Fundacio Puigvert

Barcelona, Spain

Fundacio Puigvert

Barcelona, Spain

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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-1;HEALTH-2007-2.4.1-2 | Award Amount: 3.92M | Year: 2008

Bladder cancer is a recurrent and very prevalent cancer and it generates the highest cost per patient in Europe. New genomic methods have allowed identifying new markers with potential clinical application. However, due to the use of single-marker assays and poor study design, none of these markers has made it to the clinic. FGFR3 and PIK3CA mutations, expression profiles, and microsatellite alterations in tumor tissue and urine, as well as polymorphisms in immune response genes, are very promising biomarkers that predict a tumor being present in the bladder and its likelihood of progression to invade the muscle. Here, we propose to combine the best markers of bladder cancer outcome in a prospective multicenter validation study in Spain, the Netherlands, Sweden and Denmark as genetic predictors. Pre-validation of markers has been or will be made utilizing the worlds largest bladder cancer biobank (60,000 samples from 2500 patients). To achieve enough power to rapidly generate conclusive results, 2000 patients will consecutively be enrolled, and subjected to analysis, as well as follow-up for 2-4 years. The approach is a pre-defined, standard operating procedure based, prospective study with fixed end-points and testing relatively few independent variables on tumor tissue, urine and blood. To obtain a seamless introduction into the clinic we will use a mathematical approach in which the best markers are weighted based on disease models and nomogram construction, leading to a risk score applied to each patient at each visit. The team has a very strong track record in bladder cancer research, micro-array application, nomogram construction, and bio-banking. The validated biomarkers will lead to specific recommendations for changes in patient management based on the risk scores. We estimate saving of more than 40 mill Euros annually based on a reduced frequency of cystoscopies, as well as an increased survival and a better quality of life for the patients.


Albers P.,Heinrich Heine University Düsseldorf | Albrecht W.,Rudolfstiftung | Algaba F.,Fundacio Puigvert | Bokemeyer C.,Universitatskliniken Eppendorf | And 4 more authors.
European Urology | Year: 2011

Context: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy, and follow-up of testicular cancer were established. Objective: This article is a short version of the EAU testicular cancer guidelines and summarises the main conclusions from the guidelines on the management of testicular cancer. Evidence acquisition: Guidelines were compiled by a multidisciplinary guidelines working group. A systematic review was carried out using Medline and Embase, also taking Cochrane evidence and data from the European Germ Cell Cancer Consensus Group into consideration. A panel of experts weighted the references, and a level of evidence and grade of recommendation were assigned. Results: There is a paucity of literature especially regarding longer term follow-up, and results from a number of ongoing trials are awaited. The choice of treatment centre is of the utmost importance, and treatment in reference centres within clinical trials, especially for poor-prognosis nonseminomatous germ cell tumours, provides better outcomes. For patients with clinical stage I seminoma, based on recently published data on long-term toxicity, adjuvant radiotherapy is no longer recommended as first-line adjuvant treatment. The TNM classification 2009 is recommended. Conclusions: These guidelines contain information for the standardised management of patients with testicular cancer based on the latest scientific insights. Cure rates are generally excellent, but because testicular cancer mainly affects men in their third or fourth decade of life, treatment effects on fertility require careful counselling of patients, and treatment must be tailored taking individual circumstances and patient preferences into account. © 2011 European Association of Urology.


Montes A.,Autonomous University of Barcelona | Roca G.,Autonomous University of Barcelona | Sabate S.,Fundacio Puigvert | Lao J.I.,Genomic Genetics International | And 3 more authors.
Anesthesiology | Year: 2015

