Objective: to assess the expression and prognostic value of vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2) and their receptors VEGFR-1, -2; FGFR-1, -2, as well as platelet-derived growth factor receptors (PDGFR-α, PDGFR-β) in paired samples of primary tumors and tumor thrombi in renal cell carcinoma (RCC).

Materials and methods. Expression of VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β was studied in paired surgical samples of primary tumors and tumor thrombi in 25 patients with clear cell RCC pT3a–T4N0–1M0–1 and tumor venous thrombosis by immunohistochemical assay using the appropriate Abcam/Santa Cruz Biotech antibodies from the immunohistochemical staining kit Invitrogen. Expression levels were evaluated by a semi-quantitative method (H-score). The analysis of the correlation between expression levels of VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β and RCC characteristics, as well as evaluation of their influence on the outcome of RCC were performed.

Results. VEGF-A, FGF-2, as well as VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β were expressed in the cytoplasm and on the membrane of the primary tumor and tumor thrombus cells in RCC patients. Tumor thrombus cells were characterized by lower expression of VEGFR-1, VEGFR-2, PDGFR-α (p <0.05 for all) and tendency to lower expression of VEGF-A (p = 0.060), FGF-2 (p = 0.046), FGFR-1 (p = 0.077) and FGFR-2 (p = 0.090) compared with primary tumor cells. RCC Furman grade correlated with the expression levels of VEGFR-1 (p = 0.035) and FGFR-1 (p = 0.022) in the primary tumor cells, tumor invasion into venous wall correlated with the expression levels of VEGFR-1 (p = 0.023) and FGFR-2 (p = 0.005) on the thrombus cells. VEGFR-2 overexpression in the primary tumor cells was associated with significant decrease of overall survival (OS) rate (p = 0.011). There was a tendency to OS deterioration in cases with overexpression of VEGFR-2 (p = 0.093) and VEGF-A (p = 0.095) in the tumor thrombus cells. One-year OS in patients with ³2 identified risk factors was 27.3 %, <2 risk factors – 87.5 % (p = 0.004).

Conclusion. Tumor thrombus cells in RCC patients expressed VEGF-A, FGF-2, VEGFR-1, -2; FGFR-1, -2; PDGFR-α, -β less active than the cells of the primary tumor. Overexpression of growth factors and tyrosine kinases correlated with RCC Furman grade and tumor venous wall invasion. Overexpression of VEGFR-2 in both primary tumor and thrombus cells in combination with hypoexpression of VEGF-A in the thrombus negatively influenced on OS.

Background. In the last decade, the relationship between arterial hypertension and the risk of developing kidney cancer (KC) has been pointed out. Some studies have shown that the metabolic imbalance of the components of the renal renin-angiotensin system (RAS) is associated with the development and progression of KC.

Objective: to study the state of RAS in tumor and peritumoral tissues in patients with KC on the background of arterial hypertension.

Materials and methods. In patients with localized KC T1N0M0 and grade I–II arterial hypertension without special treatment (n = 40) in the samples of tumor, peritumoral and histologically unchanged tissue, the levels of angiotensins 1, 2, 1–7 (AT1, AT2, AT(1–7)) of angiotensin-converting enzymes (ACE, ACE2) were determined by ELISA. The comparison group consisted of patients with RC without impaired blood pressure (n = 55).

Results. In patients with KC, the level of AT1 is 1.5 times higher (p <0.05), and AT2 is 1.6 times higher (p <0.05) in tumor tissue against the background of unchanged content in peritumoral tissue compared with histologically unchanged tissue. The level of ACE is higher than histologically unchanged tissue by 2.7 times, ACE2 – by 1.6 times (in all cases p <0.05), and in peritumoral tissue it is identical in histologically unchanged tissue.

In patients with KC and arterial hypertension, the level of AT1 and AT2 in the tumor tissue is 1.8 times higher (p <0.05) and 2.1 times (p <0.01), respectively, the content of AT(1–7) is 1.6 times (p <0.01). In peritumoral tissue, AT1 is 1.6 times higher (p <0.01) and AT2 is 1.9 times higher (p <0.05). The level of AT(1–7) in the peritumoral tissue is identical to the values in the histologically unchanged tissue. The content of ACE and ACE2 in tumor tissue is 3.6 and 2.9 times higher, respectively, and in peritumoral tissue is identical to that in tumor tissue. Correlation analysis revealed a reliable direct relationship in the studied groups for all parameters, while in the peritumoral tissue of hypertensive patients, the relationship between the average blood pressure and the RAS peptide and enzymes content had a higher tightness.

Conclusion. An increase in the levels of AT1 and AT2, ACE and ACE2 in the tumor tissues and peritumoral tissue in patients with localized KC, regardless of the presence of arterial hypertension at initially higher values in hypertensive patients, was shown. The presence of arterial hypertension in patients with KC changes the metabolism of local RAS in peritumoral tissue and is associated with an increase in the correlation between changes in the components of RAS and arterial hypertension.

Background. Аdvantages of the retroperitoneal approach, successfully applied in some clinics, but only a few studies on direct comparison of laparoscopic and retroperitoneoscopic radical nephrectomy.

