Ensayo clínico multicéntrico NCT03738488: modelos anatómicos 3D versus imágenes radiológicas para planificación quirúrgica en pacientes con cáncer de células renales y trombo tumoral vascular

El cáncer de células renales (CCR) con trombo tumoral vascular (TTV) es un reto terapéutico, que hace imprescindible una adecuada planificación quirúrgica. Los modelos 3D son copias impresas de la anatomía del paciente a partir de las imágenes radiológicas que podrían mejorar la planificación quirúrgica. Objetivos: Determinar si en CCR y TTV la planificación quirúrgica con modelos 3D es factible y, si en comparación con las pruebas de imagen, permite una cirugía más predecible, eficaz y costo-beneficiosa. Metodología: Ensayo clínico aleatorizado y multicéntrico, sobre una cohorte de pacientes con CCR y TTV (n=66). Brazo experimental: planificación con imagen y modelo 3D; brazo control: planificación con imagen. Se evaluó: 1) predictibilidad (concordancia entre planificación y cirugía); 2) Resultados quirúrgicos (tiempo quirúrgico, complicaciones, tiempo hospitalario). Se valoró la satisfacción de urólogos y pacientes y el coste-beneficio. Resultados Se obtuvo un modelo 3D factible para planificar y simular la cirugía. La concordancia entre planificación y cirugía fue mayor en el grupo 3D (Kappa 0,9 – 1 vs. 0 – 1). No hubo diferencias en tiempo quirúrgico (p = 0,9). Hubo menos complicaciones (p < 0,0001) y tiempo de estancia en UCI (p = 0,006) en el grupo 3D. Se demostró el coste beneficio de la impresión 3D y, tanto urólogos como pacientes, quedaron muy satisfechos con los modelos. Conclusiones • Se obtuvo un modelo 3D factible para planificación quirúrgica. • El modelo 3D demostró mayor capacidad de predicción y mejores resultados quirúrgicos. • La planificación con modelos 3D fue costo-beneficiosa y el nivel de satisfacción tanto de pacientes como urólogos fue muy elevado

Biomodelos 3D para planificación quirúrgica en pacientes con cáncer renal y afectación vascular (NCT03738488)

