CEA (CEACAM5) expression is common in muscle-invasive urothelial carcinoma of the bladder but unrelated to the disease course.

Objectives: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein that represents a promising therapeutic target. Serum measurement of shedded CEA can be utilized for monitoring of cancer patients. Material and Methods: To evaluate the potential clinical significance of CEA expression in urothelial bladder neoplasms, CEA was analysed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format. Results: CEA staining was largely absent in normal urothelial cells but was observed in 30.4% of urothelial bladder carcinomas including 406 (16.7%) with weak, 140 (5.8%) with moderate, and 192 (7.9%) with strong staining. CEA positivity occurred in 10.9% of 411 pTaG2 low-grade, 32.0% of 178 pTaG2 high-grade, and 43.0% of 93 pTaG3 tumours (p < 0.0001). In 1335 pT2-4 carcinomas, CEA positivity (34.1%) was lower than in pTaG3 tumours. Within pT2-4 carcinomas, CEA staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence free survival, and cancer specific survival (p > 0.25). Conclusion: CEA increases markedly with grade progression in pTa tumours, and expression occurs in a significant fraction of pT2-4 urothelial bladder carcinomas. The high rate of CEA positivity in pT2-4 carcinomas offers the opportunity of using CEA serum measurement for monitoring the clinical course of these cancers. Moreover, CEA positive urothelial carcinomas are candidates for a treatment by targeted anti-CEA drugs.

The clinical meaning of lymphovascular invasion: preoperative predictors and postoperative implications in prostate cancer - a retrospective study.

Introduction: Lymphovascular invasion (LVI) is a pivotal histopathological parameter in prostate cancer (PCa), holding significant prognostic implications. Our study pursued a dual objective: firstly, to identify preoperative factors associated with LVI, aiming to unveil markers facilitating the recognition of patients prone to LVI during postoperative examination; and secondly, to assess postoperative outcomes correlated with LVI. Methods: We retrospectively analyzed 861 nonmetastatic PCa patients who underwent radical prostatectomy (RP), investigating preoperative factors and postoperative outcomes. Surgical specimens were processed following established guidelines. Statistical analyses utilized non-parametric tests to assess the association between LVI and both pre- and postoperative factors. Furthermore, logistic regression analyses were utilized to develop models aimed at identifying the most significant predictors of LVI and pN1 status, respectively. Results: Numerous preoperative factors exhibited significant correlations with LVI, offering valuable clinical insights. Logistic regression identified magnetic resonance imaging (MRI)-based clinical tumor stage (cT) 3-4, biopsy Gleason Grading Group (GGG) 3-5, preoperative prostate specific antigen (PSA) ≥20 and percentage of positive biopsy cores (PPBC) ≥50% as the strongest preoperative predictors of LVI. Additionally, the study uncovered an association between LVI and postoperative outcomes, including postoperative PSA (p value <0.001), extracapsular extension (ECE) (<0.001), positive surgical margins (PSM) (<0.001), perineural invasion (PNI) (<0.001), pathological tumor stage (pT) (<0.001), pathological lymph node status (pN) (<0.001), postoperative GGG (<0.001), and operative time (0.023). Notably, the study revealed a novel and substantial association between LVI and an increased number of positive lymph nodes in pN+ patients in the univariate analysis (<0.001). Furthermore, we have found an association between LVI and pN1 status in the logistic regression analysis (odds ratio [OR] = 23.905; p <0.001). Conclusion: Our findings underscore the pivotal role of LVI in influencing the prognosis of prostate cancer (PCa). The study acknowledges the challenges associated with preoperative LVI assessment and emphasizes the need for future research to unravel the factors associated with this histopathological finding. Significantly, our research stands out as the first, to the best of our knowledge, to reveal the association between LVI and the number of positive lymph nodes in pN+ patients.

Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy.

