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Background Demographic changes are leading to an increase in geriatric urolithiasis patients aged ≥70 yr. Published data regarding their management remain sparse. In particular, for the subgroup of patients aged ≥80 yr there is a lack of evidence supporting the hypothesis that stone-removing treatment is effective, safe, and beneficial. Objective To examine the efficiency and safety of stone-removing treatment in geriatric urolithiasis patients aged ≥80 yr compared to their younger geriatric counterparts aged 70–79 yr against the background of their respective life expectancy. Design, setting, and participants Data for the study cohort were extracted from an institutional review board–approved retrospective database with 325 patients aged ≥70 yr (70–79 yr: n = 241; ≥80 yr: n = 84) consecutively admitted to hospital because of symptomatic urolithiasis from 2013 to 2018. Outcome measurements and statistical analysis Baseline characteristics, outcome and follow-up data, and survival were compared using Wilcoxon-Mann-Whitney U tests, χ2 tests, Kaplan-Meier estimation, log-rank tests, and Cox regression. Results and limitations At baseline, the incidence of infected hydronephrosis was greater among patients aged ≥80 yr (p 0.05). Survival analysis for the two groups demonstrated a 2-yr overall survival (OS) rate of 0.91 (95% confidence interval [CI] 0.75–1) for patients aged ≥80 yr and 0.97 (95% CI 0.88–1), for those aged 70–79 yr (p Conclusions Stone-removing treatment for patients aged ≥80 yr proved to be as effective and safe as for patients in their seventies. Although characterized by shorter remaining life expectancy, excellent 2-yr OS for patients aged ≥80 yr supports the hypothesis of equal benefit from stone-removing treatment when compared to septuagenarians. Patient summary There is a lack of evidence supporting the benefit of urinary stone-removing treatment for patients older than 80 yr. Our study included geriatric patients older than 70 yr with symptomatic urinary stone disease for which urinary drainage or stone removal is indicated. We compared treatment outcomes and survival between two age groups: patients aged 70–79 yr and those aged 80 yr or older. We found equivalent outcomes for the two groups and excellent 2-yr overall survival of 91% for those older than 80 yr. The study strengthens the evidence that active stone-removing therapy is safe and beneficial for these patients.

European journal of cancer 154, 227-234 (2021). doi:10.1016/j.ejca.2021.05.026, Published by Elsevier, Amsterdam [u.a.]

Background Physical activity has been positively related to malignant melanoma. However, that association may be confounded by ultraviolet radiation (UV), a variable closely related to both outdoor physical activity and malignant melanoma. We examined physical activity, grip strength and sedentary behaviour in relation to risk of malignant melanoma, accounting for relevant confounders using data from a prospective cohort study. Methods In 350,512 UK Biobank participants aged 38–73 years at baseline, physical activity was assessed with a modified version of the International Physical Activity Questionnaire Short Form, grip strength was measured with a hand dynamometer, and sedentary behaviour was recorded with three specific questions. Multivariable hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results During 7 years of follow-up, 1239 incident malignant melanoma diagnoses were recorded. Physical activity and sedentary behaviour were unrelated to malignant melanoma (HRs 1.01 (95% CI 0.95–1.07) and 1.04 (95% CI 0.97–1.12), respectively), and the initially positive association with grip strength in the basic model (HR 1.23, 95% CI 1.08–1.40) was attenuated after full adjustment (HR 1.10, 95% CI 0.96–1.26). Conclusion Physical activity, grip strength and sedentary behaviour are not associated with malignant melanoma risk.

Background Simultaneous urothelial cancer manifestation in the lower and upper urinary tract affects approximately 2% of patients. Data on the surgical benchmarks and mid-term oncological outcomes of enbloc robot-assisted radical cystectomy and nephro-ureterectomy are scarce. Methods After written informed consent was obtained, we prospectively enrolled consecutive patients undergoing enbloc radical cystectomy and nephro-ureterectomy with robotic assistance from the DaVinci Si-HD® system in a prospective institutional database and collected surgical benchmarks and oncological outcomes. Furthermore, as one console surgeon conducted all the procedures, whereas the team providing bedside assistance was composed ad hoc, we assessed the impact of this approach on the operative duration. Results Nineteen patients (9 women), with a mean age of 73 (SD: 7.5) years, underwent simultaneous enbloc robot-assisted radical cystectomy and nephro-ureterectomy. There were no cases of conversion to open surgery. In the postoperative period, we registered 2 Clavien-Dindo class 2 complications (transfusions) and 1 Clavien-Dindo class 3b complication (port hernia). After a median follow-up of 23 months, there were 3 cases of mortality and 1 case of metachronous urothelial cancer (contralateral kidney).The total operative duration did not decrease with increasing experience (r = 0.174, p = 0.534). In contrast, there was a significant, inverse, strong correlation between the console time relative to the total operative duration and the number of conducted procedures after adjusting for the degree of adhesions and the type of urinary diversion(r = -0.593, p = 0.02). Conclusions These data suggest that en bloc simultaneous robot-assisted radical cystectomy and nephro-ureterectomy can be safely conducted with satisfactory mid-term oncological outcomes. With increasing experience, improved performance was detectable for the console surgeon but not in terms of the total operative duration. Simulation training of all team members for highly complex procedures might be a suitable approach for improving team performance. Trial registration: Not applicable.

Das Peniskarzinom (PeKa) ist eine seltene Tumorentitat mit einer grosen Schwankungsbreite in der Versorgungsqualitat und hieraus resultierenden haufig suboptimalen onkologischen und funktionellen Behandlungsergebnissen. Die Fragestellung ist die Analyse der aktuellen Versorgungssituation in der klinischen Routine, Identifikation der relevanten Kernmerkmale und deren Referenzwerte der Therapiequalitat. Die Recherche bezieht sich auf relevante Peer-review-Publikationen und publizierte Kongressabstracts in Medline, Embase und anderen Datenbanken sowie der Google-Web-Suchmaschine. Die Kernqualitatsmerkmale der PeKa-Versorgung umfassen organerhaltende Chirurgie des Primartumors, invasives Leistenlymphknotenstaging und systemische Therapie. Die Konformitat dieser Parameter mit den Leitlinien ist aktuell flachendeckend niedrig. Zentrumsbildung fuhrte in manchen Regionen zu einer deutlichen Verbesserung der Behandlungsqualitat und steigender Anlehnung an die Empfehlungen der Fachgesellschaften. Zentrumsbildung und darauf basierende Netzwerke konnen zu einer deutlichen Verbesserung der Patientenversorgung fuhren. So konnen Referenzwerte fur die Kernqualitatsmerkmale der Therapie des Tumors generiert und validiert, zudem organerhaltende Chirurgie, invasives Lymphknotenstaging sowie systemische Therapie im zunehmenden Umfang eingesetzt werden. Empirisch konnte der Referenzwert fur diese 3 Qualitatskriterien bei 90 % Anlehnung an die Leitlinien angestrebt werden. Vor einer Zentrumsbildung mussen jedoch solche fur die praktische Umsetzung relevanten Aspekte wie Ubernahme der Reisekosten fur die Betroffenen, Ausgaben fur die Infrastruktur und Messinstrumente der Lebensqualitat und Patientenzufriedenheit nach Zentralisierung adressiert werden.

