Follow-up care over 12months of patients with prostate cancer in Spain. A multicenter prospective cohort study

This study was funded by an Instituto de Salud Carlos III (ISCIII) Grant PS09/01204 (Fondo de Investigación Sanitaria [FIS], Spain). Dr María José Martinez Zapata is funded by a Miguel Servet II research contract from the ISCIII (CP1120/00023). ISCIII had any role in the design or execution of the study; in the data collection, management, or interpretation; or in the writing, reviewing, or approval of the manuscript.Ailish Maher and Andrea Cervera Alepuz revised the English in a version of this manuscript. Maria José Martinez Zapata is funded by a Miguel Servet research contract (CPII20/00023). EMPARO Study Group: Coordinating investigator: Xavier Bonfill Cosp (Iberoamerican Cochrane Centre, Public Health and Clinical Epidemiology Service, Hospital de la Santa Creu i Sant Pau, IIB Sant Pau, Barcelona, Spain). Project manager: María José Martínez Zapata (Iberoamerican Cochrane Centre, IIBSant Pau, Barcelona, Spain). Clinical research assistants: Alborada Martínez (Universidad de Valencia); Enrique Morales Olivera (Escuela Andaluza de Salud Publica, Granada, Spain); Esther Canovas, Laura Muñoz, Gemma Mas, René Acosta, Ekaterina Popova (Iberoamerican Cochrane Centre, IIB Sant Pau, Barcelona, Spain); Irma Ospina (Hospital 12 de Octubre, Madrid, Spain); María José Velázquez (Hospital Donostia, Donostia, Spain); Tamara Ruiz Merlo (Hospital Ramón y Cajal, Madrid, Spain); Gael Combarros Herman, Judit Tirado Muñoz (IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain). Statistical analysis: Robin W.M. Vernooij (Iberoamerican Cochrane Centre, IIB Sant Pau, Barcelona, Spain); Javier Zamora and Claudia Coscia Requena (Hospital Ramón y Cajal, Madrid, Spain). Co-investigators: Barcelona, Spain Albert Frances (Hospital del Mar); Carola Orrego Villagran, Rosa Suñol (Instituto Universitario Avedis Donabedian); Dimelza Osorio, Gemma Sancho Pardo, Ignasi Bolívar, José Pablo Maroto, María Jesus Quintana, Cristina Martin (Hospital de la Santa Creu i Sant Pau); Ferran Algaba, Palou Redorta, Salvador Esquena (Fundació Puigvert); Jordi Bachs (Fundació Privada Hospital de la Santa Creu i Sant Pau); María José Martínez Zapata (Iberoamerican Cochrane Centre, IIB Sant Pau); Montserrat Ferrer Fores, Stefanie Schmidt, Olatz Garin, Virginia Becerra Bachito, Yolanda Pardo (IMIM-Hospital del Mar Medical Research Institute). Bilbao, Spain Amaia Martínez Galarza, José Ignacio Pijoán Zubizarreta (Hospital Universitario Cruces/BioCruces Health Research Institute). Granada, Spain Armando Suárez Pacheco, Cesar García López, José Manuel Cozar Olmo (Hospital Universitario Virgen de las Nieves); Carmen Martínez, Daysy Chang Chan, María José Sánchez Pérez (Escuela Andaluza de Salud Publica). Madrid, Spain Ana Isabel Díaz Moratinos, Angel Montero Luis, Asunción Hervás, Carmen Vallejo Ocaña, Costantino Varona, Javier Burgos, Javier Zamora, Jose Alfredo Polo Rubio, Luis López Fando Lavalle, Miguel Angel Jimenez Cidre, Muriel García, Alfonso, Nieves Plana Farras, Rosa Morera Lopez, Sonsoles Sancho Garcia, Victor Abraira, Victoria Gomez Dos Santos (Hospital Ramón y Cajal); Agustín Gómez de la Cámara, Javier de la Cruz, Juan Passas Martínez, Humberto García Muñoz, María Ángeles Cabeza Rodríguez (Hospital 12 de Octubre). San Sebastián, Spain Irune Ruiz Díaz, José Ignacio Emparanza, Juan Pablo Sanz Jaka (Hospital Universitario Donostia). Valencia, Spain Agustín Llopis González, María Morales (Universidad de Valencia); Carlos Camps, Cristina Caballero Díaz, Emilio Marqués Vidal, Francisco Sánchez Ballester, Joaquín Ulises Juan Escudero, Jorge Pastor Peidro, José López Torrecilla, María Macarena Ramos Campos, Miguel Martorell Cebollada (Consorcio Hospital General Universitario de Valencia).The therapeutic approach is crucial to prostate cancer prognosis. We describe treatments and outcomes for a Spanish cohort of patients with prostate cancer during the first 12 months after diagnosis and identify the factors that influenced the treatment they received. This multicenter prospective cohort study included patients with prostate cancer followed up for 12 months after diagnosis. Treatment was stratified by factors such as hospital, age group (<70 and ≥70 years), and D’Amico cancer risk classification. The outcomes were Eastern Cooperative Oncology Group (ECOG) performance status, adverse events (AEs), and mortality. The patient characteristics associated with the different treatment modalities were analyzed using multivariate logistic regression. We included 470 men from 7 Spanish tertiary hospitals (mean (standard deviation) age 67.8 (7.6) years), 373 (79.4%) of which received treatment (alone or in combination) as follows: surgery (n = 163; 34.7%); radiotherapy (RT) (n = 149; 31.7%); and hormone therapy (HT) (n = 142; 30.2%). The remaining patients (n = 97) were allocated to no treatment, that is, watchful waiting (14.0%) or active surveillance (5.7%). HT was the most frequently administered treatment during follow-up and RT plus HT was the most common therapeutic combination. Surgery was more frequent in patients aged <70, with lower histologic tumor grades, Gleason scores <7, and lower prostate-specific antigen levels; while RT was more frequent in patients aged ≥70 with histologic tumor grade 4, and higher ECOG scores. HT was more frequent in patients aged ≥70, with histologic tumor grades 3 to 4, Gleason score ≥8, ECOG ≥1, and higher prostate-specific antigen levels. The number of fully active patients (ECOG score 0) decreased significantly during follow-up, from 75.3% at diagnosis to 65.1% at 12 months (P < .001); 230 (48.9%) patients had at least 1 AE, and 12 (2.6%) patients died. Surgery or RT were the main curative options. A fifth of the patients received no treatment. Palliative HT was more frequently administered to older patients with higher tumor grades and higher Gleason scores. Close to half of the patients experienced an AE related to their treatment.Instituto de Salud Carlos III CP1120/00023, PS09/0120

Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tightjunction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.CTS-115 Tissue Engineering Group and by the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministry of Science and Innovation, Instituto de Salud Carlos III, grant FIS PI21/0981 (cofinanced by FEDER funds, European Union)

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma

The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p <= 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p <= 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.Ministry of Health, Andalusia Government Leonardo de la Pena 2020 research grant - Urology Research Foundation (FIU) PI-0319-201

Clinical Benefit of Tamsulosin and the Hexanic Extract of Serenoa Repens, in Combination or as Monotherapy, in Patients with Moderate/Severe LUTS-BPH: A Subset Analysis of the QUALIPROST Study

To investigate whether tamsulosin (TAM) and the hexanic extract of Serenoa repens (HESr) are more effective in combination than as monotherapy in men with moderate-to-severe lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Subset analysis of data from a 6-month, multicenter observational study. Patients received either tamsulosin (0.4 mg/day) or HESr (320 mg/day) alone or in combination. Primary endpoints were change in symptoms and quality of life. Tolerability was also assessed. Seven hundred and nine patients were available for intention to treat (ITT) analysis, 263 treated with tamsulosin, 262 with HESr, and 184 with TAM + HESr. After 6 months, International Prostate Symptom Score (IPSS) scores improved by a mean (standard deviation) of 7.2 (5.0) points in the TAM + HESr group compared to 5.7 (4.3) points with TAM alone and 5.4 (4.6) points with HESr (p < 0.001). Quality of life showed greatest improvement with combination therapy (p < 0.02). Adverse effects were reported by 1.9% of patients receiving HESr, 13.3% receiving TAM, and 12.0% receiving TAM + HESr (p < 0.001). In men with moderate/severe LUTS/BPH, combination treatment with TAM + HESr produced more effective symptom relief and greater improvement in quality of life than with either treatment alone, with acceptable tolerability

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer:A Population-Based Case-Control Study and Meta-Analysis

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTOrs9939609A, HNF1Brs7501939T, HNF1Brs757210T, HNF1Brs4430796G, and JAZF1rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10−5, p = 9.39 × 10−54, p = 5.04 × 10−54, p = 1.19 × 10−71, and p = 1.66 × 10−18, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2rs10923931T and RBMS1rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10−4 and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic com-pounds. In addition to these results, eQTL analysis revealed that the HNF1Brs7501939, HNF1Brs757210, HNF1Brs4430796, NOTCH2rs10923931, and RBMS1rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Exploring the Effect of Training in Visual Block Programming for Preservice Teachers

This study evaluates the effectiveness of visual block programming-based instruction and its possibilities in the training of future teachers. In particular, the application Scratch, a visual programming environment, was employed to introduce pre-service teachers to programming. The study followed a mixed-method design with a sample of 79 pre-service teachers. A quantitative approach was used to evaluate the gains in the participants&rsquo; knowledge of computational concepts and attitudes towards Scratch as a pedagogic tool. A qualitative analysis aimed at evaluating the participants&rsquo; knowledge concerning programming applications, and their perception about possible difficulties in the implementation of programming in educational contexts. Positive results were obtained for programming in the classroom, with significant improvements in innovation, collaboration, active learning, motivation, and fun for the students. After the experiment, the subjects highlighted Scratch as a fundamental block programming tool and the need for teacher training in this field. The need to improve the implementation of visual block programming in Education Degree curricula is supported

Gouty Tophi in the Penis: A Case Report and Review of the Literature

Gout is a metabolic disease characterized by hyperuricemia and the deposition of monosodium urate crystals in different anatomical locations. We report the case of a 61-year-old man who received consultation for gouty tophi in the penis, which is an unusual location for this type of pathology, that was resolved with the surgical removal of the tophi. We provide a review on gout and its treatment as well as other locations where atypical gouty tophi have been described