Molecular markers of systemic therapy response in urothelial carcinoma

Identification of reliable molecular biomarkers that can complement clinical practice represents a fascinating challenge in any cancer field. Urothelial carcinoma is a very heterogeneous disease and responses to systemic therapies, and outcomes after radical cystectomy are difficult to predict. Advances in molecular biology such as next generation sequencing and whole genome or transcriptomic analysis provide promising platforms to achieve a full understanding of the biology behind the disease and can identify emerging predictive biomarkers. Moreover, the ability to categorize patients' risk of recurrence after curative treatment, or even predict benefit from a conventional or targeted therapies, represents a compelling challenge that may reshape both selection for tailored treatment and disease monitoring. Progress has been made but currently no molecular biomarkers are used in the clinical setting to predict response to systemic agents in either neoadjuvant or adjuvant settings highlighting a relevant unmet need. Here, we aim to present the emerging role of molecular biomarkers in predicting response to systemic agents in urothelial carcinoma

The Role of Lymph Node Fine-Needle Aspiration in Penile Cancer in the Sentinel Node Era

Penile squamous cell carcinoma (SCC) is an uncommon condition in Western countries. Inguinal lymph nodes dissection can be curative in 20%–60% of node positive patients. However, there is a high complication rates from the dissection, thus accurate diagnosis of inguinal lymph nodes metastasis is required. Current non invasive methods to detect lymph nodes metastasis are unreliable. Dynamic Sentinel Node Biopsy (DNSB), ultrasonography (US), and fine needle aspiration (FNA) cytology were proposed to in an attempt to detect sentinel lymph node (SLN). Despite the initial high rate of false negative results, recent DSNB showed improved survival compared to wait and see policy as well as reduced mortality compared to prophylactic inguinal lymphadenectomy. In addition, the US guided FNA shown 100% of specificity in detecting clinically occult lymph nodes metastasis. We proposed an algorithm for management of lymph nodes in penile cancer and suggest that FNA with US guidance should be performed in all high risk patients and that therapeutic dissection should be performed if findings are positive

