RU2564432C1 - Method of treating oral proliferative verrucous leukoplakia - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: 30 minutes before a cryodestruction procedure, 1% nicotinic acid 0.5 ml is introduced under the mucous membrane of a leukoplakia lesion by means of a tuberculin syringe.

EFFECT: higher clinical effectiveness and reduced rate of recurrences of the disease by increasing a freezing depth of the involved tissues and enlarging a cryonecrosis area.

12 dwg, 1 ex

Description

The invention relates to medicine, namely to dentistry, and can be used in the treatment of verrucous form of leukoplakia of the oral mucosa (COP).

Oral cancer in terms of prevalence takes eighth place among all malignant neoplasms, the appearance of which is often preceded by precancerous conditions, such as leukoplakia. Leukoplakia is based on chronic inflammation, accompanied by a violation of keratinization, including hyperkeratosis and parakeratosis. Leukoplakia is an optional precancer; the verrucous form is malignant in 20-30% of cases, which requires active treatment tactics using modern methods.

There is a method of treating Verrucous leukoplakia of COPD by surgical excision (Borovsky E.V. Diseases of the mucous membrane of the oral cavity and lips / E.V. Borovsky, A.L. Mashkillayson. M .: Medicine, 2001. - 320 p.).

The disadvantage of this method is the high morbidity.

The closest in technical essence to the technical result achieved (prototype) is a method for the treatment of Verrucous leukoplakia of COPD by cryodestruction (Filyurin M.D., Tokmakova S.I., Bashtova A.A., Voblova T.V., Melnikov A.A. , Ulko TN Cryotherapy of periodontal and oral mucosa diseases with new porous autonomous applicators from titanium nickelide / Materials of the 6th international conference of maxillofacial surgeons and dentists. - S.-Pb., 2001. - P.124 )

The disadvantage of this method is the low efficiency, because relapses are possible due to insufficient depth of freezing of the affected tissues, which limit the use of cryodestruction in the practice of treating the verrucous form of leukoplakia.

The authors propose a highly effective method for the treatment of Verrucous leukoplakia of COP, which allows to increase the depth of frozen affected tissues and the cryonecrosis zone, as a result of which to increase the effectiveness of treatment and reduce the recurrence rate of the disease. The inventive method differs from the prototype in that the preliminary introduction of nicotinic acid allows to increase the depth of the frozen affected tissues and the cryonecrosis zone, thereby increasing the effectiveness of treatment and reducing the frequency of relapse of the disease.

The technical result of the proposed method is to increase the efficiency of the method due to the combined use of cryodestruction and a solution of nicotinic acid.

The technical result is achieved by the fact that before 30 minutes before cryodestruction, 0.5 ml of a 1% nicotinic acid solution is injected under the mucous membrane of the leukoplakia lesion using a tuberculin syringe.

The method is as follows.

The inventive method is illustrated by figures 1-12 in the form of pictures, from 3 to 8 figures are pictures from laboratory animals.

The figure 1 presents the introduction of a solution of nicotinic acid under the outbreak of verrucous leukoplakia of the mucous membrane of the tongue.

The figure 2 presents the cryodestruction of the focus of verrucous leukoplakia of the mucous membrane of the tongue with liquid nitrogen using an autonomous applicator made of porous titanium nickelide.

The figure 3 presents a frozen portion of the mucous membrane of the mouth of a laboratory animal immediately after cryotherapy.

The figure 4 shows the ulcer of the mucous membrane of the mouth of a laboratory animal, covered with fibrinous plaque 1 day after cryotherapy with the preliminary introduction of nicotinic acid.

The figure 5 shows necrosis of the epithelial layer and the mucous membrane itself, pronounced inflammatory cell infiltrate 1 day after cryodestruction, stained with hematoxylin and eosin, an increase of 100.

The figure 6 shows the beginning of the regeneration of the ulcer along the edges of the defect, the immature epithelium on day 11 after cryotherapy with nicotinic acid, stained with hematoxylin and eosin, magnification × 100.

The figure 7 shows the complete epithelization of cryoran on day 11 after cryotherapy in the control, stained with hematoxylin and eosin, magnification × 100.

The figure 8 presents the verrucous form of leukoplakia of the mucous membrane of the lower surface of the tongue.

The figure 9 shows the introduction of nicotinic acid under the focus of verrucous leukoplakia of the mucous membrane of the tongue.

The figure 10 shows the cryodestruction of the site of verrucous leukoplakia of the mucous membrane of the tongue with liquid nitrogen using an autonomous applicator made of porous titanium nickelide.

The figure 11 shows the regeneration of cryoran along the edges of the defect on the 11th day.

The figure 12 shows the mucous membrane of the lower surface of the tongue 1 year after treatment.

0.5 ml of a 1% nicotinic acid solution is injected under the mucous membrane of the leukoplakia lesion (Fig. 1) using a tuberculin syringe, after 30 minutes the lesion is subjected to cryodestruction (Fig. 2) with liquid nitrogen using an autonomous applicator made of porous titanium nickelide. Exposure to cryotherapy is 90-120 seconds.

