Vol 12, No 4 (2016)

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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

Molecular genetic diagnostics of clear cell renal cell carcinoma

Apanovich N.V., Peters M.V., Korotaeva A.A., Apanovich P.V., Markova A.S., Kamolov B.S., Matveev V.B., Karpukhin A.V.

Abstract

Background. On the pace of growth in Russia, renal carcinoma takes the 1st place. Approximately one third of patients at time of diagnosis have distant metastases, and relapse of the disease occurs in 30–40 %. Renal carcinoma does not manifest until later stage of the disease. More than in 50 % of cases renal carcinoma is revealed occasionally. Therefore, development of methods for quick and efficient diagnosis of the tumor is actual.

Materials and methods. The level of messenger RNA expression for several genes was studied in the surgical material of paired samples (normal tissue and a malignant renal carcinoma). Quantification of gene expression was performed by using real-time polymerase chain reaction on Step One Plus instrument (Applied Biosystems, USA) by using TaqMan® Gene Expression Assays kits (Applied Biosystems, USA).

Results. As a result of screening analysis of 200 genes expression in paired samples of renal carcinoma/normal renal tissue we selected 5 genes showing the highest frequency of increased expression in stages I–III of the development of clear renal cell carcinoma: CA9, EGLN3, HIG2, NDUFA4L2, STC2.

Conclusion. As a result of the expression study we developed a new panel, including CA9, HIG2 and STC2 genes which has high sensitivity (96.8 %) and specificity (92.9 %) for differential diagnosis of the early clear cell renal cell carcinoma on the basis of determining the level of messenger RNA expression by real-time polymerase chain reaction. This approach allows you to diagnose clear cell renal cell carcinoma quickly (within 1 day), and differentiate it from other types of renal cell cancer. In addition, it opens the possibility of non-invasive diagnosis of renal carcinoma in the future.

Cancer Urology. 2016;12(4):16-20
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Surgical treatment of Renal Cell Carcinoma (RCC) with level III–IV tumor venous thrombosis

Davydov M.I., Matveev V.B., Volkova M.I., Feoktistov P.I., Kuznetsov K.P., Nekhaev I.V., Lomidze S.V., Zhuzhginova O.V., Figurin K.M., Chernyaev V.A., Ogorodnikova E.V.

Abstract

Objective: to assess the results of nephrectomy, thrombectomy in RCC patients with level III–IV tumor venous thrombosis with and without cardiopulmonary bypass.

Materials and methods. Medical data of 167 consecutive RCC patients with level III–IV tumor venous thrombosis underwent nephrectomy thrombectomy in N.N. Blokhin Russian Cancer Research Center between 1998 and 2012 were collected. Right side tumor was in 122 (73.1 %), left side – in 42 (25.1 %), bilateral – in 3 (1.8 %) cases. The extent of thrombus was defined as intrahepatic in 82 (49.1 %), supradiaphragmatic – in 85 (50.9 %) (intrapericardial – in 44 (26.3 %), intraatrial – in 39 (23.4 %), intraventricular – in 2 (1.2 %)) cases. Nephrectomy, thrombectomy with cardiopulmonary bypass was used in 9 (5.4 %), 158 (94.6 %) patients underwent radical nephrectomy with thrombectomy without CPBP and sternotomy. Intrapericardial IVC and right atrium were exposed through transdiaphragmatic approach and providing vascular control over infradiaphragmatic IVC and renal veins.

Results. Median blood loss was 6000 (600–27 000) ml. Complications rate was 62.8 %, 90-day mortality – 13.2 %. Intraoperative complications were registered in 80 (47.9 %), postoperative – in 66 (40.5 %) (grade II – 16 (9.8 %), grade IIIb – 1 (0.6 %), grade IVа – 28 (17.2 %), grade IVb – 3 (1.8 %), grade V – 18 (11.1 %)) patients. Modified thrombectomy technique insignificantly decreased blood loss compared to thrombectomy with CPB, did nоt increase complications rate including pulmonary vein thromboembolism, or mortality. Five-year overall, cancer-specific and recurrence-free survival was 46.2, 58.3 and 47.1 %, respectively. Thrombectomy technique did nоt affect survival.

Conclusion. In selected patients with mobile thrombi transdiaphragmatic approach allows to avoid the use of CPBP and decrease surgical morbidity without survival compromising.

Cancer Urology. 2016;12(4):21-34
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A new alternating regimen in metastatic renal cell carcinoma presented through a clinical case

Sayapina M.S., Shiryaev S.V., Krylov A.S., Ryzhkov A.D., Titov D.A., Nosov D.A.

