RU2619341C1 - Method of correcting hormonal state during postcastration syndrom in patients of reproductive age with cervical cancer - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: method comprises determining the level of prolactin, estradiol, testosterone, luteinizing hormone, follicle-stimulating hormone in blood to determine background levels. Then, 72 hours prior to surgery, 250 mg of "Omnadren" preparation is intravenously administered to patients in a single dose, then 4 days after the surgery the same parameters are determined relative to the background levels and at higher levels of prolactin, testosterone, luteinizing hormone, follicle-stimulating hormone and at lower level of estradiol in blood seven sessions of xenotherapy are assigned, once a day, against the background of replacement therapy by androgen deposited preparations.

EFFECT: invention application enables to normalize the hormonal state, reduce clinical implications of postcastration syndrome, normalize neuro-vegetative and psycho-emotional disorders, improve life quality of patients with invasive cervical cancer after radical surgeries.

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Description

The invention relates to medicine, in particular to oncology, and can be used in the correction of hormonal status after radical surgical treatment of patients with cervical cancer of reproductive age in the early postoperative period.

In Russia, cervical cancer is one of the most common forms of neoplasms and accounts for 9.8% of all cancers in women, occupying the 7th place among all malignant tumors and the 3rd place among cancers in women (see E.M. Axel / / Oncogynecology. 2012. No. 1. P. 18-23).

Currently, the most common and commonly used operation worldwide for the treatment of invasive cervical cancer is expanded nerve-sparing hysterectomy with appendages with the upper third of the vagina and pelvic lymphadenectomy (see Surgery of Invasive Cervical Cancer / V.V. Kuznetsov, A.I. Lebedev, K.Yu. Morokhov, A.N. Gritsay // Practical Oncology T3 No. 3 2002. P. 178-179).

The loss of the hormonal function of the ovaries as a result of surgical castration causes complex maladaptation reactions in the neuroendocrine system (see KN Zhmakina // Gynecological endocrinology. 1980. P. 436).

After radical surgery for cervical cancer, which involves changes in the hemostatic system, the function of the nervous, cardiovascular and other body systems, the possibility of developing post-castration syndrome in patients of reproductive age is high and its consequences are unpredictable and difficult to correct (see T . I. Moiseenko, N.N. Popova, A.P. Menshenina, A.I. Shikhlyarova, N.A. Nazaralieva / Results of a grounded approach to the correction of postvariectomy syndrome in gynecological oncology patients of unproductive age // Malignant tumors; - 2015. - No. 4 (special issue 2). - P. 136).

Currently, for the treatment of post-castration syndrome, drugs specially designed for hormone replacement therapy (MHTT) are used. Despite the high effectiveness of these drugs in the treatment of post-castration syndrome, many women who use this treatment are forced to abandon it because of undesirable side effects, such as weight gain, and the development of hypertension. These changes are the result of the influence of estrogen on the renin-angiotensin-aldosterone system.

Side effects of hormone replacement therapy include breast engorgement, decrease or increase in body weight, fluid retention, edema, cholestasis, headaches. Replacement therapy has a number of contraindications: thrombosis, a history of thromboembolism, estrogen-dependent malignant tumors, breast cancer, endometrial cancer, liver and kidney diseases with impaired function, severe forms of diabetes mellitus (see Manusharova R.A. // Postovariectomy syndrome (educational allowance): Moscow. - 2004. - S. 16; Manusharova R.A. / Treatment of menopausal syndrome in Itsenko-Cushing's disease and primary obesity // Medical practice. - 1998. - No. 1. - P. 94-96; see Estimator VP / Menopausal disorders and principles of substitution ormonoterapii // Therapeutic Archives -. 1995. - №10 -. pp 70-74).

Conducted research Ulrich E.A. and Urmancheeva A.F. allow us to conclude that only short-term use of MZHT in the rehabilitation of cancer patients after specialized treatment is possible (see Ulrich E.A., Urmancheeva A.F. / Oncological aspects of menopausal hormone replacement therapy // Practical Oncology. V. 10, No. 2 . - 2009. - S. 76-8).

