To compare the expression of immune checkpoint molecules in tumor cells and tumor microenvironment and their role on prognosis among surgically treated non-metastatic clear cell renal cell carcinoma (ccRCC), papillary RCC (papRCC), and chromophobe RCC (chRCC). We retrospectively evaluated patients undergoing curative partial or radical nephrectomy for non-metastatic RCC between 2015 and 2023, who had available formalin-fixed paraffin-embedded tumor tissue and postoperative follow-up. Immunohistochemical staining was performed for PD-L1, PD-1, and CTLA-4. PD-L1 expression was evaluated using tumor proportion score, combined positive score, and immune cell score, whereas PD-1 and CTLA-4 expression were evaluated using immune cell score. Immunopositivity was defined as ≥1

INTRODUCTION:Robot-assisted partial nephrectomy (RAPN) represents the preferred minimally-invasive approach for localized renal tumors. Increasing attention has focused on optimizing parenchymal preservation, with enucleation proposed as a potentially advantageous strategy. This study aimed to compare perioperative and functional outcomes of enucleation versus enucleoresection in a large, contemporary multicenter RAPN cohort. MATERIALS AND METHODS:Data were extracted from the multicentric and multicontinental European Association of Urology Young Academic Urologists (EAU-YAU) Renal Cancer Working Party database. Patients undergoing RAPN between 2015 and 2024 with clearly documented resection technique (enucleation vs enucleoresection) were included. The resection technique was chosen based on the surgeon's preference. Perioperative, pathological, and renal functional outcomes were evaluated. Acute kidney injury (AKI - defined according to the AKIN classification) and chronic kidney disease (CKD) worsening served as primary endpoints. Logistic regression and Cox proportional hazards models were used to assess the association between surgical technique and the risk of AKI and CKD progression; Kaplan-Meier curves were used to depict time-to-event and functional outcomes, while longitudinal eGFR analyses were performed to evaluate renal function trends over time. RESULTS:Among 1260 patients, 527 (42%) underwent enucleation and 733 (58%) enucleoresection. Adoption of both techniques remained stable over time. Baseline characteristics were comparable. Enucleoresection was associated with longer ischemia time, higher intraoperative complication rates, and a lower positive surgical margin rate (5.2% vs 8.3%, p = 0.003). Postoperative AKI occurred more frequently after enucleoresection (18% vs 3%, p < 0.001), although eGFR recovery was similar at a median follow-up of 12 vs 25 months. In the overall cohort and among patients with baseline CKD stages 1-2, enucleation was associated with a lower risk of CKD progression (p < 0.001). CONCLUSIONS:Enucleation during RAPN offers a parenchyma-sparing approach with potential functional advantages, particularly in patients with preserved baseline renal function. This benefit must be balanced against a slightly higher risk of positive margins, reinforcing the necessity of thoughtful case selection and standardized surgical technique.

Background: Transperineal magnetic resonance (MRI)/ultrasound (US) fusion-guided prostate biopsy has emerged as a promising alternative to the transrectal approach by improving lesion targeting and reducing infectious complications. However, real-world data addressing factors that influence the detection of clinically significant prostate cancer (csPCa), including imaging characteristics and procedural experience, remain limited. Objective: To evaluate the diagnostic performance, safety profile, and independent predictors of csPCa detection in patients who underwent transperineal MR/US fusion-guided prostate biopsy, with particular emphasis on PIRADS category, prostate-specific antigen (PSA) level, and procedural learning curve. Methods: In this study, patient data were prospectively recorded in a routinely maintained institutional database, while the present analysis was conducted retrospectively. A total of 136 patients with clinical suspicion of prostate cancer—defined as elevated prostate-specific antigen (PSA), abnormal digital rectal examination, or PIRADS ≥3 on multiparametric MRI—underwent transperineal MR/US fusion-guided biopsy between January 2023 and October 2024. Results: Prostate cancer was detected in 45.5% of patients, whereas csPCa was identified in 32.3%. The PIRADS category emerged as the strongest independent predictor of csPCa detection, with PIRADS-5 lesions showing a significantly greater likelihood of csPCa than PIRADS-3 lesions (OR 6.70, p = 0.006). The PSA level was also independently associated with csPCa detection (OR 1.06 per ng/mL increase, p = 0.033). Although csPCa detection rates increased across learning curve groups, procedural experience was not an independent predictor after adjustment. The procedure demonstrated a favorable safety profile, with a low rate of infectious and noninfectious complications despite minimal use of antibiotic prophylaxis. The multivariable model showed moderate explanatory power and acceptable overall classification accuracy. Conclusions: Transperineal MR/US fusion-guided prostate biopsy provides reliable detection of clinically significant prostate cancer with a low complication rate and consistent performance across different stages of institutional experience. The PIRADS category and PSA level remain key determinants of csPCa detection, supporting the integration of MRI-based risk stratification into contemporary prostate cancer diagnostic methods.

