[The metastatic and advanced upper tract urothelial carcinoma-a separate entity or bladder cancer's younger sibling?] / Das metastasierte und fortgeschrittene Urothelkarzinom des oberen Harntraktes ­ eigene Entität oder doch kleine Schwester des Blasenkarzinoms?

Upper tract urothelial carcinoma (UTUC) is a cancer that is often already in an advanced stage at the time of initial diagnosis. Although urothelial carcinoma of the upper and lower urinary tracts both originate from the urothelium and have similar genetic alterations, there are significant differences in their distribution. In localized high-risk UTUC, radical nephroureterectomy is the gold standard therapy. In metastatic UTUC, major changes are emerging in sequential therapy due to the investigation of new classes of drugs. In addition to platinum-based combination chemotherapy and immunotherapy, new substances such as antibody-drug conjugates (ADCs) and FGFR inhibitors are used.

AAV-mediated gene transfer of a checkpoint inhibitor in combination with HER2-targeted CAR-NK cells as experimental therapy for glioblastoma.

Glioblastoma (GB) is the most common primary brain tumor, which is characterized by low immunogenicity of tumor cells and prevalent immunosuppression in the tumor microenvironment (TME). Targeted local combination immunotherapy is a promising strategy to overcome these obstacles. Here, we evaluated tumor-cell specific delivery of an anti-PD-1 immunoadhesin (aPD-1) via a targeted adeno-associated viral vector (AAV) as well as HER2-specific NK-92/5.28.z (anti-HER2.CAR/NK-92) cells as components for a combination immunotherapy. In co-culture experiments, target-activated anti-HER2.CAR/NK-92 cells modified surrounding tumor cells and bystander immune cells by triggering the release of inflammatory cytokines and upregulation of PD-L1. Tumor cell-specific delivery of aPD-1 was achieved by displaying a HER2-specific designed ankyrin repeat protein (DARPin) on the AAV surface. HER2-AAV mediated gene transfer into GB cells correlated with HER2 expression levels, without inducing anti-viral responses in transduced cells. Furthermore, AAV-transduction did not interfere with anti-HER2.CAR/NK-92 cell-mediated tumor cell lysis. After selective transduction of HER2+ cells, aPD-1 expression was detected at the mRNA and protein level. The aPD-1 immunoadhesin was secreted in a time-dependent manner, bound its target on PD-1-expressing cells and was able to re-activate T cells by efficiently disrupting the PD-1/PD-L1 axis. Moreover, high intratumoral and low systemic aPD-1 concentrations were achieved following local injection of HER2-AAV into orthotopic tumor grafts in vivo. aPD-1 was selectively produced in tumor tissue and could be detected up to 10 days after a single HER2-AAV injection. In subcutaneous GL261-HER2 and Tu2449-HER2 immunocompetent mouse models, administration of the combination therapy significantly prolonged survival, including complete tumor control in several animals in the GL261-HER2 model. In summary, local therapy with aPD-1 encoding HER2-AAVs in combination with anti-HER2.CAR/NK-92 cells may be a promising novel strategy for GB immunotherapy with the potential to enhance efficacy and reduce systemic side effects of immune-checkpoint inhibitors.

Three months in a high-volume tertiary orthopaedic trauma unit: What is a registrar worth?

BACKGROUND: South Africa has a high burden of traumatic injuries that is predominantly managed in the public healthcare system, despite the relative disparity in human resources between the public and private sectors. Because of budget and theatre time constraints, the trauma waiting list often exceeds 50 - 60 patients who need urgent and emergent surgery in high-volume orthopaedic trauma centres. This situation is exacerbated by other surgical disciplines using orthopaedic theatre time for life-threatening injuries because of lack of own theatre availability. One of the proposed solutions to this problem is outsourcing of some of the cases to private medical facilities. OBJECTIVES: To establish the volume of work done by an orthopaedic registrar during a 3-month trauma rotation, and to calculate the implant and theatre costs, as well as compare the salary of a registrar with the theoretical private surgeon fees for procedures performed by the registrar in the 3-month period. METHODS: In a retrospective study, the surgical logbook of a single registrar during a 3-month rotation, from 14 January to 14 April 2019, was reviewed. Surgeon fees were calculated for these procedures, according to current medical aid rates, without additional modifier codes being added. RESULTS: During the 3-month study period, a total of 157 surgical procedures was performed, ranging from total hip arthroplasty to debridement of septic hands. Surgeon fees amounted to ZAR186 565.10 per month ‒ double the gross salary of a registrar. Total implant costs amounted to ZAR1 272 667. Theatre costs were ZAR1 301 976 for the 3-month period. CONCLUSIONS: Although this analysis was conducted over a short period, it highlights the significant amount of trauma work done by a single individual at a high-volume tertiary orthopaedic trauma unit. With increasing budget constraints, pressure on theatre time and a growing population, cost-effective expansion of resources is needed. From this study, it appears that increasing capacity in the state sector could be cheaper than private outsourcing, although a more in-depth analysis needs to be conducted.

