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Cancer Urology

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Vol 13, No 1 (2017)
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https://doi.org/10.17650/1726-9776-2017-13-1

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS

16-19 3614
Abstract
Studied the structure, prevalence, trends in incidence and morphology of malignant tumors of the kidney, renal pelvis, ureters, and bladder among residents of the Kabardino-Balkaria for the period 1990–2014 years. Designed intense (coarse) and the standardized value for age and sex, the annual growth rate of morbidity, using the world standard age distribution. Standardization carried out by the direct method. Knowledge of the epidemiological and morphological characteristics allow us to proactively identify patients at early stages of disease, more effective to conduct medical examinations and preventive measures, to plan a rational treatment strategy for patients

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

20-26 8382
Abstract

The role of tumor stroma in malignant tumor pathogenesis cannot be disputed. Macrophages are one of the crucial elements of tumor stroma. Tumor-associated macrophages (TAMs) are type 2-activated macrophages (M2). They were first described in 1992. They carry CD206, CD163, FXIIIa, βIG-H3, stabilin 1, YKL-39, SI-CLP, tenascin С, LOX-1, fibronectin, MARCO, interleukin 1 receptor antagonist (IL-1RA) and other markers. Unlike proinflammatory macrophages (M1), М2 display high anti-inflammatory activity and are responsible for inflammation reaction suppression and tissue recovery in inflamed area. TAMs significantly contribute to tumor progression by stimulating cell proliferation, angiogenesis, and suppression of antitumor immune response. Identification of macrophages in renal tumors involves a limited number of markers, which doesn’t allow making a conclusive answer about their function. However, a correlation between TAMs content and a negative disease prognosis can be considered proven. Studies of M1 and M2 using different markers have shown that renal tumors contain high levels of TAMs with mixed M1/M2 phenotype. TAMs in renal tumors are highly proangiogenic and immunosuppressive. TAMs density can be used as a prognostic marker, but development of an effective treatment strategy aimed at inhibition of TAMs antitumor activity requires systemic research involving a wide panel of M1 and M2 macrophage markers. 

27-36 9729
Abstract

Objective. To evaluate short-term and long-term results of nephrectomy, thrombectomy, circular inferior vena cava (IVC) resection in patients with renal cell carcinoma (RCC) and advanced IVC tumor invasion.

Materials and methods. Medical data of 49 patients with RCC and level II–IV tumor venous thrombus with advanced IVC wall tumor invasion were analyzed. All the patients underwent nephrectomy, thrombectomy, circular IVC resection (radical – 35 (71.0 %), cytoreductive, in M+ cases – 14 (28.6 %)). Circular resection of the infrarenal IVC segment was performed in 25 (51.0 %) patients; resection of the infrarenal, perirenal and retrohepatic IVC segments with a ligation of the left renal vein (RV) – in 24 (49.0 %) patients. Perirenal IVC prosthesis was used in 2 (4.1 %) patients with initially preserved IVC blood flow, in other cases replacement of the removed IVC segment wasn’t performed due to presence of a network of venous collaterals duplicating the IVC. Patients with metastases received systemic antitumor treatment after nephrectomy, thrombectomy.

Results. Median operative time was 260 (135–580) minutes, median blood loss was 8750 (3000–27 000) ml. Severe intraoperative complications were observed in 2 (4.0 %) patients, 1 (2.0 %) patient died on the operating table due to hypovolemic shock. Postoperative complications were observed in 26 (53.2 %) cases (grade III–V in 22 (45.8 %) patients). Five-year overall and cancer-specific survival of all patients was 54.6 and 67.8 %, respectively, relapse-free survival of 35 patients with M0 category was 49.4 %. Both IVC prostheses were patent 12 months after the surgery. Function of the left kidney after ligation of the left RV was preserved at the preoperative level in all 24 patients in a median of 12 (2–120) months.

Conclusion. Nephrectomy, segmental/subtotal cavectomy with preservation of the main renal venous entries is an effective treatment method in RCC patients with advanced tumor IVC invasion. The method allows to achieve satisfactory long-term survival rates and functional results. 

37-44 10252
Abstract

Objective. Analysis of factors affecting results of inferior vena cava (IVC) thrombectomy in patients with renal cell carcinoma.

