Search

Objective: to assess the role of palliative nephrectomy in disseminated kidney cancer patients planned to undergo targeted antiangiogenic treatment. Subjects and methods . The investigation included data on 83 patients with T1-4N0 / +M1 disseminated renal cell carcinoma (RCC) who had received at least 2 targeted therapy cycles in 2009 to 2011. In 48 (57.8 %) patients, the treatment was preceded by palliative nephrectomy that was not carried out in 35 (42.2 %). Before starting targeted therapy, all the cases were confirmed to be diagnosed with clear cell RCC, with a sarcomatoid component being in 7 (8.4 %) patients. The median follow-up of all the patients was 21 (12–36) months. Results. The unremoved affected kidney in disseminated kidney cancer patients receiving targeted antiangiogenic therapy is an independent factor for the poor prognosis of progression-free (odds ratio (OR), 2.4; 95 % confidence interval (CI), 1.2–4.7) and overall (OR, 2.8; 95 % CI, 1.3–6.3) survival. Palliative nephrectomy does not improve the prognosis in patients with a low somatic status, the N+ category, and metastases into the bones and nonregional lymph nodes. Conclusion. Palliative nephrectomy in the selected patients with disseminated kidney cancer on targeted antiangiogenic therapy increases progression-free and overall survival.

The possible way to solve the problems associated with a risk from non-radical tumor removal, inadequate repair and a drastic reduction in renal function after long-term technically challenging in situ parenchymal ischemia resections is a surgical intervention into the kidney removed from the body, which has been preserved by the procedure developed for donor organs, during hypothermia that promotes a severe decrease in the intensity of oxygen-dependent processes in the renal epitheliocytes, followed by autografting of the resected kidney. The main advantages of the extracorporeal technique are the excellent ex corpora visualization of renal structures and the unrestricted time of surgery with good anti-ischemic protection. Resurgery after routine (in situ) resections yields good long-term oncological and functional results in correctly selected patients. Repeated tumor removal after extracorporeal kidney resection is a technically challenging surgical intervention undescribed in the literature.

Objective: to analyze the impact of surgical volume on functional results and cardiospecific survival rates in patients with clinically localized renal carcinoma.Subjects and methods. Four hundred and fifty-three patients with pT1–3aN0M0 renal cell carcinoma and normally functioning secondkidney who had undergone radical nephrectomy (n = 226 (49.9 %)) or kidney resection (n = 227 (50.1 %)) were selected for the investigation. The patient groups who had undergone different-volume operations were matched for gender, age, body mass index (BMI), side of involvement, tumor sizes, and baseline glomerular filtration rate (GFR) (p > for all). The median baseline Charlson index and the rate of ASA classes III–IV operative risk were significantly higher in candidates for radical nephrectomy (p < 0.05 for all), the rate of diseases affecting kidney function, pT1a category, and G1 anaplasia were higher in the kidney resection group (p < 0.0001). The median follow-up was 50 (12–224) months.Results. Within 28 days postsurgery, the rate of acute renal dysfunction (ARD) was 36.2 %. The independent risk factors of ARD were kidney resection (risk ratio (RR) = 0.210; 95 % confidence interval (CI) 0.115–0.288; р < 0.0001) and ischemia time (RR = 0.012; 95 % CI 0.004–0.021; p = 0.004). The degree of ARD after kidney resection was significantly lower than that following radical nephrectomy (p < 0.0001). In the late postoperative period, the incidence of chronic kidney disease (CKD) Stage ≥ III was 38.4 %. Its independent risk factors were low baseline GFR (RR = 0.003; 95 % CI 0.002–0.005; p < 0.0001), radical nephrectomy (RR = 0.195; 95 % CI 0.093–0.298; p < 0.0001), and ARD (RR = 0.281; 95 % CI 0.187–0.376; p = 0.0001). Ten-year specific and cardiospecific survival rates in all the patients were 98.5 and 94.9 %, respectively, and unrelated to surgical volume. The independent predictors of poor cardiospecific survival were BMI, Charlson index, and ASA risk. No relationship was found betwen cardiospecific survival and GFR in the late postoperative period.Conclusion. Kidney resection versus radical nephrectomy significantly increases the risk of severe ARD. The scope of surgical treatment for clinically localized renal cancer has not been found to affect cardiospecific survival.

