Precave: Immediate neoadjuvant instillation of chemotherapy for the prevention of non-muscle invasive bladder carcinoma recurrence: A prospective randomized clinical trial protocol

Introduction and objectives: Recurrence rates for patients presenting with non-muscle invasive bladder carcinoma (NMIBC) can be as high as 60% during the first year after a transurethral resection of bladder tumor (TURBT). Currently, an immediate postoperative instillation of chemotherapy (IPOIC) is recommended for the prevention of recurrences in patients with low to intermediate risk disease. Although in real clinical practice this specific instillation of chemotherapy has many difficulties to be standardized, including its contraindications (suspected or confirmed bladder perforation, wide or extensive resection and, continuous bladder irrigation requirement), which will only make it feasible for around 30% of patients. We propose in this controlled study, to administer an immediate neoadjuvant instillation of chemotherapy (INAIC), which can be applied technically to all patients, no matter the surgical outcomes and compare it with a control group. We expect to find a reduction in the recurrence rate in the experimental group of at least 15%. Methods: We designed a phase IV, randomized, controlled, open label clinical trial. Main inclusion criteria are: patients with a clinical diagnosis of localized, papillary-type bladder cancer (suspected low to intermediate risk) with a disease-free interval of at least 6 months. Eligible patients will be allocated into group A (INAIC plus TURBT) or group B (TURBT) using a computer-generated block randomization sequence/ratio 1:1. Time to recurrence of both groups will be analyzed and compared using Kaplan- Meier estimates, log-rank tests and, Cox-regression. Univariate and multivariate analyzes will be performed to determine factors which influence recurrence. The study has received the approval of the Ethics Committee for Drug Research (CEIm) of La Paz University Hospital and the Spanish Agency for Medicines and Health ProductsThis study received funding from grants ‘‘Rafael Molla y Rodrigo” from the Foundation for Research in Urology (Spanish Urological Association) and Immunothercan-CM(B2017/BM D3733) from the Local Government of the Community of Madrid, Madrid, Spain

Invasive management of renal cell carcinoma in von hippel-lindau disease

Introduction Patients affected by von Hippel-Lindau (VHL) disease experience an increased risk for bi-lateral, synchronous, and metachronous renal cell carcinoma (RCC). Oncologic and functional outcomes are the main goals in the management of renal masses. We present our protocol for patients with VHL disease-associated RCC alongside functional and oncologic results observed in our series. Material and methods We performed a retrospective analysis of our clinical database of patients with VHL disease-associated RCC referred to our department between June 2005 and December 2017. We offer surveillance for lesions <2 cm and active management with radiofrequency ablation (RFA) for lesions 2–3 cm, and nephron-sparing surgery (NSS), RFA or embolization techniques for lesions >3 cm or growth rate >1 cm/year. Results Our series comprises 14 patients, of whom 13 had undergone at least one invasive procedure for RCC, mean age at first intervention was 27 years (range 18–60). Overall, 30 interventions were performed in 21 kidneys: four radical nephrectomies, 13 RFAs, 12 NSSs, and one embolization. During follow-up (median time: 41 months, range: 6–149), eight patients (57%) presented with new lesions that required treatment, with a mean time between treatments of 32 ±18.5 months. No metastatic progression or need for dialysis was recorded; the success rate for RFA was 85%. Conclusions Management of VHL kidney disease by NSS is the standard of care with a cut-off at 3 cm, ablative procedures should be offered to lesions ranging 2–3 cm in size. Follow-up should be done strictly in referral centers that can provide all treatment options to renal function and control oncologic progression.This research was funded by Madrid Regional Government Research Grant [S2010/BMD-2326 IMMUNOTHERCAN-CM (B2017/BMD-3733)/FEDE

The effect of neoadjuvant chemotherapy among patients undergoing radical cystectomy for variant histology bladder cancer: A systematic review