Background: Neutrophil-to-lymphocyte ratio (NLR), a widely assessed biomarker in most common diseases, is typically evaluated before treatment initiation. However, data on NLR in the post-treatment setting is limited. Therefore, we assessed the NLR calculated after neoadjuvant chemotherapy (NAC) initiation in patients with bladder cancer (BC). We hypothesised that changes in blood cells after NAC could be a marker of tumour response and long-term survival. Materials and Methods: Our study included 214 patients who underwent NAC followed by radical cystectomy (RC) in two urological departments, wherein post-NAC NLR was used to categorize patients into the low (NLR ≤ 1.75) and high (NLR > 1.75) groups. Results: Logistic regression analysis indicated that a post-NAC NLR ≥ 1.75 is a good biomarker for pathologic response (odds ratio (OR), 0.045; p <0.001), emphasizing its ability to predict patient survival. The HRs for overall survival and cancer-specific survival were 2.387 (p = 0.048) and 2.342 (p < 0.001), respectively. Conclusions: We believe that post-NAC NLR can be used for patient stratification after NAC. Consequently, the post-NAC NLR may serve as a guide for the decision-making process regarding RC versus bladder-preserving strategies.

Assessment of the incidence and risk factors of postoperative urosepsis in patients undergoing ureteroscopic lithotripsy.

Introduction: Ureteroscopic lithotripsy (URSL) is an approved, minimally invasive, low-risk procedure for urolithiasis treatment. However, some patients may develop urinary tract infection (UTI) post-procedure, eventually leading to urosepsis. Determining the predictors of infection after URSL would help identify patients at a high risk of urosepsis, thereby enabling the early implementation of effective treatment. Therefore, we aimed to establish the incidence and predictors of urosepsis after URSL. Material and methods: We assessed 231 patients who underwent URSL using a holmium laser. The incidence of urosepsis during the 30-day post-treatment period was analysed, and potential predictors of urosepsis, including patient characteristics and individual clinical factors, were examined. Results: Statistical analysis revealed that 16.88% of patients had a confirmed positive urine culture before the procedure. Post-procedure urosepsis occurred in 4.76% of patients. Univariable analysis revealed that 3 factors were significantly associated with the risk of postoperative urosepsis: double-J stent insertion before URSL, pre-operative positive urine culture, and MDR pathogen found preoperatively. In multivariable analysis, only positive urine culture remained significantly associated with the risk of urosepsis after URSL. Conclusions: Patients with positive urine culture before URSL are at significantly higher risk of urosepsis in the postoperative period. Hence, urine culture should be routinely performed before planned endoscopic urolithiasis treatment.

PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors.

BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.

Association of Lymphovascular Invasion with Lymph Node Metastases in Prostate Cancer-Lateralization Concept.

BACKGROUND: Lymphovascular invasion (LVI) is a vital but often overlooked prognostic factor in prostate cancer. As debates on lymphadenectomy's overtreatment emerge, understanding LVI laterality gains importance. This study pioneers the investigation into PCa, aiming to uncover patterns that could influence tailored surgical strategies in the future. METHODS: Data from 96 patients with both LVI and lymph node invasion (LNI) were retrospectively analyzed. All participants underwent radical prostatectomy (RP) with modified-extended pelvic lymph node dissection (mePLND). All specimens underwent histopathological examination. The assessment of LVI was conducted separately for the right and left lobes of the prostate. Associations within subgroups were assessed using U-Mann-Whitney and Kruskal-Wallis tests, as well as Kendall's tau-b coefficient, yielding p-values and odds ratios (ORs). RESULTS: Out of the 96 patients, 61 (63.5%) exhibited exclusive left-sided lymphovascular invasion (LVI), 24 (25.0%) had exclusive right-sided LVI, and 11 (11.5%) showed bilateral LVI. Regarding nodal involvement, 23 patients (24.0%) had LNI solely on the left, 25 (26.0%) exclusively on the right, and 48 (50.0%) on both sides. A significant correlation was observed between lateralized LVI and lateralized LNI (p < 0.001), particularly in patients with right-sided LVI only. LN-positive patients with left-sided LVI tended to have higher pT stages (p = 0.047) and increased odds ratios (OR) of bilateral LNI (OR = 2.795; 95% confidence interval [CI]: 1.231-6.348) compared to those with exclusive right-sided LVI (OR = 0.692; 95% CI: 0.525-0.913). CONCLUSIONS: Unilateral LVI correlates with ipsilateral LNI in PCa patients with positive LNs, notably in cases of exclusively right-sided LVI. Left-sided LVI associates with higher pT stages and a higher percentage of bilateral LNI cases.

