Fluorescence-guided laser lithotripsy: Estimation of the potential effectiveness and safety increase based on first clinical data.

In clinically approved laser lithotripsy systems, there is no automatic monitoring of fiber position to date. We investigated whether detecting stone autofluorescence, excited by a green aiming beam, is possible via the fiber during fragmentation by continuously recording the fluorescence signal in 12 ureterosopic lithotripsy procedures. We estimated which threshold the fluorescence signal's amplitude exceeds before laser pulses with visible stone removal by retrospective inspection of the endoscope's video data. For all procedures, blocking the laser when the fluorescence amplitude is below a threshold corresponding to the signal's baseline plus its range (maximum-minimum value) would have been appropriate to suppress ineffective pulses-the energy input could have been reduced by a mean of 14% (1%-29%) without changing the operation time. Ablation of the PTFE coating of the guidewire could have been prevented three times and cutting of a wire of the retrieval basket two times.

[Immuno-oncological therapeutic options in high-risk non-muscle invasive bladder cancer]. / Immunonkologische Therapieoptionen des nicht-muskelinvasiven Urothelkarzinoms.

High-risk nonmuscle invasive bladder cancer (HR NMIBC) is an immunological malignancy. The standard therapy for HR NMIBC is based on transurethral bladder tumor resection with adjuvant Bacillus Calmette Guérin (BCG) instillation therapy. To prevent progression in case of BCG-refractory disease, early radical cystectomy is considered the therapy of choice according to the German S3 guidelines. With the advent of checkpoint inhibitors for the treatment of metastatic urological malignancies, a novel option for bladder preservation has been introduced for the treatment of HR NMIBC. The currently available data do not allow a meaningful conclusion on the long-term efficacy of PD-(L)1 (programmed cell death [ligand] 1) inhibitors due to the relatively short duration of oncological follow-up. Yet, it can be expected that checkpoint inhibitors will change the treatment algorithm of HR NMIBC in the next few years. Promising studies have been initiated to test the combination of local and systemic immunomodulation in terms of response and toxicity.

[Reports of prostate needle biopsies-what pathologists provide and urologists want]. / Befundbericht zu Prostatastanzbiopsien ­ was Pathologen liefern und Urologen wollen.

BACKGROUND: The prostate biopsy report is key for risk stratification of prostate cancer patients and subsequent therapeutic decision-making. However, due to the inclusion of a multitude of additional parameters its interpretation is becoming more challenging. OBJECTIVES: We aimed to determine how urologists currently interpret prostate biopsy reports, in particular how they consider different histopathological parameters for therapy decision-making. MATERIALS AND METHODS: A survey was sent to all urology practices in Germany with the help of the BDU (Berufsverband der Deutschen Urologen e. V.). In total, there were 106 complete responses that could be included for further analyses. RESULTS: Most urologists consider the number of positive cores and relative tumor burden (%) per core as crucial for the assessment of tumor extension. In case of targeted biopsies, the majority of urologists prefers a separate statement of positive cores per random biopsy scheme and per region of interest, respectively. The core with the highest Gleason score is mostly the basis for therapy decision-making (versus the overall Gleason score). Proportion of Gleason 4 pattern also seems to be critical for prostate cancer management. Only half of the urologists demand reporting of the new ISUP/WHO (International Society of Urological Pathology/World Health Organization) grade groups. Additional parameters claimed are Ki67, prostate-specific membrane antigen status, presence of intraductal or neuroendocrine component of the tumor. CONCLUSIONS: Our survey shows that there is no standardized reporting for prostate biopsies and that the interpretation of prostate biopsy reports varies among urologists. Further studies and guideline recommendations are necessary to establish a standardized reporting scheme for prostate biopsies.

[Rate of thrombosis and bleeding after urological surgery under standardized anticoagulation]. / Thromboserate und Blutungen in der universitären operativen Urologie unter standardisierter Antikoagulation.

