The method of treatment of uterine cervix using locoregionally citicentre

 

(57) Abstract:

The invention relates to medicine, gynecology, and can be used for the treatment of uterine cervix using locoregionally citicentre. Down for 3-4 hours daily for 10-15 days to the cervix of the patient swab with complex autologous endogenous cytokines obtained during stimulation of mononuclear cells of the patient interleukin 2, while in the presence of concomitant scar deformation and hypertrophy of the patient pre-spend defervesces cervix. This invention helps to reduce recurrence of the disease due to complete epithelization of erosion and impacts on all elements of the immune system. 1 C.p. f-crystals.

The method relates to medicine, namely to gynecology.

The uterine cervix is one of the first places in the structure of gynecological morbidity and almost every fourth patient recurs after treatment, posing a threat to the development of cervical cancer, the growth of which is celebrated at the present time in young women.

Currently, for the treatment of uterine cervix using a comprehensive treatment, providing about is electrogastrogram with subsequent stimulation of regeneration of the stratified squamous epithelium and the stimulation of immune system function, which can be done just before a radical impact on the center of the pseudo (Krasnopolsky Century. And., 1999; Prilepskaya Century. N. et al., 2001; Rudakova E. B., 2001). The most radical and effective methods of treatment of uterine are laser therapy, cryosurgery, determinely, thermocoagulation (Prilepskaya Century. N. et al., 2001).

Laser therapy. As a result of strong absorption of laser radiation by tissues is instantly heated to high temperatures, intense evaporation of interstitial and intracellular fluid, coagulation or evaporation of cellular structures with the formation of a zone of coagulation necrosis at the border with the surrounding tissues. Cleansing the surface of the cervix begins with 4-5 days and lasts 4-5 days. 14-15 day there are areas of regenerating epithelium. Ends epithelialization after 3-4 weeks (Zuev C. M., 1999).

The disadvantages of the method include the difficulty of obtaining field necrosis desired and uniform depth, the need for re-application in a large process, the dependence of the effect sizes of the hearth. The efficiency of the method depending on the size of the lesion - 83,3-96%, and after a single exposure - 52,4-94,6%. In the treatment ve steps - the increased estrogen 1.7, progesterone - 2 times, LH - 1.5-1.6 times (Zuev C. M., 1999).

Cryosurgery. The mechanism of action is the formation of intra - and extracellular ice crystals, the concentration of electrolytes and pH and crystallization of water in the organelles of cells, mechanical damage to tissues refrigerant violation of microcirculation with the development of necrosis.

The cryonecrosis is formed within 1-3 days, softened at 7-10 days. Appears bleed and have exudate associated with the expiration of lymph. Regeneration ends in 4-8 weeks. The efficiency of the method is 80-90% (Kostava M. N., 1999 [3]; Rusakevich P.F., 2000). The relapse rate is high as 20 - 40% (Kostava M. N., 1999 [3]; Summary A. N., 2000).

The shortcomings of the method is the high frequency of relapse, lack of depth of impact, rich liquid discharge with loss of potassium ions in healing (Polyakov C. A., 2001).

Electrocoagulation is traditionally the most common method of treatment of uterine cervix. The essence of the method lies in the fact that when exposed to a high-frequency current collapse diseased epithelial structure, develop reactive processes in the muscle and connective tissue. Segeplan is I. Complete epithelialization of the defect of the fabric ends to 1.5-3, and sometimes 4 months. Morphologically the process of reconstructing the structure of the cervix occurs only to 9-12 months. The efficiency of the method is 76-94% (Rusakevich P.F., 2000). The recurrence rate is 55% (Kostava M. N., 1999) [3], complications, 30-47,2% (Kostava M. N., 1999 [3]; Rusakevich P.F., 2000; Prilepskaya Century. N. et al., 2001).

The main complications: bleeding, stricture and stenosis of the cervical canal, extravasate, subepithelial hematoma, endometriosis, the formation of unsightly scars, violation of the trophic tissue, impaired reproductive function, dystocia of the cervix during childbirth, exacerbation of inflammatory processes, menstrual dysfunction, pain, prolonged course of reparative processes, leukoplakia, thermal burns, cancer of the cervix. Given the development of cicatricial processes, not recommended for young nulliparous women.