Prognostic Impact and Spatial Interplay of Immune Cells in Urothelial Cancer.

BACKGROUND: Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. OBJECTIVE: To characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Spatial immune parameters were compared with histopathological parameters and overall survival data. RESULTS AND LIMITATIONS: The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8+ cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8+ T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells. CONCLUSIONS: The density of intraepithelial CD8+ T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8+ cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8+ T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index. PATIENT SUMMARY: Quantification of intraepithelial CD8+ T cells, the strongest prognostic feature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology.

Loss of Upk1a and Upk1b expression is linked to stage progression in urothelial carcinoma of the bladder.

BACKGROUND: Uroplakin-1a (Upk1a) and uroplakin-1b (Upk1b) have recently been identified as diagnostic markers for the distinction of urothelial carcinomas from other solid tumor entities. Both proteins play an important role in the stabilization and strengthening of epithelial cells that line the bladder. METHODS: To evaluate the prognostic role of uroplakin expression in urothelial carcinomas, more than 2700 urothelial neoplasms were analyzed in a tissue microarray format by immunohistochemistry. To further assess the diagnostic role of uroplakin immunohistochemistry, results were compared with preexisting GATA3 data. RESULT: The fraction of Upk1a/Upk1b positive cases decreased slightly from pTaG2 low-grade (88% positive for Upk1a/87% positive for Upk1b) and pTaG2 high-grade (92%/89%) to pTaG3 (83%/88%; p > 0.05) and was lower in muscle-invasive (pT2-4) carcinomas (42%/64%; p < 0.0001/p < 0.0001 for pTa vs. pT2-4). Within pT2-4 carcinomas, high expression of Upk1a and Upk1b was linked to nodal metastasis and lymphatic vessel infiltration (p < 0.05) but unrelated to patient outcome. There were significant associations between Upk1a, Upk1b and GATA3 immunostaining (p < 0.0001 each), but 11% of GATA3 negative cancers were Upk1a/b positive and 8% of Upk1a/b negative cancers were GATA3 positive. Absence of GATA3/Upk1a/b staining was significantly linked to poor patient survival in the subgroup of 126 pT4 carcinomas (p = 0.0004) but not in pT2 and pT3 cancers. CONCLUSIONS: In summary, the results of our study demonstrate that Upk1a and/or Upk1b immunohistochemistry can complement GATA3 for the distinction of urothelial carcinomas. Furthermore, a progressive loss of Upk1a/b expression during stage progression and a prognostic role of the combination GATA3/Upk1a/Upk1b in pT4 carcinomas is evident.

Altered p53/p16 expression is linked to urothelial carcinoma progression but largely unrelated to prognosis in muscle-invasive tumors.