In chirurgischen Fachdisziplinen zeichnet sich im Hinblick auf die Pra- und Rehabilitation des Patienten in den letzten Dekaden ein Paradigmenwechsel ab. Insbesondere kann nach aktueller Studienlage bei komplikationstrachtigen Operationen wie der radikalen Zystektomie durch enge interdisziplinare Zusammenarbeit die perioperative Betreuung des Patienten im Sinne einer Fast-track-Genesung optimiert werden. Konzeption standardisierter Behandlungsablaufe und Erstellung eines konkreten Masnahmenkatalogs nach radikaler Zystektomie orientierend an den Leitlinien der ERAS®-Society. Das prasentierte Programm beginnt bei der praoperativen Schulung des Patienten zur optimalen korperlichen und geistigen Vorbereitung auf die Operation. Wesentliche peri- und postoperative Aspekte sind eine schonende Operationstechnik, suffiziente Schmerztherapie, fruhzeitige Mobilisierung und Kostzufuhr, zugige Entfernung von Fremdmaterial und die fruhestmogliche Ruckkehr in den Alltag. Prospektive Datenanalysen bezuglich der Wirksamkeit der etablierten Masnahmen insbesondere in Bezug auf postoperative Komplikationen und mediane Hospitalisationsdauer sind die nachste Zielsetzung.

Purpose Uveal melanoma (UM) is an orphan cancer of high unmet medical need. Current patterns of care and surveillance remain unclear as they are situated in an interdisciplinary setting. Methods A questionnaire addressing the patterns of care and surveillance in the management of patients with uveal melanoma was distributed to 70 skin cancer centers in Austria, Germany and Switzerland. Frequency distributions of responses for each item of the questionnaire were calculated. Results 44 of 70 (62.9%) skin cancer centers completed the questionnaire. Thirty-nine hospitals were located in Germany (88.6%), three in Switzerland (6.8%) and two in Austria (4.5%). The majority (68.2%) represented university hospitals. Most patients with metastatic disease were treated in certified skin cancer centers (70.7%, 29/41). Besides, the majority of patients with UM were referred to the respective skin cancer center by ophthalmologists (87.2%, 34/39). Treatment and organization of follow-up of patients varied across the different centers. 35.1% (14/37) of the centers stated to not perform any screening measures. Conclusion Treatment patterns of patients with uveal melanoma in Germany, Austria and Switzerland remain extremely heterogeneous. A guideline for the treatment and surveillance is urgently needed.

The success of cancer immunotherapy is limited by resistance to immune checkpoint blockade. We therefore conducted a genetic screen to identify genes that mediated resistance against CTLs in anti–PD-L1 treatment–refractory human tumors. Using PD-L1–positive multiple myeloma cells cocultured with tumor-reactive bone marrow–infiltrating CTL as a model, we identified calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key modulator of tumor-intrinsic immune resistance. CAMK1D was coexpressed with PD-L1 in anti–PD-L1/PD-1 treatment–refractory cancer types and correlated with poor prognosis in these tumors. CAMK1D was activated by CTL through Fas-receptor stimulation, which led to CAMK1D binding to and phosphorylating caspase-3, -6, and -7, inhibiting their activation and function. Consistently, CAMK1D mediated immune resistance of murine colorectal cancer cells in vivo. The pharmacologic inhibition of CAMK1D, on the other hand, restored the sensitivity toward Fas-ligand treatment in multiple myeloma and uveal melanoma cells in vitro. Thus, rapid inhibition of the terminal apoptotic cascade by CAMK1D expressed in anti–PD-L1–refractory tumors via T-cell recognition may have contributed to tumor immune resistance.

Objective To investigate the effect of perioperative complications involving artificial urinary sphincter (AUS) implantation on rates of explantation and continence as well as health-related quality of life (HRQOL). Materials and methods Inclusion criteria encompassed non-neurogenic, moderate-to-severe stress urinary incontinence (SUI) post radical prostatectomy and primary implantation of an AUS performed by a high-volume surgeon (>100 previous implantations). Reporting complications followed the validated Clavien-Dindo scale and Martin criteria. HRQOL was assessed by the validated IQOL score, continence by the validated ICIQ-SF score. Statistical analysis included Chi (2) test, Mann-Whitney-U test, and multivariate regression models (p

Purpose: To evaluate and compare the clinical utility of simultaneously obtained quantitative 18F-fluorodeoxyglucose positron-emission-tomography (18F-FDG PET) and diffusion-weighted imaging (DWI) datasets for the prediction of histopathological therapy response of soft tissue sarcomas (STS) under neoadjuvant isolated limb perfusion (ILP). Methods: A total of 37 patients with confirmation of a STS of the extremities underwent an 18F-FDG PET/magnetic resonance imaging (MRI) examination before (1st scan) and after (2nd scan) ILP with melphalan and TNF-α. For each patient, the maximum tumor size, metabolic activity (standardized uptake values, SUV) and diffusion-restriction (apparent diffusion restriction values, ADC) were determined in pre- and posttherapeutic examinations and percentage changes during treatment were calculated. A Mann-Whitney U test was used and receiver operating characteristic (ROC) analysis was performed to compare the results of the different quantitative parameters to predict histopathological therapy response. Results from histopathological analysis after subsequent tumor resection served as reference standard and patients were defined as responders/non-responders based on the grading scale by Salzer-Kuntschik. Results: Histopathological analysis categorized 22 (59%) patients as therapy responders (Grade I-III) and 15 (41%) patients as non-responders (Grade IV-VI). Tumors in the responder group showed a mean reduction in size of -9.7% and metabolic activity (SUVpeak: -51.9%; SUVmean: -43.8%) as well as an increase of the ADC values (ADCmin: +29.4% and ADCmean: +32.8%) under treatment. Percentage changes in the non-responder group amounted to: tumor size -6.2%; SUVpeak: -17.3%; SUVmean: -13.9%; ADCmin: +15.3% and ADCmean: +14.6%. Changes of the SUVs and ADCmean values between responders and non-responders were significantly different ( 0.05). The corresponding AUCs were 0.63 (tumor size), 0.87 (SUVpeak), 0.82 (SUVmean), 0.63 (ADCmin), 0.84 (ADCmean) and 0.89 (ratio: ADCmean/SUVpeak), respectively. Conclusion:18F-FDG PET and MR-derived quantitative imaging parameters (SUVs and ADCmean) and their combination reveal a good performance for the prediction of histopathological therapy response of STS under neoadjuvant ILP. Therefore, integrated PET/MRI could serve as a valuable tool for pretherapeutic assessment as well as monitoring of neoadjuvant treatment strategies of STS.

