Malignant of genital organs. Throphoblactic diseases. 1. Rationale: Cervical is a preventable disease yet over a quarter of a million women die of cervical cancer each year, with 90% of deaths occurring in low- and middle-income countries.Women living with HIV are at 4–5 times greater risk of developing cervical cancer. Cervical cancer has significant socioeconomic impact on the women affected as well as their families and communities. . In 2010, cervical cancer cost the global economy an estimated USD 2,7 billon. By 2030, this figure is projected to rise to USD 4,7 billion. Cervical cancer will continue to devastate the lives of many women, families and their societies if action is not taken. The new UN Global Joint Programme (Joint Programme) will implement the World Health Organization (WHO) comprehensive approach to cervical and control which consists of: introduction and scaling-up of HPV vaccination; introduction and expanding coverage of and treatment of precancerous lesions; prompt management of invasive ; access to palliative care and; monitoring using a standard set of indicators and tools to end cervical cancer. Globally, in 2015, only 12% of countries reported cervical programmes with participation rates greater than 70% with participation rates higher in high income countrie. 1. Objectives (are described in the terminology of professional activity, taking into account the system of classification of the objectives of the respective levels of cognitive, emotional and psychomotor spheres): -To analyze the main etiological and pathogenetic factors of the malignant neoplasms of genital organs and throphoblactic diseases -To explain the pathogenesis of the development of the malignant neoplasms of genital organs and throphoblactic diseases, taking into account the anatomical and morphological and physiological features of the female genital organs. -To suggest tactics of management of patients in the malignant neoplasms of genital organs of reproductive system and throphoblactic diseases. -To classify the malignant neoplasms of the , , , and throphoblactic diseases of according to current morphological and clinical classifications and ICD. -To interpret data of laboratory and instrumental examinations in the malignant diseases of the cervix, endometrium, vulva, . -To draw a diagram of “patient route” and “plan of examination” in the malignant depending on localization --To make the analysis of the methods of differential diagnosis, justification and formulation of preliminary diagnosis, as well as current approaches to the management of malignant neoplasms in women, the principles of , conservative treatment, rehabilitation measures -To make up the models of clinical cases with various malignant gynecological pathology in women of reproductive and premenopausal age. 3. The basic level of expertise, skills, abilities, required for learning the topic

(interdisciplinary integration ) The name of the previous Acquired skills disciplines Normal Anatomy Structure of female genital organs. Topography of abdominal organs and pelvic organs. Histological structure of the cervix, vulva and endometrium in normal and in pathological conditions. Notmal Physiology Physiological changes occurring in the hypothalamic- pituitary-ovarian system of women and target organs of the sex hormones action at different ages. Microbiology, Immunology Specific and nonspecific protective factors, antiviral immunity Pathological Anatomy Morphological structure of all types of benign tumors of the female genital organs. Pathological Physiology Hormonal changes in the body during the and disorders of the microbiota of the female reproductive system. Operative Surgery The main types of surgery on the female genital organs. Mechanisms of therapeutic action of physical factors (electric current, refrigerants, radiation, phototherapy). Pharmacology Groups of medications that affect the function of the hypothalamus, pituitary gland, ovaries, adrenal glands; mechanism of pharmacological action of hormonal, hemostatic, anti-inflammatory, antiviral drugs.

4. The structure of study material content (describes the study material, provides structural and logical charts, tables, figures that reflect the content of the major issues of the topic of the lesson). 4.1. The list of the major terms, parameters, characteristics to be acquired by a student to be prepared for the lesson A virulent of the cervix that histologically Adenoma consists of glands that appear well differentiated (minimal Malignum deviation adenocarcinoma). A cervix containing a large carcinoma, generally of endocervical Barrel-Shaped origin, that has replaced much of the cervix, causing its diameter Cervix to widen (usually > 4 cm). A form of in which the source is placed close to the tumor. The application may be in the form of needles implanted into the tumor (interstitial therapy) or into the or cervical canal (internal therapy). For cervical tumors, an intracervical tandem and vaginal ovoids (colpostats) are usually used. A term used to describe a tumor that begins in the endocervical Endophytic canal. A term used to describe a cervical tumor that grows on the outside Exophytic surface primarily of the cervix (portio). Extrafascial An operation that develops the pubocervical fascia to allow total removal of the cervix and uterus (class I hysterectomy). A system that delivers brachytherapy to cervical carcinomas by Fletcher-Suit use of a tandem in the cervical canal and ovoids (colpostats) in the Applicator vagina. Glassy A virulent that occurs in the cervix and Carcinoma metastasizes early in the course of the disease. A small (stage IA) carcinoma detected by microscopic Microinvasive Carcinoma examination with little or no risk of spread to regional lymph nodes (see text for detailed discussion). An operation that removes the uterus and cervix and some Modified Radical paracervical tissues but does not dissect the ureters distal to the Hysterectomy uterine artery (class II hysterectomy). An extensive pelvic operation usually employed to treat a central pelvic recurrence of cervical carcinoma after radiation. A total Pelvic exenteration involves removal of the bladder, uterus, cervix, and Exenteration rectum. An anterior exenteration spares the rectum, whereas a posterior exenteration spares the bladder. The identification of invasive disease at the site of primary therapy Persistent Tumor less than 6 months after therapy. A term used in radiation therapy of carcinoma of the cervix to Point A identify a point 2 cm above the external os of the cervix and 2 cm lateral to the cervical canal. A term used in the radiation treatment of carcinoma of the cervix Point B to identify a point 3 cm lateral to point A or 5 cm from the cervical canal. An operation that removes the uterus, upper third of the vagina, Radical cervix, and paracervical-parametrial tissues. The pelvic ureters are Hysterectomy dissected to the uterovesical junction. It is usually combined with a pelvic dissection (class III hysterectomy). The identification of invasive disease 6 months or more after Recurrent Tumor therapy. Stage I: Tumor confined to the cervix Stage IA: Microinvasion (preclinical) Summary of Stage IB: All other cases confined to the cervix Stages of Stage IIA: Tumor spread to the upper two thirds of the vagina Carcinoma. Stage IIB: Tumor spread to paracervical tissue but not to the pelvic walls Stage IIIA: Tumor spread to the lower third of the vagina Stage IIIB: Tumor spread to the pelvic wall or obstruction of either ureter by tumor Stage IV: Tumor spread to the mucosa of the bladder or rectum or outside the pelvis. A form of radiation with placement of the radioactive source at a distance from the patient (external therapy). It is usually used to Teletherapy treat the pelvis and occasionally the paraaortic nodes in patients with cervical carcinoma. Verrucous A -appearing, well-differentiated squamous malignancy that Carcinoma rarely metastasizes.

