Leukoplakia of the esophagus

If the epithelial layer of the mucous tissue of the upper digestive tract begins to intensely keratinize, then they talk about the development of esophageal leukoplakia. At the initial stage of the disease, a dense plaque is formed, which lends itself to removal and is practically not accompanied by signs of an inflammatory process. Over time, destructive changes in the mucous membrane appear on the cheeks, tongue, and in the mouth. If untreated, there is a high risk of developing a malignant process. [1]

Epidemiology

If we consider the general statistics of treatment of patients with esophageal leukoplakia, then the disease is most often found among the age group of patients from 30 to 70 years old, and more in males (more than 4% in men compared to 2% in women).

For every hundred cases of patients with diagnosed leukoplakia, up to 6% of precancerous pathologies and up to 5% of early stages of cancer can be accounted for. We are talking mainly about patients with verrucous and erosive-ulcerative type of leukoplakia of the esophagus: in such patients, the precancerous state is able to retrain into an invasive squamous cell cancer process.

Initial or progressive carcinoma of the mucous tissues of the esophagus due to intense keratinization is sometimes similar to leukoplakia. Given this, any person with suspicion of this disease is sent for histological and other studies, for the timely diagnosis of a precancerous or malignant condition.

It should be noted that esophageal leukoplakia is an extremely rare pathology when compared with oral leukoplakia. We can say that quite often these two diseases are identified, due to the commonality of clinical manifestations. In some countries, for a more accurate formulation of the diagnosis, the term "esophageal leukoplakia" is replaced by the term "epidermoid metaplasia of the esophagus".

Causes leukoplakia of the esophagus

Experts have not yet determined the exact etiology of the development of esophageal leukoplakia. However, even now we can confidently say that pathology occurs under the influence of mainly external damaging factors - in particular, thermal, mechanical or chemical irritation. The risks of the onset of the disease are significantly increased under the influence of several similar factors simultaneously. For example, leukoplakia of the esophagus and the oral cavity is often found in "hard" smokers: their mucous membrane is regularly exposed to both thermal and chemical effects of nicotine tar and cigarette smoke. [2]

If we consider in more detail, then the following reasons can lead to the development of esophageal leukoplakia:

• neurodystrophic disorders affecting mucous tissues;
• chronic inflammatory processes of the skin and mucous membranes, the digestive system;
• genetic predisposition (the so-called "familial" dyskeratosis);
• hypovitaminosis of vitamin A;
• involution of mucous tissues;
• hormonal disturbances, prolonged or severe hormonal imbalance;
• infectious lesions of the oral cavity and digestive tract;
• harmful occupational influences, including chronic occupational diseases;
• smoking, alcohol abuse;
• the use of excessively hot food, the abuse of hot seasonings and spices;
• systematic dry food intake, regular use of rough, dry food;
• dental diseases, the presence of dental implants;
• violations of the dentition or the absence of teeth, which does not allow chewing food in a quality manner;
• pathologically weakened immunity.

Risk factors

The risk group for the incidence of esophageal leukoplakia includes people over 30 years old. In childhood, pathology occurs much less frequently.

Experts identify a number of factors that can contribute to the appearance of this violation:

• viral diseases, carriage of viral infections (in particular, herpesvirus, etc.);
• infectious and inflammatory pathologies, especially with a long or chronic course;
• regular mechanical, chemical or thermal injuries (frequent repetitive gastroduodenoscopy procedures, eating too coarse dry food, or hot food, drinking aggressive liquids - for example, strong alcohol, etc.);
• systematic smoking;
• regularly provoking vomiting (for example, with eating disorders);
• occupational hazards and pathologies (inhalation of chemical vapors, dust, work with acids and alkalis);
• impaired absorption of vitamins, lack of intake of vitamins in the body;
• a sharp or severe weakening of the immune defense (in particular, in patients with HIV and other immunodeficient conditions);
• hereditary factor (the presence of a similar pathology in close relatives).

