DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
Purpose. Determination the role of the p53 expression as a prognostic factor in the development of superficial urothelial bladder carcinoma.
Materials and methods. Medical histories of 72 patients (11 women and 61 men) with diagnosed primary superficial urothelial carcinoma of the bladder I and II grade were retrospectively analyzed. All patients were undergone a repeated transurethral resection was performed in 6 weeks after the first operation. In the case of the absence of residual tumor, cystoscopy was performed every 3 months during the first year then every 3–6 months during next 5 years. The average time of follow-up was 43.2 months. According to the standard protocol an immunohistochemical study with detection of p53 was carried out on 72 sections of formalin-fixed and paraffin-embedded tumor fragments. p53 expression was also determined in 10 histologically unchanged fragments of the bladder mucosa.
Results. Depending on the percent of nuclei with p53 expression, two groups were identified. The first group included 40 tumor samples (55.5 %) with p53 expression less than 20 % and 17 tumor samples (23.6 %) without p53 expression. The second group included 15 tumor samples (20.9 %) with p53 expression more than 20 % (4 patients – 20–40 %, 8 patients – 40–60 %, 3 patients – 60–80 %). р53 expression was not determined in the all 10 samples of normal bladder tissue. During follow-up period 1 of 57 patients of the first group has a disease progression comparing with 13 of 15 patients in the second group. Patients of the both group were similar in respect with clinical characteristics. The mean time to disease progression was 17.3 months.
Conclusion. Results of the current study shows that p53 immunohistochemical marker is a prognostic factor in the development of superficial urothelial bladder carcinoma.
Background. The high rate of recurrences after visual complete transurethral resection (TUR) is a main problem in the treatment of nonmuscle-invasive bladder cancer (NMIBC). One of the factors influencing the long-term results of treatment for this pathology may be the quality of TUR, which depends on a surgeon’s experience.
Objective: to evaluate the impact of a surgeon on relapse-free survival rates after radical treatment in patients with NMIBC and to search the optimal quality criteria for TUR in this disease.
Materials and methods. The data of patients with primary or recurrent NMIBC treated using TUR with and without intravesical therapy at the N. N. Aleksandrov Republican Research and Practical Center for Oncology and Medical Radiology in 2004 to 2013 were retrospectively analyzed. The investigation included a total of 949 cases of performing organ-sparing treatment in 784 patients. The operations were made by 5 surgeons with comparable experience with TUR.
Results. At a median follow-up of 64.3 (3–124) months, the 5-year relapse-free survival rates in 5 surgical groups were 62.9 (95 % confidence interval (CI) 56.2–69.7), 53.6 (95 % CI 47.4–59.9), 51.0 (95 % CI 39.6–62.4), 46.2 (95 % CI 36.4–56.0), and 44.2 % (95 % CI 36.8–51.7), respectively (p < 0.0001). According to the data of multivariate analysis including all potential factors, the prognostic role of a surgeon’s experience retained a high level of statistical significance (p = 0.0013). The differences between the surgeons were less pronounced after resection of tumors at a low risk for recurrence. Analysis of the distribution of the recurrence rates within the first 3, 6, and 12 months after TUR in relation to the surgeon, which were stratified according to recurrence risk groups, showed that the most differing rates were observed 12 months after TUR.
Conclusion. An operating surgeon has a significant effect on the risk of recurrence after radical treatment in patients with NMIBC. In our investigation, this effect was observed in spite of the relative much experience with surgical treatment of this disease by all surgeons and the performance of operations in one highly specialized center. The differences between the surgeons are less pronounced after resection of tumors at low recurrence risk. The recurrence rates for primary single (below 10 %), recurrent or multiple (below 19 %), and for recurrent and multiple (below 32 %) tumors within the first year after surgery can be taken for the quality criteria of TUR.
Objective. The diagnostic value of vascular endothelial growth factor (VEGF) in muscle-invasive bladder cancer (MIBC) was estimated.
Materials and methods. The level of VEGF was determined by ELISA in blood serum, plasma of patients with cancer invasion within the bladder or with extra-bladder invasion before surgical treatment and of patients with recurrences and metastases or without them 12–18 months after surgical treatment.
Results. Concentration of VEGF was shown to be one of criteria of activity in this disease. Thus, increasing of VEGF level correlated with the degree of the tumor invasion being one of criteria of its aggressive character and malignancy as well as its metastatic potential. At the same time, decreasing of concentration of this biomarker in patients with MIBC in the post-operative period was followed by limitation or absence of clinical manifestation of the tumor progression.
Conclusions. Thus, detection of VEGF in blood serum, plasma can serve as the basis for development of new methods of early non-invasive diagnostics of MIBC, prognosis of its course and estimation of the efficiency of treatment.