Cutaneous melanoma is one of the most aggressive forms of skin neoplasms and represents a major cause of neoplastic or cancer death in Europe. Without adequate therapy, the 5-year survival rate is 15% when the disease metastasizes to distant organs. The objective of our study was to evaluate the status quo of the current treatment standards in stage IV melanoma and rationale for therapy decisions in Germany and Austria between January 2016 and September 2018. In this retrospective, anonymized registry, data of male and female patients with unresectable advanced/metastatic BRAF-positive cutaneous melanoma treated in the first, second, and third line with registered substances were analyzed using descriptive statistics. Ninety-nine patients (50.5% male) received a total of 172 treatment lines. The first (99 patients), second (56 patients), and third (17 patients) treatment lines were documented. Within the 80.8% of patients with stage IV melanoma, targeted therapy (TT) was more frequently administered as a first-line treatment than immunotherapy (IO) with checkpoint inhibitors (59.6% TT vs. 40.4% IO). Across all lines, patients received TT in 54.7% and IO in 43.0% of the cases. As targeted agents, dabrafenib plus trametinib was predominantly prescribed (72.3%), whereas the monotherapy with anti-programmed cell death protein 1 and anti-cytotoxic T lymphocyte-associated protein 4 antibodies or their combination was prescribed similarly often (50.0% vs. 47.3%). Most commonly, the treatment type was switched from TT to IO or vice versa upon disease progression. The most frequent rationales for prescribing either TT or IO were remission pressure (72.9%) or physician’s preference (45.0%), respectively. Disease progression was a more frequent cause of treatment discontinuation than undesired events. Patients in Germany and Austria with unresectable advanced or metastatic BRAF-mutant melanoma predominantly receive guideline-recommended treatments. TT was more frequently administered than IO while the rationale for prescribing a specific treatment type differed between the two.

Radical cystectomy (RC) has a high morbidity and leads to a significant socio-economic burden. We aimed to investigate pre-, intra-, and post-operative variables to create a novel score predicting both post-operative clinical (complications) and economic (length of hospital stay) outcome after RC. We retrospectively evaluated clinical and histopathological data of 317 patients after RC. We performed univariate and multivariate logistic regression analyses to identify variables associated with post-operative clinical (30-day morbidity according to Clavien–Dindo complications) and economic (length of hospital stay) outcome. In multivariate analysis, a high number of intraoperative transfusions (T) of packed red blood cells predicted major complications (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.10–2.58, p = 0.017), preoperative potassium (P) level predicted three or more complications (OR for high preoperative potassium 0.71, 95% CI 0.52–0.98, p = 0.037), and high drain (D) loss on post-operative day 1 predicted a longer hospital stay ≥ 22 days (OR 1.57, 95% CI 1.04–2.35, p = 0.003). The PT2D-Score was able to predict three or more complications (area under the curve: 0.70, 95% CI 0.61–0.78, p

Aims To comparatively analyse outcomes after ARGUS classic and ArgusT adjustable male sling implantation in a real-world setting. Methods Inclusion criteria encompassed: non-neurogenic, moderate-to-severe stress urinary incontinence (≥2 pads), implantation of an ARGUS classic or ArgusT male sling between 2010 and 2012 in a high-volume center (>150 previous implantations). Functional outcomes were assessed using daily pad usage, 24-hour pad testing, and International Consultation on Incontinence (ICIQ-SF) questionnaires. Continence was defined as zero pads per 24 hours. Complications were graded using Clavien-Dindo scale. For multivariate analysis, binary logistic regression models were used (P Results A total of 106 patients (n = 74 [ARGUS classic], n = 32 [ArgusT]) from four centers were eligible. Median follow-up was 44.0 months (24-64). Patient cohorts were well-balanced. We observed a statistical trend in favor of ARGUS classic regarding postoperative urine loss based on standardized 24-hour pad test (71 ± 162 g [ARGUS classic] vs 160 ± 180 g [ArgusT]); P = .066]. Dry rates were 33.3% (ARGUS classic) and 11.8% (ArgusT, P = .114). In multivariable analysis, ArgusT male sling could not be confirmed as an independent predictor of decreased success (OR, 0.587; 95% CI; 0.166-2.076, P = .408). There were no Clavien IV and V complications. Inguinal pain was significantly higher after ArgusT implantation (P = .033). Explantation rates were higher for ArgusT compared to ARGUS classic (14.0 vs 23.3%; P = .371). Longer device survival for the ARGUS classic male sling was observed in Kaplan-Meier analysis (P = .198). Conclusions In the largest comparative analysis of ARGUS classic and ArgusT male sling with the longest follow-up to date, we observed low continence rates with superior functional outcomes and decreased explantation rates after ARGUS classic implantation.

Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3–26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed.

Objective: To analyze decision-making in patients with male urinary incontinence (SUI) in centers of expertise. The artificial urinary sphincter (AUS) remains the gold standard for male patients with moderate to severe SUI but adjustable male slings are a minimally invasive treatment option with good results, hence without a high level of evidence regarding the optimal patient selection. Materials and Methods: In total, 220 patients (88 AUS; 132 adjustable slings) were investigated from the DOMINO database that underwent surgery between 2010 and 2012 in 5 urological departments that offer adjustable sling systems as well as AUS systems for patients with moderate to severe urinary incontinence. For statistical analysis, the Mann-Whitney U test was used to identify differences between both groups. Results: Patients selected for an adjustable male sling were less likely to have a neurological disease (5.3 vs. 9.1%; p = 0.030), a prior urethral stricture (22.7 vs. 50.0%; p = 0.001), a prior incontinence surgery (24.4 vs. 45.5%; p = 0.01), or a prior radiation therapy (26.5 vs. 40.1%; p = 0.001). The severity of preoperative incontinence was higher in patients selected for an AUS with a mean pad usage per day of 7.60 versus 5.80 (p < 0.001). Mean postoperative pad usage and patients’ subjective perception were comparable in both groups. Conclusion: In centers offering both options, the decision-making is mainly based upon presence of radiation therapy and previous failed incontinence surgery. Despite the more complex patient cohort selected for an AUS implantation with a possible impact on the postoperative outcome, the functional results seem to be comparable indicating a proper preoperative patient assessment and selection in this cohort.