In addition to the immediate causes of the appearance of esophageal leukoplakia, doctors highlight the special importance of risk factors that are associated with a genetic predisposition, individual characteristics and the patient's lifestyle. Timely correction or elimination of these factors can become an effective step in the prevention of this pathology: a systematic consultation with a therapist or gastroenterologist helps patients not only learn more about their state of health, but also detect the pathology as early as possible. If necessary, the doctor will immediately prescribe the appropriate diagnostic procedures and provide targeted treatment. [3]

Pathogenesis

The formation of pathological foci of leukoplakia of the esophagus is influenced by various etiological factors that have a negative effect on mucous tissues and the body as a whole. However, the pathogenetic mechanism of the disease has not been thoroughly studied: the involvement of interferons and other immunity mediators in the pathogenesis does not prove the specificity of the development of leukoplakia.

Presumably, under the influence of certain stimuli, the expression of an adhesion protein specific to epithelial tissue is disrupted. This leads to an increase in the intercellular interaction of epithelial cells, which activates the processes of cellular hyperdifferentiation.

It follows from this that excessive keratinization, physiologically abnormal, occurs, and at the same time, cellular "maturity" increases with suppression of apoptosis. As a result of these processes, keratinized cells, “long-livers”, "attached" to each other, do not peel off, dense hyperkeratotic layers are formed. [4]

Over time, as a result of various external influences, destructive changes occur in the tissues, which leads to increased cell proliferation in the basal layer. It is noteworthy that all of the above processes occur without activating the reactivity of the immune system, which is typical for leukoplakia. Considering this, the treatment of pathology should be based on the normalization of intercellular interactions.

Symptoms leukoplakia of the esophagus

For many patients, leukoplakia of the esophagus is accompanied by a pronounced decrease in the quality of life, and the danger of malignancy of the disease negatively affects the general psychological status of patients.

The main types of esophageal leukoplakia are:

• flat, or simple leukoplakia of the esophagus;
• verrucous type of disease;
• erosive and ulcerative type;
• mild leukoplakia.

Simple leukoplakia occurs most often. During an external examination, it is usually not possible to detect any pathological abnormalities. Palpation of enlargement of nearby lymph nodes is absent. During the examination of the pharyngeal area, the doctor pays attention to the mucous membrane, which normally should be sufficiently moist, shiny, and have a pale pink color. When leukoplakia of the esophagus spreads to the pharynx and oral cavity, limited light spots are formed that have clear configurations, without bulges (a kind of whitish film that cannot be separated). Often, keratosis zones spread further - to the inner surface of the cheeks and lips. Important: it is impossible to remove a whitish spot, even with the use of force.

The verrucous type of esophageal leukoplakia can develop from a simple (flat) type of pathology. Patients voice complaints of a burning sensation behind the breastbone, persistent perspiration or dryness in the throat, a feeling of discomfort when swallowing food (especially when eating dry food). Pain and other symptoms are not found. During the survey of patients, the presence of bad habits (smoking, alcohol abuse), concomitant diseases of the digestive, endocrine or cardiovascular systems is revealed.

The verrucous type of leukoplakia can occur in two variants:

• plaque leukoplakia of the esophagus (accompanied by the formation of white plaque-like foci);
• warty leukoplakia of the esophagus (dense growths are formed like warts).

It is possible to notice such changes in the mucosa only when performing endoscopy, or when the process spreads to the back of the tongue and its lateral surfaces, to the oral cavity, alveolar process, palate.

In the plaque variant, the pathological foci are limited, protrude slightly above the mucosal surface, differ in irregular configuration and clear contours.

With the warty variant, a tubercle appears above the mucous membrane, dense, it is impossible to form a fold on it. The color of the elevation ranges from whitish to deep yellow.

For the erosive type of leukoplakia of the esophagus, the formation of erosive defects and cracks is characteristic, which becomes a consequence of the lack of treatment for simple or verrucous pathology options. Due to obvious tissue damage, the patient develops pain, a burning sensation, induration, pressure. Pain occurs after exposure to absolutely any irritant - in particular, while eating and drinking. Bleeding of wounds is possible.

The first signs of esophageal leukoplakia in all people are manifested differently. Quite often, the problem appears without obvious symptoms, since it can exist unnoticed for many years.

