Method for diagnosing and treating patients suffering from superficial urinary bladder cancer

FIELD: medicine.

SUBSTANCE: method involves determining concentrations of carcinogens like aniline, toluyline, diethyl alanine, diphenyl and 1-naphtholamine in urine and urodynamic disorders and proliferative urothelium activity from Ki-67 expression degree data. High carcinogen concentrations and urodynamic disorders being detected apart from the fact of tumor removal and unchanged mucosa biopsy, transurethral prostate resection or urinary bladder neck resection is carried out. Next, liquid consumption increase in postoperative period and carcinogen contact reduction are advised. Three months later, control study is carried out. Carcinogen concentration level remaining high and no proliferative urothelium activity reduction being observed on the background of urodynamic disorders, cystectomy is to be repeatedly carried out.

EFFECT: enhanced effectiveness of treatment; high accuracy of diagnosis.


This method applies to medicine, namely to oncourology, and considers the integrated management of patients suffering from superficial bladder cancer, and can be used in practice during the examination and treatment of patients suffering from this disease.

Currently, there are many factors influencing the development of bladder cancer. Among the latter produce a mechanical effect on urately bladder (catheter, stones, foreign bodies etc), ionizing exposure, and chemical. Unsure of the role of bacteria and viruses. The most studied is the influence of various chemical compounds, which we get from food, medicines, in contact with the paint and varnish products, as well as from the environment.

Regardless of the nature of the impact of developing inflammation of the mucous membrane, accompanied by increased proliferative activity with increasing number of mutations.

Draws attention to the prevalence among patients of men over women, as well as the increase in the number of patients men with increasing age. Therefore there is a theory about the dangers of prostate (Matveev BP bladder Cancer / Beplate, Kamphuis, Obisakin. - M.: Verdana, 2001. - 13 C.). This theory involves the presence of infravesical the th obstruction, accompanied by a high concentration of urine, as well as the development of tumors in the cervix and the area of the triangle Leto, in the place of the greatest contact with urine. Among the chemical compounds produce aniline and its derivatives, acrolein, chlorine, with the most pronounced carcinogenic effect.

In connection with what is considered chronic urinary retention in patients with bladder cancer as a phenomenon, leading to the increase in the concentration of carcinogens in the urine with increasing residence time in the bladder and, as a consequence, enhance the contact of urothelia bladder with these substances. Our proposed method differs from the method proposed in the application UA 51226 A. 15.11.2002 fact that in addition to determine the proliferative activity of urothelia to forecast paid attention to the effects of carcinogens on urately, as well as the possibility to evaluate the role of prostate in increasing the concentration of carcinogens in the urine of the individual patient.

To determine the concentrations of these carcinogens and Refine their proposed role in the preoperative period to take the first urine of the day 250 ml, spending the following sample preparation. Analyze the urine sample is placed in a separating funnel, 100 ml of urine add 30 g of sodium chloride and 10 ml of chloroform, the contents of the funnel intense sun is Rehovot 15 minutes after settling chloroform extract is poured into a test tube and centrifuged for protein denaturation 20 minutes. Received centrifugal evaporated on a rotary evaporator followed by gas chromatography-mass spectrometric determination of the content of aniline, toluidine, diethylaniline, diphenyl, 1-naphthalamine using analytical equipment American company Hewllett-Packard gas chromatography-mass spectrometer-5989 Engine with mass-selective detector. Software HPG-1034 MS Chem Station series (DOS). Column of silica, capillary, chromatographic, length 30 m, internal diameter 0.25 mm, coated with stationary phase polymethylsiloxanes with 55 phenyl groups (HP-5MS). Conditions for gas chromatography-mass spectrometry analysis: the evaporation temperature of 250 degrees Celsius, the temperature of the chromatographic column 60 degrees Celsius for 1 minute. Then heating at a rate of 12 degrees per minute to 260 degrees Celsius. Mass spectra of electron impact organic compounds obtained when the energy of the mass spectrum of individual organic compounds (aniline) and ionizing electrons 70 eV and the temperature of the mass-selective detector 177 degrees Celsius. The scan range of the mass is 45-350 m/z, the number of scans per second to 1.2. The number of samples is 2, the voltage on the electronic multiplier 2700 In, the emission of 50 µa. Measure the peak area of the molecular ion, for aniline - 93 mz, for the toluidine - 106 mz, N,N-diethylaniline - 134 mz, diphenyl - 154 mz, 1-naphtylamine - 143 mz and calibration characteristics determine its mass in run (ng). Retention time: aniline - 4,22 min, toluidine lower than the 5.37 min, N,N-diethylaniline, diphenyl - 8,96 min, 1-naphtylamine - 10,71 minutes Methodology described in the paper: Determination of chemical compounds in biological environments. A collection of guidelines. - M.: Federal center of state sanitary and epidemiological surveillance Ministry of health of Russia, 2000. - 152 C. / Ed. by Acad. The Academy of natural Sciences, Prof. Zaitseva N.V., S. 4 (MUK 4.1.764-99.)

Another aspect of our methodology is the prediction, in General, interact with the application UA 51226 A. 15.11.2002.

To date, the search criteria for the prediction of bladder cancer.

