[The cancer registry notification seen from the perspective of the German Society of Uro-Oncologists (d-uo)]. / Die Krebsregistermeldung aus der Sicht der Deutschen Uro-Onkologen (d-uo).

The current cancer registry notification, which was introduced in Germany as a mandatory institution in 2015, has its starting point in the National Cancer Plan of 2008. Other milestones include the Federal Cancer Registry Data Act (2009), the Cancer Early Detection and Registry Act (2013), the Uniform Oncological Basic Data Set (2014/2021) with its modules (e.g. the module prostate carcinoma 2017) as well as the Cancer Registry Data Merger Act (2021). At the beginning of 2017, the German Society of Uro-Oncologists (d-uo) had the idea of designing a documentation platform that would enable d-uo members to report to the cancer registry and transfer data to d-uo's own database - without a double effort. The cancer registry reimburses the first notification of a tumour with € 18. As the only provider, d-uo reimburses its members for the documentation effort associated with the additional notification to d-uo with a further € 18. In addition to the basic oncological data set, further parameters were defined by d-uo. This data is collected, evaluated and interpreted as part of the VERSUS study. The realisation that the parameters of the basic data set are limited in their informative value led d-uo to establish the two national registries for urothelial carcinoma (UroNAT) and prostate carcinoma (ProNAT). This underscores d-uo's leading position in uro-oncological healthcare research in Germany.

[Real-world data on prostate cancer: the VERSUS trial by d-uo]. / Ergebnisse aus der VERSUS-Studie von d-uo am Beispiel des Prostatakarzinoms.

At the beginning of 2017, the German Society of Uro-Oncologists (d-uo) had the idea of designing a documentation platform that would enable d-uo members to report cancer cases to the cancer registry and transfer data to d-uo's own database - without a double effort. The cancer registry reimburses the first notification of a tumour with €18. As the only provider, d-uo reimburses its members for the documentation effort associated with the additional notification to d-uo with a further €18. In addition to the basic oncological data set, further parameters were defined by d-uo. This data is collected, evaluated and interpreted as part of the VERSUS study. At the end of 2022, 14,834 patients with a newly diagnosed urological tumour were included in the VERSUS study. Almost two thirds of all patients had prostate cancer. About half of all patients with prostate cancer were diagnosed as part of an early detection measure. These patients then also had more favourable tumour stages. Overall, almost every eighth patient already had metastases at the time of initial diagnosis. Data from the VERSUS study are available for 2,167 operations on prostate cancer with tumour category T2 or T3. There were 1,360 operations in patients with a T2 tumour (62.8%) and 807 operations in patients with T3 tumours (37.2%). A positive margin was present in 25.5% of all operated-on patients. In relation to tumour categories T2 and T3, the proportion of a positive resection margin was 14.3% and 44.2%, respectively. The VERSUS study will continue to provide answers to many questions from the uro-oncological field with reference to the "real world" situation in Germany.

[National Registries for Urothelial Cancer (UroNAT) and Prostate Cancer (ProNAT) by d-uo]. / Nationale Register Urothelkarzinom (UroNAT) und Prostatakarzinom (ProNAT) von d-uo.

The German Society of Uro-Oncologists ("Deutsche Uro-Onkologen e.V.", d-uo) provides a national registry for urothelial cancer (UroNat) and a national registry for prostate cancer (ProNAT). These registries aim to evaluate the standard of care for urothelial cancer of the bladder and the upper urinary tract as well as prostate cancer by office-based urologists, oncologists and outpatient hospital departments in Germany. This includes, but is not limited to, adherence to guidelines during the treatment of patients with urothelial cancer and prostate cancer. The registries aim to capture and analyse scientifically how patients with these two most frequent urological tumours are treated and how quality assurance is implemented to improve the quality of their outpatient treatment in Germany. Both registries may share basic patient data supplied by the non-interventional, prospective, multicentre VERSUS registry by d-uo, which has been ongoing since 2018 and today includes more than 15,000 patients with different urological malignancies. In the UroNAT and ProNAT registries, additional items and parameters are included to allow for more detailed analyses of outcomes of outpatient treatments in Germany, which have so far been unavailable from the German Cancer Registry. By documenting the current treatment landscape of urothelial and prostate cancer in the outpatient setting, the registries intend to identify potential improvements of patient care and to initiate their implementation into clinical practice. These non-interventional prospective registries only document daily routine diagnostics, clinical courses and procedures.

