Background: Local cancer therapy by combining real-time surgical exploration and resection with delivery of a single dose of high-energy electron irradiation entails a very precise and effective local therapeutic approach. Integrating the benefits from minimally invasive surgical techniques with the very precise delivery of intraoperative electron irradiation results in an efficient combined modality therapy. Methods: Patients with locally advanced disease, who are candidates for laparoscopic and/or thoracoscopic surgery, received an integrated multimodal management. Preoperative treatment included induction chemotherapy and/or chemoradiation, followed by laparoscopic surgery and intraoperative electron radiation therapy. Results: In a period of 5 consecutive years, 125 rectal cancer patients were treated, of which 35% underwent a laparoscopic approach. We found no differences in cancer outcomes and tolerance between the open and laparoscopic groups. Two esophageal cancer patients were treated with IOeRT during thoracoscopic resection, with the resection specimens showing intense downstaging effects. Two oligo-recurrent prostatic cancer patients (isolated nodal progression) had a robotic-assisted surgical resection and post-lymphadenectomy electron boost on the vascular and lateral pelvic wall. Conclusions: Minimally invasive and robotic-assisted surgery is feasible to combine with intraoperative electron radiation therapy and offers a new model explored with electron-FLASH beams.

Objetivos Evaluar los resultados de la prostatectomía radical asistida por robot (PRAR), y compararlos con los de la cirugía abierta (PRA) y laparoscópica (PRL). El interés no solo radica en los resultados oncológicos y funcionales de la serie, sino en la evaluación de la calidad de vida (QoL), la recuperación postoperatoria y la satisfacción personal de los pacientes con la intervención (PR), fundamentalmente. Métodos Se realizaron 685 PR en nuestro centro entre 2011-2018 (17,8% PRA, 22,2% PRL y 60% PRAR). Los pacientes fueron evaluados prospectivamente mediante seguimiento hasta abril de 2020, y con la realización un cuestionario múltiple a los 12 meses post-PR, que incluía ICIQ-SF, SHIM, IPSS, IQL y preguntas sobre el dolor, la recuperación postoperatoria y la satisfacción del paciente (SP). También se recogieron datos basales y postoperatorios relacionados con el paciente y el tratamiento, y se realizaron regresiones logísticas binomiales para las comparaciones 1 vs. 1 (PRA vs. PRAR y PRL vs. PRAR). Resultados Los pacientes tratados con PRAR tienen en general menos comorbilidades, menos agresividad tumoral, un requerimiento de mayor tiempo operatorio y un número mayor de márgenes quirúrgicos positivos que los pacientes tratados con PRA y PRL. Sin embargo, la PRAR supera a la PRA en: días de estancia hospitalaria (OR: 0,86; IC 95%: 0,80-0,94), disminución de hemoglobina (OR: 0,38; IC 95%: 0,30-0,47), tasas de transfusión (OR: 0,18; IC 95%: 0,09-0,34), complicaciones tempranas (p = 0,001), IQL (OR: 0,82; IC 95%: 0,69-0,98), función eréctil (OR: 0,41; IC 95%: 0,21-0,79), manejo del dolor (OR: 0,82; IC 95%: 0,75-0,89), recuperación postoperatoria (p < 0,001) y elección de un abordaje diferente (OR: 5,55; IC 95%: 3,14-9,80). La PRAR es superior a la PRL en: continencia urinaria (OR: 0,55; IC 95%: 0,37-0,82), IPSS (OR: 0,96; IC 95%: 0,93-0,98), IQL (OR: 0,76; IC 95%: 0,66-0,88), función eréctil (OR: 0,52; IC 95%: 0,29-0,93), recuperación posquirúrgica (p = 0,02 y 0,004), PS (p = 0,005; 0,002; y 0,03) y elección de un abordaje diferente (OR: 7,79; IC 95%: 4,63-13,13). Conclusiones Los hallazgos de nuestro estudio respaldan la efectividad de la PRAR sobre la PRL y/o la PRA de manera global, tanto en factores funcionales, como en la recuperación postoperatoria, la QoL y la PS. Los resultados oncológicos aún deben ser mejorados.

Background: Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients. Methods: Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays. Results: All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patient¿ presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine ...

