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To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy.We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival.The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004).Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Background The combination of multi-parametric MRI to locate and define suspected lesions together with their being targeted by an MRI-guided prostate biopsy has succeeded in increasing the detection rate of clinically significant disease and lowering the detection rate of non-significant prostate cancer. In this work we investigate the urologist’s learning curve of in-bore MRI-guided prostate biopsy which is considered to be a superior biopsy technique. Materials and methods Following Helsinki approval by The Chaim Sheba Medical Center ethics committee in accordance with The Sheba Medical Center institutional guidelines (5366-28-SMC) we retrospectively reviewed 110 IB-MRGpBs performed from 6/2016 to 1/2019 in a single tertiary center. All patients had a prostate multi-parametric MRI finding of at least 1 target lesion (prostate imaging reporting and data system [PI-RADS] score ≥ 3). We analyzed biopsy duration and clinically significant prostate cancer detection of targeted sampling in 2 groups of 55 patients each, once by a urologist highly trained in IB-MRGpBs and again by a urologist untrained in IB-MRGpBs. These two parameters were compared according to operating urologist and chronologic order. Results The patients’ median age was 68 years (interquartile range 62–72). The mean prostate-specific antigen level and prostate size were 8.6 ± 9.1 ng/d and 53 ± 27 cc, respectively. The mean number of target lesions was 1.47 ± 0.6. Baseline parameters did not differ significantly between the 2 urologists’ cohorts. Overall detection rates of clinically significant prostate cancer were 19%, 55%, and 69% for PI-RADS 3, 4 and 5, respectively. Clinically significant cancer detection rates did not differ significantly along the timeline or between the 2 urologists. The average duration of IB-MRGpB targeted sampling was 28 ± 15.8 min, correlating with the number of target lesions (p p Conclusions Our data suggest a very short learning curve for IB-MRGpB-targeted sampling duration, and that clinically significant cancer detection rates are not influenced by the learning curve of this technique.

Background: Numerous papers have described 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)’s sensitivity in identifying prostate cancer (PCa) recurrence. This study aimed to characterize the role of 68Ga-PSMA PET/CT in deciding to re-irradiate pelvic structures. Methods: 68Ga-PSMA PET/CT scans performed at Sheba Medical Center over seven years in 113 men were reviewed. All had undergone radiation to the prostate (70, 61.9%) or post-radical prostatectomy radiation to the prostate fossa (PF) (43, 48.1%), and had local or oligometastatic PCa recurrence and received salvage radiotherapy (SRT) based on PET/CT findings. Results: Mean age was 70.7 years. The mean grade group was 2.9; the mean prostate-specific antigen was 9.0. The 68Ga-PSMA PET/CT positive findings included: 37 (32.7%) in the prostate, 23 (20.4%) in seminal vesicles, 7 (6.2%) in the PF, and 3 (2.7%) in the seminal vesicle fossa. The mean standardized uptake value was 10.6 ± 10.2 (range: 1.4–61.6); the mean lesion size was 1.8 ± 3.5 mm (range: 0.5–5.1). SRT was directed toward the prostate and seminal vesicles in 48 (42.5%), PF in 18 (15.9%), and intrapelvic lymph node and bone in 47 (41.6%). Toxicities were mostly mild to moderate. Conclusion: 68Ga-PSMA PET/CT-identified relapse with targeted SRT was well-tolerated and may result in less onerous treatments.

Background: Laparoscopic (LP) and robot-assisted pyeloplasty (RAP) are minimally invasive techniques for correcting uretero-pelvic junction obstruction (UPJO). We retrospectively compared the clinical outcomes of all adults who underwent RAP (n = 41) to those who underwent LP (n = 24) for UPJO at our institution between 2003–2022. Methods: Age, sex, body mass index, surgical side, past abdominal/endoscopic surgeries, pre- and postoperative renal scans, pre- and postoperative serum creatinine levels, operative time (OT), presence of crossing vessels, estimated blood loss, postoperative complications, length of hospital stay, time to JJ stent removal, follow-up length, and postoperative hydronephrosis were analyzed. Results: The groups were demographically comparable. The mean total and skin-to-skin OTs (minutes) were significantly longer in the RAP group than in the LP group (242.4 ± 55 vs. 161.4 ± 40 p < 0.001; 163.7 ± 41.8 vs. 124.3 ± 30.3 p = 0.006, respectively). Hospital stay (days) was shorter in the RAP group (3.3 ± 2.1 vs. 7.3 ± 2.5 p < 0.001). Postoperative complication rates were identical for both groups. The LP group had a significantly longer follow-up period (85.2 ± 73 vs. 19 ± 14 months p < 0.001). The success rates for the LP and RAP groups were 87.5% and 90.6% (p = 0.708). Conclusions: RAP achieves equivalent results to LP, in adult patients. A longer OT may be expected with the robotic system since it can handle more complicated cases.

We thank the commenters for their important insights [...].