4.2 Theoretical questions for the lesson:

1. Basic clinical symptoms of . 2. Methods of diagnostics of vulvar cancer. 3. Methods of treatment of vulvar cancer. 4. Pathogenesis of cervical cancer. 5. Stages of cervical cancer. 6. Basic clinical symptoms of cervical cancer. 7. Methods of diagnostics of cervical cancer. 8. Methods of treatment of cervical cancer are depending on the it`s stage. 9. What are causes of ? 10. Stages of cancer of body of uterus. 11. Transfer the symptoms of cancer of body of uterus. 12. Give description of clinical and histological forms of cancer of body of uterus.. 13. What additional methods of diagnostics do use for suspicion on the cancer of body of uterus? 14. Principles of treatment of cancer of body of uterus. 15. Classification of cancer of ovaries. 16. What basic clinical symptoms of cancer of ovaries do you know? 17. Symptoms that are characteristic of primary and secondary (metastatic) . 18. Stages of distribution of ovarian cancer. 19. Principes of diagnostics of ovarian cancer. 20. Methods of treatment of ovarian cancer. 21. Basic clinical symptoms of vulvar cancer. 22. Methods of diagnostics of vulvar cancer. 23. Methods of treatment of vulvar cancer. 24. Prognosis and prevention of malignant diseases of the female genital organs. 25. Principles of clinical observation patients with malignant diseases of the female genital organs.

4.2 Practical activities (tasks) to be performed on the lesson:  To perform gynecological examination (bivalve vaginal speculum, bimanual, rectal, rectovaginal).  To collect a specific gynecological anamnesis, to evaluate the findings of laboratory tests.  To collect material from the vagina, cervix, cervical canal and urethra for cytological, and bacterioscopic studies.  To evaluate the findings of cytological, histological, virological and bacteriological studies.  To evaluate the findings of the ultrasonography of organs of the small pelvis.  To estimate the protocol of the of the cervix and vulva.  To make a plan of examination of a patient in various nosological forms of malignant pathology.  To diagnose and classify it according to the TNM and FIGO.

4.3 Topic content Cervical Carcinoma Etiology and Pathophysiology Cervical carcinoma is second most frequent reason for incidence and mortality of oncological diseases in women of developed contries. Due to major distribution of cervical carcinoma screening by means of Рар-test the incidence of and mortality from cervical carcinoma has reduced by 75 % in developed countries during the past 50 years. The most important factor, which conditions the development of cervical carcinoma, is human ; highly oncogenic types of the virus are 16, 18, 31, 33, 35, and 45. Such risk factors as early beginning of sexual life, many sexual partners, the presence of a high-risk sexual partner (promiscuous sexual life, with a person infected with human papilloma virus), and are also important. Accessory risk factors are the history of sexually transmitted infections, high parity, immunosuppression (including HIV infection), low socio-economic condition, and epidermoid of the vulva and vagina. In most cases (85–90 %) cervical carcinoma is of the epidermoid type and develops from the cells of stratified pavement , which lines the vaginal part of the uterine neck. Another type of cancer is adenocarcinoma, whose cells are similar to epithelial cells, which line the cervical canal of the uterine neck. Both indicated types of cervical carcinoma often arise in the region of junction of the pavement and cylindrical epithelium, where glandular epithelial cells lining the cervical canal of uterus are replaced with cells of the pavement epithelium of the vaginal surface of the neck due to metaplasia. It is suggested that both adenocarcinoma and epidermoid cancer develop from common precursor cells. Therefore both types of cancer are characterized by a similar course. There has been offered the following clinicopathologic classification of the pathological processes of the uterine neck. 1. Background processes: pseudoerosion, leukoplakia, polyps, flat condylomas. 2. Precancerous process – dysplasia: mild, moderate, severe. 3. Preinvasive carcinoma (intraepithelial cancer). 4. Microinvasive carcinoma. 5. Invasive carcinoma: epidermoid keratinous, epidermoid nonkeratinous, adenocarcinoma, dimorphous glandular-epidermoid (mucoepidermoid), and low differentiated. Cervical carcinoma extension is possible both as a result of direct infiltration and in the lymphatic way. Infiltration or growth of tumor may take place in the downward direction – onto the vaginal wall, forwards – onto the urinary bladder, laterally – into the parametrium and paravaginal fat. Extension outside the parametrium limits happens in the lymphatic way. In such a case there are affected external and internal iliac lymph nodes including the ones located in the obturator foramen and uterosacral ligaments, and also presacral nodes. From here the process spreads into the common iliac and paraaortal lymph nodes. The hematogenous type of dissemination is not typical of cervical carcinoma. Cervical Carcinoma Classification according to the FIGO System - Stage 0 – . - Stage І – the cancerous process does not spread outside the limits of the uterine neck (Іа – microscopic lesion foci, Іb – visible foci). - Stage ІІ – the cancerous process spreads onto the vaginal walls not affecting its lower third; infiltration of the parametrium without pelvic walls affection. - Stage III – the cancerous process affects the lower third of the vagina and spreads onto the pelvic walls; hydronephrosis/kidney block. - Stage IV – the tumor spreads outside the limits of the small pelvis; the mucous tunic of the urinary bladder or rectum is affected. Cervical Carcinoma Classification according to the TNM System (shows dimensions of the initial focus: T – tumor; condition of the regional lymph nodes: N – nodulus; the presence of remote metastases: M – ) Т – initial focus dimensions Т0 – primary tumor is not detected Tis – carcinoma in situ Т1 – cancer is limited with the uterine neck Т1а – invasive carcinoma, which can be diagnosed only by means of microscopy. Т1а1 – the invasion depth does not exceed 3 mm, the width – 7 mm. Т1а2 – the invasion depth does not exceed 5 mm, the width – 7 mm. Т1b – clinically detectable tumor limited by the neck Т1b1 – clinically detectable tumor smaller than 4 cm. Т1b2 – clinically detectable tumor larger than 4 cm. Т2 – tumor extending onto the uterine body but without invasion of the pelvic wall or of the lower third of the vagina. Т2а – without parametrium invasion. Т2b – with parametrium invasion. Т3 – the lower third of the vagina is affected and/or extension onto the pelvic wall and/or hydronephrosis. Т3а – the lower third of the vagina is affected. Т3b – extension onto the pelvic wall and/or hydronephrosis. Т4 – the mucous tunic of the urinary bladder or rectum is affected and/or extension outside the limits of the small pelvis. N – regional lymph nodes Nx – insufficient data to estimate the condition of the regional lymph nodes. N0 – there are no signs of metastatic spread to the regional lymph nodes. N1 – metastatic spread to the regional lymph nodes. М – remote metastases Мx – insufficient data to determine remote metastases. М0 – there are no signs of metastases. М1 – there are solitary metastases.

