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.

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.

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.

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.

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.

[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.

Transrectal ultrasound as diagnostic tool for the detection of local recurrence following cystectomy and urinary diversion.

OBJECTIVE: Routine follow-up after cystectomy for bladder cancer detect patients with local recurrence late in the course of disease. We set out to determine the value of transrectal ultrasound (TRUS) as diagnostic tool to diagnose local failure. PATIENTS AND METHODS: Between 1986 and 2003, radical cystectomy for bladder cancer with orthotopic diversion was performed in 642 male patients. We identified all patients that simultaneously had transabdominal ultrasound, digital rectal examination, TRUS and CT/MRI of the pelvis at the diagnosis of local recurrence. RESULTS: Mean follow-up was 59.4 months. 83/642 patients (13%) had local failure of bladder cancer during follow-up. In 48/642 patients (7.5%) the local recurrence was the first site of recurrence. 35/642 patients (5.5%) developed local failure with concomitant distant disease. 31/83 patients met the inclusion criteria. The median time between cystectomy and diagnosis of local recurrence was 13 months (2-51 months). Routine follow-up detected local recurrence in 1 asymptomatic patient. 25/31, 3/31 and 2/31 patients had pain in the lower extremities/pelvis, hematuria and urinary retention, respectively. Digital rectal examination, transabdominal ultrasound, TRUS, and CT/MRI of the pelvis were suspicious for local recurrence in 9, 7, 26, and 29 patients, respectively. CONCLUSIONS: TRUS is a highly sensitive tool in detecting local recurrence following cystectomy. It is easy to perform and inexpensive. We recommend TRUS in short intervals in all patients with high risk for local recurrence in order to detect cancer early.

[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.

[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.

[Calculating the price of a new diagnostic or therapeutic option. Example of transurethral resection of bladder tumors using photodynamic diagnostics with hexaminolevulinic acid]. / Kalkulation einer neuen Untersuchungs- und Behandlungsmethode (NUB). Analyse am Beispiel der PDD-gestützten TUR-B mit Hexaminolävulinsäure.

New diagnostic or therapeutic options (NDTOs) are remunerated separately in the German DRG system. The Institute for Remuneration in Hospitals decides which proposed NDTOs are accepted for separate remuneration for 1 year. With this acceptance, hospitals can enter negotiations with insurance companies for an individual price of the NDTO. Because there are no general recommendations for these negotiations, we present a scheme for how to calculate an NDTO, based on the example of the NDTO for transurethral resection of bladder tumors using photodynamic diagnostic with hexaminolevulinic acid.

[Relevance of hospitals participating in the DRG calculation for the development of the G-DRG system]. / Die Bedeutung der Kalkulationshäuser für die Weiterentwicklung des G-DRG-Systems.

Since the G-DRG system was established for remuneration of inpatient treatment, hospitals may offer the cost data of their cases as a database for the calculation of new DRGs. Therefore, the DRGs will be only as good as the cost data offered. These hospitals must be interested in offering perfect data, since this is the only option to optimize the DRG system.

[Transvesical malposition of a transobturator aortofemoral bypass]. / Transvesikale Fehllage eines transobturatorischen aortofemoralen Bypass.

Besides anatomical bypass procedures, extra-anatomical bypass variations are used for the surgical treatment of peripheral occlusive disease. We report the case of a 64-year-old patient who presented at our clinic with suspected primary bypass malposition.

[Terminology of lower urinary tract dysfunction and coding in the ICD-10-GM catalogue]. / Terminologie der Blasenfunktionsstörungen und Kodierung im ICD-10-GM-Katalog.

The terminology of lower urinary tract dysfunction was recommended by the AWMF and the German Society of Urology in 2004. However, there is no transfer of this terminology to diagnoses according to the classification of the ICD-10-GM catalogue. This catalogue is of major relevance for remuneration of inpatient and outpatient treatment in the German diagnosis-related groups (DRG) system. This article presents a table showing the correspondence between the current terminology and the ICD-10-GM classification. The correct coding can change the DRG remuneration by a factor of 2 to 3.

[The German diagnosis-related groups in urology: reproducibility and quality of coding]. / G-DRG-System für die Urologie : Reproduzierbarkeit und Kodierqualität.

