primarily patients from high-risk groups: squamous cell carcinoma of the esophagus, squamous cell carcinoma of the ENT organs in the anamnesis, achalasia of the cardia). Contraindications for the use of Lugol's solution - allergic reaction to iodine, hyperthyroidism; side effects - allergic reactions, irritation of the throat (in the form of a burning sensation, tingling, pain).

Methylene blue is a dye that stains blue the absorptive epithelial cells of the small and large intestine mucosa, areas of incomplete and complete intestinal metaplasia in the esophagus and stomach, except for metaplasia of the cardiac type of columnar epithelium. The main indication for the use of this dye is the diagnosis of Barrett's esophagus.

Methylene blue does not stain the unchanged flat multilayered epithelium of the esophagus, but it stains unevenly or insufficiently uniformly dysplasia and cancer within the actively absorbing epithelium. As a rule, after staining the mucosa in Barrett's esophagus, a mosaic picture of cylindrical epithelium of the cardiac type and intestinal metaplasia is revealed. It should be remembered that Barrett's cancer develops mainly in the area of intestinal metaplasia localization.

To obtain full results when performing chromoendoscopy with methylene blue, there are several options for "preparing" the mucous membrane of the esophagus and stomach before applying the methylene blue solution. First, the stomach should be cleared of mucus, which can also be stained with methylene blue. For this purpose, 2 hours before the endoscopic examination, patients are recommended to take 1.5-2 g of baking soda dissolved in 50 ml of warm water, then 1 hour before the examination - 50 ml of a 0.25% aqueous solution of methylene blue. After this, esophagogastroscopy (EGDS) is performed using the usual method. When performing an endoscopic examination, it is advisable to carefully assess the presence or absence of staining of the mucous membrane of the esophagus, stomach, identify the intensity of staining, the location and boundaries of the stained areas of the mucous membrane of the stomach and esophagus.

According to another method of preparing the gastric mucosa of patients for chromoendoscopy, a solution of acetylcysteine is first applied to remove superficial mucus, the action time of which is 2 minutes, then a 0.5% solution of methylene blue is applied. According to the next variant, chromoendoscopy with methylene blue can be successfully performed after spraying mucolytic solutions to wash out the gastric mucus, as well as to remove excess dye.

The method of endoscopic chromoscopy using a 0.5% solution of methylene blue is quite informative, especially after the endoscopist has been prepared for such a study and with his persistent desire to identify and recognize the nature of pathological changes in the mucous membrane of the esophagus and stomach in each specific case.

When preparing a patient for esophageal chromoendoscopy, instead of a mucolytic (pronase), 20 ml (for every 5 cm of the esophagus) of a 10% solution of N-asetylousteine can be sprayed through the catheter. Then it is advisable to introduce a 0.5% solution of methylene blue. Excess dye should be washed off with 50-120 ml of water or saline after 2 minutes. Staining of the mucous membrane is considered positive when a blue or violet color appears, which persists despite subsequent washing off of excess dye with saline or water. After this, an endoscopic examination of the organ under examination and targeted biopsies of pathological areas of the mucous membrane are performed.

The essence of the mucous membrane staining mechanism is the penetration of methylene blue to a significant depth through wider intercellular channels of tumor tissue (compared to the unchanged mucous membrane). Spraying methylene blue over the mucous membrane results in the blue staining of cancer areas, clearly highlighting them against the background of the unstained mucous membrane of the organ being examined. It is necessary to remember that methylene blue can also stain areas of intestinal metaplasia of the gastric mucous membrane.

Methylene blue staining of the esophageal mucosa allows one to suspect the presence of specialized intestinal-type cylindrical epithelium against the background of stratified squamous epithelium of the esophagus (based on the results of histological examination of fragments of targeted biopsies with positive staining of the mucosa), to detect dysplasia and/or early cancer based on the materials of histological examination of fragments of targeted biopsies (with weak, heterogeneous staining or in the absence of staining with methylene blue in the area of localization of specialized cylindrical epithelium on the esophageal mucosa).

Methylene blue selectively stains specialized columnar epithelium, which allows diagnosing Barrett's esophagus even in patients with very short segments of the lesion. In Barrett's esophagus, methylene blue accumulation by cells can be focal or diffuse (more than 75-80% of the mucous membrane of Barrett's esophagus is stained blue). Most of the esophageal mucosa in patients with a long segment (more than 6 cm) in Barrett's esophagus is usually stained diffusely.