Objective Nephrectomy, the standard of care for localized renal cell carcinoma (RCC), may lead to kidney function loss. Our goal was to identify prognostic biomarkers of postoperative renal function using metabolomics. Methods Metabolomics data from benign kidney parenchyma were collected prospectively from 138 patients with RCC who underwent nephrectomy at a single institution. The primary endpoint was the difference between the postoperative and preoperative estimated glomerular filtration (eGFR) rate divided by the elapsed time (eGFR slope). eGFR slope was calculated ∼2 years post-nephrectomy (GFR1), and at last follow-up (GFR2). A multivariate regularized regression model identified clinical characteristics and abundance of metabolites in baseline benign kidney parenchyma that were significantly associated with eGFR slope. Findings were validated by associating gene expression data with eGFR slope in an independent cohort (n = 58). Results Data were compiled on 78 patients (median age 62.6 years, 65.4% males). The mean follow-up was 25 ± 3.4 months for GFR1 and 69.5 ± 23.5 months for GFR2 and 17 (22%) and 32 (41%) patients showed eGFR recovery, respectively. Nephrectomy type, blood lipids, gender and 23 metabolites from benign parenchyma were significantly associated with eGFR slope. Some metabolites associated with eGFR slope overlapped with previously reported chronic kidney disease-related processes. Subgroup analysis identified unique ‘metabolite signatures’ by older age, nephrectomy type and preoperative eGFR. Conclusions Nephrectomy type, gender, blood lipids and benign parenchyma metabolites at nephrectomy were associated with long-term kidney function. On further study, these metabolites may be useful as potential biomarkers and to identify novel therapeutic targets for malignancy-associated renal disease.

Purpose: to evaluate a unique subpopulation of radical prostatectomy (RP) candidates with “negative” prostate 68Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) imaging scans and to characterize the clinical implications of misleading findings. Materials and Methods: This case-control retrospective study compared the final histological outcomes of patients with “negative” pre-RP PSMA PET/CT prostate scans (with a prostate maximal standardized uptake value [SUVmax] below the physiologic uptake) to those with an “intense” prostatic tracer uptake (with a SUVmax above the physiologic uptake). The patients underwent an RP between March 2015 and July 2019 in five academic centers. Data on the demographics, comorbidities, prostate-specific antigen (PSA) and rectal exam findings, prior biopsies, imaging results, biopsies, and RP histology results were collected. Results: Ninety-seven of the 392 patients who underwent an RP had PSMA PET/CT imaging preoperatively. Fifty-two (54%) had a “negative” uptake (in the study group), and 45 (46%) had a “positive” uptake (in the control group). Only the lesion size and SUVmax values on the PSMA PET/CT differed between the groups preoperatively. On the histological analysis, only the ISUP score, seminal vesicles invasion, T stage, and positive margin rates differed between the groups (p < 0.05), while 50 (96%) study group patients harbored clinically significant disease (ISUP ≥ 2), with an extra-prostatic disease in 24 (46%), perineural invasion in 35 (67%), and positive lymph nodes in 4 (8%). Conclusions: Disease aggressiveness generally correlated with an intense PSMA uptake on the preoperative PSMA PET/CT, but a subpopulation of patients with clinically significant cancer and aggressive characteristics showed a deceptively weak PSMA uptake. These data raise a concern about the unqualified application of PSMA PET/CT for staging RP candidates.

Background Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells (human mesenchymal stromal cells [MSCs] and endothelial colony-forming cells [ECFCs]) may potentially result in in vivo formation of vascular networks. Methods We administered renal tubule-forming cells derived from human adult and fetal kidneys (previously shown to exert a functional effect in CKD mice) into mice, alongside MSCs and ECFCs. We then assessed whether this would result in generation of "renovascular units" comprising both vessels and tubules with potential interaction. Results Directly injecting vessel-forming cells and renal tubule-forming cells into the subcutaneous and subrenal capsular space resulted in self-organization of donor-derived vascular networks that connected to host vasculature, alongside renal tubules comprising tubular epithelia of different nephron segments. Vessels derived from MSCs and ECFCs augmented in vivo tubulogenesis by the renal tubule-forming cells. In vitro coculture experiments showed that MSCs and ECFCs induced self-renewal and genes associated with mesenchymal-epithelial transition in renal tubule-forming cells, indicating paracrine effects. Notably, after renal injury, renal tubule-forming cells and vessel-forming cells infused into the renal artery did not penetrate the renal vascular network to generate vessels; only administering them into the kidney parenchyma resulted in similar generation of human renovascular units in vivo. Conclusions Combined cell therapy of vessel-forming cells and renal tubule-forming cells aimed at alleviating renal hypoxia and enhancing tubulogenesis holds promise as the basis for new renal regenerative therapies.

