RU2472424C1 - Method of choosing tactics of managing patients with cervical neoplasia - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention relates to medicine, gynecology and includes medical history taking, clinical examination, cytological test, extended colposcopy, bacterioscopic and bacteriological tests, test for sexually transmitted infections. Under colposcopy control carried out is high-speed optical coherence tomography (hOCT), with analysis of kinematic characteristics of cervical tissue, treated with 3% acetic acid: intensity, uniformity, variability, elasticity of vessels, mobility of integral image, presence and character of movement of subepithelial structures. On the basis of obtained data type of cervical tissue changes is determined. Scanning is carried out by smooth movement of OCT-device probe on entire surface of uterus (U) from cervical canal to periphery on 12 vectors of 12-hour conventional clock face in clockwise direction, starting from 12 o'clock, marking boundaries of U mucosa changes on each of them - transitions between image types: malignant, questionable, benign. Boundaries of pathological nidus are determined by application of cervical ruler, consisting of two metal plates or rods, located at 90° angle to each other, one is being shorter than the other, with applied points. Long plate is fixed in cervical canal, rotating it in clockwise direction under colposcopy control, nidus size is marked in mm on short plate scale, on 4 quadrants in accordance with conventional clock face. After that, U is treated with 2% aqueous Lugol solution and hOCT is carried out again on 12, 3, 6, 9 o'clock of conventional clock face, with control of boundaries, obtained by means of hOCT and iodine-negative sites. By means of cervical ruler size and shape of neoplasia are fixed to plan area of irradiation or excision trajectory, place for sampling of cytological material is determined. If images correspond to benign changes, photodynamic therapy is administered, in case of questionable or malignant changes - excision: electroconisation or radiowave resection on trajectory, marked during hOCT.EFFECT: methods ensures objectivity and accuracy of selection of tactics for managing patients with U neoplasia, reduction of treatment terms, reduction of manipulation trauma.3 cl, 2 ex

Description

The present invention relates to medicine, namely to diagnostics, and can be used in gynecology to select the treatment tactics for cervical pathology (CM), namely, patients with cervical intraepithelial neoplasia (CIN).

The treatment of CIN in the practical work of a gynecologist is of great importance, since the wrong treatment tactics can contribute to the progression of the neoplastic process, the development of invasive cancer of the cervical cancer, the appearance of various complications, the emergence of iatrogenic conditions, a change in social status, and additional material costs.

Currently, there are a sufficient number of methods for treating cervical pathology, however, it is important to develop new diagnostic tests that help in planning treatment choose the most gentle and organ-preserving method, which, on the one hand, is the prevention of cervical cancer (Cervical cancer), and on the other, allows a number of patients to prevent the occurrence of complications of upcoming pregnancies and childbirth occurring in women with injured surgical intervention of CM.

Cervical cancer takes the first place among tumors associated with pregnancy (Vishnevskaya E.E. 2000). The frequency of cervical cancer in pregnant women is 1 in 2 205 patients. The average age with a combination of cervical cancer with pregnancy is 28-30 years. Especially unfavorable is the fact that the number of newly diagnosed cervical cancer patients during pregnancy for more than a 30-year period remains unchanged. The course of the cancer process during pregnancy is extremely aggressive: low-grade forms of the tumor predominate, and the depth of invasion increases. In addition, with stage I cervical cancer in pregnant women, metastases to regional lymph nodes are 2 times more likely to be detected. These factors lead to the rapid spread of the cancer process.

Cervical cancer has a long period of development. In most cases, it is preceded by atypical intraepithelial changes - cervical intraepithelial neoplasia (CIN), divided into three degrees: CIN 1 - mild dysplasia of stratified squamous epithelium, CIN 2 - moderate dysplasia and CIN 3 - severe dysplasia or carcinoma in situ. The time period from CIN 1-2 to CIN 3 can be 3-8 years, from CIN 3 to microinvasive cervical cancer - 10-15 years (cytologic screening the control of cervical cancer: technical guidelines // Geneva, WHO, 1988. - 52 p .; Prorok PC Mathematical models and natural history in cervical cancer screening // Screening for Cancer of the Uterine Cervix // LARC). This suggests that there is a sufficient period of time for appropriate preventive measures that impede the development of invasive cervical cancer.

According to experts of the National Institute of Health, 80% of invasive forms of cervical cancer can be prevented with timely diagnosis and adequate treatment of CIN. At the same time, 30% of advanced forms of cervical cancer are the causes of traditional diagnostic errors (Anderson P.S. Et al, 2001).

An adequate treatment for pre-invasive carcinoma (severe dysplasia) of the cervix in women of reproductive age, according to modern concepts, is cervical conization - a simultaneous diagnostic and therapeutic procedure. (Novikova E.G., Chisov V.I., Chulkova O.V. et al. Organ-preserving treatment in gynecology. - M: VIDAR - M. 2000; 20-40.)

In the literature there are conflicting opinions about the course of pregnancy and childbirth after destructive and invasive methods of treatment. Thus, according to M. Kasum (Kasum M., Kuvacic I. Pregnancy outcome after conisation. Jugosil Ginec Perinatol 1991; 31: 1-2: 31-34), the number of urgent deliveries in patients after conical excision of the cervix is 66.2% , premature - 14.7%, spontaneous abortions - 19.1%. According to S.V. Bulgakova (Bulgakova S.V. Assessment of the reproductive status of women who underwent organ-saving oncogynecological operations: Abstract of thesis, Candidate of Medical Sciences. M. 2007; 27) the number of cases of spontaneous abortion in patients after cervical amputation amounted to 20.3%, artificial interruption - 34.4%, operative delivery - 14.1% and delivery through the natural birth canal - 29.6%.

