Design and Early Experience With a Real-World Surgical Registry.

OBJECTIVES: We describe the rationale, design, and methods and 6-year experience with a real-world surgical registry for female pelvic reconstructive and incontinence procedures and postoperative outcomes. METHODS: The primary goal of creating this registry was to establish the feasibility of prospective data capture for all urogynecologic procedures. Data captured included baseline demographics, surgical procedures, perioperative complications, and subjective and objective findings up to 36 months after surgery. RESULTS: The Pelvic Reconstruction and Incontinence Surgery ± Mesh Registry was developed over 3 years to include 194 unique variables for prospective data capture. The registry was implemented in December 2010, and data from 924 separate case events from a single surgeon were recorded, comprising 100% surgical case capture. Cases included a variety of procedures representing a comprehensive urogynecology practice on 804 unique patients. Patients who were asked to participate in long-term follow-up (n = 299) returned with attendance of 96% at 6 weeks, 64% at 6 months, 51% at 12 months, 39% at 24 months, and 22% at 36 months. CONCLUSIONS: The Pelvic Reconstruction and Incontinence Surgery ± Mesh Registry effectively captured all urogynecologic procedures for the purpose of quality improvement. This real-world tool demonstrates that 100% case capture is feasible and provides valuable information for the highly motivated surgeon, although adequate long-term follow-up is limited. Additional research is needed to better understand the role of surgical registries for quality improvement and development of patient-centered strategies to increase long-term follow-up.

Prostaglandin E2 receptor 4 mediates renal cell carcinoma intravasation and metastasis.

Treatment options for metastatic renal cell carcinoma (RCC) are limited. In this study, we investigated impact of prostaglandin E2 (PGE2) receptor 4 (EP4) on RCC metastasis. We found that knockdown of EP4 in two RCC cell lines, ACHN and SN12C, does not affect xenograft tumor take or growth rate in mice, but reduces metastasis by decreasing tumor intravasation. Using chick chorioallantoic membrane (CAM) assay, we confirmed that blockade of EP4 signaling inhibits tumor intravasation. In vitro studies associated EP4 expression and activity with RCC cell transendothelial migration (TEM). Gene expression analysis and validation assays showed that EP4 knockdown decreases expression of CD24, a ligand to the adhesion molecule P-selectin. Forced expression of CD24 in EP4 knockdown RCC rescues TEM capacity of the cells. Pharmacologic inhibition or knockdown of endothelial P-selectin blocks EP4-mediated cancer cell TEM, and inhibition of P-selectin prevents RCC tumor intravasation in CAM assay. Our results demonstrate that inhibition of EP4 attenuates the RCC intravasation and metastasis by downregulating CD24 and that P-selectin participates in tumor intravasation, implying a potential for these molecules as therapeutic targets for advanced RCC treatment.

G protein-coupled receptor kinase GRK5 phosphorylates moesin and regulates metastasis in prostate cancer.

G protein-coupled receptor kinases (GRK) regulate diverse cellular functions ranging from metabolism to growth and locomotion. Here, we report an important contributory role for GRK5 in human prostate cancer. Inhibition of GRK5 kinase activity attenuated the migration and invasion of prostate cancer cells and, concordantly, increased cell attachment and focal adhesion formation. Mass spectrometric analysis of the phosphoproteome revealed the cytoskeletal-membrane attachment protein moesin as a putative GRK5 substrate. GRK5 regulated the subcellular distribution of moesin and colocalized with moesin at the cell periphery. We identified amino acid T66 of moesin as a principal GRK5 phosphorylation site and showed that enforcing the expression of a T66-mutated moesin reduced cell spreading. In a xenograft model of human prostate cancer, GRK5 silencing reduced tumor growth, invasion, and metastasis. Taken together, our results established GRK5 as a key contributor to the growth and metastasis of prostate cancer.