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2015 CUA Abstracts

ABSTRACT: Introduction and Objectives: Optimizing targeted therapy in patients with metastatic renal cell carcinoma (RCC) would improve clinical outcomes but patient derived xenograft (PDX) models are lacking. We present a novel pre-clinical model that is superior to nude mice for accommodating RCC PDXs. This preclinical model implants RC PDXs into the chorioallantoic membrane (CAM) of avian embryos and is a patient-specific platform that could be advantageous for physicians in the future when deciding what treatment options are best for their patients. This drug panelling platform is rapid, cost-effective, and relies on the highly angiogenic CAM to support RCC PDXs. Methods: Commercial and patient derived RCC cell lines, were grown to full confluence and transduced to generate fluorescently labeled versions of each cell line. Cells were implanted into the CAM. Tumors were treated every two days by applying 10 ?L (10 ?M) of indicated drug onto the tumor onplant. The drugs that were paneled include Sunitinib, Sorafenib, Pazopanib, Axitinib and a vehicle treatment. After 7–8 days of incubation post-implantation, tumor take rate was determined by the presence of tumor growth in the CAM using a fluorescent stereoscope. Results: The highest tumor take rates were observed in the vehicle treatments of the embryos, ranging from 50–86%. Both commercial and primary cell lines saw a reduction in tumor take rate with the application of various anti-angiogenic drugs. Specifically, XP121 tumors were resistant to Sorafenib; 786-0, XP121; XP206 were resistant to Pazopanib; T258, XP121 were resistant to Sunitinib; and lastly, T258 tumors were resistant to Axitinib (Table 1). Conclusions: RCC PDXs onplanted in the CAM of avian embryos offer a robust and cost-effective platform to predict sensitivity/resistance to targeted therapies. When evaluating several patient-derived RCC cell lines, drug paneling revealed other alternative treatment options for these PDXs. More importantly, RCC PDXs that were shown to be Sunitinib-resistant in both the patient and in mouse-based PDXs, also produced the same resistance phenotype in the CAM.

SUBMITTER: Power N

PROVIDER: S-EPMC4497363 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Project description:Background: The incidence of small renal masses (SRMs) has increased in recent years in line with increased in abdominal imaging. SRMs are defined as enhancing solid lesions measuring ? 4cm. We present our experience with percutaneous renal tumour biopsy (RTB) of SRMs, which to our knowledge, is the largest to date. Methods: We reviewed our database to ascertain the incidence of benign, malignant and non-diagnostic biopsies of SRMs performed at our institution from 2001 to July 2013. A total of 519 RTBs were performed (496 SRMs). The diagnostic rate was compared over time. The accuracy of the biopsies was correlated with the definitive pathology in the cases where the biopsy led to surgery. Results: The mean size of the 519 biopsied lesions was 2.5 (±0.9) cm. The diagnostic rate at the first biopsy was 89.1% (442/496). Of the diagnostic biopsies, 116 (26.2%) were benign and 326 (73.7%) were malignant. Of the 54 non-diagnostic biopsies, 23 (42.6%) had a repeat biopsy. A diagnosis was obtained in 19 cases (82.6%; 8 [42.1%] benign, 11 [57.9%] malignant). Therefore RTB led to a diagnosis in 461 of the 496 SRMs (92.9%). Over time, there was a decrease in the rate of non-diagnostic biopsies from 15.0% to 6.0% (p>0.05). Of the available surgical pathology, there was agreement between histology in 92.5% (125/135). For the conventional cell carcinoma (n=85), there was concordance between histology and grade in 97.6% (83/85) and 96.1% (74/77), respectively. Conclusions: RTB of SRMs provided a diagnosis in 92.9% of the cases. Surgery was avoided in more than 23% of patients following RTB because of benign histology. The rate of non-diagnostic biopsies diminished over time. Finally, there was a high correlation between the biopsy and the final pathology with regards to both histology and grade. In an era where overdiagnosis and overtreatment of favourable cancers is gaining attention, routine RTB for SRM leads to diminished intervention and, going forward ,personalization of care.