Thus, the principle of adequate removal of neoplasia of the cervix with maximum organ preservation, in conditions of inadequate diagnosis, is violated towards conscious surgical organ trauma. The choice of treatment for cervical neoplasia of the uterus depends:

- from a correctly established diagnosis;

- from the possibility of a medical institution in choosing a treatment method and practical training of medical personnel;

- on the age of the patient;

- from a woman’s desire to maintain reproductive function in the future;

- from concomitant pathology (drug allergy, pacemaker, vaginal stenosis, uterine fibroids, endometriosis, etc.);

- from the phase of the menstrual cycle.

Treatment of pathological processes of the cervix includes:

- therapy of causes and associated factors;

- impact on the pathological focus, or removal of the pathological focus.

The first group includes antibacterial drug therapy (antibiotics, antiviral drugs, etc.), aimed at eliminating the concomitant inflammatory process of cervical cancer and the vagina; non-drug therapy (low-frequency ultrasound, helium-neon laser) to stimulate the regeneration of stratified squamous epithelium; hormonal treatment for ovarian dysfunction (estrogen-progestogen, progestogen drugs); stimulation of immunity (immunomodulators); rectal administration of viferon (recombinant human alpha interferon) to individuals infected with human papillomavirus (HPV); the introduction of a therapeutic recombinant HPV vaccine to suppress HPV replication and inhibit tumor proliferation (in 50% of patients with genital warts, cure was achieved after one vaccination without relapse); the use of a prophylactic vaccine against HPV to protect against infection.

To influence the pathological focus use:

- chemical coagulation,

- electrosurgical effect (diathermal or electrocoagulation),

- cryogenic effects (surface and transcervical cryodestruction),

- exposure to a high-intensity laser (laser vaporization),

- Photodynamic therapy (PDT).

All methods of treatment of cervical epithelial neoplasia (CIN) can be divided into two types: destructive, i.e. destroying the pathological tissue of the cervix (diathermocoagulation, cryodestruction, laser vaporization, PDT), and surgical, removing the pathological tissue of the cervix (knife, laser, electric and radio wave excision).

Destructive treatments for CIN

Diathermocoagulation is a method of electrosurgical coagulation of pathological areas of the cervix, based on the use of high-frequency current and active electrodes of various shapes. The method is effective in 76.7-93.7% of cases only in the treatment of injuries of the cervix localized in the ectocervix. The main disadvantage of diathermocoagulation is the inability to control the depth of tissue coagulation. The process of tissue healing after diathermocoagulation in many cases is complicated by bleeding, the formation of gross post-coagulation scars with stenoses and strictures of the cervical canal, and pain. The frequency of such complications is about 30%, and the relapse rate reaches 55%. Typical long-term complications of diathermocoagulation are menstrual irregularities, exacerbation of chronic inflammatory diseases of the pelvic organs, implantation endometriosis, and the formation of telangiectasias, which requires treatment.

Cryodestruction is based on the use of low temperatures. According to the temperature parameters used, cryotherapy is usually divided into regenerative and destructive. In the first case, a short-term dosed cold exposure is carried out in order to improve the regeneration processes in the tissues, in the second, the level of exposure to cold is lower than the tissue cryostability threshold, which leads to necrotization of cooled pathological sections of the cervix. Nitrogen, nitrous oxide and carbon dioxide are used as refrigerants. The effectiveness of the method is 80-90%. The disadvantages of the method are the small depth of exposure, trauma to the underlying tissues, the need for repeated procedures to achieve the full effect, lymphorrhea, a high probability of shortening the cervix, the displacement of the stratified squamous epithelium into the cervical canal, the occurrence of relapses of the disease, especially in women with menstrual irregularities. When endocervix is involved in the process, this type of treatment, like diathermocoagulation, is ineffective.

Laser vaporization - the impact on pathological tissues of the cervix using defocused laser radiation (over 5 mm) with a radiation power of 3-6 watts. It is carried out by nulliparous women under the age of 40 with mild dysplasia. The advantages of laser vaporization are the possibility of complete evaporation of the pathological focus, visual control of the depth of tissue destruction, the absence of prolonged edema and cicatricial deformations, which allows maintaining the full value of the cervix and its reproductive function. Of the side effects of the method, the likelihood of ulceration, bleeding, and secondary infection should be noted. As with diathermocoagulation, laser vaporization results in the release of human papillomavirus (HPV) with smoke, which requires the doctor to observe safety precautions. The effectiveness of this method, according to various sources, ranges from 60 to 98%.

Surgical treatments for CIN

Cervical conization is the excision of pathological tissue of the cervix in the form of a cone. This type of treatment is carried out using a surgical, laser, ultrasonic scalpel, diathermic and electro-radio wave loop.

Indications for conization of the cervix with CIN are the inability to fully visualize the pathological site when it spreads through the cervical canal; suspected latent invasion during colposcopy, not confirmed by biopsy; severe cervical deformity, regardless of the degree of precancerous lesion; lack of effect from previous treatments.

Diathermoelectroconization is an electrosurgical cone-shaped excision of the cervix within healthy tissue with the help of loop electrodes of various sizes.

