The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

BACKGROUND AND AIMS: In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. MATERIAL AND METHODS: All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n = 452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. RESULTS: The median turnaround time per case was 40.3 ( ± 10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1 min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1 min vs. 39.13 min; p < 0.001), the place of microscopic examination (43.0 min vs. 38.7 min; p < 0.001) and the presence of a positive margin (38.0 vs. 44.0 min; p < 0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84 min vs. 40.7 min; p = 0.09), the tumor grade (42.3 vs 39.8 min; p = 0.493) and the presence of extraprostatic extension (44.0 vs 39.8 min; p = 0.099). CONCLUSION: The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

Trial Participation is Not Associated with Better Biochemical Recurrence-free Survival in a Large Cohort of External Beam Radiotherapy-Treated Intermediate- and High-Risk Prostate Cancer Patients.

AIMS: There is a widespread belief that outcomes of cancer patients treated within clinical trials might not be representative of the outcomes obtained within standard clinical settings. We sought to investigate the effect of trial participation on biochemical recurrence (BCR) in localised, D'Amico intermediate- and high-risk prostate cancer patients treated with external beam radiotherapy (EBRT). MATERIALS AND METHODS: We relied on a study population treated with EBRT between January 2001 and January 2021 at a single tertiary care centre, stratified according to trial enrolment. Separate Kaplan-Meier and multivariable Cox regression models tested BCR-free survival at 60 months within intermediate- and high-risk EBRT patients, after adjustment for covariables. Additionally, the analyses were refitted after inverse probability treatment weighting was performed separately for both risk subgroups. RESULTS: Of 932 eligible patients, 635 (68%) and 297 (32%) had intermediate- and high-risk prostate cancer, respectively. Overall, 53% of patients were trial participants. BCR rates were 11 versus 5% (P = 0.27) and 12 versus 14% (P = 0.08) in trial participants versus non-participants for intermediate- and high-risk subgroups, respectively. Differences in patient and clinical characteristics were recorded. Trial participation status failed to reach predictor status in multivariable Cox regression models for BCR in both intermediate-risk (hazard ratio 1.34; 95% confidence interval 0.71-2.49; P = 0.4) and high-risk patients (hazard ratio 1.03; 95% confidence interval 0.45-2.34; P = 0.9). Virtually the same results were recorded in inverse probability treatment weighting cohorts. CONCLUSIONS: Relying on a large cohort of EBRT-treated intermediate- and high-risk patients, no BCR differences were recorded between trial participants and non-participants after accounting for confounders.

Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

[Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt]. / Urologische Prostatakrebsvorsorge im Rahmen der Movember-Gesundheitsinitiative 2019 am Universitätsklinikum Frankfurt.

BACKGROUND: Men die earlier than women in Germany. Men also have impaired access to cancer screening compared to women. OBJECTIVES: Our Movember campaign 2019 at University Hospital Frankfurt (UKF) aimed at improving health care awareness in the context of prostate cancer checkup. MATERIALS AND METHODS: In November 2019, every male employee of the UKF with a minimum age of 45 yrs (or 40 yrs with a first degree relative with prostate cancer) was offered a free prostate cancer checkup. This checkup contained digital rectal examination (DRE), transrectal ultrasound and PSA (prostata-specific antigen) testing. RESULTS: Overall, 121/840 employees (14.4%) participated in the Movember campaign. A first degree relative with prostate cancer was reported in overall by 14% of the participants (n = 17). At least one prior prostate cancer check up had 33%. A total of 2.5% (n = 3) had one prior negative prostate biopsy. Median age was 54 yrs (interquartile range 50-58). Median PSA level was 0.9 ng/ml and median free-PSA 0.3 ng/ml. A suspicious DRE was found in 5% (n = 6). After stratification according to age (≤ 50 yrs vs. > 50 yrs), participants over 50 yrs had a significantly higher PSA level (1.0 ng/ml vs. 0.7 ng/ml, p < 0.01) and had more frequently at least one prior prostate cancer checkup in the past (42.0 vs. 12.1%, p < 0.01). All suspicious DREs were in the cohort > 50 yrs. Overall, 32.2% (n = 39) had at least a suspicious checkup. A total of 3.3% (n = 4) had suspicious PSA levels. 17.4% (n = 21) of the participants had a suspicious PSA ratio (< 20%) only. During follow-up, 6 prostate biopsies were performed, with the detection of one case of intermediate-risk prostate cancer (Gleason 3 + 4, pT3a, pPn1, pNx, R0). CONCLUSION: Overall, 121 employees participated in our Movember Prostate cancer checkup campaign with measurement of the PSA level. Suspicious results were recorded in 32.2%. One employee was diagnosed and successfully treated with an intermediate-risk prostate cancer.