Project description:Background: Radical prostatectomy can be challenging in patients with a very large prostate. The extraperitoneal (EP) approach to a robot-assisted radical prostatectomy (RARP) is often considered more difficult than the transperitoneal approach due to the limited working space. The aim of the study is to evaluate if EP-RARP overcomes the obstacles posed by very large prostates. Methods: In this institutional review board-approved study, we queried our prospectively collected database (CAISIS) of patients who underwent EP-RARP. 1663 patients underwent EP-RARP for localized prostate cancer by a single surgeon (Jul. 2003–Dec. 2013). 55 patients with prostate pathology specimen weight >100g (group 1) were matched to an equally-sized cohort with prostate weight of <100 g (group 2). A propensity-score match using multivariate analysis was performed incorporating 10 co-variates. Data on standard pre, peri, and postoperative variables was analyzed, as well as complications classified according to the modified Clavien-Dindo classification were noted. Results: The mean PSA (9.1 ± 5.4 vs. 6.9 ± 5, p=0.03) was higher in group 1. All other patient and disease variables [Age (65.2 ± 5.6 vs. 63.3 ± 6, p=0.08), BMI (28.8 ± 3.4 vs. 29.3 ± 5, p=0.57), ASA 1/2/3 (7.2/72.7/20 vs. 10.9/69/20, p=0.8), clinical T-stage 1/2 (89/11 vs. 89/11, p=0.78), and biopsy Gleason score sum 7 (71/29 vs. 71/29, p=1) were similar in group 1 and 2 respectively. The mean prostate weight in group 1 was 120 g, while it was 58.6 g in group 2 (p<0.0001). There was no difference in the ability to perform partial or full nerve-sparing (70 vs 78 %, p=0.19) or pelvic lymphadenectomy (34.5 vs. 38.1 %, p=0.69). Post-operative pathological parameters such as Gleason score sum 7 (70.5/29.5 vs. 56.3/43.7, p=0.13), T-stage 2/3a/3b (89/7.2/1.8 vs. 87.2/10.9/1.8, p= 0.86) and positive surgical margin rates (7.2 vs. 9 %, p=1) were similar. Higher mean OR time (205.8 ± 48.6 vs 180.2 ± 43.4 mins, p=0.004) and estimated blood loss (318.4 ± 172.8 and 200.3 ± 143.5ccs, p=0.0002) were noted in group 1 compared to group 2 respectively. There were no differences in transfusion rates (1 patient transfused in group 2), rates of patients discharged on day 1 (89 vs. 94%, p=0.27), or the complications [Clavien 1–2/3–4 (11/2 vs 8/0, p=0.41)] between the two groups. Conclusions: Apart from increased operative times and blood loss, no differences in peri and postoperative parameters, and complications were found between patients with prostates > than 100 g compared to those with < 100 g undergoing EP-RARP.

Project description:Injury to peripheral nerves is not uncommon, and spinal injury with fracture dislocation of the vertebrae can damage roots as well as the cord. Both types of trauma leave the corresponding muscles denervated, resulting in a flaccid paralysis and catastrophic loss of muscle mass. When this occurs in the lower limbs, a loss of cushioning over bony prominences, combined with a deterioration in skin condition, greatly increases the risk of developing pressure sores. Furthermore, bones become osteoporotic and the wasted appearance of the affected limbs can be a source of great distress to patients. Although there has been a longstanding interest in the potential therapeutic value of electrical stimulation of denervated muscles in humans it was always regarded as impractical. In the absence of the nerve or intramuscular nerve branches the muscles must be excited directly. The charge delivery needed for this is so high that the approach has been frustrated by regulatory restrictions and a lack of suitable equipment. More recently, however, these problems were addressed, and the value of stimulation was clearly demonstrated, in a remarkable research programme pursued with the support of the EU Commission Shared Cost Project “RISE”. It is hard to explore the benefits and limitations of the technique in patient groups, which are small and inhomogeneous in age, nature and duration of injury, and compliance. Moreover, the intense surface stimulation elicits co-contraction of antagonistic muscle groups, which interferes with the measurement of force or torque. In Project “RISE”, the important clinical work1 was therefore complemented by Laboratory studies. The usual model, total sciatic section in the rat, is unsatisfactory on two counts. First, denervated rat muscles show evidence of extensive degeneration in a few months,2 differing in this respect from the muscles of other species. Denervated human muscles, in particular, do not undergo significant necrosis for at least a year post-injury (U. Carraro, personal communication), and we could confirm that this was also true of the rabbit.3 Second, most published studies of stimulation in the denervated rat start at, or soon after, the moment of lesion, which does not correspond to the clinical situation. The “RISE” experimental studies to be discussed were conducted by the Muscle Research Group, University of Liverpool, UK, in a long-term model of established selective denervation in the rabbit. The Department for Biomedical Engineering and Physics, University of Vienna, designed the implantable stimulator,4 ultrastructural studies were performed at the Interuniversity Institute of Myology, Chieti, and valuable input was provided by clinical colleagues at the Ludwig Boltzmann Institute of Electrostimulation and Physical Rehabilitation, Wilhelminenspital, Vienna, Austria. Through this joint programme we were able to assemble comprehensive physiological, histological, biochemical, and ultrastructural data on muscles subjected to selective denervation alone for up to 1 year, and muscles subjected to denervation and stimulation for up to 3 months.3,5,6 Although this data settled several issues, and may serve to take some of the guesswork out of the design of stimulation protocols for clinical use, it raised some tantalizing questions. These will be worth addressing in future studies.