Indications for performing diathermoelectroconization are a combination of background (or) precancerous processes on the cervix with its hypertrophy and post-traumatic deformation; the presence of dysplasia.

The disadvantages of this method include the inability to accurately control the depth of exposure, bleeding, a significant amount of severe scar formation, narrowing of the cervical canal, telangiectasia, the number of premature births - 14.7%, spontaneous abortions - 19.1%, spontaneous abortion - 20.3% , artificial interruption - 34.4%, operative delivery - 14.1%, a high percentage of relapses.

A serious side effect is the fact that cicatricial changes in the cervix after diathermoelectroconisation can cause premature birth. All this limits the use of diathermoelectroconization in young women who want to maintain reproductive function.

Laser conization of the cervix is carried out by a focused laser beam (1 mm) using a high-energy laser with a radiation power of 12-15 watts. The method allows to obtain tissue for morphological studies. Data on the results of laser conization are controversial.

Knife conization of the cervix with the help of a surgical scalpel allows to obtain intact cervical tissue for morphological examination, without the charred edges of the cone. The disadvantages of the method are heavy bleeding, significant trauma to the cervix, long healing periods, the formation of stenosis of the cervical canal, which ultimately leads to infertility, a decrease in the production of cervical mucus, functional inferiority of the cervix and adversely affects the course of pregnancy.

Currently, there is no consensus among clinicians regarding the management tactics of patients with CIN 1, CIN 2 and CIN 3. So, with moderate epithelial dysplasia (CIN 2) in patients under the age of 40, as a rule, diathermocoagulation, cryodestruction, laser evaporation are performed pathologically altered sections of the cervix. Patients with cervical deformity over the age of 40 years are shown knife amputation, diathermic or laser conization of the cervix. With a non-visualized transformation zone in combination with an extensive ectropion, cervical deformity, over 45 years of age, such patients undergo Sturmdorf surgery. In the presence of concomitant gynecological pathology, the volume of surgery can be increased before hysterectomy. In severe cervical epithelial dysplasia (CIN 3), immediate treatment is required. The main treatment method is conization (knife, diathermic, laser) of the cervix, followed by a thorough histological examination of the material obtained.

Today, an increase in the incidence of cervical cancer worldwide is due mainly to an increase in the incidence of diseases among women of reproductive age. The reason for this is the spread of genital papillomavirus infection due to a change in the stereotype of women’s sexual behavior, lack of a healthy lifestyle culture (early onset of sexual activity, early first birth, frequent change of sexual partners, sexually transmitted diseases). Important points that contribute to infection are urogenital infection, alcohol abuse, smoking, immunodeficiencies. The frequency of HPV infection of high and medium oncogenic risk is 38.6%. The infection rate among women of childbearing age is 27.15%. According to some authors, the risk of developing cervical cancer in women under 30 years of age with long-term persistent HPV infection of highly oncogenic strains (types 16 and 18) increases by 65 times, and after 30 years - by 130 times.

At the same time, none of the treatment methods described above leads to a complete cure for papillomavirus infection due to a significant number of multifocal lesions, which leads to a relapse of the disease.

Analyzing the presented literature data, it can be argued that so far there are no clear recommendations in the world regarding the choice of the treatment method for CIN, its adequacy. All treatments reduce the risk of cervical cancer later on, but it remains high. The high relapse rate necessitates the search for new treatments for CIN that affect both HPV and the body itself.

Photodynamic therapy (PDT) of malignant neoplasms and, in particular, CIN is a fairly new way to treat CIN. It is carried out in two stages. At the first stage, a specific drug is introduced - the so-called photosensitizer, which selectively accumulates in the tumor tissue. At the second stage, the pathologically altered region is irradiated with optical radiation with a specific wavelength specific for each photosensitizer. During irradiation, the cytotoxicity of the photosensitizer increases many times, which leads to the formation of tissue necrosis in the irradiated zone.

It is proved that PDT causes the selective death of pathological cells without damaging healthy tissues, due to the selective accumulation of a photosensitizer in pathological cells and local light supply, reduces the time of reparative processes, without the formation of scar tissue, while maintaining the anatomical integrity of the cervix and architectonics of the cervical canal. The choice of a gentle and organ-preserving method of photodynamic therapy in young women with precancerous diseases of the cervix is due to the desire to provide reliable treatment for patients with the aim of preventing relapse of the disease and the transition to a more pronounced pathological process, while maintaining menstrual and reproductive functions, which is important for women planning a birth. Thus, the selectivity of the damaging effect on the tumor, the absence of pronounced adverse reactions, the possibility of repeated laser irradiation courses, the combination of diagnostics and therapy in one procedure qualitatively distinguish PDT from traditional methods of treating patients with cervical intraepithelial neoplasias. PDT is an alternative method of organ-preserving treatment, especially in women of reproductive age. With CIN 1, tactics may be individual with possible temporary observation. Patients with CIN 3 and carcinoma should be sent for further treatment to an oncologist.

For the prototype of the present invention, a well-known method of choosing management tactics for patients with cervical neoplasia was selected, including taking an anamnesis, assessing clinical symptoms, examination, cytological examination, advanced colposcopy, bacterioscopic and bacteriological examination, examination for sexually transmitted infections (see Papillomavirus infection and diseases uterine cervix: an educational-methodological manual. / L.D. Andosova et al. - N. Novgorod: Publishing House NGMA, 2011 - 108 p.).

