Development and characterisation of an irradiation device for biomedical studies covering the solar spectrum with individual regulated spectral bands.

To understand the importance of terrestrial solar exposure on human skin, not only individual spectral components need to be considered in biomedical studies, but also the relevance of the combined action profile of the complete solar spectrum (cSS) must be established. We therefore developed a novel irradiation device that combines the emission of four individual lamps (UVB, UVA, VIS and nIR) to achieve exposure from 280 to 1400 nm with individual controllable lamps. The integrated irradiance of each spectral band is similar to the solar spectrum. The lamps can be utilised individually or in any desired combination. Here we present the design, realisation, and validation of this irradiation device as well as biological results on cellular metabolism (MTT assay), cell cycle alterations, and clonogenic growth in HaCaT cells after exposures to the individual spectral bands as well as their simultaneous combinations. Thereby, we demonstrate that UVB combined with UVA is the main determinant for the metabolic activity within cSS. Also, UVB-dependent effects dominate cell cycle regulation in cSS, whilst UVA and nIR have little influence. Lastly, also clonogenic growth is dominated by the UVB action profile in cSS, despite nIR showing modulatory activity when applied in combination with UVB. Together, this highlights the regulatory influence of the different spectral bands on the three biological endpoints and demonstrates their modulation when being part of the complete solar spectrum.

[Urological care in practices and clinics during the corona virus pandemic in Germany]. / Versorgungssituation urologischer Patienten in Praxen und Kliniken während der Coronaviruspandemie in Deutschland.

The coronavirus pandemic has had an immediate and far-reaching effect on the care of urological patients. The pandemic monitor of the German Society for Urology was able to record the restrictions on patient care in urological practices and clinics by means of regular surveys of the members. A total of 689 responses at four survey time points were included. In April there was a reduction in urological inpatients to 44% and the number of patients in practices dropped to 50%. Available operating theater capacities for urological patients were 45% in April, normalized to 90% in June and fell again to 50% in December. Elective operations could not be performed at all or only to a very limited extent in most hospitals in April and December. While urgent operations could be treated to 100% in more than 75% of the clinics in April, in December more than half of the clinics stated that they could not treat all patients with urgent indications. To some extent (8-19%) practices and clinics had to resort to a pandemic-related supraregional referral of patients. The reduction of outpatients in urological practices in April normalized to 95% in June and remained stable during the second wave of the pandemic. The increase in urological emergencies in practices observed at the beginning of the pandemic did not show up in November and December. The coronavirus pandemic has led to a significant reduction in the care of urological patients, which in particular in the second wave also affects urgent operations.

[Update of the 2Sk guidelines on the diagnostics, treatment and metaphylaxis of urolithiasis (AWMF register number 043-025) : What is new?] / Aktualisierung der S2k-Leitlinie zur Diagnostik, Therapie und Metaphylaxe der Urolithiasis (AWMF Registernummer 043-025) : Was ist neu?

The increase of medical knowledge and technical innovations together with the demographic change represent a challenge for the new conception of guidelines and clinical studies. The present S2k guidelines, which are exclusively concerned with kidney and ureteral stones, should support the treatment of urolithiasis in hospitals and private practices and provide information on urolithiasis for patients. Increasing interdisciplinary collaboration in stone treatment is also demonstrated in the number of professional and working groups participating in the update of the new guidelines. The present S2k guidelines emerged from a consensus process and demonstrate the current recommendations in step with actual practice. They provide decision-making guidance for diagnostics, treatment and metaphylactic measures based on expert opinions and available published fundamental evidence from the literature.

[Cost-effectiveness analysis of blue light cystoscopy with hexylaminolevulinate in transurethral resection of the bladder]. / Kosten-Effektivitäts-Analyse zur Verwendung der Blaulichtzystoskopie mit Hexylaminolevulinat bei der transurethralen Resektion der Harnblase.

