RU2370263C2 - Method of organism disintoxication in surgery of invasive cancer of urinary bladder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: inventions relates to medicine, in particular to surgery, and concerns disintoxication of organism at surgical treatment of patients with invasive cancer of urinary bladder. With this purpose pre-operation and post-operation intramuscular introduction of sodium salt of 5-amino-1,2,3,4-tetrahydroftalazine-1,4-dione (galavite) is carried out. Introduction is performed intramuscularly, daily in doze 0.1 g. Before operation 5 injections are made. After operation 5 injections are made, and then 10 injections every second day in the same doze.

EFFECT: due to claimed procedure of said medication introduction method ensures faster ending of catabolic phase of post-operation period with absence of side effect in patients with III-IV stage of disease.

Description

The present invention can be used in medicine, in particular during surgical treatment of patients with invasive bladder cancer

Bladder cancer is an urgent problem due to the steady increase in the incidence. From 170,000 to 200,000 new cases are registered annually in the world.

The main method of surgical treatment of superficial bladder cancer is transurethral resection of the bladder (TUR). However, the frequency of relapses after TUR is extremely high and amounts to 50-90%, and in 15-20% of patients the superficial tumor becomes invasive.

In order to reduce the recurrence rate and prevent the progression of the tumor, various options for intravesical therapy are used.

Of the known drugs, BCG vaccine has received the most recognition. Its use is highly effective, and the main disadvantage is the high frequency of adverse reactions and complications (Materials of the scientific conference "New Technologies in Medical Radiology". St. Petersburg, 2001. P.65).

However, the tolerability of such treatment is low, given the general condition of the patient before surgery, which, in particular, is due to high intoxication of the body.

Phagocytosis plays a crucial role in the elimination of conditionally pathogenic extracellular bacteria, which play a major role in the development of infectious complications in surgical patients. In addition, the activation of phagocytic cells of monocytic-macrophage origin causes the natural activation of all components of the immune system. Thus, the use of immunomodulators along with a positive effect on the body contributes to the process of its intoxication with endogenous toxins - the decay products of a malignant tumor (release of tumor necrosis factor) and worsens the general condition of the patient before surgery, as well as adversely affects the course of the postoperative period. In this regard, there is a need for specific detoxification of the body, the implementation of which is possible in the presence of invasive bladder cancer.

Known pectin drug Pecto for detoxification of the human body, based on a mixture of pectins (publ. Application No. 2003128491).

However, the use of this drug to detoxify the body in surgery for invasive bladder cancer does not give positive results.

It is known to use immunomodulators in the treatment of oncological diseases of the bladder, for example, by administering immune preparations and a solution of furacilin during transurethral resection. Moreover, after performing a transurethral resection, a three-way Foley catheter is introduced into the patient through the urethra, according to which, from the first day after the operation, a mixture of a standard solution of furacilin with 10 million ME of interferon-2 is administered. The introduction of a mixture of drugs is carried out during the first 3-5 days after surgery, bringing the total dose of interferon to 50 million ME. The method allows to exclude bladder trauma due to a single injection of a catheter and provides long-term continuous exposure to drugs without the development of immune complications (RU 2257912).

However, the method is difficult to implement and does not reduce the intoxication of the body with endogenous toxins.

There is also known a method of treating cancer, including surgery, as well as preoperative and postoperative effects on the body, which reduces the severity of intoxication (weakness, headaches, dizziness, nausea), and therefore the cost of maintaining and treating cancer patients is reduced (RU 2124373 ) The method is as follows: before starting treatment, 7 days before the operation, as well as throughout the course of any special antitumor treatment, patients additionally receive a magnetotherapy procedure every morning between 9 and 11 hours according to a certain methodology.

However, the known method is technologically complicated, the method of its use requires specially trained personnel, and in addition, the possibility of its use in the case of surgery for invasive bladder cancer has not been studied.

Analogues of the invention, the subject of which is a method of detoxifying the body in surgery for invasive bladder cancer, was not found.

The objective of the invention is to provide a method of detoxifying the body in surgery for invasive bladder cancer.

This problem is solved by the fact that preoperative and postoperative intramuscular injection of sodium salt of 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione (Galavit preparation) is performed according to the scheme: 0.1 g every day in the preoperative period 5 injections; after surgery, 0.1 g every day 5 injections, then 0.1 g every other day 10 injections.