Objective: to identify the predictors of perioperative complications and deaths in surgically treated patients with kidney cancer complicated by venous tumor thrombosis.Subjects and methods. The investigation included data on 463 kidney cancer patients with venous tumor thrombosis. The patients, median age was 57 years. The male / female ratio was 2.5:1. Perirenal, subhepatic, retrohepatic, and supradiaphragmatic tumor thrombi were diagnosed in 161 (34.8 %), 135 (29.2 %), 82 (17.7 %), and 85 (18.3 %) patients, respectively. Regional and distant metastases occurred in 90 (19.4 %) and 145 (31.3 %) cases, respectively. All the patients underwent thrombectomy, retroperitoneal lymphadenectomy; a tumor-affected kidney was removed in 452 (97.6 %) patients.Results. Median surgery duration was 259 (30–580) min; median blood loss was 3500 (100–27 000) ml. The incidence of intraoperative complications was 24.6 % (114 / 463); mortality was 0.9 % (4 / 463). The independent risk factors of intraoperative complications were cranial margin of a tumor thrombus (odds ratio (OR) 1.9; 95 % CI 1.4–2.6; p < 0.0001) and circular resection of the inferior vena cava (OR 5.8; 95 % CI 1.2–27.8; p < 0.0001). The incidence of postoperative complications was 25.7 % (118 / 459);mortality was 6.0 % (28 / 459). Resurgery was required in 31 (6.8 %) cases. Regression analysis identified the risk factors of postoperative complications (highly located cranial thrombus margin (OR 2.6; 95 % CI 1.1–6.4; p = 0.037) and lactate acidosis (OR27.1; 95 % CI 1.2–613.1; p = 0.038), postoperative death (hepatic vein thrombosis (OR 15.6; 95 % CI 4.5–54.3; p < 0.0001),lactate acidosis (OR 23.1; 95 % CI 3.4–158.4; p = 0.001) thrombus removal from the heart (OR 5.0; 95 % CI 2.1–12.2; p < 0.0001)),perioperative death (cranial thrombus margin (OR 1.9; 95 % CI 1.2–3.2); р = 0.007), contralateral renal vein thrombosis (O R 4.4;95 % CI 1.2–15.8; p = 0.025), lactate acidosis (OR 28.4; 95 % CI 4.9–165.1; p < 0.0001), and low creatinine clearance (OR 4.6;95 % CI 1.9–24.9; p = 0.017).Conclusion. Thrombectomy in patients with T3a–cNxMx kidney cancer is a technically difficult intervention associated with the high incidence of complications and death, which must be performed only in specialized centers. The identified risk factors may serve as criteria for predicting the results of thrombectomy.

Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA) before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %), pT3 – in 144 (37.3 %), pT4 – in 14 (3.6); pN+ – in 34 (8.8 %) cases. Gleason score < 7 was present in 254 (65.8 %),  7 – in 132 (34.2 %) specimens. Perineural invasion was identified in 188 (48.7 %), angiolymphatic invasion – in 126 (32.6) cases.Results. Biochemical recurrence occurred in 64 (16.6 %) out of 386 patients at a median follow-up of 30.5 (12−164) months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449); р = 0.001), Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917); p = 0.025), pN (HR 0.415 (95 % CI:0.181−0.955); p = 0.039). The patients were divided into 3 prognostic groups: good (0 factor), intermediate (1 factor), poor (2 factors) and very poor (3 factors) (AUC – 0.720 (95% CI: 0.656−0.784)). High preoperative levels VEGF ( 67 pg/ml) (р = 0.005), VEGFR2 ( 3149 pg/ml) (р = 0.036), VEGFR3 ( 2268 pg/ml) (р = 0.001), TGF-β1 ( 14473 pg/ml) (р = 0.052) were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after surgical treatment prostate cancer, further trials are needed.

Eligard (leupropelin acetate, Atrigel delivery system) is a synthetic analogue of luteinizing-hormone-realizing hormone (LHRH), which causes a rapid reduction in the level of testosterone to the concentration comparable with that after surgical castration. Eligard demonstrated a considerable advantage over other LHRH analogues in the depth of androgenic suppression and in the frequency of transient increases in testosterone levels at the beginning and during therapy. Eligard is available as 1-, 3-, and 6-month depot formulations, which allows a flexible approach to be applied to individually making up a therapy regimen. Eligard is as effective as castration therapy techniques. Treatment with this drug shows the low frequency of side effects and is well tolerated by patients.

Purpose. The primary end-points of the study were overall response rate, progressive-free and overall survival in patients received Gemcytabin (Cytogem®) and Cisplatin as first-line therapy for transitional-cell bladder cancer. Secondary end-points were toxicity and safty of the regimen. Material. From February 2005 to March 2007 25 patients with morphologically verified inoperable locally advanced and metastatic transitional-cell bladder cancer were recruited. Men-to-women ratio was 3:1. Median age of the patients was 66,5±6,8 years. All the patients received Cytogem® 1000 mg/m2 days 1, 8, 15, cisplatin 70 mg/m2 on day 2; every 28 days. No more than 6 cycles were allowed if the evidence of disease progression and unacceptable toxicity were not registered. Median follow-up was 36,2±12,1 months. Results. Complete response was observed in 2 (8%), partial — in 11 (44%), stabilization — in 10 (40%), progression — in 2 (8%) of 25 patients. Twelve- and 24-month overall survival was — 51,3% and 22,4% (median 13,4±3,5 (95% CI: 6,6—20,4) months), progressive- free survival — 26% and 13% respectively (median 8,8±1 (95% CI: 6,6—10,6) months). Toxicity was evaluated in 24 patients and occurred in all cases (grade I—II — 16 (67%), grade III—IV — 8 (33%)). The main regimen-related toxicity was hematological (neutropenia — 16 (67%) (grade I—II — 8 (33%), grade III—IV — 8 (33%)), thrombocytopenia — 14 (58%) (grade I—II — 10 (41,5%), grade III—IV — 4 (16,5%)), anemia — 7 (29%) (grade I—II — 5 (21%), grade III—IV — 2 (8%))). Hematological toxicity was not associated with com- plications in any case. Non-hematological side-effects were nausea and vomiting in 21 (88%) (grade I—II — 67%, grade III — 21%), alopecia — in 11 (44%) patients. The regimen-related toxicity was considerable and reversible. No side-effect demanded blood transfusion, antibiotic and/or growth factors administration, and hospital admission. Conclusion. Gemcytabin (Cytogem®) and Cisplatin as first-line therapy for advanced transitional-cell bladder cancer have demonstrated satisfactory efficacy and acceptable toxicity. The regimen can be recommended for the clinical practice.