To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10 mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. Included were 89 patients with D’Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3–10) mm and 1 (IQR 1–3) mm, respectively. PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

Introduction and Objective Adjuvant studies with checkpoint inhibitors have attracted new interest in accurate pathological lymph node (LN) staging in renal cell carcinoma. Sentinel lymph node (SN) studies in cN0 patients revealed the pattern of lymphatic radiotracer drainage from renal tumors. The aim of this study was to describe the location of single- or oligometastatic LN and analyze if the topography of these first landing sites matches the drainage pattern observed in SN studies of renal tumors. Materials and Methods We collected data from 8 referral centers from 1990 to 2018 of all patients with pT1-4 cN0 or cN1 M0 renal cell carcinoma with pathologically confirmed single- or oligometastases in locoregional LN. The location of LN metastases, number, size of metastatic LN, and survival were analyzed using descriptive statistics with SPSS version 22 (IBM, Chicago, IL). Results From 3,794 patients with histologically confirmed pN1, a total of 76 patients (2%) with single- or oligometastatic pN1 were identified, of whom 24 (31.6%) and 52 (68.4%) were cN0 and cN1, respectively. On the left side, LN metastases were predominantly located in the para-aortal (48.0%; 95% confidence interval [CI] 29.22–63.12%) and hilar (31.42%; 95% CI 17.4–49.4%) area. On the right side, metastases located in retrocaval (26.82%; 95% CI 14.7–43.2%), hilar (26.82%; 95% CI 14.7–43.2%), interaortocaval (26.82%; 95% CI 14.7–43.2%), and paracaval (17.07%; 95% CI 7.6–32.6%) LNs. These landing sites exactly matched the lymphatic drainage pattern of intratumorally injected radiotracer reported in SN studies for both sides. Conclusions Single- or oligometastatic LNs in renal cancer are mainly located in the hilar, retro-, para, and interaortocaval region on the right side and para-aortal region on the left side. These first landing sites match the drainage pattern reported in SN trials.

Initial deleterious effects of the COVID-19 pandemic on urologic oncology surgeries are well described, but the possible influence of vaccination efforts and those of pandemic conditions on surgical volumes is unclear. Our aim was to examine the association between changing vaccination status and COVID-19 burden throughout the pandemic and the volume of urologic oncology surgeries in Israel. This multi-center cross-sectional study included data collected from five tertiary centers between January 2019 and December 2021. All 7327 urologic oncology surgeries were included. Epidemiological data were obtained from the Israeli Ministry of Health database. A rising trend in total urologic oncology surgery volumes was observed with ensuing COVID-19 wave peaks over time (X2 = 13.184, df = 3, p = 0.004). Total monthly surgical volumes correlated with total monthly hospitalizations due to COVID-19 (R = −0.36, p = 0.015), as well as with the monthly average Oxford Stringency Index (R = −0.31, p = 0.035). The cumulative percent of vaccinations and of new COVID-19 cases per month did not correlate with total monthly urologic surgery volumes. Our study demonstrates the gradual acclimation of the Israeli healthcare system to the COVID-19 pandemic. However, hospitalizations due to COVID-19, as well as restriction stringency, correlate with lower volumes of urologic oncological surgeries, regardless of the population’s vaccination status.

Partial nephrectomy is the gold standard treatment for renal tumors less than 7 cm.To describe surgical techniques and trends of treating renal tumors less than 7 cm at our department and present the clinical outcomes of our experience with Robot-Assisted Partial Nephrectomy (RAPN).Out of an established prospective RAPN database, we retrieved demographic, clinical, surgical and pathological parameters. Operation length was defined as the time between the first surgical incision and the last suture (skin to skin). Warm ischemia time (WIT) was defined as the time between the renal artery clamping and clamp releasing. Data is presented as mean (range, standard deviation) or numeric value (%).Overall, 250 RAPN cases were recorded between the years 2013-2020. Mean tumor size was 32 mm. Mean operation length was 153 minutes. Mean warm ischemia time was 17.5 minutes. Intra-operative complication rates, including converting the surgery to an open approach or to radical nephrectomy, was low. Mean estimated blood loss was 359 cc. An increase in the utilization of the robotic approach has been recorded throughout the years, with a concurrent decrease in the open and laparoscopic approaches.RAPN is associated with lower complication rates and superior perioperative outcomes, therefore considered a good alternative to the open and laparoscopic approaches. Thus, RAPN is the gold standard treatment for renal tumors less than 7 cm at our institute.

Focal treatment for prostate cancer has been proposed as an innovative strategy that aims to achieve oncological benefit while reducing treatment-related morbidity. This treatment is suitable for patients with low and intermediate risk, organ-confined disease. Focal therapy can be categorized as follows: unifocal index lesion ablation, multifocal ablation, hemi-gland ablation or subtotal gland ablation. Different types of energies are applied in focal therapy including high intensity focal ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE) and Photodynamic therapy (PDT). In this review we will briefly present a summary of leading techniques and the available data regarding their oncological outcomes and adverse events. Whole-gland therapies were excluded from this review.