RANK-L com a marcador pronòstic en càncer de prostata

El càncer de pròstata (CaP) es actualment el primer càncer en incidència en els homes dels països desenvolupats i segueix essent la segona causa de mort per aquesta població. Les eines de les que disposem en l'actualitat per al correcte diagnòstic i estadi d'aquesta malaltia segueixen essent poc acurades ja que tot i que en la majoria de pacients aconseguim determinar les correctes mesures de tractament, encara en un elevat percentatge de pacients la modalitat de tractament segueix essent incorrecte donada la manca de marcadors que ens permetin determinar l'estat d'avenç de la malaltia. Donat que el CaP té una elevada afinitat per l'entorn ossi, els nostres esforços giren en torn a determinar quins pacients d'aquells que diagnostiquen presentaran metàstasis òssies i si d'alguna manera podríem ajudar a predir-ho. La remodelació òssia fisiològica implica la interacció de tres molècules establint un clar balanç en l'activació i desactivació dels osteoblasts i osteoclast. Aquestes tres molècules són RANK, RANKL i OPG. Disposem ja d'un fàrmac inhibidor de l'activitat de RANKL a nivell selectiu que ha demostrat incrementar els nivells de densitat òssia en estudis randomitzats en diferents tipus de malalts amb càncer i en dones sanes post menopàusiques. En el nostre treball avalua l'expressió immunohistoquímica de la molècula RANKL en el teixit de CaP de malalts amb diferents estadis de la malaltia i la correlaciona amb diferents factors predictors de metàstasi òssia o global. Bàsicament correlaciona dos grups de malalts, aquells amb malaltia òssia clínicament objectivada i aquells diagnosticats amb malaltia localitzada amb diferents graus de risc (en funció de la suma de Gleason a la biòpsia prostàtica). Aquest estudi transmet 2 conclusions clares entorn a l'expressió de RANKL en el teixit de CaP. Primerament, que l'expressió de RANKL en el teixit de CaP de malalts amb malaltia metastàtica objectivada es superior que en els malalts sense disseminació metastàtica i s'incrementa de forma paral·lela amb el grup de risc. En segon lloc, RANKL sembla jugar un paper com a predictor de metàstasi global tot i que els nostres resultats no demostren el rol en la predicció de metàstasi òssia únicament. No s'observa correlació entre la supervivència càncer-especifica i l'expressió de RANKL. Els últims estudis randomitzats utilitzats en pacients amb CaP avançat que utilitzen l'inhibidor de RANKL, demostren un avantatge en la supervivència lliure de metàstasi. Tots aquests factors ens fan pensar que un futur anàlisi d'una població semblant a la nostra amb un altre anticòs mes específic podria demostrar les diferencies que tot sembla apunta han d'existir.Prostate cancer (PC) is the most common type of cancer found in men living in developed countries and is the second leading cause of cancer death in men. None of the currently available diagnostic or staging tools used for patient characterization are fully accurate. Even though the majority of patients undergo the appropriate treatment, a high percentage could be offered other managing strategies in order to improve survival and quality of life issues. PC has proven affinity to the bone. Therefore, treatments targeting bone metastasis are likely to benefit PC patients. Bone remodeling implies the interaction of three molecules, RANK, RANKL and osteoprotegerin. These molecules establish a balance between bone formation and bone degradation by osteoblasts and osteoclasts. A RANKL inhibitor has been proven in randomized controlled trials to increase bone density in cancer patients and in postmenopausal females. Our thesis evaluates the immunohistochemical expression of RANKL in PC tissue from patients in different disease stages and correlates it with different bone and global metastasis predicting factors. We studied the expression of RANKL in two groups of patients, those with proven bone metastatic disease and those with localized disease (stratified according to Gleason score at prostate biopsy). We arrived at two primary conclusions from our analyses. First, RANKL expression in metastatic patients is higher than in non-metastatic patients; expression correlates directly with the risk of dissemination. Second, RANKL predicts overall metastasis, however it does not predict bone metastasis specifically. No correlation between cancer specific survival and RANKL expression was shown. Recent randomized trials on advanced PC patients using a RANKL inhibitor show an advantage for metastasis-free survival. Because of the results of the previously published randomized trials, we strongly believe that the use of a more specific antibody would confirm our original hypothesis

Factores predictores de días de hospitalización en pacientes con ictus

Introducción: La elevada morbilidad del ictus supone un gran coste tanto para los pacientes como para el sistema sanitario. Este estudio pretende determinar qué factores del paciente, de la enfermedad o del propio sistema sanitario se relacionan con un aumento en los días de hospitalización. Material y métodos: Estudio observacional longitudinal y prospectivo. Se analizaron todos los casos incidentes de primer ictus atendidos en un hospital comarcal durante un año (n=101). Las variables estudiadas se recogieron durante las 48 horas de ingreso de los pacientes en la unidad de Urgencias. Los factores estudiados fueron analizados mediante la comparación de las curvas de supervivencia (log-rank test) y análisis multivariante mediante regresión de Cox. Resultados: Se incluyeron 101 pacientes, permanecieron ingresados una mediana de 7 días (Media 10 días; rango 1-73), el 15,9% fueron hemorrágicos y el 84% isquémicos (29,5% infartos lacunares y el 54,5% infartos isquémicos cerebrales). Las variables que demostraron estar relacionados con los días de hospitalización fueron: edad, hipertensión, insuficiencia cardiaca, paresia o anestesia/hipoestesia facial y de las extremidades, alteración de la mirada conjugada y afectación visio-espacial. Las variables independientemente relacionadas con los días de hospitalización en el análisis multivariante fueron: infarto isquémico cerebral (HR=3,5; IC95%, 1,7-7,5), Ictus hemorrágico (HR=4,9; IC95%, 1,8-12,9), paresia de la extremidad superior (HR=4,5; IC95%, 2,3-8,8) y edad (HR=0,98; IC95%, 0,96-0,99) Conclusiones: La mayor permanencia en un hospital de agudos se relaciona principalmente con una menor edad, parálisis de la extremidad superior e ictus hemorrágico.Introduction: The high morbibity of stroke has a great economic impact in patients and healthcare. Since the main cost to healthcare is length of stay, the aim of this study was to analyse characteristics of patients, stroke and healthcare related to length of stay. Results: 101 patients were included, median length of stay was 7 days (Mean, 10 days, range 1-73), 15,9% were haemorragic strokes and 84% were ischemic strokes, (of those 25,7% were lacunar infarcts). 13% were patients with no tomographic sings of stroke. Variables associated to length of stay were: age, hypertension, heart failure, extremities and facial paresis or anesthesia/hipoesthesia, conjugate eye deviation and visual field loss. Variables independently associated to length of stay in the multivariate Cox regression model were: nonlacunar- ischemic stroke (HR=3,5; CI95%, 1,7-7,5), haemorragic stroke (HR=4,9; CI95%, 1,8-12,9) arm paresis (HR=4,5; CI95%, 2,3-8,8) and age (HR=0,98; CI95%, 0,96-0,99). Conclusions: Age, arm paresis and stroke subtype are strongly related to length of stay

