Saratov JOURNAL of Medical and Scientific Research

Fomkin R.N.

Saratov State Medical University n.a. V.I. Razumovsky, Department of Urology, Assistant Professor, Scientific Research Institute of Fundamental and Clinical Uronephrology Senior Research Assistant

Prognostic significance of the assessment of the expression of immunohistochemical markers and the degree of pathomorphism before and after treatment of patients with prostate cancer at high risk of progression

Year: 2019, volume 15 Issue: №2 Pages: 318-324
Heading: Urology Article type: Original article
Authors: Voronina E.S. , Fomkin R.N. , Bucharskaya A.B. , Palatova T.V. , Popkov V.M., Maslyakova G.N.
Organization: Saratov State Medical University
Summary:

Purpose: to analyze the expression of immunohistochemical markers in patients with prostate adenocarcinoma at high risk of progression before and after combined and combined treatment of patients with prostate specific antigen (PSA) level of blood below discriminatory. Material and methods. Examined patients (n = 80) with a diagnosis of “High-risk progression prostate cancer,” with clinical stage T3a, total score for Gleason scale from 8 to 10, the level of total PSA more than 20 ng / ml. Patients of the 1st group (n = 42) only combined surgical treatment in the scope of TUR and HIFU ablation the prostate; The 2nd group of patients (n = 38) additionally applied androgen deprivation in adjuvant mode. Results. Blood PSA, determined in patients after various methods of treatment is not always an objective indicator of its effectiveness. Immunohistochemical studies of tumor tissue for proliferative activity tumor cells, the activation of apoptosis in them, as well as the assessment of specific tumor markers and tumor suppressor genes showed that a decrease in the expression of these markers in patients with PSA values ​​of blood lower than discriminatory observed in all patients independently on the type of treatment. However, after treatment in the 1st group of patients, despite the achievement PSA level of nadir, there is a decrease in the expression of an intercellular adhesion marker E-cadherin, which indicates an increased risk of tumor metastasis, as well as increased expression of markers of the apoptosis inhibitor Bcl-2 and androgens, which indicates about the possibility of progression of tumor growth. Conclusion For a more accurate assessment therapeutic pathomorphism in patients with prostate cancer at high risk of progression, which HIFU ablation monotherapy was carried out, along with the determination of blood PSA level, it is necessary during the control biopsy of the prostate immunohistochemical studies of tumor tissue to determine the prognosis and risk of relapse.

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The value of tumor markers in prognos-ing the outcomes of treatment of patients with bladder cancer

Year: 2018, volume 14 Issue: №4 Pages: 661-666
Heading: Urology Article type: Review
Authors: Ponukalin A.N., Zakharova N.B., Skriptsova S.A., Fomkin R.N., Chekhonatskaya M.L.
Organization: Saratov State Medical University n.a. V I. Razumovsky, Scientific Research Institute of Fundamental and Clinical Uronephrology, Saratov State Medical University
Summary:

The review analyzes the recent publications of the results of the use of molecular genetic markers of bladder cancer (RMP) in clinical practice. The prospects of application of a series of molecules determined in tumor tissue, serum, urine in the diagnosis of RMP are presented. One ofthe most promising areas of finding a marker forthe diagnosis and control of treatment of RMP in recent years are the study ofthe proteomic composition of urine.

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Endoscopic correction of obstructive complications after HIFU-ablation of the prostate with holmium laser

Year: 2018, volume 14 Issue: №2 Pages: 272-277
Heading: Urology Article type: Original article
Authors: Popkov V.M., Fomkin R.N., Shatylko T.V.
Organization: Saratov State Medical University
Summary:

