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Application of One-Step Nucleic Acid Amplification (OSNA) in different cancer entities and usefulness in prostate cancer: a systematic review

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BMC CANCER 2022年第1期22卷 357-357页

作者： cuadras, merce Planas, Jacques Celma, Ana Regis, Lucas de Torres, Ines M. Semidey, M. Eugenia Trilla, Enrique Morote, Juan Vall Dhebron Univ Hosp Dept Urol Barcelona Spain Vall Dhebron Univ Hosp Dept Pathol Barcelona Spain Univ Autonoma Barcelona Dept Surg Barcelona Spain

Background Lymph node (LN) status is a key prognostic factor in the decision-making process of different cancer entities, including prostate cancer (PCa). Sectioning and haematoxylin and eosin (H&E) staining technique remain the gold standard for the evaluation of LN metastases despite some limitations, especially low sensitivity in detecting an accurate tumour burden within the LN, as well as a subjective and time-consuming result. One-step nucleic acid amplification (OSNA) quantifies mRNA copies of cytokeratin 19 (CK19) in a fast, objective, automated, and reproducible way, raising a general interest to explore its utility for lymphatic metastasis identification in different malignancies. Methods To present the latest evidence related to the detection of LN metastases in several tumours by using OSNA compared with the conventional H&E method, a systematic review of articles published since March 2021 was conducted using PubMed, Cochrane Library, and Web of Science databases. References from primary papers and review articles were checked to obtain further potential studies. Our procedure for evaluating records identified during the literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria. With the aim to design and justify future clinical routine use of OSNA in PCa, novel PCa evidence has been included in this review for the first time. Results Twenty five studies were included. LN from six different groups of tumours: breast, gastrointestinal, gynecological, lung, head and neck and prostate cancers has been assessed. OSNA was compared with post-operative formalin-fixed paraffin-embedded tissue sections with H&E staining as the reference standard. Contingency tables were created, and concordance rate, sensitivity, specificity and predictive values were reported. Seventeen studies analysed the discordant cases using different techniques. Conclusion OSNA method has a high diagnostic accuracy for the detection of LN m

关键词： One-step nucleic acid amplification OSNA Cytokeratin 19 CK19 Prostate cancer Lymph node metastases

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Homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional immunofluorescence

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CELL REPORTS 2025年第2期6卷 101937-101937页

作者： Arce-Gallego, Sara Morgado, Pablo Cresta Delgado-Serrano, Luisa Simonetti, Sara Gonzalez, Macarena Romero-Lozano, Paula Marmolejo, David Morales-Barrera, Rafael Arnau, Gisela Mir Semidey, Maria Eugenia Aguilar, Daniel Cordoba-Terreros, Sarai Mast, Richard de Albert, Matias Planas, Jacques cuadras, merce Maldonado, Xavier Suarez, Cristina Casanova-Salas, Irene Figols, Mariona Cros, Sara Mas, Alba Nonell, Lara Dienstmann, Rodrigo Nuciforo, Paolo Vivancos, Ana Llop-Guevara, Alba Carles, Joan Serra, Violeta Mateo, Joaquin Vall dHebron Inst Oncol VHIO Cellex Ctr Natzaret 115-117 Barcelona 08035 Spain Vall dHebron Inst Oncol VHIO Oncol Data Sci ODysSey Grp Barcelona Spain Vall dHebron Inst Oncol VHIO Mol Oncol Barcelona Spain Vall DHebron Univ Hosp Vall DHebron Inst Oncol VHIO Barcelona Spain Vall dHebron Inst Oncol VHIO Barcelona Spain Vall dHebron Inst Oncol VHIO Canc Genom Grp Barcelona Spain Vall dHebron Univ Hosp Dept Pathol Barcelona Spain Vall dHebron Univ Hosp Dept Radiol Barcelona Spain Vall dHebron Univ Hosp Dept Urol Barcelona Spain Vall dHebron Univ Hosp Dept Radiat Oncol Barcelona Spain Althaia Xarxa Assistencial Univ Manresa Dept Med Oncol Manresa Spain Granollers Hosp Dept Med Oncol Granollers Spain Vall dHebron Inst Oncol VHIO Bioinformat Unit Barcelona Spain Univ Vic Cent Univ Catalonia Vic Spain Vall dHebron Inst Oncol VHIO Expt Therapeut Grp Barcelona Spain

Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations, which have prognostic and predictive value. Routine clinical implementation of next-generation sequencing (NGS) is still limited. We investigated the association between genomic and functional loss of HRR, using NGS and RAD51 immunofluorescence (RAD51-IF) in 219 primary or metastatic biopsies from 187 patients with stage IV prostate cancer. NGS showed frequent genomic alterations in TP53 (40%), AR (15%), PTEN (14%), FOXA1 (12%), MYC (10%), BRCA2 (9%), ATM (8%), and BRCA1 (2%). We pursued RAD51-IF in 206 samples;of those, 139/206 (67%) were evaluable. 21% of samples had RAD51-low score compatible with HRR deficiency (HRD). RAD51-IF showed high sensitivity (71%) and specificity (86%) for BRCA1/2 alterations. Patients with RAD51-low scores experienced longer progression-free survival (PFS) on poly(ADPribose) polymerase inhibitors (PARPi) or platinum chemotherapy. RAD51-IF is feasible in routine clinical samples from patients with mPC and is associated with clinically relevant HRR gene alterations.

关键词： prostate cancer genomics BRCA2 HRR PARPi precision medicine immunofluorescence

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The position of urethrovesical anastomosis after robotic radical prostatectomy assessed by MRI predicts early functional recovery: A cohort analyses from a randomized clinical trial

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EUROPEAN JOURNAL OF RADIOLOGY 2021年 137卷 109589-109589页

作者： Regis, Lucas Salazar, Aina Planas, Jacques Celma, Ana cuadras, merce Roche, Sarai Mast, Richard Morote, Juan Trilla, Enrique Vall dHebron Univ Hosp Dept Urol Pg Vall dHebron 119 Barcelona 08035 Spain Univ Autonoma Barcelona UAB Campus UABPlaca Civ Barcelona 08193 Spain Vall dHebron Univ Hosp Dept Radiol Pg Vall dHebron 119 Barcelona 08035 Spain

Purpose: Functional and anatomical changes associated with prostate removal coincide with alterations in pelvic structures. Posterior rhabdosphincter reconstruction was designed to improve urinary continence after radical prostatectomy. The aim of this study was to determine magnetic resonance anatomic predictors of urinary recovery after radical prostatectomy, and to assess their relation to the type of reconstruction. Material and Methods: Forty patients were randomly selected from a trial (NCT03302169). Two independent radiologists determined the situation of the anastomosis in the pelvis according to MRI performed a month after the radical prostatectomy: vertical situation assessed as the distance to the line coccyx-inferior pubic margin (ACPv) and anteroposterior situation as the distance from the pubis (Distance A), and from the coccyx (Distance B). Results: The Pearson correlation of ACPv, Distance A, and B between readers were 0.975, 0.940, and 0.711, p < 0.001. Patients with the reconstruction presented more cephalic situation of the anastomosis (higher ACPv) than patients with standard reconstruction technique. A multivariate analysis was performed including age, BMI, prostate volume, PRRS, and the MRI parameters. ACPv and Distance B were the only two independent predictors of no need for any urinary protection at 6 months after the surgery. Conclusions: This is the first study that suggests positional differences according to the type of reconstruction after radical prostatectomy related to early urinary recovery. Magnetic resonance measurements to determine anastomosis positioning are reliable and have a strong correlation between readers. Anatomic MRI features are independent predictors of urinary recovery after robotic radical prostatectomy.

关键词： Early continence Magnetic resonance Posterior rhabdosphincter reconstruction Radical prostatectomy Urinary incontinence

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Impact of a Primary Care intervention on the colorectal cancer early detection programme

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GASTROENTEROLOGIA Y HEPATOLOGIA 2019年第6期42卷 351-361页