To determine genome-wide transcriptional coverage of well-characterized genes, gene candidates, and splice variants associated with invasive process on bladder carcinogenesis (BC), we investigated the whole-genome gene expression profile of high-grade Turkish BC patients. We collected high-grade bladder tumours (n = 12) and paired standard tissue samples (n = 12). To find differentially expressed genes related to bladder cancer's metastatic pattern, we performed the human whole-genome expression profiling through the Illumina Human HT-12 Expression Beadchip system. Ingenuity Pathway Systems (IPA), i-Pathway Guide and Cytoscape software were used to determine statistically significant genes, networks, biological pathways between tumour and control groups. Cyclin A2 (CCNA2), CDC20, CDC45, MMP1, MMP3, MMP9, MMP10, STAT1, STAT2, TNFRSF1A, TNFSF10, and TUBB3 were significantly upregulated in bladder cancer cases. We showed that biological reactions, including the degradation of collagen and extracellular matrix and matrix metalloproteinases activation reactions, were found the most statistically significant pathways in BC. We also determined that inflammation and cytokine signalling could be related to the progression of bladder carcinogenesis. The genes differentially expressed could be molecular indicators for early prediction of bladder carcinogenesis.

Purpose: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have emerged as important regulators of the epithelial-mesenchymal transition (EMT) and tumor progression. The present study evaluated the expression profiles of lncRNA ZEB1-AS1 and miR-200b-3p in non-muscle-invasive bladder cancer (NMIBC) tissues and investigated their associations with clinicopathological characteristics. Materials and Methods: Tumor tissues and matched adjacent normal bladder tissue were obtained from 50 patients with primary NMIBC who underwent transurethral resection of bladder tumors. Total RNA was extracted, and expression levels of ZEB1-AS1 and miR-200b-3p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Relative expression levels were calculated using the 2-ΔΔCT method. Associations between gene expression levels and clinicopathological parameters were analyzed using non-parametric statistical tests. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance. Results: ZEB1-AS1 and miR-200b-3p demonstrated significantly increased expression in tumor tissues compared with adjacent normal bladder tissue (p = 0.018 and p = 0.034, respectively). ZEB1-AS1 expression was significantly higher in high-grade tumors (p = 0.007), whereas miR-200b-3p expression was more pronounced in low-grade tumors (p = 0.015). No significant associations were identified between expression levels and tumor stage, carcinoma in situ, or variant histology. ROC analysis demonstrated modest diagnostic performance, with AUC values of 0.637 for ZEB1-AS1 and 0.624 for miR-200b-3p. Conclusions: ZEB1-AS1 and miR-200b-3p demonstrated distinct expression patterns associated with tumor grade and may contribute to EMT-associated molecular heterogeneity in NMIBC. Although the individual diagnostic performance of these markers appeared limited, the present findings provide additional insight into non-coding RNA-associated pathways and support further investigation in larger validation studies.

