Assessing Functional Outcomes of Partial Versus Radical Nephrectomy for T1b-T2 Renal Masses: Results from a Multi-institutional Collaboration.

BACKGROUND: Deterioration of renal function is associated with increased all-cause mortality. In renal masses larger than 4 cm, whether partial versus radical nephrectomy (PN vs. RN) might affect long-term functional outcomes is unknown. This study tested the association between PN versus RN and postoperative acute kidney injury (AKI), recovery of at least 90% of the preoperative estimated glomerular filtration rate (eGFR) at 1 year, upstaging of chronic kidney disease (CKD) one stage or more at 1 year, and eGFR decline of 45 ml/min/1.73 m2 or less at 1 year. METHODS: Data from 23 high-volume institutions were used. The study included only surgically treated patients with single, unilateral, localized, clinical T1b-2 renal masses. Multivariable logistic regression analyses were performed. RESULTS: Overall, 968 PN patients and 325 RN patients were identified. The rate of AKI was lower in the PN versus the RN patients (17% vs. 58%; p < 0.001). At 1 year after surgery, for the PN versus the RN patients, the rate for recovery of at least 90% of baseline eGFR was 51% versus 16%, the rate of CKD progression of ≥ 1 stage was 38% versus 65%, and the rate of eGFR decline of 45 ml/min/1.73 m2 or less was 10% versus 23% (all p < 0.001). Radical nephrectomy independently predicted AKI (odds ratio [OR], 7.61), 1-year ≥ 90% eGFR recovery (OR, 0.30), 1-year CKD upstaging (OR, 1.78), and 1-year eGFR decline of 45 ml/min/1.73 m2 or less (OR, 2.36) (all p ≤ 0.002). CONCLUSIONS: For cT1b-2 masses, RN portends worse immediate and 1-year functional outcomes. When technically feasible and oncologically safe, efforts should be made to spare the kidney in case of large renal masses to avoid the hazard of glomerular function loss-related mortality.

Intravenous indocyanine green to evaluate distal ureteral vascularity during robot-assisted radical cystectomy with intracorporeal urinary diversion.

PURPOSE: The aim of the present study is to assess the role of indocyanine green (ICG) to evaluate distal ureteral vascularity during robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion and its impact on the incidence of benign ureteroenteric strictures (UES). METHODS: The study included patients who underwent RARC for bladder cancer between 2018 and 2023. All patients included underwent intracorporeal urinary diversion with ileal conduit or neobladder. Bricker technique was performed in all ureteroenteric anastomosis. ICG was employed during the study period to evaluate ureteral vascularity. We divided patients into 2 groups depending on the utilization of ICG during surgery and compared demographic, clinicopathological and perioperative outcomes, including benign UES rates. RESULTS: We identified 221 patients that underwent RARC with intracorporeal urinary diversion. Ileal conduit was performed in 173 (78.3%) patients and neobladder in 48 (21.7%) cases. A total of 142 (64.3%) and 79 (35.7%) patients were in the non-ICG and ICG group, respectively. With a median follow-up of the entire cohort of 21.1 months, there were no differences in the rate of benign UES after RARC between the non-ICG and the ICG group (p = 0.901). In the non-ICG group, 26 (18.3%) patients developed benign UES and in the ICG group 15 (19.0%) patients. Most of the strictures appeared in the left ureter in both groups (80.8% non-ICG vs. 66.7% ICG, p = 0.599). Median time to stricture diagnosis was 4 months (IQR 3-7.25) for the non-ICG and 3 months (IQR 2-5) for the ICG group (p = 0.091). The ICG group had a slightly greater length of ureter resected compared with the non-ICG group (1.5 vs. 1.3 cm, p = 0.007). CONCLUSION: In our experience, choosing to use ICG intraoperatively to evaluate distal ureteral vascularity may not reduce the rate of benign UES after robot-assisted radical cystectomy with intracorporeal urinary diversion and Bricker ureteroileal anastomosis.

Gene variation impact on prostate cancer progression: Lymphocyte modulator, activation, and cell adhesion gene variant contribution.