The paper describes clinical examples of tuberous sclerosis and angiomyolipomas, their manifestations, and methods for their diagnosis and treatment.

Objective: to compare the results of continuous and intermittent hormone therapy (HT) in unselected patients with disseminated prostate cancer (PC).Subjects and methods. The study enrolled 113 patients with verified stage cT2b–4N0–1M0–1 PC. The median age of the patients was 70 ± 7.3 years. The median pretreatment concentration of prostate-specific antigen (PSA) was 309.8 ng/ml. The cT2 category was diagnosed in 12 (10.6 %) patients, сТ3 in 85 (75.2 %), сТ4 in 16 (14.2 %), сN+ in 32 (28.3 %), and М+ in 74 (65.5 %). At baseline, the median Gleason grade was (3.0 ± 0.8) + (4.0 ± 0.9) = 7.0 ± 1.7. All the patients received immediate HT: castration therapy was performed in 2 (1.8 %) patients, maximal androgen blockade in 96 (85 %), and antiandrogen monotherapy in 15 (13.3 %). Continuous and intermittent treatment regimens were used in 100 (70.8 %) and 33 (29.2 %) cases, respectively. The median follow-up was 31.9 ± 17.7 months.Results. The intermittent HT regimen was associated with a significant increase in overall survival versus that during continuous treatment (medians 57.8 ± 11.6 and 25.2 ± 2.8 months, respectively; p = 0.031). Overall survival benefit remained in the poor prognosis (bone pain and/or a PSA of  100 ng/ml and/or сТ4 and/or М+) group. The HT regimen failed to affect survival in the good prognosis (no bone pain, a PSA of < 100 ng/ml, сТ < T4, М0) group. Impotence was less common during intermittent treatment than during continuous ablation (68.2 and 96.2 %, respectively; p = 0.002). No relationship was found between the incidence of other complications and the HT regimen. There was no significant difference between the groups in quality-of-life indicators before and during treatment. The average cost of an intermittent course of therapy per year was significantly lower than that of a continuous course (50586.7 and 72996.0 rubles, respectively; p < 0.0001).Conclusions. Intermittent HT fails to result in a clinically relevant worsening of the quality of life, promotes better sexual function, and is economically expedient. In the poor prognosis group, intermittent treatment causes a significant increase in the time to hormone refractoriness and in overall survival rates as compared with these indicators when the continuous regimen is used. Intermittent therapy is as good as continuous ablation for overall survival among the good prognosis patients.

Targeted therapy is a standard treatment in advanced renal cell carcinoma. Stabilization is an expected response to targeted therapy. The main goal of targeted therapy is to improve progression-free survival. This purpose is served through the sequential use of targeted agents. First-line therapy agents in the good and intermediate MSKCC prognostic groups are antiangiogenic ones such as bevacizumab, sunitinib, sorafenib, pazopanib; in the poor MSKCC prognostic group treatment of choice is an mTOR inhibitor temsirolimus. The antiangiogenic agent axitinib and the mTOR inhibitor everolimus were proved to be effective as second-line therapy. Axitinib administration after anti-VEGF drugs is associated with cumulative toxicity. The efficacy of axitinib in sorafenib-refractory renal cell carcinoma has not been proven. So everolimus remains the agent of choice for second-line targeted therapy. The effect of repeated antiangiogenic therapy may be anticipated after everolimus therapy.

Objective: to study the results of sparing cystectomy in patients with urinary bladder cancer (UBC).Subjects and methods. The study has covered 82 patients with transitional-cell UBC (T1-4aN0M0) who received radiotherapy (RT) and thenunderwent radical cystectomy at the N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, in 1980 to2007. Among them there were 76 (92.7%) males and 6 (7.3%) females. The median age was 55.2±10.8 years. Superficial (T1) and inva-sive (Т2—4а) carcinomas were detected in 33 (40.2%) and 49 (59.8%) patients, respectively. Category N+ was identified in 3 (3.7%) patients.All the patients received RT to the bladder area (median total focal dose (TFD) 56±12.3 Gy) and regional metastatic zones (median TFD40.0±0.0 Gy). A full effect of irradiation was achieved in 44 (53.7%) patients, of whom 41 (93.2%) developed local relapses. All the 82patients underwent radical cystectomy: that with ureterostomy in 28 (34.1%) cases, Bricker’s operation in 45 (54.4%), Studer’s operationin 4 (4.9%), and rectal urinary bladder in 5 (6.1%). The median follow-up was 32.7±31.9 months.Results. The median interval between RT and cystectomy was 12.5±5.1 months; the median time of surgery was 360 (60—480) min; themedian blood loss was 1515.2±1227.8 ml. Intraoperative and postoperative complications developed in 10 (12.2%) and 40 (48.6%)patients, respectively. Repeated operations were performed in 7 (8.4%) cases. Mortality was 4.9%. A urinary derivation technique failed toaffect the incidence of complications and the rates of mortality (p > 0.05). Histological studies revealed transitional-cell carcinoma in thedistant specimens in 80 (97.6%) cases. Recurrences developed in 40 (48.8%) of the 82 patients following an average of 32.9 (1—150)months of cystectomy: local relapses in 5 (6.1%) cases; distant metastases in 29 (35.4%); a local relapse and distant metastases in 5 (6.1%);urethral recurrence in 1 (1.2%) patient. Five-year overall, specific, and relapse-free survivals were 43.9 (median 48.4±10.5 months), 48.5(59.9±9.3 months), and 42.8% (47.4±9.6 months), respectively. Conclusion. Sparing cystectomy with any urinary derivation technique is associated with the acceptable frequency of complications and pro-vides fair long-term results in patients who show no complete effect or who have a local UBC relapse after RT.