The specified technical problem is relevant, because allows you to improve the overall tolerability of the treatment, accelerate the completion of the catabolic phase of the postoperative period.

Injections were carried out with the drug Galavit (manufactured by CJSC Center for Contemporary Medicine Medicor) in a lyophilized dosage form for injection in vials. Immediately before use, the drug was dissolved in distilled water for injection.

The study, conducted by the Russian Scientific Center for X-ray Radiology of the Ministry of Health and Social Development of the Russian Federation under the supervision of Academician V.P. Kharchenko, included 40 patients diagnosed with bladder cancer T3-4NOMO, which were divided into 2 groups of 20 people according to the type of treatment. The groups were similar in terms of the stage of the tumor process (according to TNM classification), age, and concomitant pathology.

In group 1, 5 days before surgery (radical bricker cystoprostatvziculectomy), Galavit was administered according to the scheme: in the preoperative period, 0.1 g every day 5 injections; after surgery, 0.1 g every day 5 injections, then 0.1 g every other day 10 injections. A preliminary study was conducted in a chronic experiment in rats with the aim of determining the necessary dosage regimen. At the same time, the peripheral blood indices of male rats were studied for 1 and 2 months. The necessary dosage regimen was determined by the presence of a stable clinical condition without signs of intoxication.

In group 2, patients underwent only surgical treatment (radical bricker cystoprostatvziculectomy).

Safety and tolerability assessment of the drug was carried out throughout the study period on the basis of registration of episodes of the occurrence of adverse events while taking the drug. Each such episode was carefully analyzed for its connection with the drug.

To determine the tolerability of the therapy, each patient after treatment was interviewed by a doctor. Questions related to the time of side effects during treatment and the need to interrupt treatment. Patients were asked to evaluate the acceptability of the treatment (ease of use, effect on sleep, and performance).

Statistical processing of the results was carried out by the method of variation statistics with the calculation of the arithmetic mean error (M), average value (m), degree of freedom and probability (P). Comparison of the average values of the two samples was carried out using Student's t-test. A difference of more than 95% (P <0.05) was considered significant. Statistical processing was performed using Excel 7.0.

Significant hematological changes were revealed in the majority of patients of both groups on the first day of the postoperative period: anemia, elevated ESR, leukocytosis, increased creatinine and urea, increased bilirubin, AlAT, AsAT.

Analysis of the clinical picture of the disease in group 1 showed positive changes on the 10th day of the postoperative period.

As a result of the analysis of the dynamics of the clinical course of patients of group 2, it was revealed that only on average on day 29 (21 days in group 1) did normalization in the subjective state of patients and the clinical course of the disease occur.

The beneficial effect of detoxification was manifested in a faster rate of normalization of both the general condition of patients (treatment tolerance) and laboratory parameters. On average, among patients of group 2 on the 24th day and among patients of group 1 on the 18th day, normalization of clinical and biochemical blood parameters was noted. According to the results of the study of peripheral blood on the 30th day of the postoperative period, 16 (80%) patients of group 2 and only 4 (20%) in group 1 showed signs of intoxication of the body. Mortality in patients of group 2 was 5%, in group 1 - 0%. The average duration of postoperative stay of patients of group 1 in the hospital was 21.4 hospital days, patients of group 2 - 26.3 hospital days.

The data obtained indicate an earlier completion of the catabolic phase of the postoperative period in patients of group 1, which indicated the detoxifying effect of the drug administered by the indicated dosage regimen. Additional studies to change the accepted dosage regimen did not produce the desired result.

Thus, the comparative characteristics of the two clinical groups of patients demonstrate the established complete safety and tolerability of the total course dose of Galavit according to the specific scheme used in the surgery of invasive bladder cancer. Adding Galavit to the traditional treatment regimen provides detoxification of the body and helps to reduce the length of hospital stay.

Claims (1)

A method of detoxifying the body in surgery for invasive bladder cancer, characterized in that the preoperative and postoperative intramuscular injection of the 5-amino-1,2,3,4-tetrahydrophthalazine-1,4-dione sodium salt of 0.1 g intramuscularly every day, 5 injections before and 5 injections after surgery, then 10 injections every other day.