Project description: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 μL (10 μM) 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.

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.

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