Introduction: Androgen receptor variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC) and has shown potential as a predictive biomarker in circulating tumour cells (CTCs) isolated from the bloodstream in terms of a liquid biopsy. Studies have shown that AR-V7 is a potential surrogate for selecting drug classes for systemic treatment by detecting nuclear AR-V7 by immunofluorescence or measuring AR-V7 messenger RNA by quantitative PCR. Here, we assessed the predictive value of AR-V7 detected by classical immunohistochemistry (IHC) for treatment response. Methods: CTCs were isolated by cell separation by density gradient centrifugation from patients with metastatic CRPC (n = 26) before, while, and after undergoing a new therapy with chemotherapy (cabazitaxel or docetaxel) or antiandrogen (enzalutamide or abiraterone). CTCs were sequentially cytospun on object slides, and AR-V7 status was then detected by IHC based on a staining regime established on a 22Rv1 cell line with antibodies against CK8/18 und AR-V7. Results: AR-V7 status detected by IHC showed no predictive value for progression-free survival (PFS). Kaplan-Meier analysis revealed that there was no difference in PFS between patients found positive or negative for AR-V7. Discussion/Conclusion: AR-V7 detected by classical IHC has no predictive value for treatment response in the described setting. The future role of AR-V7 in CTCs as a biomarker in clinical routine remains elusive.

Objective: The artificial urinary sphincter (AUS) is the surgical gold standard after previously failed surgical treatment for male urinary stress incontinence. The evidence for a male sling as salvage treatment is poor, but there is a proportion of patients that refuse implantation of an AUS or have a relative contraindication. The goal of our retrospective study was an analysis of outcome and complications of patients with a secondary sling after previously failed surgery for stress urinary incontinence (SUI). Materials and Methods: Data on 186 patients who had a prior incontinence surgery were extracted from the DOMINO database. 139 patients (74.7%) received an AUS and 41 patients (22.0%) who had received a secondary sling system between 2010 and 2012 after previously failed surgery for male urinary incontinence could be identified and were further analyzed. Results: Eight patients (19.5%) received a secondary repositioning sling and 33 patients (80.5%) received a secondary adjustable sling system. A prior surgery for urethral stricture was performed in 4 patients (9.8%). No major intraoperative complications were reported. A simultaneous explantation was performed in 12 patients (29.3%). The mean number of pad reductions was 4.93 (p = 0.026). No intraoperative complications and no postoperative surgical revisions were reported. The mean follow-up of the patient cohort with a secondary sling was 16 months. Conclusion: We provide the largest cohort of male patients up to date with a secondary sling after primary failure of surgery for male SUI. Although the procedure is a rarely performed surgery and without a high level of evidence, a secondary adjustable male sling system might be a feasible option in selected patients with acceptable complication rates, whereas a valuable outcome regarding continence rates cannot be sufficiently supplied by our data.

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.

Purpose Women are underrepresented at scientific conferences, decreasing the visibility of female role models, which are vital for aspiring young female scientists. This investigation aimed to evaluate female representation at the German Society of Urology's (GSoU) annual meeting. Methods The programs of the GSoU meeting of 2011, 2018, 2019 and the virtual conference in 2020 were retrospectively quantified by gender and categorized by chair or speaker, type, and topic of the session. Descriptive analysis was applied. Univariate and multivariate analyses were performed to identify gender inequity and variables influencing gender distribution. A p value of Results A total of 2.504 chairs and speakers were invited to the GSoU meeting in 2018 and 2019. Female speakers or chairs were represented in 17.8%, indicating a gender gap of 64.7%. There were significant differences between session type, topic, and gender distribution for chairs and speakers. The topic surgical techniques were independent variables for both, underrepresented female chairs and speakers, respectively (p Conclusion There is still a significant discrepancy between gender representation at the GSoU annual meetings, and gender equity is currently not expected before 50 years. Future efforts should address the implementation of established guidelines for achieving gender equity at urological conferences.

Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.

BackgroundClear-cell renal cell carcinoma (ccRCC) is common and associated with substantial mortality. TNM stage and histopathological grading have been the sole determinants of a patient’s prognosis for decades and there are few prognostic biomarkers used in clinical routine. Management of ccRCC involves multiple disciplines such as urology, radiology, oncology, and pathology and each of these specialties generates highly complex medical data. Here, artificial intelligence (AI) could prove extremely powerful to extract meaningful information to benefit patients.ObjectiveIn the study, we developed and evaluated a multimodal deep learning model (MMDLM) for prognosis prediction in ccRCC.Design, Setting, and ParticipantsTwo mixed cohorts of non-metastatic and metastatic ccRCC patients were used: (1) The Cancer Genome Atlas cohort including 230 patients and (2) the Mainz cohort including 18 patients with ccRCC. For each of these patients, we trained the MMDLM on multiscale histopathological images, CT/MRI scans, and genomic data from whole exome sequencing.Outcome Measurements and Statistical AnalysisOutcome measurements included Harrell’s concordance index (C-index) and also various performance parameters for predicting the 5-year survival status (5YSS). Different visualization techniques were used to make our model more transparent.ResultsThe MMDLM showed great performance in predicting the prognosis of ccRCC patients with a mean C-index of 0.7791 and a mean accuracy of 83.43%. Training on a combination of data from different sources yielded significantly better results compared to when only one source was used. Furthermore, the MMDLM’s prediction was an independent prognostic factor outperforming other clinical parameters.InterpretationMultimodal deep learning can contribute to prognosis prediction in ccRCC and potentially help to improve the clinical management of this disease.Patient SummaryAn AI-based computer program can analyze various medical data (microscopic images, CT/MRI scans, and genomic data) simultaneously and thereby predict the survival time of patients with renal cancer.