作者： Luque Mellado, Francisco Jose Paino Pardal, Lidia Condomines Feliu, Isabel Tora-Rocamora, Isabel cuadras Rofastes, merce Romero Diaz, Elvira Pacheco Ortiz, Maribel Camunez Bravo, Juan Carlos Aldea, Marta Grau Cano, Jaume Abos-Herrandiz, Rafael Abril, Eva Alvarez, Cristina Antonio Alvarez, Marco Andreu, Montserrat Araujo, Isis Auge, Josep M. Aymar, Anna Bagaria, Guillermo Balaguer, Francesc Bessa, Xavier Bonilla, Montserrat Buron, Andrea Carballal, Sabela Castells, Antoni Castells, Xavier Comas, merce Costa, Rosa Cuatrecasas, Miriam Dedeu, Josep M. Estrada, Maria Garrell, Imma Gordillo, Jordi Guayta, Rafael Hernandez, Cristina Iglesias, Mar Llovet, Laura Lopez-Ceron, Maria Macia, Francesc Moreira, Leticia Moreno, Laura Francisca Murciano, M. Navarro, Gemma Ocana, Teresa Pellise, Maria Pintanell, merce Pozo, Angels Puig, Teresa Riu, Faust Rivero-Sanchez, Liseth Rodriguez, Cristina Sala, Maria Sanchez, Ariadna Seoane, Agustin Serradesanferm, Anna Sivilla, Judit Trilla, Antoni Inst Catala Salut Equipo Atenc Primaria Guineueta Barcelona Spain Hosp Clin Barcelona Serv Med Prevent & Epidemiol Barcelona Spain

Aim: To assess the effectiveness of a telephonic interview performed by primary care professionals among non-participants in the first round of the colorectal cancer early detection programme in the basic urban health area Guineueta in Barcelona, Spain. Patients and methods: The Primary Healthcare Team of La Guineueta contacted people who did not respond to the invitation to the first round of the colorectal cancer early detection programme using a standardised telephone call protocol. We analysed the impact of the intervention based on participation and diagnosed disease. Results: We made 3,327 phone calls to 2,343 people. After the intervention the participation rate was 54.9%, which meant an increase of 5.7% with respect to the participation in the usual protocol for the programme (49.2%). The intervention allowed 5 cancers, 2 high-risk neoplasms and 8 low- and intermediate-risk lesions to be diagnosed. An average of 9 phone calls was necessary to achieve the participation of one additional person. Discussion: The telephonic intervention performed by primary care professionals has significantly increased the population participation rate and the detection of neoplasms with respect to the usual colorectal cancer early detection programme protocol. (C) 2019 Elsevier Espana, S.L.U. All rights reserved.

关键词： Colorectal cancer Cancer screening Population participation Primary Care Secondary prevention

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CHEMILUMINISCENT IMMUNOASSAYS SHOULD NOT BE USED TO MEASURE SERUM TESTOSTERONE IN PROSTATE CANCER PATIENTS UNDERGOING ANDROGEN DEPRIVATION THERAPY

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JOURNAL OF UROLOGY 2018年第4期199卷 E306-E306页

作者： cuadras, merce Miret, Enric Lopez, Ricardo Comas, Imma Ferrer, Roser Planas, Jacques Celma, Ana Maldonado, Xavier Carles, Joan Regis, Lucas Morote, Juan Barcelona Spain

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ANATOMICAL BENCHMARKS IN PREOPERATIVE MAGNETIC RESONANCE IMAGING PREDICT EARLY CONTINENCE RECOVERY FOLLOWING ROBOTIC RADICAL PROSTATECTOMY

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JOURNAL OF UROLOGY 2018年第4期199卷 E43-E43页

作者： Regis, Lucas cuadras, merce Miret, Enric Lopez, Ricardo Salazar, Aina Roche, Sarai Celma, Ana Lorente, David Placer, Jose Planas, Jacques Trilla, Enrique Morote, Juan Barcelona Spain

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WHAT IS THE PREDICTIVE VALUE OF A NEGATIVE MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING IN EXCLUDING PROSTATE CANCER AT BIOPSY?

