Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma.

Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up-regulated phosphoproteins are associated with protein synthesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, minocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment.

Screening programs for renal cell carcinoma: a systematic review by the EAU young academic urologists renal cancer working group.

PURPOSE: To systematically review studies focused on screening programs for renal cell carcinoma (RCC) and provide an exhaustive overview on their clinical impact, potential benefits, and harms. METHODS: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUality In Prognosis Studies (QUIPS) tool. RESULTS: Overall, nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis. CONCLUSIONS: Despite an increasing interest in RCC screening programs from patients and clinicians there is a relative lack of studies reporting the efficacy, cost-effectiveness, and the optimal modality for RCC screening. Targeting high-risk individuals and/or combining detection of RCC with other health checks represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening.

Multidrug refractory aggressive metastatic TFE3 (+) renal cell carcinoma: A case report.

BACKGROUND: Transcription factor E3 (TFE3) related renal cell carcinomas constitute a very small percent of all renal tumors in adults. Prognosis mainly depends on the stage of the disease at the time of diagnosis which is often poor. There is yet to be a standardized treatment protocol. Treatment options include agents identical to TFE3(-) cell renal carcinoma treatment. We present a case of a young woman with a rapidly progressing metastatic TFE3 (+) renal cell carcinoma. CASE REPORT: A 31 year old female presented with abdominal mass, distension, nausea. Initial tests and tumor markers found to be normal. Abdominal CT scan revealed a left retroperitoneal mass along with three other neighboring masses in liver manifesting as metastases. Trucut biopsy and immunohistochemical staining confirmed the retroperitoneal mass as TFE3 (+) renal cell carcinoma.Management and outcome: Sunitinib, pazopanib, nivolumab, axitinib treatments are consecutively given after surgery. It is noteworthy that rapid progression was observed under nivolumab treatment. DISCUSSION: During surveillance, rapid progression is noted under consecutive immunotherapy which was unexpected. Thus, there is a need for more standardized treatment protocols and invention of new agents for management of TFE3 (+) renal cell carcinoma.

Urinary HSP70 can predict the indication of surgery in unilateral ureteropelvic junction obstruction.

BACKGROUND: Distinguishing hydronephrosis that requires surgical intervention is a clinical challenge. The aim of this study is to determine the level of urinary heat shock protein 70 (HSP70) in children who required surgery for ureteropelvic junction obstruction and its potential use as a biomarker for prediction of surgery in children with isolated unilateral hydronephrosis. METHODS: The data of 43 children with ureteropelvic junction obstruction who underwent pyeloplasty, 25 patients with non-obstructive dilation (NOD) and 30 healthy children (control group) were collected prospectively for this study. Preoperative and postoperative urinary HSP70/Cr levels were also analyzed in 30 children in the pyeloplasty group who had available follow-up information. HSP70 levels were assessed using ELISA. RESULTS: The median age of the pyeloplasty group was 13 months (IQR 7-36 months), NOD group was 42.5 months (IQR 16-73) and it was 36 months (IQR 24-47.5) in the control group. The mean preoperative urinary HSP70/Cr was significantly higher in the pyeloplasty group when compared to controls as well as the NOD group (150.6 pg/mgCr vs. 65.0 pg/mgCr and vs. 64.7 pg/mgCr, p < 0.001 and p < 0.001, respectively). The urinary HSP70 levels significantly decreased in the postoperative period (151.5 vs 79.5, p < 0.001). Using the cutoff value of 94.7 pg/mgCr, the sensitivity and specificity of urinary HSP70 for predicting the risk of surgical intervention were 69.7% and 68%, respectively (AUC = 0.689). CONCLUSION: Urinary HSP70 may be used as an adjunct tool to clinical parameters to identify patients that would require surgery due to ureteropelvic junction obstruction.

Detection of metastases in newly diagnosed prostate cancer by using 68Ga-PSMA PET/CT and its relationship with modified D'Amico risk classification.

