Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

Bladder cancer-derived interleukin-1 converts the vascular endothelium into a pro-inflammatory and pro-coagulatory surface.

BACKGROUND: Bladder cancer cells orchestrate tumour progression by pro-inflammatory cytokines. Cytokines modulate the local tumour microenvironment and increase the susceptibility of tumour distant tissues for metastasis. Here, we investigated the impact of human bladder cancer cell derived factors on the ability to modulate and activate human vascular endothelial cells. METHODS: The pro-inflammatory and pro-coagulatory potential of four different bladder cancer cell lines was accessed by qRT-PCR arrays and ELISA. Modulation and activation of endothelial cells was studied in microfluidic devices. Clinical relevance of our findings was confirmed by immune histology in tissue samples of bladder cancer patients and public transcriptome data. RESULTS: The unbalanced ratio between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1ra) in the secretome of bladder cancer cells converted the quiescent vascular endothelium into a pro-adhesive, pro-inflammatory, and pro-coagulatory surface. Microfluidic experiments showed that tumour cell induced endothelial cell activation promoted leukocyte recruitment and platelet adhesion. Human bladder cancer tissue analysis confirmed that loss of IL-1ra and elevated IL-1 expression was associated with enhanced cancer progression. CONCLUSIONS: Our data indicate that IL-1 and IL-1ra were dysregulated in bladder cancer and could facilitate tumour dissemination through endothelial cell activation. Targeting the IL-1/IL-1ra axis might attenuate tumour-mediated inflammation and metastasis formation.

Wide-field autofluorescence-guided TUR-B for the detection of bladder cancer: a pilot study.

PURPOSE: The aim of this pilot study was to assess the feasibility and value of wide-field autofluorescence imaging (AFI) for the detection of bladder cancer during transurethral resection of the bladder (TUR-B). METHODS: For imaging, the D-Light/AF System (Karl Storz GmbH, Tuttlingen, Germany) and a customized band pass filter (≈ 480-780 nm) at the eyepiece of the endoscope were used. The excitation light wavelength was 440 nm. Representative spectral measurements of tissue autofluorescence (AF) were performed using a spectrometer attached behind the AF band pass filter in selected patients. During TUR-B, cystoscopy was performed in white light (WL) followed by wide-field AFI. Lesions were classified as suspicious or normal using either modality. RESULTS: Representative spectral measurements using excitation at a wavelength of 440 nm resulted in significantly lower fluorescence intensity of malignant versus non-malignant tissue. Overall, 56 lesions (30 cancerous and 26 non-malignant) in 25 patients were assessed and classified by wide-field AFI. Papillary tumors as well as flat lesions lacked the green fluorescence seen in normal urothelium, thus emerging as "brown-reddish" areas. When compared with histopathological findings, the pooled per-lesion sensitivity and specificity for AF were 96.7 and 53.8%, respectively. For WL these values were 86.7 and 69.2%, respectively. CONCLUSION: Wide-field AFI imaging during TUR-B is simple and easy to use. Our preliminary data suggest that AFI has the potential to increase the detection rates of bladder tumors compared with WL without the need of intravesical instillation prior to the procedure.

Zonal NephRo Score: external validation for predicting complications after open partial nephrectomy.

PURPOSE: The aim of the study was to externally validate the Zonal NePhRO Score (ZNS) published in 2014 as latest and superior nephrometry score in terms of prediction of perioperative complications and outcome of open partial nephrectomies (OPNs). METHODS: We identified 200 consecutive patients who underwent OPN. Analysis of preoperative CT or MRI scans and retrospective analysis of the patients' clinical records were performed. Tumour complexity was stratified according to the ZNS into three categories: low (4-6), moderate (7-9) and high (10-12) complexity. Predictors for perioperative complications and surgical parameters were identified using univariate and multivariate logistic regression. RESULTS: Tumour complexity was graded in 19.8 % of the cases as low, in 50.3 % as moderate and in 29.9 % as high. In the multivariate analysis, ZNS was significantly associated with a higher complication rate (OR 1.25, 95 % CI 1.04-1.49, p = 0.014), longer ischaemia time (IT) (ß = 1.19, 95 % CI 0.33-2.05, p = 0.007), postoperative drop of estimated glomerular filtration rate (eGFR) (ß = -1.86, 95 % CI -3.71 to -0.01, p = 0.049) and opening of the collecting system (CS) (OR 1.72, 95 % CI 1.40-2.10, p < 0.001). In addition, age and body mass index were identified as independent predictors for complications (OR 1.03, 95 % CI 1.00-1.06, p = 0.043 and OR 1.08, 95 % CI 1.00-1.15, p = 0.031). CONCLUSION: The present study is the first external validation of the ZNS as a predictor of perioperative complications in patients undergoing OPN. A higher ZNS score was associated with a longer IT, a higher rate of opening the CS and drop of eGFR.