Objective: This study aimed to explore whether polymorphisms in hOGG1, XRCC1, and APE1 genes influenced the initiation and progression of renal cell carcinoma (RCC) and to investigate the relationship between polymorphisms of the three base excision repair (BER) genes and cigarette smoking among RCC patients. Materials and Methods: This study involved 211 controls and 97 patients. The polymorphisms of DNA repair genes hOGG1 Ser326Cys, XRCC1 Arg399Gln, and APE1 Asp148Glu were explored using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Our results showed no significant association between hOGG1 Ser326Cys polymorphism and RCC risk. There was a statistically significant association between the XRCC1 399 Gln allele and the APE1 148 Glu allele and RCC risk. In addition, the XRCC1 399 Gln allele significantly increased the initiation of RCC when accompanied by smoking status. The variant genotypes of hOGG1, XRCC1, and APE1 showed no significant association with RCC progression. Conclusion: Our findings suggest that XRCC1 and APE1 gene polymorphisms that contribute to BER pathway may regulate RCC susceptibility in a Turkish population.

Chromophobe renal cell carcinoma (chRCC) is generally considered a less aggressive renal malignancy, yet a clinically meaningful subset displays adverse outcomes. We evaluated the prognostic impact of WHO/ISUP Grade IV histology on cancer-specific survival (CSS) in a large population-based, propensity score-matched cohort. The SEER database (2000–2021) was queried for patients with chRCC. Patients were stratified according to WHO/ISUP grade into Grade IV chRCC and Grade I–III chRCC. The primary endpoint was CSS. A 2:1 nearest-neighbor PSM was performed using age, sex, race, AJCC stage, and tumor size. Fine–Gray competing-risk regression was performed in both the overall and propensity score-matched cohorts. A total of 6243 patients with chRCC were identified, including 394 (6.3

Objective: In advanced-stage testicular cancer, postchemotherapy retroperitoneal lymph node dissection (RPLND) is performed to manage residual retroperitoneal masses. This study evaluated the histopathological features and their associations with primary tumor and clinical outcomes. Methods: Postchemotherapy RPLNDs performed between 2000 and 2024 were reviewed and classified as no tumor, teratoma, nonteratomatous germ cell tumor (NTGCT), or somatic malignancy. Corresponding orchiectomy pathology and clinical data were analyzed for primary tumor, treatment, and follow-up. Results: A total of 151 RPLNDs were evaluated. Median age was 26 years (IQR: 24.7–28.4), and mean largest clinical mass diameter was 62.4 ± 38.6 mm. Diagnoses were teratoma in 87 (57.6%), no tumor in 34 (22.5%), NTGCT and teratoma in 11 (7.3%), NTGCT in 11 (7.3%), and somatic-type malignancy in 8 (5.3%). Embryonal carcinoma in orchiectomy was significantly more frequent in patients with malignancy in RPLND (P = .018). Mean number of paraffin blocks was 10.7 ± 6.62, and malignancy was significantly higher in specimens with ≥10 blocks compared to those with <10 (P = .014). Follow-up data were available for 101 (66.9%), with median follow-up of 85.5 months (IQR: 70.7–100.1); 24 (23.8%) patients died. Mortality was significantly higher in patients with malignant tumor in RPLND (50%) compared to those without malignancy (17.3%) (P = .002). In univariate logistic regression analyses, RPLND tumor diameter (odds ratio [OR]: 1.012, 95% CI: 1.004–1.021; P = .005), malignancy in RPLND (OR: 3.787, 95% CI: 1.669–8.594; P = .001), NTGCT in RPLND (OR: 3.451, 95% CI: 1.473–8.083; P = .004), and yolk sac tumor in orchiectomy (OR: 0.220, 95% CI: 0.049–0.985; P = .048) were associated with overall mortality. In multivariate analysis, only RPLND tumor diameter remained an independent predictor (OR: 1.018, 95% CI: 1.000–1.035; P = .045). Conclusion: Postchemotherapy RPLND most frequently revealed teratoma, while larger tumor diameter independently predicted malignant findings and adequate sampling increased malignancy detection. Cite this article as: Hürdoğan Ö, Cantürk Z, Ugar M, et al. Histopathological spectrum of postchemotherapy retroperitoneal lymph node dissection in testicular cancer: the impact of sampling adequacy and viable nonteratomatous germ cell tumor. Cerrahpaşa Med J, 2026, 50, 0037, doi: 10.5152/cjm.2026.26037.