BACKGROUND: The view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa. METHODS: Functionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses. RESULT: Proportional hazards regression showed that the minor CD6 rs12360861AA and CD166/ALCAM rs579565AA genotypes were associated with earlier BCR, with hazard ratios of 2.65 (95% CI: 1.39-5.05, p = 0.003) and 1.86, (95% CI: 1.02-3.39, p = 0.043), respectively. Individually, none of the analyzed SNPs was significantly associated with ISUP grade, but haplotype analyses revealed association of the CD5 rs2241002C -rs2229177T haplotype with ISUP grade ≥2, with odds ratio of 1.52 (95% CI: 1.05-2.21, p = 0.026). CONCLUSION: The results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology.

Outcomes after 20 years of experience in minimally invasive living-donor nephrectomy.

INTRODUCTION: The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002. MATERIALS AND METHODS: We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020. RESULTS: A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively. CONCLUSIONS: MILDN techniques are safe for donors and grafts, with low complication.

Cell-Free DNA as a Prognostic Biomarker for Monitoring Muscle-Invasive Bladder Cancer.

Cell-free DNA (cfDNA) has recently emerged as a real-time biomarker for diagnosis, monitoring and prediction of therapy response in tumoral disease. Here, we evaluated cfDNA as a prognostic biomarker for monitoring muscle-invasive bladder cancer (MIBC) patients at different follow-up time points. Blood samples from 37 MIBC patients who underwent radical cystectomy (RC) were collected at cystectomy and 1, 4, 12 and 24 months later. Plasma cfDNA amount and fragmentation patterns were determined. Four mutations were analyzed in cfDNA to detect circulating tumor DNA (ctDNA) during patient follow-up. During a median follow-up of 36 months, 46% of patients progressed; median time to progression was 10 months. cfDNA levels and ctDNA status four months after RC were identified as independent prognostic biomarkers of tumor progression (HR 5.290; p = 0.033) and cancer-specific survival (HR 4.199; p = 0.038), respectively. Furthermore, ctDNA clearance four months after RC was significantly associated with patients' clinical outcomes. In conclusion, cfDNA levels and ctDNA status four months after RC have prognostic implications in MIBC patients. In addition, cfDNA monitoring is useful to predict patient outcomes after RC. cfDNA analysis in the clinical setting could greatly improve MIBC patient management.

Robot-assisted kidney transplantation: update from the European Robotic Urology Section (ERUS) series.

OBJECTIVE: To report the results of the robot-assisted kidney transplantation (RAKT) experience performed in 10 European centres by members of the European Robotic Urology Section (ERUS)-RAKT group. PATIENTS AND METHODS: This is a multicentre prospective observational study of RAKT. Descriptive analysis of recipients and donor characteristics, surgical data, intraoperative outcomes, complications rate and functional results were collected and analysed. RESULTS: Between July 2015 and September 2019, 291 living-donor RAKTs were performed. Recipients were mostly male (189 [65%]), the mean Standard deviation (sd) age was 45.2 (13.35) years, the mean (sd) body mass index was 27.13 (19.28) kg/m2 , and RAKT was pre-emptive in 155 (53.8%) cases. Right and multiple arteries kidneys were used in 15.4%. The mean (sd) total surgical and re-warming time was 244 (70.5) min and 53.16 (15.27) min, respectively. In all, 17 patients presented with postoperative bleeding (5.7%). Five kidneys had delayed graft function; five (2%) were lost due to thrombosis and one due to acute rejection. Two patients had arterial stenosis, three had incisional hernias, six had ureteric stenosis, and nine had lymphoceles. Neither surgical nor re-warming times were correlated with postoperative serum creatinine levels (P > 0.05). Comparison of surgical data between the first 120 cases and the following 171 cases showed a significantly shorter total surgical time in the second group (265 vs 230 min, P = 0.005). CONCLUSIONS: This is the largest European multicentre study of RAKT with good surgical and functional results competitive with open kidney transplant series, with a relatively short learning curve when performed in centres with a wide experience in open kidney transplantation and robotic surgery.

Impact on prostate cancer clinical presentation after non-screening policies at a tertiary-care medical center- a retrospective study.

