RU2730450C1 - Method of treatment and prevention of radiation cystitis - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to radiation therapy, and aims at prevention and treatment of cystitis in pelvic radiation therapy. For the treatment and prevention of radiation cystitis Colegel-Gial and Colegel-ADL are installed during irradiation. Additionally, installation of Coletex-D hydrogel napkins and Colegel-Gial in 10–60 ml every 7–10 days and 1 day before the irradiation course are performed. During the irradiation course, under the control of the urine values, Colegel-Gial installations are performed, and 45–60 minutes later, Coletex-D hydrogel napkins 10 ml 2–3 times a week until the leucocytes in urine 20 are recorded in the visual field. If observing the achievement or exceeding of this value, the Colegel-Gial urine catheter is instilled and after 45-60 minutes, Coletex-ADL hydrogel napkins are taken 10 ml before the irradiation course. After the irradiation course, the urine parameters are controlled by the Coletex-beta hydrogel tissue 20 ml 1–2 times a week before the urine leucocyte count is determined to be no more than 6 in the female vision field and not more than 4 in the male vision field.EFFECT: use of the invention enables patient's comfort enhancement by reducing the soreness of procedures and the risk of urogenital tract injuries, improved quality of life of the patients both at the stage of radiotherapy and post-ray period, as well as higher clinical effectiveness by reducing the probability and frequency of interruptions in treatment and, consequently, reducing the risk of post-radial cystitis and reducing the recovery period of the patients and the time of disability.1 cl, 4 ex

Description

The invention relates to medicine, namely, to methods for the prevention and treatment of cystitis during radiation therapy of the pelvic organs.

Radiation cystitis is an undesirable complication of radiation therapy in cancer patients with tumors of the pelvic organs. Radiation cystitis develops during irradiation associated with tumors of the rectum (~ 60% of cases), prostate (75%), gynecological cancer (90%), reducing the quality of life of patients, requiring additional concomitant therapy, leading to a cessation of the radiation process and lengthening the process treatment and hospitalization, reducing the effectiveness of anti-cancer treatments.

Radiation cystitis develops in 5-80% of patients, starting from 1 week of irradiation upon reaching a dose of 15 Gy.

A known method for the treatment of radiation cystitis, which consists in the use of the drug Urolife (sodium hyaluronate). Both oral capsules and intravesical installations are used. In the first month of treatment for chronic cystitis, installations of "Urolife" 50 ml are performed 1-2 times a week. In the future, installations are performed 1-2 times a month for 4-6 months (Mirkin Y.B., Ponomarenko AM, Karapetyan A.V., Shumov S.Yu. Assessment of the effectiveness of glycosaminoglycan replacement therapy for radiation cystitis. Oncourology. 2018; 14 (2): 156-161. Https://doi.org/10.17650/1726-9776-2018-14-2-156-161).

However, this method has a number of limitations: oral administration reduces the local efficacy of the drug, and intravesical installations of a liquid substance shorten the time of drug exposure to the time of 1 urination. In addition, sodium hyaluronate is a mono-drug that acts only on one of the reasons leading to the formation of cystitis - a violation of the integrity of the glycosaminoglycan layer of the bladder mucosa.

A known method for the treatment of cystitis of various etiologies, including instillation of sodium alginate in the form of a gel "Colegel" containing therapeutically active drugs dioxidine, lidocaine, deoxyribonucleate, sodium hyaluronate in a therapeutically effective amount, and the installation is recommended to be carried out according to the scheme chosen depending on the etiology of cystitis. So, in case of radiation cystitis, it is recommended to install the gel preparation "Colegel-ADL" from 1 to 20 days of treatment every day, and "Colegel-DNA-L" and "Colegel-Gial" - 1 instillation 2 times a week from 21-56 days, alternating by day (RF Patent No. 2537031, IPC A61K 31/167, publ. 2014, prototype).

The disadvantage of this method is the need for daily installations of various medical devices from 1 to 20 days, which can lead to damage to the mucous membrane of the urethra and the bladder, their bacterial contamination, which in turn leads to impaired urination and a significant decrease in the quality of life due to manipulations in the background conducted radiation therapy. In extreme cases, urethral stenosis or the formation of false urinary tracts may develop, with the need for plastic surgery.