Abstract

In the article a new alternating regimen which includes alternation between interferon (INF) immunotherapy and target therapy (sunitinib) is described through a clinical case. Mentions of this type of regimen weren’t found in the literature. As a result of the regimen, treatment efficacy increased due to decreased development of resistance to targeted therapy, cumulative toxicity decreased, synergy between immunotherapy and targeted therapy was achieved, and the cost of the treatment was reduced by 50 %. Considering the above, other alternating regimens can be of interest for researchers: INF/targeted therapies (INF/axitinib, et al.), checkpoint inhibitors/targeted therapies. At the same time, randomized phase II trial ROPETAR showed that alternation of targeted therapies (pazopanib/everolimus) does not increase treatment efficacy or decrease toxicity in comparison with sequential dosing.
Cancer Urology. 2016;12(4):35-42
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Clinical and economic analysis of the 1st and 2nd target lines

D’yakov I.N., Zyryanov S.K.

Abstract

Malignant tumors represent a serious problem for healthcare system. At this time, an annual incidence of cancer rate has increased both in Russia and around the world. Renal cancer has 2 % in the structure of oncological incidence. However, in many countries we can see significant increase in oncological incidence and associated mortality. Renal cell carcinoma (RCC) takes the 2nd place after prostate tumors by the growth rate of these parameters: each year more than 200 thousand people become ill with RCC all over the world. Cytokine therapy with interleukin-2 and/or interferon alpha was the standard treatment of the advanced renal cell carcinoma until 2005. However, method of the target therapy became widespread in the last decade. This method is based on the directional drug effect on tumor cells which increases efficiency and safety of the therapy. The use of targeted therapy drugs led to a significant increase in survival rate in RCC patients. In the present review we observe clinical efficacy of the drugs used in the 1st and 2nd line of RCC treatment as well as pharmacoeconomic aspects of their application.
Cancer Urology. 2016;12(4):43-51
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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

Epidemiology of prostate cancer in the Rostov region. Spatio-temporal statistics

Arkhipova O.E., Chernogubova E.A., Chibichyan M.B., Kogan M.I.

Abstract

Background. The article presents the analysis of morbidity from prostate cancer (PC) with consideration of regional differences in the level of the health and environmental safety.

Materials and methods. Analysis was conducted of the level of incidence of PC in the Rostov region for the period 2001 to 2014. Model of conditionality of distribution of oncological diseases as ecology dependent pathologies is based on software ArcGIS 10. The constructed model has provided a number of results, significantly expanding the scope and use of medical and environmental monitoring.

Results. It has been shown that in the regions and cities of the Rostov region with a low level of medical-ecological safety observed a statistically significant increase in the incidence of PC. On the example of the Rostov region it has been shown that the level of cancer is an indicator of health and environmental safety of the area.

Conclusions. The results can serve as a basis for the directional analysis of factors causing increase risk of cancer and development on these basis strategies for monitoring and prevention of cancer diseases in the Rostov region.

Cancer Urology. 2016;12(4):52-59
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Early recovery program in the radical surgical treatment of patients with prostate cancer: experience of the specialized hospital

Nosov A.K., Reva S.A., Berkut M.V., Petrov S.B.

Abstract

Background. Currently, there are sufficient data on the favorable role of fast track program on the course of postoperative period. Nevertheless, the role of these protocols being already included in the standards of the surgical treatment of many cancers is not clear to date in oncourology in general and in the prostate cancer (PC).

Objective: to determine the effect of fast track program elements for the results of treatment in patients after radical prostatectomy.

Materials and methods. 86 radical minimally invasive (laparoscopic or endoscopic extraperitoneal) prostatectomies were performed for prostate cancer in the period from May 2015 to February 2016 in the Oncological Research Institute named after N.N. Petrov. Patients were divided into 2 groups: in patients of the 1st (n = 44) group included those with traditional surgical management fast track elements were not used at all or were used partly; in the 2nd group (n = 42) these elements were used in a whole volume. We have assessed an influence of fast track elements on the frequency of perioperative and early postoperative complications, operative time, duration of the hospitalization and duration of the stay in intensive care unit, frequency of the repeated surgical interventions, and frequency of the repeated hospitalizations within 30 days of the postoperative period.