Project description:BackgroundMaterial presented at conferences is meant to provide exposure to ongoing research that could affect medical decision making based on future outcomes. It is important then to evaluate the rates of publication from conference presentations as a measure of academic quality as such research has undergone peer review and journal acceptance. The purpose of this study is to evaluate the fate of abstracts presented at the Skeletal Society of Radiology Annual Meetings from 2010-2015.Materials and methodsConference abstracts were searched using Google, Google Scholar, and PubMed (which includes Medline) to locate the corresponding published reports. The data recorded for published studies included date published online, in print, or both; the journal in which it was published; and the 5-year journal impact factor. When an abstract was not confirmed as published, authors were contacted by email to verify its publication status or, if not published, the reason for nonpublication.ResultsA total of 162 abstracts were published out of 320 presented (50.6%) at the SSR conferences from 2010 to 2015 with 59.9% (85/142) of publications occurring within two years of the conference date (not counting abstracts published prior to conference). Mean time to publication was 19 months and is calculated by excluding the 20 (12.3%) abstracts that were published prior to the conference date. The median time to publication is 13 months (25th-75th percentile: 6.25-21.75). The top two journals publishing research studies from this conference were Skeletal Radiology and The American Journal of Roentgenology. These journals accepted 72 of the 162 (44.4%) studies for publication. Of the 14 authors who responded with 17 reasons for not publishing, the most common reasons were lack of time (7-41.2%), results not important enough (4-23.5%), publication not an aim (3-17.6%), and lack of resources (3-17.6%).DiscussionAt least half of the abstracts presented at the annual meeting for the Society of Skeletal Radiology are accepted for publication in a peer-reviewed journal. The majority (59.9%) of these publications were achieved within two years of the conference presentation. The rate at which presentations are published and the journals that accept the abstracts can potentially be used to compare the importance and quality of information at conferences.

Project description:The UK Extracellular Vesicles (UKEV) Forum meetings were born of the realization that there were a number of UK laboratories studying extracellular vesicle biology and using similar techniques but without a regular national meeting dedicated to EVs at which to share their findings. This was compounded by the fact that many of these labs were working in different fields and thus networking and sharing of ideas and best practice was sometimes difficult. The first workshop was organized in 2013 by Dr Charlotte Lawson, under the auspices of the Society for Endocrinology, led to the founding of the UKEV Forum and the organization of a British Heart Foundation sponsored 1-day conference held in London in December 2014. Although growing in size every year, the central aims of these workshops have remained the same: to provide a forum for discussion and exchange of ideas, to allow young scientists to present their data in the form of short talks and poster presentations and to discuss their work with more established scientists in the field. Here we include the presented abstracts for the 2015 1-day conference hosted by Cardiff University. This meeting was attended by approximately 130 delegates throughout the United Kingdom, but also attended by delegates from Belgium, Netherlands, France, Ireland and other nations. The day composed of plenary presentations from Prof Matthias Belting, Lund University, Sweden and Dr Guillaume van Niel, Institut Curie, Paris together with 10 short presentations from submitted abstracts. The topics covered were broad, with sessions on Mechanisms of EV production, EVs in Infection, EVs in Cancer and in Blood and Characterizing EVs in Biological fluids. This hopefully gives a reflection of the range of EV-related studies being conducted currently in the UK. There were also 33 poster presentations equally broad in subject matter. The organizers are grateful to the Life Science Research Network Wales - a Welsh government-funding scheme that part-sponsored the conference. We are also grateful to commercial sponsors, and 3 paid-presentations are included in the abstracts. The UK EV Forum is expected to become an established annual event held at different Universities across the UK and continue to attract increasing delegate numbers and abstract submissions. We look forward to the next planned conference, which will be hosted by David Carter and his colleagues at Oxford Brookes University on 13th December 2016.

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2015 CUA Abstracts

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