Background To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with particular emphasis on the prognostic effect of sentinel lymph node biopsy (SLNB), Charlson comorbidity index (CCI) and distinct tumor localisations. Methods Here we primarily describe a retrospective multicenter population-based cohort study with 402 patients having undergone resection with curative intent of HNM between 2010 and 2017. SLNB was used in the diagnosis of 79 HNM patients. Outcome was analyzed, focusing on SLNB, CCI as well as tumor localisation. Overall survival (OAS) und recurrence free survival (RFS) was examined by uni- and multivariate analysis. Results Histopathologically verified lymph node metastasis according to SLNB was associated with impaired RFS in HNM patients (p = 0.004). Especially in higher tumor stages, the sole implementation of SLNB improved survival significantly in the present cohort (p = 0.042). With most of the HNM being located in the face, melanoma of the scalp and neck could be linked to deteriorated patient’s outcome in uni- as well as multivariate analysis (p = 0.021, p = 0.004). Conclusions SLNB is a useful tool in predicting development of distant metastasis after HNM resection with curative intent. Especially in higher tumor stages, performing a SLNB ameliorated survival of HNM patients. Additionally, CCI as well as a distinct tumor localisations in HNM were identified as important risk factors in our population-based cohort study.

INTRODUCTION AND OBJECTIVE:Metastatic penile cancer (PeCa) is hallmarked by rapidly evolving resistance to chemotherapy worsening prognosis. Since PeCa is a rare disease, translational research aim...

INTRODUCTION: Immune checkpoint inhibitors (ICI) have been approved for patients with clear cell renal cell carcinoma (ccRCC), but not all patients benefit from ICI. One reason is the tumor microenvironment (TME) that has substantial influence on patient's prognosis and therapy response. Thus, we comprehensively analyzed the TME of ccRCC regarding prognostic and predictive properties. METHODS: Tumor-infiltrating CD3-positive T-cells, CD8-positive cytotoxic T-lymphocytes (CTLs), regulatory T-cells, B-cells, plasma cells, macrophages, granulocytes, programmed cell death receptor 1 (PD-1), and its ligand PD-L1 were examined in a large hospital-based series of ccRCC with long-term follow-up information (n = 756) and in another patient collective with information on response to nivolumab therapy (n = 8). Tissue microarray technique and digital image analysis were used. Relationship between immune cell infiltration and tumor characteristics, cancer-specific survival (CSS), or response to ICI was examined. RESULTS: Univariate survival analysis revealed that increased tumor-infiltrating B-cells, T-cells, and PD-1-positive cells were significantly associated with favorable CSS and high levels of intratumoral granulocytes, macrophages, cytotoxic T-cells, and PD-L1 significantly with poor CSS. High CTL or B-cell infiltration and high PD-L1 expression of ccRCC tumor cells qualified as independent prognostic biomarkers for patients' CSS. Significantly higher densities of intratumoral T-cells, CTLs, and PD-1-positive immune cells were observed in ccRCC with response to ICI compared with patients with mixed or no response (CD3: p = 0.003; CD8: p = 0.006; PD-1: p = 0.01). DISCUSSION: This study shows that subsets of tumor-infiltrating leukocytes in the TME and also PD-1/PD-L1 provide prognostic and predictive information for patients with ccRCC. Keywords: Renal cell carcinoma, Immune cell, Checkpoint inhibitor, Biomarker

Bei onkologischen Patienten liegen einer Vorstellung in der Klinik haufig urologische Notfalle zugrunde. Diese konnen durch Neoplasien des Urogenitaltrakts oder anderer Organe des Retroperitoneums bzw. Beckens bedingt sein und stellen sich als Blutbeimengung zum Urin, Harnretention oder stauungsbedingte Infektionen des Harntrakts dar. Ein schnelles diagnostisches und therapeutisches Handeln ist zur Erzielung eines gunstigen klinischen Verlaufs entscheidend. Bei Blutungen beinhalten die Masnahmen eine exakte Lokalisation und anschliesende interventionelle Versorgung der Blutungsquelle, bei Harnretention und stauungsbedingten Infektionen eine Drainage des gestauten Urins.

Background Transrectal prostate biopsy (pbx) is the most frequent outpatient procedure in the urological field. Septic complications are a major health issue. Objective To evaluate complication rates with or without an antimicrobial lubricant. Design, setting, and participants A total of 1000 patients received pbx between 2013 and 2015. Information about complications was collected by a 3-wk questionnaire. Return rate was 73.2% (n = 732). Intervention Randomization for pbx with the instillation of an antimicrobial lubricant (intervention group, n = 385) or the standard lubricant (control group, n = 347) was performed. Outcome measurements and statistical analysis Multivariable analyses assessed the association between infectious complications at biopsy and use of an antimicrobial lubricant, International Prostate Symptom Score (IPSS), history of urogenitourinary infections, and several other confounders. Results and limitations The use of an antimicrobial lubricant did not reduce infection rate. Overall complication rate was very low. Of all patients, 69.3% described the procedure as pain free. Fever ≥38.5 °C was reported in overall 1.9% of patients. Urinary retention with catheterization occurred in 3.1%. Most common complications were hematospermia (47.4%), macrohematuria (23.8%), and rectal bleeding (7.4%). Readmission rate was 1% (n = 7). In multivariable analyses, IPSS and previous infectious complications were associated with a higher risk of infectious complications. Our results stem from a large German single center and therefore are limited to this patient group. Conclusions No significant reduction was shown in infectious complications in the intervention group with the antimicrobial agent. Low incidence of those complications may be the underlying cause. Severe morbidity at pbx is uncommon. Specifically, the rate of infection was very low. Patient summary Severe complications at prostate biopsy are rare. Among participants, 69.3% had no pain. Fever was rare (1.9% of patients). Voiding issues with catheterization occurred in 3.1%. Most common complications were blood in the semen (47.4%), urine (23.8%), or stool (7.4%). Men with voiding issues or previous infectious complications had a higher risk of infectious complications.

Background In recent studies, convolutional neural networks (CNNs) outperformed dermatologists in distinguishing dermoscopic images of melanoma and nevi. In these studies, dermatologists and artificial intelligence were considered as opponents. However, the combination of classifiers frequently yields superior results, both in machine learning and among humans. In this study, we investigated the potential benefit of combining human and artificial intelligence for skin cancer classification. Methods Using 11,444 dermoscopic images, which were divided into five diagnostic categories, novel deep learning techniques were used to train a single CNN. Then, both 112 dermatologists of 13 German university hospitals and the trained CNN independently classified a set of 300 biopsy-verified skin lesions into those five classes. Taking into account the certainty of the decisions, the two independently determined diagnoses were combined to a new classifier with the help of a gradient boosting method. The primary end-point of the study was the correct classification of the images into five designated categories, whereas the secondary end-point was the correct classification of lesions as either benign or malignant (binary classification). Findings Regarding the multiclass task, the combination of man and machine achieved an accuracy of 82.95%. This was 1.36% higher than the best of the two individual classifiers (81.59% achieved by the CNN). Owing to the class imbalance in the binary problem, sensitivity, but not accuracy, was examined and demonstrated to be superior (89%) to the best individual classifier (CNN with 86.1%). The specificity in the combined classifier decreased from 89.2% to 84%. However, at an equal sensitivity of 89%, the CNN achieved a specificity of only 81.5% Interpretation Our findings indicate that the combination of human and artificial intelligence achieves superior results over the independent results of both of these systems.