Clinical Presentation Most frequently the initial manifestation of cervical carcinoma are pathological bleedings (postcoital, intermenstrual, postmenopausal). The discharge may also be watery, blood-tinged, mucous, puruloid, or have objectionable odor. The classical clinical presentation is characterized by intermittent painless metrorrhagias or “spotting”, which arises after sexual intercourse or rising . As cancerous tumor grows, bleedings become more massive, their freqency and duration increase. At the terminal stages there may appear pain in the lateral abdomen, lower extermities, dysuria, hematuria, rectal bleedings, constipations, stable edema of or both lower extremities, massive bleedings, uremia.

Diagnostics Preinvasive carcinoma is recognized with the help of a complex of diagnostic methods, which includes cytological analysis, colposcopy, hystological study of the and surgical material. Examination of patients begins with anamnesis collection: the doctor pays special attention to the reproductive function, finds the time of sexual life beginning, the number of pregnancies, deliveries and , peculiarities of their course, the history of gynecological disorders. The doctor also gets more specific information about the beginning and course of the disease, which made the appeal to the doctor. Speculum examination of the uterine neck is carried out. Cancerous tumor might have different forms. In exophytic tumor one finds tuberous formations of reddish color, not infrequently with necrotic patches looking like grey incrustation. Even delicate touch makes tumor bleed. In endophytic tumor the uterine neck is enlarged, has a dense consistensy, may be ulcerated in the region of the external orifice. Colposcopy of the tumor shows yellow-red neoplasms with clearly visible atypical blood vessels on the periphery. Cytological examination finds malignant cells. Histological study is decisive in cancer diagnostics. If microinvasive and early cervical carcinoam is suspected, one conducts diagnostic cone biopsy, which allows finding the invasion. The stage of cervical carcinoma is detected clinically (and not surgically as in other oncogynecological disorders). The complex of measures aimed at detecting the stage of cancer should include examination, palpation, colposcopy, cervical canal curettage, , cytoscopy, , intravenous pyeloureterography, radiographic examination of the and bones, and lymphography. When the tumor stage is detected, diagnostic cone biopsy is considered a part of clinical examination. Computer tomography and magnetic resonance imaging procedure are very important in treatment planning, still, they do not allow determining the cancer stage; these techniques are used to diagnose the affection of the lymph nodes and estimate the degree of tumor extension in the small pelvis. Cervical carcinoma should be differentiated with tuberculosis, hard chancre, sarcoma, disintegrating polyps, and myoma.

Treatment The choice of treatment method depends on the peculiarities of the clinical course, the degree of tumor process extension, tumor morphology, general condition of the patient, extragenital and concomitant . The following methods are used: surgical, combined, associated radiation, , and complex. In the combined method there are used two essentially different treatment methods – radiation and surgical. The complex method implies the use of all the three modes of action – surgical, radiation, and medicinal. The treatment of cervical carcinoma patients should be provided according to a clear program taking into account the sequence of providing different kinds of therapy.  Stage 0: surgical excision, laser ablation, local application of 5-FU (5- ).  Stage Iа1: simple hysterectomy. The question of ovariectomy is decided individually.  Stage Iа–ІIа: radical hysterectomy, pelvic lymphadenectomy, or radiation therapy of the pelvic organs. Extended hysterectomy consists in removal of the uterus with the appendages and upper vagina, parametral fat, regional lymph nodes located along the outer, inner, and common iliac vessels, and in the obturative fossa. In stage II the associated radiation method is used more frequently. The operation is indicated to the patients, in whom associated radiation therapy cannot be provided fully, and the degree of local tumor extension makes it possible to perform radical intervention. The only method of treating stage III cancer patients is associated radiation therapy. In stage IV symptomatic treatment is indicated. To treat cervical carcinoma patients one also uses anticancer drugs, particularly used to treat relapses and: , prospidin, and platinum preparations. Prognosis: 5-year survival rate in 1B stage cervical carcinoma patients makes 75–80 %; in 2 – 60 %; in 3 – 35–40 %; on average at all stageх – about 60 % . The prophylaxis consists in timely detection and treatment of precancerous lesions of the uterine neck. An important role is played by preventive examinations of women at maternity welfare clinics and special patient’s examination rooms, where gynecological inspection is carried out and material for cytological examination is taken.

Endometrial Carcinoma

Etiology and Pathophysiology Endometrium cancer is referred to the most spread malignant tumors of the uterine body. Other tumors arising from the endometrium or stroma cells include sarcoma. Endometrium cancer is the most frequent malignant disease of the female genital organs and the fourth most frequent oncological disease (after , carcinoma of , and colon cancer). The average age of cancer arising is 61 years; however, 20–25 % patients are in the premenopausal period. There are differentiated the following hystological types of endometrial carcinoma: adenocarcinoma (80 %), mucinous carcinoma (5 %), clear cell adenocarcinoma (5 %), papillary serous cancer (4 %), and epidermoid carcinoma (1 %). The risk factors of endometrial carcinoma in post- and premenopausal women: 1. Obesity. 2. Carbohydrate maltolerance. 3. No deliveries in the anamnesis. 4. Late menopause. 5. Estrogen therapy without gestagens. 6. Hormone-producing ovarian tumors. 7. Pelvic irradiation in the anamnesis. 8. Long-term . 9. Family history of breast, ovarian, or colon cancer. There are singled out two pathogenetic types of endometrium cancer:  type 1 – estrogen-dependent (combines with endometrium hyperplasia; declares itself with initial stages of endometrioid cancer; the risk factors are obestity, chronic anovulation, late menopause, no deliveries in the anamnesis, arterial hypertension, breast/ovarian cancer, diabetes mellitus);  type 2 – estrogen-independent (does not combine with endometrium hyperplasia; is usually detected at later stages and is referred to hystological types characterized by unfavorable prognosis – papillary, serous, clear cell). Uterine Carcinoma Classification according to the FIGO System Stage 1 – the tumor is limited with the uterine body. 1А – cancerous process is limited with the endometrium. 1В – there is invasion of less than 1\2 of myometrium thickness. 1С – there is invasion of more than 1\2 of myometrium thickness. Stage 2 – extension into the uterine neck. 2А – affection of the glandular structures of the endocervix. 2В – invasion into the uterine neck stroma. Stage 3 – local and/or regional spread. 3А – affection of the serous uterine tunic and/or presence of malignant cells in the abdominal lavage. 3В – affection of the vagina. 3С – affection of the pelvic/paraaortal lymph nodes. Stage 4А – invasion of the mucous tunic of the urinary bladder/intestine. Stage 4В – remote metastases. Uterine Carcinoma Classification according to the TNM System Т – the volume of lesion. Т0 – the primary tumor cannot be detected. Тis – preinvasive carcinoma. Т1 – the tumor is limited with the uterine body. Т1а – the tumor is limited with the endometrium. Т1b – there is invasion of less than 1\2 of myometrium thickness. Т1c – there is invasion of more than 1\2 of myometrium thickness. Т2 – the tumor spreads onto the uterine neck but not outside the limits of the uterus. Т2а – the tumor affects only the endocervical glands. Т2b – invasion of the tumor into the uterine neck stroma. Т3 – local and/or regional spread. Т3а – lesion of the serous uterine tunic and/or appendages and/or presence of malignant cells in the abdominal lavage. Т3b – metastases into the vagina. Т4 – the tumor spreads onto the mucous tunic of the urinary bladder, rectum, and/or outside the limits of the small pelvis. N – regional lymph nodes. Nx – insufficient data to estimate the condition of the regional lymph nodes. N0 – there are no signs of metastatic spread to the regional lymph nodes. N1 – metastatic spread to the regional lymph nodes. M – remote metastases Mx – insufficient data to detect remote metastases. M0 – there are no signs remote metastases. M1 – there are solitary metastases.