Geotermoelectrica the cervix is the combination of uterine cervix with her scar deformation and hypertrophy. This method represents an electrosurgical cone excision of pathologically changed tissues with the apex of the cone directed to an internal fix. Usually made of paternalistically. Complications are similar. Efficiency - 93-97% (Krasnopolsky Century. And., 1999).

Thermocoagulation. The method consists in external application of heat with a heat thermocautery 90-S. The scab sloughs after 3 weeks, complete epithelialization occurs within 4-5 weeks. The efficiency of the method is 95.8%. With this type of coagulation is insufficient depth of necrosis.

In addition visionaries methods in young women used chemical coagulation cervical colovaginal. The scab sloughs 3-5 days. Epithelialization occurs to 9 days from the moment of epithelialization and completed within 3-4 weeks. Efficacy in uncomplicated pseudo in young nulliparous women was 74.3% (Kostava M. N., 1999) [4].

Disadvantages of the method are: a lack of depth of the impact, which leads to frequent relapses, the method is not shown when a large extent of the process.

Thus, the main disadvantages of the above methods of treatment of uterine cervical cancer are as follows:

1. Lack of effectiveness with a high recurrence rate most frequently used methods of treatment. The most effective to date method of laser photocoagulation cervical relatively few DOS what I personnel and requires special training.

2. Visionaries treatments cause destruction of the tissues, without affecting the main etiopathogenetic mechanisms that require complex therapy, including immunotherapy, stimulation of regeneration.

3. Long period of healing, often rich phase discharge.

4. The development of endometriosis.

5. Cicatricial changes that violate the disclosure of the cervix during labor.

6. Inflammatory complications.

Immunotherapy in diseases of the cervix.

Taking into account the role of the immune status in the Genesis and progression of cervical cancer, the role of local immunity in cervical regeneration methods of immunomodulator therapy for the treatment of diseases of the cervix.

Known systemic and local administration of interferon preparations prior to surgery (Dee, cryo - or laser coagulation) in cervical intraepithelial neoplasia with the aim of increasing the effectiveness of treatment and reducing the frequency of relapses (Reppa S. et al., 1994; Baske J. et al., 1995), which is associated with the improvement of some immunological parameters (G. Vitale et al., 1994).

Know the use of complex autologous endogenous cytokines in the treatment of pahaloomuline human papillomavirus infection, followed by topical application of natural immunomodulators in the form of a complex autologous endogenous cytokines (CAAC), composed of IL-1, IL-2, IL-4, IL-6, TNF and IFN-γ. CAAC received by stimulating phytohemagglutinin isolated from the blood of the patient mononuclear cells. The treatment reduced the period of epithelialization laser wounds and affect different elements of the immune system, which was reflected in the increase in the number of T-lymphocytes, T-helpers, T-suppressors and serum IgA. However, the PHA has a carcinogenic effect, which can be unsafe when used for more complex endogenous cytokines.

The invention

The essence of the proposed method lies in the fact that the cervix of the patient fail swab with conditioned medium, which is a complex autologous endogenous cytokines (CAAC), for 3-4 hours. CAAC produced by stimulation of interleukin 2 (drug Roncoleukin) isolated from the blood of the patient mononuclear cells. The course of treatment is 10-15 procedures daily.

In the presence of concomitant uterine scar deformation and hypertrophy of the patient pre-spend defervesces of sakana action. Its preparation is described in the patent of Russian Federation № 2098125. CAAC made from autologous blood of the patient before treatment and Packed into 5 ml vials, bottles sealcoat and stored in a freezer until use.

The study included 120 patients with uterine cervical cancer at the age from 16 to 40 years. All patients were divided into 4 groups. The first group included 30 women, for the treatment of uterine have used locoregionally citicentre using CAATS within 10-15 days, the duration of application of 3-4 hours daily. The second group included 30 patients who were geotermoelectrica (DEA) about the pseudo cervix with associated scar deformation and hypertrophy; in the postoperative period the patient was administered topically CAAC in the same mode. The third group (the control to the first group consisted of 30 patients with uterine cervical cancer, which was administered swabs with distilled water. The fourth (second control group) - 30 patients with uterine and scar deformation and hypertrophy of the cervix, which after Dee the cervix were treated every other day for only 5% potassium permanganate solution for 7 days.

