[Oncological safety of nerve-sparing radical prostatectomy: evaluation of histopathological outcomes and recurrence-free survival].

OBJECTIVE: To evaluate histopathological outcomes and biochemical recurrence (BCR) free survival in patients after nerve-sparing radical prostatectomy (nsRP). MATERIALS AND METHODS: Prospective study group comprised 313 patients who underwent uni- or bilateral nsRP from 2014 to 2018; control group included 592 patients with clinically localized prostate cancer who underwent non-nsRP from 2014 to 2018. Mann-Whitney U-test was performed to assess continuous variables; chi-squared test was used for comparative analysis of categorical data. BCR free survival was evaluated with Kaplan-Meier method, log-rank test was used to compare survival outcomes. RESULTS: Adverse histopathological findings were lower in the study group: extracapsular extension was found in 9,4% and 18,75% (p<0,001), grade group upgrade in 23% and 29,3% (p=0,04), positive surgical margins (PSM) in 15% and 22,1% (p=0,01). Subanalysis according to cancer risk groups showed lower PSM rates in high-risk patients (15,6% and 30,3%, p=0,017) and tendency for higher PSM rates in low-risk patients in the study group with no significant difference (12,6% and 7%, p=0,16). BCR free survival after 12 months was 100% and 88,2%, after 20 months - 92,3% and 86,4%, p=0,04. PSM ratesin the study group were notsignificantly different depending on the type of surgery: 13,9% in robotic-assisted approach and 15,4% in retropubic approach, p=0,75. CONCLUSIONS: Relatively favorable histopathological outcomes and BCR free survival can be achieved after nsRP. However, obtained results could not be considered optimal and clearly indicate the need for further improvement of preoperative planning and intraoperative quality control of surgical treatment.

[Multiparametric magnetic resonance imaging markers of clinically significant prostate cancer].

Authors aimed to assess the correlation between the apparent diffusion coefficient (ADC of the tumor, ADC ratio) and final grade group (GG) after radical prostatectomy (RP), and to determine the threshold values of ADC for detecting clinically significant prostate cancer (PC) with subsequent evaluation in a prospective group. 118 patients with PC were included in the retrospective group. These patients underwent RP from 2012 to 2017 with preoperative 3 Tesla multiparametric MRI (mpMRT) with contrast enhancement in a single center. After analyzing all the MRI studies, the average values of tumor ADC and benign tissue ADC were calculated using the maps of ADC. The prospective part of the study included 60 patients with completed pre-biopsy mpMRI and subsequent RP from January 2018 to March 2019. The prospective part of the study demonstrated the effectiveness of applying the obtained diffusion coefficient thresholds. When used as a criterion for determining clinically significant prostate cancer (GG > 6), threshold value of ADC ratio had sensitivity, specificity, accuracy, positive predictive value and negative predictive value were 84%, 91%, 87%, 94% and 78% respectively.

[Diagnostic performance of 68GA-PSMA PET/CTin patients with prostate cancer].

INTRODUCTION: and aim. Most of the patients with biochemical recurrence after radical prostatectomy undergo salvage radiotherapy without guidance from imaging. In recent years, there has been an increasing role of Gallium-68 prostate specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the management of prostate cancer. This study aimed to investigate diagnostic performance of 68Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: From 2016 to 2017, 19 prostate cancer patients were evaluated by 68Ga-PSMA PET/CT at the Urology Clinic of S.P Botkin City Clinical Hospital; 17 of them had a biochemical recurrence and needed restaging of the disease. The age, prostate specific antigen (PSA) values, therapy at the time of the study, and maximum standard uptake value (SUVmax) were evaluated. RESULTS: The median age of patients was 65 years (interquartile range (IQR) 58.5-70.5), the median total PSA level was 2.36 ng/mL (IQR 1.5-4.19). In 8 of 17 patients, the PSA values did not exceed 2 ng/ml. The median time after radical prostatectomy was 33.2 months. (IQR 12-54.5). Positive PET/CT sites of recurrence were detected in 15 of 17 patients. Nine patients had only one positive site, and in six patients several positive sites were detected. Four patients with PET/CT positive pelvic lymph nodes and/or retroperitoneal space underwent salvage lymphadenectomy. Histological findings confirmed the presence of malignant growth in 3 out of 4 cases. CONCLUSION: 68Ga-PSMA PET/CT is an effective tool for the early detection of oligometastatic lesions in recurrent prostate cancer.

Structure and functional studies of the ribonuclease binase Glu43Ala/Phe81Ala mutant.

Ribonuclease from Bacillus intermedius (binase) is a small basic protein with antitumour activity. The three-dimensional structure of the binase mutant form Glu43Ala/Phe81Ala was determined at 1.98 Å resolution and its functional properties, such as the kinetic parameters characterizing the hydrolysis of polyinosinic acid and cytotoxicity towards Kasumi-1 cells, were investigated. In all crystal structures of binase studied previously the characteristic dimer is present, with the active site of one subunit being blocked owing to interactions within the dimer. In contrast to this, the new mutant form is not dimeric in the crystal. The catalytic efficiency of the mutant form is increased 1.7-fold and its cytotoxic properties are enhanced compared with the wild-type enzyme.

[X-ray diffraction and biochemical studies of W34F mutant ribonuclease binase].

The structures of two crystal modifications of the W34F mutant ribonuclease from the bacterium Bacillus intermedius (binase) were solved and refined at 1.7 and 1.1 A resolution. The kinetic parameters of the hydrolysis of substrates of different lengths (GpU, GpUp, and poly(I)) by binase and its W34F mutant were investigated and compared. The catalytic activity of the enzymes was shown to increase with increasing length of the substrate. The substitution of tryptophan for phenylalanine does not lead to a change in the activity of the enzyme but results in a decrease in the binding constants for substrates containing more than one phosphate groups. A comparison of the structure of the mutant enzyme with the previously established structures of binase and its complexes with sulfate ions and guanosine monophosphate showed that the difference in their kinetic parameters is related to the fact that the mutant ribonuclease cannot bind the second phosphate group. Both crystal modifications of the mutant binase contain dimers, like in the crystal structure of binase studied previously. In these dimers, only one enzyme molecule can bind the substrate molecule. Since the dimers were found in the crystals grown under four different conditions, it can be suggested that the enzyme can exist as dimers in solution as well. Mutants of binase, which could exclude the formation of dimers, are suggested.