PURPOSE: We aimed to investigate the diagnostic power of 68Ga-PSMA PET/CT in the detection of metastatic spread of newly diagnosed PCa, and evaluate the relationship with modified D'Amico risk classification. METHODS: We evaluated newly diagnosed PCa patients who underwent 68Ga-PSMA PET/CT prior to therapy. All images were interpreted retrospectively and areas of abnormally increased tracer uptake were documented according to PSMA-RADS version 1.0 system. Patients were divided into risk groups as low, intermediate, or high risk, according to a modification in D'Amico classification system as ISUP grade 3 tumors were included to high-risk group. 68Ga-PSMA PET/CT findings were compared among risk groups as well as PSA levels, clinical T stages, and ISUP grades. RESULTS: A total of 356 patients were included to the study with a median PSA level was 16.42 (1.29-7013) ng/ml and median Gleason score was 8 (range: 6-10). Of these, 13(3.7%), 54 (15.1%), and 289 (81.2%) were in the low-, intermediate-, and high-risk groups, respectively. Lymph node metastases were detected in 125 (35.1%) patients, and in 48 of them, metastasis was limited to pelvic lymph nodes (PLN). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were calculated as 71.4%, 100%, 95.9%, 100%, and 95.4%, respectively for the detection of PLN, based on histopathological results of 49 patients. Overall, any metastasis was detected in 47.7% of high-risk patients, while only PLN metastases were defined in 3.7% intermediate-risk patients and none of low-risk patients had any kind of metastasis. CONCLUSION: This study revealed that 68Ga-PSMA PET/CT should be routinely used in newly diagnosed high-risk PCa patients; whereas it seems to be of limited use for intermediate-risk group and useless for the low-risk group.

Clinical, surgical, pathological and follow-up features of kidney cancer patients with Von Hippel-Lindau syndrome: novel insights from a large consortium.

PURPOSE: To investigate the natural history and follow-up after kidney tumor treatment of Von Hippel-Lindau (VHL) patients. MATERIALS AND METHODS: A multi-institutional European consortium of patients with VHL syndrome included 96 non-metastatic patients treated at 9 urological departments (1987-2018). Descriptive and survival analyses were performed. RESULTS AND LIMITATIONS: Median age at VHL diagnosis was 34 years (IQR 25-43). Two patients (2.1%) showed only renal manifestations at VHL diagnosis. Concomitant involvement of Central Nervous System (CNS) vs. pancreas vs. eyes vs. adrenal gland vs. others were present in 60.4 vs. 68.7 vs. 30.2 vs. 15.6 vs. 15.6% of patients, respectively. 45% of patients had both CNS and pancreatic diseases alongside kidney. The median interval between VHL diagnosis and renal cancer treatment resulted 79 months (IQR 0-132), and median index tumor size leading to treatment was 35.5 mm (IQR 28-60). Of resected malignant tumours, 73% were low grade. Of high-grade tumors, 61.1% were large > 4 cm. With a median follow-up of 8 years, clinical renal progression rate was 11.7% and 29.3% at 5 and 10 years, respectively. Overall mortality was 4% and 7.5% at 5 and 10 years, respectively. During the follow-up, 50% of patients did not receive a second active renal treatment. Finally, 25.3% of patients had CKD at last follow-up. CONCLUSIONS: Mean period between VHL diagnosis and renal cancer detection is roughly three years, with significant variability. Although, most renal tumors are small low-grade, clinical progression and mortality are not negligible. Moreover, kidney function represents a key issue in VHL patients.

Can serum matrix metalloproteinase-9 and SMAD-2 levels predict lamina propria invasion in bladder urothelial carcinoma?

INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) has a role in the destruction of lamina propria (LP) of the bladder wall and SMAD-2 promotes cell-to-cell adhesion. This study aimed to investigate the association between LP invasion and serum protein and mRNA expression levels of MMP-9 and SMAD-2 in bladder cancer (BC) patients. METHODS: Serum samples were taken from 57 patients with suspicious BC before TUR-BT (Group 1) and 20 patients with benign diseases as control (Group 2). The mRNA expression and serum protein levels of MMP-9 and SMAD-2 were analyzed using Real-Time PCR and ELISA methods, respectively. The comparison of protein and mRNA expression levels of MMP-9 and SMAD-2 were done statistically between Group 1 and 2, as well as for different T stages of BC. RESULTS: The protein levels of MMP-9 (2448 vs 637.5 pg/mL, P = .0001) and SMAD-2 (6.85 vs 1.61 P = .0001) were significantly higher in Group 1 compared to Group 2. The mRNA expression levels of MMP-9 (P = .89) and SMAD-2 (P = .99) did not significantly differ between the groups. The protein levels of MMP-9 in T1 patients were significantly higher from both of pTa patients (P = .018) and pT2 (P = .02). The protein levels of SMAD-2 were not statistically different between T stages. Similarly, the mRNA expression levels of MMP-9 and SMAD-2 were not different between T stages. CONCLUSIONS: The protein levels of MMP-9 and SMAD-2 were increased in BC patients while mRNA expressions were not different. Furthermore, the increased protein level of MMP-9 in T1 patients was more pronounced which may be related to LP invasion of the tumor.