BACKGROUND: Photodynamic diagnosis using the optical imaging agent hexaminolevulinate (HAL, Hexvix®, Ipsen Pharma GmbH, Ettlingen, Germany) as an adjunct to white light cystoscopy (WLC) during the initial transurethral resection of bladder tumours (TURB) improves the detection rate of bladder cancer and leads to fewer recurrences. OBJECTIVES: A cost-effectiveness analysis was carried out in order to calculate the consequences for the German healthcare system. METHODS: We combined a short-term decision tree and a Markov model to evaluate outcomes over a long period of time. The alternatives investigated were HAL-assisted blue light cystoscopy (BLC) as adjunct to WLC (HAL + BLC/WLC) compared with WLC alone in patients undergoing TURB. RESULTS: HAL + BLC/WLC compared to WLC alone was associated with 0.07 incremental quality-adjusted life years (QALYs) and cost savings of 537 € per patient. CONCLUSION: HAL + BLC/WLC compared with WLC alone resulted in both cost savings and improved patient outcome rendering it the "dominant" strategy.

Interval cancers after skin cancer screening: incidence, tumour characteristics and risk factors for cutaneous melanoma.

BACKGROUND: The rate of interval cancers is an established indicator for the performance of a cancer-screening programme. METHODS: We examined the incidence, tumour characteristics and risk factors of melanoma interval cancers that occurred in participants of the SCREEN project, which was carried out 2003/2004 in Schleswig-Holstein, Germany. Data from 350 306 SCREEN participants, who had been screened negative for melanoma, were linked to data of the state cancer registry. Melanoma interval cancers were defined as melanomas diagnosed within 4-24 months after SCREEN examination. Results were compared with melanomas of the pre-SCREEN era (1999-2002), extracted from the cancer registry. RESULTS: The overall relative incidence of melanoma interval cancers in terms of observed/expected ratio was 0.93 (95% CI: 0.82-1.05; in situ: 1.61 (1.32-1.95), invasive: 0.71 (0.60-0.84)). Compared with melanomas of the pre-SCREEN era, the interval melanomas were thinner and had a slightly greater proportion of lentigo maligna melanomas whereas nodular melanomas were less frequent. INTERPRETATION: The results indicate a moderate performance of the SCREEN intervention with an excess of in situ melanomas. In part, the findings might be due to specifics of the SCREEN project, in particular a short-term follow-up of patients at high risk for melanoma.

[Inpatient therapy of urinary stones in Germany: development of the G-DRG system]. / Harnsteintherapie im stationären Bereich in Deutschland : Entwicklung des G-DRG-Systems.

BACKGROUND: The therapy of urinary stones in Germany is mostly a domain of hospitals even now. With the introduction of the German diagnosis-related groups (G-DRG) system in the years 2003/2004 an attempt was made to realize an ever-increasing fair representation and remuneration of treatment costs. Simultaneously, a declared target was to transfer all forms of treatment which did not necessitate hospital admission to the outpatient department. RESULTS: Analysis of the D-DRG data on running invoicing from all German hospitals from 2004/2005 to 2012/2013 showed an increase in case numbers of around 12% with a parallel increase in the volume of revenues of around 37%. A special feature was a reduction in the proportion of extracorporeal shockwave therapy (ESWL) as inpatient treatment with a parallel increase in the proportion of ureteroscopic and percutaneous interventions.

[Development of the 2014 G-DRG system. Departure from coding of secondary diagnoses?]. / Entwicklung des G-DRG-Systems 2014. Abkehr von der Kodierung der Nebendiagnosen?

The objective of the German DRG (diagnosis-related groups) system is to adequately reimburse hospital costs using flat rate payments. The goal is to thereby achieve the most adequate representation of hospital costs in flat rate payments. The DRG for 2014 is based on the actual number of cases treated and the costs determined from 2012. For 2014, the current changes of the DRG system for the specialty urology concerning the coding and recording of secondary diagnoses are presented and discussed.

[How can the coding quality in the DRG system be determined?]. / Wie kontrolliert man die Kodierqualität im DRG-System?

The permanent adjustments ​​since 2003 to the G-DRG system have made the system even less understandable, so that many users have the feeling of feeding data into a black box which gives them a result without them being able to actively use the system itself. While chief physicians, senior physicians, and nursing managers are responsible to management for the results of the billing, they are in most cases not involved in the steps of DRG coding and billing. From this situation, a common question arises: "How well does my department code?" This uncertainty is exploited by many commercial vendors, who offer a wide variety of approaches for DRG optimization. The goal of this work is to provide advice as to how coding quality can be determined.

Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings. MATERIALS AND METHODS: The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry. RESULTS: B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06). CONCLUSIONS: B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.

[Healthcare research in urology: state of the art 2013]. / Versorgungsforschung in der Urologie: Stand 2013.

In a field of medicine with fluid boundaries between the sectors and between the productive faculties, healthcare research is an indispensible responsibility of all participants. This can only be successful in improving the treatment quality of patients in the long-term by analysis of the treatment reality in routine daily work. This can be achieved by a closer cooperation between urologists in private practice and in hospitals in order to have a better definition of mutual treatment targets, to optimize therapy and to make a better analysis of target achievements. The importance of urologists in all fields of medical care and also for superordinate committees can only be visibly presented by the production of comprehensive objective figures and therefore to guarantee the long-term procurement of necessary resources.

UVA-induced DNA double-strand breaks result from the repair of clustered oxidative DNA damages.

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G(1)-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.

Effectiveness of skin cancer screening programmes.

Skin cancer, nonmelanoma skin cancer (NMSC) and cutaneous malignant melanoma (CMM), is the most frequent cancer worldwide. It is amenable to early detection, and screening for skin cancer has the potential to reduce mortality and morbidity. However, there are no recommendations for population-based skin cancer screening programmes due to the lack of evidence for the effectiveness from epidemiological studies. In 2008 the first nationwide screening programme for NMSC and CMM in the world was established in Germany. The decision for implementing such a programme was based on the results and evidence of a pilot study that was conducted from 2003 to 2004. The pilot study revealed that a population-based screening programme for skin cancer is feasible and effective. Careful evaluation of the nationwide programme is crucial to generate strong evidence for long-term public health benefits.

[Amendments to the German diagnosis-related groups (G-DRG) system for urology in 2012]. / Veränderungen des G-DRG-Systems für die Urologie im Jahre 2012.

The remuneration system of German diagnosis-related groups (G-DRG) is updated every year in a clearly defined process. This article presents all changes relevant for urologists in 2012.

Skin cancer screening participation and impact on melanoma incidence in Germany--an observational study on incidence trends in regions with and without population-based screening.

BACKGROUND: The SCREEN (Skin Cancer Research to provide Evidence for Effectiveness of Screening in Northern Germany) project involved population-wide skin cancer screening with whole-body examination by general physicians and dermatologists. It was conducted in the German state of Schleswig-Holstein (July 2003-June 2004), but not in the German state of Saarland. METHODS: The population-based registries of Schleswig-Holstein and Saarland provided data on melanoma incidence before, during, and after SCREEN to assess the association of skin cancer screening with incidence. RESULTS: Approximately 19% of the Schleswig-Holstein population participated in SCREEN (women: 27%, men: 10%). A total of 52% of all melanomas diagnosed during SCREEN in Schleswig-Holstein were detected as part of the project. Melanoma incidence increased during SCREEN (invasive melanoma in women: +8.9 per 100,000 (95% confidence intervals (CI): 6.1; 11.7); men: +4.0 per 100,000 (95% CI: 1.6; 6.4)) and decreased afterwards (women: -10.6 per 100,000 (95% CI: -13.3; -7.9); men: -4.1 per 100,000 (95% CI: -6.5; -1.7)). Similar changes were not observed in Saarland that had no such project. The differences between the two states were greatest among women, the group with the greater SCREEN participation. CONCLUSION: The SCREEN project had a substantial impact on melanoma incidence. This is consistent with the impact of effective screening for other cancers.

[Representation of cystectomy and urinary diversion in the G-DRG system 2010: an example for the complexity of the reimbursement system]. / Kodierung der Zystektomie im DRG-System 2010 : Ein Beispiel für die Komplexität des Abrechnungssystems.

Cystectomy and urinary diversion is an excellent example for the growing complexity of the G-DRG (German diagnosis-related groups) system. Based on different diagnoses (malignant tumor of the urinary tract, benign disease of the urinary tract, malignant tumor of the female genital tract, or malignant tumor of the male genital tract), identical cases may lead to very different codes, resulting in even more differences in reimbursement.

