Diagnostic Value of Combinatorial Markers in Colorectal Carcinoma.

Objectives: Blood-based tests have been shown to be an effective strategy for colorectal cancer (CRC) detection in screening programs. This study was aimed to test the performance of 20 blood markers including tumor antigens, inflammatory markers, and apolipoproteins as well as their combinations. Methods: In total 203 healthy volunteers and 102 patients with CRC were enrolled into the study. Differences between healthy and cancer subjects were evaluated using Wilcoxon rank-sum test. Several multivariate classification algorithms were employed using information about different combinations of biomarkers altered in CRC patients as well as age and gender of the subjects; random sub-sampling cross-validation was done to overcome overfitting problem. Diagnostic performance of single biomarkers and multivariate classification models was evaluated by receiver operating characteristic (ROC) analysis. Results: Of 20 biomarkers, 16 were significantly different between the groups (p-value ≤ 0.001); ApoA1, ApoA2 and ApoA4 levels were decreased, whereas levels of tumor antigens (e.g. carcinoembriogenic antigen) and inflammatory markers (e.g., C-reactive protein) were increased in CRC patients vs. healthy subjects. Combinatorial markers including information about all 16 significant analytes, age and gender of patients, demonstrated better performance over single biomarkers with average accuracy on test datasets ≥95% and area under ROC curve (AUROC) ≥98%. Conclusions: Combinatorial approach was shown to be a valid strategy to improve performance of blood-based CRC diagnostics. Further evaluation of the proposed models in screening programs will be performed to gain a better understanding of their diagnostic value.

Hemiablation of Localized Prostate Cancer by High-Intensity Focused Ultrasound: A Series of 35 Cases.

Prostate cancer (PrC) is one of the most common tumors diagnosed in men. The detection rate of localized PrC has been dramatically enhanced by screening and the development of visualization methods. There are currently several techniques for focal treatment available, among which the most interesting in our opinion is high-intensity focused ultrasound (HIFU). Currently, HIFU hemiablation of PrC is not an established treatment, although evidence of its effectiveness and safety is growing. We have been performing HIFU hemiablation since 2013 and here report our results to add to the evidence on the effectiveness of the technique. Between October 2013 and December 2016, we performed HIFU hemiablation of the prostate for a total of 35 patients with confirmed PrC stage

Risk factors for urethral stricture and/or bladder neck contracture after monopolar transurethral resection of the prostate for benign prostatic hyperplasia.

OBJECTIVE:: To identify risk factors for urethral stricture and/or bladder neck contracture after transurethral resection of benign prostatic hyperplasia. MATERIALS AND METHODS:: We performed a retrospective analysis of 402 patients, which underwent a monopolar transurethral resection of the prostate in the urology clinic of Sechenov First Moscow State Medical University for prostatic hyperplasia during the period 2011-2014. Urethral stricture and (or) bladder neck contracture in the postoperative period were diagnosed in 61 (15.27%) patients; 34 patients (8.6%) had urethral stricture, 20 (4.97%) bladder neck contracture, and 7 (1.7%) had a combination of urethral stricture and bladder neck contracture. In 341 of cases (84.73%), no late postoperative complications were observed. A total of 106 of the 341 patients met the inclusion criteria, hence, containing all the information necessary for analysis such as the volume of the prostate, the duration of the surgery, the size of the endoscope, data on concomitant diseases, analysis prostatic secretion, and so on. Thus, two groups were formed. Group 1 (106 patients) is the control group in which urethral strictures and/or bladder neck contractures did not occur in the long-term postoperative period and group 2 (61 patients), in which was observed the formation of these complications. To calculate the statistical significance of the differences for categorical data, Fisher criterion was used. For quantitative variables, in the case of normal data distribution, an unpaired t-test or one-way analysis of variance was used; for data having a distribution different from normal, a Mann-Whitney rank test was used. RESULTS:: Regression analysis established the significance of the influence of four factors on the development of scar-sclerotic changes of urethra and bladder neck: the tool diameter 27 Fr ( p < 0.0001), presence of prostatitis in past medical history ( p < 0.0001), prostate volume ( p = 0.003), and redraining of the bladder ( p = 0.0162). CONCLUSION:: The relationship between the diameter of the instrument, presence of chronic prostatitis in anamnesis, increased volume of the prostate, and repeated drainage of the bladder using the urethral catheter with the risk of developing scar-sclerotic changes in the urethra and/or bladder neck are statistically reliable and confirmed as a result of regression analysis.

