Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities.

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

Reoperation Rate for Residual/Regrowth Adenoma Following Transurethral Interventions for Benign Prostatic Enlargement: Results from a Systematic Review and Meta-Analysis of Comparative Randomized Studies.

Objective: To perform a systematic review to assess the incidence of reoperation rate for residual/regrowth adenoma after transurethral surgeries for benign prostatic enlargement. Materials and Methods: A systematic literature search was performed on November 12, 2023, using Cochrane Central Register of Controlled Trials, PubMed, and Scopus. We only included randomized studies comparing monopolar (M)/bipolar (B) transurethral resection of the prostate (TURP) vs ablation vs enucleation procedures. Incidence of reoperation was assessed using the Cochran-Mantel-Haenszel Method and reported as risk ratio (RR), 95% confidence interval (CI), and p-values. Statistical significance was set at p < 0.05. Evidence synthesis: Forty-eight studies were included. Six studies compared enucleation vs TURP, 41 ablation vs TURP, and 1 study enucleation vs ablation vs TURP, encompassing 457 patients in enucleation, 2259 in ablation, and 2517 in the TURP group. The pooled incidence of reoperation was 6.2%, 0.7%, 2.3%, and 4.3% after ablation, enucleation, M-TURP, and B-TURP, respectively. Meta-analysis showed that the incidence of reoperation was significantly lower in the enucleation group (RR 0.28, 95% CI 0.10-0.81, p = 0.02), but the difference accounted only in studies with follow-up between 1 and 3 years (RR 0.18, 95% CI 0.04-0.85, p = 0.03). The incidence of reoperation was significantly lower in the enucleation compared with the B-TURP group (RR 0.14, 95% CI 0.03-0.77, p = 0.02). Meta-analysis showed that the incidence of reoperation was significantly higher in the ablation group (RR 1.81, 95% CI 1.33-2.47, p = 0.0002), but there was no difference in studies with follow-up up to 1 year (odds ratio 1.78 95% CI 0.97-3.29, p = 0.06) longer than 5 years (RR 2.02, 95% CI 0.71-5.79, p = 0.19). The incidence of reoperation was significantly higher in the ablation compared with the M-TURP group (RR 1.91, 95% CI 1.44-2.54, p < 0.0001). Conclusions: In mid-term follow-up, reoperation rate for residual/regrowth adenoma was significantly lower after enucleation, although was significantly higher after ablation compared with TURP.

Extracorporeal shock wave lithotripsy, ureterolithotripsy, and percutaneous nephrolithotripsy challenges in managing spinal cord neuropathy patients. Lessons learned from a scoping review.

Introduction: We aim to review the outcomes of shock wave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotripsy (PCNL) for renal and ureteral stones in spinal cord neuropathy patients (SNP). Material and methods: A literature search was performed on 8th March 2023 using PubMed, EMBASE, and Google Scholar with no date limit. Preclinical/animal studies, reviews, letters to the editor, case reports, and meeting abstracts were excluded. Only English papers were accepted. Results: Thirty-five articles were accepted. Five studies focused on SWL, 17 on PCNL, and 6 on ureteroscopy. The remaining articles employed more than one procedure. Stone composition has shifted from struvite to the more common calcium phosphate. SWL showed a very poor stone-free rate (SFR) likely due to challenges in patient positioning, stone visualization, localization, and inability to pass fragments spontaneously. Flexible ureteroscopy and PCNL were associated with a high incidence of infectious complications, long hospital stays, high blood transfusion rate, and intensive care admissions. There were also cases of death. Both procedures were challenging due to genitourinary reconstruction, scoliosis and kyphosis, rib-cage deformity, lower limb contractures, and severe comorbidity which also affected anesthesia. SFR was lower than in non-neurological patients. Conclusions: SWL, ureterolithotripsy, and PCNL should be considered challenging procedures in SNP due to positioning issues, an increased risk of intra and peri-operative morbidity, and even mortality. Computed tomography should be recommended to assess residual fragments as it becomes imperative to minimize a re-intervention in SNP who should be preferably treated in referral centers.

Mini and Standard Percutaneous Nephrolithotomy in Obese Patients. Results from a Single-surgeon Large Series.