Clinical and pathological nodal staging score for urothelial carcinoma of the bladder: an external validation.

PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

[Infectious diseases and injuries of bladder and urinary tract]. / Infektionskrankheiten und Verletzungen der Harnblase und der ableitenden Harnwege.

Urinary tract infections are the most common infectious diseases in Germany. In most cases clarification does not rely on imaging techniques other than sonography and is made mostly based on clinical symptoms. Computed tomography (CT) and magnetic resonance imaging (MRI) can be used in selected cases to find the cause and detection or exclusion of complications, e.g. recurrent or atypical and complicated courses. The method of choice for clarification of urolithiasis is CT. Using low-dose techniques, detection or exclusion of urinary stones can be achieved with a high sensitivity and specificity as well as an acceptable level of radiation exposure. Native stone CT supplies additional fundamental information that can substantially influence further therapy planning. The diagnosis of ureteral injuries is clinically and radiologically not trivial and clarification is aided by urographic contrast media. The method of CT cystography has an important role in the diagnostics of urinary bladder injuries.

[Oncological diseases and postoperative alterations of the bladder and urinary tract]. / Onkologische Erkrankungen und postoperative Veränderungen der Harnblase und der ableitenden Harnwege.

In the challenging evaluation of upper urinary tract malignancies multidetector computed tomography (CT) has become the standard imaging method. Cross sectional imaging not only allows the detection and visualization of the tumor itself but also provides nodal and metastasis staging in one examination (one-stop-shop). The majority of urothelial carcinomas are located in the urinary bladder. In this case, CT and more recently magnetic resonance imaging (MRI) can also deliver decisive information regarding TNM classification. A combination of clinical, histological, morphological and functional parameters allows both risk stratification and a targeted therapy based on the individual tumor stage.

Standardized ex vivo comparison of different upper urinary tract biopsy devices: impact on ureterorenoscopes and tissue quality.

OBJECTIVES: To evaluate the influence of different biopsy forcipes on the deflection, irrigant flow, and optical characteristics of flexible ureterorenoscopes and to assess tissue quality for histopathologic evaluation in an ex vivo setting. MATERIALS AND METHODS: The following five different biopsy forcipes were compared: Olympus (FB-56D-1; diameter 5Fr.), R. Wolf (829.601; 3Fr.), Karl Storz Medical (11275ZE; 3Fr.), Boston Scientific (Piranha; 505-160; 3 Fr.), and Cook BIGopsy (115CM; 2.4 Fr.). The devices were tested in 3 different ureterorenoscopes: Storz 11278 VU (Flex-X(2)), Storz 11278 V (Flex-X(C)), and Wolf Cobra (7326071/-6). Tissue samples were obtained from porcine upper urinary tracts. RESULTS: Baseline irrigation flow rates with empty channels were significantly higher in the Wolf Cobra than in Storz ureterorenoscopes (30.5 vs. 23 and 21 ml/min). The BIGopsy forceps allowed for higher flow rates in both Storz ureterorenoscopes (2.2 and 1.3, respectively) when compared to the other devices (0.5 and 0.6 ml/min). The Storz and Wolf biopsy forcipes resulted in the highest impairment of the deflection angle. In all 3 ureterorenoscopes, flow rates and deflection angle were least impaired by the BIGopsy. However, BIGopsy compromised the field of view (20 % reduction vs. 12 % by others). The largest sample of renal pelvis and ureter biopsies was obtained with BIGopsy and Storz(®) forcipes, respectively. The extent of artifacts and denuded urothelium were comparable in all samples. CONCLUSIONS: The various biopsy devices showed different impacts on irrigation flow, deflection, and field of view. The Cook BIGopsy best retains irrigation flow in single-channel flexible ureterorenoscopes and deflection. However, a smaller field of view may complicate handling and tissue acquisition.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

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

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

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

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

[Enhanced imaging in urological endoscopy]. / Erweiterte Bildgebung in der urologischen Endoskopie.

White light cystoscopy and the concise documentation of pathological findings are standard diagnostic procedures in urology. Additional imaging modalities and technical innovations may support clinicians in the detection of bladder tumors. Modern endoscopy systems provide ultra-high-resolution imaging and the option of digital contrast enhancement. Photodynamic diagnostics and narrow band imaging are well-established in clinical routine and have shown significant benefits in the detection of bladder cancer. By means of multispectral imaging, different modalities can now be combined in real-time. Probe-based procedures such as optical coherence tomography (OCT) or Raman spectroscopy can further contribute to advanced imaging through an "optical biopsy" which may primarily improve diagnostics in the upper urinary tract. The aim of all techniques is to optimize the detection rate in order to achieve a more accurate diagnosis, resection and lower recurrence rates. Current research projects aim to digitalize the documentation of endoscopy and also make it more patient- and user-friendly. In the future, the use of image processing and artificial intelligence may automatically support the surgeon during endoscopy.