Multiple application of three-dimensional soft kidney models with localized kidney cancer: A pilot study.

AIM: To evaluate the effectiveness of three-dimensional printing application in urology for localized renal cancer treatment using three-dimensional printed soft models. MATERIALS AND METHODS: The study included five patients with kidney tumors. The patients were treated in the Urology Clinic of I.M. Sechenov First Moscow State Medical University from February 2016 to June 2017. Personalized three-dimensional printed models based on computed tomographic images were created. Five surgeons took part in a survey in which the utility of computed tomographic images versus three-dimensional printed models for presurgical planning was compared. A laparoscopic partial nephrectomy training using the developed three-dimensional printed models was performed by the same surgeons in a surgical training box. RESULTS: The patients underwent endoscopic surgery using laparoscopic access. The average time of surgery was 187 min. All the operations were performed with complete renal artery clamping. The average warm ischemia time was 19.5 min and the average blood loss was 170 mL. No conversions to open surgery or radical nephrectomy, and no postoperative complications and deaths were observed. All the surgical margins were negative. The tumors were morphologically identified as renal cell carcinoma in four cases and as oncocytoma in one case. CONCLUSION: The developed three-dimensional printed models allow one to evaluate the pathological anatomy of tumors more effectively. High similarity between three-dimensional models and native kidneys contribute to improvement of surgical skills necessary for partial nephrectomy. Training on the three-dimensional models also allows surgeons to facilitate selection of an optimal surgical tactics for each patient.

A Feasibility Study Utilizing the Thulium and Holmium Laser in Patients for the Treatment of Recurrent Benign Prostatic Hyperplasia after Previous Prostatic Surgery.

BACKGROUND: Transurethral resection of the prostate (TURP) is considered to be the standard treatment for patients with benign prostatic obstruction (BPO) ≤80 mL. However, up to 14.7% of the patients require secondary TURP due to recurrent BPO. The aim of our study was to describe specific features of holmium laser enucleation of the prostate (HoLEP) and thulium laser enucleation of the prostate (ThuLEP) in patients with recurrent BPO after previous prostate surgery. MATERIALS AND METHODS: A total of 768 consecutive patients from our prospective collected database were retrospectively reviewed and divided into 4 groups: group A (489 patients) and group C (253 patients) underwent primary HoLEP and ThuLEP treatment, while group B (17 patients) and D (9 patients) included patients with recurrent BPO who were treated with HoLEP and ThuLEP, respectively. RESULTS: There were no significant differences in preoperative parameters between the groups at primary (A and C) and secondary (B and D) treatment except their age. At 6-month follow-up, voiding parameters and symptom scores showed statistically significant improvements compared to baseline without differences between the groups. The mean operative time was comparable between the groups and did not differ significantly (p > 0.05). CONCLUSIONS: Laser enucleation for the treatment of recurrent BPO is feasible and seems to be a safe and effective procedure.

miR-93-3p inhibition suppresses clear cell renal cell carcinoma proliferation, metastasis and invasion.

miRNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of miR-93-3p on clear cell renal cell carcinoma (ccRCC). We found that miR-93-3p is upregulated an average of 38-fold in 138 ccRCC specimens compared to matched normal kidney tissues, which correlated with poor patient outcome. miR-93-3p inhibition reduced ccRCC cell growth, invasion, and migration in vitro and in a mouse xenograft model. A search of the TargetScan, miRanda, and PicTar databases revealed that miR-93-3p is predicted to regulate pigment epithelium-derived factor (PEDF). A direct PEDF-miR-93-3p interaction was confirmed via dual-luciferase reporter assays. Like miR-93-3p inhibition, PEDF overexpression induced cell apoptosis and inhibited migration and invasion. Additionally, co-transfection with PEDF siRNA reversed the effects of miR-93-3p inhibition in ccRCC cells. Thus, miR-93-3p is a likely ccRCC oncogene that acts by regulating PEDF. These results suggest that miR-93-3p may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.