BACKGROUND: The German diagnosis-related group (G-DRG) system is based on the belief that there is only one specific coding for each case. The aim of this study was to compare coding results of identical cases coded by different coding specialists. MATERIAL AND METHODS: Charts of six anonymous cases -- except final letter and coding -- were sent to 20 German departments of urology. They were asked to let their coding specialists do a DRG coding of these cases. The response rate was 90%. RESULTS: Each case was coded in a different way by each coding specialist. The DRG refunding varied by 6-23%. The coding differences were caused by different interpretations of definitions in the DRG system and also by inaccurate chart analysis. CONCLUSION: The present DRG system allows a wide range of interpretation, leading to aggravation of the ongoing disputes between hospitals and insurance companies.

[Photodynamic diagnostics in the urinary tract. Consensus paper of the Working Group for Oncology of the German Society for Urology]. / Photodynamische Diagnostik im Harntrakt. Konsensusempfehlungen des Arbeitskreises Onkologie der Deutschen Gesellschaft für Urologie.

Because of the frequency of occurrence and the long protracted course, bladder carcinoma is the most expensive solid tumor in terms of costs, from diagnosis to death of the patient. The most important cost factor within the total cost is the treatment of recurrent, non-muscle invasive bladder carcinoma. Photodynamic diagnosis (PDD) improves the early detection rate of non-muscle invasive bladder cancer, especially the detection of carcinoma in situ and severe dysplasia. PDD also reduces the number of residual tumors after TUR-B compared to white-light guided TUR-B and also the early recurrence rate although long-term outcome with hexylaminolaevulinic acid with regards to the general course of bladder cancer is still lacking. PDD has been used mainly for detection of bladder cancer and specifically carcinoma in situ in conjunction with diagnostic and therapeutic transurethral resection of the bladder. In 2006 hexylaminolaevulinic acid (HAL) was approved in the EU (EMEA) as a photosensitizer for the use in photodynamic diagnosis of the bladder. Several guidelines have incorporated PDD as optional form of diagnosis during endoscopy in proven or suspected bladder cancer, but no specific recommendations regarding indication and application of PDD exist. The German group of urologic oncology (AKO) invited urologists and biologists involved in the development of hexylaminolaevulinic acid as well its clinical use to participate in evaluating the data for HAL and its predecessor delta-aminolaevulinic acid (5-ALA). A consensus with regards to the indications, contraindications, technique, pre-clinical data, comparison of HAL and 5-ALA, current results, costs and follow-up was reached and are presented in this paper.

Effectiveness of information campaigns.

Skin cancer represents the most common type of cancer in the white population worldwide and the incidence has dramatically increased during the last decades. UV-radiation is believed to be the most important risk factor responsible for this trend. The prominent role of UV-radiation renders skin cancer most suitable for primary prevention, because the main risk factor can easily be avoided by sticking to simple rules for the behaviour in the sun or under artificial UV (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally especially due to the beneficial health effects of UV-irradiation like Vitamin D(3)-production, recommendations and information for the public should be as clear and as weighted as possible, through adequate messages, such as: "Love the sun and protect your skin". For that purpose the Association of Dermatological Prevention in Germany (ADP) developed the period of life programme (POLP) that defines certain age-specific target groups, with the aim to give well adapted prevention messages to the population during lifetime. Evaluation of primary prevention campaigns in Germany showed that due to continuous intervention programs during the last 16 years changes in the "sun-behaviour" of the population have been achieved leading to a reduced but sufficient exposure to solar UV-irradiation. This will then contribute to the aim of decreasing morbidity and mortality of skin cancer.

[Ureteral stricture after extracorporeal shock wave lithotripsy. Case report and overview of the spectrum of rare side effects of modern ESWL treatment]. / Ureterstriktur nach extrakorporaler Stosswellenlithotripsie. Kasuistik und Ubersicht über das Spektrum seltener Nebenwirkungen der modernen ESWL-Therapie.