Urinary Incontinence (UI) following Robot-Assisted Laparoscopic-Radical Prostatectomy (RALP) adversely affects patients' quality of life.To find parameters that predict full urinary continence (FUC) following RALP.Out of an established prospective RALP database, we retrieved and analyzed parameters that potentially predict FUC: age, Body Mass Index, American Anesthesiology Association (ASA) score, previous abdominal surgeries, pre-operative IPSS (International Prostate-Symptom Score), operative time (OT), estimated blood loss (EBL), peritoneum closure and prostate weight. FUC has been defined as 0 pads/day. Univariate analysis has been executed for comparison between patient groups, whereas multivariate analysis has been implemented for the detection of predicting factors for FUC. Data are presented as median (interquartile range) or numeric value (%).A total of 431 RALP cases were recorded between the years 2010-2019. Final analysis included 364 patients with full medical records; 81% gained FUC within 15 weeks (8-28); 96% gained FUC or used 1 pad/day within 17.5 weeks (8-36). Among those who gained FUC, smaller prostates (p=0.028) and low EBL (p=0.025) have been observed. On multivariate analysis EBL has been associated with UI (OR=0.9).Most patients gained FUC following RALP. EBL was found as risk factor for UI.

OBJECTIVE To investigate the effectiveness of combination treatment of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 immunotherapy in a mouse model of urothelial carcinoma. METHODS We used C57BL/6 mice injected with murine bladder 49 cell line. Mice were randomly allocated into four treatment groups: vascular targeted photodynamic therapy only, anti-cytotoxic T-lymphocyte-associated antigen 4 only, combination therapy and control. We carried out three separate experiments that used distinct cohorts of mice: tumor growth and development of lung metastases monitored with bioluminescent imaging (n = 91); survival evaluated with Kaplan-Meier curves (n = 111); and tumor cell population studied with flow cytometry (n = 20). In a fourth experiment, we re-challenged tumors in previously treated mice and compared tumor growth with that of naive mice. RESULTS Combination therapy provided significant benefits over the other three treatment groups: prolonged survival (P

While penile metastases are rare, PET/CT has facilitated their detection. We aimed to describe penile secondary lesions (PSL) identified by PET/CT. We reviewed 18F-FDG and Ga68-PSMA PET/CT records performed in a single center during May 2012-March 2020, for PSL. Of 16,774 18F-FDG and 1,963 Ga68-PSMA-PET scans, PSL were found in 24(0.13%) men with a mean age of 74. PSMA detected PSL in 12 with prostate cancer; FDG identified PSL in 4 with lymphoma, 3 with colorectal cancer, 2 with lung cancer, and one each with bladder cancer, pelvic sarcoma, and leukemia. Mean SUVmax of PSL was 7.9 ± 4.2 with focal uptake in 13(54%). Mean lesion size was 16.5 ± 6.8 mm; 8 at the penile root, 4 along the shaft, and 1 at the glans. CT detected loss of the penile texture in 15(63%). PSL were observed only during relapse or follow-up of disseminated disease. Among those with prostate cancer, PSA varied widely. Fifteen (62.5%) died, at a mean 13.3 ± 15.9 months following PSL demonstration, nine had non-prostate malignancies. PET/CT identified and characterized PSL in a fraction of cancer patients, most commonly those with prostate cancer. PSL universally surfaced in advanced disease, and signaled high mortality, especially in non-prostate cancers.

Little is known about oncologic outcomes following robot-assisted-radical-prostatectomy (RALP) for clinical T3 (cT3) prostate cancer.To investigate oncologic outcomes of patients with cT3 prostate cancer treated by RALP.Medical records of patients who underwent RALP from 2010 to 2018 were retrieved. cT3 cases were reviewed. Demographic and pre/postoperative pathology data were analyzed. Patients were followed in 3-6 month intervals with repeat PSA analyses. Adjuvant/salvage treatments were monitored. Biochemical recurrence (BCR) meant PSA levels of ≥ 0.2 ng/ml.Seventy-nine patients met inclusion criteria. Median age at surgery was 64 years. Preoperative PSA level was 7.14 ng/dl, median prostate weight was 54 grams, and 23 cases (29.1%) were down-staged to pathological stage T2. Positive surgical margin rate was 42%. Five patients were lost to follow-up. Median follow-up time for the remaining 74 patients was 24 months. Postoperative relapse in PSA levels occurred in 31 patients (42%), and BCR in 28 (38%). Median time to BCR was 9 months. The overall 5-year BCR-free survival rate was 61%. Predicting factors for BCR were age (hazard-ratio [HR] 0.85, 95% confidence interval [95%CI] 0.74-0.97, P = 0.017) and prostate weight (HR 1.04, 95%CI 1.01-1.08, P = 0.021). Twenty-six patients (35%) received adjuvant/salvage treatments. Three patients died from metastatic prostate cancer 31, 52, and 78 months post-surgery. Another patient died 6 months post-surgery of unknown reasons. The 5-year cancer-specific survival rate was 92.RALP is an oncologic effective procedure for cT3 prostate cancer. Adjuvant/salvage treatment is needed to achieve optimal disease-control.