Treatment is mpany applied directly to the cervix, and the patient was removed independently after 3-4 hours. All were appointed 10-15 tampons. Swabs with distilled water was administered to the patients of the 3rd group during the same time period. Patients of the 2nd group tampons with KAAZ was administered immediately after Dee cervix, and then 5-7 days of the postoperative period, at the rate of treatment using 10-15 tampons.

Treatment efficacy was assessed by patient complaints and records of the comprehensive examination, including the examination of the cervix using mirrors, colposcopy, Cytology.

Patients 1 and 3 groups colposcopy was performed at 5, 10 days of treatment, through 1, 3, 6, 9, 12, 18, 24, 30 months. after the treatment. Cytological examination in the same period, starting 1 month after treatment.

Patients 2 and 4 groups colposcopy was performed every other day for the first two weeks, then every 5 days to complete healing, then a month, and then every 3 months during the first year and every 6 months for 2 and 3 years after surgery. The first control cytological examination was performed after complete healing, then one month and subsequently simultaneously with colposcopic examination.

During therapy CAAC and th the 5 patients. The rest of the patients of the 1st group were observed reduction of the area of pathologically modified area of the cervix by 30-55% (42,75,8%). 10-15 days after treatment, complete healing in the form of a benign transformation zone was observed in 16 women out of 25, the other nine - affected area of ectocervical decreased by 75-90%. After examining through 1-1,5 months. after treatment, complete healing is not achieved only in 2 patients. When this damage zone of ectocervical remained weak, falling by more than 85-90%, and observed a typical transformation zone. It was noted the almost complete overlap of the hearth columnar epithelium stratified squamous, was determined open the ducts of glands.

Women 3 groups receiving placebo, the nature of colposcopic paintings were not changed, the area of damage was reduced.

The purpose of quantitative evaluation of the effectiveness of the use of autologous endogenous cytokines in the treatment of uterine cervical cancer, we used the index AVERAGE, which reflects the number of patients to be treated in a certain way for a certain period of time to achieve a certain effect or prevent replicastore effect (J. McQuay, R. Andrew, 1997).

The risk of relapse is reached 0.06, relative risk reduction - 0,04, the absolute risk reduction - 0,94. Indicator AVERAGE was 1.1, which confirms clinically significant effect. Complications and recurrence after treatment were observed. The treatment efficiency was 94%.

In patients of the 2nd group in the first days of treatment was observed a positive effect CAAC in the postoperative period. Discharge from the genital tract were scanty, light, does not cause discomfort. In the 4th (control) group every third patient had noted the presence of significant discharge from the genital tract with blood and a foul smell.

In patients of the 2nd group scab was thinner and more elastic compared to patients of the 4th group.

Phenomena perifocal inflammation in patients of the 2nd group were absent in patients of the 4th group was absent only every fourth.

The scab was rejected for 6-8 days (average, 6,80,5 day.) women of the 2nd group and 8-12 (average 9,40,8 day.) - patients of the 4th group (p<0,05). The rejection scab was not accompanied by the appearance of bleeding when using CAATS, while 19 patients of the 4th group a significant increase was observed discharge with primes 8-12 (average, 10,50,8) days (p<0,05). Complete epithelialization of the wound surface in patients treated topically CAAC occurred at 4-5 (4,20,9) week, whereas in the control group (4) - 6-8 (7,10,8) week after surgery (p<0,05).

Recurrence within 2.5 years of follow-up in the 2nd group was not, cytologically and abnormal colposcopic paintings were not. In the control (4) - one patient noted a recurrence of the pseudo two - signs of cervicitis. Complications and side effects in women, the second group was not observed.

The purpose of quantitative evaluation of the effectiveness of the use of autologous endogenous cytokines in the postoperative period after Dee cervix we also used the index AVERAGE.

The risk of relapse in the 3rd and 4th groups were respectively 0.05 and 0.3, and the relative risk of 0.17. Relative risk reduction compared to patients not receiving CAAC, - 83,3%, the absolute risk reduction of 0.25. Indicator AVERAGE was 4.0, which confirms clinically significant result.

Clinical example 1.

