The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Voiding Cystourethrogram Before Pyeloplasty: To Do or Not To Do?

OBJECTIVE: To assess the incidence of concomitant vesicoureteral reflux (VUR) in unilateral cases of ureteropelvic junction obstruction (UPJO) and to identify factors that predict VUR. METHODS: Files of 381 pediatric patients who underwent unilateral pyeloplasty between 2000 and 2017 were retrospectively reviewed. A total of 270 patients with available data and ≥5 years of follow-up were eligible for this study. Demographic parameters, preoperative hydronephrosis grade, renal pelvis anteroposterior diameter (APD), renal parenchymal thickness (PT), split renal functions on MAG-3 scan and VUR status were noted. The patients were divided into two groups: those with concomitant VUR (group I, n: 24, 8.9%) and those without VUR (group II, n: 246, 91.1%). RESULTS: Among 270 patients (205 boys, 75.9%) with a median age of 4 months (2-98), 197 (72.9%) had antenatal hydronephrosis. Median follow-up was 11 years (5-22). Among 24 patients with concurrent VUR, 6 (25%) had grade II VUR, whereas grade III-V VUR was detected in 18 (75%). Of these, 12 (50%) had ipsilateral VUR, 3 (12.5%) had contralateral, and 9 (37.5%) had bilateral VUR. In a median 137-month follow-up, spontaneous VUR resolution was observed in 6 (25%) patients, whereas 15 (62.5%) patients underwent endoscopic subureteral injection and 3 (12.5%) patients ureteroneocystostomy, respectively. Preoperative APD [35.5, (Inter Quantile Range) IQR (27.6-36.0) vs 26.5 IQR (25.0-35.0), P = .004] were significantly higher in group I, whereas group I had significantly lower PT [3.7, IQR (3.4-6.4) vs 5.8 IQR (4.4-6.1), P = .026]. Predictive factors for concomitant VUR were presentation with febrile UTI (odds ratio (OR): 2.769, P = .048), PT <3.95 mm (OR: 1.367, P = .043), and APD >28.8 mm (OR: 1.035, P = .001). CONCLUSION: Our results indicated that concomitant VUR and UPJO might be detected in 1 out of every 11 patients undergoing pyeloplasty, while some type of surgical intervention for VUR was required in 75% of these patients. Thus, voiding cystourethrogram prior to pyeloplasty may be limited in those presenting with febrile urinary tract infection, having higher APD and lower PT on preoperative urinary ultrasonography.

What to Expect on the Long-term Follow-up of Pediatric Pyeloplasty: Critical Time Intervals and Risk Factors.

BACKGROUND: Standard protocol for post-pyeloplasty monitoring in children and natural course of hydronephrosis resolution have not been well defined. We aimed to analyze critical time intervals and risk factors in the long-term clinical outcomes of children who were operated for ureteropelvic junction obstruction. METHODS: Files of patients who underwent open dismembered pyeloplasty between January 2000 and December 2012 and had a ≥10 years follow-up were retrospectively reviewed. Changes in SFU hydronephrosis grade, pelvis anteroposterior diameter (APD), renal parenchymal thickness, split renal functions (SRF) on MAG-3 scan as well as development of hypertension and proteinuria were noted. Complete resolution was defined as SFU grade 0-1 or APD≤10 mm or ≥50 % APD decrease. RESULTS: Overall, 223 patients (161 boys, 72.1 %) with a median age of 9 (range 1-185) months underwent unilateral pyeloplasty, whereas 14 patients (13 boys, 92.8 %) with a median age of 4 (range 2-39) months underwent bilateral pyeloplasty. Median follow-up was 13 (range 10-22) years. Complete resolution was observed in 190 patients (85.2 %). None of the cases required re-do pyeloplasty. Regarding unilateral cases, postoperative changes in hydronephrosis reached a plateau at the 60th month. Also, there was no significant difference regarding SRF between the 12th month and the 60th month (p > 0.05). Hypertension developed after a median period of 12 years in 13 (5.4 %) of the patients, while proteinuria developed in four (1.6 %) patients. Bilateral disease (HR: 2.518, p = 0.034) was found to be a significant determinant for development of hypertension and/or proteinuria. CONCLUSIONS: Our results indicated that ultrasonographic findings stabilized after the 60th month postoperatively, and SRF remained stable between the postoperative 12th and the 60th months. The risk of developing hypertension and/or proteinuria was 2.5 times greater in bilateral cases. LEVEL OF EVIDENCE: Level II.

External validation of the VENUSS prognostic model to predict recurrence after surgery in non-metastatic papillary renal cell carcinoma: A multi-institutional analysis.