[Osteoprotection in patients with non-metastatic hormone-sensitive prostate cancer (mHSPC) receiving androgen-deprivation therapy (ADT): Real-world data from Germany, presented by d-uo]. / Osteoprotektion beim nichtmetastasierten hormonsensitiven Prostatakarzinom (nmHSPC) unter androgendeprivativer Therapie (ADT): Aktuelle Daten aus Deutschland, vorgelegt von d-uo.

INTRODUCTION: Patients with prostate cancer often present with reduced bone mineral density. We herein present real-world data (RWD) regarding osteoprotection in patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) receiving androgen deprivation therapy (ADT) treated by German urologists in private practice. MATERIAL AND METHODS: This is a questionnaire-based study including members of d-uo ("Deutsche Uro-Onkologen", German uro-oncologists). Patients with nmHSPC between July 2019 and June 2020 were included. They were asked about start, type and duration of osteoprotection as well as supplementation with calcium and vitamin D. RESULTS: Between July 2019 and June 2020, a total of 3,692 patients with prostate cancer were seen at least once in one of the private practices of 15 urologists (all d-uo members). There were 844 patients (22.9%) with nmHSPC treated with ADT. Osteoprotection using denosumab or a bisphosphonate to prevent skeletal-related events (SRE) was applied in 183/844 patients (21.7%) with nmHSPC. In patients receiving osteoprotection, denosumab was chosen in 73.2% of patients and a bisphosphonate was chosen in 26.8% of patients. Supplementation with calcium and vitamin D was given in 84.7% of patients. CONCLUSION: Patients with nmHSPC received osteoprotection in 1/5 of patients. Of these, 3/4 received denosumab and 1/4 received a bisphosphonate. The majority of patients were additionally treated with calcium and vitamin D. In our study, osteoprotection in patients with nmHSPC was rather an exception.

[Osteoprotection in patients with bone metastatic castration-resistant prostate cancer (mCRPC): real-world data from Germany, presented by d-uo]. / Osteoprotektion beim ossär metastasierten kastrationsresistenten Prostatakarzinom (mCRPC): Aktuelle Daten aus Deutschland, vorgelegt von d-uo.

INTRODUCTION: Patients with bone metastasis due to prostate cancer often present allover reduced bone mineral density. Additionally, patients with bone metastatic castration-resistant prostate cancer (mCRPC) have a relevant risk for skeletal-related events (SRE). We herein present real-world data (RWD) regarding osteoprotection in mCRPC patients with bone metastasis treated by German urologists in private practice. MATERIAL AND METHODS: This is a questionnaire-based study including members of d-uo ("Deutsche Uro-Onkologen", German uro-oncologists). All patients with histologically confirmed prostate cancer seen at least once in the surveyed urology practice between July 2019 and June 2020 were included. Questions included start, type and duration of osteoprotection as well as supplementation with calcium and vitamin D. RESULTS: Between July 2019 and June 2020, a total of 3,692 patients with prostate cancer were seen at least once in 15 urology practices. There were 410 mCRPC patients (11.1%) with bone metastasis. Osteoprotection with denosumab or a bisphosphonate to prevent SRE was applied in 274/410 mCRPC patients (66.4%) with bone metastasis. In patients receiving osteoprotection, denosumab was chosen for 67.9% of patients and a bisphosphonate was chosen for 32.1%. Supplementation with calcium and vitamin D was performed in 93.4% of the patients. The median duration of treatment was 25.3 months for denosumab compared with 39.6 months for bisphosphonates. CONCLUSIONS: Patients with mCRPC with bone metastasis received osteoprotection in 2/3 of cases. Of these, 2/3 received denosumab and 1/3 received a bisphosphonate. The majority of patients were also treated with calcium and vitamin D. According to guideline recommendations regarding osteoprotection in mCRPC patients with bone metastasis, our RWD data showed some lack of guideline adherence.