TNephroureterectomy is by right considered to be the gold standard for treatment in patients with urothelial cancer of the upper urinary tract. Nevertheless, various surgical treatments are now being intensively developed and introduced into clinical practice and a possibility of using adjuvant and neoadjuvant chemotherapy is also being studied. The review summarizes data on various methods of treatment, its efficiency, long-term results and prognosis.

Objective: to compare immediate, oncological, and functional results, as well as quality of life in patients undergoing open and laparoscopic transperitoneal radical nephrectomy (RNE) for clinically localized kidney cancer (KC).Subjects and methods. Data from 426 cT1-2N0M0 KC patients after radical nephrectomy in 1991 to 2011 were retrospectively selected. Their median age was 57 years. The male/female ratio was 1.1:1. The median highest tumor diameter was 5.0±2.2 cm. RNE was carried out in all 426 patients: in 211 (49.5 %) patients through open access and in 215 (50.5 %) through transperitoneal laparoscopic one. The patient groups operated on via different accesses were matched for major signs; however, the laparoscopy group displayed a preponderance of cT1a tumors. The median follow-up was 50.0±12.3 months.Results. There were no significant differences in the frequency of intraoperative and postoperative complications of laparoscopic and open nephrectomies. The five-year overall, specific, and relapse-free survival rates in the patients who had undergone open nephrectomy were 95.4, 98.4, and 92.2 %, respectively; those in the patients who had laparoscopic nephrectomy were 94.5, 100.0, and 93.6 %, respectively (p > 0.05 for all). The incidence of acute renal dysfunction and its distribution according to the RIFLE classes, the rate of acute dialysis and that of a decrease and a continued reduction in glomerular filtration rate, as well as the distribution of patients according to the stages of chronic kidney disease after RNE did not depend on the surgical access (p > 0.05 for all). The QLQ-30 survey data show that the laparoscopic access versus the laparotomic one improves quality of life within 1 month after RNE.Conclusion. Laparoscopic transperitoneal RNE is a safe alternative to open surgery that can improve quality of life in the patients with clinically localized kidney cancer within one month after surgical intervention.

Objective: to evaluate the outcome of retroperitoneal lymph node dissection (RLND) in disseminated testicular non-seminoma patients with residual metastases after induction chemotherapy. Material and methods. The RLND performed in 1983 to 2007 were analyzed in 367 testicular non-seminoma patients with residual retroperitoneal masses after ineffective induction chemotherapy. The median age was 26.06.9 years. Orchidectomy was performed in all patients. Category N1 was regarded in 12 (3.3%) patients, N2 in 79 (21.5%), N3 in 238 (64.9%), Nx in 38 (10.4%). Distant metastases were present in 133 (36.2%) cases. The baseline tumor marker level was elevated in 328 (89.4%) patients (S1 in 169 (46.0%), S2 in 108 (29.4%), S3 in 51 (13.9%), Sx in 39 (10.6%)). According to the IGCCCG prognostic model, 149 (40.6%) patients were classified as good prognostic group, 100 (27.2%) as moderate, 77 (21.0%) as poor ones; the prognostic group was not defined in 41 (11.2%) cases who had started treatment at another facility due to data unavailability. After orchifuniculectomy, all patients received induction cisplatin-based chemotherapy which resulted in tumor shrinkage 90% - in 29 (7.9%) cases. The response was not properly assessed in 102 (27.8%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all patients (5 cm - 149 (40.6%)). The tumor markers level remained elevated following chemotherapy in 70 (19.1%) cases. All patients underwent RLND (complete in 295 (80.4%) cases). Radical RLND demanded resection of adjacent organs in 22 (5.9%) cases. Extraretroperitoneal metastases were removed simultaneously with retroperitoneal tumor in 22 (5.9%) patients. Postoperative chemotherapy was administered in 100 (27.2%) cases. The median followup was 82.1 (3-188) months. Results. Complications developed in 31 (8.5%) of the 367 of patients. Mortality rate was 0.6% (2/367 cases). Resection of the adjacent organs did not influence mortality rates. Histology revealed necrosis in 149 (40.6%), teratoma in 141 (38.4%), cancer in 77 (21.0%) specimens. The significant predictive factors for necrosis were normal levels of markers following chemotherapy, a residual mass size of < 2 cm, tumor shrinkage >90% (the accuracy of the logistic model for probability of necrosis in the removed specimen was 78%). Discordant pathologic findings between the retroperitoneum and other metastatic sites were in 3 (13.6%) of 22 cases. Ten-year overall, specific and progression- free survival (PFS) was 92.1, 92.4, and 46%, respectively. A poor and moderate prognostic group IGCCCG (p5 cm (p=0.042), presence of extraretroperitoneal metastases (pS1 (p

