Trophoblastic disease

Trophoblastic (gestational) disease is a general term for the spectrum of pregnancy-related proliferative anomalies derived from trophoblast. An important sign of trophoblastic disease is the formation of luteal ovarian cysts, which occurs in 50% of cases. Most patients have bilateral luteal cysts, which can reach large sizes and fill the entire abdominal cavity.

Epidemiology

The frequency of trophoblastic disease has a certain geographical pattern - ranging from 0.36% in Asian to 0.008% in European countries (in relation to the number of pregnancies). Such epidemiology is associated with a violation of the immune status in women with a large number of pregnancies and a short interval between them. However, an exact explanation for this fact has not yet been found.

[1], [2], [3], [4], [5], [6], [7],

Symptoms of the trophoblastic disease

The leading symptom of trophoblastic disease - after amenorrhea there is uterine bleeding, sometimes accompanied by the release of many bubbles with transparent contents.

Other symptoms of trophoblastic disease:

• pronounced early gestosis (nausea, vomiting), preeclampsia;
• the size of the uterus exceeds the expected duration of pregnancy;
• with vaginal examination - uterus of a tightly elastic consistency, longer than the expected pregnancy;
• palpation of the uterus (with large sizes - lack of signs of the fetus);
• absence of palpitation and fetal movement;
• absence of signs of the fetus in the uterus (according to ultrasound);
• qualitative and quantitative detection of chorionic gonadotropin in the urine and in the blood (with a bubble drift, the level of the chorionic gonadotropin exceeds its index in normal pregnancy by 50-100 times).
• pain in the lower abdomen with the development of chorion carcinoma;
• Symptoms caused by the predominant localization of tumor metastases (hemoptysis, neurological symptoms, etc.).

Stages

Clinical classification of chorionic carcinoma (FIGO, 1992):

• I stage - the lesion is limited to the uterus, there is no metastasis.
• II stage - the defeat extends beyond the uterus, but is still limited by the genitals.
• Stage III - metastasis to the lungs.
• IV stage - metastatic affection of other organs.

[8], [9], [10]

Forms

Trophoblastic disease includes:

• bladder skid,
• invasive (malignant) skid,
• chorionic carcinoma,
• trophoblastic tumor of the placental site.

[11], [12], [13], [14], [15],

Bumpy drift

Bubble skidding is characterized by edema and an increase in placental villi with hyperplasia of both trophoblast layers. It has two varieties - full and partial; The latter is distinguished by the presence of the fetus or its parts along with intact villi.

Invasive skidding - a bladder drift with germination of myometrium, hyperplasia of trophoblast and preservation of placental structure of villi.

With a bubble drift, luteal cysts may appear within the first 2 weeks. Their presence serves as an unfavorable prognostic sign. The reverse development of luteal cysts occurs within 3 months. After removal of the bladder skid.

Trophoblastic tumor of the placental site

The trophoblastic tumor at the site of the placenta arises from the trophoblast of the placental bed and consists predominantly of the cytotrophoblast cells, it is of low and high degree of malignancy.

[16]

Chorionic carcinoma

The chorionic carcinoma associated with pregnancy arises from the cyto- and syncytiotrophoblast, ie, from both layers of the trophoblast, is localized most often in the uterus, can occur both during and after the completion of a normal or pathological pregnancy (abortion, miscarriage, childbirth, vesicular drift, ectopic pregnancy). In the case of an ectopic pregnancy, it is localized in the tube or ovary, which is extremely rare. Chronicocarcinoma of the ovary can develop from germ cells, it is not associated with pregnancy and refers to germinogenic tumors (ie, it is not trophoblastic).

Macroscopically, the chorion carcinoma can be in the form of a knotty tumor located on the inner surface of the uterine cavity, intermuscularly, under the serous cover or in the form of diffuse outgrowths. The tumor is dark purple, has a soft consistency, does not contain blood vessels, the value is from 0.5 to 12 or more centimeters. In most cases, it is located submucous.