Purpose The aim was to study the correlation between cuff size and outcome after implantation of an AMS 800 artificial urinary sphincter. Methods A total of 473 male patients with an AMS 800 sphincter implanted between 2012 and 2014 were analyzed in a retrospective multicenter cohort study performed as part of the Central European Debates on Male Incontinence (DOMINO) Project. Results Single cuffs were implanted in 54.5% and double cuffs in 45.5% of the patients. The cuffs used had a median circumference of 4.5 cm. Within a median follow of 18 months, urethral erosion occurred in 12.8% of the cases and was associated significantly more often with small cuff sizes (P

PURPOSE To predict the persistence of storage symptoms after transurethral resection of the prostate (TURP) using a nomogram derived from the ice water test (IWT). METHODS The IWTs of 73 men with lower urinary tract symptoms and prostatic bladder outlet obstruction were retrospectively analyzed. The strength of the detrusor contraction was approximated by using the detrusor gradient of Δpdet /Δt at maximum detrusor pressure and the area under the curve. The parameters were utilized in a nomogram, which facilitated a severity categorization from 1 to 10. Patients with a positive IWT in the categories 1 to 2 were assigned to group A, categories 3 to 4 to group B and categories 5 and higher to group C. After TURP, patients with persisting storage symptoms were offered a botulinum toxin injection. RESULTS There were 32 patients (44%) with negative and 41 patients (56%) with positive IWTs. Patients with negative IWTs were classified in category 1. Regarding patients with positive IWTs, 14 (34%) were correlated to group A, 14 (34%) to group B, and 13 (32%) to group C. The necessity of a subsequent botulinum toxin injection correlated significantly with a higher nomogram category (P

Objectives Targeted therapy (TT) is an effective treatment for advanced BRAFV600-mutated melanoma, but most patients eventually acquire resistance and progress. Here, we evaluated the outcome of second-line immune checkpoint blockade (ICB) after progression on dual BRAF and MEK inhibition. Methods Patients with metastatic melanoma progressing on combined BRAF + MEK inhibition and receiving second-line ICB between 2015 and 2019 in 9 tertiary referral centres were enrolled. Demographic and clinical data and blood counts of all patients were collected retrospectively. Results We identified 99 patients with stage IV melanoma receiving ICB (nivolumab, pembrolizumab [n = 39] or ipilimumab plus nivolumab [n = 60]) after progression on combined TT. The median progression-free survival was similar in the PD-1 and ipilimumab plus nivolumab group (2.6 months [95% confidence interval {CI}, 2.0–3.1] vs. 2.0 [95% CI, 1.4–2.6], p = 0.15). The objective response rate was 18.0% in the PD-1 and 15.0% in the ipilimumab plus nivolumab group (p = 0.70). The disease control rate was 25.7% for monotherapy and 18.3% for combined ICB (p = 0.39). The median overall survival was 8.4 months (95% CI, 5.1–11.7) for patients receiving PD-1 monotherapy and 7.2 months (95% CI, 5.2–9.1) for patients receiving ipilimumab plus nivolumab (p = 0.86). The latter was associated with a higher rate of treatment-related adverse events (AEs). No significant association of laboratory values or clinicopathological characteristics with response to second-line ICB was observed. Conclusions PD-1 monotherapy and combined ipilimumab plus nivolumab show similar activity and outcome in patients with melanoma resistant to BRAF + MEK inhibition. However, combined ipilimumab plus nivolumab was associated with a higher rate of treatment-related AEs compared with monotherapy.

BACKGROUND Testicular germ cell tumor (TGCT) is one the most common solid tumors in men between the age of 15 and 35 with an overall incidence rate of 1-1.5 %. Epidemiologic studies have demonstrated different incidence patterns in western civilized countries with overall rising incidence trends. OBJECTIVE To analyze differences in regional tumor incidence rates for TGCT and perform a trend analysis for TGCT between 2003 and 2014 in Germany. MATERIAL AND METHODS TGCT cases in Germany which were diagnosed between 2003 and 2014 were provided by the Robert-Koch-Institute, Berlin. For statistical analysis, cluster and spatial scan tests according to Kulldorff were used for cases with seminoma and non-seminoma. Results are presented in administrative districts and graphically illustrated. We performed a trend-analysis in order to evaluate age-adjusted incidence trends in Germany. Tests were two-sided with a level of significance of α=0.05. RESULTS In total we included 35,066 patients. Overall, 22,634 cases had newly diagnosed seminoma and 12,432 were diagnosed as non-seminoma. Maximum incidence of seminoma and non-seminoma was observed for age-group 38-40 years and 26-28 years, respectively. No second peak for the incidences of seminoma and non-seminoma with respect to age were observed. Cluster analysis revealed areas with high and low incidence rates as well as slightly different spatial distribution in Germany between seminoma and nonseminoma. Furthermore, there was no significant increase in age-adjusted incidence rates over the reviewed time period in both cohorts. DISCUSSION In this study differences in reginal tumor incidence rates for seminoma and non-seminoma are reported with both tumor entities revealing distinct clusters. Furthermore, tumor incidence trends for seminoma and nonseminoma between 2003 and 2014 were stable which might indicate the beginning of a plateau phase for TGCT incidence rates in Germany. CONCLUSION In this analysis we were able to identify regions with significantly higher tumor incidence rates for both seminoma and non-seminoma which were specific for these two subtypes. Furthermore, trend analysis revealed a steady incidence rate for testicular cancer in Germany.