The known method is as follows.

They take an anamnesis, assess clinical symptoms, examination, cytological examination. If pathological changes or cell atypia are suspected, an extended colposcopy (CS) is performed with standard samples, a bacterioscopic and bacteriological examination, examination for sexually transmitted infections, a cytological examination of a scraping from the cervix and cervical canal is performed, according to indications, an aimed biopsy, curettage of the cervical canal is performed . In accordance with the results of the study, treatment is prescribed.

However, the known method has the following disadvantages.

The information content of cytological screening according to different authors varies from 79.2-98%, sensitivity from 50 to 87% and specificity from 69 to 90%. The coincidence of the cytological conclusion with the histological one occurs in 52% -86% of cases, between cytology and CS in 69.2%, the reliability in the initial forms of cancer ranges from 60 to 80%. The most important cytological screening problem is false negative results. False negative results are responsible for failures in the diagnosis of cervical cancer, and there is an opinion that from 13 to 31% of cervical malignancies can be associated with negative smears during the three years preceding the diagnosis.

The second mandatory method of research is an expanded CS, which, despite the presence of other endoscopic diagnostic methods in practice, is one of the leading, affordable, inexpensive, and highly informative methods for assessing the condition of the integumentary epithelium of the cervix and vagina. It is an examination of the vaginal portion of the cervix and vagina using a microscope (colposcope), which gives an increase of 7-30 times, in conditions of additional lighting. The most common technique for advanced CS is to treat the cervical mucosa with 3% or 5% acetic acid and Lugol's solution (Schiller test). These tests allow you to determine the localization of the pathological process (when it is not visible with the naked eye) for the purpose of subsequent sampling of material for cytological examination and biopsy. However, taking into account the morphogenesis of pathological processes of CM, the possibility of accurately determining the nature of the pathological process in CS and determining the area of the cervix that is to be targeted biopsy is currently being questioned. This is due to the fact that there can be several highly active zones on the CMM, therefore, it is difficult to choose the most suspicious area for biopsy.

KS is a central element of diagnostics, but deciding on the need for a biopsy and choosing a place for sampling biopsy material is a difficult task even for a highly qualified specialist (even very experienced specialists make a mistake of 26% -42% CIN 2+). This is due to the fact that the possibilities of CS are limited to false positive (from 4 to 33%) and false negative (from 15 to 62%). The CS picture is very diverse, since pathological changes in the mucous membrane of the CM are polymorphic in nature. CS signs do not have a clear specificity (sensitivity 45-65%). According to Bohman, Ya.V. (1991) - the coincidence between cytology and CS is 69.2%, between CS and histology 86.1%; according to Rusakevich P.S. (1998) - the sensitivity of the method is high and is 87% for background processes of the cervix, 90.6% for precancerous processes and 93.2% for preclinical cancer. According to Kozachenko V.P. the effectiveness of CS does not exceed 78-88% in the diagnosis of initial forms of cancer. Kokhanevich E.B. believes that CS allows excluding biopsy in 98-99% of patients with benign pathology. Foreign authors cite 81.2% of colposcopy findings with histology, colposcopy sensitivity in the diagnosis of benign pathology - 62%, CIN 1 - 43%, CIN 2 - 59%, CIN 3 - 78%, microinvasive cancer - 56%, invasive cancer - 63% With a colposcopically directed biopsy, the accuracy of diagnosis of precancerous conditions of the cervix increases by 25%. In recent years, many studies have been devoted to the “crisis” of CS, in which surgical aggression - random biopsies and wide excision of CMM - is justified as compensatory technologies.

A CM biopsy is also one of the mandatory methods for diagnosing cervical disease. Technically, a biopsy is the taking of a "piece of the cervix" in the affected area for histological examination in order to verify the pathological process. A biopsy is performed under colposcopic monitoring from areas colposcopically identified as abnormal or suspicious colposcopic manifestations. A biopsy should also be obtained from the lesion sites, where the changes have the worst manifestations at the junction of the cylindrical and stratified squamous epithelium.

There are two main ways in which the diagnosis goes, and then the choice of management tactics for patients with CM neoplasia:

1. A biopsy from suspicious sites is carried out simultaneously in the process of CS examination of the cervix, without waiting for the result of cytological examination. In this case, a false negative cytological result is compensated by colposcopic examination and biopsy. In this situation, the following results can be obtained:

- colposcopy and biopsy are positive, cytology is positive;

- colposcopy and biopsy are positive, negative cytology;

- colposcopy is positive, biopsy is negative, cytology is positive. In this case, a biopsy should be performed on another site. If you again get a negative result, with an accurate, definite, positive result of a cytological examination, it is necessary to conduct cervical conization by a method in which it is possible to obtain a histological preparation for making a final diagnosis;

- colposcopy is positive, biopsy is negative, cytology is negative. In this case, a dynamic colposcopic and cytological control is performed, and even in some cases a second biopsy of the CM.

Taking a biopsy in case of abnormal or suspicious colposcopic manifestations and positive cytology. In this case, only one combination is possible - colposcopy is negative, cytology is positive.

Diagnostic efficacy of non-targeted biopsy is estimated at 40-60%, colposcopically oriented - 65-91.8%. However, there is a high level (up to 56%) of false-positive results of targeted biopsy with the multi-focal nature of epithelial dysplasias of varying severity. Making a decision about the need for a biopsy and choosing a place for sampling biopsy material is not an easy task, even for highly qualified doctors.