Therefore offer: material taken when performing multifocal biopsy during transurethral tumor resection and correction of bladder neck, not visually changed, the mucosa of the bladder in patients with transitional cell bladder cancer be fixed in formalin solution, to prepare a slice thickness of 4 μm and paint Ki-67 using PAP-(HRP-antiperoxidase) method, using the monoclonal antibody Ki-67 Antigen firm Dako clone MIB-1, and showing the LSAB2 system company Dako. OC the NCA in the intensity of staining was carried out by cytophotometry 50 randomly selected cells of the transitional cell epithelium on the received video images of painted specimens using a computerized microscopic video Quantimet 550 IW Leica, England, for digital analysis of pathological and cytological material and advanced diagnostics with a high resolution camera that allows quantitative image analysis on real flowers or optical densities of the image format 6000 4000 pixels. The level of expression of Ki-67, we offer to evaluate in points (max-4), given the existence of a direct relationship between the expression of Ki-67 proliferative activity of urothelia (Wu T. The role of bcl-2, p-53 and Ki-67 index is predicting tumor recurrence for low superficial transitional cell bladder carcinoma. / T. Wu, J.N. Chen, Y. Lee // J. Urol. - 2000. - Vol.163. - P.758-760.) I.e. one of the tasks, we address the proposed method of treatment is the assessment of proliferative activity of urothelia with the possibility of predicting the course of bladder cancer. Only in case of detection of carcinogens in high enough concentrations to reduce the negative effects of carcinogens on urately in patients with superficial bladder cancer on the background of chronic retention of urine due to infravesical obstruction offered in addition to the transurethral resection of bladder tumors and multifocal biopsy unchanged mucosa of the bladder to perform a TOUR of the prostate or incisio at the bladder neck sclerosis. In polomer the transition period: the increase in the number of fluids and reducing the number of cigarettes, as well as reducing contact with various chemicals at work and at home with conducting follow-up research to concentrations of carcinogens in the urine and multifocal biopsy after 3 months on the above methodology, and assessment of residual urine volume. In case of changes of urodynamics in the direction of increasing the volume of residual urine with increasing concentrations of carcinogens in the postoperative period and continuing high levels of expression of Ki-67 after the treatment I propose to consider as a poor prognosis with the need for cystectomy. Analogues for the combined concentration of carcinogens in the urine and proliferative activity of urothelia order to Refine prognosis and tactics of conducting the patient were not found in literature. The disadvantages include the invasiveness of the method and the high price analysis.

Example 1

Patient K., 35, No. 2497 received 24 February 2004 in MUSIC KB diagnosed with Transitional cell bladder cancer. Hematuria. March 1, 2004. From history for the past 2 years unsuccessfully cures Trichomonas prostatitis, smokes. When preparing for surgery taken urine - 250 ml in the morning after sleep. A study by the described method, identified aniline concentration 0,0022 mg in a volume of 250 ml of urine. Residual urine volume was 80 ml

Operation: TOUR urinary PU is Ira. Incise prostate cancer. Multifocal biopsy of the bladder. The primary histological conclusion tumor 6984-87 from 02.03.04, transitional cell cancer, visually unchanged mucosa picture lymphocytic infiltration.

Material prepared and investigated by the above method.

The expression of Ki-67 made 3.67 points.

Later, the patient underwent a course of chemotherapy and treatment monopreparatami.

At follow-up at 3 months (cystoscopy, multifocal biopsy) residual urine volume is not detected, the concentration of aniline decreased to 0,00009 mg in 250 ml of urine. Re-evaluation of the proliferative activity of urothelia by the proposed method, the level of expression of Ki-67 decreased to 1.45 points. Clinically, the patient noted improvement in health and the absence of dysuria, data for recurrence of disease at the time of the survey no.

Example 2.

Patient A., 70, No. 13561, enrolled in MUS KB 1 Irkutsk 22 November 2003 with a diagnosis of Hematuria of unknown origin. History: the experience of the smoker for 35 years. In the preoperative period taken urine 250 ml in the morning after sleep, study on the above methodology and identified diphenyl 0,009 mg in a volume of 250 ml of urine, other compounds not detected. When conducting ultrasound residual urine volume was 150 ml further operation performed: trance is erlina resection of the bladder, multifocal biopsy, not visually changed, the mucosa of the bladder, as well as transurethral resection of the prostate assigned to anti-inflammatory therapy. The PHZ 35703-709 from December 2, Highly differentiated transitional cell bladder cancer, visually unchanged mucosa picture of inflammation. Ki-67 was 3.2 points.

For three months the patient received adjuvant chemotherapy, at our insistence reduced the number of consumed cigarettes from 45 to 10 eggs per day, and increased the amount of fluids you drink. At follow-up urine by this method revealed a decrease in the concentration of diphenyl to 0.00013 mg in a volume of 250 ml of urine. Residual urine volume was 20 ml Performed cystoscopy and multifocal biopsy. The expression of Ki-67 was 2 points. During follow-up examination revealed no recurrence, the patient noted improvement in health and reduction of dysuria.

The way to diagnose and treat patients suffering from superficial bladder cancer, characterized in that to determine the concentration of the following carcinogens - aniline, toluidine, diethylaniline, diphenyl, 1-naphthalamine in the urine and disturbance of outflow of urine, and assess the proliferative activity of urothelia according to the degree of expression of Ki-67 in the case of high concentrations of the carcinogen is in and disturbance of outflow of urine, in addition to the removal of the tumor and biopsy unchanged mucosa, perform transurethral resection of the prostate or resection of the bladder neck, and then recommend increasing consumption of liquid in the postoperative period to reduce contact with carcinogens, three months exercise control study and the continuing high level of carcinogens and no decrease in proliferative activity of urothelia on the background of violations of urodynamics performed another operation, the cystectomy.


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