Purpose: to improve the results of treatment of the obstructive complications (an urethra stenosis, a bladder neck sclerosis) caused by application of the high-intensity focused ultrasonic ablation (HIFU) concerning treatment of the localized prostate cancer. Material and Methods. An object of the research included 41 patients, with the infravesical obstruction (IVO) which has arisen in the postoperative period to which elimination the holmium laser is used. Results. The bladder neck was the most frequent place of obstruction. Average time before emergence of the first episode of IVO: 8.2±1.3 months. Distinctions on time before development of an episode of IVO depending on the fact of carrying out TURP before HIFU not confirmed (p=0.440). More advanced age for a moment HIFU-ablation has been associated with much higher frequency of IVO (p=0.021). Considerably smaller frequency repeated was observed by IVO at a larger ratio transurethral resection to the initial volume of a prostate (p=0.031). Duration of a laser endoscopic ure-throtomy was 27 [10-70] minutes, serious perioperative or postoperative complications were not determined. Average term before removal of a catheter of Foley: 3 [1-5] days, hospitalization duration included 4 [3-6] days. After treatment considerable improvement on indicators of the maximum speed of a stream of urine (Qmax) and volume of residual urine was observed. The total score according to the questionnaires of IPSS and QoL has considerably improved, significant changes on symptoms of accumulation are noted. After the first holmium laser urethrotomy of 80.4% of patients have noted satisfactory results without recurrence of IVO; 19.6% of patients were required a repeated laser endoscopic urethrotomy. Recurrence term after the first laser urethrotomy is on average equal to 2.5 months. Conclusion. The endoscopic urethrotomy by means of the holmium laser is safe, effective and minimum invasive type of treatment of a stenosis of a neck of the bladder / urethra after ablative cancer therapy of prostate. The advantages are the minimum of traumas of surrounding tissues and preservation of the mechanism of deduction of urine.

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Integrative approach to pre-operative determination of clinically significant prostate cancer

Year: 2015, volume 11 Issue: №3 Pages: 345-348
Heading: Proceedings of all-Russia week of science with international participants Article type: Original article
Authors: Shatylko T.V., Popkov V.M., Fomkin R.N.
Organization: Saratov State Medical University
Summary:

Aim: improvement of early diagnostics of prostate cancer by developing a technique, which makes possible to predict its clinical significance in outpatient setting before initiation of invasive procedures. Material and Methods. Clinical data of 398 patients who underwent transrectal prostate biopsy in 2012-2014 in SSMU S. R. Mirotvortsev Clinical Hospital, was used to build an artificial neural network, while its output allowed to determine whether the tumour corresponds to Epstein criteria and which D'Amico risk group it belongs to. Internal validation was performed on 80 patients, who underwent prostate biopsy in September 2014 — December 2014. Sensitivity, specificity, positive and negative predictive value of artificial neural network were calculated. Results. Accuracy of predicting adenocarcinoma presence in biopsy specimen was 93,75%; accuracy of predicting whether the cancer meets active surveillance criteria was 90%. Accuracy of predicting T stage (T1c, T2a, T2b, T2c)was 57,1%. Prediction of D'Amico risk group was accurate in 70% of cases; for low-risk cancer accuracy was 81,2%. Conclusion. Artificial neural networks may be responsible for prostate cancer risk stratification and determination of its clinical significance prior to biopsy.

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Identification of risk factors of prostate adenocarcinoma recurrence after HIFU therapy using immunohistochemical markers

Year: 2014, volume 10 Issue: №4 Pages: 654-658
Heading: Urology Article type: Original article
Authors: Popkov V.M., Maslyakova G.N., Voronin E.S., Fomkin R.N.
Organization: Saratov State Medical University
Summary:

The purpose of this study was to identify risk factors for recurrence of prostate adenocarcinoma after HIFU therapy. Material and methods: Material for the study was obtained from patients diagnosed with adenocarcinoma before and after HIFU treatment. Morphological study was conducted using a standard staining, and immunohistochemical markers: PCNA, Amacr, E-cadherin, Bel2, Andr, Estr, VEGF, P53, PCNA. Results: After treatment in 89% of patients with initial prostate volume greater than 50 cc the signs of recurrence of adenocarcinoma were showed. At low risk for D'Amico after treatment the expression of proliferation markers, VEGF, Amacr significantly decreased. With a high degree of risk — increased expression of Bel2. After treatment the expression of the following markers: PCNA, Amacr, VEGF significantly increased in the group of patients with the presence of invasion. Conclusion: Patients with initial prostate volume less than 50 cc, low risk to D'Amico, the lack of perineural and perivascular invasion have a low risk of recurrence after HIFU therapy; patients at high risk for D'Amico, the presence of perineural and perivascular invasion initial and prostate volume greater than 50 cc, low-grade cribriform form of adenocarcinoma have a high risk of recurrence of adenocarcinoma. Recurrence of adenocarcinoma develops independently of the period after HIFU therapy.