The objective of the present invention is to eliminate these disadvantages, prevent radiation reactions, reduce the severity of radiation cystitis in patients receiving radiation therapy for pelvic tumors, increase the possibility of conducting radiation therapy in full without interruption in treatment in this category of patients, reduce the likelihood of complications and increase quality of life of patients.

To solve this problem, in the treatment and prevention of radiation cystitis, including instillation of "Colegel-ADL" and "Colegel-Gial" in the process of irradiation, it was proposed to additionally carry out instillations of "Colegel-Gial" and hydrogel napkins "Coletex-D" with an interval of 45 -60 minutes, 10 ml twice before the start of irradiation: 7-10 days and 1 day before irradiation. During irradiation, under the control of urine indicators, instill "Colegel-Gial" and Hydrogel Napkins "Colegel-Gial" with an interval between injections of 45-60 minutes, 10 ml each 2-3 times a week until the registration of leukocyte counts in urine 20 in the field of view , and when this value is reached or exceeded, switch to another scheme, namely: simultaneously instill "Colegel-Gial" and Hydrogel Napkins "Coletex-ADL" 10 ml 2-3 times a week until the end of irradiation. After the completion of irradiation, it is recommended, under the control of urine indicators, to inject a hydrogel napkin "Coletex-1-β" in a volume of 20 ml 1-2 times a week until the number of leukocytes in urine is determined, no more than 6 in the field of view for women and no more than 4 in the field of view for men.

The proposed installation scheme allows you to act on the mucous membrane of the bladder and urethra, increase the radioprotective properties of healthy tissues and improve their reparative capabilities, enhance local immunity, thereby increasing the period until signs of radiation cystitis appear and reducing the duration and intensity of its existence. The introduction through the urinary catheter "Colegel-Gial" and "Koleteks-D" with an interval of 45-60 minutes ensures the highest efficiency of the administered drugs and the absence of the risk of undesirable potentiation of the effect, helps to protect and restore the glycosaminoglycan layer of the bladder, which is damaged during radiation therapy from exposure reactive biological fluid.

The use of a hydrogel napkin "Coletex-1-β" allows to stimulate post-radiation repair, local immunity, to activate the mechanisms of local nonspecific resistance, to reduce the local inflammatory reaction, to limit the spread of infection and the elimination of invading microorganisms, to ensure the restoration of the integrity of damaged tissues, to reduce the formation of cicatricial changes.

The implementation of the method is shown on specific clinical examples.

Example 1.

Patient M., 72 years old. Was admitted to the radiotherapy department with a diagnosis of cancer of the mid-ampullar rectum.

Before hospitalization, urine culture was performed - no flora was sown. The presence of 1-2 leukocytes in the field of view was noted.

Before the start of the irradiation, 7 days before the start of the irradiation, a 10 ml “Colegel-Gial” instillation was carried out through the urinary catheter, and 50 minutes after that, the “Coletex-D” hydrogel napkin was also installed in a volume of 10 ml. Similar instillations were performed 1 day before irradiation.

Beginning of radiation therapy ROD 2 Gy, SOD 54 Gy in the rectal region and 46 Gy in the area of regional metastasis.

During irradiation, under the control of urine indices, instillations of "Colegel-Gial" were carried out through the urinary catheter and, after 50 minutes, hydrogel napkins "Coletex-D", 10 ml, 2 times a week. There was no discomfort from the injection procedures.

Upon reaching the 18th session (36 Gy), complaints of discomfort during urination were noted - a feeling of incomplete emptying of the bladder, nocturia up to 3 times per night. In the analysis of urine - 25 leukocytes in the field of view.

The instillation preparations were changed. In the subsequent period of radiation therapy, instillations were carried out simultaneously through the urinary catheter "Colegel-Gial" and after 50 minutes of hydrogel napkins "Coletex-ADL" 10 ml 2 times a week until the end of irradiation. Improvement of well-being was noted after 2 days. In the control analyzes of urine, the number of leukocytes in the field of view did not exceed 20. The course of radiation therapy was completed in full.