BACKGROUND: According to the current definition of the German guideline for prevention of venous thromboembolism, urological surgery includes a high number of high-risk patients. All patients undergoing urological surgery between 2012 and 2016 were analyzed with regard to complications (bleeding or thrombosis). MATERIALS AND METHODS: This study is a retrospective and monocentric cohort study. Included were all patients who underwent surgery between 2012 and 2016 at the Urological Department at the University Hospital of Luebeck. Information was collected relating to anticoagulation, patient-specific and surgery-specific risk factors, and complications. RESULTS: In all, 3609 surgeries were analyzed: 77.8% of patients received no medical prophylaxis, 10.2% received an aggregation inhibitor, and 8.5% synthetic, unfractionated or low molecular weight heparin. Heparin was administered to 80.4% of patients after surgery. During an average hospital stay of 4.5 days, 93.3% of the patients received no change in anticoagulation. Merely 0.8% of all patients suffered from clinical thomboembolic events within 28 days. In contrast the number of bleedings was higher with 20.3% (minor: 4.8%, major: 15.5%). CONCLUSION: We found a slight risk for postoperative thromboembolism (0.8%). The risk for postoperative bleeding in contrast was 20.3%, including 15.5% major bleedings. The results are discussed in relation to the current guidelines.

[En bloc resection and vaporization techniques for the treatment of bladder cancer]. / En-bloc-Resektion und Vaporisation von Harnblasenkarzinomen.

BACKGROUND: Modifications in resection techniques may overcome obvious limitations of conventionally performed transurethral resection (e. g., tumor fragmentation) of bladder tumors or provide an easier patient treatment algorithm (e. g., tumor vaporization). OBJECTIVES: The present review article summarizes the current literature in terms of en bloc resection techniques, histopathological quality, complication rates, and oncological outcomes. MATERIALS AND METHODS: A separate data search was performed for en bloc resection (ERBT, n = 27) and vaporization (n = 15) of bladder tumors. RESULTS: In most cases, ERBT is performed in a circumferential fashion. Alternatively, ERBT may be performed by undermining the tumor base via antegrade application of short energy impulses. Based on high rates of detrusor in specimens of ERBT (90-100%), a better histopathological quality is assumed. Significant differences in perioperative complication rates have not been observed, although obturator-nerve-based bladder perforations are not seen when laser energy is used. There is a nonstatistically significant trend towards lower recurrence rates in ERBT groups. Tumor vaporization may provide a less invasive technique for older patients with recurrences of low-risk bladder cancer. It can be performed in an outpatient setting. CONCLUSIONS: ERBT may provide better histopathological quality. Tumor vaporization is performed in health care systems where reimbursement is adequate.

Substantial utilization of Facebook, Twitter, YouTube, and Instagram in the prostate cancer community.

PURPOSE: To measure the usage rate of social media (SoMe) resources in the prostate cancer community, we performed a comprehensive quantitative and qualitative assessment of SoMe activity on the topic of PCa on the four most frequented platforms. METHODS: We scanned the SoMe platforms Facebook, Twitter, YouTube, and Instagram for "prostate cancer" as a cross-sectional analysis or during a defined time period. Sources were included if their communication centered on PCa by title and content. We assessed activity measurements for each SoMe source and classified the sources into six functional categories. RESULTS: We identified 99 PCa-related Facebook groups that amassed 31,262 members and 90 Facebook pages with 283,996 "likes". On YouTube, we found 536 PCa videos accounting for 43,966,634 views, 52,655 likes, 8597 dislikes, and 12,393 comments. During a 1-year time period, 32,537 users generated 110,971 tweets on #ProstateCancer on Twitter, providing over 544 million impressions. During a 1-month time period, 638 contributors posted 1081 posts on Instagram, generating over 22,000 likes and 4,748,159 impressions. Among six functional categories, general information/support dominated the SoMe landscape on all SoMe platforms. CONCLUSION: SoMe activity on the topic of PCa on the four most frequented platforms is high. Facebook groups, YouTube videos, and Twitter tweets are mainly used for giving general information on PCa and education. High SoMe utilization in the PCa community underlines its future role for communication of PCa.