Renal cell carcinoma (RCC) is a common manifestation in Von-Hippel Lindau (VHL) syndrome, accounting for almost 30

INTRODUCTION:Bladder cancer is prevalent worldwide; however, the detailed mechanisms underlying its initiation and progression remain incompletely understood. This study aimed to investigate the expression levels of long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) and microRNA-200c (miR-200c) in tumor tissues of patients with bladder cancer and to explore their association with clinicopathologic features. METHODS:The study cohort consisted of 50 patients diagnosed with non-muscle-invasive bladder cancer. Tumor tissues and adjacent normal tissues were obtained during transurethral resection of bladder tumor. The relative expression levels of lncRNA-ATB and miR-200c were determined using quantitative reverse transcriptase-polymerase chain reaction. RESULTS:LncRNA-ATB expression was substantially higher in tumor tissues than in adjacent normal tissues. Conversely, miR-200c was upregulated in tumor tissues but showed lower expression in high-grade tumors compared with low-grade tumors. A receiver operating characteristic curve analysis indicated that lncRNA-ATB (72% sensitivity, 68% specificity) and miR-200c (68% sensitivity, 64% specificity) could distinguish tumor from normal tissues. DISCUSSION:This study is the first to concurrently evaluate lncRNA-ATB and miR-200c expression in non-muscle-invasive bladder cancer. Even in early-stage bladder cancer, alterations in the lncATB/miR-200c axis appear to be associated with tumor grade and may potentially serve as an indicator of metastatic potential.

Concurrent enzalutamide may upregulate PSMA expression and enhance the efficacy of [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT). We evaluated outcomes of PSMA-RLT with and without concurrent enzalutamide in a real-world metastatic castration-resistant prostate cancer (mCRPC) cohort. We retrospectively evaluated 208 mCRPC patients treated with [177Lu]Lu-PSMA-617 at a single institution between June 2015 and January 2026. Among them, 106 received concurrent enzalutamide and 102 without any concurrent androgen receptor pathway inhibitor. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS), PSA50 response, pain response, and toxicity. Median OS was 20.0 months in the concurrent enzalutamide group versus 12.4 months in the no-ARPI group (log-rank p = 0.082). In multivariable Cox analysis, concurrent enzalutamide was not independently associated with OS (hazard ratio 1.15, 95

BACKGROUND AND OBJECTIVE:Inferior vena cava (IVC) tumor thrombus can impact the surgical management of locally advanced renal cell carcinoma (RCC). While open surgery remains the standard for complex thrombi, minimally invasive surgery (MIS) is increasingly adopted. The aim of this review was to compare perioperative outcomes across the different surgical approaches for IVC thrombectomy in nonmetastatic RCC. METHODS:We systematically searched the PubMed, Embase, Scopus, and Web of Science databases from inception to January 10, 2025 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol was registered on PROSPERO (CRD42022330114). Retrospective and prospective studies reporting operative time (OT), estimated blood loss (EBL), complication rates, or length of stay (LOS) after IVC thrombectomy were included. A meta-analysis of proportions and a network meta-analysis (NMA) of comparative studies were performed using random-effects models. KEY FINDINGS AND LIMITATIONS:Sixty-six studies (3241 patients) were included. Conventional meta-analysis revealed that mean OT was similar across approaches (p = 0.07), while mean EBL was significantly lower with MIS (robotic: 918.2 ml; laparoscopic: 253.7 ml) than with open surgery (1488.4 ml; p < 0.001). Overall complication rates were 28.5% with robotic, 12.6% with laparoscopic, and 28.9% with open surgery (p = 0.05), with corresponding major complication rates of 5.1%, 2.8%, and 12.9% (p = 0.02). NMA revealed shorter mean OT for robotic (-58.7 min; p < 0.001) and laparoscopic (-43.3 min; p = 0.01) approaches versus open surgery, and lower odds ratios for overall complications (robotic 0.37, p = 0.01; laparoscopic 0.24, p < 0.001) with MIS. Mean LOS was also shorter with MIS (robotic: -3.8 d; laparoscopic: -4.8 d; p < 0.05). Differences in major complication rates were not significant on NMA. Limitations include the retrospective design of the studies included, selection bias favoring open surgery for advanced thrombi, and under-reporting of oncological outcomes. CONCLUSIONS AND CLINICAL IMPLICATIONS:High-quality comparative evidence on MIS for IVC thrombectomy is limited and affected by substantial selection bias, which restricts robust comparisons to open surgery. Our findings suggest that MIS is associated with favorable perioperative outcomes in carefully selected patients, mainly with Mayo I-II thrombi in experienced centers, but no definitive conclusions on their comparative effectiveness versus open surgery can be drawn.