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JOURNAL OF UROLOGY 2018年第4期199卷 E484-E484页

作者： Lopez del Campo, Ricardo cuadras Sole, merce Miret Alomar, Enric Salazar Gabarro, Aina Roche Valles, Sarai Regis Placido, Lucas Celma Domenech, Ana Lorente Garcia, David Placer Santos, Jose Planas Morin, Jacques Trilla Herrera, Enrique Morote Robles, Juan Barcelona Spain

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Hormonal response recovery after long-term androgen deprivation therapy in patients with prostate cancer

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SCANDINAVIAN JOURNAL OF UROLOGY 2016年第6期50卷 425-428页

作者： Planas, Jacques Celma, Ana Placer, Jose cuadras, merce Regis, Lucas Gasanz, Carlos Trilla, Enrique Salvador, Carlos Lorente, David Morote, Juan Univ Autonoma Barcelona Hosp Vall dHebron Dept Urol Barcelona Spain

Objective: The aim of this study was to evaluate hormonal recovery after cessation of androgen deprivation therapy (ADT) in a group of elderly prostate cancer patients. Materials and methods: Forty patients with locally advanced or metastatic prostate cancer, with a mean age of 71.5 years [95% confidence interval (CI) 69.1-73.9], were treated with ADT for a mean duration of 74.6 months (95% CI 59.7-89.5 months). Mean follow-up time after ADT cessation was 36.5 months (95% CI 30.6-42.3 months). Serum testosterone and luteinizing hormone (LH) were determined at 6 month intervals after ADT cessation. Results: After 18 months of follow-up, all patients had recovered normal LH levels, while 38% of patients still presented castration levels of testosterone (< 50 ng/dl). A multivariate analysis was performed to find factors related to testosterone recovery (testosterone >50 ng/dl). Neither age at start of ADT nor clinical stage reached statistical significance. Only time under ADT was correlated with testosterone recovery (p = .031). Kaplan-Meier curves were obtained. Mean time for testosterone recovery was 14.5 months (95% CI 6.5-22.6 months) in patients treated with ADT for less than 60 months compared to 29.3 months (95% CI 19.6-39.1 months) in patients treated with ADT for more than 60 months (log-rank p = .029). Conclusions: Age did not correlate with testosterone recovery in a group of elderly prostate cancer patients in whom ADT was stopped. Testosterone recovery after ADT cessation was significantly correlated with time under ADT treatment. Significant implications related to economic aspects of the dosage schedule may be considered.

关键词： Androgen deprivation therapy castration level luteinizing hormone prostate cancer testosterone

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Plasma idebenone monitoring in Friedreich's ataxia patients during a long-term follow-up

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BIOMEDICINE & PHARMACOTHERAPY 2021年 143卷 112143-112143页

作者： Paredes-Fuentes, Abraham J. Cesar, Sergi Montero, Raquel Latre, Cristina Genoves, Jordi Martorell, Loreto cuadras, Daniel Colom, Helena Pineda, merce del Mar O'Callaghan, Maria Sarquella-Brugada, Georgia Darling, Alejandra Artuch, Rafael Hosp St Joan de Deu Inst Recerca St Joan de Deu Clin Biochem Dept Barcelona 08950 Spain Hosp St Joan de Deu Inherited Cardiac Dis & Sudden Death Unit Arrhythmia Barcelona 08950 Spain Hosp St Joan de Deu Pharm Dept Barcelona 08950 Spain Hosp St Joan de Deu Mol Genet Dept Barcelona 08950 Spain Inst Recerca St Joan de Deu Stat Dept Barcelona 08950 Spain Univ Barcelona Fac Pharm & Food Sci Dept Pharm & Pharmaceut Technol & Phys Chem Barcelona Spain Hosp St Joan de Deu Metab & Ataxia Unit Dept Paediat Neurol Barcelona 08950 Spain Univ Girona Sch Med Med Sci Dept Girona 17004 Spain Inst Salud Carlos III Biomed Network Res Ctr Rare Dis CIBERER Madrid 28029 Spain

Introduction and objectives: Despite the growing interest and the potential benefits of idebenone as a repurposed drug for different orphan conditions, data regarding its monitoring are scarce. Our main goal was to report plasma idebenone values in a cohort of Friedreich's ataxia (FRDA) patients during a long-term follow-up. Taking advantage of this, we also assessed cardiological and neurological status together with idebenone values and genetic background. Methods: Long-term follow-up retrospective study in 27 FRDA patients with a disease onset at the paediatric age treated with idebenone by compassionate use. Plasma idebenone was measured by HPLC with electrochemical detection. Results: Median plasma idebenone values increased when doses were increased, but apparently linearity was lost in the highest dose group. Marked intraindividual and interindividual differences were observed among patients. We did not find a consistent positive effect after analysis of paired data at the beginning and the end of the study. We only found a correlation between some cardiological measures and the duration of idebenone therapy at high doses, but with uncertain significance Conclusions: The large variations observed among the different individuals involved in this study should be considered for optimization of individual dosage regimens.