[En-bloc resection of bladder tumours (ERBT): current and future perspectives]. / Die En bloc-Resektion von Blasentumoren (ERBT) ­ eine Bestandsaufnahme.

Limitations inherent in the conventional transurethral resection of bladder tumours, the standard approach for diagnosis and treatment of bladder cancer, are well known: staging errors due to insufficient resection depth as well as intravesical tumour fragmentation, both of which make histopathological evaluation difficult. The purpose of this review is to present recent clinical data on the en-bloc resection of bladder tumours (ERBT), which has been demonstrated to offer a high potential to overcome these limitations. The recent findings show that ERBT provides a good resection quality with varying detection rates for tunica muscularis, which is a surrogate marker for resection quality regarding muscle-invasive tumours. ERBT can be performed using all energy sources. Available data show no relevant difference with regard to perioperative morbidity compared with cTURB. No conclusions can be drawn regarding the impact of ERBT on recurrence as the data are partly controversial. This has to be defined by further studies.

[Should cytoreductive nephrectomy be performed in patients with metastatic renal cell carcinoma and what is the scientific rationale?] / Wann ist bei eingetretener Metastasierung des Nierenkarzinoms die operative Entfernung des Primärtumors angezeigt und gibt es eine wissenschaftliche Grundlage dafür?

Between 15 and 20% of patients diagnosed with renal cell carcinoma suffer from metastatic disease by the time of diagnosis. In the immunotherapy era, the standard treatment was to perform cytoreductive nephrectomy (CN) followed by treatment with interferon α. This was based on two prospective randomized trials and their combined analysis. Since the introduction of targeted therapy, the use of CN came into question and the number of performed CN has declined. Two trials (CARMENA and SURTIME) evaluating the role of CN in the times of targeted therapy have either closed early or are recruiting slowly and will probably not be able to answer this question. Thus, we need to focus on retrospective data consisting of several analyses with large numbers of patients. These analyses all seem to show a benefit in overall survival, and adjusted for prognostic factors CN represents an independent predictor of longer survival. A correlation between expected life span and efficacy of CN has been shown with a survival rate that is three times higher after 3 years. Only patients with low performance status, low life expectancy, cerebral metastases, and old age did not benefit from CN. Furthermore, symptom control of large primary tumors without response to systemic therapy and the fact that all reports of long-term remission or long survival rates are associated with the use of CN are theoretical aspects speaking in favor of this treatment. This leads to the recommendation to perform CN in all patients with good performance status in all important guidelines.

[Communication preferences of patients with prostate cancer : Preferences regarding the communication of bad news of patients with prostate cancer in Germany-results of an anonymous patient survey]. / Kommunikationspräferenzen von Patienten mit Prostatakrebs : Ergebnisse einer anonymen Patientenbefragung unter Patienten mit Prostatakrebs zu ihren Kommunikationspräferenzen.

BACKGROUND: The communication of bad medical news represents a burdening situation for both patients and physicians which may lead to hurdles in their communication. The questionnaire Measure of Patients' Preferences (MPP-D, validated German translation) was developed to investigate patients' preferences regarding the communication of bad news. OBJECTIVES: The preferences regarding the communication of bad news among patients with prostate cancer was assessed. MATERIALS AND METHODS: Anonymous survey, where approximately 70 office-based urologists were asked to distribute the MPP-D questionnaire to about 20 of their patients with prostate cancer. In addition, information on social demographics was retrieved in order to investigate the influence on communication preferences. RESULTS: In total, 709 questionnaires were evaluated (>50 % return). The majority of patients had clear preferences concerning privacy of the setting, completeness, and unambiguity of information provided and assessment of their subjective information needs. Larger individual differences were observed regarding preferences for emotional support offered by the physician and involvement of family which was also influenced by age and education of the patients. CONCLUSION: This is the first large, multicenter survey of prostate cancer patients in Germany regarding their preferences for communication of bad news. The results confirm previous reports on the importance of cultural affiliation, age, and education as influencing factors.