Background and objective. The division of patients with disseminated prostate cancer (PC) into prognostic groups may be potentially used for a differential approach to choosing the hormonal therapy (HT) option and regimen. This study was conducted to identify factors influencing survival, as well as prognostic groups in this category of patients.Subjects. The study enrolled 113 patients with verified cT2b–4N0–1M0–1 stage PC. Their median age was 70.0 ± 7.3 years. The median pretreatment prostate-specific antigen (PSA) concentration was 309.8 ng/ml. The stage cT2 was diagnosed in 12 (10.6 %) patients; cT3 was in 85 (75.2 %); cT4 in 16 (14.2 %); cN+ in 32 (28.3 %); М+ in 74 (65.5 %). The median baseline Gleason score was 3.0± 0.8 ± 4.0± 0.9 =7.0± 1.6. All the patients received emergency HT: castration was carried out in 2 (1.8 %) patients; maximum androgenic block and antiandrogen monotherapy were performed in 96 (85.0 %) and 15 (13.3 %), patients, respectively. The median follow-up was 31.9± 17.7 months.Results. Five-year progression-free, hormone-refractory prostate cancer-free, specific, and overall survivals (OS) were 29.7, 31.8, 39.3, and 26.0 %, respectively. Multivariate analysis has shown that OS is negatively influenced by the following factors: bone pain, stages cT4, М+, a nadir of PSA of  4 ng/ml (p < 0.05) and its baseline level of  100 ng/ml (р = 0.057). Good (no bone pain, a PSA level of < 100 ng/ml, сТ < T4, and М0) and poor (bone pain and/or a PSA level of  100 ng/ml, and/or stages cT4 and/or М+) prognostic groups were identified. The median OS in the groups was 39.8± 3.9 and 29.8± 4.2 months, respectively (р = 0.048).Conclusion. In disseminated PC, bone pain, a PSA level of 100 ng/ml, cT4 and M+, and a PSA nadir of  4 ng/ml are poor predictors of OS. The patients without these indicators belong to a good prognostic group; those have one sign or more do to a poor prognostic one.

Lucrin depot used to treat patients with prostate cancer has been investigated. The agent has been found to be highly effective, to causeadverse effects rarely, and to be well tolerated. The administration of leuproreline acetate yields the results comparable with those in the useof other luteining hormone-releasing hormone agonists and antagonists, bilateral orchiectomy, and estrogens.

Degarelix (Firmagon) (Ferring Pharmaceuticals) is a new gonadotropin-releasing hormone (GnRH) antagonist permitted and approved for use in the treatment of hormone-dependent prostate cancer. It is recommended to administer the drug subcutaneously in the abdomen in a starting dose of 240 mg, followed by monthly maintenance doses of 80 mg. The Phase III randomized trial demonstrated that degarelix had advantages over the GnRH agonist leuprorelin in the reduction rates for testosterone to castration levels and for prostate-specific antigen (PSA) levels and in the absence of the initial increase and variations of androgen concentrations during treatment. A one-year follow-up showed that the risk of PSA recurrence and death with leuprorelin was significantly higher than that with degarelix. There was a significant reduction in the risk of PSA recurrence in patients switched from leuproprorelin to degarelix. The rates of adverse reactions and treatment discontinuation in the degarelix treatment group do not differ from that in the leuprorelin group. Long-term follow-up studies are required to draw final conclusions.

Objective: to evaluate the prognostic value of microvascular and perineural invasion on radical prostatectomy specimens in prostate cancer patients. Subjects: 144 patients with prostate cancer pT1-4N0-1M0 underwent radical prostatectomy at the Cancer Center in 1997 to 2008. The median age was 60.06.4 (43-73) years. The median preoperative PSA level was 10.413.7 (0.8-95.7) ng/ml (PSA0.05). Prostate cancer recurrence developed in 19 (13.2%) of the 144 patients. Relapses were registered more frequently in patients with microvascular (from 8.1 to 20.7% respectively, p=0.028) and perineural (from 8.4 to 19.7% respectively; p=0.043) invasion. Five-year overall, specific and PSA recurrence-free survival in a group of 144 patients was 97.6, 98.3, and 82.1%, respectively. Microvascular invasion significantly decreased 5-year PSA recurrence-free survival from 90.0 to 66.8% (p=0.050), but this difference did not translate into a statistically significant reduction in overall (98.8 and 96.0%, respectively, p=0.812) and specific (100.0 and 96.0% respectively, p=0.251) survival. Perineural invasion was associated with a significant decrease in 5-year PSA recurrence-free survival from 92.4 to 68.2% (p=0.045). Overall (100.0% and 94.1% respectively, p=0.090) and specific (100.0% and 95.7% respectively, p=0.217) survival differences between the groups without and with perineural invasion did not reach statistical significance. Conclusion: microvascular and perineural invasion is associated with the worst pathological findings in prostatectomy specimens, higher recurrence rate and lower PSA recurrence-free survival in patients with prostate cancer pT1-4N0-1M0.