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.

Determination of the time for improvement in semen parameters after varicocelectomy.

This retrospective study aimed to determine the time for improvement in semen parameters after varicocelectomy. A total of 175 patients over 18 years of age, who underwent microscopic inguinal varicocelectomy in a tertiary centre between 2005 and 2016 and had post-operative follow-up data of at least 12 months, were included in the study. Serial semen analyses in the pre-operative period and at the post-operative third, sixth, ninth and 12th months were retrospectively documented. With respect to their pre-operative total motile sperm counts, the patients were classified into three subgroups as <5 million, 5-9 million and >9 million. In the overall cohort and the group with a total motile sperm count of >9 million, the semen parameters continued to improve up to the post-operative 12th month. No further significant improvement was observed after the post-operative third and sixth months for the patients with pre-operative total motile sperm counts of <5 million and 5-9 million respectively. For the candidates of varicocelectomy, the decision of treatment strategies, such as assisted reproductive technologies and waiting for spontaneous pregnancy can be based on the prediction of the time for improvement in semen parameters.

Immunoexpression of SDHB, FH, and CK20 among eosinophilic renal tumors: A tissue microarray study.

BACKGROUND: Differential diagnosis can be a challenge for eosinophilic subtypes of renal cell tumors due to their overlapping histomorphological and immunohistochemical features. We aimed to investigate the frequency of rare variants of renal cell carcinomas (RCCs) such as succinate dehydrogenase-deficient RCC (SDDRCC), hereditary leiomyomatosis and RCC (HLRCC)-associated RCC, and eosinophilic, solid, and cystic RCC (ESCRCC) in our population. MATERIALS AND METHODS: Renal tumors which could be considered in the eosinophilic tumor category were included: 91 conventional clear cell RCCs with eosinophilic cytoplasm, 72 papillary RCCs, 74 chromophobe RCCs, 88 oncocytomas, and 37 other rare subtypes. Using the tissue microarray method, succinate dehydrogenase B (SDHB), fumarate hydratase (FH), and cytokeratin 20 (CK20) antibodies were performed by immunohistochemistry. Immunohistochemistry was repeated on whole block sections for selected cases. The utility of these antibodies in the differential diagnosis was also investigated. RESULTS: Loss of SDHB expression was detected in three tumors, two of which showed typical morphology for SDDRCC. In additional two tumors, SDHB showed weak cytoplasmic expression without a mitochondrial pattern (possible-SDHB deficient). None of the tumors showed loss of FH expression. Heterogeneous reactions were observed with SDHB and FH antibodies. Only one ESCRCC was detected with diffuse CK20 positivity. CONCLUSION: SDDRCCs, HLRCC-associated RCCs, and ESCRCCs are very rare tumors depending on the population. Possible weak staining and focal loss of SDHB and FH expression should be kept in mind and genetic testing must be included for equivocal results.

Diagnostic accuracy of core biopsies of renal masses: Experience in a real-life setting from a tertiary center.

OBJECTIVE: To document and analyze diagnostic accuracy of renal core biopsy (RCB), its diagnostic correlation with resection specimens, and to question the need for immunohistochemistry (IHC) in the preoperative diagnosis of renal masses. MATERIAL AND METHOD: RCBs performed at a reference center between 2007 and 2017 were included. Pathological, clinical, and radiological data were obtained from medical records. RESULTS: Among 302 biopsies included in this study, 274 (90.7%) were diagnostic. Two hundred sixty-six were neoplastic and 179 were of primary renal origin. The most common secondary neoplasms were hematolymphoid (n = 35) and metastatic (n = 17). Sixty-nine tumors were classified as small renal masses (SRMs) (≤4 cm in diameter) and 53 of them were malignant. Nephrectomy was performed in 58 patients. Overall diagnostic accuracy between resections and RCBs was 88.7%. IHC was performed in 160 (53%) cases. In 15 of those, a definite diagnosis could not be rendered. Renal cell origin and subtype were determined by histomorphology alone in 81 and 75 cases, respectively. Sixty primary neoplasms of renal cell origin required IHC for diagnosis. CONCLUSION: RCB is a safe and highly accurate method for the diagnosis of both primary and secondary renal neoplasms. IHC is mostly required for the diagnosis of secondary tumors. Histomorphology is still the primary diagnostic tool, highly dependent on the experience of the surgical pathologist.