In other cases, leukoplakia makes itself felt with certain sensations of discomfort - for example, difficulty with swallowing, tickling and burning sensation behind the breastbone, etc. However, these signs appear, as a rule, at a relatively late stage of the disease. [5]

Stages

The stages of leukoplakia of the esophagus and oral cavity are determined by the type of disease:

1. At the first stage, light films appear on the mucous membrane, which cannot be removed with a swab. Other pathological signs are usually absent. Treatment at this stage is most effective, since only the submucous layer of the esophagus is affected.
2. The second stage is characterized by the appearance of raised tubercles, which can spread and merge. At the same time, the nearest lymph nodes can be affected.
3. At the third stage, microdamages in the form of cracks or erosion are formed in the area of the tubercles. Additional painful signs appear, such as pain, burning, provoked by particles of food and drinks entering the wounds. Against the background of constant discomfort, the patient's psycho-neurological state is disturbed, irritability and insomnia occur. Significant narrowing of the esophagus is possible.

The clinical picture at one stage or another of the leukoplakia of the esophagus can manifest itself both comprehensively and singly, since it depends on many factors: on the presence of other pathologies, on the individual characteristics of the patient, on the prevalence of the painful process, etc. Therefore, when discomfort occurs during or after use food requires professional advice from a doctor of the appropriate profile - in particular, a gastroenterologist or dentist.

Forms

The modern classification presented by the World Health Organization divides leukoplakia into a homogeneous and inhomogeneous form. The non-homogeneous form is also subdivided into erythroplakia, nodular, macular and verrucous types.

There is information that some cases of inhomogeneous leukoplakia in every second case are epithelial dysplasia and have a high risk of malignancy.

There is another classification, which suggests such a concept as "epithelial precancerous condition": it includes erythroplakia and leukoplakia. According to this histological division, leukoplakia is divided into focal epithelial hyperplasia without signs of atypical cells, as well as low, medium and severe dysplasia. Dysplasia, in turn, is characterized as squamous intraepithelial dysplasia (has three degrees of severity).

This classification is used for the pathomorphological description and supplementing the clinical diagnosis.

Complications and consequences

In the absence of the necessary treatment, or with the wrong treatment of leukoplakia, the pathological process grows, the tissues become thickened, which in the future can provoke a narrowing of the esophagus (stable stenosis of the lumen). Typical signs of deterioration are:

• the appearance of hoarseness, wheezing;
• constant coughing for no apparent reason;
• constant sensation of a foreign body in the throat;
• painful sensations, especially when trying to swallow food.

The patient begins to experience difficulties with eating, loses weight, becomes irritable, sleep is disturbed, and working capacity falls.

However, the most complex and dangerous consequence of esophageal leukoplakia can be a tumor process of malignant etiology. Most often, the complication develops against the background of the verrucous and erosive-ulcerative type of the disease. Two forms of esophageal cancer are identified:

• squamous cell carcinoma, which develops from epithelial cells that cover the lining of the esophagus;
• adenocarcinoma that occurs in the lower segment of the esophagus.

Other types of malignant processes in the esophagus are relatively rare.

But at an early stage of development, leukoplakia lends itself well to therapy, which is carried out simultaneously with the elimination of possible irritating factors, including bad habits.

Diagnostics leukoplakia of the esophagus

General diagnosis of esophageal diseases usually includes:

• collection of anamnesis;
• visual examination (inspection);
• esophagoscopy;
• electrocardiography (for differential diagnosis of chest pain);
• X-ray examination of the esophagus;
• esophagomanometry.

Tests include general blood and urine tests. If a malignant transformation is suspected, it is possible to perform a blood test for tumor markers - substances that are formed by tumor cells and are secreted into biological fluids. Tumor markers are most often found in the blood of patients suffering from oncological pathologies. [6]

Instrumental diagnostics is always effective when used in combination with other diagnostic methods. In this case, the main procedure is considered to be an endoscopic examination of the esophagus: a soft endoscope is inserted into its cavity, with the help of which a complete examination of the entire mucous tissue is performed, and even if necessary, a biopsy is taken - a tissue particle for histological analysis.