[Retrospective practice-related care research study on therapy of mCPRC with radium-223 dichloride]. / Retrospektive Versorgungsstudie von d-uo zur Therapie des mCRPC mit Radium-223-dichlorid.

During phase III study ERA-223, patients under combination therapy with radium-223 and abiraterone showed an increased risk of bone fractures and a possible higher risk of death. This observation led to a change in the German therapeutic guidelines in 2018. Radium-223 is now only allowed as a third-line monotherapy (besides ADT) in patients with metastatic castration resistant prostate cancer (mCRPC) with symptomatic bone lesions without known visceral metastases or for patients with mCRPC, for whom no other available systematic therapy is suitable. Since almost no data on practice-related care research on the use of radium-223 exist, we consulted members of d-uo (German Uro-Oncologists) over their therapy algorithms. This study analysed data of patients treated with radium-223 between 2014 and 2019. It could be shown that 50% of mCRPC-patients had received radium-223 in the past as third-line therapy. Half of these were treated in combination with new androgen receptor targeted therapies (ARTA) and no increase in bone fractures was observed. This was most likely due to the additional use of bone protecting agents. Despite the late cancer stage, treatment response was seen in almost half of the patients.

Phototoxic versus photoprotective effects of tattoo pigments in reconstructed human skin models: In vitro phototoxicity testing of tattoo pigments: 3D versus 2D.

The increasing number of tattooed persons urges the development of reliable test systems to assess tattoo associated risks. The alarming prevalence of 60 % phototoxic reactions in tattoos ask for a more comprehensive investigation of phototoxic reactions in tattooed skin. Here, we aimed to compare the cellular responses of human skin cells to ultraviolet (UV)A and UVB irradiation in doses of short to intermitted sun exposure (3-48 J/cm² and 0.05-5 J/cm², respectively) in the presence of tattoo pigments. Therefore, we used fibroblast monolayer culture (2D), our recently developed three dimensional full-thickness skin model with dermal-located tattoo pigments (TatSFT) and its dermal equivalents (TatSDE) that lack keratinocytes. We tested the most frequently used tattoo pigments carbon black, titanium dioxide (TiO2) anatase and rutile as well as Pigment Orange (P.O.)13 in ranges from 0.067 to 2.7 ng/cell in 2D. For TatSDE and TatSFT, concentrations were 1.3 ng/cell for TiO2, 0.67 ng/cell for P.O.13 and 0.067 ng/cell for carbon black. We assessed cell viability and cytokine release in all systems, and cyclobutane pyrimidine dimer (CPD) formation in TatSFT. Phototoxicity of tattoo pigments was exclusively observed in 2D, where especially TiO2 anatase induced phototoxic effects in all concentrations (0.067-2.7 ng/cell). In contrast, fibroblasts were protected from UV irradiation in TatSDE by TiO2 and carbon black. Neither toxic nor protective effects were recorded in TatSFT. P.O.13 showed altered cytokine secretion in 2D (0.067-1.3 ng/cell) and TatSDE, despite the absence of significant effects on viability in all systems. All pigments reduced the number of CPDs in TatSFT compared to the pigment-free controls. In conclusion, our study shows that within a 3D arrangement, intradermal tattoo pigments may act photoprotective despite intrinsic phototoxic properties in 2D. Thus, dermal 3D equivalents should be considered to evaluate acute tattoo pigment toxicology.

Detection of Androgen Receptor Variant 7 (ARV7) mRNA Levels in EpCAM-Enriched CTC Fractions for Monitoring Response to Androgen Targeting Therapies in Prostate Cancer.