Materials and methods. Nephrectomy with thrombectomy from IVC was performed in 53 patients (31 (58.5 %) males and 22 (41.5 %) females) with extended thrombosis. Patient age was 35–76 years (mean age 58.7 ± 10.1 years). In 36 (68 %) patients stage Т3b was determined (mean thrombus length 5.28 ±0.32 cm), in 17 (32 %) patients – stage Т3с (mean thrombus length – 13.00 ±0.71 cm). Postoperative complications were evaluated in accordance with the Clavien–Dindo classification. Calculations were performed using statistics software SPSS Statistics 16.

Results. No intraoperative complications were observed, mean blood loss was 714 (200–4000) ml. Use of the Cell Saver system allowed to perform reinfusion in the majority of patients. Blood transfusion of 200–500 ml was necessary in 15 patients. In 32 (60.3 %) patients no complications were observed. Grade I complications were observed in 2 (3.7 %) patients, grade II – in 15 (28.3 %) patients, IIIА grade – in 2 (3.7 %) patients, and grade IIIВ – in 1 (1.8 %) patient; there wasn’t any grade IV complications. Two (3.8 %) patients died of pulmonary artery thromboembolism. Correlation analysis has shown a high dependency of complications on thrombus size (r = 0.7) and blood loss volume (r = 0.6), and low dependency on tumor size (r = 0.44); complications weren’t affected by patients’ age (r = 0.1) or Karnofsky status (r = 0.0). Median overall survival was 48 months, 3-year survival was 57.1 %, median progression-free survival was 46 months, 3-year progression-free survival was 56.8 %; 90-day morbidity was absent. Three-year overall survival for рN0 was significantly higher than for рN1 (69 % vs. 25 %; р = 0.014). There was no difference in terms of survival between patients with supradiaphragmatic and subdiaphragmatic thrombi (р = 0.14).

Conclusion. Results of our study show that surgical treatment of patients with renal cell carcinoma and extended IVC thrombosis is effective. 

45-52 8279
Abstract

Background. Tumors of a solitary kidney (SK) are extremely rare. They are an absolute indication for organ-preserving treatment. Decrease in the glomerular filtration rate (GFR) and development of acute kidney injury in early postoperative period often require hemodialysis, and patients have to stay in the ICU.

Objective. Evaluation of short-term functional results and identification of factors affecting GFR decrease in the early postoperative period after partial nephrectomy for renal masses in the SK.

Materials and methods. Analysis of patients’ data with tumor of the SK who underwent open partial nephrectomy at the Oncourology Department of the N.N. Alexandrov National Cancer Centre ofBelarus in the period of 16 years was performed. The study included 136 patients.

Results. Multifactor regression analysis (including potential risk factors) revealed that the GFR decrease in the early postoperative period significantly correlated with multifocality (p = 0.028-), ischemia (p < 0.001), blood transfusion (p < 0.001), and the maximum tumor size (p = 0.006). Additional analyses didn’t show any statistically significant correlations between decrease of kidney function and duration of the SK status (n = 127; p = 0.31) or the volume of preserved parenchyma (n = 82; p = 0.77).

Conclusion. Early GFR decrease after partial nephrectomy of the SK is strongly associated with ischemia time, blood transfusion, tumor size, and multifocality. In this study, the volume of preserved parenchyma didn’t affect early functional results of the surgery. 

53-66 4523
Abstract

Objecktive. To conduct a comparative pharmacoeconomic analysis of using nivolumab (Opdivo®) as monotherapy in advanced renal cell carcinoma (RCC) in adult patients 2-line therapy.

Materials and methods. “Cost–effectiveness” was assessed using a Markov model for one patient with advanced RCC. “Cost–effectiveness” analysis, “cost–utility” analysis “budget impact” analysis were performed. Overall survival and QALYs were included into the model as the effectiveness criteria. All the direct costs were calculated from the Russian healthcare system perspective.

Results. Treatment with nivolumab was associated with lower total direct costs, less frequent adverse events compared with the combination lenvatinib + everolimus. Total costs per patient were 2 451 712 rubles and 5232592 rubles for nivolumab and the combination lenvatinib + everolimus, respectively. The incremental “cost–effectiveness” ratio was 5 561760 rubles per life-months gained and 2339823 rubles per quality-adjusted life month. A sensitivity analysis confirmed the base case results. “Budget impact” analysis showed that the using of nivolumab allows to save budget costs and to treat additional 198 patients without spending healthcare resources.