BACKGROUND: In May 2012 the US Preventive Task Force issued a 'D' recommendation against routine PSA-based early detection of prostate cancer. This recommendation was implemented progressively in our health system. The aim of this study is to define its impact on prostate cancer staging at a tertiary care institution. METHODS: A retrospective analysis was performed from 2012 until 2015 at a single center. We analyzed the total number of biopsies performed per year and the positive biopsy rate. For those patients with positive biopsies we recorded diagnostic PSA, clinical stage, ISUP grade group, nodal involvement and metastatic status at diagnosis. RESULTS: A total of 1686 biopsies were analyzed. The positive biopsy rate increased from 25% in 2012 to 40% in 2015 (p < 0.05). No change in median PSA was noticed (p = 0.627). The biopsies detected higher ISUP grades (p = 0.000). In addition, newly diagnosed prostate cancer presented a higher clinical stage (p = 0.005), higher metastatic rates (p = 0.03) and a tendency to higher lymph node involvement although not statistically significant (p = 0.09). CONCLUSION: After the 2012 recommendation, patients presented a higher probability of a prostate cancer diagnosis, with a more adverse ISUP group, clinical stage and metastatic disease. These results should be taken into consideration to implement a risk adapted strategy for prostate cancer screening.

Pathogenesis of Penile Squamous Cell Carcinoma: Molecular Update and Systematic Review.

Penile squamous cell carcinoma (PSCC) is a rare but aggressive neoplasm with dual pathogenesis (human papillomavirus (HPV)-associated and HPV-independent). The development of targeted treatment is hindered by poor knowledge of the molecular landscape of PSCC. We performed a thorough review of genetic alterations of PSCC focused on somatic mutations and/or copy number alterations. A total of seven articles have been identified which, overall, include 268 PSCC. However, the series are heterogeneous regarding methodologies employed for DNA sequencing and HPV detection together with HPV prevalence, and include, in general, a limited number of cases, which results in markedly different findings. Reported top-ranked mutations involve TP53, CDKN2A, FAT1, NOTCH-1 and PIK3CA. Numerical alterations involve gains in MYC and EGFR, as well as amplifications in HPV integration loci. A few genes including TP53, CDKN2A, PIK3CA and CCND1 harbor both somatic mutations and copy number alterations. Notch, RTK-RAS and Hippo pathways are frequently deregulated. Nevertheless, the relevance of the identified alterations, their role in signaling pathways or their association with HPV status remain elusive. Combined targeting of different pathways might represent a valid therapeutic approach in PSCC. This work calls for large-scale sequencing studies with robust HPV testing to improve the genomic understanding of PSCC.

Orthotopic Renal Transplantation: Indication, Technique and Outcomes.

PURPOSE OF REVIEW: Nowadays many ESRD patients awaiting kidney transplantation have known unsuitable iliac vessels for vascular anastomosis, due to severe atheromatosis, occupied iliac fossa, or other uncommon vascular abnormalities. In these cases, orthotopic kidney transplantation (OKT) could be the solution. RECENT FINDINGS: Since the update on OKT published in 2010, no more large series have been reported. Some small series or case reports being described in the literature. The orthotopic position has shown good recipient and graft results with acceptable complication rate in selected patients. This technique permits the possibility of kidney transplantation, in patients unfit for heterotopic kidney transplantation (HKT), and consequently the avoidance of the dialysis treatment. In this paper, we review what is new in the literature, analyzing indications, technique, and results of this surgical approach.

Cancer care pathways across seven countries in Europe: What are the current obstacles? And how can artificial intelligence help?

BACKGROUND: Cancer poses significant challenges for healthcare professionals across the disease pathway including cancer imaging. This study constitutes part of the user requirement definition of INCISIVE EU project. The project has been designed to explore the full potential of artificial intelligence (AI)-based technologies in cancer imaging to streamline diagnosis and management. The study aimed to map cancer care pathways (breast, prostate, colorectal and lung cancers) across INCISIVE partner countries, and identify bottle necks within these pathways. METHODS: Email interviews were conducted with ten oncology specialised healthcare professionals representing INCISIVE partner countries: Greece, Cyprus, Spain, Italy, Finland, the United Kingdom (UK) and Serbia. A purposive sampling strategy was employed for recruitment and data was collected between December 2020 and April 2021. Data was entered into Microsoft Excel spreadsheet to allow content examination and comparative analysis. RESULTS: The analysed pathways all shared a common characteristic: inequalities in relation to delays in cancer diagnosis and treatment. All the studied countries, except the UK, lacked official national data about diagnostic and therapeutic delays. Furthermore, a considerable variation was noted regarding the availability of imaging and diagnostic services across the seven countries. Several concerns were also noted for inefficiencies/inequalities with regards to national screening for the four investigated cancer types. CONCLUSIONS: Delays in cancer diagnosis and treatment are an ongoing challenge and a source for inequalities. It is important to have systematic reporting of diagnostic and therapeutic delays in all countries to allow the proper estimation of its magnitude and support needed to address it. Our findings also support the orientation of the current policies towards early detection and wide scale adoption and implementation of cancer screening, through research, innovation, and technology. Technologies involving AI can have a great potential to revolutionise cancer care delivery. POLICY SUMMARY: This study highlights the widespread delay in cancer diagnosis across Europe and supports the need for, systematic reporting of delays, improved availability of imaging services, and optimised national screening programs. The goal is to enhance cancer care delivery, encourage early detection, and implement research, innovation, and AI-based technologies for improved cancer imaging.