[Early cystectomy-patient selection and technique]. / Indikationen und Technik der Frühzystektomie.

Early radical cystectomy (RC) is a therapeutic option for non-muscle invasive bladder cancer (NMIBC). The 15-year overall survival after early RC in NMIBC patients is about 70%. Nevertheless, RC is associated with significant morbidity and mortality and therefore requires careful patient selection. The aim of the following review is to assess the selection process for early RC in NMIBC. Especially, the new European Association of Urology (EAU) risk calculator identifying NMIBC patients with very high risk for disease progression is described in detail. Furthermore, the technical aspects of the procedure are evaluated. A review of the current literature (PubMed) and national and international guideline recommendations was also conducted.

The HELENA study: Hexvix®-TURB vs. white-light TURB followed by intravesical adjuvant chemotherapy-a prospective randomized controlled open-label multicenter non-inferiority study.

PURPOSE: Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix® TURB followed by immediate instillation compared to white-light TURB with immediate instillation followed by maintenance ICT. METHODS: Between 07/2010 and 12/2016, 129 patients with EORTC intermediate risk non-muscle invasive bladder cancer treated with TURB were included in this multicentre phase III study. Patients were randomized and received either white-light TURB with immediate ICT followed by maintenance ICT (n = 62, 20 mg Mitomycin weekly for 6 weeks as induction phase, afterwards 20 mg/month for 6 months) or Hexvix® TURB with immediate ICT only (n = 67, 40 mg Mitomycin). Primary study endpoint was RFS after 12 months. Hexvix® TURB was counted as non-inferior to white light alone if the upper limit of the one-sided 95% confidence interval of hazard ratio was lower than 1.676. Due to the non-inferiority design, the per-protocol population was used as the primary analysis population (n = 113) RESULTS: Median follow-up was 1.81 years. Hexvix® group showed more events (recurrence or death) than white-light group (19 vs. 10) resulting in a HR of 1.29 (upper limit of one-sided 95%-CI = 2.45; pnon-inferiority = 0.249). The ITT population yielded similar results (HR = 1.67); 3.18], pnon-inferiority = 0.493). There was no significant difference in overall survival between both groups (p = 0.257). CONCLUSION: Non-inferiority of Hexvix® TURB relative to white-light TURB with maintenance Mitomycin instillation in intermediate risk urothelial carcinoma of the bladder was not proven. Hence a higher effect of maintenance ICT is to assume compared to a Hexvix®-improved TURB only, confirming its important role in patient treatment.

[Systemic treatment of bladder cancer]. / Blasenkarzinomsystemtherapie.

Cisplatin-based chemotherapy regimens represent the standard of care in patients with locally advanced or metastatic urothelial carcinoma of the bladder. However, many patients are ineligible for cisplatin due to comorbidities or performance status. Immunotherapy with checkpoint inhibitors (CPI) has become a well-established treatment alternative in metastatic bladder cancer. The following review discusses current literature and guideline recommendations based on two case studies, in order to provide practical know-how about therapy sequences and treatment processes.

[Urologic cancer care during the first wave of the COVID-19 pandemic : Role of federal cancer registration in Germany]. / Uroonkologische Therapie in der ersten Welle der COVID-19-Pandemie : Was sagen uns die Krebsregister der deutschen Bundesländer?

