Surgical experience is predictive for bladder tumour resection quality.

OBJECTIVES: To assess the resection quality of transurethral bladder tumour resection (TURBT) and the association to surgeon experience depending on the presence of detrusor muscle. METHODS: A retrospective study on 640 TURBT procedures performed at Zealand University Hospital, Denmark, from 1 January 2015 - 31 December 2016. Data included patient characteristics, procedure type, surgeon category, supervisor presence, surgical report data, pathological data, complications data and recurrence data. Analysis was performed using simple and multiple logistic regression on the association between surgeon experience and the presence of detrusor muscle in resected tissue from TURBT. RESULTS: Supervised junior residents had significant lower detrusor muscle presence (73%) compared with consultants (83%) (OR = 0.4, 95% CI = 0.21-0.83). Limitations were the retrospective design and the diversity of included TURBT. CONCLUSIONS: It was found that surgical experience predicts detrusor muscle presence and supervised junior residents performing TURBT on patients resulted in less detrusor muscle than consultants.

National Implementation of Simulator Training Improves Transurethral Resection of Bladder Tumours in Patients.

Background: Transurethral resection of bladder tumours (TURBT) is the initial diagnostic treatment for patients with bladder cancer. TURBT is not an easy procedure to master and simulator training may play a role in improving the learning curve. Objective: To implement a national training programme for simulation-based mastery learning in TURBT and explore operating theatre performance after training. Design setting and participants: From June 2019 to March 2021, 31 doctors at urology departments in Denmark performed two pretraining TURBT procedures on patients, followed by proficiency-based mastery learning on a virtual reality simulator and then two post-training TURBTs on patients. Outcome measurements and statistical analyses: Operating theatre performances were video-recorded and assessed by two independent, blinded raters using the Objective Structured Assessment for Transurethral Resection of Bladder Tumours Skills (OSATURBS) assessment tool. Paired-sample t tests were used to compare pretraining and post-training analyses and independent t tests for between-group comparisons. This trial is registered at ClinicalTrials.gov as NCT03864302. Results and limitations: Before training, novices had significantly lower performance scores in comparison to those with intermediate experience (p = 0.017) and experienced doctors (p < 0.001). After training, novices significantly improved their clinical performance score (from 11.4 to 17.1; p = 0.049, n = 10). Those with intermediate experience and experienced doctors did not benefit significantly from simulator training (p = 0.9 and p = 0.8, respectively). Conclusions: Novices improved their TURBT performance in the operating theatre after completing a proficiency-based training programme on a virtual reality simulator. Patient summary: We trained surgeons in an operation to remove bladder tumours using a virtual reality simulator. Novice doctors improved their performance significantly after the training, but the training effects for more experienced doctors were minimal. Therefore, we suggest the introduction of mandatory simulator training in the residency programme for urologists.

Validation of a Novel Assessment Tool Identifying Proficiency in Transurethral Bladder Tumor Resection: The OSATURBS Assessment Tool.

Background: Competence in transurethral resection of bladder tumors (TURB) is critical in bladder cancer management and should be ensured before independent practice. Objective: To develop an assessment tool for TURB and explore validity evidence in a clinical context. Design, Setting, and Participants: From July 2019 to March 2021, a total of 33 volunteer doctors from three hospitals were included after exemption from the regional ethics committee (REG-008-2018). Participants performed two TURB procedures on patients with bladder tumors. A newly developed assessment tool (Objective Structured Assessment for Transurethral Resection of Bladder Tumors Skills, OSATURBS) was used for direct observation assessment (DOA), self-assessment (SA), and blinded video assessment (VA). Outcome Measurements and Statistical Analysis: Cronbach's alpha and Pearson's r were calculated for across items internal consistency reliability, inter-rater reliability, and test-retest reliability. Correlation between OSATURBS scores and the operative experience was calculated with Pearson's r and a pass/fail score was established. Differences in assessment scores were explored with paired t-test and independent samples t-test. Results and Limitations: The internal consistency reliability across items Cronbach's alpha was 0.94 (n = 260, p < 0.001). Inter-rater reliability was 0.80 (n = 64, p < 0.001). Test-retest correlation was high, r = 0.71 (n = 32, p < 0.001). Relationship with TURB experience was high, r = 0.71 (n = 32, p < 0.001). Pass/fail score was 19 points. DOAs were strongly correlated with video ratings (r = 0.85, p < 0.001) but with a significant social bias with lower scores for inexperienced and higher scores for experienced participants. Participants tended to overestimate their own performances. Conclusions: OSATURBS tool for TURB can be used for assessment of surgical proficiency in the clinical setting. DOA and SA are biased, and blinded VA of TURB performances is advised. Clinical Trials NCT03864302.

Leukocyte TNFR1 and TNFR2 Expression Contributes to the Peripheral Immune Response in Cases with Ischemic Stroke.

Tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2) have been found in brain parenchyma of stroke patients, and plasma levels are increased in the acute phase of stroke. We evaluated associations between TNFR1 and TNFR2 plasma levels and stroke severity, infarct size, and functional outcome. Furthermore, we examined cellular expression of TNFR1 and TNFR2 on leukocyte subpopulations to explore the origin of the increased receptor levels. Blood samples were taken from 33 acute ischemic stroke patients and 10 healthy controls. TNFR1 and TNFR2 plasma concentrations were measured and correlated against the Scandinavian Stroke Scale at admission, infarct volume, and the modified Rankin Scale score three months after stroke onset. Classical, intermediate, and non-classical monocytes as well as neutrophils were purified, and cellular expression of TNFR1 and TNFR2 was examined using flow cytometry. TNFR1 and TNFR2 plasma levels were both increased after ischemic stroke, but we found no correlation with patient outcome measurements. Compared to healthy controls, ischemic stroke patients had decreased non-classical monocyte and neutrophil populations expressing TNFR1 and increased neutrophils expressing TNFR2, and decreased non-classical populations co-expressing both TNFR1 and TNFR2. This study supports the hypothesis of an acute immunological response orchestrated by the peripheral immune system following an ischemic stroke. However, the origin of the increased TNFR1 and TNFR2 plasma levels could not be clearly linked to peripheral monocytes or neutrophils. Future studies are needed and will help clarify the potential role as treatment target.

Acute Neurofilament Light Chain Plasma Levels Correlate With Stroke Severity and Clinical Outcome in Ischemic Stroke Patients.

Background: Ischemic stroke causes increased blood-brain barrier permeability and release of markers of axonal damage and inflammation. To investigate diagnostic and prognostic roles of neurofilament light chain (NF-L), we assessed levels of NF-L, S100B, interleukin-6 (IL-6), E-selectin, vascular endothelial growth factor-A (VEGF-A), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in patients with acute ischemic stroke or transient ischemic attack (TIA) and healthy controls. Methods: We studied neurofilament (NF) expression in 2 cases of human postmortem ischemic stroke, representing infarcts aged 3- to >7-days. In a prospective study, we measured plasma NF-L and inflammatory markers <8 h of symptom onset and at 72 h in acute ischemic stroke (n = 31), TIA (n = 9), and healthy controls (n = 29). We assessed whether NF-L, S100B, and IL-6 were associated with clinical severity on admission (Scandinavian Stroke Scale, SSS), diagnosis of ischemic stroke vs. TIA, and functional outcome at 3 months (modified Rankin Scale, mRS). Results: NF expression increased in ischemic neurons and in the infarcted brain parenchyma after stroke. Plasma NF-L levels were higher in stroke patients than in TIA patients and healthy controls, but IL-6 levels were similar. Higher acute NF-L levels were associated with lower SSS scores at admission and higher mRS scores at 3 months. No correlation was observed between NF-L and S100B, NF-L and IL-6, nor between S100B or IL-6 and SSS or mRS. Compared to controls, stroke patients had significantly higher VEGF-A and VCAM-1 at <8 h that remained elevated at 72 h, with significantly higher VEGF-A at <8 h; ICAM-1 was significantly increased at <8 h, while S100B and E-selectin were unchanged. Conclusions: Plasma NF-L levels, but not IL-6 and S100B, were significant predictors of clinical severity on admission and functional outcome at 3 months. Plasma NF-L is a promising biomarker of functional outcome after ischemic stroke.

Simulation-based training for flexible cystoscopy - A randomized trial comparing two approaches.

BACKGROUND: Simulation-based training allows trainees to experiment during training and end-of-training tests could increase motivation and retention. The aim of this trial was to determine if a simulation-based training program including directed self-regulated learning and post-testing improved clinical outcomes compared to a traditional simulation-based training program. METHODS: A randomized trial was conducted involving 32 participants without prior experience in endoscopic procedures. The intervention group practiced independently in a simulation centre and got a post-test whereas the control group received traditional instructions and demonstrations before being allowed to practice. Three weeks after the intervention the participants performed cystoscopies on two consecutive patients. Clinical performance was assessed using a global rating scale (GRS) with established evidence of validity. Independent samples t-test, Cronbach's α, Pearson's r, and paired samples t-test were used for statistical analysis. RESULTS: Twenty-five participants performed two cystoscopies on patients. There was no significant difference between the two study groups with respect to mean GRS of performance (p = 0.63, 95 % CI; -2.4-3.9). The internal consistency of the global rating scale was high, Cronbach's α = 0.91. Participants from both study groups demonstrated significant improvement between the first and second clinical procedures (p = 0.004, 95 % CI, 0.8-3.5). Eight (32%) and 15 (60%) participants demonstrated adequate clinical skills in their first and second procedure, respectively. CONCLUSIONS: No significant differences were found on the clinical transfer when comparing the two programs. Neither of our training programs was able to ensure consistent, competent performance on patients and this finding could serve as an important argument for simulation-based mastery learning where all training continues until a pre-defined level of proficiency is met. TRIAL REGISTRATIONS: The trial was submitted before enrolment of participants to the Regional Scientific Ethics Committee of the Capital Region which established that ethical approval was not necessary (H-4-2014-122). The trial was registered at Clinicaltrials.gov (NCT02411747).