[Implications of TCGA Network Data on 2nd Generation Immunotherapy Concepts Based on PD-L1 and PD-1 Target Structures]. / Implikationen der TCGA Netzwerkdaten für Zweit-Generations-Immuntherapiekonzepte auf Basis der PD-L1 und PD-1 Zielstrukturen.

The era of cytokines, given to patients with metastatic renal cell carcinoma (mRCC) as part of an unspecific immunomodulatory treatment concept, seems to have ended with the introduction of targeted therapies. However, preliminary data from studies on treatment with checkpoint inhibitors (e. g. anti-PD-1 and anti-PD-L1) may point the way to second-generation immunotherapy. The rationale of such immunomodulatory treatment is to stop or interrupt the tumour from "escaping" the body's immune defence. Thompson et al. report that increased protein expression of PD-L1 (CD274/ B7-H1) in tumour cells and tumour-infiltrating immune cells (TILs; lymphocytes and histiocytes) is associated with unfavourable clinical pathological parameters as well as poor survival. In small pilot groups of mRCC patients it was found that increased PD-L1 protein expression in tumours and TILs may be correlated with the objective response to anti-PD-1 treatment. Sometimes, however, a very wide variety of response rates was observed, which raises the question if this can be explained by individual expression levels of PD-L1 (CD 274) or PD-1 (PDCD1).Recently published data from the Cancer Genome Atlas (TCGA) Kidney Renal Clear Cell Carcinoma (KIRC) Network now provide a genome-wide data base that allows us to review or validate the molecular results obtained in clear cell renal cell carcinomas (ccRCC) to date.In this study, we analysed the TCGA KIRC mRNA expression data for PD-L1 and PD-1 for a possible association with clinical pathological parameters and the survival of 417 ccRCC patients.The mRNA expression of PD-L1 in primary nephrectomy specimens revealed no significant association with unfavourable clinical parameters. Interestingly, though, a positive correlation with patient survival was found (HR=0,59, p=0,006).These results, which partly contradict the concept applied to date, point out the necessity to ascertain the characteristics of PD-L1 and PD-1 expression at mRNA and protein level in an appropriately sized patient population and evaluate the clinical significance.

[Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?]. / Neo- oder adjuvante Chemotherapie beim Harnblasenkarzinom?

Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

Role of immunohistochemistry and fluorescence in-situ hybridization (FISH) in the diagnosis of spindle and round cell tumors of the kidney.

UNLABELLED: Spindle cell/mesenchymal tumors of the kidney are rare. The diagnosis is supported mainly by the application of ancillary techniques such as immunohistochemistry (IH) and in-situ hybridization (FISH). An accurate diagnosis is essential because early management by complete resection and adjuvant chemotherapy improves the prognosis dramatically. Synovial sarcoma and primitive neuroectodermal tumor/Ewing sarcoma are infrequent malignancies which usually present in soft tissues but rarely in the kidney. The challenge for the pathologists is to histologically differentiate between different types of sarcomas such as PNET/Ewing's sarcoma, sarcomatous dedifferentiated renal cell carcinoma, metastasis, non-Hodgkin's lymphoma, nephroblastoma and angiomyolipoma. METHODS: We report from our experience six exemplary rare cases that presented in the kidney as spindle/round cell tumors. RESULTS: We have arrived at the accurate diagnosis after performing a large panel of IH and FISH. CONCLUSION: In summary we advise an immunohistochemical panel for round/spindle cell tumors of the kidney and for unclear cases we advise to add (FISH) to get the correct diagnosis, as they are completely different regarding surgical approach and post-operative adjuvant therapy.

[C-reactive protein prior to radical cystectomy: preoperative determination of CRP]. / C-reaktives Protein vor radikaler Zystektomie : Präoperative Bestimmung von CRP.