Urologic cancer care needs to be prioritized despite multiple health care restrictions during the coronavirus disease 2019 (COVID-19) pandemic. However, therapies and procedures may be delayed and complicated. In Germany, analysis of the multiple cancer registries provides insights into the actual numbers of treated patients. We provide a review on the registration of urologic cancer care during the first wave of the COVID-19 pandemic in Germany and on potential surgical complications of urologic interventions. We found that during the year 2020 there were generally fewer registrations of newly diagnosed patients with major urologic neoplasms in a representative federal database. The number of surgical interventions in patients with renal cell carcinoma and urothelial bladder cancer decreased, whereas equal numbers of radical prostatectomies were performed when compared to the year 2019. COVID-19 may increase non-urological postoperative complications following surgical treatment of urologic malignancies; however, available data are still very limited.

[Quality assessment of radical cystectomy-opportunities, risks, challenges]. / Qualitätsparameter bei der radikalen Zystektomie ­ Chancen, Risiken, Herausforderungen.

Radical cystectomy (RC) is the standard treatment for nonmetastatic muscle-invasive urothelial carcinoma of the urinary bladder. It is associated with relevant morbidity and mortality. After RC, the 5­year overall survival rate is approximately 60%. In the context of the present work, quality parameters of RC divided into oncological/functional criteria and freedom from complications are identified and summarized. A PubMed search was performed. In addition to early criteria such as negative surgical margins, performance of pelvic lymphadenectomy, creation of a continent urinary diversion or preservation of sexual function, long-term criteria were identified such as the absence of higher-grade postoperative complications, recurrence-free survival and the preservation of health-related quality of life. The early criteria are suitable for individualized therapy planning, whereas the long-term criteria can be used for quality monitoring.

Prevalence of a postoperative troponin leak in patients with cardiac risk factors undergoing knee and hip arthroplasty in a South African population.

BACKGROUND: Patients undergoing arthroplasty may have comorbidities that put them at risk of myocardial injury after non-cardiac surgery (MINS). MINS, a new clinical concept that has a different pathophysiology from conventional myocardial infarction, is related to a supply-demand mismatch ischaemia in the perioperative setting. MINS is often a silent event, and the diagnosis relies on cardiac biomarker testing such as troponin T. The incidence is estimated at 40%, with a fourfold increase in morbidity and mortality risk 1 year post surgery. OBJECTIVES: To determine the prevalence of postoperative troponin leak in a single-centre arthroplasty unit in patients with various cardiac risk factors undergoing hip or knee arthroplasty and investigate the differences in troponin T levels between comorbidities and different types of arthroplasty, i.e. total hip replacement (THR), total knee replacement (TKR) and neck of femur (NoF) fracture hip replacement. METHODS: A prospective, cross-sectional study of patients with one or more cardiac risk factors undergoing replacement surgery was conducted from October 2017 to April 2018. Troponin levels of all included patients were recorded on days 1 and 3 post surgery using a high-sensitivity cardiac troponin T assay (Roche hs-cTnT). A level of >15 ng/L is considered abnormal and termed a positive troponin leak, while >100 ng/L is considered suspected acute coronary syndrome (ACS). RESULTS: One hundred and sixty patients (n=66 THR, n=55 NoF hip replacement, n=39 TKR) were included. Sixty-eight patients (42%) had a positive troponin leak, and in 6 of these cases ACS was suspected. The highest prevalence of troponin leak was recorded in patients undergoing NoF hip replacement (62%), followed by TKR (46%) and then THR (24%). Sixty-two patients (38%) had positive troponin levels on day 1 and 53 patients (33%) had positive levels on day 3. Important patient cardiac risk factors were identified in the presence of a positive troponin leak, with ischaemic heart disease, hypertension, diabetes, renal disease, age >65 years and atrial fibrillation being statistically most likely. CONCLUSIONS: Postoperative troponin surveillance is an inexpensive and reliable way to identify patients at risk of MINS and subsequently enhance early detection, medical optimisation and referral strategies. Simple interventions may improve outcomes and contribute to lower ACS rates and the timeous prevention of other complications. The prevalence of MINS in orthopaedic-specific patients in South Africa (SA) and other resource-constrained developing countries is unknown. Our finding of 42% positive troponin leaks raises awareness of this issue, and we recommend routine postoperative troponin surveillance for all arthroplasty units in SA.

[Is the discipline associated with self-confidence in handling rational antibiotic prescription? : Results from the MR2 study in German hospitals]. / Ist die Fachrichtung assoziiert mit der Selbstsicherheit im Umgang mit rationaler Antibiotikaverordnung? : Ergebnisse der MR2-Studien an deutschen Kliniken.