[Urology training in Germany: international comparison of educational concepts and satisfaction]. / Urologische Facharztausbildung im internationalen Vergleich: Wo stehen wir in Deutschland?

BACKGROUND: The training of residents in urology is challenged by global trends in surgical education, increasing technological developments, subspecialization of the field and working hour regulations for physicians. Currently, there is no standardized curriculum in Europe and significant international differences exist in the education of residents. OBJECTIVES: We aimed to comprehensively map the state of urological training in an international comparison. MATERIALS AND METHODS: A selective literature review was conducted using the following keywords: "urology, training, residents". RESULTS: Recent surveys have shown that urology training in Germany is subject to relatively few regulations on content, time and space when compared to other countries. A lack of a structured curriculum is considered as the main factor leading to dissatisfaction of the residents. Increasing work load, lack of surgical training and limited flexibility in family or research planning have been mentioned as barriers for successful training. CONCLUSION: Structured and validated competence assessments and not "minimum numbers of operations" may help improve surgical training. An objective nationwide examination at the end of residency may be useful for international benchmarking.

[Biopsy techniques in the upper urinary tract for the diagnosis of urothelial carcinoma: systematic review]. / Biopsietechniken im oberen Harntrakt zur Diagnostik des Urothelkarzinoms: systematische Übersicht.

BACKGROUND: The diagnostic accuracy of ureteroscopic biopsies in the upper urinary tract is limited by technical difficulties during extraction and small sample size. OBJECTIVES: To evaluate the impact of different techniques and instruments on the histopathologic quality and diagnostic yield of extracted samples as well as the predictive value of clinical grading and staging on final pathologic stage at radical nephroureterectomy. MATERIALS AND METHODS: For this systematic review, we searched PubMed and Embase databases for original publications and meeting abstracts according to the PRISMA guidelines. RESULTS: Overall, we included 23 studies which comprised a total of 1547 biopsies for the investigation of diagnostic yield and 778 patients for the assessment of grade and stage concordance. We found that the median diagnostic yields of big retrograde 2F [french] forceps, antegrade 3F forceps and baskets in combination with forceps were 92% (range 83-100), 72% (50-90) and 91% (78-94), respectively. Median rates of grade concordance and upgrading across all techniques ranged between 78-89% and 5-16%, respectively, without relevant differences. CONCLUSIONS: The choice of biopsy technique affects the ability to diagnose upper tract urothelial carcinoma. The correct determination of pathologic grading is comparable between different techniques. The combination of biopsy forceps and baskets during ureterorenoscopy seems to achieve optimal diagnostic accuracy.

[The role of the vesical imaging-reporting and data system (VI-RADS) for bladder cancer diagnostics-status quo]. / Bedeutung der VI-RADS-Klassifikation für die Bildgebung beim Harnblasenkarzinom ­ Stand der Dinge.

Initial clinical and pathological diagnostic workup of urinary bladder cancer is based on cystoscopy, transurethral resection of suspicious lesions, and computed tomography when indicated. Accurate staging is necessary for further therapeutic decision-making. This review summarizes the current status of multiparametric magnetic resonance imaging (mpMRI) and the vesical imaging-reporting and data system (VI-RADS) classification. MpMRI may improve the accuracy of assessment of local tumor invasion compared to conventional imaging alone. VI-RADS standardizes reporting of MRI staging and classifies the likelihood of muscle-invasive bladder cancer into five categories. Preliminary data suggest low interobserver variability. However, prospective multicenter studies are necessary to validate the VI-RADS classification. Progress in functional, molecular, and hybrid imaging may further improve the accuracy of clinical tumor and nodal staging for bladder cancer.

[The development of real-time multispectral imaging for the diagnostics of bladder cancer]. / Entwicklung der Echtzeitmultispektralbildgebung für die Diagnostik des Harnblasenkarzinoms.

The performance of white light (WL) cystoscopy in the diagnostics of bladder cancer can be optimized by the use of modern imaging modalities, such as photodynamic diagnostics (PDD) and narrow band imaging (NBI). Real-time multispectral imaging (rMSI) enables simultaneous imaging of reflectance and fluorescence modalities in multiple spectral bands. We created a multiparametric cystoscopy image by digital overlapping of several modalities, e.g. WL, enhanced vascular contrast (EVC), raw fluorescence mode, protoporphyrin IX and autofluorescence (AF). The technical development and the subsequent clinical implementation of rMSI required a structured preclinical evaluation process, including both ex vivo and in vivo trials before the technology can be applied in patients. This review article presents the phases of testing, validation and the first clinical application of rMSI in urological endoscopy.