Conclusion. The results of the study showed that using nivolumab (Opdivo®) as monotherapy in advanced RCC in adult patients as 2-line therapy is clinically effective and “cost–effective” method of treatment of adult patients with RCC in theRussian Federation. 

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

67-73 3613
Abstract

Introduction. To increase accuracy of disease prognosis in patients with bladder cancer we propose determination of expression level of several tumor markers. Objective is evaluation of prognostic significance of Ki-67 expression level in risk of non-muscle invasive bladder cancer recurrence.

Materials and methods. To perform immunohistochemistry analysis of Ki-67 we used surgery material of 83 patients who underwent primary transurethral bladder resection due to non-muscle invasive cancer. We performed an analysis of correlation between Ki-67 expression level in malignant tissue removed by transurethral resection and characteristics of tumor development. We evaluated the role of Ki-67 in stratification of recurrence risk by comparing the level of Ki-67 antigen expression in patients with recurrent non-muscle invasive bladder cancer and in relapse-free patients. We present evaluation of sensitivity, specificity, and prognostic value of quantitative determination of Ki-67 expression level in relation to non-muscle invasive bladder cancer recurrence.

Results. During the follow-up period, 41 cases of non-muscle invasive bladder tumor recurrence were observed. Quantitative value of the Ki-67 marker correlated with tumor differentiation grade G, malignancy grade, invasion into submucosal and muscle layers, presence of primary process, and tumor recurrence. In comparison with relapse-free patients, a significantly higher level of Ki-67 expression was observed in patients with cancer recurrence (р = 0.0035). We have determined a threshold quantitative value of Ki-67 (48 %) indicating disease recurrence. Presence of a threshold value of the Ki-67 marker showed moderate sensitivity level (less than 71 %) with relatively low specificity level (57 %). However prognostic level wasn’t high (between 63 and 65 %).

Conclusion. In patients with recurrent non-muscle invasive bladder cancer an elevated level of Ki-67 expression was observed in comparison with relapse-free patients (test sensitivity was 70.7 %). Obviously, determination of molecular biomarkers, Ki-67 in particular, can potentially help distinguish highly malignant tumors with high progression and recurrence risk, which can significantly improve treatment results for these patients. However, this problem requires further research. 

74-84 4696
Abstract

Objective. Examination of the results of surgical treatment and analysis of the surgical technique and perioperative parameters in a series of radical cystectomy on the basis of its own 15 years of experience in the formation of orthotopic and heterotopic urinary reservoir of the ileum segment by developed and patented techniques in different versions: open radical cystectomy, laparoscopic radical cystectomy and robotassisted radical cystectomy.

Materials and methods. A retrospective analysis of 310 radical cystectomy performed from 2000 to 2015, on the occasion of various pathologies of the bladder and prostate, as well as cancers of other organs (uterus, colon) with involvement in the process of bladder tumor. Plastics of the bladder was performed from the segment of the terminal ileum. Formation of orthotopic bladder was performed by the method of M.I. Vasilchenko (RF patent for invention № 2337630 “Method of orthotopic bladder plastics” by M.I. Vasilchenko). The ureters are implanted by antireflux procedure. If unable to perform orthotopic bladder plastics recovery and self-urination, patients underwent the formation of heterotopic enteral reservoir with a holding valve.

Results. It assesses the functionality and viability of organic shaped orthotopic and heterotopic urinary neocystis in the early and late postoperative periods in different versions. The proposed techniques have a beneficial effect on the improvement of the functional state and stabilization of the upper urinary tract. Analysis of morbidity and mortality was determined according to the classification of surgical complications on the Clavien–Dindo. This approach allowed to identify most of the complications and prevent an underestimation of the main negative results. Estimated oncologic efficacy of minimally invasive interventions laparoscopic radical cystectomy and robot-assisted radical cystectomy not inferior open radical cystectomy.

Conclusions. Formation of heterotopic and orthotopic bladder enteral neocystis (tank), on the proposed contact techniques is a viable alternative to the known intestinal plastics. The introduction of laparoscopic surgery techniques including robot-assisted laparoscopic operations to reduce the number of early and late postoperative complications. 