Objective: To systematically review the evidence about the effect of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) with pure urothelial carcinoma (pUC) in radical cystectomy (RC) candidates affected by variant histology (VH) bladder cancer. Methods: A review of the current literature was conducted through the Medline and National Center for Biotechnology Information (NCBI) PubMed, Scopus databases in May 2020. The updated Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed for this systematic review. Keywords used were ‘bladder cancer’, ‘bladder carcinoma’, ‘bladder tumour’ and ‘bladder cancer variants’ and ‘neoadjuvant chemotherapy’. Only original articles in English published after 2000 and reporting oncological outcomes a series of more than five patients with VH were included. We excluded series in which the oncological outcomes of patients with pUC and VH were undistinguishable. Results: The literature search identified 2231 articles. A total of 51 full-text articles were assessed for eligibility, with 17 eventually considered for systematic review, for a cohort of 450,367 patients, of which 5010 underwent NAC + RC. The median age at initial diagnosis ranged from 61 to 71 years. Most patients received cisplatin-gemcitabine, methotrexate-vinblastine-adriamycin-cisplatin, or carboplatin-based chemotherapy. Only one study reported results of neoadjuvant immunotherapy. The median follow-up ranged from 1 to 120 months. The results showed that squamous cell carcinoma (SCC) is less sensitive to NAC than pUC and that SCC predicts poorer prognosis. NAC was found to be a valid approach in treating small cell carcinoma and may have potential benefit in micropapillary carcinoma. Conclusions: NAC showed the best oncological outcomes in small cell variants and micropapillary carcinoma, while NAC survival benefit for SCC and adenocarcinoma variants needs further studies. Drawing definite considerations on the efficacy of NAC in VH is complicated due to the heterogeneity of present literature. Present results need to be confirmed in randomised controlled trial

Pinning of stripes by local structural distortions in cuprate high-Tc superconductors

We study the spin-density wave (stripe) instability in lattices with mixed low-temperature orthorhombic (LTO) and low-temperature tetragonal (LTT) crystal symmetry. Within an explicit mean-field model it is shown how local LTT regions act as pinning centers for static stripe formation. We calculate the modulations in the local density of states near these local stripe regions and find that mainly the coherence peaks and the van Hove singularity (VHS) are spatially modulated. Lastly, we use the real-space approach to simulate recent tunneling data in the overdoped regime where the VHS has been detected by utilizing local normal state regions.Comment: Conference proceedings for Stripes1

Concomitant bladder tumor is a risk factor for bladder recurrence but not upper tract

Objective: To evaluate the clinical outcomes of UTUC patients with or without concurrent bladder tumor. Design, Setting, and Participants: The Clinical Research Office of the Endourology Society-Urothelial Carcinomas of the Upper Tract (CROES-UTUC) Registry included 1134 UTUC patients with or without concurrent bladder tumor treated between 2014 and 2019. Results: In 218 (19.2%) cases, concurrent bladder tumor was present, while in 916 (80.8%) patients, no bladder cancer was found. In the multivariable Cox regression analysis, concomitant bladder tumor (hazard ratio (HR) 1.562, 95% confidence interval (CI) 0.954-2.560, p = 0.076) indicated a trend associated with recurrence-free survival for UTUC. Further data dissection confirmed that concomitant bladder tumor is a risk factor of bladder recurrence (HR 1.874, 95% CI 1.104-3.183, p = 0.020) but not UTUC recurrence (HR 0.876, 95% CI 0.292-2.625, p = 0.812). Kidney-sparing surgery (KSS) (HR 3.940, 95% CI 1.352-11.486, p = 0.012), pathological T staging >= pT2 (HR 2.840, 95% 1.039-7.763, p = 0.042) were significantly associated with UTUC recurrence. KSS does not affect bladder recurrence (HR 0.619, 95% CI 0.242-1.580, p = 0.315). A limitation is the retrospective nature of the present study analysis. Conclusions: The presence of concomitant bladder tumor does not increase risk of UTUC recurrence, but it results in an increased risk of bladder recurrence. KSS does not affect bladder recurrence and can still be considered in patients with concomitant bladder tumor

Effects of impurities and vortices on the low-energy spin excitations in high-Tc materials

We review a theoretical scenario for the origin of the spin-glass phase of underdoped cuprate materials. In particular it is shown how disorder in a correlated d-wave superconductor generates a magnetic phase by inducing local droplets of antiferromagnetic order which eventually merge and form a quasi-long range ordered state. When correlations are sufficiently strong, disorder is unimportant for the generation of static magnetism but plays an additional role of pinning disordered stripe configurations. We calculate the spin excitations in a disordered spin-density wave phase, and show how disorder and/or applied magnetic fields lead to a slowing down of the dynamical spin fluctuations in agreement with neutron scattering and muon spin rotation (muSR) experiments.Comment: 4 pages, 3 figures, submitted for SNS2010 conference proceeding