We aimed to evaluate the prognostic significance of TLR4 expression in bladder cancer, its association with genes related to EMT, and the potential regulatory role of selected microRNAs. Tumor and adjacent healthy bladder tissue samples obtained from 25 patients who underwent radical cystectomy for bladder cancer were analysed. The expression levels of TLR4, SPRR2A, SPRR1A, SPRR2B, ZEB2 and CDH1, in addition to miR-200c-3p and miR-146a-5p were measured using the RT-PCR method. Additionally, the expression of the TLR4 protein was assessed using the immunohistochemistry. Gene expression levels were comparatively analysed with regard to their association with the clinicopathological characteristics, and survival. The SPRR2A expression was significantly higher in tumour tissues compared with the levels in normal tissues (p = 0.001). TLR4 expression showed a positive correlation with SPRR1A (r = 0.603,p = 0.001), ZEB2 (r = 0.398, p = 0.049) and CDH1 (r = 0.403, p = 0.046). Notably, TLR4 expression was significantly lower in patients with lymph node metastasis (p = 0.049), while miR-200c-3p expression was considerably lower in patients with a history of smoking (p < 0.0001). Survival analyses revealed an inverse association between overall survival and SPRR2B expression (r = − 0.665,p = 0.013), whereas cancer-related mortality was associated with the decreased expression of SPRR1A (p = 0.008), and SPRR2B (p = 0.005). TLR4 expression is associated with the regulation of the genes involved in EMT, as well as with metastasis in bladder cancer. The interaction between TLR4, EMT-associated genes and microRNAs may have prognostic and therapeutic implications. However, these findings require validation in prospective larger, independent cohorts.