Aims To identify the definition for urinary continence (UC) after radical prostatectomy (RP) which reflects best patients' perception of quality of life (QoL). Methods Continence was prospectively assessed in 634 patients, 12 months after RP using the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) and the number of pads employed in a 24-hour period (pad usage). We used the one-way ANOVA technique with posthoc pairwise comparisons according to Scheffe's method (homogeneous subsets) for assessing the degree of QoL deficit related to urinary incontinence (UI). Results The continence prevalence is 64.4%, 74.1%, 88.3%, and 35.8% using "0 pads," "1 safety pad," "1 pad," and "ICIQ score 0" definitions, respectively. Pad usage is moderately strongly associated with ICIQ 1, 2, and 3 (rho = 0.744, 0.677, and 0.711, respectively; p < 0.001). Concordance between classical UC definitions is acceptable between "0 pads-ICIQ score 0" (K = 0.466), but poor for "1 safety pad" and "1 pad" (K = 0.326 and 0.137, respectively). Patients with "0 pad usage" have better QoL related to urine leakage than patients with "1 safety pad" or "1 pad" (1.41 vs. 2.44 and 3.11, respectively; p < 0.05). There were no significant differences found regarding QoL between patients with ICIQ score 0 and ICIQ score 2 (1.01 vs. 1.63; p = 0.63). Conclusions Pad usage and the ICIQ-SF's answers provide useful information. We propose a combined definition (0 pads and ICIQ score <= 2) as it is the definition with the least impact on daily QoL.

Introduction: Due to the absence of specific instruments to study the psychosocial sphere of patients undergoing extracorporeal shock wave lithotripsy (SWL), the objective of this study is to develop a satisfaction questionnaire regarding the SWL treatment from a health questionnaire which was already designed and had been previously validated. Material and methods: The design of the satisfaction questionnaire was carried out in 5 phases, based on a previously validated health scale in patients treated with SWL (ESPTL), including a total cohort of 135 patients treated at our center who received a phone interview. Phase 1: descriptive analysis of the series and scores of the 8 items of ESPTL. Phase 2: U-Mann Whitney comparison of ESPTL based on the patients' sex. Phase 3: study of ESPTL correlation with age using Spearman's Rho. Phase 4: grouping by factors of ESPTL, comparison by sex and correlation with age, as performed in phases 2 and 3 with the global score. Phase 5: obtaining the satisfaction subscate -SATISLIT-, descriptive analysis, comparison according to sex, correlation with age and linear regression model of SATISLIT with respect to ESPTL. Results: 135 patients, 85(63%) men, 50(37%) women. Median (minimum-maximum) age 56 (27-79) and ESPTL score 31 (8-39). Differences in global ESPTL score between men and women (p <.001), as well as in items 1 (p =.029), 3 (p =.002), 6 (p =.006), 7 (p =.005) and 8 (p =.025). Non-significant correlation of ESPTL regarding age. Significant correlation in items 2, 4, 5 and 8 but, very weak (<0.2). 4 factors, each one with 2 items, with statistically significant differences regarding sex in F2 (p =.001), F3 (p =.007) and F4 (p =.001). Significant correlation with age only in F1 and F3, but very weak (<0.2). Median (minimum-maximum) SATISLIT 18 (4-20). Statistically significant differences regarding patients' sex (p =.001). Non- significant correlation with age (p =.836). Significant linear regression of SATISLIT with respect to ESPTL (p <.001). Conclusions: Based on validated health questionnaire, the present work has provided a new instrument called SATISLIT for assessing patients' satisfaction after treatment with SWL. Future studies with external and temporal validation will be necessary to contrast its real clinical usefulness.