Results. The presence and the absence of preoperative preparation did not affect an incidence of intraoperative complications. Intraoperative blood loss did not lead to blood transfusions. There were no significant differences in the incidence of 30-day complications between groups. When evaluating postoperative parameters there was difference between 1st and 2nd groups in the pelvis drainage (3.3 and 0.9 days, respectively, p = 0.002), an average duration of catheterization (11.2 and 5.2 days, respectively, p = 0.0003) and duration of hospitalization (15.1 and 6.5 days, respectively, p = 0.0008).

Conclusion. Application of fast track program of perioperative management of patients with prostate cancer does not affect the frequency of intraand postoperative complications, but economically it is potentially more feasible, primarily by reducing the term of the patient stay in hospital.

Cancer Urology. 2016;12(4):60-69
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Salvage lymphadenectomy in patients with lymphogenic prostate cancer progression after radical treatment: results of a multicenter study

Alekseev B.Y., Nyushko K.M., Reva S.A., Nosov A.K., Prokhorov D.G., Andabekov T.T., Krasheninnikov A.A., Safronova E.Y., Shkol’nik M.I., Petrov S.B., Kalpinskiy A.S., Kaprin A.D.

Abstract

Prostate cancer (PC) is one of the most challenging and pressing problems of modern oncourology because of high morbidity associated with the disease. The main methods of radical treatment of patients with localized and regional PC are radical prostatectomy and beam radiation therapy, external or brachytherapy. Nonetheless, the rate of biochemical progression of the disease after radical treatment remains high and averages 27–53 %. Of the utmost importance is determination of the tumor nidus which raises the marker level. Currently, in patients with distant metastases the only widely accepted treatment method is palliative hormonal therapy (HT). However, in majority of patients marker recurrence can be associated with so-called oligometastatic progression characterized by a minimal number of detectable metastases. Research shows that surgical treatment or beam radiation therapy in selected patients of this cohort allows to significantly increase the time until HT prescription, and in some cases to abandon it altogether. The article describes the results of surgical treatment of patients subjected to salvage lymphadenectomy for oligometastatic PC progression at three centers: P.A. Hertzen Moscow Oncology Research Institute, N.N. Petrov Research Institute of Oncology and Russian Research Center for Radiology and Surgical Technologies. In the multicenter study, short-term and longterm results of surgical treatment of 57 patients were evaluated. It was shown that in some patients, salvage lymphadenectomy can be an effective treatment option significantly lengthening the time until HT prescription, and in 23.4 % of patients it can lead to long-term (12 months) stabilization of the disease and 90 % decrease in prostate-specific antigen level compared to the initial pre-surgery level without any additional forms of therapy.
Cancer Urology. 2016;12(4):70-80
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Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radical radiotherapy

Solodkiy V.A., Pavlov A.Y., Tsybul’skiy A.D.

Abstract

Studies salvage interstitial radiation therapy for recurrent prostate cancer, launched at the end of the XX century. In recent years, more and more attention is paid to high-dose-rate brachytherapy (HDR-BT) as a method of treating local recurrence.

The purpose of research – preliminary clinical results of salvage high-dose-rate brachytherapy applied in cases of suspected local recurrence or of residual tumour after radiotherapy.

Preliminary findings indicate the possibility of using HDR-BT, achieving local tumor control with low genitourinary toxicity.

Cancer Urology. 2016;12(4):81-86
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Angiotensin converting enzyme – a new prognostic marker of recurrence in the treatment of prostate cancer

Kogan M.I., Chernogubova E.A., Chibichyan M.B., Matishov D.G.

Abstract

Background. Introduction to the clinical practice of new criteria for the diagnosis and monitoring of neoplastic processes in the prostate based on the identification of informative predictors and markers of prostate cancer (PC), especially its aggressive forms, is one of the priority directions of scientific research in oncological urology. The goal – the search of new markers of aggressive forms of PC.

Materials and methods. For identification associated with PC progression indicators – potential markers clinically aggressive forms of PC was determined activity kininase II (angiotensin-converting enzyme (ACE), EC 3.4.15.1) in serum of blood with using as substrate N-(3-(2-furyl) acryloyl)-L-phenylalanyl-glycyl-glycine (FAPGG). Retrospectively evaluated ACE activity in patients with the development of biochemical recurrence and without after hormone-radiation therapy.

Results. It has been shown that the development of PC recurrence is associated with an increase in ACE activity, and the ACE activity starts to grow sooner than noted the development of biochemical recurrence. Joint determination of prostate-specific antigen and the activity of the enzyme after a month of treatment allows to select a group of patients with high risk of biochemical recurrence with sensitivity, specificity of 78.6 % (p < 0.001), respectively 94,6 % (p < 0.001).