Clinical Presentation A symptom of endometrial carcinoma are blood-tinged or puruloid discharge from the reproductive tract. In women of the childbearing age the disease declares itself with menstrual dysfunction or metrorrhagia, less frequently with intermenstrual discharge. Pain appears in disseminate process – its onset may be caused by the stretch of the uterine walls with the contents of its cavity or by compression of the nerve trunks with cancer infiltration. In case of tumor extension to the adjacent organs their dysfunction develops. At the beginning of the disease uterine dimensions may stay unaltered; later, as the process progresses, uterine mobility decreases. Diagnostics Recognition and staging of endometrial carcinoma are based on the anamnestic data, bimanual, roentgenological, hysterorsopic, cytological, and hystological examinations. Hysteroscopy is of special importance, because it allows finding tumor localization and process extent, conducting target biopsy. investigation is used to screen the process. If endometrium cancer is suspected, uterine ultrasound is to be carried out; if the echographic thickness of the endometrium is less than 5 mm, endometrial hyperplasia or carcinoma is hardly probable. Endometrium cancer should be excluded when there appear uterine bleedings in the postmenopausal period (in 20 % examined women malignant genital diseases are found). In order to detect metastases one resorts to chest radiography, computer tomography, sigmoscopy, or irrigoradiography (if palpation shows extension of the disease outside the limits of the uterus or if there is intestinal symptomatology). Radionuclide scanning of the brain, liver, and bones is carried out only if remote metastases are suspected. Endometrial carcinoma is staged in the course of surgical intervention. Treatment The most widespread method of treating endometrial carcinoma patients is surgical. If the tumor affects only the mucous tunic of the uterine body, one should carry out panhysterectomy. If the tumor affects the region of isthmus, extends to the cervical canal, or if there are roentgen signs of metastases in the regional pelvic lymph nodes, one should conduct extended panhysterectomy and lymphadenectomy of the outer, inner, and obturative lymph nodes. If the tumor affects a large area of the endometrium, in case of its evident extension into the myometrium, there is indicated combined therapy with the use of gamma-ray teletherapy in the postoperative period. In the pre- and postoperative period hormones are administered subject to the presence or absence of steroid hormone receptors in the tumor. As tumor differentiation rises, its gestagen sensitivity increases. Oxyprogesterone capronate is introduced i.m. by 1 g 3 times a week (up to 8 ml of 12.5 % oil solution) or by 500 mg daily during 2–3 months, later reducing the dose to 500 mg a week. The duration of hormonal treatment is detected individually. Gestagens of durable action may be used in the capacity of hormonal preparations (depostat, depo-provera, farlutan). If the operation and radiation therapy are contraindicated, hormonal therapy is provided during the whole life after the diagnosis is given. Associated radiation treatment may be used as an independent type of therapy only if there are contraindications to the operation and eradication of tumor is impossible because of its considerable extension into the parametral fat and ligamentous apparatus of the uterus. It consists in tele- and intracavitary irradiation of the uterus and the area of regional lymph nodes. Prognosis 5-year survival rate in endometrial carcinoma: - stage 1 – 90 %; - stage 2 – 75 %; - stage 3 – 40 %; - stage 4 – 10 %. The most important prognostic factor is the hystological type of the tumor; the second most important factor is the invasion depth; in glandular planocellular, clear cell, and papillary serous carcinomas the prognosis is worse than in adenocarcinoma. Uterine sarcoma is observed rather rarely – it makes 3–5 % of all malignant uterine tumors. Sarcoma mainly affects women at the age of 40–50 years, localizes in the uterine body. The tumor may arise in the endometrial stroma, its cellular elements, myometrium, smooth muscle and connective tissue cells. Sarcomas spread in the hematogenic and lymphogenic ways affecting the lungs, liver, vagina, bones; it may also extend into the adjacent organs. The clinical presentation depends on the location and growth rate of the tumor. In case of submucous location there arise profuse uterine bleedings, which leads to . Painfulness might be conditioned by rapid tumor enlargement. If the tumor gets infectes, body temperature rises, purulent or purulent-bloody discharge from the genital tract appears. Diagnostics. Uterine sarcoma recognition is difficult before the operation. If the uterine tumor grows quickly or in the postmenopausal period, one should first of all treat this disease. In case of submucous location of the tumor it may diagnosed by means of histological examination of the scrape. It is more difficult to give the diagnosis in case of intramural or subserous tumot location. Urgent histological examination in the course of surgical intervention allows giving a precise diagnosis. The treatment first of all consists in the surgical removal of the uterus with appendages. Additionally one may provide laser therapy in the form of gamma-ray teletherapy of the small pelvis, though it does not raise patient survival rate. Presently, in the treatment for uterine sarcoma anticancer drugs are used in different combinations. Carminomycine in combination with cyclophosphan and vincristine is rather effective. Carminomycine is administered by 10 mg i.v. twice a week (the cumulative dose is 40 mg), cyclophosphan – by 400 mg on alternate days (the cumulative dose – 2.8 g), vincristine – by 1.5 mg i.v. once a week (the cumulative dose is 4.5 mg). refresher courses are administered in 3–4 weeks.