Background. Leukoplakia or squamous metaplasia (SM) of the bladder detect with the endoscopic diagnostic with urothelial biopsy. The reason for the development of SM, besides irritation of a mucous membrane by chemical reagents or drugs, is prolonged exposure of schistosome eggs (Schistosoma haematobium), penetrating into the bladder during invasion. The most common cause of urothelial SM is urogenital schistosomiasis (US) and one of the most known and dangerous its complications is schistosomiasis bladder cancer (sBC). Features of cellular mechanisms linking the schistosomes invasion with the development of sBC are not well studied. Urothelial SM use to indicate by the presence of cancerous transformation, or may be a marker of long-term inflammation. The flow of squamous cell carcinoma of the bladder usually is accompanied by a keratinizing SM. Taking into account the socio-political conditions of the modern world and the development of tourism, the relevance of the diagnosis and treatment of patients with those diseases continues to grow.
Materials and methods. The results of observation the group of 181 residents of the Republic of Angola with gross haematuria analyzed from 2009 till 2010. US verified in all cases. We conducted urine tests for detection of schistosomes, cytological examination of urine sediment (CEUS), ultrasound and endoscopic diagnostic methods, biopsy of the urothelium. The database of the hospitals used in the statistical analysis.
Results. In 142 (78.5 %) cases uncomplicated US confirmed, at 39 (21.5 %) patients sBC revealed. Schistosomes invasion and trichomonas were combined in 21 (14.8 %) cases. Changes and thickness of the bladder wall by ultrasound were accompanied with the SM in 26.8 % cases. The combination of SM and hydronephrosis caused by ureteral stenosis due to US were founded in 2 (1.4 %) cases. The coincidence cases of PM with ultrasound picture, featuring for manifestations US did not exceed 14.1 %. Cystoscopically SM detected at 76 (53.5 %) patients. The SM confirmed by complex of CEUS, cystoscopy and ultrasound in cases of gross granulomatous mucosal changes of the bladder wall with a significant (> 8 mm) thickening of the body wall. SM verified in 25 (64.1 %) cases with sBC (median age 29.25 years). The incidence of metaplasia was directly correlated with the stage of cancer. All patients with US and sBC were treated with praziquantel 40 mg / kg and, additionally, with fluoroquinolones in non-specific bacteriuria cases (28.9 %) and with antiprotozoa’s in cases of trichomoniasis (14.8 %). Control cystoscopy performed 10 days after the end of treatment. After the course of conservative therapy all symptoms of SM disappeared,
without need to specialized surgical treatment.
Conclusion. Identifying SM in patients with sBC does not have independent clinical significance: it was founded in conjunction with other specific mucosal changes, may accompany the uncomplicated forms of US and was not detected in patients with sBC in early stages. Therefore we are not being able to use that change as specific marker of the cancer transformation. The complete regression of dysplastic urothelium changes verified at the end of conservative treatment. Further study of the structure and changes of the bladder epithelium in patients with US is very important for understand the pathogenesis of tumor growth and for keeping a high
quality of life for young patients with firstly revealed bladder cancer of parasitic nature.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
The paper provides the first interim analysis of a database including information on 806 metastatic kidney cancer patients receiving targeted therapy in the cancer facilities of the Moscow Healthcare Department. It shows a comparative analysis of the periods of first-line targeted therapy with different drugs until progression is established.
Objective – to evaluate efficacy and safety of everolimus in Russian population of unselected patients with advanced renal cell carcinoma progressing after at least 1 line of anti-angiogenic targeted therapy.
Materials and methods. In observational multicenter study CRAD001LRU03 from 17.01.2012 to 31.03.2015 in 43 centers 226 patients with advanced renal cell carcinoma with documented progression on the background or after at least 1 line of anti-angiogenic targeted therapy were included. The survey was conducted on all patients according to the practice, everolimus therapy was administered in accordance with instructions to the drug.
Results. Objective response rate was 10 %, tumor control was achieved on 69.2 % of patients. Progression-free survival median – 7.8 months. Adverse events occurred in 44.7 % of patients, reached the III–IV severity of 9.3 %, were the reason for the cancellation of everolimus therapy in 2.2 % of cases. The most frequent complications of treatment were pneumonitis (n = 5 (2.2 %)) and anemia (n = 3 (1.3 %)).
Conclusion. The observational study confirms efficacy and favorable safety profile of everolimus mTOR inhibitor in the Russian unselected patients with advanced renal cell carcinoma with progression or intolerable toxicity against background of anti-angiogenic therapy.
Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately.
Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7)) with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80) years (median age 51.0 years). The right and left adrenal glands were affected in 49 (36.9 %) and 77 (57.9 %) patients, respectively; both adrenal glands were involved in 7 (5.3 %). A group of 21 (15.8 %) people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups.
Results. The investigation analyzed treatment results in 21 (15.8 %) patients with primary malignant adrenal lesions (Group 1). The most common morphological form was adrenocortical carcinoma in 15 (11.3 %) patients (5 men and 10 women (1:2)); their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell carcinoma, Castleman’s disease, and oncocytic carcinoma. According to the tumor stage, the patients with adrenocortical carcinoma were divided as follows: Stage T1 (n = 3), Stage T2 (n = 3), Stage T3 (n = 4), and Stage T4 (n = 5). In the patients with adrenocortical carcinoma, the size of an adrenal tumor was 8.7 ± 4.9 cm; hypertension as a main clinical manifestation occurred in 5 patients; pain syndrome was observed in 10; hormonal activity was noted in 8, blood electrolyte disorders were seen in 3, and gastrointestinal manifestations were in 9 patients. In Group 1, 8 (38.1 %) patients were survivors and 13 (61.9 %) patients died. Moreover, the overall 5-year survival was 37.9 %. Five-year survival in patients with adrenocortical carcinoma was 42.4 % (6 (53.3 %) survivors and 9 (46.7 %)) dead persons); that in patients with other malignant adrenal tumors was 33.3 % (2 (33.3 %) survivors and 4 (66.7 %) dead persons).
Conclusion. Surgical removal of an adrenocortical tumor is the only treatment option that can cure a patient or considerably prolong life
particularly if the disease is detected at stage I or II.
PROSTATE CANCER
Prostate cancer (PC) is one of the most urgent problems of modern urologic oncology in Russia because of a steady rise in morbidity and mortality rates associated with this disease. Radical prostatectomy (RP) and external beam radiotherapy (EBRT) or brachytherapy are mainstay treatments in patients with localized and locally advanced PC. Just the same, the rate of lymphogenic disease progression after radical treatment is as high as 15–40 %. At the same time, a search for a tumor focus leading to an increase in the marker is extremely important. If a local recurrence is detected after previous RP, there may be salvage EBRT. After verifying the relapse after salvage EBRT or brachytherapy, RP may be recommended to patients in the specialized centers having appropriate experience with this type of surgery. In patients with distant metastases, palliative hormonal therapy has been the only conventional method so far. Nonetheless, in a considerable number of patients, a marker recurrence may be associated with the so-called oligometastatic progression of the disease, in which the number of detected metastatic foci is minimal. The clinical introduction of promising and precise diagnostic methods having high sensitivity and specificity even with the minimal levels of prostate-specific antigen, such as magnetic resonance imaging and positron tomography, could substantially increase the number of detectable patients with oligometastases and propose new therapeutic conceptions for the treatment of this contingent of patients. Recently, in the literature there have been increasingly more works suggesting the possibility of using local treatments (surgery or radiotherapy) in patients with oligometastases when the disease progresses after radical treatment. The results of investigations show that a personalized approach and surgical or radiation treatments in selected patients make it possible to increase survival prior to the use of hormonal treatment and, in a number of cases, to completely abandon the latter. The paper gives a review of the literature data dealing with this problem.
Introduction. The shear wave ultrasound elastography is a recently developed ultrasound-based method in the clinical practice, which allows the qualitative visual and quantitative measurements of tissue stiffness. In the 2010 this technology of the shear wave was called Shear Wave Elastograhpy. Due to the front of the shear waves the qualitative and quantitative assessment of the tissue stiffness is possible.
Objective is to examine the efficacy of the shear wave ultrasound elastography in the evaluation of the prevalence of the oncological disease in patients with the prostate cancer and to compare the obtained results with the routine method X-ray diagnostics.
Materials and methods. From the april 2015 in the I.M. Sechenov First Moscow State Medical University Urology Clinic there were conducted 314 shear wave ultrasound elastography examinations of the prostate. The ultrasound system Aixplorer® by SuperSonic Imagine was used. This system provides information provided by B-mode and shear wave ultrasound elastography mode. The transrectal echograms were made in 6 dimensions, so called Q-boxes (3 demensions in the every lobe on the segments from the base to the apex, according to the biopsy zone). The unit of measurement was the mean value in the kilopaskals (kPa). All the patients were randomized into 3 groups. There were 146 men with the possible prostate cancer in the first group (prospective study), 120 men with the certain diagnosis of the prostate cancer in the second group (retrospective study) and 48 healthy men in the third group (control study). In all the patients of the first and the second groups the routine complete examination, including the prostate specific antigen (PSA) level examination, digital rectal examination (DRE), doppler transrectal ultrasonography (TRUS), histoscanning and ultrasound shear wave elastography (SWE), was conducted. In the 229 patients of the first and the second groups the prostatectomy with the morphological verification of postoperative material was made. In the 63 patients of the first and the second groups the contrast-enhanced magnetic resonance imaging (MRI) of the pelvic organs was made. In the health men’s group, besides the ultrasound shear wave elastography, only the routine diagnosis methods of the prostate cancer (PSA level, TRUS and DRE) were used.
