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The survival of patients with solid tumors, such as prostate cancer (PCa), has been limited and fleeting with anti-angiogenic therapies. It was previously thought that the mechanism by which the vasculature regulates tumor growth was driven by a passive movement of oxygen and nutrients to the tumor tissue. However, previous evidence suggests that endothelial cells have an alternative role in changing the behavior of tumor cells and contributing to cancer progression. Determining the impact of molecular signals/growth factors released by endothelial cells (ECs) on established PCa cell lines in vitro and in vivo could help to explain the mechanism by which ECs regulate tumor growth. Using cell-conditioned media collected from HUVEC (HUVEC-CM), our data show the stimulated proliferation of all the PCa cell lines tested. However, in more aggressive PCa cell lines, HUVEC-CM selectively promoted migration and invasion in vitro and in vivo. Using a PCa-cell-line-derived xenograft model co-injected with HUVEC or preincubated with HUVEC-CM, our results are consistent with the in vitro data, showing enhanced tumor growth, increased tumor microvasculature and promoted metastasis. Gene set enrichment analyses from RNA-Seq gene expression profiles showed that HUVEC-CM induced a differential effect on gene expression when comparing low versus highly aggressive PCa cell lines, demonstrating epigenetic and migratory pathway enrichments in highly aggressive PCa cells. In summary, paracrine stimulation by HUVEC increased PCa cell proliferation and tumor growth and selectively promoted migration and metastatic potential in more aggressive PCa cell lines.
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INTRODUCTION AND IMPORTANCE: Castleman's disease was first reported by Benjamin Castleman et al., in 1954 and described it as a sporadic lymphoproliferative disorder. The pathophysiology to this day is still unknown, although IL-6 is suspected to play an important role. Preoperative diagnosis is challenging due to its non-specific symptoms, and that imaging cannot clearly distinguish the disease from other processes. High clinical awareness is necessary to reach a diagnosis. If the disease is localized, complete recovery can be achieved through surgery. CASE PRESENTATION: Patient is a 68-year-old woman with a three-month history of recurrent episodes of fever, myalgias, and night sweats. She started to experience lower abdominal pain and presented to the emergency room. A contrast-enhanced abdominal computed tomography revealed a 5 cm well-circumscribed focal heterogeneously enhancing hyperplastic mass between the portal vein and the inferior vena cava. After successful laparoscopic surgery, the mass was resected, and the patient fully recovered. Unicentric Castleman's disease was the final diagnosis. DISCUSSION AND CONCLUSION: Castleman's disease is an uncommon pathology with a challenging diagnosis. When approaching an abdominal mass, unicentric Castleman's disease should always be a differential diagnosis, as treatment can be curative with surgical resection. With the advent of laparoscopic and robotic surgery, these techniques can improve patients' outcomes in these rare pathologies, especially when they appear in complex regions.
RESUMEN
BACKGROUND: Integration of evidence into practice is suboptimal. Clinical pathways, defined as multidisciplinary care plans, are a method for translating evidence into local settings and have been shown to improve the value of patient care. OBJECTIVE: To describe the development of a clinical pathways programme across a large academic healthcare system. METHODS: We use a 10-step framework (grounded in the Knowledge-to-Action framework and ADAPTE Collaboration methodology for guideline adaptation) to support pathway development and dissemination, including facilitating clinical owner and stakeholder engagement, developing pathway prototypes based on rapid reviews of the existing literature, developing tools for dissemination and impact assessment. We use a cloud-based technology platform (Dorsata, Washington, DC) to assist with development and dissemination across our geographically distributed care settings and providers. Content is viewable through desktop and mobile applications. We measured programme adoption and penetration by examining number of pathways developed as well as mobile application use and pathway views. RESULTS: From 1 February 2016 to 30 April 2018, a total of 202 pathways were disseminated. The three most common clinical domains represented were oncology (46.5%, n=94), pulmonary/critical care (8.9%, n=18) and cardiovascular medicine (7.4%, n=15). Users opting to register for a personal account totalled 1279; the three largest groups were physicians (45.1%, n=504), advanced practice providers (19.5%, n=245) and nurses (19.1%, n=240). Pathway views reached an average of 2150 monthly views during the last 3 months of the period. The majority of pathways reference at least one evidence-based source (93.6%, n=180). CONCLUSIONS: A healthcare system can successfully use a framework and technology platform to support the development and dissemination of pathways across a multisite institution.