Trophoblastic Disease Trophoblastic diseases take a special place among other malignant neoplasms in . They are observed rather rarely, affect primarily young women of the childbearing age. Presently the prevalence of chorionic carcinoma in European countries makes 1:20 000–1:50 000 pregnancies. The notion “trophoblastic disease” includes: 1. Hydatid mole – complete or partial. 2. Invasive (destructuring) hydatid mole. 3. Chorionic carcinoma (chorioepithelioma), connected with pregnancy. 4. Trophobalstic tumor of the placental bed. 5. Placental bed response. 6. Hydropic degeneration. Trophoblastic Tumor Stages (International Federation of Gynecology and Obstetrics) Stage 1 – the tumor is limited by the uterus; high level of β-subunit of CG in the blood serum. 1-А: there are no risk factors; 1-В: there is one ; 1-С: there are two risk factors. Stage 2 – affection of the uterine appendages, vagina, and parametrium. 2-А: there are no risk factors; 2-В: there is one risk factor; 2-С: there are two risk factors. Stage 3 – metastases into the lungs (regardless of genital organs affection). The diagnosis is given on the basis of high level of β-subunit of CG in the blood serum, if there are radiological signs of metastases and connection of the disease with pregnancy. 3-А: there are no risk factors; 3-В: there is one risk factor; 3-С: there are two risk factors. Stage 4 – remote metastases (except for metastases into the lungs): metastases into the brain, liver, kidneys, or gastrointestinal tract. The prognosis is unfavorable; in considerable dissemination the risk of tumor resistance against anticancer drugs is high. 4-А: there are no risk factors; 4-В: there is one risk factor; 4-С: there are two risk factors. The risk factors are the level of β-subunit of CG in the blood serum exceeding 100,000 IU\L and disease duration (counted from the termination of the preceding pregnancy) longer than 6 months. The etiopathogenesis of trophoblastic disease still remains disputable and not studied completely. The probability of trophoblastic diseases onset is the highest in women of the young childbearing age or after 40 years, in cse of late menarche (after 15 years), early beginning of the sexual life (before 15 years), high parity (more than 5 deliveries), especially in case of combination of these factors. The risk of disease development rises considerably in complicated course of previous pregnancies (сspontaneous , artificial abortion, extrauterine pregnancy, etc.). Hormonal disorders, conditioned by estrogen hyperproduction by the ovarian cysts, considerably increase the frequency of malignant transformation of hydatid mole. Hydatid mole Hydatid mole is a disease of the chorion characterized by a sharp enlargement of the villi, which trasnform into racemose masses of a complex of vesicles of different size filled with a light transparent fluid. Ther are differentiated complete, partial, and invasive hydatid mole. The clinical presentation is characterized by the presence of pregnancy signs with inconformity of its term and uterine dimensions. The uterine dimensions are usually larger than normal for the given gestation term. Very often such pregnancy is accompanied by early gestosis with bright manifestations. Even at early terms women have edemas, hypertension, and proteinuria. Blood-tinged discharge is a pathognomonic symptom in hydatid mole; the discharge may of different intensity, but usually continuous. In hydatid mole vaginal examination shows dense-elastic consistency of the uterus with sites of softening. If the uterus is large, it is impossible to detect the fetal parts, auscultate its heartbeats and movements. Hydatid mole is characterized by the fromation of bilateral theca lutein ovarian cysts. They regress after hydatid mole removal. The diagnostics of hydatid mole, except for clinical symptoms, is based on the detection of a high level of chorionic gonadotropin. In the course of normal pregnancy the maximum CG level in urine falls on the 7th–11th week and does not exceed 20,000–40,000 IU per liter of urine. In hydatid mole CG concentration in urine is higher than 80,000–100,000 IU/L. Besides, CG in hydatid mole, unlike CG in physiological pregnancy, is temperature-stable, i.e. resistant to heating. Ultrasound examination is of key value. The echogram shows the enlarged uterus filled with homogeneous fine-grained tissue in the absence of a fetus, and also cystic degeneration of the ovaries. The final diagnosis is given according to the results of the histological examination of the scrape from the uterine cavity. Microscopy shows edematous chorionic villi, restrictedly vascularized; villous fluid accumulation results in the so- called “villi elephantiasis”. The treatment of hydatid mole and therapeutic approach in case of its detection mainly depends on the term of diagnosis formulation. If the uterine dimensions do not exceed 12-week pregnancy, the doctor should remove the hydatid mole with a blunt curette after cervical canal dilation. Simultaneously the doctor administers uterus-contracting drugs. If the uterus is large and hemorrhage is insignificant, in order to accelerate expulsion one administers uterus-contracting drugs (oxytocin, prostaglandins, ergometrin derivatives). If hemorrhage continues after hydatid mole expulsion, the doctor carries out careful curettage with a blunt curette. If there is no bleeding, because of the risk of uterus perforation, curettage should be better conducted the next day, when the uterus contracts. Substantial hemorrhage is an indication to immediate liberation of the uterus by means of cervical canal dilation and hydatid mole removal with the help of the digital method (if it is possible). If massive bleeding develops in large uterine dimensions and unprepared maternal passages, one should conduct minor cesarean section. In invasive hydatid mole the basic method of surgical treatment is hysterectomy. Indications to hysterectomy: threatened profuse bleeding; uterus perforation; uterus rupture by the tumor; large uterine dimensions (exceeding 12-week pregnancy); the patient older than 45 years; if 3 courses of polychemotherapy are unsuccessful irrespective of the patient’s age. Monochemotherapy. Indications: tumors limited by the uterus; the patient younger than 45 years; disease duration longer than 6 months since the last menstruation; small tumor (not larger than the uterus of 8-week pregnancy). Monochemotherapy is carried out with methotrexate (75 mg/day), dactinomycin (1,500 mcg/day), cyclophosphan (1.0 g/day), and platidiam (50 mg/day). Usually they are administered in the from of 5-day courses with 5–7-day intervals, 5–8 cycles altogether. Polychemotherapy. Indications: inefficient monotherapy (plateau or CG level increase); metastases presence; disease duration exceeding 6 months; disease development associated with delivery; a history if recurrent hydatid moles. The ЕМА-СО combination (etoposide, methotrexate, dactinomycin, cyclophosphamide and vincristine) makes complete remission possible in 83 % patients with a high risk of resistance against anticancer drugs.

