Chorionepithelioma

Chorionepithelioma is the most malignant tumor that develops from chorion elements. Chorionepithelioma grows in the form of a node that is located more often in the upper half of the body of the uterus, often in one of its corners.
Chorionepithelioma develops in 50% of patients who have experienced bladder arthritis. The incidence of bladder skidding is one case per 500 -1000, chorionepithelioma - for 50 000-60 000 pregnancies.
The etiology of chorionepithelioma is unknown.
There was an infectious disease theory, but it was found that often the observed high temperature is the result of an attached septic infection and the absorption of toxic products of necrosis. Data that could point to a viral theory is not available. It is believed that in the blood of a pregnant woman there is a special cytolytic enzyme - syncithiolisin, which under normal conditions promotes the dissolution of the chorionic elements circulating in the blood (and sometimes growing into the wall of the uterus).
The decrease in cytolytic ability with excess intake of chorionic elements possessing significant proliferative growth is, in the opinion of some authors, the cause of the development of chorionepithelioma. The tumor is associated with pregnancy and bladder drift, hormonal changes are also known for this tumor. With the intravenous administration of large doses of gonadotropic hormones to pregnant dogs, the latter develops an excessive growth of syncytium with the destructive growth of the villi of the chorion with ingrowth into the muscular membrane of the uterus and vein.
Chorionepithelioma occurs more often after a bubble drift, less often after an abortion or childbirth. The latent period is the time from the end of the last pregnancy to the development of the tumor, ranging from 3 weeks to 20 years. The age of patients varies from 17 to 60 years. Chorionepithelioma is more likely to develop in repeatedly pregnant women.Reticuloses
Histologically, the tumor consists of Langgans cells, invasive chorionic epithelium. Groups of Langgans cells can be located by the alveoli, which are surrounded by a layer of syncytium and, as it were, enclosed in a mesh. This form of chorioepithelioma is called typical. The color of the node on the cut is dark purple (the color of the placenta on the incision), the consistency is very soft, uneven.
At the so-called atypical form of the chorionepithelioma of Langgans cells, there are only syncytial elements that infiltrate the tissues of the organ. Malignancy does not differ from each other.
The tumor has no stroma and its vessels. Elements of it grow into blood vessels (the endothelium of the vessel walls is killed), infiltrate their wall, the latter is necrotic and tears, causing hemorrhage and thrombosis of the vessel. Chorionic epithelioma can give hematogenous metastases to various organs: lungs, liver, kidneys, brain, spleen, and also the vagina. A diverse and early clinic of metastases gave grounds to call chorionepithelioma a disease of metastases.


Clinic of chorionepithelioma

 