Improved survival for patients with de novo metastatic prostate cancer in the last 20 years.

INTRODUCTION: During recent years, several new life-prolonging therapeutic options have been introduced for patients with metastatic prostate cancer (mPCa). The aim of the present study was to evaluate the changes in the survival of patients diagnosed with mPCa prior to and in the early period of the implementation of these new agents. PATIENTS AND METHODS: The study population consisted of 207 men diagnosed in 1997 and 316 men diagnosed in the period 2007-2013 with de novo mPCa and managed with initial endocrine therapy. Men were followed for overall survival and PCa-specific survival. RESULTS: At the time of diagnosis, men diagnosed in the period 2007-2013 had less co-morbidity, lower prostrate-specific antigen levels and lower clinical tumour categories than men diagnosed in 1997. A significantly higher proportion of men diagnosed in 1997 were managed with surgical castration (57% versus 9%). Only one patient diagnosed in 1997 received second-line therapy compared with 81 men (26%) diagnosed in the period 2007-2013. The median overall survival was significantly longer for men diagnosed between 2007 and 2013 compared with men diagnosed in 1997 (39.4 months versus 24.2 months, p < 0.0001). Likewise, the cumulative incidence of PCa-specific death was higher among men diagnosed in 1997 compared with men diagnosed between 2007 and 2013, with 5-year cumulative incidences of 72% and 47%, respectively (p < 0.0001). CONCLUSION: Survival in men diagnosed with metastatic PCa has improved significantly over time. The improved survival can in part be explained by lead-time bias, but also by the introduction of new life-prolonging treatments.

Clinical characteristics and primary management of patients diagnosed with prostate cancer between 2007 and 2013: status from a Danish primary referral center.

BACKGROUND: The Danish Cancer Registry holds information on all prostate cancers (PCa) cases, including diagnostic TNM. However, stratification according to contemporary risk classification is not possible because histopathological grading and prostate-specific antigen (PSA) level are not registered. The objective of the study was to report clinical characteristics and primary management of men diagnosed with PCa from a primary referral center in Denmark. MATERIAL AND METHODS: Records on all men diagnosed with PCa at the Department of Urology, Frederiksberg Hospital, 1 January 2007 - 31 December 2013, were reviewed. Clinical characteristics and primary treatment were recorded. The National Comprehensive Cancer Network risk group classification was used. RESULTS: A total of 1934 men with a median age of 69 years (interquartile range 65-75) were diagnosed with PCa in the study period resulting in an incidence rate (World Standard Population) of 84/100 000. Overall, 18% were classified as low-risk, 34% as intermediate-risk, 23% as high-risk, 8% as very high-risk and 17% had metastatic disease at diagnosis. Among men age <65 years 70% had low- or intermediate-risk disease, while this was the case for 58% of men aged 65-75 and 22% of men aged >75. Metastatic disease was found in 11% of men <65 years, 17% of men 65-75 years and 23% of men >75 years. In total 73% of men with low-risk PCa were managed on watchful waiting or active surveillance. Curatively intended treatment was performed in 56% of men with intermediate-risk and 61% of men with high-risk PCa, while hormonal therapy was used in 90% of men with very high-risk and 98% of men with metastatic PCa. CONCLUSION: In a population without systematic PSA testing we found a large proportion of patients presenting with advanced PCa at diagnosis. Elderly patients presented with more advanced disease. Curative treatment was primarily used in younger men with clinically localized PCa.

The Movember campaign: Impact on referral patterns and diagnosis of prostate cancer.

AIMS: The aims of the present study were to investigate referral patterns and the diagnosis of prostate cancer (PCa) before and after the Movember campaign was initiated in Denmark. METHODS: All men (n=2817) referred to the Department of Urology at Frederiksberg Hospital with suspicion of having PCa in the period 1 January 2007-31 January 2014 were identified. Based on the referral date, patients were categorised as pre-Movember (1 January 2007-31 January 2011) and Movember (1 February 2011-31 January 2014), respectively. Annual referral-rates/100.000 inhabitants were calculated and compared with rate-ratio (RR) tests. RESULTS: The median prostate-specific antigen (PSA) at referral dropped significantly from 9.8 ng/mL in 2007-2011 to 7.9 ng/mL in 2011-2014,p< 0.001. The incidence rate of men referred with suspicion of PCa increased from 134/100.000 in the pre-Movember period to 168/100.000 in the Movember period (RR 1.25 [95% CI 1.16-1.35]). In contrast to what we anticipated, there was no increase in referral in the months following the campaign. The incidence rates of men diagnosed with PCa and low-risk PCa were similar in the Movember period and the pre-Movember period (PCa: RR 1.08 [0.97-1.21]; low-risk PCa: RR 1.29 [0.98-1.73]). CONCLUSIONS: After the initiation of the Movember campaign a significant decline in the PSA level at referral and an increase in the number of patients referred under suspicion of PCa was observed; however, only minor differences in referral patterns and PCa diagnosis were detected. The results indicate that the Movember campaign had a limited immediate effect on referral, however, it may have contributed to an increased awareness of PCa.