BACKGROUND: Most inactivating p53 mutations result in a nuclear p53 accumulation - detectable by immunohistochemistry (IHC). p53 alterations leading to a complete lack of p53 protein and absence of immunostaining do also occur - not easily detectable by IHC. p16 is upregulated in p53 inactivated cells. We hypothesized that a positive p16 IHC may help to distinguish p53 inactivation in IHC negative cases. MATERIAL AND METHODS: We investigated p53 and p16 immunostaining on 2710 urothelial bladder carcinomas in a tissue microarray format to understand their impact in relation to clinicopathological parameters of disease progression and patient outcome. RESULTS: p16 immunostaining was absent in normal urothelium but occurred in 63.5% (30.4% strong) of cancers. p16 strongly positive cases increased from pTaG2 low-grade (9.6%) to pTaG3 high-grade tumors (46.5%, p < .0001) but decreased from pTaG3 to pT4 (33.3%; p = .0030). Among pT2-4 carcinomas, p16 positivity was linked to high-grade (p = .0005) but unrelated to overall survival. p53 staining was negative in 8.4%, very weak in 15.4%, weak in 55.3%, strong in 4.7%, and very strong in 16.2% cancers. p53 negative (potentially p53 null phenotype), strong, and very strong p53 positivity increased from pTaG2 low-grade to pTaG3 high-grade tumors (p < .0001) and from pTaG3 to pT2-4 cancers (p = .0007). p53 staining was largely unrelated to histopathological parameters or patient prognosis among pT2-4 carcinomas, except of p53 strong/very strong immunostaining. p16 expression predominated in tumors with very strong, strong, and negative p53 staining and the combination of p53 negative/p16 strongly positive cancers was linked to features of tumor aggressiveness. CONCLUSION: Aberrant p53 and p16 immunostaining increases during grade and stage progression although p53 negative and p16 positive immunostaining lack prognostic significance in pT2-4 carcinomas. Potential diagnostic features are that high level p16 expression is limited to neoplastic urothelium and p53 null phenotype to aggressive cancers (grade 3 and invasive).

Influence of Neoadjuvant Chemotherapy on Survival Outcomes of Radical Cystectomy in Pathologically Proven Positive and Negative Lymph Nodes.

Patients receiving neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) typically show better survival outcomes than those undergoing immediate surgery for muscle-invasive bladder cancer. However, most studies have not considered the lymph node (LN) status when evaluating NAC's survival benefits. This study sought to delineate the impact of NAC on patients based on their pathologically determined LN status at the time of RC. We examined data from 1395 patients treated at two departments between 1991 and 2022. Of them, 481 had positive LNs. A comparison of overall survival (OS) outcomes revealed that patients without LN involvement ((y)pN0) benefited from NAC with a hazard ratio (HR) of 0.692 (95% confidence interval [CI] 0.524-0.915). In contrast, patients with (y)pN+ showed no improvement with NAC (HR 0.927, 95%CI 0.713-1.205). Notably, patients treated with NAC for stage

Adequate Pelvic Lymph Node Dissection in Radical Cystectomy in the Era of Neoadjuvant Chemotherapy: A Meta-Analysis and Systematic Review.

Radical cystectomy (RC) with pelvic lymphadenectomy (PLND) serves as the gold-standard treatment for muscle-invasive bladder cancer (MIBC). Numerous studies have shown that the number of lymph nodes (LN) removed during RC could affect patient prognosis. However, these studies confirmed the association between PLND and survival outcomes prior to the widespread adoption of neoadjuvant chemotherapy (NAC). Consequently, this study aimed to investigate the prognostic role of PLND in patients previously pretreated with NAC. A systematic review and meta-analysis were performed using PubMed, Web of Knowledge, and Scopus databases. The selected studies contained a total of 17,421 participants. The meta-analysis indicated a significant correlation between adequate PLND and overall survival in the non-NAC group. However, a survival benefit was not observed in patients undergoing RC with preoperative systemic therapy, regardless of the LN cut-off thresholds. The pooled HR for ≥10 and ≥15 LN were 0.87 (95% CI 0.75-1.01) and 0.87 (95% CI 0.76-1.00), respectively. The study results suggest that NAC mitigates the therapeutic significance of PLND, as patients pre-treated with NAC no longer gain oncological benefits from more extensive lymphadenectomy. This highlights the analogous roles of NAC and PLND in eradication of micrometastases and in prevention of distal recurrence post-RC.

Cytokeratin 20 expression is linked to stage progression and to poor prognosis in advanced (pT4) urothelial carcinoma of the bladder.