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Combination of the transurethral resection and prostate HIFU ablation at treatment of the localized cancer

Year: 2014, volume 10 Issue: №3 Pages: 450-455
Heading: Urology Article type: Original article
Authors: Popkov V.M., Fomkin R.N., Blyumberg B.l., Shatylko T.V., Sedova L.N., Abramova E.P.
Organization: Saratov State Medical University
Summary:

Research objective: to estimate results of treatment of patients with the localized form of a cancer of a prostate at a combination of a transurethral resection (TURP) and HIFU of an ablation. Objects and research methods: From February, 2009 to February, 2014 of 100 patients with the localized form of a cancer of a prostate were selected for research:
26 patients were included into HIFU and 74 group in group of the combined treatment (TURP+HIFU). Selection criteria for HIFU ablation were the localized cancer of a prostate concerning which earlier it wasn't carried out treatments, and level of a PSA at the time of statement of the diagnosis 15 ng/ml. All patients corresponding to these by criteria, were considered as candidates for treatment and inclusion in the analysis. The nadir and stability of PSA, the histologic conclusion, IPSS, quality of life and complication were estimated at time of postoperative supervision. Results: Statistically significant influence of a combination TURP+HIFU for the term of transurethral drainage of a bladder (a median of 40 days against 7 days), incontience frequency (15.4% against 6.9%), infections of urinary ways (47.9% against 11.4%) and IPSS change during the postoperative period (on the average 8.91 against 3.37) is noted. During the short period of supervision it wasn't observed considerable changes in relation to efficiency: in HIFU group the frequency of repeated sessions made 25%, in TUR/HIFU group 4%. Conclusion: HIFU therapy is modern, minimum invasive method of a cancer therapy of a prostate. The combination of a transurethral resection and HIFU ablation significantly reduces the frequency of the complications connected with treatment. Maintaining the patient after combined TURP and HIFU ablation is comparable with maintaining the patient after usual TURP.

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Prognosis of prostate gland morphology study using artificial neural network

Year: 2014, volume 10 Issue: №2 Pages: 328-332
Heading: Proceedings of all-Russia week of science with international participants Article type: Original article
Authors: Popkov V.M., Shatylko T.V., Fomkin R.N.
Organization: Saratov State Medical University
Summary:

The research goal is to optimize the management of patients with serum PSA level falling in the range of 4-10 ng/ ml by designing and educating of an artificial neural network, which may be used to predict prostate gland morphology basing on clinical, laboratory and imaging data. Material and methods. Data of 254 patients, who were admitted to the oncological Department of S. R. Mirotvortsev Clinical hospital for transrectal prostate biopsy, was collected to construct several artificial neural networks with different architecture. External validation was performed on 27 patients, who had prostate biopsy in January-February 2014. Results. One-layer network, consisting of 11 input, 9 hidden and 3 output neurons, was determined to be the most successful: in 92.6% cases it was correct in predicting prostate cancer or its absence. Input factors were evaluated according to their relative importance, from more important to less important: prostate volume, serum PSA, patient's age, prostate consistency, PSA velocity, prostate symmetry, previous negative biopsy, free serum PSA, intake of 5-alpha-reductase inhibitors. Conclusion. Artificial neural networks may be used to predict morphological findings in prostate biopsy. High PSA density and firm prostate consistency should cause suspicion of prostate cancer.