Thus, the possibilities of the known method of choosing management tactics for patients with neoplasia of the cervix are significantly limited by false negative and false positive results, which leads to low accuracy and unreasonable appointment of aggressive, invasive methods of treatment. The known method does not ensure the preservation of healthy tissue of CM, since it does not allow to determine the boundaries of the focus of the pathology, which also increases the invasiveness of treatment.

The objective of the invention is to ensure the objectivity and accuracy of the tactics of managing patients with neoplasia of the cervix, reducing treatment time and reducing the morbidity of medical manipulations.

The problem is solved in that in the known method of choosing management tactics for patients with neoplasia of the cervix uteri, including taking an anamnesis, evaluating clinical symptoms, examination, cytological examination, advanced colposcopy, bacterioscopic and bacteriological examination, examination for sexually transmitted infections, under the control of colposcopy perform high-speed optical coherence tomography (cOKT study) with the speed of the video frame using the probe of the OCT device and examine the kinematic characteristics teristics cervical tissue - intensity, uniformity and variability of tissue vascularization, vascular elasticity and mobility of the whole image, the presence and nature of the movement subepithelial structures

on the basis of which the nature of changes in cervical tissue is determined,

while using cOKT scan colposcopically healthy tissue of the cervix, treated with 3% acetic acid,

the study is carried out by smoothly moving the probe of the OCT device over the entire surface of the cervix, from the cervical canal to the periphery along 12 vectors of 12 hours of the clock face clockwise, starting from 12 hours, marking on each of them the boundaries of the speed changes of the cervix - transitions between image types: malignant, doubtful, benign,

Further, the boundaries of the pathological lesion are determined using a cervical ruler, which is made of two metal plates or rods placed at an angle of 90 ° to each other, while one plate is shorter than the other and the marks are applied on it, a long plate is fixed in the cervical canal, rotating it along clockwise under colposcopic control, note the size of the lesion in mm, focusing on the scale of the short plate, in 4 quadrants, respectively, on the clock of the conventional dial,

then the cervix is treated with a 2% aqueous Lugol solution and repeat OCTT at 12, 3, 6, 9 hours of the conditional dial, controlling the coincidence of the boundaries obtained using the OCTT study and iodine-negative sections,

using a cervical ruler, fix the size, shape of the neoplasia for planning the irradiation area or excision trajectory, determine the place for taking cytological material,

moreover, the conduct of photodynamic therapy is prescribed when obtaining images corresponding to benign changes,

and upon receipt of images corresponding to doubtful or malignant images, excision is prescribed - electroconization or radio wave resection, along the trajectory outlined during the sOKT study.

In this case, when studying the kinematic characteristics of cervical tissue, the signal backscattering intensity, the signal fading rate, the change in the size and number of subepithelial formations characterizing the uniformity and variability of tissue vascularization and vascular elasticity, the mobility of the whole image, the movement of subepithelial formations are determined

and diagnose healthy cervical tissues if there is a constant change in the size and number of subepithelial rounded formations of small diameter with a low backscattering ability, with a horizontal horizontal basal border of the lower layer of the whole image on the sOKT image,

if there are large-sized mobile subepithelial structures on the high-speed OCT image with a low ability to backscatter, with a constant change in their shapes, a low rate of fading of the tomographic signal, an indefinite form of the basal border of the lower layer, viral cervicitis is diagnosed,

a precancer is diagnosed in the absence of structural changes and the presence of oscillatory movements of the whole image and fracture of the basal border, in the absence of structural and dynamic changes and fluctuations of the entire volume of the whole image, a malignant neoplasm is diagnosed.

In this case, a high-speed OCT study is carried out at a central wavelength of 1280 nm, a power at the facility of 0.75 mW, a resolution of 15-30 μm, a scan depth of 2 mm, and a time for obtaining a high-speed OCT image of 8-10 frames per second.

The present invention meets the criteria of "novelty" and "inventive step", as the FDI did not identify sources of scientific, technical and patent literature that would discredit the novelty of the invention, as well as technical solutions with essential features of the proposed method.

The present invention allows to obtain the following technical result. The proposed method uses a new modification of the optical coherent tomograph developed at IAP RAS (Nizhny Novgorod).

A feature of the new installation is the speed of obtaining images of 8-10 frames per second in the video frame mode, which provides information not only about the structure of the object, but its functionality. The use of high-speed OCT research allows us to make a decision on the need for a biopsy and conduct the most targeted biopsy during colposcopy with all variants of cytological results. Further, the decision on tactics in these patients is made depending on the results of the biopsy.

In the case of CIN 2, and in the group planning pregnancy with CIN 1 and atypia of unclear significance, benign high-speed OCT images allowed us to abandon the biopsy and conduct photodynamic therapy in women of reproductive age with early forms of neoplasia.

In the event of an OCT study of “doubtful” or “malignant” image types, a decision was made on excision — electroconization or radio wave resection.

Our research has established that the visual boundary of neoplastic changes does not always coincide with the actual morphological boundary. Using the proposed method allows you to visualize the real border of neoplasia. We used this fact for intraoperative resection line planning.

The proposed method allows dynamic monitoring in the group of CIN 1 and in patients after organ-preserving treatment. The "good quality" of the obtained images allows you to abandon any interventions and continue monitoring.