Cytokeratin 20 (CK20) expression is limited to umbrella cells in the normal urothelium. Since CK20 is often upregulated in neoplastic urothelial cells including dysplasia and carcinoma in situ, immunohistochemical CK20 analysis is often used for the assessment of bladder biopsies. CK20 expression is a feature of luminal bladder cancer subtype, but its prognostic relevance is disputed. In this study, we investigated CK20 on >2700 urothelial bladder carcinomas in a tissue microarray format by immunohistochemistry. Cytoplasmic and membranous CK20 staining was seen in 1319 (51.8%) cancers. The fraction of CK20 positive and especially strongly positive cases increased from pTaG2 low grade (44.5% strongly positive) and pTaG2 high grade (57.7%) to pTaG3 high grade (62.3%; p = 0.0006) but was lower in muscle-invasive (pT2-4) carcinomas (51.1% in all pTa vs. 29.6% in pT2-4; p < 0.0001). Within pT2-4 carcinomas, CK20 positivity was linked to nodal metastasis and lymphatic vessel invasion (p < 0.0001 each) and to venous invasion (p = 0.0177). CK20 staining was unrelated to overall patient survival if all 605 pT2-4 carcinomas were jointly analyzed but subgroup analyses revealed a significant association of CK20 positivity with favorable prognosis in 129 pT4 carcinomas (p = 0.0005). CK20 positivity was strongly linked to the expression of GATA3 (p < 0.0001), another feature of luminal bladder cancer. The combined analysis of both parameters showed best prognosis for luminal A (CK20+/GATA3+, CK20+/GATA3-) and worst outcome for luminal B (CK20-/GATA3+) and basal/squamous (CK20-/GATA3-) in pT4 urothelial carcinomas (p = 0.0005). In summary, the results of our study demonstrate a complex role of CK20 expression in urothelial neoplasms including neoexpression in pTa tumors, a subsequent loss of CK20 expression in a subset of tumors progressing to muscle-invasion, and a stage dependent prognostic role in muscle-invasive cancers.

Did the COVID-19 Pandemic Restrict Access to Emergency Urological Services: Assessment of Reorganisation Effectiveness for Hospital Treatment.

Urolithiasis derived renal colic is a common urological condition. If treated properly, the disease resolves without complications; if not treated, it causes infection and renal failure. The COVID-19 restrictions impacted hospitalised treatment of diseases. We analysed the impact of COVID-19 on renal colic treatment at a hospital in Poland. Clinical and demographic data of patients treated during the COVID-19 era were compared with those treated before this pandemic. During the COVID-19 restrictions, renal colic patient hospital admissions fell significantly. However, more patients presented with chronic renal colic symptoms and urinary tract infections. Nevertheless, the degree of hydronephrosis and the number and location of stones did not differ between the two groups. No marked changes were observed in the chosen treatment options. The observed decrease in emergency admissions of patients with acute renal colic with a simultaneous increase in the rate of infectious stones might indicate that some patients requiring urgent medical help did not report to the emergency department or came later than they would before the pandemic, reporting more serious symptoms. One plausible explanation for this may be that the reorganisation of the healthcare system restricted access to urological care. Moreover, some patients may have delayed their visit to the hospital due to the fear of contracting the SARS-CoV-2 coronavirus.

Diminishing the Gender-Related Disparity in Survival among Chemotherapy Pre-Treated Patients after Radical Cystectomy-A Multicenter Observational Study.