You have accessJournal of UrologyKidney Cancer: Advanced (Including Drug Therapy) II (PD18)1 May 2024PD18-10 HOW IS THE EFFICACY OF PATIENT SELECTION CRITERIA FOR ADJUVANT PEMBROLIZUMAB AFTER CURATIVE SURGICAL TREATMENT OF CLEAR CELL RENAL CELL CARCINOMA WITH INTERMEDIATE TO HIGH RISK OF RECURRENCE? A REAL-LIFE DATA ANALYSIS FROM SINGLE INSTITUTIONAL EXPERIENCE Selcuk Erdem, Anil Tantekin, Firat Ozervarli, Rifat Ergul, Yasar Pazir, Ozge Hurdogan, Yasemin Ozluk, Oner Sanli, and Faruk Ozcan Selcuk ErdemSelcuk Erdem , Anil TantekinAnil Tantekin , Firat OzervarliFirat Ozervarli , Rifat ErgulRifat Ergul , Yasar PazirYasar Pazir , Ozge HurdoganOzge Hurdogan , Yasemin OzlukYasemin Ozluk , Oner SanliOner Sanli , and Faruk OzcanFaruk Ozcan View All Author Informationhttps://doi.org/10.1097/01.JU.0001008596.32809.c5.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Adjuvant pembrolizumab is recommended for reducing recurrence risk after curative surgical treatment of intermediate to high risk non-metastatic clear cell renal cell carcinoma (ccRCC). This study investigated the natural course of non-metastatic ccRCC after curative surgery in patients classified by the KEYNOTE-564 patient selection criteria. METHODS: A total of 531 curative and cytoreductive nephrectomies were performed between January 2015 and March 2023 in a tertiary single institution. After exclusion of 235 patients (n=201 non-ccRCC, n=20 incomplete follow-up, n=14 cytoreductive nephrectomy for metastatic renal tumor), a total of 296 non-metastatic ccRCC patients undergoing curative surgery were included into this study. The clinical, histopathological and survival parameters were retrospectively documented from prospectively collected real life database. Chi-square and Mann-Whitney U tests were used for the comparisons of parameters. Kaplan-Meier Analysis was used for survival outcomes. RESULTS: Overall, 76 (25.7%) patients were defined as eligible for adjuvant pembrolizumab (n=66, 86.8%; intermediate to high risk, n=10, 13.2%; high risk). The eligible patients had significantly larger median tumor size in clinical (7.5 vs. 3.9 cm, p<0.001) and pathological (7.8 vs. 3.65 cm, p<0.001) assessments, and underwent more often radical nephrectomy (95.9 vs 27.7%, p<0.001). Two-year recurrence free survival (RFS) was significantly lower (58.6 vs. 94.6%, p<0.001) in eligible patients. A total of 44 (14.9%) patients recurred in overall cohort at median follow-up of 18 months, 25 (32.9%) in eligible group and 19 (8.6%) in non-eligible group. Median pathologic tumor size were larger (9 vs 5 cm, p<0.001) and median time to recurrence were earlier (8 vs. 32 months, p<0.001) in eligible group. Fifty-one (67.1%) patients in eligible group did not experience any recurrence at a median follow-up of 18 months (IQRs:6-30 months). CONCLUSIONS: This real-life data showed that ccRCC recurred after curative surgery in 32.9% of patients defined eligible for adjuvant pembrolizumab, and in 8.5% of patients defined non-eligible. The remaining 67.1% of eligible patients did not recur at median follow-up of 18 months. These results suggested that patient selection criteria defined in KEYNOTE-564 needs to be improved to optimize cost-effectivity in the route of individualized treatment strategies. Download PPT Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e436 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Selcuk Erdem More articles by this author Anil Tantekin More articles by this author Firat Ozervarli More articles by this author Rifat Ergul More articles by this author Yasar Pazir More articles by this author Ozge Hurdogan More articles by this author Yasemin Ozluk More articles by this author Oner Sanli More articles by this author Faruk Ozcan More articles by this author Expand All Advertisement PDF downloadLoading ...

Background Renal angiomyolipoma (AML) is a benign perivascular epithelioid cell neoplasm that is often associated with tuberous sclerosis complex (TSC). Epithelioid AML (eAML), a very rare and potentially malignant variant, can be challenging to radiologically differentiate from benign AML and other renal tumors. Adverse histological features have previously been associated to poorer oncological outcomes. This study aimed to characterize this rare disease entity and validate previously reported adverse prognostic factors. Methods This multicenter, retrospective cohort study analyzed 76 patients diagnosed with eAML between 2001 and 2024 across 15 participating centers. Inclusion criteria were histological diagnosis of eAML with negative cytokeratin markers and positive melanocytic markers. Patients were stratified according to previously described adverse pathological features. Results A total of 76 patients were studied. Most were female (70%), with a median age of 48 years and, 19 patients had TSC. Median tumor size was 45 mm, with a rate of atypical epithelioid cells >70% in 26 (34.2%) patients. According to the Nese’s and Brimo’s classifications, 4% and 14% of patients were at high risk, respectively. During a median follow- up of 30-months, 5 (6.7 %) patients developed metastases, and 4 (5.3 %) died. At univariable analysis, the number of adverse pathological risk factors, according to both classifications, was significantly associated with worse metastasis free survival (MFS) and cancer specific survival (CSS). Due to the low number of events, a multivariable analysis was not carried out. Conclusions eAML is extremely rare, and primarily affects middle-aged women. This cohort validated previously described pathological risk factors for worse prognosis, suggesting that patients with multiple adverse features may require more intensive follow-up.