Competències i habilitats transversals entre geologia i arqueologia prehistòrica

En aquest treball es desenvolupa una proposta concreta per abordar alguns dels objectius pedagògics, com ara la transversalitat, el treball en equip o la necessitat d'incrementar els coneixements pràctics. La perspectiva des de la que s'ha realitzat ha estat la de la col·laboració interdisciplinària entre docents universitaris que treballen en dos àmbits científics ben diferents: geologia i arqueologia prehistòrica.S'ha desenvolupat una eina pedagògica on els estudiants poden desenvolupar habilitats i capacitats com les esmentades a partir del seguiment d'un cas d'estudi concret: la determinació i procedència dels elements petris utilitzats en la construcció del sepulcre megalític de Puigseslloses (Osona). La proposta es basa en el seguiment i la participació dels estudiants en tot el procés de la recerca: el plantejament del problema historicoarqueològic, la definició de les vies d'estudi concretes, el seu desenvolupament, l'obtenció de resultats i la seva discussió interdisciplinària.En este trabajo se desarrolla una propuesta concreta para abordar algunos de los objetivos pedagógicos, como la transversalidad, el trabajo en equipo o la necesidad de incrementar los conocimientos prácticos. La perspectiva desde la que se ha realizado ha sido la de la colaboración interdisciplinaria entre docentes universitarios que trabajan en dos ámbitos científicos bien distintos: Geología y Arqueología Prehistórica. Se ha desarrollado una herramienta pedagógica a través de la cual los estudiantes pueden desarrollar habilidades y capacidades como las mencionadas a partir del seguimiento de un caso de estudio concreto: la determinación y procedencia de los elementos pétreos utilizados en la construcción del sepulcro megalítico de Puigseslloses (Osona). La propuesta se basa en que los estudiantes sigan y participen en todo el proceso de la investigación, desde el planteamiento del problema histórico-arqueológico, la definición de las vías de estudio concretas, su desarrollo y la obtención de resultados, hasta su discusión interdisciplinaria.This study develops a specific proposal for addressing some of the educational goals of the EHEA such as transversality, teamwork and the need to increase practical knowledge. The perspective from which the study was conducted was interdisciplinary cooperation among university professors who work in two quite different fields of science: geology and prehistoric archaeology. A pedagogical tool was developed in which students can develop skills and abilities such as the ones mentioned above by pursuing a specific case study: the description and provenance of stone elements used to build the megalithic sepulchre in Puigseslloses (Osona). The proposal is based on students' following and participating in the entire research process: posing the historical-archaeological problem, defining the specific avenues of study, conducting the study, getting the results and holding an interdisciplinary discussion of these results

Impact of COVID-19 on medical education: Introducinghomo digitalis

Purpose To determine how members of the Societe Internationale d'Urologie (SIU) are continuing their education in the time of COVID-19. Methods A survey was disseminated amongst SIU members worldwide by email. Results were analyzed to examine the influence of age, practice region and settings on continuing medical education (CME) of the respondents. Results In total, 2494 respondents completed the survey. Internet searching was the most common method of CME (76%; allps = 2 platforms, with approximately 10% of the respondents using up to 5 different platforms. Urologists < 40 years old were more likely to use online literature (69%), podcasts/AV media (38%), online CME courses/webinars (40%), and social media (39%). There were regional variations in the CME modality used but no significant difference in the number of methods by region. There was no significant difference in responses between urologists in academic/public hospitals or private practice. Conclusion During COVID-19, urologists have used web-based learning for their CME. Internet learning and literature were the top frequently cited learning methods. Younger urologists are more likely to use all forms of digital learning methods, while older urologists prefer fewer methods

Radical penectomy, a compromise for life. Results from the PECAD study

Background: The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15-20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients. Methods: Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital “Sant'Andrea”, Sapienza University, Roma, Italy; “G.D'Annunzio” University, Chieti and ASL 2 Abruzzo, Hospital “S. Pio da Pietrelcina”, Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital “Spedali Civili”, Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena &amp; Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS. Results: Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5-73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1-3 and 5 (6.9%) M1. Furthermore, 61 (84.7%) had a high grade (G2-G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%. Conclusions: PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment

Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set

We combine the results of searches for the standard model Higgs boson based on the full CDF Run II data set obtained from sqrt(s) = 1.96 TeV p-pbar collisions at the Fermilab Tevatron corresponding to an integrated luminosity of 9.45/fb. The searches are conducted for Higgs bosons that are produced in association with a W or Z boson, have masses in the range 90-150 GeV/c^2, and decay into bb pairs. An excess of data is present that is inconsistent with the background prediction at the level of 2.5 standard deviations (the most significant local excess is 2.7 standard deviations).Comment: To be published in Phys. Rev. Lett (v2 contains minor updates based on comments from PRL