Chorioepithelioma Chorioepithelioma is a malignant tumor, which develops from elements of trophoblast, chorionic villi syncytium, sometimes – from the germ cells of the female and male gonads (from embryoderived mixed tumors – teratogenic chorionic carcinoma). In this connection there is detected primary in prepubertal girls, and in nonpreganant women from teratoid tumor. Secondary tumor develops from the fetal egg trophoblast, which has lost connection with the egg – became an autonomic mass with comprehensive invasive ailities. In most cases chorioepithelioma forms against the background of hydatid mole from its elements. Clinical presentation. Chorioepithelioma usually develops in 3–4 after pregnancy. It is characterized by blood-tinged discharge of different intensity, pains in the lower abdomen or other parts of bofy (in metstases into the liver, lungs, brain), body temperature rise, intoxication signs (headache, vertigo, malaise, nausea, vomiting, palpitation). Serous vaginal discharge is also typical. As tumor disintegrates, the discharge becomes purulent. Vaginal examination shows cyanosis of the mucous tunic of the vagina and vaginal part of the uterine neck, its loosening. The uterine dimensions may vary – from normal to those of 16–18-week pregnancy; the uterus is of uneven consistency, tuberous, movable, painless. The diagnostics of chorioepithelioma is based on the anamnestic data and clinical examination of the patient. Hormonal examination. The CG level is found. In chorionic carcinoma CG content in urine reaches the level of 80,000–1,200,000 IU/L, in blood its level exceeds 200 ng/ml (in healthy women the index is 1.7 ng/ml), but in some cases (in case of tumor lesion) hormone increase is not noted. Temperature-stable CG is found in half chorioepithelioma patients. Trophoblastic β-globulin detection is also an informative method. US and CT of the abdominal cavity are indicated to all patients if liver function indices are altered. Head CT allows excluding metastases into the brain. Thoracic CT sometimes detects small metastases in the lungs invisible in radiography. US makes it possible to detect the spread of primary tumor, since this noninvasive examination allows exact identification of tumor dimesnions and localization in the uterus. It is used to select patients, to whome surgical treatment is indicated. Radiologic investigations allow detecting metastases in to the lungs. Metastases may be solitary, single, and multiple; they are detected in the form of round foci, more frequently in both lungs. A promising method is detecting malignant tumor markers – substances produced by tumors. The markers of tumor growth include oncofetal – carcinoembryonal α-fetoprotein, β-choriogonin. They are found in blood with the help of monoclonal antibodies and radioimmune method. Histological examination of the uterine cavity scrape or biopsy material obtained by means of hysteroscopy. Microscopy shows chorion particles with atypical proliferates of syncytium and cytotrophoblast in the absence of stroma among them. The approach to the treatment of chorioepithelioma patients depends on the spread of the process, duration of the disease, and general condition of the patient. Absolute indications to the surgical treatment: internal or external hemorrhage, which cannot be treated conservatively; threatened rupture of the uterus or ovarian cyst with the growing tumor; large uterine dimensions, which correspond to 9–10 and more weeks of pregnancy. Relative indications: tumor resistance to chemotherapy; the patient’s age older than 40–45 years; disease duration longer than 6 months; evident intoxication as a result of tumor necrosis and infection of the affected organ. In case of a solitary node in the tumor without metastatic process there is performed hysterectomy sparing the ovaries. If metastases are suspected, and also if there are cysts in the ovaries, extirpation of the uterus with appendages is carried out. Chemotherapeutical agents are used in the regimen of mono- and polychemotherapy. In case of surgical treatment, chemotherapy is administered both in the process of conducting the operation and in the postoperative period (in 10 days after the operation). The doctor administers one preparation or combines a couple of preparations of anticancer action analogous to the ones used in hydatid mole. The treatment is provided in the form of 8–15-day courses with 10–15-day intervals between them. Presently it is possible to cure 90–95 % patients with nonmetastatic chorionic carcinoma and 80–85 % patients with metastatic chorionic carcinoma. Malignant Ovarian Tumors Malignant ovarian tumors are the main reason for the death of oncological patients. Among malignant ovarian neoplasms the leading place is taken by ovarian carcinoma – epithelial malignant tumor. These tumors develop from the cylindrical epithelium in the form of glandular or papillary masses, more frequently of solid structure. There are differentiated three variants of ovarian carcinoma: primary cancer – tumor arises directly in the ovarian tissue; secondary cancer – tumor develops in benign ovarian tumors; metastatic cancer – tumor is a metastasis of the cancer of other organs into the ovary. All metastatic ovarian tumors are considered stage ІV cancer of other organs (remote metastasis from the initial focus). Depending on the initial focus metastatic ovarian tumors are divided into four groups: metastases from tumors of epithelial structure (cancer of the stomach, intestine, biliary tracts, mammary gland, skin, etc.); metastases from tumors of connective-tissue origin (sarcoma, lymphosarcoma); metastases of neurogenic origin; hematologic neoplasms. Krukenberg’s tumor is a special new growth – it is a metastasis characterized by the presence of mucin-filled signet ring cells in combination with sarcoma-like proliferation of ovarian stroma. It is more frequently a metastasis of stomach cancer, but may also arise from other organs. Ovarian tumor more frequently extends along the peritoneum and into the greater omentum, and also by the lymphogenous and hematogenous channels. Having passed the regional lymph nodes (paraaortal, paranephral), metastases may arise in any region.

Table 1

Classification of Malignant Ovarian Tumors according to the Systems TNM and FIGO (1997)

System TNM FIGO Sign

T1 I The tumor is limited with the ovaries

T1a IA The tumor affects one ovary, there is no ascites containing malignant cells. There are no excrescences on the external surface of the capsule, the capsule is intact

T1b IB The tumor is localized only in the ovaries, there is no ascites containing malignant cells. There are no excrescences on the external surface of the capsule, the capsule is intact T1c IC The tumor affects one or both ovaries with excrescences on the capsule surface, the integrity of the capsule wall is violated, malignant cells are found in the ascetic fluid or in abdominal lavage

T2 II The tumor affects one or both ovaries extending in the small pelvis

T2a IIA Extension and/or metastasis into the uterus or uterine tubes

T2b IIB Extension of the tumor into other pelvic tissues

T2c IIC Corresponds to the stage IIА or IIВ, but there are tumor excrescences on the surface of one or both ovaries, the capsule integrity is violated, malignant cells are found in the ascetic fluid or in abdominal lavage

T3 or III The tumor affects one or both ovaries with implants along the

N1 peritoneum outside the limits of the small pelvis and/or the retroperitoneal or inguinal lymph nodes are affected. Metastases on the capsula of liver correspond to the III stage. The tumor is visually limited with the small pelvis, but its extension into the small intestine or omentum has been proved histologically