The endoscopic picture depends on the type of esophageal leukoplakia:

• With a flat form in epithelial cells, acanthosis is noted with proliferative changes in the basal and thorny layers, as well as the phenomenon of dysplasia with the dominance of parakeratosis. Outwardly, this is manifested by the formation of limited whitish spots that look like glued films.
• In the verrucous form, in contrast to the flat one, hyperkeratosis dominates. A typical cellular enlargement of the spine and basal layer is observed, against the background of slight atypia and polymorphism. In the underlying structures, the capillary network expands, there are signs of focal lymphoid infiltration with the presence of few eosinophils and plasma cells. On the mucosa, elevations of various shapes and sizes are found, compacted, of a light shade (in the form of plaques or warty growths).
• With the erosive-ulcerative form, all signs of a chronic inflammatory process with the formation of a histiocytic-lymphoid infiltrate are found. In the layer of defective epithelium, intense hyperkeratosis develops, dysplasia of the basal layer occurs, and ulcerated foci appear. The underlying tissue undergoes cellular infiltration. Endoscopic examination reveals erosion and / or cracks, sometimes bleeding. Erosive foci can have diametrical sizes from one millimeter to two centimeters. [7], [8]

Hyperplastic, parakeratosis, hyperkeratosis changes, an increase in the number of mitoses, a failure of basal polarity, nuclear polymorphism, cellular keratinization, hyperchromatism and other signs are considered by specialists as a precancerous condition. An incorrect ratio of the triad is noted, which includes proliferative activity, cell differentiation and processes of biochemical anaplasia. [9]

Differential diagnosis

The flat type of leukoplakia requires differentiation from the typical course of lichen planus, in which a characteristic morphological structure is found, a symmetrical association of polygonal papules. The predominant localization of pathological elements in lichen planus is the retromolar zone and the red lip border.

The typical type of leukoplakia is differentiated from limited hyperkeratosis, in which a flat area is formed, lined with dense scales and surrounded by a thin light eminence.

The verrucous type of leukoplakia is distinguished from candidal infection . This disease is characterized by the appearance of whitish-grayish films, tightly "sitting" on the mucous tissue. When trying to forcibly remove the film, a bright bleeding ulcerative surface opens. For additional diagnostics, cytological analysis is performed.

The erosive-ulcerative type of leukoplakia requires differentiation from a similar type of lichen planus , in which small nodules appear along the edges of pathological foci (they may also be present on the skin).

In addition, the disease should be distinguished from the manifestations of secondary syphilis, from chronic mechanical damage to the mucous membrane and reflux esophagitis, from chemical and thermal burns of the esophagus. To identify these pathologies, it is important to take into account the configuration of the foci, their elevation above the mucosal surface, the presence of shine, the separation of particles during scraping, the presence of background changes.

When making a diagnosis, it is far from always possible to base the diagnosis on an external examination and collection of the patient's anamnesis. We must not forget about such a variant of pathology as idiopathic leukoplakia of the esophagus, which develops for no apparent reason. In this case, differential diagnosis is especially important.

Not all experts note the need to separate concepts such as leukoplakia of the esophagus and oral cavity : in many ways, these terms are copied. And in the histological decoding, such a reportable symptom as "leukoplakia of the esophagus" may be completely absent: it is much more important for the treating doctor to know the nature of the histological processes - that is, as a result of which the foci of compaction were formed - as a result of atrophy, swelling, infiltration, acanthosis of the median epithelial region, hyperkeratosis surface areas of the squamous epithelial tissue of the esophagus. Information about the presence of atypical cells, dysplasia is also needed. This requires an extended approach to patient examination.

Treatment leukoplakia of the esophagus

Esophageal leukoplakia is most effectively treated with surgery using liquid nitrogen, a laser, or an electric coagulator. At the same time, cryosurgery is considered the most optimal method, since it has a minimal risk of recurrent pathology.

In the course of treatment, it is necessary to apply complex tactics. In addition to cauterization of pathological foci, it is imperative to carry out a course of antibiotic therapy, as well as to follow a strict diet for a long time with the complete exclusion of alcoholic beverages, indigestible, spicy, sour foods.