Objective: to assess the advisability and safety of transperitoneal laparoscopic nephrectomy for renal parenchymal tumors.Subjects and methods. The investigation enrolled 163 patents with clinically localized renal parenchymal tumors that had been resected through laparoscopic (n = 81 (49.7 %)) and open (n = 82 (50.3 %) accesses). The groups of patients operated on via laparoscopic and laparotomic accesses were matched for demographic characteristics, somatic status, baseline renal function, and nephrometric signs of tumor nodules, except the involved side (7 patients in the laparoscopic group had bilateral renal tumors). Renal resection was carried out in all the patients; a contralateral kidney tumor was also removed in 7 patients with a bilateral lesion (nephrectomy and kidney resection were done in 3 and 4 patients, respectively). Histological examination verified benign tumors in 15 (9.2 %) cases, renal cell carcinoma in 148 (90.8 %), including all bilateral renal tumors [рТ1а (n = 135 (91.2 %) cases; рТ1b (n = 4 (2.7 %); рТ3а (n = 9 (6.1 %)]; according to the pT category, the distribution of patients in the laparoscopic and open resection groups was even (p = 0.586). No additional treatment was performed in any case. The median follow-up was 48.2 ± 11.8 months.Results. The use of the laparoscopic access significantly increased the frequency of intraoperative complications (6.1 and 16.0 %; p = 0.037), but failed to affect that of postoperative complications (13.0 and 18.3 %, respectively; p = 0.291) versus the open access. Laparoscopic versus conventional techniques did not cause any reduction in 5-year overall, specific, and relapse-free survival rates (93.3, 100.0, 80.0 % and 97.1, 100.0, 98.5 %, respectively; р > 0.05 for all). The rate of acute renal dysfunction and its distribution by the RIFLE classes, the rate and level of a decrease in glomerular filtration rate in the late postoperative period did not depend on the surgical access (p > 0.05) for all). Questioning has shown that the laparoscopic versus laparotomic access significantly improves quality of life within one month after renal resection.Conclusion. Transperitoneal laparoscopic nephrectomy is a safe alternative to open surgery, which can improve quality of life in the patients with clinically localized kidney tumors within one month after surgical intervention.

Objective: to study the prognostic value of alterations in the VHL gene and the plasma markers hVEGF, hVEGFR2, and hVEGFR3 in patients with metastatic kidney cancer (KC) who receive targeted therapy.Subjects and methods. Paraffin blocks from 22 patients with metastatic KC who received targeted therapy were analyzed for VHL gene mutation/methylation. Polymerase chain reaction (PCR) products were sequenced using a BigDye® Terminator v 3.1, a Cycle Sequencing Kit, and an ABI3100 genetic analyzer in accordance with the Applied Biosystems protocols. VHL gene methylation was determined by methyl-sensitive PCR. The markers hVEGF, hVEGFR2, and hVEGFR3 were measured in the plasma of 43 patients before, during, and after targeted therapy, by applying the commercial DuoSet® ELISA kits (RnDSystems, USA). The results obtained were analyzed by known statistical methods, by using the package of statistical programs SPSS 13.0 for Windows. Survival was estimated by the Kaplan-Meier method. Survival differences were found by the log-rank test in the patient groups. Cox uni- and multi-factorial regression analyses were used to identify factors that were prognostically significant for survival.Results. Out of 22 patients, 10 (45.5 %) and 1 (4.5 %) were found to have VHL gene mutations or methylation, respectively. VHL gene inactivation did not affect prognosis in patients and the results of antiangiogenic therapy. Correlation analysis revealed no relationship between the concentrations of hVEGF and hVEGFR2 before and during therapy or absolute increases in hVEGF and hVEGFR2 concentrations during treatment with the frequency of progression during targeted therapy, with progression-free survival, and total life expectancy. No correlation was either found between the hVEGFR3 concentration and its changes and the results of antiangiogenic therapy. There was an inverse correlation between the pretreatment plasma hVEGFR3 level and lifetime without progression during antiangiogenic therapy (r = – 0.477, p = 0.039).Conclusion. VHL gene alterations and plasma hVEGF and hVEGFR2 levels are not predictors of a response to antiangiogenic therapy. The pretreatment plasma hVEGFR3 level correlates with progression-free survival in KC patients receiving targeted therapy.

Случай из практики

Resolution on the results of the Meeting of Experts on the treatment of castrate-resistant prostate cancer.

The medical records of 60 patients who underwent surgery to remove the lung metastases of T1-4N0-2 kidney cancer were retrospectively analyzed. The age of patients ranged from 31 to 70 years. Synchronous lung metastases were diagnosed in 20 (33.3%) cases, metachronous - in 40 (66.7%). 53 (88.3%) patients had lesions in one lung, and 7 (11.7%) patients--in both lungs. Solitary metastases were present in 41 (68.3%) patients, multiple--in 19 (31.7%). In 69.4% of cases, the size of lung metastases was more than 2 cm. Metastasis at other sites at the time of surgery on the lungs were present in 1 patient (supraclavicular lymph nodes). The primary tumor was removed in 56 (93.3%) of 60 patients. All 60 patients underwent removal of lung metastases (radical--53 [88.3%]). One patient underwent a radical supraclavicular lymph node dissection. All tumor lesions were removed in 50 (83.3%) patients. Median followup period was 20 (3-155) months. Perioperative complication rate was 6.6%; no deaths caused by complications of treatment were registered. Histologically, metastases of renal cell carcinoma were verified in all removed lesions from the lungs; 3 (5%) patients had mediastinal lymph node metastases. Five- and 10-year overall, specific and recurrence free survival rates were 36.3 and 19.1%, 38.9% and 27.2, 20.4 and 11.7%, respectively. Univariate analysis demonstrated an adverse effect of pN + category, bilateral pulmonary lesions, the presence of mediastinal lymph nodes metastases and non-radical removal of malignant lesions of the lung on the specific survival. Multivariate analysis confirmed a significant effect of radical surgery on the survival.

Blocks of preparations from 22 patients with metastatic renal cell carcinoma on target therapy were studied. The patients were examined for mutations/methylation of VHL gene. The mutations were detected in 10 (45.5%) of 22 patients, VHL methylation was found in 1 (4.5%) patient. Overall survival was 36.4 and 66.7% in the groups of patients with and without gene VHL alteration, respectively. Progression-free survival was 47.6 and 57.1%, respectively (p = 0.619), relapse-free survival--63.6 and 45.5%, respectively (p = 0.682), progression was registered in 36.4 and 54.5%, respectively (p = 0.682). Gene VHL inactivation had no effect on prognosis of the disease and results of anti-angiogenic therapy.