T3a IIIA The tumor is localized in the small pelvis, but peritoneum affection outside the limits of the small pelvis has been proved histologically

T3b IIIB Lesion of one or both ovaries with microscopic detectable implants on the peritoneum surface outside the limits of the small pelvis not larger than 2 cm in diameter

T3c or IIIC Tumor implants on the peritoneum implants outside the limits of

N1 the small pelvis larger than 2 cm in diameter and/or lesion of the retroperitoneal or inguinal lymph nodes

M1 IV Lesion of one or both ovaries with remote metastases. Cytological examination shows malignant cells in the fluid from the pleural cavity. There are tumor metastases in the liver parenchyma

Clinical presentation. High death rate in ovarian tumor is first of all explained by late diagnostics connected with the absence of distinct clinical presentation of the disease at an early stage, and complications of early diagnostics. The clinical symptoms characteristic of the late stage of process development declare themselves only when the tumor extends: weakness, fatigability, loss of appetite, body temperature rise, dysuric phenomena, dysfunction of the abdominal organs, enlargement of abdomen, ascites onset. The diagnostics of malignant ovarian tumors does not differ from the methods expounded in the chapter Ovarian Tumors and Tumor-Like Neoplasms. In the women of the risk group examinations are to be carried out 1–2 times a year with the obligatory use of transvaginal techniques of ultrasonic diagnostics allowing identifying the internal structure of an ovarian more accurately, which makes well-grounded judgment about the character of the pathological process possible. The possibilities of ultrasonic diagnostics increase when one uses color doppler mapping, which allows estimating the character of blood flow in the tumor. Malignant ovarian tumors of cystic structure are characterized by evident vascularization with color signal mosaicity in the central tumor structures because of hyperechoic inclusions and septa. Malignant ovarian tumors of solid structure are characterized by multiple vascularization foci with low indices of blood flow resistance. Additionally there may be used method of computer, magnetic resonance, and proton emission tomography. In order to assess the degree of process extension one uses the methods of endoscopy, lymphography, computer tomography, and magnetic resonance tomography. Presently, in order to diagnose malignant ovarian neoplasms biochemical and immunological methods are also used. With this purpose one studies the content of tumor markers in the blood (tumor-associated antigens: СА-125, СА-19-9, СА-72-4; oncofetal and oncoplacental antigens). СА-125 is found in 80–100 % patients with ovarian tumor, still, at the early stage of the disease specificity is not high. For this reason the marker cannot be used as a screening test. The treatment of petinets with malignant ovarian neoplasms should be strictly individualized subject to the stage of the process, morphological structure and degree of tumor differentiation, individual sensitivity of the given tumor histotype to chemotherapy, immunological status. When one chooses the method of treatment, he should take into account contraindications to the application of the methods. At all stages of the diseases complex treatment is provided: surgical, chemo- and hormonotherapy, etc. Surgical intervention is resorted to at all stages of ovarian carcinoma, including stage IV. Presently, in young women there may be conducted organ-sparing operative interventions – removal of the affected uterine appendages, resection of the unaffected ovary, and resection of the greater omentum. Such operations may be performed in stage IА and tumors of the genital cord stroma, and mucinous neoplasms. Organ-sparing operations are not recommended in stage IC epithelial tumors, and also at the low degree malignant ovarian tumor differentiation. In other cases one should perform panhysterectomy and salpingo-oophorectomy, and resection of the greater omentum. If the indicated volume of the operation is impossible, a part of the tumor is eradicated as well as accessible metastases. In such cases one conducts repeated operation after 2–3 courses of successful chemotherapy. If the patient is inoperable, the doctor carries out biopsy to detect the histological type of the tumor. One should obligatorily examine the peritoneal fluid, revise the paraaortal and pelvic lymph nodes. If they are enlarged, lymphadenectomy is to be conducted followed by histological examination. If the patient’s inoperability is suspected, at first preoperational chemotherapy is provided, which may raise the possibilities of the operative intervention. Chemotherapy is an obligatory component of the complex treatment for ovarian cancer. Patients with IA and IВ stages of the disease in case of high and moderate tumor differentiation are an exception. Cytostatic agent introduction should be begun in the nearest 2–3 weeks after the operation. The duration and intensity of chemotherapy is determined individually. A couple of chemotherapy courses are carried out, after what patients are under observation. In order to monitor treatment efficiency US is used, as well as laparoscopy, sometimes recurrent laparotomies, estimation of СА-125 antigen content. Ovarian cancer is mainly treated by the method of polychemotherapy (the use of more than two chemical preparations in one course of treatment). In ovarian cancer the medicinal combinations of cytostatic agents include usually include platinum derivatives, alkylating agents, antibiotics, etc. Except for traditional routes of chemical preparation introduction in ovarian cancer one often resorts to their intraperitoneal, and also intralymphatic introduction: these routes of introduction allow administering large doses of preparations. Simultaneously with courses of intensive chemotherapy one applies intravenous hyperhydration, disintoxication therapy controlling the function of the kidneys and heart, etc. Some chemotherapy regimens are presented in special oncogynecology guides. In the treatment for malignant ovarian tumors there is also used hormonotherapy: gestagens (in endometrioid tumors) and antiestrogens (if there are estrogen receptors in tumors). Radiation therapy is used rather rarely in malignant ovarian neoplasms. This therapy may be applied in certain structures of tumors (, granulosa cell tumor), sporadic non-removable metastases, and in the treatment of residual tumors insusceptible of chemotherapy. Ovarian cancer prevention consists in timely diagnostics and treatment for benign gonadal neoplasms.