BACKGROUND: Besides public awareness and specialist knowledge and training of physicians, their self-confidence plays a key role for clinical decision-making in the respective area. OBJECTIVE: This exploratory study investigated the influence of the discipline on differences in self-confidence in dealing with antibiotics and in the self-rated knowledge. METHODS: In 2015 the multi-institutional reconnaissance of practice with multiresistant bacteria (MR2) questionnaire containing items on antibiotic prescription and multiresistant pathogens was sent out to 1061 physicians working in departments for internal medicine, general surgery, gynecology and obstetrics and urology. In 2017 a similar MR2 survey was sent to 1268 specialist and assistant physicians in anesthesiology in Germany. Besides demographic data 4 items on self-confidence in the use of antibiotic treatment and 11 items concerning self-rated knowledge about rational antibiotic therapy and multiresistant pathogens were included in the present analysis. Logistic regression analysis, the χ2-test and the Kruskal-Wallis test were used for statistical analysis of the influence of the discipline on these items. RESULTS: The response rates were 43% (456 out of 1061) from the non-anesthetists and 56% (705 out of 1268) from the anesthetists. Of the non-anesthetists 44% and 57% of the anesthetists had had no advanced training on antibiotic stewardship during the year before the study. In the overall analysis anesthetists (mean±SD: 2.53±0.54) were significantly less self-confident about antibiotics than colleagues from other departments (internal medicine: 3.10±0.50, general surgery: 2.97±0.44, gynecology and obstetrics: 3.12±0.42 and urology: 3.15±0.44) in the unadjusted (all p<0.001) and adjusted comparison. The analysis of self-rated knowledge about rational antibiotic prescription showed similar results. Senior consultant status and advanced training in infectiology were significantly associated with self-confidence and self-rated knowledge about antibiotics. CONCLUSION: Anesthetists showed significantly less self-confidence in dealing with antibiotics than colleagues from other disciplines. Advanced training on a rational prescription of antibiotics was associated with a greater self-confidence, so that the implementation of compulsory courses on rational antibiotic stewardship in the respective residency curriculum needs to be considered.

Correction to: The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence.

In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer.

Intramedullary fixation versus anatomically contoured plating of unstable ankle fractures: a randomized control trial.

AIM: This study compared functional outcomes between anatomical shaped fibular plates and intramedullary nail fixation of adult patients who sustained unstable ankle fractures. METHODS: A prospective randomized control trial was conducted between November 2013 and December 2016 on patients that presented with an unstable ankle fractures. They were randomized into a plate-and-screw group and a fibula nail group. At each post-operative visit the wounds were reviewed, and specific outcome measures were recorded, which included (i) the patient reported outcome measure (PROM) Olerud and Molander functional score, (ii) the Grimby score, (iii) swelling around the malleoli, (iv) plantar flexion, (v) dorsiflexion, (vi) inversion, and (vi) eversion. RESULTS: Significant differences were observed in scar size (p < 0.001) and screening time (p < 0.001) whilst no differences were observed in functional and PROM measures. Although not statistically significant, of clinical value is one deep infection that occurred in the plate group, whilst no infections occurred in the nail group. CONCLUSION: Both fixation methods yielded very similar functional results with differences only in scar size, screening time and swelling. Although none of these warrant a change in surgical decision-making processes, taken together, these factors potentially influence the decisions made in terms of surgical modalities used.

Adherence to the EAU guideline recommendations for systemic chemotherapy in penile cancer: results of the E-PROPS study group survey.

OBJECTIVES: To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. MATERIALS AND METHODS: A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75-94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. RESULTS: Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010-0.001). Department size and university center status were no significant predictors for all three endpoints. CONCLUSIONS: In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.

Prediction of early (30-day) and late (30-90-day) mortality after radical cystectomy in a comprehensive cancer centre over two decades.