Results. According to the results of our study, the threshold values for the normal prostate tissue stiffness due to the ultrasound shear wave elastography were from 0 to 23 kPa, for the hyperplastic prostate – from 23.4 to 50 kPa, for the prostate cancer – from 50.5 kPa. The data analysis of the 212 patients with the verified prostate cancer showed the increase of the mean degree of tissue stiffness due to the clinical stage and tumor differentiation (Gleason scale total score). All the patients were divided into the subgroups with the certain correlation values. In patients with the Gleason scale total score < 7, the mean degree of tissue stiffness was 72 kPa (n = 63). In 57 patients with the Gleason scale total score 7, the mean degree of tissue stiffness was 69 kPa. In 48 patients with the Gleason scale total score from 8 to 10, the tissue stiffness was averagely 119 kPa. The locally advanced stage Т3–4 was determined in 44 examined patients. The tissue stiffness value correlated with the tumor differentiation rate: the index variations were from 120 to 295 kPa. On the results of this method analysis, its resistance was 90,8 % and specificity was 94,6 %. According to the comparative assessment with the other examination technics, the informative value of the ultrasound shear wave elastography is far above the DRE, the doppler TRUS and the histoscanning, but is lower than the contrast-enhanced magnetic resonance imaging.
Conclusion. In view of the above, the ultrasound shear wave elastography is a very informative method of the prostate cancer detection and it has a high rate of the agreement of the results with the contrast-enhanced magnetic resonance imaging and is more specific than the histoscanning.
The cases of the uncommon malignant disease state can take place in patients with the prostate cancer. This disease may appear at a young age and the level of the PSA may be normal (to 4 ng / ml), and also the negative clinical prognosis, due to the resistance to standard medical treatment, can take place. In the literature review there is a data on patients’ carrier status of gene BRCA1 / 2 mutation. There are 2 % of such patients and the program of the target screening of the prostate cancer and the special treatment regimen for them should be developed. According to the mechanism of action of the platinum-based drugs and the data from the studies on treatment of the BRCA1 / 2-dependent ovarian cancer in women, where the high sensitivity to the platinum-based drugs in patients with the mutations of the reparation genes of the deoxyribonucleic acid by the homologous recombination was validated, we supposed, that the defects of the deoxyribonucleic acid reparation in patients with the metastatic castration-resistant prostate cancer also might be highly sensitive to the platinum-based drugs.
This article deals with the intermediate results of the multicentral observational program on the 6-month prodrug leuprorelin acetate (Eligard 45 mg) administration. The study objective is to confirm the efficiency and safety of the Eligard 45 mg administration in patients with the prostate cancer in the clinical practice of the oncourology specialists in Russia. In 12 months of the hormone therapy with the Eligard 45 mg there was the clinically relevant decrease of the prostatic specific antigen (PSA) levels secondary to the appropriate suppression of the testosterone level lower than the castration one < 20 ng / dl. The PSA level decreased, at an average, on 82 % (from 41.4 to 7.65 ng / ml). In 89 % of patients, treated with Eligard 45 mg, the testosterone level was < 20 ng / dl. The patients», treated with Eligard 45 mg, quality of life analysis showed the improvement of this criteria in the course of the treatment. Thus, intermediate results of the multicentral observational program, proved the favorable tolerability and efficiency of the 6-month prodrug Eligard 45 mg towards the PSA and testosterone serum levels suppression in the routine clinical practice in prostate cancer patients.
CONGRESSES AND CONFERENCES
CLINICAL CASE
Leiomyosarcoma of the veins of the retroperitoneum – the rare malignant non-organ mesodermal formation, derived from the smooth-muscle tissue of the vessel wall. These slow-growing tumors with the delayed symptoms are often advanced. The leiomyosarcoma of the renal vein is the rarer oncological disease. The treatment of this condition is mainly surgical, often with the chemoradiation. In view of the rarity of these malignant diseases, the every case history review is very important for the science. There are two case history reports with the description of the diagnosis and treatment problems.
Clips are widely used in order to rapidly achieve stable hemostasis in laparoscopic/robotic surgery. This article describes a clinical case of clip migration into the bladder with calculus formation without concomitant vesicourethral anastomosis stricture in a patient after robotic radical prostatectomy.
ANNIVERSARIES
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