Conclusions. There is every reason to believe that ACE is a promising predictive marker of clinically aggressive forms of PC. The renin-angiotensin system in PC can be considered as a new therapeutic target for targeted therapy.

Cancer Urology. 2016;12(4):87-93
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APHIG: a new multiparameter index for prostate cancer

Sergeeva N.S., Skachkova T.E., Alekseev B.Y., Yurkov E.F., Pirogov S.A., Gitis V.G., Marshutina N.V., Kaprin A.D.

Abstract

Serum of 336 patients with primary prostate cancer (PC) with baseline total prostate-specific antigen level (totPSA) < 30.0 ng/ml was tested for free PSA (freePSA) and [-2]proPSA; %freePSA, %[-2]proPSA, prostate health index (phi), and a new index APHIG calculated using lab tests and taking into account age, T stage and Gleason score from biopsy were evaluated. Obtained data was compared to tumor stage (pTNM) and malignancy grade according to the Gleason score based on the final histological report after prostatectomy. APHIG has statistically significant benefits compared to PSA-associated markers for differentiation of clinically significant subgroups of PC: pT2c/pT3a/pT3b; local indolent PC/local aggressive/locally advanced/PC with regional metastases; total Gleason score 5–6/7(3 + 4)/7(4 + 3).
Cancer Urology. 2016;12(4):94-103
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Prospects of 2nd line chemotherapy personalization in patients with metastatic castration-resistant prostate cancer

Alekseev B.Y., Nyushko K.M.

Abstract

Prostate cancer (PC) is one of the most challenging and pressing problems of modern oncourology because of high morbidity associated with the disease worldwide. About 1 100 000 new cases are diagnosed each year. The main approach to treatment of locally advanced and/or metastatic PC is hormonal therapy. Androgen deprivation therapy allows to achieve stabilization in more than 90 % of patients, but average time until progression after hormonal therapy in patients with metastatic PC is about 2 years. Then patients with tumor progression accompanied by castration level of testosterone enter the stage of so-called castration-resistant PC (CRPC). Prognosis for regional CRPC is unfavorable, and it substantially lowers patients’ quality of life. Taxane-based chemotherapy remains a standard method of treatment in this patient cohort. The article reviews studies of efficacy of different doses and regimes of 2nd line chemotherapy using cabazitaxel in patients with metastatic CRPC.
Cancer Urology. 2016;12(4):104-109
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DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

The cytomorphologic classification of urinary pathology. The Paris System, 2016

Savostikova M.V., Kudaybergenova A.G., Fedoseeva E.S.

Abstract

The paper presents the Paris System for Reporting Urinary Cytology developed by the joint efforts of cytologists, pathologists and urologists in April 2016. We describe 7 accepted categories of cytological diagnoses, the risk of malignancy and recommended clinical management of patients with urinary pathology.
Cancer Urology. 2016;12(4):110-118
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Assessment of recurrence and progression risk in patients with non-muscle invasive bladder cancer

Rolevich A.I., Mirilenko L.V.

Abstract

A retrospective analysis of monitoring of patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) treated with transurethral resection (TUR) with or without restaging TUR or intravesical therapy in State Institution N.N. Alexandrov National Cancer Centre of Belarus in 2004–2012 was performed with an objective to develop a prognostic classification for NMIBC. The analysis included 921 patients. In the multivatiate analysis independent predictors of recurrence were recurrence rate, number of tumors, tumor size, grade, and tumor location in the trigone, anterior wall, dome, and prostatic urethra; predictors of progression were age, recurrence rate, tumor size, grade, and tumor location in the trigone and prostatic urethra. The patients were divided into 4 groups with low, intermediate, high and very high risk. Corrected C-index values for the developed classifications of recurrence and progression risks were 0.635 and 0.740 respectively, which were significantly higher than C-indices for the European Organization for Research and Treatment of Cancer tables.
Cancer Urology. 2016;12(4):119-130
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Спасительная цистэктомия после органосохраняющего лечения больных мышечно-инвазивным раком мочевого пузыря

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Abstract

Цель исследования – изучение целесообразности и безопасности спасительной цистэктомии после органосохраняющего лечения у больных мышечно-инвазивным раком мочевого пузыря.