Objective To assess the outreach and influence of the main recommendations of surgical governing bodies on adaptation of minimally invasive laparoscopic surgery (MIS) procedures during the coronavirus disease 2019 (COVID-19) pandemic in an anonymized multi-institutional survey. Materials and Methods International experts performing MIS were selected on the basis of the contact database of the speakers of the Friends of Israel Urology Symposium. A 24-item questionnaire was built using main recommendations of surgical societies. Total cases/1 Mio residents as well as absolute number of total cases were utilized as surrogates for the national disease burden. Statistics and plots were performed using RStudio v0.98.953. Results Sixty-two complete questionnaires from individual centers performing MIS were received. The study demonstrated that most centers were aware of and adapted their MIS management to the COVID-19 pandemic in accordance to surgical bodies’ recommendations. Hospitals from the countries with a high disease burden put these adoptions more often into practice than the others particularly regarding swabs as well as CO2 insufflation and specimen extraction procedures. Twelve respondents reported on presumed severe acute respiratory syndrome coronavirus 2 transmission during MIS generating hypothesis for further research. Conclusion Guidelines of surgical governing bodies on adaptation of MIS during the COVID-19 pandemic demonstrate significant outreach and implementation, whereas centers from the countries with a high disease burden are more often poised to modify their practice. Rapid publication and distribution of such recommendation is crucial during future epidemic threats.

Introduction: We aimed to compare systematic biopsies (SBs) of in-bore magnetic resonance-guided prostate biopsy (MRGpB) with those performed under transrectal ultrasound (TRUS) guidance in the clinical setting. Methods: Data on all 161 consecutive patients undergoing prostate biopsy in our institution between November 2017 and July 2019 were retrospectively collected. The patients were referred to biopsy due to elevated prostate-specific antigen (PSA) and/or abnormal digital rectal examination and/or at least one Prostate Imaging Reporting and Data System (PI-RADS) lesion score of ≥3 on multiparametric magnetic resonance imaging (mpMRI). We included patients with PSA levels ≤20 ng/ml and those with 8–12 core biopsies. Histology results of SBs performed by in-bore MRGpB were compared to TRUS SBs. Chi-squared, Fischer’s exact, and multivariate Pearson regression tests were used for statistical analysis (SPSS, IBM Corporation). Results: In total, 128 patients were eligible for analysis. Their median age was 68 years (interquartile range [IQR] 61.5–72), mean prostate size 55±29 cc, and mean PSA and PSA density levels 7.6±3.5 ng/ml and 0.18±0.13 ng/ml/cc, respectively. Thirty-five patients (27.3%) had suspicious digital rectal examination findings. Both biopsy groups were similar for these parameters. Thirty-eight (62.3%) MRGpB patients had a previous biopsy vs. 5 (7.1%) TRUS-SB patients (p

Importance The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population. Objective To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers. Design, Setting, and Participants Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Clinical data and pathologic characteristics were collected. Main Outcomes and Measures BRCA1/2 status was the outcome in a logistic regression, and cancer diagnoses were the independent predictors. All odds ratios (ORs) were adjusted for age, country of origin, and calendar year of the first interview. Results Among the 6902 men in the study (median [range] age, 51.6 [18-100] years), 1634 cancers were diagnosed in 1376 men (19.9%), the majority (922 of 1,376 [67%]) being BRCA2 PV carriers. Being affected by any cancer was associated with a higher probability of being a BRCA2, rather than a BRCA1, PV carrier (OR, 3.23; 95% CI, 2.81-3.70; P

Purpose Prostate multiparametric magnetic resonance imaging (mpMRI) improves diagnosis of clinically significant cancer and reduces over-detection of nonsignificant cancer. Disagreement in the interpretation of mpMRI readings is well-known, with a reported discrepancy rate of 10% to 42%. We report the clinical repercussions of this variability on prostate biopsy candidates. Materials and Methods Medical records of patients referred from 11 medical centers for MR-guided prostate biopsy (MRGpB) between October, 2017 and January, 2019 were retrospectively analyzed. Patients with at least one prostate imaging reporting and data system (PI-RADS) 3 or greater prostate lesion were selected, and the mpMRI studies (all read by others) were reviewed by our prostate mpMRI reader. Outcomes included changes in PI-RADS score and the subsequent effect on total needle samples and indication for biopsy. Results Eighty-two patients with 128 lesions were suitable for analysis (mean age 66.5 ± 7.1 years, mean PSA 6.8 ± 8.5 ng/ml). Nine (11%) patients had suspicious rectal exams (T2a). Following our prostate mpMRI reader's imaging revisions, the PI-RADS score was downgraded in 66 (52%) lesions, upgraded in 15 (12%), and unchanged in 47 (37%), leaving a total of 84 suspected lesions (kappa = 0.17). Biopsy was deferred in 22 (27%) patients, and an estimated 136.4 (34.4%) samples were avoided (P = 0.0001 for both). There was a trend toward prostate size to correlate with imaging revision and abortion of biopsy (P = 0.06) while enrollment in active surveillance correlated with proof from such outcome (P = 0.007). Conclusion These data suggest that high interobserver disagreement in prostate mpMRIs from diverse institutes significantly affects prostate biopsy practice. The clinical consequences of this discord are significant.