Expression of the androgen receptor splice variant 7 (ARV7) in circulating tumor cells (CTCs) has been associated with resistance towards novel androgen receptor (AR)-targeting therapies. While a multitude of ARV7 detection approaches have been developed, the simultaneous enumeration of CTCs and assessment of ARV7 status and the integration of validated technologies for CTC enrichment/detection into their workflow render interpretation of the results more difficult and/or require shipment to centralized labs. Here, we describe the establishment and technical validation of a novel ARV7 detection method integrating the CellSearch® technology, the only FDA-cleared CTC-enrichment method for metastatic prostate cancer available so far. A highly sensitive and specific qPCR-based assay was developed, allowing detection of ARV7 and keratin 19 transcripts from as low as a single ARV7+/K19+ cell, even after 24 h of sample storage. Clinical feasibility was demonstrated on blood samples from 26 prostate cancer patients and assay sensitivity and specificity was corroborated. Our novel approach can now be included into prospective clinical trials aimed to assess the predictive values of CTC/ARV7 measurements in prostate cancer.

In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells.

BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms. METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wild-type (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients. RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts. CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.

[Thermochemotherapy with Mitomycin C: an update on alternative treatment strategies in non-muscleinvasive bladder cancer]. / Thermochemotherapie mit Mitomycin C: Update zur Therapiealternative beim nicht-muskelinvasiven Harnblasenkarzinom.

Bladder cancer is the second most common urological malignant disease. There are various treatment strategies which, depending on tumor stage and grade, can minimize recurrence and lower progression rate. Alternative treatment modalities of instillation therapy after failure with first line Mitomycin C or BCG do exist and have become a point of interest, especially in times of shortage of agents such as BCG.This article aims to give an overview of the current existing thermotherapeutic treatment options (electroinductive and electroconductive). The article starts with the first publication presenting thermochemotherapy with Mitomycin C using the Synergo ® device and highlights the first randomized controlled study comparing Mitomycin C (Synergo ® ) with conventional BCG therapy. The article also presents data about first conductive Mitomycin C therapy using the new Combat ® and the Unithermia ® device.Finally, it discusses in which cases thermotherapy with Mitomycin C can be applied safely based upon the current available data.

RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary and metastatic prostate cancer disease.

BACKGROUND: The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level. METHODS: Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples. RESULTS: The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue. CONCLUSION: We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.

A prospective study investigating the impact of multiparametric MRI in biopsy-naïve patients with clinically suspected prostate cancer: The PROKOMB study.

BACKGROUND: In patients with suspected prostate cancer (PCa) according to current guidelines systematic transrectal ultrasound (TRUS)-guided biopsy of the prostate is performed to verify or rule out PCa. However, TRUS-guided biopsy can result in underdetection of clinically significant cancers as well as diagnosis of clinically insignificant cancers. Multiparametric MRI (mpMRI) might improve the diagnostic pathway and help to avoid unnecessary biopsies. DESIGN AND METHODS: The PROKOMB (Prostata - Kooperatives MRT-Projekt Berlin) study is a prospective two-arm multicentre study designed to evaluate the potential role of mpMRI as a triage test before biopsy. Up to 600 biopsy-naïve men with suspicion for PCa undergo mpMRI at two dedicated imaging centers. Only patients with equivocal or suspicious lesions on mpMRI undergo prostate biopsy including systematic as well as MRI-guided targeted biopsies at several different community-based urologists or hospitals. The PROKOMB study is designed to evaluate how many biopsies can be avoided, how many clinically insignificant cancers are diagnosed on prostate biopsy in patients with positive findings on mpMRI, and how many clinically significant cancers are missed using this alternative diagnostic pathway. For the purpose of this study clinically significant PCa is defined as Gleason ≥3+4 cancer. In addition, the detection rates of different techniques for MRI-guided biopsy are evaluated as well as psychological distress before mpMRI and after the diagnosis of PCa. CONCLUSION: The PROKOMB study might help in defining the role of mpMRI in biopsy-naïve patients with suspected PCa in an ambulatory care setting.

Nephron sparing surgery for renal cell carcinoma up to 7 cm in the context of guideline development: a contribution of healthcare research.

