Method of preoperative preparation of patients with cervical cancer stage iii

 

(57) Abstract:

The invention relates to medicine, in particular to cancer, and can be used for radical treatment of patients with locally advanced cancers of the cervix TCNXMABOUT. The purpose for the possibility of surgical treatment of patients performed a preliminary external irradiation dose of 10 Gy, then with an interval in 3 days - endolymphatic regionarea infusion of 0.1 mg per 1 kg of body weight methotrexate and regional - lymph vessels of the rear stop introduction of shock doses of mixtures of drugs and therapeutic doses of antioxidants with re-exposure treatments for incomplete tumor resorption and subsequent daily radiation dose of 2 Gy to achieve a total dose of external irradiation to 26-36 Gr. The method allows for the possibility of transfer of inoperable patients with locally advanced cervical cancer in operable condition, to eliminate metastases in the lymph nodes.

The invention relates to medicine, specifically to Oncology, can be used for radical treatment of patients with locally advanced cancers of the cervix.

1-T2. And only if you can't perform surgery, due to the prevalence of tumors, apply a conservative species - specific treatment radiation therapy and palliative cytotoxic effect.

Traditional in cervical cancer TCNxMaboutis combined radiation therapy, including the alternation of doses from external and intracavitary impact (A. I. Pavlov, K. N. Kostromina "cervical Cancer" (radiation therapy)". M, Medicine, 1983) in a total dose in the 80-90 Gr and TV 60-70 Gy.

However, the results of this method are a little reassuring, as more than 50% of patients have a recurrence of the disease (more frequently parametric localization) in the first 2 years after treatment. In this situation, patients may chemotherapy or, rarely, a second course of radiation therapy with palliative effect.

Known "Method of treatment of cervical cancer stage II to III.with. N 738227 from 7.02.80 year), including endolymphatic administration of medicines and associated radiation exposure, allowing you to extend disease-free period in patients.

However, these methods do not allow surgical treatment or in the outer tissues after cancericidal doses of ionizing radiation.

Thus, these methods do not provide a radical treatment of patients with cervical cancer TCNxMabout. The aim of the invention is the translation of inoperable patients with locally advanced cervical cancer TCNxMaboutin operable condition.

This goal is achieved by the fact that patients with cervical cancer stage III conduct preliminary external irradiation, remote gamma-therapy apparatus of the type AGATE-WITH two converse diamond-shaped fields 14x14 or 12x12 cm with daily irradiation dose of 2 Gy to a total dose of 10 Gy, and then in the lymphatic vessels of the upper extremities, regionalno primary tumor, enter a low-dose methotrexate in the amount of 0.1 mg per 1 kg of body weight of the patient, after 3 days, the lymph vessels of the rear stop of the lower extremities, regionalno primary tumor, enter loading dose of a mixture of drugs, consisting of 25 mg of methotrexate and 1400 mg of cyclophosphamide, together with vitamins a and E in a single therapeutic doses (50000 Me and 100 mg), respectively, with incomplete resorption of the tumor may re-consecutive repetition of three main stages - preliminary irradiation, regionarea and regional endolymphatic supply a total dose of external irradiation 26-36 Gr.

Repeated exposure with incomplete tumor resorption subsequent external irradiation also spend up to a total dose of 26-36 Gr with a daily dose of 2 Gy.

The invention "Method of preoperative preparation of patients with cervical cancer stage III" is new, because it is not known from the level of medicine in the field of conservative preoperative methods of treatment of cervical cancer stage III. The novelty of the invention lies in the fact that preoperative treatment of inoperable patients with cervical cancer stage III includes external exposure to low dose of 10 Gy with an interval of 3 days, endolymphatic regionarea the introduction of low-dose methotrexate and regional lymph vessels of the rear brake, the introduction of shock doses of mixtures of drugs and antioxidants, vitamins E and A re endolymphatic effects of incomplete resorption of the tumor, and then bringing the total dose of external irradiation to 26-36 Gr. This combination of conservative methods preoperative impact and previously unknown endolymphatic introduction of antioxidants (vitamins A and E) in combination with cytotoxic drugs is new, provides sverhsummarny positive clinical effect - allows proportionscope justification of such complex events following. From literature data it is known that small doses of ionizing radiation cause in patients with moderate stress exposure, ionizing oscillatory responses by endogenous antioxidant systems, and accompanied by an increase in revenues in the circulating direction of endogenous antioxidants (Goncharenko E. B. , Kudryashov Y. B. Hypothesis of endogenous background of radioresistance. M. , Moscow state University press, 1980) experiment revealed that after small doses of ionization immunological properties of irradiated cells of the molecular system of phagocytes, but on the contrary, they have an increased ability to immune lysis of cells of the target (A. B. Chuchalin, Gerben Century A. Interaction of intact and irradiated macrophages with lymphoid cells in the thymus. Cytology, 1985, No. 9, S. 1049-1054). (Schwartr R., Salu KP - Functinol modifications of macrophage activity ofter suble that whole - water irritation - Prx, So c. Exp. Biol. med. (N. V.) 1981 - vol. 167, p. 20-24).