Microscopically, the chorionic carcinoma has 3 histotypes: syncytial, cytotrophoblastic and mixed. Characteristic are invasion of chorionic epithelium, extensive fields of necrosis and hemorrhage, isolated clusters of Langhans cells.

[17], [18], [19], [20], [21], [22]

Complications and consequences

Taking etoposide increases the risk of developing leukemia. It should be used only in patients with severe bleeding.

[23], [24], [25]

Diagnostics of the trophoblastic disease

Diagnosis of trophoblastic disease is based on data:

• anamnesis;
• clinical examination;
• ray, histological and hormonal methods of research.

Clinically important: detailed anamnesis, gynecological examination with the detection of cyanosis of the mucous membranes of the vagina and cervix, the increase and soreness of the uterus, possible metastases.

Radiodiagnosis includes ultrasound, dopplerography, angiography, magnetic resonance imaging (MRI), and X-ray computed tomography (CT).

Ultrasound and dopplerography are informative, simple, reliable and can be used to diagnose cystic and invasive drift and chorion carcinoma, as well as metastases to the liver, kidneys, and ovaries. Being non-invasive and harmless, they are indispensable for monitoring the effectiveness of chemotherapy. Contrast angiography makes it possible to clarify the diagnosis of chorion carcinoma, especially with negative histological evidence of scraping of the endometrium and trophoblastic hormones.

[26], [27]

Treatment of the trophoblastic disease

Trophoblastic disease is one of the rare forms of malignant diseases, characterized by a high frequency of cure with chemotherapy even in the presence of distant metastases.

The main method of treatment of trophoblastic disease is chemotherapeutic, which is used both independently and in complex therapy. In the complex treatment of individual forms of trophoblastic disease, surgical and radiotherapy is used.

Principles of treatment of bladder skidding

1. Vacuum aspiration or removal of a vesical drift by scraping the uterus with the appointment of uterine contracting agents (intravenously oxytocin, etc.).
2. Hysterectomy with large dimensions of cramps, significant bleeding, no conditions for emptying the uterus; unwillingness of a woman to continue to have a pregnancy. Ovaries with teko-luteal cysts are not removed.
3. After removal of the skid, observation is carried out for two years (monitoring the content of chorionic gonadotropin in urine 1 time per month).
4. Prophylactic chemotherapy (methotrexate), after evacuation of the vesicle by means of vacuum aspiration, is performed in the following cases: age over 40 years, incompatibility of the uterus with the expected pregnancy period, presence of luteal cysts during the period of cramps, increased chorionic gonadotropin level more than 20,000 IU / ml after 2-3 evacuation or after surgical treatment of invasive drift, the lack of dynamic control of the level of chorionic gonadotropin.

Principles of treatment of chorion carcinoma

1. First-line chemotherapy (methotrexate, actinomycin D, chloram-butyl, 6-mercaptopurine, adriamycin, platinum preparations and alkaloids).
2. Surgery. Indications: profuse uterine bleeding, the tendency of the tumor to perforate, the large size of the uterus, the resistance of the tumor to ongoing chemotherapy. The volume of the operation: in young women in the presence of a tumor without metastases - extirpation of the uterus without appendages, after 40 years - extirpation of the uterus with appendages.
3. The extract is made after 3 negative tests for chorionic gonadotropin, conducted at intervals of 1 week.
4. Observation. Within 3 months. Determination of the titer of the chorionic gonadotropin (1 time in 2 weeks), then within 2 years 1 time in 6 months. Radiography of the chest 1 time in 3 months. (during a year). Contraception (COC) is recommended throughout the year.

The choice of treatment regimen is currently carried out taking into account the risk of development of tumor resistance to chemotherapy on the WHO scale.

According to the WHO scale, 3 degrees of risk of development of resistance were identified: low (score less than 5), moderate (5-7 points) and high (8 or more points).