OBJECTIVE: Recently, VENUSS (VEnous extension, NUclear Grade, Size, Stage), as a prognostic model, was defined to predict disease recurrence (DR) after curative surgery of non-metastatic papillary renal cell carcinoma (papRCC). This study aimed to validate the VENUSS prognostic model in a large multi-institutional European cohort of patients with histopathologically proven papRCC after curative surgery for non-metastatic disease. PATIENTS AND METHODS: Overall, 980 patients undergoing partial or radical nephrectomy for sporadic, unilateral and non-metastatic papRCC between 1987 and 2020 were included from 7 European tertiary institutions. The primary outcome was the prediction of DR by VENUSS score and VENUSS risk groups. Chi-square, Kruskal-Wallis, Cox-regression and Kaplan-Meier survival analyses were used in statistical methods. The Concordance (C) Index was calculated to assess model's discriminatory power. RESULTS: The median age was 64 (IQR:55-70) years and 82.6 % (n = 809) of patients were male. Median VENUSS score was 2 (IQR: 0-4), and 62.9 % (n = 617), 23.9 % (n = 234) and 13.2 % (n = 129) of patients was classified into low, intermediate and high risk according to the VENUSS model, respectively. At a median follow-up of 48 (IQR:23-88) months, the disease recurred in 6.6%, 18.8% and 63.8%, and the 5-year recurrence-free survival was 93.8%, 80.7% and 26.7% in low, intermediate and high-risk groups, respectively. (P < 0.001) Each increase in VENUSS score had 1.52-fold (95%CI:1.45-1.60, P < 0.001) DR risk. Compared with the VENUSS low risk, the intermediate risk had a 2.91-fold increased DR risk (95%CI:1.90-4.46, P < 0.001) and 17.9-fold (95%CI:12.25-26.25, P < 0.001) in high risk, while it was 6.07-fold greater in high risk vs. intermediate risk (95%CI:4.17-8.83, P < 0.001). The discrimination was 81.2% (95%CI:77.5%-84.8%) for the VENUSS score, and 78.6% (95%CI:74.8%-82.4%) for VENUSS risk groups, respectively. Both the VENUSS score and groups were well calibrated. CONCLUSIONS: This contemporary multi-institutional European large dataset validated the use of VENUSS score and VENUSS risk groups on the prediction of DR after curative surgery in patients with non-metastatic papRCC. The VENUSS prognostic model can provide valuable information for patient counselling, follow-up and patient selection for adjuvant trials.

How accurate is 68Gallium-prostate specific membrane antigen positron emission tomography / computed tomography (68Ga-PSMA PET/CT) on primary lymph node staging before radical prostatectomy in intermediate and high risk prostate cancer? A study of patient- and lymph node- based analyses.

BACKGROUND AND AIM: Gallium-68 (68Ga)-Prostate Membrane Specific Antigen Positron Emission Tomography/Computed Tomography (68Ga-PSMA PET/CT) is an emerging diagnostic modality which is gaining importance in individualized prostate cancer (PCa) management era. This study aimed to investigate the diagnostic accuracy of 68Ga-PSMA PET/CT on primary LN staging before radical prostatectomy (RP) in intermediate and high risk PCa. MATERIALS AND METHODS: The retrospectively documented 49 patients with intermediate and high risk non-metastatic PCa who had 68Ga-PSMA PET/CT before RP were enrolled into this study. The histopathology of dissected LNs was used as reference standard to evaluate the accuracy of 68Ga-PSMA PET/CT on primary LN staging, both in per-patient (n = 49) and in per-node (n = 454) analyses. The diagnostic accuracy was investigated using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and by area under the curve (AUC) provided using receiver operating curve (ROC) analysis. RESULTS: Median age was 64 (48-79) years and, median and mean PSA values were 10 (1.31-138) ng/ml and 16.2 (±19.8) ng/ml, respectively. 22 (44.9%) and 27 (55.1%) of patients had intermediate and high risk PCa, respectively. A total of 5 (10.2%) patients had histopathologically proven LN metastasis and 3 (60%) of them was detected in 68Ga-PSMA PET/CT. In per patient analysis, the sensitivity, specifity, PPV and NPV of 68Ga-PSMA PET/CT on primary LN staging were 0.60, 0.96, 0.60 and 0.96, respectively. Among overall 454 LNs, 16 (3.5 %) of them were reported as metastatic in histopathology and, 13 (2.9%) of these metastatic LNs were detected in 68Ga-PSMA PET/CT. In per-node analysis, the sensitivity, specificity, PPV and NPV of 68Ga-PSMA PET/CT on primary LN staging were 0.82, 0.99, 0.87 and 0.99, respectively. The ROC analyses found AUCs for primary LN staging as 0.777 (95%CI:0.508-1.0) in per patient analysis and, as 0.904 (95%CI:0.790 - 1.0) in per node analysis, respectively. CONCLUSION: The use of 68Ga-PSMA PET/CT has promising diagnostic accuracy on primary LN staging before RP in intermediate and high risk PCa. However, the efforts should be taken to increase sensitivity of 68Ga-PSMA PET/CT in individualized treatment era.

Impact of delay in cystoscopic surveillance on recurrence and progression rates in patients with non-muscle-invasive bladder cancer during the COVID-19 pandemic.