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.

The risk of endothelial and erectile dysfunctions in Behçet's disease: a comparative analysis of mucocutaneous and systemic patient groups.

INTRODUCTION: Behçet's disease (BD) is a chronic inflammatory disease which can be limited to only mucocutaneous tissues or can affect different systems of the body. AIM: To investigate the association of endothelial and erectile dysfunctions with BD, on the basis of comparative analysis between mucocutaneous and systemic BD. MATERIAL AND METHODS: Thirty-eight men diagnosed with BD were included in the present study. The patients were stratified into two groups as mucocutaneous BD (n = 20, MBD group), and systemic BD (n = 18, SBD group). Erectile dysfunction (ED) was assessed using the Erectile Function domain of the International Index of Erectile Function (IIEF-EF) questionnaire. The coronary flow reserve (CFR) assessment was done for analysing endothelial dysfunction (EnD), and CFR < 2 was defined as EnD. Penile Doppler ultrasonography (PDU) was performed for ED. The demographic and clinical parameters, IIEF-EF score ED classification, CFR and PDU test findings were compared between two groups. RESULTS: The median age was 34 (22-52) years in the overall population, and there was no difference between two groups (p = 0.558). Time from diagnosis was significantly longer (24 vs. 102 months, p = 0.021) and the use of immunosuppressive therapies was higher (0 vs. 70.6%, p < 0.001) in the SBD group. In overall, median CFR was 1.92 (1.1-5.96), and there was no difference between two groups (1.88 vs. 1.97, p = 0.812). The percentage of patients with CFR < 2 was similar in two groups (52.6% vs. 52.9%, p = 0.985). The ED status according to IIEF-EF was similar in two groups (45% vs. 27.8%, p = 0.538) as well as according to PDU analyses (10% vs. 16.7%, p = 0.544). CONCLUSIONS: The increased risk of endothelial, and erectile dysfunctions should be considered in men who were diagnosed with mucocutaneous and systemic BD.

The clinical predictive factors and postoperative histopathological parameters associated with upgrading after radical prostatectomy: A contemporary analysis with grade groups.

BACKGROUND AND AIM: Upgrading after radical prostatectomy (RP) is an ongoing problem since first description of Gleason score. In this retrospective study, our aim is to investigate upgrading after RP in grade groups (GG) and clinical predictive, and postoperative histopathological factors associated with GG upgrading (GGU). PATIENTS AND METHODS: A total of 753 patients undergoing RP between January 2006 and June 2019 at our institution were investigated. Overall cohort were divided into two groups according to GGU status after RP as nonupgrading and upgrading. Retrospectively documented preoperative clinical and postoperative histopathological parameters were compared between two groups. Furthermore, we investigated a subgroup of institutional cohort (n = 398) whose prostate biopsy (Pbx) and RP were performed in our institution and we also divided this cohort into two groups according to GGU status. χ2 and Mann-Whitney U tests were used for comparative analyses. The independent preoperative predictive and postoperative histopathological factors associated with GGU were investigated using multivariate logistic regression analysis. RESULTS: The total GGU was 55.8% in overall cohort and 45.2% in institutional cohort. The GGU was found as the most common in bioptic GG1 group in both overall (64.0%), and institutional (54.5%) cohorts. In multivariate analyses, the noninstitutional Pbx (odds ratio [OR] = 2.56; 95% confidence interval [CI]: 1.86-3.51; P < .001), tumor positive core numbers in Pbx (OR = 1.11; 95%CI: 1.04-1.19; P = .003), increased prostate specific antigen (PSA) density (OR = 3.59; 95%CI: 1.03-12.52, P = .045) and age (OR = 1.03; 95%CI: 1.00-1.05, P = .046) were independent clinical predictors of GGU in overall cohort whereas only increased PSA density (OR = 5.94; 95%CI: 1.28-27.50; P = .023) was independent predictor in institutional cohort. Among postoperative histopathological factors, perineural invasion (OR = 1.57; 95%CI: 1.70-3.87; P < .001 and OR = 2.53; 95%CI: 1.46-4.40; P = .001, respectively), increased maximum tumor diameter (OR = 1.46; 95%CI: 1.23-1.73; P < .001 and OR = 1.33; 95%CI: 1.07-1.66; P = .010, respectively), and high-grade prostatic intraepithelial neoplasia (HGPIN) existence at tumor surrounding tissue (OR = 1.96; 95%CI: 1.32-2.90; P = .001 and OR = 1.87; 95%CI: 1.10-3.21; P = .022, respectively) were independently associated with GGU after RP, in both of overall and institutional cohorts. CONCLUSIONS: Noninstitutional prostate biopsy, increased PSA density, higher tumor positive cores in Pbx and older age are the clinical predictors of upgrading after RP in contemporary GG. Perineural invasion, increased maximum tumor diameter, and HGPIN existence at tumor surrounding tissue are postoperative histopathological factors associated with GGU.