Our studies have also shown that at low doses is the normalization of the enzymatic antioxidant cascade of blood cells of patients with cervical cancer TCNxMabout. (Franzens E. M., Rozenko L. J., Kleiner B. I. et al. "The state of the antioxidant system of blood volnyiy". M. 1995. C. 64-72).

Known experimental evidence that small doses of methotrexate (used by us for endolymphatic introduction to upper limb), induce the action of immune lymphocytes against tumor cells (Light-Moldovan, J. , Chernyakhovsky, I. Y., 1968), as well as sensibiliser tumor cells to radiation. (Pelevin I. I., Afanasiev, G., Gottlieb C. A. Cellular factors response of tumors to radiation and chemotherapeutic effects. M. , Science, 1978, 84, 154, 259). The introduction of drugs into the lymphatic system of the lower extremities at the present time is an important component of the treatment of common malignancies.

A one-time introduction of significant doses of cytostatics in the lymphatic system of the lower extremities affects the relationship between the neuroendocrine and immunological systems (Sidorenko, Y. S., Pankov A. K., 1985; Rozenko L. J. 1985 ) Known data showing improving the effectiveness of drugs and x-irradiation in the treatment of patients with malignant head and neck tumors by combining them with vitamins a and E (Koneyama S, Hiroto. Pyu S. et. al., Oncology, 1978, V 35, N 6, p 253-257, Tsuchida T. Watanabfe E. Nakayama Hetal, neural, md. Chir (Tokyo, 1980, V. 20, N 5. p. 453).

However, endolymph the logical sick and don't know any in the world, neither CIS medical literature.

The invention involves an inventive step, so as to specialist, doctor-oncologist-gynecologist, is not obvious from the level of medicine in the field of Oncology.

The invention is industrially applicable as it can be used in health care, cancer research institutes, oncological dispensaries.

Examples of clinical application.

Patient G., 1970 R. (East. disease 5158/d) is under observation in RNII with 23.05.96 was diagnosed with cervical cancer TCNxMabout, endophytic form, vaginally-parametrable-uterine option, cytological analysis 9198953 from 23.05.96, - poorly-differentiated squamous cell carcinoma. Status lokalis admission: circular infiltration of the upper and middle third of the vagina, on the cervix - endophytic tumor 8x5 cm nodal punctulata also endophytic formations on the shiny white surface of the cervix. The vault of the vagina massively infiltrated, rear and right locking the uterus. The uterus is more, very dense, is limited in mobility. Parametrium densely infiltrated to the walls of the pelvis on both sides.

the daily dose of 2 Gy, i.e. up to a total dose of external irradiation of 10 Gy.

31.05.96, lymphatic vessels of the brush of the right hand entered 5 mg methotrexate, after 3 days, 3.06.96, lymphatic vessels of the left foot put 75 mg methotrexate, 1400 mg of cyclophosphamide, 100 mg of vitamin E and 50,000 of vitamin A.

When viewed 10.06.96, the improvement of local status - marked regression of the tumor as by reducing the size, and due to the release of vaginal infiltration vaults and vagina was practically absent, the cervix dense filling 1/2 of the vagina. The arch on the right is shortened and captures the cervix to the right. The uterus is a dense, mobile. In both settings infiltration is absent. With 10.06.96, the patient continued external irradiation apparatus AGATE-WITH a daily dose of 2 Gy to a total dose of external irradiation of 30 Gy.

9.07.96, the patient performed the operation of Wertheim. The histological conclusion: N 452785-797 from 10.07.96,

Moderately differentiated squamous cell carcinoma of the cervix without keratinization invasion of 0.4-0.5 cm, expressed lymphohistiocytic infiltration.

The mucosa of the vaginal stump has a regular structure.

In the lining of the uterine cavity in a limited area, in the second structure. To the wall of the fallopian tube adjacent tumor cells of the above-described structure. The right fallopian tube has a regular structure.

In the right ovary follicularly cyst, in a limited area is a complex cancer cells of the above-described structure.

The left ovary has a regular structure.

Fatty tissue has a regular structure.

In the lymph nodes deposits homogeneous wainfelin masses, focal fibrosis.

The patient was discharged from the hospital in III clinical group, i.e., the primary cure.

Patient C., 1960 birth (East. disease 4025 N/l) is monitored in RNII with 9.05.91, about cervical cancer TCNxMo, exophytic form, vaginally, parametrable uterine option.