PD-1 inhibition (PD-1i) is the standard of care in melanoma and other malignancies. In patients with bone metastases of solid tumors, the monoclonal antibody denosumab directed against RANKL is approved for the prevention of skeletal-related events. However, RANKL is not only relevant in osteoclastogenesis, but also has immunological effects. Hence, we aimed at investigating, whether the combination of PD-1i and denosumab produces synergistic effects in metastatic melanoma treatment. We retrospectively collected and analyzed clinical data of metastatic melanoma patients with bone metastases, who received PD-1i and denosumab therapy. 29 patients were identified with a median age of 60.7 years: 20 were male and 9 were female. 20 patients (69%) were in stage IV M1c and 9 (31%) in stage IV M1d; 52% had an increased serum LDH. 24 patients (83%) received PD-1i as first-line therapy and five patients (17%) as second- or third-line therapy. 13 patients received the triple combination nivolumab, ipilimumab and denosumab (N + I+D), 16 patients received PD-1i and denosumab (PD-1i + D). Within a median follow-up time of 19.8 months, 17 patients progressed with a median time to progression of 6 months. The objective response rate was 54% in the N + I + D group and 50% in the PD-1i + D group. Recalcification of bone metastases was radiologically observed in 18 (62%) patients. No unexpected treatment-related adverse events emerged. The combination therapy of metastatic melanoma with PD-1i and denosumab was feasible without unexpected safety issues and showed a promising efficacy signal. Further investigation in prospective studies is needed.

Tumors, including melanomas, frequently show an accelerated glucose metabolism. Mutations in the v-Raf murine sarcoma viral oncogene homolog B (BRAF), detected in about 50% of all melanomas, result in further enhancement of glycolysis. Therefore anti-metabolic substances might enhance the impact of RAF inhibitors. We have identified the two non-steroidal anti-inflammatory drugs (NSAIDs) diclofenac and lumiracoxib being able to restrict energy metabolism in human melanoma cells by targeting lactate release and oxidative phosphorylation (OXPHOS). In combination with the RAF inhibitor vemurafenib strong synergism was observed: Diclofenac as well as lumiracoxib increased the anti-glycolytic impact of vemurafenib and prevented RAF-inhibitor induced metabolic reprogramming towards OXPHOS. Consequently, both NSAIDs sensitized melanoma cells to vemurafenib triggered proliferation arrest and enhanced the anti-tumor effect of RAF inhibitors from cytostatic to cytotoxic. Furthermore the addition of NSAIDs delayed the onset of RAF inhibitor resistance, most likely by counteracting the upregulation of MITF. Our data suggest that selected NSAIDs could be a promising combination partner for MAPK pathway inhibitors for the treatment of BRAFV600E mutated melanomas.

Papillary renal cell carcinoma (PRCC) is currently divided in 2 subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the 2 subtypes. Three hundred seventy-six renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. Two hundred forty-six tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrophages and psammoma bodies) were noted. Immunohistochemical stains (MIB1, p53, Racemase, EMA, CK7, CK20, E-Cadherin) were performed using tissue microarrays. χ2-Tests, log-rank tests and uni- and multivariate Cox regression analysis were performed. Both subtypes displayed different morphological features and immunohistochemical profiles: abundant cytoplasm was more frequent in PRCC2, while foamy macrophages were more common in PRCC1. Abundant cytoplasm and presence of psammoma bodies were associated with poorer OS. PRCC1 showed more frequent CK7 expression, PRCC2 more frequent E-Cadherin, p53 and higher MIB1 expression (>15%). Expression of Racemase and CK7 was associated with better OS, while high MIB1 (>15%) was associated with poorer OS. In multivariate analysis, the only independent predictors of OS were proliferation (MIB1), tumor stage, metastasis and age at surgery. Subtype was not an independent prognostic factor. Therefore, PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2.

Introduction & objectives Percutaneous nephrostomy [ 1 ] has emerged as a pivotal approach in the therapeutic management of the obstructed urinary tract. A consecutive incorporation of ultrasonic and radiographic guidance, the approach experienced an almost ubiquitious distribution while most centers currently applying either one or both of these tools jointly. However, success of ultrasound-guidance is limited in obese patients and non-dilated uropathy. In turn, fluoroscopy usually requires an opacification of the urinary collecting system by intravenous or antegrade contrast media injection, which might be harmful for already impaired renal function, raise intrapelvic pressure and augment the risk of sepsis and hemorrhage. CT-guided PCN aids in overcoming these limitations. In the current study, we present the experience of a tertiary referral center with this technique. Materials & methods Epidemiological and clinical data of all patients treated with a CT-guided PCN of native kidneys at the University Hospital Frankfurt between October 2003 and October 2013 were retrospectively collected from the patient charts. Procedural parameters including radiological aspects, technical and therapeutic success, complication and mortality rate have been analyzed statistically. Results In total, 140 PCN procedures have been performed in 77 patients with a median age of 69 (± 13). The median body mass index was 27 with 66.6% of patients being overweight or obese. Charlson comorbidity index was 7 ranging 0-16. Indications for PCNs were obstructive uropathy (62.9), urine extravasation (22.9%), urinary tract fistulas (11.4%) and technical reasons (2.8%). In 68.8% of patients, initial diagnosis was malignancy. 56.4% of kidneys were non-dilated before puncture. In 78.4% prone position, otherwise supine oblique position (17.3%) or supine position (4.3%) was used. 71.4% of PCNs were carried out solely under local anesthesia. Technical success has been achieved in 90% with a complication rate of 3.6% (all grade minor B) and was not significantly different between dilated and non-dilated kidneys. 42.9% of fistulas and 64.3% of urinary tract leakages, healed after PCN placement. 30 days mortality rate was 5.2% without being directly associated with the PCN procedure itself. Conclusion CT-guided PCN is a feasible approach associated with low morbidity. It is particularly useful in complex clinical scenarios e.g. critically ill, newly operated or obese patients as well as non-dilated kidneys. Moreover, it represents a minimally-invasive option for treating leakages and fistulas of the urinary tract.

OBJECTIVES: To investigate the safety of robotic surgery during COVID-19 pandemic concerning new-acquired COVID-19 infections for patients and healthcare workers. PATIENTS: We performed a retrospective single-centre cohort study of patients undergoing robotic surgery in initial period of COVID-19 pandemic. Patients and Healthcare workers COVID-19 infection status was assessed by structured telephone follow-up and/or repeated nasopharyngeal swabs. RESULTS: After 61 robotic surgeries (93,5% cancer surgery), 1 patient (1.6%) had COVID-19 infection. 60 healthcare workers cumulatively exposed to 1,187 hours of robotic surgery had no infection. One patient with postoperative proof of SARS-CoV-2 had complete recovery. After this potentially contagious robotic surgery, 8 healthcare workers had no COVID-19 infection after follow-up with each 3 nasopharyngeal swabs. CONCLUSIONS: Early clinical experience of robotic surgery during COVID-19 pandemic shows that robotic surgery can be safely performed for patients and healthcare workers. Despite our results we recommend elective surgery only for verified COVID-19 negative patients. This article is protected by copyright. All rights reserved.