Thus, the proposed method allows to increase the objectivity and accuracy of the tactics of managing patients with cervical neoplasia, optimize the treatment of early cervical neoplasia in patients of reproductive age, reduce treatment time and reduce the morbidity of medical procedures, reduce the percentage of relapses.

Using intraoperative planning of the resection line will allow us to conduct the most sparing resections with a certain guarantee of adequacy, which is the prevention of local recurrence. PDT, being a minimally traumatic method, can help prevent general relapses. The proposed method is as follows.

They take an anamnesis, assess clinical symptoms, examination, cytological examination. If pathological changes or cellular atypia are suspected, a simple (overview) and then extended colposcopy is performed. A mucus and discharge from the surface of the cervix are removed with a sterile cloth and treated with 3% acetic acid. Then, under the control of colposcopy, high-speed optical coherence tomography (sOKT study) is performed. The patient is placed on a gynecological chair, a vaginal portion of the cervix is opened with a bicuspid mirror. In the proposed method, the study of CMM is carried out using the OKT-1300U device in high-speed modification, IPFRAN, Biomedtech LLC, N. Novgorod, Russia, which allows to obtain a high-speed OCT image of 8-10 frames per second (in the video frame mode). Technical parameters of the device: wavelength 1280 nm, power at the facility 0.75 mW, resolution 15-30 microns, scan depth 2 mm, image acquisition time 8-10 frames per second, interchangeable endoscopic probes with a diameter of 2.7 mm. To control the OK-tomograph and record images using a personal laptop computer. The signal received from the biological tissue is subjected to digital processing, which provides real-time obtaining of two-dimensional optical images of biological tissue - high-speed OCT images presented in a positive pseudo-color brown palette. Each received tomogram is encoded, an electronic comment is recorded containing information about the patient (last name, first name, middle name, year of birth, gynecological history, reproductive history), localization, and features of the colposcopic picture of the scan area. If necessary, a more detailed study of the marked pathological site, the probe is pressed to the zone of interest, performing its SOCT scan for 12 seconds, without moving the probe.

First, colposcopically healthy tissue of the mucous membrane is scanned for 12 seconds, firmly pressing the probe. Then the probe is smoothly and uniformly advanced from the cervical canal to the periphery of the cervix in 12 beams corresponding to 12 hours of the conditional dial, starting from 12 hours in the direction of travel (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, eleven). The kinematic characteristics of cervical tissue are analyzed - the intensity, uniformity and variability of tissue vascularization, vascular elasticity, whole image mobility, the presence and nature of movement of subepithelial structures, on the basis of which the nature of changes in cervical tissue is determined. At the same time, with the help of sOKT, the colposcopically healthy CM tissue treated with 3% acetic acid is first scanned. The study is carried out by smoothly moving the probe of the OCT device over the entire surface of the CM, from the cervical canal to the periphery along 12 vectors of 12 hours of the clock face clockwise, starting from 12 hours, marking on each of them the boundaries of the speed changes of the cervical mucosa - transitions between image types: malignant, doubtful, benign. Next, the boundaries of the pathological focus are determined using the cervical ruler. The cervical ruler is made of two metal plates or rods placed to each other at an angle of 90 °, while one metal plate is shorter than the other and marks are applied on it. The cervical rulers are divided into 3 sizes for the cervix of various sizes. A long plate is fixed in the cervical canal. Rotating it clockwise under colposcopic control, note the size of the lesion in mm, focusing on the scale of the short plate, according to 4 quadrants corresponding to the clock of the conventional dial. Then the cervix is treated with a 2% aqueous Lugol solution and repeat OCTT at 12, 3, 6, 9 hours of the conditional dial, controlling the coincidence of the boundaries obtained using OCT studies and iodine-negative sections. Using a cervical ruler, the size, shape of neoplasia for planning the irradiation area or the excision path is fixed, after which the place for taking cytological and biopsy material is determined. Photodynamic therapy is prescribed when obtaining images corresponding to benign changes. Upon receipt of images corresponding to doubtful or malignant images, excision is prescribed - electroconization or radio wave resection, along the path outlined during the conduct of the OCT study.

When studying the kinematic characteristics of cervical tissue, the signal backscattering intensity, the rate of signal extinction, the change in the magnitude and number of subepithelial formations characterizing the uniformity and variability of tissue vascularization and vascular elasticity, the mobility of the whole image, the movement of subepithelial formations are determined. Healthy cervical tissues are diagnosed if there is a constant change in the magnitude and number of subepithelial rounded formations of small diameter with a low backscattering ability with a direct horizontal basal border of the lower layer of the whole image on the sOKT image. In the presence of large-sized mobile subepithelial structures in the high-speed OCT image with a low ability to backscatter, with a constant change in their shapes, a low rate of extinction of the tomographic signal, and an uncertain shape of the basal border of the lower layer, viral cervicitis is diagnosed. A precancer is diagnosed in the absence of structural changes and the presence of oscillatory movements of the whole image and the basal border is broken. In the absence of structural and dynamic changes and fluctuations in the entire volume of the whole image, a malignant neoplasm is diagnosed.

In case of prevalence of “doubtful” “malignant image types” during a high-speed OCT study, the decision is made on excision - electroconization or radio wave resection, according to the line of resection planned during the speed study.