Background and objective: Percutaneous nephrolithotomy (PCNL) is the recommended treatment for large or complex renal stones. This study aims to evaluate the outcomes of mini PCNL in obese and nonobese patients and to compare the outcomes of mini and standard PCNL in the obese population. Methods: We retrospectively reviewed our PCNL database to identify patients who had undergone mini (Amplatz sheath size 17.5Ch) or standard (Amplatz sheath size ≥26Ch) PCNL between 2005 and 2022. First, we compared the outcomes of the two procedures in the obese (body mass index [BMI] ≥30) and nonobese (BMI<30) patients. Second, we compared the outcomes of mini and standard PCNL in the obese population. A multivariable logistic regression analysis was performed to assess the variables associated with stone-free rate (SFR) and complications. Key findings and limitations: A total of 781 patients underwent mini PCNL; there was no difference between nonobese (578) and obese (133) patients in surgical time, number of tubeless procedures, postoperative stay, SFR, and overall complication rates. Similar outcomes were also seen in the 356 patients who had undergone standard PCNL, including 276 nonobese and 80 obese patients. The comparison of mini and standard PCNL in the obese population (213 patients) showed that mini PCNL provided significant benefits in surgical time (60 vs 94 min), SFR (85% vs 63.8%), and blood transfusion rate (2% vs 10%). The multivariable analysis confirmed that mini PCNL resulted in significantly higher odds of being stone free (odds ratio [OR] 1.79) and lower odds of having a blood transfusion (OR 0.28). Conclusions and clinical implications: Obese patients can safely undergo either mini or standard PCNL; in this series, mini performed better than standard PCNL in terms of SFR and blood transfusion rates. Patient summary: In this study, we compared the outcomes of mini and standard percutaneous nephrolithotomy (PCNL) in the obese population. We found that mini PCNL had lower surgical time and blood transfusion rate, and better stone-free rate than its standard counterpart in obese patients.

Integrating the PD-L1 Prognostic Biomarker in Non-Muscle Invasive Bladder Cancer in Clinical Practice-A Comprehensive Review on State-of-the-Art Advances and Critical Issues.

Bladder cancer (BC) is one of the most prevalent cancers worldwide. Non-muscle invasive bladder cancer (NMIBC), comprising the majority of initial BC presentations, requires accurate risk stratification for optimal management. This review explores the evolving role of programmed cell death ligand 1 (PD-L1) as a prognostic biomarker in NMIBC, with a particular focus on its implications in the context of Bacillus Calmette-Guérin (BCG) immunotherapy. The literature suggests a potential association between elevated PD-L1 status and adverse outcomes, resistance to BCG treatment, and disease progression. However, conflicting findings and methodological issues highlight the heterogeneity of PD-L1 assessment in NMIBC, probably due to the complex biological mechanisms that regulate the interaction between PD-L1 and the tumor microenvironment. The identification of PD-L1 as a prognostic biomarker provides ground for tailored therapeutic interventions, including immune checkpoint inhibitors (ICIs). Nevertheless, challenges such as intratumoral heterogeneity and technical issues underscore the need for standardized protocols and larger, homogeneous trials. This review contributes to the ongoing debate on the personalized management of NMIBC patients, focusing on the advances and perspectives of incorporating PD-L1 as a biomarker in this setting.

Prognostic Value of P63 Expression in Muscle-Invasive Bladder Cancer and Association with Molecular Subtypes-Preliminary Report.

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Suction in Percutaneous Nephrolithotripsy: Evolution, Development, and Outcomes from Experimental and Clinical studies. Results from a Systematic Review.

CONTEXT: Controversy exists regarding the therapeutic benefit of suction use during percutaneous nephrolithotripsy (PCNL). OBJECTIVE: To review and highlight the options available in the use of suction for PCNL, and to discuss their strengths and limitations. EVIDENCE ACQUISITION: A systematic literature search was performed using Scopus, EMBASE, and PubMed. Thirty four studies were included. There was one ex vivo study. Among clinical studies, 24 used a vacuum/suctioning sheath and nine a handpiece suction device/direct-in-scope suction. The suction technique was employed in standard, mini-PCNL, supermini-PCNL, and enhanced supermini­PCNL techniques. EVIDENCE SYNTHESIS: Handpiece suction devices demonstrated better safety and efficiency in treating large stones than nonsuction PCNL and in a much shorter time. Trilogy and ShockPulse-SE were equally effective, safe, and versatile for standard PCNL and mini-PCNL. The heavier handpiece makes Trilogy less ergonomically friendly. Laser suction handpiece devices can potentiate laser lithotripsy by allowing for better laser control with simultaneous suction of small fragments and dust. Integrated suction-based sheaths are available in reusable and disposable forms for mini-PCNL only. Mini-PCNL with suction reported superior outcomes for operative time and stone-free rate to mini-PCNL. This also helped minimize infectious complications by a combination of intrarenal pressure reduction and faster aspiration of irrigation fluid reducing the risk of sepsis, enhance intraoperative vision, and improve lithotripsy efficiency, which makes it a very attractive evolution for PCNL. CONCLUSIONS: Suction devices in PCNL are reforming the way PCNL is being done. Adding suction to mini-PCNL reduces infectious complications and improves the stone-free rate. Our review shows that despite the limited evidence, suction techniques appear to improve PCNL outcomes. PATIENT SUMMARY: In this review, we looked at the intra- and perioperative outcomes of percutaneous nephrolithotripsy (PCNL) with the addition of suction. With better stone fragmentation and fewer postoperative infections, this technology is very useful particularly for mini-PCNL.