To compare the ability ofA multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged ( 10 mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value.Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively.PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

INTRODUCTION AND OBJECTIVE:Nephrectomy, the standard of care for localized renal cell carcinoma (RCC), may lead to kidney function loss. To identify prognostic biomarkers of postoperative renal fun...

Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism.We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria.Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range (R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association (R = 0.92) compared to patients with only a single criterion (R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated.Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia.

Background: The substantial burden of kidney disease fosters interest in new ways of screening for early disease diagnosis, especially by non-invasive imaging. Increasing evidence for an association between retinal microvascular signs and kidney disease prompted us to investigate the relevant current literature on such an association systematically by performing a meta-analysis of our findings. Methods: We scrutinized the current literature by searching PubMed and Embase databases from for clinical studies of the association between retinal microvascular signs and prevalent or incident kidney disease. After excluding cases that did not meet our criteria, we extracted relevant data from 42 published studies (9 prospective, 32 cross-sectional, and 1 retrospective). Results: Our investigation yielded significant associations between retinal vascular changes (including retinopathy and retinal vascular diameter) and kidney dysfunction (including chronic kidney disease (CKD), end-stage renal disease (ESRD), albuminuria, and estimated glomerular filtration rate (eGFR) decline). According to our meta-analysis, retinopathy was associated with ESRD (hazard ratio (HR) 2.12 (95% confidence interval CI; 1.39–3.22)) and with CKD prevalence in the general population (odds ratio (OR) 1.31 (95% CI; 1.14–1.50)), and specifically in type 2 diabetic patients (OR 1.68 (95% CI; 1.68–2.16)). CRAE was associated with prevalent CKD (OR 1.41 (95% CI; 1.09–1.82)). Conclusions: Our findings suggest that the retinal microvasculature can provide essential data about concurrent kidney disease status and predict future risk for kidney disease development and progression.

Objective To describe clinical management and outcomes of a cohort of patients with malignant mesothelioma of the tunica vaginalis testis (MMTVT) who received treatments beyond radical orchiectomy. Methods Patients with confirmed MMTVT at a single tertiary care institution were identified. Treatments, pathologic outcomes, and survival were recorded. Prognostic variables associated with survival were analyzed with a Cox proportional hazards model and Kaplan-Meier curves. Results Overall, 15 patients were included. Initial presentation was a scrotal mass in 7 of 15 (47%) and hydrocele in 5 of 15 (33%) patients. Clinical staging revealed enlarged nodes in 5 of 15 (33%) patients. Radical orchiectomy was the initial treatment in 5 of 15 (33%) patients. Positive surgical margins were found in 6 of 14 (43%) radical orchiectomies and were associated with worse survival (P = .007). The most frequent histologic subtype was epithelioid, associated with better survival (P = .048). Additional surgeries were performed on 12 of 15 (80%) patients. Pathologic examination revealed MMTVT in 6 of 12 (50%) hemiscrotectomies, 7 of 8 (88%) retroperitoneal lymph node dissections, 1 of 7 (14%) pelvic lymph node dissections, and 10 of 10 (100%) groin dissections. Five patients received adjuvant chemotherapy. Two also received adjuvant radiation therapy. Three patients with lymph node involvement remain no evidence of disease over 6 years after diagnosis. After a median follow-up of 3.5 years (interquartile range: 1.2-7.2), 5 patients have died, all of MMTVT; the median overall survival has not been reached. Common sites of relapse were lungs (5 of 7) and groin (3 of 7). Conclusion The pattern of metastatic spread of MMTVT is predominantly lymphatic. Nodes in the retroperitoneum and the groin are commonly involved. Prognosis is poor, but there may be a role for aggressive surgical resection including hemiscrotectomy, and inguinal and retroperitoneal lymph nodes.

Background To compare quality of life (QoL) indices between ureteral stent (DJS) and nephrostomy tube (PCN) inserted in the setting of acute ureteral obstruction. Methods Prospective bi-centered study. Over the span of 2 years, 45 DJS and 30 PCN patients were recruited. Quality of life was assessed by 2 questionnaires, EuroQol EQ-5D and ‘Tube symptoms’ questionnaire, at 2 time points (at discharge after drainage and before definitive treatment). Results Patients’ demographics and pre-drainage data were similar. There were no clinically significant differences in patient’s recovery between the groups, including post procedural pain, defeverence, returning to baseline renal function, and septic shock complications. More DJS patients presented to the emergency room with complaints related to their procedure compared to PCN patients. At first, DJS patients complained more of urinary discomfort while PCN patients had worse symptoms relating to mobility and personal hygiene, with both groups achieving similar overall QoL score. At second time point, PCN patients’ symptoms ameliorated while symptoms in the DJS group remained similar, translating to higher overall QoL score in the PCN group. Conclusions The two techniques had a distinct and significantly different impact on quality of life. Over time, PCN patients’ symptoms relieve and their QoL improve, while DJS patients’ symptoms persist. Specific tube related symptoms, and their dynamics over time, should be a major determinant in choosing the appropriate drainage method, especially when definitive treatment is not imminent. Electronic supplementary material The online version of this article (10.1186/s12894-019-0510-4) contains supplementary material, which is available to authorized users.