In the course of treatment, dynamic observation is performed using high-speed OCT studies in the group of CIN 1 and in patients after organ-preserving treatment. It is noted that after electroconization of the cervix, the so-called adaptive vascular hyperplasia appears, which is often perceived by practitioners as an abnormal colposcopic sign - puncture. A 12-second SOCT scan of such a site allows us to differentiate adaptive vascular hypertrophy and puncture.

Examples of specific performance are given in the form of extracts from the medical history.

1. Patient K.Yu. K. Age: 27 full years, applied as prescribed by the doctor after childbirth, because during pregnancy, according to the results of a cytological examination and colposcopy, CIN 2 was detected. At the time of examination, there were no active complaints. The gynecological history is calm. Menses from 13 years to 4 days after 30 days, profuse, painless, regular. No somatic pathology was detected. Pregnancy - 1, childbirth - 1, abortion - 0, miscarriage - 0.

Medical history: on 11/16/10 during pregnancy, an abnormal colposcopic picture was revealed. Signs of viral cervicitis. A cytological study performed on the same day showed: among the blood masses there are cells of the squamous epithelium of the surface layers and layers of a proliferating cylindrical epithelium without atypia. Antiviral treatment and control of colposcopy and cytological examination were prescribed after 2 months. Liquid cytology and oncoprotein p16ink4a determination were prescribed:

The cytogram without features, immunocytochemical determination of the p16ink4a tumor marker is a negative reaction.

Definition of tumor markers:

Oncoprotein E7 HPV 16 and 18 types - positive

Oncoprotein E7 HPV 16 and 18 types of OP - 0.56

03.16.11 during a repeated appearance 1 month after giving birth during colposcopy, it was found: There are pathological changes, islands of gentle puncture were found, an acetone-white reaction is pronounced, unstable.

Conclusion: signs of viral cervicitis.

Cytological examination of the same number: In the preparation against the background of blood masses: among unchanged squamous cells, cells of the intermediate layer with moderate dyskeratosis are found. The cytogram corresponds to CIN II, probably associated with a viral infection. Observation tactics with turnout after 2 months was chosen. The patient arrived after 5 months - 08/10/11

Colposcopy:

The vaginal portion of the cervix is cylindrical, not deformed, the external opening of the cervical canal is slit-like, deformed to form an ectropion, mucous discharge. The entire vaginal portion is covered with stratified squamous epithelium. The epithelium is uneven, opaque, slightly thickened.

The vessels are thin, tree-like, the pattern is reinforced fragmentary.

Pathological changes are: an ectropion of 1.5 cm with islands of metaplastic epithelium on the periphery. The epithelium is cloudy. Regeneration zone is insignificant, islands of gentle puncture are found.

Acetone-white reaction is pronounced, persistent.

Test with Lugol: iodine-negative zone in the specified area.

Conclusion: Ectropion, abnormal colposcopic picture.

Cytological examination (08/10/11):

In the preparation, among the blood masses, there are accumulations of a cylindrical epithelium in the form of “honeycombs” and with signs of proliferation without atypia — endocervix. Groups of accumulations of squamous epithelium with severe dyskeratosis, hyperchromia of nuclei and enlightenment of the mononuclear zone, with dyskeratosis II - ectocervix.

Cytogram of changes in squamous epithelium type CIN II, HPV - infection?

SOCT study: images of a portion of the cervical mucosa with viral cervicitis register two horizontal layers with a clear, even, continuous, contrasting border between the layers. The lower layer is brighter than the upper one, abundantly saturated with formations of various shapes of large and huge (occupying most of the image) diameter with low backscattering ability during the 12 second observation of this zone, the outlines and boundaries of huge cavities are clearly visible.

When observing the zone of interest within 12 seconds of the study, there is a constant change in the shape of these cavities, with the formation of partitions inside them, and the size remains relatively the same. This picture may indicate active structural lesions of the cervix uteri viral etiology. The basal border of the lower layer of indefinite shape. The fading speed of the tomographic signal is low.

The boundaries of the area of inflammation completely coincide with the visual colposcopic border of the pathology and the norm. 12 hours - 10 mm, 1 hour - 12 mm, 2 hours - 15 mm, 3 hours - 7 mm, 4 hours - 10 mm, 5 hours - 13 mm, 6 hours - 14 mm, 7 hours - 9 mm, 8 h - 8 mm, 9 h - 8 mm, 10 h - 10 mm, 11 h - 11 mm.

Due to the presence of an abnormal colposcopic picture, the conclusion of a cytological study, the positive results of the study of HPV oncoproteins, but at the same time a benign type of OCT image, therapeutic tactics boils down to PDT.

Dose density - 70 J / cm ²

2 zones of exposure to the light spot - above and below the cervical canal, the boundaries of which are determined using OCT speed modification.

The diameter of each zone is determined using a neckline - 2 cm

The energy density is 0.48 J / cm ²

Power = 1.5 W

Control 1 month after treatment. Normal colposcopic picture. Cytologically: single cells corresponding to CIN I, observation continues. To address the issue of a repeated PDT course.

2. Patient L.Yu. A. Age: 25 full years, appealed in connection with the referral to the oncology dispensary, because during the examination, the gynecologist at the place of residence revealed foci of change on the cervix, a smear was taken for oncocytology, the results of which revealed CIN 2-3. No active complaints.