Curcumin combined with exposure to visible light blocks bladder cancer cell adhesion and migration by an integrin dependent mechanism.

OBJECTIVE: Although the natural compound curcumin exerts antitumor properties in vitro, its clinical application is hampered due to rapid metabolism. Light exposure following curcumin application has been demonstrated to improve curcumin's bioavailability. Therefore, this investigation was directed towards evaluating whether light exposure in addition to curcumin application enhances curcumin's efficacy against bladder cancer cell adhesion and migration. MATERIALS AND METHODS: RT112, UMUC3, and TCCSUP cells were incubated with low curcumin concentrations (0.1-0.4 µg/ml) and then exposed to 1.65 J/cm2 visible light for 5 min. Controls remained untreated or were treated with curcumin or light alone. Cell adhesion to Human umbilical vein endothelial cells (HUVECs), to immobilized collagen or fibronectin and chemotactic behavior, integrin α and ß receptor expression with functional relevance, as well as focal adhesion kinase (total and phosphorylated FAK) were evaluated. RESULTS: Curcumin plus light, but neither curcumin nor light alone, significantly altered tumor cell adhesion and suppressed chemotaxis. Integrin α and ß subtypes were dissimilarly modified, depending on the cell line. Suppression of pFAK was noted in RT112 and UMUC3, but not in TCCSUP cells. The integrins α3, α5, and ß1 were involved in curcumin's regulation of adhesion and migration. Blocking studies revealed α3, α5, and ß1 to be associated with TCCSUP adhesion and migration, whereas α5 and ß1, but not α3 contributed to UMUC3 adhesion and migration. Integrin α5 and ß1 controlled RT112 chemotaxis as well, but only α5 was involved in the RT112 adhesion process. CONCLUSIONS: Combining curcumin with light exposure enhances curcumin's anti-tumor potential.

Critical analysis of a simplified Fuhrman grading scheme for prediction of cancer specific mortality in patients with clear cell renal cell carcinoma--Impact on prognosis.

INTRODUCTION AND OBJECTIVES: The traditional 4-tiered Fuhrman grading system (FGS) is widely accepted as histopathological classification for clear cell renal cell carcinoma (ccRCC) and has shown prognostic value. As intra- and inter-observer agreement are sub-optimal, simplified 2- or 3-tiered FGSs have been proposed. We aimed to validate these simplified 2- or 3-tiered FGSs for prediction of cancer-specific mortality (CSM) in a large study population from 2 European tertiary care centers. METHODS: We identified and followed-up 2415 patients with ccRCC who underwent radical or partial nephrectomy in 2 European tertiary care centers. Univariable and multivariable analyses and prognostic accuracy analyses were performed to evaluate the ability of several simplified FGSs (i.e. grades I + II vs., grades III + IV, grades I + II vs. grade III and grade IV) to predict CSM. RESULTS: Independent predictor status in multivariate analyses was proved for the simplified 2-tiered FGS (high-grade vs. low-grade), for the simplified 3-tiered FGS (grades I + II vs. grade III and grade IV) as well as for the traditional 4-tiered FGS. The prognostic accuracy of multivariable models of 77% was identical for all tested models. Prognostic accuracy of the model without FG was 75%. CONCLUSIONS: A simplified 2- or 3-tiered FGS could predict CSM as accurate as the traditional 4-tiered FGS in a large European study population. Application of new simplified 2- or 3-tiered FGS may reduce inter-observer-variability and facilitate clinical practice without compromising the ability to predict CSM in ccRCC patients after radical or partial nephrectomy.

[Patterns of care of patients with localized prostate cancer in Germany: a health care study with focus on active surveillance]. / Die Versorgung von Patienten mit lokal begrenztem Prostatakarzinom in Deutschland : Active-Surveillance-Ergebnisse einer nicht-interventionellen Versorgungsstudie.