关键词： Plasma idebenone monitoring Long-term follow-up HPLC with electrochemical detection Friedreich's ataxia

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AZATAX: Acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG)

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ANNALS OF NEUROLOGY 2019年第5期85卷 740-751页

作者： Martinez-Monseny, Antonio F. Bolasell, merce Callejon-Poo, Laura cuadras, Daniel Freniche, Veronica Itzep, Debora C. Gassiot, Susanna Arango, Pedro Casas-Alba, Didac de la Morena, Eugenia Corral, Javier Montero, Raquel Perez-Cerda, Celia Perez, Belen Artuch, Rafael Jaeken, Jaak Serrano, mercedes St Joan Deu Hosp Genet Med Dept Res Inst Barcelona Spain St Joan Deu Hosp Pediat Inst Rare Dis Res Inst Barcelona Spain Neuroesplugues Neuropsychol Unit Barcelona Spain St Joan Deu Fdn Stat Dept Barcelona Spain St Joan Deu Hosp Neuropediat Dept Res Inst Barcelona Spain St Joan Deu Hosp Hematol Lab Res Inst Barcelona Spain St Joan Deu Hosp Nephrol Dept Res Inst Barcelona Spain Murcia Univ Morales Meseguer Univ Hosp Hematol & Med Oncol ServIMIB Arrixaca Reg Blood Donat CtrCtr Biomed Res Rare Dis U-765 Murcia Spain St Joan Deu Hosp Clin Biochem Dept Res Inst Barcelona Spain Inst Salud Carlos III St Joan Deu Hosp Ctr Biomed Res Rare Dis U-703 Barcelona Spain Autonomous Univ Madrid Inst Salud Carlos III Diag Mol Dis Ctr Ctr Biomed Res Rare DisIdiPAZ U-746 Madrid Spain Katholieke Univ Leuven Univ Hosp Gasthuisberg Ctr Metab Dis Leuven Belgium

Objective Phosphomannomutase deficiency (PMM2 congenital disorder of glycosylation [PMM2-CDG]) causes cerebellar syndrome and strokelike episodes (SLEs). SLEs are also described in patients with gain-of-function mutations in the CaV2.1 channel, for which acetazolamide therapy is suggested. Impairment in N-glycosylation of CaV2.1 promotes gain-of-function effects and may participate in cerebellar syndrome in PMM2-CDG. AZATAX was designed to establish whether acetazolamide is safe and improves cerebellar syndrome in PMM2-CDG. Methods A clinical trial included PMM2-CDG patients, with a 6-month first-phase single acetazolamide therapy group, followed by a randomized 5-week withdrawal phase. Safety was assessed. The primary outcome measure was improvement in the International Cooperative Ataxia Rating Scale (ICARS). Other measures were the Nijmegen Pediatric CDG Rating Scale (NPCRS), a syllable repetition test (PATA test), and cognitive scores. Results Twenty-four patients (mean age = 12.3 +/- 4.5 years) were included, showing no serious adverse events. Thirteen patients required dose adjustment due to low bicarbonate or asthenia. There were improvements on ICARS (34.9 +/- 23.2 vs 40.7 +/- 24.8, effect size = 1.48, 95% confidence interval [CI] = 4.0-7.6, p < 0.001), detected at 6 weeks in 18 patients among the 20 responders, on NPCRS (95% CI = 0.3-1.6, p = 0.013) and on the PATA test (95% CI = 0.5-3.0, p = 0.006). Acetazolamide improved prothrombin time, factor X, and antithrombin. Clinical severity, epilepsy, and lipodystrophy predicted greater response. The randomized withdrawal phase showed ICARS worsening in the withdrawal group (effect size = 1.46, 95% CI = 2.65-7.52, p = 0.001). Interpretation AZATAX is the first clinical trial of PMM2-CDG. Acetazolamide is well tolerated and effective for motor cerebellar syndrome. Its ability to prevent SLEs and its long-term effects on kidney function should be addressed in future studies. Ann Neurol 2019;85:740-751

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