Background: Chronic postsurgical pain (CPSP) has been linked to many surgical settings. The authors aimed to analyze functional genetic polymorphisms and clinical factors that might identify CPSP risk after inguinal hernia repair, hysterectomy, and thoracotomy. Methods: This prospective multicenter cohort study enrolled 2,929 patients scheduled for inguinal hernia repair, hysterectomy (vaginal or abdominal), or thoracotomy. The main outcome was the incidence of CPSP confirmed by physical examination 4 months after surgery. The secondary outcome was CPSP incidences at 12 and 24 months. The authors also tested the associations between CPSP and 90 genetic markers plus a series of clinical factors and built a CPSP risk model. Results: Within a median of 4.4 months, CPSP had developed in 527 patients (18.0%), in 13.6% after hernia repair, 11.8% after vaginal hysterectomy, 25.1% after abdominal hysterectomy, and 37.6% after thoracotomy. CPSP persisted after a median of 14.6 months and 26.3 months in 6.2% and 4.1%, respectively, after hernia repair, 4.1% and 2.2% after vaginal hysterectomy, 9.9% and 6.7% after abdominal hysterectomy, and 19.1% and 13.2% after thoracotomy. No significant genetic differences between cases and controls were identified. The risk model included six clinical predictors: (1) surgical procedure, (2) age, (3) physical health (Short Form Health Survey-12), (4) mental health (Short Form Health Survey-12), (5) preoperative pain in the surgical field, and (6) preoperative pain in another area. Discrimination was moderate (c-statistic, 0.731; 95% CI, 0.705 to 0.755). Conclusions: Until unequivocal genetic predictors of CPSP are understood, the authors encourage systematic use of clinical factors for predicting and managing CPSP risk. © 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.


Roupret M.,Pitie Salpetrire Hospital | Roupret M.,University Pierre and Marie Curie | Zigeuner R.,Medical University of Graz | Palou J.,Fundacio Puigvert | And 6 more authors.
European Urology | Year: 2011

Context: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. Objective: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. Evidence acquisition: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. Evidence synthesis: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. Conclusions: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Yuh B.,City of Hope National Cancer Center | Wilson T.,City of Hope National Cancer Center | Bochner B.,Sloan Kettering Cancer Center | Chan K.,City of Hope National Cancer Center | And 8 more authors.
European Urology | Year: 2015

Context Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. Objective To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. Evidence acquisition Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot∗ radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. Evidence synthesis The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. Conclusions Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. Patient summary Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable. © 2014 European Association of Urology.


Agundez M.,Tumour Markers Group | Grau L.,Tumour Markers Group | Palou J.,Fundacio Puigvert | Algaba F.,Fundacio Puigvert | And 2 more authors.
European Urology | Year: 2011

Background: Bacillus Calmette-Guérin (BCG) is a standard treatment for reducing tumour recurrence and delaying progression of high-risk non-muscle-invasive bladder tumours. However, it is not clear yet which patients are more likely to respond to BCG. Objective: To evaluate the role of the methylation of 25 tumour suppressor genes (TSG) as clinical outcome predictive biomarkers in T1G3 bladder tumours treated with BCG. Design, setting, and participants: A retrospective design included 91 paraffin-embedded tumours of patients with T1G3 primary non-muscle-invasive disease undergoing nonmaintenance BCG treatment. Measurements: The methylation status of 25 TSGs was measured using a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay. Recurrence, progression into muscle-invasive tumours, and disease-specific survival (DSS) rates were analysed using univariate and multivariate tests. Results and limitations: The genes most frequently methylated included STK11 (94.5%), MSH6 (81.3%), BRCA1 (72.5%), PAX5A (68.1%), MGMT (67.0%), CDH13 (62.6%), and IGSF4 (61.5%). Methylation was newly identified in T1G3 tumours for TP73, MSH6, ESR1, PAX5A, WT1, CD44, ATM, IGSF4, CHFR, BRCA2, THBS1, PYCARD, STK11, and GATA5. Methylation for several TSGs was significantly associated with multifocality and tumour size. Patients with different methylation statuses of TSGs showed differential recurrence rates (PAX6: p = 0.025), progression rates (MSH6: p = 0.040; RB1: p = 0.042; THBS1: p = 0.041; PYCARD: p = 0.048; TP73: p = 0.048; ESR1: p = 0.036; and GATA5: p = 0.019), and DSS rates (GATA5: p = 0.037). Several combinations improved prediction for progression. Multivariate analyses indicated that among the combinations remaining as independent predictors, two genes - MSH6 and THBS1 - already provided the most significant predictive assessment for progression (p = 0.004). The major limitation of this study is related to its retrospective design. Conclusions: The methylation status of TSGs was associated with the clinical outcome of patients with T1G3 tumours undergoing BCG treatment under three clinical end points: recurrence, progression, and DSS. The methylation status of TSGs distinguished patients responding to BCG from those who may require a more aggressive therapeutic intervention. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Mazo V.,Hospital Universitari Germans Trias i Pujol | Sabate S.,Fundacio Puigvert | Canet J.,Hospital Universitari Germans Trias i Pujol
Minerva Anestesiologica | Year: 2016

Pulmonary complications are a source of greater postoperative morbidity and mortality and longer hospital stays. Although many factors have been implicated as predictors, few models have been developed with the rigorous methodology required for clinically useful tools. In this article we attempt to describe what to look for when developing or assessing a newly proposed predictive tool and to discuss what must be taken into consideration on incorporating a model into clinical practice. Above all, we stress that we still lack evidence for the clinical and cost effectiveness of many measures proposed for reducing risk or for managing complications perioperatively. For a good predictive model to truly prove its utility in clinical decision-making, such evidence is required. © 2016 EDIZIONI MINERVA MEDICA.