Extracorporeal shock wave lithotripsy (ESWL) is considered a very safe and noninvasive procedure for the treatment of urolithiasis. Achievements in the technical development of recent decades resulted in a continuous reduction of side effects. One of our patients, a woman with cystinuria, developed a temporary ureteral stricture after several sessions of ESWL. Encouraged by this observation we set out to explore--based on a MEDLINE literature search--published reports of more severe side effects observed in modern ESWL therapy. Besides hydronephrosis and renal colic the most common side effects were renal and perirenal hematomas in up to 4% in the larger series. Uncommon extrarenal complications are described mostly in case reports, which are also outlined in this report. The injury of visceral organs (liver, spleen, gut, pancreas) was published most frequently. A rupture or dissection of an abdominal aortic aneurysm as an outstanding serious complication was also reported several times. Taking obvious and well-known contraindications into consideration and carefully preparing the patients for the therapy (i.e., checking hemostasis, drug history), ESWL is a very safe procedure with a low risk of serious complications. Yet, postoperative clinical and ultrasound monitoring seems to be essential especially with respect to the increasing numbers of outpatient procedures.

[Management of erectile dysfunction after radical prostatectomy. Urologists' assessment vs patient survey responses]. / Versorgung der erektilen Dysfunktion nach radikaler Prostatektomie in Deutschland. Einschätzung durch den Urologen vs. Patientenbefragung.

INTRODUCTION: The aim of this national study was to evaluate ED management after RPX (without any postoperative adjuvant therapy or tumor relapse) from the patient's view compared to the urologist's view. MATERIAL AND METHODS: In May 2003 we queried 1063 urologists and 801 patients following radical prostatectomy without adjuvant therapy. They were asked about preserved potency without erectile aid, existing wish for ED therapy, recommended or tested erectile aid (oral, transurethral, intracorporal, vacuum constriction device[VCD], penile implant) as well as the long-term use. Return rate: patients 80.1%, urologists 26.7%. RESULTS: According to the urologists' view 9.1% of their affected patients were potent postoperatively without a device, but according to the polled patients only 4.7%. The wish to be treated for erectile dysfunction existed in the urologists' opinion in 46.1% of their patients, while they considered that 44.8% had no wish for treatment. On the other hand, 59.3% of the patients would like to be treated and only 28.5% did not want any kind of treatment. Regarding the long-term use of therapy for ED, the urologists thought that 26.1% of their patients did not receive therapy for the problem, and 69.7% of the patients stated they received no long-term therapy. Only 30.3% of the patients confirmed long-term therapy, while the urologists thought that 73.9% of the patients used an erectile aid. Definite therapy in the urologists' opinion involved: oral medication in 38.4%, MUSE in 3.6%, (SKAT) in 37.3%, VCD in 20.4%, and a prosthesis in 0.3%. Indeed 19.8% of the patients used oral medication, 1.7% MUSE, 26.7% SKAT, 50.9% VCD, and 0.9% penile implant. Considering the satisfaction of patients, urologists thought that 46.2% of the patients were satisfied with their treatment of ED, but only 28.9% of the patients were actually satisfied themselves. CONCLUSIONS: The comparison of patients' and urologists' views shows a clearly different description of the ED situation after RPX. The proportion of patients with a wish for treatment and the proportion of dissatisfied patients are much higher from the patients' view. This demonstrates an undertreatment of ED patients after RPX, which should also be taken into account under the current changes in the German health care system.

[Structured quality report of urologic clinics according to section 137 SGB V. Useful information for the patient, marketing tool of the hospitals, leverage wielded by the health insurance companies, or junk data?]. / Strukturierte Qualitätsberichte urologischer Hauptabteilungen gemäss 137 SGB V. Entscheidungshilfe für den Patienten, Marketing-Instrument der Kliniken, Druckmittel der Krankenkassen oder Datenmüll?

In 2005, German hospitals were legally obliged to publish a structured quality report on their data of 2004 including the top 10 diagnosis-related groups, top 10 diagnoses, and top 10 procedures for every specialty. The aim was to increase the transparency for patients, doctors, and health insurance companies. Comparing the quality reports of 248 departments of urology revealed very uniform distributions of diagnoses and diagnosis-related groups. There was a large variety of top 10 procedures, resulting from different interpretations of the coding system, leading to diminished accuracy. The quality reports provide coding specialists with important data, but for patients and nonspecialized doctors, this system is not helpful in improving transparency.