There is a well-documented problem of inferior outcome of muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC) in women. However, previous studies were conducted before neoadjuvant chemotherapy (NAC) was widely adopted to multidisciplinary management of MIBC. In our study, we assessed the gender-related difference in survival between patients who received NAC and those who underwent upfront RC, in two academic centers. This non-randomized, clinical follow-up study enrolled 1238 consecutive patients, out of whom 253 received NAC. We analyzed survival outcome of RC according to gender between NAC and non-NAC subgroups. We found that female gender was associated with inferior overall survival (OS), compared to males (HR, 1.234; 95%CI 1.046-1.447; p = 0.013) in the overall cohort and in non-NAC patients with ≥pT2 disease (HR, 1.220 95%CI 1.009-1.477; p = 0.041). However, no gender-specific difference was observed in patients exposed to NAC. The 5-year OS in NAC-exposed women in ≤pT1 and ≥pT2 disease, was 69.333% 95%CI (46.401-92.265) and 36.535% (13.134-59.936) respectively, compared to men 77.727% 95%CI (65.952-89.502) and 39.122% 95%CI (29.162-49.082), respectively. The receipt of NAC not only provides downstaging and prolongs patients' survival after radical treatment of MIBC but may also help to diminish the gender specific disparity.

Combined Modality Bladder-Sparing Therapy for Muscle-Invasive Bladder Cancer: How (Should) We Do It? A Narrative Review.

Organ-sparing combined-modality treatment for muscle-invasive bladder cancer remains underutilized despite high-quality evidence regarding its efficacy, safety, and preservation of quality of life. It may be offered to patients unwilling to undergo radical cystectomy, as well as those unfit for neoadjuvant chemotherapy and surgery. The treatment plan should be tailored to each patient's characteristics, with more intensive protocols offered to patients who are fit for surgery but opt for organ-sparing. After a thorough, debulking transurethral resection of the tumor and neoadjuvant chemotherapy, the response evaluation should trigger further management with either chemoradiation or early cystectomy in non-responders. A hypofractionated, continuous radiotherapy regimen of 55 Gy in 20 fractions with concurrent radiosensitizing chemotherapy with gemcitabine, cisplatin, or 5-fluorouracil and mitomycin C is currently preferred based on clinical trials. The response should be evaluated with repeated transurethral resections of the tumor bed and abdominopelvic-computed tomography after chemoradiation, with quarterly assessments during the first year. Salvage cystectomy should be offered to patients fit for surgery who failed to respond to treatment or developed a muscle-invasive recurrence. Non-muscle-invasive bladder recurrences and upper tract tumors should be treated in line with guidelines for respective primary tumors. Multiparametric magnetic resonance can be used for tumor staging and response monitoring, as it may distinguish disease recurrence from treatment-induced inflammation and fibrosis.

Loss of TROP2 and epithelial cell adhesion molecule expression is linked to grade progression in pTa but unrelated to disease outcome in pT2-4 urothelial bladder carcinomas.

Introduction: Trophoblast cell surface antigen 2 (TROP2; EpCAM2) is a transmembrane glycoprotein which is closely related to EpCAM (EpCAM; EpCAM1). Both proteins share partial overlapping functions in epithelial development and EpCAM expression but have not been comparatively analyzed together in bladder carcinomas. TROP2 constitutes the target for the antibody-drug conjugate Sacituzumab govitecan (SG; TrodelvyTM) which has been approved for treatment of metastatic urothelial carcinoma by the United States Food and Drug administration (FDA) irrespective of its TROP2 expression status. Methods: To evaluate the potential clinical significance of subtle differences in TROP2 and EpCAM expression in urothelial bladder cancer, both proteins were analyzed by multiplex fluorescence immunohistochemistry in combination with a deep-learning based algorithm for automated cell detection on more than 2,700 urothelial bladder carcinomas in a tissue microarray (TMA) format. Results: The staining pattern of TROP2 and EpCAM were highly similar. For both proteins, the staining intensity gradually decreased from pTa G2 low grade (TROP2: 68.8±36.1; EpCAM: 21.5±11.7) to pTa G2 high grade (64.6±38.0; 19.3±12.2) and pTa G3 (52.1±38.7; 16.0±13.0, p<0.001 each). In pT2-4 carcinomas, the average TROP2 and EpCAM staining intensity was intermediate (61.8±40.9; 18.3±12.3). For both proteins, this was significantly lower than in pTa G2 low grade (p<0.001 each) but also higher than in pTa G3 tumors (p=0.022 for TROP2, p=0.071 for EpCAM). Within pT2-4 carcinomas, the TROP2 and EpCAM staining level was unrelated to pT, grade, UICC-category, and overall or tumor-specific patient survival. The ratio TROP2/EpCAM was unrelated to malignant phenotype and patient prognosis. Conclusion: Our data show that TROP2 and EpCAM expression is common and highly interrelated in urothelial neoplasms. Despite of a progressive loss of TROP2/EpCAM during tumor cell dedifferentiation in pTa tumors, the lack of associations with clinicopathological parameters in pT2-4 cancer argues against a major cancer driving role of both proteins for the progression of urothelial neoplasms.