Highlights • Senior urologic-oncology surgeons worldwide risk-stratify clinic and surgeries under COVID-19. • COVID-19 pandemic significantly decreased planned attendance at professional meetings. • COVID-19 pandemic has not affected mentors’ approach towards medical education of trainees. • International committee to create a directive for coping with future challenges is advised., Objective: Ad-hoc guidelines for managing the COVID-19 pandemic are published worldwide. We investigated international applications of such policies in the urologic-oncology community. Methods: A 20-item survey was e-mailed via SurveyMonkey to 100 international senior urologic-oncology surgeons. Leaders’ policies regarding clinical/surgical management and medical education were surveyed probing demographics, affiliations, urologic-oncologic areas of interest, and current transportation restrictions. Data on COVID-19 burden were retrieved from the ECDC. Statistical analyses employed non-parametric tests (SPSS v.25.0, IBM). Results: Of 100 leaders from 17 countries, 63 responded to our survey, with 58 (92%) reporting university and/or cancer-center affiliations. Policies on new-patient visits remained mostly unchanged, while follow-up visits for low-risk diseases were mostly postponed, for example, 83.3% for small renal mass (SRM). Radical prostatectomy was delayed in 76.2% of cases, while maintaining scheduled timing for radical cystectomy (71.7%). Delays were longer in Europe than in the Americas for kidney cancer (SRM follow-up, P = 0.014), prostate cancer (new visits, P = 0.003), and intravesical therapy for intermediate-risk bladder cancer (P = 0.043). In Europe, COVID-19 burden correlated with policy adaptation, for example, nephrectomy delays for T2 disease (r = 0.5, P =0.005). Regarding education policies, trainees’ medical education was mainly unchanged, whereas senior urologists' planned attendance at professional meetings dropped from 6 (IQR 1−11) to 2 (IQR 0−5) (P < 0.0001). Conclusion: Under COVID-19, senior urologic-oncology surgeons worldwide apply risk-stratified approaches to timing of clinical and surgical schedules. Policies regarding trainee education were not significantly affected. We suggest establishment of an international consortium to create a directive for coping with such future challenges to global healthcare.

Upper urinary tract urothelial carcinomas (UTUC) tend to be present at higher age and are more often high grade with over 60% of UTUCs found to be invasive at diagnosis. In addition, concurrent bladder cancer, bladder recurrence, and contralateral UTUC can further complicate the disease course. Radical nephroureterectomy (RNU) is considered the gold standard treatment for UTUC although conservative management with kidney-sparing surgery is considered an acceptable alternative for low-risk cases. Considering the natural history of UTUC, its potentially aggressive clinical course, and accordingly, the rigorous recommendations for follow-up, there is a strong rationale applying advanced technological techniques in order to optimize cancer detection and treatment. Narrow band imaging (NBI) is an optical image enhancement technology introduced in the early 2000s. NBI uses optical filters for RGB (Red, Green, and Blue) sequential illumination and narrows its bandwidth of the spectral transmittance. The reconstructed images created are different from each of the three channels (R, G, and B) and correspond to different layers of the mucosa. The role of NBI in cystoscopy and bladder cancer was subject to several publications in the past decade, showing higher detection rate in several clinical scenarios. This chapter will cover the role for NBI in the context of urothelial cancer, focusing on upper urinary tract cancer.

Background and objectives Pre-operative kidney volume is an independent predictor of glomerular filtration rate in renal cell carcinoma patients. Compensatory renal growth (CRG) can ensue prior to nephrectomy in parallel to tumor growth and benign parenchyma loss. We aimed to test whether renal metabolite abundances significantly associate with CRG, suggesting a causative relationship. Design, setting, participants, and measurements Tissue metabolomics data from 49 patients, with a median age of 60 years, were previously collected and the pre-operative fold-change of their contra to ipsi-lateral benign kidney volume served as a surrogate for their CRG. Contra-lateral kidney volume fold-change within a 3.3 +/- 2.1 years follow-up interval was used as a surrogate for long-term CRG. Using a multivariable statistical model, we identified metabolites whose abundances significantly associate with CRG. Results Our analysis found 13 metabolites in the benign (e.g. L-urobilin, Variable Influence in Projection, VIP, score = 3.02, adjusted p = 0.017) and 163 metabolites in the malignant (e.g. 3-indoxyl-sulfate, VIP score = 1.3, adjusted p = 0.044) tissues that significantly associate with CRG. Benign/tumor fold change in metabolite abundances revealed three additional metabolites with that significantly positively associate with CRG (e.g. p-cresol sulfate, VIP score = 2.945, adjusted p = 0.033). At the pathway level, we show that fatty-acid oxidation is highly enriched with metabolites whose benign tissue abundances strongly positively associate with CRG, both pre-operatively and long term, whereas in the tumor tissue significant enrichment of dipeptides and benzoate (positive association), glycolysis/gluconeogenesis, lysolipid and nucleotide sugar pentose (negative associations) sub-pathways, were observed. Conclusion These data suggest that specific biological processes in the benign as well as in the tumor parenchyma strongly influence compensatory renal growth.