[Solitary fibrous tumour of the testes (SFT)]. / Solitärer fibröser Tumor des Hodens (SFT).

INTRODUCTION: Testicular masses in adults are most likely seminomatous or non-seminomatous germ cell tumours. Paratesticular tumours are far less frequent. Most lesions within this category are variants of fibrous pseudotumours. Solitary fibrous tumours (SFT) with characteristic (hemangiopericytoma-like) vascular structures are rare neoplasms that in the vast majority arise in the pleura, although extrapleural localisations in virtually every organ have been reported. CASE REPORT: A 64-year-old male nursing case was presented with a testicular swelling on the left side and recurrent testicular pain. Physical examination revealed a distinct mass at the left spermatic cord. The tumour marker levels were normal. The patient's history included an HIV infection as well as neurosyphilis. The sonographic examination showed a heterogeneous and hyperperfused tumour, MRI examination a 3.2 x 4.3 cm measuring heterogeneous tumour above the left epididymis. An inguinal orchiectomy was performed due to the unclear dignity. The histological examination revealed a solitary fibrous tumour. CONCLUSIONS: In cases of paratesticular tumours, rare tumours like solitary fibrous tumours have to be considered. Certainty regarding the dignity of the tumour can only be achieved by surgical exposure and excision.

The concentration of console surgeons: prospective evaluation of the loss of attention in robotic-assisted procedures.

To prospectively evaluate the possible loss of attention among console surgeons performing robotic-assisted procedures using a validated psychological test. The concentration of one console surgeon was assessed before and after 25 robotic-assisted procedures (radical prostatectomies) using the validated d2 attention test (computer-assisted, Hogrefe test systems, Germany). Error frequency, work rate, and accuracy of task performance were evaluated as parameters of the fluctuation in concentration. Data were correlated with clinical parameters, including console times, positive surgical margin rates and the use of a nerve-sparing procedure. Pre- and post-operative test results revealed no differences in the number of items performed, but a significant decline in the error-corrected performance between the pre- and post-operative tests was observed with increasing console time (p = 0.046; median console time 123 min.). No differences in the pre-operative tests for consecutive procedures (mean time between procedures 93 min.) were found, whereas the number of errors (missed items) increased in the post-operative tests (p = 0.0025). The measured differences in test results showed no association with the positive surgical margin rate. A planned nerve-sparing procedure tended to result in a lower level of concentration found in pre-operative testing (p = 0.07). Concentration decrease and loss of attention during robotic-assisted procedures can be measured validly using the d2 attention test. Longer console times lead to loss of attention but consecutive procedures do not decrease the test or surgical performance. Further studies need to address whether similar effects apply to the comparable open or other robotic procedures or to different levels of surgeons experience.

Prognostic Value of Molecular Breast Cancer Subtypes based on Her2, ESR1, PGR and Ki67 mRNA-Expression in Muscle Invasive Bladder Cancer.

INTRODUCTION: Gene expression analyses have identified similarities between bladder and breast cancer, where clinical risk stratification is based on Her2, ESR1, PGR and Ki67 expression. The aim of the study was to assess the respective marker gene expression in patients treated with radical cystectomy for muscle-invasive bladder cancer (MIBC) and to evaluate the applicability of breast cancer subtypes for MIBC risk stratification. MATERIALS & METHODS: 102 patients treated with radical cystectomy for MIBC were assessed. Using routine FFPE tissue and an IVD validated kit, mRNA expression was measured by single step RT-qPCR. Partition test were employed to define cut-off values for high or low marker gene expression. Association of expression with outcome was assessed using Kaplan-Meier analysis and multivariate cox regression analysis. Finally, we performed validation of our results in the MD-Anderson cohort (n=57). RESULTS: Cancer specific survival (CSS) was impaired in patients with high gene expression of Her2 (P=0.0009) and ESR1 (P=0.04). In the multivariate regression model Her2 expression remained significant for the prediction of CSS (HR=2.11, CI 1.11-4.21, P=0.024). Furthermore, molecular stratification by breast cancer subgroups was significant (P=0.023) for CSS prediction. Especially the differentiation between Her2-positive and Luminal A (HR=4.41, CI 1.53-18.71, P=0.004) and Luminal B (HR=1.96, CI 0.99-4.08, P=0.053) respectively was an independent prognostic parameter for CSS. External validation resulted in comparable risk stratification with differences in fractional subgroups distribution. CONCLUSION: Gene expression of Her2, ESR1, PGR, Ki67 and corresponding breast cancer subtypes allow a risk-stratification in MIBC, whereby Her2 overexpressing tumors reveal a particularly poor prognosis.