Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

A New Removable Helical Metallic Stent for the Treatment of Tracheomalacia in Children: Study in Pathological Animal Model.

BACKGROUND: Congenital tracheomalacia is a pathology with no consensus of medical or surgical approach. The permanent nature and the major complications associated with metallic stents have limited their use over the years. The purpose of this study was to evaluate the feasibility of a helical stent design removal. METHODS: Ten dogs diagnosed with tracheal collapse and treated with the helical stent were involved in the study. Animals were classified into three groups depending on stent indwelling time. Prior to the removal, endoscopic evaluation was performed to assess endothelization grade, mucous accumulation, and the presence of stenosis. During the removal, bleeding, fracture, or impossibility of removal were noted. After the removal, all macroscopic mucosal changes were recorded. RESULTS: Technical success was 100%, without any complications. Complete epithelization of the stent was visualized in 7/10 animals. The removal procedure duration ranged from 2-12 min. At post-removal endoscopy, bleeding or epithelial damage, was visualized in any case. Stent fracture during removal occurred in one animal. CONCLUSIONS: The removal of a metallic stent with spiral geometry is feasible, simple, and without complications, regardless of the degree of neo-epithelialization.

Stent traqueal biodegradable de polidioxanona. Estudio de la reactividad en conejo / Reactivity study of a biodegradable polydioxanone tracheal stent in a rabbit model

INTRODUCCIÓN: El objetivo de este estudio es evaluar la reactividad traqueal inducida por un stent traqueal biodegradable de polidioxanona. MATERIAL Y MÉTODOS: Veintidós conejos se dividieron en 3 grupos con diferentes tiempos de supervivencia (30, 60 y 90 días postimplantación). Se implantó un stent biodegradable en cada animal, excepto en uno de cada grupo (control negativo). La implantación se realizó a través de una pequeña traqueotomía y bajo control fluoroscópico. Al finalizar los tiempos de supervivencia programados se realizaron estudios de TC y anatomopatológicos. RESULTADOS: Ningún animal murió durante el procedimiento ni en el seguimiento. El stent había desaparecido en el 100% de los casos a los 90 días, en el 50% a los 60 días y en ninguno a los 30 días. En los estudios de TC se observó un grosor de la pared traqueal mayor a los 30 que a los 60 y 90 días (1,60 ± 0,41 mm en la parte central del stent frente a 1,11 ± 0,18 y 0,94 ± 0,11; p = 0,007). En el estudio anatomopatológico no se encontraron granulomas. A los 30 días se observaba cierto grado de alteración histológica, la cual se reduce a los 60 y 90 días. También se encuentran las diferencias, tanto en las TC como en la histología, entre animales con el stent presente y animales con el stent degradado. CONCLUSIONES: Los stents de polidioxanona producen una leve reacción traqueal que revierte con la degradación. El uso de estos stents biodegradables en la patología traqueal benigna es prometedor

INTRODUCTION: The objective of this study was to evaluate tracheal reactivity induced by a biodegradable polydioxanone tracheal stent. MATERIALS AND METHODS: Twenty-two rabbits were divided into 3 groups assigned to different survival times (30, 60 and 90 days post-implantation). A biodegradable stent was implanted in each animal, except for 1 of each group (negative control). Implantation was performed through a small tracheotomy under fluoroscopic control. CT and histopathological studies were scheduled at the end of survival times. RESULTS: No animal died during the procedure or follow-up. The stent had disappeared in 100% of the cases at 90 days, in 50% at 60 days, and in none at 30 days. CT studies revealed a greater tracheal wall thickness at 30 days than at 60 and 90 days (1.60 ± 0.41 mm in the central part of the stent versus 1.11 ± 0.18 and 0.94 ± 0.11; P = .007, respectively). No granulomas were observed on histopathology. Some degree of histological changes were noted at 30 days, which had reduced at 60 and 90 days. Differences were also found in both CT and histology between animals in which the stent was present and animals in which it had degraded. CONCLUSIONS: Polydioxanone stents produce a mild reaction that reverts with tracheal degradation. The use of these biodegradable stents in benign tracheal disease is promising

A new airway spiral stent designed to maintain airway architecture with an atraumatic removal after full epithelization-Research of feasibility and viability in canine patients with tracheomalacia.