A known method of treating menopausal syndrome using plasmapheresis (see T. Foteeva. Clinical and pathogenetic rationale for the treatment of menopausal syndrome using plasmapheresis: diss ... Dr. med. Sciences / TS Foteeva - M., 2012. - 244 p. ) According to Foteeva TS, plasmapheresis has a pathogenetically based therapeutic effect on patients with severe climacteric syndrome. The therapeutic effect of plasmapheresis is due to many mechanisms: removal of toxic, vasoactive substances, autoantibodies, components of destroyed tissues and cells from the microvenous bed, increased functional activity of hematopoietic, stromal immunocompetent cells, improved microcirculation (see Voinov V.A. Efferent therapy. Membrane plasmapheresis. / 5th ed., Revised and enlarged M .: OJSC "News" 2010. P. 368).

However, the execution of plasmapheresis in this aspect is most justified in patients with concomitant metabolic syndrome, with an increase in coagulation properties, a violation of rheological blood parameters, with severe dyslipidemia, the presence of autoimmune and allergic diseases (see Role of plasmapheresis and xenon therapy for the correction of acute consequences of surgical menopause in patients with neck cancer uterus / Kit O.I., Frantsuz E.M., Menshenina A.P., Moiseenko T.P., Ushakova N.D., Popova N.N., Yakushin A.V. // KubSAU, No. 117 ( 03), 2016).

Current literature data regarding the psychoemotional state of cancer patients allow us to say that most patients are in a state of increased stress and anxiety-depressive state, which requires the use of psychotherapeutic techniques (see Semionkin E.I. Stress in cancer patients. Palliative medicine and rehabilitation 2011 No. 3, p. 62). It should be noted that the lack of staffing with specialist psychotherapists in oncology hospitals does not allow us to fully provide adequate assistance to patients at the stage of early rehabilitation.

At the present stage of the development of innovative technical and medical sciences, the priority of Russian specialists is the creation and implementation of inert gas xenon in practical applications. One of the main areas of research both in Russia and abroad is to study the prospects for the use of therapeutic xenon-oxygen mixtures in regenerative medicine (see Burov N.E. Anesthesia with xenon / Burov N.E., Molchanov I.V., Potapov V.N. // Methodological recommendations of the RMAPE. 2003. S. 156).

As a result of a comprehensive study, the Russian Pharmaceutical Committee allowed the use of xenon in medical practice (Order of the Ministry of Health of the Russian Federation No. 363 of 8/10/1999). Akela-N LLC received Registration Certificate No. 99/363/4 and License No. 64/0125-L / 02 for the production and sale of XenMed medical xenon, approved the Instructions for the use of xenon and protected Pharmacopoeia Article No. 42-2891-97 from 10/08/1999 g and Pharmacopoeia article of the enterprise (FSP) No. 42-0523-5109-04. Hazard class - 4 according to GOST 12.1007.

It should be noted that xenon therapy has a pronounced antistress, hormone-modulating, antidepressant and sedative effect and is promising in the treatment of postcastration syndrome.

The medical technology for stopping postcastration syndrome in the early postoperative period is the closest in essence to the problem of treating acute and chronic stress xenon with an inert gas, which arise as a result of exposure to a complex of various psychotraumatic factors, as well as preventing the development and treatment of the negative effects of stress manifested by maladaptation syndrome, psychogenic reactions, psychosomatic diseases.

The technology is based on the use of the XeMed drug (reg. No. LS-000121) (FS No. 2010/227 dated 06/17/2010 “Method for the correction of acute and chronic stress disorders based on the inhalation of therapeutic doses of XeMed brand xenon”). Indications for the use of medical technology are: correction of emotional, behavioral and autonomic stress-induced disorders. Xenon therapy has a pronounced anti-stress effect, manifested in a decrease in the level of pathological adaptive reactions (stress, tension).

Xenon has a pronounced analgesic, sedative effect, does not cause functional and mental dependence, is biologically inert and quickly eliminated from the body unchanged (see Method for the correction of acute and chronic stress disorders based on the inhalation of therapeutic doses of XeMed brand xenon. "// Authors : Ushakov I.B., Bubeev Yu.A., Kalmanov A.S., Potapov V.N., Potapov A.V. et al. Moscow 2010.P. 3-18).

The technical result of the present invention is the correction of hormonal status, relief of symptoms of post-castration syndrome, improving the quality of life of patients after radical surgery in patients with cervical cancer in the early postoperative period.