Artificial Intelligence for Optimizing Cancer Imaging: User Experience Study.

BACKGROUND: The need for increased clinical efficacy and efficiency has been the main force in developing artificial intelligence (AI) tools in medical imaging. The INCISIVE project is a European Union-funded initiative aiming to revolutionize cancer imaging methods using AI technology. It seeks to address limitations in imaging techniques by developing an AI-based toolbox that improves accuracy, specificity, sensitivity, interpretability, and cost-effectiveness. OBJECTIVE: To ensure the successful implementation of the INCISIVE AI service, a study was conducted to understand the needs, challenges, and expectations of health care professionals (HCPs) regarding the proposed toolbox and any potential implementation barriers. METHODS: A mixed methods study consisting of 2 phases was conducted. Phase 1 involved user experience (UX) design workshops with users of the INCISIVE AI toolbox. Phase 2 involved a Delphi study conducted through a series of sequential questionnaires. To recruit, a purposive sampling strategy based on the project's consortium network was used. In total, 16 HCPs from Serbia, Italy, Greece, Cyprus, Spain, and the United Kingdom participated in the UX design workshops and 12 completed the Delphi study. Descriptive statistics were performed using SPSS (IBM Corp), enabling the calculation of mean rank scores of the Delphi study's lists. The qualitative data collected via the UX design workshops was analyzed using NVivo (version 12; Lumivero) software. RESULTS: The workshops facilitated brainstorming and identification of the INCISIVE AI toolbox's desired features and implementation barriers. Subsequently, the Delphi study was instrumental in ranking these features, showing a strong consensus among HCPs (W=0.741, P<.001). Additionally, this study also identified implementation barriers, revealing a strong consensus among HCPs (W=0.705, P<.001). Key findings indicated that the INCISIVE AI toolbox could assist in areas such as misdiagnosis, overdiagnosis, delays in diagnosis, detection of minor lesions, decision-making in disagreement, treatment allocation, disease prognosis, prediction, treatment response prediction, and care integration throughout the patient journey. Limited resources, lack of organizational and managerial support, and data entry variability were some of the identified barriers. HCPs also had an explicit interest in AI explainability, desiring feature relevance explanations or a combination of feature relevance and visual explanations within the toolbox. CONCLUSIONS: The results provide a thorough examination of the INCISIVE AI toolbox's design elements as required by the end users and potential barriers to its implementation, thus guiding the design and implementation of the INCISIVE technology. The outcome offers information about the degree of AI explainability required of the INCISIVE AI toolbox across the three services: (1) initial diagnosis; (2) disease staging, differentiation, and characterization; and (3) treatment and follow-up indicated for the toolbox. By considering the perspective of end users, INCISIVE aims to develop a solution that effectively meets their needs and drives adoption.

Incidental prostate cancer after holmium laser enucleation of the prostate: Critical analysis of independent risk factors and impact on surgical outcomes.

Objectives: The objectives of this study are to evaluate the impact of incidental prostate cancer (iPCa) and its different grade group (GG) on the surgical outcomes of holmium laser enucleation of the prostate (HoLEP) and, furthermore, to assess the independent risk factors associated with the detection of iPCa. Patients or materials and Methods: A retrospective chart review was conducted at a single institution for HoLEP cases that were performed between 2017 and 2022. Patients with a preoperative diagnosis of prostate cancer and those without baseline prostate-specific antigen (PSA) levels within 1 year were excluded. Four hundred seventeen patients were divided into three groups: benign prostatic hyperplasia-377; clinically insignificant (GG 1)-29; and clinically significant prostate cancer (GG 2-5)-11. The preoperative parameters analysed included age, body mass index, race/ethnicity, use of 5-alpha-reductase inhibitors, PSA, prostate size, PSA density, and history of negative prostate biopsy. To evaluate the association between clinical and demographic variables, a multivariable-adjusted logistic regression analysis was performed. We also assessed intraoperative and post-operative outcomes among these three groups. Results: A total of 417 patients were analysed; 40 (9.6%) patients had iPCa, of which 29 (72.5%) and 11 (27.5%) were clinically nonsignificant and significant prostate cancer, respectively. Of all the demographic and preoperative variables analysed, hypertension was significantly associated with overall prostate cancer diagnosis (p < 0.05), and no other variable including patient age, preoperative PSA, PSA density, prostate size, or prior prostate biopsy were associated with increased risk of overall prostate cancer or clinically significant prostate cancer diagnosis. Most cases of iPCa were GG1, and 34 (85%) were managed with active surveillance. Conclusion: The rate of iPCa after HoLEP was 9.6%, with most cases being GG 1 (72.5%) and managed through active surveillance. Age, prostate size, baseline PSA, and prior negative prostate biopsies were not associated with increased risk of iPCa.