BACKGROUND: Numerous studies have shown a positive correlation between elevated C-reactive protein (CRP) and systemic spread of malignancies. The goal of the current study was to assess the predictive significance of preoperative CRP in patients undergoing radical cystectomy (RC). MATERIAL AND METHODS: Preoperative CRP values were measured in 194 patients undergoing RC because of urothelial carcinoma between 1996 and 2005. Elevated CRP level was defined as ≥ 5 mg/l. RESULTS: Preoperative increased CRP values were detected in 89 (45.9%) patients and these patients were more likely to have advanced tumor stages (pT3-4), positive resection margins and positive lymph nodes. Advanced urinary diversions were more common in patients with normal CRP values. In multivariate analysis, CRP was identified as an independent prognostic indicator for poor cancer-specific survival. CONCLUSION: The results confirm previous reports that showed a prognostic significance of preoperative CRP elevation.

[Systemic therapy of metastatic bladder cancer.] / Systemische Therapie des metastasierten Blasenkarzinoms.

This review focuses on current options in the medical therapy of metastasized urothelial carcinoma of the bladder. Standard treatments as well as new, recently published therapeutic approaches are evaluated and discussed.

[Systemic therapy for metastatic renal cell carcinoma]. / Systemische Therapie des metastasierten Nierenzellkarzinoms.

A better understanding of molecular biological mechanisms involved in the pathogenesis or, respectively, prognosis of renal cell carcinoma has recently led to a fundamental change in those therapeutic options that are especially effective after systemic disemination. In this context, cytokine-based therapeutic concepts have been replaced by the so-called targeted therapeutic agents that include, above all, tyrosine kinase (TK) and mTOR inhibitors. The present contribution is intended to reflect the current state of the art in the systemic therapy for renal cell carcinoma in first- and second-line use. In addition, the increasing relevance of sequential therapy under consideration of possible side effects is discussed.

[Transurethral en bloc resection of non-muscle invasive bladder cancer. What is the state of the art?]. / Transurethrale En-bloc-Resektion nicht muskelinvasiver Harnblasenkarzinome. Wo stehen wir heute?

Bladder cancer of the urothelium is the second most common malignancy among urological tumors. In view of a worldwide aging population and the fact that increased incidence rates are associated with higher age, new socioeconomic challenges will appear. Even nowadays the treatment of bladder cancer bears the highest lifetime treatment costs per patient among all forms of cancer. In conjunction with higher comorbidity rates among older patients urologists are facing new challenges in the treatment and care of patients with bladder cancer. The standard treatment for non-muscle invasive bladder cancer (NMIBC) is monopolar transurethral resection using resection loops (TURB). Based on experience in the surgical treatment of benign prostatic hyperplasia, different concepts of en bloc resection of bladder tumors using alternative energy resources (e.g. holmium laser, thulium laser and the water-jet HybridKnife) have been developed. Goals of new treatment modalities are reduction of perioperative and postoperative comorbidities, better pathological work-up of the specimens and increased recurrence-free survival. Postulated advantages using laser devices are a more precise cutting line as well as better hemostasis. The evidential value of this review is limited due to the lack of randomized, prospective studies. However, there is a tendency towards a limitation of perioperative and postoperative morbidities as well as higher chance of well-preserved tissues for better pathohistological evaluation using en bloc resection methods. More studies with long-term follow-up periods and better randomization are needed to clarify whether en bloc strategies provide better long-term oncological survival.

[Systemic and surgical management of metastatic renal cell carcinoma]. / Systemische und operative Therapie des metastasierten Nierenzellkarzinoms.

Several targeted therapies have become available for first-line (sunitinib, bevacizumab, pazopanib, temsirolimus) and second-line (sorafenib, pazopanib, everolimus) use in recent years. The superior outcomes achieved with these targeted agents have led to replacement of the formerly administered cytokines. New developments have raised the question of whether patients benefit from sequential therapies with tyrosine kinase inhibitors and/or whether combination regimes can improve clinical outcomes. This review gives an overview of the current therapeutic options for first- and second-line treatment in metastatic RCC as well as sequential and combination therapies. Adjuvant and neoadjuvant treatment options are being discussed. Furthermore, this review addresses surgical alternatives in the treatment of RCC.