Chorionepithelioma is characterized by bloody discharge from the uterus or vagina of varying intensity. Later, and sometimes simultaneously, there is pain in the lower abdomen or other parts of the body (with metastases to the lungs, liver, brain), fever (septic state as a result of infection, more often staphylococcus), headache, vomiting, nausea, cough with phlegm or dry.
The diagnosis of chorioepithelioma is based on the data:
1) anamnesis: bleeding from the uterus, appearing after the removal of bladder drift, after abortion or childbirth, nausea, vomiting, often allocation of colostrum, pain in the lower abdomen, cough, high body temperature;
2) gynecological examination: cyanosis of the vaginal mucosa and the vaginal part of the cervix, its loosening. In the presence of metastases in the vagina, the latter protrude into the lumen of the vagina in the form of a "dark blue eye" of various sizes. Metastases can be single or multiple. Uterus of various sizes (from normal to 16-18 weeks of pregnancy), uneven consistency, bugrave (intra-wall location of tumor foci), mobile, painless. Transition of the process to the peritoneal cellulose makes the uterus immobile, infection of the chorionepithelioma is accompanied by pain in the lower abdomen and a high temperature (39-40 ° C), and sometimes a septic state, as in septic (criminal) abortion. When the tumor is submucosal, the uterus has a rounded shape, . Disintegration of the tumor spontaneous (necrobiosis) or under the influence of chemotherapy, accompanied by secretions of color of crimson jelly. Long-term blood loss, intoxication with chorionepithelioma lead to anemia and suppression of hemopoiesis.
Bloody discharge, appearing at various times after removal of bladder drift, abortion or childbirth, is a direct indication for curettage of the uterine mucosa;
3) hormonal studies: the definition of chorionic gonadotropin, which is the most reliable test in the diagnosis of the disease. The reactions of Ashgame-Tsondek and Galli-Mainini allow to determine the amount of excreted mountainsmona of at least 1700-2500 IU in 1 liter of urine. With less biological activity of the tumor, these reactions are untenable, which should be taken into account in hormonal control during treatment and subsequent dispensary observation.
Chorionic epithelioma excretes two fractions of the chorionic gonadotropin: biologically active and immunologically active. The latter is determined by the immunological inhibition of haemagglutination inhibition, which makes it possible to determine the total amount of chorionic gonadotropin.
AA Davidenko proposes to carry out the Galli-Mainini reaction with native and boiled urine. Thermostable gonadotropin is found in almost half of the patients with chorionepithelioma. For qualitative and quantitative detection of the chorionic gonadotropin, the gravimun test can also be used;
4) X-ray examination: taking into account the frequent metastasis of chorionepithelioma into the lungs, a suspected chorionepithelioma requires radiography of the lungs. Metastases can be solitary, single or multiple, pneumonia-like or in the form of a "snow blizzard";
5) pneumogynecography: increase and displacement of the uterus, deformation of its cavity, needle-like or clavate protrusions of contours, impregnation of the uterus wall with contrast agent or local thinning of it, violation of patency of the fallopian tubes. An increase in the ovarian shadow indicates the presence of luteal cysts;
6) angiography: asymmetry, tortuosity and expansion of uterine arteries, widening and deformation of the intra-wall vessels, contrasting of small vessels, capillaries and vascular cavities, presence of arterio-venous anastomoses, contrast agent retention in the tumor, widening of the draining veins. Angiography in dynamics allows to judge the effectiveness of conservative treatment and tumor regression;
7) cytological examination: the result is often positive when aspirating the contents of the uterine cavity and negative when aspirating the contents of the vagina;
8) Histological examination of scrapings from the uterus - the main method of diagnosis. It should be remembered that with intra-wall or subserous tumor location histological examination of the uterus scraping can be false-negative. There are also frequent mistakes in the study of scrapings from the uterus after an abortion or removal of a vesicle drift early. Therefore, the diagnosis of the disease should be based on clinical, hormonal, radiologic and histological studies.
Scraping of the mucous membrane of the uterus, especially repeated, should be carried out according to strict indications; it can promote dissemination of the tumor;
9) radioisotope study, conducted mainly for the purpose of topical diagnosis of liver and kidney damage. This study allows you to accurately determine the localization of metastasis in the liver and kidneys with a size of more than 2-3 cm in diameter. In addition, the functional activity of these organs is determined, which is of great importance in deciding the question of the effectiveness of chemotherapy.


Treatment of chorioepithelioma

 

Treatment with chorionepithelioma begins with chemotherapy.
Assign the following chemotherapy:
1) antifolievye antimetabolites - methotrexate and mercaptopurine. Methotrexate is prescribed by five-day courses of 20-25 mg per day, orally or intravenously. After each course of treatment, a five-seven-day break is made to restore hematopoiesis. Mercaptopurine is prescribed at 200 mg per day concomitantly with methotrexate or as an independent course of 500-600 mg per day for 5 days;
2) vegetable alkaloids: vinblastine and vincristine. Vinblastine is prescribed a ten-day course of 5 mg per day intravenously. The intervals between the courses are 7-10 days. As a rule, spend no more than 3 courses. Vincristine is prescribed in increasing doses intravenously once a week, starting with 0.5 mg and bringing up to 3.5 mg once, all for a course of 8-12 mg;
3) antitumor antibiotics: rubomycin - 40-60 mg per day intravenously for 5 days, for a course of 200-300 mg. Break between courses 5-7 days (depending on the state of hemopoiesis), only 5-6 courses. Carminomycin is administered at 10-16 mg intravenously, for a course of 75-80 mg.Leukemia
With the help of chemotherapy, it is possible to achieve a primary cure in almost half of the patients with chorioepithelioma.
In parallel with chemotherapy, it is advisable to carry out immunotherapy with retroplainet gamma globulin, 2-3 cycles (1 course consists of three injections of 3-6-9 ml once a week).
During chemotherapy, the titer of chorionic gonadotropin in the urine is determined 2 times a week, which makes it possible to establish the sensitivity of the tumor to the chemotherapy used.
Surgical treatment for chorioepithelioma is indicated with intra-abdominal or external (not responding to conservative treatment) bleeding, symptoms of a threatening rupture of the uterus or an acute abdomen (the cause of the latter may be torsion of the luteal cyst or rupture of it); large size of the uterus (over 12 weeks, with the presence of intra-wall nodes); age of patients over 40 years; tumor resistance to chemotherapy. The extent of surgical intervention depends on the degree ofinjured process. In the absence of macroscopic lesion of the ovaries, extirpation of the uterus is shown; with visible damage to the ovaries - extirpation of the uterus with bilateral ovariectomy; with suspected involvement of regional lymph nodes - extirpation of the uterus with lymphadenectomy or enlarged pangysterectomy. With a large tumor size of the uterus and suspected destruction of the vessels, it is expedient to tie the internal hypogastric arteries.
In the postoperative period, even with a sharp decrease in the titer of the chorionic gonadotropin, it is advisable to conduct 4-5 courses of chemotherapy with the aim of preventing metastases with regular hormonal and radiologic control.