This goal is achieved by the fact that upon admission to the department, patients determine the levels of prolactin, estradiol, testosterone, luteinizing hormone, follicle-stimulating hormone in the blood to determine background values, then 72 hours before surgery, 250 mg of Omnadren are administered intravenously to patients, then, 4 days after the surgical treatment, the same parameters are determined relative to the background values and with an increase in the levels of prolactin, testosterone, luteinizing of the hormone, follicle-stimulating hormone and lowering blood levels of estradiol administered seven sessions ksenonterapii, once a day, against the background of androgen replacement therapy - The depot formulations.

The invention "A method for correcting hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age" is new, as it is unknown from the prior art in the field of gynecological oncology for correcting hormonal status in patients with cervical cancer of reproductive age in the early postoperative period.

The novelty of the invention lies in the fact that in order to correct the hormonal status of patients with cervical cancer after performing radical surgical treatment in the amount of nerve-saving extirpation of the uterus with appendages with the upper third of the vagina and pelvic lymphadenectomy, a course of xenon rehabilitation therapy is carried out, which allows to stop the symptoms of post-castration syndrome and improve the quality of life patients after radical surgery.

The invention "A method for correcting hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age" is industrially applicable since it can be used in healthcare, medical institutions of oncological profile, oncology dispensaries, research institutes, and cancer centers.

"A method for correcting hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age" is as follows.

When entering a gynecological department, a patient with cervical cancer determines the level of the following hormones in the blood to determine the background values: prolactin (PL, mIU / L), estradiol (E2, pmol / L), testosterone (TST, nmol / L), luteinizing hormone ( LH, ME / L), follicle-stimulating hormone (FSH, ME / L).

Then, 72 hours before surgery, patients are intravenously injected with 250 mg of Omnadren.

4 days after performing surgical treatment, the level of the same hormones in the blood is again determined. With an increase in background blood levels of prolactin, testosterone, luteinizing hormone, follicle-stimulating hormone, and a decrease in estradiol levels, seven xenon therapy sessions are performed once a day.

Before the procedure, the patient is explained the methodology for inhalation therapy with xenon, the properties of xenon, contraindications, possible sensations and complications. To achieve a positive result, a necessary condition is to achieve maximum sealing of the inhalation circuit by fixing the face mask with a mask holder.

The procedure for the correction of hormonal status in patients with cervical cancer of reproductive age in the early postoperative period was carried out in 40 patients aged 24 to 42 years.

All patients underwent surgery: nerve-sparing panhisterectomy, pelvic lymphadenectomy. Against the background of replacement therapy with androgen-deposited drug, the patient was treated with xenon to normalize hormonal status.

Table 1 presents the results of a study of hormonal status in the same women with cervical cancer at the stages of its correction.

It was established that a week after an expanded panhisterectomy, serious changes in the hormone content occurred in the blood of patients. So, the E2 level was reduced by 2, 1 times, while the levels of PL, TST, LH, FSH were increased: TST - 3 times, LH - 2, 4 times, FSH - 5, 9 times, and also submarines 1.4 times.

3 days after the end of xenon therapy, the level of estradiol in the blood of cervical cancer patients significantly increased by 2 times, relative to this indicator immediately after surgery, against a background of a decrease in the content of LH and FSH by 2, 1 and 2.7 times, respectively. During this period of the study, a significant drop in testosterone levels by 3.6 times, and prolactin - by 1.3 times was found.

Here is a specific example of the implementation of the "Method for the correction of hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age."

Example No. 1.

Patient M., b. 1974 Received January 24, 2015 in the Department of Gynecology, RNII with complaints of periodic pain in the lower abdomen, profuse pus-like discharge from the vagina, contact hemorrhages.

Anamnesis of the disease: in December 2014, contact vaginal hemorrhages appeared, which turned into spontaneous permanent spotting. She independently applied to the FSBI RNII of the Ministry of Health of the Russian Federation. Examined by an oncogynecologist. A cervical biopsy was taken: histological examination: No. 35236-237 / 16: strata of squamous cell carcinoma, with keratinization, highly differentiated, without underlying tissue. With a diagnosis of cervical cancer T _1v2 N _x M ₀ gr 2, exophytic form - hospitalized in the Department of Oncogynecology for surgical treatment.