INTRODUCTION: If technically feasible, organ-preservation is indicated for T1 renal cell carcinoma (RCC), since partial nephrectomy (PN) is equivalent to radical nephrectomy with regard to tumor-specific survival and probably achieves better overall survival. Treatment results of a training clinic were assessed with regard to guideline adherence and treatment quality. METHODS: Based on 220 open interventions in the time periods 2006-2009 (TP1) and 2010-2013 (TP2), a retrospective single center examination was performed to determine the influence of patient-age, sex, BMI, ASA-score, preoperative eGFR, PADUA-score and surgeon's experience on PN-rate and trifecta-outcome (R0 resection, warm ischemia time ≤25 min, no intraoperative complications and no blood-transfusion and postoperative complications grade ≤1 Clavien and Dindo). RESULTS: PN-rate increased from 36.1 % in TP1 to 72.4 % in TP2. Despite significantly higher PADUA-scores in TP2 than in TP1 (p = 0.0038), the trifecta-rate did not differ significantly (TP1 65.7 %; TP2 70.8 %; p = 0.666). Only the PADUA-score exerted an independent influence on the endpoints "organ-preservation" and "trifecta-outcome". CONCLUSIONS: This study again demonstrated that the PADUA-score is a robust predictor of technical feasibility and treatment outcome for open PN. Consistent implementation of guidelines for nephron sparing surgery in RCC ≤7 cm is possible even in the setting of a training clinic and need not be associated with compromised treatment quality despite the increasing level of difficulty. Depending on the author, there are various definitions of trifecta-outcome. A uniform trifecta-concept would be desirable.

Heterogeneous PSMA expression on circulating tumor cells: a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer.

The prostate specific membrane antigen (PSMA) is the only clinically validated marker for therapeutic decisions in prostate cancer (PC). Characterization of circulating tumor cells (CTCs) obtained from the peripheral blood of PC patients might provide an alternative to tissue biopsies called "liquid biopsy". The aim of this study was to develop a reliable assay for the determination of PSMA on CTCs. PSMA expression was analyzed on tissue samples (cohort one, n = 75) and CTCs from metastatic PC patients (cohort two, n = 29). Specific signals for the expression of PSMA could be seen for different prostate cancer cell line cells (PC3, LaPC4, 22Rv1, and LNCaP) by Western blot, immunohistochemistry (IHC), immunocytochemistry (ICC), and FACS. PSMA expression was found to be significantly increased in patients with higher Gleason grade (p = 0.0011) and metastases in lymph nodes (p = 0.0000085) or bone (p = 0.0020) (cohort one). In cohort two, CTCs were detectable in 20 out of 29 samples (69 %, range from 1 - 1000 cells). Twelve out of 20 CTC-positive patients showed PSMA-positive CTCs (67 %, score 1+ to 3+). We found intra-patient heterogeneity regarding the PSMA status between CTCs and the corresponding primary tumors. The results of our study could help to address the question whether treatment decisions based on CTC PSMA profiling will lead to a measurable benefit in clinical outcome for prostate cancer patients in the near future.

Degarelix therapy for prostate cancer in a real-world setting: experience from the German IQUO (Association for Uro-Oncological Quality Assurance) Firmagon® registry.

BACKGROUND: We investigated the use of the gonadotropin-releasing hormone (GnRH) antagonist degarelix in everyday clinical practice using registry data from uro-oncology practices in Germany. METHODS: Data were analysed retrospectively from the IQUO (Association for uro-oncological quality assurance) patient registry. Data were prospectively collected from all consecutive PCa patients treated with degarelix (n = 1010) in 138 uro-oncology practices in Germany between May 2009 and December 2013. RESULTS: Median overall survival had not yet been reached in the all-patient group or in subgroups who had or had not received prior hormonal therapy (HT). Cox regression analysis showed that patients who had received prior HT (n = 542) had a 58 % increased mortality risk (hazard ratio 1.58, 95 % CI 1.20-2.09) versus patients who had not (n = 468) (p = 0.001). Also, in patients who had received prior luteinizing hormone-releasing hormone (LHRH) analogue therapy (LHRH agonists or GnRH antagonists), median time to PSA progression was shorter (209 weeks) than in those who had not received prior LHRH analogues (n = 555; median PSA progression-free survival not yet reached). Degarelix was generally well tolerated. CONCLUSIONS: Degarelix was effective and well tolerated in everyday clinical practice, confirming observations from clinical studies. Patients who received prior HT appeared to have a significantly higher mortality risk.

Relation between human papillomavirus positivity and p16 expression in head and neck carcinomas--a tissue microarray study.