To study the dynamics of structural changes in the oral mucosa after the combined use of cryodestruction and nicotinic acid, an experiment was conducted on laboratory animals - 12 chinchilla rabbits from 1.3 to 1.5 years old, weighing from 4.9 to 5.6 kg. The experimental group consisted of 6 rabbits, in which cryotherapy with liquid nitrogen in combination with nicotinic acid was used on the mucous membrane of the mouth, the control group consisted of 6 rabbits, in which cryotherapy with liquid nitrogen was used without oral injection of nicotinic acid.

The same living conditions were created for all animals: feeding, light regime, and climatic conditions with an inert habitat. To anesthetize all manipulations, a 2.5% droperidol solution was administered intramuscularly at a rate of 1 mg per animal.

Then, the mucous membrane was subjected to cryotherapy with liquid nitrogen for 60 seconds using oval cylindrical autonomous applicators of porous titanium nickelide.

Rabbits of the experimental group 30 minutes before cryodestruction under the mucous membrane of the lower lip was injected with 0.5 ml of a 1% solution of nicotinic acid. The control group used the mucous membrane of the upper lip, which was subjected to cryotherapy without prior injection of nicotinic acid.

The objects for morphological studies were sections of the mucous membrane taken from the foci of experimental damage, which were fixed in 10% neutral formalin solution. Material sampling was performed on days 2, 4, 7, 11, and 14. The resulting material was subjected to standard histological processing, pouring in paraffin and staining sections with hematoxylin and eosin, the thickness of the section was 3-5 microns. Biopsies were studied under a Nikon Eclipse E 50 light microscope at a magnification of 100 and 200 times. The healing process was photographed using a Nikon DS-Filc digital camera.

Research results

Immediately after cryotherapy, in the mucous membrane of the studied and control zones of both groups, the formation of a frozen section of white color, exceeding the diameter of the working surface of the tip of the cryoapplicator by 1-3 mm, which thawed for 40-50 seconds (Fig. 3), was noted.

After 1 day in the rabbits of the experimental group, after the combined use of nicotinic acid and cryodestruction, a mucosal defect coated with fibrinous coating was determined in the area of exposure (Fig. 4). Morphologically noted massive necrosis of the epithelium and underlying tissue with dystrophic changes along the edges of the exposure area (Fig. 5). Leukocyte infiltration with a large number of eosinophils penetrating into damaged striated muscle fibers was observed. In the superficial layers of the muscles - dystrophic changes, partial disappearance of myofibrils. The preserved muscle fibers were swollen, the sarcoplasm was homogeneous, the transverse striation was fuzzy. The number of vessels is small, in isolated cases, sludge syndrome is expressed.

In the control group at the COP site, only the phenomena of hyperemia, swelling and petechiae without ulceration were visually determined. At the light-optical level, dystrophic changes in the epithelial layer were noted: rejection of the stratum corneum, loss of layering of the epithelium, vacuolization of epithelial cells to the basal layer with the formation of blisters. Leukocyte infiltration was moderate with the appearance of single lymphocytes and monocytes. Muscle fibers without damage.

On day 4, in the experimental group after the administration of nicotinic acid, the preservation of the ulcer defect covered with fibrinous plaque was observed. Microscopically, the ulcer captured all layers of the COP. Massive leukocyte infiltration reached a depth of 3 mm. At the bottom of the ulcer, necrotic muscle fibers were traced. In the underlying tissues - a small number of vessels and extravasates. In the control group, the appearance of an ulcer with pronounced serous-purulent exudate, which penetrated the entire depth of subepithelial tissues with leukocyte infiltration of the vascular walls, was noted. At the bottom of the ulcer for a greater extent - necrotic muscle fibers.

On the 7th day in the experimental group after applying nicotinic acid, the foci of cryonecrosis were reduced and cleared of necrotic tissues. An epithelial cover appeared with a stratum corneum and signs of regeneration without a clear separation into layers. Under the epithelium, pronounced muscle tissue regeneration, proliferation of fibroblasts, single leukocytes and eosinophils were observed. In myocytes with hyperchromic nuclei, transverse striation appeared. An increase in the number of fibroblasts and fibrocytes was noted. Throughout the study area - leukocyte infiltrate.

In the control group, epithelization as a whole was completed. The tissues have scanty cellular composition, muscle fibers are regenerated, there was no infiltrate.

On the 11th day in the experimental group, when examining foci of frostbite with nicotinic acid, the onset of ulcer regeneration along the edges of the defect was noted, the epithelium was immature (Fig. 6). The bottom is covered with fibrinous-purulent exudate. Throughout, leukocyte-eosinophilic infiltrate was noted, under which granulation-type vessels were formed, some of them thick-walled. The muscle fibers along the edge of the ulcer are completely regenerated, at the bottom of the ulcer - with the initial signs of regeneration.