Comparison of Laparoscopic and Open Radical Cystectomy for Muscle-Invasive Bladder Cancer.

The goal of the study was to compare laparoscopic and open radical cystectomy in treatment of muscle-invasive bladder cancer in the Department of Urology and Oncological Urology PUM in Szczecin. A total of 78 patients in the study group underwent laparoscopic cystectomy between 2016−2018, and 81 patients from the control group had open cystectomy between 2014−2016. Both groups were comparable in terms of age, stage, and concomitant diseases. The 3 year overall survival was comparable in both groups (37.7% for laparoscopy and 44.4% for open, p = 0.64). There was no difference in positive surgical margin rate. Lymph node yield during cystectomy was higher in open cystectomy (14 vs. 11.5, p = 0.001). Post-operative blood loss and transfusion rates were lower in laparoscopic cystectomy. Decrease in hemoglobin level was lower in laparoscopy (0.9 mmol/L, p < 0.001). Intraoperative transfusion rate was 11.8% in laparoscopy vs. 34.8% in open cystectomy (p = 0.002). Operation time, duration of hospitalisation, and time to full oral alimentation were comparable in both groups. Patients with BMI > 30 kg/m2 and those with pT3-T4 cancer in the laparoscopy group had less septic complications post-operatively. Patients with ASA score ≥ 3 from the laparoscopy group had fewer reoperations due to ileus. Laparoscopic cystectomy is less invasive and offers similar oncological outcomes to the open method. Patients benefit from less tissue trauma, less blood loss, and faster recovery. The presented results, as well as other publications, should encourage a wider use of this procedure in everyday urological practice.

GATA3 expression loss is linked to stage progression but is unrelated to prognosis in muscle-invasive urothelial carcinoma of the bladder.

The transcription factor GATA binding protein 3 (GATA3) is commonly used in surgical pathology as a diagnostic marker to distinguish urothelial carcinomas from other cancer entities. However, the clinical relevance of GATA3 expression in urothelial bladder cancer is not completely clarified. In this study, we investigated GATA3 immunostaining on 2710 urothelial bladder carcinomas on a tissue microarray platform by using two different antibodies to better understand its impact in relation to pathological parameters of disease progression and patient outcome. Nuclear GATA3 immunostaining was regularly seen in normal urothelium and found in 74%/82% of interpretable urothelial neoplasms depending on the antibody used. Within pTa tumors, the rate of GATA3 positive tumors decreased with advancing grade. GATA3 positivity was seen in 98.6%/99.8% of pTaG2 low-grade, 98.6%/100% of pTaG2 high-grade, and 94.9%/99.2% of pTaG3 high-grade tumors (P = .0002). As compared to pTa tumors, GATA3 positivity was markedly less common in muscle-invasive urothelial carcinoma (59.9%/71.6%; P < .0001). Within pT2-4 cancers, high-level GATA3 immunostaining was associated with the presence of lymph node metastasis (P = .0034), and blood vessel (P = .0290) or lymphatic invasion (P = .0005) but unrelated to pT stage. GATA3 immunostaining results for both antibodies were not associated with overall survival in 586 patients treated by cystectomy for pT2-4 urothelial carcinoma. The results of our study identify GATA3 expression as a frequent event in noninvasive urothelial carcinomas with favorable tumor features. Loss of GATA3 immunostaining is linked with muscle-invasive disease but is largely unrelated to pathological parameters and patient prognosis.