Prognostic Value of PD-1 and PD-L1 Expression in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We investigated the prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma. MATERIALS AND METHODS: Tissue microarrays of 423 patients treated with extirpative surgery for high grade upper tract urothelial carcinoma from the International Upper Tract Urothelial Carcinoma collaboration were stained for PD-1 and PD-L1 using antibodies, including Cell Marque™ NAT105 diluted 1:250 and prediluted E1L3N® via immunohistochemistry. A 1% or greater staining rate of tumor infiltrating lymphocytes (PD-1) and tumor cells (PD-L1) was considered positive. Univariate and multivariate analyses were performed to assess independent prognosticators of survival outcomes. RESULTS: Median patient age was 70.0 years and median followup was 37.0 months. PD-1 and PD-L1 were positive in 37.2% and 26.2% of patients, respectively. PD-1 positivity was significantly associated with adverse pathological characteristics while PD-L1 positivity was associated with favorable pT stage. On univariate analysis PD-1 expression was associated with worse recurrence-free, cancer specific and overall survival. On multivariate analysis PD-1 expression was an independent prognosticator of cancer specific survival (HR 1.7, 95% CI 1.03-2.66, p = 0.039) and overall survival (HR 1.5, 95% CI 1.05-2.24, p = 0.029) but not recurrence-free survival (HR 1.4, 95% CI 0.9-2.16, p = 0.139). On univariate analysis PD-L1 expression was not significantly associated with survival outcomes. However, on multivariate analysis in patients with organ confined disease (pT2 or less, pN0/x and cM0), PD-L1 positivity was an independent prognosticator of recurrence-free survival (HR 0.2, 95% CI 0.06-0.98, p = 0.046) and overall survival (HR 0.3, 95% CI 0.11-0.63, p = 0.003). CONCLUSIONS: PD-1 positivity of tumor-infiltrating lymphocytes was associated with adverse pathological criteria and independent prognostication of worse survival outcomes. PD-L1 positivity of tumor cells was an independent prognosticator of favorable survival outcomes in cases of organ confined disease.

The role of water-jet dissection in improving erectile function and urinary continence after nerve-sparing prostatectomy.

OBJECTIVES: The aim of this study was to assess erectile function (EF) and urinary continence (UC) recovery after nerve-sparing retropubic radical prostatectomy (NS-RRPE) and nerve-sparing laparoscopic radical prostatectomy (NS-LRPE) depending on the neurovascular bundle (NVB) dissection technique used. METHODS: Twenty-four hour pad test was used to assess the degree of postoperative UC 1, 6 and 12 months after the surgery. For the purpose of EF assessment, International Index of Erectile Function-5 (IIEF-5) questionnaire was used. In addition, EF recovery assessment included the time needed to achieve a successful sexual intercourse with or without Inhibitors Phosphodiesterase 5 (IPDE5). A successful sexual intercourse was defined as an ability to achieve a strong erection enough for penetration and maintain erection for a long time, throughout the intercourse. Assessment was performed before the surgery and 8 and 6 months after the surgery. RESULTS: In the patient group with BNS + water jet dissection (WJD), the IIEF-5 score was considerably higher 8 weeks after the surgery (by 2.8 points) (р = 0.02). In 6 months, the difference between the group become more significant and reached 3.5 points (p = 0.01). Three months after urethral catheter removal, majority (95%) of patients in the NS-RPE + WJD group had no urinary incontinence (UI). For standard NS-RPE, that figure was 87%. Mild stress UI was observed in 5% of patients after NS-RPE + WJD and in 13% of patients after NS-RPE. Six months after urethral catheter removal, no significant differences in UC assessment were observed in the two groups. CONCLUSIONS: The implementation of WJD of NVB in clinical practice has made it possible to considerably improve the quality of life for postoperative patients due to good outcomes in terms of early UC and EF recovery.