The first stage in the treatment of disseminated germinogenic ovarian tumours (HOT) is induction chemotherapy in accordance with the IGCCCG prognosis group. Dynamic observation is indicated in case of incomplete induction in patients with seminoma excepting those with PET-positive residual tumours bigger than 3 cm to whom second-line chemotherapy or retroperitoneal lymphadenectomy is indicated. Ablation of residual tumour of any localization is indicated to patients with disseminated non-seminoma HOT (NHOT), incomplete induction, and negative level of tumour markers. The necessity of adjuvant chemotherapy in case of a viable malignant HOT in the removed tissues remains debatable. Refractory and recurring HOT are usually treated with a combination of fosfamide and vinblastine. Residual tumours need to be removed after salvation chemotherapy. Surgical treatment is the preferred option for the management of late NHOT relapses.

The only factor that demonstrates its independent influence on overall survival in our series of observations is surgical radicality (p < 0.0001). This conclusion underlines the importance of the quality of surgical treatment for the prognosis of the disease. Surgical access and scope should be individually determined by the site, sizes, and hypothetical pathomorphological characteristics of a tumor. Correct choice of surgical tactics serves as a pledge to completely remove all afflicted tissues. The efficiency of neoadjuvant and adjuvant chemotherapy for pelvic and ureteral tumors has not been proven. The additional treatment has failed to affect survival in this study.

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage50% in 7 (10.0%), 51-90% in 23 (32.9%),90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients:2 cm--5 (7.1%), 2-5 cm--25 (35.7%),5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: SS1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category SS1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage50% (p0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p0.0001), cancer in the residual mass (p0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage50% and potentially respectable residual disease.

To compare the results of radical prostatectomy and conformal radiotherapy in prostatic cancer T1-4N0-1M0, we made a retrospective study of 306 patients with prostatic cancer T1-4N0-1M0 of whom 144 (47.1%) were treated surgically (radical prostatectomy) while 162 (52.9%) were exposed to extracorporeal conformic radiotherapy. Follow-up median was 30.7 +/- 29.8 months. Five and 10-year overall, specific and PSA recurrence free survival in 306 patients was 94.0% and 90.1% (median was not achieved), 96.6% and 94.3% (median was not achieved), 66.1 and 49.2% (median was 84.0 +/- 4.4 months). In multifactorial analysis significant prognostic factors of PSA recurrence free survival were T category (p = 0.021) and Glison's sum (p = 0.002). In the subgroup of patients with local prostatic cancer there was a significant superiority of the operated patients by PSA recurrence free survival over irradiated group in baseline PSA10 ng/ ml (p = 0.015), Glison's index7 (p = 0.071) and combination of these factors (p = 0.018). A favourable prognosis factor of PSA recurrence free survival in operated patients was operative Glison's index7 (p = 0.001), among operated patients--nadir PSA1 ng/ ml (p = 0.003). Surgical and radiation treatment of local and locally advanced prostatic cancer provided satisfactory results. In the group of good prognosis (cT1-2N0, PSA10 ng/ml, Glison's sum7) radical prostatectomy gives advantage of PSA recurrence free survival. In patients with prostatic cancer cTT2, N+, Glison's index7 and PSA10 ng/ml surgical treatment and remote radiotherapy are equally effective in respect to survival free of biochemical recurrence.

The data of preoperative diagnosis and morphological examination were compared for 144 patients with prostatic carcinoma T1-4N0-XM0 subjected to radical prostatectomy in 1997-2007. In assessment of prostatic capsule invasion, sensitivity of the rectal examination was 21.7%, specificity--89.8%, diagnostic efficacy--68.1%, PPV--50.0%, NPV--70.9%, AUC under ROC curve--0.558 +/- 0.053 (p = 0.348); sensitivity of transrectal ultrasonic investigation--21.7%, specificity--89.8%, diagnostic efficacy--68.8%, PPV--52.6%, NPV--71.2%, AUC under ROC curve--0.563 +/- 0.053 (p = 0.211). Factors of a poor prognosis of prostatic capsule invasion were PSA10 ng/ml (p = 0.028) and Gleason score7 (p = 0.052). Combined use of these two parameters raises quality of preoperative assessment of category T [sensitivity--80.0%, specificity--55.1%, diagnostic efficacy--56.3%, PPV--80.4%, NPV--44.9%, AUC under ROC curve--0.624 +/- 0.049 (p = 0.017)]. Sensitivity of clinical assessment of N category was 11.1% in 100% specificity, 94.4% diagnostic efficacy, 100% PPV, 94.4% NPV, 0.556 +/- 0.107 (p = 0.577) AUC under ROC curve. A single significant prognostic factor of pN+ category was PSA10 ng/ml (p = 0.014). Sensitivity of histological examination of biopsy material in relation to true Gleason's parameter (7 or7) was 59.4%, specificity 89.3%, diagnostic efficacy 82.6%, PPV 61.3%, NPV 88.5%, AUC under ROC curve 0.743 +/- 0.056 (p0.0001). Thus, combined use of a baseline PSA concentration with a borderline value10 ng/ml and biopsy Gleason score7 raises quality of preoperative evaluation of extraprostatic tumor extension and condition of regional lymph nodes.