Objectives To describe the real-world demographic and clinical characteristics of patients with lower urinary tract symptoms (LUTS) as a result of benign prostatic hyperplasia (BPH) in Spain. Methodology This observational, retrospective, multicentre study conducted in primary care and urology clinics in Spain included men aged >= 50 years diagnosed (<= 8 years prior to study visit) with LUTS caused by BPH. The primary endpoint was demographic and clinical characteristics; secondary endpoints included disease progression and diagnostic tests across both healthcare settings. Results A total of 670 patients were included (primary care: n = 435; urology: n = 235). Most patients had moderate/severe LUTS (74.6%) and prostate volume >30 cc (81.7%), with no differences between settings. More patients had prostate-specific antigen (PSA) >= 1.5 ng/mL in primary care (74.5%) versus urology (67.7%). Progression criteria were prevalent (48.9%). Clinical criteria were more commonly used than the International Prostate Symptom Score (IPSS) to evaluate LUTS at diagnosis (primary care: clinical criteria 73.0%; IPSS: 26.9%; urology: clinical criteria 76.5%; IPSS: 23.4%). Proportion of patients with moderate/severe LUTS at diagnosis was lower using clinical criteria than IPSS, and the proportion of patients with 'worsening' LUTS (diagnosis to study visit) was higher when using clinical criteria versus IPSS. In both healthcare settings, the most commonly used diagnostic tests were general and urological clinical history and PSA. Conclusion Demographic and clinical characteristics of patients with BPH in Spain were similar in primary care and urology; however, assessment criteria to evaluate LUTS severity differ and are not completely aligned with clinical guideline recommendations. Increased use of recommended assessments may enhance optimal BPH management.

Introduction: The objective of the study was to determine the factors independently related with the development of castration resistance (CR) in prostate cancer (PC) in the medium term. Material and methods: 155 patients diagnosed with metastatic PC with a follow-up of up to 39 months. Data taken from the National PC Registry. The evaluated variables were age, PSA, nadir PSA, Gleason, perineural invasion, TNM stages, and ADT type (intermittent/continuous). Results: Mean follow-up 26,2 +/- 13,4 months. 47.1% developed early CR, with mean time until onset of 12,2 8,7 months. Univariate analysis the mean PSA was correlated with CR (290 +/- 905,1 ng/mL in non CR, 519,1 +/- 1437,2 ng/mL in CR, P < .001), mean age (73,3 +/- 8,3 years in non CR, 69,1 +/- 9,3 in CR P = .01), mean PSA nadir (15,5 +/- 57,3 ng/mL in non CR, 15,9 +/- 23,7 ng/mL in CR, p < 0,001), Gleason (in >= 8, HR:2,11. 95% CI: 1.22-3.65, p = 0.006), and T stage (in T3-T4, HR: 2.85. 95% CI: 1.57-5.19, P < .001). Multivariate analysis the independent variables associated to CR are age (HR: 0.96. 95% CI: 0.94-0.99, P = .01), PSA nadir (HR: 1.65. 95% CI: 1,43-1,91, P < .001), and T3-T4 stage (HR: 2.11. 95% CI: 1.10-4.04, P = .02). Conclusions: PSA nadir and T3-T4 tumor stage at diagnosis are associated to an increased risk of developing CR. In addition, age at diagnosis is shown as a variable that decreases risk. Therefore, an older age would be associated with lower risk probability of CR in the medium term. (C) 2019 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.

Sunitinib is one of the most widely used targeted therapeutics for renal cell carcinoma (RCC), but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in RCC, we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and after development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in silico prediction models, six predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1, and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib-desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function renders tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the six proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.

Sunitinib is one of the most widely used targeted therapeutics for renal cell-cancer (RCC) but acquired resistance against targeted therapies remains a major clinical challenge. To dissect mechanisms of acquired resistance and unravel reliable predictive biomarkers for sunitinib in renal cell-cancer (RCC), we sequenced the exons of 409 tumor-suppressor genes and oncogenes in paired tumor samples from an RCC patient, obtained at baseline and following development of acquired resistance to sunitinib. From newly arising mutations, we selected, using in-silico prediction models, 6 predicted to be deleterious, located in G6PD, LRP1B, SETD2, TET2, SYNE1 and DCC. Consistently, immunoblotting analysis of lysates derived from sunitinib-desensitized RCC cells and their parental counterparts showed marked differences in the levels and expression pattern of the proteins encoded by these genes. Our further analysis demonstrates essential roles for these proteins in mediating sunitinib cytotoxicity and shows that their loss of function render tumor cells resistant to sunitinib in vitro and in vivo. Finally, sunitinib resistance induced by continuous exposure or by inhibition of the 6 proteins was overcome by treatment with cabozantinib or a low-dose combination of lenvatinib and everolimus. Collectively, our results unravel novel markers of acquired resistance to sunitinib and clinically relevant approaches for overcoming this resistance in RCC.