Overexpression of p16 has been demonstrated to be strongly related to the presence of HPV16, 18. Squamous cell carcinoma of the head and neck has been shown to be associated with human papillomavirus (HPV) infection. The main aim of this study was to investigate the relationship between HPV presence and p16 expression in a representative collection of 60 head and neck carcinomas by tissue microarrays. The presence of HPV (HPV6, 11-low risk, HPV16, 18-high risk) was detected by applying in situ hybridisation. P-16 protein expression was detected immunohistochemically. HPV6, 11 positivity was observed in 10 out of 60 carcinomas. HPV16, 18 presence was found in 30 out of 60 tumours. P-16 expression was detected in 35 out of 60 tumours. A statistically significant relationship was demonstrated between HPV16, 18 presence and increased expression of p16. Also the HPV6, 11 presence was significantly correlated with p16 immunoreactivity. Additionally, this study demonstrates that it is possible to analyse p16 expression and HPV presence by tissue microarrays.

Altered expression of DNA double-strand repair genes Ku70 and Ku80 in carcinomas of the oral cavity.

The relevance of double-strand DNA repair genes has been demonstrated in several tumours. The main aim of this study was to analyse the expression of the heterodimers Ku70 and Ku80, building regulatory subunits of the DNA-dependent protein kinase in 40 oral carcinomas. Ku70 expression was found in 87.5% of grade 1 and grade 3 tumours and in 82.9% of grade 2 carcinomas. Ku80 presence was noted in 87.5% of grade 1 tumours, 82.9% of grade 2 tumours and in all grade 3 tumours. Ku70-positive cells were present in 90.5% of tumours without and in 80% of tumours with lymphatic metastases. A similar relationship was found for Ku80 expression. Additionally, the expression of Ku70 was highly significantly related to smoking habits. Our results demonstrated that defects of DNA double-strand repair genes play an important role in the tumour progression of oral carcinomas.

Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study.

PURPOSE: We determined if improved tumor detection using hexaminolevulinate (HAL) fluorescence cystoscopy could lead to improved treatment in patients with bladder cancer. MATERIALS AND METHODS: A total of 146 patients with known or suspected bladder cancer were assessed in this open, comparative, within patient, controlled phase III study. Patients received intravesical HAL for 1 hour and were assessed with standard white light cystoscopy and blue light fluorescence cystoscopy. All lesions were mapped onto a bladder chart and biopsies were taken from suspicious areas for assessment by an independent pathologist. An independent urologist blinded to the detection method used recommended treatment plans based on biopsy results and medical history according to European Association of Urology bladder cancer guidelines. Any differences in recommended treatment plans arising from the 2 cystoscopy methods were recorded. RESULTS: HAL imaging improved overall tumor detection. Of all tumors 96% were detected with HAL imaging compared with 77% using standard cystoscopy. This difference was particularly noticeable for dysplasia (93% vs 48%), carcinoma in situ (95% vs 68%) and superficial papillary tumors (96% vs 85%). As a result of improved detection, additional postoperative procedures were recommended in 15 patients (10%) and more extensive treatment was done intraoperatively in a further 10. Overall 17% of patients received more appropriate treatment at the time of the study following blue light fluorescence cystoscopy, that is 22% or 1 of 5 if patients without tumors were excluded. CONCLUSIONS: HAL imaging is more effective than standard white light cystoscopy for detecting bladder tumors and lesions. This leads to improved treatment in a significant number of patients (p <0.0001).

[Improvement of tardive dyskinesia after treatment with olanzapine]. / Besserung tardiver Dyskinesien unter Therapie mit Olanzapin.

Tardive dyskinesia is a severe complication of neuroleptic treatment. It may develop weeks, even years after starting a neuroleptic treatment and the symptoms may be irreversible. Neuroleptic compounds are not only used in cases of schizophrenia, but also in cases of severe depression with delusional symptoms. We want to present the case of a 67 year old female patient who developed haloperidol induced dyskinesea and stress unto the successful treatment of this complication with olanzapine in combination with paroxetine. Under this regime not only the improvement of the depression, but also of the tardive dyskinesea was impressive.