Severe dysplasia or endoscopically undetectable adenocarcinoma based on visual examination through an endofibroscope in Barrett's esophagus can be detected by histological examination of materials from multiple targeted biopsies obtained from lighter areas of staining on a blue background of dye accumulation by the esophageal mucosa. Reliable morphological signs of the mucosa of Barrett's esophagus are the presence of specialized prismatic epithelium in the form of crypts or villi covered with prismatic cells secreting mucus and goblet cells in the esophageal mucosa. This method is more effective in differentiating benign and malignant lesions of the esophageal and gastric mucosa, in the complex use of methylene blue and Congo red solutions for staining the mucosa.

Despite the fact that methylene blue is a non-toxic compound with a duration of action of 3 minutes, it is still advisable to warn patients about the possibility of the appearance of blue-green colored urine and feces (side effect) 24 hours after the examination.

Toluidine blue is used as a 1% solution when examining patients with lesions of the mucous membrane of the esophagus and stomach. Before performing chromoendoscopy (before staining with a 1% aqueous solution of toluidine blue), suspicious areas of the mucous membrane where pathological changes are suspected are sprayed with a 1% solution of acetic acid, which has a mucolytic effect, followed by washing off excess dye.

Toluidine blue is used in the examination of patients with Barrett's esophagus to detect areas of metaplasia in the esophageal mucosa. However, it should be remembered that when staining the esophageal mucosa with this dye, it is not possible to visually differentiate gastric metaplasia from intestinal metaplasia through an endofibroscope. Staining the periulcerous zone of the mucosa in blue can help differentiate a benign ulcer from an ulcerated "ulcer-like" cancer.

Congo red is a pH indicator. During chromoendoscopic examination of the stomach, this dye is used as a 0.3-0.6% solution, and it can be used alone or in combination with methylene blue. These dyes are used sequentially when examining patients. First, the gastric mucosa is stained with Congo red to identify areas of mucosal atrophy with areas of "misregulated" mucosal relief. Then, the mucosa is stained with methylene blue to determine intestinal metaplasia that accumulates the dye. Congo red as a 0.1% solution and 20 ml of a 5% sodium bicarbonate solution are applied to the surface of the mucosa, then tetragastrin is administered intramuscularly, then after 15 and 30 minutes, an endoscopic examination of the gastric mucosa is performed (after further changes in the color of the mucosa have ceased). Early gastric cancer is defined as a “bleached” area of the mucous membrane that is not stained by the two dyes mentioned above.

Phenol red is used as a 0.1% solution during gastric chromoendoscopy. During endoscopic examination, a 1.1% solution of phenol red and 5% urea are distributed evenly over the surface of the gastric mucosa, the result is assessed 2-4 minutes after application of the dye. The clinical application of this dye is the detection of Helicobacter pylori (HP) contamination of the gastric mucosa, based on the ability to determine HP by an increase in the level of urease produced by HP. A change in the color of the mucosa from yellow to red indicates the presence of HP, while areas of gastric metaplasia do not change their color.

Indigo carmine is a dye that is not absorbed but deposited in the recesses of the folds of the mucous membrane, which creates a contrasting surface. Due to this, the visibility of the heterogeneity of the changed areas is improved. Before chromoendoscopy with indigo carmine, the mucous membrane is preliminarily washed with water to remove mucus, then a 0.1-1% solution of indigo carmine is applied to the mucous membrane of the organ being examined, after which an endoscopic examination of the mucous membrane is performed with subsequent (if necessary) targeted biopsies. The main indications for biopsies: detection or suspicion of early gastric cancer; detection of atrophy of the villi of the duodenum in celiac disease; detection of pathological changes in the mucous membrane of the esophagus.

The so-called "Zoom endoscopy" (endoscopy with magnification) is useful when examining patients for more precise endoscopic revision of suspicious areas, especially after staining the mucous membrane. Increased contrast of the mucous membrane is possible by preliminary application of acetic acid (before staining) to the mucous membrane.

Unfortunately, according to our observations, chromoendoscopy does not always provide more information about the condition of the human gastrointestinal tract than a conventional endoscopic examination. Obviously, therefore, after a visual examination of the condition of the mucous membrane of the examined gastrointestinal organ, it is recommended to perform a targeted biopsy to obtain material for histological or cytological examination. To some extent, a certain "negative" attitude of endoscopists to chromoendoscopy is also due to the need to involve additional medical personnel, which leads to an increase in the duration of endoscopic examination of patients.

Prof. Yu. V. Vasiliev. Chromoendoscopy of the esophagus and stomach // International Medical Journal - No. 3 - 2012

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