[Resumen] El cáncer renal (CCR) supone el 5% de las neoplasias malignas del adulto, presentándose el 10% con trombo tumoral vascular (TTV). Ello empeora el pronóstico y supone un reto terapéutico por la complejidad del abordaje quirúrgico y morbimortalidad perioperatoria, haciendo imprescindible una adecuada planificación quirúrgica por un equipo multidisciplinar. Los biomodelos 3D son copias impresas de la anatomía del paciente fabricadas en material plástico a partir de las imágenes radiológicas. La experiencia visual y táctil que ofrecen podría mejorar la planificación quirúrgica, servir como entrenamiento y acercar la comunicación médico-paciente. Objetivos: Determinar si en CCR y TTV la planificación quirúrgica basada en pruebas de imagen y modelo 3D es factible y si en comparación con la planificación quirúrgica basada en pruebas de imagen permite realizar una cirugía más segura, predecible, eficaz y eficiente. Se plantea, además, si la simulación quirúrgica sirve como modelo de entrenamiento, si ayuda a una mejor comunicación médico-paciente y si es coste-efectiva. Metodología: El diseño del estudio es un ensayo clínico aleatorizado, multicéntrico, sobre una cohorte de pacientes diagnosticados de CCR y TTV a partir del 2019 en los Hospitales Universitarios Virgen del Rocío (HUVR) o Ramón y Cajal (HURC). El estudio tendrá una duración de 3 años y será realizado de forma conjunta por el HUVR, el HURC y el Instituto de Biomedicina de Sevilla (IBIS), en un equipo multidisciplinar integrado por urólogos, radiólogos e ingenieros. El tamaño muestral será de 51 pacientes asignados a cada uno de los brazos de estudio mediante aleatorización simple. Se valorará la seguridad, precisión y predictibilidad de la planificación quirúrgica en modelos 3D vs imagen, la eficacia en términos de resultados quirúrgicos y la eficiencia en términos de coste-efectividad. La asociación y comparación entre variables se evaluará con el test Chi-cuadrado, test exacto de Fisher, T-Student, U de Mann-Whitney, Rho de Spearman o Pearson según Biomodelos 3D 5 corresponda. Para determinar el grado de concordancia entre el TC, los modelos 3D y el órgano “vivo” según las estructuras anatómicas y características quirúrgicas se utilizará el coeficiente Kappa y el coeficiente de correlación intraclase (CCI).[Resumo] O cancro renal (CCR) supón o 5% das neoplasias malignas do adulto, presentándose o 10% con trombo tumoral vascular (TTV). Iso empeora o pronóstico e supón un reto terapéutico pola complexidade do abordaxe cirúrxico e morbimortalidade perioperatoria, facendo imprescindible unha adecuada planificación cirúrxica por un equipo multidisciplinar. Os biomodelos 3D son copias impresas da anatomía do paciente fabricadas en material plástico a partir das imaxes radiolóxicas. A experiencia visual e táctil que ofrecen podería mellorar a planificación cirúrxica, servir como adestramento e achegar a comunicación médico-paciente Obxectivos: Determinar si en CCR e TTV a planificación cirúrxica baseada en probas de imaxe e modelo 3D é factible e si en comparación coa planificación cirúrxica baseada en probas de imaxe permite realizar unha cirurxía máis segura, predicible, eficaz e eficiente. Suscítase, ademais, si a simulación cirúrxica serve como modelo de adestramento, si axuda a unha mellor comunicación médico-paciente e si é custo-efectiva Metodoloxía: O deseño do estudo é un ensaio clínico aleatorizado, multicéntrico, sobre unha cohorte de pacientes diagnosticados de CRC e TTV a partir do 2019 nos Hospitais Universitarios Virxe do Rocio (HUVR) ou Ramón e Cajal (HURC). O estudo terá unha duración de 3 anos e será realizado de forma conxunta polo HUVR, o HURC e o Instituto de Biomedicina de Sevilla (IBIS), nun equipo multidisciplinar integrado por urólogos, radiólogos e enxeñeiros . O tamaño muestral será de 51 pacientes asignados a cada un dos brazos de estudo mediante aleatorización simple. Valorarase a seguridade, precisión e predictibilidad da planificación cirúrxica en modelos 3D vs imaxe, a eficacia en termos de resultados cirúrxicos e a eficiencia en Biomodelos 3D 6 termos de custo- efectividade. A asociación e comparación entre variables avaliarase co test Chi-cadrado, test exacto de Fisher, T-Student, U de Mann-Whitney, Rho de Spearman ou Pearson segundo corresponda. Para determinar o grado de concordancia entre o TC, os modelos 3D e o órgano “vivo” segundo as estruturas anatómicas e características cirúrxicas utilizarase o coeficiente Kappa e o coeficiente de correlación intraclase (CCI).[Abstract] Renal cancer (RCC) accounts for 5% of adult malignancies, and up to 10% presents with vascular tumor thrombus (TTV). This worsens the prognosis and represents a therapeutic challenge due to the complexity of the surgical approach and perioperative morbidity and mortality, being essential an adequate surgical planning by a multidisciplinary team. 3D biomodels are printed copies of the anatomy of each patient made of plastic material from radiological images. The visual and tactile experience they offer could improve surgical planning, serve as training and bring the doctor-patient communication closer. Objectives: To determine if surgical planning based on imaging tests and 3D model is feasible in CCR and TTV and if in comparison with the surgical planning based on imaging tests, it allows a safer and a more predictable, effective and efficient surgery. It will be also analyzed if the surgical simulation serves as a training model, helps a better doctor-patient communication and if it is cost-effective. Methodology: The design of the study is a randomized, multicenter clinical trial on a cohort of patients diagnosed with RCC and TTV starting in 2019 at the University Hospitals Virgen del Rocío (HUVR) or Ramón y Cajal (HURC). The study will last for 3 years and will be carried out jointly by the HUVR, the HURC and the Institute of Biomedicine of Seville (IBIS), in a multidisciplinary team composed of urologists, radiologists and engineers. The sample size will be Biomodelos 3D 7 51 patients assigned to each of the study arms by simple randomization. The safety, precision and predictability of surgical planning in 3D vs image will be assessed, as well as effectiveness in terms of surgical results and efficiency in terms of cost-effectiveness. The association and comparison between variables will be evaluated with Chi-square test, Fisher's exact test, Student's T test, Mann-Whitney U test, Spearman's Rho or Pearson test, as appropriate. To determine the degree of concordance between the CT, the 3D models and the "living" organ according to the anatomical structures and surgical characteristics, the Kappa coefficient and the intraclass correlation coefficient (ICC) will be used.Traballo fin de mestrado (UDC.FCS). Asistencia e investigación sanitaria. Especialidade en investigación clínica. Curso 2018/201

Multiple partial nephrectomy for multifocal synchronous renal cancer in a solitary kidney

Introduction & Objectives: multifocal synchronous renal cancer on a solitary kidney represent a challenging clinical scenario. The complexity of imperative nephron-sparring surgery in this setting resides in ensuring complete excision of cancer with the maximal preservation of renal function. We aim to present a case of multiple partial nephrectomy (MPN) for multifocal synchronous renal cancer in a patient with a solitary kidney and discuss our experience of imperative partial in this setting. Materials & Methods: We present a case of a 76 years old man with a past medical history of hypertension, chronic obstructive pulmonary disease, peripheral vascular disease, left radical nephrectomy for renal mass (2006) and a right renal artery stent placement for renal artery stenosis. During his surveillance, computerized axial tomography (CAT) scan showed 3 enhancing renal masses (2.2cm, 1.5cm and 1cm, respectively). Biopsy of the largest mass was consistent in clear cell renal cell carcinoma (ccRCC). Preoperative level of creatinine was 1.4mg/dL and estimated glomerular filtration rate (eGFR) 50ml/min/1,73m2. After ablative therapy was deemed unsafe, a MPN was planned

Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy

Since prostate cancer (PCa) was described as androgen-dependent, the androgen receptor (AR) has become the mainstay of its systemic treatment: androgen deprivation therapy (ADT). Although, through recent years, more potent drugs have been incorporated, this chronic AR signaling inhibition inevitably led the tumor to an incurable phase of castration resistance. However, in the castration-resistant status, PCa cells remain highly dependent on the AR signaling axis, and proof of it is that many men with castration-resistant prostate cancer (CRPC) still respond to newer-generation AR signaling inhibitors (ARSis). Nevertheless, this response is limited in time, and soon, the tumor develops adaptive mechanisms that make it again nonresponsive to these treatments. For this reason, researchers are focused on searching for new alternatives to control these nonresponsive tumors, such as: (1) drugs with a different mechanism of action, (2) combination therapies to boost synergies, and (3) agents or strategies to resensitize tumors to previously addressed targets. Taking advantage of the wide variety of mechanisms that promote persistent or reactivated AR signaling in CRPC, many drugs explore this last interesting behavior. In this article, we will review those strategies and drugs that are able to resensitize cancer cells to previously used treatments through the use of “hinge” treatments with the objective of obtaining an oncological benefit. Some examples are: bipolar androgen therapy (BAT) and drugs such as indomethacin, niclosamide, lapatinib, panobinostat, clomipramine, metformin, and antisense oligonucleotides. All of them have shown, in addition to an inhibitory effect on PCa, the rewarding ability to overcome acquired resistance to antiandrogenic agents in CRPC, resensitizing the tumor cells to previously used ARSis

Parp Inhibitors and Radiotherapy: A New Combination for Prostate Cancer (Systematic Review)

PARPi, in combination with ionizing radiation, has demonstrated the ability to enhance cellular radiosensitivity in different tumors. The rationale is that the exposure to radiation leads to both physical and biochemical damage to DNA, prompting cells to initiate three primary mechanisms for DNA repair. Two double-stranded DNA breaks (DSB) repair pathways: (1) non-homologous end-joining (NHEJ) and (2) homologous recombination (HR); and (3) a single-stranded DNA break (SSB) repair pathway (base excision repair, BER). In this scenario, PARPi can serve as radiosensitizers by leveraging the BER pathway. This mechanism heightens the likelihood of replication forks collapsing, consequently leading to the formation of persistent DSBs. Together, the combination of PARPi and radiotherapy is a potent oncological strategy. This combination has proven its efficacy in different tumors. However, in prostate cancer, there are only preclinical studies to support it and, recently, an ongoing clinical trial. The objective of this paper is to perform a review of the current evidence regarding the use of PARPi and radiotherapy (RT) in PCa and to give future insight on this topic

Kidney Autotransplantation in the Management of Residual Retroperitoneal Mass in a Germ Cell Tumor

The main indication for kidney autotransplantation is ureteric disease, although it is also performed to treat renovascular diseases or neoplasms, such as complex intrasinusal kidney tumors or in patients with a solitary kidney. Only a few cases of kidney autotransplantation in the context of resection of complex retroperitoneal masses have been reported in the literature.[Case Presentation] We report the case of a 26-year-old man with history of nonseminomatous germ cell tumor who had undergone a left radical orchiectomy 3 months earlier. Follow-up computed tomography revealed a residual retroperitoneal postchemotherapy mass involving the renal hilum. It was surgically removed via en bloc resection and bench ex vivo nephron-sparing surgery, and subsequently autotransplantation, thereby avoiding the necessity of nephrectomy and the resulting risk of chronic kidney disease. The pathology of the excised specimen demonstrated mixed germ cell tumor, composed of immature teratoma and yolk sac tumor, and confirmed tumor-free margins.[Conclusions] This technique should be taken into account in selected patients as an alternative to radical nephrectomy when a retroperitoneal tumor is unresectable using standard surgical techniques or when a radical nephrectomy is considered, especially in patients with chronic kidney disease or solitary kidney, or in young patients who will potentially need nephrotoxic chemotherapy.Peer reviewe

Improving oncological outcomes after robot-assisted radical prostatectomy: what novel tools do we have?

The recent application of novel technologies to the robot-assisted radical prostatectomy (RARP) procedure has provided a new perspective and demonstrated potential usefulness in surgical planning, intraoperative navigation, and education of both patients and healthcare professionals, allowing for a patient-tailored prostate cancer (PCa) treatment. Integration of novel techniques into robotic surgery has improved the accuracy of surgery and has demonstrated a potential benefit in functional and oncological outcomes in patients with PCa. However, further randomized and prospective studies are needed to assess and validate the role of these technologies in clinical practice. The aim of this review is to summarize the current evidence on the new emerging techniques, such as three-dimensional (3D) imaging and printing, augmented reality (AR), and confocal microscopy (CM), and their impact on RARP and its oncological outcomes