PROSTATE CANCER

85-90 2670
Abstract

Vesicourethral anastomosis (VUA) stricture applies to late postoperative complications of radical prostatectomy significantly reduces the quality of life of patients. Factors significantly affecting the rate of stricture formation VUA are not well understood, exactly how is not fully understood the mechanism of its development. Common approach to the treatment of these patients does not exist. The most common and less traumatic treatment methods include bougienage, internal optical urethrotomy and transurethral resection VUA. Given the high rate of relapse after such endoscopic surgery by many authors to optimize surgical care to patients with VUA stricture it has been proposed, however the prevention of its development measures still exists. Developed at the Urology Department of A.I. Evdokimov Moscow State University of Medicine and Dentistry new model of urinary catheter can take place in certain methods of prevention and treatment of strictures VUA. 

91-100 5367
Abstract

Оbjective: to define the approach to the management of patients with the detected ASAP area.

Materials and methods. In the time period from 2012 through 2015, 494 patients with previously negative biopsy and remaining suspicion of prostate cancer (PCa) were examined. The patients underwent repeat 24-core multifocal prostate biopsy with taking additional tissue samples from suspicious areas detected by multiparametric magnetic resonance imaging and transrectal ultrasound. An isolated ASAP area was found in 127 (25. 7 %) of the 494 examined men. All of them were offered to perform repeat target transrectal biopsy of this area. Targeted transrectal ultrasound guided biopsy of the ASAP area was performed in 56 (44.1 %) of the 127 patients, 53 of them being included in the final analysis.

Results. PCa was diagnosed in 14 (26.4 %) of the 53 patients, their mean age being 64.4 ± 6.9 years. The average level of prostate-specific antigen (PSA) in PCa patients was 6.8 ± 3.0 ng/ml, in those with benign lesions – 9.3 ± 6.5 ng/ml; the percentage ratio of free/total PSA with PCa was 16.2 ± 7,8 %, with benign lesions – 23.3 ± 7.7 %; PSA density in PCa patients was 0.14 ± 0.07 ng/ml/cm3, in those with benign lesions – 0.15 ± 0.12 ng/ml/cm3. Therefore, with ASAP area being detected in repeat prostate biopsy samples, it is advisable that targeted extended biopsy of this area be performed. 

101-111 4685
Abstract

Introduction. Treatment of highand very-high-risk prostate cancer appears to be extremely difficult. External beam radiation therapy combined with long-term androgen deprivation therapy (ADT) plays the main role, though low treatment effectiveness compared to one of intermediateand low-risk groups pushes towards finding new treatment options and modalities.

Objective: to enlighten data from modern publications and reviews concerning combined treatment uncluding (or not) chemotherapy and different types of radiation therapy.

Risk stratification. Several organizations (NCCN, NICE, ESMO, AUA, EAU and others) offer risk stratification systems. The NCCN system includes the very-high-risk group (Т3b–T4). Nowadays high-risk is set (EAU) when stages ≥ T2c or prostatic specific antigen > 20 ng/ml or Gleason score 8–10 appear.

External beam radiation therapy. Recommended dose is ≥ 74 Gy not depending on risk group. Low overall 10-years survival rate makes searching for new effective treatments inevitable.

ADT. Long-term regimens (2–3 years) of ADT in high-risk prostate cancer is undoubtable and neccecary. Biochemical progression-free survival can be achieved by using luteinizing hormone-releasing hormone antagonists in long-term regimens.

Brachytherapy. Brachytherapy alone and its combination with external beam radiation therapy show high effectiveness concerning progressionfree survival. In high-risk group survival rates are significantly lower. Improvement can be achieved by using adjuvant long-term ADT and other systemic therapy. Nowadays the results of such clinical trials are not available.

Chemotherapy. Chemotherapy as part of combination treatment of non-metastatic hormonal-sensitive high-risk prostate cancer is proved to be effective (increasing progression-free and overall survival), but still rarely used treatment option.

Conclusion. Reviews, meta-analyses and phase III clinical trials results show improvement of progression-free survival (and some – overall survival) when using a multimodal approach with chemotherapy. Combination treatment of taxane-base chemotherapy, luteinizing hormonereleasing hormone antagonists as ADT and brachytherapy alone or with external beam radiation therapy seems to be extremely perspective and needing further investigation. 