Combined holmium laser enucleation of the prostate with high-intensity focused ultrasound in treating patients with localized prostate cancer in a prostate with volume > 60 g: Oncological and functional outcomes from single-institution study.

OBJECTIVE: To assess the efficacy and safety of combined High-Intensity Focused Ultrasound (HIFU) and Holmium Laser Enucleation of the Prostate (HoLEP) in treating patients with both localized prostate cancer (PCa) and prostate > 60 g. METHODS: All patients who underwent HIFU for treatment of localized PCa were prospectively enrolled in our study. We reviewed records of patients undergoing procedures from January 2016 to January 2023. For patients with prostate sizes > 60 g, HoLEP was offered before HIFU to prevent worsened urinary symptoms post-treatment. Oncological outcomes-prostatic-specific (PSA) kinetics, recurrence rates, treatment failure - and functional results-Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS), and urinary complications were compared between patients undergoing combined HoLEP and HIFU with those underwent HIFU-monotherapy. RESULTS: Among 100 patients, 74 underwent HIFU-monotherapy and 26 underwent the combined HoLEP and HIFU. The majority had intermediate-risk PCa (67%). Pathologic assessment of HoLEP specimens showed no tumor evidence in 57% of cases. In comparison to the HIFU-only group, the combined group exhibited significantly lower PSA metrics across various intervals, however, no differences were found regarding overall and infield recurrences and treatment failure rates. While the combined treatment initially resulted in higher incontinence rates and shorter catheterization durations (P < 0.001), no significant difference in IPSS was observed during subsequent follow-ups. CONCLUSION: HoLEP and HIFU can be safely combined for the treatment of PCa in patients with >60 g prostate volume without compromising early oncological outcomes thereby expanding the therapeutic scope of HIFU in treating patients with localized PCa and large adenomas.

Molecular and diffusion features for identification of clinically significant prostate cancer in PI-RADS 3 lesions.

BACKGROUND: The recommendation to perform biopsy of PIRADS 3 lesions has not been adopted with strength as compared to higher scored lesions on multiparametric MRI. This represents a challenging scenario and an unmet need for clinicians to apply a risk adapted approach in these cases. In the present study, we examined clinical and radiologic characteristics in men with PI-RADS 3 index lesions that can predict csPCa on mpMRI-target biopsy. METHODS: Revision of a prospective database with patients who underwent targeted and systematic biopsies from 2015 to 2023 for PI-RADS 3 lesions identified on mpMRI. Baseline variables were collected, such as PSA density (PSAd), 4Kscore, prostate size, and the apparent diffusion coefficient (ADC) value of the lesion on mpMRI. Logistic regression, receiver operating characteristic (ROC) and decision curve analyses (DCA) assessing the association between clinic-radiologic factors and csPCa were performed. RESULTS: Overall, 230 patients were included in the study and the median age was 65 years. The median prostate size and PSA were 50 g and 6.26 ng/mL, respectively. 17.4% of patients had csPCa, while 27.5% had Gleason group 1. In univariable logistic analyses, we found that age, BMI, prostate size, PSAd, ADC, and 4Kscore were significant csPCa predictors (P < 0.05). PSAd showed the best prediction performance in terms of AUC (= 0.679). On multivariable analysis, PSAd and 4Kscore were associated with csPCa. The net benefit of PSAd combined with clinical features was superior to those of other parameters. Within patients with PSAd < 0.15, 4Kscore was a statistically significant predictor of csPCa (OR = 3.25, P = 0.032). CONCLUSION: PSAd and 4Kscore are better predictors of csPCa in patients with PIRADS 3 lesions compared to ADC. The predictive role of 4Kscore is higher in patients with low PSAd. These results can assist practitioners in the risk stratification of patients with equivocal lesions to determine the need of biopsy.