BACKGROUND: Radical cystectomy (RC) is associated with substantial postoperative mortality. In this study, we analyzed early (30-day; 30 M) and late (30-90-day; 30-90 M) mortality after RC in a Dutch tertiary referral center and determined factors associated with 30 M, 30-90 M and 90-day mortality (90 M). PATIENTS AND METHODS: We identified 823 patients who underwent RC for bladder cancer in the Netherlands Cancer Institute between 1997 and 2017. Predictive factors for mortality were analyzed to identify patients with a higher mortality risk. Multivariate logistic regression analysis was performed to examine the influence of patient, surgical and histopathological variables on 30 M, 30-90 M and 90 M. RESULTS: Thirty-day mortality was 1.9% and 90 M was 6.0%. Multivariable analysis showed that age (OR 1.08, 95% CI 1.01-1.1, p = 0.002) and ASA 3-4 (OR 3.57, 95% CI 1.25-10.16, p = 0.002) were significant predictors of 30 M while higher ASA score (OR 2.9, 95% CI 1.31-6.5, p = 0.009) and higher pathological T stage (OR 8.8, 95% CI 1.9-40.4, p = 0.005) were associated with 30-90 M. Risk of 90 M was increased in patients with ASA 3-4 (OR 2.4, 95% CI 1.2-4.9, p = 0.01), pT3-4 (OR 3.1, 95% CI 1.27-7.57, p = 0.01) and positive LNs (OR 2.5, 95% CI 1.25-4.98, p = 0.009). CONCLUSIONS: Patient-related factors predicted 30 M whereas both patient-related and cancer-related factors predicted 30-90 M. This suggests that patient mix, i.e. patient- vs. cancer-related factors for 30 M and 30-90 M, should be taken into account if mortality rates are to be compared between hospitals.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

[Attending physicians in urology working at university centers or non-university centers-what are the differences? : Results of a web-based cross-sectional study at German hospitals]. / Urologische Oberärztinnen und Oberärzte an universitären oder nicht-universitären Kliniken ­ welche Unterschiede gibt es? : Ergebnisse einer webbasierten Querschnittstudie an deutschen Kliniken.

BACKGROUND: Attending physicians (AP) in urology represent a very heterogeneous group covering various clinical priorities and career objectives. To date, there are no reliable data on professional, personal and position-linked aspects of AP in urology working in university centers (univ-AP) opposed to those working in non-university centers (n-univ-AP). MATERIALS AND METHODS: The objective of this study was to analyze individual professional perspectives, professional and personal settings, specific job-related activities and individual professional goals of univ-AP opposed to n­univ-AP. Thus, a web-based survey containing 55 items was designed to perform a cross-sectional study that was then forwarded using a link which was sent via a mailing list of the German Society of Urology. The survey was available for completion by AP at German urological centers from February to April 2019. Group-specific differences were evaluated using bootstrap-adjusted multivariate logistic regression models. RESULTS: Of the 192 evaluable surveys, 61 (31.8%) and 131 (68.2%) were part of the univ-AP and n­univ-AP study group, respectively. Participating n­univ-AP compared to univ-AP held the position of AP (p = 0.022) significantly longer and were on call significantly more frequently (p < 0.001). AP in urology (self)-assessed themselves as autonomously confident in performing robotic, laparoscopic, open, endo-urologic, and plastic-reconstructive surgery in 12.4%, 25%, 59.6%, 92.1%, and 25.7%, respectively, with no significant differences between the two groups among all above mentioned surgical subdomains based on multivariate analysis. AP in urology were (very) content in 92% concerning the choice of their discipline, in 73.9% concerning their actual working circumstances, and in 60.2% concerning their level of surgical expertise. Only 27.1% and 19.9% were (very) content with the amount of available time for their personal professional development and for private affairs, respectively. As opposed to n­univ-AP, univ-AP would choose a career in clinical centers once again significantly more frequently (OR 2.87; p(BS) = 0.041), but assess the position of AP as their definitive career goal significantly less frequently (OR 0.42; p(BS) = 0.40). Univ-AP state significantly more frequently that they were running for the position of head of department or full professor (OR 5.64; p(BS) = 0.001). CONCLUSION: In this first survey study world-wide on AP in urology divided according to their academic background, similarities and variances were analyzed, baring the potential to further improve identification of AP for a career in clinical centers.

A national Health and Work Strategy: a search for evidence.