112-121 4277
Abstract

Oncological disease in the elderly is a serious challenge to the patients health and medical staff. This is due to two main reasons. First, it is the general patient condition which weakened by the aging process, usually with the multiple co-morbidities, the second reason is conducted with multiple drugs therapy of intercurrent diseases. Most often, oncologists do not seek to prescribe anticancer drugs, and mainly it concerns chemotherapy, to patients of advanced age, fearing the excess toxicity leading to adverse effects. The age 70 years and over is that cut-off to determine the elderly patient with malignancy. If we take the cases of the metastatic castration-resistant prostate cancer (mCRPC) many, if not the majority, are the patients older than 70 years, as well significant the number of very elderly patients aged over 80 years. The presence of the various medicinal agents in medical arsenal can significantly prolong survival, including such patients. As a rule, in randomized trials, which studied the drugs for the mCRPC treatment, the elderly patients were not actively involved and it had some reason, related to comorbidity. In this review the available data on the elderly and very elderly patients with mCRPC who received the treatment within the clinical trials are considered. 

REVIEW

122-133 7942
Abstract

The problem of timely diagnosis and malignancy grade evaluation of prostate cancer is especially urgent considering continuous and progredient increase in morbidity and mortality caused by this nosology, as well as difficulty of diagnostics. The conducted literature review shows that currently magnetic resonance imaging (MRI) is the leading method for diagnostics and grading of primary prostate cancer, as well as evaluation of local metastases, diagnostics of distant metastases, and identification of recurrences in the prostatic fossa after radical prostatectomy. Sensitivity and specificity of MRI are higher than in any of the other safe methods of diagnostic radiology. Active and wide-scale introduction of MRI into routine urological practice provided an impetus for development of complementary modalities and methods including fusion biopsy, targeted prostate biopsy under control of MRI, active observation, focal therapy, and other methods, significance and effectiveness of which will be determined in the future. 

CONGRESSES AND CONFERENCES

147-152 656
Abstract

Bladder cancer (BC) remains one of the most common oncourological diseases. Five-year survival for patients with Т3–4N0M0 stage remains at the level of 33–52 %. Average life span for patients with metastases is 9–26 months. Changes in application of immediate adjuvant therapy for non-muscle invasive BC were made, as well as in selection of surgical treatment: open or laparoscopic cystectomy. Results of cystectomy depending on pathohistological tumor structure were studied. Lymph nodes were more frequently affected with urothelial cancer with squamous metaplasia. The role of the number of metastatic lymph nodes after radical cystectomy in determination of treatment strategy is still open for discussion. It was shown that even 1 metastatic lymph node reduces survival by 30 % and requires adjuvant chemotherapy. Blood transfusion during radical cystectomy negatively affects immune system functioning, increases frequency of infectious complications (sepsis, pneumonia, abscess). Metastasectomy performed in cases with positive response to chemotherapy can increase patients’ life span. Median survival was 35.4 months after lesion discovery and 34.3 months after metastasectomy. Efficiency and tolerability profiles for 2 chemotherapy regimens were studied: vinflunine + gemcitabine and vinflunine + carboplatin. Comparative analysis has shown that the regimes are equally effective, no significant differences were observed. New anti-tumor drugs for patients with metastatic BC are being actively researched. In 2016 the American Society of Clinical Oncology (ASCO) presented data on atezolizumab. The drug was injected intravenously at doses 1200 mg/m23 times a week. This regimen was effective both in a patient group receiving cisplatin and in a patient group untreated with this drug. In May of 2016 atezolizumab was registered by the Food and Drug Administration (FDA) for BC treatment on a priority basis. 

CLINICAL CASE

134-138 1839
Abstract

Primary testicular tumour is unusual in elderly population. We present a case of 74 year old with adult type granulosa cell tumour, located at the right testis.  The patient had right radical inquinal orchiectomy. The tumour composed of a cystic component which had a number of different areas. Many areas showed a granulosa cell morphology with  Call-Exner bodies. Our report highlights one more challenging case of testicular tumours in elderly, which are quite problematic in terms of prognosis and management. Long-term follow up is recommended, since metastases of the disease may appear late in the clinical course.

139-146 2684
Abstract

A description of a clinical case of a complex treatment and monitoring of patient with prostate cancer at a very unfavorable initial forecast, the presence of bone metastases with a good clinical outcome. 

RESOLUTION

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ISSN 1726-9776 (Print)
ISSN 1996-1812 (Online)
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