BACKGROUND: To date, evidence on active surveillance (AS) is restricted to protocol-based studies and the current practice pattern outside medical centers is unknown. OBJECTIVES: The goal of this work was to capture the current treatment pattern of AS for localized prostate cancer (PCa) in patients managed by office-based urologists in Germany. MATERIALS AND METHODS: Our cohort consisted of 361 patients included in the AS arm of the HAROW (Hormonal Treatment, Active Surveillance, Radiation Therapy, OP, Watchful Waiting) study, an observational health service study in Germany. Descriptive characteristics and active-treatment-free survival (ATFS), surgical outcomes, and triggers for active treatment were assessed. RESULTS: Currently, only 15% of all patients with localized PCa were treated with AS. At baseline, 83% and 58% of all AS patients met the Chism and PRIAS low-risk criteria, respectively. After a median follow-up of 24 months, no systemic progression was observed, 5 patients died of non-disease-specific causes and active treatment was delivered in 20.5% of all patients. Triggers for active therapy were progression at biopsy (42%), rise in prostate-specific antigen level (27%), medical advice (16%) and patient's preference (10%), respectively. CONCLUSION: Our short-term results indicate that - in the hands of office-based urologists - active surveillance might represent a feasible treatment option for patients with localized PCa. The majority of patients were free of active treatment 2 years after AS initiation. Generally accepted inclusion and progression criteria are lacking and should be developed in order to facilitate and standardize AS in patients with low-risk PCa.

[Robot-assisted laparoscopic pyeloplasty in adults: Excellent long-term results of primary pyeloplasty]. / Roboterassistierte laparoskopische Pyeloplastik bei Erwachsenen : Exzellente Langzeitergebnisse der primären Pyeloplastik.

PURPOSE: With the development of the robot-assisted surgical technique, robot-assisted pyeloplasty (RAP) has become established as an alternative to open and laparoscopic surgery. Currently there are only a few single-center studies with larger numbers of cases and long-term results. The aim of this study was to investigate perioperative and long-term postoperative success rates of Anderson-Hynes robot-assisted pyeloplasty (RAP) at a single center. MATERIALS AND METHODS: We retrospectively reviewed our RAP experience of 61 patients performed by two surgeons between 2004 and 2013 regarding operating time, length of hospital stay, perioperative complication, and success. Overall success was measured in terms of necessary redo pyeloplasty. We also identified patients with temporary stent placement due to symptomatic hydronephrosis or with further obstruction in diuretic renography. RESULTS: Median age, operating time, and follow-up were 33 years, 195 min, and 64 months, respectively. No conversion to open procedure was necessary. The success rate was 98% (n=60) with 1 patient undergoing open redo pyeloplasty due to a recurrent stenosis. Temporary stent placement was required in 3 patients due to pyelonephritis and dilatation. CONCLUSION: Satisfying long-term success rates including low complication rates of RAP were obtained in this study. RAP presents a safe and standardized procedure for symptomatic ureteropelvic junction obstruction.

Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment.

BACKGROUND: Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status. METHODS: We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes. RESULTS: In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1-6 nodes in cT1 and 6-8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively. CONCLUSIONS: Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.

[The likelihood ratio: estimation of the impact of a diagnostic test on treatment decision]. / Die "likelihood ratio" : Beeinflussung der Therapieentscheidung durch einen diagnostischen Test.

Likelihood ratios (LRs) can be used to assess in an efficient manner the change of a pre-test probability to the post-test probability of a disease based on a given test result. For any clinical question or condition of interest, the diagnostic benefit can be calculated for each diagnostic test allowing to compare the performance of different diagnostic tests. Urologists should become familiar with the use of LR to promote a more evidence-based application of diagnostic test for different clinical scenarios. This review provides insights in the calculation and use of LR.

Tissue-based molecular markers for renal cell carcinoma.

Since the introduction of targeted therapies in renal cell carcinoma (RCC), more individualized treatment options have become available. Molecular markers might support treatment planning due to more accurate individual risk stratification. Current molecular markers in RCC were reviewed to elucidate clinical impact and future perspectives. An English-language literature review of the Medline database (1990 to September 2010) of published data on tissue-based molecular markers and RCC was undertaken. Histological types, clinical and oncological behaviour are variable in renal masses. Molecular markers offer potential for additional information in tumour detection and diagnosis, prognostic and predictive values, as well as determination of therapeutic targets. Investigations on molecular biomarkers in RCC include hypoxia inducible factor (HIF-α), vascular endothelial growth factor (VEGF), carbonic anhydrase IX (CAIX), mammalian target of rapamycin (mTOR), survivin, B7-H1, p53, matrix metalloproteinases (MMP), Insulin-like growth factor II mRNA-binding protein 3 (IMP3), Ki-67, C-reactive protein (CRP), Vimentin, Fascin, platelet count, hemoglobin level and combinations of these factors. Although some markers offer promising results, utilization in daily practice is compromised due to limited specificity, predictive accuracy and tumour histology variablity. There is an imminent need for novel molecular markers that allow accurate histologic and biologic classification of RCC to improve upon current outcomes. It is very likely that a panel of molecular markers will be used to achieve a sufficient degree of certainty in order to guide clinical decisions. A large concerted effort is required to advance the field of RCC molecular marker through systematic discovery, verification, and validation.