Optimal Management for Primary High Grade Ta Bladder Cancer: Role of re-staging TURBT and Intravesical Adjuvant Therapy.

Objective: This study aims to investigate the impact of risk group classification, restaging transurethral resection (re-TURBT), and adjuvant treatment intensity on recurrence and progression risks in high-grade Ta tumours in patients with non-muscle invasive bladder cancer (NMIBC). Materials and methods: Data from a comprehensive bladder cancer database were utilized for this study. Patients with primary high-grade Ta tumours were included. Risk groups were classified according to AUA/SUO criteria. Tumour characteristics and patient demographics were analysed using descriptive statistics. Cox proportional hazard regression models were used to assess the effect of re-TURBT and other clinical/treatment-related predictors on recurrence- and progression-free survivals. The survivals by selected predictors were estimated using Kaplan-Meier method, and groups were compared by the log-rank test. Results: Among 218 patients with high-grade Ta bladder cancer, those who underwent re-TURBT had significantly better 5-year recurrence-free survival (71.1% vs. 26.8%, p = 0.0009) and progression-free survival (98.6% vs. 73%, p = 0.0018) compared with those with initial TURBT alone. Full BCG treatment (induction and maintenance) showed lower recurrence risk, especially in high-risk patients. However, residual disease at re-TURBT did not significantly affect recurrence risk. Conclusions: This study highlights the significance of risk group classification, the role of re-TURBT, and the intensity of adjuvant treatment in the management of high-grade Ta tumours. A risk-adapted model is crucial to reduce the burden of unnecessary intravesical treatment and endoscopic procedures.

Corrigendum: Ex vivo normothermic preservation of a kidney graft from uncontrolled donation after circulatory death over 73 hours.

[This corrects the article DOI: 10.3389/fbioe.2023.1330043.].

p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis.

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively ( P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Surgical Experience and Functional Outcomes after Laparoscopic and Robot-Assisted Partial Nephrectomy: Results from a Multi-Institutional Collaboration.

Background: In patients treated with partial nephrectomy, prior evidence showed that peri-operative outcomes, such as complications and ischemia time, improved as a function of the surgical experience of the surgeon, but data on functional outcomes after surgery are still scarce. Methods: We retrospectively analyzed data of 4011 patients with a single, unilateral cT1a-b renal mass treated with laparoscopic or robot-assisted partial nephrectomy. The operations were performed by 119 surgeons at 22 participating institutions between 1997 and 2022. Multivariable models investigated the association between surgical experience (number of prior operations) and acute kidney injury (AKI) and recovery of at least 90% of baseline estimated glomerular filtration rate (eGFR) 1 yr after partial nephrectomy. The adjustment for case mix included age, Body Mass Index, preoperative serum creatinine, clinical T stage, PADUA score, warm ischemia time, pathologic tumor size, and year of surgery. Results: A total of 753 (19%) and 3258 (81%) patients underwent laparoscopic and robot-assisted partial nephrectomy, respectively. Overall, 37 (31%) and 55 (46%) surgeons contributed only to laparoscopic and robotic learning curves, respectively, whereas 27 (23%) contributed to the learning curves of both approaches. In the laparoscopic group, 8% and 55% of patients developed AKI and recovered at least 90% of their baseline eGFR, respectively. After adjusting for confounders, we did not find evidence of an association between surgical experience and AKI after laparoscopic partial nephrectomy (odds ratio [OR]: 0.9992; 95% confidence interval [CI]: 0.9963, 1.0022; p = 0.6). Similar results were found when 1-year renal function was the outcome of interest (OR: 0.9996; 95% CI: 0.9988, 1.0005; p = 0.5). Among patients who underwent robot-assisted partial nephrectomy, AKI occurred in 11% of patients, whereas 54% recovered at least 90% of their baseline eGFR. On multivariable analyses, the relationship between surgical experience and AKI after surgery was not statistically significant (OR: 1.0015; 95% CI: 0.9992, 1.0037; p = 0.2), with similar results when the outcome of interest was renal function one year after surgery (OR: 1.0001; 95% CI: 0.9980, 1.0022; p = 0.9). Virtually the same findings were found on sensitivity analyses. Conclusions: In patients treated with laparoscopic or robot-assisted partial nephrectomy, our data suggest that the surgical experience of the operating surgeon might not be a key determinant of functional recovery after surgery. This raises questions about the use of serum markers to assess functional recovery in patients with two kidneys and opens the discussion on what are the key steps of the procedure that allowed surgeons to achieve optimal outcomes since their initial cases.