Complications of chorioepithelioma

 

Chemotherapy is accompanied by various complications. In the course of treatment with antifolia drugs, leukopenia with hypo- or agranulocytosis is possible. As a consequence of granulocytopenia, angina, ulcerative stomatitis, enteritis, colitis often develop. The latter is much more frequent and in more severe form when methotrexate is administered through the mouth. Treatment is often accompanied by loss of appetite, nausea, multiple vomiting. Often observed partial or complete allopecia, conjunctivitis, toxic myositis. In the treatment of vinblastine, leukopenia is more pronounced than in the treatment of methotrexate. It is accompanied by severe agranulocytic angina, lymphadenitis. Often observed toxic myocarditis and polyneuritis.
In this regard, chemotherapy should be performed with strict hematologic control (daily count of leukocytes, an expanded blood test at least twice a week with the study of platelets). With a reduction in the number of white blood cells to 3000 in 1 mm3 treatment should be stopped.
When appointing repeated courses of chemotherapy, it is necessary to study the punctate of the bone marrow and its granulocyte series. Only these studies provide objective information about the state of hemopoiesis.


Prevention of chorioepithelioma

 

To prevent severe hematopoietic disorders, chemotherapy should be performed against a background of gemostimulating therapy (blood transfusion of fresh blood, administration of leukocyte mass, iron preparations, sodium nucleate, vitamins - thiamine, riboflavin, pyridoxine, cyanocobalamin, ascorbic acid, oxygen therapy).
Radiation therapy with chorionepithelioma should be applied strictly justified and localized. This is due to the fact that the tumor very often and early gives metastases to distant organs and the appointment of radiotherapy, which has an immunosuppressive effect, without knowledge of the localization of metastases is unacceptable. The involution of the irradiated focus can be accompanied by the progression of tumors that are inaccessible to irradiation.
Therefore, only after making sure of the accuracy of the location of the chorionepithelioma, the aim radiation therapy is prescribed, which is very effective.
With chorioepithelioma, both androgens (testosterone propionate - 1 ml of 5% solution, testate - 1 ml of 10% solution, sustanone -250 - 1 ml) and estrogens are used. Estrogens (estradiol dipropionate or synesterol) are prescribed in large doses - 200,000-300,000 IU daily for two weeks to suppress follicle-stimulating and luteinizing functions of the pituitary gland.
All patients with a bubble drift and chorionepithelioma should be on dispensary records. Control examinations (clinical, hormonal, roentgenologic, etc.) are carried out during the first 2-3 years every 2 months, especially when cured conservatively. Patients with a bladder drift after treatment consist on a dispensary account for 3 years.
In patients with chorionepithelioma, recurrences of the disease in the primary organ or distant metastasis are observed after 9 and even 12 years after primary and anti-relapse treatment. This indicates that patients with chorionepithelioma should not be removed from the register, strict follow-up care is necessary (at least once every 2-3 months) for at least 5 years. In the future, the terms of clinical, hormonal and radiological studies may change.