Материалы и методы. В исследование ретроспективно отобраны данные 130 больных переходно-клеточным раком мочевого пузыря, получавших лечение в РОНЦ им. Н.Н. Блохина в период с 1981 по 2016 г. В основную группу вошли 66 пациентов, подвергнутых спасительной цистэктомии после безуспешного органосохраняющего лечения, основанного на лучевой терапии. Лимфодиссекцию произвели 42 (63,6 %) пациентам. С целью отведения мочи выполнялись: операция Бриккера (42 (63,6 %)), операция Штудера (7 (10,6 %)), другое (17 (25,8 %)). Морфологически рак мочевого пузыря верифицирован в 62 (93,9 %) препаратах (категория Р1 – 6 (9,1 %), Р2 – 21 (31,8 %), Р3 – 25 (37,9 %), Р4 – 18 (27,2 %)); метастазы в лимфатические узлы выявлены в 11 (16,6 %) случаях. Степень анаплазии расценена как G3 в 35 (56,5 %) из 62 препаратов, содержавших опухоль. В группу сравнения включены 64 пациента, которым была выполнена радикальная цистэктомия без предшествующего лечения. Частота категорий Т3a–4b и степени анаплазии G3 была достоверно выше для всех пациентов основной группы (р < 0,0001).

Результаты. Частота интраоперационных осложнений спасительных цистэктомий составила 10,6 %, послеоперационных – 42,7 % (28 из 65) (I–II степени тяжести – 27,3 % (18 из 28), III–V степени тяжести – 15,4 % (10 из 28)). Пятилетняя общая, специфическая и безрецидивная выживаемость пациентов основной группы составила 43,7; 58,6 и 54,7 % соответственно. Независимыми факторами благоприятного прогноза выживаемости явились степень анаплазии G1–2, гидронефроз и лимфодиссекция. Рецидивы после спасительных операций развивались реже, чем после цистэктомий, выполненных без предшествующего лечения (19 (30,6 %) и 31 (48,4 %) соответственно, р = 0,031). Других статистически значимых различий результатов спасительной и радикальной цистэктомий не выявлено.

Заключение. Спасительная цистэктомия после безуспешного органосохраняющего лечения у больных мышечно-инвазивным раком мочевого пузыря ассоциирована с приемлемым операционным риском и обеспечивает удовлетворительные отдаленные результаты, сопоставимые с радикальной цистэктомией.

 

Cancer Urology. 2016;12(4):131-141
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CLINICAL CASE

A clinical case of effective surgical treatment of a female patient with stage IV kidney cancer with 50 % sarcomatoid renal cell carcinoma accompanied by liver invasion without distant metastases

Solodkiy V.A., Pavlov A.Y., Garmash S.V., Tsybul’skiy A.D., Ivashin A.D.

Abstract

The article describes a clinical case of effective surgical treatment of a 51-year-old female patient with sarcomatoid renal cell carcinoma of the right kidney accompanied by invasion into the liver. The surgical treatment consisted of right-side nephradrenalectomy with thrombectomy and hemihepatectomy. Histolopathology report revealed mixed renal cell carcinoma, comprised of clear cell (50 % of tumor tissue) and sarcomatoid (50 % of tumor tissue) grade III cancer (Fuhrman Nuclear Grade). During 36-month dynamic observation no recurrence or progression was observed.
Cancer Urology. 2016;12(4):142-145
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CONGRESSES AND CONFERENCES

Резолюция по итогам Совета экспертов по иммунотерапии распространенного рака мочевого пузыря

., ., ., ., ., ., ., ., ., ., ., ., .

Abstract

Резолюция по итогам Совета экспертов по иммунотерапии распространенного рака мочевого пузыря
Cancer Urology. 2016;12(4):146-148
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ANNIVERSARIES

70 лет Ринату Харисовичу Галееву

Abstract

Ринат Харисович родился в  1946  г. в семье лесника и сельской учительницы. Еще  ребенком он мечтал стать врачом. Окончив школу с золотой медалью, поступил в  Казанский медицинский институт. По окончании работал хирургом в г. Йош- кар-Оле, там же начал урологическую практику. По окончании ординатуры в Казан- ском медицинском институте в 30 лет стал заведующим урологического отделения Республиканской клинической больницы ТАССР. Уже в те годы его интересовали новые направления в медицине, а главным его делом стала разработка органозамещающих и  реконструктивных операций на органах мочеполовой системы. В 1985 г. Ринат Харисович защитил кандидатскую диссертацию «Реконструктивные операции при  вариантных формах почечной артерии», а в 1994 г. – докторскую диссертацию «Цистэктомия и илеоцистопластика у больных раком мочевого пузыря».
Cancer Urology. 2016;12(4):149
pages 149 views