In general, therapeutic measures for esophageal leukoplakia are local and general.

A prerequisite for effective local action is the neutralization of the damaging factor. For example, the patient should stop smoking and drinking alcohol. If this is not done, then the disease will not only progress, but also the risk of malignancy will significantly increase. Among other important points - compliance with all the rules of oral hygiene, additional sanitizing measures, the use of medications, and, if necessary, the help of a surgeon.

Specialists practice different methods of therapeutic effects on the affected areas with esophageal leukoplakia. The most common and affordable means is the application of an oil solution of vitamin A to the foci of pathology, as well as the internal intake of the combined preparation Aevit (a combination of vitamins A and E).

Radical treatment is prescribed if the leukoplakia of the esophagus has reached a critical stage, or in the case when the use of medications does not have the necessary therapeutic effect. [10]

Surgical treatment is the excision of the affected areas with a scalpel, laser beam (CO ₂  or helium-neon), electrocoagulator, cryodestructor. Several methods of exposure are possible. However, this treatment has its drawbacks: cicatricial changes are formed, tissues are deformed, the functionality of the esophagus is disrupted. Tissue recovery is usually long, the average epithelialization period is about 2 months. In the operated areas, serous edema develops, a weeping scab forms, and cellular activity, protein and carbohydrate metabolic processes are inhibited. All this directly affects the duration of the regeneration period. One more point is also important: even surgical intervention does not guarantee the further absence of relapses and does not reduce the likelihood of developing a malignant formation. [11]

Other cardinal techniques are also used - in particular, low-frequency ultrasound exposure, photodynamic treatment based on the selective destruction of modified tissues by stimulating photosensitive elements.

It should be borne in mind that the possibilities of surgical treatment are limited: first of all, we mean the peculiarities of access to the esophagus, the invasiveness of the intervention, etc. [12]

Medicinal treatment of esophageal leukoplakia

For internal administration, retinol, tocopherol in the form of oil solutions, B-group vitamins (in particular, riboflavin 0.25 g twice a day for a month) are prescribed.

It is possible to use restorative drugs, biogenic stimulants, keratoplastic agents.

Aevit	It is taken for a long time, about 1.5 months, 1 capsule per day. The second course of treatment is after 3 months. Possible side effects: fatigue, sleep disturbance, loss of appetite.
Plazmol	Injected subcutaneously, 1 ml daily or every other day. 10 injections are required for one course of treatment. Some patients may experience hypersensitive reactions to the drug (itching, rashes, fever).
Longidaza	Injected subcutaneously or intramuscularly in the amount of 3 thousand IU. The course requires from five to 25 injections. The interval between injections is 3-10 days. A second course is possible in 2-3 months. Possible side reactions: pain in the injection area, slight redness of the skin.
Lavomax (Tiloron)	The first two days take 125 mg once a day, and then 125 mg every other day. The drug has an immunomodulatory and antiviral effect. Some patients may develop allergies to the components of the drug.
Solcoseryl	Used for intravenous infusion with sodium chloride solution or 5% glucose. The dosage and frequency of administration is determined by the treating doctor. Side effects are extremely rare, slight pain in the injection area is possible.

The volume of therapy is determined by the attending doctor, depending on the form of the course of esophageal leukoplakia, on the size of the foci and on the rate of development of the disease process. Vitamin A is taken orally in the form of 3.4% oil solution of retinol acetate or 5.5% retinol palmitate 10 drops three times a day for 6-8 weeks. Repetition of the treatment course - every 4-6 months.

Physiotherapy treatment

Physiotherapeutic methods include the elimination of esophageal leukoplakia zones using diathermocoagulation or cryodestruction. Diathermocoagulation is performed intermittently, to a state in which the zones of hyperkeratosis are completely coagulated. The healing process lasts 1-1.5 weeks.

Cryodestruction is actively used today in the complex therapy of precancer conditions. The procedure has practically no contraindications; it can also be prescribed to patients suffering from complex systemic pathologies. During cryodestruction, it is possible to use contact freezing in areas that are difficult to access quickly. Temperature indicators of exposure - 160-190 ° C, duration - 1-1.5 minutes. The defrosting period is about three minutes, the healing term is up to 10 days.