Objective status: general condition is satisfactory, clear consciousness, skin integument of normal color, dry. Height = 164 cm, weight = 75 kg. No swelling. Varicose expansion of the saphenous veins of the lower extremities was not detected. Mammary glands without pathological formations. HELL 110/70 mm Hg, pulse 68 rpm, rhythmic. Heart sounds are clear, rhythmic. NPV 16 per minute, no shortness of breath. Auscultatory vesicular breathing in the lungs, no wheezing, heart sounds rhythmic, clear. The tongue is wet, clean. The abdomen on palpation is soft, painless. The liver is not enlarged, the gall bladder is not palpable, the spleen is not palpable. The chair is decorated once a day. Adequate diuresis, free urination, painless.

External genitalia without pathology. In the mirrors: the cervix is cylindrical, bleeds contact, at 5 o’clock an eroded area of about 5 mm in diameter. The body of the uterus is slightly enlarged, the usual consistency is relatively mobile, the appendages are not enlarged, the arches are free.

Psycho-emotional status: the patient is excited, closed, reluctant to answer questions, expresses concern about the upcoming operation and concern about the diagnosis of cervical cancer.

Laboratory data at admission:

1. General blood test from 01.24.2015: hemoglobin - 159 g / l; erythrocytes - 5.26⋅10 ² / l; CPU = 0.81; leukocytes - 5.09 910 ⁹ / l; platelets - 202⋅10 ⁹ / l; ESR - 20 mm / hour; p / poison - 9%; s / venom - 96%, monocytes - 11%; eosinophils 1%, lymphocytes - 33%.

2. Biochemical analysis of blood from 01.24.2015: glucose - 6.02 mmol / l; total protein - 65, g / l; total bilirubin - 14.8 mmol / l; ALT 10.8 IU / L; ACT 10.3 IU / L; blood amylase 56 U / L; CRP 1.40 mg / ml, urea 2.81 mmol / L. creatinine 85 μmol / L.

3. Hormonal background: PL - 198 mIU / L; E2 - 1008 pmol / l; TST - 4.1 nmol / l; LH - 7.7 IU / l; FSH - 5.6 IU / L.

Ultrasound of the abdominal cavity and small pelvis from 01.24.2015: the structure of the myometrium of the cervix is changed, in the lower and middle segments the hypoechoic volumetric nodal structure of the neoplasm. The size of the lesion 3.7 × 3.44 × 2 cm, volume 27.47. Vascularization of the cervix uteri: MAC parameters in the descending branches of the uterine arteries on the right and left up to 35-40 cm / s. Vascularization of the lesion: qualitative - hypointensive blood flow, the parameters of the intratumoral blood flow MAC from 12 to 35 cm / s.

01/25/2015, intravenously, 250 mg of the drug Omnadren was administered once.

On January 28, 2015, surgical treatment was performed in the amount of: laparotomy, viscerolysis, nerve-saving extirpation of the uterus with appendages with the upper third of the vagina, pelvic lymphadenectomy. The result of histological analysis: No. 51774-779 / 15: moderately differentiated cancer with an invasion of 4 mm, there are no tumor cells and metastases in the lymph nodes and along the line of resection.

Laboratory data 4 days after surgery, before xenon therapy:

1. General blood test from 02/01/2015: hemoglobin - 129 g / l; erythrocytes - 4.26⋅10 ² / l; CPU = 0.78; white blood cells - 10.44⋅10 ⁹ / l; platelets - 332⋅10 ⁹ / l; ESR - 29 mm / hour; p / poison - 20%; s / poison - 59%, monocytes - 12%; eosinophils -, lymphocytes - 9%.

2. Biochemical analysis of blood from 1.02.2015: glucose - 5.33 mmol / l; total protein - 60 g / l; total bilirubin - 10 mmol / l; ALT 14.1 IU / L; ACT 12.5 IU / L; blood amylase 54 U / L; CRP 2.5 mg / ml, urea 6.3 mmol / L, creatinine 62 μmol / L.

3. Hormonal background: PL - 292 mIU / L; E2 - 456 pmol / l; TST - 12.9 nmol / l; LH - 18 IU / L; FSH - 32 IU / L.

Psycho-emotional state: the patient is worried about chills, dizziness, not associated with a change in body position, hot flashes, lack of a full night's sleep, weakness, pain in the area of a postoperative wound, apathy and drowsiness in the afternoon.

