Leonid Rapoport

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.

RETROSPECTIVE ANALYSIS OF SHORT-TERM OUTCOMES AFTER MONOPOLAR VERSUS LASER ENDOSCOPIC ENUCLEATION OF THE PROSTATE: A SINGLE CENTER EXPERIENCE

INTRODUCTION Endoscopic enucleation of the prostate (EEP) has been recognized as a viable treatment modality for men with benign prostatic hyperplasia (BPH). The aim of our study was to compare the efficacy and functional outcomes of three different techniques of EEP, including monopolar enucleation (MEP), holmium laser enucleation of the prostate (HoLEP), and thulium laser enucleation of the prostate (ThuLEP). METHODS The study consisted of a retrospective comparison of pre- and postoperative parameters in men undergoing three types of EEP: MEP, HoLEP, and ThuLEP. Functional parameters were evaluated before and 6 months after surgery, which included the International Prostate Symptom Score, maximum flow rate, postvoid residual volume, prostate volume, and sodium levels of all patients. RESULTS A total of 551 men with the mean age of 67.1 years were included in the study. Of these, MEP was performed on 95 patients, HoLEP was performed on 254 patients, and ThuLEP on 202 patients. The mean mass of morcellated tissue obtained during the three techniques did not differ significantly (p > 0.05). Mean procedure times of ThuLEP and HoLEP were shorter than MEP demonstrating 72, 76, and 86 minutes, respectively (p < 0.01). The mean catheterization time following laser EEPs was shorter than MEP as shown by 1.3, 1.3, and 3.8 days, respectively (p < 0.01). Hospital stay times of HoLEP and ThuLEP were shorter than MEP demonstrated by 3.3, 3.4, and 6.9 days, respectively (p < 0.01). Patients after MEP had significant decrease in postoperative hemoglobin and sodium levels. All the groups showed statistically significant improvement in the aforementioned parameters following treatment. CONCLUSIONS Both techniques of laser enucleation proved to be efficacious in the management of BPH. MEP of the prostate seems to be a highly promising addition to the list of enucleation techniques and was determined to be an effective and acceptable procedure, despite a higher complication rate.

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.

A randomized trial comparing the learning curve of three endoscopic enucleation techniques (HoLEP, ThuFLEP and MEP) for BPH using mentoring approach – initial results

OBJECTIVE To assess the differences in the learning curve associated with different techniques of endoscopic enucleation of the prostate. MATERIALS AND METHODS Ninety patients were randomly assigned into 3 groups (30 patients in each): HoLEP, ThuFLEP or MEP. Inclusion criteria for the study included prostate volume <80 cc, IPSS > 20, or Qmax < 10. The EEPs were performed by 3 surgeons experienced in transurethral resection of the prostate. Assignment of surgeons to surgical technique was also randomized. None of the surgeons had prior experience in EEP. RESULTS ThuFLEP was slightly superior (with no significant difference [P > .05]) to HoLEP and MEP in terms of overall enucleation rate-1.0 g/min vs 0.8 g/min and 0.7 g/min, respectively. We observed similar enucleation rates at the initial stages of training (first 20 surgeries) with insignificant increase in ThuFLEP efficiency. At next 10 surgeries ThuFLEP and HoLEP efficiency were higher than of MEP (P < .001) without significant difference between techniques of laser EEP (P = .07). CONCLUSION Endoscopic enucleation of the prostate can be adopted safely and effectively within 30 surgeries if the technique is learned with a mentoring approach. EEP is shown to be safe and effective even in the initial stages of learning. Laser EEP (HoLEP, ThuFLEP) appears to lend itself to quicker adaptation compared MEP.

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.

MP24-10 WAVELENGTH AND PULSE SHAPE EFFECTS ON STONE FRAGMENTATION OF LASER LITHOTRIPTERS

34 and 2, respectively. Compare to direct sequence, 9 patients were reclassified into the novel genotype. However, overall 19.6% of patients still not fit into an autosomal recessive inheritance, with 2 patients possessed no mutation. CONCLUSIONS: Among 51 patients, 8 novel mutations were identified and 9 patients were reclassified into a novel genotype. However, 20% of patients did not fit into autosomal recessive genotype. Current data may suggest the potential contribution of another factor in the pathogenesis of Cystinuria.

PD42-07 COMPARATIVE IN VITRO STUDY OF HO:YAG AND TM FIBER LASER LITHOTRIPTERS IN DUSTING MODE OF OPERATION

presented as an interval scale ranging from 0 to 5 with 5 being the best response possible. We tested the instrument at our institution by administering it after routine upper tract stone cases utilizing a flexible ureteroscope. Three flexible ureteroscope categories were evaluated including: fiberoptic (Olympus URF-P5/P6), reusable digital (Storz Flex Xc), and the LithoVue disposable digital (Boston Scientific). Any urologist or trainee who used the ureteroscope during the procedure was allowed to evaluate the ureteroscope. The instrument was completed independently of each other and opinions about the ureteroscope were not discussed during the procedure. Internal consistency was assessed with Cronbach’s alpha and Pearson correlation coefficients were calculated to describe the linear relationship between items. Multivariate analyses were done to assess responses. RESULTS: A total of 34 upper tract stone cases were performed resulting in 79 evaluations. The Storz digital scored the highest of the three ureteroscopes. The image quality was very good on the LithoVue outside the patient, but we did notice some distortion when performing laser lithotripsy that impaired vision. We found no difference in the ease of ureteral access between the ureteroscopes. The instrument demonstrated internal consistency (Cronbach’s alpha 1⁄4 0.85). The mean inter-item Pearson correlation coefficient was 0.46 (0.10 to 0.88), the highest of which related maneuverability to overall satisfaction (0.88). Respondents who had completed residency scored the ureteroscopes significantly lower in the areas of maneuverability, intuitiveness and overall satisfaction (P 1⁄4 0.019, 0.003, and 0.046 respectively). CONCLUSIONS: We report our results from a pilot study evaluating a novel flexible ureteroscope evaluation instrument during clinical use. All ureteroscopes performed well on our evaluation instrument during clinical use. Further validation is needed to assess the quality of this evaluation instrument.

Near-infrared fluorescence with indocyanine green for diagnostics in urology: initial experience.

Introduction Fluorescence imaging with indocyanine green is used in urology for the detection of sentinel lymph nodes and identification of prostate margins in radical prostatectomy for delineation of resection zone and selective clamping of vessels in partial nephrectomy; for identification and evaluation of length of ureteral strictures; for assessment of perfusion and viability of anastomoses during reconstructive stage of cystectomy. Safety of this technique is proven, while its diagnostic value and usefulness is still controversial. Methods This pilot study of using the SPY Elite Fluorescence Imaging System for diagnostics was performed in the I.M. Sechenov First Moscow State Medical University. Ten patients were enrolled: four patients underwent retropubic RP and lymph node dissection, five patients underwent partial nephrectomy, and one patient underwent ureteroplasty. Fluorophore was injected transrectally with TRUS guidance during RP in order to assess the lymph nodes. During partial nephrectomy, the compound was injected intravenously to differentiate the tumor from parenchyma by its blood supply. During ureteroplasty, the indocyanine green solution was injected into the renal pelvis to dye the ureter and locate the stricture. Results Sensitivity of this technique for visualization of sentinel lymph nodes was 100%, and specificity was 73.3%. In patients who underwent partial nephrectomy, all lesions were malignant and hypofluorescent when compared with healthy parenchyma. SPY allowed us to determine the location and extension of the stricture during ureteroplasty. No hypersensitivity reactions or complications were observed during injection of the compound.

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.