Transurethral contact ureterolithotripsy in gas (СО2) medium.

BACKGROUND: Transurethral intracorporeal lithotripsy is the modality of choice for the endoscopic disintegration of large, long-standing, radiolucent or high-density stones. Despite several advantages and proven benefits of contact ureterolithotripsy/ureterolithoextraction (CULT), the application of irrigation carries significant risks of untoward perioperative events including retrograde stone migration and postoperative pyelonephritis. METHODS: We describe a new technique - endoscopic intracorporeal lithotripsy in the gas (СО2) medium. It is a prospective randomized, single blinded pilot study that included total of (n = 60) patients with urolithiasis who were allocated to either experimental or control group. Out of the total pool of patients, 30 underwent treatment with the new approach (experimental group) and other 30 (control group) had contact ureterolithotripsy in a standard of care 0.9% NaCL medium. We included patients >18 years old, with known symptomatic renal calculi disease who were eligible and scheduled for CULT and free from significant coexisting pathologies of urinary tract. RESULTS: No retrograde migration of the stone fragments into the kidney was reported in the experimental group [complications rate 0%, confidence interval (CI): 0-11.6%]. In the control group, complications were observed in eight cases (complications rate 26.7%, CI: 14.7-42.3%); retrograde migration was in five patients (16.6%), and acute pyelonephritis/exacerbation of chronic pyelonephritis was seen in three (10%) patients. There was not any acute pyelonephritis in the experimental group. Reliability of frequency differences - p = 0.0023 (χ2). CONCLUSIONS: The novel method of contact ureterolithotripsy is a safe and promising alternative to the conventional contact ureterolithotripsy in a fluid medium in a carefully selected patient population.

Postoperative Nomogram for Relapse-Free Survival in Patients with High Grade Upper Tract Urothelial Carcinoma.

PURPOSE: We developed a prognostic nomogram for patients with high grade urothelial carcinoma of the upper urinary tract after extirpative surgery. MATERIALS AND METHODS: Clinical data were available for 2,926 patients diagnosed with high grade urothelial carcinoma of the upper urinary tract who underwent extirpative surgery. Cox proportional hazard regression models identified independent prognosticators of relapse in the development cohort (838). A backward step-down selection process was applied to achieve the most informative nomogram with the least number of variables. The L2-regularized logistic regression was applied to generate the novel nomogram. Harrell's concordance indices were calculated to estimate the discriminative accuracy of the model. Internal validation processes were performed using bootstrapping, random sampling, tenfold cross-validation, LOOCV, Brier score, information score and F1 score. External validation was performed on an external cohort (2,088). Decision tree analysis was used to develop a risk classification model. Kaplan-Meier curves were applied to estimate the relapse rate for each category. RESULTS: Overall 35.3% and 30.7% of patients experienced relapse in the development and external validation cohort. The final nomogram included age, pT stage, pN stage and architecture. It achieved a discriminative accuracy of 0.71 and 0.76, and the AUC was 0.78 and 0.77 in the development and external validation cohort, respectively. Rigorous testing showed constant results. The 5-year relapse-free survival rates were 88.6%, 68.1%, 40.2% and 12.5% for the patients with low risk, intermediate risk, high risk and very high risk disease, respectively. CONCLUSIONS: The current nomogram, consisting of only 4 variables, shows high prognostic accuracy and risk stratification for patients with high grade urothelial carcinoma of the upper urinary tract following extirpative surgery, thereby adding meaningful information for clinical decision making.

The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.