BACKGROUND Prior studies examining the value of lymph node (LN) dissection (LND) in patients with urothelial carcinoma of the upper urinary tract (UTUC) have produced conflicting results. The objective of the current study was to assess the relationship between LN yield and survival among patients undergoing radical nephroureterectomy (RNU). METHODS The National Cancer Data Base was used to identify patients with non-metastatic UTUC who were treated with RNU between 2004 and 2012. The association between LN yield and overall survival (OS) was assessed using Cox proportional hazards regression, with adjustment for patient, tumor, and facility characteristics. RESULTS Of the 14,472 patients, 2926 (20%) underwent LND. The median yield was 2 LNs (interquartile range 1-6 LNs). Among the entire cohort and the LN-negative (pN0) subgroup, a higher LN yield was associated with lower all-cause mortality (multivariable hazard ratio [HR] 0.94 per 5 LNs removed, 95% confidence interval [95% CI] 0.89-1.00 [P = .034] for the entire cohort and HR 0.86, 95% CI 0.79-0.94 [P = .001] for the pN0 subgroup). Among patients with positive LNs (pN+), there was no association noted between LN yield and OS; however, positive and negative LN counts were found to be independent predictors of OS (HR 1.27 per 5 positive LNs, 95% CI 1.16-1.39 [P

Introduction: Ureteral strictures can result in obstructive nephropathy and renal function deterioration. Surgical management of ureteral defects, especially in the proximal- and mid-ureter, is particularly challenging. Our purpose was to analyze the long-term outcomes of urothelial-based reconstructive surgery for upper- and mid-ureteral defects.Methods: We conducted a retrospective analysis of a single tertiary centre’s database, including 149 patients treated for ureteral defects between 2001 and 2011. Thirty-one patients (21%) underwent complex urothelial-based surgical repairs for upper- and mid-ureter defects. Patients’ median age was 61 years. The mean length of the ureteral strictures was 2.5 cm, located in upper-, mid-ureter, or in between in 19 (61%), 10 (32%), and two (6%) patients, respectively. All patients were treated with a primary urothelial-based repair. Median followup time was 26 months. The primary outcome of the study was the long-term preservation of renal function and lack of clinical obstruction. The secondary endpoint of the study was the assessment of the intra- and postoperative complication rates.Results: Most of the lesions were benign (22, 71%), while nine strictures (29%) were malignant. Seven patients (23%) suffered from postoperative complications, five of which were infectious. The median pre- and postoperative calculated glomerular filtration rates were 66 ml/min/1.72m2 and 64ml/min/1.72m2, respectively. Success rate was 84%, defined as lack of need for re-operation or kidney drainage at the last followup.Conclusions: Upper- and mid-ureteral defects present a complex pathology necessitating experienced reconstructive surgical skills. Our data suggest good long-term results for primary urothelialbased reconstructions for these pathologies.

Objectives: To evaluate the current incidence, risk factors, management, and long-term follow-up of urinary leakage following partial nephrectomy, in order to propose an algorithm for diagnosis and evaluation of postoperative urinary leakage. Materials and Methods: The study included 752 patients who underwent elective partial nephrectomies for renal masses between the years 1988 and 2013. Patients’ demographics, clinico-pathologic variables, and operative details were collected retrospectively. The associations between urinary leakage and patients’ variables were assessed by univariate and multivariate analyses. Results: Of the 752 patients, 21 (2.8%) experienced urinary leakage; 4 of the 21 patients with urinary leakage had spontaneous resolution, 1 patient underwent nephrectomy, and 16 patients were treated by retrograde ureteral stents insertion. One of them necessitated insertion of an additional percutaneous nephrostomy and another one deserved concomitant percutaneous drainage of a perirenal urinoma. The average period of time that elapsed from the operation until the insertion of stent was 8.5 ± 4.5 days. Stents were removed 68 ± 20.5 days postoperatively. None of the patients had either persistent or repeated leakage. On univariate analysis, hilar renal masses (p Conclusion: None of the preoperative variables that were examined in this study was significantly associated with increased risk of urinary leakage. However, cumulative surgical experience was associated with lower rates of urinary leakage, suggesting that the decrease in its incidence is related to the improved surgical skills, rather than to differences in tumors’ or patients’ characteristics.