Collaborative Review: Factors Influencing Treatment Decisions for Patients with a Localized Solid Renal Mass.

CONTEXT: With the addition of active surveillance and thermal ablation (TA) to the urologist\u27s established repertoire of partial (PN) and radical nephrectomy (RN) as first-line management options for localized renal cell carcinoma (RCC), appropriate treatment decision-making has become increasingly nuanced. OBJECTIVE: To critically review the treatment options for localized, nonrecurrent RCC; to highlight the patient, renal function, tumor, and provider factors that influence treatment decisions; and to provide a framework to conceptualize that decision-making process. EVIDENCE ACQUISITION: A collaborative critical review of the medical literature was conducted. EVIDENCE SYNTHESIS: We identify three key decision points when managing localized RCC: (1) decision for surveillance versus treatment, (2) decision regarding treatment modality (TA, PN, or RN), and (3) decision on surgical approach (open vs minimally invasive). In evaluating factors that influence these treatment decisions, we elaborate on patient, renal function, tumor, and provider factors that either directly or indirectly impact each decision point. As current nomograms, based on preselected patient datasets, perform poorly in prospective settings, these tools should be used with caution. Patient decision aids are an underutilized tool in decision-making. CONCLUSIONS: Localized RCC requires highly nuanced treatment decision-making, balancing patient- and tumor-specific clinical variables against indirect structural influences to provide optimal patient care. PATIENT SUMMARY: With expanding treatment options for localized kidney cancer, treatment decision is highly nuanced and requires shared decision-making. Patient decision aids may be helpful in the treatment discussion

Reliable Prediction of Post-Operative Complications’ Rate Using the G8 Screening Tool: A Prospective Study on Elderly Patients Undergoing Surgery for Kidney Cancer

Abstract: In the last years the incidence of renal neoplasms has been steadily increasing, along with the average age of patients at the time of diagnosis. Surgical management for localized disease is becoming more challenging because of patients’ frailty. We conducted a multi-center prospective study to evaluate the role of the G8 as a screening tool in the assessment of intra and post-operative complications of elderly patients ( 70 y.o.) undergoing surgery for kidney cancer. A total of 162 patients were prospectively enrolled between January 2015 to January 2019 and divided into two study groups (frail vs. not-frail) according to their geriatric risk profile based on G8 score. Several factors (i.e., age, CCI, ASA score, preoperative anemia, RENAL score, surgical procedures, and techniques) were analyzed to identify whether any of them would configure as a statistically significant predictor of surgical complications. According to the G8 Score, 90 patients were included in the frail group. A total of 52 frail patients vs. 4 non-frail patients developed a postoperative complication of any kind (p < 0.001). Of these, 11 were major complications and all occurred in the frail group. Our results suggest that the G8 screening tool is an effective and useful instrument to predict the risk of overall complications in elderly patients prior to renal surgery