With a low risk of developing tumor resistance to chemotherapy (no metastases, small, up to 3 cm, the size of the uterine tumor, low serum HC and duration of the disease less than 4 months) monochemotherapy of the "first" line with the use of methotrexate or dactinomycin. The effectiveness of monochemotherapy varies from 68.7 to 100%.

The earliest indication of tumor resistance to chemotherapy is the absence of a decrease or increase in CG in the serum with two repeated analyzes at intervals of 1 week.

WHO scale for determining chorion carcinoma resistance to chemotherapy

Risk Factor	Number of points
	0	1	2	3
Age, years	Up to 39	Older than 39
Outcome of previous pregnancy	Bumpy drift	Abortion	Childbirth
Interval *, month	Less than 4	4-6	7-12	More than 12
Level ХГ, МU / l	Less than 10 **	10 3 -01 4	10 4 -10 5	More than 10 5
Blood group		0 or A	B or A B
The largest tumor, including a tumor of the uterus	Less than 3 cm	3-5 centimeters	More than 5 cm
Localization of metastases		Spleen, kidney	Gastrointestinal tract, liver	Brain
Number of metastases		1-3	4-8	More than 8
Previous chemotherapy			1 preparation	2 cytostatics or more

• * The interval between the end of the previous pregnancy and the beginning of chemotherapy.
• ** Low levels of chorionic gonadotropin can occur with trophoblastic tumors at the site of the placenta.

For treatment of patients with resistant forms of the tumor, various regimens of chemotherapy (line 2) are used with an increase in the dose of the drugs administered and the frequency of the courses.

With a moderate and high risk of developing tumor resistance (the presence of metastases, tumor size more than 3 cm, high chorionic gonadotropin, duration of symptoms more than 4 months, the appearance of the disease immediately after birth) combined polychemotherapy is used according to various schemes: MAC (methotrexate, dactinomycin, chlorambucine) ; EMA-CO (etoposide, dactinomycin, methotrexate, vincristine, cyclophosphamide, leucovorin), SAMOSA (hydroxyurea, dactinomycin, methotrexate, leucovorin, vincristine, cyclophosphamide, doxorubicin); PVB (cisplatin, vinblastine, bleomycin), ENMAS (etoposide, hydroxyurea, dactinomycin, methotrexate, vincristine). The most effective and less toxic combination of preparations of the 2nd line is the EMA-CO scheme.

For the treatment of resistant foci of tumors, a combination of their surgical removal and chemotherapy of the 2nd line is important. With distant metastases, combined polychemotherapy in combination with radiotherapy for the entire brain is performed in the brain; Radiation therapy is possible when metastasizing to a parameter.

Thus, surgical treatment and radiotherapy are additional methods of treatment.

Prevention

Clinical examination of patients after a bubble drift is carried out for 4 years. It is aimed at early diagnosis of a possible chorionic carcinoma and includes the following: control of the menstrual cycle, contraception for 2 years, general examination and gynecological examination, determination of serum HCG level I every 2 weeks. Before the normalization of indicators and then every 6 weeks. In the first six months, then every 8 weeks. In the next 6 months.

1 time in 4 months. - in the second year and once a year during the third and fourth year; Ultrasound of the pelvic organs and radiography of the lungs after 2 weeks. After the evacuation of a bubble drift and then once a year for the first two years. Patients who received preventive chemotherapy after a bubble drift are recommended the following observation periods: the first 3 months. - 1 time in 2 weeks, then within 3 months. - monthly, further - under the specified scheme.

Clinical examination of patients with choriocarcinoma is carried out for 5 years and also includes the management of the menopause, contraception for 2 years, a general examination with breast examination, gynecological examination, determination of serum HC in the first year, once every 3 months. For 2 years, 1 time in 4 months. In the third year and 2 times a year in the fourth and fifth years, then once a year. Ultrasound of the pelvic organs and radiography or pulmonary angioplasty of lungs 1 time in 2 months. In the first year and further 1 time per year during dispensary observation.

[28], [29], [30], [31], [32], [33]