The study objective: to compare transperitoneal and retroperitoneal access during laparoscopic radical nephrectomy.

Materials and methods. The study included 332 patients who underwent laparoscopic radical nephrectomy for renal cell carcinoma T1a–T3b. Transperitoneal access – 134, retroperitoneal – 198.

Results. The mean time of laparoscopic radical nephrectomy, as well as the time before clipping of the renal artery were significantly less in retroperitoneal access (161 ± 59 and 30 ± 24 min, respectively, compared with 178 ± 65 and 38 ± 39 min – with transperitoneal). The number of removed lymph nodes, and the number of patients detected with “positive” lymph nodes, and death from progression of disease was not significantly different between the groups transperitoneal and retroperitoneal access with an average follow-up period, 42.5 and 47.8 months respectively.

Conclusion. Despite the lower popularity retroperitoneal access, the method has advantages in enhanced recovery after surgery (ERAS), particular frequency of general perioperative complications, duration of epidural anesthesia, time of normalization of bowel function and length of hospital stay compared with transperitoneal access. The method is preferred for the old age and patients with comorbidity, especially of the cardiovascular system and respiratory organs.

Background. We have previously described an algorithm APhiG (Age of patients, Prostate health index and Gleason score), for staging of prostate cancer before treatment. The algorithm was developed by logistic regression on a training dataset and validated on a validation dataset (VD). Objective. Validation of threshold decision rules and a program for APhiG calculation on the VD.

Materials and methods. ROC curve analysis on VD (83 cases).

Results and conclusion. It was shown that sensitivity, specificity, positive and negative predictive value, diagnostic accuracy threshold decision rules and area under the curve (AUC) for APhiG in the VD (n = 83) not significantly different from those indicators in the training dataset (n = 337), which was the basis for the algorithm APhiG development.

Tolsotogo St., Saint Petersburg 197022, Russia

Background. Prostate cancer (PCa) of a high and very high risk is a potentially fatal disease that requires an active multimodal approach, including the use of neoadjuvant drug treatment. As option for this treatment is neoadjuvant chemohormonal therapy (NCHT) followed by radical prostatectomy (RPE). However, data on the oncological results of treatment of such patients are still limited and the role of neoadjuvant therapy in the treatment of high and very high-risk PCa remains not fully understood.

Objective: to assess the oncological results of treatment patients with localized and locally advanced PCa of high and very high risk after NCHT.

Materials and methods. This was a prospective randomized study: patients with PCa of high and very high-risk groups (prostate specific antigen levels (PSA) >20 ng/ml and/or Gleason score ³8 and/or clinical stage >T2c) were treated with RPE only (group RPE; n = 35) or NCHT followed by RPE (NCHT/RPE group; n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m² up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6 subcutaneous injections every 28 days). After a follow-up examination evaluating the result of the neoadjuvant regimen, patients underwent RPE with extanded lymphadenectomy.

Results. A mean follow-up was 37.08 ± 20.46 months. A statistically significant reduction of prostate specific antigen >50 % post-chemohormonal therapy was observed in all 36 cases. Lower postoperative stage was noticed in 38.5 % in NCHT/RPE group compared with 2.7 % in RPE group. Similarly, positive surgical margin rate was higher in group without neoadjuvant therapy – 40 and 25 % (RPE group). Cancerspecific survival was 97.2 % in NCHT/RPE group and 87.56 % in the RP group (p = 0.037), cancer specific survival rate – 91.4 % and 97.2 % respectively (log-rank test p = 0.22). At the same time, no statistically significant differences were obtained in 3-year recurrence free survival between groups: 38.8 % in NCHT/RPE group versus 43.6 % in the RPE group (log-rank test p = 0.36).

Conclusion. Conducting NCHT before RPE is a safe and effective strategy in patients with PCa of high and very high risk groups and could improve oncological results.

Materials and methods. From September 19, 2016 to December 27, 2019, 104 patients received cabazitaxel plus prednisone for a maximum of 10 cycles or disease progression, or unacceptable toxicity, or patient request to stop treatment. Adverse events occurring during treatment, including use of granulocytic colony stimulating factors, were collected. Prostate specific antigen response, objective tumor response (RECIST), progression-free survival and overall survival were analyzed. Treatment period was followed by a follow-up period of 82.0 (36.0–117.0) weeks.