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Возможности прогнозирования рецидива рака простаты после HIFU-аблации с помощью математического моделирования

Year: 2013, volume 9 Issue: №2 Pages: 314-320
Heading: Urology Article type: Original article
Authors: Popkov V.M., Fomkin R.N., Blumberg B.I.
Organization: Saratov State Medical University
Summary:

Research objective: Creation of mathematical prognosis of model of local relapsing tumors in patients with prostate cancer after treatment by high-intensive focused ultrasound (HIFU). Objects and Research Methods: Results of treatment are estimated at 102 patients with morphologically localized prostate cancer proved at biopsy. For the purpose to analyze interrelation of prognostic factors and postoperative morphological research of prostate control biopsies after HIFU ablation with frequent development of relapses comparative statistical research of received data has been conducted. For construction of mathematical models of relapse prognosis after HIFU of prostates two methods of mul-tifactorial analysis of the data have been used: the discriminant analysis and logistical regress. Results: While planning treatment of patients after HIFU ablation of prostates it has been necessary to estimate morphological risk factors of local relapse of a neoplasm such as preoperative level of serum PSA, the sum of Gleason, severity of disease, presence of lymphovascular and perineural invasion. The offered formulas are worth while using in revealing of probability of development of relapses. The comparative analysis of mathematical models has showed that accuracy of prognosis of results of HIFU of prostates is high enough.

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Prognostic factors in the estimation of HIFU treatment efficiency in patients with localized prostate cancer

Year: 2013, volume 9 Issue: №1 Pages: 116-121
Heading: Urology Article type: Original article
Authors: Popkov V.M., Fomkin R.N., Blyumberg B.I.
Organization: Saratov State Medical University
Summary:

Research objective: To study the role of prognostic factors in the estimation of risk development of recurrent prostate cancer after treatment by high-intensive focused ultrasound (HIUF). Objects and Research Methods: The research has included 102 patients with morphologically revealed localized prostate cancer by biopsy. They have been on treatment in Clinic of Urology of the Saratov Clinical Hospital n.a. S. R. Mirotvortsev. 102 sessions of initial operative treatment of prostate cancer by the method of HIFU have been performed. The general group of patients (n=102) has been subdivided by the method of casual distribution into two samples: group of patients with absent recurrent tumor and group of patients with the revealed recurrent tumor, by morphological research of biopsy material of residual prostate tissue after HIFU. The computer program has been used to study the signs of outcome of patients with prostate cancer. Results: Risk of development of recurrent prostate cancer has grown with the PSA level raise and its density. The index of positive biopsy columns

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Postoperative monitoring of prostate-specific antigen (PSA) after treatment with high-intensive focused ultrasound (HIFU

Year: 2012, volume 8 Issue: №4 Pages: 1001-1007
Heading: Urology Article type: Original article
Authors: Popkov V.M., Fomkin R.N., Blyumberg B.I.
Organization: Saratov State Medical University
Summary:

Research objective: to estimate efficiency of treatment of prostate cancer using high-intensive focused ultrasound on the basis of laboratory analysis of postoperative level prostate-specific antigen (PSA). Objects of research. Objects of research consisted of 110 patients treated in urological clinic of Hospital n.a. S. R. Mirotvortsev (Saratov State Medical University) during the period February, 2009 — March, 2012. Patients took 110 sessions of primary operative treatment of prostate cancer by HIFU therapy method. Technique and research methods. Concentration of PSA in blood changed in all patients every 1,5 month within 6 months after operation, irrespective of its kind (including after repeated HIFU), further — after every 3 month till one year, and later on after 6 months. We were guided by references of the International Consensus, which considers PSA level more than 0,5 ng/ml in blood after 3 months of treatment to be unsatisfactory result. We also headed for PSA level before treatment and oncological risk degree. Results. Median nadir formed 0,5 ng/ml PSA by 3 months after treatment. Patients demonstrated different indicators of PSA dynamics depending on oncological risk, stage and hormonal therapy management. Patients with low oncological risk had initially lower PSA concentration, further PSA concentration reached nadir level faster. At patients with widespread forms of prostate cancer accurate dependence of PSA concentration according to prevalence of process was traced. Time of PSA nadir amount did not differ and was marked as 12-14 weeks on average. At patients received hormonal therapy, lower value of PSA nadir was marked. The conclusion. Monitoring of PSA concentration (PSA nadir by 3 months, dynamics of PSA concentration change) is of great importance in early revealing of relapse after prostate HIFU therapy. High level of PSA nadir and PSA growth according to time period are important prognostic factors.

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