Estudio traslacional para el manejo de la obesidad utilizando el Programa de Prevención de Diabetes “Grupo de Equilibrio de Estilo de Vida” en clínicas de primer nivel y hospitales públicos de México: protocolo de estudio

Introduction: Obesity is the main modifiable risk factor for the development of chronic diseases in Mexico. Several randomized controlled trials have shown that intensive lifestyle programs are efficacious for the management of obesity. These programs include frequent sessions (14 or more contacts in the first 6 months) focused on diet and physical activity and use a behavior change protocol. However, most Mexican primary care clinics and public hospitals apply traditional treatments for obesity management with limited results on weight loss. The purpose of the study is to evaluate the effectiveness of the Diabetes Prevention Program (DPP) “Group Lifestyle Balance” for weight loss among adults with overweight and obesity from baseline to 6 months and from baseline to 12 months in primary care clinics and public hospitals from Sonora, Mexico.Material and Methods: This is a translational, multi-center, non-controlled, 6 and 12-month follow-up clinical study with a pre-test and post-test design. Healthcare providers from two primary care clinics, two hospitals and one university clinic will be trained with the DPP protocol to implement on their patients with overweight and obesity. Body weight, body mass index, waist circumference, systolic and diastolic blood pressure, depression, quality of life and stress scales will be measured in participants receiving the program at baseline, 6 and 12 months. Biochemical parameters will be measured at baseline and 12 months. The primary outcome is the change in body weight at 6 and 12 months.Discussion: This study will provide scientific evidence of the effectiveness of the DPP protocol as a model for obesity management in real world clinical practice among the adult Mexican population.Introducción: La obesidad es el principal factor de riesgo para el desarrollo de enfermedades crónicas en México. Varios ensayos clínicos controlados han mostrado que los programas intensivos de cambio de estilo de vida son eficaces para el manejo de obesidad. Estos programas incluyen sesiones frecuentes (14 o más los primeros 6 meses), centradas en hacer mejoras en la dieta y actividad física utilizando un protocolo de cambio de comportamiento. Sin embargo, la mayoría de clínicas de primer nivel y los hospitales públicos aplican tratamientos tradicionales para el manejo de obesidad que tienen resultados limitados. El propósito del estudio es evaluar la efectividad del Programa de Prevención de Diabetes “Grupo de Equilibrio de Estilo de Vida” sobre la pérdida de peso en adultos con sobrepeso y obesidad del inicio a 6 meses y del inicio a 12 meses del seguimiento en clínicas de primer nivel y hospitales públicos de Sonora, México.Material y Métodos: Este es un estudio clínico multicéntrico traslacional, no controlado con diseño pre y post-prueba a 6 y 12 meses. Los proveedores de salud de dos clínicas de primer nivel, dos hospitales públicos y una clínica universitaria serán entrenados con el protocolo del Programa de Prevención de Diabetes, para implementarlo en sus pacientes adultos con sobrepeso y obesidad. Se medirá el peso corporal, índice de masa corporal, circunferencia de cintura, presión sistólica y diastólica, así como escalas de depresión, calidad de vida y estrés, al inicio, 6 y 12 meses. Los parámetros bioquímicos se medirán al inicio y a los 12 meses. La variable de desenlace primaria será el cambio de peso a 6 y 12 meses.Discusión: Este estudio proveerá evidencia científica de la efectividad del protocolo del Programa de Prevención de Diabetes como un modelo para el manejo de obesidad en adultos mexicanos en condiciones de la práctica clínica del mundo real

False positive rate of an arrayCGH platform for single-cell preimplantation genetic screening and subsequent clinical application on day-3