PURPOSE: To evaluate the impact of delay in cystoscopic surveillance on recurrence and progression rates in non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A total of 407 patients from four high-volume centres with NMIBC that applied for follow-up cystoscopy were included in our study prospectively. Patients' demographics and previous tumour characteristics, the presence of tumour in follow-up cystoscopy, the pathology results of the latest transurethral resection of bladder tumour (if tumour was detected) and the delay in cystoscopy time were recorded. Our primary outcomes were tumour recurrences detected by follow-up cystoscopy and progression. Multivariate logistic regression analysis was performed using the possible factors identified with univariate analyses (P values ≤ .2). RESULTS: A total of 105 patients (25.8%) had tumour recurrence in follow-up cystoscopy, and 20 (5.1%) of these patients had disease progression according to grade or stage. In multivariate analysis, the number of recurrences (OR: 1.307, P < .001) and the cystoscopy delay time (62-147 days, OR: 2.424, P = .002; >147 days, OR: 4.883, P < .001) were significant risk factors for tumour recurrence on follow-up cystoscopy; the number of recurrences (OR: 1.255, P = .024) and cystoscopy delay time (>90 days, OR: 6.704, P = .002) were significant risk factors for tumour progression. CONCLUSIONS: This study showed that a 2-5 months of delay in follow-up cystoscopy increases the risk of recurrence by 2.4-fold, and delay in cystoscopy for more than 3 months increases the probability of progression by 6.7-fold. We suggest that cystoscopic surveillance should be done during the COVID-19 pandemic according to the schedule set by relevant guidelines.

The clinical impact of the COVID-19 pandemic on daily urological practice: first 3-month multicenter results from Istanbul

Background/aim: The aim of this paper was to determine the general tendencies of urology patients and effect of COVID-19 pandemic on daily urological practice at tertiary centers located in the most affected area in Turkey. Materials and methods: We retrospectively analyzed the data of 39,677 patients (group 1) that applied to 6 different large-volume tertiary centers in Istanbul for outpatient consultation, surgery, or other procedures in the 3-month period between March 16 and June 14, 2020. The distribution of the number of patients who applied to subspecialty sections of urology outpatient clinics and inpatient services were recorded by weeks. That data was compared to data obtained from 145,247 patients that applied to the same centers in the same period of the previous year (group 2). The reflection of worldwide and Turkish COVID-19 case distribution on the daily urological practice was analyzed. Results: There was a decrease in the number of patients in all subspecialty sections the in group 1 compared to group 2; however, there was a significant proportional increase in urooncology and general urology admissions. A decrease of approximately 75% was observed in the total number of surgeries (p < 0.001). We detected a negative correlation between the numbers of admission to all outpatient clinics and COVID-19 cases or deaths in Turkey (p < 0.05). The same negative correlation was present for all surgical procedures and consultations (p < 0.05). The multivariate linear regression analysis revealed that the number of cases in Turkey, and the number of deaths worldwide affect the number of outpatient clinic admissions (R2 = 0.38, p = 0.028) and urological surgery (R2 = 0.33, p = 0.020) in Turkey negatively. Conclusion: This novel pandemic has implications even for urology practice. Urological surgical procedures were more affected by COVID-19-related deaths in Turkey and worldwide. Outpatient admissions and urological surgeries decreased significantly by increasing COVID-19 case numbers in Turkey and worldwide deaths.

HLA Genotypes in Turkish Hematopoietic Cell Recipients and Likelihood of Finding a Matched Donor Through Family Searches.

OBJECTIVES: Allogeneic hematopoietic stem cell transplant is a life-saving treatment, but donor numbers in Turkey do not meet the increasing demand for this procedure. Here, our objectives were (1) to assess the frequency of HLA-matched related donors in the Turkish population and (2) to identify the HLA antigens and haplotypes that are most frequent in Turkey. MATERIALS AND METHODS: The HLA genotypes of 841 consecutive recipients and 3071 family members were retrospectively reviewed. RESULTS: Matched related donors were identified for 368/841 recipients (44%). Extended family donor searches were performed for 111/181 pediatric recipients (61%), with nonsibling matched related donors found for 23 patients (21%). Matched related donors were found for a significantly higher proportion of pediatric patients (52%) than adult patients (41%) (odds ratio of 2.5; 95% confidence interval, 1.9-4.1; P = .02). The percentage of pediatric versus adult patients with 3 or more siblings was 13% versus 46% (odds ratio of 5.6; 95% confidence interval, 3.6-8.5; P = .001). The most frequent HLA class I antigens at each locus were HLA-A*02 (20.2%), HLA-B*35 (19.5%), and HLA-C*07 (19.8%). The most frequent HLA class II antigens at each locus were HLA-DRB1*11 (21.6%) and HLA-DQB1*03 (40.2%). The most common 3-locus haplotypes were HLA-A*24 B*35 DRB1*11 (F:0.020) and HLA-A*01 B*08 DRB1*03 (F:0.015). When adult and pediatric groups were combined, the most common locus haplotypes were found in 43/345 sibling donors (12%) and in 7/23 nonsibling pediatric donors (30%) (odds ratio of 2.7; 95% confidence interval, 1.2-6.4; P = .02). CONCLUSIONS: The results indicate that, in Turkey, it can be beneficial to revise donor search algorithms to include an extended family donor search before an unrelated donor search. This type of search can be effective because of the HLA haplotype diversity in Turkey, the frequency of consanguinity, and the country's limited donor pool.