Results. 104 patients with histologically proven adenocarcinoma were enrolled and treated. All were Caucasian with a median age of 66 (range 46.0–86.0) years and a median BMI-Score of 26.8 (18.7–43.3) kg/m2. Most patients (57/104, 54.8 %) were ECOG 1. At the time of prostate cancer diagnosis, 63/104 (60.6 %) patients had metastatic disease. The median duration of therapy was 14.5 (0.1–39.0) weeks and the median number of cycles cabazitaxel was 5; 30 (28.8 %) patients received 10 cycles of treatment. Granulocytic colony stimulating factors was received by 52 (50.0 %) patients (prophylactic, n = 31; curative, n = 21). Overall, 102/104 (98.08 %) patients reported at least one treatment emergent adverse event (TEAE), 21/104 (20.19 %) grade ³III TEAEs and 12/104 (11.54 %) serious adverse events. Most TEAEs resolved but 9/104 patients discontinued treatment due to TEAE. Most common TEAEs were related to gastrointestinal system disorders (46/104 (44.23 %) patients, mainly nausea n = 40); blood and lymphatic system disorders (44 (42.31 %) patients, mainly leukopenia n = 22, anemia n = 15, neutropenia n = 11) and general disorders/administration site conditions (22 (21.15 %) patients; mainly asthenia n = 21). Main grade ³III adverse events were related to blood and lymphatic system disorders (11 (10.58 %), including one case of febrile neutropenia), general disorders/administration site conditions (6 (5.77 %), mainly asthenia) and cardiac disorders in 2 (1.92 %) patients. A prostate specific antigen decline of at least 50 % was observed in 23 out of 31 patients with evaluable prostate specific antigen measurements. The objective tumor response was observed in 29 (27.9 %) patients, including 7 (6,7 %) with complete response and 22 (21.2 %) with partial response. Treatment was completed as initially planned in 41/104 (39.4 %) patients, and 61/104 (58.7 %) reached the last follow-up visit. At the last follow-up visit, median overall survival was not reached due to a low number of events. Median progression-free survival at the end of treatment visit was 6.29 (5.1–10.45) months and reached 10.13 (5.55–19.27) months at the last follow-up visit. There was no reported death related to treatment of cabazitaxel during the period of treatment and follow-up period.

Conclusion. This prospective, multi-center, national observational, non-interventional register conducted in patients with mCRPC in Russian Federation suggests that cabazitaxel is effective with a manageable safety profile.

Objective: to analyze factors predicting complications in a series of radical cystectomies (RCs) performed for bladder cancer over a 10-year period at the National Center of Oncology (Baku).

Materials and methods. From July 2008 to December 2017 we retrospectively selected 257 consecutive cases of RC with pelvic lymphadenectomy and various options of urine diversion for bladder malignant neoplasms. Information on preoperative prognostic factors, including demographic parameters, as well as general patient health parameters, tumor characteristics and factors concerning the operation was obtained from medical records. We analyzed perioperative factors using monovariant logistic regression, where the endpoints were development of any complication (I–V degrees according to Clavien–Dindo classification), as well as severe complication (III–V grades) within 30-days after RC were considered the endpoints. After the missing data on preoperative bacteriological urinalysis were multiply imputed, a multivariate logistic regression has been performed with odds ratio (OR) calculation.

Results. During the 30-day period, complications were registered in 111 (43.2 %) patients, severe complications – in 48 (18.7 %). Multivariate analysis revealed the following independent predictors of any postoperative complications after RC: local cT4 tumor extension (OR 4.52; p = 0.002), age (OR 1.87; p = 0.017), positive bacteriological urine analysis (OR 2.16; p = 0.032) and number of performed RCs (OR 0.89; p = 0.038). Severe postoperative complications were associated with positive urine culture (OR 4.05; p = 0.002) and age (OR 2.44; p = 0.013).

Conclusion. Our study revealed the following independent factors, which were significantly associated with the risk of any complication or severe complication after RC: local cT4 tumor extension, age, positive urine bacteriological analysis before the intervention and a small number of surgeries or positive urine culture and age, respectively.

Background. Radical cystectomy is the standard treatment for muscle-invasive bladder cancer. Muscle invasion can occur in 48 % of patients. Epidemiologically, the peak incidence of bladder cancer is observed in men at the seventh decade of life. At the time of diagnosis, many of these patients have serious comorbidity. The trauma of radical cystectomy in combination with comorbidity creates an insurmountable barrier to radical treatment in a large part of patients. Refusal to use intestinal segments for urine diversion dramatically reduces the invasiveness of the intervention. However, the implementation of bilateral ureterocutaneostomy is associated with a greater frequency of pyelonephritis due to the use of external stents and scarring of the ureterocutaneostomy. A transureteroureterostomy with a unilateral ureterocutaneostomy can be a definite alternative.

Objective: to evaluate the effectiveness of cross ureteroureterostomy for urine derivation after radical cystectomy in patients with muscle-invasive bladder cancer and a high risk of perioperative complications.

Materials and methods. The article analyzes 28 cystectomies for muscle-invasive bladder cancer in patients with severe concomitant pathology who underwent transureteroureterostomy with unilateral ureterocutaneostomy for urine derivation.

 Results. It was shown that this intervention does not have high morbidity, does not increase the incidence of early postoperative complications, and relieves patients from bilateral urostoma. Among late complications, inflammatory ones predominate due to obstruction of the external stent. The authors highlight the tactics and technical aspects of managing such patients with obstructive pyelonephritis and the experience of drainage-free management.

Conclusion. Transureteroureterostomy with unilateral ureterocutaneostomy after cystectomy for muscle-invasive bladder cancer can be considered as the operation of choice in patients with a burdened comorbidity.