BACKGROUND: The Health and Safety Executive's new Health and Work Strategy is based on an up-to-date assessment of workplace health priorities. Rather than replicating traditional prioritization approaches, a broader assessment of health and work priorities was carried out using a range of stakeholders. AIMS: To develop a set of health priorities for further research and intervention activity. METHODS: Four exercises were carried out, including internal prioritization, two external web-hosted questionnaire studies of younger workers and occupational health professionals, focus groups and tele-depth interviews with workplace health and safety professionals. RESULTS: The highest rated internal priorities (weighted priority scores) were identified as mesothelioma (70), lung cancer (69.25), chronic obstructive pulmonary disease (COPD; 69), musculoskeletal disorders (MSDs; 66.25), hearing loss (65.75), stress (65.5), asthma (64.5) and hand-arm vibration syndrome (61.5). Using the three highest ranked criteria developed by occupational health professionals ((i) the preventability of the condition, (ii) the impact of the condition and (iii) the number of workers affected), mesothelioma, lung cancer, COPD, MSDs, hearing loss, stress and asthma were identified as the top seven priorities. Generic issues identified included ageing and work, obesity, newer technologies, and ethnicity and cultures of workforces. Apprentices identified stress, depression, anxiety, musculoskeletal and respiratory disorders, fatigue and workload as important workplace health considerations. CONCLUSIONS: This process identified a number of expected and new areas of health research interest. We believe the findings reflect the real world requirements of work as assessed by occupational health and safety practitioners and workers.

Long-term outcome after grafting with small intestinal submucosa and collagen fleece in patients with Peyronie's disease: a matched pair analysis.

Advanced Peyronie's disease (PD) with severe penile curvature requires grafting following plaque incision or partial plaque excision. So far, the ideal graft material has not been identified although various grafts have been studied. In this first matched pair analysis we compared the outcome after grafting with small intestinal submucosa (SIS) and self-adhesive collagen fleece (CF). We retrospectively identified 43 patients after SIS grafting with complete follow-up data sets to be eligible for the present study. A total of 43 patients after CF grafting were matched case by case to the SIS group using the degree of preoperative penile curvature as the primary matching factor. Postoperative outcome was compared with the focus on penile straightening, penile length, potency, relapse rates and long-term complications. Median degree of curvature was 80° in each group. Mean follow-up periods were 31 months after SIS and 39 months after CF grafting. The CF grafting procedure was significantly faster than SIS grafting (80 vs. 104 min, p < 0.001). No major short-term complications were observed. Both techniques gained good long-term penile straightening rates. Relapse of penile curvature was observed after SIS grafting only. Postoperative penile shortening occurred more often after SIS grafting (28% vs. 5%, p = 0.007). With a mean preoperative IIEF-5 score of 16, the SIS cohort significantly differed from the CF cohort with a mean IIEF-5 score of 19 (p = 0.016). The median IIEF-5 score improvement was higher after SIS grafting (+4.5 vs. +1, p = 0.002). Diminished penile sensation was the main long-term side effect with low rates after both procedures (9% and 7% in the SIS and CF group respectively, p = 0.100). In this first matched pair analysis both techniques showed promising long-term results. CF seems to have advantages regarding duration of surgery and preserving penile length. More comparative studies with larger collectives are desirable.

[Imaging in individualized uro-oncology]. / Bildgebung in der individualisierten Uroonkologie.

The recent introduction of new diagnostic techniques has revolutionized uro-oncolgy. In addition to multiparametric magnetic resonance imaging (mpMRI), prostate-specific membrane antigen positron-emission tomography (PSMA-PET) plays an increasingly import role in daily practice. The introduction of three-dimensional (3D) printing technologies in the context of robot-assisted uro-oncological surgery represents a first step towards individualized 3D imaging. In the era of immunotherapy, imaging is challenged by new diagnostic criteria (iRECIST) and immune-related adverse effects.

PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation.

VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression anticipated the initiation of vascular enlargement and markedly accelerated the splitting process. Interestingly, quantification during in vivo imaging suggested that a global reduction in shear stress favored the initiation of transluminal pillar formation during VEGF-induced splitting angiogenesis. Quantification of target gene expression showed that VEGF-R2 signaling output was significantly reduced by PDGF-BB co-expression compared to VEGF alone. In conclusion, PDGF-BB co-expression prevents VEGF-induced aberrant angiogenesis by modulating VEGF-R2 signaling and endothelial proliferation, thereby limiting the degree of circumferential enlargement and enabling efficient completion of vascular splitting into normal capillary networks despite high VEGF doses.