Increased One-Year Mortality Among Elderly Patients After Radical Cystectomy for Muscle-Invasive Bladder Cancer: A Retrospective, Observational Comparative Study.

Introduction: Muscle invasive bladder cancer (MIBC) is a common malignancy amongst elderly. Increasing life expectancy, prevalence of smoking, lifelong exposure to environmental pollutants and immunosenescence contribute to growing number of cases. Traditionally, radical cystectomy (RC) with pelvic lymph node dissection (PLND) constituted the mainstay of treatment for MIBC, but despite proven feasibility in elderly population, it has been associated with significant burden of morbidity, mortality, and complications. Study Objective: We aimed to re-evaluate the safety and efficacy of RC amongst the elderly patients with MIBC. Material and Methods: This single-center, retrospective, observational comparative study was conducted among 568 patients who underwent RC due to MIBC between 2003 and 2021. We evaluated the influence of chronological age (<70 vs ≥70 years) on clinical, demographic, and pathological variables related to MIBC and RC. Results: Elderly patients had similar clinical and pathological features of disease compared to their younger counterparts; nonetheless, they more often received simplified urinary diversion, ie ureterostomy (60.25% vs 39.33%, p<0.001) and had no PLND (15.76% vs 8.5%, p=0.01) during RC. Furthermore, more elderly patients were treated for secondary MIBCs and fewer had history of smoking. Severe complication and 90-day mortality rates were comparable between groups; however, the elderly had significantly higher all-cause mortality at one year post RC (46.67% vs 33.25%, p=0.003). On multivariate analysis, one-year mortality risk was independently associated with elderly age (HR=2.119, 95% CI: 1.227-3.660, p=0.007), rural residency (HR=1.760, 95% CI: 1.043-2.968, p=0.034), extravesical extension of tumor (HR=2.109, 95% CI: 1.155-3.850, p=0.015), lymph node metastasis (HR=2.268, 95% CI: 1.290-3.987, p=0.004) and omission of PLND (HR=6.064, 95% CI: 2.926-12.568, p<0.001). Conclusion: Radical cystectomy in elderly patients is associated with significant one-year mortality. Our study emphasizes the unmet need for considerate planning of treatment for MIBC in potentially vulnerable groups of elderly patients. Efforts are needed to reliably identify those unlikely to benefit from surgery and facilitate patient-centered choice of alternative therapies.

When Bodybuilding Goes Wrong-Bilateral Renal Artery Thrombosis in a Long-Term Misuser of Anabolic Steroids Treated with AngioJet Rheolytic Thrombectomy.

Bilateral renal infarction is an extremely rare condition with only few cases reported in the literature. We present a case of bilateral renal infarction affecting an otherwise healthy 34 year old bodybuilder chronically misusing testosterone and stanozolol. The patient presented with severe flank pain mimicking renal colic and biochemical features of acute kidney injury. Diagnostic workup revealed thrombosis affecting both renal arteries. Subsequently, the patient underwent a percutaneous rheolytic thrombectomy with AngioJet catheter, along with catheter-directed thrombolysis. Right-sided retroperitoneal hematoma developed as an early complication, mandating surgical exploration and nephrectomy due to kidney rupture and the unstable condition of the patient. Intensive care and continuous renal replacement therapy were instigated until a gradual improvement of the patient status and a return of kidney function was achieved. No abnormalities were found in the cardiological and hematological evaluation. We believe this is a first report of bilateral renal infarction associated with anabolic steroid misuse in an otherwise healthy individual, and a first report of AngioJet thrombectomy in bilateral thrombosis of renal arteries. It stresses the importance of a thorough diagnostic workup of colic patients and emphasizes the need for sports medicine to reach out to amateur athletes with education on the harms of doping.