Patient O. 26 years who's genitals, secondary infertility of tubal origin (first pregnancy ended in a medical abortion, complicated by metroendometrit). When examination revealed pseudo, colposcopic - ectopia in combination with diffuse obesity, increased vascular pattern and the presence of iodine-negative area. Using DNA-PCR revealed a clamidiosis. The treatment of chlamydia, then decreased effects of diffuse obesity, but not finally gone, and iodine-negative area. After treatment chlamydia was made knife cervical biopsy, which confirmed the diagnosis of pseudo.

Assigned tampons with CAAC within 10 days for 3-4 hours daily. After the third pad area ectopia there are very minor and after 5 - completely disappeared, iodine-negative site was not determined, signs of inflammation were not. Control surveys recurrence was not observed.

Patient A. 38 years has addressed the purpose of routine inspection. When examination revealed complaints of whites. Installed colposcopic the uterine cervix of the uterus, severe cicatricial deformity and hypertrophy of the cervix with the presence of atypical paintings in the form of acetabulosa epithelium. PCR detected the knife or data biopsy.

Patients received Dee of the cervix, followed by the appointment locoregionally citicentre by the method described above. It was noted the formation of thin elastic scab, the selection is very poor, bright, without admixture of blood. Signs of perifocal inflammation was not observed. The rejection scab with evidence of active epithelialization and without the occurrence of bleeding occurred in 6 days; complete healing of the 5 week. For 2.5 years recurrence is not marked.

Thus, locoregionally cytokinemia using CAATS in the treatment of uterine cervix effective, nontraumatic (the latter is especially important for young nulliparous women), does not lead to the development of complications are associated with significant financial costs.

Sources of information

1. Zuev, C. M. the Use of laser radiation for the treatment of cervical pathology //In the book: Diseases of cervix, vagina, vulva //Ed. by C. N. Prilepsky. - M., 1999. - S. 183-200.

2. Ivanyan A. N. et al. A comprehensive treatment of pathology of the cervix caused by HPV, with CO2-laser vaporization and complex autologous endogenous cytokine //Vesti coagulate in the treatment of benign diseases of the cervix //In the book: Diseases of the cervix, vagina, vulva // Ed. by C. N. Prilepsky. - M., 1999. - S. 170-177.

4. Kostava M. Treatment of benign diseases of the cervix drug solcovagin //In the book: Diseases of cervix, vagina, vulva // Ed. by C. N. Prilepsky. - M., 1999. - S. 178-183.

5. Pathology of the vagina and cervix /edited proceedings of the international conference Century. I. - M.: Medicine, 1999. - S. 146-192.

6. Polyakova Century A. Oncogynecology. - Moscow, 2001. - S. 67-92.

7. Prilepskaya Century. N. et al. Pathology of the cervix // In the book: Practical gynecology //Ed. by C. I. Kulakov, V. N. Prilepsky. - M., 2001. - N-9-39.

8. Rudakova E. B. Uterine cervix cancer // In the book: Practical gynecology //ed Kulakov Century. And., Prilepsky Century. N. - M., 2001. - S. 40-48.

9. Rusakevich P.F. disease of the cervix. - Minsk, 2000, - S. 367

10. The Summary A. N. et al. Selected lectures in obstetrics and gynecology. - M., 2000. - S. 390-409.

11. Baske J. et al. Local therapie und adjuvante interferjn therapie bei genitalen Papillomavirus infectionen //Gynacol. Geburtshilfliche Rundsch. - 1995. - V. 35, No. 2. - P. 79-84.

12. McQuay, Henry J., Moore, R. Andrew. Using numerical resalts from systematic revievs in clinical practice // Ann. Intern Med. - 1997. - V. 126. - P. 712-720.

13. Penna, S. et al. Intralesions beta-interferon treatment of cervical intraepithelial neoplasma associatied with human papillomavirus infection //Tumori - 1994. - V. 80, No. 2. - R. 146-150.

14. Vitale G. Eocene of uterine cervix by deciding on 3-4 hours daily for 10-15 days to the cervix of the patient swab with complex autologous endogenous cytokines, obtained during stimulation of mononuclear cells of the patient interleukin 2.

2. The method according to p. 1, characterized in that in the presence of concomitant scar deformation and hypertrophy of the patient pre-spend defervesces cervix.

 

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