After the completion of irradiation, under the control of urine indices, a hydrogel napkin "Coletex-1-β" in a volume of 20 ml was introduced into the bladder cavity through a urinary catheter once a week until the number of leukocytes in urine was determined 4 in the field of view. Conducting concomitant therapy was required for 19 days after the end of radiation treatment (3 leukocytes in the field of view were achieved).

The urinary catheter was removed after the completion of the drug administration, in the two-component stage - after the second drug, in the one-component stage - immediately after the injection.

According to the results of observation after 1, 5, 3 and 6 months, there are no signs of recurrence of cystitis.

Example 2.

Patient T., 69 years old. Was admitted to the radiotherapy department with a diagnosis of prostate cancer. Before hospitalization, urine culture was performed - no flora was sown. The presence of 0-1-2 leukocytes in the field of view was noted. He reported complaints of nocturia up to 4 times a night.

Similar to the description in example 1, instillations of drugs were carried out 10 and 1 day before the start of radiation therapy.

Started radiation therapy ROD 2 Gy, SOD 74 Gy for the prostate gland and 46 Gy for the area of regional metastasis with accompanying therapy according to the proposed method 3 times a week. Upon reaching 24 sessions (48 Gy), the addition of new complaints of discomfort during urination was noted - an increase in nocturia up to 5-6 times per night, a feeling of compression in the proximal urethra, and lethargy of the stream. In the analysis of urine - 31 leukocytes in the field of view.

The drugs were changed according to the proposed scheme. Improvement of well-being was noted in a day In the control analyzes of urine, the number of leukocytes in the field of view did not exceed 20. The course of radiation therapy was completed in full.

Instillations of preparations were carried out with a break between injections of 45 minutes.

Conducting concomitant instillation therapy with hydrogel napkins "Coletex-1-β" in a volume of 20 ml 1 time per week was required for 28 days after the end of radiation treatment (4 leukocytes per field of view were achieved).

At control examinations after 3, 6 and 9 months, there are no signs of recurrence of cystitis.

Example 3.

Patient S. 51 years old. Was admitted to the radiotherapy department with a diagnosis of cervical cancer. Before hospitalization, urine culture was performed - seeded with E. Coli. Reorganization was carried out. Repeated urine cultures are sterile. The presence of 0-1 leukocytes in the field of view was noted. Before the beginning of the irradiation, 8 days before the start of the irradiation, the installation of "Colegel-Gial" in the volume of 10 ml was carried out, and 55 minutes after that the installation of the hydrogel napkin "Coletex-D" also in the volume of 10 ml. Similar instillations were performed 1 day before irradiation.

Radiation therapy was started I stage ROD 2 Gy, SD 30 Gy for the pelvic area, II stage DBR 2 Gy, SD 20 Gy for the region of regional metastasis, III stage brachytherapy RR 7 Gy 1 time per week × 3 times 21 Gy with concomitant therapy according to the proposed method.

During irradiation, under the control of urine indices, instillations of "Colegel-Gial" and hydrogel napkins "Coletex-D" 10 ml 3 times a week were carried out with an interval between injections of 55 minutes. There was no discomfort from radiation therapy procedures.

Upon reaching the 25th session (50 Gy), complaints of obstruction in the urethra, increased frequency of urination during urination were noted. In the analysis of urine - 27 leukocytes in the field of view.

The instillation preparations were changed. In the subsequent period of radiation therapy, instillations of "Colegel-Gial" and hydrogel napkins "Coletex-ADL" 10 ml with an interval between injections of 55 minutes were carried out simultaneously, also 3 times a week until the end of irradiation.

There was an improvement in well-being after 3 days - a decrease in discomfort in the absence of its increase. In the control analyzes of urine, the number of leukocytes in the field of view did not exceed 20. The course of radiation therapy was completed in full.

After the completion of the irradiation, under the control of urine indices, a hydrogel napkin “Coletex-1-β” was injected into the bladder in a volume of 20 ml 2 times a week until the number of leukocytes in the urine was determined 3-3-4 in the field of view. Conducting concomitant therapy was required within 16 days after the end of radiation treatment.