Background One prominent application for deep learning–based classifiers is skin cancer classification on dermoscopic images. However, classifier evaluation is often limited to holdout data which can mask common shortcomings such as susceptibility to confounding factors. To increase clinical applicability, it is necessary to thoroughly evaluate such classifiers on out-of-distribution (OOD) data. Objective The objective of the study was to establish a dermoscopic skin cancer benchmark in which classifier robustness to OOD data can be measured. Methods Using a proprietary dermoscopic image database and a set of image transformations, we create an OOD robustness benchmark and evaluate the robustness of four different convolutional neural network (CNN) architectures on it. Results The benchmark contains three data sets—Skin Archive Munich (SAM), SAM-corrupted (SAM-C) and SAM-perturbed (SAM-P)—and is publicly available for download. To maintain the benchmark's OOD status, ground truth labels are not provided and test results should be sent to us for assessment. The SAM data set contains 319 unmodified and biopsy-verified dermoscopic melanoma (n = 194) and nevus (n = 125) images. SAM-C and SAM-P contain images from SAM which were artificially modified to test a classifier against low-quality inputs and to measure its prediction stability over small image changes, respectively. All four CNNs showed susceptibility to corruptions and perturbations. Conclusions This benchmark provides three data sets which allow for OOD testing of binary skin cancer classifiers. Our classifier performance confirms the shortcomings of CNNs and provides a frame of reference. Altogether, this benchmark should facilitate a more thorough evaluation process and thereby enable the development of more robust skin cancer classifiers.

Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer. Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.

Background Sleep apnoea and type 2 diabetes (T2D) have been linked to malignancy. The aim of the present study was to evaluate the association between sleep apnoea and incidence of malignancy in patients with T2D. Methods The DIACORE (DIAbetes COhoRtE) study is a prospective, population-based cohort study in T2D patients. In the sleep disordered breathing substudy, the apnoea–hypopnoea index (AHI), oxygen desaturation index (ODI) and percentage of night-time spent with a peripheral oxygen saturation of, In patients with type 2 diabetes, sleep apnoea is not associated with the incidence of malignancy. However, stratified analysis shows that sleep apnoea is associated with incident malignancy in females, but not in males. https://bit.ly/37RAK8V

Treatment of advanced melanoma with combined PD-1/CTLA-4 blockade commonly causes serious immune-mediated complications. Here, we identify a subset of patients predisposed to immune checkpoint blockade-related hepatitis who are distinguished by chronic expansion of effector memory CD4+ T cells (TEM cells). Pre-therapy CD4+ TEM cell expansion occurs primarily during autumn or winter in patients with metastatic disease and high cytomegalovirus (CMV)-specific serum antibody titres. These clinical features implicate metastasis-dependent, compartmentalised CMV reactivation as the cause of CD4+ TEM expansion. Pre-therapy CD4+ TEM expansion predicts hepatitis in CMV-seropositive patients, opening possibilities for avoidance or prevention. 3 of 4 patients with pre-treatment CD4+ TEM expansion who received αPD-1 monotherapy instead of αPD-1/αCTLA-4 therapy remained hepatitis-free. 4 of 4 patients with baseline CD4+ TEM expansion given prophylactic valganciclovir and αPD-1/αCTLA-4 therapy remained hepatitis-free. Our findings exemplify how pathogen exposure can shape clinical reactions after cancer therapy and how this insight leads to therapeutic innovations., Checkpoint blocking therapies are used to treat metastatic melanoma, but can have adverse immune-mediated effects, including liver pathology. Here the authors identify an expanded pool of CD4+ effector memory T cells resulting from prior CMV exposure as a risk factor for this adverse effect in these patients.

Introduction Malignant melanoma is an aggressive skin tumor with a good prognosis when treated in an early tumor stage, but has a poor prognosis with distant metastases. The incidence of malignant melanoma has increased continuously over the last decades, with little change in mortality. One explanation for this is that melanomas are increasingly detected in early stages, especially after the establishment of statutory skin cancer screening in 2008, which allows a free skin examination every 2 years for people older than 35 years. Methods In this study incidence and mortality of malignant melanoma were correlated with the dermatologist density in Bavarian administrative regions. In addition, the incidence data were compared before and after the introduction of statutory skin cancer screening. Results There was a significant correlation between the incidence of malignant melanoma and dermatologist density (r = 0.258, p = 0.044), but no correlation between mortality and dermatologist density (r = 0.201, p = 0.121). Similarly, the increase of malignant melanoma incidence following the introduction of statutory skin cancer screening in 2008 was independent of dermatologist density (r = 0.021, p = 0.873). Conclusion The dermatologist density in Bavaria correlates positively with the incidence of malignant melanoma. Despite an increased incidence, mortality was not elevated in the respective administrative regions.

Introduction Cutaneous melanoma is notorious for the development of in-transit metastases (ITM). For unknown biological reasons, ITM remain the leading tumour manifestation without progression to distant sites in some patients. Methods In total, 191 patients with initially unresectable stage III ITM and satellite metastases from 16 skin cancer centres were retrospectively evaluated for their tumour characteristics, survival and therapy response. Three groups according to disease kinetics (no distant progress, slow (>6 months) and fast ( Results Median follow-up time was 30.5 (range 0.8–154.0) months from unresectable ITM. Progression to stage IV was observed in 56.5% of cases. Patients without distant metastasis were more often female, older (>70 years) and presented as stage III with lymph node or ITM at initial diagnosis in 45.7% of cases. Melanoma located on the leg had a significantly better overall survival (OS) from time of initial diagnosis compared to non-leg localised primaries (hazard ratio [HR] = 0.61, 95% confidence interval [CI] 0.40–0.91; p = 0.017), but not from diagnosis of unresectable stage III (HR = 0.67, 95% CI 0.45–1.02; p = 0.06). Forty percent of patients received local therapy for satellite and ITM. Overall response rate (ORR) to all local first-line treatments was 38%; disease control rate (DCR) was 49%. In total, 72.3% of patients received systemic therapy for unresectable stage IIIB-D. ORR for targeted therapy (n = 19) was highest with 63.2% and DCR was 84.2% compared to an ORR of 31.4% and a DCR of 54.3% in PD-1 treated patients (n = 70). Patients receiving PD-1 and intralesional talimogene laherparepvec (n = 12) had an ORR of 41.7% and a DCR of 75%. Conclusion Patients with unresectable ITM and without distant progression are more often female, older, and have a primary on the leg. Response to PD-1 inhibitors in this cohort was lower than expected, but further investigation is required to elucidate the biology of ITM development and the interplay with the immune system.

Journal of medical internet research 23(2), e23436 (2021). doi:10.2196/23436, Published by Healthcare World, Richmond, Va.