Admission: the entire volume of the vaginal tube occupied by the tumor protruding from the genital slit, 3 cm tumor dense, hilly, covered with necrotic stinking masses, infiltration of the walls of the vagina to p/C inclusive. The uterus is more than normal, fixed, tightly included in the conglomerate, infiltrating parametrium tightly to the walls of the pelvis with 2 sides. The lumen of the intestine sharply narrowed because of compression from the outside. 10/IV - 14 IV-96, di is osudy entered 10 mg of methotrexate. 18/IV-96, left foot in lymphatic vessels 25 mg methotrexate and 100 mg Thio-Tepa, 100 mg of vitamin E and 50,000 mg of vitamin A.

During the examination the patient 23/IV-96, defined partial resorption of tumors primary tumor. 23/IV-30/IV-96 g held remote irradiation dose of 10 Gy.

2/V-96, left hand in lymphatic vessels entered 10 mg of methotrexate.

5/V-96, lymphonodi right lower limb put on 25 mg of methotrexate and 100 mg thio-Tepa, 100 mg of vitamin E and 50,000 mg of vitamin A.

Local status 12/V-96, - the cervix is fully formed. Around the cervical canal small residual tumor in the form of melkolepestnik growths 2x1 see the Infiltration of the walls of the vagina there. The vaults are available, the uterus is normal size mobile. Left parametrial space freely, the right tictacti. 15/V-19/V-96, continued remote gamma-therapy to a total dose of 30 Gy. 30/V-96 g - Wertheim operation.

Histogenesis N 306828-839 "Macroaggregate: the uterus to the cervix and b/C of the vagina, with appendages HH see in/C vaginal ulcer 0.3 cm in diameter pink color. The vagina along the line of resection. On the cervix surface ulcer 0.5 cm in diameter pink color with smooth edges. Cervical mucous Kahn who ionic 3x2,5x1,5 cyst 1 cm in diameter, filled with bloody mass, the right pipe 4x0,4 see

Microsclerotia - squamous cell carcinoma, moderately differentiated without keratinization, with severe complications, invasion > 0.3 to 0.4 cm Chronic inflammation, cystic expansion of the lumen of the glands. Hypoplasticity endometrium. In the ovary angiomatosis of the fallopian tube has a regular structure. In the ovary - angiomatosis, extensive hemorrhage, the remains of a yellow body. Fallopian tube has a regular structure. In the lymph nodes focal lipomatous sinus histiocytes, focal deposition of homogeneous easypod masses. The cervix is fully formed. Around the cervical canal small residual tumor in the form of melkokalibernyh growths 2x1 see the Infiltration of the walls of the vagina there. Arches free, uterus N values, mobile. Left parametrial space freely, the right tictacti. 15/V-19/V-96, continued remote gamma-therapy to a total dose of 30 Gy.

30/V - operation of Wertheim.

Histogenesis N 306828-839. Microreport: the uterus to the cervix and b/C of the vagina, with appendages HH see in/C vaginal ulcers 0.3 cm in diameter, pink. The vagina along the line of resection. On the cervix surface ulcers 0.5 cm in diameter pink with Gladkiy HH,5 cm; the left pipe h,4 see Right ovary 3x2,5x1,5 cyst 1 cm in diameter, filled with bloody mass, the right pipe 4x0,4 see

Microsclerotia - squamous cell carcinoma, moderately differentiated without keratinization with severe inflammation, invasion of 0.3-0.4 cm Chronic inflammation, cystic expansion of the lumen of the glands. Hypoplasticity endometritis. In the ovary angiomatosis, fallopian tube has a regular structure. In the lymph nodes focal lipomatous, sinus histiocytes, focal deposition of homogeneous eosinophilic mass.

Based on the authors 'Way of preoperative preparation of patients with cervical cancer stage III" treatment was conducted in 14 patients with cervical cancer TCNxMabout. Surgical treatment carried out in 9 women (64.3 per cent). A distinctive feature of the treatment approach is that histological examination of distant lymph nodes in 8 of 9 patients operated metastasis of the cancer is not detected. Only one (9) was found metastasis in a single lymph nodes external iliac group, and the size of the lymph node is 1,h,6 see

Technical and economic efficiency "Method of preoperative preparation of patients with cancer who were locally advanced cervical cancer TCNxMaboutin operable condition. In addition, the complex conservative impacts of the proposed method contributes to the elimination of metastases in the lymph nodes, it is possible to carry out the surgery, improves the quality of life of patients.

Method of preoperative preparation of patients with cervical cancer stage III, including remote gamma-therapy and endolymphatic chemotherapy, characterized in that the patients with cervical cancer T3NxMoconduct preliminary external daily irradiation dose of 2 Gy to a total dose of 10 Gy, then with an interval of 3 days endolymphatic regionarea primary tumor introduction to the vessels of the upper extremities 0.1 mg per 1 kg of body weight of the patient methotrexate and regional lymph vessels of the rear stop introduction of shock doses of a mixture of drugs in conjunction with therapeutic single doses of antioxidant with re-specified effect in incomplete tumor resorption and subsequent daily radiation dose of 2 Gy to achieve a total dose of external irradiation 26 - 36 Gr.

 

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1 ex

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