OBJECTIVE: Surgical management of tracheomalacia is a challenge, with current treatments still presenting numerous complications. In the field of veterinary medicine, this same pathology is present in a significant number of dogs. For this reason, we present an experimental clinical trial performed on canines with tracheobronchomalacia, using a new atraumatic removable tracheal spiral stent (SS). Both implantation procedure and clinical improvement have been analyzed in this study. METHODS: In this study, four small dogs, a mean weight of 4.89 kg and body condition scores IV-V, were included. SS was implanted by two different surgical approaches. Image and clinical follow-up have been performed during 90 days. Symptoms were evaluated from 1 to 10 every week. RESULTS: This study achieved 100% technical and clinical success. Median tracheal diameters were as follows: cervical 10.85 (3.3), inlet 7.75 (2.1), and carina 7.75 (1.9) mm, and length was 77.5 (26) mm. A 12 × 10 × 100-mm SS was implanted in all cases. Goose honk cough punctuation improved from 8 to 1; also, there were important changes in exercise intolerance, a mean weight loss of 8.76%. The values of modified Karnofsky scale varied from 50 (20) before surgery to 90 (10) after 30 days of surgery. Neither granuloma tissue nor fractures of the prosthesis was observed. CONCLUSION: The results in dogs are promising, and a new therapeutic alternative seems to be available for veterinarian field. The similarity of this disease between dogs and newborns suggests that this SS design can also be useful for human trials.

Reactivity Study of a Biodegradable Polydioxanone Tracheal Stent in a Rabbit Model. / Stent traqueal biodegradable de polidioxanona. Estudio de la reactividad en conejo.

INTRODUCTION: The objective of this study was to evaluate tracheal reactivity induced by a biodegradable polydioxanone tracheal stent. MATERIALS AND METHODS: Twenty-two rabbits were divided into 3 groups assigned to different survival times (30, 60 and 90days post-implantation). A biodegradable stent was implanted in each animal, except for 1 of each group (negative control). Implantation was performed through a small tracheotomy under fluoroscopic control. CT and histopathological studies were scheduled at the end of survival times. RESULTS: No animal died during the procedure or follow-up. The stent had disappeared in 100% of the cases at 90days, in 50% at 60days, and in none at 30days. CT studies revealed a greater tracheal wall thickness at 30days than at 60 and 90days (1.60±0.41mm in the central part of the stent versus 1.11±0.18 and 0.94±0.11; P=.007, respectively). No granulomas were observed on histopathology. Some degree of histological changes were noted at 30days, which had reduced at 60 and 90days. Differences were also found in both CT and histology between animals in which the stent was present and animals in which it had degraded. CONCLUSIONS: Polydioxanone stents produce a mild reaction that reverts with tracheal degradation. The use of these biodegradable stents in benign tracheal disease is promising.

New tracheal stainless steel stent pilot study: twelve month follow-up in a rabbit model.

BACKGROUND: Canine tracheal collapse is a complex airway pathology without promising treatment results. Currently nitinol stents are the best surgical option; however, some professionals are doubting if stent placement is the best option due to the associated complications. OBJECTIVE: Determine the technical feasibility, safety, and long-term follow-up after the implantation of a new tracheal stent designed for canine tracheal collapse. METHODS: Thirteen healthy, adult female New Zealander rabbits were involved in this pilot study.A new intra-tracheal device (Reference number 902711 patent registered as CasMin-Twine) was implanted in ten animals. Deployment was performed under general anesthesia, making a puncture incision via a 21 Gauge needle in the intra-tracheal space where the stent was introduced with a screwing process. The device was fixed to the tracheal wall with a non-absorbable suture. Computerized Tomography (CT) and an endoscopy to study structural abnormalities were performed after 30, 90 and 365 days after stent placement. RESULTS: Technical and clinical success was 100%. There was no significant change in behavior or respiratory disorders. CT studies showed no significant alterations. After the 30 days, 60% of the animals showed partial endothelization in the endoscopy study, and only one animal still presented partial endothelization after 12 months. Mucus accumulation was only present in 40% of cases and classified as low, without respiratory consequences. Only one animal presented a single granuloma at caudal stent tip. CONCLUSIONS: This new tracheal stent (CasMin-Twine) is an effective and safe procedure with promising results, and also shows the possibility of removing the device after endothelization has been produced. New studies should be carried out to evaluate the effectiveness in patients with tracheomalacia. CLINICAL SIGNIFICANCE/IMPACT: This new product can give veterinarians a new option of treatment for this complicated pathology. Minimizing specific equipment for its deployment, CasMin-Twine will be more accessible for all professionals.