The pathological upgrading after radical prostatectomy in low-risk prostate cancer patients who are eligible for active surveillance: How safe is it to depend on bioptic pathology?

BACKGROUND: Active surveillance (AS) is one of the treatment alternatives in low-risk prostate cancer (PCa). The pathological upgrading after radical prostatectomy (RP) were investigated in patients who were eligible for AS in the present study. METHODS: Between August 2006 and July 2017, 627 patients underwent RP in our institution. One hundred and thirty-six patients who were eligible for AS at the time of RP were included in this study. The previously defined AS criteria Gleason 3 + 3=6 adenocarcinoma at maximum two biopsy cores, prostate-specific antigen (PSA) < 10 ng/mL and clinical T stage ≤ 2a were used in the study. The demographics, clinical, and histopathological outcomes were retrospectively compared between two groups, which were divided in accordance with the upgrading status at final pathology as Group 1 (n = 67, upgrading) and Group 2 (n = 69, nonupgrading). RESULTS: Gleason upgrading (GU) was found in 67 (49.3%) patients, and 17 patients (12.5%) were upstaged to pT3a. The upgrading to Gleason 3 + 4 was reported in 38.7% of patients, however, 7.4%, and 3.7% of the patients were upgraded to Gleason 4 + 3, and Gleason 4 + 4, respectively. The 10.3% of the patients had extraprostatic involvement, and the rate (19.4% vs 1.4%, P = .002) was significantly higher in Group 1. PSA density (P = .001), tumor size (P < .001), tumor percentage (P < .001), apical involvement (P = .013), and perineural invasion (P < .001) in RP specimen were higher in Group 1. Multivariate analysis showed that perineural invasion (OR = 4.26; 95%CI: 1.76-10.33; P = .001) and pathologic T stage (OR = 5.45; 95%CI: 1.08-27.4; P = .04) were independently associated with GU. CONCLUSIONS: Since 12.5% of the patients upstaged to pT3a disease, and there is a possible risk of Gleason 4 pattern, upgrading of the tumor should carefully be kept in mind before offering AS to low-risk patients with PCa.

Prospective evaluation of complications in laparoscopic urology at a mid-volume institution using standardized criteria: Experience of 1023 cases including learning curve in 9 years.

AIM: To evaluate the laparoscopic operations performed in our department according to the modified Clavien classification system of complications. MATERIALS AND METHODS: Between September, 2005 and February, 2014, a total of 1023 laparoscopic cases were performed. This period was divided into three terms (Terms 1, 2 and 3 consisting of 38, 32 and 32 months, respectively). According to the European Scoring System (ESS), easy (E), slightly difficult (SD), fairly difficult (FD), difficult (D), very difficult (VD) and extremely difficult (ED) cases were 35, 88, 170, 390, 203 and 137, respectively. The perioperative complications were evaluated based on the 3 time periods, with a specific emphasis on determining the learning curve according to the modified Clavien classification system of complications. RESULTS: A total of 236 (23.1%) complications were observed according to the modified Clavien classification. The minor (Clavien I-II) and major (Clavien III, IV and V) complication rates were 20.5% (n = 210) and 2.4% (n = 26), respectively. Clavien I was the most frequently encountered type of complication (n = 120, %11.7). No significant difference was observed among all 3 time periods regarding total complication rates. The D cases had the highest complication rate compared to E, SD, FD, VD and ED cases among all three terms. The total number of complications increased significantly with increasing grade of technical difficulty according to the ESS. CONCLUSION: Complications encountered in our laparoscopic surgery experience were predominantly minor, and the rate of complications was not significantly increased during the learning curve. The present data can provide guidance and manage expectations for surgeons introducing laparoscopy into their practice.