Based on the personal experience, the authors emphasize the leading role of surgery in the treatment of patients with various malignant neoplasms of the urinary tract and masculine sexual organs. Current standard indications for surgical intervention and its scope are discussed with reference to the methods for the achievement of optimal immediate and delayed postoperative outcomes. Special emphasis is laid on the necessity of combined surgical techniques for the management of local and disseminated tumours of the urinary tract and male sexual organs. The rationale is proposed for extensive and combined operations on such neoplasms. The main avenues of further development of surgical oncosurgery are postulated with a view to improving quality of life of the treated patients.

Cystectomy in the treatment of invasive cancer of the urinary bladder is not the only therapeutic modality in this pathology. In selected patients an alternative exists--transurethral resection of the urinary bladder followed by adjuvant concurrent chemotherapy and radiotherapy. The preserving therapy can be recommended to patients over 60 years of age in the presence of a low-grade solitary tumor of a mobile wall of the urinary bladder respectable with preservation of the organ capacity.

Emergence of regional penile cancer (PC) metastases reduces late survival of PC patients from 94.4 to 83.9%. PC stage can hardly be diagnosed by clinical data significantly. Bilateral inguinal lymphadenectomy is indicated for all PC patients with enlarged and clinically negative regional lymph nodes in poorly differentiated primary tumor (G3) and stages T2-3. Follow-up can be recommended for patients with stage Tis-T1, low and moderate anaplasia (G1-2) of the primary tumor. Metastases to the iliac lymph nodes are an indication to pelvic lymphadenectomy. Preventive removal of the iliac lymph nodes in intact inguinal ones is not justified. Unremovable fixed regional lymph nodes should be exposed to radiotherapy.

Conservative penis-salvage treatment provides a complete local effect in 55% cases, preservation of the penis in 51.4% patients without a fall in long-term specific and recurrence-free survival compared to penectomy and can be recommended as an alternative to penis amputation in patients with stages Tis-T2. Removal of a penile tumor raises efficacy of salvage treatment and insignificantly increases survival. Application of surgical treatment only is associated with a high rate of local recurrences. Chemoradiotherapy in penile cancer is significantly more effective vs each method alone. Radiation in a total focal dose more than 60 Gy improves local control over the tumor. Most effective are schemes of chemotherapy based on bleomycin. Polychemotherapy has no advantages over monochemotherapy with bleomycine.

Paratesticular rabdomyosarcoma (PR), the most frequently occurring paratesticular tumor, is encountered mostly in young and middle-aged men. PR metastasizes early and is characterized by lymphogenic dissemination of the tumor with affection of the retroperitoneal lymph nodes. Orchofuniculectomy is the first-line treatment in all the patients. If the patient is metastases-free it is followed by preventive retroperitoneal lymphadenectomy with subsequent adjuvant chemoradiotherapy. In disseminated PR, combined treatment is indicated including surgical removal of metastatic foci and adjuvant chemo- or chemoradiotherapy. If surgical removal of all the tumor foci is infeasible, patients with disseminated PR undergo chemotherapy. Radiation of metastatic retroperitoneal lymph nodes is uneffective. Prognosis of PR depends on the age, stage of the disease and treatment.

Sertolioma accounts for 4.5% of all non-herminogenic testicular tumors. Sertolioma presents clinically with local symptoms (enlarged testis) which may be associated with dyshormonal symptoms. Most sertoliomas are benign, only 16.7% of them are malignant. Metastatic process is primarily lymphogenic and involves first retroperitoneal lymph nodes. Accurate histological criteria of malignancy for sertolioma have not been determined yet. The treatment should be started with orchofuniculectomy. Organ-saving operations may be performed in metastases-free children with bilateral sertoliomas. Surgical treatment is the only treatment effective in malignant sertolioma. Retroperitoneal and (or) solitary distant metastases should be removed surgically. Sertolioma is resistant to chemotherapy and is low sensitive to radiotherapy. Contrary to benign sertolioma, malignant one has poor prognosis.

By mass spectrography and pneumotachography structural variations in total lung capacity (TLC) were investigated in 7 test subjects during 7-day head-down tilt at -15 degrees. By the 7th hour of head-down tilt TLC, vital lung capacity (VLC), functional residual capacity (FRC) and residual volume (RV) decreased significantly and closing volume (CV) increased insignificantly. The CV/FRC ratio grew from 0.82 +/- 0.03 to 1.24 +/- 0.08 (P less than 0.01), indicating the closure of respiratory pathways in certain lung structures within the tidal volume. These changes in the TLC structure persisted till day 7 but the CV/FRC ratio fell down to 1.01 +/- 0.07. The above findings can clarify the mechanism responsible for a lower oxygenation of arterial blood in the head-down position. The expiratory closure of the airways within the tidal volume causes regional changes in alveolar ventilation and ventilation-perfusion relations and, consequently, a larger venous admixture and a smaller oxygen saturation of arterial blood.

The time-course variation of the water content of the lungs of seven male volunteers were examined during 7-day head-down tilt (at -15 degrees). As compared to the horizontal subjects, the tilted subjects showed a significant increase in the water content from 557 +/- 19 ml to 612 +/- +/- 63 ml by the 7th hour of the tilt. Later on the parameter gradually declined and on tilt day 7 almost returned to the pretest level, i.e., 567 +/- 46 ml. This increase in the water content during the first hours of the exposure can be attributed to the hydrostatic factors: higher pulmonary artery pressure and higher cardiac output. The increase in the water content on tilt days 3-7 can be associated with changes in the permeability of lung capillaries, drainage function of the lymphatic system of the lungs, and colloidal-osmotic pressure in the perivascular space of the lungs.