Photodynamic treatment of patients with esophageal leukoplakia is considered one of the most advanced methods. It involves the applicator application of photosensitizers to pathologically altered areas. Molecular energy concentration occurs during light exposure to waves of a certain wavelength (in accordance with the absorption limit of the dye). When released, it affects the transition of molecular oxygen from the external environment into active unstable forms - in particular, into singlet oxygen, which can destroy a microbial cell. This is a relatively new physiotherapy technique, which is not yet available in all medical institutions.

Herbal treatment

Alternative treatments for esophageal leukoplakia are not always appropriate and effective. They may only be used after approval from the attending physician. The fact is that untimely and incorrect use of medicinal plants can worsen the course of the pathological process, aggravate existing problems with the gastrointestinal tract, and cause the development of complications.

Meanwhile, the following alternative recipes are most successfully used for leukoplakia of the esophagus:

• Hemlock. [13]The inflorescences of the plant are crushed, loosely poured into a half-liter jar to the top, filled with vodka and covered with a lid. Kept in the refrigerator for three weeks. Then the tincture is filtered and taken according to the following scheme: for the first day, 2 drops of the tincture are taken in 150 ml of water, then the dose of the drug is increased by one drop every day, bringing to 40 drops per dose. After that, the amount of funds is again reduced to the original 2 drops.
• Infusion of pine needles. Fresh pine needles are collected, put into a thermos and filled with boiling water (130 g of needles per 500 ml of boiling water). Insist for 8 hours (ideally leave overnight). Then the medicine is filtered and the intake is started, drinking a couple of sips during the day in several approaches. It is advisable to prepare a fresh infusion for every day.
• Carrot and beet juice. Freshly squeezed juice from carrots and beets (about 50:50) is prepared and drunk daily, on an empty stomach, an hour before meals, 150 ml each.

Alternative medicine is best used as an adjunct to traditional treatments. It is not worth relying only on alternative recipes, especially when it comes to advanced stages of esophageal leukoplakia.

Prevention

Prevention of the development of esophageal leukoplakia involves quitting smoking, drinking alcoholic beverages, limiting the diet of spicy and acidic foods, regularly performing hygiene procedures to cleanse the oral cavity, timely treatment of any pathologies of the digestive tract. The above set of measures is supplemented with a long-term intake of an oil solution of vitamin A, or other vitamin preparations:

• Aevit - a complex of oil solutions of vitamins A and E;
• Asepta is a complex combination of vitamins, corral calcium, coenzyme Q10, herbal extracts.

Herbal extracts and essential oils of natural origin have a positive effect on the condition of the oral cavity and the whole body in general. It is recommended to use high-quality toothpastes with an antibacterial effect, which protect the mucous membrane from pathogenic bacteria and do not have a negative impact on the beneficial microflora.

It is useful to regularly rinse your mouth and consume herbal teas based on chamomile, sage, calendula, as well as other plants that have anti-inflammatory and regenerating properties.

Sea buckthorn extract and geranium essential oil are considered an excellent prophylactic agent. These funds help to maintain the normal state of the esophageal mucosa, and also have fairly strong antiseptic properties.

Forecast

Treatment for esophageal leukoplakia is carried out using various methods. In mild cases, conservative therapy can be dispensed with, based on the intake of fat-soluble vitamins (in particular, vitamin A), as well as on strengthening the body's natural defenses. The course of the pathology itself is unpredictable and individual for each patient: some sick people live with the initial stage of the disease until the end of their lives, without complaining of discomfort and worsening of their condition. And in other patients, a squamous cell cancer process may develop within a year.

If there is a suspicion of the lack of effectiveness of conservative therapy, then the doctor prescribes surgical intervention with the removal of pathological foci and their thorough histological examination.

If untreated, the risk of developing a malignant pathology increases significantly. That is why the leukoplakia of the esophagus belongs to the category of precancerous conditions. Especially dangerous in this sense is the ulcerative and verrucous type of leukoplakia, as well as the spread of pathology to the area of the tongue.