According to the results of observation carried out with a frequency of 6 weeks for 8 months, there are no signs of recurrence of cystitis.

Example 4.

Patient X. 71 years old. Was admitted to the radiotherapy department with a diagnosis of bladder cancer. Before hospitalization, urine culture was performed - sterile. The presence of 0-1 leukocytes in the field of view was noted. Before the beginning of the irradiation, 10 days before the start of the irradiation, the installation of "Colegel-Gial" in the volume of 10 ml was carried out, and 60 minutes after that the installation of the Hydrogel Napkin "Coletex-D" also in the volume of 10 ml. Similar instillations were performed 1 day before irradiation.

Beginning of radiation therapy ROD 1.8 Gy, SOD 66 Gy to the area of the bladder tumor, ROD 2 Gy, SOD 50 Gy to the area of regional metastasis.

During irradiation, under the control of urine indices, instillations of "Colegel-Gial" were carried out and, after 60 minutes, hydrogel napkins "Coletex-D" 10 ml, 2 times a week. There was no discomfort from radiation therapy procedures.

Upon reaching 24 sessions (48 Gy), complaints of obstruction in the urethra, increased frequency of urination during urination were noted. In the analysis of urine - 36 leukocytes in the field of view.

The instillation preparations were changed. In the subsequent period of radiation therapy, instillations of "Colegel-Gial" were carried out simultaneously and after 45 minutes of hydrogel napkins "Coletex-ADL", 10 ml, 2 times a week until the end of irradiation. There was an improvement in well-being after 3 days - a decrease in discomfort in the absence of its increase. In the control analyzes of urine, the number of leukocytes in the field of view did not exceed 20. The course of radiation therapy was completed in full.

After the completion of the irradiation, under the control of urine indices, a hydrogel napkin "Coletex-1-β" was injected into the bladder in a volume of 20 ml 2 times a week until the number of leukocytes in urine was determined 6 in the field of view. Conducting concomitant therapy was required within 17 days after the end of radiation treatment.

According to the observation results after 3, 6, 12 months, there are no signs of recurrence of cystitis.

During the use of this scheme, patients have been treated with: rectal cancer - 12 patients; prostate cancer - 19; cervical cancer - 7; bladder cancer - 3. All patients had a later onset of cystitis during radiation therapy, a decrease in intensity to 1 degree, with the end of radiation therapy, clinical manifestations of cystitis disappeared completely within 7 to 10 days.

Thus, the proposed method allows: to reduce the number and frequency of manipulations and catheterizations, to increase the patient's comfort by reducing the painfulness of procedures and the risk of trauma to the urinary tract. Significantly improves the quality of life of patients both at the stage of radiation therapy and in the post-radiation period. Improves the effectiveness of treatment by reducing the likelihood and frequency of treatment interruptions. Reduces the recovery time of patients and the time of disability. Reduces the risk of post-radiation cystitis. The use of the method allows the patient to return to an active social and work life earlier, reduces the disability of patients, significantly increasing the social effect of the proposed method of accompanying therapy.

Claims (1)

A method for the treatment and prevention of radiation cystitis, including the installation of "Colegel-Gial" and "Colegel-ADL" in the process of irradiation, characterized in that additionally they install the hydrogel napkin "Coletex-D" and after 45-60 minutes "Colegel-Gial" 10 ml for 7-10 days and 1 day before the start of the course of irradiation, and during the course of irradiation under the control of urine indices, installations "Colegel-Gial" are carried out and after 45-60 minutes Hydrogel napkins "Coletex-D" 10 ml 2- 3 times a week until the registration of the values of leukocytes in urine 20 in the field of view, and when determining whether this value is reached or exceeded, installations are carried out through the urinary catheter "Colegel-Gial" and after 45-60 minutes Hydrogel napkins "Coletex-ADL" 10 ml before the end of the course of irradiation, and after the completion of the course of irradiation, under the control of urine indicators, a hydrogel napkin "Coletex-beta" is injected in a volume of 20 ml 1-2 times a week until the number of leukocytes in urine is determined no more than 6 in the field of view d For women and no more than 4 per field of view for men.