[Economic aspects of the treatment of urinary stones. Results of the German Society for Shock Wave Lithotripsy]. / Okonomische Aspekte der Harnsteintherapie. Ergebnisse des Konsensusmeetings der Deutschen Gesellschaft für Stosswellenlithotrypsie (DGSWL).

Urolithiasis is the disease that leads to the largest number of inpatient treatments in urologic clinics in Germany. It is very important to know the current rules of remuneration for urinary stone therapy and to adjust the relevant clinical pathways. The German Society for Shock Wave Lithotripsy (DGSWL) stressed these economic aspects at its 2009 consensus meeting, since clinical therapy cannot be free of economic restrictions in the long term.

[Adjustment of the German DRG system in 2009]. / G-DRG-Systemanpassung 2009.

BACKGROUND: The 2009 version of the German DRG system brought significant changes for urology concerning coding of diagnoses, medical procedures and the DRG structure. In view of the political situation and considerable economic pressure, a critical analysis of the 2009 German DRG system is warranted. Analysis of relevant diagnoses, medical procedures and G-DRGs in the versions 2008 and 2009 based on the publications of the German DRG-institute (InEK) and the German Institute of Medical Documentation and Information (DIMDI). RESULTS: The relevant diagnoses, medical procedures and German DRGs in the versions 2008 and 2009 were analysed based on the publications of the German DRG Institute (InEK) and the German Institute of Medical Documentation and Information (DIMDI). Changes for 2009 focus on the development of the DRG structure, DRG validation and codes for medical procedures to be used for very complex cases. The outcome of these changes for German hospitals may vary depending in the range of activities. CONCLUSION: The German DRG system again gained complexity. High demands are made on correct and complete coding of complex urology cases. The quality of case allocation in the German DRG system was improved. On the one hand some of the old problems (e.g. enterostomata) still persist, while on the other hand new problems evolved out of the attempt to improve the case allocation of highly complex and expensive cases. Time will tell whether the increase in highly specialized DRG with low case numbers will continue to endure and reach acceptable rates of annual fluctuations.

[Complete resection of urothelial cancer metastases with curative intent]. / Metastasenchirurgie in kurativer Absicht beim Urothelkarzinom.

BACKGROUND: Recent publications suggest that a subgroup of patients can benefit from surgical removal of transitional cell carcinoma (TCC) metastases in addition to systemic chemotherapy. We report the combined experience and outcome of patients undergoing resection of TCC metastases at 15 uro-oncologic centers in Germany. MATERIALS AND METHODS: Forty-four patients with distant metastatic TCC of the bladder or upper urinary tract underwent resection of all detectable metastases in 15 different German uro-oncological centers between 1991 and 2008 in an attempt to be rendered free of disease. RESULTS: The resected metastatic sites consisted of retroperitoneal lymph nodes (56.8%), distant lymph nodes (11.3%), lung (18.2%), bone (4.5%), adrenal gland (2.3%), brain (2.3%), small intestine (2.3%), and skin (2.3%). The treatment sequence included systemic chemotherapy in 35/44 (79.5%) patients before and/or after surgery. Median survival times from initial diagnosis of metastatic TCC and subsequent resection were as follows: overall survival, 35 and 27 months, respectively; cancer-specific survival, 38 and 34 months, respectively; and progression-free survival, 19 and 15 months, respectively. Overall 5-year survival from metastasectomy for the entire cohort was 28%. Seventeen patients were still alive without progression at a median follow-up time of 8 months. Seven patients without disease progression survived for more than 2 years and remain free from tumor progression at a median of 63 months. CONCLUSION: The results in this selected cohort confirm that long-term cancer control and possibly cure can be achieved in a subgroup of patients following surgical removal of TCC metastases. However, prospective data to identify patients most likely to benefit from this aggressive therapeutic approach are lacking. Therefore, metastasectomy in patients with disseminated TCC remains investigational and should be offered only to those with limited disease as a combined-modality approach with systemic chemotherapy.