Is Holmium Laser Enucleation of the Prostate Truly Size-Independent? A Critical Evaluation at the Extreme Ends of the Spectrum.

OBJECTIVE: To assess the outcomes of holmium laser enucleation of the prostate (HoLEP) at the extremes of the size spectrum, comparing whether the results are consistent for very large and small prostates. METHODS: A retrospective review of 402 patient charts was conducted to compare the outcomes of HoLEP in patients with prostate size ≤40 g (group 1), 41-200 g (group 2), and >200 g (group 3). Various preoperative, perioperative, and postoperative variables were collected. RESULTS: HoLEP showed comparable voiding outcomes among all 3 groups, although patients with small prostates had a higher International Prostate Symptom Score during follow-up (P = .022). We noted a higher rate of perioperative blood transfusion in patients with very large prostates (P = .019) and a higher rate of transient acute urinary retention (AUR) in group 1 when compared to group 3 (P = .048). Patients with smaller prostates had a higher rate of bladder neck stenosis and urethral strictures, but the differences were not found to be statistically significant. The incidence of other complications, length of hospital stay, and catheterization duration did not differ significantly among the groups. CONCLUSION: HoLEP has consistent and safe outcomes across a wide range of prostate sizes. Although, the risk of blood transfusion is higher in patients with very large prostates and the risk of transient AUR is greater in patients with small glands, the overall efficacy and safety of HoLEP are not significantly influenced by prostate size.

Cancer care at the time of the fourth industrial revolution: an insight to healthcare professionals' perspectives on cancer care and artificial intelligence.

BACKGROUND: The integration of Artificial Intelligence (AI) technology in cancer care has gained unprecedented global attention over the past few decades. This has impacted the way that cancer care is practiced and delivered across settings. The purpose of this study was to explore the perspectives and experiences of healthcare professionals (HCPs) on cancer treatment and the need for AI. This study is a part of the INCISIVE European Union H2020 project's development of user requirements, which aims to fully explore the potential of AI-based cancer imaging technologies. METHODS: A mixed-methods research design was employed. HCPs participating in cancer care in the UK, Greece, Italy, Spain, Cyprus, and Serbia were first surveyed anonymously online. Twenty-seven HCPs then participated in semi-structured interviews. Appropriate statistical method was adopted to report the survey results by using SPSS. The interviews were audio recorded, verbatim transcribed, and then thematically analysed supported by NVIVO. RESULTS: The survey drew responses from 95 HCPs. The occurrence of diagnostic delay was reported by 56% (n = 28/50) for breast cancer, 64% (n = 27/42) for lung cancer, 76% (n = 34/45) for colorectal cancer and 42% (n = 16/38) for prostate cancer. A proportion of participants reported the occurrence of false positives in the accuracy of the current imaging techniques used: 64% (n = 32/50) reported this for breast cancer, 60% (n = 25/42) for lung cancer, 51% (n = 23/45) for colorectal cancer and 45% (n = 17/38) for prostate cancer. All participants agreed that the use of technology would enhance the care pathway for cancer patients. Despite the positive perspectives toward AI, certain limitations were also recorded. The majority (73%) of respondents (n = 69/95) reported they had never utilised technology in the care pathway which necessitates the need for education and training in the qualitative finding; compared to 27% (n = 26/95) who had and were still using it. Most, 89% of respondents (n = 85/95) said they would be opened to providing AI-based services in the future to improve medical imaging for cancer care. Interviews with HCPs revealed lack of widespread preparedness for AI in oncology, several barriers to introducing AI, and a need for education and training. Provision of AI training, increasing public awareness of AI, using evidence-based technology, and developing AI based interventions that will not replace HCPs were some of the recommendations. CONCLUSION: HCPs reported favourable opinions of AI-based cancer imaging technologies and noted a number of care pathway concerns where AI can be useful. For the future design and execution of the INCISIVE project and other comparable AI-based projects, the characteristics and recommendations offered in the current research can serve as a reference.