The increased transglutaminase 2 expression levels during initial tumorigenesis predict increased risk of metastasis and decreased disease-free and cancer-specific survivals in renal cell carcinoma.

PURPOSE: The aim of this study was to investigate the role of transglutaminase 2(TG2) in renal cell carcinoma (RCC) by comparing the immunohistochemistry staining of primary and metastatic tumor tissues. METHODS: A total of 33 metastatic RCC(mRCC) and 33 non-metastatic RCC (nmRCC) patients who were matched as closely as possible based on gender, age, nuclear grade and pathologic T stage were retrospectively investigated. TG2 immunohistochemistry staining was performed on paraffin-embedded primary tumor tissues from both patient groups and on metastatic tissues from mRCC patients. The tissues were scored from 0 to 7 according to the TG2 staining. Furthermore, the patients were stratified into two groups using median primary tumor staining score as the cutoff value: Group 1 (high risk, n = 41) and Group 2(low risk, n = 22). The clinical, histopathological and survival outcomes were compared between these risk groups using Chi-square test, t test, Mann-Whitney U test and Kaplan-Meier survival analyses. RESULTS: The median TG2 score for primary tumor was 5 for the entire study population. The median primary tumor TG2 score of the mRCC patients was significantly higher compared to the nmRCC patients (6 vs. 4, p < 0.001). The TG2 score between the primary and metastatic tissues of mRCC patients was not significantly different (6 vs. 7, p = 0.086). The percentage of metastatic patients was significantly higher in Group 1 compared to Group 2 (68.3 vs. 18.2 %, p < 0.001). Kaplan-Meier analyses showed that 5-year disease-free (34.9 vs. 92.9 %, p = 0.001) and cancer-specific (47.4 vs. 86.5 %, p = 0.04) survival rates were significantly lower in high-risk group. CONCLUSIONS: The increased expression of TG2 in primary tumor predicts metastasis in RCC patients and is also associated with a decrease in disease-free and cancer-specific survival outcomes.

Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

Diagnostic Biopsy for Small Renal Tumours: A Survey of Current European Practice.

Background and objective: Renal tumour biopsy (RTB) can help in risk stratification of renal tumours with implications for management, but its utilisation varies. Our objective was to report current practice patterns, experiences, and perceptions of RTB and research gaps regarding RTB for small renal masses (SRMs). Methods: Two web-based surveys, one for health care providers (HCPs) and one for patients, were distributed via the European Association of Urology Young Academic Urologist Renal Cancer Working Group and the European Society of Residents in Urology in January 2023. Key findings and limitations: The HCP survey received 210 responses (response rate 51%) and the patient survey 54 responses (response rate 59%). A minority of HCPs offer RTB to >50% of patients (14%), while 48% offer it in <10% of cases. Most HCPs reported that RTB influences (61.5%) or sometimes influences (37.1%) management decisions. Patients were more likely to favour active treatment if RTB showed high-grade cancer and less likely to favour active treatment for benign histology. HCPs identified situations in which they would not favour RTB, such as cystic tumours and challenging anatomic locations. RTB availability (67%) and concerns about delays to treatment (43%) were barriers to offering RTB. Priority research gaps include a trial demonstrating that RTB leads to better clinical outcomes, and better evidence that benign/indolent tumours do not require active treatment. Conclusions and clinical implications: Utilisation of RTB for SRMs in Europe is low, even though both HCPs and patients reported that RTB results can affect disease management. Improving timely access to RTB and generating evidence on outcomes associated with RTB use are priorities for the kidney cancer community. Patient summary: A biopsy of a kidney mass can help patients and doctors make decisions on treatment, but our survey found that many patients in Europe are not offered this option. Better access to biopsy services is needed, as well as more research on what happens to patients after biopsy.