In the control group, cryoran healing occurred. Microscopic examination noted epithelization, with sections of the epithelium of uneven thickness and incomplete restoration of the surface layer (Fig. 7). There are no signs of inflammation in the submucosal layer. The muscles are completely regenerated with the appearance of striated striation.

On the 14th day in the experimental group, after using nicotinic acid, cryoran was completely epithelized. The epithelium of uneven thickness, partially layered differentiation. The stratum corneum is not expressed throughout. The main part of the muscles is completely regenerated, but the striated striation has not been restored. Dystrophic changes persisted in individual muscle fibers. Extravasates were noted between muscle fibers, and fibroblasts in the deeper layers. Throughout, moderate leukocyte-eosinophilic infiltration.

In the experimental group, complete epithelization with a restored surface layer and uneven thickness was noted. Under the epithelium, muscle fibers are regenerated with restoration of transverse striation.

Thus, the study of the dynamics of the morphological changes in the SOR in the experimental group showed that, with the same exposure to liquid nitrogen, the cryo-damage zone was separated by a demarcation shaft from leukocyte infiltrate and more severe diapedetic hemorrhages than in the control group. Cryonecrosis after preliminary administration of nicotinic acid occurred earlier and was characterized by deeper penetration and damage to the muscle layer. The regeneration of cryoran after the use of nicotinic acid occurred later on 2-3 days compared with the control. This is explained by a deeper freezing of tissues in connection with the intensification of the cryogenic effect with a solution of nicotinic acid, which can contribute to improving the quality of treatment of pathological processes of the oral mucosa.

The inventive method was treated 17 patients. Patient treatment consists of a combination of cryodestruction and a 1% nicotinic acid solution. The method is as follows: 0.5 ml of a 1% solution of nicotinic acid is injected under the mucous membrane of the leukoplakia lesion using a tuberculin syringe, after 30 minutes the lesion is exposed to cryodestruction with liquid nitrogen (temperature - 196 ° C) by autonomous cryoapplicators of porous titanium nickelide according to the method of Filyurin M.D. (1995). Cryoapplication was carried out in a sitting position, without anesthesia. The affected part of the mucous membrane was frozen with full contact of the working surface of the instrument with its surface. The cryoapplicator was selected before it was saturated with refrigerant by applying the instrument to the mucosa taking into account the visual overlap of the size of the pathological element subjected to cryodestruction. Then the cryoapplicator was immersed in a thermos with liquid nitrogen, and after complete saturation was ready for operation. A single cryotherapy cycle of 90-120 seconds was required, depending on the severity of hyperkeratosis. Large surface areas were processed by overlapping cryogenic areas according to the method of the ″ Olympic rings ″ method.

To prevent wound infection, all patients were prescribed rinses with plant-derived antiseptics (calendula, chamomile, St. John's wort decoction) for the first 3-5 days, then, to stimulate tissue regeneration processes, keratoplastics were applied (vitamin A oil solution, solcoseryl).

Clinical example

Patient G., 57 years old, complains of a feeling of tightness and roughness, on the lower surface of the tongue on the right.

Anamnesis of the disease: sick for 2 years. A year ago, the affected area was subjected to cryodestruction. Relapse occurred after 4 months.

Objectively: On the mucous membrane of the lower surface of the tongue, on the right, the area of pronounced keratinization in the form of sharply defined oval-shaped plaques 2 × 4 cm in size, unevenly rising above the level of the mucous membrane, painless, not removable during scraping. The surrounding mucosa is pale pink, unchanged (Fig. 8).

Diagnosis: K13.2. Leukoplakia, Verrucous form.

Treatment: 0.5 ml of a 1% solution of nicotinic acid was injected under the mucous membrane of the leukoplakia lesion using a tuberculin syringe (Fig. 9), after 30 minutes the lesion lesion was brought up with cryosurgery liquid nitrogen autonomous cryoapplicators of porous titanium nickelide on the principle of "Olympic rings" during 90 seconds (Fig. 10). To prevent wound infection, rinses with chamomile broth in the first 3-5 days are prescribed, then solcoseryl gel applications.

After 3 days, a mucosal defect covered with fibrinous plaque was determined in the area of exposure. On the 7th day, the foci of cryonecrosis were reduced and cleared of necrotic tissue. On the 11th day, the onset of ulcer regeneration along the edges of the defect was noted (Fig. 11). On day 14, the cryoran was completely epithelized. Positive long-term results were noted during the year (Fig. 12).

The inventive method of treating the verrucous form of leukoplakia of the oral mucosa by the combined use of cryodestruction and nicotinic acid is more effective than pure cryotherapy in the treatment of foci of leukoplakia and can be used to reduce the frequency of relapse of the disease.

Claims (1)

A method for treating the verrucous form of leukoplakia of the oral mucosa by cryodestruction, characterized in that 30 ml of a 1% solution of nicotinic acid are injected under the tuberculin syringe 30 minutes before cryosurgery under the mucosa of the leukoplakia lesion.

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