The current evidence on surgical management for synchronous bilateral renal tumors: results from a scoping review.

PURPOSE: Synchronous bilateral renal masses (SBRM) account for a low percentage of kidney tumors, and there is no current recommendation for their management. The objective was to review evidence regarding the best surgical approach for SBRM in terms of type and timing of surgery. METHODS: A broad literature search was performed on 28th January 2023 using Scopus, PubMed, and EMBASE. Only English papers dealing with adults were included. Meeting abstracts were excluded. RESULTS: Twenty-four papers were accepted and included. SBRM behave less aggressively than metachronous tumors, and partial nephrectomy (PN) is the preferred therapeutic option to preserve renal function. Open, laparoscopic, and robot-assisted approaches were found to be similar in oncological outcomes, though robot-assisted surgery resulted in lower comorbidities. Same-sitting PN was demonstrated to be a safe approach, particularly in the robotic-assisted one. Finally, the same-siting and staged NSS were similar in preserving renal function. CONCLUSIONS: PN should be the desirable treatment for SBRM whenever feasible and if patients are fit, but surgeon expertise should also be taken into the account.

Clinicopathological Features and Survival Analysis in Molecular Subtypes of Muscle-Invasive Bladder Cancer.

Molecular subtyping of bladder cancer (BC) aims to capture the biological heterogeneity of this complex disease in order to provide better patient risk stratification. Immunohistochemical (IHC) markers are regarded as promising surrogates to classify BCs into luminal and basal subtypes in routine practice. We investigated the correlation between the molecular subclassification, assessed through IHC, and the conventional prognostic variables of a cohort of 93 muscle-invasive BCs (MIBCs), with a focus on the pattern of muscularis propria (MP) invasion, and evaluated their association with outcome. Basal, luminal, double-positive (DP), and double-negative (DN) phenotypes were identified according to the coordinate expression of 1 basal (CK5/6) and 2 luminal (CK20, GATA3) markers, and accounted for 33.3%, 32.3%, 3.2%, and 31.2% (Scheme #1) and 9.7%, 60.2%, 26.9%, and 3.2% (Scheme #2). There was a significant association between the pattern of MP invasion and the molecular subtypes according to Scheme #2, in that all 8 basal and DN cases, as well as 83% of DP cases, had a non-infiltrative invasion pattern. No consistent differences were observed in terms of OS and CSS between the molecular subtypes obtained through surrogate IHC markers. In keeping with previous studies, we report the correlation between the identification of BC subtypes and the presence of morphological prognostic factors, supporting the need for a comprehensive pathological evaluation, including clinicopathological and molecular parameters, in order to improve the diagnosis and management of MIBC.

HER2 Expression in Bladder Cancer: A Focused View on Its Diagnostic, Prognostic, and Predictive Role.

Bladder cancer (BC) is a heterogeneous disease from a molecular, morphological, and clinical standpoint. HER2 is a known oncogene involved in bladder carcinogenesis. Assessing HER2 overexpression as a result of its molecular changes in a routine pathology practice using immunohistochemistry might be a useful adjunct in several scenarios, namely (1) to correctly identify flat urothelial lesions and inverted urothelial lesions in the diagnostic setting; (2) to provide prognostic hints in both non-muscle invasive (NMI) and muscle invasive (MI) tumors, thus supplementing risk stratification tools, especially when evaluating higher-risk tumors such as those with variant morphology; (3) to improve antibody panels as a surrogate marker of BC molecular subtyping. Furthermore, the potential of HER2 as a therapeutic target has been only partly explored so far, in light of the ongoing development of novel target therapies.