Canet J.,Autonomous University of Barcelona | Sabate S.,Fundacio Puigvert | Mazo V.,Autonomous University of Barcelona
Minerva Anestesiologica | Year: 2013

Background. Many studies on colloids have recently been retracted, leaving us with uncertain evidence of their safety. We aimed to analyze whether intraoperative colloid administration is associated with postoperative complications. Methods. The prospectively compiled database of the ARISCAT study of a large, representative cohort of general surgical patients was reanalyzed to compare outcomes according to whether intraoperative colloids were administered or not; a propensity score was used to adjust for potential confounders. The primary outcomes were major postoperative complications. Secondary outcomes were postoperative hospital-free days within 90 days and mortality at 30 and 90 days. In a retrospective survey we asked each centers data collectors to estimate the proportions of the different colloids administered during the study period. Results. Of 2462 patients analyzed, 556 (22.6%) received some type of colloid intraoperatively. The median (25 th-75th percentile) of total fluids administered was significantly higher in patients receiving colloids (10.0 [6.9-14.1] mL·kg-1·h-1 vs. 8.8 [6.0-12.8] mL·kg-1·h-1 for patients not receiving colloids; P<0.01). The median volume of colloids administered was 7.5 (6.3-10.4) mL·kg-1. An estimated 75.7% of the patients received third-generation hydroxyethyl starches (130/0.4). Significantly associated complications, after propensity score adjustment, were atelectasis, respiratory infection, bronchospasm, arrhythmia, sepsis, paralytic ileum, and hyperglycemia. Patients receiving colloids had 1.9 fewer postoperative hospital-free days (P<0.006). There were no significant differences in 30- and 90-day mortality. Conclusion. Our study suggests an association of intraoperative colloid administration, mainly of 130/0.4 hydroxyethyl starches, with diverse major postoperative complications and longer hospital stay. Controlled studies are urgently needed to assess the safety profile of colloid use in surgical patients.


Bujons A.,Fundacio Puigvert | Caffaratti J.,Fundacio Puigvert | Garat J.M.,Fundacio Puigvert | Villavicencio H.,Fundacio Puigvert
Journal of Pediatric Urology | Year: 2014

Background Bladder tumours are rare in children, with only 0.38% of cases occurring in the first two decades of life. Objective To describe a long-term follow-up series of nine urothelial bladder tumours in children. Patients and methods We carried out a retrospective study covering the period from 1988 until 2005. We found that during this time, urothelial tumours had been diagnosed at our centre in eight patients (9 tumours) younger than 18 years old who reported an episode of haematuria. Diagnosis was attained through renal and bladder ultrasound in 85% of patients, and through cystoscopy under anaesthesia in 15%. All cases were treated by means of transurethral resection of the bladder, with ensuing follow-up using renal and bladder ultrasound and urinary cytology. Measurements Patients characteristics and outcome are evaluated. Results Single exophytic tumours were present in seven (87.5%) of the patients, located either in the lateral wall or in the trigone; one patient showed two small tumours. The pathology was as follows: two G1Ta, one G1T1, one G2T1, and five G2Ta. There were no recurrences. Conclusions Transitional cell carcinoma in childhood is of low grade and low aggressiveness. It has a good prognosis and recurrences are infrequent. We suggest performing a urinary cytology/cystoscopy every 6 months the first 2 years and urinary cytology/bladder ultrasound once a year. © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.


Patent
Fundacio Puigvert | Date: 2012-04-23

In vitro method for predicting fecundity of semen. The present invention belongs to the field of reproductive medicine, particularly related to male and female infertility. Thus, the present invention is focused on the evaluation and assessment of the sperm expression gene profile, in order to identify a specific group of genes whose expression profile is correlated with the fecundity ability of spermatozoa. This group of genes could be used as biomarkers for discriminating those samples with the worst ability to fertilize oocyte.

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