Medical history:

According to colposcopic examination: there are pathological changes - an ectopia with a diameter of 0.7 cm, with islands of turbid metaplastic epithelium on the periphery. The regeneration zone is insignificant, small closed glands are determined. Islets of rough and delicate mosaic and puncture were found. Acetone-white reaction is pronounced, persistent. Test with Lugol - iodine-negative zone in the specified area.

Conclusion: abnormal colposcopic picture. Assigned: liquid cytology and determination of oncoprotein p16ink4a:

Inflammation cytogram. Dysplasia of II-III metaplastic planar, immunocytochemical determination of the p16ink4a tumor marker - a positive reaction.

Definition of tumor markers: Oncoprotein E7 HPV 16 and 18 types - negative.

Cytological examination: Cytogram of changes in squamous epithelium according to type CIN II-III.

SOCT study: image is malignant. When conducting a 12-second sOKT study, there are no structural changes, but the entire image of the zone of interest makes oscillatory movements, and the basal border of the whole image is high, it is a strongly broken curve, giving the impression of a “pitted” edge, diagnosed with CIN and microinvasive cancer.

OCT - the boundaries of the pathology zone do not coincide with colposcopic boundaries, increasing by 2-3 mm. The boundary between norm and pathology is very clear. 1 hour - 10 mm, 2 hours - 11 mm, 3 hours - 9 mm, 4 hours - 12 mm, 5 hours - 15 mm, 6 hours - 11 mm, 7 hours - 10 mm, 8 hours - 9 mm, 9 hours - 8 mm, 10 hours - 7 mm, 11 hours - 7 mm, 12 hours - 8 mm.

Due to the presence of an abnormal colposcopic picture, the conclusion of a cytological study, the positive results of the study of HPV oncoproteins, a malignant type of OCT image, therapeutic tactics boil down to performing wide excision (loop electroconization of the cervix along the intended path) and curettage of the cervical canal.

Histological examination: In the material fragments of the cervix with the presence of cervical ectopia with focal proliferation. Fibrosis and stromal angiomatosis are noted. Stratified squamous epithelium with the phenomena of papillomatosis, acanthosis, with dysplasia of 1-2 degrees. In the epidermalization zone, a microfragment of MPE with grade 3 dysplasia.

Claims (3)

1. A method for selecting management tactics for patients with cervical neoplasia, including taking an anamnesis, assessing clinical symptoms, examination, cytological examination, advanced colposcopy, bacterioscopic and bacteriological examination, examination for sexually transmitted infections, characterized in that under the control of colposcopy they perform high-speed optical coherence tomography (SOCT study) with the speed of a video frame, using the probe of the OCT device and investigate the kinematic characteristics of cervical tissue nor - the intensity, uniformity and variability of tissue vascularization, vascular elasticity, whole image mobility, the presence and nature of the movement of subepithelial structures, on the basis of which the nature of changes in cervical tissue is determined, and with the help of SOCT, colposcopically healthy cervical tissue treated with 3% is scanned acetic acid, the study is carried out by smoothly moving the probe of the OCT device over the entire surface of the cervix from the cervical canal to the periphery along 12 vectors 12 h of the conditional dial armor in the clockwise direction, starting from 12 h, marking on each of them the boundaries of speed changes in the mucous membrane of the cervix uteri - transitions between image types: malignant, dubious, benign, then determine the boundaries of the pathological focus using a cervical ruler, which is made of two metal plates or rods placed at an angle of 90 ° to each other, while one plate is shorter than the other, and marks are applied on it; the long plate is fixed in the cervical canal, rotating it clockwise under colposcopic control, mark the lesion size in mm, focusing on the scale of the short plate, using 4 quadrants corresponding to the clock of the conditional dial, then the cervix is treated with a 2% aqueous Lugol solution and repeated with OCT 12, 3, 6, 9 hours of the conditional dial, controlling the coincidence of the boundaries obtained using the sOCT study, and iodine-negative sections, using the cervical ruler, fix the size, shape of neoplasia for planning the area of the area pathways or excision paths, determine the place for taking cytological material, and photodynamic therapy is prescribed when obtaining images corresponding to benign changes, and when receiving images corresponding to dubious or malignant images, excisions are prescribed - electroconization or radio wave resection along the path planned during SOKT studies. 2. The method according to claim 1, characterized in that in the study of the kinematic characteristics of cervical tissue, the signal backscatter intensity, the rate of signal extinction, the change in the magnitude and number of subepithelial formations characterizing the uniformity and variability of vascularization of the tissue and the elasticity of the vessels, the mobility of the whole image, the movement subepithelial formations, and healthy cervical tissues are diagnosed if there is a constant change in the magnitude and number of subepithelial in the sOKT image rounded formations of small diameter with low backscattering ability, with a direct horizontal basal border of the lower layer of the whole image, in the presence of large-sized moving subepithelial structures on the high-speed OCT image with low backscattering ability, with a constant change in their shape, low extinction rate tomographic signal, the uncertain form of the basal border of the lower layer is diagnosed with viral cervicitis, the precancer is diagnosed in the absence of structural changes available vibrational movements fragmentedness whole image and basal borders, the absence of structural and dynamic changes and oscillations in all whole image volume diagnosed malignancy. 3. The method according to claim 1, characterized in that the high-speed OCT study is carried out at a central wavelength of 1280 nm, the power at the facility is 0.75 mW, the resolution is 15-30 microns, the scanning depth is 2 mm, the time for obtaining a high-speed OCT image 8-10 frames per second.