In this work, false positive rate of an arrayCGH platform for its use in day-3 single-blastomere analysis was calculated. For this purpose, 38 embryos diagnosed as abnormal on day-3 by FISH were re-biopsied on day-4. Single-cell day-4 arrayCGH diagnosis was then performed. A successful amplification was obtained in 97.4 % (37/38) of the day-4 cells analysed by arrayCGH. Day-3 FISH and day-4 arrayCGH diagnosis were concordant in 35/37 cases. The two discordant embryos were spread and all the cells from each embryo were re-analysed by FISH on day 5. The same error rate (2.7 %) for day-3 FISH and day-4 arrayCGH was obtained when comparing day-5 FISH re-analysis. After this pre-clinical phase, the platform was used for day-3 arrayCGH clinical application in 320 patients (1,760 embryos). Day-3 amplification rate was 98.6 %. An optimal reproductive outcome was obtained when applying arrayCGH to a clinical program: clinical pregnancy rate per cycle of 38.4 % and 60.3 % per transference were obtained, with an implantation rate of 53.5 %. Overall miscarriage rate was 10.6 %. Additionally, day-5 FISH re-analysis was performed in 42 of the embryos from the clinical phase, obtaining a concordance rate of 97.6 % with day-3 arrayCGH.Electronic supplementary materialThe online version of this article (doi:10.1007/s10815-012-9918-4) contains supplementary material, which is available to authorized users

Resection Techniques During Robotic Partial Nephrectomy: A Systematic Review

CONTEXT: The resection technique used to excise tumor during robotic partial nephrectomy (RPN) is of paramount importance in achieving optimal clinical outcomes. OBJECTIVE: To provide an overview of the different resection techniques used during RPN, and a pooled analysis of comparative studies. EVIDENCE ACQUISITION: The systematic review was conducted according to established principles (PROSPERO: CRD42022371640) on November 7, 2022. A population (P: adult patients undergoing RPN), intervention (I: enucleation), comparator (C: enucleoresection or wedge resection), outcome (O: outcome measurements of interest), and study design (S) framework was prespecified to assess study eligibility. Studies reporting a detailed description of resection techniques and/or evaluating the impact of resection technique on outcomes of surgery were included. EVIDENCE SYNTHESIS: Resection techniques used during RPN can be broadly classified as resection (non-anatomic) or enucleation (anatomic). A standardized definition for these is lacking. Out of 20 studies retrieved, nine compared "standard" resection versus enucleation. A pooled analysis did not reveal significant differences in terms of operative time, ischemia time, blood loss, transfusions, or positive margins. Significant differences favoring enucleation were found for clamping management (odds ratio [OR] for renal artery clamping 3.51, 95% confidence interval [CI] 1.13-10.88; p = 0.03), overall complications (OR for occurrence 0.55, 95% CI 0.34-0.87; p = 0.01) major complications (OR for occurrence 0.39, 95% CI 0.19-0.79; p = 0.009), length of stay (weighted mean difference [WMD] -0.72 d, 95% CI -0.99 to -0.45; p < 0.001), and decrease in estimated glomerular filtration rate (WMD -2.64 ml/min, 95% CI -5.15 to -0.12; p = 0.04). CONCLUSIONS: There is heterogeneity in the reporting of resection techniques used during RPN. The urological community must improve the quality of reporting and research produced accordingly. Positive margins are not specifically related to the resection technique. Focusing on studies comparing standard resection versus enucleation, advantages with tumor enucleation in terms of avoidance of artery clamping, overall/major complications, length of stay, and renal function were found. These data should be considered when planning the RPN resection strategy. PATIENT SUMMARY: We reviewed studies on robotic surgery for partial kidney removal using different techniques to cut away the kidney tumor. We found that a technique called "enucleation" was associated with similar cancer control outcomes in comparison to the standard technique and had fewer complications, better kidney function after surgery, and a shorter hospital stay

Clinical Efficacy and Safety of Fanhdi^®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study

Objective: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. Methods: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. Results: Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. Conclusions: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patientsThe author(s) disclosed receipt of the followingfinancial support forthe research, authorship, and/or publication of this article: This workwas supported by Grifols, manufacturer of the pdVWF/FVIII,Fanhdi