7. Materials for self-control:

7.2 TEST \TASKS

TESTS A 22-year-old G1P0 presents to your clinic for follow-up of evacuation of a complete hydatidiform mole. She is asymptomatic and her examination is normal. Which of the following would be an indication to start single-agent chemotherapy? A. a rise in hCG titers B. a plateau of hCG titers for 1 week C. return of hCG titer to normal at 6 weeks after evacuation D. appearance of liver metastasis E. appearance of brain metastasis 2.A 20-year-old G1P0 presents to your clinic for follow-up for a suction dilation and curettage for an incomplete abortion. She is asymptomatic without any , fever, or chills. Her examination is normal. The pathology report reveals trophoblastic proliferation and hydropic degeneration with the absence of vasculature; no fetal tissue is identified. A chest x-ray is negative for any evidence of metastatic disease. Which of the following is the best next step in her management? A. weekly human chorionic gonadotropin (hCG) titers B. hysterectomy C. single-agent chemotherapy D. combination chemotherapy E. radiation therapy 3.A 26-year-old woman complains of having bloody discharges from the genitals for the last 14 days, abdominal pain, general fatiguability, weakness, weight loss, body temperature rise, chest pain, obstructed respiration. 5 weeks ago she underwent induced abortion in the 6-7 week of gestation. Objectively: the patient is pale and inert. Bimanual examination revealed that the uterus was enlarges up to 8-9 weeks of gestation. In blood: Hb- 72 g/l. Urine test for chorionic gonadotropin gave the positive result. What is the most likely diagnosis? A. chorioepithelioma B. metroendometritis C. uterus perforation D. uterine fibromyoma E. uterine carcinoma 4.A 45 y.o. woman complains of contact bleedings during 5 months. On speculum examination:hyperemia of uterus cervix, looks like cauliflower, bleeds on probing. On bimanual examination: cervix is of densed consistensy, uterus body isn't enlarged, mobile, nonpalpable adnexa, parametrium is free, deep fornixes. What is the most likely diagnosis? A. cancer of cervix of uterus B. cancer of body of uterus C. fibromatous node which is being born D. cervical pregnancy E. polypose of cervix of uterus 5.A 58-year-old female patient came to the antenatal clinic with complaints of bloody light-red discharges from the genital tracts. Menopause is 12 years. Gynaecological examination found externalia and vagina to have age involution; uterine cervix was unchanged, there were scant bloody discharges from uterine cervix, uterus was of normal size; uterine appendages were not palpable; parametria were free. What is the most likely diagnosis? A. uterine carcinoma B. atrophic colpitis C. abnormalities of menstrual cycle with climacteric character D. cervical carcinoma E. granulosa cell tumor of ovary 6.The results of a separate diagnostic curettage of the mucous of the uterus' cervix and body made up in connection with bleeding in a postmenopausal period: the scrape of the mucous of the cervical canal revealed no pathology, in endometrium - the highly differentiated adenocarcinoma was found. Metastases are not found. What method of treatment is the most correct? A. surgical treatment and hormonotherapy B. surgical treatment + chemotherapy C. surgical treatment and radial therapy D. radial therapy E. all of the above 7.A 48 year old female patient complains about contact haemorrhage. Speculum examination revealed hypertrophy of uterus cervix. It resembles of cauliflower, it is dense and can be easily injured. Bimanual examination revealed that fornices were shortened, uterine body was nonmobile. What is the most probable diagnosis? A. cervical carcinoma B. metrofibroma C. endometriosis D. cervical pregnancy E. cervical papillomatosis 8.Laparotomy was performed to a 54 y.o. woman on account of big formation in pelvis that turned out to be one-sided ovarian tumor along with considerable omental metastases. The most appropriate intraoperative tactics involves: A. ablation of omentum, uterus and both ovaries with tubes B. biopsy of omentum C. biopsy of an ovary D. ablation of an ovary and omental metastases E. ablation of omentum and both ovaries with tubes 9.A 43 y.o. patient complains of formation and pain in the right mammary gland, rise of temperature up to $37,2^0C$ during the last 3 months. Condition worsens before the menstruation. On examination: edema of the right breast, hyperemia, retracted nipple. Unclear painful infiltration is palpated in the lower quadrants. What is the most probable diagnosis? A. cancer of the right mammary gland B. right-side acute mastitis C. right-side chronic mastitis D. premenstrual syndrome E. tuberculosis of the right mammary gland

10.A 43 y.o. woman complains of contact hemorrhages during the last 6 months. Bimanual examination: cervix of the uterus is enlarged, its mobility is reduced. Mirrors showed the following: cervix of the uterus is in the form of cauliflower. Chrobak and Schiller tests are positive. What is the most probable diagnosis? A. cancer of cervix of the uterus B. polypus of the cervis of the uterus C. cervical pregnancy D. nascent fibroid E. leukoplakia

3.A 40-year-old woman complains of yellow color discharges from the vagina. Bimanual examination: no pathological changes. Smear test: and mixed flora. Colposcopy: two hazy fields on the front labium, with a negative Iodum probing. What is your tactics? A. treatment of specific colpitis with the subsequent biopsy B. diathermocoagulation of the cervix uteri C. specific treatment of Trichomonas colpitis D. cervix ectomy E. cryolysis of cervix uter TASKS 1. A 68-year-old patient consulted a doctor about a tumour in her left mammary gland. Objectively: in the upper internal quadrant of the left mammary gland there is a neoplasm up to 2,5 cm in diameter, dense, uneven, painless on palpation. Regional lymph nodes are not enlarged. What is the most likely diagnosis? 2. Which process represents the IIIb type of smear at oncocytological examination? 3. A 55-year-old woman came to a gynecologist with complaints of leukorrhea and bloody discharge from the vagina after 5 years of menopause. Anamnesis states no pregnancies. Bimanual examination: the uterus and uteri- ne appendages are without changes. During diagnostic curettage of the uterine cavity the physician scraped off enchephaloid matter. What is the most likely diagnosis in this case? 4. At woman, 54 years, after the separate diagnostic scraping of mucus shell of uterus and cervical canal in connection with non-cyclic uterine bleeding found out adenocarcinoma. What volume of inspection and treatment does it follow to offer this patient? What does the volume of medical interference depend vid? 5. Woman 52, which during 7 did not have monthly, noticed periodic appearance of insignificant blood colors excretions from vagini. At a review doctor – a gynaecologist found out no changes from the side of genitaliy. However, taking into account age of sick and appearance of blood colors excretions after 7- of annual menopauzi, suspected the cancer of body of uterus and took a selection from an uterus for cytological research. On a next day an answer is got, that atypical cages are present in a stroke. The sick was immediately directed to gynaecological permanent establishment for the separate diagnostic scraping off of cavity of uterus with the purpose of clarification of diagnosis. Diagnosis. 6. For the last 3 years with a medical and diagnostic purpose the separate diagnostic scraping off of cervical channel and cavity of uterus was 5 times conducted. An answer of histological research after every scraping off is polipoz of endometria. Conservative treatment is uneffective. Diagnosis. Plan of subsequent treatment. 7.Woman, 50 years, acted to the gynaecological separation with complaints about pain at the bottom of stomach. For 5-6 months noticed multiplying a stomach. Had 3 births, 4 abortions. Long time treated oneself concerning inflammation of appendages of uterus. Last 2 years for a gynaecologist did not inspect. Objectively: a skin is pale. Lights, heart without features. A stomach is sickly in lower departments, a free liquid is determined in an abdominal region. At a vaginal inspection neck and vagina without features. An uterus is included in the conglomerate of tumours, separately not