Neurovegetative assessment-35 points, psycho-emotional - 16 points, which corresponds to a severe form of postcastration syndrome.

Seven xenon inhalations were carried out with an oxygen mixture (02.02.2015 - 02.02.2015), the maximum achieved xenon percentage was 25%, the duration of the procedures was 20 minutes on average, and the average xenon consumption was 1.9 liters. Hemodynamics and heart rate did not go beyond the physiological norm. There were no oxygenation disorders during inhalation.

The psychoemotional effect was achieved after the first treatment session, the patient noted an improvement in general condition and mood, a decrease in pain in the area of the postoperative wound, normalization of night sleep after three procedures, after a course of therapy - an increase in concentration and activity, optimism and a positive attitude to continue treatment.

Laboratory data 3 days after the completion of xenon therapy:

1. General blood test from 02/08/2015: hemoglobin - 124 g / l; erythrocytes - 4.27⋅10 ² / l; CPU = 0.82; white blood cells - 6.79⋅10 ⁹ / l; platelets - 351⋅10 ⁹ / l; ESR - 12 mm / hour; p / poison - 9%; s / venom - 59%, monocytes - 10%; eosinophils - 2, lymphocytes - 20%.

2. Biochemical analysis of blood from 02/08/2015: glucose - 5.33 mmol / l; total protein - 63 g / l; total bilirubin - 12.2 mmol / l; ALT 10.1 IU / L; ACT 10.5 IU / L; blood amylase 52 U / L; CRP 1.5 mg / ml, urea 3.3 mmol / L, creatinine 52 μmol / L.

3. Hormonal background: PL - 200 mIU / l; E2 - 960 pmol / l; TST - 3.0 nmol / L; LH - 8.9 IU / l; FSH - 6.1 IU / L.

Neurovegetative assessment-12 points, psychoemotional - 8, which corresponds to a mild degree of postcastration syndrome. The EEG recorded a decrease in delta activity, an increase in the power indicator in the beta frequency range, which corresponds to the optimal active wakefulness of a person.

In adjuvant mode, combined radiation therapy was performed on the pelvic area in full. The treatment was satisfactory.

At the control turnout on 05/10/2016, the patient's condition is satisfactory, the patient does not complain. Height = 164 cm, weight = 75 kg. Consciousness is clear, the skin is pale, dry. No swelling. Varicose expansion of the saphenous veins of the lower extremities was not detected. There is no lymphostasis. The mammary glands are without features. HELL 110/70 mm Hg, pulse 74 min, rhythmic. Heart sounds are clear, rhythmic. NPV 14 per minute, no shortness of breath. The vesicular breathing, no wheezing. The tongue is wet, clean. The abdomen is soft, painless. The liver is not enlarged. Adequate diuresis, free urination, painless. Status genitalis: external genitalia without pathology. In the mirrors: the vaginal stump is formed, completely epithelized, smooth, macroscopically without signs of relapse.

SRKT data from 05/10/2016: pathological formations are not located in the pelvis; retroperitoneal lymph nodes are not enlarged.

Psycho-emotional state: a sufficient level of social and family adaptation, it works, it adequately relates to the disease, it does not notice symptoms of post-castration syndrome.

Technical and economic efficiency “A method for correcting hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age” consists in normalizing hormonal status, regression of clinical manifestations of post-castration syndrome, normalizing neurovegetative and psychoemotional disorders, improving the quality of life of patients with invasive cervical cancer after radical surgery through the use of inert gas therapy xenon in the early postoperative period.

Claims (1)

A method for correcting hormonal status in post-castration syndrome in patients with cervical cancer of reproductive age, which consists in the fact that patients entering the department determine the levels of prolactin, estradiol, testosterone, luteinizing hormone, follicle-stimulating hormone in the blood to determine the background values, then 72 hours before of surgical intervention, patients are intravenously injected with 250 mg of the drug "Omnadren", then 4 days after the surgical treatment is determined e and the figures with respect to the background values and at higher levels of prolactin, testosterone, luteinizing hormone, follicle-stimulating hormone and decreases in estradiol levels in the blood appoint seven sessions ksenonterapii, once a day, against the background of androgen replacement therapy, drugs deposited.